FN Thomson Reuters Web of Science™ VR 1.0 PT J AU Akyuz, N Kekatpure, MV Liu, J Sheinkopf, SJ Quinn, BT Lala, MD Kennedy, D Makris, N Lester, BM Kosofsky, BE AF Akyuz, Nurunisa Kekatpure, Minal V. Liu, Jie Sheinkopf, Stephen J. Quinn, Brian T. Lala, Meenakshi D. Kennedy, David Makris, Nikos Lester, Barry M. Kosofsky, Barry E. TI Structural Brain Imaging in Children and Adolescents following Prenatal Cocaine Exposure: Preliminary Longitudinal Findings SO DEVELOPMENTAL NEUROSCIENCE LA English DT Article DE Structural brain imaging; Prenatal cocaine exposure; Developing brain; Magnetic resonance imaging; Prenatal cocaine ID HUMAN CEREBRAL-CORTEX; MATERNAL LIFE-STYLE; HEAD CIRCUMFERENCE; BLOOD-FLOW; MRI; MORPHOLOGY; OUTCOMES; TOBACCO; SYSTEM; VOLUME AB The brain morphometry of 21 children, who were followed from birth and underwent structural brain magnetic resonance imaging at 8-10 years, was studied. This cohort included 11 children with prenatal cocaine exposure (CE) and 10 noncocaine-exposed children (NCE). We compared the CE versus NCE groups using FreeSurfer to automatically segment and quantify the volume of individual brain structures. In addition, we created a pediatric atlas specifically for this population and demonstrate the enhanced accuracy of this approach. We found an overall trend towards smaller brain volumes among CE children. The volume differences were significant for cortical gray matter, the thalamus and the putamen. Here, reductions in thalamic and putaminal volumes showed a robust inverse correlation with exposure levels, thus highlighting effects on dopamine-rich brain regions that form key components of brain circuitry known to play important roles in behavior and attention. Interestingly, head circumferences (HCs) at birth as well as at the time of imaging showed a tendency for smaller size among CE children. HCs at the time of imaging correlated well with the cortical volumes for all subjects. In contrast, HCs at birth were predictive of the cortical volume only for the CE group. A subgroup of these subjects (6 CE, 4 NCE) was also scanned at 13-15 years of age. In subjects who were scanned twice, we found that the trend for smaller structures continued into teenage years. We found that the differences in structural volumes between the CE and NCE groups are largely diminished when the HCs are controlled for or matched by study design. Participants in this study were drawn from a unique longitudinal cohort and, while the small sample size precludes strong conclusions regarding the longitudinal findings reported, the results point to reductions in HCs and in specific brain structures that persist through teenage years in children who were exposed to cocaine in utero. (C) 2014 S. Karger AG, Basel C1 [Akyuz, Nurunisa; Kekatpure, Minal V.; Quinn, Brian T.; Lala, Meenakshi D.; Kosofsky, Barry E.] Weill Cornell Med Coll, Dept Neurol & Neurosci, New York, NY USA. [Akyuz, Nurunisa; Kekatpure, Minal V.; Quinn, Brian T.; Lala, Meenakshi D.; Kosofsky, Barry E.] Weill Cornell Med Coll, Dept Pediat, New York, NY USA. [Akyuz, Nurunisa] Weill Cornell Med Coll, Dept Physiol & Biophys, New York, NY USA. [Liu, Jie; Sheinkopf, Stephen J.; Lester, Barry M.] Brown Univ, Women & Infants Hosp, Warren Alpert Med Sch, Ctr Study Children Risk, Providence, RI USA. [Kennedy, David; Makris, Nikos] Massachusetts Gen Hosp, Ctr Morphometr Anal, Charlestown, MA USA. RP Kosofsky, BE (reprint author), New York Presbyterian Hosp, Weill Cornell Med Coll, Div Child Neurol, 525 East 68th St,Box 91, New York, NY 10021 USA. EM bar2009@med.cornell.edu RI Liu, Jie/K-3142-2015; OI Akyuz, Nurunisa/0000-0002-6340-1915 FU NIH [DA000354, DA17905, U10-DA-024119-01, U10-HD-27904, R01 MH083320, P30 HD004147]; NICHD [N01-HD-2-3159] FX This work was in part supported by NIH grants DA000354 and DA17905 (B.E.K.) and U10-DA-024119-01, U10-HD-27904 (to BML), NICHD contract N01-HD-2-3159 (to BML), and NIH R01 MH083320 and P30 HD004147 (D.K.). NR 55 TC 2 Z9 2 U1 1 U2 8 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0378-5866 EI 1421-9859 J9 DEV NEUROSCI-BASEL JI Dev. Neurosci. PY 2014 VL 36 IS 3-4 BP 316 EP 328 DI 10.1159/000362685 PG 13 WC Developmental Biology; Neurosciences SC Developmental Biology; Neurosciences & Neurology GA AM7BR UT WOS:000340020200016 PM 24994509 ER PT J AU Counter, SA Buchanan, LH Ortega, F Chiriboga, R Correa, R Collaguaso, MA AF Counter, S. Allen Buchanan, Leo H. Ortega, Fernando Chiriboga, Roberto Correa, Rommy Angela Collaguaso, Maria TI LEAD LEVELS IN THE BREAST MILK OF NURSING ANDEAN MOTHERS LIVING IN A LEAD-CONTAMINATED ENVIRONMENT SO JOURNAL OF TOXICOLOGY AND ENVIRONMENTAL HEALTH-PART A-CURRENT ISSUES LA English DT Article ID ZINC PROTOPORPHYRIN LEVELS; BLOOD LEAD; POOLED-ANALYSIS; MATERNAL BLOOD; EXPOSURE; INFANT; CHILDREN; BONE; LACTATION; PREGNANCY AB Concentrations of lead (Pb) in breast milk (PbM) and blood (PbB) were measured in a current cohort of lactating mothers living in Andean communities where women of childbearing age engage in the occupational use of Pb, and compared to results obtained in earlier studies. Mean PbM concentration in the current group of breastfeeding mothers tested in 2012/2013 was 3.73 mu g/L (SD: 7.3; range: 0.049-28.04), and significantly lower than the 9.83 mu g/L (SD: 12.75; range: 0.2-49) previously observed in breastfeeding mothers in the study area from 1999 to 2007. Breastfeeding women in the current cohort showed an average PbM/PbB ratio of 3.6%, which is in agreement with other studies. The mean PbB level obtained for the current cohort was 7.8 mu g/dl (SD: 5.2; range: 1.4-21), and significantly lower than the mean PbB level of 20.8 mu g/dl (SD: 16.4; range: 4-73) obtained for the comparison group of breastfeeding mothers tested between 1999 and 2007. A correlation of .687 between paired PbM and maternal PbB was found, indicating that maternal PbB level is a significant predictor of PbM. Current PbM levels remain higher than international averages, but indicate that maternal Pb exposure has declined over time in the environmentally Pb-contaminated study area. The current reduction in Pb in milk and blood of breastfeeding mothers may be due to adherence to a Pb-exposure education and prevention program initiated by the authors in the study area years earlier, as well as recent improvements in local health care delivery. C1 [Counter, S. Allen] Harvard Univ, Sch Med, Biol Labs, Dept Neurol, Cambridge, MA 02138 USA. [Counter, S. Allen] Massachusetts Gen Hosp, Dept Neurophysiol, Boston, MA 02114 USA. [Buchanan, Leo H.] Univ Massachusetts, Sch Med, Dept Pediat, Eunice Kennedy Shriver Ctr, Worcester, MA USA. [Buchanan, Leo H.] Harvard Univ Hlth Serv, Dept Otolaryngol, Cambridge, MA USA. [Ortega, Fernando] Univ San Francisco Quito, Colegio Artes Liberales, Escuela Salud Publ, Colegio Ciencias Salud,Escuela Med, Quito, Ecuador. [Ortega, Fernando] Univ San Francisco Quito, Galapagos Inst Arts & Sci GAIAS, Quito, Ecuador. [Chiriboga, Roberto] Pujili Hosp & Hlth Dist, Cotopaxi, Ecuador. [Correa, Rommy; Angela Collaguaso, Maria] Subctr Salud, Pujili, Cotopaxi, Ecuador. RP Counter, SA (reprint author), Harvard Univ, Sch Med, Biol Labs, Dept Neurol, 16 Divin Ave, Cambridge, MA 02138 USA. EM allen_counter@harvard.edu FU National Institutes of Health (NIH) [P30 HD04147] FX LHB is supported in part by National Institutes of Health (NIH) grant P30 HD04147. NR 50 TC 4 Z9 4 U1 2 U2 7 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 530 CHESTNUT STREET, STE 850, PHILADELPHIA, PA 19106 USA SN 1528-7394 EI 1087-2620 J9 J TOXICOL ENV HEAL A JI J. Toxicol. Env. Health Part A PY 2014 VL 77 IS 17 BP 993 EP 1003 DI 10.1080/15287394.2014.897281 PG 11 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA AN0MW UT WOS:000340279700001 PM 25072821 ER PT S AU Yueh, FY Tripathi, MM Singh, JP AF Yueh, Fang Y. Tripathi, Markandey M. Singh, Jagdish P. BE Musazzi, S Perini, U TI Combustion Applications of Laser-Induced Breakdown Spectroscopy SO LASER-INDUCED BREAKDOWN SPECTROSCOPY: THEORY AND APPLICATIONS SE Springer Series in Optical Sciences LA English DT Article; Book Chapter ID EQUIVALENCE RATIO MEASUREMENTS; CONTINUOUS-EMISSION MONITOR; METHANE-AIR FLAMES; AEROSOL-PARTICLES; UNBURNED CARBON; FLY-ASH; PLASMA SPECTROSCOPY; ELEMENTAL ANALYSIS; DIFFUSION FLAMES; PULVERIZED COAL AB The Laser induced breakdown spectroscopy (LIBS) has been applied to combustion product and flame diagnostics. In this chapter, combustion applications of LIBS in past 30 years were reviewed. The various issues including experimental parameters and data processing methods that are important to combustion applications were discussed. Possible other applications that are important to combustion have also been addressed. C1 [Yueh, Fang Y.; Singh, Jagdish P.] Mississippi State Univ, Inst Clean Energy Technol, Starkville, MS 39759 USA. [Tripathi, Markandey M.] Harvard Univ, Sch Med, Wellman Ctr Photomed, Massachusetts Gen Hosp, Boston, MA 02114 USA. [Yueh, Fang Y.; Singh, Jagdish P.] King Saud Univ, Dept Phys, Riyadh, Saudi Arabia. RP Singh, JP (reprint author), Mississippi State Univ, Inst Clean Energy Technol, Starkville, MS 39759 USA. EM yueh@icet.msstate.edu; tripathi.markandey@mgh.harvard.edu; singh@icet.msstate.edu NR 70 TC 0 Z9 0 U1 0 U2 1 PU SPRINGER-VERLAG BERLIN PI BERLIN PA HEIDELBERGER PLATZ 3, D-14197 BERLIN, GERMANY SN 0342-4111 BN 978-3-642-45085-3; 978-3-642-45084-6 J9 SPRINGER SER OPT SCI PY 2014 VL 182 BP 489 EP 509 DI 10.1007/978-3-642-45085-3_18 D2 10.1007/978-3-642-45085-3 PG 21 WC Optics; Spectroscopy SC Optics; Spectroscopy GA BA7WP UT WOS:000337815500019 ER PT J AU Dacey, ML Kennedy, MA Polak, R Phillips, EM AF Dacey, Marie L. Kennedy, Mary A. Polak, Rani Phillips, Edward M. TI Physical activity counseling in medical school education: a systematic review SO MEDICAL EDUCATION ONLINE LA English DT Review DE medical school education; physical activity; exercise; counseling; systematic review ID STUDENTS; HEALTH; CARE; CURRICULA; INTERVENTIONS; COMPETENCE; DOCTORS; HABITS AB Background: Despite a large evidence base to demonstrate the health benefits of regular physical activity (PA), few physicians incorporate PA counseling into office visits. Inadequate medical training has been cited as a cause for this. This review describes curricular components and assesses the effectiveness of programs that have reported outcomes of PA counseling education in medical schools. Methods: The authors systematically searched MEDLINE, EMBASE, PsychINFO, and ERIC databases for articles published in English from 2000 through 2012 that met PICOS inclusion criteria of medical school programs with PA counseling skill development and evaluation of outcomes. An initial search yielded 1944 citations, and 11 studies representing 10 unique programs met criteria for this review. These studies were described and analyzed for study quality. Strength of evidence for six measured outcomes shared by multiple studies was also evaluated, that is, students' awareness of benefits of PA, change in students' attitudes toward PA, change in personal PA behaviors, improvements in PA counseling knowledge and skills, self-efficacy to conduct PA counseling, and change in attitude toward PA counseling. Results: Considerable heterogeneity of teaching methods, duration, and placement within the curriculum was noted. Weak research designs limited an optimal evaluation of effectiveness, that is, few provided pre-/post-intervention assessments, and/or included control comparisons, or met criteria for intervention transparency and control for risk of bias. The programs with the most evidence of improvement indicated positive changes in students' attitudes toward PA, their PA counseling knowledge and skills, and their self-efficacy to conduct PA counseling. These programs were most likely to follow previous recommendations to include experiential learning, theoretically based frameworks, and students' personal PA behaviors. Conclusions: Current results provide some support for previous recommendations, and current initiatives are underway that build upon these. However, evidence of improvements in physician practices and patient outcomes is lacking. Recommendations include future directions for curriculum development and more rigorous research designs. C1 [Dacey, Marie L.] MCPHS Univ, Sch Arts & Sci, Dept Psychol, Boston, MA 02115 USA. [Dacey, Marie L.; Kennedy, Mary A.; Polak, Rani; Phillips, Edward M.] Joslin Diabet Ctr, Inst Lifestyle Med, Boston, MA 02215 USA. [Polak, Rani] Maccabi Hlth Serv, Dept Family Med, Jerusalem, Israel. [Polak, Rani] Hebrew Univ Jerusalem, Dept Family Med, Jerusalem, Israel. [Phillips, Edward M.] Harvard Univ, Sch Med, Boston, MA USA. RP Dacey, ML (reprint author), MCPHS Univ, Sch Arts & Sci, 179 Longwood Ave, Boston, MA 02115 USA. EM Marie.dacey@mcphs.edu NR 44 TC 7 Z9 7 U1 2 U2 9 PU CO-ACTION PUBLISHING PI JARFALLA PA RIPVAGEN 7, JARFALLA, SE-175 64, SWEDEN SN 1087-2981 J9 MED EDUC ONLINE JI Med. Educ. Online PY 2014 VL 19 AR 24325 DI 10.3402/meo.v19.24325 PG 14 WC Education & Educational Research SC Education & Educational Research GA AM9LB UT WOS:000340202000001 PM 25062944 ER PT J AU Leavitt, VM Cirnigliaro, C Cohen, A Farag, A Brooks, M Wecht, JM Wylie, GR Chiaravalloti, ND DeLuca, J Sumowski, JF AF Leavitt, V. M. Cirnigliaro, C. Cohen, A. Farag, A. Brooks, M. Wecht, J. M. Wylie, G. R. Chiaravalloti, N. D. DeLuca, J. Sumowski, J. F. TI Aerobic exercise increases hippocampal volume and improves memory in multiple sclerosis: Preliminary findings SO NEUROCASE LA English DT Article DE Multiple sclerosis; Aerobic; Memory; Functional connectivity; Hippocampus AB Multiple sclerosis leads to prominent hippocampal atrophy, which is linked to memory deficits. Indeed, 50% of multiple sclerosis patients suffer memory impairment, with negative consequences for quality of life. There are currently no effective memory treatments for multiple sclerosis either pharmacological or behavioral. Aerobic exercise improves memory and promotes hippocampal neurogenesis in nonhuman animals. Here, we investigate the benefits of aerobic exercise in memory-impaired multiple sclerosis patients. Pilot data were collected from two ambulatory, memory-impaired multiple sclerosis participants randomized to non-aerobic (stretching) and aerobic (stationary cycling) conditions. The following baseline/follow-up measurements were taken: high-resolution MRI (neuroanatomical volumes), fMRI (functional connectivity), and memory assessment. Intervention was 30-minute sessions 3 times per week for 3 months. Aerobic exercise resulted in 16.5% increase in hippocampal volume and 53.7% increase in memory, as well as increased hippocampal resting-state functional connectivity. Improvements were specific, with no comparable changes in overall cerebral gray matter (+2.4%), non-hippocampal deep gray matter structures (thalamus, caudate: -4.0%), or in non-memory cognitive functioning (executive functions, processing speed, working memory: changes ranged from -11% to +4%). Non-aerobic exercise resulted in relatively no change in hippocampal volume (2.8%) or memory (0.0%), and no changes in hippocampal functional connectivity. This is the first evidence for aerobic exercise to increase hippocampal volume and connectivity and improve memory in multiple sclerosis. Aerobic exercise represents a cost-effective, widely available, natural, and self-administered treatment with no adverse side effects that may be the first effective memory treatment for multiple sclerosis patients. C1 [Leavitt, V. M.; Cohen, A.; Wylie, G. R.; Chiaravalloti, N. D.; DeLuca, J.; Sumowski, J. F.] Kessler Fdn, Res Ctr, W Orange, NJ 07052 USA. [Leavitt, V. M.; Wylie, G. R.; Chiaravalloti, N. D.; DeLuca, J.; Sumowski, J. F.] Rutgers New Jersey Med Sch, Newark, NJ USA. [Cirnigliaro, C.; Farag, A.; Brooks, M.; Wecht, J. M.] James J Peters VA Med Ctr, Bronx, NY USA. [Cirnigliaro, C.] Kessler Inst Rehabil, W Orange, NJ USA. RP Leavitt, VM (reprint author), Kessler Fdn, Res Ctr, Neuropsychol & Neurosci Lab, 300 Execut Dr,Suite 70, W Orange, NJ 07052 USA. EM vleavitt@kesslerfoundation.org NR 7 TC 20 Z9 20 U1 3 U2 23 PU ROUTLEDGE JOURNALS, TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXFORDSHIRE, ENGLAND SN 1355-4794 EI 1465-3656 J9 NEUROCASE JI Neurocase PY 2014 VL 20 IS 6 BP 695 EP 697 DI 10.1080/13554794.2013.841951 PG 3 WC Clinical Neurology; Psychiatry; Psychology SC Neurosciences & Neurology; Psychiatry; Psychology GA AN0IW UT WOS:000340269000010 PM 24090098 ER PT J AU Maramaldi, P Sobran, A Scheck, L Cusato, N Lee, I White, E Cadet, TJ AF Maramaldi, Peter Sobran, Alexandra Scheck, Lisa Cusato, Natalie Lee, Irene White, Erina Cadet, Tamara J. TI Interdisciplinary Medical Social Work: A Working Taxonomy SO SOCIAL WORK IN HEALTH CARE LA English DT Article DE medical social work; interdisciplinary teams; participatory research ID PRIMARY-CARE; COLLABORATION; PHYSICIANS; HEALTH; PERCEPTIONS; MANAGEMENT; DISCHARGE; QUALITY; ROLES; TEAM AB Findings from a year-long exploratory study aimed at describing universal functions of medical social work with interdisciplinary teams in acute care settings are reported here. A universal taxonomy of interdisciplinary social work skills and competencies was empirically identified through a participatory action research framework. Findings support previous conceptual descriptions of medical social work's overarching and historical role to help interdisciplinary teams in acute care to consider patients' home environment, knowledge, beliefs, culture, and resources during assessment, treatment, and discharge planning. The empirically determined taxonomy reported is intended to provide social workers a framework with which to articulate and evaluate their core competencies on interdisciplinary medical teams. C1 [Maramaldi, Peter] Harvard Univ, Sch Dent Med, Simmons Coll, Sch Social Work,Sch Publ Hlth, Boston, MA 02115 USA. [Sobran, Alexandra; Scheck, Lisa; Cusato, Natalie; Lee, Irene] Massachusetts Gen Hosp, Dept Social Work, Boston, MA 02114 USA. [White, Erina] Boston Childrens Hosp, Simmons Sch Social Work, Boston, MA USA. [Cadet, Tamara J.] Harvard Univ, Sch Dent Med, Simmons Coll, Sch Social Work, Boston, MA 02115 USA. RP Maramaldi, P (reprint author), Harvard Univ, Sch Dent Med, Simmons Coll, Sch Social Work,Sch Publ Hlth, 300 Fenway, Boston, MA 02115 USA. EM peter.maramaldi@simmons.edu NR 58 TC 2 Z9 2 U1 3 U2 19 PU ROUTLEDGE JOURNALS, TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXFORDSHIRE, ENGLAND SN 0098-1389 EI 1541-034X J9 SOC WORK HEALTH CARE JI Soc. Work Health Care PY 2014 VL 53 IS 6 BP 532 EP 551 DI 10.1080/00981389.2014.905817 PG 20 WC Social Work SC Social Work GA AN0DR UT WOS:000340253300002 PM 25050659 ER PT J AU Gunda, V Frederick, DT Bernasconi, MJ Wargo, JA Parangi, S AF Gunda, Viswanath Frederick, Dennie T. Bernasconi, Maria J. Wargo, Jennifer A. Parangi, Sareh TI A Potential Role for Immunotherapy in Thyroid Cancer by Enhancing NY-ESO-1 Cancer Antigen Expression SO THYROID LA English DT Article ID CANCER/TESTIS ANTIGENS; METASTATIC MELANOMA; TUMOR-ANTIGEN; CTL RESPONSE; T-CELLS; PHASE-I; RESISTANCE; CARCINOMA; BRAF; RECOGNITION AB Background: NY-ESO-1 is one of the most immunogenic members of the cancer/testis antigen family and its levels can be increased after exposure to demethylating and deacetylating agents. This cytoplasmic antigen can serve as a potent target for cancer immunotherapy and yet has not been well studied in differentiated thyroid cancer cells. Methods: We studied the baseline expression of NY-ESO-1 messenger RNA and protein before and after exposure to 5-aza-2'-deoxycytidine (DAC) (72 hours) in a panel of thyroid cancer cell lines using quantitative polymerase chain reaction and Western blot. HLA-A2+, NY-ESO-1+ thyroid cell lines were then co-cultured with peripheral blood lymphocytes transduced with NY-ESO-1 specific T-cell receptor (TCR) and assayed for interferon-gamma and Granzyme-B release in the medium. SCID mice injected orthotopically with BCPAP cells were treated with DAC to evaluate for NY-ESO-1 gene expression in vivo. Results: None of the thyroid cancer cell lines showed baseline expression of NY-ESO-1. Three cell lines, BCPAP, TPC-1, and 8505c, showed an increase in NY-ESO-1 gene expression with DAC treatment and were found to be HLA-A2 positive. DAC-treated target BCPAP and TPC-1 tumor cells with up-regulated NY-ESO-1 levels were able to mount an appropriate interferon-gamma and Granzyme-B response upon co-culture with the NY-ESO-1-TCR-transduced peripheral blood lymphocytes. In vivo DAC treatment was able to increase NY-ESO-1 expression in an orthotopic mouse model with BCPAP cells. Conclusion: Our data suggest that many differentiated thyroid cancer cells can be pressed to express immune antigens, which can then be utilized in TCR-based immunotherapeutic interventions. C1 [Gunda, Viswanath; Frederick, Dennie T.; Bernasconi, Maria J.; Parangi, Sareh] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Boston, MA 02115 USA. [Wargo, Jennifer A.] Univ Texas MD Anderson Canc Ctr, Dept Surg Oncol & Genom Med, Houston, TX 77030 USA. RP Parangi, S (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Endocrine Surg Unit, Wang ACC 460,15 Parkman St, Boston, MA 02115 USA. EM sparangi@mgh.harvard.edu FU National Institute of Health [NIH-NCI R01 1R01CA149738-01A1] FX We thank Paul Lin and Gideon Bollag of Plexxikon for providing PLX4720 and sharing their expertise. This work was supported by The National Institute of Health grant to S. Parangi (NIH-NCI R01 1R01CA149738-01A1). NR 44 TC 4 Z9 7 U1 0 U2 1 PU MARY ANN LIEBERT, INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1050-7256 EI 1557-9077 J9 THYROID JI Thyroid PY 2014 VL 24 IS 8 BP 1241 EP 1250 DI 10.1089/thy.2013.0680 PG 10 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA AM9JM UT WOS:000340197700006 PM 24811699 ER PT J AU Gordon, JH Leung, AM Hale, AR Pearce, EN Braverman, LE He, XM Belfort, MB Nelson, SM Brown, RS AF Gordon, Joshua H. Leung, Angela M. Hale, Andrea R. Pearce, Elizabeth N. Braverman, Lewis E. He, Xuemei Belfort, Mandy B. Nelson, Sara M. Brown, Rosalind S. TI No Difference in Urinary Iodine Concentrations Between Boston-Area Breastfed and Formula-Fed Infants SO THYROID LA English DT Article ID PREGNANT-WOMEN; CHILDREN; SUPPLEMENTATION; DEFICIENCY; EXCRETION; OUTCOMES; DIETS; MILK AB Background: Thyroid hormone is essential for normal mental and physical development in infancy and childhood and is dependent on adequate iodine intake. During the first few months of life, infants are reliant on breastmilk and/or infant formula as their sole sources of dietary iodine. The iodine status of U. S. infants has not been well studied. Methods: This was a cross-sectional study of 95 breastfed and/or formula-fed infants less than 3 months of age in the Boston area. We measured iodine content from infants' single spot urine samples and assessed associations with infant feeding type as well as maternal demographic data, salt and multivitamin use, smoking status, and diet. Results: The median infant urine iodine concentration was 197.5 mu g/L (range 40-897.5 mu g/L). Median infant urine iodine concentrations were similar between infants who were exclusively breastfed (n = 39, 203.5 mu g/L; range 61.5-395.5 mu g/L), formula-fed (n = 44, 182.5 mu g/L; range 40-897.5 mu g/L), and mixed (n = 10, 197.8 mu g/L; range 123-592.5) (p = 0.88). There were no significant correlations of infant urinary iodine with maternal salt or multivitamin use (regularly or in the past 24 hours), active or secondhand cigarette smoke exposures, infant weight, infant length, or recent maternal ingestion of common iodine-containing foods, although the correlations with iodine-containing foods are difficult to accurately determine due to the small sample sizes of these variables. Conclusions: Both breastfed and formula-fed infants less than 3 months of age in the Boston area were generally iodine sufficient. Larger studies are needed to confirm these observations among infants nationwide and elucidate other factors that may contribute to infant iodine nutrition. C1 [Gordon, Joshua H.; Hale, Andrea R.; Brown, Rosalind S.] Boston Childrens Hosp, Div Endocrinol, Boston, MA USA. [Leung, Angela M.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Med, Div Endocrinol, Los Angeles, CA 90095 USA. [Pearce, Elizabeth N.; Braverman, Lewis E.; He, Xuemei] Boston Univ, Sch Med, Sect Endocrinol Diabet & Nutr, Boston, MA 02118 USA. [Belfort, Mandy B.] Boston Childrens Hosp, Div Newborn Med, Boston, MA USA. [Nelson, Sara M.] Massachusetts Gen Hosp, Dept Pediat, Boston, MA 02114 USA. RP Leung, AM (reprint author), VA Greater Los Angeles Healthcare Syst, Dept Med, Div Endocrinol, 111D,11301 Wilshire Blvd, Los Angeles, CA 90073 USA. EM amleung@mednet.ucla.edu OI Leung, Angela M./0000-0001-8935-9332 FU National Institutes of Health [7K23HD06855204, K23DK083817] FX This study was supported by National Institutes of Health 7K23HD06855204 (A.M.L.) and K23DK083817 (M.B.B.). The authors also wish to thank Dr. John Cloherty and the patients and staff at Longwood Pediatrics and the Massachusetts General Hospital (MGH)-Chelsea Health Care Clinic for their invaluable contributions to this study. NR 19 TC 4 Z9 4 U1 0 U2 9 PU MARY ANN LIEBERT, INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1050-7256 EI 1557-9077 J9 THYROID JI Thyroid PY 2014 VL 24 IS 8 BP 1309 EP 1313 DI 10.1089/thy.2014.0026 PG 5 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA AM9JM UT WOS:000340197700014 PM 24801116 ER PT J AU Liwanpo, L Ro, C Haq, S Hershman, JM AF Liwanpo, Llanyee Ro, Cynthia Haq, Salman Hershman, Jerome M. TI Sunitinib Does Not Block Thyroid Peroxidase in Patients SO THYROID LA English DT Letter ID HYPOTHYROIDISM C1 [Liwanpo, Llanyee] Vet Affairs Greater Los Angeles Healthcare Syst, Dept Endocrinol, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, David Geffen Sch Med, Dept Med, Los Angeles, CA 90095 USA. RP Liwanpo, L (reprint author), Vet Affairs Greater Los Angeles Healthcare Syst, Dept Endocrinol, Los Angeles, CA 90073 USA. NR 7 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 1050-7256 EI 1557-9077 J9 THYROID JI Thyroid PY 2014 VL 24 IS 8 BP 1325 EP 1326 DI 10.1089/thy.2014.0006 PG 2 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA AM9JM UT WOS:000340197700017 PM 24521256 ER PT J AU Cattaneo, Z Bona, S Monegato, M Pece, A Vecchi, T Herbert, AM Merabet, LB AF Cattaneo, Zaira Bona, Silvia Monegato, Maura Pece, Alfredo Vecchi, Tomaso Herbert, Andrew M. Merabet, Lotfi B. TI Visual symmetry perception in early onset monocular blindness SO VISUAL COGNITION LA English DT Article DE Monocular blindness; Symmetry; Gestalt perception; Plasticity; Binocularity ID CONTRAST LETTER THRESHOLDS; EYE ENUCLEATED SUBJECTS; MIRROR SYMMETRY; ELECTROPHYSIOLOGICAL INDEXES; UNILATERAL ENUCLEATION; BILATERAL SYMMETRY; CORTEX; DISCRIMINATION; AESTHETICS; OBSERVERS AB Symmetry detection is impaired by abnormal binocular vision development such as in amblyopia. However, the detection of symmetry has never been investigated in cases where input from one eye is profoundly compromised. Testing monocularly blind (MB) individuals represents a unique opportunity to investigate whether symmetry salience relies on a normally developed binocular visual system. In a visual symmetry detection task using dot patterns, congenitally MB showed comparable accuracy to normally sighted individuals viewing monocularly. This included better detection of vertically than horizontally symmetric patterns. However, the MB were slower than controls in detecting a symmetrical pattern. In a control target-detection task, no significant differences in performance were observed between these groups. Overall, normal developing binocular vision does not appear necessary for the visual system to detect the presence of visual symmetry. However, optimal detection mechanisms may be dependent on binocular summation or other processes dependent on input from both eyes. C1 [Cattaneo, Zaira] Univ Milano Bicocca, Dept Psychol, I-20126 Milan, Italy. [Cattaneo, Zaira; Vecchi, Tomaso] Natl Neurol Inst, Brain Connect Ctr, Pavia, Italy. [Bona, Silvia] Aalto Univ, Sch Sci, Brain Res Unit, OV Lounasmaa Lab, Aalto Espoo, Finland. [Monegato, Maura; Pece, Alfredo] Melegnano Hosp, Dept Ophthalmol, Milan, Italy. [Vecchi, Tomaso] Univ Pavia, Dept Brain & Behav Sci, I-27100 Pavia, Italy. [Herbert, Andrew M.] Rochester Inst Technol, Dept Psychol, Rochester, NY 14623 USA. [Merabet, Lotfi B.] Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Lab Visual Neuroplast,Dept Ophthalmol, Boston, MA USA. RP Cattaneo, Z (reprint author), Univ Milano Bicocca, Dept Psychol, Piazza Ateneo Nuovo 1, I-20126 Milan, Italy. EM zaira.cattaneo@unimib.it NR 45 TC 2 Z9 2 U1 0 U2 6 PU ROUTLEDGE JOURNALS, TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXFORDSHIRE, ENGLAND SN 1350-6285 EI 1464-0716 J9 VIS COGN JI Vis. Cogn. PY 2014 VL 22 IS 7 BP 963 EP 974 DI 10.1080/13506285.2014.938712 PG 12 WC Psychology, Experimental SC Psychology GA AM9LC UT WOS:000340202100006 ER PT J AU Ng, TSC Lin, AP Koerte, IK Pasternak, O Liao, H Merugumala, S Bouix, S Shenton, ME AF Ng, Thomas S. C. Lin, Alexander P. Koerte, Inga K. Pasternak, Ofer Liao, Huijun Merugumala, Sai Bouix, Sylvain Shenton, Martha E. TI Neuroimaging in repetitive brain trauma SO ALZHEIMERS RESEARCH & THERAPY LA English DT Review ID MAGNETIC-RESONANCE-SPECTROSCOPY; POSITRON-EMISSION-TOMOGRAPHY; SPORTS-RELATED CONCUSSION; CEREBRAL GLUCOSE-METABOLISM; TENSOR IMAGING FINDINGS; HIGH-SCHOOL FOOTBALL; WHITE-MATTER; ALZHEIMERS-DISEASE; COGNITIVE IMPAIRMENT; PROFESSIONAL BOXERS AB Sports-related concussions are one of the major causes of mild traumatic brain injury. Although most patients recover completely within days to weeks, those who experience repetitive brain trauma (RBT) may be at risk for developing a condition known as chronic traumatic encephalopathy (CTE). While this condition is most commonly observed in athletes who experience repetitive concussive and/or subconcussive blows to the head, such as boxers, football players, or hockey players, CTE may also affect soldiers on active duty. Currently, the only means by which to diagnose CTE is by the presence of phosphorylated tau aggregations post-mortem. Non-invasive neuroimaging, however, may allow early diagnosis as well as improve our understanding of the underlying pathophysiology of RBT. The purpose of this article is to review advanced neuroimaging methods used to investigate RBT, including diffusion tensor imaging, magnetic resonance spectroscopy, functional magnetic resonance imaging, susceptibility weighted imaging, and positron emission tomography. While there is a considerable literature using these methods in brain injury in general, the focus of this review is on RBT and those subject populations currently known to be susceptible to RBT, namely athletes and soldiers. Further, while direct detection of CTE in vivo has not yet been achieved, all of the methods described in this review provide insight into RBT and will likely lead to a better characterization (diagnosis), in vivo, of CTE than measures of self-report. C1 [Ng, Thomas S. C.; Lin, Alexander P.; Liao, Huijun; Merugumala, Sai] Harvard Univ, Brigham & Womens Hosp, Sch Med, Ctr Clin Spect,Dept Radiol, Boston, MA 02115 USA. [Ng, Thomas S. C.] Univ So Calif, Keck Sch Med, Los Angeles, CA 90033 USA. [Lin, Alexander P.; Koerte, Inga K.; Pasternak, Ofer; Bouix, Sylvain; Shenton, Martha E.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Psychiat,Psychiat Neuroimaging Lab, Boston, MA 02215 USA. [Lin, Alexander P.; Koerte, Inga K.; Pasternak, Ofer; Bouix, Sylvain; Shenton, Martha E.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Radiol,Psychiat Neuroimaging Lab, Boston, MA 02215 USA. [Koerte, Inga K.] Univ Munich, Inst Clin Radiol, D-81377 Munich, Germany. [Shenton, Martha E.] VA Boston Healthcare Syst, Res & Dev, Brockton, MA 02130 USA. RP Lin, AP (reprint author), Harvard Univ, Brigham & Womens Hosp, Sch Med, Ctr Clin Spect,Dept Radiol, 4 Blackfan Circle, Boston, MA 02115 USA. EM aplin@partners.org FU USC-Caltech joint MD/PhD program; Congressionally Directed Medical Research Program (CDMRP) Psychological Health Award [W81XWH-10-1-0835]; Center for Integration of Medicine & Innovation Technology Innovations Award [W23RYX-8225-N601]; NIH [R01-NS078337, P41RR013218, P41EB015902, R01 MH082918]; CDMRP Traumatic Brain Award [W81XWH-1-2-0063]; VA; CDMRP PTSD/TBI Clinical Consortium [W81XWH-07-CC-CS-DoD]; NARSAD young investigator grant from the Brain and Behavior Research Foundation; Else Kroner-Fresenius Stiftung, Germany FX TSCN is funded by the USC-Caltech joint MD/PhD program. APL is funded in part by Congressionally Directed Medical Research Program (CDMRP) Psychological Health Award (W81XWH-10-1-0835) and the Center for Integration of Medicine & Innovation Technology Innovations Award (W23RYX-8225-N601). APL and MES are funded in part by an NIH grant R01-NS078337, CDMRP Traumatic Brain Award (W81XWH-1-2-0063) entitled 'Tau Imaging of Traumatic Encephalopathy' and a VA Merit Award entitled 'Development of MR Biomarkers of Brain Injury in Acute and Chronic mTBI'. MES, SB and OP are funded in part by a CDMRP PTSD/TBI Clinical Consortium (W81XWH-07-CC-CS-DoD). OP is funded in part by NIH grants P41RR013218 and P41EB015902, and by a NARSAD young investigator grant from the Brain and Behavior Research Foundation. IKK is funded by the Else Kroner-Fresenius Stiftung, Germany. SB is also funded by NIH grant R01 MH082918. NR 119 TC 12 Z9 12 U1 4 U2 14 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1758-9193 J9 ALZHEIMERS RES THER JI Alzheimers Res. Ther. PY 2014 VL 6 IS 1 AR 10 DI 10.1186/alzrt239 PG 15 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA AM4DB UT WOS:000339801600010 PM 25031630 ER PT S AU Dorsey, R Graham, G Glied, S Meyers, D Clancy, C Koh, H AF Dorsey, Rashida Graham, Garth Glied, Sherry Meyers, David Clancy, Carolyn Koh, Howard BE Fielding, JE TI Implementing Health Reform: Improved Data Collection and the Monitoring of Health Disparities SO ANNUAL REVIEW OF PUBLIC HEALTH, VOL 35 SE Annual Review of Public Health LA English DT Review; Book Chapter DE data standards; Affordable Care Act; demographic data; population-based surveys ID LIMITED ENGLISH PROFICIENCY; PRIMARY LANGUAGE; UNITED-STATES; GENDER-DIFFERENCES; INTELLECTUAL DISABILITIES; MEASUREMENT ISSUES; SEX DIFFERENTIALS; DATA STANDARDS; PUBLIC-HEALTH; MEDICAL-CARE AB The relative lack of standards for collecting data on population subgroups has not only limited our understanding of health disparities, but also impaired our ability to develop policies to eliminate them. This article provides background about past challenges to collecting data by race/ethnicity, primary language, sex, and disability status. It then discusses how passage of the Affordable Care Act has provided new opportunities to improve data-collection standards for the demographic variables of interest and, as such, a better understanding of the characteristics of populations served by the U. S. Department of Health and Human Services (HHS). The new standards have been formally adopted by the Secretary of HHS for application in all HHS-sponsored population health surveys involving self-reporting. The new data-collection standards will not only promote the uniform collection and utilization of demographic data, but also help the country shape future programs and policies to advance public health and to reduce disparities. C1 [Dorsey, Rashida] US Dept HHS, Off Minor Hlth, Rockville, MD 20852 USA. [Graham, Garth] Univ Florida, Dept Med, Gainesville, FL 32611 USA. [Glied, Sherry] NYU, Robert F Wagner Grad Sch Publ Serv, New York, NY 10012 USA. [Meyers, David] US Dept HHS, Agcy Healthcare Res & Qual, Rockville, MD 20850 USA. [Clancy, Carolyn] US Dept Vet Affairs, Off Qual Safety & Value, Washington, DC 20420 USA. [Koh, Howard] US Dept HHS, Off Assistant Secretary Hlth, Washington, DC 20201 USA. RP Dorsey, R (reprint author), US Dept HHS, Off Minor Hlth, Rockville, MD 20852 USA. EM Rashida.Dorsey@hhs.gov; Garth.Graham@medicine.ufl.edu; sherry.glied@nyu.edu; David.Meyers@ahrq.hhs.gov; Carolyn.Clancy@va.gov; Howard.Koh@hhs.gov NR 101 TC 3 Z9 3 U1 3 U2 13 PU ANNUAL REVIEWS PI PALO ALTO PA 4139 EL CAMINO WAY, PO BOX 10139, PALO ALTO, CA 94303-0897 USA SN 0163-7525 BN 978-0-8243-2735-4 J9 ANNU REV PUBL HEALTH JI Annu. Rev. Public Health PY 2014 VL 35 BP 123 EP 138 DI 10.1146/annurev-publhealth-032013-182423 PG 16 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA BA4SB UT WOS:000336207500009 PM 24365094 ER PT S AU Harris, JR Hannon, PA Beresford, SAA Linnan, LA McLellan, DL AF Harris, Jeffrey R. Hannon, Peggy A. Beresford, Shirley A. A. Linnan, Laura A. McLellan, Deborah L. BE Fielding, JE TI Health Promotion in Smaller Workplaces in the United States SO ANNUAL REVIEW OF PUBLIC HEALTH, VOL 35 SE Annual Review of Public Health LA English DT Review; Book Chapter DE chronic disease; exercise; obesity; prevention and control; tobacco; workplace ID WORKING WELL TRIAL; SMOKING-CESSATION INTERVENTION; WORKSITE OBESITY PREVENTION; RANDOMIZED CONTROLLED-TRIAL; DIRECTIONS-SMALL-BUSINESS; LOW-WAGE INDUSTRIES; BEHAVIOR-CHANGE; MIDSIZED EMPLOYERS; TOBACCO USE; WORKERS AB Most American workplaces are smaller, with fewer than 1,000 employees. Many of these employees are low-wage earners and at increased risk for chronic diseases. Owing to the challenges smaller workplaces face to offering health-promotion programs, their employees often lack access to health-promotion opportunities available at larger workplaces. Many smaller employers do not offer health insurance, which is currently the major funding vehicle for health-promotion services. They also have few health-promotion vendors to serve them and low internal capacity for, and commitment to, delivery of on-site programs. The programs they offer, whether aimed at health promotion alone or integrated with health protection, are rarely comprehensive and are understudied. Research priorities for health promotion in smaller workplaces include developing programs feasible for the smallest workplaces with fewer than 20 employees. Policy priorities include incentives for smaller workplaces to implement comprehensive programs and an ongoing system for monitoring and evaluation. C1 [Harris, Jeffrey R.; Hannon, Peggy A.; Beresford, Shirley A. A.] Univ Washington, Sch Publ Hlth, Dept Hlth Serv, Seattle, WA 98105 USA. [Linnan, Laura A.] Univ N Carolina, Gillings Sch Publ Hlth, Dept Hlth Behav, Chapel Hill, NC 27599 USA. [McLellan, Deborah L.] Dana Farber Canc Inst, Ctr Community Based Res, Boston, MA 02215 USA. RP Harris, JR (reprint author), Univ Washington, Sch Publ Hlth, Dept Hlth Serv, Seattle, WA 98105 USA. EM jh7@uw.edu; peggyh@uw.edu; beresfrd@u.washington.edu; linnan@email.unc.edu; deborah_mclellan@dfci.harvard.edu OI Harris, Jeffrey/0000-0001-8728-7195 FU NCCDPHP CDC HHS [U48 DP001911]; NCI NIH HHS [R01 CA105835]; NHLBI NIH HHS [R01 HL79491]; NIAAA NIH HHS [T32 AA007567]; NIOSH CDC HHS [U19 OH008861] NR 77 TC 20 Z9 20 U1 2 U2 15 PU ANNUAL REVIEWS PI PALO ALTO PA 4139 EL CAMINO WAY, PO BOX 10139, PALO ALTO, CA 94303-0897 USA SN 0163-7525 BN 978-0-8243-2735-4 J9 ANNU REV PUBL HEALTH JI Annu. Rev. Public Health PY 2014 VL 35 BP 327 EP 342 DI 10.1146/annurev-publhealth-032013-182416 PG 16 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA BA4SB UT WOS:000336207500020 PM 24387086 ER PT J AU Edwards, J Vess, J Reger, G Cernich, A AF Edwards, Joe Vess, James Reger, Greg Cernich, Alison TI The Use of Virtual Reality in the Military's Assessment of Service Members With Traumatic Brain Injury: Recent Developments and Emerging Opportunities SO APPLIED NEUROPSYCHOLOGY-ADULT LA English DT Article DE assessment; ecological validity; military psychology; traumatic brain injury; virtual reality ID COMPUTERIZED NEUROPSYCHOLOGICAL ASSESSMENT; ECOLOGICAL VALIDITY; EXECUTIVE DYSFUNCTION; COGNITIVE IMPAIRMENTS; DRIVING ASSESSMENT; CLINICAL NEUROPSYCHOLOGY; TASK-PERFORMANCE; REHABILITATION; ENVIRONMENT; SIMULATOR AB Traumatic brain injury (TBI) is a common event in the current extended conflicts by American service members, with estimates that as many as 300,000 have sustained combat-related concussions during Operation Iraqi Freedom and Operation Enduring Freedom. The limited ecological validity of traditional neuropsychological assessment measures presents a challenge to effective postconcussion evaluation of service members in relation to fitness-for-duty decisions or rehabilitation needs. Virtual reality (VR) technology offers a promising opportunity to advance the field of functional assessment for TBI. This article reviews the current professional literature on VR applications for TBI assessment, with special emphasis on those that are particularly relevant to U.S. service members. VR affords several advantages for clinical use. These include assessment of complex sets of cognitive and behavioral functions rather than the isolated components assessed by traditional measures; more precise control over the standardized presentation of task stimuli and the recording of response data; and enhanced ecological validity that can lead to more useful assessment data in the applied contexts faced by the U.S. military. C1 [Edwards, Joe] TBI Clin, Dept Behav Hlth, Ft Wainwright, AK USA. [Vess, James; Reger, Greg] Natl Ctr Telehlth & Technol, Emerging Technol Program, Tacoma, WA 98431 USA. [Cernich, Alison] US Dept Vet Affairs, Mental Hlth Serv, Silver Spring, MD USA. [Cernich, Alison] Univ Maryland, Sch Med, Dept Neurol, Baltimore, MD 21201 USA. [Cernich, Alison] Univ Maryland, Sch Med, Dept Psychiat, Baltimore, MD 21201 USA. [Cernich, Alison] Def Ctr Excellence Psychol Hlth, Silver Spring, MD USA. [Cernich, Alison] TBI, Silver Spring, MD USA. RP Vess, J (reprint author), Natl Ctr Telehlth & Technol, Emerging Technol Program, 9933 West Hayes St, Tacoma, WA 98431 USA. EM james.d.vess3.civ@mail.mil NR 106 TC 3 Z9 4 U1 1 U2 17 PU ROUTLEDGE JOURNALS, TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXFORDSHIRE, ENGLAND SN 0908-4282 EI 1532-4826 J9 APPL NEUROPSYCH-ADUL JI Appl. Neuropsychol.-Adult PY 2014 VL 21 IS 3 BP 220 EP 230 DI 10.1080/09084282.2013.796554 PG 11 WC Clinical Neurology; Psychology SC Neurosciences & Neurology; Psychology GA AM9VN UT WOS:000340229200006 PM 25084846 ER PT J AU Hersey, P Ribas, A Hodi, FS Kefford, R Hamid, O Daud, A Wolchok, JD Hwu, WJ Gangadhar, TC Patnaik, A Joshua, AM Weber, J Dronca, R Zarour, H Gergich, K Li, X Iannone, R Kang, SP Ebbinghaus, S Robert, C AF Hersey, P. Ribas, A. Hodi, F. S. Kefford, R. Hamid, O. Daud, A. Wolchok, J. D. Hwu, W. -J. Gangadhar, T. C. Patnaik, A. Joshua, A. M. Weber, J. Dronca, R. Zarour, H. Gergich, K. Li, X. Iannone, R. Kang, S. P. Ebbinghaus, S. Robert, C. TI EFFICACY AND SAFETY OF THE ANTI-PD-1 MONOCLONAL ANTIBODY MK-3475 IN 411 PATIENTS (pts) WITH MELANOMA SO ASIA-PACIFIC JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract C1 [Hersey, P.] Univ Sydney, Sydney, NSW 2006, Australia. [Ribas, A.] Univ Calif Los Angeles, Los Angeles, CA USA. [Hodi, F. S.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Kefford, R.] Univ Sydney, Westmead Hosp, Crown Princess Mary Canc Ctr, Sydney, NSW 2006, Australia. [Kefford, R.] Univ Sydney, Melanoma Inst Australia, Sydney, NSW 2006, Australia. [Hamid, O.] Angeles Clin & Res Inst, Los Angeles, CA USA. [Daud, A.] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Wolchok, J. D.] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. [Hwu, W. -J.] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. [Gangadhar, T. C.] Univ Penn, Abramson Canc Ctr, Philadelphia, PA 19104 USA. [Patnaik, A.] South Texas Accelerated Res Therapeut, San Antonio, TX USA. [Joshua, A. M.] Princess Margaret Canc Ctr, Toronto, ON, Canada. [Weber, J.] Univ S Florida, H Lee Moffitt Canc Ctr, Tampa, FL 33682 USA. [Dronca, R.] Mayo Clin, Rochester, MN USA. [Zarour, H.] Univ Pittsburgh, Pittsburgh, PA USA. [Gergich, K.; Li, X.; Iannone, R.; Kang, S. P.; Ebbinghaus, S.] Merck & Co Inc, Whitehouse Stn, NJ USA. [Robert, C.] Univ Paris Sud, Inst Gustave Roussy, Villejuif, France. NR 0 TC 1 Z9 1 U1 0 U2 6 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1743-7555 EI 1743-7563 J9 ASIA-PAC J CLIN ONCO JI Asia-Pac. J. Clin. Oncol. PY 2014 VL 10 SU 6 SI SI BP 48 EP 49 PG 2 WC Oncology SC Oncology GA AM2YC UT WOS:000339716500015 ER PT J AU Stopeck, A Lipton, A Fizazi, K Smith, MR Shore, ND Martin, M Vadhan-Raj, S Zhou, K Balakumaran, A Braun, AH AF Stopeck, A. Lipton, A. Fizazi, K. Smith, M. R. Shore, N. D. Martin, M. Vadhan-Raj, S. Zhou, K. Balakumaran, A. Braun, A. H. TI DENOSUMAB VERSUS ZOLEDRONIC ACID FOR PREVENTING SKELETAL-RELATED EVENTS IN PATIENTS WITH METASTATIC BONE DISEASE: SUBGROUP ANALYSES BY BASELINE CHARACTERISTICS SO ASIA-PACIFIC JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract C1 [Stopeck, A.] Univ Arizona, Ctr Canc, Tucson, AZ USA. [Lipton, A.] Penn State Hershey Med Ctr, Hershey, PA USA. [Fizazi, K.] Univ Paris 11, Inst Gustave Roussy, Dept Canc Med, Villejuif, France. [Smith, M. R.] Massachusetts Gen Hosp, Ctr Canc, Dept Hematol, Boston, MA USA. [Smith, M. R.] Massachusetts Gen Hosp, Ctr Canc, Dept Oncol, Boston, MA USA. [Shore, N. D.] Atlantic Urol Clin, Carolina Urol Res Ctr, Myrtle Beach, SC USA. [Martin, M.] Inst Invest Sanitaria Gregorio Maranon, Madrid, Spain. [Vadhan-Raj, S.] Univ Texas MD Anderson Canc Ctr, Dept Sarcoma Med Oncol, Sect Cytokines & Support Oncol, Houston, TX 77030 USA. [Zhou, K.; Balakumaran, A.; Braun, A. H.] Amgen Inc, Thousand Oaks, CA 91320 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1743-7555 EI 1743-7563 J9 ASIA-PAC J CLIN ONCO JI Asia-Pac. J. Clin. Oncol. PY 2014 VL 10 SU 6 SI SI BP 50 EP 50 PG 1 WC Oncology SC Oncology GA AM2YC UT WOS:000339716500018 ER PT J AU Davis, I Stockler, M Martin, A Long, A Yip, S Coskinas, X Sweeney, C AF Davis, I. Stockler, M. Martin, A. Long, A. Yip, S. Coskinas, X. Sweeney, C. TI RANDOMISED PHASE 3 TRIAL OF ENZALUTAMIDE IN FIRST LINE ANDROGEN DEPRIVATION THERAPY FOR METASTATIC PROSTATE CANCER: THE ANZUP ENZAMET STUDY SO ASIA-PACIFIC JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract C1 [Davis, I.] Monash Univ, Melbourne, Vic 3004, Australia. [Stockler, M.; Martin, A.; Long, A.; Yip, S.; Coskinas, X.] Univ Sydney, NHMRC Clin Trials Ctr, Sydney, NSW 2006, Australia. [Sweeney, C.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Yip, S.] Sydney Catalyst Translat Canc Res Ctr, Sydney, NSW, Australia. RI Stockler, Martin/N-3859-2016 OI Stockler, Martin/0000-0003-3793-8724 NR 0 TC 0 Z9 0 U1 0 U2 2 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1743-7555 EI 1743-7563 J9 ASIA-PAC J CLIN ONCO JI Asia-Pac. J. Clin. Oncol. PY 2014 VL 10 SU 6 SI SI BP 54 EP 55 PG 2 WC Oncology SC Oncology GA AM2YC UT WOS:000339716500028 ER PT J AU Williams, S Davis, I Sweeney, C Stockler, M Martin, A Long, A Yip, S Coskinas, X Nguyen, P AF Williams, S. Davis, I. Sweeney, C. Stockler, M. Martin, A. Long, A. Yip, S. Coskinas, X. Nguyen, P. TI RANDOMISED PHASE 3 TRIAL OF ENZALUTAMIDE IN ANDROGEN DEPRIVATION THERAPY WITH RADIATION THERAPY FOR HIGH RISK, CLINICALLY LOCALISED, PROSTATE CANCER: THE ANZUP ENZARAD STUDY SO ASIA-PACIFIC JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract C1 [Williams, S.] Peter MacCallum Canc Ctr, Melbourne, Vic, Australia. [Davis, I.] Monash Univ, Melbourne, Vic 3004, Australia. [Sweeney, C.; Nguyen, P.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Stockler, M.; Martin, A.; Long, A.; Yip, S.; Coskinas, X.] Univ Sydney, Natl Hlth & Med Res Council Clin Trials Ctr, Sydney, NSW 2006, Australia. RI Stockler, Martin/N-3859-2016 OI Stockler, Martin/0000-0003-3793-8724 NR 0 TC 0 Z9 0 U1 0 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1743-7555 EI 1743-7563 J9 ASIA-PAC J CLIN ONCO JI Asia-Pac. J. Clin. Oncol. PY 2014 VL 10 SU 6 SI SI BP 67 EP 68 PG 2 WC Oncology SC Oncology GA AM2YC UT WOS:000339716500066 ER PT J AU O'Malley, JT Burgess, BJ Zhu, MY Curtin, HD Nadol, JB AF O'Malley, Jennifer T. Burgess, Barbara J. Zhu, Meng-Yu Curtin, Hugh D. Nadol, Joseph B., Jr. TI Correlation between Histologic and Radiographic Reconstruction of Intracochlear Electrode Position in Human Temporal Bones SO AUDIOLOGY AND NEURO-OTOLOGY LA English DT Article DE Temporal bone; Cochlear implant; Intracochlear length; Computed tomography; Multiplanar reconstruction; Histology; Celloidin ID COCHLEAR IMPLANT ELECTRODE; COMPUTED-TOMOGRAPHY; PROTEOMIC ANALYSIS; ARRAY POSITION; CT; HISTOPATHOLOGY; INSERTION; LOCALIZATION; VERIFICATION; MORPHOLOGY AB In our laboratory, human temporal bone specimens from patients who in life have undergone cochlear implantation are routinely processed with the implant in situ, embedded in Araldite, sectioned at 20 mu m and serially photographed during cutting, stained with toluidine blue and mounted on glass slides. From the images, two-dimensional and three-dimensional reconstructions can be made and a very accurate implant insertion depth can be calculated from the three-dimensional reconstructions. However, this method precludes subsequent special stains and further molecular investigations of the tissue including proteomics and immunostaining, which is now possible with celloidin-embedded tissue. In this study, we correlated measurement of the implant array insertion depth calculated from histologic three-dimensional reconstruction with that measured from three-dimensional radiologic multiplanar reconstruction. Four human temporal bones with cochlear implants underwent postfixation preprocessing CT imaging with a Siemens Somatom Sensation Scanner. The CT scans from these four bones were downloaded into the Voxar software application, reformatted using the multiplanar reconstruction tool, viewed in three dimensions and measurements of intracochlear insertion lengths of the implants were obtained. The bones were processed routinely for in situ Araldite embedding, serial images were made of the block during sectioning, postprocessed using PV-Wave (R) software, aligned with Amira (R) software, and used to create histologic three-dimensional reconstructions. From these three-dimensional reconstructions, the insertion depth of the electrode array was mathematically calculated. The range of insertion depths was 15.9 mm (case 1) to 26.6 mm (case 4). The two methods, radiographic multiplanar reconstruction and three-dimensional reconstruction, differed by 0.4-0.9%. This provides confidence that important localization information about the electrode in situ can be gleaned from CT scans, thereby allowing us to extract the implants prior to processing for celloidin embedment and allow further techniques such as special stains and immunostaining to be accomplished in order to evaluate molecular mechanisms involved in cochlear implantation. (C) 2014 S. Karger AG, Basel C1 [O'Malley, Jennifer T.; Burgess, Barbara J.; Zhu, Meng-Yu; Nadol, Joseph B., Jr.] Massachusetts Eye & Ear Infirm, Dept Otolaryngol, Boston, MA 02114 USA. [Curtin, Hugh D.] Massachusetts Eye & Ear Infirm, Dept Radiol, Boston, MA 02114 USA. [Curtin, Hugh D.] Harvard Univ, Sch Med, Dept Radiol, Boston, MA 02115 USA. [Nadol, Joseph B., Jr.] Harvard Univ, Sch Med, Dept Otol & Laryngol, Boston, MA 02115 USA. RP O'Malley, JT (reprint author), Massachusetts Eye & Ear Infirm, 243 Charles St, Boston, MA 02114 USA. EM Jennifer_O'Malley@MEEI.Harvard.edu FU NIDCD/NIH [RO1DC000152] FX This work was supported by NIDCD/NIH grant RO1DC000152. NR 26 TC 3 Z9 3 U1 0 U2 2 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 1420-3030 EI 1421-9700 J9 AUDIOL NEURO-OTOL JI Audiol. Neuro-Otol. PY 2014 VL 19 IS 3 BP 184 EP 192 DI 10.1159/000358003 PG 9 WC Audiology & Speech-Language Pathology; Neurosciences; Otorhinolaryngology SC Audiology & Speech-Language Pathology; Neurosciences & Neurology; Otorhinolaryngology GA AM6AA UT WOS:000339941600004 PM 24686209 ER PT J AU Min, L Hodi, FS AF Min, Le Hodi, F. Stephen TI Anti-PD1 Following Ipilimumab for Mucosal Melanoma: Durable Tumor Response Associated with Severe Hypothyroidism and Rhabdomyolysis SO CANCER IMMUNOLOGY RESEARCH LA English DT Article ID ADVERSE EVENTS; SAFETY; CANCER; ANTIBODY AB Treatment with fully human monoclonal antibodies against programmed death 1 (PD1) receptor has shown great promise for a number of advanced malignancies. Although inflammatory adverse events have been well described with anti-CTL antigen 4 (CTLA4) therapy, experience with the range of adverse effects of anti-PD1 remains comparatively limited. Here, we report on a patient with advanced mucosal melanoma who received four doses of MK-3475, a fully human monoclonal antibody against PD1, and experienced a durable near-complete response but developed severe hypothyroidism, rhabdomyolysis, and acute kidney injury. To our knowledge, this is the first case reported of a patient with advanced mucosal melanoma who responded to anti-PD1 therapy. With the promising antitumor effects of anti-PD1 in a wide array of tumors, we expect an increasing number of patients to be exposed to anti-PD1 therapies. Recognition of infrequent presentations of adverse events such as elevated creatine kinase levels and thyroid disorders in patients who receive anti-PD1 therapy is important. (C) 2013 AACR. C1 [Min, Le] Brigham & Womens Hosp, Div Endocrinol Diabet & Hypertens, Boston, MA 02115 USA. [Hodi, F. Stephen] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. RP Min, L (reprint author), Brigham & Womens Hosp, Div Endocrinol Diabet & Hypertens, 221 Longwood Ave, Boston, MA 02115 USA. EM lmin1@partners.org FU NIH KO8 Mentored Clinical Scientist Development award [5K08HD070957]; Malcolm and Emily Mac Naught Fund for Melanoma Research at the Dana-Farber Cancer Institute FX This work was partly supported by an NIH KO8 Mentored Clinical Scientist Development award (5K08HD070957) to L. Min, and by the The Malcolm and Emily Mac Naught Fund for Melanoma Research at the Dana-Farber Cancer Institute to F.S. Hodi. The patient was on a clinical trial supported by Merck with funds to the institution. NR 14 TC 35 Z9 36 U1 1 U2 1 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 2326-6066 EI 2326-6074 J9 CANCER IMMUNOL RES JI Cancer Immunol. Res. PD JAN PY 2014 VL 2 IS 1 BP 15 EP 18 DI 10.1158/2326-6066.CIR-13-0146 PG 4 WC Oncology; Immunology SC Oncology; Immunology GA AM7FS UT WOS:000340030900003 PM 24778161 ER PT J AU Akoudad, S Ikram, MA Koudstaal, PJ Hofman, A Niessen, WJ Greenberg, SM van der Lugt, A Vernooij, MW AF Akoudad, Saloua Ikram, Mohammad Arfan Koudstaal, Peter J. Hofman, Albert Niessen, Wiro J. Greenberg, Steven M. van der Lugt, Aad Vernooij, Meike W. TI Cerebral Microbleeds Are Associated with the Progression of Ischemic Vascular Lesions SO CEREBROVASCULAR DISEASES LA English DT Article DE Cerebral microbleeds; White matter lesions; Lacunes; Magnetic resonance imaging; Epidemiology ID WHITE-MATTER LESIONS; SMALL VESSEL DISEASE; BRAIN-TISSUE SEGMENTATION; INTRACEREBRAL HEMORRHAGE; AMYLOID ANGIOPATHY; ROTTERDAM SCAN; RISK-FACTORS; MRI; UPDATE; STROKE AB Background: Despite their different appearance on imaging, hemorrhagic and ischemic vascular lesions frequently co-occur in the brain and are hypothesized to progress concurrently. Although silent hemorrhagic and ischemic vascular brain lesions are highly prevalent in the general population, the concomitant progression of these lesions has only been studied to a limited extent in this population. We therefore aimed to investigate whether pre-existing and incident cerebral microbleeds (CMBs) are related to the progression of ischemic lesions in the general population. Methods: In the prospective population-based Rotterdam Scan Study, 803 individuals aged >= 60 years underwent magnetic resonance imaging at baseline and after an average interval of 3.4 years. The presence of microbleeds and lacunes was visually rated by trained research physicians, and white matter lesions (WMLs) were automatically segmented at both time points. Logistic regression was used to investigate the association of microbleeds with incident lacunes, and linear regression was used to investigate the relation between microbleeds and progression of WML volume. All analyses were adjusted for age, sex and the time interval between baseline and follow-up scanning. The analyses were repeated after additional adjustments for cardiovascular risk factors: blood pressures; total and high-density lipoprotein cholesterol; smoking; diabetes mellitus; lipid lowering, antihypertensive and antiplatelet medications, and apolipoprotein E epsilon 4. The analyses involving WMLs were also adjusted for intracranial volume. Results: We found that pre-existing microbleeds in any location of the brain were related to a higher incidence of lacunes (odds ratio [OR] adjusted for age, sex and scan interval: 4.67; 95% confidence interval [CI]: 1.84-11.85). Pre-existing microbleeds were not related to progression of WML volume (mean difference in WML volume increase: -0.03; 95% CI: -0.15 to 0.09). Additional adjustments for cardiovascular risk factors did not change the results considerably. Incident microbleeds in any location of the brain were associated with a higher incidence of lacunes (OR: 9.18; 95% CI: 3.61-23.35), whereas only incident microbleeds located in cortico-subcortical regions were related to progression of WML volume (mean difference in WML volume increase: 0.41; 95% CI: 0.21-0.62). Again, adjustments for cardiovascular risk factors did not change the results significantly. Conclusions: Our findings suggest that in the general population, CMBs serve as a predictor of ischemic brain lesions and may represent an imaging marker of active vasculopathy. These results support the hypothesis of a common underlying pathway in the development of ischemic and hemorrhagic brain lesions. (C) 2014 S. Karger AG, Basel C1 [Akoudad, Saloua; Ikram, Mohammad Arfan; Hofman, Albert; Vernooij, Meike W.] Erasmus MC, Univ Med Ctr, Dept Epidemiol, NL-3000 CA Rotterdam, Netherlands. [Akoudad, Saloua; Ikram, Mohammad Arfan; Niessen, Wiro J.; van der Lugt, Aad; Vernooij, Meike W.] Erasmus MC, Univ Med Ctr, Dept Radiol, NL-3000 CA Rotterdam, Netherlands. [Akoudad, Saloua; Ikram, Mohammad Arfan; Koudstaal, Peter J.] Erasmus MC, Univ Med Ctr, Dept Neurol, NL-3000 CA Rotterdam, Netherlands. [Niessen, Wiro J.] Erasmus MC, Univ Med Ctr, Dept Med Informat, NL-3000 CA Rotterdam, Netherlands. [Niessen, Wiro J.] Delft Univ Technol, Fac Sci Appl, Dept Imaging Sci & Technol, Delft, Netherlands. [Greenberg, Steven M.] Massachusetts Gen Hosp, Dept Neurol, J Philip Kistler Stroke Res Ctr, Boston, MA 02114 USA. RP Vernooij, MW (reprint author), Erasmus MC, Univ Med Ctr, Off Secretariat Epidemiol, 28-18,POB 2040, NL-3000 CA Rotterdam, Netherlands. EM m.vernooij@erasmusmc.nl RI Vernooij, Meike/E-4061-2016 FU Erasmus MC, University Medical Center, and Erasmus University Rotterdam; Netherlands Organization for Scientific Research (NWO); Netherlands Organization for Health Research and Development (ZonMw); Research Institute for Diseases in the Elderly (RIDE); Netherlands Genomics Initiative; Ministry of Education, Culture and Science; Ministry of Health, Welfare and Sports; European Commission (DG XII); Municipality of Rotterdam; Erasmus MC, University Medical Center; Netherlands Heart Foundation, ZonMw; Internationaal Parkinson Fonds; Internationale Stichting Alzheimer Onderzoek [12533] FX The Rotterdam Study is supported by the Erasmus MC, University Medical Center, and Erasmus University Rotterdam, the Netherlands Organization for Scientific Research (NWO), the Netherlands Organization for Health Research and Development (ZonMw), the Research Institute for Diseases in the Elderly (RIDE), the Netherlands Genomics Initiative, the Ministry of Education, Culture and Science, the Ministry of Health, Welfare and Sports, the European Commission (DG XII) and the Municipality of Rotterdam. The current study is supported by a research fellowship (M.W.V.) from the Erasmus MC, University Medical Center, the Netherlands Heart Foundation, ZonMw, the Internationaal Parkinson Fonds and the Internationale Stichting Alzheimer Onderzoek (grant 12533). NR 33 TC 19 Z9 20 U1 0 U2 3 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 1015-9770 EI 1421-9786 J9 CEREBROVASC DIS JI Cerebrovasc. Dis. PY 2014 VL 37 IS 5 BP 382 EP 388 DI 10.1159/000362590 PG 7 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA AM2GC UT WOS:000339666900011 PM 24970709 ER PT J AU Rothschild, AJ Raskin, J Wang, CN Marangell, LB Fava, M AF Rothschild, Anthony J. Raskin, Joel Wang, Chia-Ning Marangell, Lauren B. Fava, Maurizio TI The relationship between change in apathy and changes in cognition and functional outcomes in currently non-depressed S SRI-treated patients with major-depressive disorder SO COMPREHENSIVE PSYCHIATRY LA English DT Article ID SCALE; RELIABILITY; VALIDITY; QUESTIONNAIRE; SSRI AB Aims: Apathy in the context of treated major depressive disorder (MDD) is a frequently observed phenomenon in clinical practice. This study aimed to assess the validity of the Rothschild Scale for Antidepressant Tachyphylaxis (R) (RSAT) and the Massachusetts General Hospital Cognitive and Physical Functioning Questionnaire (CPFQ) for measuring apathy, and to assess the relationship between apathy and possible contributing factors, in patients with MDD and residual apathy in the absence of depressed mood. Methods: The underlying structure and validity of the RSAT and CPFQ were assessed via factor analysis and correlation with the Apathy Evaluation Scale Clinician rated version (AES-C) in 483 patients who had previously responded to treatment with a selective serotonin reuptake inhibitor. The relationship between apathy and contributing variables was investigated via structural equation modeling. Correlation and regression analyses were conducted to examine the relationship between the Sheehan Disability Scale (SDS) and the RSAT, CPFQ, and AES-C. Results: The RSAT and CPFQ were validated with the AES-C with respect to energy and motivation. The latent variable "Energy and Interest", based on the energy, motivation, and interest items (RSAT and CPFQ), was a major contributing factor to apathy. Improvements in function (SDS) were significantly correlated with, and predicted by, improvements in apathy and cognitive and physical functioning (assessed by the RSAT, CPFQ, and AES-C). Conclusions: These analyses provide further information on apathy and its assessment in the context of treated MDD. A better understanding of apathy will aid further investigation of this phenomenon and, ultimately, determination of the most appropriate approach for its clinical management. (C) 2014 Elsevier Inc. All rights reserved. C1 [Rothschild, Anthony J.] Univ Massachusetts, Sch Med, Dept Psychiat, Worcester, MA 01604 USA. [Raskin, Joel] Eli Lilly Canada, Lilly Res Labs, Toronto, ON, Canada. [Wang, Chia-Ning] Eli Lilly China, Shanghai, Peoples R China. [Marangell, Lauren B.] Lilly USA LLC, Eli Lilly & Co, Indianapolis, IN USA. [Marangell, Lauren B.] Univ Texas Hlth Sci Ctr Houston, Sch Med, Houston, TX 77030 USA. [Fava, Maurizio] Massachusetts Gen Hosp, Depress Clin & Res Program, Boston, MA 02114 USA. RP Rothschild, AJ (reprint author), Univ Massachusetts, Sch Med, Dept Psychiat, 328 Shrewsbury St, Worcester, MA 01604 USA. EM Anthony.Rothschild@umassmemorial.org FU Eli Lilly and Company; Eli Lilly Australia FX This study (F1J-CR-HMGM) was sponsored by Eli Lilly and Company, manufacturer/licensee of duloxetine (Cymbalta (R)). In compliance with the Uniform Requirements for Manuscripts, established by the International Committee of Medical Journal Editors, the sponsor of this study did not impose any impediment, directly or indirectly, on the publication of the study's results. Medical writing assistance was provided by Justine Southby, PhD, and Serina Stretton, PhD, CMPP, of ProScribe Medical Communications and was funded by Eli Lilly Australia. ProScribe's services complied with international guidelines for Good Publication Practice (GPP2). NR 17 TC 16 Z9 16 U1 0 U2 5 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0010-440X EI 1532-8384 J9 COMPR PSYCHIAT JI Compr. Psychiat. PD JAN PY 2014 VL 55 IS 1 BP 1 EP 10 DI 10.1016/j.comppsych.2013.08.008 PG 10 WC Psychiatry SC Psychiatry GA AM5VO UT WOS:000339929300001 PM 24268564 ER PT J AU Boyd, JE Adler, EP Otilingam, PG Peters, T AF Boyd, Jennifer E. Adler, Emerald P. Otilingam, Poomi G. Peters, Townley TI Internalized Stigma of Mental Illness (ISMI) Scale: A multinational review SO COMPREHENSIVE PSYCHIATRY LA English DT Article ID QUALITY-OF-LIFE; SCHIZOPHRENIA SPECTRUM DISORDERS; 14 EUROPEAN COUNTRIES; SELF-STIGMA; BIPOLAR DISORDER; PERCEIVED DISCRIMINATION; PSYCHOMETRIC PROPERTIES; TREATMENT SEEKING; SUBSTANCE-ABUSE; GAMIAN-EUROPE AB The Internalized Stigma of Mental Illness (ISMI) scale is a 29-item questionnaire measuring self-stigma among persons with psychiatric disorders. It was developed with substantial consumer input and has been widely used, but its psychometric qualities have not been comprehensively evaluated across multiple versions. Here we review the 55 known versions, and provide the 47 available versions, including: Arabic, Armenian, Bengali, Bulgarian, Chinese (Mainland, Taiwan, Hong Kong), Croatian, Dutch, English (USA, South Africa), Estonian, Farsi, Finnish, French, German, Greek, Hebrew, Hindi, Japanese, Khmer, Korean, Lithuanian, Lugandan, Maltese, Polish, Portuguese (Portugal, Brazil), Romanian, Russian, Samoan, Slovenian, Spanish (Spain), Swahili, Swedish, Tongan, Turkish, Urdu, and Yoruba, and qualitative English and Swahili versions, as well as versions for depression, schizophrenia, substance abuse, eating disorders, epilepsy, inflammatory bowel disease, leprosy, smoking, parents and caregivers of people with mental illness, and ethnicity. The various versions show reliability and validity across a wide range of languages, cultures, and writing systems. The most commonly reported findings of studies using the ISMI are that internalized stigma correlates with higher depression, lower self esteem, and higher symptom severity. Initial studies of ways to reduce internalized stigma are promising and warrant further investigation. Published by Elsevier Inc. C1 [Boyd, Jennifer E.; Otilingam, Poomi G.; Peters, Townley] San Francisco VA Med Ctr, Mental Hlth Serv, San Francisco, CA 94121 USA. [Boyd, Jennifer E.] Univ Calif San Francisco, Dept Psychiat, San Francisco, CA 94121 USA. [Adler, Emerald P.] Vet Affairs Palo Alto Hlth Care Syst, Natl Ctr Post Traumat Stress Disorder, Menlo Pk, CA 94025 USA. [Peters, Townley] Alliant Int Univ, Calif Sch Profess Psychol, Clin Psychol, San Francisco, CA 94133 USA. RP Boyd, JE (reprint author), San Francisco VA Med Ctr, Mental Hlth Serv, San Francisco, CA 94121 USA. EM jennifer.boyd@ucsf.edu NR 85 TC 43 Z9 43 U1 9 U2 49 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0010-440X EI 1532-8384 J9 COMPR PSYCHIAT JI Compr. Psychiat. PD JAN PY 2014 VL 55 IS 1 BP 221 EP 231 DI 10.1016/j.comppsych.2013.06.005 PG 11 WC Psychiatry SC Psychiatry GA AM5VO UT WOS:000339929300027 PM 24060237 ER PT J AU Joshi, A Barsuglia, JP Mather, MJ Jimenez, EE Shapira, J Mendez, MF AF Joshi, Aditi Barsuglia, Joseph P. Mather, Michelle J. Jimenez, Elvira E. Shapira, Jill Mendez, Mario F. TI Evaluation of Emotional Blunting in Behavioral Variant Frontotemporal Dementia Compared to Alzheimer's Disease SO DEMENTIA AND GERIATRIC COGNITIVE DISORDERS LA English DT Article DE Scale for Emotional Blunting; Dementia; Caregiver ID QUALITY-OF-LIFE; DIAGNOSTIC-CRITERIA; CAREGIVER BURDEN; RATING-SCALES; CONSENSUS AB Background: Emotional blunting is a major clinical feature of behavioral variant frontotemporal dementia (bvFTD). Assessing the change in emotional blunting may facilitate the differential diagnosis of this disorder and can quantify a major source of distress for the patients' caregivers and families. Methods: We evaluated investigator ratings on the Scale for Emotional Blunting (SEB) for 13 patients with bvFTD versus 18 patients with early-onset Alzheimer's disease (AD). The caregivers also performed SEB ratings for both the patients' premorbid behavior (before dementia onset) and the patients' behavior on clinical presentation (after dementia onset). Results: Before the onset of dementia, the caregivers reported normal SEB scores for both dementia groups. After the onset of dementia, both caregivers and investigators reported greater SEB scores for the bvFTD patients compared to the AD patients. The patients were rated to be much more emotionally blunted by the bvFTD caregivers than by the investigators. A change of >= 15 in the caregiver SEB ratings suggests bvFTD. The change in caregiver SEB ratings was positively correlated with bifrontal hypometabolism on FDG-PET scans. Conclusions: Changes in the caregiver assessment of emotional blunting with dementia onset can distinguish patients with bvFTD from those with AD, and they may better reflect the impact of emotional blunting than similar assessments made by clinicians/investigators. (C) 2014 S. Karger AG, Basel C1 [Mather, Michelle J.; Jimenez, Elvira E.; Shapira, Jill; Mendez, Mario F.] VA Greater Angeles Healthcare Syst, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, David Geffen Sch Med, Psychiat & Biobehav Sci, Los Angeles, CA 90073 USA. [Joshi, Aditi; Barsuglia, Joseph P.; Mather, Michelle J.; Jimenez, Elvira E.; Shapira, Jill; Mendez, Mario F.] VA Greater Angeles Healthcare Syst, Los Angeles, CA 90073 USA. RP Mendez, MF (reprint author), VA Greater Angeles Healthcare Syst, 11301 Wilshire Blvd, Los Angeles, CA 90073 USA. EM mmendez@ucla.edu OI Barsuglia, Joseph/0000-0001-7337-9486 FU NIA [R01AG034499-04]; VA GRECC Advanced Fellowship FX This study was supported by NIA Grant No. R01AG034499-04 and the VA GRECC Advanced Fellowship in Geriatrics Award (J.B.). We acknowledge Dr. Natalie Wolcott for neuropsychological evaluations. NR 35 TC 4 Z9 4 U1 2 U2 4 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 1420-8008 EI 1421-9824 J9 DEMENT GERIATR COGN JI Dement. Geriatr. Cogn. Disord. PY 2014 VL 38 IS 1-2 BP 79 EP 88 DI 10.1159/000357838 PG 10 WC Geriatrics & Gerontology; Clinical Neurology; Psychiatry SC Geriatrics & Gerontology; Neurosciences & Neurology; Psychiatry GA AM5JN UT WOS:000339893700009 PM 24603498 ER PT B AU Guinan, EC MacMillan, ML AF Guinan, Eva C. MacMillan, Margaret L. BE Smith, FO Reaman, GH Racadio, JM TI Graft Versus Host Disease: From Basics to the Clinic SO HEMATOPOIETIC CELL TRANSPLANTATION IN CHILDREN WITH CANCER SE Pediatric Oncology LA English DT Article; Book Chapter ID BONE-MARROW-TRANSPLANTATION; STEM-CELL TRANSPLANTATION; NECROSIS-FACTOR-ALPHA; UMBILICAL-CORD BLOOD; MINOR HISTOCOMPATIBILITY ANTIGENS; CONSENSUS DEVELOPMENT PROJECT; WORKING GROUP-REPORT; REGULATORY T-CELLS; UNRELATED DONORS; RISK-FACTORS C1 [Guinan, Eva C.] Dana Farber Canc Inst, Dept Radiat Oncol, Boston, MA 02215 USA. [Guinan, Eva C.] Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02215 USA. [Guinan, Eva C.] Harvard Univ, Sch Med, Boston, MA USA. [MacMillan, Margaret L.] Univ Minnesota, Sch Med, Dept Pediat, Blood & Marrow Transplant Program, Minneapolis, MN 55455 USA. RP Guinan, EC (reprint author), Dana Farber Canc Inst, Dept Radiat Oncol, 450 Brookline Ave, Boston, MA 02215 USA. EM eva_guinan@dfci.harvard.edu NR 124 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER-VERLAG BERLIN PI BERLIN PA HEIDELBERGER PLATZ 3, D-14197 BERLIN, GERMANY BN 978-3-642-39920-6; 978-3-642-39919-0 J9 PEDIATR ONCOL-BERLIN PY 2014 BP 57 EP 75 DI 10.1007/978-3-642-39920-6_4 D2 10.1007/978-3-642-39920-6 PG 19 WC Oncology; Pediatrics SC Oncology; Pediatrics GA BA9JP UT WOS:000339484900005 ER PT B AU Yanik, GA Cooke, KR Ho, VT Richardson, PG AF Yanik, Gregory A. Cooke, Kenneth R. Ho, Vincent T. Richardson, Paul G. BE Smith, FO Reaman, GH Racadio, JM TI Pulmonary and Hepatic Complications of Hematopoietic Cell Transplantation SO HEMATOPOIETIC CELL TRANSPLANTATION IN CHILDREN WITH CANCER SE Pediatric Oncology LA English DT Article; Book Chapter ID BONE-MARROW-TRANSPLANTATION; IDIOPATHIC-PNEUMONIA-SYNDROME; VERSUS-HOST-DISEASE; TISSUE-PLASMINOGEN-ACTIVATOR; BRONCHIOLITIS OBLITERANS SYNDROME; DIFFUSE ALVEOLAR HEMORRHAGE; RESPIRATORY SYNCYTIAL VIRUS; ACUTE LUNG INJURY; HIGH-DOSE CHEMOTHERAPY; AIR-FLOW OBSTRUCTION C1 [Yanik, Gregory A.] Univ Michigan, Ctr Canc, Blood & Marrow Transplant Program, Ann Arbor, MI 48109 USA. [Cooke, Kenneth R.] Johns Hopkins Univ, Sch Med, Sidney Kimmel Comprehens Canc Ctr Johns Hopkins, Pediat Blood & Marrow Transplantat Program, Baltimore, MD 21287 USA. [Ho, Vincent T.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02215 USA. [Richardson, Paul G.] Dana Farber Canc Inst, Jerome Lipper Multiple Myeloma Ctr, Dept Med Oncol, Boston, MA 02215 USA. RP Richardson, PG (reprint author), Dana Farber Canc Inst, Jerome Lipper Multiple Myeloma Ctr, Dept Med Oncol, Boston, MA 02215 USA. EM gyanik@umich.edu; kcooke5@jhmi.edu; vincent_ho@dfci.harvard.edu; paul_richardson@dfci.harvard.edu NR 168 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER-VERLAG BERLIN PI BERLIN PA HEIDELBERGER PLATZ 3, D-14197 BERLIN, GERMANY BN 978-3-642-39920-6; 978-3-642-39919-0 J9 PEDIATR ONCOL-BERLIN PY 2014 BP 77 EP 102 DI 10.1007/978-3-642-39920-6_5 D2 10.1007/978-3-642-39920-6 PG 26 WC Oncology; Pediatrics SC Oncology; Pediatrics GA BA9JP UT WOS:000339484900006 ER PT B AU Baker, KS Petryk, A Fisher, VL Duncan, C Carpenter, PA AF Baker, K. Scott Petryk, Anna Fisher, Vicki L. Duncan, Christine Carpenter, Paul A. BE Smith, FO Reaman, GH Racadio, JM TI Late Effects in Survivors After Hematopoietic Cell Transplantation in Childhood SO HEMATOPOIETIC CELL TRANSPLANTATION IN CHILDREN WITH CANCER SE Pediatric Oncology LA English DT Article; Book Chapter ID BONE-MARROW-TRANSPLANTATION; VERSUS-HOST-DISEASE; TOTAL-BODY IRRADIATION; LONG-TERM SURVIVORS; OF-THE-LITERATURE; THROMBOTIC THROMBOCYTOPENIC PURPURA; ACUTE-LYMPHOBLASTIC-LEUKEMIA; HIGH-DOSE CHEMOTHERAPY; CHRONIC KIDNEY-DISEASE; FOCAL NODULAR HYPERPLASIA C1 [Baker, K. Scott; Carpenter, Paul A.] Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA. [Petryk, Anna] Univ Minnesota, Minneapolis, MN USA. [Fisher, Vicki L.] VLF Oncol & BMT Consultants, Medina, OH USA. [Duncan, Christine] Dana Farber Canc Ctr, Boston, MA USA. RP Baker, KS (reprint author), Fred Hutchinson Canc Res Ctr, 1124 Columbia St, Seattle, WA 98104 USA. EM ksbaker@fhcrc.org NR 331 TC 0 Z9 0 U1 0 U2 1 PU SPRINGER-VERLAG BERLIN PI BERLIN PA HEIDELBERGER PLATZ 3, D-14197 BERLIN, GERMANY BN 978-3-642-39920-6; 978-3-642-39919-0 J9 PEDIATR ONCOL-BERLIN PY 2014 BP 133 EP 169 DI 10.1007/978-3-642-39920-6_7 D2 10.1007/978-3-642-39920-6 PG 37 WC Oncology; Pediatrics SC Oncology; Pediatrics GA BA9JP UT WOS:000339484900008 ER PT S AU Kreklywich, CN Smith, PP Jones, CB Cornea, A Orloff, SL Streblow, DN AF Kreklywich, Craig N. Smith, Patricia P. Jones, Carmen Baca Cornea, Anda Orloff, Susan L. Streblow, Daniel N. BE Yurochko, AD Miller, WE TI Fluorescence-Based Laser Capture Microscopy Technology Facilitates Identification of Critical In Vivo Cytomegalovirus Transcriptional Programs SO HUMAN CYTOMEGALOVIRUSES: METHODS AND PROTOCOLS SE Methods in Molecular Biology LA English DT Article; Book Chapter DE Laser capture microscopy; Cytomegalovirus; Green fluorescence protein; Microarray analysis ID TRANSPLANT VASCULAR SCLEROSIS; CHRONIC REJECTION; GENE-EXPRESSION; ALLOGRAFT RECIPIENTS; HEART-TRANSPLANTS; INFECTION; LATENCY; ATHEROSCLEROSIS; DISEASE; GENOME AB Cytomegalovirus gene expression in highly permissive, cultured fibroblasts occurs in three kinetic classes known as immediate early, early, and late. Infection of these cells results in a predictable transcriptional program leading to high levels of virus production. Infection of other, so-called, nonpermissive cell types results in a transcriptional program that either fails to produce virus particles or production is substantially reduced compared to fibroblasts. We have found that CMV gene expression profiles in tissues from infected hosts differ greatly from those observed in infected tissue culture cells. The number of viral genes expressed in tissues is much more limited, and the number of highly active genes does not correlate with viral DNA load. Additionally, viral gene expression in vivo is tissue selective with no two tissues expressing the exact same viral gene profile. Thus, in vivo CMV gene expression appears to be governed by mechanisms that are still uncharacterized. Cytomegalovirus remains in a persistent phase for the lifetime of the host. During this phase only a limited number of host cells are infected, and it is very difficult to detect CMV gene expression in whole tissues without sub-fractionating infected vs. uninfected cells. Herein, we describe the development of a fluorescence-based laser capture microscopy technique coupled with small sample size microarray analysis to determine the viral gene expression in 50-100 infected cells isolated from frozen RCMV-infected tissue sections. C1 [Kreklywich, Craig N.; Smith, Patricia P.; Jones, Carmen Baca; Orloff, Susan L.; Streblow, Daniel N.] Oregon Hlth & Sci Univ, Vaccine & Gene Therapy Inst, Dept Mol Microbiol & Immunol, Beaverton, OR USA. [Kreklywich, Craig N.; Orloff, Susan L.] Oregon Hlth & Sci Univ, Dept Surg, Portland, OR 97201 USA. [Cornea, Anda] Oregon Hlth & Sci Univ, Oregon Natl Primate Res Ctr, Beaverton, OR USA. [Orloff, Susan L.] Portland VA Med Ctr, Portland, OR USA. RP Kreklywich, CN (reprint author), Oregon Hlth & Sci Univ, Vaccine & Gene Therapy Inst, Dept Mol Microbiol & Immunol, Beaverton, OR USA. FU NCRR NIH HHS [S10 RR027503, P51 RR000163]; NHLBI NIH HHS [HL-66238-01, HL-083194, R01 HL083194, R01 HL066238] NR 24 TC 1 Z9 1 U1 0 U2 2 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DR, STE 208, TOTOWA, NJ 07512-1165 USA SN 1064-3745 BN 978-1-62703-788-4; 978-1-62703-787-7 J9 METHODS MOL BIOL JI Methods Mol. Biol. PY 2014 VL 1119 BP 217 EP 237 DI 10.1007/978-1-62703-788-4_13 D2 10.1007/978-1-62703-788-4 PG 21 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Virology SC Biochemistry & Molecular Biology; Virology GA BA8RJ UT WOS:000338506900014 PM 24639226 ER PT J AU Salazar, GMM Tan, CS Spearman, K Wicky, S Wu, S AF Salazar, Gloria Maria Martinez Tan, Chieh Suai Spearman, Kenneth Wicky, Stephen Wu, Steven TI Safety of percutaneous tunneled hemodialysis catheter procedures in patients receiving concurrent clopidogrel therapy SO JOURNAL OF VASCULAR ACCESS LA English DT Article DE Bleeding complications; Chronic kidney disease; Clopidogrel; Dialysis access ID CENTRAL VENOUS CATHETERS; ANTIPLATELET THERAPY; DIALYSIS PATIENTS; RENAL-DISEASE; RISK; GUIDELINES; MANAGEMENT; ASPIRIN; INTERVENTIONS; METAANALYSIS AB Purpose: Patients on clopidogrel are at increased risk of bleeding. This study was commenced to assess the incidence of bleeding in dialysis patients who underwent tunneled hemodialysis catheter procedures while on clopidogrel therapy. Methods: This is a single center retrospective study of 25 (10 men, 15 women; median age 70) dialysis patients in whom clopidogrel could not be discontinued and underwent tunneled hemodialysis catheter insertion, removal or exchange between the period March 2010 to November 2011. The medical records of patients were reviewed and complications were classified according to the Society of Interventional Radiology system. Fifty-three procedures (22 insertions, 11 exchanges and 20 removals) were performed in these patients. The pre-procedural median platelet count, International Normalized Ratio and partial thromboplastin time were 195x10(3)/dL (range 50-666), 1.1 (range 0.9-3.3) and 26.3 seconds (range 22.5-69.8) respectively. Results and Conclusions: Forty-six procedures were performed in patients on clopidogrel and aspirin treatment. Five procedures were performed in patients while on clopidogrel in combination with aspirin and warfarin, and two procedures were performed with patients on clopidogrel alone. There were no documented bleeding complications from tunneled hemodialysis catheter procedures performed in patients on concurrent clopidogrel therapy in our study. Further prospective assessment with a larger cohort is necessary in order to validate these findings. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Vasc Imaging & Intervent, Boston, MA 02114 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Nephrol, Boston, MA 02114 USA. [Wu, Steven] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Med & Radiol, Boston, MA 02114 USA. RP Wu, S (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Med & Radiol, 55 Fruit St, Boston, MA 02114 USA. EM swu1@partners.org NR 21 TC 3 Z9 3 U1 0 U2 0 PU WICHTIG EDITORE PI MILAN PA 72/74 VIA FRIULI, 20135 MILAN, ITALY SN 1129-7298 EI 1724-6032 J9 J VASC ACCESS JI J. Vasc. Access PD JAN-FEB PY 2014 VL 15 IS 1 BP 33 EP 37 DI 10.5301/jva.5000164 PG 5 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA AM6TC UT WOS:000339996800008 ER PT J AU Wylie, KP Rojas, DC Ross, RG Hunter, SK Maharajh, K Cornier, MA Tregellas, JR AF Wylie, Korey P. Rojas, Donald C. Ross, Randal G. Hunter, Sharon K. Maharajh, Keeran Cornier, Marc-Andre Tregellas, Jason R. TI Reduced brain resting-state network specificity in infants compared with adults SO NEUROPSYCHIATRIC DISEASE AND TREATMENT LA English DT Article DE functional connectivity magnetic resonance imaging; networks; development; infancy; resting-state; connectivity AB Purpose: Infant resting-state networks do not exhibit the same connectivity patterns as those of young children and adults. Current theories of brain development emphasize developmental progression in regional and network specialization. We compared infant and adult functional connectivity, predicting that infants would exhibit less regional specificity and greater internetwork communication compared with adults. Patients and methods: Functional magnetic resonance imaging at rest was acquired in 12 healthy, term infants and 17 adults. Resting-state networks were extracted, using independent components analysis, and the resulting components were then compared between the adult and infant groups. Results: Adults exhibited stronger connectivity in the posterior cingulate cortex node of the default mode network, but infants had higher connectivity in medial prefrontal cortex/anterior cingulate cortex than adults. Adult connectivity was typically higher than infant connectivity within structures previously associated with the various networks, whereas infant connectivity was frequently higher outside of these structures. Internetwork communication was significantly higher in infants than in adults. Conclusion: We interpret these findings as consistent with evidence suggesting that resting-state network development is associated with increasing spatial specificity, possibly reflecting the corresponding functional specialization of regions and their interconnections through experience. C1 [Wylie, Korey P.; Rojas, Donald C.; Ross, Randal G.; Hunter, Sharon K.; Maharajh, Keeran; Tregellas, Jason R.] Univ Colorado, Dept Psychiat, Aurora, CO 80045 USA. [Cornier, Marc-Andre] Univ Colorado, Dept Med, Div Endocrinol Diabet & Metab, Aurora, CO USA. [Tregellas, Jason R.] Denver Vet Affairs Med Ctr, Denver, CO USA. RP Tregellas, JR (reprint author), Univ Colorado, Dept Psychiat, Box F456,Anschutz Med Campus,13001 E 17th Ave, Aurora, CO 80045 USA. EM jason.tregellas@ucdenver.edu RI Tregellas, Jason/J-3637-2015; OI Rojas, Don/0000-0001-6560-9616 FU National Institutes of Health [R01 MH082820, R01 MH081920, R01 DK089095, P50 MH086383]; Brain Research Foundation; Blowitz-Ridgeway Foundation FX Support for this research came from National Institutes of Health grants R01 MH082820, R01 MH081920, R01 DK089095, and P50 MH086383; the Brain Research Foundation; and the Blowitz-Ridgeway Foundation. The financial sponsors had no role in the design, data collection analysis, data interpretation, or writing of the manuscript or decision to submit the manuscript for publication. NR 2 TC 9 Z9 9 U1 0 U2 7 PU DOVE MEDICAL PRESS LTD PI ALBANY PA PO BOX 300-008, ALBANY, AUCKLAND 0752, NEW ZEALAND SN 1178-2021 J9 NEUROPSYCH DIS TREAT JI Neuropsychiatr. Dis. Treat. PY 2014 VL 10 BP 1349 EP 1359 DI 10.2147/NDT.S63773 PG 11 WC Clinical Neurology; Psychiatry SC Neurosciences & Neurology; Psychiatry GA AM5TX UT WOS:000339924600001 PM 25092980 ER PT J AU Tan, SM Altschuler, G Zhao, TY Ang, HS Yang, H Lim, B Vardy, L Hide, W Thomson, AM Lareu, RR AF Tan, Shen Mynn Altschuler, Gabriel Zhao, Tian Yun Ang, Haw Siang Yang, Henry Lim, Bing Vardy, Leah Hide, Winston Thomson, Andrew M. Lareu, Ricky R. TI Divergent LIN28-mRNA associations result in translational suppression upon the initiation of differentiation SO NUCLEIC ACIDS RESEARCH LA English DT Article ID EMBRYONIC STEM-CELLS; RNA-BINDING PROTEIN; SELF-RENEWAL; MESSENGER-RNAS; IN-VITRO; LIN28; MICRORNA; EXPRESSION; LIN-28; PLURIPOTENCY AB LIN28 function is fundamental to the activity and behavior of human embryonic stem cells (hESCs) and induced pluripotent stem cells. Its main roles in these cell types are the regulation of translational efficiency and let-7 miRNA maturation. However, LIN28-associated mRNA cargo shifting and resultant regulation of translational efficiency upon the initiation of differentiation remain unknown. An RNA-immunoprecipitation and microarray analysis protocol, eRIP, that has high specificity and sensitivity was developed to test endogenous LIN28-associated mRNA cargo shifting. A combined eRIP and polysome analysis of early stage differentiation of hESCs with two distinct differentiation cues revealed close similarities between the dynamics of LIN28 association and translational modulation of genes involved in the Wnt signaling, cell cycle, RNA metabolism and proteasomal pathways. Our data demonstrate that change in translational efficiency is a major contributor to early stages of differentiation of hESCs, in which LIN28 plays a central role. This implies that eRIP analysis of LIN28-associated RNA cargoes may be used for rapid functional quality control of pluripotent stem cells under manufacture for therapeutic applications. C1 [Tan, Shen Mynn; Lim, Bing; Thomson, Andrew M.] ASTAR, Genome Inst Singapore, Singapore 138672, Singapore. [Altschuler, Gabriel; Hide, Winston] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. [Zhao, Tian Yun; Vardy, Leah] ASTAR, Inst Med Biol, Singapore 138648, Singapore. [Ang, Haw Siang; Yang, Henry] Natl Univ Singapore NUS, Canc Sci Inst, Singapore 117599, Singapore. [Lareu, Ricky R.] NUS, Yong Loo Lin Sch Med, Dept Orthoped Surg, NUS Tissue Engn Program, Singapore 119228, Singapore. [Lareu, Ricky R.] Curtin Univ, CHIRI Biosci, Sch Pharm, Bentley, WA 6102, Australia. RP Tan, SM (reprint author), Harvard Univ, Sch Med, Boston Childrens Hosp, Program Cellular & Mol Med, Boston, MA 02115 USA. EM Shenmynn.Tan@childrens.harvard.edu; whide@hsph.harvard.edu; Ricky.Lareu@curtin.edu.au FU Singapore Stem Cell Consortium [SSCC-06-006]; Curtin University FX Singapore Stem Cell Consortium [SSCC-06-006 to A.T. and R.L.]. Funding for open access charge: Curtin University. NR 60 TC 2 Z9 3 U1 0 U2 2 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0305-1048 EI 1362-4962 J9 NUCLEIC ACIDS RES JI Nucleic Acids Res. PY 2014 VL 42 IS 12 BP 7997 EP 8007 DI 10.1093/nar/gku430 PG 11 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA AM2XA UT WOS:000339713200042 PM 24860167 ER PT J AU Backenroth, D Homsy, J Murillo, LR Glessner, J Lin, E Brueckner, M Lifton, R Goldmuntz, E Chung, WK Shen, YF AF Backenroth, Daniel Homsy, Jason Murillo, Laura R. Glessner, Joe Lin, Edwin Brueckner, Martina Lifton, Richard Goldmuntz, Elizabeth Chung, Wendy K. Shen, Yufeng TI CANOES: detecting rare copy number variants from whole exome sequencing data SO NUCLEIC ACIDS RESEARCH LA English DT Article ID CONGENITAL HEART-DISEASE; GENOME-WIDE; COUNT DATA; MODEL; DISCOVERY; RISK; SNP AB We present CANOES, an algorithm for the detection of rare copy number variants from exome sequencing data. CANOES models read counts using a negative binomial distribution and estimates variance of the read counts using a regression-based approach based on selected reference samples in a given dataset. We test CANOES on a family-based exome sequencing dataset, and show that its sensitivity and specificity is comparable to that of XHMM. Moreover, the method is complementary to Gaussian approximation-based methods (e.g. XHMM or CoNIFER). When CANOES is used in combination with these methods, it will be possible to produce high accuracy calls, as demonstrated by a much reduced and more realistic de novo rate in results from trio data. C1 [Backenroth, Daniel; Lin, Edwin; Shen, Yufeng] Columbia Univ, Med Ctr, Dept Syst Biol, New York, NY 10032 USA. [Backenroth, Daniel; Lin, Edwin; Shen, Yufeng] Columbia Univ, Med Ctr, Dept Biomed Informat, New York, NY 10032 USA. [Backenroth, Daniel; Shen, Yufeng] Columbia Univ, Med Ctr, JP Sulzberger Columbia Genome Ctr, New York, NY 10032 USA. [Homsy, Jason] Massachusetts Gen Hosp, Cardiovascular Res Ctr, Boston, MA 02114 USA. [Murillo, Laura R.] Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA. [Murillo, Laura R.] Icahn Sch Med Mt Sinai, Dept Pediat & Genet, Boston, MA 02115 USA. [Murillo, Laura R.] Icahn Sch Med Mt Sinai, Dept Gen Sci, Boston, MA 02115 USA. [Glessner, Joe] Childrens Hosp Philadelphia, Ctr Appl Gen, Philadelphia, PA 19104 USA. [Lin, Edwin; Chung, Wendy K.] Columbia Univ, Med Ctr, Dept Pediat, New York, NY 10032 USA. [Lin, Edwin; Chung, Wendy K.] Columbia Univ, Med Ctr, Dept Med, New York, NY 10032 USA. [Brueckner, Martina; Lifton, Richard] Yale Univ, Sch Med, Dept Genet, New Haven, CT 06510 USA. [Lifton, Richard] Yale Univ, Howard Hughes Med Inst, New Haven, CT 06510 USA. [Goldmuntz, Elizabeth] Univ Penn, Perelman Sch Med, Dept Pediat, Philadelphia, PA 19104 USA. RP Chung, WK (reprint author), Columbia Univ, Med Ctr, Dept Pediat, New York, NY 10032 USA. EM wkc15@cumc.columbia.edu FU Department of Systems Biology at Columbia University; JP Sulzberger Columbia Genome Center; National Institutes of Health (NIH); National Heart, Lung and Blood Institute (NHLBI); Pediatric Cardiac Genomics Consortium [U01-HL098147, U01-HL098153, U01-HL098163, U01-HL098123, U01-HL098162]; Harvard Medical School FX Department of Systems Biology at Columbia University [to Y.S.]; JP Sulzberger Columbia Genome Center [to D.B.]; National Institutes of Health (NIH); National Heart, Lung and Blood Institute (NHLBI); Pediatric Cardiac Genomics Consortium [U01-HL098147 to J.H., U01-HL098153 to E.G., J.G., U01-HL098163 to W.K.C., Y.S., E.L., U01-HL098123 to L.R.M., U01-HL098162 to M.B., R.L.]. John S. LaDue Memorial Fellowship at Harvard Medical School [ to J.H.]. Funding for open access charge: Department startup package for new faculty. NR 22 TC 10 Z9 10 U1 0 U2 2 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0305-1048 EI 1362-4962 J9 NUCLEIC ACIDS RES JI Nucleic Acids Res. PY 2014 VL 42 IS 12 AR e97 DI 10.1093/nar/gku345 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA AM2XA UT WOS:000339713200001 PM 24771342 ER PT J AU Warren, M Martindale, R AF Warren, Malissa Martindale, Robert BE Faber, P Siervo, M TI Enteral and parenteral feeding protocols SO NUTRITION IN CRITICAL CARE LA English DT Article; Book Chapter ID INTENSIVE-CARE-UNIT; CONTROLLED-TRIAL; ENERGY DEFICIT; NUTRITION; IMPLEMENTATION; MULTICENTER; DELIVERY; THERAPY; IMPACT C1 [Warren, Malissa] Portland VA Med Ctr, Portland, OR 97239 USA. [Martindale, Robert] Oregon Hlth & Sci Univ, Div Gen Surg, Portland, OR 97201 USA. RP Warren, M (reprint author), Portland VA Med Ctr, Portland, OR 97239 USA. NR 13 TC 0 Z9 0 U1 0 U2 0 PU CAMBRIDGE UNIV PRESS PI CAMBRIDGE PA THE PITT BUILDING, TRUMPINGTON ST, CAMBRIDGE CB2 1RP, CAMBS, ENGLAND BN 978-1-107-66901-7 PY 2014 BP 43 EP 51 D2 10.1017/CBO9781139342452 PG 9 WC Critical Care Medicine; Nutrition & Dietetics SC General & Internal Medicine; Nutrition & Dietetics GA BA9KT UT WOS:000339513400006 ER PT J AU Cheema, TA Fecci, PE Ning, JF Rabkin, SD AF Cheema, Tooba A. Fecci, Peter E. Ning, Jianfang Rabkin, Samuel D. TI Immunovirotherapy for the treatment of glioblastoma SO ONCOIMMUNOLOGY LA English DT Editorial Material DE cancer stem cells; glioma; herpes simplex virus; interleukin-12; oncolytic virus; Treg ID ONCOLYTIC VIRUS THERAPY; MALIGNANT GLIOMA; MODELS AB We have recently described a new murine model of glioblastoma, generated by the implantation of syngeneic glioblastoma stem cells into immunocompetent mice, that recapitulates the salient histopathological and immunological features of the human disease. We employed this model to demonstrate the multifaceted activity of an oncolytic herpes simplex virus genetically modified to express interleukin-12, G47 Delta-IL12. C1 [Cheema, Tooba A.; Fecci, Peter E.; Ning, Jianfang; Rabkin, Samuel D.] Massachusetts Gen Hosp, Dept Neurosurg, Brain Tumor Res Ctr, Boston, MA 02114 USA. [Cheema, Tooba A.; Ning, Jianfang; Rabkin, Samuel D.] Harvard Univ, Sch Med, Boston, MA USA. [Cheema, Tooba A.] Momenta Pharmaceut, Cambridge, MA USA. RP Rabkin, SD (reprint author), Massachusetts Gen Hosp, Dept Neurosurg, Brain Tumor Res Ctr, Boston, MA 02114 USA. EM rabkin@mgh.harvard.edu OI rabkin, samuel/0000-0003-2344-2795 FU NCI NIH HHS [R01 CA160762]; NINDS NIH HHS [R01 NS032677] NR 10 TC 5 Z9 5 U1 1 U2 1 PU LANDES BIOSCIENCE PI AUSTIN PA 1806 RIO GRANDE ST, AUSTIN, TX 78702 USA SN 2162-4011 EI 2162-402X J9 ONCOIMMUNOLOGY JI OncoImmunology PD JAN PY 2014 VL 3 IS 1 AR e27218 DI 10.4161/onci.27218 PG 3 WC Oncology; Immunology SC Oncology; Immunology GA AM6DP UT WOS:000339952700003 PM 24575383 ER PT S AU Wheeler, JB Ikonomidis, JS Jones, JA AF Wheeler, Jason B. Ikonomidis, John S. Jones, Jeffrey A. BE Halper, J TI Connective Tissue Disorders and Cardiovascular Complications: The Indomitable Role of Transforming Growth Factor-Beta Signaling SO PROGRESS IN HERITABLE SOFT CONNECTIVE TISSUE DISEASES SE Advances in Experimental Medicine and Biology LA English DT Article; Book Chapter DE Shprintzen-Goldberg syndrome hereditary hemorrhagic telangiectasia (HHT); Marfan syndrome (MFS); Loeys-Dietz syndrome (LDS); Primary pulmonary hypertension; Fibrodysplasia ossificans progressiva (FOP); Familial thoracic aortic aneurysm and dissection syndrome (FTAAD); Smad; TGF-beta receptor; Curacao diagnostic criteria ID HEREDITARY HEMORRHAGIC TELANGIECTASIA; SHPRINTZEN-GOLDBERG-SYNDROME; THORACIC AORTIC-ANEURYSMS; LATENT TGF-BETA; PULMONARY ARTERIOVENOUS-MALFORMATIONS; ARTERIAL-TORTUOSITY-SYNDROME; SMOOTH-MUSCLE-CELLS; MARFAN-SYNDROME; EXTRACELLULAR-MATRIX; BINDING-PROTEIN AB Marfan Syndrome (MFS) and Loeys-Dietz Syndrome (LDS) represent heritable connective tissue disorders that cosegregate with a similar pattern of cardiovascular defects (thoracic aortic aneurysm, mitral valve prolapse/regurgitation, and aortic root dilatation with regurgitation). This pattern of cardiovascular defects appears to be expressed along a spectrum of severity in many heritable connective tissue disorders and raises suspicion of a relationship between the normal development of connective tissues and the cardiovascular system. Given the evidence of increased transforming growth factor-beta (TGF-beta) signaling in MFS and LDS, this signaling pathway may represent the common link in this relationship. To further explore this hypothetical link, this chapter will review the TGF-beta signaling pathway, heritable connective tissue syndromes related to TGF-beta receptor (TGFBR) mutations, and discuss the pathogenic contribution of TGF-beta to these syndromes with a primary focus on the cardiovascular system. C1 [Wheeler, Jason B.; Ikonomidis, John S.; Jones, Jeffrey A.] Med Univ S Carolina, Div Cardiothorac Surg, Charleston, SC 29425 USA. [Jones, Jeffrey A.] Ralph H Johnson Vet Affairs Med Ctr, Charleston, SC 29425 USA. RP Jones, JA (reprint author), Med Univ S Carolina, Div Cardiothorac Surg, Strom Thurmond Res Bldg,114 Doughty St,Suite 326, Charleston, SC 29425 USA. EM jonesja@musc.edu FU BLRD VA [I01 BX000904]; NHLBI NIH HHS [R01 HL102121, T32 HL007260]; NIA NIH HHS [R01 AG036954] NR 158 TC 8 Z9 8 U1 0 U2 6 PU SPRINGER-VERLAG BERLIN PI BERLIN PA HEIDELBERGER PLATZ 3, D-14197 BERLIN, GERMANY SN 0065-2598 BN 978-94-007-7893-1; 978-94-007-7892-4 J9 ADV EXP MED BIOL JI Adv.Exp.Med.Biol. PY 2014 VL 802 BP 107 EP 127 DI 10.1007/978-94-007-7893-1_8 D2 10.1007/978-94-007-7893-1 PG 21 WC Cell Biology; Genetics & Heredity SC Cell Biology; Genetics & Heredity GA BA9GG UT WOS:000339357300008 PM 24443024 ER PT J AU Martin, PI Treglia, E Naeser, MA Ho, MD Baker, EH Martin, EG Bashir, S Pascual-Leone, A AF Martin, Paula I. Treglia, Ethan Naeser, Margaret A. Ho, Michael D. Baker, Errol H. Martin, Elizabeth G. Bashir, Shahid Pascual-Leone, Alvaro TI Language improvements after TMS plus modified CILT: Pilot, open-protocol study with two, chronic nonfluent aphasia cases SO RESTORATIVE NEUROLOGY AND NEUROSCIENCE LA English DT Article DE TMS; speech therapy; constraint-induced language therapy; aphasia; stroke rehabilitation ID TRANSCRANIAL MAGNETIC STIMULATION; NONINVASIVE BRAIN-STIMULATION; CONSTRAINT-INDUCED APHASIA; INDUCED MOVEMENT THERAPY; MELODIC INTONATION THERAPY; POSTSTROKE APHASIA; STROKE PATIENTS; UNAFFECTED HEMISPHERE; QUANTITATIVE-ANALYSIS; ANOMIA TREATMENT AB Purpose: The purpose of this study was to investigate: 1) the feasibilty of administering a modified CILT (mCILT) treatment session immediately after TMS; and 2) if this combined therapy could improve naming and elicited propositional speech in chronic, nonfluent aphasia. Methods: Two chronic stroke patients with nonfluent aphasia (mild-moderate and severe) each received twenty minutes of rTMS to suppress the right pars triangularis, followed immediately by three hours of mCILT (5 days/week, 2 weeks). (Each patient had received TMS alone, 2-6 years prior.) Language evaluations were performed pre- TMS+mCILT, and post- at 1-2 months, and 6 or 16 months. Results: Both patients showed significant improvements in naming pictures, and elicited propositional speech at 1-2 months post- TMS+mCILT. The improved naming was still present at 6 months post- TMS+mCILT for P2; but not at 16 months post- TMS+ mCILT for P1. Conclusions: It is feasible to administer mCILT for three hours immediately after a TMS session. It is unknown if the significant improvements in naming pictures, and elicited propositional speech were associated with the second series of TMS, or this first series of mCILT, or a combination of both. A larger, sham controlled clinical trial is warranted. C1 [Martin, Paula I.; Treglia, Ethan; Naeser, Margaret A.; Ho, Michael D.; Baker, Errol H.; Martin, Elizabeth G.] VA Boston Healthcare Syst, Boston, MA 02130 USA. [Martin, Paula I.; Treglia, Ethan; Naeser, Margaret A.; Ho, Michael D.; Baker, Errol H.; Martin, Elizabeth G.] Harold Goodglass Boston Univ, Aphasia Res Ctr, Boston, MA USA. [Martin, Paula I.; Treglia, Ethan; Naeser, Margaret A.; Ho, Michael D.; Baker, Errol H.; Martin, Elizabeth G.] Boston Univ, Sch Med, Dept Neurol, Boston, MA 02118 USA. [Bashir, Shahid; Pascual-Leone, Alvaro] Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Berenson Allen Ctr Noninvas Brain Stimulat, Boston, MA 02215 USA. [Pascual-Leone, Alvaro] UAB, Inst Univ Neurorehabil Guttmann, Badalona, Spain. RP Martin, PI (reprint author), VA Boston Healthcare Syst, Aphasia Res Ctr, 12-A,150 So Huntington Ave, Boston, MA 02130 USA. EM paulak@bu.edu RI Bashir, Shahid/E-7212-2014 FU National Institute on Deafness and Other Communication Disorders of the National Institutes of Health, Bethesda, MD [RO1 DC05672]; Medical Research Service, Department of Veterans Affairs, Washington; K24 NIH award [RRO18875]; BBVA Chair in Translational Medicine, Harvard Clinical and Translational Science [UL1 RR025758, RO1-NS 47754, RO1-NS 20068]; Harvard-Thorndike General Clinical Research Center [NCRR MO1 RR01032]; NIH [P30 DC05207]; National Institute on Deafness and Other Communication Disorders FX Research reported in this publication was supported in part under Award Number RO1 DC05672 from the National Institute on Deafness and Other Communication Disorders of the National Institutes of Health, Bethesda, MD. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health; Other support for this publication includes a grant from the Medical Research Service, Department of Veterans Affairs, Washington, D. C. (to M. A. N.); a K24 NIH award (RRO18875), BBVA Chair in Translational Medicine, Harvard Clinical and Translational Science Center (UL1 RR025758), RO1-NS 47754, and RO1-NS 20068 (to A. P.-L.); the Harvard-Thorndike General Clinical Research Center (NCRR MO1 RR01032); and NIH grant P30 DC05207, National Institute on Deafness and Other Communication Disorders (to the Harold Goodglass Boston University Aphasia Research Center). The authors thank the following people for their contributions to the study: Kristine Lundgren, Sc. D., for CILT study and design consultation; Elina Kaplan, B. S., and Mallory Finley, B. A., for data collection. NR 63 TC 3 Z9 3 U1 3 U2 18 PU IOS PRESS PI AMSTERDAM PA NIEUWE HEMWEG 6B, 1013 BG AMSTERDAM, NETHERLANDS SN 0922-6028 EI 1878-3627 J9 RESTOR NEUROL NEUROS JI Restor. Neurol. Neurosci. PY 2014 VL 32 IS 4 BP 483 EP 505 DI 10.3233/RNN-130365 PG 23 WC Neurosciences SC Neurosciences & Neurology GA AM7FT UT WOS:000340031000004 PM 25015701 ER PT S AU Gul, RM Oral, E Muratoglu, OK AF Gul, Rizwan M. Oral, Ebru Muratoglu, Orhun K. BE Qaisar, S Khan, AN Mukhtar, EA TI Oxidation resistant peroxide cross-linked UHMWPE produced by blending and surface diffusion SO 13TH INTERNATIONAL SYMPOSIUM ON ADVANCED MATERIALS (ISAM 2013) SE IOP Conference Series-Materials Science and Engineering LA English DT Proceedings Paper CT 13th International Symposium on Advanced Materials (ISAM) CY SEP 23-27, 2013 CL Islamabad, PAKISTAN SP Inst Space Technol, Amber Chem Ind Ltd, Ap Ways, Askari Bank Ltd, Engn Horizons, Forward Enterprises, Hamdard Fdn, Higher Educ Commiss, M S OVETEK, Natl Bank Pakistan, Natl Talent Pool, Pakistan Sci Fdn, Peoples Steel Mills Ltd, Profess Syst Ltd ID MOLECULAR-WEIGHT POLYETHYLENE; VITAMIN-E; WEAR; LINKING AB Ultra-high molecular weight polyethylene (UHMWPE) has been widely used as acetabular cup in total hip replacement (THR) and tibial component in total knee replacement (TKR). Crosslinking of UHMWPE has been successful used to improve its wear performance leading to longer life of orthopedic implants. Crosslinking can be performed by radiation or organic peroxides. Peroxide crosslinking is a convenient process as it does not require specialized equipment and the level of crosslinking can be manipulated by changing the amount of peroxide added. However, there is concern about the long-term stability of these materials due to possible presence of by-products. Vitamin E has been successfully used to promote long-term oxidative stability of UHMWPE. In this study, UHMWPE has been crosslinked using organic peroxide in the presence of Vitamin E to produce an oxidation resistant peroxide crosslinked material. Crosslinking was performed both in bulk by mixing peroxide and resin, and only on the surface using diffusion of peroxides. The results show that UHMWPE can be crosslinked using organic peroxides in the presence of vitamin E by both methods. However, the level of crosslinking decreases with the increase in vitamin E content. The wear resistance increases with the increase in crosslink density, and oxidation resistance significantly increases due to the presence of vitamin E. C1 [Gul, Rizwan M.] Univ Engn & Technol, Dept Mech Engn, Peshawar, Pakistan. [Oral, Ebru; Muratoglu, Orhun K.] Massachusetts Gen Hosp, Harris Orthopaed Lab, Boston, MA 02114 USA. RP Gul, RM (reprint author), Univ Engn & Technol, Dept Mech Engn, Peshawar, Pakistan. EM rgul@nwfpuet.edu.pk FU Harris Orthopaedic Laboratory; Fulbright Scholar Program FX The authors acknowledge Harris Orthopaedic Laboratory for providing funds and Fulbright Scholar Program for providing fellowship for Rizwan M. Gul to conduct the research. NR 9 TC 0 Z9 0 U1 1 U2 7 PU IOP PUBLISHING LTD PI BRISTOL PA DIRAC HOUSE, TEMPLE BACK, BRISTOL BS1 6BE, ENGLAND SN 1757-8981 J9 IOP CONF SER-MAT SCI PY 2014 VL 60 AR UNSP 012015 DI 10.1088/1757-899X/60/1/012015 PG 7 WC Materials Science, Multidisciplinary SC Materials Science GA BA9MV UT WOS:000339568300015 ER PT J AU Colvin, RB Traum, AZ Taheri, D Jafari, M Dolatkhah, S AF Colvin, Robert B. Traum, Avram Z. Taheri, Diana Jafari, Mohsen Dolatkhah, Shahaboddin TI Granulomatous Interstitial Nephritis as a Manifestation of Crohn Disease SO ARCHIVES OF PATHOLOGY & LABORATORY MEDICINE LA English DT Article ID INFLAMMATORY-BOWEL-DISEASE; TUBULOINTERSTITIAL NEPHRITIS; 5-AMINOSALICYLIC ACID; RENAL-FUNCTION; MESALAZINE; ADOLESCENT AB Granulomatous interstitial nephritis is a rare extraintestinal manifestation of Crohn disease that has been described previously in 4 patients. We report a 23-year-old man with a history of Crohn disease since age 6 years who was admitted to the hospital for weight loss, fever, and bloody diarrhea in the midst of a recent flare up during the past 2 months. Investigations revealed anemia, high erythrocyte sedimentation rate, high C-reactive protein level, and an elevated serum creatinine level. Histopathologic examination of tissue specimens obtained at renal biopsy demonstrated granulomatous interstitial nephritis. Crohn disease needs to be in the differential diagnosis of granulomatous interstitial nephritis and can be a manifestation of drug allergy or the Crohn disease itself. C1 [Colvin, Robert B.; Taheri, Diana] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Pathol, Boston, MA USA. [Traum, Avram Z.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Nephrol, Boston, MA USA. [Taheri, Diana] Isfahan Kidney Dis Res Ctr, Esfahan, Iran. [Taheri, Diana; Jafari, Mohsen] Isfahan Univ Med Sci, Sch Med, Dept Pathol, Esfahan 8168788131, Iran. [Dolatkhah, Shahaboddin] Isfahan Univ Med Sci, Fac Med, Esfahan 8168788131, Iran. RP Taheri, D (reprint author), Isfahan Univ Med Sci, Isfahan Kidney Dis Res Ctr, Dept Pathol, Esfahan 8168788131, Iran. EM d_taheri@med.mui.ac.ir NR 22 TC 5 Z9 6 U1 0 U2 2 PU COLL AMER PATHOLOGISTS PI NORTHFIELD PA C/O KIMBERLY GACKI, 325 WAUKEGAN RD, NORTHFIELD, IL 60093-2750 USA SN 0003-9985 EI 1543-2165 J9 ARCH PATHOL LAB MED JI Arch. Pathol. Lab. Med. PD JAN PY 2014 VL 138 IS 1 BP 125 EP 127 DI 10.5858/arpa.2012-0224-CR PG 3 WC Medical Laboratory Technology; Medicine, Research & Experimental; Pathology SC Medical Laboratory Technology; Research & Experimental Medicine; Pathology GA AM0QA UT WOS:000339549400018 PM 24377821 ER PT S AU Kaplan, A Sanz, R Ferraro, GB Alchini, R Fournier, AE AF Kaplan, Andrew Sanz, Ricardo Ferraro, Gino B. Alchini, Ricardo Fournier, Alyson E. BE Murray, AJ TI Neurite Outgrowth and Growth Cone Collapse Assays to Assess Neuronal Responses to Extracellular Cues SO AXON GROWTH AND REGENERATION: METHODS AND PROTOCOLS SE Methods in Molecular Biology LA English DT Article; Book Chapter DE Primary neuronal cultures; Axon; Regeneration; Growth cone; Myelin; Dorsal root ganglia; Microdissection; Neurite length; Neural development ID AXON REGENERATION; RECEPTOR 1; NOGO-A; MYELIN; INHIBITION; CNS; IDENTIFICATION; PROTEOGLYCANS; CLEAVAGE; PROTEIN AB The identification of molecular processes involved in regulating neurite outgrowth is an active area of interest for investigators studying neural development and regeneration. In vitro assays designed to measure growth cone morphology and neurite length are frequently used to assess neuronal responses to developmental guidance cues and inhibitory cues that exist in the adult CNS. Here, we describe the procedures to assess morphological responses of cultured dorsal root ganglion neurons to attractive and repellent cues, with a focus on repellents found in the injured adult CNS. The chapter describes methods to culture the DRGs, apply inhibitory ligands, and assess morphological responses. These assays provide biological readouts to assess the capacity of a molecule to act as an inhibitory or growth promoting cue. The readouts can be used as screening tools to aid in the identification of novel targets or drugs for promoting nerve regeneration. C1 [Kaplan, Andrew; Sanz, Ricardo; Alchini, Ricardo; Fournier, Alyson E.] McGill Univ, Montreal Neurol Inst, Dept Neurol & Neurosurg, Montreal, PQ H3A 2B4, Canada. [Ferraro, Gino B.] Massachusetts Gen Hosp, Dept Radiat Oncol, Edwin L Steele Lab Tumor Biol, Boston, MA 02114 USA. [Ferraro, Gino B.] Harvard Univ, Sch Med, Boston, MA USA. RP Kaplan, A (reprint author), McGill Univ, Montreal Neurol Inst, Dept Neurol & Neurosurg, Montreal, PQ H3A 2B4, Canada. FU Canadian Institutes of Health Research NR 27 TC 0 Z9 0 U1 1 U2 5 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DR, STE 208, TOTOWA, NJ 07512-1165 USA SN 1064-3745 BN 978-1-4939-0777-9; 978-1-4939-0776-2 J9 METHODS MOL BIOL JI Methods Mol. Biol. PY 2014 VL 1162 BP 43 EP 56 DI 10.1007/978-1-4939-0777-9_4 D2 10.1007/978-1-4939-0777-9 PG 14 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA BA9GH UT WOS:000339358700005 PM 24838957 ER PT S AU Krause, DS DeLelys, ME Preffer, FI AF Krause, Daniela S. DeLelys, Michelle E. Preffer, Frederic I. BE Beksac, M TI Flow Cytometry for Hematopoietic Cells SO BONE MARROW AND STEM CELL TRANSPLANTATION, 2ND EDITION SE Methods in Molecular Biology LA English DT Article; Book Chapter DE Flow cytometry; Diagnostic immunophenotyping; Hematopoietic malignancies; Hematopathology; Immunodeficiencies; Hematopoietic stem cells; Bone marrow transplantation; Paroxysmal nocturnal hemoglobinuria; Amnis imaging cytometry; CyTOF mass cytometry; Gemstone probability state model ID PAROXYSMAL-NOCTURNAL HEMOGLOBINURIA; ACUTE MYELOID-LEUKEMIA; MYELODYSPLASTIC SYNDROMES; MASS CYTOMETRY; PRACTICAL GUIDELINES; ANTIGEN-EXPRESSION; EXPANDING FRONTIER; MULTIPLE-MYELOMA; BONE-MARROW; TRANSPLANTATION AB Within the last 25 years, flow cytometry and fluorescence-activated cell sorting have emerged as both routine diagnostic tools in clinical medicine and as advanced analytic tools critical in performing scientific research. This chapter aims at summarizing the use of flow cytometry in benign and malignant hematology and the monitoring of inherited and acquired immunodeficiency states. Numerous figures are provided from our laboratories at Massachusetts General Hospital that illustrate examples of these conditions. The chapter also describes novel flow cytometry-based imaging techniques, the combination of flow cytometry and mass spectrography, new software tools, and some future directions and applications of advanced instrumentation for flow cytometry. C1 [Krause, Daniela S.; DeLelys, Michelle E.; Preffer, Frederic I.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. RP Krause, DS (reprint author), Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. FU NCI NIH HHS [K08 CA138916-02]; NCRR NIH HHS [1S10RR020936-01]; NIH HHS [1S10OD012027] NR 48 TC 2 Z9 2 U1 0 U2 3 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DR, STE 208, TOTOWA, NJ 07512-1165 USA SN 1064-3745 BN 978-1-4614-9437-9; 978-1-4614-9436-2 J9 METHODS MOL BIOL JI Methods Mol. Biol. PY 2014 VL 1109 BP 23 EP 46 DI 10.1007/978-1-4614-9437-9_2 D2 10.1007/978-1-4614-9437-9 PG 24 WC Cell & Tissue Engineering; Cell Biology SC Cell Biology GA BA6BE UT WOS:000337086400003 PM 24473776 ER PT B AU Murphy, JE Sequist, LV Chabner, BA AF Murphy, Janet E. Sequist, Lecia V. Chabner, Bruce A. BE Figg, WD McLeod, HL TI The Role of Phase III Trials in Modern Drug Development SO HANDBOOK OF ANTICANCER PHARMACOKINETICS AND PHARMACODYNAMICS, 2ND EDITION SE Cancer Drug Discovery and Development LA English DT Article; Book Chapter DE Targeted therapies; Phase III trials; Genotyping of tumors; Ethical considerations in trial design ID CELL LUNG-CANCER; GASTROINTESTINAL STROMAL TUMORS; METASTATIC COLORECTAL-CANCER; CHRONIC MYELOID-LEUKEMIA; CHRONIC MYELOGENOUS LEUKEMIA; EML4-ALK FUSION GENE; EARLY STOPPING RULES; ABL TYROSINE KINASE; DESIGN TASK-FORCE; IMATINIB MESYLATE AB While the backbone of cancer treatment remains cytotoxic chemotherapy, modern cancer research has increased our understanding of the molecular pathogenesis of cancer and, in some cases, identified driver oncogenes. The small molecule imatinib, for example, which specifically targets the BCR-ABL and CKIT kinases, has revolutionized the treatment of chronic myelogenous leukemia and gastrointestinal stromal tumors. In this chapter, we review the traditional path to drug development and FDA approval. We discuss the many disease settings in which the long road from phase I to phase III clinical trials remains relevant. We then explore two case studies: lung cancer and melanoma, in which identification of oncogene-addicted pathways allowed for phase I trial design with cohorts enriched with patients who harbored translocations/mutations in EML4-ALK and BRAF, respectively, with rapid appreciation of antitumor activity and an abbreviated path to drug approval. Here, the traditional phase III model is less relevant. We explore the ethics of drug development in the targeted therapy era and offer several solutions for accelerating drug evaluation where oncogene-directed therapy holds great promise in selected patients. C1 [Murphy, Janet E.; Sequist, Lecia V.] Harvard Univ, Sch Med, Boston, MA 02114 USA. [Murphy, Janet E.; Sequist, Lecia V.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Chabner, Bruce A.] Harvard Univ, Massachusetts Gen Hosp, MGH Canc Ctr, Dept Med,Med Sch, Boston, MA 02114 USA. RP Chabner, BA (reprint author), Harvard Univ, Massachusetts Gen Hosp, MGH Canc Ctr, Dept Med,Med Sch, 55 Fruit St,Mailstop LRH 214, Boston, MA 02114 USA. EM bchabner@partners.org NR 76 TC 0 Z9 0 U1 0 U2 0 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DR, STE 208, TOTOWA, NJ 07512-1165 USA BN 978-1-4614-9135-4; 978-1-4614-9134-7 J9 CANCER DRUG DISCOV D JI Canc. Drug. Disc. Dev. PY 2014 BP 763 EP 783 DI 10.1007/978-1-4614-9135-4_38 D2 10.1007/978-1-4614-9135-4 PG 21 WC Oncology; Pharmacology & Pharmacy SC Oncology; Pharmacology & Pharmacy GA BA6CE UT WOS:000337095300038 ER PT B AU Wang, XQ Singh, A AF Wang, Xiaoqin Singh, Ajay BE Marchevsky, AM Wick, MR TI Imaging of the mediastinum SO PATHOLOGY OF THE MEDIASTINUM LA English DT Article; Book Chapter ID RADIOLOGIC-PATHOLOGICAL CORRELATION; THORACIC LYMPH-NODES; GERM-CELL TUMORS; COMPUTED-TOMOGRAPHY; AORTIC INJURY; EXTRAMEDULLARY HEMATOPOIESIS; ANTERIOR MEDIASTINUM; NEUROGENIC TUMORS; CT EVALUATION; MRI FINDINGS C1 [Wang, Xiaoqin] Univ Kentucky, Lexington, KY 40536 USA. [Singh, Ajay] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. RP Wang, XQ (reprint author), Univ Kentucky, Lexington, KY 40536 USA. NR 67 TC 0 Z9 0 U1 0 U2 0 PU CAMBRIDGE UNIV PRESS PI CAMBRIDGE PA THE PITT BUILDING, TRUMPINGTON ST, CAMBRIDGE CB2 1RP, CAMBS, ENGLAND BN 978-1-107-03153-1; 978-1-107-05430-1 PY 2014 BP 4 EP 24 PG 21 WC Pathology; Respiratory System SC Pathology; Respiratory System GA BA7JZ UT WOS:000337609300003 ER PT B AU Lewandrowski, K AF Lewandrowski, Kent BE Marchevsky, AM Wick, MR TI Clinical pathology of disorders of the mediastinum SO PATHOLOGY OF THE MEDIASTINUM LA English DT Article; Book Chapter ID HYPERPARATHYROIDISM; DISEASE; TUMORS C1 [Lewandrowski, Kent] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Lewandrowski, Kent] Harvard Univ, Sch Med, Boston, MA USA. RP Lewandrowski, K (reprint author), Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 25 TC 0 Z9 0 U1 0 U2 0 PU CAMBRIDGE UNIV PRESS PI CAMBRIDGE PA THE PITT BUILDING, TRUMPINGTON ST, CAMBRIDGE CB2 1RP, CAMBS, ENGLAND BN 978-1-107-03153-1; 978-1-107-05430-1 PY 2014 BP 276 EP 284 PG 9 WC Pathology; Respiratory System SC Pathology; Respiratory System GA BA7JZ UT WOS:000337609300016 ER PT S AU Guinan, JJ AF Guinan, John J., Jr. BE Popper, AN Fay, RR TI Cochlear Mechanics, Otoacoustic Emissions, and Medial Olivocochlear Efferents: Twenty Years of Advances and Controversies Along with Areas Ripe for New Work SO PERSPECTIVES ON AUDITORY RESEARCH SE Springer Handbook of Auditory Research LA English DT Article; Book Chapter ID AUDITORY-NERVE RESPONSES; OUTER HAIR-CELLS; NORMAL-HEARING; FREQUENCY; HUMANS; AMPLIFICATION; DEPENDENCE; PHYSIOLOGY; MEMBRANE; MODELS C1 [Guinan, John J., Jr.] Massachusetts Eye & Ear Infirm, Eaton Peabody Lab, Boston, MA 02114 USA. [Guinan, John J., Jr.] Harvard Univ, Sch Med, Dept Otol & Laryngol, Boston, MA 02115 USA. RP Guinan, JJ (reprint author), Massachusetts Eye & Ear Infirm, Eaton Peabody Lab, Boston, MA 02114 USA. EM jjg@epl.meei.harvard.edu NR 37 TC 0 Z9 0 U1 0 U2 3 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013, UNITED STATES SN 0947-2657 BN 978-1-4614-9102-6; 978-1-4614-9101-9 J9 SPRINGER HANDB AUDIT JI Springer Handb. Audit. Res. PY 2014 VL 50 BP 229 EP 246 DI 10.1007/978-1-4614-9102-6_13 D2 10.1007/978-1-4614-9102-6 PG 18 WC Audiology & Speech-Language Pathology; Neurosciences SC Audiology & Speech-Language Pathology; Neurosciences & Neurology GA BA8LQ UT WOS:000338281900013 ER PT S AU Rosowski, JJ Nakajima, HH Cheng, JT AF Rosowski, John J. Nakajima, Hideko H. Cheng, Jeffrey T. BE Popper, AN Fay, RR TI Current Topics in the Study of Sound Conduction to the Inner Ear SO PERSPECTIVES ON AUDITORY RESEARCH SE Springer Handbook of Auditory Research LA English DT Article; Book Chapter ID HUMAN MIDDLE-EAR; SEMICIRCULAR CANAL DEHISCENCE; HUMAN TYMPANIC MEMBRANE; ENERGY REFLECTANCE MEASUREMENTS; TIME-AVERAGED HOLOGRAPHY; MALLEUS-INCUS-COMPLEX; FINITE-ELEMENT MODEL; HUMAN TEMPORAL BONES; WIDE-BAND; OSSICULAR CHAIN C1 [Rosowski, John J.; Nakajima, Hideko H.; Cheng, Jeffrey T.] Harvard Univ, Sch Med, Dept Otol & Laryngol, Boston, MA 02114 USA. [Rosowski, John J.; Nakajima, Hideko H.; Cheng, Jeffrey T.] Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. RP Rosowski, JJ (reprint author), Harvard Univ, Sch Med, Dept Otol & Laryngol, Boston, MA 02114 USA. EM John_Rosowski@meei.harvard.edu; Heidi_Nakajima@meei.harvard.edu; Tao_Cheng@meei.harvard.edu NR 122 TC 1 Z9 1 U1 0 U2 6 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013, UNITED STATES SN 0947-2657 BN 978-1-4614-9102-6; 978-1-4614-9101-9 J9 SPRINGER HANDB AUDIT JI Springer Handb. Audit. Res. PY 2014 VL 50 BP 493 EP 511 DI 10.1007/978-1-4614-9102-6_26 D2 10.1007/978-1-4614-9102-6 PG 19 WC Audiology & Speech-Language Pathology; Neurosciences SC Audiology & Speech-Language Pathology; Neurosciences & Neurology GA BA8LQ UT WOS:000338281900026 ER PT B AU Hurley, BP AF Hurley, Bryan P. BE Tappia, PS Dhalla, NS TI Phospholipase A(2) Activity Exhibited by a Bacterial Virulence Protein That Enters and Operates Within a Variety of Host Cells SO PHOSPHOLIPASES IN HEALTH AND DISEASE SE Advances in Biochemistry in Health and Disease LA English DT Article; Book Chapter DE Phospholipase A(2); ExoU; Pseudomonas aeruginosa; Eicosanoids ID PSEUDOMONAS-AERUGINOSA EXOU; AIRWAY EPITHELIAL-CELLS; III SECRETION SYSTEM; CYTOTOXIN EXOU; ACUTE PNEUMONIA; REGULATOR ALGR; DOMAIN; LUNG; ACTIVATION; TOXIN AB Phospholipase A(2) (PLA(2)) is a pivotal enzyme in human health and disease. With approximately 30 isoforms exhibiting PLA(2) activity expressed within or secreted by a variety of cell and tissue types, the functional signifi cance of this enzyme is multifaceted. Mammalian PLA(2) s are known contributors during host-pathogen interactions during infectious disease processes. Interestingly, several bacterial pathogens themselves express PLA(2) enzymes that exhibit a patatin domain and have sequence similarity to cytosolic and calcium-independent PLA(2) s. The most prominent example termed ExoU is expressed by Pseudomonas aeruginosa and operates exclusively in eukaryotic host cells. ExoU serves as a potent cytotoxin expressed by P. aeruginosa clinical isolates most associated with severe acute pneumonia and microbial keratitis. The PLA(2) activity of ExoU is responsible for this potent toxicity and is also capable of mediating host production of eicosanoids and stimulating cytokine and chemokine production in a variety of cell types. Efforts are underway to better understand and potentially neutralize these potent microbial PLA(2) virulence factors. C1 [Hurley, Bryan P.] Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. [Hurley, Bryan P.] Massachusetts Gen Hosp, Mucosal Immunol & Biol Res Ctr, Charlestown, MA 02129 USA. RP Hurley, BP (reprint author), Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. EM bphurley@partners.org NR 59 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013, UNITED STATES BN 978-1-4939-0464-8; 978-1-4939-0463-1 J9 ADV BIOCHEM HEALTH D JI Adv. Biochem. Health Dis. PY 2014 VL 10 BP 135 EP 146 DI 10.1007/978-1-4939-0464-8_8 D2 10.1007/978-1-4939-0464-8 PG 12 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA BA6DX UT WOS:000337109500009 ER PT S AU Kirienko, NV Cezairliyan, BO Ausubel, FM Powell, JR AF Kirienko, Natalia V. Cezairliyan, Brent O. Ausubel, Frederick M. Powell, Jennifer R. BE Filloux, A Ramos, JL TI Pseudomonas aeruginosa PA14 Pathogenesis in Caenorhabditis elegans SO PSEUDOMONAS: METHODS AND PROTOCOLS SE Methods in Molecular Biology LA English DT Article; Book Chapter DE Caenorhabditis elegans; Pseudomonas aeruginosa; PA14; Fast Killing; Slow Killing; Liquid Killing; Innate immunity; Pathogenesis ID BACTERIAL; INFECTION; DEATH; MODEL; PAO1 AB The nematode Caenorhabditis elegans is a simple model host for studying the interaction between bacterial pathogens such as Pseudomonas aeruginosa and the metazoan innate immune system. Powerful genetic and molecular tools in both C. elegans and P. aeruginosa facilitate the identification and analysis of bacterial virulence factors as well as host defense factors. Here we describe three different assays that use the C. elegans-P. aeruginosa strain PA14 host-pathogen system. Fast Killing is a toxin-mediated death that depends on a diffusible toxin produced by PA14 but not on live bacteria. Slow Killing is due to an active infection in which bacteria colonize the C. elegans intestinal lumen. Liquid Killing is designed for high-throughput screening of chemical libraries for anti-infective compounds. Each assay has unique features and, interestingly, the PA14 virulence factors involved in killing are different in each assay. C1 [Kirienko, Natalia V.; Cezairliyan, Brent O.; Ausubel, Frederick M.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Genet, Boston, MA 02114 USA. [Kirienko, Natalia V.; Cezairliyan, Brent O.; Ausubel, Frederick M.] Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. [Powell, Jennifer R.] Gettysburg Coll, Dept Biol, Gettysburg, PA 17325 USA. RP Kirienko, NV (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Genet, Boston, MA 02114 USA. NR 20 TC 8 Z9 8 U1 2 U2 9 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DR, STE 208, TOTOWA, NJ 07512-1165 USA SN 1064-3745 BN 978-1-4939-0473-0; 978-1-4939-0472-3 J9 METHODS MOL BIOL JI Methods Mol. Biol. PY 2014 VL 1149 BP 653 EP 669 DI 10.1007/978-1-4939-0473-0_50 D2 10.1007/978-1-4939-0473-0 PG 17 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA BA8TQ UT WOS:000338667400051 PM 24818940 ER PT S AU Hazan, R Maura, D Que, YA Rahme, LG AF Hazan, Ronen Maura, Damien Que, Yok Ai Rahme, Laurence G. BE Filloux, A Ramos, JL TI Assessing Pseudomonas aeruginosa Persister/Antibiotic Tolerant Cells SO PSEUDOMONAS: METHODS AND PROTOCOLS SE Methods in Molecular Biology LA English DT Article; Book Chapter DE Antibiotic tolerance; Bacterial persistence; Quorum sensing; Small molecules; High-throughput screen; Antibiotics; Anti-virulence; Anti-infectives; Proliferation; Virulence; Infection ID PERSISTER CELLS; BACTERIAL PERSISTENCE; ANTIBIOTIC TOLERANCE; FLOW-CYTOMETRY; RPOS GENE; BIOFILMS; GROWTH; PCR AB Bacterial persistence, which is observed in a broad range of microbial species, is the capacity of a bacterial cell subpopulation called "persisters" to tolerate exposure to normally lethal concentrations of bactericidal antibiotics. This ability, which is not due to antibiotic-resistant mutants, has been implicated in antibiotic treatment failures and may account for latent, chronic, and relapsing infections. Antibiotic tolerant/Persister (AT/P) cells have been notoriously difficult to study due to their low frequency and transient nature. This chapter describes the main methods used to isolate and study Pseudomonas aeruginosa AT/P cells and discusses new technologies that may ease research of P. aeruginosa persisters in the near future. C1 [Hazan, Ronen] Hebrew Univ Jerusalem, Inst Dent Sci, Jerusalem, Israel. [Hazan, Ronen; Maura, Damien; Que, Yok Ai; Rahme, Laurence G.] Harvard Univ, Sch Med, Dept Surg, Boston, MA 02115 USA. [Hazan, Ronen; Maura, Damien; Que, Yok Ai; Rahme, Laurence G.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Hazan, Ronen] Massachusetts Gen Hosp, Shriners Burns Inst, Boston, MA 02114 USA. [Hazan, Ronen; Maura, Damien; Que, Yok Ai; Rahme, Laurence G.] Harvard Univ, Sch Med, Dept Microbiol & Immunobiol, Boston, MA USA. [Hazan, Ronen; Maura, Damien; Que, Yok Ai; Rahme, Laurence G.] Shriners Hosp Children, Boston, MA USA. [Hazan, Ronen] Israeli Inst Adv Res, IYAR, Rehovot, Israel. RP Hazan, R (reprint author), Hebrew Univ Jerusalem, Inst Dent Sci, Campus Hadassah, Jerusalem, Israel. FU NIAID NIH HHS [R33 AI105902, AI105902, R56 AI063433, R56AI063433] NR 33 TC 0 Z9 1 U1 2 U2 4 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DR, STE 208, TOTOWA, NJ 07512-1165 USA SN 1064-3745 BN 978-1-4939-0473-0; 978-1-4939-0472-3 J9 METHODS MOL BIOL JI Methods Mol. Biol. PY 2014 VL 1149 BP 699 EP 707 DI 10.1007/978-1-4939-0473-0_54 D2 10.1007/978-1-4939-0473-0 PG 9 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA BA8TQ UT WOS:000338667400055 PM 24818944 ER PT J AU Patel, SR Sierra-Mercado, D Martinez-Rubio, C Eskandar, EN AF Patel, Shaun R. Sierra-Mercado, Demetrio Martinez-Rubio, Clarissa Eskandar, Emad N. BE Fried, I Rutishauser, U Cerf, M Kreiman, G TI Human Single Neuron Reward Processing in the Basal Ganglia and Anterior Cingulate SO SINGLE NEURON STUDIES OF THE HUMAN BRAIN: PROBING COGNITION LA English DT Article; Book Chapter ID MEDIAL FRONTAL-CORTEX; HUMAN NUCLEUS-ACCUMBENS; VENTRAL TEGMENTAL AREA; MULTISOURCE INTERFERENCE TASK; EVENT-RELATED FMRI; PREFRONTAL CORTEX; DECISION-MAKING; DOPAMINE NEURONS; COGNITIVE CONTROL; MONETARY REWARD C1 [Patel, Shaun R.; Sierra-Mercado, Demetrio; Martinez-Rubio, Clarissa; Eskandar, Emad N.] Massachusetts Gen Hosp, Dept Neurosurg, Boston, MA 02114 USA. [Patel, Shaun R.] Boston Univ, Sch Med, Dept Anat & Neurobiol, Boston, MA 02215 USA. RP Patel, SR (reprint author), Massachusetts Gen Hosp, Dept Neurosurg, Boston, MA 02114 USA. NR 108 TC 1 Z9 1 U1 0 U2 4 PU MIT PRESS PI CAMBRIDGE PA FIVE CAMBRIDGE CENTER, CAMBRIDGE, MA 02142 USA BN 978-0-262-02720-5 PY 2014 BP 205 EP 228 PG 24 WC Neurosciences SC Neurosciences & Neurology GA BA9MJ UT WOS:000339554700013 ER PT J AU Schaefer, E Chung, RT AF Schaefer, Esperance Chung, Raymond T. BE Thomas, HC Lok, ASF Locarnini, SA Zuckerman, AJ TI Development of anti-HCV drugs SO VIRAL HEPATITIS, 4TH EDITION LA English DT Article; Book Chapter ID HEPATITIS-C VIRUS; GENOTYPE 1 INFECTION; DEPENDENT RNA-POLYMERASE; PROTEASE-INHIBITOR; CRYSTAL-STRUCTURE; VIRAL-HEPATITIS; BI 201335; REPLICATION; RESISTANCE; NUCLEOSIDE AB The treatment of chronic hepatitis C virus (HCV) infection has undergone dramatic changes recently. Treatment advances have been enabled by an enhanced understanding of the viral life cycle. Novel anti-HCV drugs fall broadly into two categories: direct acting antivirals (DAAs) and host-targeted antivirals (HTAs). The first of these to enter the clinic are agents that block the HCV NS3/4A protease: telaprevir and boceprevir. Several other classes of DAAs are under development, including inhibitors of the NS5B RNA-dependent RNA polymerase (nucleos(t)ide and nonnucleoside inhibitors) and agents that target the viral NS5A protein. Also under investigation are drugs that block host factors required for the viral life cycle, such as antagonists of cyclophilin A and micro-RNA-122. These new classes of drugs have been identified because of a foundation of knowledge of underlying protein structure and activity, but also by using unbiased discovery approaches, and have resulted in an ever-enlarging armamentarium against HCV. C1 [Schaefer, Esperance; Chung, Raymond T.] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Schaefer, E (reprint author), Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 59 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL SCIENCE PUBL PI OXFORD PA OSNEY MEAD, OXFORD OX2 0EL, ENGLAND BN 978-0-470-67295-2 PY 2014 BP 377 EP 391 PG 15 WC Gastroenterology & Hepatology; Infectious Diseases; Virology SC Gastroenterology & Hepatology; Infectious Diseases; Virology GA BA5VL UT WOS:000337034100027 ER PT J AU Deshpande, A Nelson, D Corless, CL Deshpande, V O'Brien, MJ AF Deshpande, Anita Nelson, Dylan Corless, Christopher L. Deshpande, Vikram O'Brien, Michael J. TI Leiomyoma of the Gastrointestinal Tract With Interstitial Cells of Cajal A Mimic of Gastrointestinal Stromal Tumor SO AMERICAN JOURNAL OF SURGICAL PATHOLOGY LA English DT Article DE leiomyoma; gastrointestinal stromal tumor; KIT; DOG1 ID DIFFERENTIAL-DIAGNOSIS; ESOPHAGEAL LEIOMYOMA; MESENCHYMAL TUMORS; EXPERIENCE; COMMON; DOG1; KIT AB Leiomyomas (LMs) of the gastrointestinal tract arise within the muscularis mucosae (superficial) and muscularis propria (deep). There are isolated reports of KIT-positive cells, presumed interstitial cells of Cajal (ICCs), within gastrointestinal LMs. We have encountered esophageal LMs with a high proportion of KIT-positive and DOG1-positive spindleshaped cells, an appearance that mimicked gastrointestinal stromal tumor. Our aim was to explore the prevalence of ICCs in LMs of the gastrointestinal tract and the etiopathogenic significance of these cells in this benign neoplasm. We identified 34 esophageal LMs (28 deep, 6 superficial), 8 gastric LMs, and 5 small-bowel LMs (all lesions in muscularis propria). We performed immunohistochemical staining studies for desmin, DOG1, and KIT on these neoplasms. We also evaluated 12 superficial colonic LMs. ICCs were distinguished from mast cells on the basis of morphology (elongated and occasionally branching spindle-shaped cells) and the presence of DOG1 reactivity. Four cases were screened for mutations in PDGFRA exons 12, 14, and 18 and KIT exons 9, 11, 13, and 17. ICCs were identified in all deep esophageal LMs and constituted an average of 20% of the lesional cells; focally, these cells comprised >50% of cells. The density of these cells was significantly higher than the background muscularis propria, and hyperplasia of ICCs was not identified in the adjacent muscle. ICCs were identified in 6 of 8 gastric LMs and 1 of 5 small-bowel LMs and were entirely absent in all superficial esophageal and colonic/rectal LMs. There were no mutations in KIT or PDGFRA. ICCs are universally present in deep esophageal LMs, and thus these neoplasms could be mistaken for gastrointestinal stromal tumors, particularly on biopsy samples, an error associated with adverse clinical consequences. ICCs are also identified in gastric and intestinal LMs, albeit in a smaller proportion of cases. Colonization and hyperplasia by non-neoplastic ICCs likely account for this phenomenon. C1 [Deshpande, Anita; O'Brien, Michael J.] Boston Med Ctr, Dept Pathol & Lab Med, Boston, MA USA. [Deshpande, Vikram] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Deshpande, Vikram] Harvard Univ, Sch Med, Boston, MA 02114 USA. [Nelson, Dylan; Corless, Christopher L.] Oregon Hlth & Sci Univ, Dept Pathol, Portland, OR 97201 USA. RP Deshpande, V (reprint author), Massachusetts Gen Hosp, Dept Pathol, 55 Fruit St, Boston, MA 02114 USA. EM vdeshpande@partners.org NR 14 TC 11 Z9 11 U1 1 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0147-5185 EI 1532-0979 J9 AM J SURG PATHOL JI Am. J. Surg. Pathol. PD JAN PY 2014 VL 38 IS 1 BP 72 EP 77 PG 6 WC Pathology; Surgery SC Pathology; Surgery GA AL2VF UT WOS:000338983000009 PM 24145645 ER PT J AU Nazarian, RM Primiani, A Doyle, LA Linskey, KR Duncan, LM Odze, RD Zukerberg, LR AF Nazarian, Rosalynn M. Primiani, Andrea Doyle, Leona A. Linskey, Katy R. Duncan, Lyn M. Odze, Robert D. Zukerberg, Lawrence R. TI Cytokeratin 17 An Adjunctive Marker of Invasion in Squamous Neoplastic Lesions of the Anus SO AMERICAN JOURNAL OF SURGICAL PATHOLOGY LA English DT Article DE anal squamous cell carcinoma; anal intraepithelial neoplasia; cytokeratin 17; basaloid; invasion ID CERVICAL INTRAEPITHELIAL NEOPLASIA; CELL CARCINOMA; KERATIN EXPRESSION; PATTERNS; EPITHELIA; CANCER; OVEREXPRESSION; RADIOTHERAPY; DIAGNOSIS AB Diagnosing anal squamous cell carcinoma (SCC), which is often preceded by anal intraepithelial neoplasia (AIN), may be challenging in small biopsies. Cytokeratin 17 (CK17) is a basal/myoepithelial cell keratin induced in activated keratinocytes and associated with disease progression in SCC of the uterine cervix, esophagus, and oral cavity. We investigated the utility of CK17 in diagnosing invasion in anal squamous neoplastic lesions. Immunohistochemical staining for CK17 was evaluated in 11 AINs, 12 invasive SCCs, 8 invasive SCCs with basaloid features (BSCC), and 2 invasive pure basaloid carcinomas. The pattern of staining was scored as surface/central, peripheral/rim, diffuse, or absent. All cases of invasive SCC and BSCC stained positive for CK17. Eleven of 12 (92%) SCCs showed diffuse staining, and 1 of 12 (8%) showed peripheral staining. Six of 8 (75%) BSCCs showed diffuse staining, and 2 of 8 (25%) showed peripheral staining. Both pure basaloid carcinomas were negative for CK17. One of 11 (9%) AINs was diffusely positive for CK17; all other AINs had surface or absent CK17. Of the 6 patients with concurrent AIN and invasive carcinoma, superficial expression of CK17 was present in 1 AIN, whereas all invasive components showed diffuse staining. The sensitivity and specificity of CK17 for identifying invasion in SCC and BSCC was 100% and 91%, respectively. Peripheral or diffuse staining for CK17 is a useful marker of invasion in anal squamous neoplastic lesions. A potential pitfall in the utility of CK17 is that the pure basaloid variant of anal carcinoma is negative for CK17. C1 [Nazarian, Rosalynn M.; Primiani, Andrea; Linskey, Katy R.; Duncan, Lyn M.; Zukerberg, Lawrence R.] Massachusetts Gen Hosp, Pathol Serv, Boston, MA 02114 USA. [Nazarian, Rosalynn M.; Primiani, Andrea; Doyle, Leona A.; Linskey, Katy R.; Duncan, Lyn M.; Odze, Robert D.; Zukerberg, Lawrence R.] Harvard Univ, Sch Med, Boston, MA USA. [Doyle, Leona A.; Odze, Robert D.] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. RP Nazarian, RM (reprint author), Massachusetts Gen Hosp, Dermatopathol Unit, 55 Fruit St,Warren 829A, Boston, MA 02114 USA. EM rmnazarian@partners.org FU Immugen FX Conflicts of Interest and Source of Funding: L.R.Z. receives funding for consultancy work for Immugen and serves as an expert testimony. R.D.O. has served as an expert witness. For the remaining authors none were declared. NR 29 TC 7 Z9 7 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0147-5185 EI 1532-0979 J9 AM J SURG PATHOL JI Am. J. Surg. Pathol. PD JAN PY 2014 VL 38 IS 1 BP 78 EP 85 PG 8 WC Pathology; Surgery SC Pathology; Surgery GA AL2VF UT WOS:000338983000010 PM 24335642 ER PT J AU Liang, WY Arnason, T Lauwers, GY AF Liang, Wen-Yih Arnason, Thomas Lauwers, Gregory Y. TI Re: Practical Utility and Objectivity Does Evaluation of Peritoneal Elastic Laminal Invasion in Colorectal Cancer Overcome These Contrary Problems? In Reply SO AMERICAN JOURNAL OF SURGICAL PATHOLOGY LA English DT Letter C1 [Liang, Wen-Yih] Taipei Vet Gen Hosp, Dept Pathol & Lab Med, Taipei, Taiwan. [Liang, Wen-Yih] Natl Yang Ming Univ, Sch Med, Dept Pathol, Taipei, Taiwan. [Liang, Wen-Yih; Arnason, Thomas; Lauwers, Gregory Y.] Massachusetts Gen Hosp, Dept Pathol, Gastrointestinal Pathol Serv, Boston, MA 02114 USA. [Liang, Wen-Yih; Arnason, Thomas; Lauwers, Gregory Y.] Harvard Univ, Sch Med, Boston, MA USA. RP Liang, WY (reprint author), Taipei Vet Gen Hosp, Dept Pathol & Lab Med, Taipei, Taiwan. NR 2 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0147-5185 EI 1532-0979 J9 AM J SURG PATHOL JI Am. J. Surg. Pathol. PD JAN PY 2014 VL 38 IS 1 BP 145 EP 145 PG 1 WC Pathology; Surgery SC Pathology; Surgery GA AL2VF UT WOS:000338983000020 PM 24335646 ER PT S AU Feldman, HH Haas, M Gandy, S Schoepp, DD Cross, AJ Mayeux, R Sperling, RA Fillit, H van de Hoef, DL Dougal, S Nye, JS AF Feldman, Howard H. Haas, Magali Gandy, Sam Schoepp, Darryle D. Cross, Alan J. Mayeux, Richard Sperling, Reisa A. Fillit, Howard van de Hoef, Diana L. Dougal, Sonya Nye, Jeffrey S. CA One Mind Res New York Acad Sci GP Annals New York Acad Sci TI Alzheimer's disease research and development: a call for a new research roadmap SO ANNALS REPORTS SE Annals of the New York Academy of Sciences LA English DT Article; Book Chapter DE Alzheimer's disease; dementia; research and development; therapy; treatment; economics; epidemiology ID DEMENTIA; BIOMARKERS; CASCADE; HEALTH; BRAIN; IVIG AB Epidemiological projections of the prevalence ofAlzheimer's disease (AD) and related dementias, the rapidly expanding population over the age of 65, and the enormous societal consequence on health, economics, and community foretell of a looming global public health crisis. Currently available treatments for AD are symptomatic, with modest effect sizes and limited impact on longer term disease outcomes. There have been no newly approved pharmaceutical treatments in the last decade, despite enormous efforts to develop disease-modifying treatments directed at Alzheimer's-associated pathology. An unprecedented collaborative effort of government, regulators, industry, academia, and the community at-large is needed to address this crisis and to develop an actionable plan for rapid progress toward successfully developing effective treatments. Here, we map out a course of action in four key priority areas, including (1) addressing the fundamental mechanisms of disease, with the goal of developing a core set of research tools, a framework for data sharing, and creation of accessible validated and replicated disease models; (2) developing translational research that emphasizes rapid progress in disease model development and better translation from preclinical to clinical stages, deploying leading technologies to more accurately develop predictive models; (3) preventing AD through the development of robust methods and resources to advance trials and creating fundamental resources such as continuous adaptive trials, registries, data repositories, and instrument development; and (4) innovating public/private partnerships and global collaborations, with mechanisms to incentivize collaborations and investments, develop larger precompetitive spaces, and more rapid data sharing. C1 [Feldman, Howard H.] Univ British Columbia, Fac Med, Div Neurol, Vancouver, BC, Canada. [Haas, Magali] One Mind Res, Seattle, WA USA. [Gandy, Sam] Icahn Sch Med Mt Sinai, New York, NY 10029 USA. [Gandy, Sam] James J Peters VA Med Ctr, New York, NY USA. [Schoepp, Darryle D.] Merck & Co Inc, N Wales, PA USA. [Cross, Alan J.] AstraZeneca Pharmaceut LP, Wilmington, DE USA. [Mayeux, Richard] Columbia Univ, Gertrude H Sergievsky Ctr, Dept Neurol, New York, NY 10027 USA. [Sperling, Reisa A.] Harvard Univ, Sch Med, Dept Neurol, Ctr Alzheimer Res & Treatment, Boston, MA 02115 USA. [Fillit, Howard] Alzheimers Drug Discovery Fdn, New York, NY USA. [van de Hoef, Diana L.] New York Acad Sci, New York, NY USA. [Dougal, Sonya] NYU, Langone Med Ctr, Steven & Alexandra Cohen Vet Ctr, New York, NY USA. [Nye, Jeffrey S.] Johnson & Johnson Innovat, Janssen R&D LLC, Titusville, NJ USA. RP Feldman, HH (reprint author), S151 Univ British Columbia Hosp, 2211 Wesbrook Mall, Vancouver, BC V6T 2B5, Canada. EM howard.feldman@ubc.ca RI Cross, Alan/L-5456-2016; OI Cross, Alan/0000-0002-2992-2258; Feldman, Howard/0000-0002-9258-4538 FU One Mind for Research; New York Academy of Sciences FX The authors gratefully acknowledge the contributions of the medical writing agency Percolation Communications LLC, who produced the first draft of this paper. They were funded by One Mind for Research and the New York Academy of Sciences to integrate all the historical notes, minutes, and interviews from the workshops conducted in 2011-12, sponsored by One Mind for Research. The subsequent drafts were advanced to final form by the lead and co-authors. The authors also acknowledge in-kind support from PricewaterhouseCoopers. NR 24 TC 9 Z9 10 U1 3 U2 16 PU BLACKWELL SCIENCE PUBL PI OXFORD PA OSNEY MEAD, OXFORD OX2 0EL, ENGLAND SN 0077-8923 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 2014 VL 1313 BP 1 EP 16 DI 10.1111/nyas.12424 PG 16 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA BA8GQ UT WOS:000338100700001 PM 24754377 ER PT J AU Singh, JA AF Singh, Jasvinder A. TI Facilitators and barriers to adherence to urate-lowering therapy in African-Americans with gout: a qualitative study SO ARTHRITIS RESEARCH & THERAPY LA English DT Article ID NOMINAL GROUP TECHNIQUE; SERUM URATE; GENERAL-PRACTICE; MEDICATION USE; CARE; MANAGEMENT; PATIENT; HEALTH; SEX; HYPERURICEMIA AB Introduction: Limited literature exists for qualitative studies of medication adherence in gout, especially in African-Americans. The aim of this study was to examine the facilitators and barriers to adherence to urate-lowering therapy (ULT) in African-Americans with gout. Methods: In this study, nine nominal groups lasting 1 to 1.5 hours each were conducted in African-Americans with gout, six with low ULT and three with high ULT adherence (medication possession ratios of <0.80 or >= 0.80, respectively). Patients presented, discussed, combined and rank ordered their concerns. A qualitative analysis was performed. Results: This study included 43 patients with mean age 63.9 years (standard deviation, 9.9), 67% men, who participated in nine nominal groups (seven in men, two in women): African-American men (n = 30); African-American women (n = 13). The main facilitators to ULT adherence (three groups) were the recognition of the need to take ULT regularly to prevent gout flares, prevent pain from becoming chronic/severe and to have less dietary restriction; the lack of side effects from ULT; trust in physicians; and avoiding the need to seek emergent/urgent care for flares. Patients achieved high ULT adherence by organizing their pills using the pillbox and the incorporation of ULT intake into their routine to prevent forgetting. The main barriers to optimal ULT adherence were (six groups): doubts about effectiveness of ULT, concerns about cost and side effects, concomitant medications, forgetfulness, refilling the prescriptions on time, pill size and difficulty in swallowing, competing priorities, patient preference for alternative medicines (that is, cherry juice) and frequent travel. Conclusions: Identification of facilitators and barriers to high ULT adherence in African-Americans with gout in this study lays the foundation for designing interventions to improve ULT adherence in racial minorities. C1 [Singh, Jasvinder A.] Birmingham VA Med Ctr, Med Serv, Birmingham, AL 35233 USA. [Singh, Jasvinder A.] Univ Alabama Birmingham, Sch Med, Dept Med, Birmingham, AL USA. [Singh, Jasvinder A.] Univ Alabama Birmingham, Sch Publ Hlth, Dept Epidemiol, Birmingham, AL 35294 USA. [Singh, Jasvinder A.] Mayo Clin, Coll Med, Dept Orthoped Surg, Rochester, MN USA. RP Singh, JA (reprint author), Birmingham VA Med Ctr, Med Serv, 805B,510 20th St S, Birmingham, AL 35233 USA. EM Jasvinder.md@gmail.com FU resources and use of facilities at the Birmingham VA Medical Center, Birmingham, AL, USA; Agency for Health Quality and Research Center for Education and Research on Therapeutics (AHRQ CERTs) [U19 HS021110]; National Institute of Arthritis, Musculoskeletal and Skin Diseases (NIAMS) [P50 AR060772, U34 AR062891]; National Institute of Aging (NIA) [U01 AG018947]; National Cancer Institute (NCI) [U10 CA149950]; Patient Centered Outcomes Research Institute (PCORI) [CE-1304-6631] FX I thank Dr. Isabel Scarinci for her comments on this manuscript, Bridgett Alday for contacting patients and providing support for conducting the nominal groups, Ana Oliviera and Aseem Bharat for help conducting the nominal groups and Mary Elkins for the administrative oversight. I thank the patients and several colleagues who provided informal input into drafting the question for the nominal groups. This material is the result of work supported by a grant from the Division of Rheumatology at the University of Alabama at Birmingham. JAS is supported by the resources and use of facilities at the Birmingham VA Medical Center, Birmingham, AL, USA. JAS is supported by grants from the Agency for Health Quality and Research Center for Education and Research on Therapeutics (AHRQ CERTs) U19 HS021110, National Institute of Arthritis, Musculoskeletal and Skin Diseases (NIAMS) P50 AR060772 and U34 AR062891, National Institute of Aging (NIA) U01 AG018947, and National Cancer Institute (NCI) U10 CA149950 and research contract CE-1304-6631 from Patient Centered Outcomes Research Institute (PCORI). NR 41 TC 8 Z9 8 U1 0 U2 1 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1478-6354 EI 1478-6362 J9 ARTHRITIS RES THER JI Arthritis Res. Ther. PY 2014 VL 16 IS 2 AR R82 DI 10.1186/ar4524 PG 13 WC Rheumatology SC Rheumatology GA AL2YZ UT WOS:000338993100035 PM 24678765 ER PT B AU Welch, BM Kawamoto, K Drohan, B Hughes, KS AF Welch, Brandon M. Kawamoto, Kensaku Drohan, Brian Hughes, Kevin S. BE Greenes, RA TI Clinical Decision Support for Personalized Medicine SO CLINICAL DECISION SUPPORT: THE ROAD TO BROAD ADOPTION, 2ND EDITION LA English DT Article; Book Chapter ID GENETIC RISK-ASSESSMENT; ELECTRONIC HEALTH RECORDS; PRIMARY-CARE PHYSICIANS; FAMILY-HISTORY; OVARIAN-CANCER; COLORECTAL-CANCER; COMPUTER SUPPORT; BREAST-CANCER; GRAIDS TRIAL; MANAGEMENT C1 [Welch, Brandon M.] Univ Utah, Dept Biomed Informat, Program Personalized Hlth Care, Salt Lake City, UT 84112 USA. [Kawamoto, Kensaku] Univ Utah, Univ Utah Hlth Care & Biomed Informat, Salt Lake City, UT USA. [Drohan, Brian] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Hughes, Kevin S.] Harvard Univ, Massachusetts Gen Hosp, Bermuda Canc Genet & Risk Assessment Clin, Avon Comprehens Breast Evaluat Ctr,Sch Med, Boston, MA USA. RP Welch, BM (reprint author), Univ Utah, Dept Biomed Informat, Program Personalized Hlth Care, Salt Lake City, UT 84112 USA. OI Hughes, Kevin/0000-0003-4084-6484 NR 92 TC 1 Z9 2 U1 1 U2 5 PU ELSEVIER ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA BN 978-0-12-800542-2; 978-0-12-398476-0 PY 2014 BP 383 EP 413 PG 31 WC Computer Science, Interdisciplinary Applications; Health Care Sciences & Services; Medical Informatics SC Computer Science; Health Care Sciences & Services; Medical Informatics GA BA6TO UT WOS:000337278900016 ER PT B AU Lieb, JG AF Lieb, John G., II BE Adler, DG TI The Structure and Function of the Modern Colonoscope SO CORE CONCEPTS IN COLONOSCOPY LA English DT Article; Book Chapter ID HISTORY C1 [Lieb, John G., II] Univ Penn, Philadelphia, PA 19104 USA. [Lieb, John G., II] Philadelphia Vet Affairs Med Ctr, Philadelphia, PA USA. RP Lieb, JG (reprint author), Univ Penn, Philadelphia, PA 19104 USA. NR 6 TC 0 Z9 0 U1 0 U2 0 PU SLACK INC PI THOROFARE PA 6900 GROVE ROAD, THOROFARE, NJ 08086-9447 USA BN 978-1-61711-614-8 PY 2014 BP 1 EP 11 PG 11 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA BA5ZM UT WOS:000337068200001 ER PT J AU Chou, SHY Lo, EH Ning, MM AF Chou, Sherry Hsiang-Yi Lo, Eng H. Ning, MingMing TI Plasma-type gelsolin in subarachnoid hemorrhage: novel biomarker today, therapeutic target tomorrow? SO CRITICAL CARE LA English DT Editorial Material ID OUTCOMES; STROKE; ACTIN AB There is growing interest in the potential neuroprotective properties of gelsolin. In particular, plasma-type gelsolin (pGSN) can ameliorate deleterious inflammatory response by scavenging pro-inflammatory signals such as actin and lipopolysaccharide. In a recent issue of Critical Care, Pan and colleagues report an important association between pGSN and subarachnoid hemorrhage (SAH) disease severity, and found pGSN to be a novel and promising biomarker for SAH clinical outcome. Previous research shows pGSN may be actively degraded by neurovascular proteases such as matrix metalloproteinases in the cerebral spinal fluid of SAH patients. Taken together, these results suggest that pGSN is not only a novel marker of SAH clinical outcome, but may also play an active mechanistic role in SAH, and potentially serve as a future therapeutic target. C1 [Chou, Sherry Hsiang-Yi] Brigham & Womens Hosp, Dept Neurol, Boston, MA 02115 USA. [Chou, Sherry Hsiang-Yi; Lo, Eng H.; Ning, MingMing] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. RP Ning, MM (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Neurol, 15 Parkman St, Boston, MA 02114 USA. EM ning@hms.harvard.edu RI Chou, Sherry/G-5779-2015 FU NINDS NIH HHS [K23 NS073806] NR 12 TC 0 Z9 0 U1 0 U2 1 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1466-609X EI 1364-8535 J9 CRIT CARE JI Crit. Care PY 2014 VL 18 IS 1 AR 101 DI 10.1186/cc13178 PG 2 WC Critical Care Medicine SC General & Internal Medicine GA AL2YP UT WOS:000338991900001 PM 24393331 ER PT J AU So-Armah, KA Chang, J Alcorn, C Lo Re, V Baker, JV Tracy, R Butt, AA Agan, BK Rimland, D Gibert, CL Goetz, MB Oursler, KK Rodriguez-Barradas, MC Kuller, LH Brown, ST Stein, JH Skanderson, M Justice, AC Freiberg, MS AF So-Armah, Kaku A. Chang, Joyce Alcorn, Charles Lo Re, Vincent Baker, Jason V. Tracy, Russell Butt, Adeel A. Agan, Brian K. Rimland, David Gibert, Cynthia L. Goetz, Matthew B. Oursler, Krisann K. Rodriguez-Barradas, Maria C. Kuller, Lewis H. Brown, Sheldon T. Stein, James H. Skanderson, Melissa Justice, Amy C. Freiberg, Matthew S. TI HIV Infection, Antiretroviral Therapy Initiation and Longitudinal Changes in Biomarkers of Organ Function SO CURRENT HIV RESEARCH LA English DT Article DE Clinical biomarkers; chronic diseases of aging; HIV infection; lipids ID IMMUNODEFICIENCY-VIRUS-INFECTION; DISEASE PROGRESSION; SERUM-LIPIDS; COHORT; VETERANS; RISK; COMORBIDITIES; INDIVIDUALS; COINFECTION; PREVALENCE AB Background: HIV is associated with end-organ diseases of aging via unclear mechanisms. Longitudinally assessing how HIV infection and ART initiation affect biomarkers of end organ function/disease could clarify these mechanisms. We investigated longitudinal changes in clinical biomarkers following 1) HIV infection and 2) ART initiation with evidence of viral suppression. Methods: Cohort: Veterans Aging Cohort Study Virtual Cohort (VACS VC). VACS VC is a longitudinal cohort of HIV infected (HIV+) and race-ethnicity, sex, age, and clinical site-matched uninfected Veterans enrolled in the same calendar year. Inclusion criteria: a negative and successively positive (>six months) HIV antibody test. We used Wilcoxon signed-rank tests to analyze 1) the effect of HIV infection on lipids, renal, hepatic and hematologic/cardiovascular biomarkers and 2) whether ART initiation with HIV-1 RNA<500 cpm reverts any changes back to pre-HIV levels Results: 422 Veterans had at least 1 biomarker measurement available prior to HIV infection and prior to ART initiation. 297 had at least 1 biomarker measurement available prior to HIV infection and after ART initiation with evidence of viral suppression. Mean age prior to HIV infection was 43 years. HIV infection was associated with reduction in total cholesterol, HDL cholesterol, LDL cholesterol, serum albumin, ALT, platelet count, hemoglobin and elevation of FIB-4 score and triglycerides. These changes occurred without significant changes in BMI. ART initiation (with HIV-1 RNA<500cpm) did not reverse alteration in triglycerides, LDL cholesterol, hemoglobin, or FIB-4 to pre-HIV infection levels. Conclusions: HIV infection is associated with longitudinal changes in serum levels of several biomarkers of end-organ function/disease and mortality. Multiple biomarkers (triglycerides, LDL cholesterol, hemoglobin, and FIB-4) remain altered from levels prior to HIV infection levels even following inititiation of ART and evidence of viral suppression. These results give insights into underlying mechanisms of increased risk for aging-related chronic diseases in the context of HIV infection. C1 [So-Armah, Kaku A.; Justice, Amy C.] Yale Univ, Sch Med, New Haven, CT USA. [Chang, Joyce; Butt, Adeel A.; Freiberg, Matthew S.] Univ Pittsburgh, Sch Med, Dept Med, Pittsburgh, PA 15213 USA. [Chang, Joyce; Alcorn, Charles] Univ Pittsburgh, Grad Sch Publ Hlth, Dept Biostat, Pittsburgh, PA 15261 USA. [Lo Re, Vincent] Univ Penn, Sch Med, Dept Med, Div Infect Dis, Philadelphia, PA 19104 USA. [Lo Re, Vincent] Univ Penn, Sch Med, Dept Biostat & Epidemiol, Ctr Clin Epidemiol & Biostat, Philadelphia, PA 19104 USA. [Baker, Jason V.] Univ Minnesota, Dept Med, Minneapolis, MN 55455 USA. [Baker, Jason V.] Hennepin Cty Med Ctr, Minneapolis, MN 55415 USA. [Tracy, Russell] Univ Vermont, Dept Biochem, Burlington, VT 05405 USA. [Butt, Adeel A.] VA Pittsburgh Healthcare Syst, Ctr Hlth Equ Res & Promot, Pittsburgh, PA USA. [Butt, Adeel A.] Sheikh Khalifa Med City, Dept Med, Abu Dhabi, U Arab Emirates. [Agan, Brian K.] Uniformed Serv Univ Hlth Sci, Infect Dis Clin Res Program, Bethesda, MD 20814 USA. [Rimland, David] Emory Univ, Sch Med, Dept Med, Div Infect Dis,VA Med Ctr, Atlanta, GA USA. [Gibert, Cynthia L.] Washington DC Vet Affairs Med Ctr, Washington, DC USA. [Gibert, Cynthia L.] George Washington Univ, Sch Med, Washington, DC USA. [Goetz, Matthew B.] Vet Affairs Greater Los Angeles Hlth Care Syst, Los Angeles, CA USA. [Goetz, Matthew B.] Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90095 USA. [Oursler, Krisann K.] Baltimore Vet Affairs Med Ctr, Baltimore, MD USA. [Rodriguez-Barradas, Maria C.] Michael E DeBakey VA Med Ctr, Infect Dis Sect, Houston, TX USA. [Rodriguez-Barradas, Maria C.] Baylor Coll Med, Dept Med, Houston, TX 77030 USA. [Kuller, Lewis H.; Freiberg, Matthew S.] Univ Pittsburgh, Grad Sch Publ Hlth, Dept Epidemiol, Pittsburgh, PA USA. [Brown, Sheldon T.] James J Peters Vet Affairs Med Ctr, Bronx, NY USA. [Brown, Sheldon T.] Mt Sinai Sch Med, New York, NY USA. [Stein, James H.] Univ Wisconsin, Sch Med & Publ Hlth, Madison, WI USA. [Skanderson, Melissa; Justice, Amy C.] VA Connecticut Healthcare Syst, New Haven, CT USA. RP Freiberg, MS (reprint author), 230 McKee Pl, Pittsburgh, PA 15213 USA. EM freibergms@upmc.edu RI Lo Re, Vincent/N-7817-2015; OI Agan, Brian/0000-0002-5114-1669; Goetz, Matthew/0000-0003-4542-992X FU National Heart, Lung, and Blood Institute at the National Institutes of Health (NIH) [HL095136-04]; National Institute on Alcohol Abuse and Alcoholism at the NIH [AA013566-10, AA020790, AA020794] FX This work was supported by grant HL095136-04 from the National Heart, Lung, and Blood Institute at the National Institutes of Health (NIH) and grants AA013566-10, AA020790, and AA020794 from the National Institute on Alcohol Abuse and Alcoholism at the NIH. NR 31 TC 7 Z9 7 U1 3 U2 7 PU BENTHAM SCIENCE PUBL LTD PI SHARJAH PA EXECUTIVE STE Y-2, PO BOX 7917, SAIF ZONE, 1200 BR SHARJAH, U ARAB EMIRATES SN 1570-162X EI 1873-4251 J9 CURR HIV RES JI Curr. HIV Res. PY 2014 VL 12 IS 1 BP 50 EP 59 PG 10 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA AL5MN UT WOS:000339178000006 PM 25034208 ER PT J AU Brownstein, CA Beggs, AH Homer, N Merriman, B Yu, TW Flannery, KC DeChene, ET Towne, MC Savage, SK Price, EN Holm, IA Luquette, LJ Lyon, E Majzoub, J Neupert, P McCallie, D Szolovits, P Willard, HF Mendelsohn, NJ Temme, R Finkel, RS Yum, SW Medne, L Sunyaev, SR Adzhubey, I Cassa, CA de Bakker, PIW Duzkale, H Dworzynski, P Fairbrother, W Francioli, L Funke, BH Giovanni, MA Handsaker, RE Lage, K Lebo, MS Lek, M Leshchiner, I MacArthur, DG McLaughlin, HM Murray, MF Pers, TH Polak, PP Raychaudhuri, S Rehm, HL Soemedi, R Stitziel, NO Vestecka, S Supper, J Gugenmus, C Klocke, B Hahn, A Schubach, M Menzel, M Biskup, S Freisinger, P Deng, M Braun, M Perner, S Smith, RJH Andorf, JL Huang, J Ryckman, K Sheffield, VC Stone, EM Bair, T Black-Ziegelbein, EA Braun, TA Darbro, B DeLuca, AP Kolbe, DL Scheetz, TE Shearer, AE Sompallae, R Wang, K Bassuk, AG Edens, E Mathews, K Moore, SA Shchelochkov, OA Trapane, P Bossler, A Campbell, CA Heusel, JW Kwitek, A Maga, T Panzer, K Wassink, T Van Daele, D Azaiez, H Booth, K Meyer, N Segal, MM Williams, MS Tromp, G White, P Corsmeier, D Fitzgerald-Butt, S Herman, G Lamb-Thrush, D McBride, KL Newsom, D Pierson, CR Rakowsky, AT Maver, A Lovrecic, L Palandacic, A Peterlin, B Torkamani, A Wedell, A Huss, M Alexeyenko, A Lindvall, JM Magnusson, M Nilsson, D Stranneheim, H Taylan, F Gilissen, C Hoischen, A van Bon, B Yntema, H Nelen, M Zhang, WD Sager, J Zhang, L Blair, K Kural, D Cariaso, M Lennon, GG Javed, A Agrawal, S Ng, PC Sandhu, KS Krishna, S Veeramachaneni, V Isakov, O Halperin, E Friedman, E Shomron, N Glusman, G Roach, JC Caballero, J Cox, HC Mauldin, D Ament, SA Rowen, L Richards, DR San Lucas, FA Gonzalez-Garay, ML Caskey, CT Bai, Y Huang, Y Fang, F Zhang, Y Wang, ZY Barrera, J Garcia-Lobo, JM Gonzalez-Lamuno, D Llorca, J Rodriguez, MC Varela, I Reese, MG De la Vega, FM Kiruluta, E Cargill, M Hart, RK Sorenson, JM Lyon, GJ Stevenson, DA Bray, BE Moore, BM Eilbeck, K Yandell, M Zhao, HY Hou, L Chen, XW Yan, XT Chen, MJ Li, C Yang, C Gunel, M Li, PN Kong, Y Alexander, AC Albertyn, ZI Boycott, KM Bulman, DE Gordon, PMK Innes, AM Knoppers, BM Majewski, J Marshall, CR Parboosingh, JS Sawyer, SL Samuels, ME Schwartzentruber, J Kohane, IS Margulies, DM AF Brownstein, Catherine A. Beggs, Alan H. Homer, Nils Merriman, Barry Yu, Timothy W. Flannery, Katherine C. DeChene, Elizabeth T. Towne, Meghan C. Savage, Sarah K. Price, Emily N. Holm, Ingrid A. Luquette, Lovelace J. Lyon, Elaine Majzoub, Joseph Neupert, Peter McCallie, David, Jr. Szolovits, Peter Willard, Huntington F. Mendelsohn, Nancy J. Temme, Renee Finkel, Richard S. Yum, Sabrina W. Medne, Livija Sunyaev, Shamil R. Adzhubey, Ivan Cassa, Christopher A. de Bakker, Paul I. W. Duzkale, Hatice Dworzynski, Piotr Fairbrother, William Francioli, Laurent Funke, Birgit H. Giovanni, Monica A. Handsaker, Robert E. Lage, Kasper Lebo, Matthew S. Lek, Monkol Leshchiner, Ignaty MacArthur, Daniel G. McLaughlin, Heather M. Murray, Michael F. Pers, Tune H. Polak, Paz P. Raychaudhuri, Soumya Rehm, Heidi L. Soemedi, Rachel Stitziel, Nathan O. Vestecka, Sara Supper, Jochen Gugenmus, Claudia Klocke, Bernward Hahn, Alexander Schubach, Max Menzel, Mortiz Biskup, Saskia Freisinger, Peter Deng, Mario Braun, Martin Perner, Sven Smith, Richard J. H. Andorf, Janeen L. Huang, Jian Ryckman, Kelli Sheffield, Val C. Stone, Edwin M. Bair, Thomas Black-Ziegelbein, E. Ann Braun, Terry A. Darbro, Benjamin DeLuca, Adam P. Kolbe, Diana L. Scheetz, Todd E. Shearer, Aiden E. Sompallae, Rama Wang, Kai Bassuk, Alexander G. Edens, Erik Mathews, Katherine Moore, Steven A. Shchelochkov, Oleg A. Trapane, Pamela Bossler, Aaron Campbell, Colleen A. Heusel, Jonathan W. Kwitek, Anne Maga, Tara Panzer, Karin Wassink, Thomas Van Daele, Douglas Azaiez, Hela Booth, Kevin Meyer, Nic Segal, Michael M. Williams, Marc S. Tromp, Gerard White, Peter Corsmeier, Donald Fitzgerald-Butt, Sara Herman, Gail Lamb-Thrush, Devon McBride, Kim L. Newsom, David Pierson, Christopher R. Rakowsky, Alexander T. Maver, Ales Lovrecic, Luca Palandacic, Anja Peterlin, Borut Torkamani, Ali Wedell, Anna Huss, Mikael Alexeyenko, Andrey Lindvall, Jessica M. Magnusson, Mans Nilsson, Daniel Stranneheim, Henrik Taylan, Fulya Gilissen, Christian Hoischen, Alexander van Bon, Bregje Yntema, Helger Nelen, Marcel Zhang, Weidong Sager, Jason Zhang, Lu Blair, Kathryn Kural, Deniz Cariaso, Michael Lennon, Greg G. Javed, Asif Agrawal, Saloni Ng, Pauline C. Sandhu, Komal S. Krishna, Shuba Veeramachaneni, Vamsi Isakov, Ofer Halperin, Eran Friedman, Eitan Shomron, Noam Glusman, Gustavo Roach, Jared C. Caballero, Juan Cox, Hannah C. Mauldin, Denise Ament, Seth A. Rowen, Lee Richards, Daniel R. San Lucas, F. Anthony Gonzalez-Garay, Manuel L. Caskey, C. Thomas Bai, Yu Huang, Ying Fang, Fang Zhang, Yan Wang, Zhengyuan Barrera, Jorge Garcia-Lobo, Juan M. Gonzalez-Lamuno, Domingo Llorca, Javier Rodriguez, Maria C. Varela, Ignacio Reese, Martin G. De la Vega, Francisco M. Kiruluta, Edward Cargill, Michele Hart, Reece K. Sorenson, Jon M. Lyon, Gholson J. Stevenson, David A. Bray, Bruce E. Moore, Barry M. Eilbeck, Karen Yandell, Mark Zhao, Hongyu Hou, Lin Chen, Xiaowei Yan, Xiting Chen, Mengjie Li, Cong Yang, Can Gunel, Murat Li, Peining Kong, Yong Alexander, Austin C. Albertyn, Zayed I. Boycott, Kym M. Bulman, Dennis E. Gordon, Paul M. K. Innes, A. Micheil Knoppers, Bartha M. Majewski, Jacek Marshall, Christian R. Parboosingh, Jillian S. Sawyer, Sarah L. Samuels, Mark E. Schwartzentruber, Jeremy Kohane, Isaac S. Margulies, David M. TI An international effort towards developing standards for best practices in analysis, interpretation and reporting of clinical genome sequencing results in the CLARITY Challenge SO GENOME BIOLOGY LA English DT Article ID BURROWS-WHEELER TRANSFORM; DE-NOVO MUTATIONS; WHOLE-GENOME; GENETIC-VARIATION; CENTRONUCLEAR MYOPATHY; READ ALIGNMENT; TITIN GENE; EXOME; DISEASE; VARIANTS AB Background: There is tremendous potential for genome sequencing to improve clinical diagnosis and care once it becomes routinely accessible, but this will require formalizing research methods into clinical best practices in the areas of sequence data generation, analysis, interpretation and reporting. The CLARITY Challenge was designed to spur convergence in methods for diagnosing genetic disease starting from clinical case history and genome sequencing data. DNA samples were obtained from three families with heritable genetic disorders and genomic sequence data were donated by sequencing platform vendors. The challenge was to analyze and interpret these data with the goals of identifying disease-causing variants and reporting the findings in a clinically useful format. Participating contestant groups were solicited broadly, and an independent panel of judges evaluated their performance. Results: A total of 30 international groups were engaged. The entries reveal a general convergence of practices on most elements of the analysis and interpretation process. However, even given this commonality of approach, only two groups identified the consensus candidate variants in all disease cases, demonstrating a need for consistent fine-tuning of the generally accepted methods. There was greater diversity of the final clinical report content and in the patient consenting process, demonstrating that these areas require additional exploration and standardization. Conclusions: The CLARITY Challenge provides a comprehensive assessment of current practices for using genome sequencing to diagnose and report genetic diseases. There is remarkable convergence in bioinformatic techniques, but medical interpretation and reporting are areas that require further development by many groups. C1 [Brownstein, Catherine A.; Beggs, Alan H.; Yu, Timothy W.; DeChene, Elizabeth T.; Towne, Meghan C.; Savage, Sarah K.; Price, Emily N.; Holm, Ingrid A.; Margulies, David M.] Res Connect, Div Genet & Genom, Boston, MA 02127 USA. [Brownstein, Catherine A.; Beggs, Alan H.; Yu, Timothy W.; DeChene, Elizabeth T.; Towne, Meghan C.; Savage, Sarah K.; Price, Emily N.; Holm, Ingrid A.; Margulies, David M.] Harvard Univ, Sch Med, Boston Childrens Hosp, Manton Ctr Orphan Dis Res, Boston, MA USA. [Homer, Nils] Claritas Genom, Boston, MA USA. [Merriman, Barry] Life Technol, Carlsbad, CA USA. [Flannery, Katherine C.; Luquette, Lovelace J.; Kohane, Isaac S.] Harvard Univ, Sch Med, Ctr Biomed Informat, Boston, MA USA. [Lyon, Elaine] Univ Utah, Sch Med, ARUP Labs, Salt Lake City, UT USA. [Majzoub, Joseph] Harvard Univ, Sch Med, Boston Childrens Hosp, Div Endocrinol, Boston, MA USA. [Neupert, Peter] Microsoft Corp, Microsoft Hlth Solut Grp, Seattle, WA USA. [McCallie, David, Jr.] Cerner Corp, Med Informat, Kansas City, MO USA. [Szolovits, Peter] MIT, Dept Elect Engn & Comp Sci, Cambridge, MA 02139 USA. [Willard, Huntington F.] Duke Univ, Duke Inst Genome Sci & Policy, Durham, NC USA. [Mendelsohn, Nancy J.; Temme, Renee] Childrens Hosp & Clin Minnesota, Dept Med Genet, Minneapolis, MN USA. [Finkel, Richard S.] Nemours Childrens Hosp, Div Neurol, Orlando, FL USA. [Yum, Sabrina W.] Childrens Hosp Philadelphia, Div Neurol, Philadelphia, PA 19104 USA. [Yum, Sabrina W.] Univ Penn, Perelmen Sch Med, Dept Neurol, Philadelphia, PA 19104 USA. [Medne, Livija] Childrens Hosp Philadelphia, Div Neurol, Philadelphia, PA 19104 USA. [Sunyaev, Shamil R.; Adzhubey, Ivan; Cassa, Christopher A.; de Bakker, Paul I. W.; Giovanni, Monica A.; Leshchiner, Ignaty; Murray, Michael F.; Polak, Paz P.; Raychaudhuri, Soumya; Stitziel, Nathan O.; Vestecka, Sara] Harvard Univ, Brigham & Womens Hosp, Sch Med, Div Genet, Boston, MA 02115 USA. [de Bakker, Paul I. W.; Francioli, Laurent] Univ Med Ctr Utrecht, Dept Med Genet, Utrecht, Netherlands. [Duzkale, Hatice; Funke, Birgit H.; Lebo, Matthew S.; Leshchiner, Ignaty; McLaughlin, Heather M.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Lab Mol Med,Partners Healthcare Ctr Personalized, Boston, MA 02115 USA. [Dworzynski, Piotr] Tech Univ Denmark, Dept Syst Biol, Ctr Biol Sequence Anal, DK-2800 Lyngby, Denmark. [Fairbrother, William; Soemedi, Rachel] Brown Univ, Ctr Computat Mol Biol, Providence, RI 02912 USA. [Handsaker, Robert E.] Harvard Univ, Sch Med, Dept Genet, Boston, MA USA. [Lage, Kasper] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Pediat Surg Res Labs, Boston, MA USA. [Lek, Monkol; MacArthur, Daniel G.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Analyt & Translat Genet Unit, Boston, MA USA. [Pers, Tune H.] Childrens Hosp Boston, Div Endocrinol, Boston, MA USA. [Pers, Tune H.] Childrens Hosp Boston, Ctr Basic & Translat Obes Res, Boston, MA USA. [Supper, Jochen; Gugenmus, Claudia; Klocke, Bernward; Hahn, Alexander] Genomatix Software GmbH, Munich, Germany. [Supper, Jochen; Schubach, Max; Menzel, Mortiz; Biskup, Saskia; Freisinger, Peter] CeGaT GmbH, Tubingen, Germany. [Freisinger, Peter] Childrens Hosp Reutlingen, Reutlingen, Germany. [Deng, Mario; Braun, Martin; Perner, Sven] Univ Hosp Bonn, Inst Pathol, Dept Prostate Canc Res, Bonn, Germany. [Smith, Richard J. H.; Andorf, Janeen L.; Sheffield, Val C.; Stone, Edwin M.; Bair, Thomas; Black-Ziegelbein, E. Ann; Darbro, Benjamin; DeLuca, Adam P.; Kolbe, Diana L.; Scheetz, Todd E.; Shearer, Aiden E.; Sompallae, Rama; Bassuk, Alexander G.; Edens, Erik; Mathews, Katherine; Moore, Steven A.; Shchelochkov, Oleg A.; Trapane, Pamela; Bossler, Aaron; Campbell, Colleen A.; Heusel, Jonathan W.; Kwitek, Anne; Maga, Tara; Panzer, Karin; Wassink, Thomas; Van Daele, Douglas; Azaiez, Hela; Booth, Kevin; Meyer, Nic] Univ Iowa, Carver Coll Med, Iowa Inst Human Genet, Iowa City, IA USA. [Huang, Jian] Univ Iowa, Coll Liberal Arts & Sci, Iowa Inst Human Genet, Iowa City, IA USA. [Ryckman, Kelli] Univ Iowa, Coll Publ Hlth, Dept Epidemiol, Iowa Inst Human Genet, Iowa City, IA USA. [Sheffield, Val C.; Stone, Edwin M.] Univ Iowa, Howard Hughes Med Inst, Iowa City, IA 52242 USA. [Braun, Terry A.] Univ Iowa, Coll Engn, Iowa Inst Human Genet, Iowa City, IA USA. [Wang, Kai] Univ Iowa, Coll Publ Hlth, Dept Biostat, Iowa Inst Human Genet, Iowa City, IA USA. [Segal, Michael M.] SimulConsult, Chestnut Hill, MA USA. [Williams, Marc S.; Tromp, Gerard] Geisinger Hlth Syst, Danville, PA USA. [White, Peter; Corsmeier, Donald; Fitzgerald-Butt, Sara; Herman, Gail; Lamb-Thrush, Devon; McBride, Kim L.; Newsom, David; Pierson, Christopher R.; Rakowsky, Alexander T.] Ohio State Univ, Dept Pediat, Nationwide Childrens Hosp, Columbus, OH 43210 USA. [Maver, Ales; Lovrecic, Luca; Palandacic, Anja; Peterlin, Borut] Univ Med Ctr Ljubljana, Dept Obstet & Gynecol, Clin Inst Med Genet, Ljubljana, Slovenia. [Torkamani, Ali] Scripps Res Inst, Scripps Translat Sci Inst, La Jolla, CA 92037 USA. [Wedell, Anna; Magnusson, Mans; Nilsson, Daniel; Stranneheim, Henrik; Taylan, Fulya] Karolinska Inst, Dept Mol Med & Surg, Sci Life Lab, Stockholm, Sweden. [Wedell, Anna; Magnusson, Mans; Stranneheim, Henrik] Karolinska Univ Hosp, Ctr Inherited Metab Disorders, Stockholm, Sweden. [Wedell, Anna; Magnusson, Mans; Nilsson, Daniel; Stranneheim, Henrik; Taylan, Fulya] Karolinska Inst, Ctr Mol Med, Stockholm, Sweden. [Huss, Mikael] Stockholm Univ, Dept Biochem & Biophys, Sci Life Lab, S-10691 Stockholm, Sweden. [Alexeyenko, Andrey] Royal Inst Technol, Sch Biotechnol, Sci Life Lab, Stockholm, Sweden. [Lindvall, Jessica M.] Karolinska Inst, Dept Biosci & Nutr, Huddinge, Sweden. [Nilsson, Daniel] Karolinska Univ Hosp, Dept Clin Genet, Stockholm, Sweden. [Gilissen, Christian; Hoischen, Alexander; van Bon, Bregje; Yntema, Helger; Nelen, Marcel] Radboud Univ Nijmegen, Med Ctr, Dept Human Genet, NL-6525 ED Nijmegen, Netherlands. [Zhang, Weidong; Sager, Jason] Sanofi, Cambridge, MA USA. [Zhang, Lu; Blair, Kathryn; Kural, Deniz] Seven Bridges Genom Inc, Cambridge, MA USA. [Cariaso, Michael; Lennon, Greg G.] River Rd Bio, Potomac, MD USA. [Javed, Asif; Agrawal, Saloni; Ng, Pauline C.] ASTAR, Computat & Math Biol Genome Inst Singapore, Singapore, Singapore. [Sandhu, Komal S.; Krishna, Shuba; Veeramachaneni, Vamsi] Strand Life Sci, Bangalore, Karnataka, India. [Isakov, Ofer; Halperin, Eran; Friedman, Eitan; Shomron, Noam] Tel Aviv Univ, IL-69978 Tel Aviv, Israel. [Glusman, Gustavo; Roach, Jared C.; Caballero, Juan; Cox, Hannah C.; Mauldin, Denise; Ament, Seth A.; Rowen, Lee] Inst Syst Biol, Seattle, WA USA. [Richards, Daniel R.] Ingenu Syst, Redwood City, CA USA. [San Lucas, F. Anthony] Univ Texas MD Anderson Canc Ctr, Dept Epidemiol, Univ Texas Grad Sch Biomed Sci, Houston, TX 77030 USA. [Gonzalez-Garay, Manuel L.] UTHealth, Brown Fdn Inst Mol Med, Ctr Mol Imaging, Div Next Generat Sequencing, Houston, TX USA. [Caskey, C. Thomas] Baylor Coll Med, Dept Mol & Human Genet, Houston, TX 77030 USA. [Bai, Yu; Huang, Ying] Regeneron Pharmaceut Inc, Tarrytown, NY USA. [Fang, Fang] Stanford Univ, Sch Med, Palo Alto, CA 94304 USA. [Zhang, Yan; Wang, Zhengyuan] NHLBI, NIH, Bethesda, MD 20892 USA. [Barrera, Jorge; Garcia-Lobo, Juan M.; Rodriguez, Maria C.; Varela, Ignacio] Inst Biomed & Biotecnol Cantabria IBBTEC, Santander, Cantabria, Spain. [Barrera, Jorge; Garcia-Lobo, Juan M.; Rodriguez, Maria C.; Varela, Ignacio] CSIC, Santander, Cantabria, Spain. [Barrera, Jorge; Garcia-Lobo, Juan M.; Llorca, Javier; Rodriguez, Maria C.; Varela, Ignacio] Univ Cantabria, E-39005 Santander, Cantabria, Spain. [Barrera, Jorge; Garcia-Lobo, Juan M.; Rodriguez, Maria C.; Varela, Ignacio] SODERCAN, Santander, Cantabria, Spain. [Garcia-Lobo, Juan M.] Univ Cantabria, Dept Biol Mol, E-39005 Santander, Cantabria, Spain. [Gonzalez-Lamuno, Domingo] Univ Cantabria, Dept Ciencias Med & Quirurg, Div Pediat, E-39005 Santander, Cantabria, Spain. [Gonzalez-Lamuno, Domingo] Hosp Univ Marques Valdecilla, IFIMAV Inst Formac & Invest Marques Valdecilla, Santander, Cantabria, Spain. [Llorca, Javier] CIBER Epidemiol & Salud Publ CIBERESP, Santander, Cantabria, Spain. [Llorca, Javier] Inst Formac & Invest Marques Valdecilla IFIMAV, Santander, Cantabria, Spain. [Reese, Martin G.; De la Vega, Francisco M.; Kiruluta, Edward] Omicia Inc, Emeryville, CA USA. [De la Vega, Francisco M.] Real Time Genom Inc, San Bruno, CA USA. [Cargill, Michele; Hart, Reece K.; Sorenson, Jon M.] InVitae, San Francisco, CA 94107 USA. [Lyon, Gholson J.] Stanley Inst Cognit Genom, Cold Spring Harbor Lab, New York, NY USA. [Lyon, Gholson J.] Utah Fdn Biomed Res, Salt Lake City, UT USA. [Stevenson, David A.] Univ Utah, Sch Med, Dept Pediat, Salt Lake City, UT USA. [Bray, Bruce E.] Univ Utah, Sch Med, Div Cardiol, Salt Lake City, UT USA. [Bray, Bruce E.] Univ Utah, Sch Med, Dept Biomed Informat, Salt Lake City, UT USA. [Moore, Barry M.; Yandell, Mark] Univ Utah, Sch Med, Dept Human Genet, Eccles Inst Human Genet, Salt Lake City, UT 84132 USA. [Moore, Barry M.; Eilbeck, Karen] Univ Utah, Sch Med, Salt Lake City, UT USA. [Zhao, Hongyu; Hou, Lin; Yang, Can] Yale Univ, Sch Publ Hlth, Dept Biostat, New Haven, CT USA. [Chen, Xiaowei; Chen, Mengjie; Li, Cong] Yale Univ, Program Computat Biol & Bioinformat, New Haven, CT USA. [Yan, Xiting] Yale Univ, Keck Lab, Biostat Resource, New Haven, CT USA. [Gunel, Murat] Yale Univ, Sch Med, Dept Neurosurg, New Haven, CT USA. [Gunel, Murat] Yale Univ, Sch Med, Dept Neurobiol, New Haven, CT USA. [Li, Peining] Yale Univ, Sch Med, Dept Genet, New Haven, CT 06510 USA. [Kong, Yong] Yale Univ, WM Keck Fdn Biotechnol Resource Lab, Dept Mol Biophys & Biochem, New Haven, CT USA. [Alexander, Austin C.] Pearlgen Inc, Durham, NC USA. [Albertyn, Zayed I.] Novocraft Technol Sdn Bhd, Selangor, Malaysia. [Boycott, Kym M.; Bulman, Dennis E.; Sawyer, Sarah L.] Univ Ottawa, Childrens Hosp Eastern Ontario, Res Inst, Ottawa, ON, Canada. [Gordon, Paul M. K.; Innes, A. Micheil; Parboosingh, Jillian S.] Univ Calgary, ACHRI, Calgary, AB, Canada. [Innes, A. Micheil; Parboosingh, Jillian S.] Univ Calgary, Dept Med Genet, Calgary, AB, Canada. [Knoppers, Bartha M.] McGill Univ, Ctr Genom & Policy, Montreal, PQ, Canada. [Majewski, Jacek; Schwartzentruber, Jeremy] McGill Univ, Montreal, PQ, Canada. [Majewski, Jacek; Schwartzentruber, Jeremy] Genome Quebec Innovat Ctr, Montreal, PQ, Canada. [Marshall, Christian R.] Univ Toronto, Hosp Sick Children, Ctr Appl Genom, McLaughlin Ctr, Toronto, ON M5G 1X8, Canada. [Samuels, Mark E.] Univ Montreal, CHU Ste Justine, Ctr Rech, Dept Med, Montreal, PQ, Canada. RP Beggs, AH (reprint author), Res Connect, Div Genet & Genom, Boston, MA 02127 USA. EM beggs@enders.tch.harvard.edu; isaac_kohane@harvard.edu; David.Margulies@childrens.harvard.edu RI van Bon, Bregje/Q-2445-2015; Alexeyenko, Andrey/F-1924-2016; Varela, Ignacio/G-1699-2016; Fang, Fang/G-7679-2016; Gilissen, Christian/E-5246-2012; innes, allan micheil/A-9955-2017; Garcia Lobo, Juan/K-2727-2014; Rodriguez, Maria-Cruz/K-6533-2014; Llorca, Javier/F-7371-2011; YANG, Can/J-8790-2014; de Bakker, Paul/B-8730-2009; McBride, Kim/A-5879-2008; White, Peter/E-4301-2011; peterlin, borut/C-6086-2011; Nilsson, Daniel/B-8365-2009; Hoischen, Alexander/D-1282-2013; Yntema, H.G./L-4771-2015; Nelen, Marcel/L-4542-2015; OI Alexeyenko, Andrey/0000-0001-8812-6481; Varela, Ignacio/0000-0002-0969-506X; Gilissen, Christian/0000-0003-1693-9699; Blair, Kate/0000-0003-0766-0952; Lindvall, Jessica/0000-0002-5042-8481; Glusman, Gustavo/0000-0001-8060-5955; Bradley, Maria/0000-0001-7192-5041; Garcia Lobo, Juan/0000-0002-9187-0671; Rodriguez, Maria-Cruz/0000-0001-6778-1663; Llorca, Javier/0000-0001-8569-861X; YANG, Can/0000-0003-3368-3082; de Bakker, Paul/0000-0001-7735-7858; McBride, Kim/0000-0002-8407-8942; White, Peter/0000-0002-5218-5903; peterlin, borut/0000-0001-7824-4978; Nilsson, Daniel/0000-0001-5831-385X; Hoischen, Alexander/0000-0002-8072-4476; Kong, Yong/0000-0002-2881-5274; Stitziel, Nathan/0000-0002-4963-8211; Schwartzentruber, Jeremy/0000-0002-6183-2092; Taylan, Fulya/0000-0002-2907-0235; Huss, Mikael/0000-0003-0839-2451; Yu, Timothy/0000-0003-2988-7701; Lebo, Matthew/0000-0002-9733-5207; Hart, Reece/0000-0003-3463-0775 FU Gene Partnership; Manton Center for Orphan Disease Research at Boston Children's Hospital; Center for Biomedical Informatics at Harvard Medical School FX This work was supported by funds provided through the Gene Partnership and the Manton Center for Orphan Disease Research at Boston Children's Hospital and the Center for Biomedical Informatics at Harvard Medical School and by generous donations in-kind of genomic sequencing services by Life Technologies (Carlsbad, CA, USA) and Complete Genomics (Mountain View, CA, USA). All the authors would especially like to thank the families for their participation and resulting critical contributions to this study. The study organizers would also like to thank Elizabeth Andrews and Keri Steadman for seminal contributions to the contest planning, Peter Kang for assistance tabulating patient phenotypes, Lindsay Swanson for assistance with return of results, and Elizabeth Torosian for help with manuscript preparation. This manuscript is dedicated to the memory of David Newsom. NR 69 TC 34 Z9 34 U1 2 U2 27 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1465-6906 EI 1474-760X J9 GENOME BIOL JI Genome Biol. PY 2014 VL 15 IS 3 AR R53 DI 10.1186/gb-2014-15-3-r53 PG 18 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA AL2UP UT WOS:000338981300014 PM 24667040 ER PT S AU Shah, DI Paw, BH AF Shah, Dhvanit I. Paw, Barry H. BE Ferreira, GC Kadish, KM Smith, KM Guilard, R TI Zebrafish as a Genetic Model of Hematopoiesis and Human Red Blood Cell Diseases SO HANDBOOK OF PORPHYRIN SCIENCE WITH APPLICATIONS TO CHEMISTRY, PHYSICS, MATERIALS SCIENCE, ENGINEERING, BIOLOGY AND MEDICINE, VOL 27: ERYTHROPOIESIS, HEME AND APPLICATIONS TO BIOMEDICINE SE Handbook of Porphyrin Science LA English DT Article; Book Chapter ID ZINC-FINGER NUCLEASES; TRANSGENIC ZEBRAFISH; VASCULAR DEVELOPMENT; HEREDITARY HEMOCHROMATOSIS; DEFINITIVE HEMATOPOIESIS; VERTEBRATE DEVELOPMENT; DEVELOPMENTAL BIOLOGY; SIDEROBLASTIC ANEMIA; FERROPORTIN DISEASE; POSITIONAL CLONING C1 [Shah, Dhvanit I.; Paw, Barry H.] Harvard Univ, Sch Med, Dept Med, Div Hematol,Brigham & Womens Hosp, Boston, MA 02115 USA. [Paw, Barry H.] Harvard Univ, Sch Med, Dept Med, Div Hematol Oncol, Boston, MA 02115 USA. [Paw, Barry H.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. RP Shah, DI (reprint author), Harvard Univ, Sch Med, Dept Med, Div Hematol,Brigham & Womens Hosp, Boston, MA 02115 USA. EM bpaw@rics.bwh.harvard.edu NR 107 TC 0 Z9 0 U1 0 U2 1 PU WORLD SCIENTIFIC PUBL CO PTE LTD PI SINGAPORE PA PO BOX 128 FARRER RD, SINGAPORE 9128, SINGAPORE SN 1793-9518 BN 978-981-4407-78-6 J9 HANDB PORPHYR SCI PY 2014 VL 27 BP 85 EP 115 PG 31 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA BA5QY UT WOS:000336962200005 ER PT S AU St Denis, TG Huang, YY Hamblin, MR AF St Denis, Tyler G. Huang, Ying-Ying Hamblin, Michael R. BE Ferreira, GC Kadish, KM Smith, KM Guilard, R TI Cyclic Tetrapyrroles in Photodynamic Therapy: The Chemistry of Porphyrins and Related Compounds in Medicine SO HANDBOOK OF PORPHYRIN SCIENCE WITH APPLICATIONS TO CHEMISTRY, PHYSICS, MATERIALS SCIENCE, ENGINEERING, BIOLOGY AND MEDICINE, VOL 27: ERYTHROPOIESIS, HEME AND APPLICATIONS TO BIOMEDICINE SE Handbook of Porphyrin Science LA English DT Article; Book Chapter ID TIN ETHYL ETIOPURPURIN; GRAM-POSITIVE BACTERIA; 5-AMINOLEVULINIC ACID-DERIVATIVES; BASAL-CELL CARCINOMA; ASPARTYL CHLORIN E6; MOUSE-TUMOR MODEL; IN-VIVO; PROTOPORPHYRIN-IX; CANINE PROSTATE; SINGLET OXYGEN C1 [St Denis, Tyler G.] Columbia Univ, Dept Chem, New York, NY 10027 USA. [St Denis, Tyler G.; Huang, Ying-Ying; Hamblin, Michael R.] Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA. [Huang, Ying-Ying; Hamblin, Michael R.] Harvard Univ, Sch Med, Dept Dermatol, Boston, MA 02115 USA. [Huang, Ying-Ying] Guangxi Med Univ, Aesthet & Plast Ctr, Nanning, Peoples R China. [Hamblin, Michael R.] MIT, Harvard Mit Div Hlth Sci & Technol, Cambridge, MA 02139 USA. RP St Denis, TG (reprint author), Columbia Univ, Dept Chem, New York, NY 10027 USA. EM hamblin@helix.mgh.harvard.edu NR 223 TC 3 Z9 3 U1 1 U2 7 PU WORLD SCIENTIFIC PUBL CO PTE LTD PI SINGAPORE PA PO BOX 128 FARRER RD, SINGAPORE 9128, SINGAPORE SN 1793-9518 BN 978-981-4407-78-6 J9 HANDB PORPHYR SCI PY 2014 VL 27 BP 255 EP 301 PG 47 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA BA5QY UT WOS:000336962200009 ER PT J AU Kim, S Saad, M Tsuang, DW Wijsman, EM AF Kim, Sulgi Saad, Mohamad Tsuang, Debby W. Wijsman, Ellen M. TI Visualization of Haplotype Sharing Patterns in Pedigree Samples SO HUMAN HEREDITY LA English DT Article DE IBD; Linkage analysis; Gene mapping; Sampling subjects; Sequencing; Sequence ID LINKAGE ANALYSIS; GENETIC-LINKAGE; COMPLEX DISEASE; RARE VARIANTS; SCHIZOPHRENIA; TRAITS; MAPS; ERA AB Objectives: A particular approach to the visualization of descent of founder DNA copies in a pedigree has been suggested, which helps to understand haplotype sharing patterns among subjects of interest. However, the approach does not provide the information in an ideal format to show haplotype sharing patterns. Therefore, we aimed to find an efficient way to visualize such sharing patterns and to demonstrate that our tool provides useful information for finding an informative subset of subjects for a sequence study. Methods: The visualization package, SharedHap, computes and visualizes a novel metric, the SharedHap proportion, which quantifies haplotype sharing among a set of subjects of interest. We applied SharedHap to simulated and real pedigree datasets to illustrate the approach. Results: SharedHap successfully represents haplotype sharing patterns that contribute to linkage signals in both simulated and real datasets. Using the visualizations we were also able to find ideal sets of subjects for sequencing studies. Conclusions: Our novel metric that can be computed using the SharedHap package provides useful information about haplotype sharing pat-terns among subjects of interest. The visualization of the SharedHap proportion provides useful information in pedigree studies, allowing for a better selection of candidate subjects for use in further sequencing studies. (C) 2014 S. Karger AG, Basel C1 [Kim, Sulgi; Saad, Mohamad; Wijsman, Ellen M.] Univ Washington, Dept Med, Div Med Genet, Seattle, WA 98195 USA. [Tsuang, Debby W.] Univ Washington, Dept Psychiat & Behav Sci, Seattle, WA 98195 USA. [Wijsman, Ellen M.] Univ Washington, Sch Publ Hlth, Dept Biostat, Seattle, WA 98195 USA. [Wijsman, Ellen M.] Univ Washington, Sch Med, Dept Genome Sci, Seattle, WA 98195 USA. [Tsuang, Debby W.] Vet Affairs Puget Sound Hlth Care Syst, Geriatr Res Educ & Clin Ctr, Seattle, WA USA. RP Wijsman, EM (reprint author), Univ Washington, Dept Med, Div Med Genet, Box 359460, Seattle, WA 98195 USA. EM wijsman@u.washington.edu RI Tsuang, Debby/L-7234-2016 OI Tsuang, Debby/0000-0002-4716-1894 FU US Department of Veterans Affairs, Office of Research Development, Biomedical Laboratory Research; NIH [R01MH065558, P50AG005136]; VISN-20 MIRECC FX This work was supported by a US Department of Veterans Affairs, Office of Research Development, Biomedical Laboratory Research merit review; VISN-20 MIRECC, and NIH grants No. R01MH065558 and P50AG005136. The funding agencies did not play a role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 30 TC 0 Z9 0 U1 0 U2 2 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0001-5652 EI 1423-0062 J9 HUM HERED JI Hum. Hered. PY 2014 VL 78 IS 1 BP 1 EP 8 DI 10.1159/000358171 PG 8 WC Genetics & Heredity SC Genetics & Heredity GA AL7OA UT WOS:000339322500001 PM 24969160 ER PT J AU Marshall, GA Lorius, N Locascio, JJ Hyman, BT Rentz, DM Johnson, KA Sperling, RA AF Marshall, Gad A. Lorius, Natacha Locascio, Joseph J. Hyman, Bradley T. Rentz, Dorene M. Johnson, Keith A. Sperling, Reisa A. CA Alzheimer's Dis Neuroimaging Initi TI Regional Cortical Thinning and Cerebrospinal Biomarkers Predict Worsening Daily Functioning Across the Alzheimer's Disease Spectrum SO JOURNAL OF ALZHEIMERS DISEASE LA English DT Article DE Alzheimer's disease; cerebrospinal fluid; instrumental activities of daily living; magnetic resonance imaging; mild cognitive impairment ID MILD-COGNITIVE-IMPAIRMENT; INSTRUMENTAL ACTIVITIES; EVERYDAY FUNCTION; DEMENTIA; FLUID; COMMUNITY; DECLINE; TAU AB Background: Impairment in instrumental activities of daily living (IADL) heralds the transition from mild cognitive impairment (MCI) to dementia and is a major source of burden for both the patient and caregiver. Objective: To investigate the relationship between IADL and regional cortical thinning and cerebrospinal fluid (CSF) Alzheimer's disease (AD) biomarkers cross-sectionally and longitudinally in clinically normal (CN) elderly, MCI, and mild AD dementia subjects. Methods: Two hundred and twenty nine CN, 395 MCI, and 188 AD dementia subjects participating in the Alzheimer's Disease Neuroimaging Initiative underwent baseline magnetic resonance imaging, baseline lumbar puncture, and clinical assessments, including the Functional Activities Questionnaire used to measure IADL, every 6 to 12 months up to 3 years. General linear regression and mixed effects models were employed. Results: IADL impairment was associated with the interactions between lower inferior temporal cortical thickness and diagnosis (p < 0.0001), greater lateral occipital cortical thickness and diagnosis (p < 0.0001), and greater amyloid-beta 1-42 (A beta(1-42)) and diagnosis (p = 0.0002) at baseline (driven by AD dementia). Lower baseline supramarginal (p = 0.02) and inferior temporal (p = 0.05) cortical thickness, lower A beta(1-42) (p < 0.0001), and greater total tau (t-tau) (p = 0.02) were associated with greater rate of IADL impairment over time. Conclusions: Temporal atrophy is associated with IADL impairment in mild AD dementia at baseline, while baseline parietal and temporal atrophy, lower CSF A beta(1-42), and greater t-tau predict worsening IADL impairment over time across the AD spectrum. These results emphasize the importance of assessing IADL at the stage of MCI and even at the transition from CN to MCI. C1 [Marshall, Gad A.; Lorius, Natacha; Rentz, Dorene M.; Johnson, Keith A.; Sperling, Reisa A.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Ctr Alzheimer Res & Treatment, Boston, MA 02115 USA. [Marshall, Gad A.; Lorius, Natacha; Rentz, Dorene M.; Johnson, Keith A.; Sperling, Reisa A.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Neurol, Boston, MA 02115 USA. [Marshall, Gad A.; Lorius, Natacha; Locascio, Joseph J.; Hyman, Bradley T.; Rentz, Dorene M.; Johnson, Keith A.; Sperling, Reisa A.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Massachusetts Alzheimers Dis Res Ctr, Boston, MA USA. [Marshall, Gad A.; Lorius, Natacha; Locascio, Joseph J.; Hyman, Bradley T.; Rentz, Dorene M.; Sperling, Reisa A.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Neurol, Boston, MA USA. [Johnson, Keith A.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiol, Boston, MA USA. RP Marshall, GA (reprint author), Brigham andWomens Hosp, Ctr Alzheimer Res & Treatment, 221 Long wood Ave,BL-104, Boston, MA 02115 USA. EM gamarshall@partners.org FU Rosalinde and Arthur Gilbert Foundation/AFAR New Investigator Awards in Alzheimer's Disease [R01 AG027435, K23 AG033634, K24 AG035007]; Massachusetts Alzheimer's Disease Research Center [P50 AG005134]; Harvard Aging Brain Study [P01 AGO36694]; Alzheimer's disease Neuroimaging Initiative (ADNI) (NIH) [U01 AG024904]; Janssen Alzheimer Immunotherapy; Wyeth/Pfizer Pharmaceuticals; Bristol-Myers-Squibb FX This study was supported by R01 AG027435, K23 AG033634, K24 AG035007, the Rosalinde and Arthur Gilbert Foundation/AFAR New Investigator Awards in Alzheimer's Disease, the Massachusetts Alzheimer's Disease Research Center (P50 AG005134), the Harvard Aging Brain Study (P01 AGO36694), and the Alzheimer's disease Neuroimaging Initiative (ADNI) (NIH Grant U01 AG024904) (See Supplementary Material).; The authors have received research salary support from Janssen Alzheimer Immunotherapy (GAM, DMR), Wyeth/Pfizer Pharmaceuticals (GAM, DMR), and Bristol-Myers-Squibb (RAS). NR 22 TC 9 Z9 9 U1 0 U2 6 PU IOS PRESS PI AMSTERDAM PA NIEUWE HEMWEG 6B, 1013 BG AMSTERDAM, NETHERLANDS SN 1387-2877 EI 1875-8908 J9 J ALZHEIMERS DIS JI J. Alzheimers Dis. PY 2014 VL 41 IS 3 BP 719 EP 728 DI 10.3233/JAD-132768 PG 10 WC Neurosciences SC Neurosciences & Neurology GA AL7QG UT WOS:000339329100009 PM 24685624 ER PT J AU Lee, GJ Lu, PH Mather, MJ Shapira, J Jimenez, E Leow, AD Thompson, PM Mendez, MF AF Lee, Grace J. Lu, Po H. Mather, Michelle J. Shapira, Jill Jimenez, Elvira Leow, Alex D. Thompson, Paul M. Mendez, Mario F. TI Neuroanatomical Correlates of Emotional Blunting in Behavioral Variant Frontotemporal Dementia and Early-Onset Alzheimer's Disease SO JOURNAL OF ALZHEIMERS DISEASE LA English DT Article DE Alzheimer's disease; early onset; emotional blunting; frontotemporal dementia; magnetic resonance imaging ID TENSOR-BASED MORPHOMETRY; DIAGNOSTIC-CRITERIA; LOBAR DEGENERATION; SOCIAL-BEHAVIOR; DYSFUNCTION; DISORDERS; EMPATHY; COGNITION; SYMPTOMS; PATTERNS AB Background: Emotional blunting is a characteristic feature of behavioral variant frontotemporal dementia (bvFTD) and can help discriminate between patients with bvFTD and other forms of younger-onset dementia. Objective: We compared the presence of emotional blunting symptoms in patients with bvFTD and early-onset Alzheimer's disease (AD), and investigated the neuroanatomical associations between emotional blunting and regional brain volume. Methods: Twenty-five individuals with bvFTD (n = 11) and early-onset AD (n = 14) underwent magnetic resonance imaging (MRI) and were rated on symptoms of emotional blunting using the Scale for Emotional Blunting (SEB). The two groups were compared on SEB ratings and MRI-derived brain volume using tensor-based morphometry. Voxel-wise linear regression was performed to determine neuroanatomical correlates of SEB scores. Results: The bvFTD group had significantly higher SEB scores compared to the AD group. On MRI, bvFTD patients had smaller bilateral frontal lobe volume compared to AD patients, while AD patients had smaller bilateral temporal and left parietal volume than bvFTD patients. In bvFTD, SEB ratings were strongly correlated with right anterior temporal volume, while the association between SEB and the right orbitofrontal cortex was non-significant. Conclusions: Symptoms of emotional blunting were more prevalent in bvFTD than early-onset AD patients. These symptoms were particularly associated with right-sided atrophy, with significant involvement of the right anterior temporal region. Based on these findings, the SEB appears to measure symptoms of emotional blunting that are localized to the right anterior temporal lobe. C1 [Lee, Grace J.] Loma Linda Univ, Sch Behav Hlth, Dept Psychol, Loma Linda, CA 92350 USA. [Lu, Po H.; Mather, Michelle J.; Shapira, Jill; Jimenez, Elvira; Mendez, Mario F.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Neurol, Los Angeles, CA 90095 USA. [Mather, Michelle J.; Shapira, Jill; Jimenez, Elvira; Mendez, Mario F.] Greater Los Angeles VA Healthcare Syst, West Los Angeles, CA USA. [Leow, Alex D.] Univ Illinois, Dept Psychiat, Chicago, IL 60612 USA. [Leow, Alex D.] Univ Illinois, Dept Bioengn, Chicago, IL USA. [Thompson, Paul M.] Keck Sch Med USC, Inst Neuroimaging & Informat, Lab NeuroImaging, Los Angeles, CA USA. RP Lee, GJ (reprint author), 11130 Anderson St,Cent Bldg, Loma Linda, CA 92350 USA. EM gracelee@llu.edu RI Leow, Alex/K-3236-2014 OI Leow, Alex/0000-0002-5660-8651 FU NIH from the National Institute of Aging (NIA) [K23-AG028727, R01-AG034499]; Alzheimer's Disease Research Center [P50 AG-16570]; California Alzheimer's Disease Centers; Department of Veterans Affairs FX This work was supported by NIH grants K23-AG028727 and R01-AG034499 from the National Institute of Aging (NIA), the Alzheimer's Disease Research Center grant P50 AG-16570, California Alzheimer's Disease Centers, and the Department of Veterans Affairs. NR 34 TC 7 Z9 7 U1 0 U2 5 PU IOS PRESS PI AMSTERDAM PA NIEUWE HEMWEG 6B, 1013 BG AMSTERDAM, NETHERLANDS SN 1387-2877 EI 1875-8908 J9 J ALZHEIMERS DIS JI J. Alzheimers Dis. PY 2014 VL 41 IS 3 BP 793 EP 800 DI 10.3233/JAD-132219 PG 8 WC Neurosciences SC Neurosciences & Neurology GA AL7QG UT WOS:000339329100016 PM 24685626 ER PT J AU Park, YK Park, S Wu, HG Kim, S AF Park, Yang-Kyun Park, Soyeon Wu, Hong-Gyun Kim, Siyong TI A new plan quality index for dose painting radiotherapy SO JOURNAL OF APPLIED CLINICAL MEDICAL PHYSICS LA English DT Article DE dose painting; plan quality index; plan achievement; homogeneity index ID INTENSITY-MODULATED RADIOTHERAPY; NECK-CANCER; 2D/3D REGISTRATION; RANK CORRELATION; MERIT FUNCTION; NORMAL-TISSUE; HEAD; THERAPY; IMRT; ESCALATION AB Dose painting radiotherapy is considered a promising radiotherapy technology that enables more targeted dose delivery to tumor rich regions while saving critical normal tissues. Obviously, dose painting planning would be more complicated and hard to be evaluated with current plan quality index systems that were developed under the paradigm of uniform dose prescription. In this study, we introduce a new plan quality index, named "index of achievement (IOA)" that assesses how close the planned dose distribution is to the prescribed one in a dose painting radiotherapy plan. By using voxel-based comparison between planned and prescribed dose distributions in its formulation, the index allows for a single-value evaluation regardless of the number of prescribed dose levels, which cannot be achieved with the conventional indices such as conventional homogeneity index. Benchmark calculations using patient data demonstrated feasibility of the index not only for contour-based dose painting plans, but also for dose painting by numbers plans. Also, it was shown that there is strong correlation between the new index and conventional indices, which indicates a potential of the new index as an alternative to conventional ones in general radiotherapy plan evaluation. C1 [Park, Yang-Kyun] Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. [Park, Soyeon] Seoul Natl Univ, Interdisciplinary Program Radiat Appl Life Sci, Seoul, South Korea. [Wu, Hong-Gyun] Seoul Natl Univ, Dept Radiat Oncol, Seoul, South Korea. [Kim, Siyong] Virginia Commonwealth Univ, Dept Radiat Oncol, Richmond, VA 23298 USA. RP Kim, S (reprint author), Virginia Commonwealth Univ, Dept Radiat Oncol, 401 Coll St,POB 980058, Richmond, VA 23298 USA. EM siyongkim@gmail.com NR 28 TC 2 Z9 2 U1 0 U2 4 PU MULTIMED INC PI TORONTO PA 66 MARTIN ST, TORONTO, ON L9T 2R2, CANADA SN 1526-9914 J9 J APPL CLIN MED PHYS JI J. Appl. Clin. Med. Phys PY 2014 VL 15 IS 4 BP 316 EP 325 PG 10 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA AL7QA UT WOS:000339328400027 ER PT J AU Halabi, T Lu, HM AF Halabi, Tarek Lu, Hsiao-Ming TI Automating checks of plan check automation SO JOURNAL OF APPLIED CLINICAL MEDICAL PHYSICS LA English DT Article DE plan check automation; chart review; quality assurance AB While a few physicists have designed new plan check automation solutions for their clinics, fewer, if any, managed to adapt existing solutions. As complex and varied as the systems they check, these programs must gain the full confidence of those who would run them on countless patient plans. The present automation effort, planCheck, therefore focuses on versatility and ease of implementation and verification. To demonstrate this, we apply planCheck to proton gantry, stereotactic proton gantry, stereotactic proton fixed beam (STAR), and IMRT treatments. C1 [Halabi, Tarek; Lu, Hsiao-Ming] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA 02114 USA. RP Halabi, T (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA 02114 USA. EM thalabi@mgh.harvard.edu NR 7 TC 2 Z9 2 U1 0 U2 1 PU MULTIMED INC PI TORONTO PA 66 MARTIN ST, TORONTO, ON L9T 2R2, CANADA SN 1526-9914 J9 J APPL CLIN MED PHYS JI J. Appl. Clin. Med. Phys PY 2014 VL 15 IS 4 BP 392 EP 399 PG 8 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA AL7QA UT WOS:000339328400035 ER PT J AU Schoo, LA van Zandvoort, MJE Reijmer, YD Biessels, GJ Kappelle, LJ Postma, A AF Schoo, Linda A. van Zandvoort, Martine J. E. Reijmer, Yael D. Biessels, Geert Jan Kappelle, L. Jaap Postma, Albert TI Absolute and relative temporal order memory for performed activities following stroke SO JOURNAL OF CLINICAL AND EXPERIMENTAL NEUROPSYCHOLOGY LA English DT Article DE Temporal order memory; Episodic memory; Event memory; Relative order memory; Stroke ID SERIAL POSITION FUNCTION; EPISODIC MEMORY; RECOGNITION MEMORY; SIMILAR PRINCIPLES; SEMANTIC MEMORY; FREE-RECALL; EVENTS; LONG; BRAIN; DISCRIMINATION AB Reconstructing the temporal order of events is a crucial part of episodic memory. The temporal dimension, however, is often discarded in clinical settings, and measurements of true temporal aspects of episodic memory are scarce. The present study assessed temporal memory in stroke patients and in age-and education-matched healthy controls. Both groups underwent a standardized neuropsychological examination. We asked participants afterwards to reconstruct the order of tests they had performed, measured in absolute temporal order (event placed on correct moment in sequence) and relative temporal order (event placed correctly relative to directly preceding and following events). The aim of the study was to examine how serial-position curve effects (measuring absolute temporal order anchored in exact time) and how relative temporal order memory (anchored to other events) may differ in a group of cerebral stroke patients. Another aim was to link temporal order memory deficits with established neuropsychological measures of cognitive functioning. Although item identification was comparable in both groups, absolute temporal order memory was impaired in patients: A total of 43% of the patients lacked the expected primacy and recency effects (serial position effect). In addition, relative temporal order memory was affected in this group as well, F(1, 70) = 4.08, p < .05; 25% of the patients were impaired in reconstructing the relative temporal order (p = .019, Fisher's Exact Test). Both absolute and relative temporal order memory performance related to the domains of executive functioning and memory. Our results suggest that it is important to test both absolute and relative temporal order memory, especially because these types of memory depend on different anchors, either on time or on adjacent events. C1 [Schoo, Linda A.; van Zandvoort, Martine J. E.; Postma, Albert] Helmholz Inst, Dept Expt Psychol, NL-3584 CS Utrecht, Netherlands. [Schoo, Linda A.; van Zandvoort, Martine J. E.; Postma, Albert] Univ Utrecht, NL-3584 CS Utrecht, Netherlands. [Schoo, Linda A.; van Zandvoort, Martine J. E.; Biessels, Geert Jan; Kappelle, L. Jaap; Postma, Albert] Univ Med Ctr, Brain Ctr Rudolf Magnus, Dept Neurol, Utrecht, Netherlands. [Reijmer, Yael D.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, J Philip Kistler Stroke Res Ctr, Boston, MA USA. RP Schoo, LA (reprint author), Helmholz Inst, Heidelberglaan 2, NL-3584 CS Utrecht, Netherlands. EM l.a.schoo@uu.nl NR 36 TC 0 Z9 0 U1 0 U2 5 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 530 CHESTNUT STREET, STE 850, PHILADELPHIA, PA 19106 USA SN 1380-3395 EI 1744-411X J9 J CLIN EXP NEUROPSYC JI J. Clin. Exp. Neuropsychol. PY 2014 VL 36 IS 6 BP 648 EP 658 DI 10.1080/13803395.2014.925093 PG 11 WC Psychology, Clinical; Clinical Neurology; Psychology SC Psychology; Neurosciences & Neurology GA AL2WV UT WOS:000338987200009 PM 24925480 ER PT J AU Costantini, A Pompili, M Innamorati, M Zezza, MC Di Carlo, A Sher, L Girardi, P AF Costantini, Anna Pompili, Maurizio Innamorati, Marco Zezza, Maria Cristina Di Carlo, Alessandra Sher, Leo Girardi, Paolo TI Psychiatric Pathology and Suicide Risk in Patients with Cancer SO JOURNAL OF PSYCHOSOCIAL ONCOLOGY LA English DT Article DE psychoncology; cancer; psychiatry; suicide ID TERMINALLY-ILL; PSYCHOLOGICAL DISTRESS; DEPRESSION; PREVALENCE; REGISTER; SCALE AB The aims of the study were to assess sociodemographic and clinical factors associated with suicidal ideation in patients with cancer who required a psycho-oncological support. Among 504 participants, there were 136 (23 men and 113 women) cancer patients who completed psychological assessment when admitted to the Psycho-oncology Outpatient Clinic between 2006 and 2011. Suicidal ideation was assessed by Item 9 of the Brief Symptom Inventory, Hopelessness was assessed by the hopelessness subscale of the Mini-Mental Adjustment to Cancer Scale, and Depression was assessed by the depression subscale of the Hospital and Anxiety Depression Scale. Around 30% of this sample reported affective symptoms and around 20% reported suicidal ideation and hopelessness. Patients who reported suicidal ideation were more hopeless (18.8 +/- 6.7vs. 15.7 +/- 5.2; t(134) = 2.54; p < 0.05) and reported more depression (11.8 +/- 4.8vs. 6.8 +/- 4.1; t(134) = 5.30; p < 0.001). It is evident that cancer can result in a strong psychological distress in the patient. It is important, therefore, that cancer patients receive a proper assistance and psychological support and that both the possible presence of depression and suicidal ideation are constantly monitored. C1 [Costantini, Anna; Zezza, Maria Cristina; Di Carlo, Alessandra] Univ Roma La Sapienza, Psychooncol Unit, St Andrea Hosp, I-00189 Rome, Italy. [Pompili, Maurizio; Innamorati, Marco; Girardi, Paolo] Univ Roma La Sapienza, Dept Neurosci Mental Hlth & Sensory Funct, Suicide Prevent Ctr, St Andrea Hosp, I-00189 Rome, Italy. [Sher, Leo] Mt Sinai Sch Med, New York, NY USA. [Sher, Leo] James J Peters Vet Adm Med Ctr, New York, NY USA. RP Pompili, M (reprint author), Univ Roma La Sapienza, Dept Neurosci Mental Hlth & Sensory Funct, Suicide Prevent Ctr, St Andrea Hosp, Via Grottarossa 1035, I-00189 Rome, Italy. EM maurizio.pompili@uniroma1.it OI Pompili, Maurizio/0000-0003-1886-4977 NR 33 TC 3 Z9 3 U1 2 U2 5 PU ROUTLEDGE JOURNALS, TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXFORDSHIRE, ENGLAND SN 0734-7332 EI 1540-7586 J9 J PSYCHOSOC ONCOL JI J. Psychosoc. Oncol. PY 2014 VL 32 IS 4 BP 383 EP 395 DI 10.1080/07347332.2014.917136 PG 13 WC Psychology, Social SC Psychology GA AL4KD UT WOS:000339100900001 PM 24797891 ER PT J AU Pogoda, TK Iverson, KM Meterko, M Baker, E Hendricks, AM Stolzmann, KL Krengel, M Charns, MP Amara, J Kimerling, R Lew, HL AF Pogoda, Terri K. Iverson, Katherine M. Meterko, Mark Baker, Errol Hendricks, Ann M. Stolzmann, Kelly L. Krengel, Maxine Charns, Martin P. Amara, Jomana Kimerling, Rachel Lew, Henry L. TI Concordance of clinician judgment of mild traumatic brain injury history with a diagnostic standard SO JOURNAL OF REHABILITATION RESEARCH AND DEVELOPMENT LA English DT Article DE American Congress of Rehabilitation Medicine guidelines; blast injuries; comprehensive traumatic brain injury evaluation; diagnosis; mild traumatic brain injury; neurobehavioral manifestations; non-blast injuries; posttraumatic stress disorder; psychological factors; Veterans ID POSTTRAUMATIC-STRESS-DISORDER; PERSISTENT POSTCONCUSSIVE SYMPTOMS; IRAQ; AFGHANISTAN; VETERANS; DEPLOYMENT; MILITARY; ASSOCIATION; PREVALENCE; CHALLENGES AB The concordance of Department of Veterans Affairs (VA) clinician judgment of mild traumatic brain injury (mTBI) history with American Congress of Rehabilitation Medicine (ACRM)-based criteria was examined for Operation Iraqi Freedom (OIF) and Operation Enduring Freedom (OEF) Veterans. In order to understand inconsistencies in agreement, we also examined the associations between evaluation outcomes and conceptually relevant patient characteristics, deployment-related events, current self-reported health symptoms, and suspected psychiatric conditions. The Veteran sample comprised 14,026 OIF/OEF VA patients with deployment-related mTBI history (n = 9,858) or no history of mTBI (n = 4,168) as defined by ACRM-based criteria. In the majority of cases (76.0%), clinician judgment was in agreement with the ACRM-based criteria. The most common inconsistency was between clinician judgment (no) and ACRM-based criteria (yes) for 21.3% of the patients. Injury etiology, current self-reported health symptoms, and suspected psychiatric conditions were additional factors associated with clinician diagnosis and ACRM-based criteria disagreement. Adherence to established diagnostic guidelines is essential for accurate determination of mTBI history and for understanding the extent to which mTBI symptoms resolve or persist over time in OIF/OEF Veterans. C1 [Pogoda, Terri K.; Meterko, Mark; Baker, Errol; Stolzmann, Kelly L.; Charns, Martin P.] Dept Vet Affairs VA Boston Hlthcare Syst, Ctr Healthcare Org & Implementat Res, Boston, MA USA. [Pogoda, Terri K.; Meterko, Mark; Hendricks, Ann M.; Charns, Martin P.] Boston Univ, Sch Publ Hlth, Dept Hlth Policy & Management, Boston, MA USA. [Iverson, Katherine M.] VA Boston Healthcare Syst, Natl Ctr Posttraumat Stress Disorder, Boston, MA 02130 USA. [Iverson, Katherine M.] Boston Univ, Sch Med, Dept Psychiat, Boston, MA 02118 USA. [Pogoda, Terri K.; Hendricks, Ann M.] VA Boston Healthcare Syst, Boston, MA 02130 USA. [Krengel, Maxine] VA Boston Healthcare Syst, Res & Dev Serv, Boston, MA 02130 USA. [Krengel, Maxine] Boston Univ, Sch Med, Dept Neurol, Boston, MA 02118 USA. [Amara, Jomana] Naval Postgrad Sch, Def Resource Management Inst, Monterey, CA USA. [Kimerling, Rachel] VA Palo Alto Healthcare Syst, Natl Ctr Posttraumat Stress Disorder, Palo Alto, CA USA. [Kimerling, Rachel] VA Palo Alto Healthcare Syst, Ctr Hlth Care Evaluat, Palo Alto, CA USA. [Lew, Henry L.] Virginia Commonwealth Univ, Dept Phys Med & Rehabil, Def & Vet Brain Injury Ctr, Richmond, VA USA. [Lew, Henry L.] Univ Hawaii Manoa, John A Burns Sch Med, Dept Commun Sci & Disorders, Honolulu, HI 96822 USA. RP Pogoda, TK (reprint author), VA Boston Healthcare Syst, 150 S Huntington Ave 152M, Boston, MA 02130 USA. EM terri.pogoda@va.gov OI Kimerling, Rachel/0000-0003-0996-4212 FU VA Office of Research and Development, Health Services Research and Development Service [SDR 08-405]; Health Services Research and Development Service Career Development Award [CDA-2, 10-029] FX This material was based on work supported by the VA Office of Research and Development, Health Services Research and Development Service (grant SDR 08-405). Dr. Iverson's contribution was supported by a Health Services Research and Development Service Career Development Award (CDA-2; 10-029). NR 43 TC 4 Z9 4 U1 2 U2 3 PU JOURNAL REHAB RES & DEV PI BALTIMORE PA DEPT OF VETERANS AFFAIRS REHABIL RES & DEVELOP CTR 103 SOUTH GAY STREET, BALTIMORE, MD 21202-4051 USA SN 0748-7711 EI 1938-1352 J9 J REHABIL RES DEV JI J. Rehabil. Res. Dev. PY 2014 VL 51 IS 3 BP 363 EP 375 DI 10.1682/JRRD.2013.05.0115 PG 13 WC Rehabilitation SC Rehabilitation GA AL5KL UT WOS:000339172400005 PM 25019660 ER PT S AU Jakobs, TC AF Jakobs, Tatjana C. BE Bakota, L Brandt, R TI Analysis of Morphology and Structural Remodeling of Astrocytes SO LASER SCANNING MICROSCOPY AND QUANTITATIVE IMAGE ANALYSIS OF NEURONAL TISSUE SE Neuromethods LA English DT Article; Book Chapter DE Astrocyte remodeling; Single-cell labeling techniques; Reactive astrocytes; Protoplasmic astrocytes; Fibrous astrocytes ID CENTRAL-NERVOUS-SYSTEM; RETINAL GANGLION-CELLS; RAT OPTIC-NERVE; TRANSGENIC MICE; QUANTITATIVE-ANALYSIS; REACTIVE ASTROCYTES; RECEPTOR SUBUNITS; VISUAL-CORTEX; GENE GUN; BRAIN AB For a long time, the morphological study of astrocytes relied on immunostaining for astrocyte markers like GFAP, vimentin, or S100 beta. Though powerful, this method has several drawbacks, most notably that it does not reveal the full extent of individual cells. Modern labeling techniques and the availability of transgenic mice have circumvented this difficulty. Single-cell labeling techniques have revealed normal and reactive astrocytes in their true three-dimensional structure. It has furthermore become clear that astrocyte reactivity is a complex process that depends on the type of astrocyte, the nature of the injury, and the time that has passed since injury. Protoplasmic astrocytes tile the brain parenchyma and maintain their domain organization after at least some types of injury. Fibrous astrocytes do not tile and show a biphasic reaction to injury: a first phase of process retraction followed by a second phase of re-extension of processes. C1 Harvard Univ, Sch Med, Dept Ophthalmol, Massachusetts Eye & Ear Infirm, Boston, MA 02115 USA. RP Jakobs, TC (reprint author), Harvard Univ, Sch Med, Dept Ophthalmol, Massachusetts Eye & Ear Infirm, Boston, MA 02115 USA. NR 69 TC 0 Z9 0 U1 1 U2 4 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DR, STE 208, TOTOWA, NJ 07512-1165 USA SN 0893-2336 BN 978-1-4939-0381-8; 978-1-4939-0380-1 J9 NEUROMETHODS JI Neuromethods PY 2014 VL 87 BP 129 EP 143 DI 10.1007/978-1-4939-0381-8_6 D2 10.1007/978-1-4939-0381-8 PG 15 WC Neurosciences; Neuroimaging SC Neurosciences & Neurology GA BA6DV UT WOS:000337107800008 ER PT S AU Rakvongthai, Y Worstell, W El Fakhri, G Ouyang, J AF Rakvongthai, Yothin Worstell, William El Fakhri, Georges Ouyang, Jinsong BE Whiting, BR Hoeschen, C Kontos, D TI A spectral CT technique using balanced K-edge filter set SO MEDICAL IMAGING 2014: PHYSICS OF MEDICAL IMAGING SE Proceedings of SPIE LA English DT Proceedings Paper CT Medical Imaging - Physics of Medical Imaging CY FEB 17-20, 2014 CL San Diego, CA SP Soc Photo Opt Instrumentat Engn, Modus Med Devices Inc, XIFIN Inc, Ventana Med Systems Inc, Intrace Med, Caresteam, GE Healthcare DE Spectral CT; multi-energy CT; K-edge filtering; quasi-monoenergetic x-ray; balanced filters; Ross filters; Ross spectrometer ID COMPUTED-TOMOGRAPHY; DETECTORS AB In this work, we propose a novel spectral computed tomography (CT) approach that combines a conventional CT scanner with a Ross spectrometer to obtain quasi-monoenergetic measurements. The Ross spectrometer, which is a generalization of a Ross filter pair, is a set of balanced K-edge filters whose thicknesses are such that the transmitted spectra through any two filters are nearly identical except in the energy band between their respective K-edges. The proposed approach is based on these specially designed filters, which are used to synthesize a set of quasi-monoenergetic sinograms whose reconstruction yields energy-dependent attenuation coefficient (mu(E)) images. In this way, we are able to collect data using conventional CT data acquisition electronics, then to synthesize spectral CT datasets with highly stable, rate-independent energy bin boundaries. This approach avoids the chromatic distortion due to event pile-up which can cause difficulties with single photon spectrometry-based methods. To validate our Ross Spectrometer CT concept, we performed phantom studies and acquired data with a balanced filter set consisting of thin foils of silver, tin, cerium, dysprosium and tungsten. For each energy bin, a synthesized quasi-monoenergetic CT image was reconstructed using the filtered back projection (FBP) algorithm operating on the logarithmic ratio of corresponding energy-resolved intensity and blank sinogram pairs. The reconstructed attenuation coefficients showed satisfactorily good agreement with NIST reference values of mu(E) for water. The proposed spectral CT technique is potentially feasible and holds promise to provide a more accurate and cost-effective alternative to single-photon counting spectral CT techniques. C1 [Rakvongthai, Yothin; Worstell, William; El Fakhri, Georges; Ouyang, Jinsong] Massachusetts Gen Hosp, Div Nucl Med & Mol Imaging, Ctr Adv Med Imaging Sci, Boston, MA 02114 USA. RP Rakvongthai, Y (reprint author), Massachusetts Gen Hosp, Div Nucl Med & Mol Imaging, Ctr Adv Med Imaging Sci, 55 Fruit St, Boston, MA 02114 USA. EM ouyang.jinsong@mgh.harvard.edu NR 13 TC 0 Z9 0 U1 0 U2 5 PU SPIE-INT SOC OPTICAL ENGINEERING PI BELLINGHAM PA 1000 20TH ST, PO BOX 10, BELLINGHAM, WA 98227-0010 USA SN 0277-786X BN 978-0-8194-9826-7 J9 PROC SPIE PY 2014 VL 9033 AR 90335M DI 10.1117/12.2043747 PG 6 WC Optics; Physics, Applied; Radiology, Nuclear Medicine & Medical Imaging SC Optics; Physics; Radiology, Nuclear Medicine & Medical Imaging GA BA8VD UT WOS:000338775800189 ER PT J AU Kalia, A Hopkins, R Jin, D Yazzolino, L Verma, S Merabet, L Phillips, F Sinha, P AF Kalia, Amy Hopkins, Rose Jin, David Yazzolino, Lindsay Verma, Svena Merabet, Lotfi Phillips, Flip Sinha, Pawan TI Perception of Tactile Graphics: Embossings Versus Cutouts SO MULTISENSORY RESEARCH LA English DT Article DE Shape; haptics; low vision; blindnesss; object recognition ID PICTURE-RECOGNITION; PATTERN PERCEPTION; BLIND; IDENTIFICATION; OBJECTS AB Graphical information, such as illustrations, graphs, and diagrams, are an essential complement to text for conveying knowledge about the world. Although graphics can be communicated well via the visual modality, conveying this information via touch has proven to be challenging. The lack of easily comprehensible tactile graphics poses a problem for the blind. In this paper, we advance a hypothesis for the limited effectiveness of tactile graphics. The hypothesis contends that conventional graphics that rely upon embossings on two-dimensional surfaces do not allow the deployment of tactile exploratory procedures that are crucial for assessing global shape. Besides potentially accounting for some of the shortcomings of current approaches, this hypothesis also serves a prescriptive purpose by suggesting a different strategy for conveying graphical information via touch, one based on cutouts. We describe experiments demonstrating the greater effectiveness of this approach for conveying shape and identity information. These results hold the potential for creating more comprehensible tactile drawings for the visually impaired while also providing insights into shape estimation processes in the tactile modality. C1 [Kalia, Amy; Jin, David; Sinha, Pawan] MIT, Dept Brain & Cognit Sci, Cambridge, MA 02139 USA. [Hopkins, Rose; Phillips, Flip] Skidmore Coll, Dept Psychol, Saratoga Springs, NY 12866 USA. [Yazzolino, Lindsay; Merabet, Lotfi] Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Boston, MA USA. [Verma, Svena] Acton Boxborough Reg High Sch, Acton, MA USA. RP Kalia, A (reprint author), MIT, Dept Brain & Cognit Sci, 77 Massachusetts Ave, Cambridge, MA 02139 USA. EM akalia@mit.edu FU James McDonnell Foundation; National Eye Institute [F32EY019622, R01EY020517] FX This study was supported by grants from the James McDonnell Foundation (PS) and the National Eye Institute (F32EY019622 to AK, R01EY020517 to PS). NR 15 TC 1 Z9 1 U1 0 U2 2 PU BRILL ACADEMIC PUBLISHERS PI LEIDEN PA PLANTIJNSTRAAT 2, P O BOX 9000, 2300 PA LEIDEN, NETHERLANDS SN 2213-4794 EI 2213-4808 J9 MULTISENS RES JI Multisens. Res. PY 2014 VL 27 IS 2 BP 111 EP 125 DI 10.1163/22134808-00002450 PG 15 WC Biophysics; Psychology; Psychology, Experimental SC Biophysics; Psychology GA AL4TH UT WOS:000339127200002 PM 25296474 ER PT J AU Woodard, LD Landrum, CR Amspoker, AB Ramsey, D Naik, AD AF Woodard, LeChauncy D. Landrum, Cassie R. Amspoker, Amber B. Ramsey, David Naik, Aanand D. TI Interaction between functional health literacy, patient activation, and glycemic control SO PATIENT PREFERENCE AND ADHERENCE LA English DT Article DE health literacy; diabetes mellitus; self-care; veterans ID DIABETES SELF-MANAGEMENT; SCREENING QUESTIONS; IDENTIFY PATIENTS; OLDER PATIENTS; MELLITUS; OUTCOMES; CARE; COMMUNICATION; ASSOCIATION; VALIDATION AB Background: Functional health literacy (FHL) and patient activation can impact diabetes control through enhanced diabetes self-management. Less is known about the combined effect of these characteristics on diabetes outcomes. Using brief, validated measures, we examined the interaction between FHL and patient activation in predicting glycosylated hemoglobin (HbA(1c)) control among a cohort of multimorbid diabetic patients. Methods: We administered a survey via mail to 387 diabetic patients with coexisting hypertension and ischemic heart disease who received outpatient care at one regional VA medical center between November 2010 and December 2010. We identified patients with the study conditions using the International Classification of Diseases-Ninth Revision-Clinical Modification (ICD-9-CM) diagnoses codes and Current Procedure Terminology (CPT) -procedures codes. Surveys were returned by 195 (50.4%) patients. We determined patient activation levels based on participant responses to the 13-item Patient Activation Measure and FHL levels using the single-item screening question, "How confident are you filling out medical forms by yourself?" We reviewed patient medical records to assess glycemic control. We used multiple logistic regression to examine whether activation and FHL were individually or jointly related to HbA(1c) control. Results: Neither patient activation nor FHL was independently related to glycemic control in the unadjusted main effects model; however, the interaction between the two was significantly associated with glycemic control (odds ratio 1.05 [95% confidence interval 1.01-1.09], P=0.02). Controlling for age, illness burden, and number of primary care visits, the combined effect of these measures on glycemic control remained significant (odds ratio 1.05 [95% confidence interval 1.01-1.09], P=0.02). Conclusion: The interaction between FHL and patient activation is associated with HbA1c control beyond the independent effects of these parameters alone. A personalized approach to diabetes management incorporating these characteristics may increase patient-centered care and improve outcomes for patients with diabetes. C1 Baylor Coll Med, Michael E DeBakey Vet Affairs Med Ctr, Ctr Innovat Qual Effectiveness & Safety, Vet Affairs Hlth Serv Res & Dev, Houston, TX 77030 USA. Baylor Coll Med, Dept Med, Sect Hlth Serv Res, Houston, TX 77030 USA. RP Woodard, LD (reprint author), MEDVAMC 152,2002 Holcombe Blvd, Houston, TX 77030 USA. EM lwoodard@bcm.edu FU Veterans Affairs Health Services Research and Development (VA HSRD) [PPO 09-316]; Houston VA HSR&D Center for Innovations in Quality, Effectiveness, and Safety [CIN13-413] FX This work was supported by a Veterans Affairs Health Services Research and Development (VA HSR&D) pilot grant PPO 09-316 (LDW) and the Houston VA HSR&D Center for Innovations in Quality, Effectiveness, and Safety (CIN13-413). The authors are grateful to Sylvia Hysong for assistance with development of the survey, and to Tracy Urech and Omolola Adepoju, all of the Houston VA HSR&D Center for Innovations in Quality, Effectiveness and Safety for assistance with manuscript review. NR 35 TC 4 Z9 4 U1 2 U2 9 PU DOVE MEDICAL PRESS LTD PI ALBANY PA PO BOX 300-008, ALBANY, AUCKLAND 0752, NEW ZEALAND SN 1177-889X J9 PATIENT PREFER ADHER JI Patient Prefer. Adherence PY 2014 VL 8 BP 1019 EP 1024 DI 10.2147/PPA.S63954 PG 6 WC Medicine, General & Internal SC General & Internal Medicine GA AL8LX UT WOS:000339391500001 PM 25092966 ER PT J AU Belaise, C Gatti, A Chouinard, VA Chouinard, G AF Belaise, Carlotta Gatti, Alessia Chouinard, Virginie-Anne Chouinard, Guy TI Persistent Postwithdrawal Disorders Induced by Paroxetine, a Selective Serotonin Reuptake Inhibitor, and Treated with Specific Cognitive Behavioral Therapy SO PSYCHOTHERAPY AND PSYCHOSOMATICS LA English DT Letter ID DISCONTINUATION; ANXIETY C1 [Belaise, Carlotta; Gatti, Alessia] Univ Bologna, Dept Psychol, IT-40127 Bologna, Italy. [Chouinard, Virginie-Anne] Harvard Univ, Massachusetts Gen Hosp, Sch Med, McLean Adult Psychiat Residency Training Program, Boston, MA USA. [Chouinard, Guy] McGill Univ, Dept Psychiat, Montreal, PQ, Canada. [Chouinard, Guy] McGill Univ, Dept Med, Montreal, PQ, Canada. [Chouinard, Guy] Univ Montreal, Res Ctr, Univ Mental Hlth Inst Montreal, Montreal, PQ, Canada. RP Belaise, C (reprint author), Univ Bologna, Dept Psychol, Viale Berti Pichat 5, IT-40127 Bologna, Italy. EM carlotta.belaise@unibo.it NR 10 TC 10 Z9 10 U1 0 U2 0 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0033-3190 EI 1423-0348 J9 PSYCHOTHER PSYCHOSOM JI Psychother. Psychosom. PY 2014 VL 83 IS 4 BP 247 EP 248 DI 10.1159/000362317 PG 2 WC Psychiatry; Psychology SC Psychiatry; Psychology GA AL2SY UT WOS:000338976900006 PM 24968739 ER PT J AU Triant, VA AF Triant, Virginia A. TI Epidemiology of Coronary Heart Disease in Patients With Human Immunodeficiency Virus SO REVIEWS IN CARDIOVASCULAR MEDICINE LA English DT Article DE Human immunodeficiency virus; Coronary heart disease; Antiretroviral therapy; Risk factors; Cardiovascular disease; Inflammation ID ACUTE MYOCARDIAL-INFARCTION; HIV-INFECTED INDIVIDUALS; POPULATION-BASED COHORT; HEALTH-CARE-SYSTEM; ANTIRETROVIRAL THERAPY; CARDIOVASCULAR-DISEASE; INCREASED RISK; CEREBROVASCULAR EVENTS; HEPATITIS-C; DRUGS AB As a growing number of patients infected with human immunodeficiency virus (HIV) have access to antiretroviral therapy and achieve virologic suppression, the focus of clinical care is shifting from treating the infectious complications of advanced immunodeficiency to managing and preventing chronic disease. The aging of the HIV-positive population and increased rates of chronic disease complications in the setting of HIV infection have increased the impact of noncommunicable diseases such as coronary heart disease (CHD). The effect of HIV on CHD is independent of traditional cardiovascular risk factors and antiretroviral medications and is likely due in part to the chronic inflammation and immune activation underlying HIV infection. This article describes the current state of epidemiologic knowledge on CHD in HIV infection. It highlights key studies in the field and summarizes epidemiologic data with respect to traditional and novel CHD risk factors, specialized clinical subgroups, and broader cardiovascular outcomes. C1 [Triant, Virginia A.] Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA. [Triant, Virginia A.] Massachusetts Gen Hosp, Div Gen Med, Boston, MA 02114 USA. [Triant, Virginia A.] Harvard Univ, Sch Med, Boston, MA USA. RP Triant, VA (reprint author), Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA. FU Gilead Sciences, Inc. FX Publication of this article was made possible by generous support from Gilead Sciences, Inc. NR 35 TC 11 Z9 11 U1 0 U2 4 PU MEDREVIEWS, LLC PI NEW YORK PA 1370 BROADWAY, STE 900, NEW YORK, NY 10018 USA SN 1530-6550 J9 REV CARDIOVASC MED JI Rev. Cardiovasc. Med. PY 2014 VL 15 SU 1 BP S1 EP S8 PG 8 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA AL6GQ UT WOS:000339231000001 PM 24987859 ER PT S AU Pittet, MJ Nahrendorf, M Swirski, FK AF Pittet, Mikael J. Nahrendorf, Matthias Swirski, Filip K. BE Rose, NR TI The journey from stem cell to macrophage SO YEAR IN IMMUNOLOGY: MYELOID CELLS AND INFLAMMATION SE Annals of the New York Academy of Sciences LA English DT Article; Book Chapter DE macrophage; monocyte; hematopoesis ID TISSUE-RESIDENT MACROPHAGES; CD11B(+) DENDRITIC CELLS; INNATE IMMUNE-SYSTEM; STIMULATING FACTOR-I; BONE-MARROW NICHE; HEMATOPOIETIC STEM; INFLAMMATORY MONOCYTES; TRANSCRIPTION FACTOR; STEADY-STATE; ATHEROSCLEROTIC LESIONS AB Essential protectors against infection and injury, macrophages can also contribute to many common and fatal diseases. Here, we discuss the mechanisms that control different types of macrophage activities in mice. We follow the cells' maturational pathways over time and space and elaborate on events that influence the type of macrophage eventually settling a particular destination. The nature of the precursor cells, developmental niches, tissues, environmental cues, and other connecting processes appear to contribute to the identity of macrophage type. Together, the spatial and developmental relationships of macrophages compose a topo-ontogenic map that can guide our understanding of their biology. C1 Massachusetts Gen Hosp, Ctr Syst Biol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Pittet, MJ (reprint author), Massachusetts Gen Hosp, Richard B Simches Res Ctr, Ctr Syst Biol, 185 Cambridge St, Boston, MA 02114 USA. EM mpittet@mgh.harvard.edu; mnahrendorf@mgh.harvard.edu; fwsirski@mgh.harvard.edu FU US National Institutes of Health (NIH) [R01-AI084880, P50-CA086355, U54-CA126515, R01-HL096576, R01-HL095629, R01-HL095612, R56-AI104695] FX This work was supported in part by US National Institutes of Health (NIH) Grants R01-AI084880, P50-CA086355, and U54-CA126515 (to M.J.P.); R01-HL096576 and R01-HL095629 (to M.N.); and R01-HL095612 and R56-AI104695 (to F.K.S.). NR 150 TC 13 Z9 13 U1 1 U2 16 PU BLACKWELL SCIENCE PUBL PI OXFORD PA OSNEY MEAD, OXFORD OX2 0EL, ENGLAND SN 0077-8923 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 2014 VL 1319 BP 1 EP 18 DI 10.1111/nyas.12393 PG 18 WC Immunology SC Immunology GA BA8GP UT WOS:000338098700002 PM 24673186 ER PT J AU Breyer, BN Cohen, BE Bertenthal, D Rosen, RC Neylan, TC Seal, KH AF Breyer, Benjamin N. Cohen, Beth E. Bertenthal, Daniel Rosen, Raymond C. Neylan, Thomas C. Seal, Karen H. TI Sexual Dysfunction in Male Iraq and Afghanistan War Veterans: Association with Posttraumatic Stress Disorder and Other Combat-Related Mental Health Disorders: A Population-Based Cohort Study SO JOURNAL OF SEXUAL MEDICINE LA English DT Article DE Combat; Posttraumatic Stress Disorder; Sexual Dysfunction; Military Service ID RISK; PTSD; CARE; DIAGNOSES; PREVALENCE; OPERATION; SYMPTOMS; SERVICES AB Introduction Mental health disorders are prevalent in the United States, Iraq, and Afghanistan war veterans. Mental illness, including posttraumatic stress disorder (PTSD) with or without psychiatric medications, can increase the risk for male sexual dysfunction, threatening quality of life. Aims We sought to determine the prevalence and correlates of sexual dysfunction among male Iraq and Afghanistan veterans. Methods We performed a retrospective cohort study of 405,275 male Iraq and Afghanistan veterans who were new users of U.S. Department of Veterans Affairs healthcare from October 7, 2001 to September 30, 2009 and had 2-year follow-up. Main Outcome Measures We determined the independent association of mental health diagnoses and sexual dysfunction after adjusting for sociodemographic and military service characteristics, comorbidities, and medications. Results Veterans with PTSD were more likely to have a sexual dysfunction diagnosis, be prescribed medications for sexual dysfunction, or both (10.6%), compared with veterans having a mental diagnosis other than PTSD (7.2%), or no mental health diagnosis (2.3%). In a fully adjusted model, PTSD increased the risk of sexual dysfunction by more than threefold (adjusted risk ratio = 3.61, 95% CI = 3.48-3.75). Veterans with mental health disorders, particularly PTSD, were at the highest risk of sexual dysfunction when prescribed psychiatric medications (adjusted risk ratio = 4.59, 95% CI = 4.41-4.77). Conclusions Among U.S. combat veterans, mental health disorders, particularly PTSD, increased the risk of sexual dysfunction independent of the use of psychiatric medications. C1 [Breyer, Benjamin N.; Rosen, Raymond C.] Univ Calif San Francisco, Dept Urol, San Francisco, CA 94143 USA. [Cohen, Beth E.; Seal, Karen H.] Univ Calif San Francisco, Dept Med, San Francisco, CA 94143 USA. [Cohen, Beth E.; Neylan, Thomas C.; Seal, Karen H.] Univ Calif San Francisco, Dept Psychiat, San Francisco, CA 94143 USA. [Cohen, Beth E.; Bertenthal, Daniel; Neylan, Thomas C.; Seal, Karen H.] San Francisco VA Med Ctr, San Francisco, CA USA. [Rosen, Raymond C.] New England Res Inst, Watertown, MA 02172 USA. RP Breyer, BN (reprint author), Univ Calif San Francisco, Dept Urol, 400 Parnassus Ave,A610, San Francisco, CA 94143 USA. EM bbreyer@urology.ucsf.edu FU NIDDK NIH HHS [K12 DK083021] NR 36 TC 8 Z9 8 U1 4 U2 4 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 JAN PY 2014 VL 11 IS 1 BP 75 EP 83 DI 10.1111/jsm.12201 PG 9 WC Urology & Nephrology SC Urology & Nephrology GA AE9ML UT WOS:000334331800009 PM 23679562 ER PT J AU De Berardinis, B Magrini, L Zampini, G Zancla, B Salerno, G Cardelli, P Di Stasio, E Gaggin, HK Belcher, A Parry, BA Nagurney, JT Januzzi, JL Di Somma, S AF De Berardinis, Benedetta Magrini, Laura Zampini, Giorgio Zancla, Benedetta Salerno, Gerardo Cardelli, Patrizia Di Stasio, Enrico Gaggin, Hanna K. Belcher, Arianna Parry, Blair A. Nagurney, John T. Januzzi, James L., Jr. Di Somma, Salvatore TI Usefulness of Combining Galectin-3 and BIVA Assessments in Predicting Short- and Long-Term Events in Patients Admitted for Acute Heart Failure SO BIOMED RESEARCH INTERNATIONAL LA English DT Article ID MYOCARDIAL FIBROSIS; NATRIURETIC PEPTIDE; EUROPEAN-SOCIETY; PROGNOSTIC VALUE; HF-ACTION; ASSOCIATION; BIOMARKERS; COACH AB Introduction. Acute heart failure (AHF) is associated with a higher risk for the occurrence of rehospitalization and death. Galectin-3 (GAL3) is elevated in AHF patients and is an indicator in predicting short-term mortality. The total body water using bioimpedance vector analysis (BIVA) is able to identify mortality within AHF patients. The aim of this study was to evaluate the short- and long-term predictive value of GAL3, BIVA, and the combination of both in AHF patients in Emergency Department (ED). Methods. 205 ED patients with AHF were evaluated by testing for B type natriuretic peptide (BNP) and GAL3. The primary endpoint was death and rehospitalization at 30, 60, 90, and 180 days and 12 and 18 months. AHF patients were evaluated at the moment of ED arrival with clinical judgment and GAL3 and BIVA measurement. Results. GAL3 level was significantly higher in patients >71 years old, and with eGFR < 30 cc/min. The area under the curve (AUC) of GAL3 + BIVA, GAL3 and BIVA for death and rehospitalization both when considered in total and when considered serially for the follow-up period showed that the combination has a better prognostic value. Kaplan-Meier survival curve for GAL3 values >17.8 ng/mL shows significant survival difference. At multivariate Cox regression analysis GAL3 is an independent variable to predict death + rehospitalization with a value of 32.24 ng/mL at 30 days (P < 0.005). Conclusion. In patients admitted for AHF an early assessment of GAL3 and BIVA seems to be useful in identifying patients at high risk for death and rehospitalization at short and long term. Combining the biomarker and the device could be of great utility since they monitor the severity of two pathophysiological different mechanisms: heart fibrosis and fluid overload C1 [De Berardinis, Benedetta; Magrini, Laura; Zampini, Giorgio; Zancla, Benedetta; Di Somma, Salvatore] Sapienza Univ Rome, St Andreas Hosp, Dept Med Surg Sci & Translat Med, I-00189 Rome, Italy. [Salerno, Gerardo; Cardelli, Patrizia] Sapienza Univ Rome, St Andreas Hosp, Clin & Mol Med Dept, I-00189 Rome, Italy. [Di Stasio, Enrico] Univ Cattolica Sacro Cuore, Inst Biochem & Clin Biochem, I-00168 Rome, Italy. [Gaggin, Hanna K.; Belcher, Arianna; Januzzi, James L., Jr.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. [Parry, Blair A.; Nagurney, John T.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Emergency Med, Boston, MA 02114 USA. RP Di Somma, S (reprint author), Sapienza Univ Rome, St Andreas Hosp, Dept Med Surg Sci & Translat Med, Via Grottarossa 1035-1039, I-00189 Rome, Italy. EM salvatore.disomma@uniroma1.it NR 31 TC 6 Z9 6 U1 0 U2 1 PU HINDAWI PUBLISHING CORPORATION PI NEW YORK PA 410 PARK AVENUE, 15TH FLOOR, #287 PMB, NEW YORK, NY 10022 USA SN 2314-6133 EI 2314-6141 J9 BIOMED RES INT JI Biomed Res. Int. PY 2014 AR 983098 DI 10.1155/2014/983098 PG 10 WC Biotechnology & Applied Microbiology; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Research & Experimental Medicine GA AL1KL UT WOS:000338884200001 ER PT J AU Ojeda, M Ding, D AF Ojeda, Manoela Ding, Dan TI Temporal Parameters Estimation for Wheelchair Propulsion Using Wearable Sensors SO BIOMED RESEARCH INTERNATIONAL LA English DT Article ID SPINAL-CORD-INJURY; CARPAL-TUNNEL-SYNDROME; UPPER EXTREMITY PAIN; SHOULDER PAIN; LONG-TERM; ACTIVITY MONITOR; USERS; BIOMECHANICS; PARAPLEGIA; VALIDATION AB Due to lower limb paralysis, individuals with spinal cord injury (SCI) rely on their upper limbs for mobility. The prevalence of upper extremity pain and injury is high among this population. We evaluated the performance of three triaxis accelerometers placed on the upper arm, wrist, and under the wheelchair, to estimate temporal parameters of wheelchair propulsion. Twenty-six participants with SCI were asked to push their wheelchair equipped with a SMART(Wheel). The estimated stroke number was compared with the criterion from video observations and the estimated push frequency was compared with the criterion from the SMARTWheel. Mean absolute errors (MAE) and mean absolute percentage of error (MAPE) were calculated. Intraclass correlation coefficients and Bland-Altman plots were used to assess the agreement. Results showed reasonable accuracies especially using the accelerometer placed on the upper arm where the MAPE was 8.0% for stroke number and 12.9% for push frequency. The ICC was 0.994 for stroke number and 0.916 for push frequency. The wrist and seat accelerometer showed lower accuracy with a MAPE for the stroke number of 10.8% and 13.4% and ICC of 0.990 and 0.984, respectively. Results suggested that accelerometers could be an option for monitoring temporal parameters of wheelchair propulsion. C1 [Ojeda, Manoela; Ding, Dan] VA Pittsburgh Healthcare Syst, Pittsburgh, PA 15206 USA. RP Ojeda, M (reprint author), VA Pittsburgh Healthcare Syst, 6425 Penn Ave,Suite 400, Pittsburgh, PA 15206 USA. EM manola.ojeda@gmail.com FU National Institute of Disability and Rehabilitation Research's Rehabilitation Engineering Research Center on Spinal Cord Injury [H133E070024]; Human Engineering Research Laboratories, VA Pittsburgh Healthcare System FX The authors gratefully acknowledge that this research was supported by the National Institute of Disability and Rehabilitation Research's Rehabilitation Engineering Research Center on Spinal Cord Injury (no. H133E070024). The work was also supported by the Human Engineering Research Laboratories, VA Pittsburgh Healthcare System. The contents do not represent the views of the Department of Veterans Affairs or the United States Government. They also would like to acknowledge the contributions of Jui-Te Lin, Vijeta Parvatikar, and Annmarie Kelleher. NR 37 TC 1 Z9 1 U1 2 U2 3 PU HINDAWI PUBLISHING CORPORATION PI NEW YORK PA 410 PARK AVENUE, 15TH FLOOR, #287 PMB, NEW YORK, NY 10022 USA SN 2314-6133 EI 2314-6141 J9 BIOMED RES INT JI Biomed Res. Int. PY 2014 AR 645284 DI 10.1155/2014/645284 PG 10 WC Biotechnology & Applied Microbiology; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Research & Experimental Medicine GA AL1ET UT WOS:000338869300001 ER PT J AU Lipinski, B Pretorius, E AF Lipinski, Boguslaw Pretorius, Etheresia TI Iron-induced fibrin formation may explain vascular pathology in Alzheimer's disease SO FOLIA NEUROPATHOLOGICA LA English DT Letter C1 [Lipinski, Boguslaw] Harvard Univ, Sch Med, Joslin Diabet Ctr, Boston, MA 02115 USA. [Pretorius, Etheresia] Univ Pretoria, Fac Hlth Sci, ZA-0007 Arcadia, South Africa. 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 RI Pretorius, Etheresia/P-2978-2016 OI Pretorius, Etheresia/0000-0002-9108-2384 NR 6 TC 2 Z9 2 U1 0 U2 1 PU TERMEDIA PUBLISHING HOUSE LTD PI POZNAN PA WENEDOW ST 9-1, POZNAN, 61-614, POLAND SN 1641-4640 EI 1509-572X J9 FOLIA NEUROPATHOL JI Folia Neuropathol. PY 2014 VL 52 IS 2 BP 205 EP 205 DI 10.5114/fn.2014.43792 PG 1 WC Neurosciences; Pathology SC Neurosciences & Neurology; Pathology GA AL0GE UT WOS:000338804600011 PM 25118906 ER PT S AU O'Dell, WG Govindarajan, ST Salgia, A Hegde, S Prabhakaran, S Finol, EA White, RJ AF O'Dell, Walter G. Govindarajan, Sindhuja Tirumalai Salgia, Ankit Hegde, Satyanarayan Prabhakaran, Sreekala Finol, Ender A. White, R. James BE Ourselin, S Styner, MA TI Traversing and labeling interconnected vascular tree structures from 3D medical images SO MEDICAL IMAGING 2014: IMAGE PROCESSING SE Proceedings of SPIE LA English DT Proceedings Paper CT Conference on Medical Imaging - Image Processing CY FEB 16-18, 2014 CL San Diego, CA SP SPIE, Modus Med Devices Inc, XIFIN, Inc, Ventana Med Syst Inc, Intrace Med DE image processing; vascular morphology; lung imaging; pulmonary arterial hypertension; tree structure ID PULMONARY ARTERIAL-HYPERTENSION; PLEXIFORM LESIONS; NATIONAL-HEART; LUNG; STIFFNESS; PATHOGENESIS; ENHANCEMENT; MECHANISMS; DISEASES; VESSELS AB Purpose: Detailed characterization of pulmonary vascular anatomy has important applications for the diagnosis and management of a variety of vascular diseases. Prior efforts have emphasized using vessel segmentation to gather information on the number or branches, number of bifurcations, and branch length and volume, but accurate traversal of the vessel tree to identify and repair erroneous interconnections between adjacent branches and neighboring tree structures has not been carefully considered. In this study, we endeavor to develop and implement a successful approach to distinguishing and characterizing individual vascular trees from among a complex intermingling of trees. Methods: We developed strategies and parameters in which the algorithm identifies and repairs false branch inter-tree and intra-tree connections to traverse complicated vessel trees. A series of two-dimensional (2D) virtual datasets with a variety of interconnections were constructed for development, testing, and validation. To demonstrate the approach, a series of real 3D computed tomography (CT) lung datasets were obtained, including that of an anthropomorphic chest phantom; an adult human chest CT; a pediatric patient chest CT; and a micro-CT of an excised rat lung preparation. Results: Our method was correct in all 2D virtual test datasets. For each real 3D CT dataset, the resulting simulated vessel tree structures faithfully depicted the vessel tree structures that were originally extracted from the corresponding lung CT scans. Conclusion: We have developed a comprehensive strategy for traversing and labeling interconnected vascular trees and successfully implemented its application to pulmonary vessels observed using 3D CT images of the chest. C1 [O'Dell, Walter G.] Univ Florida, Coll Med, Dept Radiat Oncol, Gainesville, FL 32611 USA. [Govindarajan, Sindhuja Tirumalai] Massachusetts Gen Hosp, Dept Radiol, Boston, MA USA. [Salgia, Ankit] Johnson & Johnson Ltd, Bombay, Maharashtra, India. [Hegde, Satyanarayan; Prabhakaran, Sreekala] Univ Florida, Coll Med, Dept Pediat, Gainesville, FL USA. [Finol, Ender A.] Univ Texas, Dept Biomed Engn, San Antonio, TX USA. [White, R. James] Univ Rochester Med Ctr, Sch Med & Dent, Pulm Dis & Crit Care, Aab Cardiovascular Inst & Dept Med, Rochester, NY USA. RP O'Dell, WG (reprint author), Univ Florida, Coll Med, Dept Radiat Oncol, Gainesville, FL 32611 USA. RI Finol, Ender/C-4585-2016 OI Finol, Ender/0000-0002-0811-9482 FU UF Health Cancer Center; UF Foundation; AHA Scientist Development Grant [073540N] FX The authors wish to acknowledge the dedicated work of Deborah Haight in preparing the rat micro-CT dataset. Dr. O'Dell is funded by the UF Health Cancer Center and the UF Foundation. Dr. White was supported by an AHA Scientist Development Grant 073540N. The authors would also like to thank Kate Casey-Sawicki and the staff in the Research Office in the UF Department of Radiation Oncology for editing this manuscript and preparing it for publication. NR 39 TC 1 Z9 1 U1 0 U2 1 PU SPIE-INT SOC OPTICAL ENGINEERING PI BELLINGHAM PA 1000 20TH ST, PO BOX 10, BELLINGHAM, WA 98227-0010 USA SN 0277-786X BN 978-0-8194-9827-4 J9 PROC SPIE PY 2014 VL 9034 AR UNSP 90343C DI 10.1117/12.2044140 PG 15 WC Optics; Imaging Science & Photographic Technology; Radiology, Nuclear Medicine & Medical Imaging SC Optics; Imaging Science & Photographic Technology; Radiology, Nuclear Medicine & Medical Imaging GA BA8RZ UT WOS:000338543300114 ER PT S AU Davis, SC Sexton, K Chapman, MS Maytin, E Hasan, T Pogue, BW AF Davis, Scott C. Sexton, Kristian Chapman, Michael Shane Maytin, Edward Hasan, Tayyaba Pogue, Brian W. BE Kessel, DH Hasan, T TI Pulsed light imaging for wide-field dosimetry of photodynamic therapy in the skin SO OPTICAL METHODS FOR TUMOR TREATMENT AND DETECTION: MECHANISMS AND TECHNIQUES IN PHOTODYNAMIC THERAPY XXIII SE Proceedings of SPIE LA English DT Proceedings Paper CT Conference on Optical Methods for Tumor Treatment and Detection - Mechanisms and Techniques in Photodynamic Therapy XXIII CY FEB 01-03, 2014 CL San Francisco, CA SP SPIE DE Photodynamic therapy; dosimetry; fluorescence imaging; protoporphyrin IX; skin cancer ID ORGAN TRANSPLANT RECIPIENTS; DELTA-AMINOLEVULINIC-ACID; ACTINIC KERATOSIS; FLUORESCENCE; CANCER AB Photodynamic therapy using aminoluvelinic acid (ALA) is an FDA-approved treatment for actinic keratoses, pre-cancerous skin lesions which pose a significant risk for immuno-compromised individuals, such as organ transplant recipients. While PDT is generally effective, response rates vary, largely due to variations in the accumulation of the photosensitizer protoporphyrin IX (PpIX) after ALA application. The ability to quantify PpIX production before treatment could facilitate the use of additional interventions to improve outcomes. While many groups have demonstrated the ability to image PpIX in the clinic, these systems generally require darkening the room lights during imaging, which is unpopular with clinicians. We have developed a novel wide-field imaging system based on pulsed excitation and gated acquisition to image photosensitizer activity in the skin. The tissue is illuminated using four pulsed LED's to excite PpIX, and the remitted light acquired with a synchronized ICCD. This approach facilitates real-time background subtraction of ambient light, precluding the need to darken the exam room. Delivering light in short bursts also allows the use of elevated excitation intensity while remaining under the maximum permissible exposure limits, making the modality more sensitive to photosensitizer fluorescence than standard approaches. Images of tissue phantoms indicate system sensitivity down to 250nM PpIX and images of animals demonstrate detection of PpIX fluorescence in vivo under normal room light conditions. C1 [Davis, Scott C.; Sexton, Kristian; Pogue, Brian W.] Dartmouth Coll, Thayer Sch Engn, Hanover, NH 03755 USA. [Chapman, Michael Shane] Dartmouth Hitchcock Med Ctr, Dept Dermatol, Lebanon, NH USA. [Maytin, Edward] Biomed Engn, Cleveland, OH USA. [Hasan, Tayyaba] Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA USA. RP Davis, SC (reprint author), Dartmouth Coll, Thayer Sch Engn, Hanover, NH 03755 USA. EM scott.c.davis@dartmouth.edu; brian.w.pogue@dartmouth.edu FU National Institutes of Health [R01 CA109558, P01 CA084203]; Department of Defense award [W81XWH-09-1-0661] FX This work was funded by the National Institutes of Health grants R01 CA109558 and P01 CA084203, and Department of Defense award W81XWH-09-1-0661. NR 11 TC 0 Z9 0 U1 0 U2 3 PU SPIE-INT SOC OPTICAL ENGINEERING PI BELLINGHAM PA 1000 20TH ST, PO BOX 10, BELLINGHAM, WA 98227-0010 USA SN 0277-786X BN 978-0-8194-9844-1 J9 PROC SPIE PY 2014 VL 8931 AR UNSP 89310W DI 10.1117/12.2040174 PG 6 WC Oncology; Optics; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Optics; Radiology, Nuclear Medicine & Medical Imaging GA BA8OF UT WOS:000338336500011 ER PT S AU DSouza, AV Flynn, BP Gunn, JR Samkoe, KS Anand, S Maytin, EV Hasan, T Pogue, BW AF DSouza, Alisha V. Flynn, Brendan P. Gunn, Jason R. Samkoe, Kimberley S. Anand, Sanjay Maytin, Edward V. Hasan, Tayyaba Pogue, Brian W. BE Kessel, DH Hasan, T TI ALA-PpIX variability quantitatively imaged in A431 epidermoid tumors using in vivo ultrasound fluorescence tomography and ex vivo assay SO OPTICAL METHODS FOR TUMOR TREATMENT AND DETECTION: MECHANISMS AND TECHNIQUES IN PHOTODYNAMIC THERAPY XXIII SE Proceedings of SPIE LA English DT Proceedings Paper CT Conference on Optical Methods for Tumor Treatment and Detection - Mechanisms and Techniques in Photodynamic Therapy XXIII CY FEB 01-03, 2014 CL San Francisco, CA SP SPIE DE Aminolevulinic acid; protoporphyrin IX; ultrasound-guided; fluorescence; carcinoma ID ACID AB Treatment monitoring of Aminolevunilic-acid (ALA) - Photodynamic Therapy (PDT) of basal-cell carcinoma (BCC) calls for superficial and subsurface imaging techniques. While superficial imagers exist for this purpose, their ability to assess PpIX levels in thick lesions is poor; additionally few treatment centers have the capability to measure ALA-induced PpIX production. An area of active research is to improve treatments to deeper and nodular BCCs, because treatment is least effective in these. The goal of this work was to understand the logistics and technical capabilities to quantify PpIX at depths over 1mm, using a novel hybrid ultrasound-guided, fiber-based fluorescence molecular spectroscopic-tomography system. This system utilizes a 633nm excitation laser and detection using filtered spectrometers. Source and detection fibers are collinear so that their imaging plane matches that of ultrasound transducer. Validation with phantoms and tumor-simulating fluorescent inclusions in mice showed sensitivity to fluorophore concentrations as low as 0.025 mu g/ml at 4mm depth from surface, as presented in previous years. Image-guided quantification of ALA-induced PpIX production was completed in subcutaneous xenograft epidermoid cancer tumor model A431 in nude mice. A total of 32 animals were imaged in-vivo, using several time points, including pre-ALA, 4-hours post-ALA, and 24-hours post-ALA administration. On average, PpIX production in tumors increased by over 10-fold, 4-hours post-ALA. Statistical analysis of PpIX fluorescence showed significant difference among all groups; p<0.05. Results were validated by ex-vivo imaging of resected tumors. Details of imaging, analysis and results will be presented to illustrate variability and the potential for imaging these values at depth. C1 [DSouza, Alisha V.; Flynn, Brendan P.; Gunn, Jason R.; Pogue, Brian W.] Dartmouth Coll, Thayer Sch Engn, Hanover, NH 03755 USA. [Samkoe, Kimberley S.; Pogue, Brian W.] Dartmouth Coll, Geisel Sch Med, Dept Surg, Hanover, NH USA. [Anand, Sanjay; Maytin, Edward V.] Cleveland Clin Lerner Res Inst, Dept Biomed Engn, Hanover, NH USA. [Hasan, Tayyaba] Massachusetts Gen Hosp, Harvard Med Sch, Wellman Ctr Photomed, Boston, MA USA. RP DSouza, AV (reprint author), Dartmouth Coll, Thayer Sch Engn, Hanover, NH 03755 USA. FU NIH [P01 CA084203] FX This work was financially supported by NIH research grant P01 CA084203. NR 7 TC 0 Z9 0 U1 0 U2 4 PU SPIE-INT SOC OPTICAL ENGINEERING PI BELLINGHAM PA 1000 20TH ST, PO BOX 10, BELLINGHAM, WA 98227-0010 USA SN 0277-786X BN 978-0-8194-9844-1 J9 PROC SPIE PY 2014 VL 8931 AR UNSP 893114 DI 10.1117/12.2037800 PG 7 WC Oncology; Optics; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Optics; Radiology, Nuclear Medicine & Medical Imaging GA BA8OF UT WOS:000338336500017 ER PT J AU McMullin, RP Wittner, BS Yang, CW Denton-Schneider, BR Hicks, D Singavarapu, R Moulis, S Lee, J Akbari, MR Narod, SA Aldape, KD Steeg, PS Ramaswamy, S Sgroi, DC AF McMullin, Ryan P. Wittner, Ben S. Yang, Chuanwei Denton-Schneider, Benjamin R. Hicks, Daniel Singavarapu, Raj Moulis, Sharon Lee, Jeongeun Akbari, Mohammad R. Narod, Steven A. Aldape, Kenneth D. Steeg, Patricia S. Ramaswamy, Sridhar Sgroi, Dennis C. TI A BRCA1 deficient-like signature is enriched in breast cancer brain metastases and predicts DNA damage-induced poly (ADP-ribose) polymerase inhibitor sensitivity SO BREAST CANCER RESEARCH LA English DT Article ID CENTRAL-NERVOUS-SYSTEM; GENE-EXPRESSION; MUTATION CARRIERS; PARP INHIBITOR; 1ST RECURRENCE; TEMOZOLOMIDE; SURVIVAL; REPAIR; IMMUNOPHENOTYPE; TRASTUZUMAB AB Introduction: There is an unmet clinical need for biomarkers to identify breast cancer patients at an increased risk of developing brain metastases. The objective is to identify gene signatures and biological pathways associated with human epidermal growth factor receptor 2-positive (HER2+) brain metastasis. Methods: We combined laser capture microdissection and gene expression microarrays to analyze malignant epithelium from HER2+ breast cancer brain metastases with that from HER2+ nonmetastatic primary tumors. Differential gene expression was performed including gene set enrichment analysis (GSEA) using publicly available breast cancer gene expression data sets. Results: In a cohort of HER2+ breast cancer brain metastases, we identified a gene expression signature that anti-correlates with overexpression of BRCA1. Sequence analysis of the HER2+ brain metastases revealed no pathogenic mutations of BRCA1, and therefore the aforementioned signature was designated BRCA1 Deficient-Like (BD-L). Evaluation of an independent cohort of breast cancer metastases demonstrated that BD-L values are significantly higher in brain metastases as compared to other metastatic sites. Although the BD-L signature is present in all subtypes of breast cancer, it is significantly higher in BRCA1 mutant primary tumors as compared with sporadic breast tumors. Additionally, BD-L signature values are significantly higher in HER2-/ER- primary tumors as compared with HER2+/ER+ and HER2-/ER+ tumors. The BD-L signature correlates with breast cancer cell line pharmacologic response to a combination of poly (ADP-ribose) polymerase (PARP) inhibitor and temozolomide, and the signature outperformed four published gene signatures of BRCA1/2 deficiency. Conclusions: A BD-L signature is enriched in HER2+ breast cancer brain metastases without pathogenic BRCA1 mutations. Unexpectedly, elevated BD-L values are found in a subset of primary tumors across all breast cancer subtypes. Evaluation of pharmacological sensitivity in breast cancer cell lines representing all breast cancer subtypes suggests the BD-L signature may serve as a biomarker to identify sporadic breast cancer patients who might benefit from a therapeutic combination of PARP inhibitor and temozolomide and may be indicative of a dysfunctional BRCA1-associated pathway. C1 [McMullin, Ryan P.; Yang, Chuanwei; Denton-Schneider, Benjamin R.; Hicks, Daniel; Singavarapu, Raj; Moulis, Sharon; Lee, Jeongeun; Sgroi, Dennis C.] Massachusetts Gen Hosp, Mol Pathol Unit, Charlestown, MA 02129 USA. [McMullin, Ryan P.; Wittner, Ben S.; Yang, Chuanwei; Moulis, Sharon; Lee, Jeongeun; Ramaswamy, Sridhar; Sgroi, Dennis C.] Massachusetts Gen Hosp, Ctr Canc Res, Charlestown, MA 02129 USA. [McMullin, Ryan P.; Yang, Chuanwei; Moulis, Sharon; Lee, Jeongeun; Sgroi, Dennis C.] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. [Wittner, Ben S.; Ramaswamy, Sridhar] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. [Akbari, Mohammad R.; Narod, Steven A.] Womens Coll Hosp, Res Inst, Familial Breast Canc Res, Dept Neurosurg, Toronto, ON M5G 1N8, Canada. [Aldape, Kenneth D.] Texas Med Ctr, MD Anderson Canc Ctr, Houston, TX 77021 USA. [Steeg, Patricia S.] NCI, Womens Canc Sect, Mol Pharmacol Lab, Bethesda, MD 20892 USA. RP Sgroi, DC (reprint author), Massachusetts Gen Hosp, Mol Pathol Unit, 73 High St, Charlestown, MA 02129 USA. EM dsgroi@partners.org FU Department of Defense Breast Cancer Research Program Center of Excellence Grant [W81XW1T-06-2-0033]; Avon Foundation; Susan G. Komen for the Cure; NIH/National Cancer Institute FX Funding for the authors and project were provided through Department of Defense Breast Cancer Research Program Center of Excellence Grant W81XW1T-06-2-0033 (to DCS, PSS and KDA), the Avon Foundation (to DCS), the Susan G. Komen for the Cure (to DCS) and NIH/National Cancer Institute (to DCS). NR 49 TC 10 Z9 10 U1 1 U2 4 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1465-542X EI 1465-5411 J9 BREAST CANCER RES JI Breast Cancer Res. PY 2014 VL 16 IS 2 AR R25 DI 10.1186/bcr3625 PG 10 WC Oncology SC Oncology GA AL2YF UT WOS:000338990900010 PM 24625110 ER PT J AU Jackevicius, CA Le, J Nazer, L Hess, K Wang, J Law, AV AF Jackevicius, Cynthia A. Le, Jennifer Nazer, Lama Hess, Karl Wang, Jeffrey Law, Anandi V. TI A Formal Mentorship Program for Faculty Development SO AMERICAN JOURNAL OF PHARMACEUTICAL EDUCATION LA English DT Article DE mentorship; mentor; protege; pharmacy; faculty ID MENTORING MATTER; METAANALYSIS; MENTEES AB Objective. To describe the development, implementation, and evaluation of a formal mentorship program at a college of pharmacy. Methods. After extensive review of the mentorship literature within the health sciences, a formal mentorship program was developed between 2006 and 2008 to support and facilitate faculty development. The voluntary program was implemented after mentors received training, and mentors and proteges were matched and received an orientation. Evaluation consisted of conducting annual surveys and focus groups with mentors and proteges. Results. Fifty-one mentor-protege pairs were formed from 2009 to 2012. A large majority of the mentors (82.8%-96.9%) were satisfied with the mentorship program and its procedures. The majority of the proteges (>= 70%) were satisfied with the mentorship program, mentor-protege relationship, and program logistics. Both mentors and proteges reported that the proteges most needed guidance on time management, prioritization, and work-life balance. While there were no significant improvements in the proteges' number of grant submissions, retention rates, or success in promotion/tenure, the total number of peer-reviewed publications by junior faculty members was significantly higher after program implementation (mean of 7 per year vs 21 per year, p=0.03) in the college's pharmacy practice and administration department. Conclusions. A formal mentorship program was successful as measured by self-reported assessments of mentors and proteges. C1 [Jackevicius, Cynthia A.; Le, Jennifer; Nazer, Lama; Hess, Karl; Wang, Jeffrey; Law, Anandi V.] Western Univ Hlth Sci, Pomona, CA USA. [Jackevicius, Cynthia A.] VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. [Jackevicius, Cynthia A.] Univ Toronto, Univ Hlth Network, Inst Clin Evaluat Sci, Toronto, ON, Canada. [Le, Jennifer] Univ Calif San Diego, La Jolla, CA 92093 USA. [Le, Jennifer] Long Beach Mem Med Ctr, Long Beach, CA USA. [Le, Jennifer] Miller Childrens Hosp, Long Beach, CA USA. [Nazer, Lama] King Hussein Canc Ctr, Amman, Jordan. RP Jackevicius, CA (reprint author), FCSHP Western Univ Hlth Sci, Coll Pharm, 309 E Second St, Pomona, CA 91766 USA. EM cjackevicius@westernu.edu NR 17 TC 4 Z9 4 U1 1 U2 6 PU AMER ASSOC COLL PHARMACY PI ALEXANDRIA PA 1426 PRINCE STREET, ALEXANDRIA, VA 22314-2815 USA SN 0002-9459 EI 1553-6467 J9 AM J PHARM EDUC JI Am. J. Pharm. Educ. PY 2014 VL 78 IS 5 AR 100 PG 7 WC Education, Scientific Disciplines; Pharmacology & Pharmacy SC Education & Educational Research; Pharmacology & Pharmacy GA AK4XW UT WOS:000338428800011 PM 24954940 ER PT J AU Li, XN Yang, HS Huang, HL Zhu, T AF Li, Xiaoni Yang, Hongshun Huang, Hailiang Zhu, Tao TI CELLCOUNTER: Novel Open-Source Software for Counting Cell Migration and Invasion In Vitro SO BIOMED RESEARCH INTERNATIONAL LA English DT Article ID IMAGE-ANALYSIS; METASTASIS AB Transwell Boyden chamber based migration/invasion assay is a simple and extensively used approach for the characterization of cell motility in vitro. Cell motility is quantified by counting the number of cells that pass through the filter membrane. The counting is usually performed manually, which is laborious and error prone. We have therefore developed CELLCOUNTER, an application that is capable of recognizing and counting the total number of cells through an intuitive graphical user interface. The counting can be performed in batch, and the counting results can be visualized and further curated manually. CELLCOUNTER will be helpful in streamlining the experimental process and improving the reliability of the data acquisition. C1 [Li, Xiaoni; Zhu, Tao] USTC, Hefei Natl Lab Phys Sci Microscale, Hefei, Anhui, Peoples R China. [Li, Xiaoni; Zhu, Tao] USTC, Sch Life Sci, Hefei, Anhui, Peoples R China. [Yang, Hongshun] USTC, Sch Informat Sci & Technol, Hefei, Anhui, Peoples R China. [Huang, Hailiang] Massachusetts Gen Hosp, Analyt & Translat Genet Unit, Boston, MA 02114 USA. [Huang, Hailiang] Broad Inst MIT & Harvard, Program Med & Populat Genet, Cambridge, MA USA. RP Huang, HL (reprint author), Massachusetts Gen Hosp, Analyt & Translat Genet Unit, Boston, MA 02114 USA. EM hhuang@atgu.mgh.harvard.edu; zhut@ustc.edu.cn FU National Key Scientific Program of China [2012CB934002, 2010CB912804]; National Natural Science Foundation of China [81272925] FX The authors thank Dr. Zhiming Pi for helpful advice to improve this software. They would also like to thank the members of their laboratories for contributing to the development of the software and this paper. This work was supported by the National Key Scientific Program of China (2012CB934002, 2010CB912804) and National Natural Science Foundation of China (81272925). NR 18 TC 0 Z9 0 U1 0 U2 7 PU HINDAWI PUBLISHING CORPORATION PI NEW YORK PA 410 PARK AVENUE, 15TH FLOOR, #287 PMB, NEW YORK, NY 10022 USA SN 2314-6133 EI 2314-6141 J9 BIOMED RES INT JI Biomed Res. Int. PY 2014 AR 863564 DI 10.1155/2014/863564 PG 6 WC Biotechnology & Applied Microbiology; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Research & Experimental Medicine GA AK7RW UT WOS:000338626400001 ER PT J AU Zhang, GL Sun, J Chitkushev, L Brusic, V AF Zhang, Guang Lan Sun, Jing Chitkushev, Lou Brusic, Vladimir TI Big Data Analytics in Immunology: A Knowledge-Based Approach SO BIOMED RESEARCH INTERNATIONAL LA English DT Article ID PREDICTION; EPITOPE; SUPERTYPES; MOLECULES; HUMANS AB With the vast amount of immunological data available, immunology research is entering the big data era. These data vary in granularity, quality, and complexity and are stored in various formats, including publications, technical reports, and databases. The challenge is to make the transition from data to actionable knowledge and wisdom and bridge the knowledge gap and application gap. We report a knowledge-based approach based on a framework called KB-builder that facilitates data mining by enabling fast development and deployment of web-accessible immunological data knowledge warehouses. Immunological knowledge discovery relies heavily on both the availability of accurate, up-to-date, and well-organized data and the proper analytics tools. We propose the use of knowledge-based approaches by developing knowledgebases combining well-annotated data with specialized analytical tools and integrating them into analytical workflow. A set of well-defined workflow types with rich summarization and visualization capacity facilitates the transformation from data to critical information and knowledge. By using KB-builder, we enabled streamlining of normally time-consuming processes of database development. The knowledgebases built using KB-builder will speed up rational vaccine design by providing accurate and well-annotated data coupled with tailored computational analysis tools and workflow. C1 [Zhang, Guang Lan; Chitkushev, Lou; Brusic, Vladimir] Boston Univ, Metropolitan Coll, Dept Comp Sci, Boston, MA 02215 USA. [Sun, Jing] Harvard Univ, Sch Med, Dana Farber Canc Inst, Canc Vaccine Ctr, Boston, MA 02115 USA. RP Brusic, V (reprint author), Boston Univ, Metropolitan Coll, Dept Comp Sci, Boston, MA 02215 USA. EM vbrusic@bu.edu NR 42 TC 1 Z9 1 U1 2 U2 30 PU HINDAWI PUBLISHING CORP PI NEW YORK PA 410 PARK AVENUE, 15TH FLOOR, #287 PMB, NEW YORK, NY 10022 USA SN 2314-6133 EI 2314-6141 J9 BIOMED RES INT JI Biomed Res. Int. PY 2014 AR 437987 DI 10.1155/2014/437987 PG 9 WC Biotechnology & Applied Microbiology; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Research & Experimental Medicine GA AK6JR UT WOS:000338534400001 ER PT J AU Aljuboori, Z Zeng, X Han, I Ropper, AE Yu, D Anderson, JE Ifedigbo, E Choi, AMK Teng, YD AF Aljuboori, Z. Zeng, X. Han, I. Ropper, A. E. Yu, D. Anderson, J. E. Ifedigbo, E. Choi, A. M. K. Teng, Y. D. TI Interneuron Protection Resulting From Low-Dose Carbon Monoxide Inhalation in Rat Spinal Cord Injury SO CELL TRANSPLANTATION LA English DT Meeting Abstract C1 [Aljuboori, Z.; Zeng, X.; Han, I.; Ropper, A. E.; Yu, D.; Anderson, J. E.; Teng, Y. D.] Harvard Univ, Sch Med, Dept Neurosurg, Brigham & Womens Hosp Boston, Boston, MA USA. [Aljuboori, Z.; Zeng, X.; Han, I.; Ropper, A. E.; Yu, D.; Anderson, J. E.; Teng, Y. D.] VA Boston Healthcare Syst, Div Spinal Cord Injury Res, Boston, MA USA. [Han, I.] Cha Univ, Dept Neurosurg, Gyeonggi Do, South Korea. [Ifedigbo, E.; Choi, A. M. K.] Harvard Univ, Sch Med, Div Pulm & Crit Care Med, Brigham & Womens Hosp Boston, Boston, MA USA. [Teng, Y. D.] Harvard Univ, Sch Med, Dept PM&R, Spaulding Rehabil Hosp, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU COGNIZANT COMMUNICATION CORP PI PUTNAM VALLEY PA 18 PEEKSKILL HOLLOW RD, PO BOX 37, PUTNAM VALLEY, NY 10579 USA SN 0963-6897 EI 1555-3892 J9 CELL TRANSPLANT JI Cell Transplant. PY 2014 VL 23 IS 6 BP 762 EP 762 PG 1 WC Cell & Tissue Engineering; Medicine, Research & Experimental; Transplantation SC Cell Biology; Research & Experimental Medicine; Transplantation GA AK5RM UT WOS:000338484000011 ER PT J AU Sharma, HS Muresanu, D Nozari, A Patnaik, R Mossler, H Sharma, A AF Sharma, H. S. Muresanu, D. Nozari, A. Patnaik, R. Moessler, H. Sharma, A. TI Nanoparticles Aggravate Cardiac Arrest-Induced Blood-Brain Barrier Breakdown, Edema Formation, and Neuronal Injuries: Neuroprotective Effects of a Multimodal Drug Cerebrolysin SO CELL TRANSPLANTATION LA English DT Meeting Abstract C1 [Sharma, H. S.; Sharma, A.] Univ Uppsala Hosp, Uppsala, Sweden. [Muresanu, D.] Univ Med & Pharm, Cluj Napoca, Romania. [Nozari, A.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Patnaik, R.] Banaras Hindu Univ, Indian Inst Technol, Varanasi 221005, Uttar Pradesh, India. [Moessler, H.] Ever NeuroPharma, Oberburgau, Austria. RI Sharma, Hari/G-4508-2016 NR 0 TC 0 Z9 0 U1 0 U2 0 PU COGNIZANT COMMUNICATION CORP PI PUTNAM VALLEY PA 18 PEEKSKILL HOLLOW RD, PO BOX 37, PUTNAM VALLEY, NY 10579 USA SN 0963-6897 EI 1555-3892 J9 CELL TRANSPLANT JI Cell Transplant. PY 2014 VL 23 IS 6 BP 782 EP 783 PG 2 WC Cell & Tissue Engineering; Medicine, Research & Experimental; Transplantation SC Cell Biology; Research & Experimental Medicine; Transplantation GA AK5RM UT WOS:000338484000070 ER PT J AU Capelletti, M Gelsomino, F Tiseo, M AF Capelletti, M. Gelsomino, F. Tiseo, M. TI MET and ALK as Targets for the Treatment of NSCLC SO CURRENT PHARMACEUTICAL DESIGN LA English DT Article DE NSCLC; hepatocyte growth factor; MET; ALK rearrangements; EML4-ALK gene; kinase inhibitors; targeted therapies ID CELL-LUNG-CANCER; HEPATOCYTE GROWTH-FACTOR; ANAPLASTIC LYMPHOMA KINASE; RECEPTOR TYROSINE KINASE; GENE COPY NUMBER; FACTOR SCATTER FACTOR; EML4-ALK FUSION VARIANTS; WILD-TYPE EGFR; NF-KAPPA-B; C-MET AB Cell proliferation, survival, differentiation, migration and metabolism are some of the fundamental cellular processes tightly controlled by the activity of tyrosine-kinase receptors (RTKs). The aberrant signaling of RTKs contributes to cancer growth and survival and has become important target for therapeutic approaches. Well-characterized kinase molecular target in lung cancer, in particular in non-small cell lung cancer (NSCLC), is the activated epidermal growth factor receptor (EGFR) pathway. More recently, the oncogenic role of other two tyrosine-kinases, the hepatocyte growth factor receptor (MET) and the anaplastic lymphoma kinase (ALK), has been recognized. Many different therapeutic strategies have been investigated with the goal to inhibit these receptors, subsequent downstream signaling cascades and arrest tumor growth. This review will discuss the MET and ALK pathways, the different strategies of their inhibition and the potential approaches to overcome acquired resistance to kinase inhibitors in these two genes. C1 [Capelletti, M.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Gelsomino, F.] Fdn IRCCS, Ist Nazl Tumori, Med Oncol Unit 1, Dept Med Oncol, Milan, Italy. [Tiseo, M.] Univ Hosp Parma, Med Oncol Unit, I-43100 Parma, Italy. RP Tiseo, M (reprint author), Univ Hosp Parma, Med Oncol Unit, Via Gramsci 14, I-43100 Parma, Italy. EM mtiseo@ao.pr.it NR 199 TC 1 Z9 1 U1 0 U2 5 PU BENTHAM SCIENCE PUBL LTD PI SHARJAH PA EXECUTIVE STE Y-2, PO BOX 7917, SAIF ZONE, 1200 BR SHARJAH, U ARAB EMIRATES SN 1381-6128 EI 1873-4286 J9 CURR PHARM DESIGN JI Curr. Pharm. Design PY 2014 VL 20 IS 24 BP 3914 EP 3932 PG 19 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA AK5FS UT WOS:000338450700007 PM 24138716 ER PT J AU Kieran, MW Gordon, LB Kleinman, ME AF Kieran, Mark W. Gordon, Leslie B. Kleinman, Monica E. TI The role of the farnesyltransferase inhibitor lonafarnib in the treatment of Progeria SO EXPERT OPINION ON ORPHAN DRUGS LA English DT Article DE clinical trial; farnesyltransferase inhibitor; Hutchinson-Gilford progeria syndrome; lonafarnib; Progeria; SCH66336 ID HUTCHINSON-GILFORD-PROGERIA; FARNESYL-PROTEIN TRANSFERASE; ADVANCED SOLID TUMORS; PULSE-WAVE VELOCITY; LAMIN-A; PHASE-I; MOUSE MODEL; PRELAMIN-A; AMELIORATES DISEASE; NUCLEAR MECHANICS AB Introduction: Hutchinson-Gilford progeria syndrome (Progeria) is a rare autosomal dominant premature aging disease caused by the generation of progerin, a farnesylated, disease-generating counterpart to the nuclear protein lamin A. Areas covered: The farnesyltransferase inhibitor (FTI) lonafarnib (SCH66336) is thought to reduce the deleterious effects of progerin by inhibiting the transfer of the farnesyl group onto this abnormal pre-lamin A molecule. The results of the first prospective clinical trial of lonafarnib in children with Progeria have recently been reported. In this review, the biologic basis of Progeria and the rational use of the FTI lonafarnib in this disease will be discussed. The results of this trial will be considered both in the context of the areas where lonafarnib demonstrated activity and areas of lack of response, as well as the toxicity of this agent. Expert opinion: The FTI lonafarnib has demonstrated significant clinical activity in patients with Progeria. This approach will be only the first step in the long-term treatment of these patients as the field moves toward treating the underlying genetic abnormalities. New clinical trials combining multiple agents to better modulate the production of progerin are now underway. C1 [Kieran, Mark W.] Dana Farber Canc Inst, Boston, MA 02215 USA. [Kieran, Mark W.] Boston Childrens Hosp, Boston, MA USA. [Gordon, Leslie B.; Kleinman, Monica E.] Boston Childrens Hosp, Dept Anesthesia, Div Crit Care Med, Boston, MA 02115 USA. [Gordon, Leslie B.] Brown Univ, Warren Alpert Med Sch, Dept Pediat, Hasbro Childrens Hosp, Providence, RI 02903 USA. RP Kieran, MW (reprint author), Dana Farber Canc Inst, 450 Brookline Ave,Rm D-3154, Boston, MA 02215 USA. EM mark_kieran@dfci.harvard.edu OI Kieran, Mark/0000-0003-2184-7692 FU Progeria Research Foundation; Dana-Farber Cancer Institute; Boston Children's Hospital; Merck Pharmaceutical FX MW Kieran has a consultancy agreement with Merck. LB Gordon is the mother of a child with Progeria. This work has been supported by the Progeria Research Foundation, Dana-Farber Cancer Institute, Boston Children's Hospital and Merck Pharmaceutical. NR 93 TC 1 Z9 1 U1 7 U2 18 PU TAYLOR & FRANCIS LTD PI ABINGDON PA 2-4 PARK SQUARE, MILTON PARK, ABINGDON OR14 4RN, OXON, ENGLAND SN 2167-8707 J9 EXPERT OPIN ORPHAN D JI Exp. Opin. Orphan Drugs PD JAN PY 2014 VL 2 IS 1 BP 95 EP 105 DI 10.1517/21678707.2014.872028 PG 11 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA AK2VV UT WOS:000338278600009 ER PT J AU Rineh, A Kelso, MJ Vatansever, F Tegos, GP Hamblin, MR AF Rineh, Ardeshir Kelso, Michael J. Vatansever, Fatma Tegos, George P. Hamblin, Michael R. TI Clostridium difficile infection: molecular pathogenesis and novel therapeutics SO EXPERT REVIEW OF ANTI-INFECTIVE THERAPY LA English DT Review DE bile acids; binary toxin; Clostridium difficile; fecal transplant; monoclonal antibody; pathogenicity locus; photodynamic therapy; probiotics; spore germination; toxin A and B ID ANTIBIOTIC-ASSOCIATED DIARRHEA; SELECTIVE ANTIMICROBIAL PHOTOSENSITIZERS; FECAL MICROBIOTA TRANSPLANTATION; DOMAIN ANTIBODY FRAGMENTS; HEAVY-CHAIN ANTIBODIES; BILE-ACID METABOLISM; B-POSITIVE STRAINS; TOXIN-B; PSEUDOMEMBRANOUS COLITIS; PHOTODYNAMIC THERAPY AB The Gram-positive anaerobic bacterium Clostridium difficile produces toxins A and B, which can cause a spectrum of diseases from pseudomembranous colitis to C. difficile-associated diarrhea. A limited number of C. difficile strains also produce a binary toxin that exhibits ADP ribosyltransferase activity. Here, the structure and the mechanism of action of these toxins as well as their role in disease are reviewed. Nosocomial C. difficile infection is often contracted in hospital when patients treated with antibiotics suffer a disturbance in normal gut microflora. C. difficile spores can persist on dry, inanimate surface for months. Metronidazole and oral vancomycin are clinically used for treatment of C. difficile infection but clinical failure and concern about promotion of resistance are motivating the search for novel non-antibiotic therapeutics. Methods for controlling both toxins and spores, replacing gut microflora by probiotics or fecal transplant, and killing bacteria in the anaerobic gut by photodynamic therapy are discussed. C1 [Rineh, Ardeshir; Vatansever, Fatma; Tegos, George P.; Hamblin, Michael R.] Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA. [Rineh, Ardeshir; Kelso, Michael J.] Univ Wollongong, Sch Chem, Wollongong, NSW 2522, Australia. [Vatansever, Fatma; Tegos, George P.; Hamblin, Michael R.] Harvard Univ, Sch Med, Dept Dermatol, Boston, MA 02115 USA. [Tegos, George P.] Univ New Mexico, Sch Med, Dept Pathol, Albuquerque, NM 87131 USA. [Tegos, George P.] Univ New Mexico, Ctr Mol Discovery, Albuquerque, NM 87131 USA. [Hamblin, Michael R.] MIT, Harvard Mit Div Hlth Sci & Technol, Cambridge, MA 02139 USA. RP Hamblin, MR (reprint author), Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA. EM hamblin@helix.mgh.harvard.edu OI Kelso, Michael/0000-0001-7809-6637; Hamblin, Michael/0000-0001-6431-4605 FU US NIH [R01AI050875] FX Research in the Hamblin laboratory is supported by US NIH grant R01AI050875. 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 216 TC 14 Z9 16 U1 6 U2 25 PU EXPERT REVIEWS PI LONDON PA UNITEC HOUSE, 3RD FL, 2 ALBERT PLACE, FINCHLEY CENTRAL, LONDON N3 1QB, ENGLAND SN 1478-7210 EI 1744-8336 J9 EXPERT REV ANTI-INFE JI Expert Rev. Anti-Infect. Ther. PD JAN PY 2014 VL 12 IS 1 BP 131 EP 150 DI 10.1586/14787210.2014.866515 PG 20 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA AK2ZK UT WOS:000338289500011 PM 24410618 ER PT J AU Lee, JY Moore, P Kusek, J Barry, M AF Lee, Jeannette Y. Moore, Page Kusek, John Barry, Michael CA CAMUS Study Grp TI Treatment Assignment Guesses by Study Participants in a Double-Blind Dose Escalation Clinical Trial of Saw Palmetto SO JOURNAL OF ALTERNATIVE AND COMPLEMENTARY MEDICINE LA English DT Article ID BENIGN PROSTATIC HYPERPLASIA; RANDOMIZED CONTROLLED TRIAL; ASSOCIATION SYMPTOM INDEX; DUTASTERIDE; COMBINATION; FINASTERIDE; THERAPY; PLACEBO AB Objectives: This report assesses participant perception of treatment assignment in a randomized, double-blind, placebo-controlled trial of saw palmetto for the treatment of benign prostatic hyperplasia (BCM). Design: Participants randomized to receive saw palmetto were instructed to take one 320mg gelcap daily for the first 24 weeks, two 320mg gelcaps daily for the second 24 weeks, and three 320mg gelcaps daily for the third 24 weeks. Study participants assigned to placebo were instructed to take the same number of matching placebo gelcaps in each time period. At 24, 48, and 72 weeks postrandomization, the American Urological Association Symptom Index (AUA-SI) was administered and participants were asked to guess their treatment assignment. Settings: The study was conducted at 11 clinical centers in North America. Participants: Study participants were men, 45 years and older, with moderate to low severe BPH symptoms, randomized to saw palmetto (N = 151) or placebo (N = 155). Outcome measures: Treatment arms were compared with respect to the distribution of participant guesses of treatment assignment. Results: For participants assigned to saw palmetto, 22.5%, 24.7%, and 29.8% correctly thought they were taking saw palmetto, and 37.3%, 40.0%, and 44.4% incorrectly thought they were on placebo at 24, 48, and 72 weeks, respectively. For placebo participants, 21.8%, 27.4%, and 25.2% incorrectly thought they were on saw palmetto, and 41.6%, 39.9%, and 42.6% correctly thought they were on placebo at 24, 48, and 72 weeks, respectively. The treatment arms did not vary with respect to the distributions of participants who guessed they were on saw palmetto (p = 0.823) or placebo (p = 0.893). Participants who experienced an improvement in AUA-SI were 2.16 times more likely to think they were on saw palmetto. Conclusions: Blinding of treatment assignment was successful in this study. Improvement in BPH-related symptoms was associated with the perception that participants were taking saw palmetto. C1 [Lee, Jeannette Y.; Moore, Page] Univ Arkansas Med Sci, Dept Biostat, Little Rock, AR 72205 USA. [Kusek, John] NIDDK, Bethesda, MD USA. [Barry, Michael] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Lee, JY (reprint author), Univ Arkansas Med Sci, Dept Biostat, 4301 W Markham, Little Rock, AR 72205 USA. EM jylee@uams.edu FU National Institutes of Health, National Institute of Diabetes and Digestive and Kidney Diseases, National Center for Complementary and Alternative Medicine [U01 DK63778, U01 DK63788, U01 DK63795, U01 DK63797, U01 DK63825, U01 DK63831, U01 DK63833, U01 DK63835, U01 DK63840, U01 DK63862, U01 DK63866, U01 DK63883]; Office of Dietary Supplements FX This study was funded by grants U01 DK63778, U01 DK63788, U01 DK63795, U01 DK63797, U01 DK63825, U01 DK63831, U01 DK63833, U01 DK63835, U01 DK63840, U01 DK63862, U01 DK63866, and U01 DK63883 from the National Institutes of Health, National Institute of Diabetes and Digestive and Kidney Diseases, National Center for Complementary and Alternative Medicine, and the Office of Dietary Supplements. Saw palmetto fruit extract and matching placebo were donated by Rottapharm/Madaus, Cologne, Germany. The authors wish to express their appreciation to the full CAMUS study team.6 NR 18 TC 0 Z9 0 U1 0 U2 4 PU MARY ANN LIEBERT, INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1075-5535 EI 1557-7708 J9 J ALTERN COMPLEM MED JI J. Altern. Complement Med. PD JAN PY 2014 VL 20 IS 1 BP 48 EP 52 DI 10.1089/acm.2012.0284 PG 5 WC Integrative & Complementary Medicine SC Integrative & Complementary Medicine GA AK3SZ UT WOS:000338346300008 PM 23383975 ER PT J AU Pizzolato, R Hirsch, JA Romero, JM AF Pizzolato, Raffaella Hirsch, Joshua A. Romero, Javier M. TI Imaging challenges of carotid artery in-stent restenosis SO JOURNAL OF NEUROINTERVENTIONAL SURGERY LA English DT Review ID ULTRASOUND VELOCITY CRITERIA; DIGITAL-SUBTRACTION-ANGIOGRAPHY; CODED DUPLEX SONOGRAPHY; RANDOMIZED-TRIAL; CT ANGIOGRAPHY; FOLLOW-UP; REVASCULARIZATION ENDARTERECTOMY; PATIENT CHARACTERISTICS; SURGERY TRIAL; BRAIN-LESIONS AB Internal carotid artery stenosis is an established risk factor for stroke. Therefore, carotid artery revascularization has an important role in the prevention and treatment of stroke. For the treatment of carotid artery stenosis, carotid artery stenting (CAS) has currently gained acceptance as a safe alternative to carotid endarterectomy (CEA), particularly in patients at high surgical risk. Duplex ultrasonography (DUS) is a non-invasive technique with standardized criteria used for the diagnosis of carotid atheromatous disease as well as for the detection of restenosis after carotid revascularization. Restenosis rates vary widely in the literature. Different studies indicated that restenosis following CAS was higher than following CEA, although the Carotid Revascularization Endarterectomy Versus Stenting Trial (CREST) reported similar restenosis frequency after 2 years of follow-up. Given these results, DUS may have a significant role in the follow-up of CAS patients. Conventional carotid artery DUS velocity criteria are thought to be less accurate in patients who have undergone CAS and many authors proposed different criteria for grading in-stent restenosis (ISR). This review presents the advantages of CAS, the current practice of carotid revascularization, CAS complications and risks, and DUS criteria for carotid artery ISR. After analyzing multiple relevant studies that proposed sonographic criteria for grading at least 70% ISR, we can conclude that a peak systolic velocity value of 300-350 cm/s could be used as a relatively good and sensitive predictor of high grade ISR. C1 [Pizzolato, Raffaella; Hirsch, Joshua A.; Romero, Javier M.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Neuroradiol, Boston, MA 02114 USA. [Pizzolato, Raffaella] Univ Roma La Sapienza, Dept Neurol & Psychiat, I-00185 Rome, Italy. [Hirsch, Joshua A.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Intervent Neuroradiol, Boston, MA 02114 USA. [Romero, Javier M.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Neurovasc Lab, Boston, MA 02114 USA. RP Romero, JM (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Neuroradiol, Boston, MA 02114 USA. EM jmromero@partners.org NR 68 TC 2 Z9 2 U1 0 U2 5 PU BMJ PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 1759-8478 EI 1759-8486 J9 J NEUROINTERV SURG JI J. NeuroInterventional Surg. PD JAN PY 2014 VL 6 IS 1 BP 32 EP 41 DI 10.1136/neurintsurg-2012-010618 PG 10 WC Neuroimaging; Surgery SC Neurosciences & Neurology; Surgery GA AK2ZL UT WOS:000338289800017 PM 23299108 ER PT J AU Hirsch, JA Silva, E Nicola, GN Barr, RM Bello, JA Manchikanti, L Donovan, WD AF Hirsch, Joshua A. Silva, Ezequiel, III Nicola, Gregory N. Barr, Robert M. Bello, Jacqueline A. Manchikanti, Laxmaiah Donovan, William D. TI The RUC: a primer for neurointerventionalists SO JOURNAL OF NEUROINTERVENTIONAL SURGERY LA English DT Review AB The Relative Value Scale Update Committee (RUC) plays a critical role in determining physician payment. When the Centers for Medicare and Medicaid Services (CMS) transitioned to paying physicians based on the Resource-Based Relative Value Scale, the American Medical Association developed this unique multispecialty committee. Physicians at the RUC determine the resources required to provide physician services and recommend appropriate payment for those services. The RUC then submits its recommendations to CMS. Physicians have thus been important in determining relative value and hence payment for the services they provide. C1 [Hirsch, Joshua A.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Neuroendovasc Program, Boston, MA 02114 USA. [Silva, Ezequiel, III] Univ Texas Hlth Sci Ctr San Antonio, Dept Radiol, South Texas Radiol Grp, San Antonio, TX 78229 USA. [Nicola, Gregory N.] Hackensack Univ, Med Ctr, Hackensack, NJ USA. [Barr, Robert M.] Mecklenburg Radiol Associates, Charlotte, NC USA. [Bello, Jacqueline A.] Montefiore Med Ctr, Albert Einstein Coll Med, Bronx, NY 10467 USA. [Manchikanti, Laxmaiah] Pain Management Ctr Paducah, Paducah, KY USA. [Donovan, William D.] Norwich Diagnost Imaging Associates, Norwich, CT USA. RP Hirsch, JA (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Neuroendovasc Program, Boston, MA 02114 USA. EM Hirsch@snisonline.org NR 13 TC 14 Z9 14 U1 0 U2 3 PU BMJ PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 1759-8478 EI 1759-8486 J9 J NEUROINTERV SURG JI J. NeuroInterventional Surg. PD JAN PY 2014 VL 6 IS 1 BP 61 EP 64 DI 10.1136/neurintsurg-2012-010636 PG 4 WC Neuroimaging; Surgery SC Neurosciences & Neurology; Surgery GA AK2ZL UT WOS:000338289800022 PM 23335447 ER PT J AU Chandra, RV Meyers, PM Hirsch, JA Abruzzo, T Eskey, CJ Hussain, MS Lee, SK Narayanan, S Bulsara, KR Gandhi, CD Do, HM Prestigiacomo, CJ Albuquerque, FC Frei, D Kelly, ME Mack, WJ Pride, GL Jayaraman, MV AF Chandra, Ronil V. Meyers, Philip M. Hirsch, Joshua A. Abruzzo, Todd Eskey, Clifford J. Hussain, M. Shazam Lee, Seon-Kyu Narayanan, Sandra Bulsara, Ketan R. Gandhi, Chirag D. Do, Huy M. Prestigiacomo, Charles J. Albuquerque, Felipe C. Frei, Donald Kelly, Michael E. Mack, William J. Pride, G. Lee Jayaraman, Mahesh V. CA Soc NeuroInterventional Surg TI Vertebral augmentation: report of the Standards and Guidelines Committee of the Society of NeuroInterventional Surgery SO JOURNAL OF NEUROINTERVENTIONAL SURGERY LA English DT Editorial Material ID PERCUTANEOUS VERTEBROPLASTY; PAIN RELIEF; PALLIATIVE RADIOTHERAPY; COMPRESSION FRACTURES; RANDOMIZED-TRIAL; BONE METASTASES; VERTOS II; BED REST; COMPLICATIONS; EPIDEMIOLOGY C1 [Chandra, Ronil V.] Monash Med Ctr, Melbourne, Vic, Australia. [Meyers, Philip M.] Columbia Univ, Dept Radiol & Neurol Surg, New York, NY USA. [Hirsch, Joshua A.] Massachusetts Gen Hosp, Neuro Endovasc Program, Boston, MA 02114 USA. [Abruzzo, Todd] Univ Cincinnati, Dept Neurosurg, Cincinnati, OH USA. [Eskey, Clifford J.] Dartmouth Hitchcock Med Ctr, Dept Radiol Neurol & Neurosurg, Lebanon, NH 03766 USA. [Hussain, M. Shazam] Cleveland Clin, Cerebrovasc Ctr, Cleveland, OH 44106 USA. [Lee, Seon-Kyu] Univ Chicago, Dept Radiol, Chicago, IL 60637 USA. [Narayanan, Sandra] Wayne State Univ, Sch Med, Dept Neurosurg, Detroit, MI USA. [Narayanan, Sandra] Wayne State Univ, Sch Med, Dept Neurol, Detroit, MI 48201 USA. [Bulsara, Ketan R.] Yale Univ, Sch Med, Dept Neurosurg, New Haven, CT USA. [Gandhi, Chirag D.] Univ Med & Dent New Jersey, New Jersey Med Sch, Neurol Inst New Jersey, Newark, NJ 07103 USA. [Do, Huy M.] Stanford Univ, Med Ctr, Dept Radiol & Neurosurg, Stanford, CA 94305 USA. [Prestigiacomo, Charles J.] Univ Med & Dent New Jersey, New Jersey Med Sch, Dept Neurol Surg, Newark, NJ 07103 USA. [Albuquerque, Felipe C.] Barrow Neurol Inst, Div Neurol Surg, Phoenix, AZ 85013 USA. [Frei, Donald] Radiol Imaging Associates, Dept Intervent Neuroradiol, Englewood, CO USA. [Kelly, Michael E.] Univ Saskatchewan, Royal Univ Hosp, Dept Neurosurg, Saskatoon, SK, Canada. [Mack, William J.] Univ So Calif, Dept Neurosurg, Los Angeles, CA USA. [Pride, G. Lee] UT Southwestern, Dept Neuroradiol, Dallas, TX USA. [Jayaraman, Mahesh V.] Brown Univ, Warren Alpert Sch Med, Providence, RI 02912 USA. RP Jayaraman, MV (reprint author), Brown Univ, Warren Alpert Sch Med, Providence, RI 02912 USA. EM MJayaraman@Lifespan.org NR 34 TC 5 Z9 5 U1 0 U2 3 PU BMJ PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 1759-8478 EI 1759-8486 J9 J NEUROINTERV SURG JI J. NeuroInterventional Surg. PD JAN PY 2014 VL 6 IS 1 DI 10.1136/neurintsurg-2013-011012 PG 9 WC Neuroimaging; Surgery SC Neurosciences & Neurology; Surgery GA AK2ZL UT WOS:000338289800012 PM 24198272 ER PT J AU Hirsch, JA Gonzalez, RG AF Hirsch, Joshua A. Gonzalez, R. Gilberto TI Understanding IMS III: old data shed new light on a futile trial SO JOURNAL OF NEUROINTERVENTIONAL SURGERY LA English DT Editorial Material ID TISSUE-PLASMINOGEN-ACTIVATOR; FOCAL CEREBRAL-ISCHEMIA; LARGE VESSEL OCCLUSIONS; INTERVENTIONAL MANAGEMENT; MATRIX-METALLOPROTEINASE; STROKE; TPA; REVASCULARIZATION; THROMBOLYSIS; BRAIN C1 [Hirsch, Joshua A.] Massachusetts Gen Hosp, NeuroEndovasc Program, Boston, MA 02114 USA. [Gonzalez, R. Gilberto] Massachusetts Gen Hosp, Dept Neuroradiol, Boston, MA 02114 USA. RP Hirsch, JA (reprint author), Massachusetts Gen Hosp, NeuroEndovasc Program, 55 Fruit St,Gray 241B, Boston, MA 02114 USA. EM hirsch@snisonline.org NR 17 TC 2 Z9 2 U1 0 U2 0 PU BMJ PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 1759-8478 EI 1759-8486 J9 J NEUROINTERV SURG JI J. NeuroInterventional Surg. PD JAN PY 2014 VL 6 IS 1 DI 10.1136/neurintsurg-2012-010594 PG 2 WC Neuroimaging; Surgery SC Neurosciences & Neurology; Surgery GA AK2ZL UT WOS:000338289800010 PM 23204012 ER PT J AU Miller, TS Brook, AL Riedel, CH Hirsch, JA Yoo, AJ AF Miller, Todd S. Brook, Allan L. Riedel, Christian H. Hirsch, Joshua A. Yoo, Albert J. TI Expanding the role of NCCT in acute stroke imaging: thrombus length measurement and its potential impact on current practice SO JOURNAL OF NEUROINTERVENTIONAL SURGERY LA English DT Editorial Material ID ACUTE ISCHEMIC-STROKE; TISSUE-PLASMINOGEN ACTIVATOR; INTRAARTERIAL; THROMBOLYSIS; RECANALIZATION; ASSOCIATION; WINDOW; ARTERY C1 [Miller, Todd S.] Albert Einstein Coll Med, Dept Radiol, Bronx, NY 10467 USA. [Brook, Allan L.] Montefiore Med Ctr, Dept Radiol, Bronx, NY 10467 USA. [Riedel, Christian H.] Univ Kiel, Dept Neuroradiol, Kiel, Germany. [Hirsch, Joshua A.; Yoo, Albert J.] Massachusetts Gen Hosp, Dept Intervent Neuroradiol Endovasc Neurosurg, Boston, MA 02114 USA. RP Miller, TS (reprint author), Montefiore Med Ctr, Albert Einstein Coll Med, Dept Radiol, 111 East 210th St, Bronx, NY 10463 USA. EM tmiller@montefiore.org NR 23 TC 2 Z9 2 U1 0 U2 1 PU BMJ PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 1759-8478 EI 1759-8486 J9 J NEUROINTERV SURG JI J. NeuroInterventional Surg. PD JAN PY 2014 VL 6 IS 1 DI 10.1136/neurintsurg-2012-010531 PG 2 WC Neuroimaging; Surgery SC Neurosciences & Neurology; Surgery GA AK2ZL UT WOS:000338289800011 PM 23558864 ER PT J AU Lopez, SA Hernley, LR Bearrick, EN Tanenbaum, LM Thomas, MAC Toussaint, TA Romano, JJ Hanumara, NC Slocum, AH AF Lopez, S. A. Hernley, L. R. Bearrick, E. N. Tanenbaum, L. M. Thomas, M. A. C. Toussaint, T. A. Romano, J. J. Hanumara, N. C. Slocum, A. H. TI Design, prototyping, and evaluation of a collapsible device for single-operator sheathing of ultrasound probes SO MECHANICAL SCIENCES LA English DT Article AB During interventional ultrasound-guided procedures, sterility is maintained by covering the transducer head and cord with a sterile sheath. The current sheathing technique is cumbersome, requires an assistant to complete, and poses a risk of tangling the probe cord and breaching the sterile barrier. This paper presents the design, proof-of-concept prototyping, and evaluation of a probe holder and cartridge-style, single-use applicator that enables faster, more reliable, single-user sheathing of ultrasound probes, with a decreased risk of compromising sterility. C1 [Lopez, S. A.; Hernley, L. R.; Bearrick, E. N.; Thomas, M. A. C.; Toussaint, T. A.; Hanumara, N. C.; Slocum, A. H.] MIT, Dept Mech Engn, Cambridge, MA 02139 USA. [Tanenbaum, L. M.] MIT, Hlth Sci & Technol Dept, Cambridge, MA 02139 USA. [Romano, J. J.] Massachusetts Gen Hosp, Hosp Med, Boston, MA 02114 USA. RP Lopez, SA (reprint author), MIT, Dept Mech Engn, Cambridge, MA 02139 USA. EM saulopez@mit.edu FU CIMIT under US Army Medical Research Acquisition Activity Cooperative Agreement [W81XWH-09-2-0001] FX This work was supported by CIMIT under US Army Medical Research Acquisition Activity Cooperative Agreement W81XWH-09-2-0001. The information contained herein does not necessarily reflect the position or policy of the Government and no official endorsement should be inferred. NR 20 TC 0 Z9 0 U1 1 U2 4 PU COPERNICUS GESELLSCHAFT MBH PI GOTTINGEN PA BAHNHOFSALLEE 1E, GOTTINGEN, 37081, GERMANY SN 2191-9151 EI 2191-916X J9 MECH SCI JI Mech. Sci. PY 2014 VL 5 IS 1 BP 7 EP 13 DI 10.5194/ms-5-7-2014 PG 7 WC Engineering, Mechanical SC Engineering GA AK3PK UT WOS:000338336800002 ER PT J AU Wortzel, HS Arciniegas, DB AF Wortzel, Hal S. Arciniegas, David B. TI The DSM-5 approach to the evaluation of traumatic brain injury and its neuropsychiatric sequelae SO NEUROREHABILITATION LA English DT Article DE Traumatic brain injury; cognition disorders; DSM-5 ID MONTREAL COGNITIVE ASSESSMENT; MINI-MENTAL-STATE; MILD HEAD-INJURY; COMPUTED-TOMOGRAPHY; POSTCONCUSSIONAL DISORDER; INTRACRANIAL INJURY; UNIFIED DEFINITION; IV CRITERIA; MANAGEMENT; RECOVERY AB INTRODUCTION: The advent of the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) is accompanied by substantial changes in the approach taken in this manual to traumatic brain injury (TBI) and its neuropsychiatric sequelae. OBJECTIVE: This article reviews the issues pertaining to the treatment of TBI in the DSM-5, and changes relative to the outgoing DSM-IV-TR. The primary context for discussion of TBI in the DSM-5 is the section on Neurocognitive Disorders, where a basic framework is provided for the retrospective diagnosis of TBI and characterization of the clinical presentation as a Mild or Major Neurocognitive Disorder. The distinctions between these conditions rest not on the initial severity of TBI but instead on the severity of posttraumatic cognitive impairments and their effects on everyday function. The text succinctly reviews the epidemiology, phenomenology, and natural history of TBI and highlights the need to consider the differential diagnosis for persistent postconcussive symptoms. CONCLUSION: The approach taken to the diagnosis of TBI and its neuropsychiatric consequences in the DSM-5 is improved substantially over that of the DSM-IV-TR, and it is likely to improve the evaluations of persons with TBI by mental health professionals. However, challenges borne of this approach are likely to be revealed as it is implemented in everyday practice and will guide the development of this section of DSM-5.1. C1 [Wortzel, Hal S.] Denver Vet Affairs Med Ctr, Denver, CO USA. [Wortzel, Hal S.] Univ Colorado, Sch Med, Dept Psychiat, Div Forens Psychiat, Aurora, CO USA. [Wortzel, Hal S.; Arciniegas, David B.] Univ Colorado, Sch Med, Dept Psychiat, Neuropsychiat Serv, Aurora, CO USA. [Wortzel, Hal S.; Arciniegas, David B.] Baylor Coll Med, Menninger Dept Psychiat & Behav Sci, Beth K & Stuart C Yudofsky Div Neuropsychiat, Houston, TX 77030 USA. [Arciniegas, David B.] TIRR Mem Hermann, Brain Injury Res Ctr, Houston, TX USA. RP Wortzel, HS (reprint author), Denver Vet Hosp, VISN 19 MIRECC,1055 Clermont St, Denver, CO 80220 USA. EM hal.wortzel@ucdenver.edu FU Veterans Health Administration's VISN-19 MIRECC; National Institute on Disability and Rehabilitation Research (NIDRR) [H133A120020, H133A130047] FX Support for this work was provided by the Veterans Health Administration's VISN-19 MIRECC (HSW) and National Institute on Disability and Rehabilitation Research (NIDRR) grants H133A120020 and H133A130047 (DBA). The content is solely the responsibility of the authors and does not necessarily represent the official views of the Department of Veterans Affairs or NIDRR. NR 60 TC 3 Z9 3 U1 2 U2 13 PU IOS PRESS PI AMSTERDAM PA NIEUWE HEMWEG 6B, 1013 BG AMSTERDAM, NETHERLANDS SN 1053-8135 EI 1878-6448 J9 NEUROREHABILITATION JI Neurorehabilitation PY 2014 VL 34 IS 4 BP 613 EP 623 DI 10.3233/NRE-141086 PG 11 WC Clinical Neurology; Rehabilitation SC Neurosciences & Neurology; Rehabilitation GA AK5CY UT WOS:000338443100003 PM 24820171 ER PT J AU Maier, MM He, H Schafer, SD Ward, TT Zaman, A AF Maier, Marissa M. He, Haiou Schafer, Sean D. Ward, Thomas T. Zaman, Atif TI Hepatitis C treatment eligibility among HIV-hepatitis C virus coinfected patients in Oregon: a population-based sample SO AIDS CARE-PSYCHOLOGICAL AND SOCIO-MEDICAL ASPECTS OF AIDS/HIV LA English DT Article DE coinfection; eligibility; hepatitis C; HIV; treatment ID HUMAN-IMMUNODEFICIENCY-VIRUS; ALPHA-2A PLUS RIBAVIRIN; INJECTION-DRUG USERS; INFECTED PATIENTS; LIVER-DISEASE; PEGINTERFERON; TELAPREVIR; IMPACT; CARE; MORTALITY AB Approximately 287,000 individuals in the USA are coinfected with HIV and hepatitis C. Recently, new hepatitis C regimens have become available, increasing rates of sustained virologic response in the monoinfected, with studies evaluating their success in the coinfected under way. Previous investigators estimated eligibility for hepatitis C therapy among the coinfected patients, but all had significant methodological limitations. Our study is the first to use a multi-year, statewide, population-based sample to estimate treatment eligibility, and the first to estimate eligibility in the setting of an interferon-free regimen. In a population-based sample of 161 patients infected with HIV and hepatitis C living in Oregon during 2007-2010, 21% were eligible for hepatitis C therapy. Despite the anticipation surrounding an interferon-sparing regimen, eligibility assuming an interferon-free regimen increased only to 26%, largely due to multiple simultaneous contraindications. Obesity was described for the first time as being associated with decreased eligibility (OR: 0.11). Active alcohol abuse was the most common contraindication (24%); uncontrolled mental health (22%), recent injection drug use (21%), poor antiretroviral adherence (22%), and infection (21%) were also common excluding conditions. When active drug or alcohol abuse was excluded as contraindications to therapy, the eligibility rate was 34%, a 62% increase. Assuming an interferon-free regimen and the exclusion of active drug or alcohol abuse as contraindications to therapy, the eligibility rate increased to 42%. Despite the availability of direct-acting anti-viral regimens, eligibility rates in HIV-hepatitis C virus (HCV) coinfection are modest. Many factors precluding hepatitis C therapy are reversible, and targeted interventions could result in increased eligibility. C1 [Maier, Marissa M.] Oregon Hlth & Sci Univ, Div Infect Dis, Portland, OR 97201 USA. [He, Haiou] Oregon Hlth Author, Program Design & Evaluat Serv, Portland, OR USA. [Schafer, Sean D.] Oregon Hlth Author, HIV STD TB Program, Portland, OR USA. [Ward, Thomas T.] Portland VA Med Ctr, Infect Dis Sect, Portland, OR USA. [Zaman, Atif] Oregon Hlth & Sci Univ, Div Gastroenterol & Hepatol, Portland, OR 97201 USA. RP Maier, MM (reprint author), Oregon Hlth & Sci Univ, Div Infect Dis, Portland, OR 97201 USA. EM maierma@ohsu.edu NR 30 TC 4 Z9 4 U1 1 U2 1 PU ROUTLEDGE JOURNALS, TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXFORDSHIRE, ENGLAND SN 0954-0121 EI 1360-0451 J9 AIDS CARE JI Aids Care-Psychol. Socio-Med. Asp. Aids-Hiv PY 2014 VL 26 IS 9 BP 1178 EP 1185 DI 10.1080/09540121.2014.892563 PG 8 WC Health Policy & Services; Public, Environmental & Occupational Health; Psychology, Multidisciplinary; Respiratory System; Social Sciences, Biomedical SC Health Care Sciences & Services; Public, Environmental & Occupational Health; Psychology; Respiratory System; Biomedical Social Sciences GA AJ8NO UT WOS:000337962500017 PM 24601687 ER PT J AU Mowlds, DS Patel, MS Khalsa, B Foe-Parker, JE Salibian, AA Rama, A Jafari, F Whealon, MD Hoyt, DB Stamos, MJ Endres, JE Smith, BR AF Mowlds, Donald S. Patel, Madhukar S. Khalsa, Bhavraj Foe-Parker, Jennifer E. Salibian, Ara A. Rama, Asheen Jafari, Fariba Whealon, Matthew D. Hoyt, David B. Stamos, Michael J. Endres, Jill E. Smith, Brian R. TI Preparing Senior Medical Students for Surgical Internship: the Value of a Half-day Intervention SO AMERICAN SURGEON LA English DT Article; Proceedings Paper CT 36th Annual Meeting of the Association-of-VA-Surgeons CY APR 01-03, 2012 CL Miami Beach, FL SP Assoc VA Surg C1 [Mowlds, Donald S.; Khalsa, Bhavraj; Foe-Parker, Jennifer E.; Whealon, Matthew D.; Stamos, Michael J.; Endres, Jill E.; Smith, Brian R.] Univ Calif Irvine, Irvine Med Ctr, Dept Surg, Orange, CA 92668 USA. [Patel, Madhukar S.] Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. [Salibian, Ara A.; Rama, Asheen; Jafari, Fariba] Univ Calif Irvine, Irvine Sch Med, Irvine, CA USA. [Hoyt, David B.] Amer Coll Surg Chicago, Chicago, IL USA. [Smith, Brian R.] Vet Affairs Long Beach Healthcare Syst, Long Beach, CA USA. RP Smith, BR (reprint author), Univ Calif Irvine, Irvine Med Ctr, 5901 East 7th St,Box 12112, Long Beach, CA 90822 USA. EM Brian.Smith11@va.gov NR 3 TC 0 Z9 0 U1 0 U2 1 PU SOUTHEASTERN SURGICAL CONGRESS PI CUMMING PA 115 SAMARITAN DR, #200, CUMMING, GA 30040-2354 USA SN 0003-1348 EI 1555-9823 J9 AM SURGEON JI Am. Surg. PD JAN PY 2014 VL 80 IS 1 BP 102 EP 104 PG 3 WC Surgery SC Surgery GA AJ5PQ UT WOS:000337738000037 PM 24401528 ER PT J AU Gandhi, PU Pinney, S AF Gandhi, Parul U. Pinney, Sean TI Management of Chronic Heart Failure: Biomarkers, Monitors, and Disease Management Programs SO ANNALS OF GLOBAL HEALTH LA English DT Review DE biomarkers; cardiac monitors; disease management programs; heart failure; natriuretic peptides ID BRAIN NATRIURETIC PEPTIDE; GELATINASE-ASSOCIATED LIPOCALIN; HOSPITALIZED-PATIENTS; AMBULATORY PATIENTS; CLINICAL-OUTCOMES; PROGNOSTIC VALUE; ELDERLY-PATIENTS; SERUM SODIUM; CYSTATIN-C; TROPONIN-T AB Background: The management of patients with heart failure has been evolving given the complex nature of the disease and the increasing number of patients. Findings: Biomarkers, and in particular the natriuretic peptides, have been studied to assist with diagnosis, chronic management, and prognosis in patients with heart failure. Several new biomarkers are emerging and may be used individually or in combination with the natriuretic peptides. The use of cardiac monitoring devices and disease management programs is being established to assist in the care of patients with chronic heart failure. Interventions using phone calls, telemedicine devices, intracardiac pressure monitors, and implantable cardioverter defibrillators have been investigated. Conclusions: The combination of biomarkers, monitoring devices, and disease management programs shows promise for improving care in this challenging patient population. C1 [Gandhi, Parul U.] Massachusetts Gen Hosp, Boston, MA 02114 USA. Mt Sinai Sch Med, New York, NY USA. RP Gandhi, PU (reprint author), Massachusetts Gen Hosp, Boston, MA 02114 USA. EM pgandhi2@partners.org NR 55 TC 2 Z9 2 U1 1 U2 4 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 2214-9996 J9 ANN GLOB HEALTH JI Ann. Glob. Health PD JAN-FEB PY 2014 VL 80 IS 1 BP 46 EP 54 DI 10.1016/j.aogh.2013.12.005 PG 9 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA AJ8GA UT WOS:000337939600007 PM 24751564 ER PT J AU Lou, E Johnson, M Sima, C Gonzalez-Espinoza, R Fleisher, M Kris, MG Azzoli, CG AF Lou, Emil Johnson, Melissa Sima, Camelia Gonzalez-Espinoza, Rita Fleisher, Martin Kris, Mark G. Azzoli, Christopher G. TI Serum biomarkers for assessing histology and outcomes in patients with metastatic lung cancer SO CANCER BIOMARKERS LA English DT Article DE Lung cancer; biomarkers; biomarker panel; CYFRA 21-1; SCCL-Ag ID NEURON-SPECIFIC ENOLASE; GASTRIN-RELEASING PEPTIDE; CELL CARCINOMA ANTIGEN; CARCINOEMBRYONIC ANTIGEN; TUMOR-MARKERS; CYFRA 21.1; DIAGNOSIS; SCC; CEA; IMMUNOASSAY AB BACKGROUND: Serum biomarkers are not in routine clinical use for diagnosis, prognosis, or treatment selection in lung cancer. OBJECTIVE: We examined serum protein biomarkers from patients with metastatic lung cancer to determine whether they correlate with progression-free survival (PFS), overall survival (OS), or histologic subtype. METHODS: Serum samples were collected prior to chemotherapy from 153 patients with metastatic lung cancer treated at Memorial Sloan-Kettering Cancer Center. Serum biomarkers were selected for ELISA testing based on their availability in a CLIA-certified clinical laboratory: ProGRP, SCC-Ag, NSE, CYFRA 21-1, TIMP1, and HE4. Pretreatment biomarker levels were correlated with outcome using proportional hazards analysis and tumor histology using logistic regression analysis. RESULTS: Univariate analysis indicated that only higher levels of CYFRA 21-1 were significantly associated with worsened PFS (HR 1.3, 95% CI 1.1-1.5, p < 0.01) and OS (HR 1.4, 95% CI 1.2-1.7, p < 0.001). Multivariate analysis of NSE, CYFRA 21-1, and TIMP1 indicated that CYFRA21-1 remained independently associated with lower OS (HR 1.3, 95% CI 1.1-1.6, p < 0.01). Univariate analysis indicated that ProGRP (OR 3.3, 95% CI 1.7-6.5, p < 0.001) and NSE (OR 4.8, 95% CI 2.6-8.8, p < 0.0001) had the highest probabilities of differentiating SCLC from NSCLC. Multivariate analysis of these two markers demonstrated that they predicted SCLC histology with 94% accuracy. Univariate analysis showed that only SCCL-Ag distinguished squamous cell histology from adenocarcinoma (OR 4.4, 95% CI 1.7-11.5, p < 0.01). CONCLUSIONS: Serum CYFRA 21-1 may be useful in predicting patient survival, and serum ProGRP, NSE 21-1, and SCCL-Ag may be helpful in distinguishing between lung cancer sub-types. C1 [Lou, Emil] Univ Minnesota, Dept Med, Div Hematol Oncol & Transplantat, Minneapolis, MN 55455 USA. [Johnson, Melissa] Northwestern Univ, Feinberg Sch Med, Dept Med, Chicago, IL 60611 USA. [Sima, Camelia] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. [Gonzalez-Espinoza, Rita; Fleisher, Martin] Mem Sloan Kettering Canc Ctr, Dept Lab Med, New York, NY 10021 USA. [Kris, Mark G.] Weill Cornell Med Coll, Mem Sloan Kettering Canc Ctr, Div Solid Tumor Oncol, Thorac Oncol Serv,Dept Med, New York, NY USA. [Azzoli, Christopher G.] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. RP Azzoli, CG (reprint author), 55 Fruit St, Boston, MA 02114 USA. EM cazzoli@partners.org OI Kris, Mark/0000-0002-7317-5341 FU Philanthropic funds FX Philanthropic funds provided to the MSKCC Thoracic Oncology Service. NR 20 TC 6 Z9 8 U1 0 U2 3 PU IOS PRESS PI AMSTERDAM PA NIEUWE HEMWEG 6B, 1013 BG AMSTERDAM, NETHERLANDS SN 1574-0153 EI 1875-8592 J9 CANCER BIOMARK JI Cancer Biomark. PY 2014 VL 14 IS 4 BP 207 EP 214 DI 10.3233/CBM-140399 PG 8 WC Oncology SC Oncology GA AJ7XY UT WOS:000337916100003 PM 24934363 ER PT J AU Sachs, DH Kawai, T Sykes, M AF Sachs, David H. Kawai, Tatsuo Sykes, Megan TI Induction of Tolerance through Mixed Chimerism SO COLD SPRING HARBOR PERSPECTIVES IN MEDICINE LA English DT Article ID BONE-MARROW-TRANSPLANTATION; HEMATOPOIETIC-CELL TRANSPLANTATION; VERSUS-HOST-DISEASE; MAJOR HISTOCOMPATIBILITY COMPLEX; RECIPIENT LEUKOCYTE INFUSIONS; TOTAL LYMPHOID IRRADIATION; RENAL-ALLOGRAFT TOLERANCE; WHOLE-BODY IRRADIATION; CD8(+) T-CELLS; ANTIGEN-PRESENTING CELLS AB "Mixed chimerism" refers to a state in which the lymphohematopoietic system of the recipient of allogeneic hematopoietic stem cells comprises a mixture of host and donor cells. This state is usually attained through either bone marrow or mobilized peripheral blood stem cell transplantation. Although numerous treatment regimens have led to transplantation tolerance in mice, the induction of mixed chimerism is currently the only treatment modality that has been successfully extended to large animals and to the clinic. Here we describe and compare the use of mixed chimerism to establish transplantation tolerance in mice, pigs, monkeys, and in the clinic. We also attempt to correlate the mechanisms involved in achieving tolerance with the nature of the tolerance that has resulted in each case. C1 [Sachs, David H.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Transplantat Biol Res Ctr, Boston, MA 02129 USA. [Kawai, Tatsuo] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Transplant Ctr, Boston, MA 02115 USA. [Sykes, Megan] Columbia Univ, Med Ctr, Columbia Ctr Translat Immunol, New York, NY 10032 USA. RP Sachs, DH (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Transplantat Biol Res Ctr, Boston, MA 02129 USA. EM sachs@helix.mgh.harvard.edu NR 139 TC 29 Z9 30 U1 1 U2 5 PU COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT PI COLD SPRING HARBOR PA 1 BUNGTOWN RD, COLD SPRING HARBOR, NY 11724 USA SN 2157-1422 J9 CSH PERSPECT MED JI Cold Spring Harb. Perspect. Med. PD JAN PY 2014 VL 4 IS 1 AR a015529 DI 10.1101/cshperspect.a015529 PG 19 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA AJ9HD UT WOS:000338017900005 PM 24384815 ER PT J AU Zackowski, KM Cameron, M Wagner, JM AF Zackowski, Kathleen M. Cameron, Michelle Wagner, Joanne M. TI 2nd International Symposium on Gait and Balance in Multiple Sclerosis: interventions for gait and balance in MS SO DISABILITY AND REHABILITATION LA English DT Article DE Physical therapy; rehabilitation; walking ID FUNCTIONAL ELECTRICAL-STIMULATION; RANDOMIZED CONTROLLED-TRIAL; DEFICIT HYPERACTIVITY DISORDER; DWELLING OLDER-PEOPLE; SPINAL-CORD-INJURY; PARKINSONS-DISEASE; DOUBLE-BLIND; LOCOMOTOR ADAPTATIONS; MANAGEMENT PROGRAM; ACCIDENTAL FALLS AB Purpose: To provide a review of the 2nd International Symposium on Gait and Balance in Multiple Sclerosis (MS), emphasizing interventions in gait and balance for people with MS. Method: Review of current research on interventions used with people having MS and with people having other disorders that may provide novel insights into improving gait and balance and preventing falls in people with MS (pwMS). Results: Nine speakers provided evidence-based recommendations for interventions aimed at improving gait and balance dysfunction. Speaker recommendations covered the following areas: balance rehabilitation, self-management, medications, functional electrical stimulation, robotics, sensory augmentation, gait training with error feedback and fall prevention. Conclusions: The causes of gait and balance dysfunction in pwMS are multifactorial and therefore may benefit from a wide range of interventions. The symposium provides avenues for exchange of evidence and clinical experience that is critical in furthering physical rehabilitation including gait and balance dysfunction in MS. C1 [Zackowski, Kathleen M.] Johns Hopkins Univ, Kennedy Krieger Inst, Sch Med, Dept Phys Med & Rehabil, Baltimore, MD 21205 USA. [Cameron, Michelle] Oregon Hlth & Sci Univ, Dept Neurol, Portland, OR 97201 USA. [Cameron, Michelle] Portland VA Med Ctr, Portland, OR 97201 USA. [Wagner, Joanne M.] St Louis Univ, Dept Phys Therapy & Athlet Training, Doisy Coll Hlth Sci, St Louis, MO 63103 USA. RP Zackowski, KM (reprint author), Johns Hopkins Univ, Kennedy Krieger Inst, Sch Med, 707 N Broadway,G-05, Baltimore, MD 21205 USA. EM zackowski@kennedykrieger.org FU Acorda Therapeutics; Sun Pharmaceuticals; Biogen Idec. FX Kathleen Zackowski has research grant support from the Acorda Therapeutics, Biogen Idec., and Sun Pharmaceuticals. Michelle Cameron has received honorarium and travel for speaking and consultation from Acorda Therapeutics. Joanne Wagner has received honorarium for speaking from Acorda Therapeutics. The 2nd International Symposium on Gait and Balance was in-part supported by Acorda Therapeutics through an educational grant. Additional expenses were covered by registration and exhibit fees. NR 59 TC 0 Z9 0 U1 2 U2 8 PU INFORMA HEALTHCARE PI LONDON PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND SN 0963-8288 EI 1464-5165 J9 DISABIL REHABIL JI Disabil. Rehabil. PY 2014 VL 36 IS 13 BP 1128 EP 1132 DI 10.3109/09638288.2013.833306 PG 5 WC Rehabilitation SC Rehabilitation GA AJ5VJ UT WOS:000337757600011 PM 24041009 ER PT J AU Shao, HJ Zhang, YY Dong, YL Yu, BW Xia, WM Xie, ZC AF Shao, Haijun Zhang, Yiying Dong, Yuanlin Yu, Buwei Xia, Weiming Xie, Zhongcong TI Chronic Treatment with Anesthetic Propofol Improves Cognitive Function and Attenuates Caspase Activation in Both Aged and Alzheimer's Disease Transgenic Mice SO JOURNAL OF ALZHEIMERS DISEASE LA English DT Article DE Aging; Alzheimer's disease; amyloid-beta protein; anesthesia; apoptosis; mitochondria; neurodegeneration; propofol ID CELL-DEATH; GABA(A) RECEPTORS; MOUSE MODEL; PARKINSONS-DISEASE; PROTEIN EXPRESSION; CEREBRAL-ISCHEMIA; PRECURSOR PROTEIN; APOPTOSIS; BRAIN; MEMORY AB There is a need to seek new treatment(s) for Alzheimer's disease (AD). A recent study showed that AD patients may have decreased levels of functional GABA receptors. Propofol, a commonly used anesthetic, is a GABA receptor agonist. We therefore set out to perform a proof of concept study to determine whether chronic treatment with propofol (50 mg/kg/week) can improve cognitive function in both aged wild-type (WT) and AD transgenic (Tg) mice. Propofol was administrated to the WT and AD Tg mice once a week for 8 or 12 weeks, respectively. Morris water maze was used to assess the cognitive function of the mice following the propofol treatment. Activation of caspase-3, caspase-9, and caspase-8 was investigated using western blot analysis at the end of the propofol treatment. In the mechanistic studies, effects of propofol, amyloid-beta protein (A beta), and GABA receptor antagonist flumazenil on caspase-3 activation and opening of the mitochondrial permeability transition pore were assessed in H4 human neuroglioma and mouse neuroblastoma cells by western blot analysis and flow cytometry. Here we showed that the propofol treatment improved cognitive function and attenuated brain caspase-3 and caspase-9 activation in both aged WT and AD Tg mice. Propofol attenuated A beta-induced caspase-3 activation and opening of the mitochondrial permeability transition pore in the cells, and flumazenil inhibited the propofol's effects. These results suggested that propofol might improve cognitive function via attenuating the A beta-induced mitochondria dysfunction and caspase activation, which explored the potential that anesthetic propofol could improve cognitive function in elderly and AD patients. C1 [Shao, Haijun; Zhang, Yiying; Dong, Yuanlin; Xie, Zhongcong] Massachusetts Gen Hosp, Geriatr Anesthesia Res Unit, Dept Anesthesia Crit Care & Pain Med, Charlestown, MA 02129 USA. [Shao, Haijun; Zhang, Yiying; Dong, Yuanlin; Xie, Zhongcong] Harvard Univ, Sch Med, Charlestown, MA 02129 USA. [Shao, Haijun; Yu, Buwei] Shanghai Jiao Tong Univ, Dept Anesthesiol, Ruijin Hosp, Sch Med, Shanghai 200030, Peoples R China. [Xia, Weiming] Dept Vet Affairs, Med Res & Dev Serv, Bedford, MA USA. [Xia, Weiming] Geriatr Res Educ & Clin Ctr, Bedford, MA USA. RP Xie, ZC (reprint author), Massachusetts Gen Hosp, Geriatr Anesthesia Res Unit, Dept Anesthesia Crit Care & Pain Med, 149 13th St,Room 4310, Charlestown, MA 02129 USA. EM zxie@mgh.harvard.edu RI xia, weiming/E-5465-2016 OI xia, weiming/0000-0002-7463-3295 FU NIA NIH HHS [R21AG038994, R01 AG041274, R21 AG029856, R21 AG038994]; NIDDK NIH HHS [P30 DK040561]; NIGMS NIH HHS [R01 GM088801] NR 61 TC 5 Z9 6 U1 1 U2 6 PU IOS PRESS PI AMSTERDAM PA NIEUWE HEMWEG 6B, 1013 BG AMSTERDAM, NETHERLANDS SN 1387-2877 EI 1875-8908 J9 J ALZHEIMERS DIS JI J. Alzheimers Dis. PY 2014 VL 41 IS 2 BP 499 EP 513 DI 10.3233/JAD-132792 PG 15 WC Neurosciences SC Neurosciences & Neurology GA AJ7YN UT WOS:000337918000015 PM 24643139 ER PT J AU Wang, J Varghese, M Ono, K Yamada, M Levine, S Tzavaras, N Gong, B Hurst, WJ Blitzer, RD Pasinetti, GM AF Wang, Jun Varghese, Merina Ono, Kenjiro Yamada, Masahito Levine, Samara Tzavaras, Nikos Gong, Bing Hurst, William J. Blitzer, Robert D. Pasinetti, Giulio Maria TI Cocoa Extracts Reduce Oligomerization of Amyloid-beta: Implications for Cognitive Improvement in Alzheimer's Disease SO JOURNAL OF ALZHEIMERS DISEASE LA English DT Article DE Amyloid; diet therapy; oligomerization; polyphenols; synapses ID FLAVANOL-RICH COCOA; TETRAHYDROXYSTILBENE GLUCOSIDE; ANTIOXIDANT CAPACITY; SYNAPTIC PLASTICITY; MEMORY; PERFORMANCE; CHOCOLATE; PRODUCTS; PROCYANIDIN; POLYPHENOLS AB Background: Alzheimer's disease (AD) is the most common age-related neurodegenerative disorder, characterized by pathological aggregates of amyloid peptide-beta (A beta) and tau protein. Currently available therapies mediate AD symptoms without modifying disease progression. Polyphenol-rich diets are reported to reduce the risk for AD. Objective: In the present study, we investigated the AD disease-modifying effects of cocoa, a rich source of flavanols, which are a class of polyphenols. We hypothesized that cocoa extracts interfere with amyloid-beta oligomerization to prevent synaptic deficits. Methods: We tested the effects of three different cocoa extracts, viz. Natural, Dutched, and Lavado extracts, on A beta(42) and A beta(40) oligomerization, using photo-induced cross-linking of unmodified proteins technique. To assess the effects of cocoa extracts on synaptic function, we measured long term potentiation in mouse brain hippocampal slices exposed to oligomeric A beta. Results: Our results indicate that cocoa extracts are effective in preventing the oligomerization of A beta, with Lavado extract being most effective. Lavado extract, but not Dutched extract, was effective in restoring the long term potentiation response reduced by oligomeric A beta. Conclusion: Our findings indicate that cocoa extracts have multiple disease-modifying properties in AD and present a promising route of therapeutic and/or preventative initiatives. C1 [Wang, Jun; Varghese, Merina; Levine, Samara; Gong, Bing; Pasinetti, Giulio Maria] Icahn Sch Med Mt Sinai, Dept Neurol, New York, NY 10029 USA. [Tzavaras, Nikos; Blitzer, Robert D.] Icahn Sch Med Mt Sinai, Dept Pharmacol & Syst Therapeut, New York, NY 10029 USA. [Wang, Jun; Pasinetti, Giulio Maria] James J Peters Vet Affairs Med Ctr, Geriatr Res Educ & Clin Ctr, Bronx, NY USA. [Ono, Kenjiro; Yamada, Masahito] Kanazawa Univ, Grad Sch Med Sci, Dept Neurol & Neurobiol & Aging, Kanazawa, Ishikawa, Japan. [Hurst, William J.] Hershey Co, Hershey Ctr Hlth & Nutr, Hershey, PA USA. RP Pasinetti, GM (reprint author), Mt Sinai Sch Med, Dept Neurol, 1 Gustave L Levy Pl,Box 1137, New York, NY 10029 USA. EM giulio.pasinetti@mssm.edu NR 37 TC 11 Z9 13 U1 5 U2 22 PU IOS PRESS PI AMSTERDAM PA NIEUWE HEMWEG 6B, 1013 BG AMSTERDAM, NETHERLANDS SN 1387-2877 EI 1875-8908 J9 J ALZHEIMERS DIS JI J. Alzheimers Dis. PY 2014 VL 41 IS 2 BP 643 EP 650 DI 10.3233/JAD-132231 PG 8 WC Neurosciences SC Neurosciences & Neurology GA AJ7YN UT WOS:000337918000027 PM 24957018 ER PT J AU Vaudreuil, NJ Ledoux, WR Roush, GC Whittaker, EC Sangeorzan, BJ AF Vaudreuil, Nicholas J. Ledoux, William R. Roush, Grant C. Whittaker, Eric C. Sangeorzan, Bruce J. TI Comparison of Transfer Sites for Flexor Digitorum Longus in a Cadaveric Adult Acquired Flatfoot Model SO JOURNAL OF ORTHOPAEDIC RESEARCH LA English DT Article DE posterior tibial tendon dysfunction; flexor digitorum longus transfer; PTTD; FDL; gait simulation ID POSTERIOR TIBIAL-TENDON; CALCANEAL OSTEOTOMY; GAIT SIMULATOR; DYSFUNCTION; HINDFOOT; FOOT; KINEMATICS; DEFORMITY; PRESSURE; ARCH AB Posterior tibialis tendon (PTT) dysfunction (PTTD) is associated with adult acquired flatfoot deformity. PTTD is commonly treated with a flexor digitorum longus (FDL) tendon transfer (FDLTT) to the navicular (NAV), medial cuneiform (CUN), or distal residuum of the degraded PTT (rPTT). We assessed the kinetic and kinematic outcomes of these three attachment sites using cadaveric gait simulation. Three transfer locations (NAV, CUN, rPTT) were tested on seven prepared flatfoot models using a robotic gait simulator (RGS). The FDLTT procedures were simulated by pulling on the PTT with biomechanically realistic FDL forces (rPTT) or by pulling on the transected FDL tendon after fixation to the navicular or medial cuneiform (NAV and CUN, respectively). Plantar pressure and foot bone motion were quantified. Peak plantar pressure significantly decreased from the flatfoot condition at the first metatarsal (NAV) and hallux (CUN). No difference was found in the medial-lateral center of pressure. Kinematic findings showed minimal differences between flatfoot and FDLTT specimens. The three locations demonstrated only minimal differences from the flatfoot condition, with the NAV and CUN procedures resulting in decreased medial pressures. Functionally, all three surgical procedures performed similarly. Published 2013 by Wiley Periodicals, Inc. on behalf of the Orthopaedic Research Society. C1 [Vaudreuil, Nicholas J.; Ledoux, William R.; Roush, Grant C.; Whittaker, Eric C.; Sangeorzan, Bruce J.] VA Puget Sound, RR&D Ctr Excellence Limb Loss Prevent & Prosthet, Seattle, WA 98108 USA. [Vaudreuil, Nicholas J.] Univ Washington, Sch Med, Seattle, WA 98195 USA. [Ledoux, William R.; Roush, Grant C.] Univ Washington, Dept Mech Engn, Seattle, WA 98195 USA. [Ledoux, William R.; Sangeorzan, Bruce J.] Univ Washington, Dept Orthopaed & Sports Med, Seattle, WA 98195 USA. RP Ledoux, WR (reprint author), VA Puget Sound, RR&D Ctr Excellence Limb Loss Prevent & Prosthet, Seattle, WA 98108 USA. EM wrledoux@u.washington.edu RI Ledoux, William/K-6815-2015 OI Ledoux, William/0000-0003-4982-7714 FU Department of Veterans Affairs Rehabilitation Research and Development Service [A4843C]; University of Washington Medical Student Research Training Program FX Grant sponsor: Department of Veterans Affairs Rehabilitation Research and Development Service; Grant number: A4843C; Grant sponsor: University of Washington Medical Student Research Training Program. NR 30 TC 1 Z9 1 U1 1 U2 10 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0736-0266 EI 1554-527X J9 J ORTHOP RES JI J. Orthop. Res. PD JAN PY 2014 VL 32 IS 1 BP 102 EP 109 DI 10.1002/jor.22488 PG 8 WC Orthopedics SC Orthopedics GA AK0EW UT WOS:000338086700014 PM 24115238 ER PT J AU Joshi, SK Kim, HT Feeley, BT Liu, XH AF Joshi, Sunil K. Kim, Hubert T. Feeley, Brian T. Liu, Xuhui TI Differential Ubiquitin-Proteasome and Autophagy Signaling Following Rotator Cuff Tears and Suprascapular Nerve Injury SO JOURNAL OF ORTHOPAEDIC RESEARCH LA English DT Article DE rotator cuff tear; denervation; muscle atrophy; ubiquitin-proteasome; autophagy ID SKELETAL-MUSCLE ATROPHY; DENERVATION ATROPHY; FATTY INFILTRATION; PROTEIN-SYNTHESIS; RAT MODEL; DEGRADATION; REPAIR; IDENTIFICATION; SUPRASPINATUS; ACTIVATION AB Previous studies have evaluated role of Akt/mTOR signaling in rotator cuff muscle atrophy and determined that there was differential in signaling following tendon transection (TT) and suprascapular nerve (SSN) denervation (DN), suggesting that atrophy following TT and DN was modulated by different protein degradation pathways. In this study, two muscle proteolytic systems that have been shown to be potent regulators of muscle atrophy in other injury models, the ubiquitin-proteasome pathway and autophagy, were evaluated following TT and DN. In addition to examining protein degradation, this study assessed protein synthesis rate following these two surgical models to understand how the balance between protein degradation and synthesis results in atrophy following rotator cuff injury. In contrast to the traditional theory that protein synthesis is decreased during muscle atrophy, this study suggests that protein synthesis is up-regulated in rotator cuff muscle atrophy following both surgical models. While the ubiquitin-proteasome pathway was a major contributor to the atrophy seen following DN, autophagy was a major contributor following TT. The findings of this study suggest that protein degradation is the primary factor contributing to atrophy following rotator cuff injury. However, different proteolytic pathways are activated if SSN injury is involved. (C) 2013 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. C1 [Joshi, Sunil K.; Kim, Hubert T.; Feeley, Brian T.; Liu, Xuhui] San Francisco VA Med Ctr, Dept Vet Affairs, San Francisco, CA 94153 USA. [Joshi, Sunil K.; Kim, Hubert T.; Feeley, Brian T.; Liu, Xuhui] Univ Calif San Francisco, Dept Orthopaed Surg, San Francisco, CA 94158 USA. RP Liu, XH (reprint author), San Francisco VA Med Ctr, Dept Vet Affairs, 4150 Clement St, San Francisco, CA 94153 USA. EM Liux@orthosurg.ucsf.edu FU Veterans Affairs RR & D Merit Review Grant [RX000195]; NIH/NIAMS RO3 [AR060871-02]; Orthopaedic Research and Education Foundation FX Grant sponsor: Veterans Affairs RR & D Merit Review Grant; Grant number: RX000195; Grant sponsor: NIH/NIAMS RO3; Grant number: AR060871-02; Grant sponsor: Orthopaedic Research and Education Foundation. NR 43 TC 9 Z9 9 U1 0 U2 6 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0736-0266 EI 1554-527X J9 J ORTHOP RES JI J. Orthop. Res. PD JAN PY 2014 VL 32 IS 1 BP 138 EP 144 DI 10.1002/jor.22482 PG 7 WC Orthopedics SC Orthopedics GA AK0EW UT WOS:000338086700019 PM 24018537 ER PT J AU Issadore, D Park, YI Shao, H Min, C Lee, K Liong, M Weissleder, R Lee, H AF Issadore, D. Park, Y. I. Shao, H. Min, C. Lee, K. Liong, M. Weissleder, R. Lee, H. TI Magnetic sensing technology for molecular analyses SO LAB ON A CHIP LA English DT Review ID CIRCULATING TUMOR-CELLS; IRON-OXIDE NANOPARTICLES; CORE-SHELL NANOPARTICLES; SPIN-VALVE SENSORS; BIOMEDICAL APPLICATIONS; HALL SENSOR; ULTRASENSITIVE DETECTION; BIOLOGICAL APPLICATIONS; RAPID DETECTION; RESONANCE AB Magnetic biosensors, based on nanomaterials and miniature electronics, have emerged as a powerful diagnostic platform. Benefiting from the inherently negligible magnetic background of biological objects, magnetic detection is highly selective even in complex biological media. The sensing thus requires minimal sample purification and yet achieves a high signal-to-background contrast. Moreover, magnetic sensors are also well-suited for miniaturization to match the size of biological targets, which enables sensitive detection of rare cells and small amounts of molecular markers. We herein summarize recent advances in magnetic sensing technologies, with an emphasis on clinical applications in point-of-care settings. Key components of sensors, including magnetic nanomaterials, labeling strategies and magnetometry, are reviewed. C1 [Issadore, D.] Univ Penn, Sch Engn & Appl Sci, Philadelphia, PA 19104 USA. [Park, Y. I.; Shao, H.; Min, C.; Lee, K.; Liong, M.; Weissleder, R.; Lee, H.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Syst Biol, Boston, MA 02114 USA. [Weissleder, R.] Harvard Univ, Sch Med, Dept Syst Biol, Boston, MA 02114 USA. RP Weissleder, R (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Syst Biol, Boston, MA 02114 USA. EM rweissleder@mgh.harvard.edu; hlee@mgh.harvard.edu RI Issadore, David/L-8451-2014; Lee, Kyungheon/E-3863-2013 FU National Science Scholarship awarded by the Agency for Science, Technology and Research, Singapore; NIH [R01HL113156, R01EB004626, R01EB010011, HHSN268201000044C, U54CA119349, K12CA087723-09, T32-CA79443] FX The authors thank R. M. Westervelt ( Harvard) for helpful discussion. H. Shao 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 the NIH grants R01HL113156, R01EB004626, R01EB010011, HHSN268201000044C, U54-CA119349, K12CA087723-09, and T32-CA79443. NR 105 TC 20 Z9 20 U1 7 U2 65 PU ROYAL SOC CHEMISTRY PI CAMBRIDGE PA THOMAS GRAHAM HOUSE, SCIENCE PARK, MILTON RD, CAMBRIDGE CB4 0WF, CAMBS, ENGLAND SN 1473-0197 EI 1473-0189 J9 LAB CHIP JI Lab Chip PY 2014 VL 14 IS 14 BP 2385 EP 2397 DI 10.1039/c4lc00314d PG 13 WC Biochemical Research Methods; Chemistry, Multidisciplinary; Nanoscience & Nanotechnology SC Biochemistry & Molecular Biology; Chemistry; Science & Technology - Other Topics GA AJ9NH UT WOS:000338037900002 PM 24887807 ER PT B AU Chee, YE Eliott, D AF Chee, Yewlin E. Eliott, Dean BE Hariprasad, SM TI Retinal Vein Occlusion Clinical Trials Historical Perspective and Current Relevance SO MANAGEMENT OF RETINAL VEIN OCCLUSION: CURRENT CONCEPTS LA English DT Article; Book Chapter ID ARGON-LASER PHOTOCOAGULATION; MACULAR EDEMA SECONDARY; ISOVOLEMIC HEMODILUTION; PANRETINAL PHOTOCOAGULATION; INTRAVITREAL TRIAMCINOLONE; NATURAL-HISTORY; STANDARD-CARE; BRANCH; MANAGEMENT; NEOVASCULARIZATION C1 [Chee, Yewlin E.] Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Boston, MA 02138 USA. RP Chee, YE (reprint author), Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Boston, MA 02138 USA. NR 53 TC 0 Z9 0 U1 0 U2 1 PU SLACK INC PI THOROFARE PA 6900 GROVE ROAD, THOROFARE, NJ 08086-9447 USA BN 978-1-61711-616-2 PY 2014 BP 19 EP 32 PG 14 WC Ophthalmology SC Ophthalmology GA BA3PO UT WOS:000334564400003 ER PT S AU Nappi, JJ Ryu, Y Yoshida, H AF Naeppi, Janne J. Ryu, Yasuji Yoshida, Hiroyuki BE Aylward, S Hadjiiski, LM TI Progressive region-based colon extraction for computer-aided detection and quantitative imaging in cathartic and non-cathartic CT colonography SO MEDICAL IMAGING 2014: COMPUTER-AIDED DIAGNOSIS SE Proceedings of SPIE LA English DT Proceedings Paper CT Conference on Medical Imaging - Computer-Aided Diagnosis CY FEB 18-20, 2014 CL San Diego, CA SP SPIE, Modus Med Devices Inc, XIFIN, Inc, Ventana Med Syst Inc, Intrace Med DE Colon; segmentation; extraction; quantitative imaging; CT colonography; virtual colonoscopy; fecal tagging; non-cathartic ID DISTENSION; CAD AB Automated colon extraction is an important first step for applications of computer-aided detection (CADe) and quantitative imaging in computed tomographic colonography (CTC). However, previously developed colon extraction algorithms have various limitations. We developed a new fully automated progressive region-based (PRB) method to extract the complete region of colon from CTC images while minimizing the presence of extra-colonic components. The method can be used to provide the target region for CADe as well as to provide quantitative imaging information about the colon. In the method, extra-colonic components are excluded from the abdominal region by use of anatomy-based extraction methods, visible lumen regions of the colon and small bowel are decomposed into material-based subregions, a colon pathway is tracked from the anus to cecum by use of algorithms of progressively increasing complexity using anatomy-based landmarks, segmental features, and region-based tracking algorithms, and the extracted lumen region is perfected into a complete lumen by use of a discrete level-set algorithm. The method was tested with 15 challenging cathartic and non-cathartic fecal-tagging CTC cases. Preliminary results indicate that the PRB method can outperform our previously developed centerline-based tracking method in colon extraction. C1 [Naeppi, Janne J.; Ryu, Yasuji; Yoshida, Hiroyuki] Massachusetts Gen Hosp, Dept Radiol, Imaging Res 3D, Boston, MA 02114 USA. RP Nappi, JJ (reprint author), Massachusetts Gen Hosp, Dept Radiol, Imaging Res 3D, 25 New Chardon St,Suite 400C, Boston, MA 02114 USA. EM janne.nappi@mgh.harvard.edu; yoshida.hiro@mgh.harvard.edu NR 12 TC 0 Z9 0 U1 0 U2 0 PU SPIE-INT SOC OPTICAL ENGINEERING PI BELLINGHAM PA 1000 20TH ST, PO BOX 10, BELLINGHAM, WA 98227-0010 USA SN 0277-786X BN 978-0-8194-9828-1 J9 PROC SPIE PY 2014 VL 9035 AR 90352X DI 10.1117/12.2043890 PG 8 WC Engineering, Electrical & Electronic; Optics; Radiology, Nuclear Medicine & Medical Imaging SC Engineering; Optics; Radiology, Nuclear Medicine & Medical Imaging GA BA7XB UT WOS:000337842400100 ER PT J AU Mobo, BH Foster, LA Rabesa, MJ AF Mobo, B. H. Foster, L. A. Rabesa, M. J. TI Occupational hazards associated with endoscope high-level disinfection: Case vignettes, review of literature and recommendations for mitigation SO WORK-A JOURNAL OF PREVENTION ASSESSMENT & REHABILITATION LA English DT Article DE Endoscope technicians; denatonium benzoate; ortho-phthalaldehyde; proteinase subtilisin; isopropyl alcohol ID GASTROINTESTINAL ENDOSCOPY; INFECTION; ASTHMA AB BACKGROUND: High-level disinfection is crucial in preventing instrument-related infections. However, inadequate process and practice may expose technicians to chemicals and other hazards. OBJECTIVE: The aim of this article is to describe the health effects related to high-level disinfection, the process of identifying hazards and safer practice recommendations. PARTICIPANTS: Two endoscope technicians with different clinical presentations were evaluated for workplace exposures. METHODS: In addition to acute clinical care, corroborative information was obtained through walkthrough and observing patients performing their daily tasks, interview of co-workers, environmental assessment and review of published literature. Recommendations for improvement and clinical follow up were made. RESULTS: Clinical evaluation and workplace assessment identified potential exposures to: denatonium benzoate, ortho-phthalaldehyde, proteinase subtilisin, and isopropyl alcohol. Environmental monitoring showed adequate ventilation but with potential for acute high-level exposure to high-level disinfectants. Ergonomic stressors and noise were addressed. Following work restrictions and work practice changes, both patients were able to return to work without recurrence of symptoms. CONCLUSION: The occupational hazards of working in an endoscopy disinfection unit include chemicals that are irritants and/or allergenic. In addition to bioengineering controls, administrative controls and proper respiratory and dermal protections may mitigate exposure and allow workers to continue working safely. C1 [Mobo, B. H.; Foster, L. A.; Rabesa, M. J.] Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Boston, MA 02215 USA. RP Mobo, BH (reprint author), BIDMC Employee Occupat Hlth Serv, 110 Francis St,Suite 6C, Boston, MA 02215 USA. EM jaymobo@yahoo.com NR 17 TC 0 Z9 0 U1 2 U2 2 PU IOS PRESS PI AMSTERDAM PA NIEUWE HEMWEG 6B, 1013 BG AMSTERDAM, NETHERLANDS SN 1051-9815 EI 1875-9270 J9 WORK JI Work PY 2014 VL 48 IS 2 BP 255 EP 260 DI 10.3233/WOR-131618 PG 6 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA AJ7WR UT WOS:000337911800012 PM 23531579 ER PT S AU Fusar-Poli, P Carpenter, WT Woods, SW McGlashan, TH AF Fusar-Poli, P. Carpenter, W. T. Woods, S. W. McGlashan, T. H. BE Cannon, TD Widiger, T TI Attenuated Psychosis Syndrome: Ready for DSM-5.1? SO ANNUAL REVIEW OF CLINICAL PSYCHOLOGY, VOL 10 SE Annual Review of Clinical Psychology LA English DT Article; Book Chapter DE psychosis; schizophrenia; prodromal; high risk; prevention; attenuated psychosis syndrome ID ULTRA-HIGH-RISK; RANDOMIZED CONTROLLED-TRIAL; MILD COGNITIVE IMPAIRMENT; MAGNETIC-RESONANCE SPECTROSCOPY; 1ST EPISODE PSYCHOSIS; BASIC SYMPTOMS BSABS; CLINICAL HIGH-RISK; AT-RISK; 1ST-EPISODE PSYCHOSIS; COMPREHENSIVE ASSESSMENT AB Prodromal features of the schizophrenia syndrome have been described for a century, and work in the past two decades has produced a substantial literature based on these features to identify individuals at increased risk for developing a psychotic disorder. Sometimes conceptualized as a "risk state" and sometimes as early manifestations of a "disorder," the work has been conducted with several related but different constructs. Early in the preparation of the fifth edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-5) public comment was sought on the proposal to create a new disorder termed attenuated psychosis syndrome (APS), and a range of issues emerged that generated interesting and important controversies. In this review, these criticisms are fully discussed, the APS concept is explicated; data relating to reliability, validity, and treatment are updated; the heterogeneity of APS is considered; and alternative views of the construct are presented with an emphasis on developmental pattern with timing for primary and secondary prevention and early treatment. Areas of future research are identified, and a potential roadmap for inclusion in DSM-5.1 is traced. C1 [Fusar-Poli, P.] Kings Coll London, Inst Psychiat, Dept Psychosis Studies, London SE5 8AF, England. [Fusar-Poli, P.] South London & Maudsley SLaM NHS Fdn Trust, OASIS Prodromal Team, London SE5 8AF, England. [Carpenter, W. T.] Univ Maryland, Sch Med, Maryland Psychiat Res Ctr, Baltimore, MD 21228 USA. [Carpenter, W. T.] US Dept Vet Affairs, VISN Mental Illness Res & Clin Ctr 5, Baltimore, MD 21201 USA. [Woods, S. W.; McGlashan, T. H.] Yale Univ, Sch Med, Dept Psychiat, Connecticut Mental Hlth Ctr, New Haven, CT 06519 USA. RP Fusar-Poli, P (reprint author), Kings Coll London, Inst Psychiat, Dept Psychosis Studies, London SE5 8AF, England. EM p.fusar@libero.it FU NIMH NIH HHS [U01 MH082022] NR 134 TC 35 Z9 37 U1 7 U2 20 PU ANNUAL REVIEWS PI PALO ALTO PA 4139 EL CAMINO WAY, PO BOX 10139, PALO ALTO, CA 94303-0897 USA SN 1548-5943 BN 978-0-8243-3910-4 J9 ANNU REV CLIN PSYCHO JI Annu. Rev. Clin. Psychol. PY 2014 VL 10 BP 155 EP 192 DI 10.1146/annurev-clinpsy-032813-153645 PG 38 WC Psychology, Clinical; Psychology SC Psychology GA BA4XX UT WOS:000336428200008 PM 24471375 ER PT S AU Griffith, JW Sokol, CL Luster, AD AF Griffith, Jason W. Sokol, Caroline L. Luster, Andrew D. BE Littman, DR Yokoyama, WM TI Chemokines and Chemokine Receptors: Positioning Cells for Host Defense and Immunity SO ANNUAL REVIEW OF IMMUNOLOGY, VOL 32 SE Annual Review of Immunology LA English DT Review; Book Chapter DE chemoattractants; cell migration; cell trafficking; immune regulation; lymph node; inflammation ID REGULATORY T-CELLS; EXPERIMENTAL AUTOIMMUNE ENCEPHALOMYELITIS; HIGH ENDOTHELIAL VENULES; PERIPHERAL LYMPH-NODES; CENTRAL-NERVOUS-SYSTEM; INDUCED AIRWAY INFLAMMATION; CD1D-RESTRICTED NKT CELLS; INFL AMMATORY ARTHRITIS; TISSUE HOMING RECEPTORS; MICE LACKING EXPRESSION AB Chemokines are chemotactic cytokines that control the migratory patterns and positioning of all immune cells. Although chemokines were initially appreciated as important mediators of acute inflammation, we now know that this complex system of approximately 50 endogenous chemokine ligands and 20 G protein-coupled seven-transmembrane signaling receptors is also critical for the generation of primary and secondary adaptive cellular and humoral immune responses. Recent studies demonstrate important roles for the chemokine system in the priming of naive T cells, in cell fate decisions such as effector and memory cell differentiation, and in regulatory T cell function. In this review, we focus on recent advances in understanding how the chemokine system orchestrates immune cell migration and positioning at the organismic level in homeostasis, in acute inflammation, and during the generation and regulation of adoptive primary and secondary immune responses in the lymphoid system and peripheral nonlymphoid tissue. C1 [Griffith, Jason W.; Sokol, Caroline L.; Luster, Andrew D.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Immunol & Inflammatory Dis,Div Rheumatol Alle, Boston, MA 02114 USA. RP Griffith, JW (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Immunol & Inflammatory Dis,Div Rheumatol Alle, Boston, MA 02114 USA. EM jwgriffith@mgh.harvard.edu; clsokol@mgh.harvard.edu; aluster@mgh.harvard.edu NR 256 TC 207 Z9 216 U1 18 U2 65 PU ANNUAL REVIEWS PI PALO ALTO PA 4139 EL CAMINO WAY, PO BOX 10139, PALO ALTO, CA 94303-0897 USA SN 0732-0582 BN 978-0-8243-3032-3 J9 ANNU REV IMMUNOL JI Annu. Rev. Immunol. PY 2014 VL 32 BP 659 EP 702 DI 10.1146/annurev-immunol-032713-120145 PG 44 WC Immunology SC Immunology GA BA4XV UT WOS:000336427400022 PM 24655300 ER PT S AU Chmielecki, J Meyerson, M AF Chmielecki, Juliann Meyerson, Matthew BE Caskey, CT TI DNA Sequencing of Cancer: What Have We Learned? SO ANNUAL REVIEW OF MEDICINE, VOL 65 SE Annual Review of Medicine LA English DT Review; Book Chapter DE genomics; mutations; rearrangements; pathways; cancer ID CELL LUNG-CANCER; CHRONIC MYELOID-LEUKEMIA; CHRONIC LYMPHOCYTIC-LEUKEMIA; COMPREHENSIVE GENOMIC CHARACTERIZATION; GASTROINTESTINAL STROMAL TUMORS; METASTATIC COLORECTAL-CANCER; TRANSCRIPTION FACTOR GENES; LINEAGE-SURVIVAL ONCOGENE; TERT PROMOTER MUTATIONS; BREAST-CANCER AB DNA sequencing has taught us much about the structure of cancer genomes and enabled the discovery of novel genes that drive and maintain tumorigenesis. With the advent and application of next-generation massively parallel sequencing technologies, one can rapidly generate and analyze data from the cellular "-omes": genomes, exomes, and transcriptomes. This review highlights recent genomic discoveries in signal transduction, metabolism, epigenetic modifications, cell cycle and genome maintenance, RNA processing, and transcription. Additionally, genomic sequencing has revealed the complexity of the cancer genome and has enabled the discovery of functional rearrangements with therapeutic and diagnostic potentials. C1 [Chmielecki, Juliann; Meyerson, Matthew] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Chmielecki, Juliann; Meyerson, Matthew] Broad Inst Harvard & Massachusetts Inst Technol, Canc Program, Cambridge, MA 02142 USA. [Meyerson, Matthew] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. [Meyerson, Matthew] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. RP Chmielecki, J (reprint author), Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. EM matthew_meyerson@dfci.harvard.edu NR 136 TC 18 Z9 19 U1 0 U2 10 PU ANNUAL REVIEWS PI PALO ALTO PA 4139 EL CAMINO WAY, PO BOX 10139, PALO ALTO, CA 94303-0897 USA SN 0066-4219 BN 978-0-8243-0565-9 J9 ANNU REV MED JI Annu. Rev. Med. PY 2014 VL 65 BP 63 EP 79 DI 10.1146/annurev-med-060712-200152 PG 17 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA BA4OD UT WOS:000336053000005 PM 24274178 ER PT S AU Tomer, Y AF Tomer, Yaron BE Abbas, AK Galli, SJ Howley, PM TI Mechanisms of Autoimmune Thyroid Diseases: From Genetics to Epigenetics SO ANNUAL REVIEW OF PATHOLOGY: MECHANISMS OF DISEASE, VOL 9 SE Annual Review of Pathology-Mechanisms of Disease LA English DT Review; Book Chapter DE autoimmunity; thyroid; Graves disease; Hashimoto's thyroiditis ID SINGLE-NUCLEOTIDE POLYMORPHISM; LYMPHOID TYROSINE PHOSPHATASE; GRAVES-DISEASE; RHEUMATOID-ARTHRITIS; ASSOCIATION ANALYSIS; INHIBITORY FUNCTION; WHICKHAM SURVEY; UNITED-STATES; DANISH TWINS; T-CELLS AB Recent advances in our understanding of genetic-epigenetic interactions have unraveled new mechanisms underlying the etiology of complex autoimmune diseases. Autoimmune thyroid diseases (AITDs) are highly prevalent, affecting 1% to 5% of the population. The major AITDs include Graves disease (GD) and Hashimoto's thyroiditis (HT); although these diseases contrast clinically, their pathogenesis involves shared immunogenetic mechanisms. Genetic data point to the involvement of both shared and unique genes. Among the shared susceptibility genes, HLA-DR beta 1-Arg74 (human leukocyte antigen DR containing an arginine at position beta 74) confers the strongest risk. Recent genome-wide analyses have revealed new putative candidate genes. Epigenetic modulation is emerging as a major mechanism by which environmental factors interact with AITD susceptibility genes. Dissecting the genetic-epigenetic interactions underlying the pathogenesis of AITD is essential to uncover new therapeutic targets. C1 [Tomer, Yaron] Mt Sinai Med Ctr, Dept Med, Div Endocrinol, New York, NY 10029 USA. [Tomer, Yaron] James J Peters VA Med Ctr, Bronx, NY 10468 USA. RP Tomer, Y (reprint author), Mt Sinai Med Ctr, Dept Med, Div Endocrinol, New York, NY 10029 USA. EM yaron.tomer@mssm.edu FU NIDDK NIH HHS [R01 DK061659, DK067555, DK073681, DK61659, R01 DK067555, R01 DK073681] NR 63 TC 28 Z9 28 U1 2 U2 17 PU ANNUAL REVIEWS PI PALO ALTO PA 4139 EL CAMINO WAY, PO BOX 10139, PALO ALTO, CA 94303-0897 USA SN 1553-4006 BN 978-0-8243-4309-5 J9 ANNU REV PATHOL-MECH JI Annu. Rev. Pathol.-Mech Dis. PY 2014 VL 9 BP 147 EP 156 DI 10.1146/annurev-pathol-012513-104713 PG 10 WC Pathology SC Pathology GA BA4OG UT WOS:000336055900007 PM 24460189 ER PT S AU Mahajan, VS Mattoo, H Deshpande, V Pillai, SS Stone, JH AF Mahajan, Vinay S. Mattoo, Hamid Deshpande, Vikram Pillai, Shiv S. Stone, John H. BE Abbas, AK Galli, SJ Howley, PM TI IgG4-Related Disease SO ANNUAL REVIEW OF PATHOLOGY: MECHANISMS OF DISEASE, VOL 9 SE Annual Review of Pathology-Mechanisms of Disease LA English DT Review; Book Chapter DE storiform fibrosis; IgG4-related disease; rituximab; obliterative phlebitis; Fab arm exchange; autoimmune pancreatitis ID HELICOBACTER-PYLORI INFECTION; FAB-ARM EXCHANGE; PRIMARY SCLEROSING CHOLANGITIS; REGULATORY IMMUNE-REACTIONS; ABDOMINAL AORTIC-ANEURYSM; PRIMARY SJOGRENS-SYNDROME; ANTIGEN-PRESENTING CELLS; FC-GAMMA RECEPTORS; AUTOIMMUNE PANCREATITIS; SYSTEMIC-DISEASE AB Immunoglobulin G4 (IgG4)-related disease (IgG4-RD) is an immune-mediated condition that can affect almost any organ and is now being recognized with increasing frequency. IgG4-RD is characterized by a lymphoplasmacytic infiltrate composed of IgG4(+) plasma cells, storiform fibrosis, obliterative phlebitis, and mild to moderate eosinophilia. The diagnosis of IgG4-RD unifies many eponymous fibroinflammatory conditions that had previously been thought to be confined to single organs. IgG4-RD lesions are infiltrated by T helper cells, which likely cause progressive fibrosis and organ damage. IgG4 antibodies are generally regarded as noninflammatory. Although autoreactive IgG4 antibodies are observed in IgG4-RD, there is no evidence that they are directly pathogenic. Rituximab-induced B cell depletion in IgG4-RD leads to rapid clinical and histological improvement accompanied by swift declines in serum IgG4 concentrations. Although IgG autoantibodies against various exocrine gland antigens have been described in IgG4-RD, whether they are members of the IgG4 subclass is unknown. The contribution of autoantibodies to IgG4-RD remains unclear. C1 [Mahajan, Vinay S.; Mattoo, Hamid; Pillai, Shiv S.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Canc, Boston, MA 02115 USA. [Deshpande, Vikram] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Pathol, Boston, MA USA. [Stone, John H.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Rheumatol Allergy & Immunol,Dept Med, Boston, MA USA. RP Mahajan, VS (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Canc, Boston, MA 02115 USA. EM pillai@helix.mgh.harvard.edu; jhstone@partners.org NR 159 TC 80 Z9 88 U1 7 U2 19 PU ANNUAL REVIEWS PI PALO ALTO PA 4139 EL CAMINO WAY, PO BOX 10139, PALO ALTO, CA 94303-0897 USA SN 1553-4006 BN 978-0-8243-4309-5 J9 ANNU REV PATHOL-MECH JI Annu. Rev. Pathol.-Mech Dis. PY 2014 VL 9 BP 315 EP + DI 10.1146/annurev-pathol-012513-104708 PG 34 WC Pathology SC Pathology GA BA4OG UT WOS:000336055900014 PM 24111912 ER PT J AU Wang, JM Tao, J Chen, DD Cai, JJ Irani, K Wang, QD Yuan, H Chen, AF AF Wang, Jie-Mei Tao, Jun Chen, Dan-Dan Cai, Jing-Jing Irani, Kaikobad Wang, Qinde Yuan, Hong Chen, Alex F. TI MicroRNA miR-27b Rescues Bone Marrow-Derived Angiogenic Cell Function and Accelerates Wound Healing in Type 2 Diabetes Mellitus SO ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY LA English DT Article DE microRNAs; diabetes mellitus; type 2; wound healing ID ENDOTHELIAL PROGENITOR CELLS; VIVO REENDOTHELIALIZATION CAPACITY; OXIDATIVE STRESS; HIGH GLUCOSE; IN-VIVO; PROTEIN THROMBOSPONDIN-1; MYOCARDIAL-INFARCTION; UP-REGULATION; MICE; EXPRESSION AB Objective-Vascular precursor cells with angiogenic potentials are important for tissue repair, which is impaired in diabetes mellitus. MicroRNAs are recently discovered key regulators of gene expression, but their role in vascular precursor cell-mediated angiogenesis in diabetes mellitus is unknown. We tested the hypothesis that the microRNA miR-27b rescues impaired bone marrow-derived angiogenic cell (BMAC) function in vitro and in vivo in type 2 diabetic mice. Approach and Results-BMACs from adult male type 2 diabetic db/db and from normal littermate db/+ mice were used. miR-27b expression was decreased in db/db BMACs. miR-27b mimic improved db/db BMAC function, including proliferation, adhesion, tube formation, and delayed apoptosis, but it did not affect migration. Elevated thrombospondin-1 (TSP-1) protein in db/db BMACs was suppressed on miR-27b mimic transfection. Inhibition of miR-27b in db/+ BMACs reduced angiogenesis, which was reversed by TSP-1 small interfering RNA (siRNA). miR-27b suppressed the pro-oxidant protein p66(shc) and mitochondrial oxidative stress, contributing to its protection of BMAC function. miR-27b also suppressed semaphorin 6A to improve BMAC function in diabetes mellitus. Luciferase binding assay suggested that miR-27b directly targeted TSP-1, TSP-2, p66(shc), and semaphorin 6A. miR-27b improved topical cell therapy of diabetic BMACs on diabetic skin wound closure, with a concomitant augmentation of wound perfusion and capillary formation. Normal BMAC therapy with miR-27b inhibition demonstrated reduced efficacy in wound closure, perfusion, and capillary formation. Local miR-27b delivery partly improved wound healing in diabetic mice. Conclusions-miR-27b rescues impaired BMAC angiogenesis via TSP-1 suppression, semaphorin 6A expression, and p66shc-dependent mitochondrial oxidative stress and improves BMAC therapy in wound healing in type 2 diabetic mice. C1 [Wang, Jie-Mei; Chen, Dan-Dan; Wang, Qinde; Chen, Alex F.] Univ Pittsburgh, Sch Med, Dept Surg, Pittsburgh, PA USA. [Chen, Alex F.] Vet Affairs Pittsburgh Healthcare Syst, Vasc Surg Res, Pittsburgh, PA USA. [Wang, Jie-Mei; Tao, Jun] Sun Yat Sen Univ, Affiliated Hosp 1, Dept Hypertens & Vasc Dis, Guangzhou 510275, Guangdong, Peoples R China. [Wang, Jie-Mei; Chen, Dan-Dan; Cai, Jing-Jing; Wang, Qinde; Yuan, Hong; Chen, Alex F.] Cent S Univ, Dept Cardiol, Changsha 410013, Hunan, Peoples R China. [Wang, Jie-Mei; Chen, Dan-Dan; Cai, Jing-Jing; Wang, Qinde; Yuan, Hong; Chen, Alex F.] Cent S Univ, Xiangya Hosp 3, Ctr Clin Pharmacol, Changsha 410013, Hunan, Peoples R China. [Irani, Kaikobad] Univ Iowa, Dept Internal Med, Div Cardiovasc Med, Carver Coll Med, Iowa City, IA 52242 USA. RP Chen, AF (reprint author), Cent S Univ, Xiangya Hosp 3, 138 Tong Zi Bo Rd, Changsha 410013, Hunan, Peoples R China. EM afychen@yahoo.com OI Irani, Kaikobad/0000-0001-9194-7387; WANG, JIEMEI/0000-0002-8723-4410 FU National Institutes of Health (NIH)/National Institute of General Medical Sciences [R01 GM077352]; Department of Veterans Affairs [I01RX000244, 1I01RX000652]; American Diabetes Association [7-11-BS-23]; National Science Foundation of China [81130004]; NIH [1R21CA158650]; China Overseas Scholarship [20070320]; American Heart Association [0920110G, 13SDG16930098] FX This work was supported, in part, by the National Institutes of Health (NIH)/National Institute of General Medical Sciences R01 GM077352 (to A. F. Chen), Department of Veterans Affairs Rehabilitation Research and Development Merit Awards I01RX000244 and 1I01RX000652 (to A. F. Chen), American Diabetes Association Research Award 7-11-BS-23 (to A. F. Chen), the National Science Foundation of China Key Research Project 81130004 (to A. F. Chen), and NIH 1R21CA158650 (to Q. D. Wang). Dr Jie-Mei Wang was the awardee of China Overseas Scholarship 20070320, American Heart Association Postdoctoral Fellowship 0920110G, and American Heart Association Scientist Development Grant 13SDG16930098. NR 61 TC 24 Z9 27 U1 0 U2 11 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1079-5642 EI 1524-4636 J9 ARTERIOSCL THROM VAS JI Arterioscler. Thromb. Vasc. Biol. PD JAN PY 2014 VL 34 IS 1 BP 99 EP + DI 10.1161/ATVBAHA.113.302104 PG 30 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA AJ5NO UT WOS:000337731100015 PM 24177325 ER PT J AU Park, M Vittinghoff, E Ganz, P Peralta, CA Whooley, M Shlipak, MG AF Park, Meyeon Vittinghoff, Eric Ganz, Peter Peralta, Carmen A. Whooley, Mary Shlipak, Michael G. TI Role of Soluble Endothelial Cell-Selective Adhesion Molecule Biomarker in Albuminuria and Kidney Function Changes in Patients With Coronary Artery Disease The Heart and Soul Study SO ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY LA English DT Article DE albuminuria; atherosclerosis; kidney diseases ID CARDIOVASCULAR-DISEASE; RENAL-DISEASE; DYSFUNCTION; RISK; OUTCOMES; ATHEROSCLEROSIS; ASSOCIATIONS; POPULATION; MORTALITY; EVENTS AB Objective-Endothelial dysfunction is a possible mechanism to explain the association between atherosclerosis and kidney disease. This study evaluated circulating soluble endothelial cell-selective adhesion molecule (sESAM), a marker of endothelial dysfunction, as a risk factor for kidney function decline and albuminuria. Approach and Results-In the Heart and Soul Study, we measured sESAM from baseline serum samples and defined elevated levels of sESAM by the highest quartile (quartile 4 [Q4]: >65.4 ng/mL). We evaluated the associations of high sESAM with baseline estimated glomerular filtration rate (eGFR) and ratio of urine albumin to creatinine (ACR), and with longitudinal changes in eGFR and ACR. Among 990 participants with sESAM measurements, median sESAM was 54.5 ng/mL (interquartile range, 45.3-65.8). After multivariable adjustment, elevated levels of sESAM were strongly and independently associated with baseline reduced eGFR <60 mL/min per 1.73 m(2) (odds ratio [OR], 11.44; P<0.0001) and ACR >= 30 mg/g (OR, 5.23; P<0.0001). Associations of sESAM (Q4 versus quartile 1 [Q1]) with change in ACR (beta=54.47; P<0.0001) were also significant after full adjustment. The association with change in eGFR (1.56%; P=0.0049) was not statistically significant after application of the Bonferroni correction for multiple markers. In unadjusted models, sESAM was associated with rapid kidney function loss, defined as 3% annual eGFR decline (OR, 2.28; P=0.0003), although this was attenuated by adjustment (OR, 2.11; P=0.0095). Conclusions-sESAM is associated with albuminuria and reduced kidney function in both cross-sectional and longitudinal analyses. These findings implicate endothelial dysfunction as a potential contributor to the elevated kidney disease risk in persons with cardiovascular disease. C1 [Park, Meyeon; Peralta, Carmen A.] Univ Calif San Francisco, Div Nephrol, San Francisco, CA 94143 USA. [Vittinghoff, Eric; Whooley, Mary; Shlipak, Michael G.] Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA. [Ganz, Peter; Whooley, Mary; Shlipak, Michael G.] Univ Calif San Francisco, Dept Med, San Francisco, CA 94143 USA. [Ganz, Peter] San Francisco Gen Hosp, Div Cardiol, San Francisco, CA 94110 USA. [Whooley, Mary; Shlipak, Michael G.] San Francisco VA Med Ctr, San Francisco, CA USA. RP Park, M (reprint author), 521 Parnassus Ave,C443,Box 0532, San Francisco, CA 94143 USA. EM meyeon.park@ucsf.edu FU Meyeon Park's NIH/NIDDK [F32DK093231]; American Heart Association [11POST7230046]; NIH/NIDDK [1K23DK082793]; NIH [R01 DK080662, 1 P50 DA036109]; Department of Veteran Affairs (Epidemiology Merit Review Program), Washington, DC; National Heart, Lung, and Blood Institute, Bethesda, MD [R01 HL-079235]; Robert Wood Johnson Foundation (Generalist Physician Faculty Scholars Program), Princeton, NJ; American Federation for Aging Research (Paul Beeson Faculty Scholars in Aging Research Program), New York, NY; Ischemia Research and Education Foundation, South San Francisco, CA; [R01 AG034853-04]; [5R01AG027002-06]; [5R01DK087961-02] FX This work was supported by Meyeon Park's NIH/NIDDK F32DK093231 and American Heart Association 11POST7230046 (to M. Park). M. S. is supported by R01 AG034853-04, 5R01AG027002-06, and 5R01DK087961-02. C. P. is funded by NIH/NIDDK 1K23DK082793. P. G. is funded by NIH R01 DK080662 and NIH 1 P50 DA036109. The Heart and Soul Study was funded by the Department of Veteran Affairs (Epidemiology Merit Review Program), Washington, DC; grant R01 HL-079235 from the National Heart, Lung, and Blood Institute, Bethesda, MD; the Robert Wood Johnson Foundation (Generalist Physician Faculty Scholars Program), Princeton, NJ; the American Federation for Aging Research (Paul Beeson Faculty Scholars in Aging Research Program), New York, NY; and the Ischemia Research and Education Foundation, South San Francisco, CA. NR 28 TC 7 Z9 8 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1079-5642 EI 1524-4636 J9 ARTERIOSCL THROM VAS JI Arterioscler. Thromb. Vasc. Biol. PD JAN PY 2014 VL 34 IS 1 BP 231 EP 236 DI 10.1161/ATVBAHA.113.301806 PG 6 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA AJ5NO UT WOS:000337731100031 PM 24177327 ER PT J AU Bukulmez, H Khan, F Bartels, CF Murakami, S Ortiz-Lopez, A Sattar, A Haqqi, TM Warman, ML AF Buekuelmez, Huelya Khan, Fozia Bartels, Cynthia F. Murakami, Shunichi Ortiz-Lopez, Adriana Sattar, Abdus Haqqi, Tariq M. Warman, Matthew L. TI Protective Effects of C-Type Natriuretic Peptide on Linear Growth and Articular Cartilage Integrity in a Mouse Model of Inflammatory Arthritis SO ARTHRITIS & RHEUMATOLOGY LA English DT Article ID JUVENILE RHEUMATOID-ARTHRITIS; TUMOR-NECROSIS-FACTOR; HUMAN OSTEOARTHRITIS CHONDROCYTES; INTERLEUKIN-1-BETA-INDUCED ACTIVATION; FACTOR-ALPHA; BONE-GROWTH; FACTOR SOX9; EXPRESSION; RECEPTOR; CNP AB Objective. The C-type natriuretic peptide (CNP) signaling pathway is a major contributor to postnatal skeletal growth in humans. This study was undertaken to investigate whether CNP signaling could prevent growth delay and cartilage damage in an animal model of inflammatory arthritis. Methods. We generated transgenic mice that overexpress CNP (B6. SJL-Col2a1-NPPC) in chondrocytes. We introduced the CNP transgene into mice with experimental systemic inflammatory arthritis (K/BxN T cell receptor [TCR]) and determined the effect of CNP overexpression in chondrocytes on the severity of arthritis, cartilage damage, and linear growth. We also examined primary chondrocyte cultures for changes in gene and protein expression resulting from CNP overexpression. Results. K/BxN TCR mice exhibited linear growth delay (P < 0.01) compared to controls, and this growth delay was correlated with the severity of arthritis. Diminished chondrocyte proliferation and matrix production was also seen in K/BxN TCR mice. Compared to non-CNP-transgenic mice, K/BxN TCR mice with overexpressed CNP had milder arthritis, no growth delay, and less cartilage damage. Primary chondrocytes from mice overexpressing CNP were less sensitive to inflammatory cytokines than wild-type mouse chondrocytes. Conclusion. CNP overexpression in chondrocytes can prevent endochondral growth delay and protect against cartilage damage in a mouse model of inflammatory arthritis. Pharmacologic or biologic modulation of the CNP signaling pathway may prevent growth retardation and protect cartilage in patients with inflammatory joint diseases, such as juvenile idiopathic arthritis. C1 [Buekuelmez, Huelya; Haqqi, Tariq M.] Metrohlth Med Ctr, Cleveland, OH 44106 USA. [Buekuelmez, Huelya; Khan, Fozia; Bartels, Cynthia F.; Murakami, Shunichi; Sattar, Abdus; Haqqi, Tariq M.] Case Western Reserve Univ, Cleveland, OH 44106 USA. [Ortiz-Lopez, Adriana] Joslin Diabet Ctr, Boston, MA 02215 USA. [Ortiz-Lopez, Adriana; Warman, Matthew L.] Harvard Univ, Sch Med, Boston, MA USA. [Warman, Matthew L.] Boston Childrens Hosp, Howard Hughes Med Inst, Boston, MA USA. RP Bukulmez, H (reprint author), Metrohlth Med Ctr, Dept Pediat, 2500 MetroHlth Dr, Cleveland, OH 44106 USA. EM hxb38@case.edu OI Haqqi, Tariq/0000-0003-3506-6133 FU Arthritis National Research Foundation; NIH (National Institute of Arthritis and Musculoskeletal and Skin Diseases grant) [K08-AR0-53943-01]; NIH (National Center for Complementary and Alternative Medicine grants) [R01-AT-0036227, R01-AT-005520, R21-AT-004026] FX Supported by the Arthritis National Research Foundation and the NIH (National Institute of Arthritis and Musculoskeletal and Skin Diseases grant K08-AR0-53943-01 and National Center for Complementary and Alternative Medicine grants R01-AT-0036227, R01-AT-005520, and R21-AT-004026). NR 48 TC 6 Z9 6 U1 2 U2 4 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 2326-5191 EI 2326-5205 J9 ARTHRITIS RHEUMATOL JI Arthritis Rheumatol. PD JAN PY 2014 VL 66 IS 1 BP 78 EP 89 DI 10.1002/art.38199 PG 12 WC Rheumatology SC Rheumatology GA AJ0PB UT WOS:000337356300012 PM 24449577 ER PT J AU Loggia, ML Berna, C Kim, J Cahalan, CM Gollub, RL Wasan, AD Harris, RE Edwards, RR Napadow, V AF Loggia, Marco L. Berna, Chantal Kim, Jieun Cahalan, Christine M. Gollub, Randy L. Wasan, Ajay D. Harris, Richard E. Edwards, Robert R. Napadow, Vitaly TI Disrupted Brain Circuitry for Pain-Related Reward/Punishment in Fibromyalgia SO ARTHRITIS & RHEUMATOLOGY LA English DT Article ID VENTRAL TEGMENTAL AREA; DOPAMINE ACTIVITY; CONNECTIVITY; ANALGESIA; RESPONSES; NETWORK; PERCEPTION; MECHANISMS; MANAGEMENT; NEURONS AB Objective. While patients with fibromyalgia (FM) are known to exhibit hyperalgesia, the central mechanisms contributing to this altered pain processing are not fully understood. This study was undertaken to investigate potential dysregulation of the neural circuitry underlying cognitive and hedonic aspects of the subjective experience of pain, such as anticipation of pain and anticipation of pain relief. Methods. Thirty-one FM patients and 14 controls underwent functional magnetic resonance imaging, while receiving cuff pressure pain stimuli on the leg calibrated to elicit a pain rating of similar to 50 on a 100-point scale. During the scan, subjects also received visual cues informing them of the impending onset of pain (pain anticipation) and the impending offset of pain (relief anticipation). Results. Patients exhibited less robust activation during both anticipation of pain and anticipation of relief within regions of the brain commonly thought to be involved in sensory, affective, cognitive, and painmodulatory processes. In healthy controls, direct searches and region-of-interest analyses of the ventral tegmental area revealed a pattern of activity compatible with the encoding of punishment signals: activation during anticipation of pain and pain stimulation, but deactivation during anticipation of pain relief. In FM patients, however, activity in the ventral tegmental area during periods of pain and periods of anticipation (of both pain and relief) was dramatically reduced or abolished. Conclusion. FM patients exhibit disrupted brain responses to reward/punishment. The ventral tegmental area is a source of reward-linked dopaminergic/gamma-aminobutyric acid-releasing (GABAergic) neurotransmission in the brain, and our observations are compatible with reports of altered dopaminergic/GABAergic neurotransmission in FM. Reduced reward/punishment signaling in FM may be related to the augmented central processing of pain and reduced efficacy of opioid treatments in these patients. C1 [Loggia, Marco L.; Napadow, Vitaly] Brigham & Womens Hosp, Massachusetts Gen Hosp, Boston, MA 02115 USA. [Loggia, Marco L.; Berna, Chantal; Kim, Jieun; Cahalan, Christine M.; Gollub, Randy L.; Wasan, Ajay D.; Edwards, Robert R.; Napadow, Vitaly] Harvard Univ, Sch Med, Boston, MA USA. [Berna, Chantal; Kim, Jieun; Gollub, Randy L.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Cahalan, Christine M.; Wasan, Ajay D.; Edwards, Robert R.] Brigham & Womens Hosp, Boston, MA 02115 USA. [Harris, Richard E.] Univ Michigan, Ann Arbor, MI 48109 USA. RP Loggia, ML (reprint author), Massachusetts Gen Hosp, 149 13th St,Suite 2301, Charlestown, MA 02129 USA. EM marco@nmr.mgh.harvard.edu OI Gollub, Randy L./0000-0002-9434-4044 FU National Center for Complementary and Alternative Medicine, NIH [R01-AT-004714, P01-AT-002048, P01-AT-006663, R01-AT-005280, R01-AG-034982, R21-AR-057920]; Pfizer FX Supported by the National Center for Complementary and Alternative Medicine, NIH (grants R01-AT-004714, P01-AT-002048, P01-AT-006663, R01-AT-005280, R01-AG-034982, and R21-AR-057920).; Dr. Harris has received consulting fees, speaking fees, and/or honoraria (less than $10,000), as well as grant support, from Pfizer. NR 50 TC 24 Z9 26 U1 3 U2 6 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 2326-5191 EI 2326-5205 J9 ARTHRITIS RHEUMATOL JI Arthritis Rheumatol. PD JAN PY 2014 VL 66 IS 1 BP 203 EP 212 DI 10.1002/art.38191 PG 10 WC Rheumatology SC Rheumatology GA AJ0PB UT WOS:000337356300024 PM 24449585 ER PT J AU Khosroshahi, A Cheryk, LA Carruthers, MN Edwards, JA Bloch, DB Stone, JH AF Khosroshahi, Arezou Cheryk, Lynn A. Carruthers, Mollie N. Edwards, Judith A. Bloch, Donald B. Stone, John H. TI Spuriously Low Serum IgG4 Concentrations Caused by the Prozone Phenomenon in Patients With IgG4-Related Disease SO ARTHRITIS & RHEUMATOLOGY LA English DT Article ID AUTOIMMUNE PANCREATITIS; CLINICOPATHOLOGICAL ENTITY; DIAGNOSIS; FEATURES AB Objective. To determine the frequency of the prozone effect in patients with IgG4-related disease (IgG4-RD). Methods. After identifying the prozone effect in an index patient with IgG4-RD, we examined additional samples to determine the frequency of this phenomenon. Thirty-eight serum samples obtained from patients with IgG4-RD whose results had been reported previously were retested. The serum IgG4 concentrations determined by this repeat analysis were compared with the originally reported values. Results. In 10 (26%) of 38 patients, the originally reported IgG4 values were falsely low; the prozone effect was identified in each of these 10 samples. Correction of the prozone effect by sample dilution led to revision of the mean serum IgG4 concentration in the 10 samples, from 26 mg/dl to 2,008 mg/dl (normal range 2.4-121 mg/dl). All 10 patients whose samples were affected by the prozone effect had active IgG4-RD. Failure to detect the elevated serum IgG4 concentrations had a direct impact on the decision not to institute treatment in these patients. Conclusion. The prozone effect may lead to major underestimations of IgG4 concentrations in patients with IgG4-RD and offers a potential explanation for the poor correlation observed between disease activity and serum IgG4 levels in some patients. This phenomenon should be considered if the serum IgG4 measurement appears discordant with the clinicopathologic diagnosis and the clinical assessment of disease activity. C1 [Khosroshahi, Arezou] Emory Univ, Sch Med, Atlanta, GA USA. [Khosroshahi, Arezou; Carruthers, Mollie N.; Bloch, Donald B.; Stone, John H.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Khosroshahi, Arezou; Carruthers, Mollie N.; Bloch, Donald B.; Stone, John H.] Harvard Univ, Sch Med, Boston, MA USA. [Cheryk, Lynn A.; Edwards, Judith A.] Mayo Med Labs, Andover, MA USA. RP Stone, JH (reprint author), Massachusetts Gen Hosp, Rheumatol Unit, Yawkey 2,55 Fruit St, Boston, MA 02114 USA. EM jhstone@partners.org NR 21 TC 37 Z9 39 U1 1 U2 2 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 2326-5191 EI 2326-5205 J9 ARTHRITIS RHEUMATOL JI Arthritis Rheumatol. PD JAN PY 2014 VL 66 IS 1 BP 213 EP 217 DI 10.1002/art.38193 PG 5 WC Rheumatology SC Rheumatology GA AJ0PB UT WOS:000337356300025 PM 24431286 ER PT J AU Darling, CE Mercado, JAS Quiroga-Castro, W Tecco, GF Zelaya, FR Conci, EC Sala, JP Smith, CS Michelson, AD Whittaker, P Welch, RD Przyklenk, K AF Darling, Chad E. Sala Mercado, Javier A. Quiroga-Castro, Walter Tecco, Gabriel F. Zelaya, Felix R. Conci, Eduardo C. Sala, Jose P. Smith, Craig S. Michelson, Alan D. Whittaker, Peter Welch, Robert D. Przyklenk, Karin TI Point-of-care assessment of platelet reactivity in the emergency department may facilitate rapid rule-out of acute coronary syndromes: a prospective cohort pilot feasibility study SO BMJ OPEN LA English DT Article ID ELEVATION MYOCARDIAL-INFARCTION; COMPUTED-TOMOGRAPHY ANGIOGRAPHY; ASSOCIATION TASK-FORCE; ACUTE CHEST-PAIN; ARTERY-DISEASE; CARDIOVASCULAR-DISEASE; ADENOSINE-DIPHOSPHATE; ANTIPLATELET THERAPY; RISK STRATIFICATION; PRACTICE GUIDELINES AB Objective: Accurate, efficient and cost-effective disposition of patients presenting to emergency departments (EDs) with symptoms suggestive of acute coronary syndromes (ACS) is a growing priority. Platelet activation is an early feature in the pathogenesis of ACS; thus, we sought to obtain an insight into whether point-of-care testing of platelet function: (1) may assist in the rule-out of ACS; (2) may provide additional predictive value in identifying patients with non-cardiac symptoms versus ACS-positive patients and (3) is logistically feasible in the ED. Design: Prospective cohort feasibility study. Setting: Two urban tertiary care sites, one located in the USA and the second in Argentina. Participants: 509 adult patients presenting with symptoms of ACS. Main outcome measures: Platelet reactivity was quantified using the Platelet Function Analyzer-100, with closure time (seconds required for blood, aspirated under high shear, to occlude a 150 mu m aperture) serving as the primary endpoint. Closure times were categorised as 'normal' or 'prolonged', defined objectively as the 90th centile of the distribution for all participants enrolled in the study. Diagnosis of ACS was made using the standard criteria. The use of antiplatelet agents was not an exclusion criterion. Results: Closure times for the study population ranged from 47 to 300 s, with a 90th centile value of 138 s. The proportion of patients with closure times >= 138 s was significantly higher in patients with non-cardiac symptoms (41/330; 12.4%) versus the ACS-positive cohort (2/105 (1.9%); p=0.0006). The specificity of 'prolonged' closure times (>= 138 s) for a diagnosis of non-cardiac symptoms was 98.1%, with a positive predictive value of 95.4%. Multivariate analysis revealed that the closure time provided incremental, independent predictive value in the rule-out of ACS. Conclusions: Point-of-care assessment of platelet reactivity is feasible in the ED and may facilitate the rapid rule-out of ACS in patients with prolonged closure times. C1 [Darling, Chad E.; Whittaker, Peter; Przyklenk, Karin] Univ Massachusetts, Sch Med, Dept Emergency Med, Worcester, MA 01605 USA. [Sala Mercado, Javier A.; Whittaker, Peter; Welch, Robert D.; Przyklenk, Karin] Wayne State Univ, Sch Med, Cardiovasc Res Inst, Detroit, MI USA. [Sala Mercado, Javier A.; Przyklenk, Karin] Wayne State Univ, Sch Med, Dept Physiol, Detroit, MI 48201 USA. [Sala Mercado, Javier A.; Quiroga-Castro, Walter; Tecco, Gabriel F.; Zelaya, Felix R.; Conci, Eduardo C.; Sala, Jose P.] Inst Modelo Cardiol Privado SRL, Div Cardiol, Cordoba, Argentina. [Smith, Craig S.] Univ Massachusetts, Sch Med, Dept Cardiovasc Med, Worcester, MA USA. [Michelson, Alan D.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Div Hematol Oncol,Ctr Platelet Res Studies,Boston, Boston, MA 02115 USA. [Whittaker, Peter; Welch, Robert D.; Przyklenk, Karin] Wayne State Univ, Sch Med, Dept Emergency Med, Detroit, MI USA. RP Przyklenk, K (reprint author), Univ Massachusetts, Sch Med, Dept Emergency Med, Worcester, MA 01605 USA. EM kprzykle@med.wayne.edu RI Whittaker, Peter/F-1234-2011 OI Whittaker, Peter/0000-0002-5627-2166 FU Society for Academic Emergency Medicine (SAEM), Des Plaines, Illinois, USA FX Siemens Inc provided the Emergency Department at the University of Massachusetts Medical School and the Cardiology Department, Instituto Modelo de Cardiologia Privado SRL with PFA-100 devices on a loan basis, as well as partial support for the purchase of test cartridges used in this study. CED was supported in part by a Research Training Grant from the Society for Academic Emergency Medicine (SAEM), Des Plaines, Illinois, USA. NR 43 TC 0 Z9 0 U1 0 U2 1 PU BMJ PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 2044-6055 J9 BMJ OPEN JI BMJ Open PY 2014 VL 4 IS 1 AR e003883 DI 10.1136/bmjopen-2013-003883 PG 9 WC Medicine, General & Internal SC General & Internal Medicine GA AJ0RP UT WOS:000337363700004 PM 24441051 ER PT J AU Flaherty, L Hamid, O Linette, G Schuchter, L Hallmeyer, S Gonzalez, R Cowey, CL Pavlick, A Kudrik, F Curti, B Lawson, D Chapman, PB Margolin, K Ribas, A McDermott, D Flaherty, K Cranmer, L Hodi, FS Day, BM Linke, R Hainsworth, J AF Flaherty, Lawrence Hamid, Omid Linette, Gerald Schuchter, Lynn Hallmeyer, Sigrun Gonzalez, Rene Cowey, C. Lance Pavlick, Anna Kudrik, Fred Curti, Brendan Lawson, David Chapman, Paul B. Margolin, Kim Ribas, Antoni McDermott, David Flaherty, Keith Cranmer, Lee Hodi, F. Stephen Day, Bann-Mo Linke, Rolf Hainsworth, John TI A Single-Arm, Open-Label, Expanded Access Study of Vemurafenib in Patients With Metastatic Melanoma in the United States SO CANCER JOURNAL LA English DT Article DE Melanoma/drug therapy; melanoma/genetics; BRAF protein; human; neoplasm metastasis/drug therapy; brain neoplasms/secondary; brain neoplasms/drug therapy; vemurafenib/therapeutic use; vemurafenib/adverse effects; clinical trial; humans ID SURVIVAL AB Purpose: This open-label, multicenter study was designed to allow access to vemurafenib for patients with metastatic melanoma, bridging the time between end of enrollment in the phase III registration trial (December 2010) and commercial availability following US Food and Drug Administration approval of vemurafenib for the treatment of unresectable or metastatic BRAF(V600)-mutated melanoma (August 2011). Patients and Methods: Eligible patients had metastatic melanoma with a BRAF(V600) mutation (detected by the cobas 4800 BRAF(V600) Mutation Test). Unlike previous vemurafenib trials, patients with poor performance status (PS) and treated brain metastases were permitted. Enrolled patients received oral vemurafenib 960 mg twice daily. Results: Of 374 patients enrolled at 29 US sites (December 2010 to October 2011), 371 patients received vemurafenib and were followed up for a median of 2.8 months (the study had a prespecified end upon vemurafenib approval and commercial availability). At baseline, most patients (75%) had stage M1c disease, and 19% had an Eastern Cooperative Oncology Group PS of 2 or 3; 72% of patients had received prior systemic therapy for metastatic melanoma, 27% received prior ipilimumab, and 29% radiotherapy for prior brain metastases. Because reassessment data to confirm response were not available for most patients, point estimates of objective response rate (ORR) are reported. Among 241 efficacy-evaluable patients, the ORR was 54% (median time to response, 1.9 months). The ORR in non-central nervous system sites in patients with previously treated brain metastases (n = 68) was 53%. The ORR in prior ipilimumab-treated patients (n = 68) was 52%. For patients with PS of 0 or 1 (n = 210) and 2 or 3 (n = 31), the ORRs were 55%, and 42%, respectively. The safety profile observed was consistent with that reported in previous studies. The number of patients with grade 3 or 4 treatment-related adverse events was higher in patients with PS 2 or 3 than in those with PS 0 or 1 (10% vs. 5%, respectively). Adverse events requiring a dose reduction (at least 1 level) occurred in 11% of patients, and 9 patients (2%) experienced events leading to vemurafenib withdrawal, including 2 with repeated QT interval prolongation. Discussion: This study confirmed the established rapid and high tumor response rate achievable with vemurafenib in BRAF(V600) mutation-positive metastatic melanoma. Several groups not included in previous studies, including patients with previously treated brain metastases, Eastern Cooperative Oncology Group PS 2 to 3, or previous ipilimumab treatment had benefitted from vemurafenib similar to the overall population. No new safety signals were detected. C1 [Flaherty, Lawrence] Wayne State Univ, Karmanos Canc Ctr, Detroit, MI USA. [Hamid, Omid] Angeles Clin & Res Inst, Los Angeles, CA USA. [Linette, Gerald] Washington Univ, St Louis, MO USA. [Schuchter, Lynn] Univ Penn, Philadelphia, PA 19104 USA. [Hallmeyer, Sigrun] Oncol Specialists SC, Park Ridge, IL USA. [Gonzalez, Rene] Univ Colorado, Ctr Canc, Aurora, CO USA. [Cowey, C. Lance] Texas Oncol PA, Baylor Sammons Canc Ctr, Dallas, TX USA. [Pavlick, Anna] NYU, Med Ctr, New York, NY 10016 USA. [Kudrik, Fred] South Carolina Oncol Associates, Columbia, SC USA. [Curti, Brendan] Providence Portland Med Ctr, Portland, OR USA. [Lawson, David] Emory Univ, Winship Canc Inst, Atlanta, GA 30322 USA. [Chapman, Paul B.] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. [Margolin, Kim] Seattle Canc Care Alliance, Seattle, WA USA. [Ribas, Antoni] Univ Calif Los Angeles, Sch Med, Los Angeles, CA USA. [McDermott, David] Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. [Flaherty, Keith] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Cranmer, Lee] Univ Arizona, Ctr Canc, Tucson, AZ USA. [Hodi, F. Stephen] Dana Farber Canc Inst, Boston, MA 02115 USA. [Day, Bann-Mo; Linke, Rolf] Genentech Inc, San Francisco, CA 94080 USA. [Linke, Rolf] SFJ Pharma Grp, Pleasanton, CA USA. [Hainsworth, John] Sarah Cannon Res Inst, Nashville, TN USA. RP Flaherty, L (reprint author), Karmanos Canc Inst, Div Hematol & Oncol, 4100 John R-4HWCRC, Detroit, MI 48201 USA. EM flaherty@karmanos.org FU Roche/Genentech, Inc.; Merck; Roche/Genentech; Genentech; Prometheus Pharmaceuticals; National Institutes of Health; Genentech/Roche; GSK FX Conflicts of Interest and Source of Funding: Support for third-party writing assistance for this manuscript was provided by Roche/Genentech, Inc. L. F. has received grant support and has served on the board of Merck; has consulted for Roche-Genentech, BMS, GSK, Genomic Health, and Merck; and has received payment for lectures for Roche/Genentech. O.H. has received grant support from Genentech and is a consultant and has received payment for speaker bureaus for Genentech. G. L. is a speaker for Roche/Genentech. S. H. is a speaker for Novartis and BMS. R. G. has received grant support from Roche/Genentech and has been a past consultant and received past support for travel for Roche/Genentech. C. L. C. has consulted and been a speaker for Roche/Genentech. A. P. has received grant support and financial support for being a consultant and providing review activities. B. C. has been a past consultant for BMS and Prometheus Pharmaceuticals and is awaiting grants from Prometheus Pharmaceuticals and the National Institutes of Health. D. L. has attended advisory boards for Roche/Genentech, has received support for study expenses, and has received grants for ongoing clinical trials. P. B. C. has received grant and travel support and has consulted for Genentech/Roche. K. M. has received grant support from Roche/Genentech. A. R. has consulted for Roche/Genentech, with the honoraria paid to his institution, and received financial support for travel. D. M. has received financial support for past consultancy. K. F. received grant support from and consults for Roche/Genentech. L. C. has received grant support from Roche/Genentech, with funds going to his institution, is a consultant for GSK and Merck, is on a speaker bureau; is a consultant for Roche/Genentech, Merck, BMS, and Prometheus; and has received research funding from Roche/Genentech and BMS for study protocols, with funds going to his institution. F. S. H. has received financial support for travel to meetings, served as a nonpaid consultant to Roche/Genentech, and received clinical trial support from Genentech/Roche. B.-M. D. is an employee of Genentech Inc and has received stock/stock options. R. L. is a previous employee of Roche/Genentech and received stock/stock options. J.H. received grant support from Roche/Genentech. F. K. and L. S. have disclosed that they have no significant relationships with, or financial interest in, any commercial companies pertaining to this article. NR 11 TC 9 Z9 9 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1528-9117 EI 1540-336X J9 CANCER J JI Cancer J. PD JAN-FEB PY 2014 VL 20 IS 1 BP 18 EP 24 PG 7 WC Oncology SC Oncology GA AJ4YZ UT WOS:000337687700004 PM 24445759 ER PT J AU Foley, JM Heck, AL AF Foley, Jessica M. Heck, Andrew L. TI Neurocognitive Disorders in Aging: A Primer on DSM-5 Changes and Framework for Application to Practice SO CLINICAL GERONTOLOGIST LA English DT Review DE aging; cognitive assessment; gerontology; neurological disorders; neuropsychological tests ID MILD COGNITIVE IMPAIRMENT; ALZHEIMERS-DISEASE; FRONTOTEMPORAL DEMENTIA; VASCULAR DEMENTIA; NEUROPSYCHIATRIC SYMPTOMS; INTERNATIONAL WORKSHOP; DIAGNOSTIC-CRITERIA; FRONTAL VARIANT; OLDER-ADULTS; LEWY BODIES AB Cognitive screening and brief cognitive assessment is an important skill for practitioners across gerontology disciplines. Results of such screening can then point to possible referral points for additional assessment and treatment. The recently released DSM-5 diagnostic criteria for neurocognitive disorders provide a new context for interpreting screening and incorporate many changes from the previous editionincluding an increased reliance on cognitive assessment. In this article we first describe these changes from DSM-IV to DSM-5. Next we link these changes to the practice of cognitive screening and brief cognitive assessment. We then describe how cognitive screening can be embedded in an assessment framework that includes attention to symptom expression, normal aging, medical and psychiatric comorbidities, and base rates. It is increasingly likely that gerontology healthcare practitioners will encounter neurocognitive compromise in their practice. Thus, clinical care should incorporate services including cognitive screening and assessment, broad based differential diagnosis considering DSM-5, and appropriate referral. C1 [Foley, Jessica M.] VA Boston Hlth Care Syst, Boston, MA USA. [Foley, Jessica M.] Harvard Univ, Sch Med, Boston, MA 02130 USA. [Heck, Andrew L.] Piedmont Geriatr Hosp, Piedmont, VA USA. [Heck, Andrew L.] Virginia Commonwealth Univ, Piedmont, VA USA. RP Foley, JM (reprint author), Harvard Univ, Sch Med, VA Boston Healthcare Syst, Dept Psychiat, 150 S Huntington Ave, Boston, MA 02130 USA. EM jessicafoley@gmail.com NR 73 TC 1 Z9 1 U1 1 U2 4 PU ROUTLEDGE JOURNALS, TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXFORDSHIRE, ENGLAND SN 0731-7115 EI 1545-2301 J9 CLIN GERONTOLOGIST JI Clin. Gerontol. PY 2014 VL 37 IS 4 BP 317 EP 346 DI 10.1080/07317115.2014.907595 PG 30 WC Geriatrics & Gerontology; Gerontology; Psychiatry SC Geriatrics & Gerontology; Psychiatry GA AJ4YN UT WOS:000337686200001 ER PT J AU Schulz, R Rosen, J Klinger, J Musa, D Castle, NG Kane, AL Lustig, A AF Schulz, Richard Rosen, Jules Klinger, Julie Musa, Donald Castle, Nicholas G. Kane, April L. Lustig, Amy TI Effects of a Psychosocial Intervention on Caregivers of Recently Placed Nursing Home Residents: A Randomized Controlled Trial SO CLINICAL GERONTOLOGIST LA English DT Article DE caregiving; complicated grief; long-term care ID QUALITY-OF-LIFE; COMPLICATED GRIEF; ADVANCED DEMENTIA; COOPERATIVE COMMUNICATION; DEPRESSIVE SYMPTOMS; FAMILY INVOLVEMENT; ALZHEIMERS-DISEASE; STAFF PERCEPTIONS; CARE; TRANSITION AB Many caregivers continue to provide care and support to their care recipients after institutional placement. A two-group randomized controlled trial was carried out to test the efficacy of a psychosocial intervention for informal caregivers whose care recipients resided in a long-term care facility. The intervention was delivered during the 6-month period following baseline assessment. Follow-up assessments were carried out at 6, 12, and 18 months. Primary outcomes were caregiver depression, anxiety, burden, and complicated grief. Significant time effects were found for all three primary outcomes showing that caregiver depression, anxiety, and burden improved over time. No treatment effects were found for these outcomes. However, complicated grief was significantly lower for caregivers in the treatment condition. C1 [Schulz, Richard; Rosen, Jules; Klinger, Julie; Musa, Donald; Castle, Nicholas G.; Kane, April L.] Univ Pittsburgh, Pittsburgh, PA 15260 USA. [Lustig, Amy] Philadelphia Vet Affairs Med Ctr, Philadelphia, PA USA. RP Schulz, R (reprint author), Univ Pittsburgh, Dept Psychiat, 3343 Forbes Ave, Pittsburgh, PA 15260 USA. EM schulz@pitt.edu FU National Institute of Nursing Research [NR009573] FX This work was supported by a grant from the National Institute of Nursing Research (NR009573). NR 44 TC 4 Z9 4 U1 8 U2 23 PU ROUTLEDGE JOURNALS, TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXFORDSHIRE, ENGLAND SN 0731-7115 EI 1545-2301 J9 CLIN GERONTOLOGIST JI Clin. Gerontol. PY 2014 VL 37 IS 4 BP 347 EP 367 DI 10.1080/07317115.2014.907594 PG 21 WC Geriatrics & Gerontology; Gerontology; Psychiatry SC Geriatrics & Gerontology; Psychiatry GA AJ4YN UT WOS:000337686200002 PM 25071302 ER PT J AU Gyurko, R Van Dyke, TE AF Gyurko, Robert Van Dyke, Thomas E. TI The Role of Polyunsaturated omega-3 Fatty Acid Eicosapentaenoic Acid-Derived Resolvin E1 (RvE1) in Bone Preservation SO CRITICAL REVIEWS IN IMMUNOLOGY LA English DT Article DE lipid mediator; bone resorption; inflammation; osteoclast; periodontal disease ID N-3 FATTY-ACIDS; PRORESOLVING LIPID MEDIATORS; RESORB CALCIFIED MATRICES; FORMATION IN-VITRO; LEUKOTRIENE B-4; OSTEOCLAST DIFFERENTIATION; PROSTAGLANDIN E-2; 5-LIPOXYGENASE METABOLITES; OSTEOPROTEGERIN LIGAND; ANTIINFLAMMATORY DRUGS AB Resolvin E1 (RvE1) is a recently discovered lipid-derived mediator that is endogenously synthesized from the polyunsaturated fatty acid eicosapentaenoic acid. RvE1 is locally generated in response to inflammation where it enhances the resolution phase of inflammation by diminishing neutrophil chemotaxis and by enhancing nonphlogistic macrophage-directed clearance of apoptotic neutrophils. RvE1 was also found to be effective in preventing and restoring bone loss in the inflammatory bone disease periodontitis. This review examines experimental evidence on RvE1's actions in bone. Current data indicate that in addition to anti-inflammatory actions, RvE1 also directly acts on bone cells and promotes bone preservation. C1 [Gyurko, Robert] Tufts Univ, Dept Periodontol, Boston, MA 02111 USA. [Van Dyke, Thomas E.] Forsyth Inst, Cambridge, MA USA. RP Gyurko, R (reprint author), Tufts Univ, Sch Dent Med, Dept Periodontol, 1 Kneeland St, Boston, MA 02111 USA. EM rgyurko@gmail.com FU National Institutes of Health [R01DE015566, R01DE019938] FX This work was supported by grants from the National Institutes of Health (R01DE015566 and R01DE019938 to T.V.D.). NR 68 TC 5 Z9 5 U1 0 U2 3 PU BEGELL HOUSE INC PI REDDING PA 50 CROSS HIGHWAY, REDDING, CT 06896 USA SN 1040-8401 EI 2162-6472 J9 CRIT REV IMMUNOL JI Crit. Rev. Immunol. PY 2014 VL 34 IS 4 BP 347 EP 357 PG 11 WC Immunology SC Immunology GA AJ4KJ UT WOS:000337644800004 PM 24941160 ER PT J AU Teng, E Yamasaki, TR Tran, M Hsiao, JJ Sultzer, DL Mendez, MF AF Teng, Edmond Yamasaki, Tritia R. Tran, Michelle Hsiao, Julia J. Sultzer, David L. Mendez, Mario F. TI Cerebrospinal Fluid Biomarkers in Clinical Subtypes of Early-Onset Alzheimer's Disease SO DEMENTIA AND GERIATRIC COGNITIVE DISORDERS LA English DT Article DE Early-onset Alzheimer's disease; Logopenic progressive aphasia; Posterior cortical atrophy; Cerebrospinal fluid; Biological markers; Amyloid; Tau ID POSTERIOR CORTICAL ATROPHY; PRIMARY PROGRESSIVE APHASIA; CSF BIOMARKERS; TAU; DIAGNOSIS; PRESENTATIONS; THREONINE-181; PATHOLOGY; VARIANTS; DEMENTIA AB Background/Aims: Accurate diagnosis of sporadic early-onset Alzheimer's disease (EOAD) can be challenging, and cerebrospinal fluid (CSF) biomarkers may assist in this process. We compared CSF indices between three EOAD subtypes: amnestic, logopenic progressive aphasia (LPA), and posterior cortical atrophy (PCA). Methods: We identified 21 amnestic EOAD, 20 LPA, and 12 PCA patients with CSF data, which included amyloid beta(1-42) (A beta 42), total tau (t-tau), phospho-tau(181) (p-tau), and A beta 42/t-tau index (ATI) levels. Results: A beta 42 and ATI levels were similar across groups, but t-tau and p-tau levels were significantly lower in PCA patients. Conclusions: The A beta 42 and ATI data confirm the commonality of the A beta pathology in EOAD. The lower tau indices in PCA patients may reflect differences in the distribution of neurofibrillary tangles or rates of neurodegeneration. (C) 2013 S. Karger AG, Basel C1 [Teng, Edmond; Yamasaki, Tritia R.; Tran, Michelle; Hsiao, Julia J.; Sultzer, David L.; Mendez, Mario F.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Neurol, Los Angeles, CA 90095 USA. [Mendez, Mario F.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Psychiat, Los Angeles, CA 90095 USA. [Teng, Edmond; Hsiao, Julia J.; Sultzer, David L.; Mendez, Mario F.] Vet Affairs Greater Los Angeles Healthcare Syst, Los Angeles, CA 90095 USA. RP Teng, E (reprint author), West Los Angeles VA Healthcare Ctr, Neurobehav Serv 116AF, 11301 Wilshire Blvd, Los Angeles, CA 90073 USA. EM eteng@ucla.edu FU National Institute on Aging [R01 AG034499, K08 AG34628]; NIA; AFAR; John A. Hartford Foundation; Atlantic Philanthropies; Starr Foundation; VA Merit Review FX The authors would like to thank Po-Heng Tsai, Elvira Jimenez, and Michelle Mather for their assistance with data management. This work was supported by the National Institute on Aging [R01 AG034499 (to M.F.M.) and K08 AG34628 (to E.T.; jointly sponsored by the NIA, AFAR, the John A. Hartford Foundation, the Atlantic Philanthropies, the Starr Foundation, and an anonymous donor)], and a VA Merit Review (to M.F.M.). NR 41 TC 8 Z9 8 U1 0 U2 2 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 1420-8008 EI 1421-9824 J9 DEMENT GERIATR COGN JI Dement. Geriatr. Cogn. Disord. PY 2014 VL 37 IS 5-6 BP 307 EP 314 DI 10.1159/000355555 PG 8 WC Geriatrics & Gerontology; Clinical Neurology; Psychiatry SC Geriatrics & Gerontology; Neurosciences & Neurology; Psychiatry GA AJ6IL UT WOS:000337795500006 PM 24401901 ER PT J AU Bankoff, SM Pantalone, DW AF Bankoff, Sarah M. Pantalone, David W. TI Patterns of Disordered Eating Behavior in Women by Sexual Orientation: A Review of the Literature SO EATING DISORDERS LA English DT Review ID BODY-IMAGE; MINORITY WOMEN; HETEROSEXUAL WOMEN; GAY MEN; WEIGHT; GENDER; ATTITUDES; IMPLICIT; LESBIANS; OBESITY AB Most disordered eating research has focused on White, heterosexual women. More empirical work is needed to better understand disordered eating among women of diverse backgrounds. Given evidence of disparities between heterosexual and sexual minority (i.e., non-heterosexual) women in other health behaviors (e. g., tobacco use) and outcomes (e.g., cardiovascular disease), it appears important to study disordered eating behaviors among sexual minority women. In this article, we review the extant literature on disordered eating behaviors in women across sexual orientations, with a focus on research examining potential mechanisms of disparities in disordered eating, including awareness and internalization of sociocultural norms. C1 [Bankoff, Sarah M.] VA Boston Healthcare Syst, Psychol Serv, Boston, MA 02130 USA. [Pantalone, David W.] Univ Massachusetts, Dept Psychol, Boston, MA 02125 USA. [Pantalone, David W.] Fenway Hlth, Fenway Inst, Boston, MA USA. RP Bankoff, SM (reprint author), VA Boston Healthcare Syst, Psychol Serv 116B, 150 S Huntington Ave, Boston, MA 02130 USA. EM sarah.bankoff@va.gov NR 52 TC 1 Z9 1 U1 3 U2 14 PU ROUTLEDGE JOURNALS, TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXFORDSHIRE, ENGLAND SN 1064-0266 EI 1532-530X J9 EAT DISORD JI Eat. Disord PY 2014 VL 22 IS 3 BP 261 EP 274 DI 10.1080/10640266.2014.890458 PG 14 WC Psychology, Clinical; Psychiatry; Psychology SC Psychology; Psychiatry GA AJ2RN UT WOS:000337507900006 PM 24617312 ER PT J AU Akhavanfard, S Vargas, SO Han, M Nitta, M Chang, CB Le, LP Fazlollahi, L Nguyen, Q Ma, YQ Cosper, A Dias-Santagata, D Han, JY Bergethon, K Borger, DR Ellisen, LW Pomeroy, SL Haber, DA Iafrate, AJ Rivera, MN AF Akhavanfard, Sara Vargas, Sara O. Han, Moonjoo Nitta, Mai Chang, Clarice B. Le, Long P. Fazlollahi, Ladan Quan Nguyen Ma, Yunqing Cosper, Arjola Dias-Santagata, Dora Han, Jae Y. Bergethon, Kristin Borger, Darrell R. Ellisen, Leif W. Pomeroy, Scott L. Haber, Daniel A. Iafrate, A. John Rivera, Miguel N. TI Inactivation of the tumor suppressor WTX in a subset of pediatric tumors SO GENES CHROMOSOMES & CANCER LA English DT Article ID BECKWITH-WIEDEMANN-SYNDROME; WILMS-TUMOR; WNT/BETA-CATENIN; OSTEOPATHIA STRIATA; MUTATIONAL ANALYSIS; CRANIAL SCLEROSIS; GENE; RHABDOMYOSARCOMA; HEPATOBLASTOMA; CANCER AB WTX is a tumor suppressor gene expressed during embryonic development and inactivated in 20-30% of cases of Wilms tumor, the most common pediatric kidney cancer. WTX has been implicated in several cellular processes including Wnt signaling, WT1 transcription, NRF2 degradation, and p53 function. Given that WTX is widely expressed during embryonic development and has been recently shown to regulate mesenchymal precursor cells in several organs, we tested for the potential involvement of WTX in a panel of pediatric tumors and adult sarcomas. A total of 353 tumors were screened for WTX deletions by fluorescence in situ hybridization (FISH). Discrete somatic WTX deletions were identified in two cases, one hepatoblastoma and one embryonal rhabdomyosarcoma, and confirmed by array comparative genomic hybridization. Direct sequencing of the full WTX open reading frame in 24 hepatoblastomas and 21 embryonal rhabdomyosarcomas did not identify additional mutations in these tumor types. The presence of WTX mRNA was confirmed in hepatoblastomas and embryonal rhabdomyosarcomas without WTX deletions by RNA-in situ hybridization. Notably, tumors with evidence of WTX inactivation, Wilms tumor, hepatoblastoma and rhabdomyosarcoma, are primitive tumors that resemble undifferentiated precursor cells and are linked to overgrowth syndromes. These results indicate that WTX inactivation occurs in a wider variety of tumor types than previously appreciated and point to shared pathogenic mechanisms between a subset of pediatric malignancies. (c) 2013 Wiley Periodicals, Inc. C1 [Akhavanfard, Sara; Han, Moonjoo; Nitta, Mai; Chang, Clarice B.; Le, Long P.; Fazlollahi, Ladan; Cosper, Arjola; Dias-Santagata, Dora; Han, Jae Y.; Bergethon, Kristin; Iafrate, A. John; Rivera, Miguel N.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Akhavanfard, Sara; Borger, Darrell R.; Ellisen, Leif W.; Haber, Daniel A.; Rivera, Miguel N.] Massachusetts Gen Hosp, Ctr Canc, Boston, MA USA. [Akhavanfard, Sara; Vargas, Sara O.; Le, Long P.; Fazlollahi, Ladan; Dias-Santagata, Dora; Borger, Darrell R.; Ellisen, Leif W.; Pomeroy, Scott L.; Haber, Daniel A.; Iafrate, A. John; Rivera, Miguel N.] Harvard Univ, Sch Med, Boston, MA 02114 USA. [Vargas, Sara O.] Childrens Hosp, Dept Pathol, Boston, MA 02115 USA. [Quan Nguyen; Ma, Yunqing] Affymetrix, Santa Clara, CA USA. [Pomeroy, Scott L.] Childrens Hosp, Dept Neurol, Boston, MA 02115 USA. [Rivera, Miguel N.] Broad Inst Harvard & MIT, Cambridge, MA USA. RP Iafrate, AJ (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, 55 Fruit St,GRJ1015, Boston, MA 02114 USA. EM aiafrate@partners.org; mnrivera@partners.org FU NIH/NCI [P50CA101942, R01CA109467]; Massachusetts General Hospital; Burroughs Wellcome Fund; Howard Hughes Medical Institute; NIDDK; Affymetrix FX Supported by: NIH/NCI Grant numbers: P50CA101942 (DFHCC Kidney Cancer SPORE), R01CA109467; Massachusetts General Hospital, Burroughs Wellcome Fund, Howard Hughes Medical Institute, NIDDK, Affymetrix. NR 37 TC 3 Z9 4 U1 0 U2 4 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1045-2257 EI 1098-2264 J9 GENE CHROMOSOME CANC JI Gene Chromosomes Cancer PD JAN PY 2014 VL 53 IS 1 BP 67 EP 77 DI 10.1002/gcc.22118 PG 11 WC Oncology; Genetics & Heredity SC Oncology; Genetics & Heredity GA AJ5PM UT WOS:000337737300006 PM 24249259 ER PT J AU Martin, LA Moye, J Street, RL Naik, AD AF Martin, Lindsey Ann Moye, Jennifer Street, Richard L., Jr. Naik, Aanand D. TI Reconceptualizing Cancer Survivorship Through Veterans' Lived Experiences SO JOURNAL OF PSYCHOSOCIAL ONCOLOGY LA English DT Article DE cancer survivorship; cancer care; older adults; Veterans; illness narratives; qualitative; quality of life ID LIFE-HISTORY NARRATIVES; BREAST-CANCER; WOMEN; CHAOS; INTERVENTION; REFLECTIONS; RESTITUTION; OUTCOMES; QUEST; AGE AB This study assessed the biopsychosocial impact of cancer on Veteran older adult survivors by garnering their accounts of their illness experiences. A narrative analysis of 73 cancer diagnosis and treatment stories reveals five "paths" Veterans are taking 18 months postdiagnosis. These paths indicate that cancer survivorship cannot be conceptualized as a one-size-fits-all experience but rather is a process of Veterans understanding and making sense of the effects of cancer on their lives. Our future goal is to develop a screening tool to help clinicians identify a patient's "path" to tailor survivorship care to meet specific needs. C1 [Martin, Lindsey Ann; Street, Richard L., Jr.; Naik, Aanand D.] Michael E DeBakey VAMC, Houston, TX 77030 USA. [Martin, Lindsey Ann; Street, Richard L., Jr.; Naik, Aanand D.] Baylor Coll Med, Dept Med, Houston, TX 77030 USA. [Moye, Jennifer] VA Boston Hlth Care Syst, Brockton, MA USA. [Moye, Jennifer] Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA. [Street, Richard L., Jr.] Texas A&M Univ, Dept Commun, College Stn, TX USA. RP Martin, LA (reprint author), Michael E DeBakey VAMC, 2002 Holcombe Blvd 152, Houston, TX 77030 USA. EM Lindsey.Martin@bcm.edu RI Moye, Jennifer/F-2240-2017 OI Moye, Jennifer/0000-0002-3434-347X FU RRD VA [I01 RX000104] NR 52 TC 2 Z9 2 U1 1 U2 4 PU ROUTLEDGE JOURNALS, TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXFORDSHIRE, ENGLAND SN 0734-7332 EI 1540-7586 J9 J PSYCHOSOC ONCOL JI J. Psychosoc. Oncol. PY 2014 VL 32 IS 3 BP 289 EP 309 DI 10.1080/07347332.2014.897782 PG 21 WC Psychology, Social SC Psychology GA AJ3MK UT WOS:000337570500003 PM 24611460 ER PT S AU Tsao, S Gajawelli, N Hwang, DH Kriger, S Law, M Chui, H Weiner, M Lepore, N AF Tsao, Sinchai Gajawelli, Niharika Hwang, Darryl Hwa Kriger, Stephen Law, Meng Chui, Helena Weiner, Michael Lepore, Natasha BE Law, MY Cook, TS TI Mapping of ApoE4 Related White Matter Damage using Diffusion MRI SO MEDICAL IMAGING 2014: PACS AND IMAGING INFORMATICS: NEXT GENERATION AND INNOVATIONS SE Proceedings of SPIE LA English DT Proceedings Paper CT Conference on Medical Imaging - PACS and Imaging Informatics - Next Generation and Innovations CY FEB 18-20, 2014 CL San Diego, CA SP SPIE, Modus Med Devices Inc, XIFIN Inc, Ventana Med Syst Inc, Intrace Med DE DTI; Diffusion MRI; MRI; Alzheimer's Disease; Dementia; ApoE; Neuroimaging AB ApoliopoproteinE epsilon 4 (ApoE-epsilon 4) polymorphism is the most well known genetic risk factor for developing Alzheimers Disease. The exact mechanism through which ApoE epsilon 4 increases AD risk is not fully known, but may be related to decreased clearance and increased oligomerization of A beta. By making measurements of white matter integrity via diffusion MR and correlating the metrics in a voxel-based statistical analysis with ApoE-epsilon 4 genotype (whilst controlling for vascular risk factor, gender, cognitive status and age) we are able to identify changes in white matter associated with carrying an ApoE epsilon 4 allele. We found potentially significant regions (P-uncorrected < 0.05) near the hippocampus and the posterior cingulum that were independent of voxels that correlated with age or clinical dementia rating (CDR) status suggesting that ApoE may affect cognitive decline via a pathway in dependent of normal aging and acute insults that can be measured by CDR and Framingham Coronary Risk Score (FCRS). C1 [Tsao, Sinchai] Univ Washington, Seattle, WA 98195 USA. [Gajawelli, Niharika; Hwang, Darryl Hwa; Law, Meng; Chui, Helena; Lepore, Natasha] Univ South Calif, Los Angeles, CA 90089 USA. [Gajawelli, Niharika; Lepore, Natasha] Childrens Hosp Los Angeles, Los Angeles, CA USA. [Kriger, Stephen; Weiner, Michael] San Francisco VA Med Ctr, Ctr Nerodegenerat Dis, San Francisco, CA USA. RP Tsao, S (reprint author), Univ Washington, Seattle, WA 98195 USA. EM mail@SinchaiTsao.com; lepore@usc.edu FU National Institute of Biomedical Imaging and Bioengineering [5R21EB013456-02]; [5P01AG012435-18] FX This work hasbeen supported by USC ADRC's National Institutes of Aging Program Grant 5P01AG012435-18 as well as National Institute of Biomedical Imaging and Bioengineering grant 5R21EB013456-02 NR 1 TC 3 Z9 3 U1 0 U2 0 PU SPIE-INT SOC OPTICAL ENGINEERING PI BELLINGHAM PA 1000 20TH ST, PO BOX 10, BELLINGHAM, WA 98227-0010 USA SN 0277-786X BN 978-0-8194-9832-8 J9 PROC SPIE PY 2014 VL 9039 AR UNSP 90390H DI 10.1117/12.2043925 PG 5 WC Optics; Radiology, Nuclear Medicine & Medical Imaging SC Optics; Radiology, Nuclear Medicine & Medical Imaging GA BA7IY UT WOS:000337584000014 PM 25076830 ER PT S AU Yoshida, H Wu, Y Cai, WL AF Yoshida, Hiroyuki Wu, Yin Cai, Wenli BE Law, MY Cook, TS TI Analysis of scalability of high-performance 3D image processing platform for virtual colonoscopy SO MEDICAL IMAGING 2014: PACS AND IMAGING INFORMATICS: NEXT GENERATION AND INNOVATIONS SE Proceedings of SPIE LA English DT Proceedings Paper CT Conference on Medical Imaging - PACS and Imaging Informatics - Next Generation and Innovations CY FEB 18-20, 2014 CL San Diego, CA SP SPIE, Modus Med Devices Inc, XIFIN Inc, Ventana Med Syst Inc, Intrace Med DE 3D imaging processing; high-performance computing; performance scalability; virtual colonoscopy AB One of the key challenges in three-dimensional (3D) medical imaging is to enable the fast turn-around time, which is often required for interactive or real-time response. This inevitably requires not only high computational power but also high memory bandwidth due to the massive amount of data that need to be processed. For this purpose, we previously developed a software platform for high-performance 3D medical image processing, called HPC 3D-MIP platform, which employs increasingly available and affordable commodity computing systems such as the multicore, cluster, and cloud computing systems. To achieve scalable high-performance computing, the platform employed size-adaptive, distributable block volumes as a core data structure for efficient parallelization of a wide range of 3D-MIP algorithms, supported task scheduling for efficient load distribution and balancing, and consisted of a layered parallel software libraries that allow image processing applications to share the common functionalities. We evaluated the performance of the HPC 3D-MIP platform by applying it to computationally intensive processes in virtual colonoscopy. Experimental results showed a 12-fold performance improvement on a workstation with 12-core CPUs over the original sequential implementation of the processes, indicating the efficiency of the platform. Analysis of performance scalability based on the Amdahl's law for symmetric multicore chips showed the potential of a high performance scalability of the HPC 3D-MIP platform when a larger number of cores is available. C1 [Yoshida, Hiroyuki] Massachusetts Gen Hosp, 3D Imaging Res, Dept Radiol, 25 New Chardon St,Suite 400C, Boston, MA 02114 USA. [Yoshida, Hiroyuki] Massachusetts Gen Hosp, Harvard Med Sch, Boston, MA 02114 USA. RP Yoshida, H (reprint author), Massachusetts Gen Hosp, 3D Imaging Res, Dept Radiol, 25 New Chardon St,Suite 400C, Boston, MA 02114 USA. EM yoshida.hiro@mgh.harvard.edu FU National Cancer Institute at the National Institutes of Health [R01CA131718] FX The project described was supported in part by grant R01CA131718 from the National Cancer Institute at the National Institutes of Health. NR 8 TC 0 Z9 0 U1 0 U2 1 PU SPIE-INT SOC OPTICAL ENGINEERING PI BELLINGHAM PA 1000 20TH ST, PO BOX 10, BELLINGHAM, WA 98227-0010 USA SN 0277-786X BN 978-0-8194-9832-8 J9 PROC SPIE PY 2014 VL 9039 AR UNSP 90390U DI 10.1117/12.2043869 PG 6 WC Optics; Radiology, Nuclear Medicine & Medical Imaging SC Optics; Radiology, Nuclear Medicine & Medical Imaging GA BA7IY UT WOS:000337584000026 PM 24910506 ER PT J AU Muurling, T Stankovic, KM AF Muurling, Tjeerd Stankovic, Konstantina M. TI Metabolomic and Network Analysis of Pharmacotherapies for Sensorineural Hearing Loss SO OTOLOGY & NEUROTOLOGY LA English DT Article DE ERK1/2; Ingenuity pathway analysis; Metabolomic analysis; Network medicine; Sensorineural hearing loss; Tretinoin ID RETINOIC ACID; DEXAMETHASONE; ORGANIZATION; MICROARRAY; EXPRESSION; MEDICINE; DEAFNESS; SYSTEMS; PATHWAY AB Hypothesis: Different pharmacotherapies for sensorineural hearing loss (SNHL) are interconnected in metabolic networks with molecular hubs. Background: Sensorineural hearing loss is the most common sensory deficit worldwide. Dozens of drugs have shown efficacy against SNHL in animal studies and a few in human studies. Analyzing metabolic networks that interconnect these drugs will point to and prioritize development of new pharmacotherapies for human SNHL. Methods: Drugs that have shown efficacy in treating mammalian SNHL were identified through PubMed literature searches. The drugs were analyzed using the metabolomic analysis and the "grow-tool function" in ingenuity pathway analysis (IPA). The top 3 most interconnected molecules and drugs (i.e., the hubs) within the generated networks were considered important targets for the treatment of SNHL. Results: A total of 70 drugs were investigated with IPA. The metabolomic analysis revealed 2 statistically significant networks (Networks 1 and 2). A network analysis using the "grow-tool function" generated one statistically significant network (Network 3). Hubs of these networks were as follows: P38 mitogen-activated protein kinases (P38 MAPK), p42/p44 MAP kinase (ERK1/2) and glutathione for Network 1; protein kinase B (Akt), nuclear factor kappa B (NFkB) and ERK for Network 2; and dexamethasone, tretinoin, and cyclosporin A for Network 3. Conclusion: Metabolomic and network analysis of the existing pharmacotherapies for SNHL has pointed to and prioritized a number of potential novel targets for treatment of SNHL. C1 [Muurling, Tjeerd; Stankovic, Konstantina M.] Harvard Univ, Sch Med, Dept Otol & Laryngol, Boston, MA 02115 USA. [Muurling, Tjeerd; Stankovic, Konstantina M.] Massachusetts Eye & Ear Infirm, Dept Otolaryngol, Boston, MA 02114 USA. [Muurling, Tjeerd] Leiden Univ, Med Ctr, Dept Otorhinolaryngol, Leiden, Netherlands. RP Stankovic, KM (reprint author), Massachusetts Eye & Ear Infirm, 243 Charles St, Boston, MA 02114 USA. EM konstantina_stankovic@meei.harvard.edu FU NIDCD [K08 DC010419]; Bertarelli Foundation FX NIDCD K08 DC010419 (to K. M. S.) and the Bertarelli Foundation (to K. M. S.). NR 27 TC 6 Z9 6 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1531-7129 EI 1537-4505 J9 OTOL NEUROTOL JI Otol. Neurotol. PD JAN PY 2014 VL 35 IS 1 BP 1 EP 6 PG 6 WC Clinical Neurology; Otorhinolaryngology SC Neurosciences & Neurology; Otorhinolaryngology GA AJ5BB UT WOS:000337694300013 PM 24335929 ER PT J AU Plotkin, SR Merker, VL Muzikansky, A Barker, FG Slattery, W AF Plotkin, Scott R. Merker, Vanessa L. Muzikansky, Alona Barker, Fred G., II Slattery, William, III TI Natural History of Vestibular Schwannoma Growth and Hearing Decline in Newly Diagnosed Neurofibromatosis Type 2 Patients SO OTOLOGY & NEUROTOLOGY LA English DT Article DE Natural history; Neurofibromatosis 2-Vestibular schwannoma; Word recognition score ID MANAGEMENT; CONSORTIUM; RATES AB Objective: To determine the rate of growth in vestibular schwannomas and the rate of hearing decline in neurofibromatosis type 2 (NF2) patients not undergoing active treatment Study Design: Prospective study. Setting: Data were collected at 10 NF2 centers, including hospital-based, academic, and tertiary care centers. Patients: 120 NF2 patients with 200 vestibular schwannomas. Outcome Measures: Hearing decline, defined as a decrease in word recognition score outside the 95% critical difference compared with baseline, and radiographic progression, defined as a 20% or greater increase in tumor volume compared with baseline. Results: During a total of 313.4 patient-years of follow-up, the rate of hearing decline was 5% at 1 year, 13% at 2 years, and 16% at 3 years; the rate of tumor progression was 31% at 1 year, 64% at 2 years, and 79% at 3 years. For this cohort, the median time to tumor progression (14 mo) was significantly shorter than the median time to hearing decline (62.0 mo). Conclusion: These data provide potentially useful information for the design of clinical trials for NF2 vestibular schwannoma. C1 [Plotkin, Scott R.; Merker, Vanessa L.] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. [Plotkin, Scott R.; Merker, Vanessa L.] Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA. [Muzikansky, Alona] Massachusetts Gen Hosp, Ctr Biostat, Boston, MA 02114 USA. [Barker, Fred G., II] Massachusetts Gen Hosp, Neurosurg Serv, Boston, MA 02114 USA. [Slattery, William, III] House Clin, Los Angeles, CA USA. RP Plotkin, SR (reprint author), Massachusetts Gen Hosp, Yawkey 9E,55 Fruit St, Boston, MA 02114 USA. EM splotkin@partners.org FU Department of Defense [DAMD 17-98-1-8612] FX The NF2 Natural History Consortium was supported by the Department of Defense award number DAMD 17-98-1-8612 to WS. NR 28 TC 16 Z9 16 U1 2 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 1531-7129 EI 1537-4505 J9 OTOL NEUROTOL JI Otol. Neurotol. PD JAN PY 2014 VL 35 IS 1 BP E50 EP E56 PG 7 WC Clinical Neurology; Otorhinolaryngology SC Neurosciences & Neurology; Otorhinolaryngology GA AJ5BB UT WOS:000337694300009 PM 24335938 ER PT J AU Remenschneider, A Santos, F AF Remenschneider, Aaron Santos, Felipe TI Pneumocephalus, Hearing Loss, and Vertigo After Airline Flight in a Patient With Superior Canal Dehiscence SO OTOLOGY & NEUROTOLOGY LA English DT Editorial Material C1 [Remenschneider, Aaron; Santos, Felipe] Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Otol & Laryngol, Boston, MA 02114 USA. RP Remenschneider, A (reprint author), Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Otol & Laryngol, 243 Charles St, Boston, MA 02114 USA. EM aaron_remenschneider@meei.harvard.edu NR 4 TC 1 Z9 1 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1531-7129 EI 1537-4505 J9 OTOL NEUROTOL JI Otol. Neurotol. PD JAN PY 2014 VL 35 IS 1 BP E60 EP E61 PG 2 WC Clinical Neurology; Otorhinolaryngology SC Neurosciences & Neurology; Otorhinolaryngology GA AJ5BB UT WOS:000337694300011 PM 23989000 ER PT J AU Wood, GC Boucher, AB Johnson, JL Wisniewski, JN Magnotti, LJ Croce, MA Swanson, JM Boucher, BA Fabian, TC AF Wood, G. Christopher Boucher, Andrew B. Johnson, Jessica L. Wisniewski, Jennifer N. Magnotti, Louis J. Croce, Martin A. Swanson, Joseph M. Boucher, Bradley A. Fabian, Timothy C. TI Effectiveness of Pseudoephedrine as Adjunctive Therapy for Neurogenic Shock After Acute Spinal Cord Injury: A Case Series SO PHARMACOTHERAPY LA English DT Article DE pseudoephedrine; vasopressor; neurogenic shock; spinal cord injury; bradycardia; hypotension ID SYMPTOMATIC BRADYCARDIA; MANAGEMENT; AMINOPHYLLINE; COMPLICATIONS; ASYSTOLE; TETRAPLEGIA AB STUDY OBJECTIVE To evaluate the effectiveness of pseudoephedrine as adjunctive therapy for neurogenic shock in patients with acute spinal cord injury (SCI). DESIGN Case series. SETTING Academic medical center. PATIENTS Thirty-eight patients admitted to the trauma intensive care unit between September 2005 and October 2012 with an acute SCI and who received more than 1 day of pseudoephedrine for one or more of the following: treatment of bradycardia (heart rate < 50 beats/min), treatment of hypotension (systolic blood pressure < 90 mm Hg), or were receiving intravenous vasopressor support. MEASUREMENTS AND MAIN RESULTS The effect of adjunctive pseudoephedrine (PSE) was categorized as a success if vasopressors were discontinued after the initiation of PSE or improvement in the number of episodes of bradycardia was noted after the initiation of PSE as evidenced by decreased use of atropine. The effect of pseudoephedrine was categorized as a failure if it did not meet one of the criteria for success. The effect of pseudoephedrine was categorized as inconclusive if there were confounding factors such as vasopressors being restarted for another indication after initial discontinuation. Pseudoephedrine was successful in 31/38 (82%) patients, failed in 2/38 (5%) patients, and had inconclusive results in 5/38 (13%) patients. The mean +/- SD time to successful weaning of intravenous vasopressors was 7 +/- 7 days. Daily maximum pseudoephedrine doses ranged from 60-720 mg. Mean +/- SD duration of pseudoephedrine therapy was 32 +/- 23 days (range 2-135 days), with 64.5% of surviving patients discharged while receiving pseudoephedrine. CONCLUSION These data suggest that pseudoephedrine is an effective adjunctive therapy in facilitating the discontinuation of intravenous vasopressors and/or atropine in patients with acute SCI with neurogenic shock, although patients will typically require long durations of therapy. C1 [Wood, G. Christopher; Swanson, Joseph M.; Boucher, Bradley A.] Univ Tennessee, Dept Clin Pharm, Coll Pharm, Hlth Sci Ctr, Memphis, TN 38163 USA. [Boucher, Andrew B.] Univ Tennessee, Hlth Sci Ctr, Coll Med, Memphis, TN 38163 USA. [Johnson, Jessica L.] MedStar Union Mem Hosp, Dept Pharm, Baltimore, MD USA. [Wisniewski, Jennifer N.] Ralph H Johnson Vet Affairs Med Ctr, Serv Pharm, Charleston, SC USA. [Magnotti, Louis J.; Croce, Martin A.; Fabian, Timothy C.] Univ Tennessee, Dept Surg, Coll Med, Hlth Sci Ctr, Memphis, TN 38163 USA. RP Wood, GC (reprint author), Univ Tennessee, Dept Clin Pharm, Coll Pharm, Hlth Sci Ctr, 881 Madison Ave, Memphis, TN 38163 USA. EM cwood@uthsc.edu NR 23 TC 0 Z9 0 U1 1 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0277-0008 EI 1875-9114 J9 PHARMACOTHERAPY JI Pharmacotherapy PD JAN PY 2014 VL 34 IS 1 BP 89 EP 93 DI 10.1002/phar.1335 PG 5 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA AJ2UJ UT WOS:000337518800012 PM 23918202 ER PT S AU Jorge, AES Hamblin, MR Parizotto, NA Kurachi, C Bagnato, VS AF Jorge, Ana Elisa S. Hamblin, Michael R. Parizotto, Nivaldo A. Kurachi, Cristina Bagnato, Vanderlei S. BE Choi, B Kollias, N Zeng, H Kang, HW Wong, BJF Ilgner, JF Tearney, GJ Gregory, KW Marcu, L Mandelis, A TI Photodynamic therapy improves the ultraviolet-irradiated hairless mice skin SO PHOTONIC THERAPEUTICS AND DIAGNOSTICS X SE Proceedings of SPIE LA English DT Proceedings Paper CT Conference on Photonic Therapeutics and Diagnostics X CY FEB 01-02, 2014 CL San Francisco, CA SP SPIE DE photodynamic therapy; UV-irradiated skin; hairless mice; histopathology; epidermal thickening; dermal collagen density ID DELTA-AMINOLEVULINIC-ACID; INTENSE PULSED-LIGHT; 5-AMINOLEVULINIC ACID; TOPICAL APPLICATION; MOUSE SKIN; PHOTOREJUVENATION; PHOTODAMAGE AB Chronic exposure to ultraviolet (UV) sunlight causes skin photoaging. In light of this fact, photodynamic therapy (PDT) is an emerging modality for treating cancer and other skin conditions, however its response on photoaged skin has not been fully illustrated by means of histopathology. For this reason, the aim of this study was analyze whether PDT can play a role on a mouse model of photoaging. Hence, SKH-1 hairless mice were randomly allocated in two groups, UV and UV/PDT. The mice were daily exposed to an UV light source (280-400 nm: peak at 350 nm) for 8 weeks followed by a single PDT session using 20% 5-aminolevulinic acid (ALA) topically. After the proper photosensitizer accumulation within the tissue, a non-coherent red (635 nm) light was performed at 75 J/cm(2) and, after 14 days, skin samples were excised and processed for light microscopy, and their sections were stained with hematoxylin-eosin (HE) and Masson's Trichrome. As a result, we observed a substantial epidermal thickening and an improvement in dermal collagen density by deposition of new collagen fibers on UV/PDT group. These findings strongly indicate epidermal and dermal restoration, and consequently skin restoration. In conclusion, this study provides suitable evidences that PDT improves the UV-irradiated hairless mice skin, supporting this technique as an efficient treatment for photoaged skin. C1 [Jorge, Ana Elisa S.] Univ Sao Paulo, Programa Posgrad Interunidades Bioengn, Sao Carlos, SP, Brazil. [Jorge, Ana Elisa S.; Kurachi, Cristina; Bagnato, Vanderlei S.] Univ Sao Paulo, Inst Fis Sao Carlos, Sao Carlos, SP, Brazil. [Jorge, Ana Elisa S.; Hamblin, Michael R.] Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA USA. [Hamblin, Michael R.] Harvard Univ, Med Sch, Dept Dermatol, Boston, MA USA. [Hamblin, Michael R.] Harvard MIT Div Hlth Sci & Technol, Cambridge, MA USA. [Parizotto, Nivaldo A.] Univ Fed Sao Carlos, Sao Carlos, SP, Brazil. RP Jorge, AES (reprint author), Univ Sao Paulo, Programa Posgrad Interunidades Bioengn, Sao Carlos, SP, Brazil. RI Kurachi, Cristina/G-3731-2012; Bagnato, Vanderlei/C-3133-2012; PARIZOTTO, Nivaldo/D-5347-2014; USP, CePOF/J-3608-2015; Sao Carlos Institute of Physics, IFSC/USP/M-2664-2016; OI PARIZOTTO, Nivaldo/0000-0003-1774-9053; Hamblin, Michael/0000-0001-6431-4605 FU CAPES [BEX 9117/12-1]; FAPESP; CNPq FX This work was financially supported by CAPES (BEX 9117/12-1 process), FAPESP and CNPq (Brazilian government funding programs). The authors are grateful to Professor Irene Kochevar, Ph. D. (Wellman Center for Photomedicine/Harvard Medical School) for borrowing the UV source for the experiment setup; Bill Farinelli (Wellman Center for Photomedicine) for helping with the UV lamps radiation assessment; and also to Lilian Moriyama, Ph. D., and Natalia Inada, Ph. D., for assistance in the PDT protocol. NR 25 TC 0 Z9 0 U1 0 U2 9 PU SPIE-INT SOC OPTICAL ENGINEERING PI BELLINGHAM PA 1000 20TH ST, PO BOX 10, BELLINGHAM, WA 98227-0010 USA SN 0277-786X BN 978-0-8194-9839-7 J9 PROC SPIE PY 2014 VL 8926 AR UNSP 89260N DI 10.1117/12.2040297 PG 6 WC Optics; Radiology, Nuclear Medicine & Medical Imaging SC Optics; Radiology, Nuclear Medicine & Medical Imaging GA BA7IP UT WOS:000337574500009 ER PT S AU Tichauer, KM Kanick, SC Deharvengt, SJ Samkoe, KS Hasan, T Stan, RV Pogue, BW AF Tichauer, Kenneth M. Kanick, Stephen C. Deharvengt, Sophie J. Samkoe, Kimberley S. Hasan, Tayyaba Stan, Radu V. Pogue, Brian W. BE Choi, B Kollias, N Zeng, H Kang, HW Wong, BJF Ilgner, JF Tearney, GJ Gregory, KW Marcu, L Mandelis, A TI Quantitative fluorescence molecular imaging in highly light-absorbing melanomas using a dual-tracer kinetic modeling normalization method SO PHOTONIC THERAPEUTICS AND DIAGNOSTICS X SE Proceedings of SPIE LA English DT Proceedings Paper CT Conference on Photonic Therapeutics and Diagnostics X CY FEB 01-02, 2014 CL San Francisco, CA SP SPIE DE planar fluorescence imaging; multiple reporter; mouse xenograft model; plasmalemmal vesicle associated protein (PV1) ID ANGIOGENESIS; EXPRESSION; DELIVERY; BARRIERS; AGENTS; TUMORS AB Tissues with high light absorption, such as melanomas, present a significant challenge to fluorescence imaging approaches that seek to estimate molecular expression in vivo, since any fluorescence originating in the tissue will suffer substantial attenuation prior to detection. This can lead to sizable underestimations in estimated fluorescent tracer concentration in these tissues using conventional fluorescence imaging. In this study, a dual-tracer fluorescence imaging approach was employed to correct for severe tissue absorption by 1) using simultaneous injection and imaging of an untargeted tracer to normalize tissue absorption effects on the targeted tracer, and 2) using kinetic modeling that capitalizes on subtle differences in the dynamics of targeted and untargeted tracer uptake to quantify targeted molecule concentrations in the high absorbing tissue. Monte Carlo simulation and kinetic models demonstrated that the effect of optical properties on the approach could be eliminated by a pixel-by-pixel normalization of the targeted and untargeted tracer uptakes prior to 5 min post-tracer injection for fluorescence planar dynamic imaging. C1 [Tichauer, Kenneth M.] IIT, Dept Biomed Engn, 3255 S Dearborn St, Chicago, IL 60616 USA. [Kanick, Stephen C.; Samkoe, Kimberley S.; Pogue, Brian W.] Dartmouth Coll, Thayer Sch Engn, Hanover, NH 03755 USA. [Deharvengt, Sophie J.] Geisel Sch Med, Dept Pathol, Hanover, NH 03755 USA. [Samkoe, Kimberley S.; Pogue, Brian W.] Geisel Sch Med, Dept Surg, Hanover, NH 03755 USA. [Hasan, Tayyaba; Stan, Radu V.; Pogue, Brian W.] Massachusetts Gen Hosp, Wellman Inst Photomed, Boston, MA 02114 USA. RP Tichauer, KM (reprint author), IIT, Dept Biomed Engn, 3255 S Dearborn St, Chicago, IL 60616 USA. RI Stan, Radu/E-8876-2011 OI Stan, Radu/0000-0003-2969-1725 NR 17 TC 0 Z9 0 U1 0 U2 6 PU SPIE-INT SOC OPTICAL ENGINEERING PI BELLINGHAM PA 1000 20TH ST, PO BOX 10, BELLINGHAM, WA 98227-0010 USA SN 0277-786X BN 978-0-8194-9839-7 J9 PROC SPIE PY 2014 VL 8926 AR UNSP 89260T DI 10.1117/12.2037424 PG 7 WC Optics; Radiology, Nuclear Medicine & Medical Imaging SC Optics; Radiology, Nuclear Medicine & Medical Imaging GA BA7IP UT WOS:000337574500012 ER PT J AU Zhou, JG Wu, SJ Chen, X Liu, CL Sheen, J Shan, LB He, P AF Zhou, Jinggeng Wu, Shujing Chen, Xin Liu, Chenglong Sheen, Jen Shan, Libo He, Ping TI The Pseudomonas syringae effector HopF2 suppresses Arabidopsis immunity by targeting BAK1 SO PLANT JOURNAL LA English DT Article DE bacterial effector; pattern-triggered immunity; BAK1; BIK1; MAPK cascade; Pseudomonas syringae; Arabidopsis thaliana ID PLANT INNATE IMMUNITY; RECOGNITION RECEPTOR FLS2; III EFFECTOR; PROTEIN-KINASE; PV. TOMATO; PATHOGEN VIRULENCE; DISEASE RESISTANCE; CYTOPLASMIC KINASE; FLAGELLIN; RIN4 AB Pseudomonas syringae delivers a plethora of effector proteins into host cells to sabotage immune responses and modulate physiology to favor infection. The P.syringae pv. tomato DC3000 effector HopF2 suppresses Arabidopsis innate immunity triggered by multiple microbe-associated molecular patterns (MAMP) at the plasma membrane. We show here that HopF2 possesses distinct mechanisms for suppression of two branches of MAMP-activated MAP kinase (MAPK) cascades. In addition to blocking MKK5 (MAPK kinase5) activation in the MEKK1 (MAPK kinase kinase 1)/MEKKs-MKK4/5-MPK3/6 cascade, HopF2 targets additional component(s) upstream of MEKK1 in the MEKK1-MKK1/2-MPK4 cascade and the plasma membrane-localized receptor-like cytoplasmic kinase BIK1 and its homologs. We further show that HopF2 directly targets BAK1, a plasma membrane-localized receptor-like kinase that is involved in multiple MAMP signaling. The interaction between BAK1 and HopF2 and between two other P.syringae effectors, AvrPto and AvrPtoB, was confirmed in vivo and in vitro. Consistent with BAK1 as a physiological target of AvrPto, AvrPtoB and HopF2, the strong growth defects or lethality associated with ectopic expression of these effectors in wild-type Arabidopsis transgenic plants were largely alleviated in bak1 mutant plants. Thus, our results provide genetic evidence to show that BAK1 is a physiological target of AvrPto, AvrPtoB and HopF2. Identification of BAK1 as an additional target of HopF2 virulence not only explains HopF2 suppression of multiple MAMP signaling at the plasma membrane, but also supports the notion that pathogen virulence effectors act through multiple targets in host cells. C1 [Zhou, Jinggeng; He, Ping] Texas A&M Univ, Dept Biochem & Biophys, College Stn, TX 77843 USA. [Zhou, Jinggeng; He, Ping] Texas A&M Univ, Inst Plant Genom & Biotechnol, College Stn, TX 77843 USA. [Wu, Shujing; Chen, Xin; Liu, Chenglong; Shan, Libo] Texas A&M Univ, Dept Plant Pathol & Microbiol, College Stn, TX 77843 USA. [Wu, Shujing; Chen, Xin; Liu, Chenglong; Shan, Libo] Texas A&M Univ, Inst Plant Genom & Biotechnol, College Stn, TX 77843 USA. [Wu, Shujing] Shandong Agr Univ, Lab Apple Mol Biol & Biotechnol, Natl Res Ctr Apple Engn & Technol, State Key Lab Crop Biol,Coll Hort Sci & Engn, Tai An 271018, Shandong, Peoples R China. [Sheen, Jen] Harvard Univ, Dept Genet, Sch Med, Boston, MA 02114 USA. [Sheen, Jen] Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. [Sheen, Jen] Massachusetts Gen Hosp, Ctr Computat & Integrat Biol, Boston, MA 02114 USA. RP He, P (reprint author), Texas A&M Univ, Dept Biochem & Biophys, College Stn, TX 77843 USA. EM pinghe@tamu.edu FU US National Institutes of Health [R01 GM70567, R01GM092893]; US National Science Foundation [IOS-1030250]; Robert A. Welch Foundation [A-1795]; US Department of Agriculture National Institute of Food and Agriculture [2012-67013-19433] FX We thank Jianming Li (Department of Molecular, Cellular, and Developmental Biology, University of Michigan, Ann Arbor, MI 48109, USA) for pBAK1-BAK1-GFP transgenic plant seeds, and two anonymous reviewers for their constructive comments and suggestions, which helped us to improve the manuscript. This work was supported by funding from the US National Institutes of Health (R01 GM70567) to J.S., the US National Science Foundation (IOS-1030250) and the Robert A. Welch Foundation (A-1795) to L. S., and the US National Institutes of Health (R01GM092893) and the US Department of Agriculture National Institute of Food and Agriculture (2012-67013-19433) to P.H. NR 61 TC 21 Z9 21 U1 7 U2 48 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0960-7412 EI 1365-313X J9 PLANT J JI Plant J. PD JAN PY 2014 VL 77 IS 2 BP 235 EP 245 DI 10.1111/tpj.12381 PG 11 WC Plant Sciences SC Plant Sciences GA AJ3DI UT WOS:000337545400006 PM 24237140 ER PT J AU del Re, EC Bergen, SE Mesholam-Gately, RI Niznikiewicz, MA Goldstein, JM Woo, TU Shenton, ME Seidman, LJ McCarley, RW Petryshen, TL AF del Re, E. C. Bergen, S. E. Mesholam-Gately, R. I. Niznikiewicz, M. A. Goldstein, J. M. Woo, T. U. Shenton, M. E. Seidman, L. J. McCarley, R. W. Petryshen, T. L. TI Analysis of schizophrenia-related genes and electrophysiological measures reveals ZNF804A association with amplitude of P300b elicited by novel sounds SO TRANSLATIONAL PSYCHIATRY LA English DT Article ID 1ST EPISODE SCHIZOPHRENIA; WHOLE-GENOME ASSOCIATION; CLINICAL HIGH-RISK; AUDITORY P300; BIPOLAR DISORDER; COMMON VARIANTS; 1ST-EPISODE SCHIZOPHRENIA; NEUROCOGNITIVE PHENOTYPES; VAL158MET POLYMORPHISM; MISMATCH NEGATIVITY AB Several genes have recently been identified as risk factors for schizophrenia (SZ) by genome-wide association studies (GWAS), including ZNF804A which is thought to function in transcriptional regulation. However, the downstream pathophysiological changes that these genes confer remain to be elucidated. In 143 subjects (68 clinical high risk, first episode or chronic cases; 75 controls), we examined the association between 21 genetic markers previously identified by SZ GWAS or associated with putative intermediate phenotypes of SZ against three event-related potential (ERP) measures: mismatch negativity (MMN), amplitude of P300 during an auditory oddball task, and P300 amplitude during an auditory novelty oddball task. Controlling for age and sex, significant genetic association surpassing Bonferroni correction was detected between ZNF804A marker rs1344706 and P300 amplitude elicited by novel sounds (beta = 4.38, P = 1.03 x 10(-4)), which is thought to index orienting of attention to unexpected, salient stimuli. Subsequent analyses revealed that the association was driven by the control subjects (beta = 6.35, P = 9.08 x 10(-5)), and that the risk allele was correlated with higher novel P300b amplitude, in contrast to the significantly lower amplitude observed in cases compared to controls. Novel P300b amplitude was significantly correlated with a neurocognitive measure of auditory attention under interference conditions, suggesting a relationship between novel P300b amplitude and higher-order attentional processes. Our results suggest pleiotropic effects of ZNF804A on risk for SZ and neural mechanisms that are indexed by the novel P300b ERP component. C1 [del Re, E. C.; Niznikiewicz, M. A.; Shenton, M. E.; McCarley, R. W.] VA Boston Healthcare Syst, Brockton, MA USA. [del Re, E. C.; Bergen, S. E.; Mesholam-Gately, R. I.; Niznikiewicz, M. A.; Goldstein, J. M.; Woo, T. U.; Seidman, L. J.; McCarley, R. W.; Petryshen, T. L.] Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA. [Bergen, S. E.; Petryshen, T. L.] Massachusetts Gen Hosp, Ctr Human Genet Res, Psychiat & Neurodev Genet Unit, Boston, MA 02114 USA. [Bergen, S. E.; Petryshen, T. L.] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. [Bergen, S. E.] Karolinska Inst, Med Epidemiol & Biostat Dept, Stockholm, Sweden. [Mesholam-Gately, R. I.; Seidman, L. J.] Beth Israel Deaconess Med Ctr, Dept Psychiat, Publ Psychiat Div, Massachusetts Mental Hlth Ctr, Boston, MA 02215 USA. [Goldstein, J. M.] Brigham & Womens Hosp, Connors Ctr Womens Hlth & Gender Biol, Boston, MA 02115 USA. [Goldstein, J. M.] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. [Goldstein, J. M.; Seidman, L. J.] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. [Woo, T. U.] McLean Hosp, Program Cellular Neuropathol, Belmont, MA 02178 USA. [Woo, T. U.] Beth Israel Deaconess Med Ctr, Dept Psychiat, Boston, MA 02215 USA. [Shenton, M. E.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Psychiat, Boston, MA 02115 USA. [Shenton, M. E.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Radiol, Boston, MA 02115 USA. RP Petryshen, TL (reprint author), Massachusetts Gen Hosp, Ctr Human Genet Res, 185 Cambridge St, Boston, MA 02114 USA. EM petryshen@chgr.mgh.harvard.edu RI McCarley, Robert/N-5562-2014; OI McCarley, Robert/0000-0001-5705-7495; Bergen, Sarah/0000-0002-5888-0034 FU National Institute of Mental Health of the National Institutes of Health [1P50 MH080272, U01 MH081928, 1R01 MH092380]; Massachusetts General Hospital Executive Committee on Research Interim Support Fund award; NARSAD Young Investigator [19753] FX This research was supported by the National Institute of Mental Health of the National Institutes of Health under Award Numbers 1P50 MH080272 (RWM), U01 MH081928 (LJS) and 1R01 MH092380 (TLP). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. Genotyping was funded by a Massachusetts General Hospital Executive Committee on Research Interim Support Fund award (TLP). SEB is partially supported by NARSAD Young Investigator Grant 19753. We thank all subjects for their participation in the study. We also thank the clinical and data management staff from the Boston CIDAR study and the Commonwealth Research Center, including: Matcheri Keshavan, Joanne Wojcik, Ann Cousins, Michelle Friedman-Yakoobian, Anthony J Giuliano, Andrea Gnong Granato, Lauren Gibson, Sarah Hornbach, Julia Schutt, Kristy Klein, Maria Hiraldo, Grace Francis, Corin Pilo, Rachael Serur, Grace Min, Alison Thomas, and Molly Franz. We also thank Tamara Tasoff, Beril Yaffe, and Danbee Kim for electrophysiology assistance (Harvard), and Kimberly Chambert (Broad Institute of MIT and Harvard), Patience Gallagher, Steve Haddad, Brian Galloway, and Jenna Tarasoff (Massachusetts General Hospital) for genotyping assistance. NR 100 TC 14 Z9 14 U1 4 U2 18 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 2158-3188 J9 TRANSL PSYCHIAT JI Transl. Psychiatr. PD JAN PY 2014 VL 4 AR e346 DI 10.1038/tp.2013.117 PG 9 WC Psychiatry SC Psychiatry GA AJ2RL UT WOS:000337507500008 PM 24424392 ER PT J AU Hadjikhani, N Zurcher, NR Rogier, O Hippolyte, L Lemonnier, E Ruest, T Ward, N Lassalle, A Gillberg, N Billstedt, E Helles, A Gillberg, C Solomon, P Prkachin, KM Gillberg, C AF Hadjikhani, N. Zuercher, N. R. Rogier, O. Hippolyte, L. Lemonnier, E. Ruest, T. Ward, N. Lassalle, A. Gillberg, N. Billstedt, E. Helles, A. Gillberg, C. Solomon, P. Prkachin, K. M. Gillberg, C. TI Emotional contagion for pain is intact in autism spectrum disorders SO TRANSLATIONAL PSYCHIATRY LA English DT Article DE autism; emotion perception; fMRI; pain ID ASPERGER-SYNDROME; COGNITIVE EMPATHY; NEURAL SYSTEMS; DIAGNOSTIC INTERVIEW; FUNCTIONING AUTISM; FACIAL EXPRESSIONS; BRAIN MECHANISMS; FUSIFORM GYRUS; MIRROR NEURON; ADULTS AB Perceiving others in pain generally leads to empathic concern, consisting of both emotional and cognitive processes. Empathy deficits have been considered as an element contributing to social difficulties in individuals with autism spectrum disorders (ASD). Here, we used functional magnetic resonance imaging and short video clips of facial expressions of people experiencing pain to examine the neural substrates underlying the spontaneous empathic response to pain in autism. Thirty-eight adolescents and adults of normal intelligence diagnosed with ASD and 35 matched controls participated in the study. In contrast to general assumptions, we found no significant differences in brain activation between ASD individuals and controls during the perception of pain experienced by others. Both groups showed similar levels of activation in areas associated with pain sharing, evidencing the presence of emotional empathy and emotional contagion in participants with autism as well as in controls. Differences between groups could be observed at a more liberal statistical threshold, and revealed increased activations in areas involved in cognitive reappraisal in ASD participants compared with controls. Scores of emotional empathy were positively correlated with brain activation in areas involved in embodiment of pain in ASD group only. Our findings show that simulation mechanisms involved in emotional empathy are preserved in high-functioning individuals with autism, and suggest that increased reappraisal may have a role in their apparent lack of caring behavior. C1 [Hadjikhani, N.; Zuercher, N. R.; Rogier, O.; Hippolyte, L.; Ruest, T.; Lassalle, A.] Ecole Polytech Fed Lausanne, Brain Mind Inst, CH-1015 Lausanne, Switzerland. [Hadjikhani, N.; Gillberg, N.; Billstedt, E.; Helles, A.; Gillberg, C.; Gillberg, C.] Univ Gothenburg, Sahlgrenska Acad, Gillberg Neuropsychiat Ctr, Gothenburg, Sweden. [Hadjikhani, N.; Zuercher, N. R.; Ward, N.] Harvard Univ, Sch Med, Athinoula A Martinos Ctr Biomed Imaging, Massachusetts Gen Hosp, Charlestown, MA 02129 USA. [Lemonnier, E.] Univ Bretagne Occidentale, Lab Neurosci Brest, EA4685, Brest, France. [Solomon, P.] McMaster Univ, Sch Rehabil Sci, Hamilton, ON, Canada. [Prkachin, K. M.] Univ No British Columbia, Hlth Psychol Lab, Prince George, BC V2L 5P2, Canada. RP Hadjikhani, N (reprint author), Harvard Univ, Sch Med, Athinoula A Martinos Ctr Biomed Imaging, 149,13th St, Charlestown, MA 02129 USA. EM nouchine@nmr.mgh.harvard.edu RI Centre d'imagerie Biomedicale, CIBM/B-5740-2012; OI Hadjikhani, Nouchine/0000-0003-4075-3106 FU Swiss National Science Foundation [PP00P3-130191]; Velux Stiftung; Centre d'Imagerie BioMedicale (CIBM) of the University of Lausanne (UNIL); Swiss Federal Institute of Technology Lausanne (EPFL); Swedish Science Council; Canadian Institutes of Health Research; Foundation Rossi Di Montalera FX We thank all participants and their families. We also thank K. Metrailler for her support in participants' recruitment, C. Burget for her administrative assistance, A. Lissot and J. Snyder for their help in data analysis and technical support, and K. B. Jensen for her insightful comments on the manuscript. This work was supported by the Swiss National Science Foundation (PP00P3-130191 to NH), the Velux Stiftung, the Centre d'Imagerie BioMedicale (CIBM) of the University of Lausanne (UNIL), the Swiss Federal Institute of Technology Lausanne (EPFL), the Swedish Science Council, as well as the Foundation Rossi Di Montalera. Preparation of the facial pain videos was supported by a grant from the Canadian Institutes of Health Research. The funders had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; and preparation, review, or approval of the manuscript. NR 88 TC 22 Z9 24 U1 17 U2 54 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 2158-3188 J9 TRANSL PSYCHIAT JI Transl. Psychiatr. PD JAN PY 2014 VL 4 AR e343 DI 10.1038/tp.2013.113 PG 9 WC Psychiatry SC Psychiatry GA AJ2RL UT WOS:000337507500005 PM 24424389 ER PT J AU Jensen, KP Stein, MB Kranzler, HR Yang, BZ Farrer, LA Gelernter, J AF Jensen, K. P. Stein, M. B. Kranzler, H. R. Yang, B. Z. Farrer, L. A. Gelernter, J. TI The alpha-endomannosidase gene (MANEA) is associated with panic disorder and social anxiety disorder SO TRANSLATIONAL PSYCHIATRY LA English DT Article DE anxiety; behavior; cocaine; gene expression; mannosidosis; mannosidase ID INTERNATIONAL NEUROPSYCHIATRIC INTERVIEW; NATIONAL-COMORBIDITY-SURVEY; WHOLE GENOME ASSOCIATION; DSM-IV; SEMISTRUCTURED ASSESSMENT; PSYCHIATRIC-DISORDERS; ALCOHOLISM SSADDA; DRUG-DEPENDENCE; MANNOSIDOSIS; IDENTIFICATION AB Unbiased genome-wide approaches can provide novel insights into the biological pathways that are important for human behavior and psychiatric disorder risk. The association of alpha-endomannosidase gene (MANEA) variants and cocaine-induced paranoia (CIP) was initially described in a study that used a whole-genome approach. Behavioral effects have been reported for other mannosidase genes, but MANEA function in humans and the clinical potential of the previous findings remain unclear. We hypothesized that MANEA would be associated with psychiatric phenotypes unrelated to cocaine use. We used a multi-stage association study approach starting with four psychiatric disorders to show an association between a MANEA single-nucleotide polymorphism (SNP; rs1133503) and anxiety disorders. In the first study of 2073 European American (EA) and 2459 African American subjects mostly with comorbid drug or alcohol dependence, we observed an association in EAs of rs1133503 with panic disorder (PD) (191 PD cases, odds ratio (OR) = 1.7 (95% confidence interval (CI): 1.22-2.41), P = 0.002). We replicated this finding in an independent sample of 142 PD cases (OR = 1.53 (95% CI: 1.00-2.31), P = 0.043) and extended it in an independent sample of 131 generalized social anxiety disorder cases (OR = 2.15 (95% CI: 1.27-3.64), P = 0.004). MANEA alleles and genotypes were also associated with gene expression differences in whole blood cells. Using publically available data, we observed a consistent effect on expression in brain tissue. We conclude that pathways involving a-endomannosidase warrant further investigation in relation to anxiety disorders. C1 [Jensen, K. P.; Yang, B. Z.; Gelernter, J.] Yale Univ, Sch Med, Dept Psychiat, Div Human Genet, New Haven, CT USA. [Jensen, K. P.; Yang, B. Z.; Gelernter, J.] VA CT Healthcare Ctr, West Haven, CT USA. [Stein, M. B.] Univ Calif San Diego, Dept Psychiat, La Jolla, CA 92093 USA. [Stein, M. B.] Univ Calif San Diego, Dept Family & Prevent Med, La Jolla, CA 92093 USA. [Kranzler, H. R.] Univ Penn, Dept Psychiat, Perelman Sch Med, Philadelphia, PA 19104 USA. [Kranzler, H. R.] Philadelphia VA Med Ctr, MIRECC VISN4, Philadelphia, PA USA. [Farrer, L. A.] Boston Univ, Sch Med & Publ Hlth, Dept Med, Boston, MA 02215 USA. [Farrer, L. A.] Boston Univ, Sch Med & Publ Hlth, Dept Neurol, Boston, MA 02215 USA. [Farrer, L. A.] Boston Univ, Sch Med & Publ Hlth, Dept Ophthalmol, Boston, MA 02215 USA. [Farrer, L. A.] Boston Univ, Sch Med & Publ Hlth, Dept Genet & Genom, Boston, MA 02215 USA. [Farrer, L. A.] Boston Univ, Sch Med & Publ Hlth, Dept Epidemiol, Boston, MA 02215 USA. [Farrer, L. A.] Boston Univ, Sch Med & Publ Hlth, Dept Biostat, Boston, MA 02215 USA. [Gelernter, J.] Yale Univ, Sch Med, Dept Genet, New Haven, CT 06510 USA. [Gelernter, J.] Yale Univ, Sch Med, Dept Neurobiol, New Haven, CT USA. RP Gelernter, J (reprint author), Yale Univ, Sch Med, Div Human Genet Psychiat, Dept Psychiat,VA CT Healthcare Ctr 116A2, 950 Campbell Ave, West Haven, CT 06516 USA. EM joel.gelernter@yale.edu OI Farrer, Lindsay/0000-0001-5533-4225 FU National Institutes of Health [N01-HG-65403, RC2 DA028909 DA12849, DA12690, DA18432, AA017535, AA11330, DA24758, MH64122, T32 MH014276, MH057858, MH058915, MH070022, MH057835, MH072952]; VA MERIT award FX Data from the CALM study were provided by the respective PIs: Michelle Craske PhD (UCLA), Peter Roy-Byrne MD (U Washington) and Greer Sullivan MD, MSPH (University of Arkansas for Medical Sciences). Genotyping services for some parts of the study were provided by the Center for Inherited Disease Research (CIDR). CIDR is fully funded through a federal contract from the National Institutes of Health to The Johns Hopkins University (contract number N01-HG-65403). This work was supported in part by NIH grants, RC2 DA028909 DA12849, DA12690, DA18432, AA017535, AA11330, DA24758, MH64122, T32 MH014276, MH057858, MH058915, MH070022, MH057835, MH64122, MH072952 and a VA MERIT award. NR 36 TC 3 Z9 3 U1 5 U2 9 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 2158-3188 J9 TRANSL PSYCHIAT JI Transl. Psychiatr. PD JAN PY 2014 VL 4 AR e353 DI 10.1038/tp.2013.122 PG 6 WC Psychiatry SC Psychiatry GA AJ2RL UT WOS:000337507500015 PM 24473444 ER PT J AU Mimiaga, MJ White, JM Krakower, DS Biello, KB Mayer, KH AF Mimiaga, Matthew J. White, Jaclyn M. Krakower, Douglas S. Biello, Katie B. Mayer, Kenneth H. TI Suboptimal awareness and comprehension of published preexposure prophylaxis efficacy results among physicians in Massachusetts SO AIDS CARE-PSYCHOLOGICAL AND SOCIO-MEDICAL ASPECTS OF AIDS/HIV LA English DT Article DE preexposure prophylaxis; PrEP; physicians; HIV; prevention ID HIV PREVENTION; UNITED-STATES; MEN; SEX; ATTITUDES; BEHAVIOR AB In 2010, the centre for the AIDS Programme of Research in South Africa (CAPRISA) 004 and iPrEx trials (microbicide gel containing tenofovir and oral pill containing tenofovir-emtricitabine, respectively) demonstrated that antiretroviral preexposure prophylaxis (PrEP) reduced the risk of HIV acquisition among high-risk individuals. To determine the facilitators and barriers to PrEP provision by health-care providers, we conducted an online, quantitative survey of Massachusetts-area physicians following the publication of the CAPRISA and iPrEx results. We assessed awareness and comprehension of efficacy data, prescribing experience, and anticipated provision of oral and topical PrEP among physicians, as well as demographic and behavioral factors associated with PrEP awareness and prescribing intentions. The majority of HIV specialists and generalist physicians were aware of data from these PrEP trials and able to correctly interpret the results, however, correct interpretation of findings tended to vary according to specialty (i.e., HIV specialists had greater awareness than generalists). In addition, provider concerns regarding PrEP efficacy and safety, as well its ability to divert funds from other HIV prevention resources, were associated with decreased intentions to prescribe both oral and topical PrEP. Findings suggest that a substantial proportion of physicians who may have contact with at-risk individuals may benefit from interventions that provide accurate data on the risks and benefits of PrEP in order to facilitate effective PrEP discussions with their patients. Future studies to develop and test interventions aimed at health-care providers should be prioritized to optimize implementation of PrEP in clinical settings. C1 [Mimiaga, Matthew J.] Harvard Univ, Sch Med, Dept Psychiat, Massachusetts Gen Hosp, Boston, MA 02115 USA. [Mimiaga, Matthew J.; Biello, Katie B.] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. [Mimiaga, Matthew J.; White, Jaclyn M.; Biello, Katie B.; Mayer, Kenneth H.] Fenway Hlth, Fenway Inst, Boston, MA USA. [Krakower, Douglas S.; Mayer, Kenneth H.] Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Div Infect Dis, Boston, MA 02215 USA. RP Mimiaga, MJ (reprint author), Harvard Univ, Sch Med, Dept Psychiat, Massachusetts Gen Hosp, Boston, MA 02115 USA. EM mmimiaga@hsph.harvard.edu FU NIAID NIH HHS [T32 AI007433, AI 007433]; NIMH NIH HHS [K23 MH098795, K23 MH098795-01] NR 24 TC 17 Z9 17 U1 0 U2 5 PU ROUTLEDGE JOURNALS, TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXFORDSHIRE, ENGLAND SN 0954-0121 EI 1360-0451 J9 AIDS CARE JI Aids Care-Psychol. Socio-Med. Asp. Aids-Hiv PY 2014 VL 26 IS 6 BP 684 EP 693 DI 10.1080/09540121.2013.845289 PG 10 WC Health Policy & Services; Public, Environmental & Occupational Health; Psychology, Multidisciplinary; Respiratory System; Social Sciences, Biomedical SC Health Care Sciences & Services; Public, Environmental & Occupational Health; Psychology; Respiratory System; Biomedical Social Sciences GA AI9BJ UT WOS:000337221100003 PM 24116985 ER PT J AU Keller, SC Momplaisir, F Lo Re, V Newcomb, C Liu, Q Ratcliffe, SJ Long, JA AF Keller, Sara C. Momplaisir, Florence Lo Re, Vincent Newcomb, Craig Liu, Qing Ratcliffe, Sarah J. Long, Judith A. TI Colorectal cancer incidence and screening in US Medicaid patients with and without HIV infection SO AIDS CARE-PSYCHOLOGICAL AND SOCIO-MEDICAL ASPECTS OF AIDS/HIV LA English DT Article DE HIV; colorectal cancer; non-AIDS defining malignancies; Medicaid; colorectal cancer screening ID HUMAN-IMMUNODEFICIENCY-VIRUS; UNITED-STATES; CARE; DIAGNOSIS; POPULATION; SERVICES; ADULTS; OLDER; RISK; AIDS AB Non-AIDS defining malignancies, particularly colorectal cancer (CRC), may be more prevalent among persons living with HIV (PLWH). Further, PLWH may be less likely to receive CRC screening (CRCS). We studied the epidemiology of CRC and CRCS patterns in PLWH and HIV-uninfected persons in a large US Medicaid population. We performed a matched cohort study examining CRC incidence in 2006 and CRCS between 1999 and 2007. Study participants were continuously enrolled in the Medicaid programs of California, Florida, New York, Ohio, and Pennsylvania. All PLWH enrollees were matched to five randomly sampled HIV-uninfected enrollees on 5-year age group, gender, and state. Adjusted odds ratios (AORs) for incident CRC (adjusted for comorbidity index) and the presence of CRCS (adjusted for comorbidity index and years in the data-set) among PLWH compared to HIV-uninfected enrollees were calculated. PLWH were not more likely to be diagnosed with CRC after adjusting for comorbidity index (unadjusted OR: 1.73, 95% confidence interval [CI]: 1.37-2.19; AOR 1.29; 95% CI: 0.98-1.70). While CRCS rates were low overall, PLWH were more likely to have received CRCS in unadjusted analyses (35.8% vs. 33.7%; OR 1.10, 95% CI: 1.07-1.13). This relationship was reversed after adjusting for comorbidity index and years in the data-set (AOR: 0.80, 95% CI: 0.77-0.83). Limitations of the study include a focus on the Medicaid population, an inability to detect fecal occult blood tests (FOBT), and having half of patients between 50 and 55 years of age. In conclusion, PLWH were not more likely to be diagnosed with CRC, but in adjusted analyses, were less likely to have received CRCS. As we showed a low rate of CRCS overall in this Medicaid population, researchers, clinicians, and policy-makers should improve access to and uptake of CRCS among all Medicaid patients, and particularly among PLWH. C1 [Keller, Sara C.; Lo Re, Vincent] Univ Penn, Perelman Sch Med, Div Infect Dis, Philadelphia, PA 19104 USA. [Momplaisir, Florence] Temple Univ, Sch Med, Div Infect Dis, Villanova, PA USA. [Newcomb, Craig; Liu, Qing; Ratcliffe, Sarah J.] Univ Penn, Perelman Sch Med, Dept Biostat & Clin Epidemiol, Philadelphia, PA 19104 USA. [Long, Judith A.] Univ Penn, Perelman Sch Med, Div Gen Internal Med, Philadelphia VA Ctr Hlth Equ Res & Promot, Philadelphia, PA 19104 USA. RP Keller, SC (reprint author), Univ Penn, Perelman Sch Med, Div Infect Dis, Philadelphia, PA 19104 USA. EM skeller9@jhmi.edu RI Lo Re, Vincent/N-7817-2015; OI Ratcliffe, Sarah/0000-0002-6644-8284 FU NCATS NIH HHS [UL1 TR000003]; NCI NIH HHS [KM1 CA156715]; NCRR NIH HHS [UL1 RR024134]; NIAID NIH HHS [P30 AI045008] NR 32 TC 3 Z9 3 U1 2 U2 5 PU ROUTLEDGE JOURNALS, TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXFORDSHIRE, ENGLAND SN 0954-0121 EI 1360-0451 J9 AIDS CARE JI Aids Care-Psychol. Socio-Med. Asp. Aids-Hiv PY 2014 VL 26 IS 6 BP 716 EP 722 DI 10.1080/09540121.2013.855700 PG 7 WC Health Policy & Services; Public, Environmental & Occupational Health; Psychology, Multidisciplinary; Respiratory System; Social Sciences, Biomedical SC Health Care Sciences & Services; Public, Environmental & Occupational Health; Psychology; Respiratory System; Biomedical Social Sciences GA AI9BJ UT WOS:000337221100007 PM 24188387 ER PT J AU Ojikutu, B Holman, J Kunches, L Landers, S Perlmutter, D Ward, M Fant, G Hirschhorn, L AF Ojikutu, Bisola Holman, Jeremy Kunches, Laureen Landers, Stewart Perlmutter, Dianne Ward, Melina Fant, Gregory Hirschhorn, Lisa TI Interdisciplinary HIV care in a changing healthcare environment in the USA SO AIDS CARE-PSYCHOLOGICAL AND SOCIO-MEDICAL ASPECTS OF AIDS/HIV LA English DT Article DE HIV; AIDS; interdisciplinary care; multidisciplinary care; medical home AB HIV remains a complex disease that requires comprehensive, coordinated care to ensure optimal outcomes. In the USA, interdisciplinary models of care have developed over time to optimize treatment outcomes. These models may be increasingly important in an era of healthcare reform in the USA. A qualitative study of nine clinical sites funded by the Ryan White HIV/AIDS Program (RWHAP), the federally funded "safety net" program for uninsured and underinsured people living with HIV, was undertaken to identify components of successful models of interdisciplinary HIV care. Findings suggest that these include: (1) patient-centered, one-stop-shop approaches with integrated or co-located services; (2) diverse teams of clinical and nonclinical providers; (3) a site culture that promotes a stigma reducing environment for clients; (4) the availability of a comprehensive array of medical, behavioral health, and psychosocial services; (5) effective communication strategies, including electronic health records (EHRs); and (6) a focus on quality. The importance of RWHAP funding in sustaining these programs is highlighted. C1 [Ojikutu, Bisola; Holman, Jeremy; Kunches, Laureen; Landers, Stewart; Perlmutter, Dianne; Ward, Melina; Hirschhorn, Lisa] John Snow Inc, Boston, MA 02210 USA. [Ojikutu, Bisola; Hirschhorn, Lisa] Harvard Univ, Sch Med, Boston, MA USA. [Fant, Gregory] Vet Hlth Adm, US Dept Vet Affairs, Washington, DC USA. RP Ojikutu, B (reprint author), John Snow Inc, Boston, MA 02210 USA. EM bojikutu@jsi.com FU PHS HHS [HHSH250200646026I] NR 10 TC 4 Z9 4 U1 1 U2 9 PU ROUTLEDGE JOURNALS, TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXFORDSHIRE, ENGLAND SN 0954-0121 EI 1360-0451 J9 AIDS CARE JI Aids Care-Psychol. Socio-Med. Asp. Aids-Hiv PY 2014 VL 26 IS 6 BP 731 EP 735 DI 10.1080/09540121.2013.855299 PG 5 WC Health Policy & Services; Public, Environmental & Occupational Health; Psychology, Multidisciplinary; Respiratory System; Social Sciences, Biomedical SC Health Care Sciences & Services; Public, Environmental & Occupational Health; Psychology; Respiratory System; Biomedical Social Sciences GA AI9BJ UT WOS:000337221100009 PM 24191727 ER PT J AU Dworkin, SL Lu, T Grabe, S Kwena, Z Mwaura-Muiru, E Bukusi, E AF Dworkin, Shari L. Lu, Tiffany Grabe, Shelly Kwena, Zachary Mwaura-Muiru, Esther Bukusi, Elizabeth TI What community-level strategies are needed to secure women's property rights in Western Kenya? Laying the groundwork for a future structural HIV prevention intervention SO AIDS CARE-PSYCHOLOGICAL AND SOCIO-MEDICAL ASPECTS OF AIDS/HIV LA English DT Article DE structural interventions; HIV prevention; gender relations; property and inheritance rights ID EMPOWERMENT; HIV/AIDS; VIOLENCE AB Despite the recognized need for structural-level HIV prevention interventions that focus on economic empowerment to reduce women's HIV risks, few science-based programs have focused on securing women's land ownership as a primary or secondary HIV risk reduction strategy. The current study focused on a community-led land and property rights model that was implemented in two rural areas of western Kenya where HIV prevalence was high (24-30%) and property rights violations were common. The program was designed to reduce women's HIV risk at the community level by protecting and enhancing women's access to and ownership of land. Through in-depth interviews with 50 program leaders and implementers of this program we sought to identify the strategies that were used to prevent, mediate, and resolve property rights violations. Results included four strategies: (1) rights-based education of both women and men individually and at the community level, (2) funeral committees that intervene to prevent property grabbing and disinheritance, (3) paralegal training of traditional leaders and community members and local adjudication of cases of property rights violations, and (4) referring property rights violations to the formal justice system when these are not resolved at the community level. Study participants underscored that local mediation of cases resulted in a higher success rate than women experienced in the formal court system, underscoring the importance of community-level solutions to property rights violations. The current study assists researchers in understanding the steps needed to prevent and resolve women's property rights violations so as to bolster the literature on potential structural HIV prevention interventions. Future research should rigorously test property rights programs as a structural HIV prevention intervention. C1 [Dworkin, Shari L.] Univ Calif San Francisco, Dept Social & Behav Sci, San Francisco, CA 94117 USA. [Lu, Tiffany] Massachusetts Gen Hosp, Dept Med, Residency Training Program, Boston, MA 02114 USA. [Grabe, Shelly] Univ Calif Santa Cruz, Dept Psychol, Santa Cruz, CA 95064 USA. [Kwena, Zachary; Bukusi, Elizabeth] Kenya Govt Med Res Ctr, Ctr Microbiol Res, Nairobi, Kenya. [Mwaura-Muiru, Esther] GROOTS Kenya, Nairobi, Kenya. RP Dworkin, SL (reprint author), Univ Calif San Francisco, Dept Social & Behav Sci, San Francisco, CA 94117 USA. EM shari.dworkin@ucsf.edu FU NIAID NIH HHS [P30-AI027763, P30 AI027763] NR 21 TC 3 Z9 3 U1 1 U2 6 PU ROUTLEDGE JOURNALS, TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXFORDSHIRE, ENGLAND SN 0954-0121 EI 1360-0451 J9 AIDS CARE JI Aids Care-Psychol. Socio-Med. Asp. Aids-Hiv PY 2014 VL 26 IS 6 BP 754 EP 757 DI 10.1080/09540121.2013.845286 PG 4 WC Health Policy & Services; Public, Environmental & Occupational Health; Psychology, Multidisciplinary; Respiratory System; Social Sciences, Biomedical SC Health Care Sciences & Services; Public, Environmental & Occupational Health; Psychology; Respiratory System; Biomedical Social Sciences GA AI9BJ UT WOS:000337221100013 PM 24116828 ER PT J AU Gilligan, CJ Rathmell, JP AF Gilligan, Christopher J. Rathmell, James P. TI On the Fabric of the Human Body and Modern Ultrasound Imaging SO ANESTHESIOLOGY LA English DT Editorial Material ID CERVICAL-SPINE; JOINT PAIN; INJECTIONS C1 [Rathmell, James P.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Anesthesia Crit Care & Pain Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Anaesthesia, Boston, MA 02115 USA. RP Rathmell, JP (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Anesthesia Crit Care & Pain Med, Boston, MA 02115 USA. EM rathmell.james@mgh.harvard.edu NR 6 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0003-3022 EI 1528-1175 J9 ANESTHESIOLOGY JI Anesthesiology PD JAN PY 2014 VL 120 IS 1 BP 10 EP 11 DI 10.1097/ALN.0000436118.90260.45 PG 2 WC Anesthesiology SC Anesthesiology GA AI9EE UT WOS:000337231400005 PM 24071618 ER PT J AU Lee, S Yang, HS Sasakawa, T Khan, MAS Khatri, A Kaneki, M Martyn, JAJ AF Lee, Sangseok Yang, Hong-seuk Sasakawa, Tomoki Khan, Mohammed A. S. Khatri, Ashok Kaneki, Masao Martyn, J. A. Jeevendra TI Immobilization with Atrophy Induces De Novo Expression of Neuronal Nicotinic alpha 7 Acetylcholine Receptors in Muscle Contributing to Neurotransmission SO ANESTHESIOLOGY LA English DT Article ID NEUROMUSCULAR-TRANSMISSION; SKELETAL-MUSCLE; FETAL; INFLAMMATION; DENERVATION; MECHANISMS; ANTIBODIES; ADULT; TOXIN; MICE AB Background: Mature acetylcholine receptor (AChR) isoform normally mediates muscle contraction. The hypothesis that alpha 7AChRs up-regulate during immobilization and contribute to neurotransmission was tested pharmacologically using specific blockers to mature (waglerin-1), immature (alpha A-OIVA), and alpha 7AChRs (methyllycaconitine), and nonspecific muscle AChR antagonist, alpha-bungarotoxin. Methods: Mice were immobilized; contralateral limbs were controls. Fourteen days later, anesthetized mice were mechanically ventilated. Nerve-stimulated tibialis muscle contractions on both sides were recorded, and blockers enumerated above sequentially administered via jugular vein. Data are mean +/- standard error. Results: Immobilization (N = 7) induced tibialis muscle atrophy (40.6 +/- 2.8 vs. 52.1 +/- 2.0 mg; P < 0.01) and decrease of twitch tension (34.8 +/- 1.1 vs. 42.9 +/- 1.5 g; P < 0.01). Waglerin-1 (0.3 +/- 0.05 mu g/g) significantly (P = 0.001; N = 9) depressed twitch tension on contralateral (>= 97%) versus immobilized side (approximately 45%). Additional waglerin-1 (total dose 1.06 +/- 0.12 mu g/g or approximately 15.0 x ED50 in normals) could not depress twitch of 80% or greater on immobilized side. Immature AChR blocker, alpha A-OIVA (17.0 +/- 0.25 mu g/g) did not change tension bilaterally. Administration of a-bungarotoxin (N = 4) or methyllycaconitine (N = 3) caused 96% or greater suppression of the remaining twitch tension on immobilized side. Methyllycaconitine, administered first (N = 3), caused equipotent inhibition by waglerin-1 on both sides. Protein expression of alpha 7AChRs was significantly (N = 3; P < 0.01) increased on the immobilized side. Conclusions: Ineffectiveness of waglerin-1 suggests that the twitch tension during immobilization is maintained by receptors other than mature AChRs. Because alpha A-OIVA caused no neuromuscular changes, it can be concluded that immature AChRs contribute minimally to neurotransmission. During immobilization approximately 20% of twitch tension is maintained by up-regulation of alpha-bungarotoxin- and methyllycaconitine-sensitive alpha 7AChRs. C1 [Lee, Sangseok; Yang, Hong-seuk; Sasakawa, Tomoki; Khan, Mohammed A. S.] Shriners Hosp Children, Massachusetts Gen Hosp, Boston, MA 02114 USA. [Lee, Sangseok; Yang, Hong-seuk; Sasakawa, Tomoki; Khan, Mohammed A. S.; Kaneki, Masao; Martyn, J. A. Jeevendra] Harvard Univ, Sch Med, Boston, MA USA. [Khatri, Ashok] Massachusetts Gen Hosp, Peptide Core Facil, Boston, MA 02114 USA. [Kaneki, Masao] Massachusetts Gen Hosp, Signal Transduct Lab, Boston, MA 02114 USA. [Martyn, J. A. Jeevendra] Shriners Hosp Children, Massachusetts Gen Hosp, Clin & Biochem Pharmacol Lab, Boston, MA 02114 USA. RP Martyn, JAJ (reprint author), Shriners Hosp Children, Dept Anesthesiol, Room 206,51 Blossom St, Boston, MA 02114 USA. EM jmartyn@partners.org OI Lee, Sangseok/0000-0001-7023-3668 FU Shriners Hospitals for Children(R) Research Philanthropy, Tampa, Florida; National Institutes of Health, Bethesda, Maryland [RO1 GM 05882, P50-GM2500]; In-Je Research and Scholarship Foundation, In-Je Re University, Seoul, South Korea FX Supported in part by grants from Shriners Hospitals for Children (R) Research Philanthropy, Tampa, Florida, and by the National Institutes of Health, Bethesda, Maryland (RO1 GM 05882 and P50-GM2500-Project 1) (to Dr. Martyn). Dr. Lee was supported by In-Je Research and Scholarship Foundation, In-Je Re University, Seoul, South Korea. NR 33 TC 5 Z9 6 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0003-3022 EI 1528-1175 J9 ANESTHESIOLOGY JI Anesthesiology PD JAN PY 2014 VL 120 IS 1 BP 76 EP 85 DI 10.1097/ALN.0000000000000025 PG 10 WC Anesthesiology SC Anesthesiology GA AI9EE UT WOS:000337231400015 PM 24126263 ER PT J AU Haydar, B Charnin, J Voepel-Lewis, T Baker, K AF Haydar, Bishr Charnin, Jonathan Voepel-Lewis, Terri Baker, Keith TI Resident Characterization of Better-than- and Worse-than-Average Clinical Teaching SO ANESTHESIOLOGY LA English DT Article ID PROMOTION CRITERIA; FEEDBACK; EDUCATORS; FACULTY; PERCEPTIONS; TEACHERS AB Background: Clinical teachers and trainees share a common view of what constitutes excellent clinical teaching, but associations between these behaviors and high teaching scores have not been established. This study used residents' written feedback to their clinical teachers, to identify themes associated with above-or below-average teaching scores. Methods: All resident evaluations of their clinical supervisors in a single department were collected from January 1, 2007 until December 31, 2008. A mean teaching score assigned by each resident was calculated. Evaluations that were 20% higher or 15% lower than the resident's mean score were used. A subset of these evaluations was reviewed, generating a list of 28 themes for further study. Two researchers then, independently coded the presence or absence of these themes in each evaluation. Interrater reliability of the themes and logistic regression were used to evaluate the predictive associations of the themes with above-or below-average evaluations. Results: Five hundred twenty-seven above-average and 285 below-average evaluations were evaluated for the presence or absence of 15 positive themes and 13 negative themes, which were divided into four categories: teaching, supervision, interpersonal, and feedback. Thirteen of 15 positive themes correlated with above-average evaluations and nine had high interrater reliability (Intraclass Correlation Coefficient >0.6). Twelve of 13 negative themes correlated with below-average evaluations, and all had high interrater reliability. On the basis of these findings, the authors developed 13 recommendations for clinical educators. Conclusions: The authors developed 13 recommendations for clinical teachers using the themes identified from the above- and below-average clinical teaching evaluations submitted by anesthesia residents. C1 [Haydar, Bishr; Voepel-Lewis, Terri] Univ Michigan, Dept Anesthesiol, Ann Arbor, MI 48109 USA. [Charnin, Jonathan; Baker, Keith] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Anesthesia Crit Care & Pain Med, Boston, MA USA. RP Baker, K (reprint author), Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, Gray Bigelow 444,55 Fruit St, Boston, MA 02114 USA. EM khbaker@partners.org OI Haydar, Bishr/0000-0003-2709-189X NR 25 TC 5 Z9 5 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0003-3022 EI 1528-1175 J9 ANESTHESIOLOGY JI Anesthesiology PD JAN PY 2014 VL 120 IS 1 BP 120 EP 128 DI 10.1097/ALN.0b013e31829b34bd PG 9 WC Anesthesiology SC Anesthesiology GA AI9EE UT WOS:000337231400020 PM 23838713 ER PT J AU Blum, RH Boulet, JR Cooper, JB Muret-Wagstaff, SL AF Blum, Richard H. Boulet, John R. Cooper, Jeffrey B. Muret-Wagstaff, Sharon L. CA Harvard Assessment Anesthesia TI Simulation-based Assessment to Identify Critical Gaps in Safe Anesthesia Resident Performance SO ANESTHESIOLOGY LA English DT Article ID ANESTHETISTS NONTECHNICAL SKILLS; HEALTH-CARE; CLINICAL SKILLS; EXPERIENCE; PHYSICIANS; EDUCATION; BOARD; REMEDIATION; RELIABILITY; STATEMENT AB Background: Valid methods are needed to identify anesthesia resident performance gaps early in training. However, many assessment tools in medicine have not been properly validated. The authors designed and tested use of a behaviorally anchored scale, as part of a multiscenario simulation-based assessment system, to identify high-and low-performing residents with regard to domains of greatest concern to expert anesthesiology faculty. Methods: An expert faculty panel derived five key behavioral domains of interest by using a Delphi process (1) Synthesizes information to formulate a clear anesthetic plan; (2) Implements a plan based on changing conditions; (3) Demonstrates effective interpersonal and communication skills with patients and staff; (4) Identifies ways to improve performance; and (5) Recognizes own limits. Seven simulation scenarios spanning pre-to-postoperative encounters were used to assess performances of 22 first-year residents and 8 fellows from two institutions. Two of 10 trained faculty raters blinded to trainee program and training level scored each performance independently by using a behaviorally anchored rating scale. Residents, fellows, facilitators, and raters completed surveys. Results: Evidence supporting the reliability and validity of the assessment scores was procured, including a high generalizability coefficient (rho(2) = 0.81) and expected performance differences between first-year resident and fellow participants. A majority of trainees, facilitators, and raters judged the assessment to be useful, realistic, and representative of critical skills required for safe practice. Conclusion: The study provides initial evidence to support the validity of a simulation-based performance assessment system for identifying critical gaps in safe anesthesia resident performance early in training. C1 [Blum, Richard H.] Boston Childrens Hosp, Dept Anesthesiol Perioperat & Pain Med, Boston, MA 02115 USA. [Blum, Richard H.; Cooper, Jeffrey B.; Muret-Wagstaff, Sharon L.] Harvard Univ, Sch Med, Boston, MA USA. [Boulet, John R.] Fdn Advancement Int Med Educ & Res, Philadelphia, PA USA. [Cooper, Jeffrey B.] Ctr Med Simulat, Charlestown, MA USA. [Cooper, Jeffrey B.] Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, Boston, MA 02114 USA. [Muret-Wagstaff, Sharon L.] Beth Israel Deaconess Med Ctr, Dept Anesthesia Crit Care & Pain Med, Boston, MA 02215 USA. RP Blum, RH (reprint author), Boston Childrens Hosp, Dept Anesthesiol Perioperat & Pain Med, 300 Longwood Ave, Boston, MA 02115 USA. EM richard.blum@childrens.harvard.edu FU Anaesthesia Chairs' Education Fund; Beth Israel Deaconess Medical Center; Brigham and Women's Hospital; Boston Children's Hospital; Massachusetts General Hospital, Boston, Massachusetts; Anesthesia Patient Safety Foundation; American Society of Anesthesiologists Endowed Research Award; Ellison C. Pierce, Jr., M.D., Research Award; Cathedral Fund; Newton Centre, Massachusetts FX Supported by the Anaesthesia Chairs' Education Fund, Beth Israel Deaconess Medical Center, Brigham and Women's Hospital, Boston Children's Hospital, Massachusetts General Hospital, Boston, Massachusetts; Anesthesia Patient Safety Foundation, American Society of Anesthesiologists Endowed Research Award; Ellison C. Pierce, Jr., M.D., Research Award; The Cathedral Fund, Newton Centre, Massachusetts; and the authors' respective departments. NR 56 TC 13 Z9 14 U1 0 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0003-3022 EI 1528-1175 J9 ANESTHESIOLOGY JI Anesthesiology PD JAN PY 2014 VL 120 IS 1 BP 129 EP 141 DI 10.1097/ALN.0000000000000055 PG 13 WC Anesthesiology SC Anesthesiology GA AI9EE UT WOS:000337231400021 PM 24398731 ER PT J AU Minehart, RD Rudolph, J Pian-Smith, MCM Raemer, DB AF Minehart, Rebecca D. Rudolph, Jenny Pian-Smith, May C. M. Raemer, Daniel B. TI Improving Faculty Feedback to Resident Trainees during a Simulated Case A Randomized, Controlled Trial of an Educational Intervention SO ANESTHESIOLOGY LA English DT Article ID PERFORMANCE; STRATEGIES; DYNAMICS; SPEAKING; IMPACT; TEAMS AB Background: Although feedback conversations are an essential component of learning, three challenges make them difficult: the fear that direct task feedback will harm the relationship with the learner, overcoming faculty cognitive biases that interfere with their eliciting the frames that drive trainees' performances, and time pressure. Decades of research on developmental conversations suggest solutions to these challenges: hold generous inferences about learners, subject one's own thinking to test by making it public, and inquire directly about learners' cognitive frames. Methods: The authors conducted a randomized, controlled trial to determine whether a 1-h educational intervention for anesthesia faculty improved feedback quality in a simulated case. The primary outcome was an analysis of the feedback conversation between faculty and a simulated resident (actor) by using averages of six elements of a Behaviorally Anchored Rating Scale and an objective structured assessment of feedback. Seventy-one Harvard faculty anesthesiologists from five academic hospitals participated. Results: The intervention group scored higher when averaging all ratings. Scores for individual elements showed that the intervention group performed better in maintaining a psychologically safe environment (4.3 +/- 1.21 vs. 3.8 +/- 1.16; P = 0.001), identifying and exploring performance gaps (4.1 +/- 1.38 vs. 3.7 +/- 1.34; P = 0.048), and they more frequently emphasized the professionalism error of failing to call for help over the clinical topic of anaphylaxis (66 vs. 41%; P = 0.008). Conclusions: Quality of faculty feedback to a simulated resident was improved in the interventional group in a number of areas after a 1-h educational intervention, and this short intervention allowed a group of faculty to overcome enough discomfort in addressing a professionalism lapse to discuss it directly. C1 [Minehart, Rebecca D.] Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, Boston, MA 02114 USA. Ctr Med Simulat, Boston, MA USA. RP Minehart, RD (reprint author), Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, GRJ 440,55 Fruit St, Boston, MA 02114 USA. EM rminehart@partners.org FU Foundation for Anesthesia Education and Research (FAER) Research in Education Grant (REG): FAER REG Minehart; Foundation for Anesthesia Education and Research, Rochester, Minnesota FX This work was funded by a Foundation for Anesthesia Education and Research (FAER) Research in Education Grant (REG): FAER REG 08/15/2008 Minehart.; The authors thank the significant contributions of the faculty and staff at the Center for Medical Simulation, Boston, Massachusetts; the support of the Foundation for Anesthesia Education and Research, Rochester, Minnesota, which made possible this work; and Roy Phitayakorn, M. D., M. H. P. E., Harvard Medical School, Massachusetts General Hospital, Boston, Massachusetts, Laura K. Rock, M. D., Harvard Medical School, Beth Israel Deaconess Medical Center, Boston, Massachusetts, Andres T. Navedo-Rivera, M. D., Harvard Medical School, Children's Hospital Boston, Boston, Massachusetts, and Amy Smith, D.N.P., M.S.N., C.N.M., Clinical Learning and Simulation Centers, Boston College, William F. Connell School of Nursing, Chestnut Hill, Massachusetts. NR 58 TC 8 Z9 9 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0003-3022 EI 1528-1175 J9 ANESTHESIOLOGY JI Anesthesiology PD JAN PY 2014 VL 120 IS 1 BP 160 EP 171 DI 10.1097/ALN.0000000000000058 PG 12 WC Anesthesiology SC Anesthesiology GA AI9EE UT WOS:000337231400024 PM 24398734 ER PT S AU Avci, P Gupta, GK Kawakubo, M Hamblin, MR AF Avci, Pinar Gupta, Gaurav K. Kawakubo, Masayoshi Hamblin, Michael R. BE Chen, WR TI Photodynamic therapy for melanoma: efficacy and immunologic effects SO BIOPHOTONICS AND IMMUNE RESPONSES IX SE Proceedings of SPIE LA English DT Proceedings Paper CT Conference on Biophotonics and Immune Responses IX CY FEB 03, 2014 CL San Francisco, CA SP SPIE DE photodynamic therapy; melanoma ID CANCER-TREATMENT; LASER IMMUNOTHERAPY; ANTITUMOR IMMUNITY; METASTATIC TUMORS; BACTERIOCHLORIN; APOPTOSIS; EPIDEMIC; MODALITY; CELLS; B16 AB Malignant melanoma is one of the fastest growing cancers and if it cannot be completely surgically removed the prognosis is bleak. Melanomas are known to be particularly resistant to both chemotherapy and radiotherapy. Various types of immunotherapy have however been investigated with mixed reports of success. Photodynamic therapy (PDT) has also been tested against melanoma, again with mixed effects as the melanin pigment is thought to act as both an optical shield and as an antioxidant. We have been investigating PDT against malignant melanoma in mouse models. We have compared B16F10 melanoma syngenic to C57BL/6 mice and S91 Cloudman melanoma syngenic to DBA2 mice. We have tested the hypothesis that S91 will respond better than B16 because of higher expression of immunocritical molecules such as MHC-1, tyrosinase, tyrosinase related protein-2 gp100, and intercellular adhesion molecule-1. Some of these molecules can act as tumor rejection antigens that can be recognized by antigen-specific cytotoxic CD8 T cells that have been stimulated by PDT. Moreover it is possible that DBA2 mice are intrinsically better able to mount an anti-tumor immune response than C57BL/6 mice. We are also studying intratumoral injection of photosensitzers such as benzoporphyrin monoacid ring A and comparing this route with the more usual route of intravenous administration. C1 [Avci, Pinar; Gupta, Gaurav K.; Kawakubo, Masayoshi; Hamblin, Michael R.] Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA. RP Avci, P (reprint author), Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA. OI Hamblin, Michael/0000-0001-6431-4605 NR 25 TC 1 Z9 1 U1 2 U2 4 PU SPIE-INT SOC OPTICAL ENGINEERING PI BELLINGHAM PA 1000 20TH ST, PO BOX 10, BELLINGHAM, WA 98227-0010 USA SN 0277-786X BN 978-0-8194-9857-1 J9 PROC SPIE PY 2014 VL 8944 AR 894403 DI 10.1117/12.2041328 PG 10 WC Immunology; Optics; Radiology, Nuclear Medicine & Medical Imaging SC Immunology; Optics; Radiology, Nuclear Medicine & Medical Imaging GA BA6GS UT WOS:000337138100001 ER PT J AU Bhan, I AF Bhan, Ishir TI Vitamin D Binding Protein and Bone Health SO INTERNATIONAL JOURNAL OF ENDOCRINOLOGY LA English DT Review ID MINERAL DENSITY; GC-GLOBULIN; PLASMA-CONCENTRATIONS; POSTMENOPAUSAL WOMEN; 25-HYDROXYVITAMIN D; SERUM; 1,25-DIHYDROXYVITAMIN-D; POLYMORPHISM; ASSOCIATION; PHENOTYPE AB Vitamin D binding protein (DBP) is the major carrier protein of 25-hydroxyvitamin D (25(OH) D) in the circulation, where it may serve roles in maintaining stable levels during times of decreased 25(OH) availability and in regulating delivery of 25(OH) D to target tissues. Several genetic polymorphisms of DBP have been described that lead to phenotypic changes in the protein that may affect affinity, activity, and concentration. These polymorphisms have been linked with alterations in bone density in several populations. One of the mechanisms by which DBP may alter bone health involves regulating vitaminDbioavailability. DBP-bound vitamin is thought to be relatively unavailable to target tissues, and thus alterations in DBP levels or affinity could lead to changes in vitamin D bioactivity. As a result, functional vitamin D status may differ greatly between individuals with similar total 25(OH) D levels. Additionally, DBP may have independent roles on macrophage and osteoclast activation. This review will summarize recent findings about DBP with respect to measures of bone density and health. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA 02114 USA. RP Bhan, I (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, 5 Suite 750,50 Staniford St, Boston, MA 02114 USA. EM ibhan@mgh.harvard.edu OI Bhan, Ishir/0000-0002-9596-9652 NR 33 TC 13 Z9 13 U1 0 U2 2 PU HINDAWI PUBLISHING CORPORATION PI NEW YORK PA 410 PARK AVENUE, 15TH FLOOR, #287 PMB, NEW YORK, NY 10022 USA SN 1687-8337 EI 1687-8345 J9 INT J ENDOCRINOL JI Int. J. Endocrinol. PY 2014 AR 561214 DI 10.1155/2014/561214 PG 5 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA AJ0UZ UT WOS:000337373000001 ER PT J AU Striebel, JM Kalapatapu, RK AF Striebel, Joan M. Kalapatapu, Raj K. TI THE ANTI-SUICIDAL POTENTIAL OF BUPRENORPHINE: A CASE REPORT SO INTERNATIONAL JOURNAL OF PSYCHIATRY IN MEDICINE LA English DT Article DE buprenorphine; suicidality; pain; depression ID STRESS; DEPRESSION; DYNORPHIN; PAIN; RISK AB The very strong relationship between suicide, depressive disorders, and substance use disorders is well recognized. Certain pain syndromes are significantly associated with suicide, irrespective of co-occurring medical or psychiatric diagnosis. Chronic pain, depression, substance use disorders, and suicide appear to involve overlapping neural pathways and brain regions that function in the processing of emotional and physical pain, as well as maintaining reward and anti-reward circuitry. In this article, we employ a clinical case to illustrate how various stressors disrupted the balance between pain and opioid-facilitated analgesia. This disruption resulted in excessive use of short-acting opioids to treat pain with ensuing allostatic overload and culmination in chronic suicidal ideation with a suicide attempt. Sublingual buprenorphine was selected to treat the opioid use disorder. We propose that the unique pharmacodynamics of this drug served to stabilize dysregulated neural circuits, neurotransmitters, and neuropeptides, allowing the mitigation of pain, assuaging opioid cravings, easing depression, and resolving suicidal ideation. To our knowledge, this is the first case report to describe the possible anti-suicidal effect of sublingual buprenorphine. C1 [Striebel, Joan M.; Kalapatapu, Raj K.] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Striebel, Joan M.; Kalapatapu, Raj K.] San Francisco VA Med Ctr, San Francisco, CA 94121 USA. RP Striebel, JM (reprint author), San Francisco VA Med Ctr, Dept Psychiat, Opioid Replacement Treatment Clin, 4150 Clement St,Mailstop 116F,Bldg 1, San Francisco, CA 94121 USA. EM joan.striebel@gmail.com FU ACGME-accredited Fellowship in Addiction Psychiatry at the University of California, San Francisco; [K23DA034883] FX Dr. Striebel is currently funded by the ACGME-accredited Fellowship in Addiction Psychiatry at the University of California, San Francisco. Dr. Kalapatapu is currently funded by K23DA034883. NR 16 TC 3 Z9 3 U1 1 U2 1 PU BAYWOOD PUBL CO INC PI AMITYVILLE PA 26 AUSTIN AVE, PO BOX 337, AMITYVILLE, NY 11701 USA SN 0091-2174 EI 1541-3527 J9 INT J PSYCHIAT MED JI Int. J. Psychiatr. Med. PY 2014 VL 47 IS 2 BP 169 EP 174 DI 10.2190/PM.47.2.g PG 6 WC Psychiatry SC Psychiatry GA AI8MP UT WOS:000337171200001 PM 25084802 ER PT J AU Matejkowski, J Fairfax-Columbo, J Cullen, SW Marcus, SC Solomon, PL AF Matejkowski, Jason Fairfax-Columbo, Jaymes Cullen, Sara W. Marcus, Steven C. Solomon, Phyllis L. TI Exploring the potential of stricter gun restrictions for people with serious mental illness to reduce homicide in the United States SO JOURNAL OF FORENSIC PSYCHIATRY & PSYCHOLOGY LA English DT Article DE gun violence; serious mental illness; multiple-victim homicide ID VIOLENCE; RISK AB This study explores the potential that current efforts to limit access to firearms for individuals with serious mental illness (SMI) have for reducing overall rates of murder by firearm in the United States. Official arrest, court and health records provided data on personal and offense characteristics of 95 individuals with SMI and 423 without, all of whom had been convicted of murder in the State of Indiana between 1990 and 2002. Bivariate analyses examined differences between the two groups and logistic regression models examined the relationship between SMI and offense characteristics. Compared to those without, a relatively small proportion of convicted murderers had a diagnosis indicating SMI. The presence of SMI was associated with reduced likelihood of targeting a stranger and was not associated with having multiple-victims or firearm use. Focusing on access to firearms exclusively by individuals with SMI will have little impact on multiple-victim or firearm-related homicides. C1 [Matejkowski, Jason] Univ Kansas, Sch Social Welf, Lawrence, KS 66045 USA. [Fairfax-Columbo, Jaymes] Drexel Univ, Dept Psychol, Philadelphia, PA 19104 USA. [Cullen, Sara W.; Solomon, Phyllis L.] Univ Penn, Sch Social Policy & Practice, Philadelphia, PA 19104 USA. [Marcus, Steven C.] Univ Penn, Philadelphia Vet Affairs Med Ctr, Ctr Hlth Equ Res & Promot, Philadelphia, PA 19104 USA. [Marcus, Steven C.] Univ Penn, Sch Social Policy & Practice, Philadelphia, PA 19104 USA. RP Matejkowski, J (reprint author), Univ Kansas, Sch Social Welf, Lawrence, KS 66045 USA. EM jmate@ku.edu NR 20 TC 3 Z9 3 U1 2 U2 6 PU ROUTLEDGE JOURNALS, TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXFORDSHIRE, ENGLAND SN 1478-9949 EI 1478-9957 J9 J FORENSIC PSYCHI PS JI J. Forensic Psychiatry Psychol. PY 2014 VL 25 IS 3 BP 362 EP 369 DI 10.1080/14789949.2014.909868 PG 8 WC Criminology & Penology; Psychiatry SC Criminology & Penology; Psychiatry GA AI9JD UT WOS:000337248000007 ER PT J AU Jenkins, JA Gordon, AJ AF Jenkins, Jennifer A. Gordon, Adam J. TI Advancing the Peer Review Process: A Multifaceted Approach to Improving Quality SO SUBSTANCE ABUSE LA English DT Editorial Material ID RANDOMIZED CONTROLLED-TRIAL; MASKING AUTHOR IDENTITY; BLIND C1 [Jenkins, Jennifer A.; Gordon, Adam J.] VA Pittsburgh Healthcare Syst, Ctr Hlth Equ Res & Promot, Pittsburgh, PA 15240 USA. [Gordon, Adam J.] Univ Pittsburgh, Sch Med, Pittsburgh, PA USA. RP Gordon, AJ (reprint author), VA Pittsburgh Healthcare Syst, Univ Dr C,Bldg 30, Pittsburgh, PA 15240 USA. EM adam.gordon@va.gov NR 13 TC 0 Z9 0 U1 2 U2 5 PU ROUTLEDGE JOURNALS, TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXFORDSHIRE, ENGLAND SN 0889-7077 EI 1547-0164 J9 SUBST ABUS JI Subst. Abus. PY 2014 VL 35 IS 2 BP 105 EP 107 DI 10.1080/08897077.2014.898978 PG 3 WC Substance Abuse SC Substance Abuse GA AI9HY UT WOS:000337244900001 PM 24580113 ER PT J AU Gordon, AJ Broyles, LM AF Gordon, Adam J. Broyles, Lauren M. TI A Physician-Centered Approach to Addiction Identification and Treatment Misses the Opportunity for Interdisciplinary Solutions SO SUBSTANCE ABUSE LA English DT Editorial Material C1 [Gordon, Adam J.] VA Pittsburgh Healthcare Syst, Ctr Hlth Equ Res & Promot, Pittsburgh, PA 15240 USA. Univ Pittsburgh, Sch Med, Pittsburgh, PA USA. RP Gordon, AJ (reprint author), VA Pittsburgh Healthcare Syst, Ctr Hlth Equ Res & Promot, Univ Dr C,Bldg 30, Pittsburgh, PA 15240 USA. EM adam.gordon@va.gov NR 10 TC 1 Z9 1 U1 0 U2 0 PU ROUTLEDGE JOURNALS, TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXFORDSHIRE, ENGLAND SN 0889-7077 EI 1547-0164 J9 SUBST ABUS JI Subst. Abus. PY 2014 VL 35 IS 2 BP 108 EP 109 DI 10.1080/08897077.2014.898976 PG 2 WC Substance Abuse SC Substance Abuse GA AI9HY UT WOS:000337244900002 PM 24580098 ER PT J AU Dulin, PL Gonzalez, VM Campbell, K AF Dulin, Patrick L. Gonzalez, Vivian M. Campbell, Kendra TI Results of a Pilot Test of a Self-Administered Smartphone-Based Treatment System for Alcohol Use Disorders: Usability and Early Outcomes SO SUBSTANCE ABUSE LA English DT Article DE Alcohol intervention; M-health; self-administered; smartphone; usability ID PERSONALIZED-FEEDBACK INTERVENTIONS; RANDOMIZED CONTROLLED-TRIAL; PROBLEM DRINKERS; DSM-IV; DRINKING; FEASIBILITY; DEPENDENCE; DIAGNOSIS; BARRIERS; STUDENTS AB .Background: This paper provides results from a pilot study focused on assessing early-stage effectiveness and usability of a smartphone-based intervention system that provides a stand-alone, self-administered intervention option, the Location-Based Monitoring and Intervention for Alcohol Use Disorders (LBMI-A). The LBMI-A provided numerous features for intervening with ongoing drinking, craving, connection with supportive others, managing life problems, high-risk location alerting, and activity scheduling. Methods: Twenty-eight participants, ranging in age from 22 to 45, who met criteria for an alcohol use disorder used an LBMI-A-enabled smartphone for 6 weeks. Results: Participants indicated the LBMI-A intervention modules were helpful in highlighting alcohol use patterns. Tools related to managing alcohol craving, monitoring consumption, and identifying triggers to drink were rated by participants as particularly helpful. Participants also demonstrated significant reductions in hazardous alcohol use while using the system (56% of days spent hazardously drinking at baseline vs. 25% while using the LBMI-A) and drinks per day diminished by 52%. Conclusions: Implications for system improvement as well as suggestions for designing ecological momentary assessment and intervention systems for substance use disorders are discussed. C1 [Dulin, Patrick L.; Gonzalez, Vivian M.] Univ Alaska Anchorage, Dept Psychol, Anchorage, AK 99508 USA. [Campbell, Kendra] San Francisco VA Med Ctr, Dept Family Med, San Francisco, CA USA. RP Dulin, PL (reprint author), Univ Alaska Anchorage, Dept Psychol, 3211 Providence Dr, Anchorage, AK 99508 USA. EM afpld@uaa.alaska.edu RI Emchi, Karma/Q-1952-2016 FU National Institute of Alcohol Abuse and Alcoholism (NIAAA) [RC2 AA019422-02] FX This project was funded by the National Institute of Alcohol Abuse and Alcoholism (NIAAA), grant RC2 AA019422-02. NR 31 TC 17 Z9 18 U1 6 U2 18 PU ROUTLEDGE JOURNALS, TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXFORDSHIRE, ENGLAND SN 0889-7077 EI 1547-0164 J9 SUBST ABUS JI Subst. Abus. PY 2014 VL 35 IS 2 BP 168 EP 175 DI 10.1080/08897077.2013.821437 PG 8 WC Substance Abuse SC Substance Abuse GA AI9HY UT WOS:000337244900014 PM 24821354 ER PT J AU Kertesz, SG Austin, EL Pollio, DE Holmes, SK White, B Lukas, CV AF Kertesz, S. G. Austin, E. L. Pollio, D. E. Holmes, S. K. White, B. Lukas, C. VanDeusen TI Housing, Housing Vouchers, and the H-SOLVE Study: Homeless Solutions in a VA Environment SO SUBSTANCE ABUSE LA English DT Meeting Abstract C1 [Kertesz, S. G.; Austin, E. L.] Birmingham VAMC, Birmingham, AL USA. [Pollio, D. E.] Univ Alabama, Tuscaloosa, AL 35487 USA. [Holmes, S. K.; White, B.; Lukas, C. VanDeusen] Boston VAMC, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 4 PU ROUTLEDGE JOURNALS, TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXFORDSHIRE, ENGLAND SN 0889-7077 EI 1547-0164 J9 SUBST ABUS JI Subst. Abus. PY 2014 VL 35 IS 2 BP 194 EP 195 PG 2 WC Substance Abuse SC Substance Abuse GA AI9HY UT WOS:000337244900020 ER PT J AU Merlin, J Turan, J Herbey, I Westfall, A Starrels, J Kertesz, S Mugavero, M Saag, M Ritchie, C AF Merlin, Jessica Turan, Janet Herbey, Ivan Westfall, Andrew Starrels, Joanna Kertesz, Stefan Mugavero, Michael Saag, Michael Ritchie, Christine TI Provider Documentation of Aberrant Drug-Related Behaviors in Patients Referred to an HIV/Chronic Pain Clinic SO SUBSTANCE ABUSE LA English DT Meeting Abstract C1 [Merlin, Jessica; Turan, Janet; Herbey, Ivan; Westfall, Andrew; Kertesz, Stefan; Mugavero, Michael; Saag, Michael] Univ Alabama Birmingham, Birmingham, AL USA. [Starrels, Joanna] Albert Einstein Coll Med, New York, NY USA. [Ritchie, Christine] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Kertesz, Stefan] Birmingham VA Med Ctr, Birmingham, AL USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU ROUTLEDGE JOURNALS, TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXFORDSHIRE, ENGLAND SN 0889-7077 EI 1547-0164 J9 SUBST ABUS JI Subst. Abus. PY 2014 VL 35 IS 2 BP 199 EP 199 PG 1 WC Substance Abuse SC Substance Abuse GA AI9HY UT WOS:000337244900033 ER PT J AU Broyles, LM Wieland, M Confer, A Youk, A Gordon, A AF Broyles, Lauren Matukaitis Wieland, Melissa Confer, Andrea Youk, Ada Gordon, Adam TI Holes in the Pipeline: Addressing Recruitment Challenges for an Alcohol Brief Intervention Trial in the Acute Care Setting SO SUBSTANCE ABUSE LA English DT Meeting Abstract C1 [Broyles, Lauren Matukaitis; Gordon, Adam] VA Pittsburgh Healthcare Syst, Pittsburgh, PA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ROUTLEDGE JOURNALS, TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXFORDSHIRE, ENGLAND SN 0889-7077 EI 1547-0164 J9 SUBST ABUS JI Subst. Abus. PY 2014 VL 35 IS 2 BP 208 EP 208 PG 1 WC Substance Abuse SC Substance Abuse GA AI9HY UT WOS:000337244900058 ER PT J AU Bichara, DA Pomerantseva, I Zhao, X Zhou, LB Kulig, KM Tseng, A Kimura, AM Johnson, MA Vacanti, JP Randolph, MA Sundback, CA AF Bichara, David A. Pomerantseva, Irina Zhao, Xing Zhou, Libin Kulig, Katherine M. Tseng, Alan Kimura, Anya M. Johnson, Matthew A. Vacanti, Joseph P. Randolph, Mark A. Sundback, Cathryn A. TI Successful Creation of Tissue-Engineered Autologous Auricular Cartilage in an Immunocompetent Large Animal Model SO TISSUE ENGINEERING PART A LA English DT Article ID FIBROBLAST-GROWTH-FACTOR; EAR-SHAPED CARTILAGE; IN-VITRO; ACID SCAFFOLDS; RECONSTRUCTION; CHONDROCYTES; VIVO; IMPLANTS; REPAIR; FIBRIN AB Tissue-engineered cartilage has historically been an attractive alternative treatment option for auricular reconstruction. However, the ability to reliably generate autologous auricular neocartilage in an immunocompetent preclinical model should first be established. The objectives of this study were to demonstrate engineered autologous auricular cartilage in the immunologically aggressive subcutaneous environment of an immunocompetent animal model, and to determine the impact of in vitro culture duration of chondrocyte-seeded constructs on the quality of neocartilage maturation in vivo. Auricular cartilage was harvested from eight adult sheep; chondrocytes were isolated, expanded in vitro, and seeded onto fibrous collagen scaffolds. Constructs were cultured in vitro for 2, 6, and 12 weeks, and then implanted autologously in sheep and in control nude mice for 6 and 12 weeks. Explanted tissue was stained with hematoxylin and eosin, safranin O, toluidine blue, collagen type II, and elastin. DNA and glycosaminoglycans (GAGs) were quantified. The quality of cartilage engineered in sheep decreased with prolonged in vitro culture time. Superior cartilage formation was demonstrated after 2 weeks of in vitro culture; the neocartilage quality improved with increased implantation time. In nude mice, neocartilage resembled native sheep auricular cartilage regardless of the in vitro culture length, with the exception of elastin expression. The DNA quantification was similar in all engineered and native cartilage (p > 0.1). All cartilage engineered in sheep had significantly less GAG than native cartilage (p < 0.02); significantly more GAG was observed with increased implantation time (p < 0.02). In mice, the GAG content was similar to that of native cartilage and became significantly higher with increased in vitro or in vivo durations (p < 0.02). Autologous auricular cartilage was successfully engineered in the subcutaneous environment of an ovine model using expanded chondrocytes seeded on a fibrous collagen scaffold after a 2-week in vitro culture period. C1 [Bichara, David A.; Zhao, Xing; Johnson, Matthew A.; Randolph, Mark A.] Massachusetts Gen Hosp, Plast Surg Res Lab, Boston, MA 02114 USA. [Bichara, David A.; Pomerantseva, Irina; Zhao, Xing; Vacanti, Joseph P.; Randolph, Mark A.; Sundback, Cathryn A.] Harvard Univ, Sch Med, Boston, MA USA. [Pomerantseva, Irina; Zhou, Libin; Kulig, Katherine M.; Tseng, Alan; Kimura, Anya M.; Vacanti, Joseph P.; Sundback, Cathryn A.] Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. [Zhou, Libin] 513 Hosp PLA, Dept Stomatol, Lanzhou, Gansu, Peoples R China. RP Vacanti, JP (reprint author), Massachusetts Gen Hosp, Plast Surg Res Lab, 55 Fruit St, Boston, MA 02114 USA. EM jvacanti@partners.org OI Johnson, Matthew/0000-0002-0264-8498 FU Armed Forces Institute of Regenerative Medicine [W81XWH-08-2-0034]; China Scholarship Council FX This research was sponsored by the Armed Forces Institute of Regenerative Medicine award number W81XWH-08-2-0034. The U.S. Army Medical Research Acquisition Activity, 820 Chandler St., Fort Detrick MD 21702-5014 is the awarding and administering acquisition office. The content of this article does not necessarily reflect the position or the policy of the Government, and no official endorsement should be inferred. Libin Zhou was sponsored by the China Scholarship Council for his study at the Massachusetts General Hospital. The fibrous collagen scaffolds were generously provided by the Kensey Nash Corporation. NR 47 TC 10 Z9 10 U1 0 U2 7 PU MARY ANN LIEBERT, INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1937-3341 EI 1937-335X J9 TISSUE ENG PT A JI Tissue Eng. Part A PD JAN PY 2014 VL 20 IS 1-2 BP 303 EP 312 DI 10.1089/ten.tea.2013.0150 PG 10 WC Cell & Tissue Engineering; Biotechnology & Applied Microbiology; Cell Biology SC Cell Biology; Biotechnology & Applied Microbiology GA AI9TO UT WOS:000337280600028 PM 23980800 ER PT J AU Jofe, S Mack, JW AF Jofe, Steven Mack, Jennifer W. TI Deliberation and the Life Cycle of Informed Consent SO HASTINGS CENTER REPORT LA English DT Article ID I CANCER TRIALS C1 [Jofe, Steven] Univ Penn, Perelman Sch Med, Philadelphia, PA 19104 USA. [Jofe, Steven] Childrens Hosp Philadelphia, Philadelphia, PA USA. [Mack, Jennifer W.] Harvard Univ, Sch Med, Cambridge, MA 02138 USA. [Mack, Jennifer W.] Dana Farber Canc Inst, Boston, MA USA. [Mack, Jennifer W.] Boston Childrens Hosp, Boston, MA USA. RP Jofe, S (reprint author), Univ Penn, Perelman Sch Med, Philadelphia, PA 19104 USA. OI Joffe, Steven/0000-0002-0667-7384 NR 8 TC 0 Z9 0 U1 1 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0093-0334 EI 1552-146X J9 HASTINGS CENT REP JI Hastings Cent. Rep. PD JAN PY 2014 VL 44 IS 1 BP 33 EP 35 DI 10.1002/hast.253 PG 3 WC Ethics; Health Care Sciences & Services; Medical Ethics; Social Sciences, Biomedical SC Social Sciences - Other Topics; Health Care Sciences & Services; Medical Ethics; Biomedical Social Sciences GA AF3JN UT WOS:000334608300014 ER PT J AU Nicholas, CR McLaren, DG Gawrysiak, MJ Rogers, BP Dougherty, JH Nash, MR AF Nicholas, Christopher R. McLaren, Donald G. Gawrysiak, Michael J. Rogers, Baxter P. Dougherty, John H. Nash, Michael R. TI Functional neuroimaging of personally-relevant stimuli in a paediatric case of impaired awareness SO BRAIN INJURY LA English DT Article DE Brain imaging; brain injury; cognition; consciousness; paediatric; neurology; self-referential ID PERSISTENT VEGETATIVE STATE; MINIMALLY CONSCIOUS STATE; OWN NAME; BRAIN; SELF; LANGUAGE; FMRI; CHILDREN; PATIENT; SCALE AB Background: Functional neuroimaging studies have observed preserved neural activation to personally relevant stimuli in patients within the disorders of consciousness (DOC) spectrum. As the majority of studies have focused on adult DOC patients, little is known about preserved activation in the developing brain of children with impaired consciousness. Case study: The aim of this study is to use fMRI to measure preserved neural activation to personally relevant stimuli (subject's own name and familiar voice) in a paediatric patient who sustained a traumatic brain injury and anoxic-ischaemia following a motor vehicle accident at 18 months of age rendering her probable for minimally conscious state. Contrasts revealed activation in the right middle frontal gyrus when hearing the subject's own name and the anterior supramarginal gyrus when hearing a familiar voice. Conclusion: This study provides preliminary support for fMRI as a method to measure preserved cognitive functioning in paediatric DOC patients. C1 [Nicholas, Christopher R.] William S Middleton Mem Vet Adm Med Ctr, GRECC, Madison, WI USA. [Nicholas, Christopher R.] Univ Wisconsin, Sch Med & Publ Hlth, Madison, WI 53792 USA. [McLaren, Donald G.] ENRM VA Med Ctr, GRECC, Bedford, MA USA. [McLaren, Donald G.] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. [McLaren, Donald G.] Harvard Univ, Sch Med, Boston, MA USA. [Gawrysiak, Michael J.] Philadelphia Vet Med Ctr, MIRECC, Philadelphia, PA USA. [Rogers, Baxter P.] Vanderbilt Univ, Inst Imaging Sci, Nashville, TN 37235 USA. [Rogers, Baxter P.] Vanderbilt Univ Sch Med, Dept Radiol & Radiol Sci, Nashville, TN USA. [Dougherty, John H.] Univ Tennessee, Med Ctr, Cole Neurosci Ctr, Knoxville, TN USA. [Nash, Michael R.] Univ Tennessee, Dept Psychol, Knoxville, TN 37996 USA. RP Nicholas, CR (reprint author), Univ Wisconsin, Alzheimers Dis Res Ctr, 600 Highland Dr, Madison, WI 53792 USA. EM psynich@gmail.com OI McLaren, Donald/0000-0002-0566-4610 FU Cole Neuroscience Gift fund FX This research would not have been possible without the generous financial support of the Cole Neuroscience Gift fund. The authors report no conflicts of interest. NR 23 TC 5 Z9 5 U1 0 U2 2 PU INFORMA HEALTHCARE PI LONDON PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND SN 0269-9052 EI 1362-301X J9 BRAIN INJURY JI Brain Inj. PY 2014 VL 28 IS 8 BP 1135 EP 1138 DI 10.3109/02699052.2014.890745 PG 4 WC Neurosciences; Rehabilitation SC Neurosciences & Neurology; Rehabilitation GA AI6KP UT WOS:000336983200017 PM 24655307 ER PT J AU Kataoka, A Tan, T Zeng, X Garcia, M Seybolt, M Sullivan, S Guerrero, J Handschumacher, M Levine, R Hung, J AF Kataoka, Akihisa Tan, Timothy Zeng, Xin Garcia, Michael Seybolt, Margo Sullivan, Suzanne Guerrero, Jose Handschumacher, Mark Levine, Robert Hung, Judy TI Development and Application of Polymer-Matrix Device to Remodel Left Ventricular - Mitral Valve Apparatus in Ischemic Mitral Regurgitation SO CARDIOLOGY LA English DT Meeting Abstract C1 [Kataoka, Akihisa; Tan, Timothy; Zeng, Xin; Garcia, Michael; Seybolt, Margo; Sullivan, Suzanne; Guerrero, Jose; Handschumacher, Mark; Levine, Robert; Hung, Judy] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0008-6312 EI 1421-9751 J9 CARDIOLOGY JI Cardiology PY 2014 VL 128 IS 2 BP 155 EP 155 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA AI0GB UT WOS:000336523100107 ER PT J AU Morrel, WG Ge, L Ward, A Zhang, ZH Pantoja, J Gulati, S Grossi, EA Ratcliffe, MB AF Morrel, William G. Ge, Liang Ward, Alison Zhang, Zhihong Pantoja, Joe Gulati, Sarthak Grossi, Eugene A. Ratcliffe, Mark B. TI Effect of Mitral Annuloplasty Ring Shape and Size on Leaflet and Myofiber Stress Following Repair of Posterior Leaflet Prolapse: A Patient-Specific Finite-Element Simulation SO CARDIOLOGY LA English DT Meeting Abstract C1 [Morrel, William G.; Ge, Liang; Pantoja, Joe; Ratcliffe, Mark B.] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Ward, Alison; Grossi, Eugene A.] NYU Sch Med, New York, NY USA. [Zhang, Zhihong] San Francisco VA Med Ctr, San Francisco, CA USA. [Gulati, Sarthak] Univ Calif Los Angeles, Los Angeles, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0008-6312 EI 1421-9751 J9 CARDIOLOGY JI Cardiology PY 2014 VL 128 IS 2 BP 161 EP 162 PG 2 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA AI0GB UT WOS:000336523100122 ER PT J AU Tan, T Nunes, MC Handschumacher, M Hung, J AF Tan, Timothy Nunes, Maria C. Handschumacher, Mark Hung, Judy TI Left Atrial Mid Cross Sectional Area and Left Atrial Shape Index: Novel Echocardiographic Measures Which Mechanistically Reflect Risk of Atrial Fibrillation and Stroke SO CARDIOLOGY LA English DT Meeting Abstract C1 [Tan, Timothy; Nunes, Maria C.; Handschumacher, Mark; Hung, Judy] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0008-6312 EI 1421-9751 J9 CARDIOLOGY JI Cardiology PY 2014 VL 128 IS 2 BP 164 EP 164 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA AI0GB UT WOS:000336523100128 ER PT J AU Holland, JP Vasdev, N AF Holland, Jason P. Vasdev, Neil TI Charting the mechanism and reactivity of zirconium oxalate with hydroxamate ligands using density functional theory: implications in new chelate design SO DALTON TRANSACTIONS LA English DT Article ID GENERALIZED GRADIENT APPROXIMATION; EXCHANGE-CORRELATION FUNCTIONALS; EFFECTIVE CORE POTENTIALS; POSITRON-EMISSION-TOMOGRAPHY; COMPACT EFFECTIVE POTENTIALS; EXPONENT BASIS-SETS; CORRELATION-ENERGY; THERMOCHEMICAL KINETICS; MOLECULAR CALCULATIONS; IMMUNO-PET AB The reaction of [Zr-89(C2O4)(4)](4-) with the tris-hydroxamate ligand desferrioxamine B (DFO) provides the basis of radiolabelling biological vectors such as antibodies and proteins with the radionuclide Zr-89 for positron emission tomography imaging. In this work, density functional theory methods were used to investigate the mechanism of reaction from [Zr(C2O4)(4)](4-) to Zr(MeAHA)(4) by ligand substitution with N-methyl acetohydroxamate (MeAHA). Calculations were performed under simulated basic and acidic conditions. Ligand substitution under basic conditions was found to be thermodynamically feasible with an overall calculated change in solvation free energy, Delta G(sol) = -97 kJ mol(-1) using the B3LYP/DGDZVP methodology and a water continuum solvation model. In contrast, an acid-mediated mechanism of ligand substitution was found to be thermodynamically non-feasible. Molecular orbital analysis provides a rationale for the difference in thermodynamic stability between [Zr(C2O4)(4)](4-) and Zr(MeAHA)(4). Overall, the DFT calculations are consistent with observed experimental Zr-89-radiolabelling reactions and suggest that computational methods may prove useful in designing novel chelates for increasing the thermodynamic and kinetic stability of Zr-89-complexes in vivo. C1 [Holland, Jason P.; Vasdev, Neil] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Nucl Med & Mol Imaging,Dept Radiol, Boston, MA 02114 USA. RP Holland, JP (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Nucl Med & Mol Imaging,Dept Radiol, 55 Fruit St,White 427, Boston, MA 02114 USA. EM holland.jason@mgh.harvard.edu; jasonpholland@gmail.com OI Holland, Jason/0000-0002-0066-219X FU Ivan Greguric; Australian National Science and Technology Organisation (ANSTO, Sydney) FX We thank Dr Eszter Boros, Dr T. Lee Collier and David Hill for helpful discussions. We thank Dr Ivan Greguric and the Australian National Science and Technology Organisation (ANSTO, Sydney) for providing financial support (JPH). NR 76 TC 6 Z9 6 U1 4 U2 17 PU ROYAL SOC CHEMISTRY PI CAMBRIDGE PA THOMAS GRAHAM HOUSE, SCIENCE PARK, MILTON RD, CAMBRIDGE CB4 0WF, CAMBS, ENGLAND SN 1477-9226 EI 1477-9234 J9 DALTON T JI Dalton Trans. PY 2014 VL 43 IS 26 BP 9872 EP 9884 DI 10.1039/c4dt00733f PG 13 WC Chemistry, Inorganic & Nuclear SC Chemistry GA AI8DG UT WOS:000337135600010 PM 24722728 ER PT J AU Scognamiglio, G Cantile, M Scala, S Cecere, S Russo, F Collina, F Marra, L Sabbatino, F Botti, G Franco, R AF Scognamiglio, Giosue Cantile, Monica Scala, Stefania Cecere, Sabrina Russo, Federica Collina, Francesca Marra, Laura Sabbatino, Francesco Botti, Gerardo Franco, Renato TI Tissue micro arrays for immunohistochemical detection of inflammatory infiltrates in renal cell carcinoma SO INTERNATIONAL JOURNAL OF CLINICAL AND EXPERIMENTAL MEDICINE LA English DT Letter C1 [Scognamiglio, Giosue; Cantile, Monica; Russo, Federica; Collina, Francesca; Marra, Laura; Botti, Gerardo; Franco, Renato] Ist Nazl Tumori Fdn G Pascale, Pathol Unit, I-80131 Naples, Italy. [Scala, Stefania] Ist Nazl Tumori Fdn G Pascale, Dept Oncol Immunol, I-80131 Naples, Italy. [Cecere, Sabrina] Ist Nazl Tumori Fdn G Pascale, Dept Med Oncol, I-80131 Naples, Italy. [Sabbatino, Francesco] Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. RP Cantile, M (reprint author), Ist Nazl Tumori Fdn G Pascale, Pathol Unit, Via Mariano Semmola, I-80131 Naples, Italy. EM monican-tile@libero.it OI Franco, Renato/0000-0002-8340-3184; Scognamiglio, Giosue/0000-0003-4376-111X NR 5 TC 2 Z9 2 U1 2 U2 3 PU E-CENTURY PUBLISHING CORP PI MADISON PA 40 WHITE OAKS LN, MADISON, WI 53711 USA SN 1940-5901 J9 INT J CLIN EXP MED JI Int. J. Clin. Exp. Med. PY 2014 VL 7 IS 4 BP 1175 EP 1179 PG 5 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA AI3DV UT WOS:000336740600057 PM 24955204 ER PT J AU Sylvia, LG Shesler, LW Peckham, AD Grandin, T Kahn, DA AF Sylvia, Louisa Grandin Shesler, Leah W. Peckham, Andrew D. Grandin, Temple Kahn, David A. TI Adjunctive Deep Touch Pressure for Comorbid Anxiety in Bipolar Disorder: Mediated by Control of Sensory Input? SO JOURNAL OF PSYCHIATRIC PRACTICE LA English DT Article DE deep touch pressure; bipolar disorder; anxiety; comorbidity ID AUTISM SPECTRUM DISORDERS; DEFICIT HYPERACTIVITY DISORDER; OVER-RESPONSIVITY; CHILDREN; PSYCHOSIS; EFFICACY; MASSAGE AB Previous studies have shown that individuals with autism spectrum disorders and attention-deficit/hyperactivity disorder (ADHD) experience sensory over-responsivity (SOR) in which a heightened response is evoked by stimuli in the environment. These individuals also display symptoms of anxiety such as irritability, avoidance, and sweating. Deep touch pressure, a technique in which firm touch is applied to the body either by the self or by a machine, has been shown to improve functioning and reduce symptoms of anxiety in these populations. A patient presenting with bipolar I disorder and comorbid anxiety, ADHD, and dyslexia was taught deep touch pressure strategies to alleviate severe symptoms of sensory over-responsivity and anxiety. The patient reported that the techniques were helpful as they allowed her to cope with potentially overwhelming situations in her environment. Clinician-rated functioning also improved over the course of treatment. This case study suggests that deep touch pressure may be useful in patients with bipolar disorder who have SOR and anxiety as comorbid conditions. C1 [Sylvia, Louisa Grandin; Shesler, Leah W.; Peckham, Andrew D.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Sylvia, Louisa Grandin] Harvard Univ, Sch Med, Cambridge, MA 02138 USA. [Grandin, Temple] Colorado State Univ, Ft Collins, CO 80523 USA. [Kahn, David A.] Columbia Univ Coll Phys & Surg, New York, NY 10032 USA. RP Sylvia, LG (reprint author), Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 33 TC 1 Z9 1 U1 1 U2 8 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1527-4160 EI 1538-1145 J9 J PSYCHIATR PRACT JI J. Psychiatr. Pract. PD JAN PY 2014 VL 20 IS 1 BP 71 EP 77 DI 10.1097/01.pra.0000442942.01479.ce PG 7 WC Psychiatry SC Psychiatry GA AI4AN UT WOS:000336807600011 PM 24419314 ER PT J AU Bauman, WA La Fountaine, MF Spungen, AM AF Bauman, William A. La Fountaine, Michael F. Spungen, Ann M. TI Age-related prevalence of low testosterone in men with spinal cord injury SO JOURNAL OF SPINAL CORD MEDICINE LA English DT Article DE Spinal cord injuries; Testosterone replacement therapy; Paraplegia; Tetraplegia; Aging ID HORMONE-BINDING-GLOBULIN; CARDIOVASCULAR-DISEASE RISK; SERUM TESTOSTERONE; BODY-COMPOSITION; OLDER MEN; PITUITARY; PARAPLEGIA; DEFICIENCY; AXIS; HYPOGONADISM AB Objective: To describe the relationship of advancing age in persons with chronic spinal cord injury (SCI) on the prevalence of low testosterone in men with SCI compared to historical normative data from able-bodied men in the general population. Design: Retrospective, cross-sectional study. Two hundred forty-three healthy, non-ambulatory outpatient men with chronic SCI from age of 21 to 78 years were included in this retrospective analysis. Results: Forty-six percent of men with SCI were identified as having low serum total testosterone concentrations (total testosterone <11.3 nmol/l). The age-related decline in SCI for total serum testosterone concentration was 0.6%/year compared to 0.4%/year in the Massachusetts Male Aging Study. Between the third and eighth decade of life, men with SCI had a 15, 39, 50, 53, 58, and 57% prevalence rate of low serum total testosterone, which is higher than values reported for each decade of life for able-bodied men in the Baltimore Longitudinal Study on Aging. Conclusion: Compared with the general population, low serum total testosterone concentration occurs earlier in life in men with SCI, at a higher prevalence by decade of life, and their age-related decline in circulating total testosterone concentration is greater. Studies of T replacement therapy in men with SCI should assist in determining the possible functional and clinical benefits from reversing low serum total testosterone concentration. C1 [Bauman, William A.; La Fountaine, Michael F.; Spungen, Ann M.] James J Peters Vet Affairs Med Ctr, Natl Ctr Excellence Med Consequences Spinal Cord, Dept Vet Affairs, Rehabil Res & Dev Serv, Bronx, NY USA. [Bauman, William A.; La Fountaine, Michael F.; Spungen, Ann M.] James J Peters VA Med Ctr, Med Serv, Bronx, NY USA. [Bauman, William A.; La Fountaine, Michael F.; Spungen, Ann M.] Mt Sinai Sch Med, Dept Med, New York, NY USA. [Bauman, William A.; Spungen, Ann M.] Mt Sinai Sch Med, Dept Rehabil Med, New York, NY USA. [La Fountaine, Michael F.] Seton Hall Univ, Sch Hlth & Med Sci, Dept Phys Therapy, S Orange, NJ 07079 USA. RP Bauman, WA (reprint author), VA RR&D Natl Ctr Excellence Med Consequences Spin, Bronx, NY 10468 USA. EM william.bauman@va.gov FU Rehabilitation Research & Development (RR& D) Center of Excellence for the Medical Consequences of Spinal Cord Injury [B2648C, B9212C]; Department of Veterans Affairs Rehabilitation Research & Development Service FX The authors thank the James J Peters VA Medical Center, Bronx, NY, and the Department of Veterans Affairs Rehabilitation Research & Development Service for their support. This work was funded by a Rehabilitation Research & Development (RR& D) Center of Excellence for the Medical Consequences of Spinal Cord Injury (# B2648C and B9212C). NR 39 TC 11 Z9 13 U1 1 U2 2 PU MANEY PUBLISHING PI LEEDS PA STE 1C, JOSEPHS WELL, HANOVER WALK, LEEDS LS3 1AB, W YORKS, ENGLAND SN 1079-0268 EI 2045-7723 J9 J SPINAL CORD MED JI J. Spinal Cord. Med. PD JAN PY 2014 VL 37 IS 1 BP 32 EP 39 DI 10.1179/2045772313Y.0000000122 PG 8 WC Clinical Neurology SC Neurosciences & Neurology GA AI8CJ UT WOS:000337132500005 PM 24090163 ER PT J AU Hegde, M Jindal, R Bhushan, A Bale, SS McCarty, WJ Golberg, I Usta, OB Yarmush, ML AF Hegde, Manjunath Jindal, Rohit Bhushan, Abhinav Bale, Shyam Sundhar McCarty, William J. Golberg, Inna Usta, O. Berk Yarmush, Martin L. TI Dynamic interplay of flow and collagen stabilizes primary hepatocytes culture in a microfluidic platform SO LAB ON A CHIP LA English DT Article ID SANDWICH CONFIGURATION; NONPARENCHYMAL CELLS; RAT HEPATOCYTES; LIVER; HEPATOTOXICITY; BIOREACTOR; VIABILITY; SYSTEMS; MODEL; ARRAY AB The creation of stable flow cultures of hepatocytes is highly desirable for the development of platforms for drug toxicity screening, bio-artificial liver support devices, and models for investigating liver physiology and pathophysiology. Given that hepatocytes cultured using the collagen overlay or in 'sandwich' configuration maintain a wide range of differentiated functions, we describe a simple method for adapting this culture configuration within a microfluidic device. The device design consists of a porous membrane sandwiched between two layers of PDMS resulting in a two-chambered device. In the bottom chamber, hepatocytes are cultured in the collagen sandwich configuration, while the top chamber is accessible for flow. We demonstrate that hepatocytes cultured under flow exhibit higher albumin and urea secretions and induce cytochrome P450 1A1 activity in comparison to static cultures. Furthermore, over two weeks, hepatocytes cultured under flow show a well-connected cellular network with bile canaliculi formation, whereas static cultures show formation of gaps in the cellular network that progressively increase over time. Although enhanced functional response of hepatocytes cultured under flow has been observed in multiple prior studies, the exact mechanism for this flow induced effect remains unknown. In our work, we identified that hepatocytes secrete a higher level of collagen in the flow cultures; inhibiting collagen secretion within the flow cultures reduced albumin secretion and restored the appearance of gaps in the cellular network similar to the static cultures. These results demonstrate the importance of the increased collagen secretion by hepatocytes cultured under flow as a mechanism to maintain a well-connected cellular network and a differentiated function. C1 [Hegde, Manjunath; Jindal, Rohit; Bhushan, Abhinav; Bale, Shyam Sundhar; McCarty, William J.; Golberg, Inna; Usta, O. Berk; Yarmush, Martin L.] Harvard Univ, Sch Med, Shriners Hosp Children, Ctr Engn Med,Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Jindal, R (reprint author), Harvard Univ, Sch Med, Shriners Hosp Children, Ctr Engn Med,Massachusetts Gen Hosp, 51 Blossom St, Boston, MA 02114 USA. EM ireis@sbi.org; rjindal@mgh.harvard.edu RI Hegde, Manjunath/M-3038-2014; USTA, O. Berk/A-5818-2008; OI Hegde, Manjunath/0000-0002-5396-2241; USTA, O. Berk/0000-0001-9328-568X; McCarty, William/0000-0002-3671-0616 FU National Institutes of Health (NIH) [5UH2TR000503, K99DK095984, F32DK098905]; Shriner's Hospital for Children; MGH BioMEMS Resource Center in fabricating microdevices FX This work was supported by grants from the National Institutes of Health (NIH)(5UH2TR000503), (K99DK095984 for AB and F32DK098905 for WJM) and the Shriner's Hospital for Children (BU). We thank Dr. Keuye Shen for sharing his expertise in using a laser cutter. We acknowledge support from the MGH BioMEMS Resource Center in fabricating microdevices. The authors have no professional or financial conflicts of interest to disclose. NR 29 TC 19 Z9 19 U1 4 U2 28 PU ROYAL SOC CHEMISTRY PI CAMBRIDGE PA THOMAS GRAHAM HOUSE, SCIENCE PARK, MILTON RD, CAMBRIDGE CB4 0WF, CAMBS, ENGLAND SN 1473-0197 EI 1473-0189 J9 LAB CHIP JI Lab Chip PY 2014 VL 14 IS 12 BP 2033 EP 2039 DI 10.1039/c4lc00071d PG 7 WC Biochemical Research Methods; Chemistry, Multidisciplinary; Nanoscience & Nanotechnology SC Biochemistry & Molecular Biology; Chemistry; Science & Technology - Other Topics GA AI3DG UT WOS:000336738900008 PM 24770663 ER PT S AU Akl, TJ Wilson, MA Ericson, MN Cote, GL AF Akl, Tony J. Wilson, Mark A. Ericson, M. Nance Cote, Gerard L. BE Cote, GL TI Photoplethysmography beyond Perfusion and Oxygenation Monitoring: Pulse Wave Analysis for Hepatic Graft Monitoring SO OPTICAL DIAGNOSTICS AND SENSING XIV: TOWARD POINT-OF-CARE DIAGNOSTICS SE Proceedings of SPIE LA English DT Proceedings Paper CT Conference on Optical Diagnostics and Sensing XIV - Toward Point-of-Care Diagnostics CY FEB 03-06, 2014 CL San Francisco, CA SP SPIE DE Photoplethysmography; Pulse waveform; Pulse analysis; Compliance; Graft monitoring ID LIVER-TRANSPLANTATION; IMPLANTABLE SENSOR; CONTOUR ANALYSIS; DISEASE; MICROCIRCULATION; QUANTIFICATION; ELASTOGRAPHY; FIBROSIS; FINGER AB Photoplethysmography is a technique widely used in monitoring perfusion and blood oxygen saturation based on the amplitude of the pulsatile signal at one or multiple wavelengths. However, the pulsatile signal carries in its waveform a substantial amount of information about the mechanical properties of the tissue and vasculature under investigation that is still yet to be utilized to its full potential. In this work, we present the feasibility of pulse wave analysis for the application of monitoring hepatic implants and diagnosing graft complications. In particular, we demonstrate the utility of computing the slope of the pulse during the diastole phase to assess compliance changes in tissue. This hypothesis was tested in a series of in vitro experiments using a polydimethylsiloxane based phantom mimicking the optical and mechanical properties of the portal vein. The emptying time decreased from 148.1 ms for phantoms with compliance of 12 KPa to 97.5 ms for phantoms with compliance of 61 KPa. These compliance levels mimic those seen for normal and fibrotic hepatic tissue respectively. C1 [Akl, Tony J.; Cote, Gerard L.] Texas A&M Univ, Dept Biomed Engn, College Stn, TX 77843 USA. [Wilson, Mark A.] Univ Pittsburgh, Dept Surg, Pittsburgh, PA USA. [Wilson, Mark A.] VA Pittsburgh Healthcare Syst, Pittsburgh, PA USA. [Ericson, M. Nance] Oak Ridge Natl Lab, Oak Ridge, TN USA. RP Akl, TJ (reprint author), Texas A&M Univ, Dept Biomed Engn, College Stn, TX 77843 USA. RI Ericson, Milton/H-9880-2016 OI Ericson, Milton/0000-0002-6628-4865 FU bioengineering research partnership (BRP); NIH [5R01-GM077150] FX This research was funded by a bioengineering research partnership (BRP) grant from NIH, (#5R01-GM077150). NR 28 TC 0 Z9 0 U1 0 U2 2 PU SPIE-INT SOC OPTICAL ENGINEERING PI BELLINGHAM PA 1000 20TH ST, PO BOX 10, BELLINGHAM, WA 98227-0010 USA SN 0277-786X BN 978-0-8194-9864-9 J9 PROC SPIE PY 2014 VL 8951 AR UNSP 895103 DI 10.1117/12.2039611 PG 6 WC Optics; Radiology, Nuclear Medicine & Medical Imaging SC Optics; Radiology, Nuclear Medicine & Medical Imaging GA BA5JX UT WOS:000336740800002 ER PT J AU Becker, A Roghmann, F Ravi, P Tian, Z Kluth, LA Gandaglia, G Noldus, J Dahlem, R Schlomm, T Graefen, M Karakiewicz, PI Trinh, QD Sun, M AF Becker, Andreas Roghmann, Florian Ravi, Praful Tian, Zhe Kluth, Luis Alexander Gandaglia, Giorgio Noldus, Joachim Dahlem, Roland Schlomm, Thorsten Graefen, Markus Karakiewicz, Pierre I. Quoc-Dien Trinh Sun, Maxine TI Delay in Nephrectomy and Cancer Control Outcomes in Elderly Patients with Small Renal Masses SO UROLOGIA INTERNATIONALIS LA English DT Article DE Renal cell carcinoma; Nephrectomy; Observation; Treatment delay; Survival ID ACTIVE SURVEILLANCE; CELL CARCINOMA; NATURAL-HISTORY; KIDNEY CANCER; TUMORS; INTERVENTION; EPIDEMIOLOGY; MANAGEMENT; SURVIVAL; SURGERY AB Objective: To examine the impact of nephrectonny delay on the survival of patients with small renal masses. Methods: Relying on the Surveillance, Epidemiology, and End Results Medicare-linked database, 6,237 patients with pT1a renal cell carcinoma who underwent radical or partial nephrectomy were identified (1988-2005). Nephrectomy delay was dichotomized as <= 3 vs. >3 months. Uni- and multivariate Cox regression analyses tested the effect of delayed nephrectomy on cancer-specific mortality (CSM). In sub-analyses, various other time from diagnosis to nephrectomy cut-offs were modelled: (a) <= 12 vs. >12 month, (b) <= 2 vs. >2 months, (c)<= 4 vs. >4 months, (d) <= 6 vs. >6 months, (e) <= 12 vs. >12 months or (f) continuously coded. Results: In univariate analyses, nephrectomy delay >3 months was associated with a higher risk of CSM (hazard ratio [HR]: 2.07; 95% confidence interval [Cl]: 1.58-2.72; p < 0.001). However, after multivariate adjustment, a nephrectomy delay >3 months was not significantly associated with a higher risk of CSM (HR: 1.33; 95% Cl: 0.96 1.86; p = 0.09). The lack of a relationship between nephrectomy delay and CSM after multivariate adjustment persisted even in various sub-analyses of other categorizations for nephrectomy delay. Conclusions: In the case of eventual nephrectomy delay among patients with small renal masses, CSM is unaffected. (C) 2014 S. Karger AG, Basel C1 [Becker, Andreas; Roghmann, Florian; Tian, Zhe; Gandaglia, Giorgio; Karakiewicz, Pierre I.; Quoc-Dien Trinh; Sun, Maxine] Univ Montreal, Canc Prognost & Hlth Outcomes Unit, Ctr Hlth, Montreal, PQ H2X 3J4, Canada. [Karakiewicz, Pierre I.] Univ Montreal, Dept Urol, Ctr Hlth, Montreal, PQ H2X 3J4, Canada. [Becker, Andreas; Schlomm, Thorsten; Graefen, Markus] Prostate Canc Ctr Hamburg Eppendorf, Martini Clin, Hamburg, Germany. [Roghmann, Florian; Noldus, Joachim] Ruhr Univ Bochum, Marienhosp, Dept Urol, Herne, Germany. [Dahlem, Roland] Univ Hosp Hamburg Eppendorf, Dept Urol, Hamburg, Germany. [Ravi, Praful] West Middlesex Univ Hosp, London, England. [Kluth, Luis Alexander] Med Univ Vienna, Dept Urol, Vienna, Austria. [Quoc-Dien Trinh] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Surg,Div Urol,Dana Farber Canc Inst, Boston, MA 02115 USA. RP Becker, A (reprint author), Univ Montreal, Canc Prognost & Hlth Outcomes Unit, Hlth Ctr CHUM, 1058 Rue St Denis, Montreal, PQ H2X 3J4, Canada. EM a.becker@uke.de FU University of Montreal Health Centre Urology Specialists; Fonds de la Recherche en Sante du Quebec; University of Montreal Department of Surgery; University of Montreal Health Centre (CHUM) Foundation FX Pierre I. Karakiewicz is partially supported by the University of Montreal Health Centre Urology Specialists, Fonds de la Recherche en Sante du Quebec, the University of Montreal Department of Surgery and the University of Montreal Health Centre (CHUM) Foundation. NR 31 TC 2 Z9 2 U1 2 U2 3 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0042-1138 EI 1423-0399 J9 UROL INT JI Urol.Int. PY 2014 VL 92 IS 4 BP 455 EP 461 DI 10.1159/000356175 PG 7 WC Urology & Nephrology SC Urology & Nephrology GA AI5YU UT WOS:000336947700014 PM 24602994 ER PT S AU Wee, S Dhanak, D Li, HT Armstrong, SA Copeland, RA Sims, R Baylin, SB Liu, XLS Schweizer, L AF Wee, Susan Dhanak, Dash Li, Haitao Armstrong, Scott A. Copeland, Robert A. Sims, Robert Baylin, Stephen B. Liu, Xiaole Shirley Schweizer, Liang GP New York Acad Sci TI Targeting epigenetic regulators for cancer therapy SO ANNALS REPORTS SE Annals of the New York Academy of Sciences LA English DT Article; Book Chapter DE epigenetic regulators; cancer therapy; drug discovery; DOT1L; EZH; MLL ID CHRONIC LYMPHOCYTIC-LEUKEMIA; MLL-REARRANGED LEUKEMIA; CHROMATIN MODIFICATIONS; BINDING MODULES; CELLS; EZH2; METHYLATION; INHIBITION; DOT1L; EPIGENOME AB Human gene expression patterns are controlled and coordinated by the activity of a diverse array of epigenetic regulators, including histone methyltransferases, acetyltransferases, and chromatin remodelers. Deregulation of these epigenetic pathways can lead to genome-wide changes in gene expression, with serious disease consequences. In recent years, research has suggested that cross talk between genomic (i.e., for example, mutations, translocations) and epigenomic factors may drive the etiology of both hematologic malignancies and solid tumors. Current work in translational research seeks to identify epigenetic regulators whose aberrant activity contributes to oncogenesis, including the histone methyltransferases DOT1L and EZH2 and the bromodomain-containing BET family, and to develop drugs that inhibit the aberrant activity of these regulators. Preclinical and clinical studies using small-molecule inhibitors of epigenetic regulators have underscored their value for therapeutic intervention, and these inhibitors can also be used to drive further studies into dissecting the functions of epigenetic factors in normal and cancer cells. C1 [Wee, Susan; Schweizer, Liang] Bristol Myers Squibb Co, Princeton, NJ 08543 USA. [Dhanak, Dash] Janssen Pharmaceut, Spring House, PA USA. [Li, Haitao] Tsinghua Univ, Beijing 100084, Peoples R China. [Armstrong, Scott A.] Mem Sloan Kettering Canc Ctr, Leukemia Ctr, New York, NY 10021 USA. [Copeland, Robert A.] Epizyme Inc, Cambridge, MA USA. [Sims, Robert] Constellat Pharmaceut, Cambridge, MA USA. [Baylin, Stephen B.] Johns Hopkins Univ, Sch Med, Baltimore, MD USA. [Liu, Xiaole Shirley] Dana Farber Canc Inst, Boston, MA 02115 USA. RP Schweizer, L (reprint author), Bristol Myers Squibb Co, Drug Discovery, R&D, POB 4000, Princeton, NJ 08543 USA. EM liang.schweizer@bms.com RI Li, Haitao/B-2668-2012 OI Li, Haitao/0000-0001-6741-293X NR 27 TC 34 Z9 35 U1 2 U2 11 PU BLACKWELL SCIENCE PUBL PI OXFORD PA OSNEY MEAD, OXFORD OX2 0EL, ENGLAND SN 0077-8923 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 2014 VL 1309 BP 30 EP 36 DI 10.1111/nyas.12356 PG 7 WC Medicine, Research & Experimental; Nutrition & Dietetics SC Research & Experimental Medicine; Nutrition & Dietetics GA BA2LN UT WOS:000333646100003 PM 24571255 ER PT S AU Shrestha, A Lee, REC Megeney, LA AF Shrestha, Amit Lee, Robin E. C. Megeney, Lynn A. BE Bozhkov, PV Salvesen, G TI Monitoring the Proteostasis Function of the Saccharomyces cerevisiae Metacaspase Yca1 SO CASPASES, PARACASPASES, AND METACASPASES: METHODS AND PROTOCOLS SE Methods in Molecular Biology LA English DT Article; Book Chapter DE Aggregates; Filtration; Heat stress; Immunoprecipitation; Metacaspase; Proteostasis; Protocols; Vacuole morphology ID PROTEIN DISAGGREGATION; YEAST; HSP104; APOPTOSIS; FAMILIES; SYSTEM; ALTERS; HSP26 AB The functional versatility of metacaspase proteases has been established by reports of their involvement in non-apoptotic cellular processes, in addition to their canonical role in apoptosis/programmed cell death. While the budding yeast metacaspase Yca1 has been well characterized for its role in cell death regulation, more recent examinations suggest that the protease may be involved in key processes that increase survival and fitness. More specifically, examinations suggest that Yca1 is central to maintaining cellular proteostasis as it interacts with major components involved in protein biosynthesis and functions to limit aggregate deposition. Here, we describe the methods utilized to analyze the role Yca1 in proteostasis. C1 [Shrestha, Amit; Megeney, Lynn A.] Ottawa Hosp, Res Inst, Regenerat Med Program, Sprott Ctr Stem Cell Res, Ottawa, ON, Canada. [Shrestha, Amit; Megeney, Lynn A.] Univ Ottawa, Dept Cellular & Mol Med, Ottawa, ON, Canada. [Lee, Robin E. C.] Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA. [Lee, Robin E. C.] Dana Farber Canc Inst, Ctr Canc Syst Biol, Boston, MA 02115 USA. [Lee, Robin E. C.] Harvard Univ, Sch Med, Dept Genet, Boston, MA USA. RP Shrestha, A (reprint author), Ottawa Hosp, Res Inst, Regenerat Med Program, Sprott Ctr Stem Cell Res, Ottawa, ON, Canada. NR 20 TC 0 Z9 0 U1 0 U2 1 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DR, STE 208, TOTOWA, NJ 07512-1165 USA SN 1064-3745 BN 978-1-4939-0357-3; 978-1-4939-0356-6 J9 METHODS MOL BIOL JI Methods Mol. Biol. PY 2014 VL 1133 BP 223 EP 235 DI 10.1007/978-1-4939-0357-3_14 D2 10.1007/978-1-4939-0357-3 PG 13 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA BA2YB UT WOS:000333984900015 PM 24567105 ER PT S AU Finn, NA Kemp, ML AF Finn, Nnenna A. Kemp, Melissa L. BE Nagar, S Argikar, UA Tweedie, DJ TI Systems Biology Approaches to Enzyme Kinetics: Analyzing Network Models of Drug Metabolism SO ENZYME KINETICS IN DRUG METABOLISM: FUNDAMENTALS AND APPLICATIONS SE Methods in Molecular Biology LA English DT Article; Book Chapter DE Doxorubicin; Systems biology; Network model; P-glycoprotein; Sensitivity analysis ID P-GLYCOPROTEIN; REDOX-REGULATION; STATE; CELL; THIOREDOXIN; GLUTATHIONE AB Intracellular drug metabolism involves transport, bioactivation, conjugation, and other biochemical steps. The dynamics of these steps are each dependent on a number of other cellular factors that can ultimately lead to unexpected behavior. In this review, we discuss the confounding processes and coupled reactions within bioactivation networks that require a systems-level perspective in order to fully understand the time-varying behavior. When converting known in vitro characteristics of drug-enzyme interactions into descriptions of cellular systems, features such as substrate availability, cell-to-cell variability, and intracellular redox state deserve special focus. An example of doxorubicin bioactivation is used for discussing points of consideration when constructing and analyzing network models of drug metabolism. C1 [Finn, Nnenna A.] Emory Univ, Dept Med, Div Cardiol, Atlanta, GA 30322 USA. [Finn, Nnenna A.] US Dept Vet Affairs, Atlanta VA Med Ctr, Decatur, GA USA. [Kemp, Melissa L.] Georgia Inst Technol, Wallace H Coulter Dept Biomed Engn, Atlanta, GA 30332 USA. [Kemp, Melissa L.] Emory Univ, Atlanta, GA 30322 USA. RP Finn, NA (reprint author), Emory Univ, Dept Med, Div Cardiol, Atlanta, GA 30322 USA. NR 27 TC 0 Z9 0 U1 0 U2 2 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DR, STE 208, TOTOWA, NJ 07512-1165 USA SN 1064-3745 BN 978-1-62703-757-0; 978-1-62703-758-7 J9 METHODS MOL BIOL JI Methods Mol. Biol. PY 2014 VL 1113 BP 317 EP 334 DI 10.1007/978-1-62703-758-7_15 D2 10.1007/978-1-62703-758-7 PG 18 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Pharmacology & Pharmacy; Toxicology SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy; Toxicology GA BA2LX UT WOS:000333653000017 PM 24523119 ER PT J AU Hook, G Yu, J Toneff, T Kindy, M Hook, V AF Hook, Gregory Yu, Jin Toneff, Thomas Kindy, Mark Hook, Vivian TI Brain Pyroglutamate Amyloid-beta is Produced by Cathepsin B and is Reduced by the Cysteine Protease Inhibitor E64d, Representing a Potential Alzheimer's Disease Therapeutic SO JOURNAL OF ALZHEIMERS DISEASE LA English DT Article DE Pyroglutamate amyloid-beta; cathepsin B; BACE1; A beta PP; protease; transgenic AD mice; inhibitor; cysteine protease; secretion ID REGULATED SECRETORY VESICLES; IMPROVES MEMORY DEFICITS; APP TRANSGENIC MICE; PRECURSOR PROTEIN; WILD-TYPE; A-BETA; MOUSE MODEL; IN-VIVO; CHROMAFFIN CELLS; SELECTIVE INHIBITOR AB Pyroglutamate amyloid-beta peptides (pGlu-A beta) are particularly pernicious forms of amyloid-beta peptides (A beta) present in Alzheimer's disease (AD) brains. pGlu-A beta peptides are N-terminally truncated forms of full-length A beta peptides (flA beta((1-40/42))) in which the N-terminal glutamate is cyclized to pyroglutamate to generate pGlu-A beta((3-40/42)). beta-secretase cleavage of amyloid-beta precursor protein (A beta PP) produces flA beta((1-40/42)), but it is not yet known whether the beta-secretase BACE1 or the alternative beta-secretase cathepsin B (CatB) participate in the production of pGlu-A beta. Therefore, this study examined the effects of gene knockout of these proteases on brain pGlu-A beta levels in transgenic A beta PPLon mice, which express A beta PP isoform 695 and have the wild-type (wt) beta-secretase activity found in most AD patients. Knockout or overexpression of the CatB gene reduced or increased, respectively, pGlu-A beta((3-40/42)), flA beta((1-40/42)), and pGlu-A beta plaque load, but knockout of the BACE1 gene had no effect on those parameters in the transgenic mice. Treatment of A beta PPLon mice with E64d, a cysteine protease inhibitor of CatB, also reduced brain pGlu-A beta((3-42)), flA beta((1-40/42)), and pGlu-A beta plaque load. Treatment of neuronal-like chromaffin cells with CA074Me, an inhibitor of CatB, resulted in reduced levels of pGlu-A beta((3-40)) released from the activity-dependent, regulated secretory pathway. Moreover, CatB knockout and E64d treatment has been previously shown to improve memory deficits in the A beta PPLon mice. These data illustrate the role of CatB in producing pGlu-A beta and flA beta that participate as key factors in the development of AD. The advantages of CatB inhibitors, especially E64d and its derivatives, as alternatives to BACE1 inhibitors in treating AD patients are discussed. C1 [Hook, Gregory] Amer Life Sci Pharmaceut, La Jolla, CA USA. [Yu, Jin; Kindy, Mark] Med Univ S Carolina, Dept Neurosci, Charleston, SC 29425 USA. [Yu, Jin; Kindy, Mark] Ralph H Johnson VA Med Ctr, Charleston, SC USA. [Toneff, Thomas; Hook, Vivian] Univ Calif San Diego, Skaggs Sch Pharm & Pharmaceut Sci, Dept Neurosci, La Jolla, CA 92093 USA. [Toneff, Thomas; Hook, Vivian] Univ Calif San Diego, Skaggs Sch Pharm & Pharmaceut Sci, Dept Pharmacol, La Jolla, CA 92093 USA. RP Hook, V (reprint author), Univ Calif San Diego, Skaggs Sch Pharm & Pharmaceut Sci, 9500 Gilman Dr,MC 0744, La Jolla, CA 92093 USA. EM vhook@ucsd.edu FU NIH [R44AG032784, R01ES016774-02, R21AG042828]; VA Merit Review [1I01RX000331-01]; Alzheimer's Association award FX The authors wish to thank Christoph Peters, MD, of the Albert Ludwig University, Freiburg, Germany for providing the cathepsin B deficient mice and to Steven Jacobsen at AstraZeneca Neuroscience for his critical thinking and insightful comments on the work. This work was supported in part by grants from the NIH, composed of R44AG032784 to American Life Science Pharmaceuticals (ALSP) (GH), R01ES016774-02 (MSK), and R21AG042828 (VH), as well as a VA Merit Review 1I01RX000331-01 (MSK) and an Alzheimer's Association award (VH). G. Hook has equity interest in ALSP. V. Hook is the Chair of ALSP's Scientific Advisory Board and holds equity in ALSP, and the relationship has been disclosed to the Univ. of Calif., San Diego. NR 123 TC 17 Z9 17 U1 0 U2 10 PU IOS PRESS PI AMSTERDAM PA NIEUWE HEMWEG 6B, 1013 BG AMSTERDAM, NETHERLANDS SN 1387-2877 EI 1875-8908 J9 J ALZHEIMERS DIS JI J. Alzheimers Dis. PY 2014 VL 41 IS 1 BP 129 EP 149 DI 10.3233/JAD-131370 PG 21 WC Neurosciences SC Neurosciences & Neurology GA AI5PH UT WOS:000336921000010 PM 24595198 ER PT J AU Harris, CJ Voss, K Murchison, C Ralle, M Frahler, K Carter, R Rhoads, A Lind, B Robinson, E Quinn, JF AF Harris, Christopher J. Voss, Kellen Murchison, Charles Ralle, Martina Frahler, Kate Carter, Raina Rhoads, Allison Lind, Betty Robinson, Emily Quinn, Joseph F. TI Oral Zinc Reduces Amyloid Burden in Tg2576 Mice SO JOURNAL OF ALZHEIMERS DISEASE LA English DT Article DE Alzheimer's disease; amyloid-beta protein; copper; transgenic mice ID TARGETING A-BETA; ALZHEIMERS-DISEASE; TRANSGENIC MICE; PRECURSOR PROTEIN; WILSON-DISEASE; 3XTG-AD MICE; DOUBLE-BLIND; MOUSE MODEL; COPPER; BRAIN AB The aggregation of amyloid-beta in Alzheimer's disease can be affected by free transition metals such as copper and zinc in the brain. Addition of copper and zinc with amyloid acts to increase aggregation and copper additionally promotes the formation of reactive oxygen species. We propose that reduction of brain copper by blocking uptake of copper from the diet is a viable strategy to regulate the formation of insoluble amyloid-beta in the brain of Tg2576 mice. Mice were treated with regimens of zinc acetate, which acts with metallothionein to block copper uptake in the gut, at various times along their lifespan to model prevention and treatment paradigms. We found that the mice tolerated zinc acetate well over the six month course of study. While we did not observe significant changes in cognition and behavior, there was a reduction in insoluble amyloid-beta in the brain. This observation coincided with a reduction in brain copper and interestingly no change in brain zinc. Our findings show that blocking copper uptake from the diet can redistribute copper from the brain and reduce amyloid-beta aggregation. C1 [Quinn, Joseph F.] Portland VA Med Ctr, Dept Neurol, Portland, OR USA. [Quinn, Joseph F.] Portland VA Med Ctr, Parkinsons Dis Res Educ & Clin Care Ctr PADRECC, Portland, OR USA. [Harris, Christopher J.; Voss, Kellen; Murchison, Charles; Frahler, Kate; Carter, Raina; Rhoads, Allison; Lind, Betty; Quinn, Joseph F.] Oregon Hlth & Sci Univ, Dept Neurol, Portland, OR 97201 USA. [Ralle, Martina; Robinson, Emily] Oregon Hlth & Sci Univ, Dept Mol & Med Genet, Portland, OR 97201 USA. RP Quinn, JF (reprint author), Oregon Hlth & Sci Univ, Dept Neurol, CR-131,3181 SW Sam Jackson Pk Rd, Portland, OR 97201 USA. EM quinnj@ohsu.edu FU U.S. Department of Veterans Affairs Merit Review; NIH/NIA [T32AG023477]; NINDS NeuroNext [1U10NS077350, S10RR025512-01] FX This work is supported in part by the U.S. Department of Veterans Affairs Merit Review (JFQ), NIH/NIA T32AG023477 (KV) (P.I. Dr. Henryk Urbanski), NINDS NeuroNext 1U10NS077350 (CM) and S10RR025512-01 (MR). We would also like to acknowledge Nora Gray for her critical reading of the manuscript. NR 43 TC 6 Z9 6 U1 0 U2 4 PU IOS PRESS PI AMSTERDAM PA NIEUWE HEMWEG 6B, 1013 BG AMSTERDAM, NETHERLANDS SN 1387-2877 EI 1875-8908 J9 J ALZHEIMERS DIS JI J. Alzheimers Dis. PY 2014 VL 41 IS 1 BP 179 EP 192 DI 10.3233/JAD-131703 PG 14 WC Neurosciences SC Neurosciences & Neurology GA AI5PH UT WOS:000336921000014 PM 24595193 ER PT J AU Teodorescu, M Xie, AL Sorkness, CA Robbins, J Reeder, S Gong, YS Fedie, JE Sexton, A Miller, B Huard, T Hind, J Bioty, N Peterson, E Kunselman, SJ Chinchilli, VM Soler, X Ramsdell, J Loredo, J Israel, E Eckert, DJ Malhotra, A AF Teodorescu, Mihaela Xie, Ailiang Sorkness, Christine A. Robbins, JoAnne Reeder, Scott Gong, Yuanshen Fedie, Jessica E. Sexton, Ann Miller, Barb Huard, Tiffany Hind, Jaqueline Bioty, Nora Peterson, Emily Kunselman, Susan J. Chinchilli, Vernon M. Soler, Xavier Ramsdell, Joe Loredo, Jose Israel, Elliott Eckert, Danny J. Malhotra, Atul TI Effects of Inhaled Fluticasone on Upper Airway during Sleep and Wakefulness in Asthma: A Pilot Study SO JOURNAL OF CLINICAL SLEEP MEDICINE LA English DT Article DE Asthma; lung; inhaled corticosteroid; genioglossus; sleep apnea; obstructive ID OF-LIFE QUESTIONNAIRE; WATER-FAT SEPARATION; DAYTIME SLEEPINESS; LUNG-VOLUME; APNEA; IDEAL; PRESSURE; AGE; COLLAPSIBILITY; POPULATION AB Study Objective: Obstructive sleep apnea is prevalent among people with asthma, but underlying mechanisms remain unknown. Inhaled corticosteroids may contribute. We tested the effects of orally inhaled fluticasone propionate (FP) on upper airway (UAW) during sleep and wakefulness. Study design: 16-week single-arm study. Participants: 18 (14 females, mean [+/- SD] age 26 +/- 6 years) corticosteroid-naive subjects with mild asthma (FEV1 89 +/- 8% predicted). Interventions: High dose (1,760 mcg/day) inhaled FP. Measurements: (1) UAW collapsibility (passive critical closing pressure [Pcrit]); (2) tongue strength (maximum isometric pressure-Pmax, in KPa) and endurance-time (in seconds) able to maintain 50% Pmax across 3 trials (Ttot)-at anterior and posterior locations; (3) fat fraction and volume around UAW, measured by magnetic resonance imaging in three subjects. Results: Pcrit overall improved (became more negative) (mean +/- SE) (-8.2 +/- 1.1 vs. -12.2 +/- 2.2 cm H2O, p = 0.04); the response was dependent upon baseline characteristics, with older, male gender, and worse asthma control predicting Pcrit deterioration (less negative). Overall, Pmax increased (anterior p = 0.02; posterior p = 0.002), but Ttot generally subsided (anterior p = 0.0007; posterior p = 0.06), unrelated to Pcrit response. In subjects studied with MRI, fat fraction and volume increased by 20.6% and 15.4%, respectively, without Pcrit changes, while asthma control appeared improved. Conclusions: In this study of young, predominantly female, otherwise healthy subjects with well-controlled asthma and stiff upper airways, 16-week high dose FP treatment elicited Pcrit changes which may be dependent upon baseline characteristics, and determined by synchronous and reciprocally counteracting local and lower airway effects. The long-term implications of these changes on sleep disordered breathing severity remain to be determined. C1 [Teodorescu, Mihaela] William S Middleton Mem Vet Adm Med Ctr, Med Serv, James B Skatrud Pulm Sleep Res Lab, Madison, WI USA. [Teodorescu, Mihaela; Sorkness, Christine A.; Robbins, JoAnne; Sexton, Ann; Miller, Barb; Huard, Tiffany; Hind, Jaqueline] Univ Wisconsin, Sch Med & Publ Hlth, Dept Med, Madison, WI 53792 USA. [Teodorescu, Mihaela] Univ Wisconsin, Sch Med & Publ Hlth, Ctr Sleep Med & Sleep Res Wisconsin Sleep, Madison, WI 53792 USA. [Xie, Ailiang; Gong, Yuanshen; Fedie, Jessica E.] Univ Wisconsin, Sch Med & Publ Hlth, Madison, WI 53792 USA. [Sorkness, Christine A.] Univ Wisconsin, Sch Pharm, Madison, WI 53792 USA. [Robbins, JoAnne; Hind, Jaqueline] William S Middleton Mem Vet Adm Med Ctr, GRECC, Madison, WI USA. [Reeder, Scott] Univ Wisconsin, Sch Med & Publ Hlth, Dept Radiol, Madison, WI 53792 USA. [Reeder, Scott] Univ Wisconsin, Sch Med & Publ Hlth, Dept Med Phys, Madison, WI 53792 USA. [Reeder, Scott] Univ Wisconsin, Sch Med & Publ Hlth, Dept Biomed Engn, Madison, WI 53792 USA. [Bioty, Nora; Peterson, Emily; Kunselman, Susan J.; Chinchilli, Vernon M.] Penn State Univ, Coll Med, Hershey, PA USA. [Soler, Xavier; Ramsdell, Joe; Loredo, Jose; Malhotra, Atul] Univ Calif San Diego, Dept Med, San Diego, CA 92103 USA. [Israel, Elliott; Eckert, Danny J.; Malhotra, Atul] Harvard Univ, Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. [Eckert, Danny J.] Neurosci Res Australia, Sydney, NSW, Australia. RP Teodorescu, M (reprint author), Univ Wisconsin, Sch Med & Publ Hlth, K4-910 CSC 9988,600 Highland Ave, Madison, WI 53792 USA. EM mt3@medicine.wisc.edu RI Eckert, Danny/A-6145-2012; OI Eckert, Danny/0000-0003-3503-2363; Reeder, Scott/0000-0003-4728-8171 FU NIH-NHLBI Asthma Clinical Research Network, University of Wisconsin Clinical Skills Development Core [1 U10 HL074212-01]; Clinical and Translational Science Award (CTSA) through NIH/NCRR [UL1RR025011, UL1TR000427]; William S. Middleton Memorial VA Hospital, Madison FX This was not an industry supported study. This work was performed at the University of Wisconsin and William S. Middleton Memorial VA Hospital, Madison, Wisconsin. This work was funded by the 1 U10 HL074212-01 NIH-NHLBI Asthma Clinical Research Network, University of Wisconsin Clinical Skills Development Core; the Clinical and Translational Science Award (CTSA) program, formerly through NIH/NCRR UL1RR025011, and now through NIH/NCATS UL1TR000427; additional resources from the William S. Middleton Memorial VA Hospital, Madison. The content of this article is solely the responsibility of the authors and does not represent the views of the Department of Veterans Affairs, NIH or the United States Government. The authors have indicated no financial conflicts of interest. NR 59 TC 6 Z9 6 U1 1 U2 3 PU AMER ACAD SLEEP MEDICINE PI WESTCHESTER PA ONE WESTBROOK CORPORATE CTR, STE 920, WESTCHESTER, IL 60154 USA SN 1550-9389 EI 1550-9397 J9 J CLIN SLEEP MED JI J. Clin. Sleep Med. PY 2014 VL 10 IS 2 BP 183 EP + DI 10.5664/jcsm.3450 PG 15 WC Clinical Neurology SC Neurosciences & Neurology GA AH9VY UT WOS:000336494300010 PM 24533002 ER PT J AU Quan, SF Budhiraja, R Clarke, DP Goodwin, JL Gottlieb, DJ Nichols, DA Simon, RD Smith, TW Walsh, JK Kushida, CA Phillips, B AF Quan, Stuart F. Budhiraja, Rohit Clarke, Denise P. Goodwin, James L. Gottlieb, Daniel J. Nichols, Deborah A. Simon, Richard D. Smith, Terry W. Walsh, James K. Kushida, Clete A. Phillips, Barbara TI You Still Need More than CPAP for OSA Patients to Lose Weight SO JOURNAL OF CLINICAL SLEEP MEDICINE LA English DT Letter ID POSITIVE AIRWAY PRESSURE; OBSTRUCTIVE SLEEP-APNEA C1 [Quan, Stuart F.; Clarke, Denise P.; Gottlieb, Daniel J.] Brigham & Womens Hosp, Div Sleep Med, Boston, MA 02115 USA. [Quan, Stuart F.; Clarke, Denise P.; Gottlieb, Daniel J.] Harvard Univ, Sch Med, Boston, MA USA. [Quan, Stuart F.; Budhiraja, Rohit; Goodwin, James L.; Smith, Terry W.] Univ Arizona, Arizona Resp Ctr, Tucson, AZ USA. [Nichols, Deborah A.; Kushida, Clete A.] Stanford Univ, Stanford, CA 94305 USA. [Simon, Richard D.] Providence St Mary Med Ctr, Walla Walla, WA USA. [Walsh, James K.] St Lukes Hosp, Chesterfield, MO USA. [Gottlieb, Daniel J.] VA Boston Healthcare Syst, Boston, MA USA. [Phillips, Barbara] Univ Kentucky, Coll Med, Div Pulm Crit Care & Sleep Med, Lexington, KY USA. RP Quan, SF (reprint author), Harvard Univ, Sch Med, Div Sleep Med, 401 Pk Dr,2nd Floor East, Boston, MA 02215 USA. EM Stuart_Quan@hms.harvard.edu NR 10 TC 0 Z9 0 U1 0 U2 1 PU AMER ACAD SLEEP MEDICINE PI WESTCHESTER PA ONE WESTBROOK CORPORATE CTR, STE 920, WESTCHESTER, IL 60154 USA SN 1550-9389 EI 1550-9397 J9 J CLIN SLEEP MED JI J. Clin. Sleep Med. PY 2014 VL 10 IS 3 BP 349 EP 349 DI 10.5664/jcsm.3552 PG 1 WC Clinical Neurology SC Neurosciences & Neurology GA AH9WB UT WOS:000336494700019 PM 24634638 ER PT J AU Geary, K Keller, A Knaub, L Reusch, J AF Geary, K. Keller, A. Knaub, L. Reusch, J. TI IMPAIRED MITOCHONDRIAL DYNAMICS IN DIABETIC VASCULATURE SO JOURNAL OF INVESTIGATIVE MEDICINE LA English DT Meeting Abstract CT Western Regional Meeting of the American-Federation-for-Medical-Research CY JAN 23-25, 2014 CL Carmel, CA SP Amer Federat Med Res C1 [Geary, K.; Keller, A.; Knaub, L.; Reusch, J.] Univ Colorado, Aurora, CO USA. [Geary, K.; Keller, A.; Knaub, L.; Reusch, J.] Denver VA Med Ctr, Denver, CO USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1081-5589 EI 1708-8267 J9 J INVEST MED JI J. Invest. Med. PD JAN PY 2014 VL 62 IS 1 MA 14 BP 147 EP 148 PG 2 WC Medicine, General & Internal; Medicine, Research & Experimental SC General & Internal Medicine; Research & Experimental Medicine GA AH7AP UT WOS:000336284900027 ER PT J AU Ballon-Landa, E Bergman, J Lorenz, KA Saucedo, J Saigal, C Bennett, CJ Litwin, MS AF Ballon-Landa, E. Bergman, J. Lorenz, K. A. Saucedo, J. Saigal, C. Bennett, C. J. Litwin, M. S. TI COMMUNITY-PARTNERED COLLABORATION TO BUILD AN INTEGRATED PALLIATIVE CARE CLINIC: THE VIEW FROM UROLOGY SO JOURNAL OF INVESTIGATIVE MEDICINE LA English DT Meeting Abstract CT Western Regional Meeting of the American-Federation-for-Medical-Research CY JAN 23-25, 2014 CL Carmel, CA SP Amer Federat Med Res C1 [Ballon-Landa, E.] UC Irvine Sch Med, Irvine, CA USA. [Bergman, J.; Saucedo, J.; Saigal, C.; Bennett, C. J.; Litwin, M. S.] Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90095 USA. [Bergman, J.; Lorenz, K. A.; Saigal, C.; Bennett, C. J.] VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. [Lorenz, K. A.; Saigal, C.] RAND Corp, Santa Monica, CA USA. [Ballon-Landa, E.; Litwin, M. S.] Univ Calif Los Angeles, Fielding Sch Publ Hlth, Los Angeles, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1081-5589 EI 1708-8267 J9 J INVEST MED JI J. Invest. Med. PD JAN PY 2014 VL 62 IS 1 MA 148 BP 188 EP 188 PG 1 WC Medicine, General & Internal; Medicine, Research & Experimental SC General & Internal Medicine; Research & Experimental Medicine GA AH7AP UT WOS:000336284900160 ER PT J AU Utzschneider, KM Largajolli, A Bertoldo, A Leonetti, D McNeely, M Fujimoto, W Cobelli, C Kahn, SE Boyko, E AF Utzschneider, K. M. Largajolli, A. Bertoldo, A. Leonetti, D. McNeely, M. Fujimoto, W. Cobelli, C. Kahn, S. E. Boyko, E. TI OGTT MODELED BETA-CELL FUNCTION MEASURES PREDICT INCIDENT DIABETES SO JOURNAL OF INVESTIGATIVE MEDICINE LA English DT Meeting Abstract CT Western Regional Meeting of the American-Federation-for-Medical-Research CY JAN 23-25, 2014 CL Carmel, CA SP Amer Federat Med Res C1 [Utzschneider, K. M.; Kahn, S. E.; Boyko, E.] VA Puget Sound Hlth Care Syst, Seattle, WA USA. [Utzschneider, K. M.; Leonetti, D.; McNeely, M.; Fujimoto, W.; Kahn, S. E.; Boyko, E.] Univ Washington, Seattle, WA 98195 USA. [Largajolli, A.; Bertoldo, A.; Cobelli, C.] Univ Padua, Padua, Italy. NR 0 TC 0 Z9 0 U1 2 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1081-5589 EI 1708-8267 J9 J INVEST MED JI J. Invest. Med. PD JAN PY 2014 VL 62 IS 1 MA 201 BP 203 EP 203 PG 1 WC Medicine, General & Internal; Medicine, Research & Experimental SC General & Internal Medicine; Research & Experimental Medicine GA AH7AP UT WOS:000336284900211 ER PT J AU Tashjian, VC Kaiser, W Spiegel, B AF Tashjian, V. C. Kaiser, W. Spiegel, B. TI ANALYSIS OF ABDOMINAL ACOUSTIC AND MOTOR PROFILES OF PATIENTS WITH POSTOPERATIVE ILEUS USING THE NOVEL ABSTATS MONITORING SYSTEM SO JOURNAL OF INVESTIGATIVE MEDICINE LA English DT Meeting Abstract CT Western Regional Meeting of the American-Federation-for-Medical-Research CY JAN 23-25, 2014 CL Carmel, CA SP Amer Federat Med Res C1 [Tashjian, V. C.; Spiegel, B.] Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90095 USA. [Spiegel, B.] VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. [Kaiser, W.; Spiegel, B.] UCLA VA, Los Angeles, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1081-5589 EI 1708-8267 J9 J INVEST MED JI J. Invest. Med. PD JAN PY 2014 VL 62 IS 1 MA 212 BP 207 EP 207 PG 1 WC Medicine, General & Internal; Medicine, Research & Experimental SC General & Internal Medicine; Research & Experimental Medicine GA AH7AP UT WOS:000336284900222 ER PT J AU Bayona, E Keller, T Clavijo, R Shelton, J Bergman, J Bennett, CJ AF Bayona, E. Keller, T. Clavijo, R. Shelton, J. Bergman, J. Bennett, C. J. TI THE USE OF REMOTE ACCESS CLINICS TO TREAT AND INFORM MEN WITH SEXUAL DYSFUNCTION SO JOURNAL OF INVESTIGATIVE MEDICINE LA English DT Meeting Abstract CT Western Regional Meeting of the American-Federation-for-Medical-Research CY JAN 23-25, 2014 CL Carmel, CA SP Amer Federat Med Res C1 [Bayona, E.; Clavijo, R.; Shelton, J.; Bergman, J.; Bennett, C. J.] Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90095 USA. [Keller, T.; Clavijo, R.; Shelton, J.; Bergman, J.; Bennett, C. J.] Greater Los Angeles VA Med Ctr, Los Angeles, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1081-5589 EI 1708-8267 J9 J INVEST MED JI J. Invest. Med. PD JAN PY 2014 VL 62 IS 1 MA 278 BP 226 EP 226 PG 1 WC Medicine, General & Internal; Medicine, Research & Experimental SC General & Internal Medicine; Research & Experimental Medicine GA AH7AP UT WOS:000336284900288 ER PT J AU Cooper, LA Page, ST Amory, JK Anawalt, BD Matsumoto, AM AF Cooper, L. A. Page, S. T. Amory, J. K. Anawalt, B. D. Matsumoto, A. M. TI BODY MASS INDEX HAS A GREATER INFLUENCE THAN AGING ON SERUM SHBG AND TOTAL TESTOSTERONE IN MEN: IMPLICATIONS FOR THE BIOCHEMICAL DIAGNOSIS OF HYPOGONADISM IN OLDER OBESE MEN SO JOURNAL OF INVESTIGATIVE MEDICINE LA English DT Meeting Abstract CT Western Regional Meeting of the American-Federation-for-Medical-Research CY JAN 23-25, 2014 CL Carmel, CA SP Amer Federat Med Res C1 [Cooper, L. A.; Page, S. T.; Amory, J. K.; Anawalt, B. D.; Matsumoto, A. M.] Univ Washington, Seattle, WA 98195 USA. [Cooper, L. A.; Matsumoto, A. M.] Vet Affairs Puget Sound Hlth Care Syst, Seattle, WA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1081-5589 EI 1708-8267 J9 J INVEST MED JI J. Invest. Med. PD JAN PY 2014 VL 62 IS 1 MA 354 BP 249 EP 249 PG 1 WC Medicine, General & Internal; Medicine, Research & Experimental SC General & Internal Medicine; Research & Experimental Medicine GA AH7AP UT WOS:000336284900364 ER PT J AU Gray, AM Banks, WA AF Gray, A. M. Banks, W. A. TI MECHANISMS OF INFLAMMATION IN BLOOD-BRAIN BARRIER DISRUPTION SO JOURNAL OF INVESTIGATIVE MEDICINE LA English DT Meeting Abstract CT Western Regional Meeting of the American-Federation-for-Medical-Research CY JAN 23-25, 2014 CL Carmel, CA SP Amer Federat Med Res C1 [Gray, A. M.; Banks, W. A.] Univ Washington, Sch Med, Seattle, WA USA. [Gray, A. M.; Banks, W. A.] Vet Affairs Puget Sound Hlth Care Syst, Seattle, WA USA. NR 0 TC 0 Z9 0 U1 2 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1081-5589 EI 1708-8267 J9 J INVEST MED JI J. Invest. Med. PD JAN PY 2014 VL 62 IS 1 MA 469 BP 283 EP 284 PG 2 WC Medicine, General & Internal; Medicine, Research & Experimental SC General & Internal Medicine; Research & Experimental Medicine GA AH7AP UT WOS:000336284900479 ER PT J AU Falcone, JA Salameh, TS Banks, WA AF Falcone, J. A. Salameh, T. S. Banks, W. A. TI INTRANASAL ADMINISTRATION AS A ROUTE FOR DRUG DELIVERY TO THE BRAIN: EVIDENCE FOR A UNIQUE PATHWAY FOR ALBUMIN SO JOURNAL OF INVESTIGATIVE MEDICINE LA English DT Meeting Abstract CT Western Regional Meeting of the American-Federation-for-Medical-Research CY JAN 23-25, 2014 CL Carmel, CA SP Amer Federat Med Res C1 [Salameh, T. S.; Banks, W. A.] VA Puget Sound, Seattle, WA USA. [Falcone, J. A.; Salameh, T. S.; Banks, W. A.] Univ Washington, Sch Med, Seattle, WA USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1081-5589 EI 1708-8267 J9 J INVEST MED JI J. Invest. Med. PD JAN PY 2014 VL 62 IS 1 MA 471 BP 284 EP 284 PG 1 WC Medicine, General & Internal; Medicine, Research & Experimental SC General & Internal Medicine; Research & Experimental Medicine GA AH7AP UT WOS:000336284900481 ER PT J AU Fischer, BL Hoyt, WT Maucieri, L Kind, AJ Gunter-Hunt, G Swader, TC Gangnon, RE Gleason, CE AF Fischer, Barbara L. Hoyt, William T. Maucieri, Lawrence Kind, Amy J. Gunter-Hunt, Gail Swader, Teresa Chervenka Gangnon, Ronald E. Gleason, Carey E. TI Performance-based assessment of falls risk in older veterans with executive dysfunction SO JOURNAL OF REHABILITATION RESEARCH AND DEVELOPMENT LA English DT Article DE American Geriatrics Society falls-risk guidelines; cognitive impairment; executive function; falls; falls-risk identification; falls prevention; older adults; physical therapy; Timed Up and Go test; veterans ID COGNITIVE IMPAIRMENT; NORMATIVE DATA; GO TEST; GAIT; ATTENTION; AGE; VALIDATION; EDUCATION; MOBILITY; ADULTS AB Falling is a serious hazard for older veterans that may lead to severe injury, loss of independence, and death. While the American Geriatrics Society (AGS) provides guidelines to screen individuals at risk for falls, the guidelines may be less successful with specific subgroups of patients. In a veteran sample, we examined whether the Timed Up and Go (TUG) test, including a modified version, the TUG-Cognition, effectively detected potential fallers whose risk was associated with cognitive deficits. Specifically, we sought to determine whether TUG tasks and AGS criteria were differentially associated with executive dysfunction, whether the TUG tasks identified potential fallers outside of those recognized by AGS criteria, and whether these tasks distinguished groups of fallers. Participants included 120 mostly male patients referred to the Memory Assessment Clinic because of cognitive impairment. TUG-Cognition scores were strongly associated with executive dysfunction and differed systematically between fallers grouped by number of falls. These findings suggest that the TUG-Cognition shows promise in identifying fallers whose risk is related to or compounded by cognitive impairment. Future research should study the predictive validity of these measures by following patients prospectively. C1 [Fischer, Barbara L.; Kind, Amy J.; Gunter-Hunt, Gail; Swader, Teresa Chervenka; Gleason, Carey E.] William S Middleton Mem Vet Adm Med Ctr, Geriatr Res Educ & Clin Ctr, Madison, WI USA. [Hoyt, William T.] Univ Wisconsin, Dept Counseling Psychol, Madison, WI USA. [Maucieri, Lawrence] Governors State Univ, Dept Psychol & Counseling, University Pk, PA USA. [Kind, Amy J.; Gleason, Carey E.] Univ Wisconsin, Dept Med, Sch Med & Publ Hlth, Madison, WI USA. [Gangnon, Ronald E.] Univ Wisconsin, Dept Biostat, Madison, WI USA. [Gangnon, Ronald E.] Univ Wisconsin, Dept Med Informat & Populat Hlth Sci, Madison, WI USA. RP Fischer, BL (reprint author), Wm S Middleton Mem VA Hosp, GRECC, 2500 Overlook Terrace, Madison, WI 53705 USA. EM Barbara.fischer@va.gov FU Wisconsin Alzheimer Disease Research Center; VA GRECC Advanced Fellowship FX Dr. Gleason's time was supported by the Wisconsin Alzheimer Disease Research Center. Dr. Fischer's time was supported by a VA GRECC Advanced Fellowship. NR 29 TC 1 Z9 1 U1 3 U2 11 PU JOURNAL REHAB RES & DEV PI BALTIMORE PA DEPT OF VETERANS AFFAIRS REHABIL RES & DEVELOP CTR 103 SOUTH GAY STREET, BALTIMORE, MD 21202-4051 USA SN 0748-7711 EI 1938-1352 J9 J REHABIL RES DEV JI J. Rehabil. Res. Dev. PY 2014 VL 51 IS 2 BP 263 EP 274 DI 10.1682/JRRD.2013.03.0075 PG 12 WC Rehabilitation SC Rehabilitation GA AI3ZM UT WOS:000336804700011 PM 24933724 ER PT J AU Shorkey, CT Uebel, M AF Shorkey, Clayton T. Uebel, Michael TI History and Development of Instructional Technology and Media in Social Work Education SO JOURNAL OF SOCIAL WORK EDUCATION LA English DT Article ID TELEVISION; TAPE; INTERVIEWS; CLASSROOM; STUDENTS; RECALL AB Since the mid-20th century, instructional technologies and educational media in social work education have undergone significant development with the goals of improving learning and performance and enhancing access. This growth has been marked by technical advances in hardware and by innovations in media, or so-called soft formats. Current distance education and Web-based instructional programs allow for the enrichment of onsite instructional activities as well as open possibilities for the ever-expanding outreach of social work educational programs. The article describes the evolution of instructional technology and media in social work and reviews the historical contributions of 8 pioneering schools. C1 [Shorkey, Clayton T.] Univ Texas Austin, Austin, TX 78712 USA. [Uebel, Michael] US Dept Vet Affairs, Cent Texas Vet Hlth Care Syst, Washington, DC USA. RP Shorkey, CT (reprint author), Univ Texas Austin, Sch Social Work, 1 Univ Stn D3500, Austin, TX 78712 USA. EM cshorkey@mail.utexas.edu NR 100 TC 2 Z9 2 U1 4 U2 15 PU ROUTLEDGE JOURNALS, TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXFORDSHIRE, ENGLAND SN 1043-7797 EI 2163-5811 J9 J SOC WORK EDUC JI J. Soc. Work Educ. PY 2014 VL 50 IS 2 BP 247 EP 261 DI 10.1080/10437797.2014.885248 PG 15 WC Education & Educational Research; Social Work SC Education & Educational Research; Social Work GA AI2JV UT WOS:000336684800005 ER PT J AU Sally, MB Ewing, T Crutchfield, M Patel, MS Raza, S De La Cruz, S Zatarain, J Malinoski, DJ AF Sally, Mitchell B. Ewing, Tyler Crutchfield, Megan Patel, Madhukar S. Raza, Shariq De La Cruz, Salvador Zatarain, John Malinoski, Darren Jay CA United Network Organ Sharing UNOS TI Determining optimal threshold for glucose control in organ donors after neurologic determination of death: A United Network for Organ Sharing Region 5 Donor Management Goals Workgroup prospective analysis SO JOURNAL OF TRAUMA AND ACUTE CARE SURGERY LA English DT Article; Proceedings Paper CT 72nd Annual Meeting of the American-Association-for-the-Surgery-of-Trauma CY SEP 18-23, 2013 CL San Francisco, CA SP Amer Assoc Surg Trauma DE Donor management goals; hyperglycemia; transplant graft outcomes ID CRITICALLY-ILL PATIENTS; INTENSIVE INSULIN THERAPY; GLYCEMIC CONTROL; BRAIN-DEATH; CARE-UNIT; HYPERGLYCEMIA; NUMBER; MORTALITY; IMPACT AB BACKGROUND: The appropriate level of glucose control in organ donors after neurologic determination of death (DNDD) remains uncertain. We hypothesized that a glucose target of 180 mg/dL would be appropriate for optimizing organ transplantation rates and outcomes. METHODS: Demographic, critical care, organ transplantation, and graft outcome data were prospectively collected on all DNDDs in United Network for Organ Sharing (UNOS) Region 5 from 2010 to 2012. Glucose levels were assessed at four time points in the organ donation process. The primary outcome measure was having four or more organs transplanted per donor (OTPD). Univariate analyses were conducted to determine the relationship between glucose levels and OTPD, organ transplantation rates, and graft function. Multivariate analyses were performed to determine independent predictors of four or more OTPDs. Glucose levels were analyzed at the following cutoff points: 150 or less, 180, and 200 mg/dL. Results with a p < 0.05 are listed. RESULTS: A total of 1,611 DNDDs had a mean (SD) age of 38 (17) years and 3.4 (1.7) OTPDs. Forty-one percent had four or more OTPDs. Glucose levels of 150 mg/dL or less were not associated with differences in organ use. Levels of 180 mg/dL or less were associated with more OTPDs (3.5 vs. 3.2), a higher rate of four or more OTPDs (42% vs. 34%), and more heart (34% vs. 28%), pancreas (18% vs. 11%), and kidney (85% vs. 81%) use. Levels of 200 mg/dL or less revealed similar results. However, only a level of 180 mg/dL or less was an independent predictor of four or more OTPDs (odds ratio, 1.4). All three levels were associated with higher kidney graft survival after a mean (SD) of 10 (6.0) months of follow-up (97% vs. 95%). CONCLUSION: Hyperglycemia is common in DNDDs and is associated with lower organ transplantation rates and worse graft outcomes. Targeting a glucose level of 180 mg/dL or less seems to preserve outcomes and is consistent with general critical care guidelines. (Copyright (C) 2014 by Lippincott Williams & Wilkins) C1 [Sally, Mitchell B.; Crutchfield, Megan; De La Cruz, Salvador; Zatarain, John; Malinoski, Darren Jay] Portland VA Med Ctr, Surg Crit Care Sect, Portland, OR 97207 USA. [Sally, Mitchell B.; De La Cruz, Salvador; Zatarain, John; Malinoski, Darren Jay] Oregon Hlth & Sci Univ, Dept Surg, Portland, OR 97201 USA. [Ewing, Tyler] Univ Calif Davis, Sch Med, Sacramento, CA 95817 USA. [Patel, Madhukar S.] Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. [Raza, Shariq] Temple Univ, Dept Surg, Philadelphia, PA 19122 USA. RP Malinoski, DJ (reprint author), Portland VA Med Ctr, POB 1034 Mail Code P3ANES, Portland, OR 97207 USA. EM Darren.Malinoski@va.gov FU PHS HHS [R380T10586, 234-2005-37011C] NR 21 TC 5 Z9 5 U1 1 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 2163-0755 EI 2163-0763 J9 J TRAUMA ACUTE CARE JI J. Trauma Acute Care Surg. PD JAN PY 2014 VL 76 IS 1 BP 62 EP 68 DI 10.1097/TA.0b013e3182ab0d9b PG 7 WC Critical Care Medicine; Surgery SC General & Internal Medicine; Surgery GA AH8JN UT WOS:000336384200014 PM 24368358 ER PT J AU King, DR AF King, David R. TI Re: Outcomes following "rescue" superselective angioembolization in hemodynamically unstable patients Reply SO JOURNAL OF TRAUMA AND ACUTE CARE SURGERY LA English DT Letter C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Knight Surg Res Lab,Div Trauma Emergency Surg & S, Boston, MA 02163 USA. RP King, DR (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Knight Surg Res Lab,Div Trauma Emergency Surg & S, Boston, MA 02163 USA. OI King, David/0000-0003-1028-1478 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 2163-0755 EI 2163-0763 J9 J TRAUMA ACUTE CARE JI J. Trauma Acute Care Surg. PD JAN PY 2014 VL 76 IS 1 BP 248 EP 249 PG 3 WC Critical Care Medicine; Surgery SC General & Internal Medicine; Surgery GA AH8JN UT WOS:000336384200047 PM 24368389 ER PT J AU Jung, YL Luquette, LJ Ho, JWK Ferrari, F Tolstorukov, M Minoda, A Issner, R Epstein, CB Karpen, GH Kuroda, MI Park, PJ AF Jung, Youngsook L. Luquette, Lovelace J. Ho, Joshua W. K. Ferrari, Francesco Tolstorukov, Michael Minoda, Aki Issner, Robbyn Epstein, Charles B. Karpen, Gary H. Kuroda, Mitzi I. Park, Peter J. TI Impact of sequencing depth in ChIP-seq experiments SO NUCLEIC ACIDS RESEARCH LA English DT Article ID HUMAN GENOME AB In a chromatin immunoprecipitation followed by high-throughput sequencing (ChIP-seq) experiment, an important consideration in experimental design is the minimum number of sequenced reads required to obtain statistically significant results. We present an extensive evaluation of the impact of sequencing depth on identification of enriched regions for key histone modifications (H3K4me3, H3K36me3, H3K27me3 and H3K9me2/me3) using deep-sequenced datasets in human and fly. We propose to define sufficient sequencing depth as the number of reads at which detected enrichment regions increase < 1% for an additional million reads. Although the required depth depends on the nature of the mark and the state of the cell in each experiment, we observe that sufficient depth is often reached at < 20 million reads for fly. For human, there are no clear saturation points for the examined datasets, but our analysis suggests 40-50 million reads as a practical minimum for most marks. We also devise a mathematical model to estimate the sufficient depth and total genomic coverage of a mark. Lastly, we find that the five algorithms tested do not agree well for broad enrichment profiles, especially at lower depths. Our findings suggest that sufficient sequencing depth and an appropriate peak-calling algorithm are essential for ensuring robustness of conclusions derived from ChIP-seq data. C1 [Jung, Youngsook L.; Luquette, Lovelace J.; Ho, Joshua W. K.; Ferrari, Francesco; Park, Peter J.] Harvard Univ, Sch Med, Ctr Biomed Informat, Boston, MA 02115 USA. [Jung, Youngsook L.; Ho, Joshua W. K.; Tolstorukov, Michael; Kuroda, Mitzi I.; Park, Peter J.] Brigham & Womens Hosp, Div Genet, Boston, MA 02115 USA. [Jung, Youngsook L.; Ho, Joshua W. K.; Tolstorukov, Michael; Kuroda, Mitzi I.; Park, Peter J.] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Tolstorukov, Michael] Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. [Minoda, Aki; Karpen, Gary H.] Univ Calif Berkeley, Lawrence Berkeley Natl Lab, Div Life Sci, Dept Genome Dynam, Berkeley, CA 94720 USA. [Minoda, Aki; Karpen, Gary H.] Univ Calif Berkeley, Dept Mol & Cell Biol, Berkeley, CA 94720 USA. [Issner, Robbyn; Epstein, Charles B.] Broad Inst MIT & Harvard, Cambridge, MA 02142 USA. [Park, Peter J.] Childrens Hosp, Informat Program, Boston, MA 02115 USA. RP Park, PJ (reprint author), Harvard Univ, Sch Med, Ctr Biomed Informat, Boston, MA 02115 USA. EM peter_park@harvard.edu RI Ferrari, Francesco/H-5007-2012; Minoda, Aki/D-5335-2017 OI Ferrari, Francesco/0000-0002-9811-3753; Minoda, Aki/0000-0002-2927-5791 FU [U01HG004258]; [R01GM101958]; [R01GM082798] FX This work was supported by U01HG004258 to G.K., R01GM101958 to M.K., and R01GM082798 to P.J.P. Funding for open access charge: institutional grant to P.J.P. NR 19 TC 15 Z9 15 U1 2 U2 13 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0305-1048 EI 1362-4962 J9 NUCLEIC ACIDS RES JI Nucleic Acids Res. PY 2014 VL 42 IS 9 AR e74 DI 10.1093/nar/gku178 PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA AH9WI UT WOS:000336495400001 PM 24598259 ER PT J AU Hasegawa, K Tsugawa, Y Brown, DFM Mansbach, JM Camargo, CA AF Hasegawa, Kohei Tsugawa, Yusuke Brown, David F. M. Mansbach, Jonathan M. Camargo, Carlos A., Jr. TI Temporal Trends in Emergency Department Visits for Bronchiolitis in the United States, 2006 to 2010 SO PEDIATRIC INFECTIOUS DISEASE JOURNAL LA English DT Article DE bronchiolitis; emergency department; incidence; hospitalization; charge ID RESPIRATORY SYNCYTIAL VIRUS; PROSPECTIVE MULTICENTER; REGIONAL-VARIATION; ADMISSION RATES; VIRAL ETIOLOGY; INFANTS; CHILDREN; HOSPITALIZATIONS; MANAGEMENT; RISK AB Background: To examine temporal trends in emergency departments (EDs) visits for bronchiolitis among US children between 2006 and 2010. Methods: Serial, cross-sectional analysis of the Nationwide Emergency Department Sample, a nationally representative sample of ED patients. We used International Classification of Diseases, Ninth Revision, Clinical Modification code 466.1 to identify children <2 years of age with bronchiolitis. Primary outcome measures were rate of bronchiolitis ED visits, hospital admission rate and ED charges. Results: Between 2006 and 2010, weighted national discharge data included 1,435,110 ED visits with bronchiolitis. There was a modest increase in the rate of bronchiolitis ED visits, from 35.6 to 36.3 per 1000 person-years (2% increase; P-trend = 0.008), due to increases in the ED visit rate among children from 12 months to 23 months (24% increase; P-trend <0.001). By contrast, there was a significant decline in the ED visit rate among infants (4% decrease; P-trend <0.001). Although unadjusted admission rate did not change between 2006 and 2010 (26% in both years), admission rate declined significantly after adjusting for potential patient-and ED-level confounders (adjusted odds ratio for comparison of 2010 with 2006, 0.84; 95% confidence interval: 0.76-0.93; P <0.001). Nationwide ED charges for bronchiolitis increased from $337 million to $389 million (16% increase; P-trend <0.001), adjusted for inflation. This increase was driven by a rise in geometric mean of ED charges per case from $887 to $1059 (19% increase; P-trend <0.001). Conclusions: Between 2006 and 2010, we found a divergent temporal trend in the rate of bronchiolitis ED visits by age group. Despite a significant increase in associated ED charges, ED-associated hospital admission rates for bronchiolitis significantly decreased over this same period. C1 [Hasegawa, Kohei; Brown, David F. M.; Camargo, Carlos A., Jr.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Hasegawa, Kohei; Tsugawa, Yusuke; Brown, David F. M.; Camargo, Carlos A., Jr.] Harvard Univ, Sch Med, Boston, MA 02114 USA. [Tsugawa, Yusuke; Mansbach, Jonathan M.] Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. [Tsugawa, Yusuke] St Lukes Life Sci Inst, Ctr Clin Epidemiol, Tokyo, Japan. [Mansbach, Jonathan M.] Boston Childrens Hosp, Boston, MA USA. RP Hasegawa, K (reprint author), Harvard Univ, Dept Emergency Med, Massachusetts Gen Hosp, Sch Med, 326 Cambridge St,Suite 410, Boston, MA 02114 USA. EM khasegawa1@partners.org FU Eleanor and Miles Shore Fellowship Program (Boston, MA); St. Luke's Life Science Institute (Tokyo); NIH (Bethesda, MD) [U01 AI-87881] FX K.H. was supported, in part, by Eleanor and Miles Shore Fellowship Program (Boston, MA). Y.T. was supported, in part, by St. Luke's Life Science Institute (Tokyo). J.M.M. and C. A. C were supported, in part, by NIH U01 AI-87881 (Bethesda, MD). The funding organizations 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 article. The authors have no other funding or conflicts of interest to disclose. NR 41 TC 17 Z9 17 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0891-3668 EI 1532-0987 J9 PEDIATR INFECT DIS J JI Pediatr. Infect. Dis. J. PD JAN PY 2014 VL 33 IS 1 BP 11 EP 18 DI 10.1097/INF.0b013e3182a5f324 PG 8 WC Immunology; Infectious Diseases; Pediatrics SC Immunology; Infectious Diseases; Pediatrics GA AH9ZP UT WOS:000336505700008 PM 23934206 ER PT J AU Somayaji, D Cloyes, KG AF Somayaji, Darryl Cloyes, Kristin Gates TI Uniting Postcolonial, Discourse, and Linguistic Theory to Explore Participation of African Americans in Cancer Research as an Effect of Social and Historical Race Relationships SO ADVANCES IN NURSING SCIENCE LA English DT Article DE African American; cancer research; discourse analysis; race; social identity ID CLINICAL-TRIALS; UNDERREPRESENTED POPULATIONS; SCREENING TRIAL; RECRUITMENT; HEALTH; SCHOLARSHIP; INCLUSION; KNOWLEDGE; PROSTATE; PRAXIS AB This article uses a historical framework of postcolonialism; discourse analytic concepts (significance, identity, and relationships); and 5 social and cultural linguistic principles of emergence, positionality, indexicality, relationality, and partialness as a theoretical and methodological triangulation approach to data analysis of focus group discussion. Exemplars of focus group data from a study exploring African American participation in research demonstrate the application of this combined framework as a useful tool for analysis. This approach allows for examination of identity and interaction and generates a more rigorous and complete understanding of how individuals use language to construct identity as participants or nonparticipants in research. C1 [Somayaji, Darryl] Univ Massachusetts, Phyllis F Cantor Ctr, Dana Farber Canc Inst, Boston, MA 02115 USA. [Somayaji, Darryl] Roswell Pk Canc Inst, New York, NY USA. Univ Utah, Coll Nursing, Salt Lake City, UT 84112 USA. RP Somayaji, D (reprint author), Univ Massachusetts, Phyllis F Cantor Ctr, Dana Farber Canc Inst, 450 Brookline Ave,L522, Boston, MA 02115 USA. EM darryl_somayaji@dfci.harvard.edu FU American Cancer Society [113737-DSCN-07-131-01-SCN, 117201-DSCNR-07-137-03-SCN] FX American Cancer Society Doctoral Degree Scholarship in Cancer Nursing Award ID: 113737-DSCN-07-131-01-SCN; 117201-DSCNR-07-137-03-SCN. NR 32 TC 2 Z9 2 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0161-9268 EI 1550-5014 J9 ADV NURS SCI JI Adv. Nurs. Sci. PD JAN-MAR PY 2014 VL 37 IS 1 BP 32 EP 47 DI 10.1097/ANS.0000000000000015 PG 16 WC Nursing SC Nursing GA AH2VH UT WOS:000335979300006 PM 24469087 ER PT J AU Longmire, CVF Drye, LT Frangakis, CE Martin, BK Meinert, CL Mintzer, JE Munro, CA Porsteinsson, AP Rabins, PV Rosenberg, PB Schneider, LS Weintraub, D Lyketsos, CG AF Longmire, Crystal V. Flynn Drye, Lea T. Frangakis, Constantine E. Martin, Barbara K. Meinert, Curtis L. Mintzer, Jacobo E. Munro, Cynthia A. Porsteinsson, Anton P. Rabins, Peter V. Rosenberg, Paul B. Schneider, Lon S. Weintraub, Daniel Lyketsos, Constantine G. CA DIADS-2 Res Grp TI Is Sertraline Treatment or Depression Remission in Depressed Alzheimer Patients Associated with Improved Caregiver Well Being? Depression in Alzheimer's Disease Study 2 SO AMERICAN JOURNAL OF GERIATRIC PSYCHIATRY LA English DT Article DE Sertraline; depression; Alzheimer disease; caregivers; DIADS-2 ID RANDOMIZED CONTROLLED-TRIAL; QUALITY-OF-LIFE; NEUROPSYCHIATRIC SYMPTOMS; PHARMACOLOGICAL-TREATMENT; COGNITIVE IMPAIRMENT; FAMILY CAREGIVERS; DEMENTIA PATIENTS; DOUBLE-BLIND; BURDEN; HEALTH AB Objective: We wanted to assess if sertraline treatment (versus placebo) or remission of depression at 12 weeks (versus nonremission) in Alzheimer patients is associated with improved caregiver well being. Methods: We conducted a randomized, double-blind, placebo-controlled clinical trial of the efficacy and safety of sertraline for the treatment of depression in individuals with Alzheimer disease in five clinical research sites across the United States. Participants were caregivers of patients enrolled in the Depression in Alzheimer's Disease Study 2 (N = 131). All caregivers received standardized psychosocial support throughout the study. Caregiver outcome measures included depression (Beck Depression Inventory), distress (Neuropsychiatric Inventory), burden (Zarit Burden Interview), and quality of life (Medical Outcomes Study Short Form Health Survey). Results: Fifty-nine percent of caregivers were spouses, 63.4% were women, and 64.1% were white. Caregivers of patients in both treatment groups had significant reductions in distress scores over the 24-week study period, but there was not a greater benefit for caregivers of patients taking sertraline. However, caregivers of patients whose depression was in remission at week 12 had greater declines in distress scores over the 24 weeks than caregivers of patients whose depression did not remit by week 12. Conclusion: Patient treatment with sertraline was not associated with significantly greater reductions in caregiver distress than placebo treatment. Distress but not level of depression or burden lessened for all caregivers regardless of remission status and even more so for those who cared for patients whose depression remitted. Results imply an interrelationship between caregiver distress and patient psychiatric outcomes. C1 [Longmire, Crystal V. Flynn] Med Univ S Carolina, Dept Neurosci, Charleston, SC 29425 USA. [Mintzer, Jacobo E.] Med Univ S Carolina, Coll Hlth Sci, Charleston, SC 29425 USA. [Drye, Lea T.; Frangakis, Constantine E.; Martin, Barbara K.; Meinert, Curtis L.; Lyketsos, Constantine G.] Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Baltimore, MD USA. [Mintzer, Jacobo E.] Ralph H Johnson Vet Affairs Med Ctr, Div Psychiat, Charleston, SC USA. [Munro, Cynthia A.; Rabins, Peter V.; Rosenberg, Paul B.; Lyketsos, Constantine G.] Johns Hopkins Univ, Sch Med, Baltimore, MD USA. [Porsteinsson, Anton P.] Univ Rochester, Sch Med, Rochester, NY USA. [Schneider, Lon S.] Univ So Calif, Keck Sch Med, Los Angeles, CA 90033 USA. [Schneider, Lon S.] Univ So Calif, Dept Psychiat & Behav Sci, Los Angeles, CA USA. [Schneider, Lon S.] Univ So Calif, Dept Neurol, Los Angeles, CA USA. [Schneider, Lon S.] Univ So Calif, Leonard Davis Sch Gerontol, Los Angeles, CA USA. [Weintraub, Daniel] Univ Penn, Perelman Sch Med, Philadelphia, PA 19104 USA. [Weintraub, Daniel] Philadelphia Vet Affairs Med Ctr, Parkinsons Dis Res Educ & Clin Ctr, Philadelphia, PA USA. [Weintraub, Daniel] Philadelphia Vet Affairs Med Ctr, Mental Illness Res Educ & Clin Ctr, Philadelphia, PA USA. RP Longmire, CVF (reprint author), Med Univ S Carolina, Dept Neurosci, Alzheimers Res Program, 5900 Core Rd,Ste 203, N Charleston, SC 29406 USA. EM crystalflynn@hotmail.com NR 44 TC 2 Z9 2 U1 0 U2 4 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1064-7481 EI 1545-7214 J9 AM J GERIAT PSYCHIAT JI Am. J. Geriatr. Psychiatr. PD JAN PY 2014 VL 22 IS 1 BP 14 EP 24 DI 10.1016/j.jagp.2013.02.014 PG 11 WC Geriatrics & Gerontology; Gerontology; Psychiatry SC Geriatrics & Gerontology; Psychiatry GA AH3UJ UT WOS:000336050800003 ER PT J AU Chopra, MP Zhang, HM Kaiser, AP Moye, JA Llorente, MD Oslin, DW Spiro, A AF Chopra, Mohit P. Zhang, Hongmei Kaiser, Anica Pless Moye, Jennifer A. Llorente, Maria D. Oslin, David W. Spiro, Avron, III TI PTSD Is a Chronic, Fluctuating Disorder Affecting the Mental Quality of Life in Older Adults SO AMERICAN JOURNAL OF GERIATRIC PSYCHIATRY LA English DT Article DE Course; geriatric; posttraumatic stress disorder; quality of life; trajectory ID POSTTRAUMATIC-STRESS-DISORDER; PRIMARY-CARE; ALCOHOL-USE; VETERANS; HEALTH; DEPRESSION; SYMPTOMS; EXPOSURE; ILLNESS; TRAUMA AB Objectives: Examine the longitudinal course of posttraumatic stress disorder (PTSD) in older adults and its influence on mental health quality of life (MHQoL). Design: Evaluation performed at baseline, and 3 and 6 months postrandomization as part of a longitudinal trial. Participants and settings: A total of 1,185 participants, with a mean (+/-SD) age of 73.53 (+/-5.98) years, at seven primary care sites (including five Veterans Affairs clinics), were divided into four groups, namely, no trauma (n = 661), trauma only (n = 319), partial PTSD (n = 114), and PTSD (n = 81), based on reports of trauma and associated PTSD symptoms. Measurements: The prevalence of comorbid depression, anxiety, and alcohol use disorders, assessed using the Diagnostic and Statistical Manual, Fourth Edition, criteria and changes in MHQoL, as assessed by the Short Form-36 mental component score. Results: At baseline, the PTSD group had higher frequencies of comorbid depression and anxiety disorders and worse MHQoL than the other groups. Both chronic (participants diagnosed with PTSD at all three assessments) and fluctuating (participants moving to or from one of the other groups) trajectories of course were observed during the follow-up period, which appeared to be separate from that of the comorbid disorders. Even after accounting for those comorbid disorders, PTSD had an independent association with poorer MHQoL at multiple time points, especially in men, whereas trauma without PTSD symptoms (trauma only) had better MHQoL. Conclusions: PTSD had chronic and fluctuating courses, with negative effects on MHQoL, while partial PTSD might represent a transitional state, underscoring the need to better identify and treat PTSD at any phase in later life. C1 [Chopra, Mohit P.] Boston Univ, Sch Med, Dept Psychiat, Boston, MA 02118 USA. [Kaiser, Anica Pless; Moye, Jennifer A.] Boston Univ, Sch Med, Dept Psychol, Boston, MA 02118 USA. [Spiro, Avron, III] Boston Univ, Sch Med, Massachusetts VA Epidemiol Res & Informat Ctr, Boston, MA 02118 USA. [Chopra, Mohit P.; Kaiser, Anica Pless; Spiro, Avron, III] Boston Univ, Sch Med, Dept Psychiat, VA Boston Healthcare Syst, Boston, MA 02118 USA. [Spiro, Avron, III] Boston Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA USA. [Chopra, Mohit P.; Moye, Jennifer A.] Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA. [Zhang, Hongmei] Univ S Carolina, Dept Biostat, Arnold Sch Publ Hlth, Columbia, SC 29208 USA. [Llorente, Maria D.] Washington DC VA Med Ctr, Washington, DC USA. [Oslin, David W.] Univ Penn Hlth Syst, Philadelphia VA Med Ctr, VISN MIRECC 4, Philadelphia, PA USA. [Oslin, David W.] Univ Penn Hlth Syst, Dept Psychiat, Philadelphia, PA USA. RP Chopra, MP (reprint author), Geriatr Mental Hlth, 35C,940 Belmont St, Brockton, MA 02301 USA. EM mpchopra@hotmail.com RI Moye, Jennifer/F-2240-2017 OI Moye, Jennifer/0000-0002-3434-347X NR 36 TC 12 Z9 12 U1 5 U2 14 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1064-7481 EI 1545-7214 J9 AM J GERIAT PSYCHIAT JI Am. J. Geriatr. Psychiatr. PD JAN PY 2014 VL 22 IS 1 BP 86 EP 97 DI 10.1016/j.jagp.2013.01.064 PG 12 WC Geriatrics & Gerontology; Gerontology; Psychiatry SC Geriatrics & Gerontology; Psychiatry GA AH3UJ UT WOS:000336050800010 PM 24314889 ER PT J AU Hahn, RT Abraham, T Adams, MS Bruce, CJ Glas, KE Lang, RM Reeves, ST Shanewise, JS Siu, SC Stewart, W Picard, MH AF Hahn, Rebecca T. Abraham, Theodore Adams, Mark S. Bruce, Charles J. Glas, Kathryn E. Lang, Roberto M. Reeves, Scott T. Shanewise, Jack S. Siu, Samuel C. Stewart, William Picard, Michael H. TI Guidelines for Performing a Comprehensive Transesophageal Echocardiographic Examination: Recommendations from the American Society of Echocardiography and the Society of Cardiovascular Anesthesiologists SO ANESTHESIA AND ANALGESIA LA English DT Article ID LEFT ATRIAL APPENDAGE; CONGENITAL HEART-DISEASE; PATENT FORAMEN OVALE; AORTIC-VALVE IMPLANTATION; CARDIAC SURGICAL-PATIENTS; BENZOCAINE-INDUCED METHEMOGLOBINEMIA; TIME 3-DIMENSIONAL ECHOCARDIOGRAPHY; UPPER GASTROINTESTINAL ENDOSCOPY; FUNCTIONAL MITRAL REGURGITATION; OF-CARDIOLOGY FOUNDATION C1 [Hahn, Rebecca T.; Shanewise, Jack S.] Columbia Univ, New York, NY 10027 USA. [Abraham, Theodore] Johns Hopkins Univ, Baltimore, MD USA. [Adams, Mark S.; Picard, Michael H.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Bruce, Charles J.] Mayo Clin, Rochester, MN USA. [Glas, Kathryn E.] Emory Univ, Sch Med, Atlanta, GA USA. [Lang, Roberto M.] Univ Chicago, Chicago, IL 60637 USA. [Reeves, Scott T.] Med Univ S Carolina, Charleston, SC 29425 USA. [Siu, Samuel C.] Univ Western Ontario, London, ON, Canada. [Stewart, William] Cleveland Clin, Cleveland, OH 44106 USA. RP Hahn, RT (reprint author), Columbia Univ, New York, NY 10027 USA. OI Picard, Michael/0000-0002-9264-3243 NR 172 TC 30 Z9 30 U1 1 U2 10 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 JAN PY 2014 VL 118 IS 1 BP 21 EP 68 DI 10.1213/ANE.0000000000000016 PG 48 WC Anesthesiology SC Anesthesiology GA AG4NC UT WOS:000335395700008 PM 24356157 ER PT J AU Culley, DJ Fahy, BG Xie, ZC Lekowski, R Buetler, S Liu, XX Cohen, NH Crosby, G AF Culley, Deborah J. Fahy, Brenda G. Xie, Zhongcong Lekowski, Robert Buetler, Sascha Liu, Xiaoxia Cohen, Neal H. Crosby, Gregory TI Academic Productivity of Directors of ACGMEAccredited Residency Programs in Surgery and Anesthesiology SO ANESTHESIA AND ANALGESIA LA English DT Article ID INDEX AB BACKGROUND: Scholarly activity is expected of program directors of Accreditation Council for Graduate Medical Education (ACGME)-accredited residency training programs. Anesthesiology residency programs are cited more often than surgical programs for deficiencies in academic productivity. We hypothesized that this may in part reflect differences in scholarly activity between program directors of anesthesiology and surgical trainings programs. To test the hypothesis, we examined the career track record of current program directors of ACGME-accredited anesthesiology and surgical residency programs at the same institutions using PubMed citations and funding from the National Institutes of Health (NIH) as metrics of scholarly activity. METHODS: Between November 1, 2011 and December 31, 2011, we obtained data from publicly available Web sites on program directors at 127 institutions that had ACGME-accredited programs in both anesthesiology and surgery. Information gathered on each individual included year of board certification, year first appointed program director, academic rank, history of NIH grant funding, and number of PubMed citations. We also calculated the h-index for a randomly selected subset of 25 institution-matched program directors. RESULTS: There were no differences between the groups in number of years since board certification (P = 0.42), academic rank (P = 0.38), or years as a program director (P = 0.22). However, program directors in anesthesiology had less prior or current NIH funding (P = 0.002), fewer total and education-related PubMed citations (both P < 0.001), and a lower h-index (P = 0.001) than surgery program directors. Multivariate analysis revealed that the publication rate for anesthesiology program directors was 43% (95% confidence interval, 0.31-0.58) that of the corresponding program directors of surgical residency programs, holding other variables constant. CONCLUSIONS: Program directors of anesthesiology residency programs have considerably less scholarly activity in terms of peer-reviewed publications and federal research funding than directors of surgical residency programs. As such, this study provides further evidence for a systemic weakness in the scholarly fabric of academic anesthesiology. C1 [Culley, Deborah J.; Lekowski, Robert; Buetler, Sascha; Liu, Xiaoxia] Brigham & Womens Hosp, Dept Anesthesiol, Boston, MA 02115 USA. [Fahy, Brenda G.] Univ Florida, Dept Anesthesiol, Coll Med, Gainesville, FL USA. [Xie, Zhongcong] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Anesthesia & Crit Care, Boston, MA USA. [Cohen, Neal H.] Univ Calif San Francisco, Dept Anesthesia & Perioperat Care, San Francisco, CA 94143 USA. [Crosby, Gregory] Harvard Univ, Brigham & Womens Hosp, Dept Anesthesiol, Sch Med, Boston, MA 02115 USA. RP Culley, DJ (reprint author), Brigham & Womens Hosp, 75 Francis St, Boston, MA 02115 USA. EM dculley@zeus.bwh.harvard.edu FU NIA NIH HHS [R01 AG041274]; NIGMS NIH HHS [R01 GM088801, R01 GM088817] NR 11 TC 8 Z9 8 U1 0 U2 0 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 JAN PY 2014 VL 118 IS 1 BP 200 EP 205 DI 10.1213/ANE.0b013e3182a8fab5 PG 6 WC Anesthesiology SC Anesthesiology GA AG4NC UT WOS:000335395700023 PM 24247229 ER PT J AU Nair, BG Horibe, M Newman, SF Wu, WY Peterson, GN Schwid, HA AF Nair, Bala G. Horibe, Mayumi Newman, Shu-Fang Wu, Wei-Ying Peterson, Gene N. Schwid, Howard A. TI Anesthesia Information Management System- Based Near Real-Time Decision Support to Manage Intraoperative Hypotension and Hypertension SO ANESTHESIA AND ANALGESIA LA English DT Article ID NONCARDIAC SURGERY; DOCUMENTATION; ALERTS; NOTIFICATION; DEFINITIONS; PERFORMANCE; MORTALITY; DURATION; QUALITY; RECORDS AB BACKGROUND: Intraoperative hypotension and hypertension are associated with adverse clinical outcomes and morbidity. Clinical decision support mediated through an anesthesia information management system (AIMS) has been shown to improve quality of care. We hypothesized that an AIMS-based clinical decision support system could be used to improve management of intraoperative hypotension and hypertension. METHODS: A near real-time AIMS-based decision support module, Smart Anesthesia Manager (SAM), was used to detect selected scenarios contributing to hypotension and hypertension. Specifically, hypotension (systolic blood pressure <80 mm Hg) with a concurrent high concentration (>1.25 minimum alveolar concentration [MAC]) of inhaled drug and hypertension (systolic blood pressure >160 mm Hg) with concurrent phenylephrine infusion were detected, and anesthesia providers were notified via pop-up computer screen messages. AIMS data were retrospectively analyzed to evaluate the effect of SAM notification messages on hypotensive and hypertensive episodes. RESULTS: For anesthetic cases 12 months before (N = 16913) and after (N = 17132) institution of SAM messages, the median duration of hypotensive episodes with concurrent high MAC decreased with notifications (Mann Whitney rank sum test, P = 0.031). However, the reduction in the median duration of hypertensive episodes with concurrent phenylephrine infusion was not significant (P = 0.47). The frequency of prolonged episodes that lasted >6 minutes (sampling period of SAM), represented in terms of the number of cases with episodes per 100 surgical cases (or percentage occurrence), declined with notifications for both hypotension with >1.25 MAC inhaled drug episodes ( = -0.26% [confidence interval, -0.38% to -0.11%], P < 0.001) and hypertension with phenylephrine infusion episodes ( = -0.92% [confidence interval, -1.79% to -0.04%], P = 0.035). For hypotensive events, the anesthesia providers reduced the inhaled drug concentrations to <1.25 MAC 81% of the time with notifications compared with 59% without notifications (P = 0.003). For hypertensive episodes, although the anesthesia providers' reduction or discontinuation of the phenylephrine infusion increased from 22% to 37% (P = 0.030) with notification messages, the overall response was less consistent than the response to hypotensive episodes. CONCLUSIONS: With automatic acquisition of arterial blood pressure and inhaled drug concentration variables in an AIMS, near real-time notification was effective in reducing the duration and frequency of hypotension with concurrent >1.25 MAC inhaled drug episodes. However, since phenylephrine infusion is manually documented in an AIMS, the impact of notification messages was less pronounced in reducing episodes of hypertension with concurrent phenylephrine infusion. Automated data capture and a higher frequency of data acquisition in an AIMS can improve the effectiveness of an intraoperative clinical decision support system. C1 [Nair, Bala G.; Newman, Shu-Fang; Peterson, Gene N.; Schwid, Howard A.] Univ Washington, Dept Anesthesiol & Pain Med, Seattle, WA 98195 USA. [Horibe, Mayumi] VA Puget Sound Hlth Care Syst, Dept Anesthesiol, Seattle, WA USA. [Wu, Wei-Ying] Natl Dong Hwa Univ, Dept Appl Math, Hualien, Taiwan. RP Nair, BG (reprint author), Univ Washington, Dept Anesthesiol & Pain Med, BB-1469 Hlth Sci Bldg,Mail Box 356540, Seattle, WA 98195 USA. EM nairbg@uw.edu FU University of Washington FX This research was partly supported by Laura Cheney Patient Safety Grant provided by the University of Washington. NR 27 TC 16 Z9 16 U1 0 U2 2 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 JAN PY 2014 VL 118 IS 1 BP 206 EP 214 DI 10.1213/ANE.0000000000000027 PG 9 WC Anesthesiology SC Anesthesiology GA AG4NC UT WOS:000335395700024 PM 24247227 ER PT J AU Blute, ML Prestipino, AL AF Blute, Michael L. Prestipino, Ann L. TI Factors Associated With Adoption of Robotic Surgical Technology in US Hospitals and Relationship to Radical Prostatectomy Procedure Volume SO ANNALS OF SURGERY LA English DT Editorial Material C1 [Blute, Michael L.; Prestipino, Ann L.] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Blute, ML (reprint author), Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 11 TC 1 Z9 1 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0003-4932 EI 1528-1140 J9 ANN SURG JI Ann. Surg. PD JAN PY 2014 VL 259 IS 1 BP 7 EP 9 DI 10.1097/SLA.0000000000000390 PG 3 WC Surgery SC Surgery GA AH6NC UT WOS:000336246600013 PM 24326746 ER PT J AU Kim, KW Park, SH Pyo, J Yoon, SH Byun, JH Lee, MG Krajewski, KM Ramaiya, NH AF Kim, Kyung Won Park, Seong Ho Pyo, Junhee Yoon, Soon Ho Byun, Jae Ho Lee, Moon-Gyu Krajewski, Katherine M. Ramaiya, Nikhil H. TI Imaging Features to Distinguish Malignant and Benign Branch-Duct Type Intraductal Papillary Mucinous Neoplasms of the Pancreas A Meta-analysis SO ANNALS OF SURGERY LA English DT Article DE Branch duct; consensus guidelines; intraductal papillary mucinous neoplasm; meta-analysis; pancreas ID INTERNATIONAL CONSENSUS GUIDELINES; DIFFERENTIAL-DIAGNOSIS; COMPUTED-TOMOGRAPHY; PREDICTIVE FACTORS; CLINICOPATHOLOGICAL FEATURES; MR CHOLANGIOPANCREATOGRAPHY; ENDOSCOPIC ULTRASONOGRAPHY; TREATMENT STRATEGY; HELICAL CT; FOLLOW-UP AB Objective: To systematically determine the imaging findings for distinguishing malignant and benign branch-duct type intraductal papillary mucinous neoplasms (BD-IPMNs), including mixed type, and their diagnostic value through meta-analysis of published studies. Background: Management of BD-IPMNs, including mixed type, largely relies on imaging findings. The current knowledge on imaging findings to distinguish malignant and benign BD-IPMNs has weak evidence and is mostly from scattered individual retrospective studies. Methods: Thorough literature search in Ovid-MEDLINE and EMBASE databases was conducted to identify studies where findings of computed tomography, magnetic resonance imaging, and endoscopic ultrasonography of BD-IPMNs with or without main pancreatic duct (MPD) dilatation were correlated with surgical/pathological findings. Review of 1128 article candidates, including full-text review of 102 articles, identified 23 eligible articles with a total of 1373 patients for meta-analysis. Dichotomous data regarding distinction between malignant and benign BD-IPMNs were pooled using random effects model to obtain the diagnostic odds ratios (DORs) and their 95% confidence intervals (CIs) of various individual imaging findings for diagnosing malignant BD-IPMN. Results: Presence of mural nodules revealed the highest pooled DOR (95% CI) of 6.0 (4.1-8.8) followed by MPD dilatation [3.4 (2.3-5.2)], thick septum/wall [unadjusted, 3.3 (1.5-6.9); publication bias-adjusted, 2.3 (0.9-5.5)], and cyst size greater than 3 cm [2.3 (1.5-3.5)]. Multilocularity and multiplicity of the cystic lesions did not reveal statistically significant association with malignancy. Conclusions: Presence of mural nodules should be regarded highly suspicious for malignancy warranting a surgical excision whereas cyst size greater than 3 cm, MPD dilatation (5-9 mm), or thick septum/wall may better be managed by careful observation and/or further evaluation. C1 [Kim, Kyung Won; Park, Seong Ho; Byun, Jae Ho; Lee, Moon-Gyu] Univ Ulsan, Dept Radiol, Coll Med, Asan Med Ctr, Seoul 138736, South Korea. [Kim, Kyung Won; Park, Seong Ho; Byun, Jae Ho; Lee, Moon-Gyu] Univ Ulsan, Res Inst Radiol, Coll Med, Asan Med Ctr, Seoul 138736, South Korea. [Kim, Kyung Won; Krajewski, Katherine M.; Ramaiya, Nikhil H.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Imaging, Boston, MA 02115 USA. [Pyo, Junhee] Tufts Med Ctr, Inst Clin Res & Hlth Policy Studies, Boston, MA USA. [Yoon, Soon Ho] Seoul Natl Univ Hosp, Dept Radiol, Seoul 110744, South Korea. RP Park, SH (reprint author), Univ Ulsan, Dept Radiol, Coll Med, Asan Med Ctr, 88 Olymp Ro 43 Gil, Seoul 138736, South Korea. EM parksh.radiology@gmail.com OI Park, Seong Ho/0000-0002-1257-8315 FU GE Healthcare; Dongkook Pharmaceutical FX S.H.P. has received research grants from GE Healthcare and Dongkook Pharmaceutical, which are unrelated to the submitted work. There is nothing to disclose for the other authors, and the authors declare no conflicts of interest. NR 60 TC 52 Z9 53 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0003-4932 EI 1528-1140 J9 ANN SURG JI Ann. Surg. PD JAN PY 2014 VL 259 IS 1 BP 72 EP 81 DI 10.1097/SLA.0b013e31829385f7 PG 10 WC Surgery SC Surgery GA AH6NC UT WOS:000336246600022 PM 23657084 ER PT J AU Han, C Yu, ZJ Duan, ZF Kan, QC AF Han, Chao Yu, Zujiang Duan, Zhenfeng Kan, Quancheng TI Role of MicroRNA-1 in Human Cancer and Its Therapeutic Potentials SO BIOMED RESEARCH INTERNATIONAL LA English DT Review ID MUSCLE-SPECIFIC MICRORNA; SQUAMOUS-CELL CARCINOMA; HUMAN COLON-CANCER; PROSTATE-CANCER; BLADDER-CANCER; DOWN-REGULATION; COLORECTAL-CANCER; GENE-THERAPY; LUNG-CANCER; MYOGENIC DIFFERENTIATION AB While the mechanisms of human cancer development are not fully understood, evidence of microRNA (miRNA, miR) dysregulation has been reported in many human diseases, including cancer. miRs are small noncoding RNA molecules that regulate posttranscriptional gene expression by binding to complementary sequences in the specific region of gene mRNAs, resulting in downregulation of gene expression. Not only are certain miRs consistently dysregulated across many cancers, but they also play critical roles in many aspects of cell growth, proliferation, metastasis, apoptosis, and drug resistance. Recent studies from our group and others revealed that miR-1 is frequently downregulated in various types of cancer. Through targeting multiple oncogenes and oncogenic pathways, miR-1 has been demonstrated to be a tumor suppressor gene that represses cancer cell proliferation and metastasis and promotes apoptosis by ectopic expression. In this review, we highlight recent findings on the aberrant expression and functional significance of miR-1 in human cancers and emphasize its significant values for therapeutic potentials. C1 [Han, Chao; Yu, Zujiang; Kan, Quancheng] Zhengzhou Univ, Affiliated Hosp 1, Dept Clin Pharmacol, Zhengzhou 450052, Peoples R China. [Duan, Zhenfeng] Massachusetts Gen Hosp, Sarcoma Biol Lab, Ctr Sarcoma & Connect Tissue Oncol, Boston, MA 02114 USA. RP Kan, QC (reprint author), Zhengzhou Univ, Affiliated Hosp 1, Dept Clin Pharmacol, Zhengzhou 450052, Peoples R China. EM quanchengkan@yeah.net NR 83 TC 17 Z9 17 U1 2 U2 6 PU HINDAWI PUBLISHING CORPORATION PI NEW YORK PA 410 PARK AVENUE, 15TH FLOOR, #287 PMB, NEW YORK, NY 10022 USA SN 2314-6133 EI 2314-6141 J9 BIOMED RES INT JI Biomed Res. Int. PY 2014 AR 428371 DI 10.1155/2014/428371 PG 11 WC Biotechnology & Applied Microbiology; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Research & Experimental Medicine GA AI1GQ UT WOS:000336598700001 ER PT J AU Taylor, BA Zaleski, AL Capizzi, JA Ballard, KD Troyanos, C Baggish, AL D'Hemecourt, PA Dada, MR Thompson, PD AF Taylor, Beth A. Zaleski, Amanda L. Capizzi, Jeffrey A. Ballard, Kevin D. Troyanos, Christopher Baggish, Aaron L. D'Hemecourt, Pierre A. Dada, Marcin R. Thompson, Paul D. TI Influence of chronic exercise on carotid atherosclerosis in marathon runners SO BMJ OPEN LA English DT Article DE Sports Medicine ID INTIMA-MEDIA THICKNESS; PHYSICAL-ACTIVITY; BLOOD-PRESSURE; CARDIORESPIRATORY FITNESS; HEALTHY-MEN; ARTERY WALL; RISK; AGE; ADULTS; PROGRESSION AB Objectives The effect of habitual, high-intensity exercise training on the progression of atherosclerosis is unclear. We assessed indices of vascular health (central systolic blood pressure (SBP) and arterial stiffness as well as carotid intima-medial thickness (cIMT)) in addition to cardiovascular risk factors of trained runners versus their untrained spouses or partners to evaluate the impact of exercise on the development of carotid atherosclerosis. Setting field study at Boston Marathon. Participants 42 qualifiers (mean ageSD: 4613years, 21 women) for the 2012 Boston Marathon and their sedentary domestic controls (4612years, n=21 women). Outcomes We measured medical and running history, vital signs, anthropometrics, blood lipids, C reactive protein (CRP), 10years Framingham risk, central arterial stiffness and SBP and cIMT. Results Multiple cardiovascular risk factors, including CRP, non-high-density lipoprotein cholesterol, triglycerides, heart rate, body weight and body mass index (all p<0.05), were reduced in the runners. The left and right cIMT, as well as central SBP, were not different between the two groups (all p>0.31) and were associated with age (all r0.41; p<0.01) and Framingham risk score (all r0.44; p<0.01) independent of exercise group (all p>0.08 for interactions). The amplification of the central pressure waveform (augmentation pressure at heart rate 75bpm) was also not different between the two groups (p=0.07) but was related to age (p<0.01) and group (p=0.02) in a multiple linear regression model. Conclusions Habitual endurance exercise improves the cardiovascular risk profile, but does not reduce the magnitude of carotid atherosclerosis associated with age and cardiovascular risk factors. C1 [Taylor, Beth A.; Zaleski, Amanda L.; Capizzi, Jeffrey A.; Ballard, Kevin D.; Dada, Marcin R.; Thompson, Paul D.] Hartford Hosp, Dept Cardiol, Henry Low Heart Ctr, Hartford, CT 06115 USA. [Taylor, Beth A.] Univ Hartford, Dept Hlth Sci, Bloomfield, NJ USA. [Troyanos, Christopher; D'Hemecourt, Pierre A.] Childrens Hosp, Boston, MA 02115 USA. [Baggish, Aaron L.] Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. RP Taylor, BA (reprint author), Hartford Hosp, Dept Cardiol, Henry Low Heart Ctr, Hartford, CT 06115 USA. EM beth.taylor@hhchealth.org OI Ballard, Kevin/0000-0001-7587-1220 FU Hartford Hospital Small Research Grant FX This research was funded by a Hartford Hospital Small Research Grant. NR 28 TC 12 Z9 12 U1 1 U2 8 PU BMJ PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 2044-6055 J9 BMJ OPEN JI BMJ Open PY 2014 VL 4 IS 2 DI 10.1136/bmjopen-2013-004498 PG 6 WC Medicine, General & Internal SC General & Internal Medicine GA AF1FF UT WOS:000334459100022 ER PT J AU Grubman, A James, SA James, J Duncan, C Volitakis, I Hickey, JL Crouch, PJ Donnelly, PS Kanninen, KM Liddell, JR Cotman, SL de Jonge, MD White, AR AF Grubman, A. James, S. A. James, J. Duncan, C. Volitakis, I. Hickey, J. L. Crouch, P. J. Donnelly, P. S. Kanninen, K. M. Liddell, J. R. Cotman, S. L. de Jonge, M. D. White, A. R. TI X-ray fluorescence imaging reveals subcellular biometal disturbances in a childhood neurodegenerative disorder SO CHEMICAL SCIENCE LA English DT Article ID NEURONAL CEROID-LIPOFUSCINOSIS; GENETICALLY ENCODED SENSORS; ALZHEIMERS-DISEASE BRAIN; ZINC TRANSPORTER; TRANSMEMBRANE PROTEIN; ENDOPLASMIC-RETICULUM; BINDING-PROTEIN; CALCIUM-BINDING; S100B PROTEIN; CELLULAR ZINC AB Biometals such as zinc, iron, copper and calcium play key roles in diverse physiological processes in the brain, but can be toxic in excess. A hallmark of neurodegeneration is a failure of homeostatic mechanisms controlling the concentration and distribution of these elements, resulting in overload, deficiency or mislocalization. A major roadblock to understanding the impact of altered biometal homeostasis in neurodegenerative disease is the lack of rapid, specific and sensitive techniques capable of providing quantitative subcellular information on biometal homeostasis in situ. Recent advances in X-ray fluorescence detectors have provided an opportunity to rapidly measure biometal content at subcellular resolution in cell populations using X-ray Fluorescence Microscopy (XFM). We applied this approach to investigate subcellular biometal homeostasis in a cerebellar cell line isolated from a natural mouse model of a childhood neurodegenerative disorder, the CLN6 form of neuronal ceroid lipofuscinosis, commonly known as Batten disease. Despite no global changes to whole cell concentrations of zinc or calcium, XFM revealed significant subcellular mislocalization of these important biological second messengers in cerebellar Cln6(nclf) (CbCln6(nclf)) cells. XFM revealed that nuclear-to-cytoplasmic trafficking of zinc was severely perturbed in diseased cells and the subcellular distribution of calcium was drastically altered in CbCln6nclf cells. Subtle differences in the zinc K-edge X-ray Absorption Near Edge Structure (XANES) spectra of control and CbCln6nclf cells suggested that impaired zinc homeostasis may be associated with an altered ligand set in CbCln6nclf cells. Importantly, a zinc-complex, ZnII(atsm), restored the nuclear-to-cytoplasmic zinc ratios in CbCln6nclf cells via nuclear zinc delivery, and restored the relationship between subcellular zinc and calcium levels to that observed in healthy control cells. ZnII(atsm) treatment also resulted in a reduction in the number of calcium-rich puncta observed in CbCln6nclf cells. This study highlights the complementarities of bulk and single cell analysis of metal content for understanding disease states. We demonstrate the utility and broad applicability of XFM for subcellular analysis of perturbed biometal metabolism and mechanism of action studies for novel therapeutics to target neurodegeneration. C1 [Grubman, A.; James, J.; Duncan, C.; Crouch, P. J.; Liddell, J. R.; White, A. R.] Univ Melbourne, Dept Pathol, Parkville, Vic 3010, Australia. [James, S. A.; de Jonge, M. D.] Australian Synchrotron, Clayton, Vic 3168, Australia. [James, S. A.] CSIRO, Mat Sci & Engn & Preventat Hlth Flagship, Clayton, Vic 3168, Australia. [Volitakis, I.] Univ Melbourne, Florey Inst Neurosci & Mental Hlth, Parkville, Vic 3010, Australia. [Hickey, J. L.; Donnelly, P. S.] Univ Melbourne, Sch Chem, Parkville, Vic 3010, Australia. [Hickey, J. L.; Donnelly, P. S.] Univ Melbourne, Inst Mol Sci & Biotechnol Bio21, Parkville, Vic 3010, Australia. [Kanninen, K. M.] Univ Eastern Finland, AI Virtanen Inst Mol Sci, FI-70211 Kuopio, Finland. [Cotman, S. L.] Massachusetts Gen Hosp, Ctr Human Genet Res, Mol Neurogenet Unit, Boston, MA 02114 USA. RP White, AR (reprint author), Univ Melbourne, Dept Pathol, Parkville, Vic 3010, Australia. EM arwhite@unimelb.edu.au RI de Jonge, Martin/C-3400-2011; White, Anthony/P-5596-2016; James, Simon/J-5320-2012; OI White, Anthony/0000-0003-1802-9891; James, Simon/0000-0001-9369-3288; Grubman, Alexandra/0000-0003-4408-4499; Liddell, Jeffrey/0000-0002-0798-5338 FU National Health and Medical Research Council of Australia (NHMRC) [628946]; National Institutes of Health: National Institute of Neurological Disorders Stroke [R01NS073813]; ARC Future Fellowship [FT100100674] FX Parts of this work were performed at the XFM beamline at the Australian Synchrotron, Victoria, Australia. This work was supported by the National Health and Medical Research Council of Australia (NHMRC) [628946] and the National Institutes of Health: National Institute of Neurological Disorders & Stroke [R01NS073813]. ARW is a recipient of an ARC Future Fellowship [FT100100674]. The funding sources had no influence in study design; collection, analysis, and interpretation of data; writing the report; or the decision to submit the report for publication. Patent protection has previously been sought by the University of Melbourne for the use of bis(-thiosemicarbazones) for treatment of diseases. ARW and PSD are co-inventors on this patent application PCT/AU2007/001792, which is the subject of a commercialization contract between the University and a private company. The company has not funded nor contributed to research described in this manuscript. NR 95 TC 16 Z9 16 U1 2 U2 24 PU ROYAL SOC CHEMISTRY PI CAMBRIDGE PA THOMAS GRAHAM HOUSE, SCIENCE PARK, MILTON RD, CAMBRIDGE CB4 0WF, CAMBS, ENGLAND SN 2041-6520 EI 2041-6539 J9 CHEM SCI JI Chem. Sci. PY 2014 VL 5 IS 6 BP 2503 EP 2516 DI 10.1039/c4sc00316k PG 14 WC Chemistry, Multidisciplinary SC Chemistry GA AH6QA UT WOS:000336254500053 PM 24976945 ER PT B AU Knutsen, J Frye, D Sobel, DM AF Knutsen, John Frye, Douglas Sobel, David M. BE Saracho, ON TI THEORY OF LEARNING, THEORY OF TEACHING, AND THEORY OF MIND How Social-Cognitive Development Influences Children's Understanding of Learning and Teaching SO CONTEMPORARY PERSPECTIVES ON RESEARCH IN THEORY OF MIND IN EARLY CHILDHOOD EDUCATION SE Contemporary Perspectives in Early Childhood Education LA English DT Article; Book Chapter ID FALSE BELIEF; BEHAVIORAL REENACTMENT; KNOWLEDGE ACQUISITION; FAILED ATTEMPTS; AUTISM; PRESCHOOLERS; INTENTIONS; DISTINCTION; DISCOVERY; SELF C1 [Knutsen, John] Massachusetts Gen Hosp Children MGH, Ctr Child & Adolescent Hlth Res & Policy, Boston, MA 02114 USA. [Knutsen, John] Harvard Med Sch HMS, Boston, MA USA. [Knutsen, John] Univ Penn, Philadelphia, PA 19104 USA. [Frye, Douglas] Univ Penn, Grad Sch Educ, Interdisciplinary Studies Human Dev Program, Philadelphia, PA 19104 USA. [Sobel, David M.] Brown Univ, Dept Cognit Linguist & Psychol Sci, Providence, RI 02912 USA. RP Knutsen, J (reprint author), Massachusetts Gen Hosp Children MGH, Ctr Child & Adolescent Hlth Res & Policy, Boston, MA 02114 USA. NR 100 TC 1 Z9 1 U1 0 U2 3 PU INFORMATION AGE PUBLISHING-IAP PI CHARLOTTE PA PO BOX 79049, CHARLOTTE, NC 28271-7047 USA BN 978-1-62396-511-2; 978-1-62396-512-9 J9 CONTEMP PERSPECT EAR PY 2014 BP 269 EP 290 PG 22 WC Education & Educational Research SC Education & Educational Research GA BA2KZ UT WOS:000333573800012 ER PT J AU Schalock, PC Dunnick, CA Nedorost, S Brod, B Warshaw, E Mowad, C AF Schalock, Peter C. Dunnick, Cory A. Nedorost, Susan Brod, Bruce Warshaw, Erin Mowad, Christen CA Amer Contact Dermatitis Soc Core A TI American Contact Dermatitis Society: Core Allergen SeriesVQuestions SO DERMATITIS LA English DT Letter C1 [Schalock, Peter C.] Harvard Univ, Sch Med, Dept Dermatol, Massachusetts Gen Hosp, Boston, MA 02115 USA. [Dunnick, Cory A.] Univ Colorado Denver, Dept Dermatol, Denver, CO USA. [Dunnick, Cory A.] Denver VA Med Ctr, Denver, CO USA. [Nedorost, Susan] Univ Hosp Cleveland, Dept Dermatol, Case Med Ctr, Cleveland, OH 44106 USA. [Brod, Bruce] Univ Penn, Dept Dermatol, Philadelphia, PA 19104 USA. [Warshaw, Erin] Univ Minnesota, Dept Dermatol, Minneapolis, MN 55455 USA. [Mowad, Christen] Geisinger Hlth Syst, Dept Dermatol, Danville, PA USA. RP Schalock, PC (reprint author), Massachusetts Gen Hosp, Dept Dermatol, BAR622,55 Fruit St, Boston, MA 02114 USA. EM schalock.prof@gmail.com OI Schalock, Peter/0000-0001-8953-4639 NR 1 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1710-3568 EI 2162-5220 J9 DERMATITIS JI Dermatitis PD JAN-FEB PY 2014 VL 25 IS 1 BP 39 EP 39 DI 10.1097/DER.0000000000000004 PG 1 WC Dermatology SC Dermatology GA AH6BD UT WOS:000336214800010 PM 24407062 ER PT J AU Grant, RW Clark, NG Desouza, CV Funnell, MM Goldfine, AB Laffel, L Marks, JB McCall, AL McWilliams, JR Pop-Busui, R Rasouli, N Rodriguez, H Simmons, DL Stankaitis, J Urbanski, P Fradkin, J Chiang, J Dunbar, S AF Grant, Richard W. Clark, Nathaniel G. Desouza, Cyrus V. Funnell, Martha M. Goldfine, Allison B. Laffel, Lori Marks, Jennifer B. McCall, Anthony L. McWilliams, Janis R. Pop-Busui, Rodica Rasouli, Neda Rodriguez, Henry Simmons, Debra L. Stankaitis, Joseph Urbanski, Patti Fradkin, Judith Chiang, Jane Dunbar, Stephanie TI Professional Practice Committee for the 2014 Clinical Practice Recommendations SO DIABETES CARE LA English DT Article C1 [Grant, Richard W.] Kaiser Permanente, Div Res, Oakland, CA 94612 USA. [Clark, Nathaniel G.] Jordan Hosp, Plymouth, MA USA. [Desouza, Cyrus V.] Univ Nebraska Med Ctr, Omaha, NE USA. [Desouza, Cyrus V.] Omaha VA Med Ctr, Omaha, NE USA. [Funnell, Martha M.; Pop-Busui, Rodica] Univ Michigan, Ann Arbor, MI 48109 USA. [Goldfine, Allison B.; Laffel, Lori] Joslin Diabet Ctr, Boston, MA 02215 USA. [Laffel, Lori] Harvard Univ, Sch Med, Boston, MA USA. [Marks, Jennifer B.] Miami VA, Miami, FL USA. [Marks, Jennifer B.] Univ Miami, Miller Sch Med, Diabet Res Inst, Miami, FL 33136 USA. [McCall, Anthony L.] Univ Virginia, Charlottesville, VA USA. [Rasouli, Neda] Univ Colorado, Denver, CO 80202 USA. [Rasouli, Neda] VA Eastern Colorado Hlth Care Syst, Denver, CO USA. [Rodriguez, Henry] Univ S Florida, Tampa, FL USA. [Simmons, Debra L.] Univ Utah, VA Salt Lake City Hlth Care Syst, Salt Lake City, UT USA. [Stankaitis, Joseph] Monroe Plan Med Care, Pittsford, NY USA. [Urbanski, Patti] Pbu consulting LLC, Cloquet, MN USA. [Fradkin, Judith] NIDDK, Bethesda, MD 20892 USA. [Chiang, Jane; Dunbar, Stephanie] ADA, Alexandria, VA USA. RP Grant, RW (reprint author), Kaiser Permanente, Div Res, Oakland, CA 94612 USA. FU AHRQ; NIDDK; Novo Nordisk; Asahi Kasei Pharma America; NHLBI; ADA; Daiichi Sankyo; Merck; Bayer; NIH; NICHD; T1D Exchange; Lilly; T1D Exchange Clinic Registry; Sanofi; Eli Lilly; LaunchPad; Bristol-Myers Squibb; Pfizer; Novartis; TrialNet; Helmsley Trust; New York Health Foundation; CDC; Takeda; Halozyme Therapeutics; Bristol-Myers Squibb/AstraZeneca Diabetes; Hygeia Inc.; Boehringer Ingelheim; GlaxoSmithKline; Johnson Johnson; Animas/LifeScan; Intuity Medical; Bayer Diagnostics; Oshadi Administrative Devices; Menarini; JDRF (International Advisory Board); LifeScan; Roche; Amgen; Janssen Pharmaceuticals, Inc.; AstraZeneca; Roche Diagnostics; TPG National Payor Roundtable; Celgene; Gilead; Medtronic; YourEncore Network FX Richard W. Grant, MD, MPH (Chair); AHRQ#, NIDDK#; Cyrus V. Desouza, MBBS; NIDDK#, Novo Nordisk#, Asahi Kasei Pharma America#; Allison B. Goldfine, MD; NIDDK#, NHLBI#, ADA#, Daiichi Sankyo#, Merck (site investigator); Lori Laffel, MD, MPH; Bayer#, NIH#, NIDDK#, NICHD#, T1D Exchange; B. Marks, MD; Lilly#, NIH#, NIDDK#, T1D Exchange Clinic Registry#; Anthony L. McCall, MD, PhD; Sanofi#, Eli Lilly#, NIDDK#, LaunchPad (UVA internal grant); Rodica Pop-Busui, MD, PhD; Bristol-Myers Squibb#, NIDDK#, NHLBI#; Neda Rasouli, MD; Novo Nordisk#, Bristol-Myers Squibb#, Merck#, NIDDK#, Pfizer#; Henry Rodriguez, MD; NIH#, Bristol-Myers Squibb#, Daiichi Sankyo#, Novartis#, Novo Nordisk#, TrialNet, Helmsley Trust; Joseph Stankaitis, MD, MPH; New York Health Foundation#, CDC#; C.V.D.; Novo Nordisk, Takeda; M.M.F.; Eli Lilly, Halozyme Therapeutics, Bristol-Myers Squibb/AstraZeneca Diabetes, Hygeia Inc., Boehringer Ingelheim, GlaxoSmithKline, Johnson & Johnson, Animas/LifeScan, Intuity Medical, Novo Nordisk, Bayer Diagnostics; L.L.; Oshadi Administrative Devices, Eli Lilly, Menarini, Johnson & Johnson, JDRF (International Advisory Board), Bristol-Myers Squibb, LifeScan, Sanofi, Roche, Novo Nordisk, Boehringer Ingelheim; J.B.M.; Amgen; R.P.-B.; T1D Exchange; Janssen Pharmaceuticals, Inc.; AstraZeneca; H.R.; Roche Diagnostics; J.S.; TPG National Payor Roundtable; Amgen; Celgene; Gilead; Janssen Pharmaceuticals, Inc.; P.U.; Eli Lilly; Medtronic; YourEncore Network; Janssen Pharmaceuticals, Inc. NR 0 TC 0 Z9 0 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 JAN PY 2014 VL 37 SU 1 BP S154 EP S155 PG 2 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA AI0EG UT WOS:000336518400014 ER PT J AU Haas, L Maryniuk, M Beck, J Cox, CE Duker, P Edwards, L Fisher, EB Hanson, L Kent, D Kolb, L McLaughlin, S Orzeck, E Piette, JD Rhinehart, AS Rothman, R Sklaroff, S Tomky, D Youssef, G AF Haas, Linda Maryniuk, Melinda Beck, Joni Cox, Carla E. Duker, Paulina Edwards, Laura Fisher, Edwin B. Hanson, Lenita Kent, Daniel Kolb, Leslie McLaughlin, Sue Orzeck, Eric Piette, John D. Rhinehart, Andrew S. Rothman, Russell Sklaroff, Sara Tomky, Donna Youssef, Gretchen CA 2012 Stand Revision Task Force TI National Standards for Diabetes Self-Management Education and Support SO DIABETES CARE LA English DT Article ID RANDOMIZED-CONTROLLED-TRIAL; CHRONIC CARE MODEL; CHRONIC DISEASE MANAGEMENT; QUALITY-OF-LIFE; AFRICAN-AMERICAN; GLYCEMIC CONTROL; CLINICAL CHARACTERISTICS; MEDICARE BENEFICIARIES; REGISTERED DIETITIANS; COMPLICATIONS TRIAL C1 [Haas, Linda] VA Puget Sound Hlth Care Syst Hosp & Specialty Me, Seattle, WA 98104 USA. [Maryniuk, Melinda] Joslin Diabet Ctr, Boston, MA 02215 USA. [Beck, Joni] Univ Oklahoma, Hlth Sci Ctr, Coll Med, Edmond, OK USA. [Cox, Carla E.] Western Montana Clin, Missoula, MT USA. [Duker, Paulina] Amer Diabet Assoc, Diabet Educ Clin Programs, Alexandria, VA USA. [Edwards, Laura] Ctr Hlth North Carolina, Apex, NC USA. [Fisher, Edwin B.] Univ N Carolina, Gillings Sch Global Publ Hlth, Amer Acad Family Phys Fdn, Peers Progress, Chapel Hill, NC USA. [Fisher, Edwin B.] Univ N Carolina, Gillings Sch Global Publ Hlth, Dept Hlth Behav, Chapel Hill, NC USA. [Hanson, Lenita] Ultracare Endocrine & Diabet Consultants, Venice, FL USA. [Kent, Daniel] Grp Hlth Cent Specialty Clin, Seattle, WA USA. [Kolb, Leslie] Amer Assoc Diabet Educators, Diabet Educ Accreditat Program, Chicago, IL USA. [McLaughlin, Sue] On Site Hlth & Wellness LLC, Omaha, NE USA. [Orzeck, Eric] Endocrinol Associates, Houston, TX USA. [Piette, John D.] VA Ctr Clin Management Res, Ann Arbor, MI USA. [Piette, John D.] Univ Michigan Hlth Syst, Ann Arbor, MI USA. [Rhinehart, Andrew S.] Johnston Mem Diabet Care Ctr, Abingdon, VA USA. [Rothman, Russell] Vanderbilt Univ, Med Ctr, Ctr Hlth Serv Res, Nashville, TN USA. [Tomky, Donna] ABQ Hlth Partners, Dept Endocrinol & Diabet, Albuquerque, NM USA. [Youssef, Gretchen] MedStar Hlth, MedStar Diabet Inst, Washington, DC USA. RP Haas, L (reprint author), VA Puget Sound Hlth Care Syst Hosp & Specialty Me, Seattle, WA 98104 USA. EM linda.haas@va.gov; melinda.maryniuk@joslin.harvard.edu NR 161 TC 59 Z9 67 U1 5 U2 34 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 JAN PY 2014 VL 37 SU 1 BP S144 EP S153 DI 10.2337/dc14-S144 PG 10 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA AI0EG UT WOS:000336518400013 PM 24357210 ER PT S AU Olesen, OV Wilm, J Paulsen, RR Hojgaard, L Larsen, R AF Olesen, Oline V. Wilm, Jakob Paulsen, Rasmus R. Hojgaard, Liselotte Larsen, Rasmus BE Douglass, MR King, PS Lee, BL TI DLP Technology Application: 3D Head Tracking and Motion Correction in Medical Brain Imaging SO EMERGING DIGITAL MICROMIRROR DEVICE BASED SYSTEMS AND APPLICATIONS VI SE Proceedings of SPIE LA English DT Proceedings Paper CT Conference on Emerging Digital Micromirror Device Based Systems and Applications VI CY FEB 04-05, 2014 CL San Francisco, CA SP SPIE, Samsung Adv Inst Technol, DLP Texas Instruments DE Structured light; computer vision system; head tracking; motion correction; phase shift interferometry; infrared DLP projection; positron emission tomography ID OPTICAL TRACKING; PET IMAGES; SYSTEM; INTERFEROMETRY; CAMERA; RANGE AB We demonstrate a tracking prototype system based on DLP Technology for medical brain imaging. The system referred to as Tracoline has been tested for motion correction in position emission tomography (PET) on phantom and human studies. This work summaries the complete system from the technical design to the used calibration and pose estimation methods, and finally the clinical demonstration. The Tracoline system is based on the Pico DLP light projector reengineered to project at near infrared wavelengths to maintain patient comfort. The system uses the principle of a structured light surface scanner to track the subject. Partial 3D surface representations of the forehead are computed from projection of a set of phase-shifted cosine patterns. The system returns the relative head poses used for motion compensation in the post processed medical image reconstruction or can potentially be used to feed the medical scanner on the fly for prospective motion compensation. The major advantage of the presented system for this particular application is; it does not rely on markers compared to other demonstrated systems. This makes the Tracoline system attractive for clinical use since time consuming and error prone marker attachment is avoided. In-situ dynamic PET data of a healthy subject shows significant reduction of acquisition artifacts. C1 [Olesen, Oline V.; Wilm, Jakob; Paulsen, Rasmus R.; Larsen, Rasmus] Tech Univ Denmark, Dept Appl Math & Comp Sci, DK-2800 Lyngby, Denmark. [Olesen, Oline V.; Wilm, Jakob; Hojgaard, Liselotte] Univ Copenhagen, Dept Clin Psysiol Nucl Med & PET, Copenhagen, Denmark. [Olesen, Oline V.] Massachusetts Gen Hosp, Athinoula AMartinos Ctr Biomed Imaging, Dept Radiol, Boston, MA 02114 USA. RP Olesen, OV (reprint author), Tech Univ Denmark, Dept Appl Math & Comp Sci, DK-2800 Lyngby, Denmark. EM ovol@dtu.dk OI Larsen, Rasmus/0000-0001-8507-0523 NR 33 TC 0 Z9 0 U1 0 U2 5 PU SPIE-INT SOC OPTICAL ENGINEERING PI BELLINGHAM PA 1000 20TH ST, PO BOX 10, BELLINGHAM, WA 98227-0010 USA SN 0277-786X BN 978-0-8194-9892-2 J9 PROC SPIE PY 2014 VL 8979 AR UNSP 897904 DI 10.1117/12.2035374 PG 11 WC Optics; Radiology, Nuclear Medicine & Medical Imaging SC Optics; Radiology, Nuclear Medicine & Medical Imaging GA BA4NH UT WOS:000336032300002 ER PT J AU Jaffe, AE Irizarry, RA AF Jaffe, Andrew E. Irizarry, Rafael A. TI Accounting for cellular heterogeneity is critical in epigenome-wide association studies SO GENOME BIOLOGY LA English DT Article ID DNA METHYLATION; GENE-EXPRESSION; HUMAN BRAIN; AGE; DISEASES; CANCER; TISSUE; BIRTH AB Background: Epigenome-wide association studies of human disease and other quantitative traits are becoming increasingly common. A series of papers reporting age-related changes in DNA methylation profiles in peripheral blood have already been published. However, blood is a heterogeneous collection of different cell types, each with a very different DNA methylation profile. Results: Using a statistical method that permits estimating the relative proportion of cell types from DNA methylation profiles, we examine data from five previously published studies, and find strong evidence of cell composition change across age in blood. We also demonstrate that, in these studies, cellular composition explains much of the observed variability in DNA methylation. Furthermore, we find high levels of confounding between age-related variability and cellular composition at the CpG level. Conclusions: Our findings underscore the importance of considering cell composition variability in epigenetic studies based on whole blood and other heterogeneous tissue sources. We also provide software for estimating and exploring this composition confounding for the Illumina 450k microarray. C1 [Jaffe, Andrew E.] Johns Hopkins Bloomberg Sch Publ Hlth, Lieber Inst Brain Dev, Baltimore, MD 21205 USA. [Jaffe, Andrew E.] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Biostat, Baltimore, MD 21205 USA. [Irizarry, Rafael A.] Harvard Univ, Sch Publ Hlth, Dana Farber Canc Inst, Boston, MA 02115 USA. [Irizarry, Rafael A.] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. RP Jaffe, AE (reprint author), Johns Hopkins Bloomberg Sch Publ Hlth, Lieber Inst Brain Dev, Johns Hopkins Med Campus, Baltimore, MD 21205 USA. EM andrew.jaffe@libd.org; rafa@jimmy.harvard.edu RI Jaffe, Andrew/L-3089-2016 OI Jaffe, Andrew/0000-0001-6886-1454 FU Lieber Institute for Brain Development Intramural Research Fund; National Institute of Health (NIH): National Institute of General Medical Sciences [2R01GM083084]; National Human Genome Research Institute/Center for Inherited Disease Research [1X01HG006605-01] FX Lieber Institute for Brain Development Intramural Research Fund, National Institute of Health (NIH): National Institute of General Medical Sciences (2R01GM083084) and National Human Genome Research Institute/Center for Inherited Disease Research (1X01HG006605-01). NR 31 TC 191 Z9 191 U1 5 U2 19 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1465-6906 EI 1474-760X J9 GENOME BIOL JI Genome Biol. PY 2014 VL 15 IS 2 AR R31 DI 10.1186/gb-2014-15-2-r31 PG 9 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA AH6QU UT WOS:000336256600014 PM 24495553 ER PT J AU Primiani, A Dias-Santagata, D Iafrate, AJ Kradin, RL AF Primiani, Andrea Dias-Santagata, Dora Iafrate, A. John Kradin, Richard L. TI Pulmonary adenocarcinoma mutation profile in smokers with smoking-related interstitial fibrosis SO INTERNATIONAL JOURNAL OF CHRONIC OBSTRUCTIVE PULMONARY DISEASE LA English DT Article DE lung; cancer; smoking; SRIF ID RESOLUTION COMPUTED-TOMOGRAPHY; POPULATION-BASED COHORT; LUNG-CANCER; SYSTEMIC-SCLEROSIS; RESPIRATORY BRONCHIOLITIS; EMPHYSEMA; PNEUMONIA; DISEASE; CARCINOMA; PATHOGENESIS AB Cigarette smoking is an established cause of lung cancer. However, pulmonary fibrosis is also an independent risk factor for the development of lung cancer. Smoking-related interstitial fibrosis (SRIF) has recently been reported. We hypothesized that adenocarcinomas in lungs with SRIF might show distinct molecular changes and examined the molecular phenotype of 168 resected lung adenocarcinomas in lungs with and without SRIF. The diagnosis of SRIF was determined by histological examination, based on the presence of alveolar septal thickening, due to pauci-inflamed, hyalinized, "ropy" collagen, in areas of lung greater than 1 cm away from the tumor. Tumors were concomitantly examined genotypically for mutations in genes frequently altered in cancer, including EGFR and KRAS, by SNaPshot and by fluorescence in situ hybridization for possible ALK rearrangements. Fluorescence in situ hybridization for ROS1 rearrangement (n = 36) and/or MET amplification (n = 31) were performed when no mutation was identified by either SNaPshot or ALK analysis. Sixty-five cases (38.7%) showed SRIF, which was distributed in all lobes of the lungs examined. No differences were observed in sex, average age, or smoking history in patients with and without SRIF. There was no difference in either the percent or types of adenocarcinoma genetic mutations in patients with SRIF versus those without. This data suggests that SRIF does not represent an independent risk factor for the development of the major known and targeted mutations seen in pulmonary adenocarcinoma. However, additional research is required to investigate the potential significance of SRIF in the pathogenesis of lung cancer. C1 [Primiani, Andrea; Dias-Santagata, Dora; Iafrate, A. John; Kradin, Richard L.] Massachusetts Gen Hosp, Pathol Serv, Boston, MA 02114 USA. [Kradin, Richard L.] Massachusetts Gen Hosp, Pulm Med Crit Care Unit, Dept Med, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Kradin, RL (reprint author), Massachusetts Gen Hosp, Pathol Serv, 55 Fruit St,Warren 253, Boston, MA 02114 USA. EM rkradin@partners.org NR 46 TC 0 Z9 0 U1 0 U2 0 PU DOVE MEDICAL PRESS LTD PI ALBANY PA PO BOX 300-008, ALBANY, AUCKLAND 0752, NEW ZEALAND SN 1178-2005 J9 INT J CHRONIC OBSTR JI Int. J. Chronic Obstr. Pulm. Dis. PY 2014 VL 9 BP 525 EP 530 DI 10.2147/COPD.S61932 PG 6 WC Respiratory System SC Respiratory System GA AH9DH UT WOS:000336440800001 PM 24920890 ER PT J AU Buzon, MJ Yang, Y Ouyang, ZY Sun, H Seiss, K Rogich, J Le Gall, S Pereyra, F Rosenberg, ES Yu, XG Lichterfeld, M AF Buzon, Maria J. Yang, Yue Ouyang, Zhengyu Sun, Hong Seiss, Katherine Rogich, Jerome Le Gall, Sylvie Pereyra, Florencia Rosenberg, Eric S. Yu, Xu G. Lichterfeld, Mathias TI Susceptibility to CD8 T-Cell-Mediated Killing Influences the Reservoir of Latently HIV-1-Infected CD4 T Cells SO JAIDS-JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES LA English DT Article DE cytotoxic T cells; HIV-1; viral reservoir; viral persistence ID HIV-INFECTED INDIVIDUALS; ANTIRETROVIRAL THERAPY; IMMUNE CONTROL; REPLICATION; CONTROLLERS; NONPROGRESSORS; PERSISTENCE; ACTIVATION; INHIBITION; RESPONSES AB Background: HIV-1 establishes a lifelong infection in the human body, but host factors that influence viral persistence remain poorly understood. Cell-intrinsic characteristics of CD4 T cells, the main target cells for HIV-1, may affect the composition of the latent viral reservoir by altering the susceptibility to CD8 T-cell-mediated killing. Results: We observed that susceptibilities of CD4 T cells to CD8 T-cell-mediated killing, as determined in direct ex vivo assays, were significantly higher in persons with natural control of HIV-1 (elite controllers) than in individuals effectively treated with antiretroviral therapy. These differences were most pronounced in naive and in terminally differentiated CD4 T cells and corresponded to a reduced viral reservoir size in elite controllers. Interestingly, the highest susceptibility to CD8 T-cell-mediated killing and lowest reservoirs of cell-associated HIV-1 DNA was consistently observed in elite controllers expressing the protective HLA class I allele B57. Conclusions: These data suggest that the functional responsiveness of host CD4 T cells to cytotoxic effects of HIV-1-specific CD8 T cells can contribute to shaping the structure and composition of the latently infected CD4 T-cell pool. C1 [Buzon, Maria J.; Yang, Yue; Rosenberg, Eric S.; Lichterfeld, Mathias] Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA. [Buzon, Maria J.; Yang, Yue; Ouyang, Zhengyu; Sun, Hong; Seiss, Katherine; Rogich, Jerome; Le Gall, Sylvie; Pereyra, Florencia; Yu, Xu G.] Ragon Inst MGH MIT & Harvard, Boston, MA USA. [Sun, Hong] China Med Univ, Affiliated Hosp 1, Lab AIDS Immunol, Shenyang, Peoples R China. [Pereyra, Florencia] Brigham & Womens Hosp, Div Infect Dis, Boston, MA 02115 USA. RP Lichterfeld, M (reprint author), Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA. EM mlichterfeld@partners.org RI Ouyang, Zhengyu/P-3576-2014; Buzon, Maria J/G-8286-2015 OI Buzon, Maria J/0000-0003-4427-9413 FU European Molecular Biology Organization; US National Institutes of Health [AI093203, AI098487]; Clinical Scientist Development Award from the Doris Duke Charitable Foundation [2009034]; American Foundation for AIDS Research [108302-51-RGRL]; Bill and Melinda Gates Foundation; Mark and Lisa Schwartz Foundation; International HIV Controller Study FX The authors have no conflicts of interest to disclose. M.J.B. is supported by a fellowship award from the European Molecular Biology Organization. M. L. is supported by the US National Institutes of Health (AI093203, AI098487), by the Clinical Scientist Development Award from the Doris Duke Charitable Foundation (grant number 2009034), and by the American Foundation for AIDS Research (grant 108302-51-RGRL). Recruitment of HIV-1 controllers was supported by the Bill and Melinda Gates Foundation, the Mark and Lisa Schwartz Foundation, and the International HIV Controller Study. NR 34 TC 2 Z9 2 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1525-4135 EI 1077-9450 J9 JAIDS-J ACQ IMM DEF JI JAIDS PD JAN 1 PY 2014 VL 65 IS 1 BP 1 EP 9 DI 10.1097/QAI.0b013e3182a1bc81 PG 9 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA AG8DY UT WOS:000335650200002 PM 23846565 ER PT J AU Morasco, BJ O'Neil, ME Duckart, JP Ganzini, L AF Morasco, Benjamin J. O'Neil, Maya E. Duckart, Jonathan P. Ganzini, Linda TI Comparison of Health Service Use Among Veterans With Methamphetamine Versus Alcohol Use Disorders SO JOURNAL OF ADDICTION MEDICINE LA English DT Article DE health service utilization; comorbidity; medical care; alcohol abuse; methamphetamine abuse ID MEDICAL ADVICE; ADMINISTRATIVE DATA; COMORBIDITY; SYMPTOMS; LEAVE; CARE; CONSUMPTION; IMPROVEMENT; PREVALENCE; RETENTION AB Objectives: Methamphetamine use disorders (MUD) are associated with severe health effects and psychiatric comorbidities, but little is known about the health care utilization of patients with MUD. The goal of this study was to describe health service use among veterans with MUD relative to a group of veterans with an alcohol use disorder (AUD). Methods: Using Veterans Affairs (VA) administrative data, we identified 718 patients who were diagnosed with MUD and had confirmatory drug testing. Data were compared with those of 744 patients who had diagnoses of an AUD also with confirmatory testing. We examined diagnoses and medical utilization for 5 years after their index date. Results: Patients with MUD and laboratory-confirmed recent use were younger and more likely to be diagnosed with a mood disorder, posttraumatic stress disorder, and a psychotic-spectrum disorder (all P values < 0.05). After statistical controls, patients with MUD were more likely to have an inpatient hospitalization (80% vs 70%, odds ratio [OR] = 1.8; 95% confidence interval [CI] = 1.4-2.3), discharge from an inpatient admission against medical advice (23.4% vs 8.3%, OR = 2.6, 95% CI = 1.9-3.7), receive care at 3 or more VA medical centers (13.1% vs 5.4%, OR = 2.3, 95% CI = 1.5-3.5), have a behavioral flag in the medical record (5.6% vs 1.1%, OR = 4.6, 95% CI = 2.1-10.6), and have more total missed appointments in the 5-year study period (M = 33.1 vs M = 23.5, P < 0.001). Conclusions: Among veterans with substance use disorders, those with MUD and laboratory-confirmed recent use have additional behavioral, health care utilization, and psychiatric characteristics that need to be considered in developing programs of care. C1 [Morasco, Benjamin J.; O'Neil, Maya E.; Ganzini, Linda] Portland VA Med Ctr, Mental Hlth & Clin Neurosci Div, Portland, OR USA. [Morasco, Benjamin J.; O'Neil, Maya E.; Ganzini, Linda] Oregon Hlth & Sci Univ, Dept Psychiat, Portland, OR 97201 USA. [Morasco, Benjamin J.; O'Neil, Maya E.; Duckart, Jonathan P.; Ganzini, Linda] Portland VA Med Ctr, Portland Ctr Study Chron Comorbid Mental & Phys D, Portland, OR USA. RP Morasco, BJ (reprint author), Portland VA Med Ctr R&D99, 3710 SW US Vet Hosp Rd, Portland, OR 97239 USA. EM benjamin.morasco@va.gov FU National Institute on Drug Abuse as part of the Methamphetamine Research Center at the Portland VA Medical Center [018165]; Oregon Health & Science University; VA Health Services Research and Development service [REA 06-174]; National Institute on Drug Abuse [K23DA023467] FX Supported in part by award 018165 from the National Institute on Drug Abuse to Drs. Ganzini and Morasco, as part of the Methamphetamine Research Center at the Portland VA Medical Center and Oregon Health & Science University. Dr Ganzini, Dr O'Neil, and Mr Duckart were supported in part by grant REA 06-174 from the VA Health Services Research and Development service. Dr Morasco received funding from grant K23DA023467 from the National Institute on Drug Abuse. NR 25 TC 0 Z9 0 U1 3 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1932-0620 EI 1935-3227 J9 J ADDICT MED JI J. Addict. Med. PD JAN-FEB PY 2014 VL 8 IS 1 BP 47 EP 52 DI 10.1097/ADM.0000000000000005 PG 6 WC Substance Abuse SC Substance Abuse GA AG8UB UT WOS:000335692600007 PM 24365802 ER PT J AU Winey, B Bussiere, M AF Winey, Brian Bussiere, Marc TI Geometric and dosimetric uncertainties in intracranial stereotatctic treatments for multiple nonisocentric lesions SO JOURNAL OF APPLIED CLINICAL MEDICAL PHYSICS LA English DT Article DE patient setup; radiosurgery; dosimetric errors ID STEREOTACTIC RADIATION-THERAPY; MODULATED ARC THERAPY; BRAIN METASTASES; GUIDED RADIOSURGERY; REAL-TIME; FRAMELESS; RADIOTHERAPY; CONSEQUENCES; RAPIDARC; SYSTEM AB The purpose of this study was to determine the effects of geometric uncertainties of patient position on treatments of multiple nonisocentric intracranial lesions. The average distance between lesions in patients with multiple targets was determined by a retrospective survey of patients with multiple lesions. Retrospective patient imaging data from fractionated stereotactic patients were used to calculate interfractional and intrafractional patient position uncertainty. Three different immobilization devices were included in the positioning study. The interfractional and intrafractional patient positioning error data were used to calculate the geometric offset of a lesion located at varying distances from the mechanical isocenter for treatments of multiple lesions with a single arc, assuming that no intrafractional position correction is employed during an arc rotation. Dosimetric effects were studied using two representative lesions of two sizes, 6 mm and 13 mm maximum dimensions, and prescribed to 20 Gy and 18 Gy, respectively. Distances between lesions ranged from < 10 mm to 150 mm, which would correspond to a range of isocenter to lesion separations of < 10 mm to 75 mm, assuming an isocenter located at the geometric mean. In the presence of a full six degree of freedom patient correction system, the effects of the intrafractional patient positioning uncertainties were less than 1.8 mm (3.6 mm) for 1 sigma (2 sigma) deviations for lesion spacing up to 75 mm assuming a quadratic summation of 1 sigma and 2 sigma. Without the benefit of a six DOF correction device, only correcting for three translations, the effects of the intrafractional patient positioning uncertainties were within 3.1 mm (7.2 mm) for 1 sigma (2s) deviations for distances up to 75 mm. 1s and 2s deviations along all six axes were observed in 3.6% and 0.3%, respectively, of 974 fractions analyzed. Dosimetric effects for 2 mm and 4 mm offsets were most significant for the small lesion with minimum dose (D-min) decreasing from 20 Gy to 13.6 Gy and 5.7 Gy and volume receiving the prescription (V-20Gy) reducing from 100% to 57% and 16%, respectively. The dosimetric effects on the larger lesion were less pronounced with D-min reducing from 18 Gy to 17.5 Gy and 14.2 Gy, and V-18Gy reducing from 100% to 98.3% and 85.4%, for 2 mm and 4 mm offsets, respectively. In the 1s scenario (3.6% of patients) angular uncertainties in patient positioning can introduce 1.0 mm shifts in the location of the lesion position at distances of 75 mm, compared to an isocentric treatment even with a full six DOF correction. Without the ability to correct angular positioning errors, a lesion positioned 75 mm away from the mechanical isocenter can be located in 3.6% of patients > 3.0 mm distant from the planned position. Dosimetric results depend upon the distance from isocenter and the size of the target. Single isocenter treatments for multiple lesions should be considered only when full six DOF corrections can be applied, the intrafractional immobilization precision is well quantified, and a PTV expansion is included for more distant lesions to account for unavoidable residual patient positioning uncertainties. C1 Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Winey, B (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Radiat Oncol, 30 Fruit St, Boston, MA 02114 USA. EM winey.brian@mgh.harvard.edu NR 21 TC 1 Z9 1 U1 0 U2 4 PU MULTIMED INC PI TORONTO PA 66 MARTIN ST, TORONTO, ON L9T 2R2, CANADA SN 1526-9914 J9 J APPL CLIN MED PHYS JI J. Appl. Clin. Med. Phys PY 2014 VL 15 IS 3 BP 122 EP 132 PG 11 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA AH3SA UT WOS:000336044300014 PM 28297360 ER PT J AU Thrailkill, K Bunn, RC Lumpkin, C Wahl, E Cockrell, G Morris, L Kahn, CR Fowlkes, J Nyman, JS AF Thrailkill, Kathryn Bunn, R. Clay Lumpkin, Charles, Jr. Wahl, Elizabeth Cockrell, Gael Morris, Lindsey Kahn, C. Ronald Fowlkes, John Nyman, Jeffry S. TI Loss of Insulin Receptor in Osteoprogenitor Cells Impairs Structural Strength of Bone SO JOURNAL OF DIABETES RESEARCH LA English DT Article ID ALKALINE-PHOSPHATASE ACTIVITY; DIABETIC METABOLIC STATE; COLLAGEN-SYNTHESIS; GLUCOSE-TRANSPORT; CORTICAL BONE; FRACTURE; RAT; MODULATION; RISK; LINE AB Type 1 diabetes mellitus (T1D) is associated with decreased bone mineral density, a deficit in bone structure, and subsequently an increased risk of fragility fracture. These clinical observations, paralleled by animal models of T1D, suggest that the insulinopenia of T1D has a deleterious effect on bone. To further examine the action of insulin signaling on bone development, we generated mice with an osteoprogenitor-selective (osterix-Cre) ablation of the insulin receptor (IR), designated OIRKO. OIRKO mice exhibited an 80% decrease in IR in osteoblasts. Prenatal elimination of IR did not affect fetal survival or gross morphology. However, loss of IR in mouse osteoblasts resulted in a postnatal growth-constricted phenotype. By 10-12 weeks of age, femurs of OIRKO mice were more slender, with a thinner diaphyseal cortex and, consequently, a decrease in whole bone strength when subjected to bending. In male mice alone, decreased metaphyseal trabecular bone, with thinner and more rodlike trabeculae, was also observed. OIRKO mice did not, however, exhibit abnormal glucose tolerance. The skeletal phenotype of the OIRKO mouse appeared more severe than that of previously reported bone-specific IR knockdown models, and confirms that insulin receptor expression in osteoblasts is critically important for proper bone development and maintenance of structural integrity. C1 [Thrailkill, Kathryn; Bunn, R. Clay; Lumpkin, Charles, Jr.; Wahl, Elizabeth; Cockrell, Gael; Morris, Lindsey; Fowlkes, John] Univ Arkansas Med Sci, Dept Pediat, Little Rock, AR 72205 USA. [Thrailkill, Kathryn] Arkansas Childrens Hosp, Little Rock, AR 72202 USA. [Lumpkin, Charles, Jr.; Wahl, Elizabeth] Arkansas Childrens Hosp, Res Inst, Little Rock, AR 72202 USA. [Morris, Lindsey] Vanderbilt Univ, Sch Med, Dept Med, Div Diabet Endocrinol & Metab, Nashville, TN USA. [Kahn, C. Ronald] Joslin Diabet Ctr, Boston, MA 02215 USA. [Kahn, C. Ronald] Harvard Univ, Sch Med, Boston, MA USA. [Nyman, Jeffry S.] Vanderbilt Univ, Med Ctr, VA Tennessee Valley Hlth Care Syst, Nashville, TN USA. [Nyman, Jeffry S.] Vanderbilt Univ, Med Ctr, Dept Orthopaed Surg & Rehabil, Nashville, TN USA. [Nyman, Jeffry S.] Vanderbilt Univ, Med Ctr, Ctr Bone Biol, Nashville, TN USA. RP Thrailkill, K (reprint author), Univ Arkansas Med Sci, Dept Pediat, Little Rock, AR 72205 USA. EM thrailkillkathrynm@uams.edu FU National Institutes of Health [R01 DK084045, C06RR16517]; Martha Ann Pugh Diabetes Research Fund; Arkansas Biosciences Institute; Children's University Medical Group Grant Program [36112] FX This work was supported by grants from the National Institutes of Health (R01 DK084045 to John Fowlkes and C06RR16517 to ACHRI), the Martha Ann Pugh Diabetes Research Fund (to Kathryn Thrailkill), the Arkansas Biosciences Institute (to John Fowlkes), and the Children's University Medical Group Grant Program (no. 36112 to John Fowlkes). This data was presented in part at the 42nd Annual International Sun Valley Workshop on Musculoskeletal Biology of the International Bone and Mineral Society (Sun Valley, Idaho, 2012). NR 29 TC 10 Z9 10 U1 1 U2 1 PU HINDAWI PUBLISHING CORPORATION PI NEW YORK PA 410 PARK AVENUE, 15TH FLOOR, #287 PMB, NEW YORK, NY 10022 USA SN 2314-6745 EI 2314-6753 J9 J DIABETES RES JI J. Diabetes Res. PY 2014 AR 703589 DI 10.1155/2014/703589 PG 9 WC Endocrinology & Metabolism; Medicine, Research & Experimental SC Endocrinology & Metabolism; Research & Experimental Medicine GA AI0KH UT WOS:000336535700001 ER PT J AU Zhu, JH Lim, KM Gordon, BR Wang, DY Lee, HP AF Zhu, Jian Hua Lim, Kian Meng Gordon, Bruce R. Wang, De Yun Lee, Heow Pueh TI Effects of Anterior Ethmoidectomy with and without Antrotomy and Uncinectomy on Nasal and Maxillary Sinus Airflows: a CFD Study SO JOURNAL OF MEDICAL AND BIOLOGICAL ENGINEERING LA English DT Article DE Endoscopic sinus surgery (ESS); Ethmoidectomy; Uncinectomy; Antrotomy; Maxillary sinus; Computational fluid dynamics (CFD) ID NANOPARTICLE DEPOSITION; VENTILATION; SURGERY; TURBINECTOMY; OUTCOMES; OSTIUM AB The effects of anterior ethmoidectomy, alone or combined with antrotomy and uncinectomy, on nasal and sinus airflow patterns were investigated using computational fluid dynamics (CFD) analysis of computed tomography scan-based three-dimensional nasal model reconstructions. The velocity, pressure, and airflow distribution, and airflow pathlines were evaluated. In model I, operated and non-operated airways were compared. In model II, the maxillary sinus was artificially sealed to evaluate the effects of ethmoidectomy alone. For both models, CFD simulations showed that post-op middle meatus airflow patterns were strongly affected, with higher air velocity, lower pressure, and larger-sized vortices, and the overall middle meatus airflow was redistributed laterally into the sinus cavities and away from the septum and superior meatus. Airflow rates at other intranasal sites were unaffected. The increase in post-op maxillary ventilation is larger than those in normal sinuses and sinuses with accessory ostia. Uncinectomy and antrotomy affect only local airflow within the antrum. In conclusion, middle meatus endoscopic sinus surgery (ESS) increases air exchange between sinuses and the nasal airway, increases middle meatus airflow at the expense of superior meatal flow, and produces vortices in the antrum and ethmoid. However, both ethmoidectomy and antrotomy/uncinectomy affect only local airflow, with negligible influence far from the operation site. These computed changes help us understand where dryness and mucus crusting is likely to occur following middle meatus ESS. C1 [Zhu, Jian Hua; Lim, Kian Meng; Lee, Heow Pueh] Natl Univ Singapore, Dept Mech Engn, Singapore 117576, Singapore. [Gordon, Bruce R.] Harvard Univ, Massachusetts Eye & Ear Infirm, Dept Otol & Laryngol, Boston, MA 02138 USA. [Gordon, Bruce R.] Cape Cod Hosp, Div Otolaryngol, Hyannis, MA 02601 USA. [Wang, De Yun] Natl Univ Singapore, Dept Otolaryngol, Singapore 117574, Singapore. [Lee, Heow Pueh] Natl Univ Singapore Suzhou, Res Inst, Jiangsu, Peoples R China. RP Zhu, JH (reprint author), Natl Univ Singapore, Dept Mech Engn, Singapore 117576, Singapore. EM jhzhu.me@gmail.com RI Lim, Kian-Meng/B-2556-2010; Lee, Heow Pueh/I-7834-2014 OI Lim, Kian-Meng/0000-0003-4311-9223; Lee, Heow Pueh/0000-0002-4380-3888 FU Ministry of Education, Singapore [T208A3103] FX The authors acknowledge the support by the Academic Research Grant (T208A3103) from the Ministry of Education, Singapore. This research was approved by the relevant Institutional Review Board. NR 17 TC 2 Z9 2 U1 0 U2 9 PU SPRINGER HEIDELBERG PI HEIDELBERG PA TIERGARTENSTRASSE 17, D-69121 HEIDELBERG, GERMANY SN 1609-0985 EI 2199-4757 J9 J MED BIOL ENG JI J. Med. Biol. Eng. PY 2014 VL 34 IS 2 BP 144 EP 149 DI 10.5405/jmbe.1710 PG 6 WC Engineering, Biomedical SC Engineering GA AH3KO UT WOS:000336022400008 ER PT J AU Leatherman, SM Liang, MH Krystal, JH Lew, RA Valley, D Thwin, SS Rosenheck, RA AF Leatherman, Sarah M. Liang, Matthew H. Krystal, John H. Lew, Robert A. Valley, Danielle Thwin, Soe Soe Rosenheck, Robert A. CA CSP 555 Investigators TI Differences in Treatment Effect Among Clinical Subgroups in a Randomized Clinical Trial of Long-Acting Injectable Risperidone and Oral Antipsychotics in Unstable Chronic Schizophrenia SO JOURNAL OF NERVOUS AND MENTAL DISEASE LA English DT Article DE Oral antipsychotics; injectable risperidone; subgroups; schizophrenia ID SCHIZOAFFECTIVE DISORDER; OPEN-LABEL; RELAPSE; THERAPY; DEPOT; PREVENTION; INSTRUMENT; EFFICACY; TABLETS; SAFETY AB A long-term randomized trial of unstable patients with schizophrenia found no benefit of long-acting injectable (LAI) risperidone over oral treatment in preventing or delaying time to psychiatric hospitalizations or on clinical outcomes. The initial analyses did not examine whether benefits of LAI emerged in selected subgroups. Patients with schizophrenia or schizoaffective disorder who had been hospitalized within the past 2 years or judged to be at risk for hospitalization because of increasing psychiatric service use were randomly assigned to LAI risperidone 12.5 to 50 mg per injection biweekly or to the psychiatrist's choice of oral antipsychotics and followed for up to 2 years. The primary endpoint was psychiatric rehospitalization. Symptoms, quality of life, and global functioning were assessed through blinded videoconference interviews. Cox's regression and mixed effects models were used to assess difference in treatment effect within 12 subgroups defined by hospitalization at study entry, substance abuse, race, symptom severity, quality of life, body mass index, age, race or sex, or reported medication compliance. Mixed models and Cox's regression using up to 24 months of follow-up data showed no significant differences in treatment effect in 10 of 12 subgroups on psychiatric symptoms, quality of life, or time to hospitalization. With adjustment for multiple comparisons, treatment effect differed by race on substance use outcomes, with white participants showing more benefit from LAI than other groups. LAI risperidone showed no superiority to psychiatrist's choice of oral treatment in most clinically defined subgroups, although the white patients benefited more than the other groups on substance abuse outcomes. C1 [Leatherman, Sarah M.; Liang, Matthew H.; Lew, Robert A.; Valley, Danielle; Thwin, Soe Soe] CSPCC, Massachusetts Vet Epidemiol & Res Informat Ctr MA, Boston, MA USA. [Krystal, John H.; Rosenheck, Robert A.] Yale Univ, Sch Med, New Haven, CT USA. [Krystal, John H.; Rosenheck, Robert A.] Vet Affairs VA Connecticut Healthcare Syst, West Haven, CT USA. RP Leatherman, SM (reprint author), VA Boston Healthcare Syst, MAVERIC MAV 151, 150 South Huntington Ave, Boston, MA 02130 USA. EM sarah.leatherman@va.gov FU Veterans Affairs Cooperative Studies Program; Ortho-McNeil Janssen Scientific Affairs, LLC; Eli Lilly; Janssen Pharmaceutica; Astra-Zeneca; Wyeth Pharmaceuticals FX This study was supported by the Veterans Affairs Cooperative Studies Program and an unrestricted grant from Ortho-McNeil Janssen Scientific Affairs, LLC. Risperdal Consta was donated by Ortho-McNeil Janssen Scientific Affairs, LLC, to the Department of Veterans Affairs.; Robert Rosenheck has received research support from Eli Lilly, Janssen Pharmaceutica, Astra-Zeneca, and Wyeth Pharmaceuticals. He has been a consultant to GlaxoSmithKline, Bristol Myers Squibb, Organon, and Janssen Pharmaceutica. He provided expert testimony for the plaintiffs in UFCW Local 1776 and Participating Employers Health and Welfare Fund et al. versus Eli Lilly and Company; for the respondent in Eli Lilly Canada Inc versus Novapharm Ltd and Minister of Health; and for the Patent Medicines Prices Review Board, Canada and in the matter of Janssen Ortho Inc and "Risperdal Consta." NR 22 TC 5 Z9 6 U1 2 U2 8 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0022-3018 EI 1539-736X J9 J NERV MENT DIS JI J. Nerv. Ment. Dis. PD JAN PY 2014 VL 202 IS 1 BP 13 EP 17 DI 10.1097/NMD.0000000000000069 PG 5 WC Clinical Neurology; Psychiatry SC Neurosciences & Neurology; Psychiatry GA AH8GM UT WOS:000336375000003 PM 24375206 ER PT J AU Morley, JF Duda, JE AF Morley, James F. Duda, John E. TI Use of Hyposmia and Other Non-Motor Symptoms to Distinguish between Drug-Induced Parkinsonism and Parkinson's Disease SO JOURNAL OF PARKINSONS DISEASE LA English DT Review DE Autonomic nervous system diseases; cognitive disorders; olfaction disorders; Parkinson disease; Parkinsonian syndrome; secondary ID NEUROLEPTIC-INDUCED PARKINSONISM; OLFACTORY DYSFUNCTION; IDENTIFICATION; SCINTIGRAPHY; ASSOCIATION; PERSISTENT; DISORDER; RISK AB Drug-induced Parkinsonism (DIP) secondary to antipsychotics and other dopamine antagonists is common and can be clinically indistinguishable from idiopathic Parkinson's disease (PD). Making the correct diagnosis is essential as it has important implications both for management of the underlying psychiatric condition and potentially lifelong therapy with antiparkinsonian agents. Additionally, because Parkinsonism does not always resolve with withdrawal of the offending agent or can recur years later, DIP may sometimes represent unmasking of incipient PD. The problem is increasing in scope as antipsychotic drugs are prescribed for a widening variety of indications, and understanding the factors that distinguish pharmacologic from degenerative Parkinsonism represents a significant unmet need. In this review, we discuss the rationale and evidence for using pre-clinical manifestations of PD, particularly non-motor symptoms, to distinguish between the conditions. C1 [Morley, James F.] Philadelphia VA Med Ctr, Parkinsons Dis Res Educ & Clin Ctr, Philadelphia, PA 19104 USA. [Duda, John E.] Univ Penn, Perelman Sch Med, Dept Neurol, Philadelphia, PA 19104 USA. RP Morley, JF (reprint author), Philadelphia VA Med Ctr, Parkinsons Dis Res Educ & Clin Ctr, 3900 Woodland Ave,Mail Stop 127, Philadelphia, PA 19104 USA. EM James.morley@va.gov NR 38 TC 2 Z9 2 U1 2 U2 4 PU IOS PRESS PI AMSTERDAM PA NIEUWE HEMWEG 6B, 1013 BG AMSTERDAM, NETHERLANDS SN 1877-7171 EI 1877-718X J9 J PARKINSON DIS JI J. Parkinsons Dis. PY 2014 VL 4 IS 2 BP 169 EP 173 DI 10.3233/JPD-130299 PG 5 WC Neurosciences SC Neurosciences & Neurology GA AH8SW UT WOS:000336409500006 PM 24284418 ER PT J AU Janne, PA Paz-Ares, L Oh, Y Eschbach, C Hirsh, V Enas, N Brail, L von Pawel, J AF Jaenne, Pasi A. Paz-Ares, Luis Oh, Yun Eschbach, Corinna Hirsh, Vera Enas, Nathan Brail, Leslie von Pawel, Joachim TI Randomized, Double-Blind, Phase II Trial Comparing Gemcitabine-Cisplatin plus the LTB4 Antagonist LY293111 versus Gemcitabine-Cisplatin plus Placebo in First-Line Non-Small-Cell Lung Cancer SO JOURNAL OF THORACIC ONCOLOGY LA English DT Article DE Cisplatin; Gemcitabine; hemotherapy; Leukotriene receptor agonist; Lung cancer; LY293111; Peroxisome proliferators; Activated receptor agonist ID B-4 RECEPTOR ANTAGONIST; SOLID TUMORS; COMBINATION; APOPTOSIS; LIGANDS; PROTEIN; GAMMA AB Introduction: In this phase II study, patients with stage IIIB/IV non-small-cell lung cancer were randomly assigned (1:1:1) to receive LY293111 (200 mg twice daily [200 LY293111] or 600 mg twice daily [600 LY293111]) or placebo for 7 days, followed by concurrent cisplatin (75 mg/m2; day 1) and gemcitabine (1250 mg/m2; days 1 and 8), every 21 days.The primary endpoint was progression-free survival, (PFS), with 75% power to detect 33% improvement compared with placebo (5 months). Methods: Of 200 randomized patients, 195 were treated. Demographics were well balanced across treatment arms: 65% of the patients were men; median age was 62 years; 85% had stage IV disease; and patients had an Eastern Cooperative Oncology Group performance status of 0 (36%) or 1 (64%). Results: The most frequent study drug-related toxicities were nausea, vomiting, and fatigue. Response rates were similar across treatment arms (200 LY293111: 20%; 600 LY293111: 25%; placebo: 31%). Conclusions: Median PFS (95% confidence interval) was not significantly different across treatment arms (200 LY293111: 4.6 months [3.2-5.0]; 600 LY293111: 5.6 months [4.1-6.8]; placebo: 6.0 months [5.2-7.5]). LY293111 combined with gemcitabine-cisplatin did not increase median PFS compared with placebo plus gemcitabine-cisplatin in patients with non-small-cell lung cancer. C1 [Jaenne, Pasi A.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02215 USA. [Jaenne, Pasi A.] Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. [Paz-Ares, Luis] Univ Seville, IBIS, Virgen del Rocio Hosp, Seville, Spain. [Paz-Ares, Luis] CSIC, E-41080 Seville, Spain. [Oh, Yun] Canc Care Ctr Frederick, Frederick, MD USA. [Eschbach, Corinna] Asklepios Klin Harburg, Hamburg, Germany. [Hirsh, Vera] Royal Victoria Hosp, Div Med Oncol, Montreal, PQ H3A 1A1, Canada. [Enas, Nathan; Brail, Leslie] Eli Lilly & Co, Indianapolis, IN 46285 USA. [von Pawel, Joachim] Asklepios Klinikum Gauting, Munich, Germany. RP Janne, PA (reprint author), Dana Farber Canc Inst, 450 Brookline Ave,HIM223, Boston, MA 02215 USA. EM pjanne@partners.org RI IBIS, NUEVAS TERAPIA/P-3415-2015 FU Eli Lilly and Company, Indianapolis, Indiana FX Financial support for this work was provided by Eli Lilly and Company, Indianapolis, Indiana. NR 15 TC 6 Z9 6 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 1556-0864 EI 1556-1380 J9 J THORAC ONCOL JI J. Thorac. Oncol. PD JAN PY 2014 VL 9 IS 1 BP 126 EP 131 DI 10.1097/JTO.0000000000000037 PG 6 WC Oncology; Respiratory System SC Oncology; Respiratory System GA AG6SC UT WOS:000335547700023 PM 24346102 ER PT J AU Swirski, FK AF Swirski, Filip K. TI Monocyte recruitment and macrophage proliferation in atherosclerosis SO KARDIOLOGIA POLSKA LA English DT Review ID LOW-DENSITY-LIPOPROTEIN; RECEPTOR-DEFICIENT MICE; IN-VIVO; REDUCES ATHEROSCLEROSIS; MYOCARDIAL-INFARCTION; SCAVENGER RECEPTORS; CELL-PROLIFERATION; LESION DEVELOPMENT; PROGENITOR CELLS; APOLIPOPROTEIN-E C1 [Swirski, Filip K.] Massachusetts Gen Hosp, Ctr Syst Biol, Boston, MA 02114 USA. [Swirski, Filip K.] Harvard Univ, Sch Med, Boston, MA USA. RP Swirski, FK (reprint author), Massachusetts Gen Hosp, Ctr Syst Biol, Boston, MA 02114 USA. EM fswirski@mgh.harvard.edu FU US National Institutes of Health (NIH) [R01-HL095612, R56-AI104695] FX This work was supported by US National Institutes of Health (NIH) grants R01-HL095612, R56-AI104695. NR 52 TC 2 Z9 4 U1 1 U2 6 PU VIA MEDICA PI GDANSK PA UL SWIETOKRZYSKA 73, 80-180 GDANSK, POLAND SN 0022-9032 EI 1897-4279 J9 KARDIOL POL JI Kardiol. Pol. PY 2014 VL 72 IS 4 BP 311 EP 314 DI 10.5603/KP.a2014.0021 PG 4 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA AH8HR UT WOS:000336378500001 PM 24526549 ER PT J AU Keebler, D Revill, P Braithwaite, S Phillips, A Blaser, N Borquez, A Cambiano, V Ciaranello, A Estill, J Gray, R Hill, A Keiser, O Kessler, J Menzies, NA Nucifora, KA Vizcaya, LS Walker, S Welte, A Easterbrook, P Doherty, M Hirnschall, G Hallett, TB AF Keebler, Daniel Revill, Paul Braithwaite, Scott Phillips, Andrew Blaser, Nello Borquez, Annick Cambiano, Valentina Ciaranello, Andrea Estill, Janne Gray, Richard Hill, Andrew Keiser, Olivia Kessler, Jason Menzies, Nicolas A. Nucifora, Kimberly A. Vizcaya, Luisa Salazar Walker, Simon Welte, Alex Easterbrook, Philippa Doherty, Meg Hirnschall, Gottfried Hallett, Timothy B. TI Cost-effectiveness of different strategies to monitor adults on antiretroviral treatment: a combined analysis of three mathematical models SO LANCET GLOBAL HEALTH LA English DT Article ID RESOURCE-LIMITED SETTINGS; CD4 CELL COUNT; STRATALL ANRS 12110/ESTHER; NON-INFERIORITY TRIAL; VIRAL LOAD; HIV TREATMENT; IMMUNOLOGICAL CRITERIA; VIROLOGICAL FAILURE; THERAPY; AFRICA AB Background WHO's 2013 revisions to its Consolidated Guidelines on antiretroviral drugs recommend routine viral load monitoring, rather than clinical or immunological monitoring, as the preferred monitoring approach on the basis of clinical evidence. However, HIV programmes in resource-limited settings require guidance on the most cost-effective use of resources in view of other competing priorities such as expansion of antiretroviral therapy coverage. We assessed the cost-effectiveness of alternative patient monitoring strategies. Methods We evaluated a range of monitoring strategies, including clinical, CD4 cell count, and viral load monitoring, alone and together, at different frequencies and with different criteria for switching to second-line therapies. We used three independently constructed and validated models simultaneously. We estimated costs on the basis of resource use projected in the models and associated unit costs; we quantified impact as disability-adjusted life years (DALYs) averted. We compared alternatives using incremental cost-effectiveness analysis. Findings All models show that clinical monitoring delivers significant benefit compared with a hypothetical baseline scenario with no monitoring or switching. Regular CD4 cell count monitoring confers a benefit over clinical monitoring alone, at an incremental cost that makes it affordable in more settings than viral load monitoring, which is currently more expensive. Viral load monitoring without CD4 cell count every 6-12 months provides the greatest reductions in morbidity and mortality, but incurs a high cost per DALY averted, resulting in lost opportunities to generate health gains if implemented instead of increasing antiretroviral therapy coverage or expanding antiretroviral therapy eligibility. Interpretation The priority for HIV programmes should be to expand antiretroviral therapy coverage, firstly at CD4 cell count lower than 350 cells per mu L, and then at a CD4 cell count lower than 500 cells per mu L, using lower-cost clinical or CD4 monitoring. At current costs, viral load monitoring should be considered only after high antiretroviral therapy coverage has been achieved. Point-of-care technologies and other factors reducing costs might make viral load monitoring more affordable in future. C1 [Keebler, Daniel; Welte, Alex] Univ Stellenbosch, Natl Res Fdn Ctr Excellence Epidemiol Modelling &, South African Dept Sci & Technol, ZA-7600 Stellenbosch, South Africa. [Revill, Paul; Walker, Simon] Univ York, Ctr Hlth Econ, York YO10 5DD, N Yorkshire, England. [Braithwaite, Scott; Kessler, Jason; Nucifora, Kimberly A.] NYU, Sch Med, New York, NY USA. [Phillips, Andrew; Cambiano, Valentina] UCL, Res Dept Infect & Populat Hlth, London, England. [Blaser, Nello; Estill, Janne; Keiser, Olivia; Vizcaya, Luisa Salazar] Univ Bern, Inst Social & Prevent Med, Div Int & Environm Hlth, Bern, Switzerland. [Borquez, Annick; Hallett, Timothy B.] Univ London Imperial Coll Sci Technol & Med, Dept Infect Dis Epidemiol, London W2 1PG, England. [Ciaranello, Andrea] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Gray, Richard] Univ New S Wales, Kirby Inst, Sydney, NSW, Australia. [Hill, Andrew] Univ Liverpool, Liverpool L69 3BX, Merseyside, England. [Menzies, Nicolas A.] Harvard Univ, Sch Publ Hlth, Ctr Hlth Decis Sci, Boston, MA 02115 USA. [Easterbrook, Philippa; Doherty, Meg; Hirnschall, Gottfried] WHO, HIV Programme, CH-1211 Geneva, Switzerland. RP Hallett, TB (reprint author), Univ London Imperial Coll Sci Technol & Med, Sch Publ Hlth, Norfolk Pl,St Marys Campus, London W2 1PG, England. EM timothy.hallett@imperial.ac.uk RI Phillips, Andrew/B-4427-2008; OI Phillips, Andrew/0000-0003-2384-4807; Blaser, Nello/0000-0001-9489-1657; Keiser, Olivia/0000-0001-8191-2789; Salazar-Vizcaya, Luisa/0000-0003-0527-0141 FU National Institutes of Health; National Institute of Allergy and Infectious Disease (NIAID) [K01 AI078754]; DfiD [202037]; UNITAID FX Funding for ALC was provided by the National Institutes of Health, including the National Institute of Allergy and Infectious Disease (NIAID) through K01 AI078754. The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH. PR received funding from DfiD (grant 202037). LS received funding from UNITAID. We thank the following people for their participation and input over the course of the Guidelines process: Ellen McRobie, Teri Roberts, Jen Cohn, Brooke Nichols, Theresa Rossouw, Gesine Meyer-Rath, David van de Vijver, and Gert Van Zyl. VC and AP thank UCL Research Computing Services (Legion Cluster) and input to the HIV Synthesis model from Deborah Ford, Alec Miners, Paul Revill, Fumiyo Nakagawa, and Deenan Pillay. NR 41 TC 25 Z9 25 U1 1 U2 5 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 2214-109X J9 LANCET GLOB HEALTH JI Lancet Glob. Health PD JAN PY 2014 VL 2 IS 1 BP E35 EP E43 DI 10.1016/S2214-109X(13)70048-2 PG 9 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA AH8YK UT WOS:000336423900016 PM 25104633 ER PT J AU Anagnostou, T Arvanitis, M Kourkoumpetis, TK Desalermos, A Carneiro, HA Mylonakis, E AF Anagnostou, Theodora Arvanitis, Marios Kourkoumpetis, Themistoklis K. Desalermos, Athanasios Carneiro, Herman A. Mylonakis, Eleftherios TI Nocardiosis of the Central Nervous System Experience From a General Hospital and Review of 84 Cases From the Literature SO MEDICINE LA English DT Review ID IMMUNODEFICIENCY-VIRUS-INFECTION; KIDNEY-TRANSPLANT RECIPIENT; FARCINICA BRAIN-ABSCESS; OF-THE-LITERATURE; CEREBRAL NOCARDIOSIS; IMMUNOCOMPETENT PATIENT; TRANSVALENSIS INFECTION; LABORATORY FEATURES; RISK-FACTORS; ASTEROIDES AB Central nervous system (CNS) nocardiosis is a rare disease entity caused by the filamentous bacteria Nocardia species. We present a case series of 5 patients from our hospital and a review of the cases of CNS nocardiosis reported in the literature from January 2000 to December 2011. Our results indicate that CNS nocardiosis can occur in both immunocompromised and immunocompetent individuals and can be the result of prior pulmonary infection or can exist on its own. The most common predisposing factors are corticosteroid use (54% of patients) and organ transplantation (25%). Presentation of the disease is widely variable, and available diagnostic tests are far from perfect, often leading to delayed detection and initiation of treatment. The optimal therapeutic approach is still undetermined and depends on speciation, but lower mortality and relapse rates have been reported with a combination of targeted antimicrobial treatment including trimethoprim/sulfomethoxazole (TMP-SMX) for more than 6 months and neurosurgical intervention. C1 [Anagnostou, Theodora; Kourkoumpetis, Themistoklis K.; Desalermos, Athanasios; Carneiro, Herman A.; Mylonakis, Eleftherios] Brown Univ, Warren Alpert Med Sch, Rhode Isl Hosp, Dept Med,Infect Dis Div, Providence, RI 02903 USA. [Anagnostou, Theodora; Arvanitis, Marios; Mylonakis, Eleftherios] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Med,Infect Dis Div, Boston, MA USA. RP Mylonakis, E (reprint author), Brown Univ, Warren Alpert Med Sch, Rhode Isl Hosp, 593 Eddy St, Providence, RI 02903 USA. EM emylonakis@lifespan.org NR 114 TC 10 Z9 11 U1 0 U2 5 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0025-7974 EI 1536-5964 J9 MEDICINE JI Medicine (Baltimore) PD JAN PY 2014 VL 93 IS 1 BP 19 EP 32 DI 10.1097/MD.0000000000000012 PG 14 WC Medicine, General & Internal SC General & Internal Medicine GA AH6ON UT WOS:000336250400003 PM 24378740 ER PT J AU Kiatpongsan, S Carlson, K Feibelmann, S Sepucha, K AF Kiatpongsan, Sorapop Carlson, Karen Feibelmann, Sandra Sepucha, Karen TI Decision aid reduces misperceptions about hormone therapy: a randomized controlled trial SO MENOPAUSE-THE JOURNAL OF THE NORTH AMERICAN MENOPAUSE SOCIETY LA English DT Article DE Decision aid; Hormone therapy; Menopause; Shared decision making; Menopausal symptom management ID QUALITY-OF-LIFE; MENOPAUSAL TRANSITION; POSTMENOPAUSAL WOMEN; FULL CIRCLE; SYMPTOMS; ESTROGEN AB Objective: This study aims to evaluate the role of a decision aid intervention in knowledge of menopausal symptom management. Methods: Five hundred fifteen US women who had menopausal symptoms and had discussed symptom management with providers within the past 12 months were assigned to either receive a decision aid or not. Participants completed a telephone survey 2 weeks after enrollment to assess knowledge. Overall knowledge scores and knowledge scores for general symptoms, benefits of hormone therapy, and risks of HT were compared between the decision aid arm and the control arm. Results: Four hundred one women completed the survey. Participants in the decision aid arm had a significantly higher mean (SD) knowledge score (63.3% [18.4%]) compared with the control arm (57.5% [16.4%]; P = 0.001). Specifically, participants in the decision aid arm had significantly higher scores for general symptoms (mean difference, 11.0; 95% CI, 5.3 to 16.6; P < 0.001) and knowledge about benefits of HT (mean difference, 4.2; 95% CI, 0.03 to 8.5; P = 0.048) compared with the control arm. However, scores on knowledge about HT risks were not different between the arms (mean difference, 2.1; 95% CI, -3.0 to 7.2; P = 0.422). Conclusions: The decision aid arm has greater knowledge of menopausal symptom management compared with the control arm, although the difference is small. In general, there is a considerable lack of knowledge about menopausal symptoms and HT risks. C1 [Kiatpongsan, Sorapop] Chulalongkorn Univ, Fac Med, Dept Obstet & Gynecol, Bangkok 10330, Thailand. [Kiatpongsan, Sorapop] Harvard Interfac Initiat Hlth Policy, Cambridge, MA USA. [Carlson, Karen; Feibelmann, Sandra; Sepucha, Karen] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Carlson, Karen; Sepucha, Karen] Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Sepucha, K (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Gen Med, Boston, MA 02114 USA. EM ksepucha@partners.org FU Informed Medical Decisions Foundation FX This work was supported by the Informed Medical Decisions Foundation. NR 26 TC 2 Z9 2 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1072-3714 EI 1530-0374 J9 MENOPAUSE JI Menopause-J. N. Am. Menopause Soc. PD JAN PY 2014 VL 21 IS 1 BP 33 EP 38 DI 10.1097/gme.0000000000000129 PG 6 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA AH6AQ UT WOS:000336213500007 PM 24326281 ER PT J AU Newton, KM Carpenter, JS Guthrie, KA Anderson, GL Caan, B Cohen, LS Ensrud, KE Freeman, EW Joffe, H Sternfeld, B Reed, SD Sherman, S Sammel, MD Kroenke, K Larson, JC LaCroix, AZ AF Newton, Katherine M. Carpenter, Janet S. Guthrie, Katherine A. Anderson, Garnet L. Caan, Bette Cohen, Lee S. Ensrud, Kristine E. Freeman, Ellen W. Joffe, Hadine Sternfeld, Barbara Reed, Susan D. Sherman, Sheryl Sammel, Mary D. Kroenke, Kurt Larson, Joseph C. LaCroix, Andrea Z. TI Methods for the design of vasomotor symptom trials: the Menopausal Strategies: Finding Lasting Answers to Symptoms and Health network SO MENOPAUSE-THE JOURNAL OF THE NORTH AMERICAN MENOPAUSE SOCIETY LA English DT Article DE Menopause; Yoga; Exercise; Hot flashes; Clinical trial network; Vasomotor symptoms; Study design; Methodology ID RANDOMIZED CONTROLLED-TRIAL; SLEEP QUALITY INDEX; HOT FLASHES; BREAST-CANCER; DOUBLE-BLIND; CHECKLIST HSCL; BRIEF PAIN; PHASE-III; VALIDATION; LIFE AB Objective: This report describes the Menopausal Strategies: Finding Lasting Answers to Symptoms and Health network and methodological issues addressed in designing and implementing vasomotor symptom trials. Methods: Established in response to a National Institutes of Health request for applications, the network was charged with conducting rapid throughput randomized trials of novel and understudied available interventions postulated to alleviate vasomotor and other menopausal symptoms. Included are descriptions of and rationale for criteria used for interventions and study selection, common eligibility and exclusion criteria, common primary and secondary outcome measures, consideration of placebo response, establishment of a biorepository, trial duration, screening and recruitment, statistical methods, and quality control. All trial designs are presented, including the following: (1) a randomized, double-blind, placebo-controlled clinical trial designed to evaluate the effectiveness of the selective serotonin reuptake inhibitor escitalopram in reducing vasomotor symptom frequency and severity; (2) a two-by-three factorial design trial to test three different interventions (yoga, exercise, and omega-3 supplementation) for the improvement of vasomotor symptom frequency and bother; and (3) a three-arm comparative efficacy trial of the serotonin-norepinephrine reuptake inhibitor venlafaxine and low-dose oral estradiol versus placebo for reducing vasomotor symptom frequency. The network's structure and governance are also discussed. Conclusions: The methods used in and the lessons learned from the Menopausal Strategies: Finding Lasting Answers to Symptoms and Health trials are shared to encourage and support the conduct of similar trials and to encourage collaborations with other researchers. C1 [Newton, Katherine M.] Grp Hlth Res Inst, Seattle, WA USA. [Carpenter, Janet S.] Indiana Univ, Sch Nursing, Indianapolis, IN 46204 USA. [Guthrie, Katherine A.; Anderson, Garnet L.; Larson, Joseph C.; LaCroix, Andrea Z.] Fred Hutchinson Canc Res Ctr, Data Coordinating Ctr, Seattle, WA 98104 USA. [Caan, Bette; Sternfeld, Barbara] Kaiser Permanente No Calif, Div Res, Oakland, CA USA. [Cohen, Lee S.; Joffe, Hadine] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. [Ensrud, Kristine E.] Univ Minnesota, VA Med Ctr, Minneapolis, MN USA. [Freeman, Ellen W.] Univ Penn, Sch Med, Dept Obstet Gynecol, Philadelphia, PA 19104 USA. [Freeman, Ellen W.] Univ Penn, Sch Med, Dept Psychiat, Philadelphia, PA 19104 USA. [Reed, Susan D.] Univ Washington, Sch Publ Hlth & Community Med, Dept Obstet Gynecol, Seattle, WA 98195 USA. [Reed, Susan D.] Univ Washington, Sch Publ Hlth & Community Med, Dept Epidemiol, Seattle, WA 98195 USA. [Sherman, Sheryl] NIA, US Natl Inst Hlth, Bethesda, MD 20892 USA. [Sammel, Mary D.] Univ Penn, Sch Med, Ctr Clin Epidemiol & Stat, Philadelphia, PA 19104 USA. [Kroenke, Kurt] VA Ctr Excellence Implementing Evidence Based Pra, Indianapolis, IN USA. [Kroenke, Kurt] Indiana Univ Sch Med, Indianapolis, IN 46202 USA. RP Newton, KM (reprint author), Grp Hlth Res Inst, Seattle, WA USA. EM newton.k@ghc.org FU National Institutes of Health, National Institute on Aging; Eunice Kennedy Shriver National Institute of Child Health and Human Development; National Center for Complementary and Alternative Medicine; Office of Research on Women's Health [U01 AG032656, U01AG032659, U01AG032669, U01AG032682, U01AG032699, U01AG032700] FX This study was funded by the National Institutes of Health as a cooperative agreement issued by the National Institute on Aging, the Eunice Kennedy Shriver National Institute of Child Health and Human Development, the National Center for Complementary and Alternative Medicine, and the Office of Research on Women's Health (U01 AG032656, U01AG032659, U01AG032669, U01AG032682, U01AG032699, and U01AG032700). NR 59 TC 22 Z9 22 U1 2 U2 5 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 1072-3714 EI 1530-0374 J9 MENOPAUSE JI Menopause-J. N. Am. Menopause Soc. PD JAN PY 2014 VL 21 IS 1 BP 45 EP 58 DI 10.1097/gme.0b013e31829337a4 PG 14 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA AH6AQ UT WOS:000336213500009 PM 23760428 ER PT J AU Lu, KH Skates, S Hernandez, MA Bedi, D Bevers, T Leeds, L Moore, R Granai, C Harris, S Newland, W Adeyinka, O Geffen, J Deavers, MT Sun, CC Horick, N Fritsche, H Bast, RC AF Lu, Karen H. Skates, Steven Hernandez, Mary A. Bedi, Deepak Bevers, Therese Leeds, Leroy Moore, Richard Granai, Cornelius Harris, Steven Newland, William Adeyinka, Olasunkanmi Geffen, Jeremy Deavers, Michael T. Sun, Charlotte C. Horick, Nora Fritsche, Herbert Bast, Robert C., Jr. TI A 2-Stage Ovarian Cancer Screening Strategy Using the Risk of Ovarian Cancer Algorithm (ROCA) Identifies Early-Stage Incident Cancers and Demonstrates High Positive Predictive Value EDITORIAL COMMENT SO OBSTETRICAL & GYNECOLOGICAL SURVEY LA English DT Editorial Material AB Diagnosis of ovarian cancer at an early stage is associated with a rate of survival of 75% or higher. Most women with this cancer are diagnosed at a late stage when long-term cure rates are less than 30%. Currently, there are no proven screening strategies for the early detection for ovarian cancer. A definitive diagnosis requires invasive surgery and removal of the ovaries. Any screening strategy for this cancer must minimize false positives to decrease the number of unnecessary operations. Measurement of fixed cut-point levels of carbohydrate antigen 125 (CA-125), an ovarian tumor marker, and an abnormal transvaginal ultrasound (TVS) finding have been used as a screening strategy for ovarian cancer; however, neither has sufficient specificity. Recent studies have shown that the sensitivity and specificity of screening with CA-125 can be improved when rising CA-125 levels, even within a reference range, are used to prompt TVS. The Risk of Ovarian Cancer Algorithm (ROCA) is a computer algorithm that quantifies the risk of developing ovarian cancer in postmenopausal women at normal risk who are screened for this cancer. The aim of this single-arm prospective study was to determine if a 2-step strategy that incorporates change of CA-125 levels over time and age has sufficient specificity and positive predictive value for estimating the risk of ovarian cancer in a population of postmenopausal women at normal risk. A small fraction of women with high-risk ROCA scores were referred for TVS as the second step of this strategy. Participants had an annual CA-125 blood test. Based on the ROCA score, women were triaged into the 1 of following 3 groups: a low-risk group (which would require return in 1 year for a CA-125 test), an intermediate-risk group (which would require women to repeat their CA-125 test in 3 months), or a high-risk group (which would require TVS and referral to a gynecologic oncologist). The decision for surgery was made by the gynecologic oncologist. The final study sample was composed of 4051 participants who were evaluated over 11 years (2001-2011). The average annual rate for triage to a CA-125 test in 3 months (intermediate-risk group) was 5.8%, and the average annual rate for triage to TVS and review by a gynecologic oncologist (high-risk group) was 0.9%. Ten women with suspicious TVS findings underwent surgery: 3 of these women had benign ovarian tumors, 2 had stage I ovarian serous tumors of low malignant potential, 4 had early-stage high-grade invasive ovarian cancers, and 1 patient was subsequently found to have endometrial cancer. The specificity with the 2-stage screening strategy was 99.9% (95% confidence interval [CI], 99.7%-100%). All 4 of the invasive ovarian cancers were found in women with normal, low-risk ROCA scores who had returned for annual CA-125 tests for at least 3 years prior to the rising CA-125 values. These data show that ROCA followed by TVS identifies early-stage incident ovarian cancer with excellent specificity and positive predictive value in a population of postmenopausal women at normal risk for ovarian cancer. C1 [Lu, Karen H.; Sun, Charlotte C.] Univ Texas MD Anderson Canc Ctr, Dept Gynecol Oncol & Reprod Med, Houston, TX 77030 USA. [Skates, Steven; Horick, Nora] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Biostat, Boston, MA USA. [Hernandez, Mary A.; Fritsche, Herbert; Bast, Robert C., Jr.] Univ Texas MD Anderson Canc Ctr, Off Translat Res, Houston, TX 77030 USA. [Bedi, Deepak] Univ Texas MD Anderson Canc Ctr, Dept Diagnost Radiol, Houston, TX 77030 USA. [Bevers, Therese] Univ Texas MD Anderson Canc Ctr, Dept Clin Canc Prevent, Houston, TX 77030 USA. [Leeds, Leroy] OGA Med Ctr, Houston, TX USA. [Moore, Richard; Granai, Cornelius] Brown Univ, Women & Infants Hosp, Providence, RI USA. [Harris, Steven] OB GYN Associates Dallas, Dallas, TX USA. [Newland, William] Iowa Clin, Womens Clin, W Des Moines, IA USA. [Adeyinka, Olasunkanmi] Univ Texas Family Phys, Houston, TX USA. [Geffen, Jeremy] Geffen Canc Ctr & Res Inst, Vero Beach, FL USA. Univ Texas MD Anderson Canc Ctr, Dept Pathol & Clin Pathol, Houston, TX 77030 USA. Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. RP Lu, KH (reprint author), Univ Texas MD Anderson Canc Ctr, Dept Gynecol Oncol & Reprod Med, Houston, TX 77030 USA. RI Bast, Robert/E-6585-2011 OI Bast, Robert/0000-0003-4621-8462 NR 0 TC 0 Z9 0 U1 1 U2 9 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0029-7828 EI 1533-9866 J9 OBSTET GYNECOL SURV JI Obstet. Gynecol. Surv. PD JAN PY 2014 VL 69 IS 1 BP 26 EP 27 DI 10.1097/01.ogx.0000442828.54138.67 PG 2 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA AH6RM UT WOS:000336258400014 ER PT J AU Freitag, SK Lee, H Lee, NG Johnstone, MA Sires, BS AF Freitag, Suzanne K. Lee, Henry Lee, Nahyoung Grace Johnstone, Murray A. Sires, Bryan S. TI Retrospective Review of Eyelash Number in Patients Who Have Undergone Full-Thickness Eyelid Resection SO OPHTHALMIC PLASTIC AND RECONSTRUCTIVE SURGERY LA English DT Article ID BIMATOPROST 0.03-PERCENT; GROWTH; HAIR; LATANOPROST; ERLOTINIB; FOLLICLES AB Purpose: The purpose of this study was to determine whether a localized full-thickness eyelid excision results in a proportional decrease in the total number of eyelashes or whether a full complement of visible lashes persists, thus suggesting a compensatory increase in the anagen/telogen ratio among the remaining follicles. Methods: A retrospective chart review was performed on 38 patients who underwent full-thickness eyelid resections repaired with primary eyelid closure for either benign or malignant eyelid lesions. Demographic and surgical data were collected, postoperative eyelid photographs were reviewed, and eyelashes were counted. Results: There were 10 upper eyelids and 28 lower eyelids in 10 men and 28 women, with an average age of 57.9 years (range, 14-86 years). The lesion pathology was benign in 21 cases (55%) and malignant in 17 cases (45%). The full-thickness defect involved <25% of the eyelid in 16 cases (42%) and >25% of the eyelid in 22 cases (58%). The follow-up period ranged from 50 to 319 days, with an average of 94 days. In contralateral controls, upper eyelids had an average of 72.1 lashes and lower eyelids had an average of 38.2 lashes, and there was no statistical significance between men and women. In lower lids that underwent <25% resection, control lids had an average of 37.3 lashes and operative lids had 37.1 lashes. In lower lids that underwent >25% resection, control lids had an average of 38.7 lashes and operative lids had 34.2 lashes. This represents an 11.6% decrease and was statistically significant. In upper eyelids that underwent <25% resection and >25% resection, control eyelids had an average of 74.9 lashes and 69.3 lashes and operative eyelids had 77.6 lashes and 69.1 lashes, respectively. Finally, lash count was compared by benign versus malignant pathologic diagnosis. In upper eyelids with benign lesions and malignant lesions, control eyelids had an average of 73.8 lashes and 65.3 lashes and operative eyelids had 74.6 lashes and 68.3 lashes, respectively. In lower eyelids with benign pathology and malignant lesions, control eyelids had an average of 34.5 lashes and 41.4 lashes and operative eyelids had 33.8 lashes and 36.8 lashes. This represents an 11.1% decrease and was statistically significant. Conclusions: Full-thickness excision of eyelid margin tissue including lashes does not usually affect postoperative lash numbers. Because the total number of follicles is reduced, the percentage of lashes in the anagen versus the resting or telogen phase apparently increases compared with the preoperative state. This eyelash study contributes to the growing body of literature on the poorly understood topic of hair follicle cycle regulation. C1 [Freitag, Suzanne K.; Lee, Nahyoung Grace] Harvard Univ, Sch Med, Dept Ophthalmol, Massachusetts Eye & Ear Infirm, Boston, MA USA. [Lee, Henry; Sires, Bryan S.] Allure Laser Ctr, Kirkland, WA USA. [Lee, Henry; Sires, Bryan S.] Medispa, Kirkland, WA USA. [Lee, Henry; Johnstone, Murray A.; Sires, Bryan S.] Univ Washington, Dept Ophthalmol, Seattle, WA 98195 USA. RP Freitag, SK (reprint author), Massachusetts Eye & Ear Infirm, Ophthalm Plast Surg Serv, 243 Charles St, Boston, MA 02114 USA. EM Suzanne_Freitag@meei.harvard.edu FU Heed Ophthalmic Foundation FX Dr. Nahyoung Grace Lee is a 2013-2014 Heed Fellow and received support from the Heed Ophthalmic Foundation. The remaining authors do not disclose financial or conflict of interest. NR 25 TC 2 Z9 2 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0740-9303 EI 1537-2677 J9 OPHTHAL PLAST RECONS JI Ophthalmic Plast. Reconstr. Surg. PD JAN-FEB PY 2014 VL 30 IS 1 BP 1 EP 6 DI 10.1097/IOP.0b013e3182a650bb PG 6 WC Ophthalmology; Surgery SC Ophthalmology; Surgery GA AG6WN UT WOS:000335559600001 PM 24398479 ER PT J AU Yoon, MK McCulley, TJ AF Yoon, Michael K. McCulley, Timothy J. TI Autologous Dermal Grafts as Posterior Lamellar Spacers in the Management of Lower Eyelid Retraction SO OPHTHALMIC PLASTIC AND RECONSTRUCTIVE SURGERY LA English DT Article ID HARD PALATE MUCOSA; GRAVES OPHTHALMOPATHY; ANIMAL RESEARCH; RECONSTRUCTION; SURGERY; EFFICACY; MATRIX AB Purpose: To determine the safety and efficacy of autologous postauricular dermal grafts as posterior lamellar spacing material in patients with lower eyelid retraction. Methods: At a tertiary care institution, 10 eyelids of 10 patients (7 men, 3 women; mean 56 years, range 24-78) who underwent repair of lower eyelid retraction using a postauricular dermal graft between July 2008 and December 2010 were retrospectively assessed. Data collected included patient demographics, etiology of retraction, and surgical history. Outcome measures included preoperative and postoperative eyelid position and surgery-related complications. Results: Postoperative results were favorable: mean preoperative inferior scleral show was 3.3 2.6 mm compared with 0.3 +/- 1.2 mm postoperatively, p = 0.004 (paired t test). Mean follow up was 39.2 weeks (range 12-94). Complications included keratinization of the graft with vellus hair growth (n = 1) and ectropion (n = 1), both corrected with minor surgical interventions. One patient achieved overcorrection but declined further treatment. No donor site complications were encountered. Conclusions: These data suggest postauricular dermal grafts are effective posterior lamellar spacers in the correction of eyelid retraction. They have adequate rigidity whilst maintaining sufficient pliability to mold to the globe. Resorption, common to acellular dermis matrix allografts and xenografts, was not encountered. Donor site complications were not encountered. Complications shared with other material include overcorrection and ectropion. Complications unique to autologous dermis include keratinization and hair growth. C1 [Yoon, Michael K.] Harvard Univ, Sch Med, Dept Ophthalmol, Boston, MA USA. [Yoon, Michael K.] Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. [McCulley, Timothy J.] Johns Hopkins Univ, Sch Med, Wilmer Eye Inst, Baltimore, MD 21205 USA. RP Yoon, MK (reprint author), 243 Charles St,10th Floor, Boston, MA 02114 USA. EM michael_yoon@meei.harvard.edu NR 32 TC 4 Z9 4 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0740-9303 EI 1537-2677 J9 OPHTHAL PLAST RECONS JI Ophthalmic Plast. Reconstr. Surg. PD JAN-FEB PY 2014 VL 30 IS 1 BP 64 EP 68 DI 10.1097/IOP.0000000000000012 PG 5 WC Ophthalmology; Surgery SC Ophthalmology; Surgery GA AG6WN UT WOS:000335559600027 PM 24398491 ER PT J AU Yoon, MK McCulley, TJ AF Yoon, Michael K. McCulley, Timothy J. TI Reply Re: "Secondary Tarsoconjunctival Graft: A Modification to the Cutler-Beard Procedure" SO OPHTHALMIC PLASTIC AND RECONSTRUCTIVE SURGERY LA English DT Letter C1 [Yoon, Michael K.] Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Ophthalmol, Boston, MA 02138 USA. RP Yoon, MK (reprint author), Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Ophthalmol, Boston, MA 02138 USA. EM michael_yoon@meei.harvard.edu NR 1 TC 0 Z9 0 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0740-9303 EI 1537-2677 J9 OPHTHAL PLAST RECONS JI Ophthalmic Plast. Reconstr. Surg. PD JAN-FEB PY 2014 VL 30 IS 1 BP 74 EP 74 DI 10.1097/IOP.0000000000000083 PG 1 WC Ophthalmology; Surgery SC Ophthalmology; Surgery GA AG6WN UT WOS:000335559600032 PM 24398496 ER PT J AU Fay, A De Castro, DK AF Fay, Aaron De Castro, Dawn K. TI Reply Re: "A Modified Lacrimal Sac Implant for High-Risk Dacryocystorhinostomy" SO OPHTHALMIC PLASTIC AND RECONSTRUCTIVE SURGERY LA English DT Letter ID FRONTAL-SINUS STENTS; EXTERNAL DACRYOCYSTORHINOSTOMY; LONG C1 [Fay, Aaron] Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. RP Fay, A (reprint author), Massachusetts Eye & Ear Infirm, 243 Charles St, Boston, MA 02114 USA. EM aaron_fay@meei.harvard.edu NR 11 TC 0 Z9 0 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0740-9303 EI 1537-2677 J9 OPHTHAL PLAST RECONS JI Ophthalmic Plast. Reconstr. Surg. PD JAN-FEB PY 2014 VL 30 IS 1 BP 75 EP 76 DI 10.1097/IOP.0000000000000085 PG 2 WC Ophthalmology; Surgery SC Ophthalmology; Surgery GA AG6WN UT WOS:000335559600034 PM 24398498 ER PT J AU Borodic, GE Caruso, P Acquadro, M Chick, S AF Borodic, Gary E. Caruso, Paul Acquadro, Martin Chick, Sarah TI Parry-Romberg Syndrome Vasculopathy and Its Treatment With Botulinum Toxin SO OPHTHALMIC PLASTIC AND RECONSTRUCTIVE SURGERY LA English DT Article ID PROGRESSIVE FACIAL HEMIATROPHY; SCLERODERMA EN COUP; RAYNAUDS-PHENOMENON; SABRE; PAIN; THERAPY AB Parry-Romberg syndrome is a rare condition characterized by progressive, hemifacial atrophy, hair loss, enophthalmos, retinal vasculopathy occasionally associated with hemicranial pain syndrome (secondary trigeminal neuralgia). The cause of the condition is unknown; however, substantial evidence suggests that vasculopathy plays a significant role in the genesis of the neurologic damage and facial lipodystrophy. Herein describes a case of Parry-Romberg syndrome treated with repetitive botulinum type A toxin injections, with almost complete resolution of severe chronic pain. C1 [Borodic, Gary E.; Caruso, Paul] Harvard Univ, Sch Med, Dept Ophthalmol, Massachusetts Eye & Ear Infirm, Quincy, MA 02169 USA. [Caruso, Paul] Massachusetts Gen Hosp, Dept Neuroradiol, Boston, MA 02114 USA. [Acquadro, Martin] Tufts Univ, Sch Med, St Elizabeths Hosp, Dept Anesthesia, Brighton, MA USA. RP Borodic, GE (reprint author), Harvard Univ, Sch Med, 1261 Furnace Brook Pkwy, Quincy, MA 02169 USA. EM borodic@aol.com NR 25 TC 4 Z9 4 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0740-9303 EI 1537-2677 J9 OPHTHAL PLAST RECONS JI Ophthalmic Plast. Reconstr. Surg. PD JAN-FEB PY 2014 VL 30 IS 1 BP E22 EP E25 DI 10.1097/IOP.0b013e31828de9c0 PG 4 WC Ophthalmology; Surgery SC Ophthalmology; Surgery GA AG6WN UT WOS:000335559600017 PM 23719195 ER PT J AU Kikuchi, K Hettmer, S Aslam, MI Michalek, JE Laub, W Wilky, BA Loeb, DM Rubin, BP Wagers, AJ Keller, C AF Kikuchi, Ken Hettmer, Simone Aslam, M. Imran Michalek, Joel E. Laub, Wolfram Wilky, Breelyn A. Loeb, David M. Rubin, Brian P. Wagers, Amy J. Keller, Charles TI Cell-Cycle Dependent Expression of a Translocation-Mediated Fusion Oncogene Mediates Checkpoint Adaptation in Rhabdomyosarcoma SO PLOS GENETICS LA English DT Article ID NEGATIVE ALVEOLAR RHABDOMYOSARCOMA; POLO-LIKE KINASE; RISK STRATIFICATION; MUSCLE-CELLS; MOUSE MODEL; CHILDREN; ADOLESCENTS; TARGET; CHEMOTHERAPY; LEUKEMIA AB Rhabdomyosarcoma is the most commonly occurring soft-tissue sarcoma in childhood. Most rhabdomyosarcoma falls into one of two biologically distinct subgroups represented by alveolar or embryonal histology. The alveolar subtype harbors a translocation-mediated PAX3:FOXO1A fusion gene and has an extremely poor prognosis. However, tumor cells have heterogeneous expression for the fusion gene. Using a conditional genetic mouse model as well as human tumor cell lines, we show that that Pax3:Foxo1a expression is enriched in G2 and triggers a transcriptional program conducive to checkpoint adaptation under stress conditions such as irradiation in vitro and in vivo. Pax3:Foxo1a also tolerizes tumor cells to clinically-established chemotherapy agents and emerging molecularly-targeted agents. Thus, the surprisingly dynamic regulation of the Pax3:Foxo1a locus is a paradigm that has important implications for the way in which oncogenes are modeled in cancer cells. C1 [Kikuchi, Ken; Aslam, M. Imran; Keller, Charles] Oregon Hlth & Sci Univ, Dept Pediat, Pape Family Pediat Res Inst, Pediat Canc Biol Program, Portland, OR 97201 USA. [Hettmer, Simone; Wagers, Amy J.] Harvard Univ, Howard Hughes Med Inst, Cambridge, MA 02138 USA. [Hettmer, Simone; Wagers, Amy J.] Harvard Univ, Dept Stem Cell & Regenerat Biol, Cambridge, MA 02138 USA. [Hettmer, Simone; Wagers, Amy J.] Joslin Diabet Ctr, Boston, MA 02215 USA. [Hettmer, Simone] Childrens Hosp, Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. [Hettmer, Simone] Childrens Hosp, Div Pediat Hematol Oncol, Boston, MA 02115 USA. [Michalek, Joel E.] Univ Texas Hlth Sci Ctr San Antonio, Dept Epidemiol & Biostat, San Antonio, TX 78229 USA. [Laub, Wolfram] Oregon Hlth & Sci Univ, Dept Radiat Med, Portland, OR 97201 USA. [Wilky, Breelyn A.] Johns Hopkins Univ, Sidney Kimmel Comprehens Canc Ctr, Div Med Oncol, Baltimore, MD USA. [Loeb, David M.] Johns Hopkins Univ, Sidney Kimmel Comprehens Canc Ctr, Div Pediat Oncol, Baltimore, MD USA. [Rubin, Brian P.] Cleveland Clin Fdn, Dept Anat Pathol, Taussig Canc Ctr, Cleveland, OH 44195 USA. [Rubin, Brian P.] Cleveland Clin Fdn, Dept Mol Genet, Taussig Canc Ctr, Cleveland, OH 44195 USA. [Rubin, Brian P.] Cleveland Clin Fdn, Lerner Res Inst, Cleveland, OH 44195 USA. RP Kikuchi, K (reprint author), Oregon Hlth & Sci Univ, Dept Pediat, Pape Family Pediat Res Inst, Pediat Canc Biol Program, Portland, OR 97201 USA. EM keller@ohsu.edu OI Kikuchi, Ken/0000-0003-3097-7480 FU NCI [5R01CA133229]; Burroughs-Wellcome Fund; Harvard Stem Cell Institute; Beckman Foundation; Hope Street Kids; P.A.L.S. Bermuda/St. Baldrick's; ALSF; Bear Necessities FX This work was supported by NCI award 5R01CA133229 (to CK) as well as by grants from the Burroughs-Wellcome Fund, Harvard Stem Cell Institute, and Beckman Foundation (to AJW), and by Hope Street Kids, P.A.L.S. Bermuda/St. Baldrick's, ALSF and Bear Necessities (to SH). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 37 TC 11 Z9 13 U1 0 U2 1 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1553-7390 EI 1553-7404 J9 PLOS GENET JI PLoS Genet. PD JAN PY 2014 VL 10 IS 1 AR e1004107 DI 10.1371/journal.pgen.1004107 PG 13 WC Genetics & Heredity SC Genetics & Heredity GA AI0GU UT WOS:000336525000062 PM 24453992 ER PT J AU Kurki, MI Gaal, EI Kettunen, J Lappalainen, T Menelaou, A Anttila, V van't Hof, FNG von und zu Fraunberg, M Helisalmi, S Hiltunen, M Lehto, H Laakso, A Kivisaari, R Koivisto, T Ronkainen, A Rinne, J Kiemeney, LAL Vermeulen, SH Kaunisto, MA Eriksson, JG Aromaa, A Perola, M Lehtimaki, T Raitakari, OT Salomaa, V Gunel, M Dermitzakis, ET Ruigrok, YM Rinkel, GJE Niemela, M Hernesniemi, J Ripatti, S de Bakker, PIW Palotie, A Jaaskelainen, JE AF Kurki, Mitja I. Gaal, Emilia Ilona Kettunen, Johannes Lappalainen, Tuuli Menelaou, Androniki Anttila, Verneri van't Hof, Femke N. G. von und zu Fraunberg, Mikael Helisalmi, Seppo Hiltunen, Mikko Lehto, Hanna Laakso, Aki Kivisaari, Riku Koivisto, Timo Ronkainen, Antti Rinne, Jaakko Kiemeney, Lambertus A. L. Vermeulen, Sita H. Kaunisto, Mari A. Eriksson, Johan G. Aromaa, Arpo Perola, Markus Lehtimaki, Terho Raitakari, Olli T. Salomaa, Veikko Gunel, Murat Dermitzakis, Emmanouil T. Ruigrok, Ynte M. Rinkel, Gabriel J. E. Niemela, Mika Hernesniemi, Juha Ripatti, Samuli de Bakker, Paul I. W. Palotie, Aarno Jaaskelainen, Juha E. TI High Risk Population Isolate Reveals Low Frequency Variants Predisposing to Intracranial Aneurysms SO PLOS GENETICS LA English DT Article ID GENOME-WIDE ASSOCIATION; ABDOMINAL AORTIC-ANEURYSM; SUBARACHNOID HEMORRHAGE; CARDIOVASCULAR RISK; SEQUENCE VARIANT; IDENTIFIES 3; AGE; SUSCEPTIBILITY; DISEASE; LOCI AB 3% of the population develops saccular intracranial aneurysms (sIAs), a complex trait, with a sporadic and a familial form. Subarachnoid hemorrhage from sIA (sIA-SAH) is a devastating form of stroke. Certain rare genetic variants are enriched in the Finns, a population isolate with a small founder population and bottleneck events. As the sIA-SAH incidence in Finland is >2x increased, such variants may associate with sIA in the Finnish population. We tested 9.4 million variants for association in 760 Finnish sIA patients (enriched for familial sIA), and in 2,513 matched controls with case-control status and with the number of sIAs. The most promising loci (p<5E-6) were replicated in 858 Finnish sIA patients and 4,048 controls. The frequencies and effect sizes of the replicated variants were compared to a continental European population using 717 Dutch cases and 3,004 controls. We discovered four new high-risk loci with low frequency lead variants. Three were associated with the case-control status: 2q23.3 (MAF 2.1%, OR 1.89, p 1.42x10-9); 5q31.3 (MAF 2.7%, OR 1.66, p 3.17x10-8); 6q24.2 (MAF 2.6%, OR 1.87, p 1.87x10-11) and one with the number of sIAs: 7p22.1 (MAF 3.3%, RR 1.59, p 6.08x-9). Two of the associations (5q31.3, 6q24.2) replicated in the Dutch sample. The 7p22.1 locus was strongly differentiated; the lead variant was more frequent in Finland (4.6%) than in the Netherlands (0.3%). Additionally, we replicated a previously inconclusive locus on 2q33.1 in all samples tested (OR 1.27, p 1.87x10-12). The five loci explain 2.1% of the sIA heritability in Finland, and may relate to, but not explain, the increased incidence of sIA-SAH in Finland. This study illustrates the utility of population isolates, familial enrichment, dense genotype imputation and alternate phenotyping in search for variants associated with complex diseases. C1 [Kurki, Mitja I.; Koivisto, Timo; Ronkainen, Antti; Rinne, Jaakko; Jaaskelainen, Juha E.] Kuopio Univ Hosp, NeuroCtr, SF-70210 Kuopio, Finland. [Kurki, Mitja I.; Jaaskelainen, Juha E.] Univ Eastern Finland, Inst Clin Med, Kuopio, Finland. [Kurki, Mitja I.] Univ Eastern Finland, AI Virtanen Inst Mol Sci, Dept Neurobiol, Kuopio, Finland. [Gaal, Emilia Ilona; Lehto, Hanna; Laakso, Aki; Kivisaari, Riku; Niemela, Mika; Hernesniemi, Juha] Univ Helsinki, Cent Hosp, Dept Neurosurg, Helsinki, Finland. [Kettunen, Johannes; Anttila, Verneri; Kaunisto, Mari A.; Perola, Markus; Ripatti, Samuli; Palotie, Aarno] Univ Helsinki, Inst Mol Med Finland FIMM, Helsinki, Finland. [Kettunen, Johannes; Aromaa, Arpo; Perola, Markus; Salomaa, Veikko; Ripatti, Samuli] Natl Inst Hlth & Welf, Dept Chron Dis Prevent, Helsinki, Finland. [Lappalainen, Tuuli; Dermitzakis, Emmanouil T.] Univ Geneva, Sch Med, Dept Genet Med & Dev, CH-1211 Geneva, Switzerland. [Menelaou, Androniki; de Bakker, Paul I. W.] Univ Med Ctr Utrecht, Dept Med Genet, Utrecht, Netherlands. [Anttila, Verneri; Palotie, Aarno] Massachusetts Gen Hosp, Dept Med, Analyt & Translat Genet Unit, Boston, MA 02114 USA. [Anttila, Verneri; Palotie, Aarno] Harvard Univ, Sch Med, Boston, MA USA. [Anttila, Verneri; de Bakker, Paul I. W.; Palotie, Aarno] Broad Inst Harvard & MIT, Program Med & Populat Genet, Cambridge, MA USA. [van't Hof, Femke N. G.; Ruigrok, Ynte M.; Rinkel, Gabriel J. E.] Univ Med Ctr Utrecht, Rudolf Magnus Inst Neurosci, Dept Neurol & Neurosurg, UMC Utrecht Stroke Ctr, Utrecht, Netherlands. [von und zu Fraunberg, Mikael; Helisalmi, Seppo; Hiltunen, Mikko] Univ Eastern Finland, Inst Clin Med, Kuopio, Finland. [Kiemeney, Lambertus A. L.] Radboud Univ Nijmegen, Med Ctr, Dept Urol, NL-6525 ED Nijmegen, Netherlands. [Kiemeney, Lambertus A. L.; Vermeulen, Sita H.] Radboud Univ Nijmegen, Med Ctr, Dept Hlth Evidence, NL-6525 ED Nijmegen, Netherlands. [Kaunisto, Mari A.; Eriksson, Johan G.] Folkhalsan Res Ctr, Helsinki, Finland. [Eriksson, Johan G.] Natl Inst Hlth & Welf, Dept Chron Dis Prevent, Helsinki, Finland. [Eriksson, Johan G.] Univ Helsinki, Dept Gen Practice & Primary Hlth Care, Helsinki, Finland. [Eriksson, Johan G.] Vasa Cent Hosp, Dept Internal Med, Vaasa, Finland. [Eriksson, Johan G.] Univ Helsinki, Cent Hosp, Unit Gen Practice, Helsinki, Finland. [Perola, Markus] Univ Tartu, Estonian Genome Ctr, EE-50090 Tartu, Estonia. [Lehtimaki, Terho] Tampere Univ Hosp, Fimlab Labs, Dept Clin Chem, Tampere, Finland. [Lehtimaki, Terho] Univ Tampere, FIN-33101 Tampere, Finland. [Raitakari, Olli T.] Univ Turku, Dept Clin Physiol & Nucl Med, Turku, Finland. [Raitakari, Olli T.] Turku Univ Hosp, FIN-20520 Turku, Finland. [Raitakari, Olli T.] Univ Turku, Res Ctr Appl & Prevent Cardiovasc Med, Turku, Finland. [Raitakari, Olli T.] Turku Univ, Cent Hosp, Turku, Finland. [Gunel, Murat] Yale Univ, Sch Med, Howard Hughes Med Inst, Dept Neurosurg,Dept Neurobiol, New Haven, CT 06510 USA. [Gunel, Murat] Yale Univ, Sch Med, Howard Hughes Med Inst, Dept Genet,Program Neurogenet, New Haven, CT 06510 USA. [Ripatti, Samuli] Univ Helsinki, Hjelt Inst, Helsinki, Finland. [de Bakker, Paul I. W.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Div Genet,Dept Med, Boston, MA 02115 USA. [de Bakker, Paul I. W.] Univ Med Ctr Utrecht, Dept Epidemiol, Utrecht, Netherlands. [Palotie, Aarno] Wellcome Trust Sanger Inst, Dept Human Genet, Cambridge, England. RP Kurki, MI (reprint author), Kuopio Univ Hosp, NeuroCtr, SF-70210 Kuopio, Finland. EM mitja.kurki@uef.fi RI de Bakker, Paul/B-8730-2009; Niemela, Mika/F-2539-2015; Ripatti, Samuli/H-9446-2014; Vermeulen, H.H.M./L-4716-2015; OI de Bakker, Paul/0000-0001-7735-7858; Niemela, Mika/0000-0003-1526-0684; Ripatti, Samuli/0000-0002-0504-1202; Anttila, Verneri/0000-0002-0073-4675; Lappalainen, Tuuli/0000-0002-7746-8109; Eriksson, Johan/0000-0002-2516-2060; Kaunisto, Mari/0000-0002-6946-9195 FU Academy of Finland; Paivikki and Sakari Sohlberg Foundation; Kuopio University Hospital; Dutch Heart Foundation [2008B004]; NWO-VENI grant by the Netherlands Organization for Scientific Research (NWO) [91610016]; Wellcome Trust; Orion Farmos Research Foundation; Health Research Council of the Academy of Finland; EVO of Kuopio University Hospital [5772708]; University of Eastern Finland (UEF-Brain); Sigrid Juselius Foundation; Finnish Foundation for Cardiovascular Research FX This research was funded by grants from the Academy of Finland, the Paivikki and Sakari Sohlberg Foundation, and the Kuopio University Hospital (MIK, MvuzF, JEJ), Dutch Heart Foundation (NHS) (project no. 2008B004) (FNGvH), a NWO-VENI grant by the Netherlands Organization for Scientific Research (NWO) (project no. 91610016) (YMR), the Wellcome Trust (AP, VA), the Orion Farmos Research Foundation (VA), Health Research Council of the Academy of Finland (MH), EVO grant 5772708 of Kuopio University Hospital (MH), the Strategic Funding of the University of Eastern Finland (UEF-Brain, MH), Sigrid Juselius Foundation (MH) and Finnish Foundation for Cardiovascular Research (VS). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 61 TC 16 Z9 16 U1 0 U2 3 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1553-7390 EI 1553-7404 J9 PLOS GENET JI PLoS Genet. PD JAN PY 2014 VL 10 IS 1 AR e1004134 DI 10.1371/journal.pgen.1004134 PG 12 WC Genetics & Heredity SC Genetics & Heredity GA AI0GU UT WOS:000336525000071 PM 24497844 ER PT J AU Kubala, SA Patil, SU Shreffler, WG Hurley, BP AF Kubala, S. A. Patil, S. U. Shreffler, W. G. Hurley, B. P. TI Pathogen induced chemo-attractant hepoxilin A(3) drives neutrophils, but not eosinophils across epithelial barriers SO PROSTAGLANDINS & OTHER LIPID MEDIATORS LA English DT Article DE Neutrophils; Eosinophils; Eicosanoids; Hepoxilin A3; Leukotriene B4; Prostaglandin D2 ID TRANSEPITHELIAL MIGRATION; PHOSPHOLIPASE A(2); INTESTINAL EPITHELIA; LUNG INFECTION; INFLAMMATION; CELLS; TRANSMIGRATION; PROSTAGLANDINS; LEUKOTRIENES; TYPHIMURIUM AB Pathogen induced migration of neutrophils across mucosal epithelial barriers requires epithelial production of the chemotactic lipid mediator, hepoxilin A(3) (HXA(3))center dot HXA(3) is an eicosanoid derived from arachidonic acid. Although eosinophils are also capable of penetrating mucosal surfaces, eosinophilic infiltration occurs mainly during allergic processes whereas neutrophils dominate mucosal infection. Both neutrophils and eosinophils can respond to chemotactic gradients of certain eicosanoids, however, it is not known whether eosinophils respond to pathogen induced lipid mediators such as HXA(3). In this study, neutrophils and eosinophils were isolated from human blood and placed on the basolateral side of polarized epithelial monolayers grown on permeable Transwell filters and challenged by various chemotactic gradients of distinct lipid mediators. We observed that both cell populations migrated across epithelial monolayers in response to a leukotriene B-4 (LTB4) gradient, whereas only eosinophils migrated toward a prostaglandin D-2 (PGD(2)) gradient. Interestingly, while pathogen induced neutrophil trans-epithelial migration was substantial, pathogen induced eosinophil trans-epithelial migration was not observed. Further, gradients of chemotactic lipids derived from pathogen infected epithelial cells known to be enriched for HXA(3) as well as purified HXA(3) drove significant numbers of neutrophils across epithelial barriers, whereas eosinophils failed to respond to these gradients. These data suggest that although the eicosanoid HXA(3) serves as an important neutrophil chemo-attractant at mucosal surfaces during pathogenic infection, HXA3 does not appear to exhibit chemotactic activity toward eosinophils. (c) 2013 Elsevier Inc. All rights reserved. C1 [Kubala, S. A.; Shreffler, W. G.; Hurley, B. P.] Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. [Kubala, S. A.; Patil, S. U.; Shreffler, W. G.] Massachusetts Gen Hosp, Ctr Immunol & Inflammatory Dis, Charlestown, MA 02129 USA. [Kubala, S. A.; Patil, S. U.; Shreffler, W. G.] Massachusetts Gen Hosp, Food Allergy Ctr, Charlestown, MA 02129 USA. [Hurley, B. P.] Massachusetts Gen Hosp, Mucosal Immunol & Biol Res Ctr, Charlestown, MA 02129 USA. RP Hurley, BP (reprint author), Massachusetts Gen Hosp, Mucosal Immunol & Biol Res Ctr, CNY 114 114-3503, Charlestown, MA 02129 USA. EM bphurley@partners.org FU NIH grant [R01 AI095338]; Nutrition Obesity Research Center at Harvard [P30 DK040561] FX We thank Waheed Pirzai for expert technical assistance. We thank Mark E. Kusek MD and Michael A. Pazos PhD for critical review of the manuscript. This work acknowledges NIH grant R01 AI095338 for financial support. We also acknowledge support from Nutrition Obesity Research Center at Harvard (P30 DK040561) and we thank Dr. Ronald E. Kleinman MD, Physician in Chief of Massachusetts General Hospital for Children for support. NR 47 TC 2 Z9 2 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1098-8823 EI 2212-196X J9 PROSTAG OTH LIPID M JI Prostaglandins Other Lipid Mediat. PD JAN PY 2014 VL 108 BP 1 EP 8 DI 10.1016/j.prostaglandins.2013.11.001 PG 8 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA AH9PP UT WOS:000336474600001 PM 24315875 ER PT J AU Maire, CL Ramkissoon, S Hayashi, M Haidar, S Ramkissoon, L DiTomaso, E Ligon, KL AF Maire, Cecile L. Ramkissoon, Shakti Hayashi, Marika Haidar, Sam Ramkissoon, Lori DiTomaso, Emmanuelle Ligon, Keith L. TI Pten Loss in Olig2 Expressing Neural Progenitor Cells and Oligodendrocytes Leads to Interneuron Dysplasia and Leukodystrophy SO STEM CELLS LA English DT Article DE Hypermyelination; Olig2; Pten; Interneurons; Leukodystrophy ID LHERMITTE-DUCLOS-DISEASE; CENTRAL-NERVOUS-SYSTEM; TUMOR-SUPPRESSOR GENE; MOUSE MODEL; STEM-CELLS; SOMA SIZE; IN-VIVO; BRAIN; DIFFERENTIATION; MYELINATION AB Therapeutic modulation of phosphatidylinositol 3-kinase (PI3K)/PTEN signaling is currently being explored for multiple neurological indications including brain tumors and seizure disorders associated with cortical malformations. The effects of PI3K/PTEN signaling are highly cell context dependent but the function of this pathway in specific subsets of neural stem/progenitor cells generating oligodendroglial lineage cells has not been fully studied. To address this, we created Olig2-cre:Pten(fl/fl) mice that showed a unique pattern of Pten loss and PI3K activation in Olig2-lineage cells. Olig2-cre:Pten(fl/fl) animals progressively developed central nervous system white matter hypermyelination by 3 weeks of age leading to later onset leukodystrophy, chronic neurodegeneration, and death by 9 months. In contrast, during immediate postnatal development, oligodendroglia were unaffected but abnormal and accelerated differentiation of lateral subventricular zone stem cells produced calretinin-positive interneuron dysplasia. Neural stem cells isolated from Olig2-cre:Pten(fl/fl) mice also exhibited accelerated differentiation and proliferation into calretinin-positive interneurons and oligodendrocytes indicating such effects are cell autonomous. Opposition of the pathway by treatment of human primary neural progenitor cells (NPCs) with the PI3K inhibitor, NVP-BKM120, blocked in vitro differentiation of neurons and oligodendroglia indicating PI3K/PTEN effects on NPCs can be bidirectional. In summary, our results suggest Pten is a developmental rheostat regulating interneuron and oligodendroglial differentiation and support testing of PI3K modulating drugs as treatment for developmental and myelination disorders. However, such agents may need to be administered at ages that minimize potential effects on early stem/progenitor cell development. Stem Cells2014;32:313-326 C1 [Maire, Cecile L.; Ramkissoon, Shakti; Hayashi, Marika; Haidar, Sam; Ramkissoon, Lori; Ligon, Keith L.] Dana Farber Canc Inst, Ctr Mol Oncol Pathol, Dept Med Oncol, Boston, MA 02215 USA. [Ramkissoon, Shakti; Ligon, Keith L.] Brigham & Womens Hosp, Div Neuropathol, Dept Pathol, Boston, MA 02115 USA. [Ramkissoon, Shakti; Ligon, Keith L.] Childrens Hosp Boston, Boston, MA USA. [DiTomaso, Emmanuelle] Novartis Inst Biomed Res, Basel, Switzerland. [Ramkissoon, Shakti; Ligon, Keith L.] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. RP Ligon, KL (reprint author), Dana Farber Canc Inst, Ctr Mol Oncol Pathol, 450 Brookline Ave JFB 215B, Boston, MA 02215 USA. EM keith_ligon@dfci.harvard.edu FU NIH [5T32HL007627-28]; American Brain Tumor Association FX We wish to thank Tom Roberts and Jean Zhao for technical advice and comments on the manuscript. We thank Marian Slaney, Mei Zheng, Colleen Ford, and Brant Douglas in the BWH Pathology Department for specialized histopathology staining and expertise in electron microscopy. We also would like to thank the DF/HCC Rodent Histopathology Core as well as Edward Fox at the DF/HCC Microarray Core. Financial support for this study was provided by NIH R01 (K. L. L., C. L. M.), 5T32HL007627-28 (S. R.), and the American Brain Tumor Association (L.R.). NR 43 TC 5 Z9 7 U1 0 U2 2 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1066-5099 EI 1549-4918 J9 STEM CELLS JI Stem Cells PD JAN PY 2014 VL 32 IS 1 BP 313 EP 326 DI 10.1002/stem.1590 PG 14 WC Cell & Tissue Engineering; Biotechnology & Applied Microbiology; Oncology; Cell Biology; Hematology SC Cell Biology; Biotechnology & Applied Microbiology; Oncology; Hematology GA AG2GI UT WOS:000335233900029 PM 24395742 ER PT S AU Depauw, N Clasie, B Madden, T Rosenfeld, A Kooy, H AF Depauw, N. Clasie, B. Madden, T. Rosenfeld, A. Kooy, H. GP IOP TI GMC ['gimik]: a one-variable Monte Carlo dose algorithm for proton therapy SO XVII INTERNATIONAL CONFERENCE ON THE USE OF COMPUTERS IN RADIATION THERAPY (ICCR 2013) SE Journal of Physics Conference Series LA English DT Proceedings Paper CT 17th International Conference on the Use of Computers in Radiation Therapy (ICCR) CY MAY 06-09, 2013 CL Australasian Coll Phys Scientists & Engineers Med, Melbourne, AUSTRALIA SP Australian Inst Radiography, Royal Australian & New Zealand Coll Radiologists, Varian Med Syst, Brainlab, Elekta, Australian Govt Initiat, Australian Clin Dosimetry Serv HO Australasian Coll Phys Scientists & Engineers Med AB This work presents the CPU implementation of GMC ['gimik]: a fast yet accurate one-variable Monte Carlo dose algorithm for proton therapy to be incorporated into our in-house treatment planning system, Astroid. GMC is based on a simple mathematical model using the formulated proton scattering power and tabulated data of empirical depth-dose distributions. These Bragg peaks determine the energy deposited along the particle's track. The polar scattering angle is based on the particle's local energy and the voxel's density, while the azimuthal component of that scattering angle is the single variable in GMC, uniformly distributed from 0 to 2 pi. The halo effect of the beam, currently not implemented, will consider large scattering angles and secondary protons for a small percentage of the incident histories. GMC shows strong agreement with both the empirical data and GEANT4-based simulations. Its current CPU implementation runs at similar to 300 m.s(-1), approximately ten times faster than GEANT4. Significant speed improvement is expected with the upcoming implementation of multi-threading and the portage to the GPU architecture. In conclusion, a one-variable Monte Carlo dose algorithm was produced for proton therapy dose computations. Its simplicity allows for fast dose computation while conserving accuracy against heterogeneities, hence drastically improving the current algorithms used in treatment planning systems. C1 [Depauw, N.; Clasie, B.; Madden, T.; Kooy, H.] Massachusetts Gen Hosp, Francis H Burr Proton Therape Ctr, Dept Radiat Oncol, Boston, MA 02114 USA. [Depauw, N.; Rosenfeld, A.] Univ Wollongong, Ctr Med Radiat Res, Wollongong, NSW 2522, Australia. RP Depauw, N (reprint author), Massachusetts Gen Hosp, Francis H Burr Proton Therape Ctr, Dept Radiat Oncol, Boston, MA 02114 USA. EM ndepauw@partners.org NR 3 TC 0 Z9 0 U1 0 U2 1 PU IOP PUBLISHING LTD PI BRISTOL PA DIRAC HOUSE, TEMPLE BACK, BRISTOL BS1 6BE, ENGLAND SN 1742-6588 J9 J PHYS CONF SER PY 2014 VL 489 AR UNSP 012010 DI 10.1088/1742-6596/489/1/012010 PG 5 WC Physics, Applied; Radiology, Nuclear Medicine & Medical Imaging SC Physics; Radiology, Nuclear Medicine & Medical Imaging GA BA4LN UT WOS:000335976400010 ER PT S AU Rit, S Oliva, MV Brousmiche, S Labarbe, R Sarrut, D Sharp, GC AF Rit, S. Oliva, M. Vila Brousmiche, S. Labarbe, R. Sarrut, D. Sharp, G. C. GP IOP TI The Reconstruction Toolkit (RTK), an open-source cone-beam CT reconstruction toolkit based on the Insight Toolkit (ITK) SO XVII INTERNATIONAL CONFERENCE ON THE USE OF COMPUTERS IN RADIATION THERAPY (ICCR 2013) SE Journal of Physics Conference Series LA English DT Proceedings Paper CT 17th International Conference on the Use of Computers in Radiation Therapy (ICCR) CY MAY 06-09, 2013 CL Australasian Coll Phys Scientists & Engineers Med, Melbourne, AUSTRALIA SP Australian Inst Radiography, Royal Australian & New Zealand Coll Radiologists, Varian Med Syst, Brainlab, Elekta, Australian Govt Initiat, Australian Clin Dosimetry Serv HO Australasian Coll Phys Scientists & Engineers Med ID RADIOTHERAPY; ALGORITHM AB We propose the Reconstruction Toolkit (RTK, http://www.openrtk.org), an open-source toolkit for fast cone-beam CT reconstruction, based on the Insight Toolkit (ITK) and using GPU code extracted from Plastimatch. RTK is developed by an open consortium (see affiliations) under the non-contaminating Apache 2.0 license. The quality of the platform is daily checked with regression tests in partnership with Kitware, the company supporting ITK. Several features are already available: Elekta, Varian and IBA inputs, multi-threaded Feldkamp-David-Kress reconstruction on CPU and GPU, Parker short scan weighting, multi-threaded CPU and GPU forward projectors, etc. Each feature is either accessible through command line tools or C++ classes that can be included in independent software. A MIDAS community has been opened to share CatPhan datasets of several vendors (Elekta, Varian and IBA). RTK will be used in the upcoming cone-beam CT scanner developed by IBA for proton therapy rooms. Many features are under development: new input format support, iterative reconstruction, hybrid Monte Carlo / deterministic CBCT simulation, etc. RTK has been built to freely share tomographic reconstruction developments between researchers and is open for new contributions. C1 [Rit, S.; Oliva, M. Vila; Sarrut, D.] Univ Lyon 1, CREATIS, CNRS UMR5220, Inserm U1044,INSA Lyon,Ctr Leon Berard, Lyon, France. [Oliva, M. Vila; Brousmiche, S.; Labarbe, R.] Catholic Univ Louvain, ICTEAM Inst, iMagX Project, Louvain, Belgium. [Labarbe, R.] IBA, Louvain, Belgium. [Sharp, G. C.] Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. RP Rit, S (reprint author), Univ Lyon 1, CREATIS, CNRS UMR5220, Inserm U1044,INSA Lyon,Ctr Leon Berard, Lyon, France. EM simon.rit@creatis.insa-lyon.fr RI Rit, Simon/H-9410-2014; Sarrut, David/F-4849-2010 OI Sarrut, David/0000-0002-4854-4141 FU iMagX; IBA; UCLouvain [1017266]; Walloon Region of Belgium FX Funding for this project has been provided by iMagX, a private-public partnership between IBA and the UCLouvain funded by the convention #1017266 with the Walloon Region of Belgium. NR 10 TC 13 Z9 14 U1 0 U2 3 PU IOP PUBLISHING LTD PI BRISTOL PA DIRAC HOUSE, TEMPLE BACK, BRISTOL BS1 6BE, ENGLAND SN 1742-6588 J9 J PHYS CONF SER PY 2014 VL 489 AR UNSP 012079 DI 10.1088/1742-6596/489/1/012079 PG 4 WC Physics, Applied; Radiology, Nuclear Medicine & Medical Imaging SC Physics; Radiology, Nuclear Medicine & Medical Imaging GA BA4LN UT WOS:000335976400079 ER PT S AU Earle, CC Travis, LB Constine, LS AF Earle, Craig C. Travis, Lois B. Constine, Louis S. BE Rubin, P Constine, LS Marks, LB TI Prologue: Surviving Cancer: SEER Statistics SO ALERT - ADVERSE LATE EFFECTS OF CANCER TREATMENT, VOL 1: GENERAL CONCEPTS AND SPECIFIC PRECEPTS SE Medical Radiology Diagnostic Imaging LA English DT Editorial Material; Book Chapter ID RANDOMIZED CONTROLLED-TRIAL; ROUTINE FOLLOW-UP; BREAST-CANCER; PRIMARY-CARE; GENERAL-PRACTICE; SPECIALIST CARE AB The number of cancer survivors is increasing rapidly because of a combination of demographic forces, public health success, and improving medical treatments. Projections are that the oncology workforce will be unable to meet the demand for cancer care in coming decades. Survivorship care planning can improve the quality of care and open up the possibility for survivorship care to be delivered by an array of health care providers. C1 [Earle, Craig C.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Travis, Lois B.] NCI, Div Canc Epidemiol & Genet, NIH, DHHS, Bethesda, MD 20892 USA. [Constine, Louis S.] Univ Rochester, Med Ctr, James P Wilmot Canc Ctr, Dept Radiat Oncol, Rochester, NY 14642 USA. RP Earle, CC (reprint author), Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. EM craig_earle@dfci.harvard.edu NR 16 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER-VERLAG BERLIN PI BERLIN PA HEIDELBERGER PLATZ 3, D-14197 BERLIN, GERMANY SN 0942-5373 BN 978-3-540-72313-4; 978-3-540-72314-1 J9 MED RADIOL DIAGN IMA PY 2014 BP 1 EP 7 DI 10.1007/978-3-540-72314-1_1 D2 10.1007/978-3-540-72314-1 PG 7 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA BA2AA UT WOS:000333208500004 ER PT S AU Ng, AK Hudson, MM AF Ng, Andrea K. Hudson, Melissa M. BE Rubin, P Constine, LS Marks, LB TI BioSurveillance and Longitudinal Lifelong Guidelines SO ALERT - ADVERSE LATE EFFECTS OF CANCER TREATMENT, VOL 1: GENERAL CONCEPTS AND SPECIFIC PRECEPTS SE Medical Radiology Diagnostic Imaging LA English DT Article; Book Chapter ID LONG-TERM SURVIVORS; QUALITY-OF-LIFE; CHILDHOOD-CANCER SURVIVOR; NON-HODGKIN-LYMPHOMA; ANDROGEN-DEPRIVATION THERAPY; SURGICAL ADJUVANT BREAST; CORONARY-ARTERY-DISEASE; 2ND MALIGNANT NEOPLASM; CELL SKIN CANCERS; TESTICULAR-CANCER AB Given the increased risk of a wide range of late effects faced by cancer survivors, lifelong follow-up of these patients are essential. Existing guidelines are largely based on the known types of late effects, their temporal trend and modifying risk factors after specific treatments for various primary malignancies. Well-established follow-up guidelines exist for survivors of pediatric malignancies, most of which are based on prior treatment exposures. Less data are available on the optimal follow-up strategies for survivors of adult-onset cancer. Additional efforts are needed to prospectively evaluate the feasibility and efficacy of the follow-up recommendations including screening and prevention strategies. Need to initiate transition from multidisciplinary oncology to medical community care through individualized survivorship care plan (p 5, paragraph 1). Community health care providers are unfamiliar with health risks associated with cancer survivors and need to be supplemented by patient education and self advocacy (p 5, paragraph 2, 3). Currently, deficiencies include lack of standard definitions of toxicity, use of variable testing strategies, inconsistency as to evaluation time in relation to therapeutic exposures (p 6, paragraph 1). Early identification leads to early intervention for late onset therapy-related complications (p 6, paragraph 4). NCCN guidelines provide follow-up algorithms for cancer relapse rather than late effects of treatment (p 8, paragraph 1). Long-term surveillance guidelines beyond 5 years are available for 15 different cancers and again are designed for detecting cancer recurrence (p 9, paragraph 2). Second malignant neoplasms (SMN) have been most actively pursued in Hodgkin's lymphoma survivors (breast cancer and lung cancer) (p 10, paragraph 3, p 11, paragraph 1, p 12). SMN skin cancers are increased in Hodgkin's lymphoma and TBI/BMT survivors (p 13). SMN uterine cancer is increased in breast cancer survivors on estrogen therapy by 50 % in high-risk women (p 19). Cardiovascular disease complications are seen after radiation in breast cancer and Hodgkin's lymphoma survivors, with varied guidelines for annual blood pressure, serum glucose and lipid screening, and utility of baseline stress test/echocardiogram (p 16). Endocrine deficiencies after head and neck radiation leads to 30-40 % risk of hypothyroidism (p 18). Osteopenia can occur due to increased bone turnover in treatment-induced ovarian ablation and prostate cancer treated with gonadotrophin-releasing hormone agonists (p 18). Osteonecrosis and bone fracture can occur after radiation doses of 60 Gy and have been shown in survivors of cervix cancer (p 18). Psychosocial distress issues include fear, anxiety, suicidal ideation, depression, highlighting importance of implementing routine psychological screening and access to mental health professionals (p 20). Future Directions Recognize need for adult guidelines in follow-up of cancer survivors, especially those treated by radiation +/- chemotherapy and surgery (p 20). Need information on feasibility, level of compliance efficacy, cost-effectiveness for surveillance strategies (p 20). Optimal types of testing and interventions, their timing and frequency needs to be better defined and assessed in prospective cohorts of cancer survivors (p 20). Develop internet contact and resources that may provide optimal means to maintain contact for long-term follow-up of cancer survivors in our highly mobile society (p 20). C1 [Ng, Andrea K.] Dana Farber Harvard Canc Ctr, Boston, MA 02115 USA. [Hudson, Melissa M.] St Jude Childrens Res Hosp, Canc Survivorship Div, Memphis, TN 38105 USA. RP Ng, AK (reprint author), Dana Farber Harvard Canc Ctr, 75 Francis St ASB1-L2, Boston, MA 02115 USA. EM ang@lroc.harvard.edu NR 145 TC 0 Z9 0 U1 0 U2 3 PU SPRINGER-VERLAG BERLIN PI BERLIN PA HEIDELBERGER PLATZ 3, D-14197 BERLIN, GERMANY SN 0942-5373 BN 978-3-540-72313-4; 978-3-540-72314-1 J9 MED RADIOL DIAGN IMA PY 2014 BP 153 EP 169 DI 10.1007/978-3-540-72314-1_10 D2 10.1007/978-3-540-72314-1 PG 17 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA BA2AA UT WOS:000333208500013 ER PT S AU Travis, LB Ng, AK AF Travis, Lois B. Ng, Andrea K. BE Rubin, P Constine, LS Marks, LB TI The Bioepidemiology of Multiple Primary Cancers SO ALERT - ADVERSE LATE EFFECTS OF CANCER TREATMENT, VOL 1: GENERAL CONCEPTS AND SPECIFIC PRECEPTS SE Medical Radiology Diagnostic Imaging LA English DT Article; Book Chapter ID SURGICAL ADJUVANT BREAST; ACUTE MYELOID-LEUKEMIA; LONG-TERM SURVIVORS; SOFT-TISSUE SARCOMA; HODGKINS-DISEASE; RADIATION-THERAPY; TESTICULAR-CANCER; LUNG-CANCER; CONTRALATERAL BREAST; 2ND MALIGNANCIES AB The number of cancer survivors with second or higher order cancers is increasing, with these malignancies now comprising about 16 % (or 1 in 6) incident cancers reported to the population-based registries of the National Cancer Institute's (NCI's) Surveillance, Epidemiology, and End Results (SEER) Program. In a recent review of over two million cancer survivors who were reported to the NCI's SEER Program (1973-2000), the relative risk of subsequent neoplasms was significantly elevated (Observed to expected ratio = 1.14; 95 % C.I. = 1.14-1.15.). Twenty-five years after first cancer diagnosis, the cumulative incidence of all second cancers was 13.7 %. Second cancers can reflect the late effects of therapy, the impact of lifestyle choices (e.g., tobacco use), host factors, environmental determinants, and the operation of joint effects, including gene-environment and gene-gene interactions. A sizable proportion of all subsequent cancers in the review of the SEER program data developed among cancer survivors with initial cancers that are strongly related to tobacco and/or alcohol use. In the SEER program review, cancer treatment among all older adults taken together did not appear to be linked with a sizable excess of subsequent cancers, but children and young adults appeared to be particularly susceptible to the carcinogenic effects of therapy. In the present chapter, we highlight recent analytic studies of subsequent malignancies following HL and testicular cancer as well as cancers of breast and prostate. C1 [Travis, Lois B.] Univ Rochester, Med Ctr, Dept Radiat Oncol, Rochester, NY 14642 USA. [Ng, Andrea K.] Harvard Univ, Sch Med, Dept Radiat Oncol, Brigham & Womens Hosp,Dana Farber Canc Inst, Boston, MA 02115 USA. RP Travis, LB (reprint author), Univ Rochester, Med Ctr, Dept Radiat Oncol, 265 Crittenden Blvd,CU 420318, Rochester, NY 14642 USA. EM lois_travis@urmc.rochester.edu NR 87 TC 0 Z9 0 U1 0 U2 1 PU SPRINGER-VERLAG BERLIN PI BERLIN PA HEIDELBERGER PLATZ 3, D-14197 BERLIN, GERMANY SN 0942-5373 BN 978-3-540-72313-4; 978-3-540-72314-1 J9 MED RADIOL DIAGN IMA PY 2014 BP 227 EP 239 DI 10.1007/978-3-540-72314-1_15 D2 10.1007/978-3-540-72314-1 PG 13 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA BA2AA UT WOS:000333208500018 ER PT S AU Hodgson, DC Ng, A Travis, LB AF Hodgson, David C. Ng, Andrea Travis, Lois B. BE Rubin, P Constine, LS Marks, LB TI Radiation-Related Second Primary Cancers: Clinical Perspectives SO ALERT - ADVERSE LATE EFFECTS OF CANCER TREATMENT, VOL 1: GENERAL CONCEPTS AND SPECIFIC PRECEPTS SE Medical Radiology Diagnostic Imaging LA English DT Article; Book Chapter ID LONG-TERM SURVIVORS; ACUTE LYMPHOBLASTIC-LEUKEMIA; SURGICAL ADJUVANT BREAST; ACUTE MYELOID-LEUKEMIA; ATOMIC-BOMB SURVIVORS; NON-HODGKINS-LYMPHOMA; EXTENDED FOLLOW-UP; INTENSITY-MODULATED RADIOTHERAPY; INVOLVED-FIELD RADIOTHERAPY; CAUSE-SPECIFIC MORTALITY AB Radiation therapy (RT) is a major treatment used in the curative management of many cancer types. As survival rates for many forms of cancer continue to improve, there is increasing clinical attention being directed toward the risk of delayed radiation-induced second cancer (SC). Survivors of Hodgkin lymphoma, leukemia, cervix cancer, and breast cancer treated with RT have been shown, to varying degrees, to experience increased risks of SC. Important improvements in the analysis of risk can aid clinical interpretation: in particular, emphasis on the cumulative incidence of SC, and appropriate adjustment for competing causes of death can provide more clinically meaningful insight into the burden of SC than descriptions of the relative risk. The nature of the dose-risk relationship for normal tissues exposed to intermediate and high dose is uncertain, although there are emerging data that the risk may increase with increasing dose above 10 Gy. A better understanding of the risk associated with doses in this range will be an important component of developing RT treatments that limit the risk of SC and also for understanding the potential risk associated with newer treatments, such as intensity modulated radiation therapy (IMRT). Further research is required to better understand how the interaction of RT and chemotherapy or biologic agents may affect SC risk, and to identify the genetic contributors to the development of SC. C1 [Hodgson, David C.] Univ Toronto, Princess Margaret Hosp, Dept Radiat Oncol, Toronto, ON M5G 2M9, Canada. [Ng, Andrea] Harvard Univ, Sch Med, Dept Radiat Oncol, Brigham & Womens Hosp, Boston, MA 02115 USA. [Ng, Andrea] Dana Farber Canc Inst, Boston, MA 02115 USA. [Travis, Lois B.] Univ Rochester, James P Wilmot Canc Ctr, Dept Radiat Oncol, Rochester, NY 14642 USA. RP Hodgson, DC (reprint author), Univ Toronto, Princess Margaret Hosp, Dept Radiat Oncol, 610 Univ Ave, Toronto, ON M5G 2M9, Canada. EM David.Hodgson@rmp.uhn.on.ca NR 123 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER-VERLAG BERLIN PI BERLIN PA HEIDELBERGER PLATZ 3, D-14197 BERLIN, GERMANY SN 0942-5373 BN 978-3-540-72313-4; 978-3-540-72314-1 J9 MED RADIOL DIAGN IMA PY 2014 BP 241 EP 255 DI 10.1007/978-3-540-72314-1_16 D2 10.1007/978-3-540-72314-1 PG 15 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA BA2AA UT WOS:000333208500019 ER PT J AU Ordulu, Z Wong, KE Currall, BB Ivanov, AR Pereira, S Althari, S Gusella, JF Talkowski, ME Morton, CC AF Ordulu, Z. Wong, K. E. Currall, B. B. Ivanov, A. R. Pereira, S. Althari, S. Gusella, J. F. Talkowski, M. E. Morton, C. C. TI Describing Sequencing Results of Structural Chromosome Rearrangements with a Suggested Next-Gen Cytogenetic Nomenclature SO CYTOGENETIC AND GENOME RESEARCH LA English DT Meeting Abstract CT 43rd Biennial American Cytogenetics Conference CY MAY 04-07, 2014 CL Asheville, NC C1 [Ordulu, Z.; Wong, K. E.; Currall, B. B.; Ivanov, A. R.; Pereira, S.; Althari, S.; Morton, C. C.] Brigham & Womens Hosp, Dept Obstet Gynecol & Reprod Biol, Boston, MA 02115 USA. [Morton, C. C.] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. [Gusella, J. F.; Talkowski, M. E.] Broad Inst Harvard & MIT, Dept Neurol, Boston, MA USA. [Gusella, J. F.] Broad Inst Harvard & MIT, Dept Genet, Boston, MA USA. [Gusella, J. F.; Talkowski, M. E.; Morton, C. C.] Broad Inst Harvard & MIT, Program Med & Populat Genet, Boston, MA USA. [Ordulu, Z.; Currall, B. B.; Gusella, J. F.; Talkowski, M. E.; Morton, C. C.] Harvard Univ, Sch Med, Boston, MA USA. [Gusella, J. F.; Talkowski, M. E.] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 1424-8581 EI 1424-859X J9 CYTOGENET GENOME RES JI Cytogenet. Genome Res. PY 2014 VL 142 IS 3 MA 3 PG 1 WC Cell Biology; Genetics & Heredity SC Cell Biology; Genetics & Heredity GA AH3VS UT WOS:000336054700012 ER PT J AU Farr, SA Erickson, MA Niehoff, ML Banks, WA Morley, JE AF Farr, Susan A. Erickson, Michelle A. Niehoff, Michael L. Banks, William A. Morley, John E. TI Central and Peripheral Administration of Antisense Oligonucleotide Targeting Amyloid-beta Protein Precursor Improves Learning and Memory and Reduces Neuroinflammatory Cytokines in Tg2576 (A beta PPswe) Mice SO JOURNAL OF ALZHEIMERS DISEASE LA English DT Article DE Antisense oligonucleotide; Tg2576; learning; memory; T-maze; object recognition; oxidative stress; blood brain barrier; cytokines ID BLOOD-BRAIN-BARRIER; RECEPTOR-RELATED PROTEIN-1; TRANSGENIC MOUSE MODEL; ALZHEIMERS-DISEASE; FRONTOTEMPORAL DEMENTIA; COGNITIVE DEFICITS; OXIDATIVE STRESS; SPATIAL MEMORY; SAMP8 MICE; IN-VIVO AB Alzheimer's disease (AD) is a progressive neurodegenerative disease. Currently, there are no therapies to stop or reverse the symptoms of AD. We have developed an antisense oligonucleotide (OL-1) against the amyloid-beta protein precursor (A beta PP) that can decrease A beta PP expression and amyloid-beta protein (A beta) production. This antisense rapidly crosses the blood-brain barrier, reverses learning and memory impairments, reduces oxidative stress, and restores brain-to-blood efflux of A beta in SAMP8 mice. Here, we examined the effects of this A beta PP antisense in the Tg2576 mouse model of AD. We administered the OL-1 antisense into the lateral ventricle 3 times at 2week intervals. Seventy-two hours after the third injection, we tested learning and memory in T-maze foot shock avoidance. In the second study, we injected the mice with OL-1 antisense 3 times at 2-week intervals via the tail vein. Seventy-two hours later, we tested learning and memory T-maze, novel object recognition, and elevated plus maze. At the end of behavioral testing, brain tissue was collected. OL-1 antisense administered centrally improved acquisition and retention of T-maze foot shock avoidance. OL-1 antisense administered via tail vein improved learning and memory in both T-maze foot shock avoidance and novel object-place recognition. In the elevated plus maze, the mice which received OL-1 antisense spent less time in the open arms and had fewer entries into the open arms indicating reduced disinhibitation. Biochemical analyses reveal significant reduction of A beta PP signal and a reduction of measures of neuroinflammation. The current findings support the therapeutic potential of OL-1 A beta PP antisense. C1 [Farr, Susan A.] VA Med Ctr, Res & Dev Serv, St Louis, MO USA. [Farr, Susan A.; Niehoff, Michael L.; Morley, John E.] St Louis Univ, Sch Med, Div Geriatr Med, Dept Internal Med, St Louis, MO 63106 USA. [Erickson, Michelle A.; Banks, William A.] Vet Affairs Puget Sound Hlth Care Syst, GRECC, Seattle, WA USA. [Erickson, Michelle A.; Banks, William A.] Univ Washington, Sch Med, Dept Internal Med, Div Gerontol & Geriatr Med, Seattle, WA USA. [Morley, John E.] St Louis Univ, Sch Med, Dept Internal Med, Div Endocrinol, St Louis, MO 63106 USA. RP Farr, SA (reprint author), St Louis Univ, Sch Med, VA Med Ctr St Louis, 915 North Grand Blvd,151-JC, St Louis, MO 63106 USA. EM farrsa@slu.edu FU VA Merit Review FX This work was supported by VA Merit Review. NR 48 TC 10 Z9 10 U1 0 U2 6 PU IOS PRESS PI AMSTERDAM PA NIEUWE HEMWEG 6B, 1013 BG AMSTERDAM, NETHERLANDS SN 1387-2877 EI 1875-8908 J9 J ALZHEIMERS DIS JI J. Alzheimers Dis. PY 2014 VL 40 IS 4 BP 1005 EP 1016 DI 10.3233/JAD-131883 PG 12 WC Neurosciences SC Neurosciences & Neurology GA AH6SW UT WOS:000336262000018 PM 24577464 ER PT J AU Block, C Fabrizio, K Bagley, B Hannah, J Camp, S Mindingall, N Labbe, D Lokken, K AF Block, Cady Fabrizio, Katherine Bagley, Beau Hannah, Joanna Camp, Susan Mindingall, Nazaren Labbe, Don Lokken, Kristine TI Assessment of Veteran and Caregiver Knowledge About Mild Traumatic Brain Injury in a VA Medical Center SO JOURNAL OF HEAD TRAUMA REHABILITATION LA English DT Article DE attitudes; knowledge; practice; health knowledge; veterans; military personnel; brain injuries ID POSTCONCUSSION SYNDROME; INFORMATIONAL CASCADES; WAR VETERANS; MISCONCEPTIONS; CONCUSSION; IRAQ; AFGHANISTAN; SURVIVORS; TERMINOLOGY; DEPLOYMENT AB Objective: To examine the accuracy of knowledge about mild traumatic brain injury (TBI) of veterans and their friends/family members. Setting: VA Medical Center. Participants: One hundred veterans and 50 of their friends/family members. Design: Cross-sectional survey. Main Measures: A 60-item questionnaire was created by drawing both from the Neurobehavioral Symptom Inventory and from a brain injury knowledge survey developed for use with the general public. Results: Both groups were equally able to identify true mild TBI items, but both also endorsed numerous items not typical of a mild injury. Self-reported prior TBI and receipt of TBI education were unrelated to the level of knowledge. For both groups, knowing another individual with TBI was unrelated to other aspects of mild TBI knowledge. Only 1 in 5 veterans endorsed receiving brain injury education while in the military. Conclusion: Results of this study may assist in the development of targeted TBI educational interventions for veterans and their friends/family members within the Veterans Affairs system. Ultimately, increased knowledge about mild TBI improves the likelihood that veterans receive care congruent with their needs and may potentially improve outcomes for those with mild TBI. C1 [Block, Cady; Fabrizio, Katherine; Labbe, Don] Univ Alabama Birmingham, Div Med Clin Psychol, Dept Psychol, Birmingham, AL 35294 USA. [Bagley, Beau; Hannah, Joanna; Camp, Susan; Mindingall, Nazaren; Lokken, Kristine] Birmingham Vet Affairs Med Ctr, Dept Phys Med & Rehabil, Birmingham, AL USA. RP Block, C (reprint author), Univ Alabama Birmingham, Div Med Clin Psychol, CH 201,1530 3rd Ave S, Birmingham, AL 35294 USA. EM cblock@uab.edu OI Block, Cady/0000-0001-7168-6116 NR 48 TC 2 Z9 2 U1 1 U2 7 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0885-9701 EI 1550-509X J9 J HEAD TRAUMA REHAB JI J. Head Trauma Rehabil. PD JAN-FEB PY 2014 VL 29 IS 1 BP 76 EP 88 DI 10.1097/HTR.0b013e3182886d78 PG 13 WC Clinical Neurology; Rehabilitation SC Neurosciences & Neurology; Rehabilitation GA AH1OC UT WOS:000335889400013 PM 23524877 ER PT J AU Fortier, CB Amick, MM Grande, L McGlynn, S Kenna, A Morra, L Clark, A Milberg, WP McGlinchey, RE AF Fortier, Catherine Brawn Amick, Melissa M. Grande, Laura McGlynn, Susan Kenna, Alexandra Morra, Lindsay Clark, Alexandra Milberg, William P. McGlinchey, Regina E. TI The Boston Assessment of Traumatic Brain Injury-Lifetime (BAT-L) Semistructured Interview: Evidence of Research Utility and Validity SO JOURNAL OF HEAD TRAUMA REHABILITATION LA English DT Article DE assessment; OEF/OIF; veterans; blast; traumatic brain injury (TBI) ID POSTTRAUMATIC-STRESS-DISORDER; TBI IDENTIFICATION; BLAST; SOLDIERS; IRAQ; MECHANISMS; SEQUELAE AB Objective: Report the prevalence of lifetime and military-related traumatic brain injuries (TBIs) in Operation Enduring Freedom and Operation Iraqi Freedom (OEF/OIF) veterans and validate the Boston Assessment of TBI-Lifetime (BAT-L). Setting: The BAT-L is the first validated, postcombat, semistructured clinical interview to characterize head injuries and diagnose TBIs throughout the life span. Participants: Community-dwelling convenience sample of 131 OEF/OIF veterans. Design: TBI criteria (alteration of mental status, posttraumatic amnesia, and loss of consciousness) were evaluated for all possible TBIs, including a novel evaluation of blast exposure. Main Measures: BAT-L, Ohio State University TBI Identification Method (OSU-TBI-ID). Results: About 67% of veterans incurred a TBI in their lifetime. Almost 35% of veterans experienced at least 1 military-related TBI; all were mild in severity, 40% of them were due to blast, 50% were due to some other (ie, blunt) mechanism, and 10% were due to both types of injuries. Predeployment TBIs were frequent (45% of veterans). There was strong correspondence between the BAT-L and the OSU-TBI-ID (Cohen kappa = 0.89; Kendall tau-b = 0.95). Interrater reliability of the BAT-L was strong (kappa s >0.80). Conclusions: The BAT-L is a valid instrument with which to assess TBI across a service member's lifetime and captures the varied and complex nature of brain injuries across OEF/OIF veterans' life span. C1 [Fortier, Catherine Brawn; Amick, Melissa M.; Kenna, Alexandra; Morra, Lindsay; Clark, Alexandra; Milberg, William P.; McGlinchey, Regina E.] VA Boston Healthcare Syst, Translat Res Ctr TBI & Stress Disorders & Geriatr, Educ & Clin Ctr, Boston, MA 02130 USA. [Grande, Laura] VA Boston Healthcare Syst, Psychol Serv, Boston, MA 02130 USA. [McGlynn, Susan] VA Boston Healthcare Syst, Phys Med & Rehabil Serv, Boston, MA 02130 USA. [Fortier, Catherine Brawn; Milberg, William P.; McGlinchey, Regina E.] Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA. [Amick, Melissa M.; Grande, Laura; McGlynn, Susan] Boston Univ, Sch Med, Dept Psychiat, Boston, MA 02118 USA. RP Fortier, CB (reprint author), VA Boston Healthcare Syst, Translat Res Ctr TBI & Stress Disorders & Geriatr, Educ & Clin Ctr 182, 150 S Huntington Ave, Boston, MA 02130 USA. EM Catherine_Fortier@hms.harvard.edu RI McGlinchey, Regina/R-1971-2016 FU Translational Research Center for TBI and Stress Disorders, a VA Rehabilitation Research and Development Traumatic Brain Injury Center of Excellence [B6796-C]; NIH [NIA K01AG024898]; VA Merit Review Award FX This research was support by the Translational Research Center for TBI and Stress Disorders, a VA Rehabilitation Research and Development Traumatic Brain Injury Center of Excellence (B6796-C), NIH NIA K01AG024898, and VA Merit Review Award to Regina McGlinchey. We thank Wally Musto for his championship of our work among military personnel and his tireless recruitment efforts on our behalf. We also acknowledge the contributions of Drs Heidi Terrio and Doug Katz for their guidance in the development and analysis of the BAT-L. NR 20 TC 19 Z9 19 U1 1 U2 6 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0885-9701 EI 1550-509X J9 J HEAD TRAUMA REHAB JI J. Head Trauma Rehabil. PD JAN-FEB PY 2014 VL 29 IS 1 BP 89 EP 98 DI 10.1097/HTR.0b013e3182865859 PG 10 WC Clinical Neurology; Rehabilitation SC Neurosciences & Neurology; Rehabilitation GA AH1OC UT WOS:000335889400014 PM 23535389 ER PT J AU Thilly, WG Gostjeva, EV Koledova, VV Zukerberg, LR Chung, D Fomina, JN Darroudi, F Stollar, BD AF Thilly, William G. Gostjeva, Elena V. Koledova, Vera V. Zukerberg, Lawrence R. Chung, Daniel Fomina, Janna N. Darroudi, Firouz Stollar, B. David TI Metakaryotic stem cell nuclei use pangenomic dsRNA/DNA intermediates in genome replication and segregation SO ORGANOGENESIS LA English DT Article DE dsRNA/DNA; amitosis; genome replication; stem cells; metakaryotic; differentiation; development ID RNA-DNA HYBRIDS; POLYTENE CHROMOSOMES; CANCER; STRANDS; CONFORMATIONS; ANTIBODIES; CHROMATIDS; ORIGINS; BINDING; MICE AB Bell shaped nuclei of metakaryotic cells double their DNA content during and after symmetric and asymmetric amitotic fissions rather than in the separate, pre-mitotic S-phase of eukaryotic cells. A parsimonious hypothesis was tested that the two anti-parallel strands of each chromatid DNA helix were first segregated as ssDNA-containing complexes into sister nuclei then copied to recreate a dsDNA genome. Metakaryotic nuclei that were treated during amitosis with RNase A and stained with acridine orange or fluorescent antibody to ssDNA revealed large amounts of ssDNA. Without RNase treatment metakaryotic nuclei in amitosis stained strongly with an antibody complex specific to dsRNA/DNA. Images of amitotic figures co-stained with dsRNA/DNA antibody and DAPI indicated that the entire interphase dsDNA genome (B-form helices) was transformed into two dsRNA/DNA genomes (A-form helices) that were segregated in the daughter cell nuclei then retransformed into dsDNA. As this process segregates DNA strands of opposite polarity in sister cells it hypothetically offers a sequential switching mechanism within the diverging stem cell lineages of development. C1 [Thilly, William G.; Gostjeva, Elena V.; Koledova, Vera V.] MIT, Dept Biol Engn, Lab Metakaryot Biol, Cambridge, MA 02139 USA. [Zukerberg, Lawrence R.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Chung, Daniel] Massachusetts Gen Hosp, Gastorointestinal Unit, Boston, MA 02114 USA. [Fomina, Janna N.; Darroudi, Firouz] Leiden Univ, Ctr Med, Dept Toxicogenet, Leiden, Netherlands. [Stollar, B. David] Tufts Univ, Sch Med, Dept Dev Mol & Chem Biol, Boston, MA 02111 USA. RP Thilly, WG (reprint author), MIT, Dept Biol Engn, Lab Metakaryot Biol, 77 Massachusetts Ave, Cambridge, MA 02139 USA. EM thilly@mit.edu FU Leiden University Medical Centre; United Therapeutics Corporation of Silver Spring, MD, USA FX These efforts were supported initially by personal funds (Gostjeva EV, Thilly WG) and internal funds of the Leiden University Medical Centre (Fomina JN, Darroudi F). Three of us (Gostjeva EV, Thilly WG, Koledova VV) have been supported at MIT since 2007 by a research contract to study metakaryotic phenomena in human diseases from the United Therapeutics Corporation of Silver Spring, MD, USA. We acknowledge useful scientific discussions with Drs Martine Rothblatt, Mary Smith (United Therapeutics), Ray Kurzweil and Aaron Kleiner (Kurzweil Technologies, Wellesley, MA, USA), Christopher F Nicodemus (AIT Strategies, Franconia, NH, USA), Dr James L Sherley (The Adult Stem Cell Technolgy Center, LLC, Boston, MA, USA), Prof Kari Hemminki, Deutsch Zentrum fur Krebs Forschung, Heidelberg, Germany and the late Prof David Schauer (MIT). NR 38 TC 2 Z9 2 U1 0 U2 2 PU LANDES BIOSCIENCE PI AUSTIN PA 1806 RIO GRANDE ST, AUSTIN, TX 78702 USA SN 1547-6278 EI 1555-8592 J9 ORGANOGENESIS JI Organogenesis PD JAN 1 PY 2014 VL 10 IS 1 BP 44 EP 52 DI 10.4161/org.27684 PG 9 WC Biochemistry & Molecular Biology; Developmental Biology; Engineering, Biomedical SC Biochemistry & Molecular Biology; Developmental Biology; Engineering GA AH2OF UT WOS:000335960100007 PM 24418910 ER PT S AU Kobayashi, T Kronenberg, HM AF Kobayashi, Tatsuya Kronenberg, Henry M. BE Hilton, MJ TI Overview of Skeletal Development SO SKELETAL DEVELOPMENT AND REPAIR: METHODS AND PROTOCOLS SE Methods in Molecular Biology LA English DT Article; Book Chapter DE Bone development; Chondrocyte; Osteoblast; Mouse; Mesenchymal condensation; Method; Skeletal development; Transcription factor; Signaling ID ENDOCHONDRAL BONE-FORMATION; CONTROLS CHONDROCYTE HYPERTROPHY; HORMONE-RELATED PEPTIDE; GROWTH-PLATE; OSTEOBLAST DIFFERENTIATION; CONSTITUTIVE ACTIVATION; PARATHYROID-HORMONE; LIMB DEVELOPMENT; VERTEBRATE LIMB; MICE AB Development of cartilage and bone, the core components of the mouse skeletal system, depends on the well-coordinated proliferation and differentiation of skeletogenic cells, including chondrocytes and osteoblasts. These cells differentiate from common progenitor cells originating in the mesoderm and neural crest. Multiple signaling pathways and transcription factors tightly regulate differentiation and proliferation of skeletal cells. In this chapter, we overview the process of mouse skeletal development and discuss major regulators of skeletal cells at each developmental stage. C1 [Kobayashi, Tatsuya; Kronenberg, Henry M.] Harvard Univ, Massachusetts Gen Hosp, Boston, MA 02115 USA. RP Kobayashi, T (reprint author), Harvard Univ, Massachusetts Gen Hosp, Boston, MA 02115 USA. NR 52 TC 12 Z9 12 U1 1 U2 6 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DR, STE 208, TOTOWA, NJ 07512-1165 USA SN 1064-3745 BN 978-1-62703-988-8; 978-1-62703-989-5 J9 METHODS MOL BIOL JI Methods Mol. Biol. PY 2014 VL 1130 BP 3 EP 12 DI 10.1007/978-1-62703-989-5_1 D2 10.1007/978-1-62703-989-5 PG 10 WC Biochemistry & Molecular Biology; Cell & Tissue Engineering SC Biochemistry & Molecular Biology; Cell Biology GA BA1SC UT WOS:000333037600002 PM 24482161 ER PT J AU Chen, JJ Marsh, L AF Chen, Jack J. Marsh, Laura TI Anxiety in Parkinson's disease: identification and management SO THERAPEUTIC ADVANCES IN NEUROLOGICAL DISORDERS LA English DT Review DE Anxiety; neurology; Parkinson's disease; psychiatry ID COGNITIVE-BEHAVIORAL THERAPY; ON-OFF PHENOMENON; NONMOTOR SYMPTOMS; DEPRESSION SCALE; HOSPITAL ANXIETY; DIAGNOSTIC-CRITERIA; CONTROLLED-TRIAL; RATING-SCALES; RISK; COMORBIDITY AB Anxiety disturbances are recognized as common psychiatric comorbidities in Parkinson's disease (PD) and contribute to significant impairments in areas of cognitive, functional, motor and social performance. Anxiety in PD results in reduced quality of life, higher levels of care dependency and increased caregiver burden. Surprisingly, there is a paucity of treatment data. In one randomized, controlled study, bromazepam was found to be effective for anxiety in PD. However, usage of benzodiazepines in the PD population is limited by potential risk of confusion and falls. There are no controlled studies of selective serotonin reuptake inhibitors (SSRIs) for anxiety in PD. However, results from uncontrolled studies suggest that SSRIs are effective for anxiety in PD, although in these studies anxiety outcomes were secondary. This review underscores that, given the high prevalence of anxiety disturbances in PD, there is a significant paucity of treatment data for this population. Additional studies are warranted. In the meantime, clinicians should rely on empiric assessments of known risks and putative benefits to guide treatment decisions. Cognitive and behavioral therapies (with or without pharmacotherapy) have demonstrated efficacy and warrant consideration. When feasible, a targeted and individualized multimodal approach utilizing psychotherapeutic interventions along with pharmacologic therapies should be considered. C1 [Chen, Jack J.] Loma Linda Univ, Sch Med, Loma Linda, CA 92350 USA. [Chen, Jack J.] Loma Linda Univ, Sch Pharm, Loma Linda, CA 92350 USA. [Marsh, Laura] Baylor Coll Med, Michael E DeBakey Vet Affairs Med Ctr, Houston, TX 77030 USA. [Marsh, Laura] Baylor Coll Med, Dept Psychiat, Houston, TX 77030 USA. [Marsh, Laura] Baylor Coll Med, Dept Neurol, Houston, TX 77030 USA. RP Chen, JJ (reprint author), Loma Linda Univ, Sch Med, Shyrock Hall 225, Loma Linda, CA 92350 USA. EM jjchen@llu.edu NR 66 TC 21 Z9 21 U1 5 U2 11 PU SAGE PUBLICATIONS LTD PI LONDON PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND SN 1756-2856 EI 1756-2864 J9 THER ADV NEUROL DISO JI Ther. Adv. Neurol. Disord. PD JAN PY 2014 VL 7 IS 1 BP 52 EP 59 DI 10.1177/1756285613495723 PG 8 WC Clinical Neurology SC Neurosciences & Neurology GA AH0SD UT WOS:000335829700005 PM 24409202 ER PT S AU Durr, NJ Gonzalez, G Lim, D Traverso, G Nishioka, NS Vakoc, BJ Parot, V AF Durr, Nicholas J. Gonzalez, German Lim, Daryl Traverso, Giovanni Nishioka, Norman S. Vakoc, Benjamin J. Parot, Vicente BE VoDinh, T MahadevanJansen, A Grundfest, WS TI System for Clinical Photometric Stereo Endoscopy SO ADVANCED BIOMEDICAL AND CLINICAL DIAGNOSTIC AND SURGICAL GUIDANCE SYSTEMS XII SE Proceedings of SPIE LA English DT Proceedings Paper CT Conference on Advanced Biomedical and Clinical Diagnostic and Surgical Guidance Systems XII CY FEB 02-04, 2014 CL San Francisco, CA SP SPIE DE Topography; stereo; computer vision; computer aided detection; endoscopy; colonoscopy AB Photometric stereo endoscopy is a technique that captures information about the high-spatial-frequency topography of the field of view simultaneously with a conventional color image. Here we describe a system that will enable photometric stereo endoscopy to be clinically evaluated in the large intestine of human patients. The clinical photometric stereo endoscopy system consists of a commercial gastroscope, a commercial video processor, an image capturing and processing unit, custom synchronization electronics, white light LEDs, a set of four fibers with diffusing tips, and an alignment cap. The custom pieces that come into contact with the patient are composed of biocompatible materials that can be sterilized before use. The components can then be assembled in the endoscopy suite before use. The resulting endoscope has the same outer diameter as a conventional colonoscope (14 mm), plugs into a commercial video processor, captures topography and color images at 15 Hz, and displays the conventional color image to the gastroenterologist in real-time. We show that this system can capture a color and topographical video in a tubular colon phantom, demonstrating robustness to complex geometries and motion. The reported system is suitable for in vivo evaluation of photometric stereo endoscopy in the human large intestine. C1 [Durr, Nicholas J.; Gonzalez, German; Lim, Daryl; Parot, Vicente] MIT, Madrid MIT Vis Consortium M, 77 Massachusetts Ave,35-749, Cambridge, MA 02139 USA. [Durr, Nicholas J.; Gonzalez, German; Lim, Daryl; Vakoc, Benjamin J.; Parot, Vicente] Massachusetts Gen Hosp, Harvard Med Sch, Wellman Ctr Photomed, Boston, MA 02114 USA. [Traverso, Giovanni; Nishioka, Norman S.] Massachusetts Gen Hosp, Harvard Med Sch, Div Gastroenterol, Boston, MA 02114 USA. [Traverso, Giovanni] MIT, Koch Inst Integrat Cancer Res, Dept Chem Engn, Cambridge, MA 02139 USA. RP Durr, NJ (reprint author), MIT, Madrid MIT Vis Consortium M, 77 Massachusetts Ave,35-749, Cambridge, MA 02139 USA. EM ndurr@mit.edu OI , /0000-0002-9261-6667 FU Comunidad de Madrid through Madrid-MIT FX This work has been financially supported by the Comunidad de Madrid through the Madrid-MIT M+Vision Consortium. We thank the M+Vision IDEA3 faculty panel for their assistance in developing this project. We would like to thank Pentax for providing the endoscopic equipment used for this research, and in particular Mr. Mike Fina for facilitating access to the equipment. NR 8 TC 0 Z9 0 U1 0 U2 2 PU SPIE-INT SOC OPTICAL ENGINEERING PI BELLINGHAM PA 1000 20TH ST, PO BOX 10, BELLINGHAM, WA 98227-0010 USA SN 0277-786X BN 978-0-8194-9848-9 J9 PROC SPIE PY 2014 VL 8935 AR UNSP 89351F DI 10.1117/12.2038119 PG 6 WC Optics; Radiology, Nuclear Medicine & Medical Imaging SC Optics; Radiology, Nuclear Medicine & Medical Imaging GA BA4ED UT WOS:000335493700027 ER PT J AU Jung, M AF Jung, Minsoo TI Associations of Self-rated Health and Socioeconomic Status with Information Seeking and Avoiding Behavior among Post-Treatment Cancer Patients SO ASIAN PACIFIC JOURNAL OF CANCER PREVENTION LA English DT Article DE Health information seeking; health information avoidance; self-rated health; health communication ID FACTOR SURVEILLANCE SYSTEM; QUALITY-OF-LIFE; BREAST-CANCER; SURVIVORS; AVOIDANCE; NEEDS; DETERMINANTS; PREFERENCES; EXPERIENCES; POPULATION AB This study investigated how self-rated health and socioeconomic status are associated with behaviour of cancer survivors regarding desire for information. For this association, we compared survivors who did not seek information about cancer with those who did. We examined how sociodemographic, socioeconomic, cancer-related, and health information factors are associated with self-rated health (SRH) by health information seeking/avoiding behavior in a survey of 502 post-treatment cancer patients. In the information seeking group, all four factors exhibited significant relationships with SRH. SRH values were significantly high for women (p<0.05), non-Hispanic White (p<0.05), and educated (p<0.01) participants, and for those who had high self-efficacy to use health information by themselves (p<0.01). Furthermore, in the information avoiding group, not only were there no significant relationships between socioeconomic status (SES) and SRH, but there were negative associations between their attitude/capacity and the SRH. In terms of communication equity, the promotion of information seeking behavior can be an effective way to reduce health disparities that are caused by social inequalities. Information avoiding behavior, however, does not exhibit a negative contribution toward the relationship between SRH and SES. Information seeking behavior was positively associated with SRH, but avoiding behavior was not negatively associated. We thus need to eliminate communication inequalities using health intervention to support information seeking behavior, while simultaneously providing support for avoiders. C1 [Jung, Minsoo] Dongduk Womens Univ, Dept Hlth Sci, Seoul, South Korea. [Jung, Minsoo] Dana Farber Canc Inst, Ctr Community Based Res, Boston, MA 02115 USA. RP Jung, M (reprint author), Dongduk Womens Univ, Dept Hlth Sci, Seoul, South Korea. EM mins.jung@gmail.com NR 41 TC 4 Z9 4 U1 3 U2 15 PU ASIAN PACIFIC ORGANIZATION CANCER PREVENTION PI GYEONGGI-DO PA APJCP HEAD OFFICE, KOREAN NATL CANCER CENTER, 323 ILAN -RO, ILSANDONG-GU, GOYANG-SI, GYEONGGI-DO, 410-769, SOUTH KOREA SN 1513-7368 J9 ASIAN PAC J CANCER P JI Asian Pac. J. Cancer Prev. PY 2014 VL 15 IS 5 BP 2231 EP 2238 DI 10.7314/APJCP.2014.15.5.2231 PG 8 WC Oncology SC Oncology GA AG8EI UT WOS:000335651200057 PM 24716962 ER PT J AU Ricardo, AC Yang, W Lora, CM Gordon, EJ Diamantidis, CJ Ford, V Kusek, JW Lopez, A Lustigova, E Nessel, L Rosas, SE Steigerwalt, S Theurer, J Zhang, XM Fischer, MJ Lash, JP Investigators, C AF Ricardo, Ana C. Yang, Wei Lora, Claudia M. Gordon, Elisa J. Diamantidis, Clarissa J. Ford, Virginia Kusek, John W. Lopez, Amada Lustigova, Eva Nessel, Lisa Rosas, Sylvia E. Steigerwalt, Susan Theurer, Jacqueline Zhang, Xiaoming Fischer, Michael J. Lash, James P. Investigators, C. R. I. C. TI Limited health literacy is associated with low glomerular filtration in the Chronic Renal Insufficiency Cohort (CRIC) study SO CLINICAL NEPHROLOGY LA English DT Article DE chronic kidney disease; health literacy ID CHRONIC KIDNEY-DISEASE; MANAGED CARE ENROLLEES; DIALYSIS PATIENTS; SELF-MANAGEMENT; KNOWLEDGE; PREVALENCE; MORTALITY; OUTCOMES; RISK; LINE AB Background: Low health literacy in the general population is associated with increased risk of death and hospitalization. The evaluation of health literacy in individuals with predialysis chronic kidney disease (CKD) is limited. Methods: We conducted a cross-sectional study to evaluate the associations of limited health literacy with kidney function and cardiovascular disease (CVD) risk factors in 2,340 non-Hispanic (NH) Whites and Blacks aged 21 - 74 years with mild-to-moderate CKD. Limited health literacy was defined as a Short Test of Functional Health Literacy in Adults (STOFHLA) score <= 22. Outcomes evaluated included estimated glomerular filtration rate (eGFR), 24-hour urine protein excretion, and CVD risk factors. Results: The prevalence of limited health literacy was 28% in NH-Blacks and 5% in NH-Whites. Compared with participants with adequate health literacy, those with limited health literacy were more likely to have lower eGFR (34 vs. 42 mL/min/1.73 m(2)); higher urine protein/24-hours (0.31 vs. 0.15 g); and higher self-reported CVD (61 vs. 37%); and were less likely to have BP < 130/80 mmHg (51 vs. 58%); p <= 0.01 for each comparison. After adjustment, limited health literacy was associated with self-reported CVD (OR 1.51, 95% CI 1.13 - 2.03) and lower eGFR (beta -2.47, p = 0.03). Conclusion: In this CKD cohort, limited health literacy was highly prevalent, especially among NH-Blacks, and it was associated with lower eGFR and a less favorable CVD risk factor profile. Further studies are needed to better understand these associations and inform the development of health literacy interventions among individuals with CKD. C1 [Ricardo, Ana C.; Lora, Claudia M.; Lopez, Amada; Fischer, Michael J.; Lash, James P.] Univ Illinois, Dept Med, Chicago, IL 60616 USA. [Yang, Wei; Ford, Virginia; Nessel, Lisa; Zhang, Xiaoming] Univ Penn, Ctr Clin Epidemiol & Biostat, Philadelphia, PA 19104 USA. [Gordon, Elisa J.] Northwestern Univ, Feinberg Sch Med, Chicago, IL 60611 USA. [Diamantidis, Clarissa J.] Univ Maryland, Sch Med, Baltimore, MD 21201 USA. [Kusek, John W.] NIDDK, NIH, Bethesda, MD 20892 USA. [Lustigova, Eva] Tulane Univ, New Orleans, LA 70118 USA. [Rosas, Sylvia E.] Univ Penn, Philadelphia VA Med Ctr, Dept Med, Philadelphia, PA 19104 USA. [Steigerwalt, Susan] St Johns Hlth Syst, Detroit, MI USA. [Theurer, Jacqueline] MetroHlth Med Ctr, Dept Med, Div Nephrol, Cleveland, OH USA. [Fischer, Michael J.] Jesse Brown VA Med Ctr, Ctr Management Complex Chron Care, Chicago, IL USA. RP Ricardo, AC (reprint author), Univ Illinois, Nephrol Sect, 820 South Wood St,Room 470, Chicago, IL 60616 USA. EM aricar2@uic.edu FU National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) [5U01DK060990, 5U01DK060984, 5U01DK06102, 5U01DK061021, 5U01DK061028, 5U01DK60980, 5U01DK060963, 5U01DK060902]; HCRIC [R01 DK072231]; institutional Clinical Translational Science Awards (CTSA); National Institutes of Health (NIH) [UL1 RR-025005, GRCR M01 RR-16500, UL1 RR-024989, GCRC M01 RR-000042, CTSA UL1 RR-024986, M01 RR-013987-06, RR-05096, UCSF-CTSI UL1 RR-024131, 5K24DK002651]; National Center for Minority Health and Health Disparities, NIH; Department of Veterans Affairs Health Services Research and Development Service (MJF Career Development Award) FX This work was funded under a cooperative agreement from the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) (5U01DK060990, 5U01DK060984, 5U01DK06102, 5U01DK061021, 5U01DK061028, 5U01DK60980, 5U01DK060963, 5U01DK060902) and an R01 DK072231 (HCRIC). In addition, this work was supported in part by institutional Clinical Translational Science Awards (CTSA) and other National Institutes of Health (NIH) grants: Johns Hopkins University UL1 RR-025005; University of Maryland GRCR M01 RR-16500; Case Western Reserve University Clinical and Translational Science Collaborative (University Hospitals of Cleveland, Cleveland Clinic Foundation, and MetroHealth) UL1 RR-024989; University of Michigan GCRC M01 RR-000042, CTSA UL1 RR-024986; University of Illinois at Chicago Clinical Research Center, M01 RR-013987-06; Tulane/LSU/Charity Hospital General Clinical Research Center RR-05096; University of Pennsylvania CTSA UL1 RR-024134; Kaiser NIH/NCRR UCSF-CTSI UL1 RR-024131, 5K24DK002651. Additional support was provided by the National Center for Minority Health and Health Disparities, NIH, and Department of Veterans Affairs Health Services Research and Development Service (MJF Career Development Award). NR 38 TC 11 Z9 12 U1 5 U2 12 PU DUSTRI-VERLAG DR KARL FEISTLE PI DEISENHOFEN-MUENCHEN PA BAHNHOFSTRASSE 9 POSTFACH 49, D-82032 DEISENHOFEN-MUENCHEN, GERMANY SN 0301-0430 J9 CLIN NEPHROL JI Clin. Nephrol. PD JAN PY 2014 VL 81 IS 1 BP 30 EP 37 DI 10.5414/CN108062 PG 8 WC Urology & Nephrology SC Urology & Nephrology GA AG5FL UT WOS:000335444800004 PM 24219913 ER PT B AU Grush, A Bayes, J AF Grush, Artem Bayes, Joseph BE Henderson, BA TI ANESTHESIA FOR CATARACT SURGERY SO ESSENTIALS OF CATARACT SURGERY, SECOND EDITION LA English DT Article; Book Chapter ID PENETRATING OCULAR INJURY; LOCAL-ANESTHESIA; PERIBULBAR ANESTHESIA; RETROBULBAR ANESTHESIA; PERIOCULAR ANESTHESIA; REGIONAL ANESTHESIA; RISK-FACTORS; COMPLICATIONS; HYALURONIDASE; INJECTIONS C1 [Grush, Artem] Massachusetts Eye & Ear Infirm, Surgictr, Boston, MA 02114 USA. [Grush, Artem; Bayes, Joseph] Harvard Univ, Sch Med, Boston, MA USA. RP Grush, A (reprint author), Massachusetts Eye & Ear Infirm, Surgictr, Boston, MA 02114 USA. NR 40 TC 0 Z9 0 U1 0 U2 1 PU SLACK INC PI THOROFARE PA 6900 GROVE ROAD, THOROFARE, NJ 08086-9447 USA BN 978-1-61711-067-2 PY 2014 BP 31 EP 43 PG 13 WC Ophthalmology; Surgery SC Ophthalmology; Surgery GA BA1TA UT WOS:000333060600004 ER PT B AU McClintic, SM Shapiro, B Tam, DY Naseri, A AF McClintic, Scott M. Shapiro, Brett Tam, Diamond Y. Naseri, Ayman BE Henderson, BA TI INCISION CONSTRUCTION SO ESSENTIALS OF CATARACT SURGERY, SECOND EDITION LA English DT Article; Book Chapter ID CORNEAL CATARACT INCISIONS; INTRAOCULAR-LENS IMPLANTATION; SCLERAL TUNNEL INCISION; SELF-SEALING INCISIONS; CLEAR CORNEAL; RETROBULBAR ANESTHESIA; ANTERIOR-CHAMBER; COHERENCE TOMOGRAPHY; INDUCED ASTIGMATISM; TOPICAL ANESTHESIA C1 [McClintic, Scott M.] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Shapiro, Brett] Univ Calif San Francisco, Sch Med, San Francisco, CA 94143 USA. [Tam, Diamond Y.] Univ Toronto, Toronto, ON, Canada. [Naseri, Ayman] Univ Calif San Francisco, San Francisco VA Med Ctr, San Francisco, CA 94143 USA. RP McClintic, SM (reprint author), Univ Calif San Francisco, San Francisco, CA 94143 USA. NR 84 TC 0 Z9 0 U1 0 U2 0 PU SLACK INC PI THOROFARE PA 6900 GROVE ROAD, THOROFARE, NJ 08086-9447 USA BN 978-1-61711-067-2 PY 2014 BP 51 EP 67 PG 17 WC Ophthalmology; Surgery SC Ophthalmology; Surgery GA BA1TA UT WOS:000333060600006 ER PT B AU Edgington, BD Mahesh, S Goldstein, MH AF Edgington, Bryan D. Mahesh, Sankaranarayana Goldstein, Michael H. BE Henderson, BA TI SUTURED INTRAOCULAR LENSES SO ESSENTIALS OF CATARACT SURGERY, SECOND EDITION LA English DT Article; Book Chapter ID FIXATION; IMPLANTATION; SUPPORT; ABSENCE C1 [Edgington, Bryan D.] Portland VA Med Ctr, Casey Eye Inst, Portland, OR 97239 USA. [Mahesh, Sankaranarayana] George Washington Univ, Washington, DC USA. [Goldstein, Michael H.] New England Eye Ctr, Cornea & External Dis Serv, Boston, MA USA. [Goldstein, Michael H.] Tufts Univ, Sch Med, Boston, MA 02111 USA. RP Edgington, BD (reprint author), Portland VA Med Ctr, Casey Eye Inst, Portland, OR 97239 USA. NR 13 TC 0 Z9 0 U1 0 U2 0 PU SLACK INC PI THOROFARE PA 6900 GROVE ROAD, THOROFARE, NJ 08086-9447 USA BN 978-1-61711-067-2 PY 2014 BP 193 EP 206 PG 14 WC Ophthalmology; Surgery SC Ophthalmology; Surgery GA BA1TA UT WOS:000333060600019 ER PT B AU Chen, SH Pineda, R AF Chen, Sherleen H. Pineda, Roberto, II BE Henderson, BA TI THE SMALL PUPIL SO ESSENTIALS OF CATARACT SURGERY, SECOND EDITION LA English DT Article; Book Chapter ID CORNEAL CATARACT-SURGERY; IRIS RETRACTORS; PHACOEMULSIFICATION; PSEUDOEXFOLIATION; PUPILLOPLASTY; EXTRACTION C1 [Chen, Sherleen H.] Harvard Univ, Sch Med, Cambridge, MA 02138 USA. [Chen, Sherleen H.] Massachusetts Eye & Ear Infirm, Comprehens Ophthalmol & Cataract Consultat Serv, Boston, MA USA. RP Chen, SH (reprint author), Harvard Univ, Sch Med, Cambridge, MA 02138 USA. NR 17 TC 0 Z9 0 U1 0 U2 1 PU SLACK INC PI THOROFARE PA 6900 GROVE ROAD, THOROFARE, NJ 08086-9447 USA BN 978-1-61711-067-2 PY 2014 BP 235 EP 247 PG 13 WC Ophthalmology; Surgery SC Ophthalmology; Surgery GA BA1TA UT WOS:000333060600022 ER PT J AU Zuurbier, L Gutierrez, A Mullighan, CG Cante-Barrett, K Gevaert, AO de Rooi, J Li, YL Smits, WK Buijs-Gladdines, JGCAM Sonneveld, E Look, AT Horstmann, M Pieters, R Meijerink, JPP AF Zuurbier, Linda Gutierrez, Alejandro Mullighan, Charles G. Cante-Barrett, Kirsten Gevaert, A. Olivier de Rooi, Johan Li, Yunlei Smits, Willem K. Buijs-Gladdines, Jessica G. C. A. M. Sonneveld, Edwin Look, A. Thomas Horstmann, Martin Pieters, Rob Meijerink, Jules P. P. TI Immature MEF2C-dysregulated T-cell leukemia patients have an early T-cell precursor acute lymphoblastic leukemia gene signature and typically have non-rearranged T-cell receptors SO HAEMATOLOGICA LA English DT Article ID CLINICAL-SIGNIFICANCE; ALL REVEALS; EXPRESSION; MUTATIONS; TCR; PROTOCOL; ALPHA; ONCOGENES; CHILDREN; SUBGROUP AB Three distinct immature T-cell acute lymphoblastic leukemia entities have been described including cases that express an early T-cell precursor immunophenotype or expression profile, immature MEF2C-dysregulated T-cell acute lymphoblastic leukemia cluster cases based on gene expression analysis (immature cluster) and cases that retain non-rearranged TRG@ loci. Early T-cell precursor acute lymphoblastic leukemia cases exclusively overlap with immature cluster samples based on the expression of early T-cell precursor acute lymphoblastic leukemia signature genes, indicating that both are featuring a single disease entity. Patients lacking TRG@ rearrangements represent only 40% of immature cluster cases, but no further evidence was found to suggest that cases with absence of bi-allelic TRG@ deletions reflect a distinct and even more immature disease entity. Immature cluster/early T-cell precursor acute lymphoblastic leukemia cases are strongly enriched for genes expressed in hematopoietic stem cells as well as genes expressed in normal early thymocyte progenitor or double negative-2A T-cell subsets. Identification of early T-cell precursor acute lymphoblastic leukemia cases solely by defined immunophenotypic criteria strongly underestimates the number of cases that have a corresponding gene signature. However, early T-cell precursor acute lymphoblastic leukemia samples correlate best with a CD1 negative, CD4 and CD8 double negative immunophenotype with expression of CD34 and/or myeloid markers CD13 or CD33. Unlike various other studies, immature cluster/early T-cell precursor acute lymphoblastic leukemia patients treated on the COALL-97 protocol did not have an overall inferior outcome, and demonstrated equal sensitivity levels to most conventional therapeutic drugs compared to other pediatric T-cell acute lymphoblastic leukemia patients. C1 [Zuurbier, Linda; Cante-Barrett, Kirsten; Li, Yunlei; Smits, Willem K.; Buijs-Gladdines, Jessica G. C. A. M.; Pieters, Rob; Meijerink, Jules P. P.] Sophia Childrens Univ Hosp, Erasmus MC Rotterdam, Dept Pediat Oncol Hematol, Rotterdam, Netherlands. [Gutierrez, Alejandro; Look, A. Thomas] Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. [Gutierrez, Alejandro; Look, A. Thomas] Childrens Hosp, Div Hematol Oncol, Boston, MA 02115 USA. [Mullighan, Charles G.] St Jude Childrens Res Hosp, Dept Pathol, Memphis, TN 38105 USA. [Gevaert, A. Olivier] Stanford Univ, Sch Med, CCSB, Stanford, CA 94305 USA. [Gevaert, A. Olivier] Stanford Univ, Sch Med, Dept Radiol, Stanford, CA 94305 USA. [de Rooi, Johan] Erasmus MC, Dept Biostat, Rotterdam, Netherlands. [de Rooi, Johan] Erasmus MC, Dept Bioinformat, Rotterdam, Netherlands. [Sonneveld, Edwin; Pieters, Rob] DCOG, The Hague, Netherlands. [Horstmann, Martin] German Cooperat Study Grp Childhood Acute Lymphob, Hamburg, Germany. [Horstmann, Martin] Univ Med Ctr Hamburg Eppendorf, Childrens Canc Ctr Hamburg, Clin Pediat Hematol & Oncol, Res Inst, Hamburg, Germany. RP Meijerink, JPP (reprint author), Sophia Childrens Univ Hosp, Erasmus MC Rotterdam, Dept Pediat Oncol Hematol, Rotterdam, Netherlands. EM j.meijerink@erasmusmc.nl RI Meijerink, Jules/D-4393-2017; OI Meijerink, Jules/0000-0002-6860-798X; Gutierrez, Alejandro/0000-0002-0249-9007; Mullighan, Charles/0000-0002-1871-1850 FU Children Cancer Free Foundation [KIKA2007-012, KIKA2008-029, KIKA2010-82]; Dutch Cancer Society [AMC2008-4265]; NIH [CA167124]; DOD [CA120215]; William Lawrence Blanche Hughes Foundation FX This work was supported by the The Children Cancer Free Foundation, Stichting Kinderen Kankervrij (KiKa): project ns. KIKA2007-012 (LZ), KIKA2008-029 (KC-B and WKS), and KIKA2010-82 (YL) and the Dutch Cancer Society Project n. AMC2008-4265 (JB-G). AG is supported by NIH grant CA167124, DOD grant CA120215, an award from the William Lawrence Blanche Hughes Foundation, and is a Research Fellow of the Gabrielle's Angel Foundation for Cancer Research. NR 41 TC 15 Z9 15 U1 3 U2 4 PU FERRATA STORTI FOUNDATION PI PAVIA PA VIA GIUSEPPE BELLI 4, 27100 PAVIA, ITALY SN 0390-6078 J9 HAEMATOLOGICA JI Haematologica PD JAN PY 2014 VL 99 IS 1 BP 94 EP 102 DI 10.3324/haematol.2013.090233 PG 9 WC Hematology SC Hematology GA AH1OL UT WOS:000335890500019 PM 23975177 ER PT J AU Alexander, BM D'Andrea, AD AF Alexander, Brian M. D'Andrea, Alan D. BE Gelmann, EP Sawyers, CL Rauscher, FJ TI DNA repair inhibition in anti-cancer therapeutics SO MOLECULAR ONCOLOGY: CAUSES OF CANCER AND TARGETS FOR TREATMENT LA English DT Article; Book Chapter ID DEPENDENT PROTEIN-KINASE; PHASE-I TRIAL; FANCONI-ANEMIA PATHWAY; ACUTE MYELOID-LEUKEMIA; ADVANCED SOLID TUMORS; POLY(ADP-RIBOSE) POLYMERASE-1 INHIBITOR; ADP-RIBOSE POLYMERASE; CANCER-CELLS; HOMOLOGOUS RECOMBINATION; DAMAGE RESPONSE C1 [Alexander, Brian M.; D'Andrea, Alan D.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Radiat Oncol, Boston, MA 02115 USA. RP Alexander, BM (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Radiat Oncol, 44 Binney St, Boston, MA 02115 USA. NR 103 TC 0 Z9 0 U1 0 U2 0 PU PRINCETON UNIV PRESS PI PRINCETON PA 41 WILLIAM ST, PRINCETON, NJ 08540 USA BN 978-0-521-87662-9 PY 2014 BP 936 EP 944 PG 9 WC Oncology SC Oncology GA BA1DD UT WOS:000332401400091 ER PT B AU Freire, MO Van Dyke, TE AF Freire, Marcelo O. Van Dyke, Thomas E. BE Glick, M TI The Mechanisms Behind Oral-Systemic Interactions SO ORAL-SYSTEMIC HEALTH CONNECTION: A GUIDE TO PATIENT CARE LA English DT Article; Book Chapter ID JOINT EFP/AAP WORKSHOP; PERIODONTAL-DISEASE; RESOLVIN D1; INDUCED COLITIS; INFLAMMATORY MECHANISMS; PATHOGENIC MECHANISMS; LOCAL INFLAMMATION; LIPID MEDIATORS; VASCULAR EVENTS; RESOLUTION C1 [Freire, Marcelo O.] Forsyth Inst, Dept Appl Oral Sci, Cambridge, MA 02142 USA. [Freire, Marcelo O.] Harvard Univ, Sch Dent Med, Dept Oral Med Infect & Immun, Boston, MA 02115 USA. [Van Dyke, Thomas E.] Dept Appl Oral Sci, Cambridge, MA USA. RP Freire, MO (reprint author), Forsyth Inst, Dept Appl Oral Sci, Cambridge, MA 02142 USA. NR 74 TC 0 Z9 0 U1 0 U2 1 PU SLACK INC PI THOROFARE PA 6900 GROVE ROAD, THOROFARE, NJ 08086-9447 USA BN 978-0-86715-650-8 PY 2014 BP 103 EP 119 PG 17 WC Dentistry, Oral Surgery & Medicine; Primary Health Care SC Dentistry, Oral Surgery & Medicine; General & Internal Medicine GA BA1PM UT WOS:000332802500006 ER PT B AU Lamster, IB Fennoy, I Tavares, M AF Lamster, Ira B. Fennoy, Ilene Tavares, Mary BE Glick, M TI Obesity: The Oral-Systemic Connection SO ORAL-SYSTEMIC HEALTH CONNECTION: A GUIDE TO PATIENT CARE LA English DT Article; Book Chapter ID OBSTRUCTIVE SLEEP-APNEA; BODY-MASS INDEX; SUGAR-SWEETENED BEVERAGES; CARDIOVASCULAR RISK-FACTORS; GINGIVAL CREVICULAR FLUID; CORONARY-HEART-DISEASE; HUMAN ADIPOSE-TISSUE; DENTAL-CARIES; WEIGHT-GAIN; PERIODONTAL-DISEASE C1 [Lamster, Ira B.] Mailman Sch Publ Hlth, New York, NY 10032 USA. [Lamster, Ira B.] Columbia Univ, Coll Dent Med, New York, NY USA. [Fennoy, Ilene] Columbia Univ Coll Phys & Surg, Columbia Univ Med Ctr, New York, NY 10032 USA. [Tavares, Mary] Forsyth Inst, Cambridge, MA USA. [Tavares, Mary] Harvard Univ, Sch Dent Med, Boston, MA 02115 USA. RP Lamster, IB (reprint author), Mailman Sch Publ Hlth, New York, NY 10032 USA. NR 218 TC 0 Z9 0 U1 0 U2 2 PU SLACK INC PI THOROFARE PA 6900 GROVE ROAD, THOROFARE, NJ 08086-9447 USA BN 978-0-86715-650-8 PY 2014 BP 157 EP 185 PG 29 WC Dentistry, Oral Surgery & Medicine; Primary Health Care SC Dentistry, Oral Surgery & Medicine; General & Internal Medicine GA BA1PM UT WOS:000332802500009 ER PT J AU Dinkel, J Drier, A Khalilzadeh, O Perlbarg, V Czernecki, V Gupta, R Gomas, F Sanchez, P Dormont, D Galanaud, D Stevens, RD Puybasset, L AF Dinkel, J. Drier, A. Khalilzadeh, O. Perlbarg, V. Czernecki, V. Gupta, R. Gomas, F. Sanchez, P. Dormont, D. Galanaud, D. Stevens, R. D. Puybasset, L. CA NICER Neuro Imaging Coma Emergence TI Long-Term White Matter Changes after Severe Traumatic Brain Injury: A 5-Year Prospective SO AMERICAN JOURNAL OF NEURORADIOLOGY LA English DT Article ID DIFFUSE AXONAL INJURY; SPATIAL STATISTICS; HEAD TRAUMA; ANISOTROPY; NEUROPLASTICITY; MODERATE; TIME AB The authors used DTI to study posttraumatic white matter changes over a 5-year period. Thirteen patients with severe injuries acutely showed significant fractional anisotropy decreases in the corpus callosum and corona radiata when compared with controls. These abnormalities progressed at 2 years and then remained stable until 5 years. The DTI abnormalities correlated with sequelae such as amnesia, aphasia, and dyspraxia. BACKGROUND AND PURPOSE: Extensive white matter damage has been documented in patients with severe traumatic brain injury, yet how this damage evolves in the long term is not well understood. We used DTI to study white matter changes at 5 years after traumatic brain injury. MATERIALS AND METHODS: There were 8 healthy control participants and 13 patients with severe traumatic brain injury who were enrolled in a prospective observational study, which included clinical assessment and brain MR imaging in the acute setting (< 6 weeks) and 2 years and 5 years after injury. Only subjects with mild to moderate disability or no disability at 1 year were included in this analysis. DTI parameters were measured in 20 different brain regions and were normalized to values obtained in an age-matched control group. RESULTS: In the acute setting, fractional anisotropy was significantly lower in the genu and body of the corpus callosum and in the bilateral corona radiata in patients compared with control participants, whereas radial diffusivity was significantly (P < .05) higher in these tracts. At 2 years, fractional anisotropy in these tracts had further decreased and radial diffusivity had increased. No significant changes were detected between 2 and 5 years after injury. The baseline radial diffusivity and fractional anisotropy values in the anterior aspect of the brain stem, genu and body of the corpus callosum, and the right and left corona radiata were significantly (P < .05) associated with neurocognitive sequelae (including amnesia, aphasia, and dyspraxia) at year 5. CONCLUSIONS: DTI changes in major white matter tracts persist up to 5 years after severe traumatic brain injury and are most pronounced in the corpus callosum and corona radiata. Limited structural change is noted in the interval between 2 and 5 years. C1 [Dinkel, J.; Khalilzadeh, O.; Gupta, R.] Harvard Univ, Sch Med, Dept Radiol, Massachusetts Gen Hosp, Boston, MA 02115 USA. [Dinkel, J.] Univ Heidelberg Hosp, Dept Radiol, Heidelberg, Germany. [Drier, A.; Dormont, D.; Galanaud, D.] Grp Hosp Pitie Salpetriere, AP HP, Dept Neuroradiol, Paris, France. [Czernecki, V.] Grp Hosp Pitie Salpetriere, AP HP, Dept Neurol, Paris, France. [Sanchez, P.; Puybasset, L.] Grp Hosp Pitie Salpetriere, AP HP, Dept Anesthesiol & Intens Care, Paris, France. [Perlbarg, V.] Univ Paris 06, INSERM, UMRS 678, F-75013 Paris, France. [Czernecki, V.] Univ Paris 06, INSERM, CRICM UMR S975, F-75013 Paris, France. [Gomas, F.] Louis Mourier Hosp, Dept Anesthesiol & Intens Care, Colombes, France. [Stevens, R. D.] Johns Hopkins Univ, Sch Med, Dept Anesthesiol Crit Care Med, Div Neurosci Crit Care, Baltimore, MD USA. RP Puybasset, L (reprint author), Univ Paris 06, Grp Hosp Pitie Salpetriere, Dept Anesthesie Reanimat, 47-83 Bd Hop, F-75013 Paris, France. EM louis.puybasset@psl.aphp.fr FU French Ministry of Health [P051061 [2005]]; Assistance Publique-Hopitaux de Paris FX This study was funded by a grant from the French Ministry of Health (Projet Hospitalier de Recherche Clinique registration # P051061 [2005]) and from departmental funds from the Assistance Publique-Hopitaux de Paris. NR 30 TC 14 Z9 15 U1 0 U2 5 PU AMER SOC NEURORADIOLOGY PI DENVILLE PA PO BOX 3000, DENVILLE, NJ 07834-9349 USA SN 0195-6108 EI 1936-959X J9 AM J NEURORADIOL JI Am. J. Neuroradiol. PD JAN PY 2014 VL 35 IS 1 BP 23 EP 29 DI 10.3174/ajnr.A3616 PG 7 WC Clinical Neurology; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA AD9ER UT WOS:000333568100007 PM 23846796 ER PT J AU Kelly, HR Hamberg, LM Hunter, GJ AF Kelly, H. R. Hamberg, L. M. Hunter, G. J. TI 4D-CT for Preoperative Localization of Abnormal Parathyroid Glands in Patients with Hyperparathyroidism: Accuracy and Ability to Stratify Patients by Unilateral versus Bilateral Disease in Surgery-Naiv and Re-Exploration Patients SO AMERICAN JOURNAL OF NEURORADIOLOGY LA English DT Article ID 4-DIMENSIONAL COMPUTED-TOMOGRAPHY; 4D-COMPUTED TOMOGRAPHY; ADENOMAS; NECK; CT AB BACKGROUND AND PURPOSE: 4D-CT is an emerging technique that uses high-resolution images, multiplanar reformats, and perfusion characteristics to identify abnormal parathyroid glands in patients with hyperparathyroidism. This study evaluates the accuracy of 4D-CT for localization and lateralization of abnormal parathyroid glands in preoperative planning for minimally invasive parathyroidectomy vs bilateral neck exploration at a tertiary referral center. MATERIALS AND METHODS: Radiology, pathology, and operative reports were retrospectively reviewed for 208 patients with hyperparathyroidism who underwent 4D-CT and parathyroid surgery between May 2008 and January 2012. 4D-CT performance in localizing side and site was determined by use of surgical and pathologic findings as a reference. RESULTS: Of 208 patients, 155 underwent initial surgery and 53 underwent re-exploration parathyroid surgery. No lesions were found in 8 patients (3.8%). A total of 284 lesions were found in 200 patients; 233 were correctly localized by 4D-CT (82.0%). Of the 200 patients with parathyroid lesions, 146 underwent unilateral and 54 bilateral neck exploration. 4D-CT correctly identified unilateral vs bilateral disease in 179 (89.5%) of 200. 4D-CT correctly localized parathyroid lesions in 126 of the unilateral cases (86.3%). In the re-exploration cohort, 4D-CT correctly identified unilateral vs bilateral disease in 46 (95.8%) of 48. There was no statistically significant difference in subgroups stratified by surgery type (primary or subsequent) and number of scan phases (3 or 4) (P > .56). CONCLUSIONS: 4D-CT leverages modern high-resolution CT scanning and dynamic contrast enhancement to localize abnormal parathyroid glands in patients with hyperparathyroidism of any cause and can be used for planning minimally invasive parathyroidectomy vs bilateral neck exploration. C1 [Kelly, H. R.; Hunter, G. J.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Diagnost Neuroradiol, Boston, MA USA. [Kelly, H. R.] Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Radiol, Boston, MA USA. [Hamberg, L. M.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Radiol, Boston, MA 02115 USA. RP Kelly, HR (reprint author), Massachusetts Gen Hosp, Div Neuroradiol, 55 Fruit St,GRB-273A, Boston, MA 02114 USA. EM hkelly2@partners.org NR 21 TC 18 Z9 18 U1 0 U2 3 PU AMER SOC NEURORADIOLOGY PI DENVILLE PA PO BOX 3000, DENVILLE, NJ 07834-9349 USA SN 0195-6108 EI 1936-959X J9 AM J NEURORADIOL JI Am. J. Neuroradiol. PD JAN PY 2014 VL 35 IS 1 BP 176 EP 181 DI 10.3174/ajnr.A3615 PG 6 WC Clinical Neurology; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA AD9ER UT WOS:000333568100033 PM 23868155 ER PT J AU Manasawala, M Cunnane, ME Curtin, HD Moonis, G AF Manasawala, M. Cunnane, M. E. Curtin, H. D. Moonis, G. TI Imaging Findings in Auto-Atticotomy SO AMERICAN JOURNAL OF NEURORADIOLOGY LA English DT Article ID CHOLESTEATOMA AB BACKGROUND AND PURPOSE: An acquired attic cholesteatoma may spontaneously drain externally into the external auditory canal, leaving a cavity in the attic with the shape of the original cholesteatoma but now filled with air, a phenomenon referred to as nature's atticotomy or auto-atticotomy. We describe and quantify the CT appearance of the auto-atticotomy cavity as it pertains to the appearance of the scutum and the lateral attic wall. MATERIALS AND METHODS: Twenty-one patients with erosion of the scutum and loss of the lower attic wall on MDCT were identified during a 5-year span. Images were assessed for measureable widening of the space between the ossicles and the lower lateral attic wall in the axial and coronal planes. Three measurements of the lateral attic were made on the axial images. Findings were compared with the same measurements in 20 control subjects. RESULTS: The 21 patients had a characteristic blunting of the scutum with loss of the lower lateral attic wall and widening of the lateral attic, consistent with an auto-atticotomy. There was a statistically significant (P < .001) widening of the lateral attic dimensions in the axial plane in the patients with auto-atticotomy. CONCLUSIONS: Spontaneously evacuated cholesteatoma may mimic a surgical atticotomy on MDCT. Scutal erosion and attic enlargement with a smoothly contoured bony remodeling of the lower lateral attic wall in a patient with no history of surgery suggest that a cholesteatoma was previously present and spontaneously drained. C1 [Manasawala, M.] Abington Mem Hosp, Dept Radiol, Abington, PA 19001 USA. [Moonis, G.] Beth Israel Deaconess Med Ctr, Dept Radiol, Boston, MA 02215 USA. [Cunnane, M. E.; Curtin, H. D.; Moonis, G.] Massachusetts Eye & Ear Infirm, Dept Radiol, Boston, MA 02215 USA. RP Moonis, G (reprint author), Massachusetts Eye & Ear Infirm, Dept Radiol, 243 Charles St, Boston, MA 02215 USA. EM gmoonis@bidmc.harvard.edu FU Mt. Sinai Hospital FX Mary E. Cunnane-UNRELATED: Other: WorldCare Clinical, Comments: payment for reviewing radiology studies on patients entered into drug trials for head and neck cancer. Hugh D. Curtin-UNRELATED: Payment for Lectures (including service on Speakers Bureaus): I lecture in Continuing Medical Education but am not sponsored by any company and do not get paid for lecturing; I am not on any Speakers Bureaus, Royalties: none other than books and lecturing; nothing from outside companies related to health care, Travel/Accommodations/Meeting Expenses Unrelated to Activities Listed: If I lecture outside Boston, someone is usually paying meeting expenses and travel (various universities). The International Institute for Continuing Medical Education pays for my travel to a meeting sponsored by Mt. Sinai Hospital. NR 16 TC 0 Z9 0 U1 0 U2 1 PU AMER SOC NEURORADIOLOGY PI DENVILLE PA PO BOX 3000, DENVILLE, NJ 07834-9349 USA SN 0195-6108 EI 1936-959X J9 AM J NEURORADIOL JI Am. J. Neuroradiol. PD JAN PY 2014 VL 35 IS 1 BP 182 EP 185 DI 10.3174/ajnr.A3791 PG 4 WC Clinical Neurology; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA AD9ER UT WOS:000333568100034 PM 24231849 ER PT J AU Jotwani, V Scherzer, R Abraham, A Estrella, MM Bennett, M Devarajan, P Anastos, K Cohen, MH Nowicki, M Sharma, A Young, M Tien, PC Grunfeld, C Parikh, CR Shlipak, MG AF Jotwani, Vasantha Scherzer, Rebecca Abraham, Alison Estrella, Michelle M. Bennett, Michael Devarajan, Prasad Anastos, Kathryn Cohen, Mardge H. Nowicki, Marek Sharma, Anjali Young, Mary Tien, Phyllis C. Grunfeld, Carl Parikh, Chirag R. Shlipak, Michael G. TI Does HIV infection promote early kidney injury in women? SO ANTIVIRAL THERAPY LA English DT Article ID GELATINASE-ASSOCIATED LIPOCALIN; RENAL-DISEASE; MOLECULE-1 KIM-1; CARDIAC-SURGERY; CYSTATIN-C; ANTIRETROVIRAL THERAPY; URINE NGAL; BIOMARKER; NEPHROPATHY; INTERLEUKIN-18 AB Background: In HIV-infected women, urine concentrations of novel tubulointerstitial injury markers, interleukin-18 (IL-18) and kidney injury marker-1 (KIM-1), are associated with kidney function decline and all-cause mortality. We hypothesized that HIV-infected individuals with preserved kidney filtration function would have more extensive kidney injury, as determined by urine injury markers, compared to the uninfected controls, and that risk factors for tubulointerstitial injury would differ from risk factors for albuminuria. Methods: In this cross-sectional study, we compared urine concentrations of IL-18, KIM-1 and albumin-tocreatinine ratio (ACR) in 908 HIV-infected and 289 HIV-uninfected women enrolled in the Women's Interagency HIV Study, utilizing stored urine specimens from visits between 1999 and 2000. Results: After multivariate-adjusted linear regression analysis, mean urine concentrations were higher in HIV-infected individuals by 38% for IL-18 (P<0.0001), 12% for KIM-1 (P=0.081) and 47% for ACR (P<0.0001). Higher HIV RNA level (15% per 10-fold increase; P<0.0001), lower CD4(+) lymphocyte count (8% per doubling; P=0.0025), HCV infection (30%; P=0.00018) and lower high-density lipoprotein (5% per 10 mg/dl; P=0.0024) were each associated with higher IL-18 concentrations. In contrast, hypertension (81%; P<0.0001) and diabetes (47%; P=0.018) were among the strongest predictors of higher ACR, though HIV RNA level (15% per 10-fold increase; P=0.0004) was also associated with higher ACR. Conclusions: HIV-infected women had more extensive tubulointerstitial and glomerular injury than uninfected women, but the associated factors differed among the urine biomarkers. Combinations of urinary biomarkers should be investigated to further characterize early kidney injury in HIV-infected women. C1 [Jotwani, Vasantha; Scherzer, Rebecca; Tien, Phyllis C.; Grunfeld, Carl; Shlipak, Michael G.] San Francisco VA Med Ctr, Dept Med, San Francisco, CA 94121 USA. [Jotwani, Vasantha; Scherzer, Rebecca; Grunfeld, Carl; Shlipak, Michael G.] Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA. [Abraham, Alison] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD USA. [Estrella, Michelle M.] Johns Hopkins Sch Med, Dept Med, Baltimore, MD USA. [Bennett, Michael; Devarajan, Prasad] Cincinnati Childrens Hosp Med Ctr, Div Nephrol & Hypertens, Cincinnati, OH 45229 USA. [Anastos, Kathryn] Montefiore Med Ctr, Albert Einstein Coll Med, Dept Med, Bronx, NY 10467 USA. [Anastos, Kathryn] Albert Einstein Coll Med, Dept Epidemiol & Populat Hlth, Bronx, NY 10467 USA. [Cohen, Mardge H.] Stroger Hosp, Dept Med, Chicago, IL USA. [Cohen, Mardge H.] Rush Univ, Chicago, IL 60612 USA. [Nowicki, Marek] Univ So Calif, Dept Med, Los Angeles, CA USA. [Sharma, Anjali] Suny Downstate Med Ctr, Dept Med, Div Infect Dis, Brooklyn, NY 11203 USA. [Young, Mary] Georgetown Univ, Med Ctr, Dept Med, Div Infect Dis & Travel Med, Washington, DC 20007 USA. [Parikh, Chirag R.] Yale Univ, Dept Med, Nephrol Sect, New Haven, CT 06520 USA. [Parikh, Chirag R.] Yale Univ, Program Appl Translat Res, New Haven, CT USA. RP Shlipak, MG (reprint author), San Francisco VA Med Ctr, Dept Med, San Francisco, CA 94121 USA. EM Michael.Shlipak@ucsf.edu FU NCRR NIH HHS [UL1 RR024131]; NIA NIH HHS [1R01 AG034853-01A2, R01 AG034853]; NIAID NIH HHS [U01-AI-34993, P30 AI027763, U01 AI034993, U01 AI035004, U01 AI042590, U01-AI-35004, U01 AI031834, U01 AI034989, U01 AI034994, U01-AI-31834, U01-AI-34989, U01-AI-34994]; NICHD NIH HHS [U01 HD032632, U01-HD-42590, U01-HD-32632]; NIDDK NIH HHS [P50 DK096418, T32 DK007219] NR 52 TC 4 Z9 4 U1 1 U2 2 PU INT MEDICAL PRESS LTD PI LONDON PA 2-4 IDOL LANE, LONDON EC3R 5DD, ENGLAND SN 1359-6535 J9 ANTIVIR THER JI Antivir. Ther. PY 2014 VL 19 IS 1 BP 79 EP 87 DI 10.3851/IMP2677 PG 9 WC Infectious Diseases; Pharmacology & Pharmacy; Virology SC Infectious Diseases; Pharmacology & Pharmacy; Virology GA AG2FP UT WOS:000335231800008 PM 23970313 ER PT J AU Chang, HH Tseng, W Cui, J Costenbader, K Ho, IC AF Chang, Hui-Hsin Tseng, William Cui, Jing Costenbader, Karen Ho, I-Cheng TI Altered expression of protein tyrosine phosphatase, non-receptor type 22 isoforms in systemic lupus erythematosus SO ARTHRITIS RESEARCH & THERAPY LA English DT Article ID SINGLE-NUCLEOTIDE POLYMORPHISM; GENOME-WIDE ASSOCIATION; T-CELL-ACTIVATION; RHEUMATOID-ARTHRITIS; SUSCEPTIBILITY LOCI; AUTOIMMUNE-DISEASE; PTPN22; DOMAIN; LYP; CLASSIFICATION AB Introduction: A C-to-T single nucleotide polymorphism (SNP) located at position 1858 of human protein tyrosine phosphatase, non-receptor type 22 (PTPN22) complementary DNA (cDNA) is associated with an increased risk of systemic lupus erythematosus (SLE). How the overall activity of PTPN22 is regulated and how the expression of PTPN22 differs between healthy individuals and patients with lupus are poorly understood. Our objectives were to identify novel alternatively spliced forms of PTPN22 and to examine the expression of PTPN22 isoforms in healthy donors and patients with lupus. Methods: Various human PTPN22 isoforms were identified from the GenBank database or amplified directly from human T cells. The expression of these isoforms in primary T cells and macrophages was examined with real-time polymerase chain reaction. The function of the isoforms was determined with luciferase assays. Blood samples were collected from 49 subjects with SLE and 15 healthy controls. Correlation between the level of PTPN22 isoforms in peripheral blood and clinical features of SLE was examined with statistical analyses. Results: Human PTPN22 was expressed in several isoforms, which differed in their level of expression and subcellular localization. All isoforms except one were functionally interchangeable in regulating NFAT activity. SLE patients expressed higher levels of PTPN22 than healthy individuals and the levels of PTPN22 were negatively correlated with the Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index (SLICC-DI). Conclusions: The overall activity of PTPN22 is determined by the functional balance among all isoforms. The levels of PTPN22 isoforms in peripheral blood could represent a useful biomarker of SLE. C1 [Chang, Hui-Hsin; Tseng, William; Cui, Jing; Costenbader, Karen; Ho, I-Cheng] Brigham & Womens Hosp, Dept Med, Div Rheumatol Immunol & Allergy, Boston, MA 02115 USA. [Chang, Hui-Hsin; Cui, Jing; Costenbader, Karen; Ho, I-Cheng] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Ho, I-Cheng] VA Boston Healthcare Syst, Rheumatol Sect, Boston, MA 02130 USA. RP Ho, IC (reprint author), Brigham & Womens Hosp, Dept Med, Div Rheumatol Immunol & Allergy, 1 Jimmy Fund Way, Boston, MA 02115 USA. EM iho@partners.org FU NCATS NIH HHS [8UL1TR000170-05]; NIAMS NIH HHS [P60 AR047782] NR 30 TC 4 Z9 4 U1 0 U2 1 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1478-6354 EI 1478-6362 J9 ARTHRITIS RES THER JI Arthritis Res. Ther. PY 2014 VL 16 IS 1 AR R14 DI 10.1186/ar4440 PG 12 WC Rheumatology SC Rheumatology GA AG1BA UT WOS:000335148700014 PM 24433447 ER PT J AU Kitahara, CM Linet, MS Brenner, AV Wang, SS Melin, BS Wang, ZM Inskip, PD Freeman, LEB Braganza, MZ Carreon, T Feychting, M Gaziano, JM Peters, U Purdue, MP Ruder, AM Sesso, HD Shu, XO Waters, MA White, E Zheng, W Hoover, RN Fraumeni, JF Chatterjee, N Yeager, M Chanock, SJ Hartge, P Rajaraman, P AF Kitahara, Cari M. Linet, Martha S. Brenner, Alina V. Wang, Sophia S. Melin, Beatrice S. Wang, Zhaoming Inskip, Peter D. Freeman, Laura E. Beane Braganza, Melissa Z. Carreon, Tania Feychting, Maria Gaziano, J. Michael Peters, Ulrike Purdue, Mark P. Ruder, Avima M. Sesso, Howard D. Shu, Xiao-Ou Waters, Martha A. White, Emily Zheng, Wei Hoover, Robert N. Fraumeni, Joseph F., Jr. Chatterjee, Nilanjan Yeager, Meredith Chanock, Stephen J. Hartge, Patricia Rajaraman, Preetha TI Personal History of Diabetes, Genetic Susceptibility to Diabetes, and Risk of Brain Glioma: A Pooled Analysis of Observational Studies SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID GENOME-WIDE ASSOCIATION; CENTRAL-NERVOUS-SYSTEM; INSULIN-RESISTANCE; PHYSICIANS HEALTH; CANCER INCIDENCE; TUMORS; VARIANTS; MELLITUS; COHORT; LOCI AB Background: Brain glioma is a relatively rare and fatal malignancy in adulthood with few known risk factors. Some observational studies have reported inverse associations between diabetes and subsequent glioma risk, but possible mechanisms are unclear. Methods: We conducted a pooled analysis of original data from five nested case-control studies and two case-control studies from the United States and China that included 962 glioma cases and 2,195 controls. We examined self-reported diabetes history in relation to glioma risk, as well as effect modification by seven glioma risk associated single-nucleotide polymorphisms(SNP). We also examined the associations between 13 diabetes risk associated SNPs, identified from genome-wide association studies, and glioma risk. Odds ratios (OR) and 95% confidence intervals (CI) were calculated using multivariable-adjusted logistic regression models. Results: We observed a 42% reduced risk of glioma for individuals with a history of diabetes (OR = 0.58; 95% CI, 0.40-0.84). The association did not differ by sex, study design, or after restricting to glioblastoma, the most common histological subtype. We did not observe any significant per-allele trends among the 13 diabetes related SNPs examined in relation to glioma risk. Conclusion: These results support an inverse association between diabetes history and glioma risk. The role of genetic susceptibility to diabetes cannot be excluded, and should be pursued in future studies together with other factors that might be responsible for the diabetes-glioma association. Impact: These data suggest the need for studies that can evaluate, separately, the association between type 1 and type 2 diabetes and subsequent risk of adult glioma. Cancer Epidemiol Biomarkers Prev; 23(1); 47-54. (C) 2013 AACR. C1 [Kitahara, Cari M.; Linet, Martha S.; Brenner, Alina V.; Wang, Zhaoming; Inskip, Peter D.; Freeman, Laura E. Beane; Braganza, Melissa Z.; Purdue, Mark P.; Hoover, Robert N.; Fraumeni, Joseph F., Jr.; Chatterjee, Nilanjan; Yeager, Meredith; Chanock, Stephen J.; Hartge, Patricia; Rajaraman, Preetha] NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. [Wang, Zhaoming; Yeager, Meredith; Chanock, Stephen J.] SAIC Frederick Inc, Core Genotyping Facil, NCI, Gaithersburg, MD USA. [Wang, Sophia S.] City Hope & Beckman Res Inst, Dept Populat Sci, Div Canc Etiol, Duarte, CA USA. [Carreon, Tania; Ruder, Avima M.; Waters, Martha A.] NIOSH, Ctr Dis Control & Prevent, Cincinnati, OH 45226 USA. [Gaziano, J. Michael; Sesso, Howard D.] Harvard Univ, Brigham & Womens Hosp, Div Prevent Med, Sch Med, Boston, MA 02115 USA. [Gaziano, J. Michael; Sesso, Howard D.] Harvard Univ, Brigham & Womens Hosp, Div Aging, Sch Med, Boston, MA 02115 USA. [Gaziano, J. Michael] VA Boston Healthcare Syst, Geriatr Res Educ & Clin Ctr, Res & Informat Ctr, Massachusetts Vet Epidemiol, Boston, MA USA. [Peters, Ulrike] Univ Washington, Fred Hutchinson Canc Res Ctr, Seattle, WA 98195 USA. [Peters, Ulrike; White, Emily] Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA. [Shu, Xiao-Ou; Zheng, Wei] Vanderbilt Univ, Med Ctr, Nashville, TN USA. [Melin, Beatrice S.] Umea Univ, Dept Radiat Sci, Umea, Sweden. [Feychting, Maria] Karolinska Inst, Inst Environm Med, S-10401 Stockholm, Sweden. RP Kitahara, CM (reprint author), Div Canc Epidemiol & Genet, 9609 Med Ctr Dr,Room 7E-566, Bethesda, MD 20892 USA. EM meinholdc@mail.nih.gov RI Purdue, Mark/C-9228-2016; Kitahara, Cari/R-8267-2016 OI Purdue, Mark/0000-0003-1177-3108; FU National Institutes of Health [CA 97193, CA 34944, CA 40360, HL 26490, HL 34595]; Division of Cancer Epidemiology and Genetics; Division of Cancer Prevention; National Cancer Institute; NIH; DHHS; NIOSH operating funds; National Cancer Institute [K05CA154337]; NIH Office of Dietary Supplements FX The authors thank all investigators who contributed data for the GliomaScan study.; For PHS: The PHS is supported by grants CA 97193, CA 34944, CA 40360, HL 26490, and HL 34595 from the National Institutes of Health. For PLCO: This research was supported by the Intramural Research Program of the Division of Cancer Epidemiology and Genetics and by contracts from the Division of Cancer Prevention, National Cancer Institute, NIH, DHHS.; For NIOSH: This research was supported by NIOSH operating funds. The contributions of former laboratory director Mary Ann Butler are gratefully acknowledged. The findings and conclusions in this report are those of the author(s) and do not necessarily represent the views of the National Institute for Occupational Safety and Health.; For VITAL: Grant K05CA154337 is funded by the National Cancer Institute (NCI) and the NIH Office of Dietary Supplements (ODS). NR 37 TC 10 Z9 10 U1 0 U2 7 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1055-9965 EI 1538-7755 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD JAN PY 2014 VL 23 IS 1 BP 47 EP 54 DI 10.1158/1055-9965.EPI-13-0913 PG 8 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA AG0ZB UT WOS:000335143400006 PM 24220915 ER PT J AU Liedke, PER Finkelstein, DM Szymonifka, J Barrios, CH Chavarri-Guerra, Y Bines, J Vasconcelos, C Simon, SD Goss, PE AF Liedke, Pedro E. R. Finkelstein, Dianne M. Szymonifka, Jackie Barrios, Carlos H. Chavarri-Guerra, Yanin Bines, Jose Vasconcelos, Claudia Simon, Sergio D. Goss, Paul E. TI Outcomes of Breast Cancer in Brazil Related to Health Care Coverage: A Retrospective Cohort Study SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID RANDOMIZED-TRIALS; 15-YEAR SURVIVAL; DIAGNOSIS; STAGE; RECURRENCE; MORTALITY; WOMEN AB Background: Breast cancer is the most common malignancy in women in Brazil. Differences between patients with public versus private healthcare coverage about general characteristics, disease presentation, treatment of primary tumors, and clinical outcomes have not been fully investigated. Methods: A national, retrospective cohort of 3,142 patients drawn from a representative sample of Brazilian medical centers was selected. Clinical and demographic data and type of healthcare coverage were retrieved by chart review. Groups were compared using the x(2) test. The log-rank test was used for comparison of disease-free survival (DFS), postrelapse, and overall survival (OS). Multivariate Cox regression modeling with adjustment for patient characteristics and stage at diagnosis was performed. All P values are two sided. Results: Patients with public health coverage presented with more advanced disease at diagnosis (P < 0.001). DFS and OS for patients presenting with stage 0-II disease did not differ according to the type of healthcare coverage, whereas a significant difference in outcomes was seen for stage III-IV patients (P = 0.002 and P = 0.008, respectively). In a Cox multivariate analysis, no association was found for the type of health coverage with either DFS or OS, but there was an association for postrelapse survival (P < 0.001). Conclusion: In Brazil, patients with breast cancer with public health coverage present with more advanced disease, and this possibly explains worse DFS and OS when compared with those with private coverage. Impact: Earlier diagnosis and treatment of breast cancer could improve outcomes of women with public health coverage in Brazil. (C)2013 AACR. C1 [Liedke, Pedro E. R.; Barrios, Carlos H.; Bines, Jose; Vasconcelos, Claudia; Simon, Sergio D.] Brazilian Breast Canc Study Grp GBECAM, Sao Paulo, Brazil. [Simon, Sergio D.] Fed Univ Sao Paulo UNIFESP, Sao Paulo, Brazil. [Liedke, Pedro E. R.] Hosp Clin Porto Alegre, Porto Alegre, RS, Brazil. [Barrios, Carlos H.] PUCRS Sch Med Porto Alegre, Porto Alegre, RS, Brazil. [Bines, Jose] Natl Canc Inst Brazil INCA, Rio De Janeiro, RJ, Brazil. [Liedke, Pedro E. R.; Chavarri-Guerra, Yanin; Goss, Paul E.] Massachusetts Gen Hosp, Avon Int Breast Canc Program, Boston, MA 02114 USA. [Finkelstein, Dianne M.; Szymonifka, Jackie] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Biostat Unit, Boston, MA USA. RP Goss, PE (reprint author), Massachusetts Gen Hosp, Ctr Canc, 55 Fruit St,Lawrence House,LRH 302, Boston, MA 02114 USA. EM pgoss@partners.org FU Roche Brazil; Avon Foundation; GBECAM FX This work was supported by Roche Brazil through a grant provided to GBECAM. P. E. R. Liedke, J. Symonifka, D. Finkelsein, Y. Chavarri-Guerra, and P. E. Goss are supported through the MGH-AVON International Breast Cancer Program, funded by the Avon Foundation, NY. C. H. Barrios, J. Bines, C. Vasconcelos, and S. D. Simon received grant support through GBECAM. NR 21 TC 14 Z9 14 U1 0 U2 4 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1055-9965 EI 1538-7755 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD JAN PY 2014 VL 23 IS 1 BP 126 EP 133 DI 10.1158/1055-9965.EPI-13-0693 PG 8 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA AG0ZB UT WOS:000335143400014 PM 24165578 ER PT J AU Motiwala, SR Sarma, A Januzzi, JL O'Donoghue, ML AF Motiwala, Shweta R. Sarma, Amy Januzzi, James L. O'Donoghue, Michelle L. TI Biomarkers in ACS and Heart Failure: Should Men and Women Be Interpreted Differently? SO CLINICAL CHEMISTRY LA English DT Review ID CARDIAC TROPONIN-T; ELEVATION MYOCARDIAL-INFARCTION; EMERGENCY-DEPARTMENT PRIDE; 3RD UNIVERSAL DEFINITION; CORONARY-ARTERY-DISEASE; HIGHLY SENSITIVE ASSAY; SEX-BASED DIFFERENCES; LONG-TERM MORTALITY; NATRIURETIC-PEPTIDE; EJECTION FRACTION AB BACKGROUND: Sex-based differences exist in the circulating concentrations of certain novel and established biomarkers in patients with acute coronary syndromes (ACS) and heart failure (HF). However, to date, few studies have compared the diagnostic and prognostic utility of these markers in men vs women. CONTENT: This mini-review contains a discussion of the published reports of studies that have explored whether differences in biomarker concentrations exist between men and women with ACS or HF. It also examines those studies that have compared the utility of biomarkers for diagnosis or risk stratification in women vs men. Because biomarkers are often used to make therapeutic and triage decisions in patient care, the potential clinical implications for any observed differences in biomarker reference limits for men and women is discussed. SUMMARY: Although the concentration distributions may differ between men and women for certain biomarkers in clinical use, the clinical implications of these observations remain unclear. Because elements of the pathophysiology of ACS and HF may differ between the sexes, further research is needed to better evaluate the diagnostic and prognostic utility of biomarkers in men vs women. (C) 2013 American Association for Clinical Chemistry C1 [Motiwala, Shweta R.] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. [Sarma, Amy] Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. [Januzzi, James L.] Massachusetts Gen Hosp, Div Cardiovasc, Boston, MA 02114 USA. [O'Donoghue, Michelle L.] Brigham & Womens Hosp, Div Cardiovasc, Boston, MA 02115 USA. RP Januzzi, JL (reprint author), Massachusetts Gen Hosp, 55 Fruit St, Boston, MA 02114 USA. EM jjanuzzi@partners.org; modonoghue@partners.org NR 48 TC 10 Z9 10 U1 4 U2 7 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 JAN PY 2014 VL 60 IS 1 BP 35 EP 43 DI 10.1373/clinchem.2013.202531 PG 9 WC Medical Laboratory Technology SC Medical Laboratory Technology GA AG0ZZ UT WOS:000335145900011 PM 24255075 ER PT J AU Perlis, RH AF Perlis, Roy H. TI Pharmacogenomic Testing and Personalized Treatment of Depression SO CLINICAL CHEMISTRY LA English DT Review ID STAR-ASTERISK-D; ANTIDEPRESSANT EFFICACY; GENETIC-VARIATION; SEXUAL DYSFUNCTION; TREATMENT OUTCOMES; ABCB1 GENE; DISORDER; ASSOCIATION; COMMON; POLYMORPHISM AB BACKGROUND: There is wide variation in antidepressant efficacy and tolerability during the treatment of major depressive disorder, a brain disease associated with significant morbidity and mortality risk. The ability to rapidly identify optimal treatment, thereby shortening the time to symptomatic remission, could reduce these risks and associated costs. CONTENT: Up to 42% of variance in antidepressant response is associated with common genetic variation, and there are over 10 psychotropic medications for which the US Food and Drug Administration-approved labeling reflects a genetic test. Most published studies have examined functional variations in genes of the cytochrome p450 system, relevant to metabolism of many antidepressants. However, there are few data supporting the clinical usefulness of specific pharmacogenetic tests. Randomized trials and cost-effectiveness studies are emerging, but larger-scale studies are needed. Specific challenges in translating genetic association results to clinical practice include need for replication to address risk of type I error, overestimation of effect sizes, absence of data from generalizable cohorts, and absence of comparative data that would suggest one specific intervention over another. Several opportunities to accelerate development and validation of new tools for stratification remain, including integration of these tests with clinical data or other biomarkers and application of electronic health records for test development and investigation. SUMMARY: Although common genetic variation, particularly in genes of the cytochrome p450 system, has been associated with antidepressant response, evidence that this variation may be successfully applied to guide treatment selection is just emerging. Larger-scale studies facilitated by informatics tools will clarify the usefulness of such tests. (C) 2013 American Association for Clinical Chemistry C1 Massachusetts Gen Hosp, Ctr Expt Drugs & Diagnost, Boston, MA 02114 USA. RP Perlis, RH (reprint author), Massachusetts Gen Hosp, Ctr Expt Drugs & Diagnost, 185 Cambridge St,6th Floor, Boston, MA 02114 USA. EM rperlis@partners.org FU NIMH [R01MH100286, R01MH086026] FX R. H. Perlis, NIMH R01MH100286 and R01MH086026 and the Stanley Center for Psychiatric Research. NR 42 TC 11 Z9 12 U1 0 U2 15 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 JAN PY 2014 VL 60 IS 1 BP 53 EP 59 DI 10.1373/clinchem.2013.204446 PG 7 WC Medical Laboratory Technology SC Medical Laboratory Technology GA AG0ZZ UT WOS:000335145900013 PM 24281779 ER PT J AU May, EAB Bonaca, MP Jarolim, P Antman, EM Braunwald, E Giugliano, RP Newby, LK Sabatine, MS Morrow, DA AF May, Erin A. Bohula Bonaca, Marc P. Jarolim, Petr Antman, Elliott M. Braunwald, Eugene Giugliano, Robert P. Newby, L. Kristin Sabatine, Marc S. Morrow, David A. TI Prognostic Performance of a High-Sensitivity Cardiac Troponin I Assay in Patients with Non-ST-Elevation Acute Coronary Syndrome SO CLINICAL CHEMISTRY LA English DT Article ID T ASSAY; GENERAL-POPULATION; DECISION-MAKING; CHEST-PAIN; RISK; MORTALITY; PREDICT; DISEASE AB BACKGROUND: High-sensitivity assays for cardiac troponin enable more precise measurement of very low concentrations and improved diagnostic accuracy. However, the prognostic value of these measurements, particularly at low concentrations, is less well defined. METHODS: We evaluated the prognostic performance of a new high-sensitivity cardiac troponin I (hs-cTnI) assay (Abbott ARCHITECT) compared with the commercial fourth generation cTnT assay in 4695 patients with non-ST-segment elevation acute coronary syndromes (NSTE-ACS) from the EARLY-ACS (Early Glycoprotein IIb/IIIa Inhibition in NSTE-ACS) and SEPIA-ACS1-TIMI 42 (Otamixaban for the Treatment of Patients with NSTE-ACS) trials. The primary end-point was cardiovascular death or new myocardial infarction (MI) at 30 days. Baseline cardiac troponin was categorized at the 99th percentile reference limit (26 ng/L for hs-cTnI; 10 ng/L for cTnT) and at sex-specific 99th percentiles for hs-cTnI. RESULTS: All patients at baseline had detectable hs-cTnI compared with 94.5% with detectable cTnT. With adjustment for all other elements of the TIMI risk score, patients with hs-cTnI >= 99th percentile had a 3.7-fold higher adjusted risk of cardiovascular death or MI at 30 days relative to patients with hs-cTnI >= 99th percentile (9.7% vs 3.0%; odds ratio, 3.7; 95% CI, 2.3-5.7; P < 0.001). Similarly, when stratified by categories of hs-cTnI, very low concentrations demonstrated a graded association with cardiovascular death or MI (P-trend < 0.001). Use of sex-specific cutpoints did not improve prognostic performance. Patients with negative fourth generation cTnT (< 10 ng/L) but hs-cTnI >= 26 ng/L were at increased risk of cardiovascular death/MI compared to those with hs-cTnI <26 ng/L (9.2% vs 2.9%, P = 0.002). CONCLUSIONS: Application of this hs-cTnI assay identified a clinically relevant higher risk of recurrent events among patients with NSTE-ACS, even at very low troponin concentrations. (C) 2013 American Association for Clinical Chemistry C1 [May, Erin A. Bohula; Bonaca, Marc P.; Antman, Elliott M.; Braunwald, Eugene; Giugliano, Robert P.; Sabatine, Marc S.; Morrow, David A.] Brigham & Womens Hosp, TIMI Study Grp, Div Cardiovasc, Dept Med, Boston, MA 02115 USA. [Jarolim, Petr] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. [Newby, L. Kristin] Duke Univ, Duke Clin Res Inst, Durham, NC USA. RP May, EAB (reprint author), Brigham & Womens Hosp, TIMI Study Grp, Div Cardiovasc, 75 Francis St, Boston, MA 02115 USA. EM ebohula@partners.org FU National Institutes of Health [RC1HL099692]; Schering Plough and Merck and Company for EARLY ACS, Abbott Laboratories; Schering Plough and Merck and Company for EARLY ACS FX Sanofi-Aventis, funding to institution for support of SEPIA-ACS1-TIMI 42 trial, research funding from Schering Plough and Merck and Company for EARLY ACS, Abbott Laboratories; L. K. Newby, research funding from Schering Plough and Merck and Company for EARLY ACS, see https://www.dcri.org/about-us/conflict-of-interest. M. S. Sabatine, research reported in this publication was supported by the National Institutes of Health under award number RC1HL099692. NR 21 TC 27 Z9 27 U1 0 U2 2 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 JAN PY 2014 VL 60 IS 1 BP 158 EP 164 DI 10.1373/clinchem.2013.206441 PG 7 WC Medical Laboratory Technology SC Medical Laboratory Technology GA AG0ZZ UT WOS:000335145900028 ER PT J AU Liu, CH Ren, JQ Liu, CM Liu, PK AF Liu, Christina H. Ren, Jiaqian Liu, Charng-Ming Liu, Philip K. TI Intracellular gene transcription factor protein-guided MRI by DNA aptamers in vivo SO FASEB JOURNAL LA English DT Article DE AP1 knockout; attention; monoamine oxidase A; stress; transgenic mice ID LIVING BRAINS; CELL TRACKING; LIVE ANIMALS; ACUTE STRESS; EXPRESSION; PROBES; AMPHETAMINE; CONTRAST; EXPOSURE; DELIVERY AB The mechanisms by which transcription factor (TF) protein AP-1 modulates amphetamine's effects on gene transcription in living brains are unclear. We describe here the first part of our studies to investigate these mechanisms, specifically, our efforts to develop and validate aptamers containing the binding sequence of TF AP-1 (5ECdsAP1), in order to elucidate its mechanism of action in living brains. This AP-1-targeting aptamer, as well as a random sequence aptamer with no target (5ECdsRan) as a control, was partially phosphorothioate modified and tagged with superparamagnetic iron oxide nanoparticles (SPIONs), gold, or fluorescein isothiothianate contrast agent for imaging. Optical and transmission electron microscopy studies revealed that 5ECdsAP1 is taken up by endocytosis and is localized in the neuronal endoplasmic reticulum. The results of magnetic resonance imaging (MRI) with SPION-5ECdsAP1 revealed that neuronal AP-1 TF protein levels were elevated in neurons of live male C57black6 mice after amphetamine exposure; however, pretreatment with SCH23390, a dopaminergic receptor antagonist, suppressed this elevation. As studies in transgenic mice with neuronal dominant-negative A-FOS mutant protein, which has no binding affinity for the AP-1 sequence, showed a completely null MRI signal in the striatum, we can conclude that the MR signal reflects specific binding between the 5ECdsAP1 aptamer and endogenous AP-1 protein. Together, these data lend support to the application of 5ECdsAP1 aptamer for intracellular protein-guided imaging and modulation of gene transcription, which will thus allow investigation of the mechanisms of signal transduction in living brains.Liu, C. H., Ren, J., Liu, C.-M., Liu, P. K. Intracellular gene transcription factor protein-guided MRI by DNA aptamers in vivo. C1 [Liu, Christina H.; Ren, Jiaqian; Liu, Charng-Ming; Liu, Philip K.] Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Dept Radiol, Charlestown, MA 02129 USA. RP Liu, PK (reprint author), Massachusetts Gen Hosp, CNY149 2301 Thirteenth St, Charlestown, MA 02129 USA. EM philipl@nmr.mgh.harvard.edu OI Liu, Christina/0000-0002-5723-177X FU U.S. National Institutes of Health (NIH) [R01DK43351, R01DK57521]; National Institute on Drug Abuse [R01DA029889]; National Institute of Biomedical Imaging and Bioengineering [R01EB013768]; National Center for Alternative Medicine of the NIH [AT004974] FX The authors thank Dr. M. Schwartzchild for allowing them to use the locomotion detection device. The authors also thank Dr. C. Vinson (National Cancer Institute, Frederick, MD, USA) for use of the double-transgenic A-FOS mutant mouse strain, Dr. H. Prentice for reading and critical evaluation, and Ms. N. Eusemann for assistance with editing the manuscript. The authors appreciate the help of M. McKee with TEM and the availability of the Massachusetts General Hospital Microscopy Core [supported by U.S. National Institutes of Health (NIH) grants R01DK43351 and R01DK57521]. This project was supported by research grants from the National Institute on Drug Abuse (R01DA029889), the National Institute of Biomedical Imaging and Bioengineering (R01EB013768), and the National Center for Alternative Medicine (AT004974) of the NIH. NR 30 TC 9 Z9 9 U1 4 U2 13 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 EI 1530-6860 J9 FASEB J JI Faseb J. PD JAN PY 2014 VL 28 IS 1 BP 464 EP 473 DI 10.1096/fj.13-234229 PG 10 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA AD8OS UT WOS:000333526100043 PM 24115049 ER PT J AU Liao, GX van Driel, B Magelky, E O'Keeffe, MS Malefyt, RD Engel, P Herzog, RW Mizoguchi, E Bhan, AK Terhorst, C AF Liao, Gongxian van Driel, Boaz Magelky, Erica O'Keeffe, Michael S. Malefyt, Rene de Waal Engel, Pablo Herzog, Roland W. Mizoguchi, Emiko Bhan, Atul K. Terhorst, Cox TI Glucocorticoid-induced TNF receptor family- related protein ligand regulates the migration of monocytes to the inflamed intestine SO FASEB JOURNAL LA English DT Article DE GITR-L; TNFSF18; macrophage; experimental colitis ID CD4(+) T-CELLS; DENDRITIC CELLS; INFLAMMATORY SITES; SPLENIC RESERVOIR; BONE-MARROW; GITR; COLITIS; MICE; EXPRESSION; MACROPHAGES AB Glucocorticoid-induced TNF receptor family-related protein (GITR) regulates the function of both T cells and antigen-presenting cells (APCs), while the function of GITR ligand (GITR-L) is largely unknown. Here we evaluate the role of GITR-L, whose expression is restricted to APCs, in the development of enterocolitis. On injecting naive CD4(+) T cells, GITR-L(-/-)Rag(-/-) mice develop a markedly milder colitis than Rag(-/-) mice, which correlates with a 50% reduction of Ly6C(+)CD11b(+)MHCII(+) macrophages in the lamina propria and mesenteric lymph nodes. The same result was observed in CD40-induced acute colitis and during peritonitis, suggesting an altered monocyte migration. In line with these observations, the number of nondifferentiated monocytes was approximately 3-fold higher in the spleen of GITR-L(-/-)Rag(-/-) mice than in Rag(-/-) mice after CD40 induction. Consistent with the dynamic change in the formation of an active angiotensin II type 1 receptor (AT1) dimer in GITR-L-/- splenic monocytes during intestinal inflammation, the migratory capability of splenic monocytes from GITR-L-deficient mice was impaired in an in vitro transwell migration assay. Conversely, GITR-L reduces the number of splenic Ly6C(hi) monocytes, concomitantly with an increase in AT1 dimers. We conclude that GITR-L regulates the number of proinflammatory macrophages in sites of inflammation by controlling the egress of monocytes from the splenic reservoir.Liao, G., van Driel, B., Magelky, E., O'Keeffe, M. S., de Waal Malefyt, R., Engel, P., Herzog, R. W., Mizoguchi, E., Bhan, A. K., Terhorst, C. Glucocorticoid-induced TNF receptor family-related protein ligand regulates the migration of monocytes to the inflamed intestine. C1 [Liao, Gongxian; van Driel, Boaz; Magelky, Erica; O'Keeffe, Michael S.; Terhorst, Cox] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Beth Israel Deaconess Med Ctr,Div Immunol, Boston, MA 02115 USA. [Mizoguchi, Emiko] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Gastrointestinal Unit,Dept Med, Boston, MA 02115 USA. [Bhan, Atul K.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Pathol, Boston, MA 02115 USA. [Malefyt, Rene de Waal] Merck Res Labs, Biol Discovery, Palo Alto, CA USA. [Engel, Pablo] Univ Barcelona, Sch Med, Dept Cell Biol Immunol & Neurosci, Immunol Unit, Barcelona, Spain. [Herzog, Roland W.] Univ Florida, Dept Pediat, Gainesville, FL USA. RP Liao, GX (reprint author), Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Div Immunol, 3 Blackfan Circle,CLS 928, Boston, MA 02115 USA. EM gliao@bidmc.harvard.edu; cterhors@bidmc.harvard.edu FU U.S. National Institutes of Health [R01 DK-52510, P01 HL078810, 5T32DK007760, P30 DK-43351] FX The authors thank members of the C. T. laboratory for helpful discussions and the Beth Israel Deaconess Medical Center histology core for processing colon tissue slides with H&E staining. This work was sponsored by the U.S. National Institutes of Health (R01 DK-52510 to C. T., P01 HL078810 to C. T. and R. H., 5T32DK007760 to G. L., and P30 DK-43351 to A. B., C. T., and E. M.). The authors declare no conflicts of interest. NR 40 TC 7 Z9 8 U1 1 U2 8 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 EI 1530-6860 J9 FASEB J JI Faseb J. PD JAN PY 2014 VL 28 IS 1 BP 474 EP 484 DI 10.1096/fj.13-236505 PG 11 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA AD8OS UT WOS:000333526100044 PM 24107315 ER PT J AU Azzalini, L Abbara, S Ghoshhajra, BB AF Azzalini, Lorenzo Abbara, Suhny Ghoshhajra, Brian B. TI Ultra-Low Contrast Computed Tomographic Angiography (CTA) With 20-mL Total Dose for Transcatheter Aortic Valve Implantation (TAVI) Planning SO JOURNAL OF COMPUTER ASSISTED TOMOGRAPHY LA English DT Article DE transcatheter aortic valve replacement; computed tomographic angiography; high-pitch dual-source; renal failure; low contrast ID TUBE POTENTIAL SELECTION; IMAGE-QUALITY; CONSENSUS DOCUMENT; DEFINITIONS; ATTENUATION; ARTERIES AB Transcatheter aortic valve implantation workup includes assessment of the aorta and the iliofemoral arteries by computed tomographic angiography. An important group of transcatheter aortic valve implantation candidates have severe renal failure. We tested a novel computed tomographic angiography protocol (128-detector-row dual-source scanner, high-pitch helical mode) with ultralow contrast volume (20 mL) in 8 patients, compared with 8 controls. Contrast-to-noise ratio and subjective image quality, albeit lower than in the controls, were suitable for interpretation in the ultralow contrast volume group throughout all measured locations. C1 [Azzalini, Lorenzo; Abbara, Suhny; Ghoshhajra, Brian B.] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. [Azzalini, Lorenzo] Massachusetts Gen Hosp, Ctr Heart, Boston, MA 02114 USA. [Azzalini, Lorenzo] Univ Autonoma Barcelona, Dept Med, E-08193 Barcelona, Spain. RP Ghoshhajra, BB (reprint author), Massachusetts Gen Hosp, Cardiac MR PET CT Program, Clin Cardiac CT & MRI, 55 Fruit St,GRB 295, Boston, MA 02114 USA. EM bghoshhajra@partners.org NR 18 TC 12 Z9 12 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0363-8715 EI 1532-3145 J9 J COMPUT ASSIST TOMO JI J. Comput. Assist. Tomogr. PD JAN-FEB PY 2014 VL 38 IS 1 BP 105 EP 109 DI 10.1097/RCT.0b013e3182a14358 PG 5 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA AG4KY UT WOS:000335389700018 PM 24378883 ER PT J AU Pourjabbar, S Singh, S Singh, AK Johnston, RP Shenoy-Bhangle, AS Do, S Padole, A Blake, MA Persson, A Kalra, MK AF Pourjabbar, Sarvenaz Singh, Sarabjeet Singh, Anand K. Johnston, Rocio P. Shenoy-Bhangle, Anuradha S. Do, Synho Padole, Atul Blake, Michael A. Persson, Anders Kalra, Mannudeep K. TI Preliminary Results: Prospective Clinical Study to Assess Image-Based Iterative Reconstruction for Abdominal Computed Tomography Acquired at 2 Radiation Dose Levels SO JOURNAL OF COMPUTER ASSISTED TOMOGRAPHY LA English DT Article DE radiation dose reduction; multidetector CT; iterative reconstruction technique ID POWER SPECTRA; CT; REDUCTION; ALGORITHM; ABDOMEN; RISKS; MDCT AB Objective The objective of this study was to compare image quality for abdominal computed tomographic (CT) images acquired at 200 and 50 mA s and reconstructed with image-based iterative reconstruction. Materials and Methods In this institutional review board-approved prospective study, 22 patients (mean [SD] age, 64.3 [14.4] years; male-female ratio, 12:10) gave informed consent for acquisition of additional abdominal CT images on 64-slice multi-detector CT (MDCT) (Siemens Definition Flash). Standard-dose images were acquired at 200 quality reference mA s, whereas low-dose images were acquired at 50 mA s (all series: 120 kV; 5-mm section thickness; pitch, 0.9:1). The low-dose images were reconstructed with a nonlinear 3-dimensional iterative image reconstruction (3D-IIR) (SafeCT; MedicVision, Tirat Carmel, Israel) (4 settings, namely, A1, A2, A3, and A4) and were assessed by 3 abdominal radiologists for lesion detection, image noise, and visibility of small structures. CATPHAN 500 was scanned at the respective doses to obtain noise spectral density and modulation transfer function. Results Subjective image noise was unacceptable at 50-mA s filtered back projection and improved to average in 50-mA s A1 and minimal or no noise in 50-mA s A4. However, the visibility of small structures was similar to standard-dose filtered back projection images on 50-mA s A2. Objective image noise was reduced to 66% for the 50-mA s 3D-IIR images (9.08 [2.3]/26.75 [6.8]). The modulation transfer function curve demonstrated resolution improvement in the low-dose images with the 3D-IIR technique, whereas the noise spectral density curve confirmed noise suppression in the 50-mA s 3D-IIR images. Conclusions Three-dimensional iterative image reconstruction helps to lower image noise without affecting the visibility of small structures at "moderate" settings. Diagnostically acceptable abdominal CT examinations can be acquired at 75% lower-radiation dose with the help of the image-based iterative reconstruction technique. C1 [Pourjabbar, Sarvenaz; Singh, Sarabjeet; Singh, Anand K.; Johnston, Rocio P.; Shenoy-Bhangle, Anuradha S.; Do, Synho; Padole, Atul; Blake, Michael A.; Kalra, Mannudeep K.] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. [Persson, Anders] Linkopings Univ US, Ctr Med Image Sci & Visualizat, Linkoping, Sweden. RP Pourjabbar, S (reprint author), Massachusetts Gen Hosp, Dept Radiol, 55 Fruit St, Boston, MA 02114 USA. EM spourjabbar@partners.org NR 19 TC 6 Z9 6 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0363-8715 EI 1532-3145 J9 J COMPUT ASSIST TOMO JI J. Comput. Assist. Tomogr. PD JAN-FEB PY 2014 VL 38 IS 1 BP 117 EP 122 DI 10.1097/RCT.0b013e3182a17629 PG 6 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA AG4KY UT WOS:000335389700020 PM 24424560 ER PT S AU Sawhney, MK Hamblin, MR AF Sawhney, Mossum K. Hamblin, Michael R. BE Hamblin, MR Carroll, JD Arany, P TI Low-level light therapy (LLLT) for cosmetics and dermatology SO MECHANISMS FOR LOW-LIGHT THERAPY IX SE Proceedings of SPIE LA English DT Proceedings Paper CT Conference on Mechanisms for Low-Light Therapy IX CY FEB 01-02, 2014 CL San Francisco, CA SP SPIE ID NEON LASER IRRADIATION; FOLLICLE STEM-CELLS; NEAR-IR RADIATION; HAIR FOLLICLE; ANDROGENETIC ALOPECIA; LED PHOTOMODULATION; MAMMALIAN-CELLS; CLINICAL-TRIAL; NITRIC-OXIDE; PHOTOTHERAPY AB Over the last few years, low-level laser (light) therapy (LLLT) has been demonstrated to be beneficial to the field of aesthetic medicine, specifically aesthetic dermatology. LLLT encompasses a broad spectrum of procedures, primarily cosmetic, which provide treatment options for a myriad of dermatological conditions. Dermatological disorders involving inflammation, acne, scars, aging and pigmentation have been investigated with the assistance of animal models and clinical trials. The most commercially successful use of LLLT is for managing alopecia (hair loss) in both men and women. LLLT also seems to play an influential role in procedures such as lipoplasty and liposuction, allowing for noninvasive and nonthermal methods of subcutaneous fat reduction. LLLT offers a means to address such conditions with improved efficacy versatility and no known side-effects; however comprehensive literature reports covering the utility of LLLT are scarce and thus the need for coverage arises. C1 [Sawhney, Mossum K.; Hamblin, Michael R.] Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA. RP Sawhney, MK (reprint author), Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA. OI Hamblin, Michael/0000-0001-6431-4605 NR 68 TC 1 Z9 1 U1 1 U2 8 PU SPIE-INT SOC OPTICAL ENGINEERING PI BELLINGHAM PA 1000 20TH ST, PO BOX 10, BELLINGHAM, WA 98227-0010 USA SN 0277-786X BN 978-0-8194-9845-8 J9 PROC SPIE PY 2014 VL 8932 AR 89320X DI 10.1117/12.2041330 PG 12 WC Biophysics; Optics; Radiology, Nuclear Medicine & Medical Imaging SC Biophysics; Optics; Radiology, Nuclear Medicine & Medical Imaging GA BA3KX UT WOS:000334338800018 ER PT S AU Picone, R Baum, B McKendry, R AF Picone, Remigio Baum, Buzz McKendry, Rachel BE Piel, M Thery, M TI Plasma Microcontact Patterning (P mu CP): A Technique for the Precise Control of Surface Patterning at Small-Scale SO MICROPATTERNING IN CELL BIOLOGY, PT A SE Methods in Cell Biology LA English DT Review; Book Chapter ID CELLS; MICROSTRUCTURES; PROTEINS AB Plasma microcontact patterning (P mu CP) is a simple, efficient, and cost-effective method for the precise patterning of molecules on surfaces. It combines the use of low-pressure plasma with an elastomeric 3D mask to spatially control the removal of molecules, such as proteins, from a surface. The entire P mu CP process is subdivided into three main steps: surface precoating, plasma micropatterning, and a surface post-coating step. Surfaces are first precoated with a molecular species and then placed in close contact with the 3D mask. This allows the formation of two distinct regions: an un-masked open-region which is accessible to the plasma, from which the surface layer is removed, and, a contact region which is physically protected from exposure to the plasma. In the final step, a second molecule is added to back-fill the pattern generated through plasma-treatment. The P mu CP technique allows the patterning of virtually any organic molecules on different surface materials and geometries (e.g., flat, curved surfaces, and 3D microstructures). Moreover, it is a simple and robust procedure. The main advantages of this approach over traditional microcontact printing are twofold: The stability of molecule binding to plasma-treated surfaces, and the separation of the surface functionalization step from the actual micropatterning step, which enables the precise control of concentration and uniformity of patterned molecules. In conclusion, P mu CP is a simple way to generate surface patterns that are highly reproducible, stable and uniform, making it a useful method for many applications. C1 [Picone, Remigio] Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA 02115 USA. [Picone, Remigio] Howard Hughes Med Inst, Dept Pediat Oncol, Boston, MA 02115 USA. [Picone, Remigio] Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. [Picone, Remigio; McKendry, Rachel] UCL, London Ctr Nanotechnol, London, England. [Picone, Remigio; McKendry, Rachel] UCL, Dept Med, London, England. [Picone, Remigio; Baum, Buzz] UCL, Mol Cell Biol Lab, MRC, London, England. [Picone, Remigio] UCL, CoMPLEX, London, England. RP Picone, R (reprint author), Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA 02115 USA. NR 16 TC 3 Z9 3 U1 1 U2 13 PU ELSEVIER ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA SN 0091-679X BN 978-0-12-416742-1 J9 METHOD CELL BIOL JI Methods Cell Biol. PY 2014 VL 119 BP 73 EP 90 DI 10.1016/B978-0-12-416742-1.00005-6 PG 18 WC Cell Biology SC Cell Biology GA BA0XT UT WOS:000332345600005 PM 24439280 ER PT J AU Jawaid, A Paganoni, S Hauser, C Schulz, PE AF Jawaid, Ali Paganoni, Sabrina Hauser, Cecile Schulz, Paul E. TI Trials of Antidliabetic Drugs in Amyotrophic Lateral Sclieros: Proceed with Caution? SO NEURODEGENERATIVE DISEASES LA English DT Review ID BODY-MASS INDEX; TRANSGENIC MOUSE MODEL; HEXOKINASE-II; SCLEROSIS; ALS; SURVIVAL; DISMUTASE; RISK; FAT; DYSLIPIDEMIA AB Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disorder with limited therapeutic options. Clinical trials of several drugs shown to be effective in the superoxide dismutase (SOD1) model of ALS have shown no or negative effects when tested in humans. Here we discuss the role of pioglitazone, a peroxisome proliferator-activated receptor-gamma agonist, which failed to show efficacy in a recently published phase II clinical trial of ALS patients. The antioxidant and anti-inflammatory properties of pioglitazone make it an attractive therapeutic candidate for neurodegenerative disorders. However, its antidiabetic and antidyslipidemic effects might be detrimental, as emerging evidence suggests that some features of the metabolic syndrome may be protective in ALS. A number of clinical studies show that dyslipidemia, high body mass index, and possibly diabetes mellitus type 2 are associated with better clinical outcomes in ALS. This is further corroborated by studies on transgenic animal models and immortalized neuronal cell lines. Finally, the intricate interplay between glucose/lipid metabolism and susceptibility to oxidative damage in neurons warrants a judicious approach in further trials of antidiabetic drugs in ALS. (C) 2013 S. Karger AG, Basel C1 [Jawaid, Ali; Hauser, Cecile] Univ Zurich, Brain Res Inst, Swiss Fed Inst Technol, CH-8057 Zurich, Switzerland. [Paganoni, Sabrina] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Neurol Clin Res Inst,Dept Neurol, Boston, MA USA. [Paganoni, Sabrina] Harvard Univ, Spaulding Rehabil Hosp, Sch Med, Dept Phys Med & Rehabil, Boston, MA USA. [Paganoni, Sabrina] VA Boston Healthcare Syst, Boston, MA USA. [Schulz, Paul E.] UTHealth, Dept Neurol, Houston, TX USA. RP Jawaid, A (reprint author), Univ Zurich, ETH, Swiss Fed Inst Technol, Brain Res Inst, Winterthurerstr 190, CH-8057 Zurich, Switzerland. EM alijawaid84@gmail.com FU NICHD NIH HHS [K12 HD001097] NR 35 TC 9 Z9 9 U1 0 U2 2 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 1660-2854 EI 1660-2862 J9 NEURODEGENER DIS JI Neurodegener. Dis. PY 2014 VL 13 IS 4 BP 205 EP 208 DI 10.1159/000353158 PG 4 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA AG3AM UT WOS:000335288200001 PM 24107404 ER PT S AU Jung, Y Brack, AS AF Jung, Yunjoon Brack, Andrew S. BE Rendl, M TI Cellular Mechanisms of Somatic Stem Cell Aging SO STEM CELLS IN DEVELOPMENT AND DISEASE SE Current Topics in Developmental Biology LA English DT Review; Book Chapter ID NF-KAPPA-B; MITOCHONDRIAL-DNA MUTATIONS; HEMATOPOIETIC STEM; SELF-RENEWAL; LIFE-SPAN; SKELETAL-MUSCLE; SATELLITE-CELL; CAENORHABDITIS-ELEGANS; PROGENITOR PROLIFERATION; SACCHAROMYCES-CEREVISIAE AB Tissue homeostasis and regenerative capacity rely on rare populations of somatic stem cells endowed with the potential to self-renew and differentiate. During aging, many tissues show a decline in regenerative potential coupled with a loss of stem cell function. Cells including somatic stem cells have evolved a series of checks and balances to sense and repair cellular damage to maximize tissue function. However, during aging the mechanisms that protect normal cell function begin to fail. In this review, we will discuss how common cellular mechanisms that maintain tissue fidelity and organismal lifespan impact somatic stem cell function. We will highlight context-dependent changes and commonalities that define aging, by focusing on three age-sensitive stem cell compartments: blood, neural, and muscle. Understanding the interaction between extrinsic regulators and intrinsic effectors that operate within different stem cell compartments is likely to have important implications for identifying strategies to improve health span and treat age-related degenerative diseases. C1 [Jung, Yunjoon; Brack, Andrew S.] Massachusetts Gen Hosp, Ctr Regenerat Med, Boston, MA 02114 USA. [Brack, Andrew S.] Harvard Univ, Sch Med, Boston, MA USA. [Brack, Andrew S.] Harvard Stem Cell Inst, Boston, MA USA. RP Brack, AS (reprint author), Massachusetts Gen Hosp, Ctr Regenerat Med, Boston, MA 02114 USA. FU NIAMS NIH HHS [R01 AR060868, R01 AR061002] NR 176 TC 19 Z9 19 U1 3 U2 9 PU ELSEVIER ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA SN 0070-2153 BN 978-0-12-416022-4 J9 CURR TOP DEV BIOL JI Curr. Top. Dev. Biol. PY 2014 VL 107 BP 405 EP 438 DI 10.1016/B978-0-12-416022-4.00014-7 PG 34 WC Developmental Biology SC Developmental Biology GA BA1FN UT WOS:000332424400014 PM 24439814 ER PT J AU Young, S Vos, SS Cantrell, M Shaw, R AF Young, Shardae Vos, Susan S. Cantrell, Matthew Shaw, Robert TI Factors Associated With Students' Perception of Preceptor Excellence SO AMERICAN JOURNAL OF PHARMACEUTICAL EDUCATION LA English DT Article DE preceptor; experiential education; evaluation; quality assurance ID PHARMACY EDUCATION; QUALITY AB Objectives. To identify factors associated with preceptor excellence as rated by student pharmacists and to assess the correlation of excellent ratings with years as pharmacist, specialty certification, and faculty appointment status. Methods. A retrospective analysis of student pharmacist evaluations of preceptors from May 2009 to May 2012 was completed to determine factors associated with preceptor excellence. Results. Preceptors who showed an interest in teaching, related to the student as an individual, encouraged discussion, were accessible, provided feedback, served as a role model, were organized, and/or spent increased time with students were more likely to be rated excellent. Conclusion. Serving as role models and showing an interest in teaching demonstrated the strongest association with being an excellent preceptor. Identifying factors students associate with preceptor excellence may result in enhanced preceptor recruitment, development, and training. C1 [Young, Shardae] South Texas Vet Hlth Care Syst, San Antonio, TX USA. [Vos, Susan S.] Univ Iowa, Coll Pharm, Iowa City, IA 52242 USA. [Cantrell, Matthew; Shaw, Robert] Univ Iowa, Iowa City VA Healthcare Syst, Iowa City, IA USA. RP Vos, SS (reprint author), Univ Iowa, Coll Pharm, Dept Pharm Practice & Sci, 115 S Grand Ave,S413 PHAR, Iowa City, IA 52242 USA. EM susan-vos@uiowa.edu NR 20 TC 5 Z9 5 U1 2 U2 6 PU AMER ASSOC COLL PHARMACY PI ALEXANDRIA PA 1426 PRINCE STREET, ALEXANDRIA, VA 22314-2815 USA SN 0002-9459 EI 1553-6467 J9 AM J PHARM EDUC JI Am. J. Pharm. Educ. PY 2014 VL 78 IS 3 AR 53 PG 6 WC Education, Scientific Disciplines; Pharmacology & Pharmacy SC Education & Educational Research; Pharmacology & Pharmacy GA AF8ZK UT WOS:000335004300006 PM 24761014 ER PT S AU Guo, SZ Lok, J Liu, Y Hayakawa, K Leung, W Xing, CH Ji, XM Lo, EH AF Guo, Shuzhen Lok, Josephine Liu, Yi Hayakawa, Kazuhide Leung, Wendy Xing, Changhong Ji, Xunming Lo, Eng H. BE Milner, R TI Assays to Examine Endothelial Cell Migration, Tube Formation, and Gene Expression Profiles SO CEREBRAL ANGIOGENESIS: METHODS AND PROTOCOLS SE Methods in Molecular Biology LA English DT Article; Book Chapter DE Angiogenesis; Endothelial cells; Matrigel matrix; Tube formation; Migration; Transcriptome; Microparticles ID IN-VITRO; ANGIOGENESIS; DIFFERENTIATION; MICROPARTICLES; MEMBRANE; RNA AB Common methods for studying angiogenesis in vitro include the tube formation assay, the migration assay, and the study of the endothelial genome. The formation of capillary-like tubes in vitro on basement membrane matrix mimics many steps of the angiogenesis process in vivo and is used widely as a screening test for angiogenic or antiangiogenic factors. Other assays related to the study of angiogenesis include the cell migration assay, the study of gene expression changes during the process of angiogenesis, and the study of endothelial-derived microparticles. Protocols for these procedures will be described here. C1 [Guo, Shuzhen; Liu, Yi; Hayakawa, Kazuhide; Leung, Wendy; Xing, Changhong; Lo, Eng H.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Neuroprotect Res Lab,Dept Radiol & Neurol, Boston, MA USA. [Lok, Josephine] Harvard Univ, Sch Med, Dept Pediat, Massachusetts Gen Hosp, Boston, MA 02115 USA. [Ji, Xunming] Capital Med Univ, Xuanwu Hosp, Cerebrovasc Res Ctr, Beijing, Peoples R China. RP Guo, SZ (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Neuroprotect Res Lab,Dept Radiol & Neurol, Boston, MA USA. FU NINDS NIH HHS [R01 NS076694, K08 NS057339, P01 NS055104, R37 NS037074] NR 14 TC 3 Z9 3 U1 0 U2 0 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DR, STE 208, TOTOWA, NJ 07512-1165 USA SN 1064-3745 BN 978-1-4939-0319-1; 978-1-4939-0320-7 J9 METHODS MOL BIOL JI Methods Mol. Biol. PY 2014 VL 1135 BP 393 EP 402 DI 10.1007/978-1-4939-0320-7_32 D2 10.1007/978-1-4939-0320-7 PG 10 WC Neurosciences SC Neurosciences & Neurology GA BA0WJ UT WOS:000332323000033 PM 24510881 ER PT J AU Scognamiglio, G Cantile, M Scala, S Cecere, S Russo, F Collina, F Marra, L Sabbatino, F Botti, G Franco, R AF Scognamiglio, Giosue Cantile, Monica Scala, Stefania Cecere, Sabrina Russo, Federica Collina, Francesca Marra, Laura Sabbatino, Francesco Botti, Gerardo Franco, Renato TI Tissue Micro Arrays for immunohistochemical detection of inflammatory infiltrates in renal cell carcinoma SO INTERNATIONAL JOURNAL OF CLINICAL AND EXPERIMENTAL PATHOLOGY LA English DT Letter C1 [Scognamiglio, Giosue; Cantile, Monica; Russo, Federica; Collina, Francesca; Marra, Laura; Botti, Gerardo; Franco, Renato] Ist Nazl Tumori Fdn G Pascale, Pathol Unit, I-80131 Naples, Italy. [Scala, Stefania] Ist Nazl Tumori Fdn G Pascale, Dept Oncol Immunol, I-80131 Naples, Italy. [Cecere, Sabrina] Ist Nazl Tumori Fdn G Pascale, Dept Med Oncol, I-80131 Naples, Italy. [Sabbatino, Francesco] Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. RP Cantile, M (reprint author), Ist Nazl Tumori Fdn G Pascale, Pathol Unit, Via Mariano Semmola, I-80131 Naples, Italy. EM monican-tile@libero.it RI Scala, Stefania/K-1380-2016; Scognamiglio, Giosue/K-8247-2016; Sabbatino, Francesco/F-4992-2014; OI Scala, Stefania/0000-0001-9524-2616; Scognamiglio, Giosue/0000-0003-4376-111X; Sabbatino, Francesco/0000-0001-6431-8278; Franco, Renato/0000-0002-8340-3184 NR 5 TC 0 Z9 0 U1 0 U2 0 PU E-CENTURY PUBLISHING CORP PI MADISON PA 40 WHITE OAKS LN, MADISON, WI 53711 USA SN 1936-2625 J9 INT J CLIN EXP PATHO JI Int. J. Clin. Exp. Pathol. PY 2014 VL 7 IS 4 BP 1814 EP 1818 PG 5 WC Oncology; Pathology SC Oncology; Pathology GA AG2DZ UT WOS:000335227600063 PM 24817986 ER PT J AU Hedgire, SS McDermott, S Wojtkiewicz, GR Abtahi, SM Harisinghani, M Gaglia, JL AF Hedgire, Sandeep S. McDermott, Shaunagh Wojtkiewicz, Gregory R. Abtahi, Seyed Mahdi Harisinghani, Mukesh Gaglia, Jason L. TI Evaluation of renal quantitative T2*changes on MRI following administration of ferumoxytol as a T2*contrast agent SO INTERNATIONAL JOURNAL OF NANOMEDICINE LA English DT Article DE USPIO; ferumoxytol; renal MRI; T2*weighted imaging ID SUPERPARAMAGNETIC IRON-OXIDE; RAT MODEL; KIDNEY; ANGIOGRAPHY; INFLAMMATION; NEPHROPATHY; REJECTION; CONTRAST; FAILURE AB Purpose: To evaluate the time-dependent changes in regional quantitative T2* maps of the kidney following intravenous administration of ferumoxytol. Materials and methods: Twenty-four individuals with normal kidney function underwent T2*-weighted MRI of the kidney before, immediately after, and 48 hours after intravenous administration of ferumoxytol at a dose of 4 mg/kg (group A, n= 12) or 6 mg/kg (group B, n= 12). T2* values were statistically analyzed using two-tailed paired t-tests. Results: In group A, the percentage changes from baseline to immediate post and baseline to 48 hours were 85.3% and 64.2% for the cortex and 90.8% and 64.6% for the medulla, respectively. In group B, the percentage changes from baseline to immediate post and baseline to 48 hours were 85.2% and 73.4% for the cortex and 94.5% and 74% for the medulla, respectively. This difference was significant for both groups (P < 0.0001). Conclusion: There is significant and differential uptake of ferumoxytol in the cortex and medulla of physiologically normal kidneys. This differential uptake may offer the ability to interrogate renal cortex and medulla with possible clinical applications in medical renal disease and transplant organ assessment. We propose an organ of interest based dose titration of ferumoxytol to better differentiate circulating from intracellular ferumoxytol particles. C1 [Hedgire, Sandeep S.; McDermott, Shaunagh; Wojtkiewicz, Gregory R.; Abtahi, Seyed Mahdi; Harisinghani, Mukesh] Richard B Simches Res Ctr, Massachusetts Gen Hosp, Ctr Syst Biol, Boston, MA USA. [Gaglia, Jason L.] Joslin Diabet Ctr, Boston, MA 02215 USA. RP Gaglia, JL (reprint author), Joslin Diabet Ctr, 1 Joslin Pl, Boston, MA 02215 USA. EM jason.gaglia@joslin.harvard.edu OI Gaglia, Jason/0000-0003-2904-312X FU grants from the US National Institutes of Health via the Dana Farber/Harvard Cancer Center Specialized Program of Research Excellence in Gastrointestinal Cancers [P50CA127003, P01AI054904] FX This research was made possible by grants from the US National Institutes of Health P50CA127003 via the Dana Farber/Harvard Cancer Center Specialized Program of Research Excellence in Gastrointestinal Cancers and P01AI054904. NR 20 TC 2 Z9 2 U1 0 U2 1 PU DOVE MEDICAL PRESS LTD PI ALBANY PA PO BOX 300-008, ALBANY, AUCKLAND 0752, NEW ZEALAND SN 1178-2013 J9 INT J NANOMED JI Int. J. Nanomed. PY 2014 VL 9 BP 2101 EP 2107 DI 10.2147/IJN.S61460 PG 7 WC Nanoscience & Nanotechnology; Pharmacology & Pharmacy SC Science & Technology - Other Topics; Pharmacology & Pharmacy GA AF8YP UT WOS:000335002200002 PM 24812510 ER PT J AU Lin, M Zhao, Y Liu, M Qiu, MS Dong, YQ Duan, ZF Li, YH Pingguan-Murphy, B Lu, TJ Xu, F AF Lin, Min Zhao, Ying Liu, Ming Qiu, MuShu Dong, YuQing Duan, ZhenFeng Li, Ying Hui Pingguan-Murphy, Belinda Lu, Tian Jian Xu, Feng TI Synthesis of upconversion NaYF4:Yb3+,Er3+ particles with enhanced luminescent intensity through control of morphology and phase SO JOURNAL OF MATERIALS CHEMISTRY C LA English DT Article ID FLUORESCENT NANOPARTICLES; BIOMEDICAL APPLICATIONS; DRUG-DELIVERY; MICROCRYSTALS; EMISSION; CELLS; MICROSTRUCTURES; NANOCRYSTALS; FABRICATION; MULTICOLOR AB Preparation of well-defined NaYF4 crystals with bright upconversion emission remains a major challenge. The complicated chemical reactions as well as the effect of structure, phase and morphology on the emission efficiency require fine tuning of multiple parameters during the growth of NaYF4 crystals. In this study, we successfully synthesized NaYF4:Yb3+,Er3+ microcrystals with well-controlled morphologies (e. g., sphere and tube) and enhanced luminescent intensity through tuning pH values and ion concentrations in the initial reaction solution. With increasing reaction time, the phase of NaYF4:Yb3+,Er3+ changes from cubic to hexagonal, while the morphology follows the change from spheres to microtubes and then to microrods. Upon excitation by 980 nm infrared light, hexagonal NaYF4:Yb3+,Er3+ microtubes show a significant enhancement in green upconversion emission, which is much stronger than that observed in particles with other morphologies. This phase and morphology dependent strong upconversion emission holds great potential for applications in photonic devices and bioanalyses. C1 [Lin, Min; Qiu, MuShu; Xu, Feng] Xi An Jiao Tong Univ, Sch Life Sci & Technol, Minist Educ, Key Lab Biomed Informat Engn, Xian 710049, Peoples R China. [Lin, Min; Zhao, Ying; Qiu, MuShu; Dong, YuQing; Lu, Tian Jian; Xu, Feng] Xi An Jiao Tong Univ, Bioinspired Engn & Biomech Ctr, Xian 710049, Peoples R China. [Liu, Ming] Xi An Jiao Tong Univ, Key Lab Minist Educ, Elect Mat Res Lab, Xian 710049, Peoples R China. [Liu, Ming] Xi An Jiao Tong Univ, Int Ctr Dielect Res, Xian 710049, Peoples R China. [Duan, ZhenFeng] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Sarcoma & Connect Tissue Oncol, Cambridge, MA 02138 USA. [Li, Ying Hui] Chinese Astronaut Res & Training Ctr, State Key Lab Space Med Fundamentals & Applicat, Beijing 100094, Peoples R China. [Pingguan-Murphy, Belinda] Univ Malaya, Fac Engn, Dept Biomed Engn, Kuala Lumpur 50603, Malaysia. RP Xu, F (reprint author), Xi An Jiao Tong Univ, Sch Life Sci & Technol, Minist Educ, Key Lab Biomed Informat Engn, Xian 710049, Peoples R China. EM tjlu@mail.xjtu.edu.cn; fengxu@mail.xjtu.edu.cn RI Xu, Feng/C-7430-2011; Lu, Tian Jian/E-6063-2016; Liu, Ming/B-4143-2009; Xu, Feng/H-4468-2011 OI Liu, Ming/0000-0002-6310-948X; Xu, Feng/0000-0003-4351-0222 FU National Natural Science Foundation of China [11372243]; National 111 Project of China [B06024]; Major International Joint Research Program of China [11120101002]; Key (Key grant) Project of Chinese Ministry of Education [313045]; South Wisdom Valley Innovative Research Team Program, International Science & Technology Cooperation Program of China [2013DFG02930]; National Instrumentation Program [2013YQ190467]; Fundamental Research Funds for the Central Universities [2012jdhz46]; Ministry of Higher Education (MOHE), Government of Malaysia [UM.C/HIR/MOHE/ENG/44]; China Young 1000-Talent Program and Program for New Century Excellent Talents in University [NCET-12-0437] FX This work was financially supported by the National Natural Science Foundation of China (11372243), the National 111 Project of China (B06024), the Major International Joint Research Program of China (11120101002), the Key (Key grant) Project of Chinese Ministry of Education (313045), the South Wisdom Valley Innovative Research Team Program, International Science & Technology Cooperation Program of China (2013DFG02930), National Instrumentation Program (2013YQ190467), and the Fundamental Research Funds for the Central Universities (2012jdhz46). B. P-M. received funding from the Ministry of Higher Education (MOHE), Government of Malaysia, under the high impact research grant (UM.C/HIR/MOHE/ENG/44). FX was also partially supported by the China Young 1000-Talent Program and Program for New Century Excellent Talents in University (NCET-12-0437). The SEM and TEM work was done at International Center for Dielectric Research (ICDR), Xi'an Jiaotong University, Xi'an, China. The authors also thank Ms. Dai Yan Zhu, Ms. Lu Lu and Mr. Ma Chuan Sheng for their help in using SEM and TEM. NR 35 TC 22 Z9 22 U1 6 U2 65 PU ROYAL SOC CHEMISTRY PI CAMBRIDGE PA THOMAS GRAHAM HOUSE, SCIENCE PARK, MILTON RD, CAMBRIDGE CB4 0WF, CAMBS, ENGLAND SN 2050-7526 EI 2050-7534 J9 J MATER CHEM C JI J. Mater. Chem. C PY 2014 VL 2 IS 19 BP 3671 EP 3676 DI 10.1039/c4tc00129j PG 6 WC Materials Science, Multidisciplinary; Physics, Applied SC Materials Science; Physics GA AF8XZ UT WOS:000335000300001 ER PT J AU Dobkin, BHK Nadeau, SE Behrman, AL Wu, SS Rose, DK Bowden, M Studenski, S Lu, XM Duncan, PW AF Dobkin, Bruce H. K. Nadeau, Stephen E. Behrman, Andrea L. Wu, Samuel S. Rose, Dorian K. Bowden, Mark Studenski, Stephanie Lu, Xiaomin Duncan, Pamela W. TI Prediction of responders for outcome measures of Locomotor Experience Applied Post Stroke trial SO JOURNAL OF REHABILITATION RESEARCH AND DEVELOPMENT LA English DT Article DE community ambulation; exercise; functional walking level; gait speed; LEAPS; outcome measures; physical therapy; quality of life; stroke rehabilitation; walking ID GAIT; REHABILITATION; SPEED; HETEROGENEITY; INTERVENTION; RELIABILITY; MANAGEMENT AB The Locomotor Experience Applied Post Stroke rehabilitation trial found equivalent walking outcomes for body weight-supported treadmill plus overground walking practice versus home-based exercise that did not emphasize walking. From this large database, we examined several clinically important questions that provide insights into recovery of walking that may affect future trial designs. Using logistic regression analyses, we examined predictors of response based on a variety of walking speed-related outcomes and measures that captured disability, physical impairment, and quality of life. The most robust predictor was being closer at baseline to the primary outcome measure, which was the functional walking speed thresholds of 0.4 m/s (household walking) and 0.8 m/s (community walking). Regardless of baseline walking speed, a younger age and higher Berg Balance Scale score were relative predictors of responding, whether operationally defined by transitioning beyond each speed boundary or by a continuous change or a greater than median increase in walking speed. Of note, the cutoff values of 0.4 and 0.8 m/s had no particular significance compared with other walking speed changes despite their general use as descriptors of functional levels of walking. No evidence was found for any difference in predictors based on treatment group. C1 [Dobkin, Bruce H. K.] Univ Calif Los Angeles, Geffen Sch Med, Dept Neurol, Los Angeles, CA 90095 USA. [Nadeau, Stephen E.] Univ Florida, Coll Med, Dept Neurol, Gainesville, FL 32611 USA. [Nadeau, Stephen E.; Rose, Dorian K.] Malcom Randall Dept Vet Affairs VA Med Ctr, Res Serv, Gainesville, FL USA. [Behrman, Andrea L.] Univ Louisville, Dept Neurol Surg, Louisville, KY 40292 USA. [Wu, Samuel S.; Lu, Xiaomin] Univ Florida, Dept Biostat, Gainesville, FL USA. [Rose, Dorian K.] Univ Florida, Dept Phys Therapy, Gainesville, FL USA. [Bowden, Mark] Med Univ S Carolina, Dept Hlth Sci, Charleston, SC 29425 USA. [Bowden, Mark] Med Univ S Carolina, Div Phys Therapy, Charleston, SC 29425 USA. [Bowden, Mark] Ralph H Johnson VA Med Ctr, Charleston, SC USA. [Studenski, Stephanie] Univ Pittsburgh, Dept Internal Med, Pittsburgh, PA USA. [Studenski, Stephanie] VA Pittsburgh Hlth Syst, Ctr Geriatr Res Educ & Clin, Pittsburgh, PA USA. [Duncan, Pamela W.] Wake Forest Univ, Dept Neurol, Winston Salem, NC 27109 USA. RP Dobkin, BHK (reprint author), Univ Calif Los Angeles, Geffen Sch Med, Dept Neurol, 710 Westwood Plaza, Los Angeles, CA 90095 USA. EM bdobkin@mednet.ucla.edu FU National Institute of Neurologic Diseases and Stroke; National Center for Medical Rehabilitation Research [RO1 NS050506] FX Funding/Support: This material was based on work supported by the National Institute of Neurologic Diseases and Stroke and the National Center for Medical Rehabilitation Research (grant RO1 NS050506). NR 23 TC 10 Z9 10 U1 1 U2 2 PU JOURNAL REHAB RES & DEV PI BALTIMORE PA DEPT OF VETERANS AFFAIRS REHABIL RES & DEVELOP CTR 103 SOUTH GAY STREET, BALTIMORE, MD 21202-4051 USA SN 0748-7711 EI 1938-1352 J9 J REHABIL RES DEV JI J. Rehabil. Res. Dev. PY 2014 VL 51 IS 1 BP 39 EP 50 DI 10.1682/JRRD.2013.04.0080 PG 12 WC Rehabilitation SC Rehabilitation GA AF8GB UT WOS:000334952600004 PM 24805892 ER PT J AU Malherbe, G Steel, HC Cassol, S de Oliveira, T Seebregts, CJ Anderson, R Cassol, E Rossouw, TM AF Malherbe, Glen Steel, Helen C. Cassol, Sharon de Oliveira, Tulio Seebregts, Christopher J. Anderson, Ronald Cassol, Edana Rossouw, Theresa M. TI Circulating Biomarkers of Immune Activation Distinguish Viral Suppression from Nonsuppression in HAART-Treated Patients with Advanced HIV-1 Subtype C Infection SO MEDIATORS OF INFLAMMATION LA English DT Article ID CD4(+) T-CELLS; PLASMACYTOID DENDRITIC CELLS; MICROBIAL TRANSLOCATION; ANTIRETROVIRAL THERAPY; DISEASE PROGRESSION; INNATE IMMUNITY; RECONSTITUTION; CHEMOKINES; DNA; REPLICATION AB Few studies have examined immune activation profiles in patients with advanced HIV-1 subtype C infection or assessed their potential to predict responsiveness to HAART. BioPlex, ELISA, and nephelometric procedures were used to measure plasma levels of inflammatory biomarkers in HIV-1 subtype C-infected patients sampled before and after 6 months of successful HAART (n = 20); in patients failing HAART (n = 30); and in uninfected controls (n = 8). Prior to HAART, CXCL9, CXCL10, beta 2M, sTNF-R1, TGF-beta 1, IFN-gamma, IL-6, TNF, and sCD14 were significantly elevated in HIV-1-infected patients compared to controls (P < 0.01). All of these markers, with the exception of sTNF-R1, were also elevated in patients failing HAART (P < 0.05). The persistently elevated levels of CXCL9, CXCL10, and beta 2M in patients failing therapy in the setting of a marked reduction in these markers in patients on successful HAART suggest that they may be useful not only to monitor immune activation during HAART, but also to distinguish between good and poor responders. In the case of sCD14 and TGF-beta 1, the levels of these biomarkers remained persistently elevated despite HAART-induced virological suppression, a finding that is consistent with ongoing monocyte-macrophage activation, underscoring a potential role for adjuvant anti-inflammatory therapy. C1 [Malherbe, Glen; Steel, Helen C.; Cassol, Sharon; Anderson, Ronald; Rossouw, Theresa M.] Univ Pretoria, Fac Hlth Sci, Dept Immunol, Unit Inflammat & Immun,MRC, ZA-0001 Pretoria, South Africa. [de Oliveira, Tulio] Africa Ctr Hlth & Populat Studies, ZA-3935 Mtubatuba, South Africa. [Seebregts, Christopher J.] Jembi Hlth Syst NPC, ZA-7945 Cape Town, South Africa. [Seebregts, Christopher J.] Univ KwaZulu Natal, Sch Math Stat & Comp Sci, ZA-3600 Westville, South Africa. [Cassol, Edana] Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02215 USA. RP Rossouw, TM (reprint author), Univ Pretoria, Fac Hlth Sci, Dept Immunol, Unit Inflammat & Immun,MRC, ZA-0001 Pretoria, South Africa. EM ducati999@mweb.co.za FU Delegation of the European Union to South Africa [2007/147-790]; Medical Research Council of South Africa [61509] FX This research and selected researchers (Glen Malherbe, Sharon Cassol, Tulio de Oliveira, Christopher Seebregts, Edana Cassol, and Theresa M Rossouw) were partially funded by a Grant from the Delegation of the European Union to South Africa: "Drug Resistance Surveillance and Treatment Monitoring Network for the Public Sector HIV Antiretroviral Treatment Programme in the Free State," Sante 2007/147-790 and Medical Research Council of South Africa, Unlocking the Future 61509. The information contained in the paper has not been presented previously. NR 39 TC 7 Z9 7 U1 0 U2 2 PU HINDAWI PUBLISHING CORPORATION PI NEW YORK PA 410 PARK AVENUE, 15TH FLOOR, #287 PMB, NEW YORK, NY 10022 USA SN 0962-9351 EI 1466-1861 J9 MEDIAT INFLAMM JI Mediat. Inflamm. PY 2014 AR 198413 DI 10.1155/2014/198413 PG 7 WC Cell Biology; Immunology SC Cell Biology; Immunology GA AF5NC UT WOS:000334759200001 ER PT S AU Veyrac, A Besnard, A Caboche, J Davis, S Laroche, S AF Veyrac, Alexandra Besnard, Antoine Caboche, Jocelyne Davis, Sabrina Laroche, Serge BE Khan, ZU Muly, EC TI The Transcription Factor Zif268/Egr1, Brain Plasticity, and Memory SO MOLECULAR BASIS OF MEMORY SE Progress in Molecular Biology and Translational Science LA English DT Review; Book Chapter ID IMMEDIATE-EARLY GENE; LONG-TERM POTENTIATION; ANTERIOR CINGULATE CORTEX; MESSENGER-RNA EXPRESSION; MEDIAL PREFRONTAL CORTEX; BORN HIPPOCAMPAL-NEURONS; DENTATE GRANULE CELLS; REMOTE SPATIAL MEMORY; RAT NUCLEUS-ACCUMBENS; ADULT OLFACTORY-BULB AB The capacity to remember our past experiences and organize our future draws on a number of cognitive processes that allow our brain to form and store neural representations that can be recalled and updated at will. In the brain, these processes require mechanisms of neural plasticity in the activated circuits, brought about by cellular and molecular changes within the neurons activated during learning. At the cellular level, a wealth of experimental data accumulated in recent years provides evidence that signaling from synapses to nucleus and the rapid regulation of the expression of immediate early genes encoding inducible, regulatory transcription factors is a key step in the mechanisms underlying synaptic plasticity and the modification of neural networks required for the laying down of memories. In the activated neurons, these transcriptional event are thought to mediate the activation of selective gene programs and subsequent synthesis of proteins, leading to stable functional and structural remodeling of the activated networks, so that the memory can later be reactivated upon recall. Over the past few decades, novel insights have been gained in identifying key transcriptional regulators that can control the genomic response of synaptically activated neurons. Here, as an example of this approach, we focus on one such activity-dependent transcription factor, Zif268, known to be implicated in neuronal plasticity and memory formation. We summarize current knowledge about the regulation and function of Zif268 in different types of brain plasticity and memory processes. C1 [Veyrac, Alexandra; Davis, Sabrina; Laroche, Serge] CNRS, Ctr Neurosci Paris Sud, UMR 8195, F-91405 Orsay, France. [Veyrac, Alexandra; Davis, Sabrina; Laroche, Serge] Univ Paris 11, Ctr Neurosci Paris Sud, UMR 8195, Orsay, France. [Besnard, Antoine] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Harvard Stem Cell Inst,Ctr Regenerat Med, Boston, MA USA. [Caboche, Jocelyne] INSERM, UMRS 952, Paris, France. [Caboche, Jocelyne] CNRS, UMR7224, Paris, France. [Caboche, Jocelyne] Univ Paris 06, Paris, France. RP Veyrac, A (reprint author), CNRS, Ctr Neurosci Paris Sud, UMR 8195, F-91405 Orsay, France. RI Litaudon, Philippe/M-6421-2014 NR 240 TC 37 Z9 39 U1 7 U2 19 PU ELSEVIER ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA SN 1877-1173 BN 978-0-12-420170-5 J9 PROG MOL BIOL TRANSL JI Prog. Molec. Biol. Transl. Sci. PY 2014 VL 122 BP 89 EP 129 DI 10.1016/B978-0-12-420170-5.00004-0 PG 41 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA BA2GW UT WOS:000333379800004 PM 24484699 ER PT J AU Sconocchia, G Eppenberger-Castori, S Zlobec, I Karamitopoulou, E Arriga, R Coppola, A Caratelli, S Spagnoli, GC Lauro, D Lugli, A Han, JY Iezzi, G Ferrone, C Ferlosio, A Tornillo, L Droeser, R Rossi, P Attanasio, A Ferrone, S Terracciano, L AF Sconocchia, Giuseppe Eppenberger-Castori, Serenella Zlobec, Inti Karamitopoulou, Eva Arriga, Roberto Coppola, Andrea Caratelli, Sara Spagnoli, Giulio Cesare Lauro, Davide Lugli, Alessandro Han, Junyi Iezzi, Giandomenica Ferrone, Cristina Ferlosio, Amedeo Tornillo, Luigi Droeser, Raoul Rossi, Piero Attanasio, Antonio Ferrone, Soldano Terracciano, Luigi TI HLA Class II Antigen Expression in Colorectal Carcinoma Tumors as a Favorable Prognostic Marker SO NEOPLASIA LA English DT Article ID RENAL-CELL CARCINOMA; CYTOTOXIC T-CELLS; DR EXPRESSION; CANCER PATIENTS; IMPROVED SURVIVAL; IN-SITU; INFILTRATING LYMPHOCYTES; ABERRANT EXPRESSION; MONONUCLEAR-CELLS; GENE-EXPRESSION AB The goal of this study was to determine the frequency of HLA class II antigen expression in colorectal carcinoma (CRC) tumors, its association with the clinical course of the disease, and the underlying mechanism(s). Two tissue microarrays constructed with 220 and 778 CRC tumors were stained with HLA-DR, DQ, and DP antigen-specific monoclonal antibody LGII-612.14, using the immunoperoxidase staining technique. The immunohistochemical staining results were correlated with the clinical course of the disease. The functional role of HLA class II antigens expressed on CRC cells was analyzed by investigating their in vitro interactions with immune cells. HLA class II antigens were expressed in about 25% of the 220 and 21% of the 778 tumors analyzed with an overall frequency of 23%. HLA class II antigens were detected in 19% of colorectal adenomas. Importantly, the percentage of stained cells and the staining intensity were significantly lower than those detected in CRC tumors. However, HLA class II antigen staining was weakly detected only in 5.4% of 37 normal mucosa tissues. HLA class II antigen expression was associated with a favorable clinical course of the disease. In vitro stimulation with interferon gamma (IFN gamma) induced HLA class II antigen expression on two of the four CRC cell lines tested. HLA class II antigen expression on CRC cells triggered interleukin-1 beta (IL-1 beta) production by resting monocytes. HLA class II antigen expression in CRC tumors is a favorable prognostic marker. This association may reflect stimulation of IL-1 beta production by monocytes. C1 [Sconocchia, Giuseppe; Caratelli, Sara] CNR, Dept Biomed, Inst Translat Pharmacol, Lab Tumor Immunol & Immunotherapy, I-00133 Rome, Italy. [Eppenberger-Castori, Serenella; Tornillo, Luigi; Terracciano, Luigi] Univ Basel, Inst Pathol, Basel, Switzerland. [Zlobec, Inti; Karamitopoulou, Eva; Lugli, Alessandro] Univ Bern, Inst Pathol, Bern, Switzerland. [Karamitopoulou, Eva] Univ Athens, Sch Med, Dept Pathol 1, GR-11527 Athens, Greece. [Arriga, Roberto; Coppola, Andrea; Lauro, Davide; Attanasio, Antonio] Univ Roma Tor Vergata, Dept Syst Med, Rome, Italy. [Spagnoli, Giulio Cesare; Han, Junyi; Iezzi, Giandomenica; Droeser, Raoul] Univ Basel, Inst Surg Res & Hosp Management, Basel, Switzerland. [Han, Junyi] Tongji Univ, Shangai East Hosp, Dept Gastroenterol, Shanghai, Peoples R China. [Ferrone, Cristina; Ferrone, Soldano] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Surg, Boston, MA USA. [Ferlosio, Amedeo] Univ Roma Tor Vergata, Dept Biopathol, Rome, Italy. [Rossi, Piero] Univ Roma Tor Vergata, Dept Expt Med & Surg, Rome, Italy. RP Sconocchia, G (reprint author), CNR, Dept Biomed, Inst Translat Pharmacol, Lab Tumor Immunol & Immunotherapy, Via Fosso del Cavaliere 100, I-00133 Rome, Italy. EM giuseppe.sconocchia@ift.cnr.it OI Lauro, Davide/0000-0002-8597-4415; Tornillo, Luigi/0000-0003-3610-3733; Ferlosio , Amedeo /0000-0002-9604-7238 FU Italian Association for Cancer Research (AIRC) [IG10555]; Academic Leaders Training Program of Pudong Health Bureau (Shanghai, PR China) [PEWd2010-05]; Swiss National Fond Professorship grant; Dr Hans-Altschuler Stiftung; Werner und Hedy Berger-Janser Stiftung; Swiss National Fond FX This work was supported by the Italian Association for Cancer Research (AIRC; grant IG10555 to G. S.). J.H. has been supported by the Academic Leaders Training Program of Pudong Health Bureau (Shanghai, PR China; grant PEWd2010-05). G. I. is partially supported by a Swiss National Fond Professorship grant. R. A. D. is partially supported by a grant from the Dr Hans-Altschuler Stiftung and the Werner und Hedy Berger-Janser Stiftung. L. M. T. and L. T. are partially funded by a Swiss National Fond grant to LTe. The authors have no conflicts of interest to declare. NR 61 TC 10 Z9 10 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1522-8002 EI 1476-5586 J9 NEOPLASIA JI Neoplasia PD JAN PY 2014 VL 16 IS 1 BP 31 EP U61 DI 10.1593/neo.131568 PG 13 WC Oncology SC Oncology GA AF6VX UT WOS:000334853800004 PM 24563618 ER PT J AU Kang, SW Lee, S Na, JH Yoon, HI Lee, DE Koo, H Cho, YW Kim, SH Jeong, SY Kwon, IC Choi, K Kim, K AF Kang, Sun-Woong Lee, Sangmin Na, Jin Hee Yoon, Hwa In Lee, Dong-Eun Koo, Heebeom Cho, Yong Woo Kim, Sun Hwa Jeong, Seo Young Kwon, Ick Chan Choi, Kuiwon Kim, Kwangmeyung TI Cell Labeling and Tracking Method without Distorted Signals by Phagocytosis of Macrophages SO THERANOSTICS LA English DT Article DE cell labeling; cell tracking; metabolic glycoengineering; click chemistry; chemical reporter ID EMBRYONIC STEM-CELLS; FREE CLICK CHEMISTRY; IN-VIVO; SIALIC-ACID; COPPER-FREE; APOPTOTIC CELLS; NANOPARTICLES; PROTEINS; SURFACES; GLYCANS AB Cell labeling and tracking are important processes in understanding biologic mechanisms and the therapeutic effect of inoculated cells in vivo. Numerous attempts have been made to label and track inoculated cells in vivo; however, these methods have limitations as a result of their biological effects, including secondary phagocytosis of macrophages and genetic modification. Here, we investigated a new cell labeling and tracking strategy based on metabolic glycoengineering and bioorthogonal click chemistry. We first treated cells with tetra-acetylated N-azidoacetyl-D-mannosamine to generate unnatural sialic acids with azide groups on the surface of the target cells. The azide-labeled cells were then transplanted to mouse liver, and dibenzyl cyclooctyne-conjugated Cy5 (DBCO-Cy5) was intravenously injected into mice to chemically bind with the azide groups on the surface of the target cells in vivo for target cell visualization. Unnatural sialic acids with azide groups could be artificially induced on the surface of target cells by glycoengineering. We then tracked the azide groups on the surface of the cells by DBCO-Cy5 in vivo using bioorthogonal click chemistry. Importantly, labeling efficacy was enhanced and false signals by phagocytosis of macrophages were reduced. This strategy will be highly useful for cell labeling and tracking. C1 [Kang, Sun-Woong] Korea Inst Toxicol, Next Generat Pharmaceut Res Ctr, Taejon, South Korea. [Lee, Sangmin; Na, Jin Hee; Kim, Sun Hwa; Kwon, Ick Chan; Choi, Kuiwon; Kim, Kwangmeyung] Korea Inst Sci & Technol, Ctr Theragnosis, Biomed Res Inst, Seoul 136791, South Korea. [Yoon, Hwa In; Cho, Yong Woo] Hanyang Univ, Dept Chem Engn, Ansan, South Korea. [Lee, Dong-Eun] Korea Atom Energy Res Inst, Adv Radiat Technol Inst, Jeonbuk, South Korea. [Koo, Heebeom] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Wellman Ctr Photomed, Boston, MA USA. [Jeong, Seo Young] Kyung Hee Univ, Dept Life & Nanopharmaceut Sci, Seoul, South Korea. [Kwon, Ick Chan] Korea Univ, KIST Sch, Seoul, South Korea. RP Kim, K (reprint author), Korea Inst Sci & Technol, Ctr Theragnosis, Biomed Res Inst, 39-1 Hawolgok Dong, Seoul 136791, South Korea. EM kim@kist.re.kr FU Fusion Technology Project [2010-50201]; M.D.-Ph.D. Program [2010-0019864]; Global Research Laboratory through the National Research Foundation of Korea (NRF); Ministry of Science, ICT (Information and Communication Technologies); KIST FX This work was supported by the Fusion Technology Project (2010-50201), M.D.-Ph.D. Program (2010-0019864), and Global Research Laboratory through the National Research Foundation of Korea (NRF) funded by the Ministry of Science, ICT (Information and Communication Technologies) and Future Planning and Intramural Research Program (KIST Young Fellow) of KIST. NR 40 TC 9 Z9 9 U1 2 U2 28 PU IVYSPRING INT PUBL PI LAKE HAVEN PA PO BOX 4546, LAKE HAVEN, NSW 2263, AUSTRALIA SN 1838-7640 J9 THERANOSTICS JI Theranostics PY 2014 VL 4 IS 4 BP 420 EP 431 DI 10.7150/thno.7265 PG 12 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA AF4ES UT WOS:000334664800005 PM 24578725 ER PT J AU Alhosaini, M Walter, JS Singh, S Dieter, RS Hsieh, AM Leehey, DJ AF Alhosaini, Mohamad Walter, James S. Singh, Sanjay Dieter, Robert S. Hsieh, Annming Leehey, David J. TI Hypomagnesemia in Hemodialysis Patients:Role of Proton Pump Inhibitors SO AMERICAN JOURNAL OF NEPHROLOGY LA English DT Article DE Magnesium; Hemodialysis; Proton pump inhibitors ID SERUM MAGNESIUM CONCENTRATION; PERITONEAL-DIALYSIS PATIENTS; PARATHYROID-HORMONE SECRETION; CHRONIC KIDNEY-DISEASE; ADYNAMIC BONE-DISEASE; MAINTENANCE HEMODIALYSIS; SIGNIFICANT PREDICTOR; PHOSPHATE BINDER; RENAL FAILURE; CALCIUM AB Background: Recent observations have associated hypomagnesemia with increased risk of cardiovascular morbidity and mortality in hemodialysis patients. Methods: We did a 3-month chart review of 62 chronic hemodialysis patients at a single US hospital. All were dialyzed using a dialysate [Mg] of 0.75-1.0 mEq/1. Patients were divided into two groups: hypomagnesemic (mean predialysis plasma [Mg] <1.5 mEq/1) and non-hypomagnesemic (mean predialysis plasma [Mg] >= 1.5 mEq/1). Results: All patients were male; mean age was 64.3 +/- 8.7 years and the majority (73%) diabetic. 24 patients (39%) had hypomagnesemia and 38 (61%) were not hypomagnesemic. There were no significant differences between the two groups in age, diabetes status, blood pressure, duration of dialysis, plasma calcium, phosphorus, albumin, intact parathyroid hormone (PTH), dialysis adequacy (Kt/V), or dietary protein intake (as estimated by normalized protein catabolic rate, nPCR). However, use of proton pump inhibitors (PPIs) was significantly associated with hypomagnesemia (plasma [Mg] 1.48 +/- 0.16 mEq/1 in the PPI group vs. 1.65 +/- 0.26 mEq/I in the non-PPI group, p = 0.007). Adjustment for age, diabetes status, duration of dialysis, plasma albumin, Kt/V, nPCR, and diuretic use did not affect the association between PPI use and hypomagnesemia. Conclusions: Use of PPIs in patients dialyzed using a dialysate [Mg] of 0.75-1.0 mEq/1 is associated with hypomagnesemia. We suggest monitoring plasma [Mg] in patients taking PPIs, with discontinuation of the medication if possible and/or adjustment of dialysate [Mg] to normalize plasma [Mg]. (C) 2014 S. Karger AG, Basel C1 [Alhosaini, Mohamad; Dieter, Robert S.; Hsieh, Annming; Leehey, David J.] US Dept Vet Affairs, Vet Affairs Edward Hines Jr Hosp, Dept Med, Hines, IL 60141 USA. [Walter, James S.; Singh, Sanjay] US Dept Vet Affairs, Vet Affairs Edward Hines Jr Hosp, Dept Res, Hines, IL 60141 USA. [Singh, Sanjay] East West Univ, Chicago, IL USA. RP Leehey, DJ (reprint author), Vet Affairs Hosp, 111-L, Hines, IL 60141 USA. EM dleehey@lumc.edu NR 44 TC 14 Z9 14 U1 0 U2 10 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0250-8095 EI 1421-9670 J9 AM J NEPHROL JI Am. J. Nephrol. PY 2014 VL 39 IS 3 BP 204 EP 209 DI 10.1159/000360011 PG 6 WC Urology & Nephrology SC Urology & Nephrology GA AE7DK UT WOS:000334156700003 PM 24577494 ER PT J AU Ferdinand, KC Rodriguez, F Nasser, SA Caballero, AE Puckrein, GA Zangeneh, F Mansour, M Foody, JM Pemu, PE Ofili, EO AF Ferdinand, Keith C. Rodriguez, Fatima Nasser, Samar A. Caballero, A. Enrique Puckrein, Gary A. Zangeneh, Farhad Mansour, Michael Foody, JoAnne Micale Pemu, Priscilla E. Ofili, Elizabeth O. TI Cardiorenal Metabolic Syndrome and Cardiometabolic Risks in Minority Populations SO CARDIORENAL MEDICINE LA English DT Review DE Cardiorenal metabolic syndrome; Cardiometabolic risk; Metabolic syndrome; Racial/ethnic minorities; Disparities ID CORONARY-HEART-DISEASE; BODY-MASS INDEX; CARDIOVASCULAR-DISEASE; DIABETES-MELLITUS; ASIAN-AMERICANS; UNITED-STATES; SOUTH ASIANS; PREVALENCE; ASSOCIATION; FRAMINGHAM AB Cardiovascular disease (CVD), including heart disease and stroke, is the leading cause of death in the USA, regardless of self-determined race/ethnicity, and largely driven by cardiometabolic risk (CMR) and cardiorenal metabolic syndrome (CRS). The primary drivers of increased CMR include obesity, hypertension, insulin resistance, hyperglycemia, dyslipidemia, chronic kidney disease as well as associated adverse behaviors of physical inactivity, smoking, and unhealthy eating habits. Given the importance of CRS for public health, multiple stakeholders, including the National Minority Quality Forum (the Forum), the American Association of Clinical Endocrinologists (AACE), the American College of Cardiology (ACC), and the Association of Black Cardiologists (ABC), have developed this review to inform clinicians and other health professionals of the unique aspects of CMR in racial/ethnic minorities and of potential means to improve CMR factor control, to reduce CRS and CVD in diverse populations, and to provide more effective, coordinated care. This paper highlights CRS and CMR as sources of significant morbidity and mortality (particularly in racial/ethnic minorities), associated health-care costs, and an evolving index tool for cardiometabolic disease to determine geographical and environmental factors. Finally, this work provides a few examples of interventions potentially successful at reducing disparities in cardiometabolic health.(c) 2013 S. Karger AG, Basel C1 [Ferdinand, Keith C.] Tulane Univ, Sch Med, New Orleans, LA 70112 USA. [Rodriguez, Fatima] Brigham & Womens Hosp, Boston, MA 02115 USA. [Caballero, A. Enrique] Harvard Univ, Sch Med, Joslin Diabet Ctr, Latino Diabet Initiat, Boston, MA 02115 USA. [Nasser, Samar A.; Foody, JoAnne Micale] George Washington Univ, Sch Med & Hlth Serv, Dept Clin Res & Leadership, Washington, DC USA. [Zangeneh, Farhad] George Washington Univ, Sch Med & Hlth Serv, Dept Med, Washington, DC USA. [Puckrein, Gary A.] Natl Minor Qual Forum, Washington, DC USA. [Mansour, Michael] Univ Mississippi, Med Ctr, Dept Med, Jackson, MS 39216 USA. [Mansour, Michael] Delta Reg Med Ctr, Greenville, MS USA. [Pemu, Priscilla E.; Ofili, Elizabeth O.] Morehouse Sch Med, Dept Med, Atlanta, GA 30310 USA. RP Ferdinand, KC (reprint author), Tulane Univ, Sch Med, 1430 Tulane Ave,SL-48, New Orleans, LA 70112 USA. EM kferdina@tulane.edu FU National Institute on Minority Health and Health Disparities (NIMHD) [8U54MD007588, 8R25MD007589-10]; National Center for Advancing Translational Sciences (NCATS) [UL1TR000454]; Boehringer Ingelheim FX E.O.O. and P.E.P. are supported in part by the National Institute on Minority Health and Health Disparities (NIMHD, grant No. 8U54MD007588 and 8R25MD007589-10). Moreover, they are also supported in part by the National Center for Advancing Translational Sciences (NCATS, grant No. UL1TR000454). Both NIMHD and NCATS are components of the National Institutes of Health (NIH). The contents of this paper are solely the responsibility of the authors and do not necessarily represent the official views of NIMHD, NCATS, or NIH.; Boehringer Ingelheim provided funding to the ACC for the CardioMetabolic Health Alliance. NR 55 TC 11 Z9 11 U1 1 U2 8 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 1664-3828 EI 1664-5502 J9 CARDIORENAL MED JI CardioRenal Med. PY 2014 VL 4 IS 1 BP 1 EP 11 DI 10.1159/000357236 PG 11 WC Cardiac & Cardiovascular Systems; Urology & Nephrology SC Cardiovascular System & Cardiology; Urology & Nephrology GA AE7DI UT WOS:000334156500001 PM 24847329 ER PT J AU Cooper, JN Evans, RW Brooks, MM Fried, L Holmes, C Barinas-Mitchell, E Sutton-Tyrrell, K AF Cooper, Jennifer N. Evans, Rhobert W. Brooks, Maria Mori Fried, Linda Holmes, Chris Barinas-Mitchell, Emma Sutton-Tyrrell, Kim TI Associations between arterial stiffness and platelet activation in normotensive overweight and obese young adults SO CLINICAL AND EXPERIMENTAL HYPERTENSION LA English DT Article DE Arterial stiffness; obesity; platelet activation; pulse wave velocity; weight loss ID INTIMA-MEDIA THICKNESS; PULSE-WAVE VELOCITY; ALL-CAUSE MORTALITY; CARDIOVASCULAR-DISEASE; BETA-THROMBOGLOBULIN; URINARY SODIUM; PLASMA-LEVELS; SHEAR-STRESS; VOLUME; ATHEROSCLEROSIS AB Obese individuals have elevated platelet activation and arterial stiffness, but the strength and temporality of the relationship between these factors remain unclear. We aimed to determine the effect of increased arterial stiffness on circulating platelet activity in overweight/obese young adults. This analysis included 92 participants (mean age 40 years, 60 women) in the Slow Adverse Vascular Effects of excess weight (SAVE) trial, a clinical trial examining the effects of a lifestyle intervention with or without sodium restriction on vascular health in normotensive overweight/obese young adults. Carotid-femoral (cf), brachial-ankle (ba) and femoral-ankle (fa) pulse wave velocity (PWV) served as measures of arterial stiffness and were measured at baseline and 6, 12 and 24 months follow-up. Platelet activity was measured as plasma b-thromboglobulin (beta-TG) at 24 months. Higher plasma beta-TG was correlated with greater exposure to elevated cfPWV (p = 0.02) and baPWV (p = 0.04) during the preceding two years. After adjustment for serum leptin, greater exposure to elevated baPWV remained significant (p = 0.03) and exposure to elevated cfPWV marginally significant (p = 0.054) in predicting greater plasma b-TG. Greater arterial stiffness, particularly central arterial stiffness, predicts greater platelet activation in overweight/obese individuals. This relationship might partly explain the association between increased arterial stiffness and incident atherothrombotic events. C1 [Cooper, Jennifer N.; Evans, Rhobert W.; Brooks, Maria Mori; Fried, Linda; Barinas-Mitchell, Emma; Sutton-Tyrrell, Kim] Univ Pittsburgh, Grad Sch Publ Hlth, Dept Epidemiol, Pittsburgh, PA USA. [Cooper, Jennifer N.; Brooks, Maria Mori] Univ Pittsburgh, Grad Sch Publ Hlth, Dept Biostat, Pittsburgh, PA 15261 USA. [Cooper, Jennifer N.] Nationwide Childrens Hosp, Ctr Innovat Pediat Practice, Columbus, OH 43205 USA. [Fried, Linda] VA Pittsburgh Healthcare Syst, Univ Drive Div, Pittsburgh, PA USA. [Holmes, Chris] Univ Vermont, Coll Med, Colchester Res Facil, Pittsburgh, PA USA. RP Cooper, JN (reprint author), Nationwide Childrens Hosp, Ctr Innovat Pediat Practice, JWest 4915, Columbus, OH 43205 USA. EM jennifer.cooper@nationwidechildrens.org OI Barinas-Mitchell, Emma/0000-0002-7280-7781; Brooks, Maria/0000-0002-2030-7873 FU National Heart, Lung, and Blood Institute of the National Institutes of Health [R01 HL077525, F31 HL106986] FX Grant Support: This work was supported by grants R01 HL077525 and F31 HL106986 from the National Heart, Lung, and Blood Institute of the National Institutes of Health. NR 34 TC 1 Z9 1 U1 0 U2 1 PU INFORMA HEALTHCARE PI LONDON PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND SN 1064-1963 EI 1525-6006 J9 CLIN EXP HYPERTENS JI Clin. Exp. Hypertens. PY 2014 VL 36 IS 3 BP 115 EP 122 DI 10.3109/10641963.2013.789045 PG 8 WC Pharmacology & Pharmacy; Peripheral Vascular Disease SC Pharmacology & Pharmacy; Cardiovascular System & Cardiology GA AF2AT UT WOS:000334515700001 PM 23654212 ER PT J AU Kim, MB Hong, TS Wo, JY AF Kim, Miranda B. Hong, Theodore S. Wo, Jennifer Y. TI Treatment of Stage II-III Rectal Cancer Patients SO CURRENT ONCOLOGY REPORTS LA English DT Article DE Radiation therapy; Node-positive rectal cancer; Preoperative chemotherapy; Postoperative chemotherapy; Rectal cancer; Colorectal cancer ID POSTOPERATIVE ADJUVANT CHEMOTHERAPY; TOTAL MESORECTAL EXCISION; MEDIAN FOLLOW-UP; PREOPERATIVE RADIOTHERAPY; RADIATION-THERAPY; RANDOMIZED-TRIAL; LOCAL EXCISION; CARCINOMA; CHEMORADIOTHERAPY; FLUOROURACIL AB The role and sequencing of radiotherapy in the management of T3-4 or node- positive rectal cancer has evolved over the last few decades. Given the significant local failure rate following surgery alone, both preoperative and postoperative chemotherapy and radiotherapy have been studied to decrease local and systemic failure and improve survival in these patients. This review discusses current indications and controversies for treatment of stage II-III rectal cancer patients. C1 [Kim, Miranda B.; Hong, Theodore S.; Wo, Jennifer Y.] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Wo, JY (reprint author), Massachusetts Gen Hosp, 100 Blossom St, Boston, MA 02114 USA. EM jwo@partners.org NR 61 TC 1 Z9 1 U1 1 U2 4 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1523-3790 EI 1534-6269 J9 CURR ONCOL REP JI Curr. Oncol. Rep. PD JAN PY 2014 VL 16 IS 1 AR 362 DI 10.1007/s11912-013-0362-0 PG 9 WC Oncology SC Oncology GA AE7HN UT WOS:000334168200005 PM 24323626 ER PT J AU Tolaney, S AF Tolaney, Sara TI New HER2-Positive Targeting Agents in Clinical Practice SO CURRENT ONCOLOGY REPORTS LA English DT Article DE Breast cancer; Trastuzumab; Pertuzumab; Trastuzumab emtansine; Trastuzumab-DM1; HER2-positive; Lapatinib; Neratinib; Afatinib; MM-302; Everolimus ID METASTATIC BREAST-CANCER; PERTUZUMAB PLUS TRASTUZUMAB; PHASE-II; MONOCLONAL-ANTIBODY; ADJUVANT CHEMOTHERAPY; CELL-LINES; OPEN-LABEL; RECEPTOR; LAPATINIB; HERCEPTIN AB Overexpression of human epidermal growth factor occurs in approximately 20-25 % of invasive breast cancers. This subtype of breast cancer has been associated with poor clinical outcomes. The development of trastuzumab, a humanized monoclonal antibody that binds to the extracellular domain of human epidermal growth factor receptor 2 (HER2), revolutionized outcomes of patients with HER2-positive breast cancer; however, many patients with HER2-positive metastatic breast cancer eventually become resistant to it. Several newer anti-HER2 agents have been developed, including lapatinib, pertuzumab, and trastuzumab emtansine. These exciting advances in drug development for HER2-positive breast cancer have also led to many challenges, including how to optimally sequence and combine HER2-targeted agents. C1 Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02215 USA. RP Tolaney, S (reprint author), Dana Farber Canc Inst, Dept Med Oncol, 450 Brookline Ave,Yawkey 1257, Boston, MA 02215 USA. EM stolaney@partners.org FU Genentech FX Sara M. Tolaney has received research funding from Genentech. NR 40 TC 9 Z9 9 U1 1 U2 14 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1523-3790 EI 1534-6269 J9 CURR ONCOL REP JI Curr. Oncol. Rep. PD JAN PY 2014 VL 16 IS 1 AR 359 DI 10.1007/s11912-013-0359-8 PG 7 WC Oncology SC Oncology GA AE7HN UT WOS:000334168200002 PM 24442625 ER PT J AU Hedgire, SS Mino-Kenudson, M Elmi, A Thayer, S Fernandez-del Castillo, C Harisinghani, MG AF Hedgire, Sandeep S. Mino-Kenudson, Mari Elmi, Azadeh Thayer, Sarah Fernandez-del Castillo, Carlos Harisinghani, Mukesh G. TI Enhanced primary tumor delineation in pancreatic adenocarcinoma using ultrasmall super paramagnetic iron oxide nanoparticle-ferumoxytol: an initial experience with histopathologic correlation SO INTERNATIONAL JOURNAL OF NANOMEDICINE LA English DT Article DE pancreatic cancer; tumor margin; neoadjuvant therapy; borderline resectable pancreatic cancer ID MINIMAL POSTOPERATIVE COMPLICATIONS; LONG-TERM SURVIVAL; RADIOFREQUENCY ABLATION; SURGEONS CONTRIBUTION; CANCER; MARGIN; CARCINOMA; THERAPY; CT; INDICATORS AB Purpose: To evaluate the role of ferumoxytol-enhanced magnetic resonance imaging (MRI) in delineating primary pancreatic tumors in patients undergoing preoperative neoadjuvant therapy. Materials and methods: Eight patients with pancreatic adenocarcinoma were enrolled in this study, and underwent MRI scans at baseline, immediate post, and at the 48 hour time point after ferumoxytol injection with quantitative T2* sequences. The patients were categorized into two groups; group A received preoperative neoadjuvant therapy and group B did not. The T2* of the primary pancreatic tumor and adjacent parenchyma was recorded at baseline and the 48 hour time point. After surgery, the primary tumors were assessed histopathologically for fibrosis and inflammation. Results: The mean T2* of the primary tumor and adjacent parenchyma at 48 hours in group A were 22.11 ms and 16.34 ms, respectively; in group B, these values were 23.96 ms and 23.26 ms, respectively. The T2* difference between the tumor and adjacent parenchyma in group A was more pronounced compared to in group B. The tumor margins were subjectively more distinct in group A compared to group B. Histopathologic evaluation showed a rim of dense fibrosis with atrophic acini at the periphery of the lesion in group A. Conversely, intact tumor cells/glands were present at the periphery of the tumor in group B. Conclusion: Ferumoxytol-enhanced MRI scans in patients receiving preoperative neoadjuvant therapy may offer enhanced primary tumor delineation, contributing towards achieving disease-free margin at the time of surgery, and thus improving the prognosis of pancreatic carcinomas. C1 [Hedgire, Sandeep S.; Elmi, Azadeh; Harisinghani, Mukesh G.] Massachusetts Gen Hosp, Dept Abdominal Imaging & Intervent, Boston, MA 02114 USA. [Mino-Kenudson, Mari] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Thayer, Sarah; Fernandez-del Castillo, Carlos] Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. RP Hedgire, SS (reprint author), Massachusetts Gen Hosp, Dept Abdominal Imaging & Intervent, 55 Fruit St, Boston, MA 02114 USA. EM hedgire.sandeep@mgh.harvard.edu FU Dana-Farber/Harvard Cancer Center Gastrointestinal Cancers SPORE FX The Dana-Farber/Harvard Cancer Center Gastrointestinal Cancers SPORE funded the study. NR 34 TC 8 Z9 8 U1 0 U2 4 PU DOVE MEDICAL PRESS LTD PI ALBANY PA PO BOX 300-008, ALBANY, AUCKLAND 0752, NEW ZEALAND SN 1178-2013 J9 INT J NANOMED JI Int. J. Nanomed. PY 2014 VL 9 BP 1891 EP 1896 DI 10.2147/IJN.S59788 PG 6 WC Nanoscience & Nanotechnology; Pharmacology & Pharmacy SC Science & Technology - Other Topics; Pharmacology & Pharmacy GA AF2ZI UT WOS:000334580600001 PM 24790431 ER PT S AU Laoui, S Bag, S Dantiste, O Frenette, M Hatamimoslehabadi, M Bellinger-Buckley, S Tseng, JC Rochford, J Yelleswarapu, C AF Laoui, Samir Bag, Seema Dantiste, Olivier Frenette, Mathieu Hatamimoslehabadi, Maryam Bellinger-Buckley, Stephanie Tseng, Jen-Chieh Rochford, Jonathan Yelleswarapu, Chandra BE Achilefu, S Raghavachari, R TI BODIPY derivatives as molecular photoacoustic contrast agents SO REPORTERS, MARKERS, DYES, NANOPARTICLES, AND MOLECULAR PROBES FOR BIOMEDICAL APPLICATIONS VI SE Proceedings of SPIE LA English DT Proceedings Paper CT Conference on Reporters, Markers, Dyes, Nanoparticles, and Molecular Probes for Biomedical Applications VI CY FEB 02-05, 2014 CL San Francisco, CA SP SPIE DE Molecular contrast agents; Fluorescence quenching; Photoacoustic imaging; Bodipy; Nonlinear; photoacoustics ID SENTINEL LYMPH-NODES; IN-VIVO DETECTION; GOLD NANOCAGES; CARBON NANOTUBES; INDOCYANINE GREEN; DRUG-DELIVERY; LIVING MICE; TOMOGRAPHY; NANOPARTICLES; CANCER AB Photoacoustic imaging (PAI) is emerging as a key in vivo imaging technique. Endogenous contrast agents alone are insufficient to obtain high contrast images necessitating a need for synthetic exogenous contrast agents. In recent years a great deal of research has been devoted to the development of nanoparticle based contrast agents with little effort on molecular systems. Here we report on the design and evaluation of BODIPY inspired molecular photoacoustic contrast agents (MPACs). Through chemical modification of the established BODIPY fluorophore, increasing its vibrational freedom and appending with non-emissive functionalities, it is demonstrated that the S-0 -> S-1 absorbed excitation energy is redirected towards a nonradiative excited-state decay pathway. Optical and photoacoustic characterization of the modified BODIPY MPACs demonstrates a stronger photoacoustic signal compared to the corresponding fluorescent BODIPY probes. C1 [Laoui, Samir; Dantiste, Olivier; Hatamimoslehabadi, Maryam; Yelleswarapu, Chandra] Univ Massachusetts, Dept Phys, 100 Morrissey Blvd, Boston, MA 02125 USA. [Bag, Seema; Frenette, Mathieu; Bellinger-Buckley, Stephanie; Rochford, Jonathan] Univ Massachusetts, Dept Chem, Boston, MA 02125 USA. [Tseng, Jen-Chieh] Dana Farber Canc Inst, Lurie Family Imaging Ctr, Boston, MA 02125 USA. RP Laoui, S (reprint author), Univ Massachusetts, Dept Phys, 100 Morrissey Blvd, Boston, MA 02125 USA. EM Jonthan.rochford@umb.edu; Chandra.yelleswarapu@umb.edu NR 47 TC 0 Z9 0 U1 1 U2 14 PU SPIE-INT SOC OPTICAL ENGINEERING PI BELLINGHAM PA 1000 20TH ST, PO BOX 10, BELLINGHAM, WA 98227-0010 USA SN 0277-786X BN 978-0-8194-9869-4 J9 PROC SPIE PY 2014 VL 8956 DI 10.1117/12.2040057 PG 9 WC Nanoscience & Nanotechnology; Optics; Radiology, Nuclear Medicine & Medical Imaging SC Science & Technology - Other Topics; Optics; Radiology, Nuclear Medicine & Medical Imaging GA BA3BW UT WOS:000334099100004 ER PT S AU Tichauer, KM Diop, M Elliott, JT Samkoe, KS Hasan, T St Lawrence, K Pogue, BW AF Tichauer, Kenneth M. Diop, Mamadou Elliott, Jonathan T. Samkoe, Kimberley S. Hasan, Tayyaba St Lawrence, Keith Pogue, Brian W. BE Achilefu, S Raghavachari, R TI Dual-tracer receptor concentration imaging using tracers with different tissue delivery kinetics SO REPORTERS, MARKERS, DYES, NANOPARTICLES, AND MOLECULAR PROBES FOR BIOMEDICAL APPLICATIONS VI SE Proceedings of SPIE LA English DT Proceedings Paper CT Conference on Reporters, Markers, Dyes, Nanoparticles, and Molecular Probes for Biomedical Applications VI CY FEB 02-05, 2014 CL San Francisco, CA SP SPIE DE planar fluorescence imaging; multiple reporter; mouse xenograft model; plasmalemmal vesicle associated; protein (PV1) ID TUMORS; MODEL; AGENTS AB Simultaneous dynamic fluorescent imaging of a suitable untargeted tracer in conjunction with any molecular targeted fluorescent agent has been shown to be a powerful approach for quantifying cancer-specific cell surface receptors in vivo in the presence of non-specific uptake and tracer delivery variability. The identification of a "suitable" untargeted tracer (i.e., one having equivalent plasma and tissue delivery pharmacokinetics to the targeted tracer) for every targeted tracer, however, may not always be feasible or could require extensive testing. This work presents a "deconvolution" approach capable of correcting for plasma and tissue-delivery pharmacokinetic differences between tracers by quantifying dynamic differences in targeted and untargeted tracer uptake in a receptor-free tissue (one devoid of targeted molecular species) and correcting uptake in all other tissues accordingly. This deconvolution correction approach is evaluated in theoretical models and explored in an in vivo mouse xenograft model of human glioma. In the animal experiments, epidermal growth factor receptor (EGFR: a receptor known to be overexpressed in the investigated glioma cell line) was targeted using a fluorescent tracer with very different plasma pharmacokinetics than a second untargeted fluorescent tracer. Without correcting for these differences, the dual-tracer approach yielded substantially higher estimations of EGFR concentration in all tissues than expected; however, deconvolution correction was able to produce estimates that matched ex vivo validation. C1 [Tichauer, Kenneth M.] IIT, Dept Biomed Engn, 3255 S Dearborn St, Chicago, IL 60616 USA. [Diop, Mamadou; St Lawrence, Keith; Pogue, Brian W.] Western Univ, Dept Med Biophys, London, ON N6A 3K7, Canada. [Elliott, Jonathan T.; Samkoe, Kimberley S.] Dartmouth Coll, Thayer Sch Engn, Hanover, NH 03755 USA. [Samkoe, Kimberley S.; Pogue, Brian W.] Geisel Sch Med, Dept Pathol & Surg, Hanover, NH 03755 USA. [Pogue, Brian W.] Massachusetts Gen Hosp, Wellman Inst Photomed, Boston, MA 02114 USA. RP Tichauer, KM (reprint author), IIT, Dept Biomed Engn, 3255 S Dearborn St, Chicago, IL 60616 USA. NR 19 TC 0 Z9 0 U1 0 U2 3 PU SPIE-INT SOC OPTICAL ENGINEERING PI BELLINGHAM PA 1000 20TH ST, PO BOX 10, BELLINGHAM, WA 98227-0010 USA SN 0277-786X BN 978-0-8194-9869-4 J9 PROC SPIE PY 2014 VL 8956 DI 10.1117/12.2037427 PG 6 WC Nanoscience & Nanotechnology; Optics; Radiology, Nuclear Medicine & Medical Imaging SC Science & Technology - Other Topics; Optics; Radiology, Nuclear Medicine & Medical Imaging GA BA3BW UT WOS:000334099100002 ER PT J AU David, SP Chu, IM Lancaster, T Stead, LF Evins, AE Prochaska, JJ AF David, Sean P. Chu, Isabella M. Lancaster, Tim Stead, Lindsay F. Evins, A. Eden Prochaska, Judith J. TI Systematic review and meta-analysis of opioid antagonists for smoking cessation SO BMJ OPEN LA English DT Article DE naltrexone; smoking cessation; opioid antagonists; smoking abstinence; tobacco ID NICOTINE REPLACEMENT THERAPY; CIGARETTE-SMOKING; ABSTINENCE SYNDROME; NALTREXONE AUGMENTATION; ALCOHOL DEPENDENCE; RANDOMIZED-TRIAL; WEIGHT-GAIN; NALOXONE; SMOKERS; BEHAVIOR AB Objectives This meta-analysis sought to evaluate the efficacy of opioid antagonists in promoting long-term smoking cessation. Post-treatment abstinence was examined as a secondary outcome and effects on withdrawal symptoms, craving and reduced consumption were also explored. Design The search strategy for this meta-analysis included clinical trials (published and unpublished data) in the Cochrane Tobacco Addiction Group Specialized Register and MEDLINE. Participants Adult smokers. Interventions We included randomised trials comparing opioid antagonists to placebo or an alternative therapy for smoking cessation and reported data on abstinence for a minimum of 6 months. Primary and secondary outcome measures Outcomes included smoking abstinence at long-term follow-up (primary); abstinence at end of treatment (secondary); and effects on withdrawal, craving and smoking consumption (exploratory). Results 8 trials with a total of 1213 participants were included. Half the trials examined the benefit of adding naltrexone versus placebo to nicotine replacement therapy (NRT). There was no significant difference between naltrexone and placebo alone (relative risk (RR) 1.00; 95% CI 0.66 to 1.51) or as an adjunct to NRT (RR 0.95; 95% CI 0.70 to 1.30), with an overall pooled estimate of RR 0.97; 95% CI 0.76 to 1.24. Findings for naltrexone effects on withdrawal, craving and reduced smoking were equivocal. Conclusions The findings indicate no beneficial effect of naltrexone alone or as an adjunct to NRT on short-term or long-term smoking abstinence. While further trials may narrow the confidence limits, they are unlikely to appreciably alter the conclusion. C1 [David, Sean P.] Stanford Univ, Ctr Educ Family & Community Med, Stanford, CA 94305 USA. [David, Sean P.; Chu, Isabella M.] Stanford Univ, Stanford Gen Med Disciplines, Stanford, CA 94305 USA. [Lancaster, Tim; Stead, Lindsay F.] Univ Oxford, Dept Primary Care Hlth Sci, Oxford, England. [Evins, A. Eden] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. [Prochaska, Judith J.] Stanford Univ, Stanford Prevent Res Ctr, Stanford, CA 94305 USA. RP David, SP (reprint author), Stanford Univ, Ctr Educ Family & Community Med, Stanford, CA 94305 USA. EM spdavid@stanford.edu OI David, Sean/0000-0002-4922-2603 NR 53 TC 4 Z9 4 U1 3 U2 7 PU BMJ PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 2044-6055 J9 BMJ OPEN JI BMJ Open PY 2014 VL 4 IS 3 DI 10.1136/bmjopen-2013-004393 PG 9 WC Medicine, General & Internal SC General & Internal Medicine GA AE4BA UT WOS:000333921300016 ER PT J AU Sun, M Karakiewicz, PI Sammon, JD Sukumar, S Gervais, MK Nguyen, PL Choueiri, TK Menon, M Trinh, QD AF Sun, Maxine Karakiewicz, Pierre I. Sammon, Jesse D. Sukumar, Shyam Gervais, Mai-Kim Nguyen, Paul L. Choueiri, Toni K. Menon, Mani Quoc-Dien Trinh TI Disparities in selective referral for cancer surgeries: implications for the current healthcare delivery system SO BMJ OPEN LA English DT Article DE Health Services Administration & Management ID HIGH-VOLUME HOSPITALS; UNITED-STATES; RADICAL PROSTATECTOMY; OPERATIVE MORTALITY; OUTCOMES; QUALITY; DATABASES; RESECTION; TRENDS; IMPACT AB Objectives Among considerable efforts to improve quality of surgical care, expedited measures such as a selective referral to high-volume institutions have been advocated. Our objective was to examine whether racial, insurance and/or socioeconomic disparities exist in the use of high-volume hospitals for complex surgical oncological procedures within the USA. Design, setting and participants Patients undergoing colectomy, cystectomy, oesophagectomy, gastrectomy, hysterectomy, lung resection, pancreatectomy or prostatectomy were identified retrospectively, using the Nationwide Inpatient Sample, between years 1999 and 2009. This resulted in a weighted estimate of 2 508 916 patients. Primary outcome measures Distribution of patients according to race, insurance and income characteristics was examined according to low-volume and high-volume hospitals (highest 20% of patients according to the procedure-specific mean annual volume). Generalised linear regression models for prediction of access to high-volume hospitals were performed. Results Insurance providers and county income levels varied differently according to patients' race. Most Caucasians resided in wealthier counties, regardless of insurance types (private/Medicare), while most African Americans resided in less wealthy counties (<=$24 999), despite being privately insured. In general, Caucasians, privately insured, and those residing in wealthier counties (>=$45 000) were more likely to receive surgery at high-volume hospitals, even after adjustment for all other patient-specific characteristics. Depending on the procedure, some disparities were more prominent, but the overall trend suggests a collinear effect for race, insurance type and county income levels. Conclusions Prevailing disparities exist according to several patient and sociodemographic characteristics for utilisation of high-volume hospitals. Efforts should be made to directly reduce such disparities and ensure equal healthcare delivery. C1 [Sun, Maxine; Karakiewicz, Pierre I.] Univ Montreal, Ctr Hlth, Canc Prognost & Hlth Outcomes Unit, Montreal, PQ, Canada. [Sammon, Jesse D.; Sukumar, Shyam; Menon, Mani] Henry Ford Hlth Syst, Vattikuti Urol Inst, Detroit, MI USA. [Gervais, Mai-Kim] Univ Montreal, Ctr Hlth, Div Gen Surg, Montreal, PQ, Canada. [Nguyen, Paul L.] Harvard Univ, Brigham & Womens Hosp, Dana Farber Canc Inst, Dept Radiat Oncol,Med Sch, Boston, MA 02115 USA. [Choueiri, Toni K.] Harvard Univ, Brigham & Womens Hosp, Dana Farber Canc Inst, Dept Med Oncol,Med Sch, Boston, MA 02115 USA. [Quoc-Dien Trinh] Harvard Univ, Brigham & Womens Hosp, Dana Farber Canc Inst, Dept Surg,Div Urol,Med Sch, Boston, MA 02115 USA. RP Sun, M (reprint author), Univ Montreal, Ctr Hlth, Canc Prognost & Hlth Outcomes Unit, Montreal, PQ, Canada. EM mcw.sun@umontreal.ca NR 34 TC 10 Z9 10 U1 1 U2 2 PU BMJ PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 2044-6055 J9 BMJ OPEN JI BMJ Open PY 2014 VL 4 IS 3 DI 10.1136/bmjopen-2013-003921 PG 10 WC Medicine, General & Internal SC General & Internal Medicine GA AE4BA UT WOS:000333921300065 ER PT J AU Manchikanti, L Falco, FJE Hansen, H Hirsch, JA AF Manchikanti, Laxmaiah Falco, Frank J. E. Hansen, Hans Hirsch, Joshua A. TI The Tragedy Of The Sustained Growth Rate Formula Continues Into 2014: Is There Hope For Repeal? SO PAIN PHYSICIAN LA English DT Editorial Material C1 [Manchikanti, Laxmaiah] Pain Management Ctr Paducah, Paducah, KY USA. [Manchikanti, Laxmaiah] Univ Louisville, Louisville, KY 40292 USA. [Falco, Frank J. E.] Mid Atlantic Spine & Pain Phys, Newark, DE USA. [Falco, Frank J. E.] Temple Univ Hosp & Med Sch, Philadelphia, PA 19140 USA. [Hansen, Hans] Pain Relief Ctr, Conover, NC USA. [Hirsch, Joshua A.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Hirsch, Joshua A.] Harvard Univ, Sch Med, Boston, MA USA. RP Manchikanti, L (reprint author), 2831 Lone Oak Rd, Paducah, KY 42003 USA. EM drlm@thepainmd.com NR 15 TC 7 Z9 7 U1 0 U2 0 PU AM SOC INTERVENTIONAL PAIN PHYSICIANS PI PADUCAH PA 81 LAKEVIEW DR, PADUCAH, KY 42001 USA SN 1533-3159 J9 PAIN PHYSICIAN JI Pain Physician PD JAN-FEB PY 2014 VL 17 IS 1 BP E21 EP E26 PG 6 WC Anesthesiology; Clinical Neurology SC Anesthesiology; Neurosciences & Neurology GA AE2OY UT WOS:000333814000003 PM 24452655 ER PT J AU Manchikanti, L Atluri, S Hansen, H Benyamin, RM Falco, FJE Helm, S Kaye, AD Hirsch, JA AF Manchikanti, Laxmaiah Atluri, Sairam Hansen, Hans Benyamin, Ramsin M. Falco, Frank J. E. Helm, Standiford Kaye, Alan D. Hirsch, Joshua A. TI Opioids In Chronic Noncancer Pain: Have We Reached A Boiling Point Yet? SO PAIN PHYSICIAN LA English DT Editorial Material ID PHYSICIANS ASIPP GUIDELINES; UNITED-STATES; BACK-PAIN; CONTROLLED SUBSTANCES; AMERICAN SOCIETY; OVERDOSE DEATHS; MEDICAL USE; PRESCRIPTION; ABUSE; ANALGESICS C1 [Manchikanti, Laxmaiah] Pain Management Ctr Paducah, Paducah, KY USA. [Manchikanti, Laxmaiah] Univ Louisville, Louisville, KY 40292 USA. [Atluri, Sairam] Tristate Spine Care Inst, Cincinnati, OH USA. [Hansen, Hans] Pain Relief Ctr, Conover, NC USA. [Benyamin, Ramsin M.] Millennium Pain Ctr, Bloomington, IL USA. [Benyamin, Ramsin M.] Univ Illinois, Urbana, IL 61801 USA. [Falco, Frank J. E.] Mid Atlantic Spine & Pain Phys, Newark, DE USA. [Falco, Frank J. E.] Temple Univ Hosp & Med Sch, Philadelphia, PA 19140 USA. [Helm, Standiford] Helm Ctr Pain Management, Laguna Hills, CA USA. [Kaye, Alan D.] LSU Hlth Sci Ctr, New Orleans, LA USA. [Hirsch, Joshua A.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Hirsch, Joshua A.] Harvard Univ, Sch Med, Boston, MA USA. RP Manchikanti, L (reprint author), 2831 Lone Oak Rd, Paducah, KY 42003 USA. EM drlm@thepainmd.com NR 93 TC 22 Z9 22 U1 1 U2 6 PU AM SOC INTERVENTIONAL PAIN PHYSICIANS PI PADUCAH PA 81 LAKEVIEW DR, PADUCAH, KY 42001 USA SN 1533-3159 J9 PAIN PHYSICIAN JI Pain Physician PD JAN-FEB PY 2014 VL 17 IS 1 BP E1 EP E10 PG 10 WC Anesthesiology; Clinical Neurology SC Anesthesiology; Neurosciences & Neurology GA AE2OY UT WOS:000333814000001 PM 24452651 ER PT J AU Manchikanti, L Hansen, H Benyamin, RM Falco, FJE Kaye, AD Hirsch, JA AF Manchikanti, Laxmaiah Hansen, Hans Benyamin, Ramsin M. Falco, Frank J. E. Kaye, Alan D. Hirsch, Joshua A. TI Declining Value of Work of Interventional Pain Physicians SO PAIN PHYSICIAN LA English DT Editorial Material ID MANAGEMENT C1 [Manchikanti, Laxmaiah] Pain Management Ctr Paducah, Paducah, KY USA. [Manchikanti, Laxmaiah] Univ Louisville, Louisville, KY 40292 USA. [Hansen, Hans] Pain Relief Ctr, Conover, NC USA. [Benyamin, Ramsin M.] Millennium Pain Ctr, Bloomington, IL USA. [Benyamin, Ramsin M.] Univ Illinois, Urbana, IL 61801 USA. [Falco, Frank J. E.] Mid Atlantic Spine & Pain Phys, Newark, DE USA. [Falco, Frank J. E.] Temple Univ Hosp & Med Sch, Philadelphia, PA 19140 USA. [Kaye, Alan D.] LSU Hlth Sci Ctr, New Orleans, LA USA. [Hirsch, Joshua A.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Hirsch, Joshua A.] Harvard Univ, Sch Med, Boston, MA USA. RP Manchikanti, L (reprint author), 2831 Lone Oak Rd, Paducah, KY 42003 USA. EM drlm@thepainmd.com NR 21 TC 6 Z9 6 U1 0 U2 0 PU AM SOC INTERVENTIONAL PAIN PHYSICIANS PI PADUCAH PA 81 LAKEVIEW DR, PADUCAH, KY 42001 USA SN 1533-3159 J9 PAIN PHYSICIAN JI Pain Physician PD JAN-FEB PY 2014 VL 17 IS 1 BP E11 EP E19 PG 9 WC Anesthesiology; Clinical Neurology SC Anesthesiology; Neurosciences & Neurology GA AE2OY UT WOS:000333814000002 PM 24452654 ER PT J AU Barnes, JA Abramson, JS AF Barnes, Jeffrey A. Abramson, Jeremy S. TI R-CHOP: Does One Size Fit All in Diffuse Large B Cell Lymphoma? SO ACTA HAEMATOLOGICA LA English DT Editorial Material ID NON-HODGKIN-LYMPHOMA; RITUXIMAB-CHOP; CHEMOTHERAPY; THERAPY; TRIAL; CYCLOPHOSPHAMIDE; MULTICENTER; VINCRISTINE; DOXORUBICIN; STANDARD C1 Massachusetts Gen Hosp, Ctr Canc, Ctr Lymphoma, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Abramson, JS (reprint author), Massachusetts Gen Hosp, Ctr Canc, 55 Fruit St,Yawkey 9A, Boston, MA 02114 USA. EM jabramson@partners.org NR 20 TC 0 Z9 0 U1 0 U2 0 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0001-5792 EI 1421-9662 J9 ACTA HAEMATOL-BASEL JI Acta Haematol. PY 2014 VL 131 IS 3 BP 153 EP 155 DI 10.1159/000355325 PG 3 WC Hematology SC Hematology GA AD8VY UT WOS:000333545000004 PM 24192325 ER PT J AU Niesten, MEF Hamberg, LM Silverman, JB Lou, KV McCall, AA Windsor, A Curtin, HD Herrmann, BS Grolman, W Nakajima, HH Lee, DJ AF Niesten, Marlien E. F. Hamberg, Leena M. Silverman, Joshua B. Lou, Kristina V. McCall, Andrew A. Windsor, Alanna Curtin, Hugh D. Herrmann, Barbara S. Grolman, Wilko Nakajima, Hideko H. Lee, Daniel J. TI Superior Canal Dehiscence Length and Location Influences Clinical Presentation and Audiometric and Cervical Vestibular-Evoked Myogenic Potential Testing SO AUDIOLOGY AND NEURO-OTOLOGY LA English DT Article DE Superior canal dehiscence, size; Superior canal dehiscence, location; Length, auditory; Audiometry; Cervical vestibular-evoked myogenic potential ID PRESSURE-INDUCED VERTIGO; COMPUTED-TOMOGRAPHY; BONE DEHISCENCE; HEARING-LOSS; CVEMPS; MODEL; SIZE; CT AB Superior canal dehiscence (SCD) is caused by an absence of bony covering of the arcuate eminence or posteromedial aspect of the superior semicircular canal. However, the clinical presentation of SCD syndrome varies considerably, as some SCD patients are asymptomatic and others have auditory and/or vestibular complaints. In order to determine the basis for these observations, we examined the association between SCD length and location with: (1) auditory and vestibular signs and symptoms; (2) air conduction (AC) loss and air-bone gap (ABG) measured by pure-tone audiometric testing, and (3) cervical vestibular-evoked myogenic potential (cVEMP) thresholds. 104 patients (147 ears) underwent SCD length and location measurements using a novel method of measuring bone density along 0.2-mm radial CT sections. We found that patients with auditory symptoms have a larger dehiscence (median length: 4.5 vs. 2.7 mm) with a beginning closer to the ampulla (median location: 4.8 vs. 6.4 mm from ampulla) than patients with no auditory symptoms (only vestibular symptoms). An increase in AC threshold was found as the SCD length increased at 250 Hz (95% CI: 1.74.7), 500 Hz (95% CI: 0.7-3.5) and 1,000 Hz (95% CI: 0.0-2.5), and an increase in ABG as the SCD length increased at 250 Hz (95% CI: 2.0-5.3), 500 Hz (95% CI: 1.6-4.6) and 1,000 Hz (95% CI: 1.3-3.3) was also seen. Finally, a larger dehiscence was associated with lowered cVEMP thresholds at 250 Hz (95% CI: -4.4 to -0.3), 500 Hz (95% CI: -4.1 to -1.0), 750 Hz (95% CI: -4.2 to -0.7) and 1,000 Hz (95% CI: -3.6 to -0.5) and a starting location closer to the ampulla at 250 Hz (95% CI: 1.3-5.1), 750 Hz (95% CI: 0.2-3.3) and 1,000 Hz (95% CI: 0.6-3.5). These findings may help to explain the variation of signs and symptoms seen in patients with SCD syndrome. (C) 2014 S. Karger AG, Basel C1 [Niesten, Marlien E. F.; Grolman, Wilko] Univ Med Ctr, Dept Otorhinolaryngol Head & Neck Surg, Utrecht, Netherlands. [Niesten, Marlien E. F.; Grolman, Wilko] Rudolf Magnus Inst Neurosci, NL-3508 TA Utrecht, Netherlands. [Niesten, Marlien E. F.; Silverman, Joshua B.; Lou, Kristina V.; McCall, Andrew A.; Windsor, Alanna; Curtin, Hugh D.; Herrmann, Barbara S.; Nakajima, Hideko H.; Lee, Daniel J.] Harvard Univ, Sch Med, Dept Otol & Laryngol, Boston, MA 02115 USA. [Niesten, Marlien E. F.; Silverman, Joshua B.; Lou, Kristina V.; McCall, Andrew A.; Windsor, Alanna; Lee, Daniel J.] Massachusetts Eye & Ear Infirm, Dept Otolaryngol, Boston, MA 02114 USA. [Hamberg, Leena M.; Curtin, Hugh D.] Massachusetts Eye & Ear Infirm, Dept Radiol, Boston, MA 02114 USA. [Herrmann, Barbara S.] Massachusetts Eye & Ear Infirm, Dept Audiol, Boston, MA 02114 USA. [Nakajima, Hideko H.] Massachusetts Eye & Ear Infirm, Eaton Peabody Lab, Boston, MA 02114 USA. RP Lee, DJ (reprint author), Massachusetts Eye & Ear Infirm, Dept Otolaryngol, 243 Charles St, Boston, MA 02114 USA. EM daniel_lee@meei.harvard.edu OI Grolman, Wilko/0000-0002-3524-3526 FU NIDCD NIH HHS [R01 DC004798, R01 DC013303, R03 DC011158] NR 25 TC 10 Z9 10 U1 1 U2 7 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 1420-3030 EI 1421-9700 J9 AUDIOL NEURO-OTOL JI Audiol. Neuro-Otol. PY 2014 VL 19 IS 2 BP 97 EP 105 DI 10.1159/000353920 PG 9 WC Audiology & Speech-Language Pathology; Neurosciences; Otorhinolaryngology SC Audiology & Speech-Language Pathology; Neurosciences & Neurology; Otorhinolaryngology GA AD8KW UT WOS:000333515900004 PM 24434937 ER PT J AU Banerjee, S Buhrlage, SJ Huang, HT Deng, XM Zhou, WJ Wang, JH Traynor, R Prescott, AR Alessi, DR Gray, NS AF Banerjee, Sourav Buhrlage, Sara J. Huang, Hai-Tsang Deng, Xianming Zhou, Wenjun Wang, Jinhua Traynor, Ryan Prescott, Alan R. Alessi, Dario R. Gray, Nathanael S. TI Characterization of WZ4003 and HTH-01-015 as selective inhibitors of the LKB1-tumour-suppressor-activated NUAK kinases SO BIOCHEMICAL JOURNAL LA English DT Article DE AMP-activated protein kinase (AMPK); AMPK-related kinase 5 (ARK5); kinase inhibitor; kinase profiling; liver kinase B1 (LKB1); myosin phosphate-targeting subunit 1(MYPT1); sucrose-non-fermenting protein kinase/AMPK-related protein kinase (SNARK) ID PROTEIN-KINASE; AMPK; PATHWAY; PHOSPHORYLATION; ASSOCIATION; EXPRESSION; INVASION; ROLES; CELLS; ARK5 AB The related NUAK1 and NUAK2 are members of the AMPK (AMP-activated protein kinase) family of protein kinases that are activated by the LKB1 (liver kinase B1) tumour suppressor kinase. Recent work suggests they play important roles in regulating key biological processes including Myc-driven tumorigenesis, senescence, cell adhesion and neuronal polarity. In the present paper we describe the first highly specific protein kinase inhibitors of NUAK kinases namely WZ4003 and HTH-01-015. WZ4003 inhibits both NUAK isoforms (IC50 for NUAK1 is 20 nM and for NUAK2 is 100 nM), whereas HTH-01-015 inhibits only NUAK1 (IC50 is 100 nM). These compounds display extreme selectivity and do not significantly inhibit the activity of 139 other kinases that were tested including ten AMPK family members. In all cell lines tested, WZ4003 and HTH-01-015 inhibit the phosphorylation of the only well-characterized substrate, MYPT1 (myosin phosphate-targeting subunit 1) that is phosphorylated by NUAK1 at Sex(445). We also identify a mutation (A195T) that does not affect basal NUAK1 activity, but renders it similar to 50-fold resistant to both WZ4003 and HTH-01-015. Consistent with NUAK1 mediating the phosphorylation of MYPT1 we find that in cells overexpressing drug-resistant NUAK1[A195T], but not wild-type NUAK1, phosphorylation of MYPT1 at Ser(445) is no longer suppressed by WZ4003 or HTH-01-015. We also demonstrate that administration of WZ4003 and HTH-01-015 to MEFs (mouse embryonic fibroblasts) significantly inhibits migration in a wound-healing assay to a similar extent as NUAK1-knockout. WZ4003 and HTH-01-015 also inhibit proliferation of MEFs to the same extent as NUAK1 knockout and U2OS cells to the same extent as NUAK1 shRNA knockdown. We find that WZ4003 and HTH-01-015 impaired the invasive potential of U2OS cells in a 3D cell invasion assay to the same extent as NUAK1 knockdown. The results of the present study indicate that WZ4003 and HTH-01-015 will serve as useful chemical probes to delineate the biological roles of the NUAK kinases. C1 [Banerjee, Sourav; Traynor, Ryan; Alessi, Dario R.] Univ Dundee, Coll Life Sci, MRC Prot Phosphorylat & Ubiguitylat Unit, Dundee DD1 5EH, Scotland. [Buhrlage, Sara J.; Huang, Hai-Tsang; Deng, Xianming; Zhou, Wenjun; Wang, Jinhua; Gray, Nathanael S.] Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA. [Buhrlage, Sara J.; Huang, Hai-Tsang; Deng, Xianming; Zhou, Wenjun; Wang, Jinhua; Gray, Nathanael S.] Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA. [Prescott, Alan R.] Univ Dundee, Coll Life Sci, Div Cell Signalling & Immunol, Dundee DD1 5EH, Scotland. RP Alessi, DR (reprint author), Univ Dundee, Coll Life Sci, MRC Prot Phosphorylat & Ubiguitylat Unit, Dow St, Dundee DD1 5EH, Scotland. EM d.r.alessi@dundee.ac.uk; Nathanael_Gray@dfci.harvard.edu OI Prescott, Alan/0000-0002-0747-7317; Alessi, Dario/0000-0002-2140-9185; Banerjee, Sourav/0000-0003-2043-2989 FU Medical Research Council; Linde Family Foundation; Friends for Life; AstraZeneca; Boehringer-Ingelheim; GlaxoSmithKline; Merck KgaA; Janssen Pharmaceutica; Pfizer FX This work was supported by the Medical Research Council (to D.R.A.), the pharmaceutical companies supporting the Division of Signal Transduction Therapy Unit (AstraZeneca, Boehringer-Ingelheim, GlaxoSmithKline, Merck KgaA, Janssen Pharmaceutica and Pfizer) (to D.R.A.), Linde Family Foundation (to N.S.G.) and Friends for Life (to N.S.G.). NR 36 TC 8 Z9 8 U1 1 U2 4 PU PORTLAND PRESS LTD PI LONDON PA THIRD FLOOR, EAGLE HOUSE, 16 PROCTER STREET, LONDON WC1V 6 NX, ENGLAND SN 0264-6021 EI 1470-8728 J9 BIOCHEM J JI Biochem. J. PD JAN 1 PY 2014 VL 457 BP 215 EP 225 DI 10.1042/BJ20131152 PN 1 PG 11 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA AE1GN UT WOS:000333717900021 PM 24171924 ER PT J AU Bras, LED Toba, H Baicu, CF Zile, MR Weintraub, ST Lindsey, ML Bradshaw, AD AF Bras, Lisandra E. de Castro Toba, Hiroe Baicu, Catalin F. Zile, Michael R. Weintraub, Susan T. Lindsey, Merry L. Bradshaw, Amy D. TI Age and SPARC Change the Extracellular Matrix Composition of the Left Ventricle SO BIOMED RESEARCH INTERNATIONAL LA English DT Article ID RAT LEFT-VENTRICLE; VI COLLAGEN; IV COLLAGEN; MYOCARDIAL FIBROSIS; BASEMENT-MEMBRANES; FIBRILLAR COLLAGEN; HYPERTROPHY; PRESSURE; NETWORK; STIFFNESS AB Secreted protein acidic and rich in cysteine (SPARC), a collagen-binding matricellular protein, has been implicated in procollagen processing and deposition. The aim of this study was to investigate age-and SPARC-dependent changes in protein composition of the cardiac extracellular matrix (ECM). We studied 6 groups of mice (n = 4/group): young (4-5 months old), middle-aged (11-12 m.o.), and old (18-29 m.o.) C57BL/6J wild type (WT) and SPARC null. The left ventricle (LV) was decellularized to enrich for ECM proteins. Protein extracts were separated by SDS-PAGE, digested in-gel, and analyzed by HPLC-ESI-MS/MS. Relative quantification was performed by spectral counting, and changes in specific proteins were validated by immunoblotting. We identified 321 proteins, of which 44 proteins were extracellular proteins. Of these proteins, collagen III levels were lower in the old null mice compared to WT, suggestive of a role for SPARC in collagen deposition. Additionally, fibrillin showed a significant increase in the null middle-aged group, suggestive of increased microfibril deposition in the absence of SPARC. Collagen VI increased with age in both genotypes (>3-fold), while collagen IV showed increased age-associated levels only in the WT animals (4-fold, P < 0.05). These changes may explain the previously reported age-associated increases in LV stiffness. In summary, our data suggest SPARC is a possible therapeutic target for aging induced LV dysfunction. C1 [Bras, Lisandra E. de Castro; Toba, Hiroe; Lindsey, Merry L.] Univ Mississippi, Med Ctr, Mississippi Ctr Heart Res, Jackson, MS 39216 USA. [Bras, Lisandra E. de Castro; Toba, Hiroe; Weintraub, Susan T.; Lindsey, Merry L.] Univ Texas Hlth Sci Ctr San Antonio UTHSCA, San Antonio Cardiovasc Prote Ctr, San Antonio, TX 78229 USA. [Toba, Hiroe] Kyoto Pharmaceut Univ, Dept Clin Pharmacol, Div Pathol Sci, Kyoto 607, Japan. [Baicu, Catalin F.; Zile, Michael R.; Bradshaw, Amy D.] Med Univ S Carolina, Gazes Cardiac Res Inst, Dept Med, Div Cardiol, Charleston, SC 29425 USA. [Zile, Michael R.; Bradshaw, Amy D.] Ralph H Johnson Dept Vet Affairs Med Ctr, Charleston, SC 29401 USA. [Weintraub, Susan T.] UTHSCSA, Dept Biochem, San Antonio, TX 78229 USA. [Lindsey, Merry L.] GV Sonny Montgomery Vet Affairs Med Ctr, Res Serv, Jackson, MS 39216 USA. RP Lindsey, ML (reprint author), Univ Mississippi, Med Ctr, Mississippi Ctr Heart Res, Jackson, MS 39216 USA. EM mllindsey@umc.edu; bradshad@musc.edu FU AHA [14SDG18860050]; NIH/NHLBI HHSN [268201000036C (N01-HV-00244)]; Biomedical Laboratory Research, Development Service of the Veterans Affairs Office of Research and Development Awards [5I01BX000505, 1I01BX001385]; [HL075360]; [HL51971] FX The authors acknowledge support from AHA for 14SDG18860050 to LEDCB, from NIH/NHLBI HHSN 268201000036C (N01-HV-00244) for the San Antonio Cardiovascular Proteomics Center, HL075360, and HL51971 to MLL, and from the Biomedical Laboratory Research, Development Service of the Veterans Affairs Office of Research and Development Awards 5I01BX000505 to MLL and 1I01BX001385 to ADB. Mass spectrometry analyses were conducted in the UTHSCSA Institutional Mass Spectrometry Laboratory. The expert technical assistance of Kevin W. Hakala, Trevi A. Ramirez, and Elizabeth Flynn is gratefully acknowledged. NR 40 TC 0 Z9 0 U1 0 U2 3 PU HINDAWI PUBLISHING CORPORATION PI NEW YORK PA 410 PARK AVENUE, 15TH FLOOR, #287 PMB, NEW YORK, NY 10022 USA SN 2314-6133 EI 2314-6141 J9 BIOMED RES INT JI Biomed Res. Int. PY 2014 AR 810562 DI 10.1155/2014/810562 PG 7 WC Biotechnology & Applied Microbiology; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Research & Experimental Medicine GA AE3YK UT WOS:000333914200001 ER PT J AU Laurie, CC Laurie, CA Smoley, SA Carlson, EE Flinn, I Fridley, BL Greisman, HA Gribben, JG Jelinek, DF Nelson, SC Paietta, E Schaid, D Sun, ZX Tallman, MS Weinshilboum, R Kay, NE Shanafelt, TD AF Laurie, Cathy C. Laurie, Cecelia A. Smoley, Stephanie A. Carlson, Erin E. Flinn, Ian Fridley, Brooke L. Greisman, Harvey A. Gribben, John G. Jelinek, Diane F. Nelson, Sarah C. Paietta, Elisabeth Schaid, Dan Sun, Zhuoxin Tallman, Martin S. Weinshilboum, Richard Kay, Neil E. Shanafelt, Tait D. TI Acquired chromosomal anomalies in chronic lymphocytic leukemia patients compared with more than 50,000 quasi-normal participants SO CANCER GENETICS LA English DT Article DE Chromosomal aberration; chromosomal mosaic; chronic lymphocytic leukemia; cancer precursor condition; cytogenetics ID COMPARATIVE GENOMIC HYBRIDIZATION; B-CELL LYMPHOCYTOSIS; PHASE-III TRIAL; US INTERGROUP; FOLLOW-UP; CANCER; E2997; CYCLOPHOSPHAMIDE; ABNORMALITIES; FLUDARABINE AB Pretherapy patients with chronic lymphocytic leukemia (CLL) from US Intergroup trial E2997 were analyzed with single nucleotide polymorphism microarrays to detect acquired chromosomal anomalies. The four CLL-typical anomalies (11q-, +12, 13q-, and 17p-) were found at expected frequencies. Acquired anomalies in other regions account for 70% of the total detected anomalies, and their number per participant has a significant effect on progression-free survival after adjusting for the effects of 17p-(and other covariates). These results were compared with those from a previous study of more than 50,000 participants from the GENEVA consortium of genome-wide association studies, which analyzed individuals with a variety of medical conditions and healthy controls. The percentage of individuals with acquired anomalies is vastly different between the two studies (GENEVA 0.8%; E2997 80%). The composition of the anomalies also differs, with GENEVA having a higher percentage of acquired uniparental disomies and a lower percentage of deletions. The four common CLL anomalies are among the most frequent in GENEVA participants, some of whom may have CLL-precursor conditions or early stages of CLL. However, the patients from E2997 (and other studies of symptomatic CLL) have recurrent acquired anomalies that were not found in GENEVA participants, thus identifying genomic changes that may be unique to symptomatic stages of CLL. C1 [Laurie, Cathy C.; Laurie, Cecelia A.; Nelson, Sarah C.] Univ Washington, Dept Biostat, Seattle, WA 98195 USA. [Smoley, Stephanie A.] Mayo Clin, Dept Lab Med & Pathol, Cytogenet Lab, Rochester, MN USA. [Carlson, Erin E.; Fridley, Brooke L.; Schaid, Dan] Mayo Clin, Dept Hlth Sci Res, Rochester, MN USA. [Flinn, Ian] Sarah Cannon Res Inst, Nashville, TN USA. [Fridley, Brooke L.] Univ Kansas, Med Ctr, Kansas City, KS 66103 USA. [Greisman, Harvey A.] Univ Washington, Dept Lab Med, Seattle, WA 98195 USA. [Greisman, Harvey A.] PhenoPath Labs, Seattle, WA USA. [Gribben, John G.] Univ London, Bails Canc Inst, London, England. [Jelinek, Diane F.; Kay, Neil E.; Shanafelt, Tait D.] Mayo Clin, Div Hematol, Rochester, MN USA. [Jelinek, Diane F.] Mayo Clin, Dept Immunol, Rochester, MN USA. [Paietta, Elisabeth] Montefiore Med Ctr, North Div, Bronx, NY 10467 USA. [Sun, Zhuoxin] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA. [Tallman, Martin S.] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. [Weinshilboum, Richard] Mayo Clin, Div Clin Pharmacol, Rochester, MN USA. RP Laurie, CC (reprint author), Univ Washington, Dept Biostat, Seattle, WA 98195 USA. EM cclaurie@u.washington.edu RI Fridley, Brooke/D-8315-2015 OI Fridley, Brooke/0000-0001-7739-7956 FU [U01-HG 005157]; [P01-GM099568]; [HD52953]; [HD57192]; [U01-DE-018993]; [R01-DE016148]; [R01-DE014899]; [U01-DE018903]; [U10-CA02115]; [P01-CA81538]; [R01-CA136591]; [CA21115]; [CA114737]; [R01-CA138461]; [U19-GM61388]; [R01-GM28157]; [CA132780]; [CA95241]; [U01-HG005137] FX The authors thank all clinical investigators and patients who participated in the Eastern Cooperative Oncology Group clinical trial E2997. We also thank Gordon W. Dewald (deceased) for his work on the early stages of this study. We thank Jeffrey C. Murray, Terri H. Beaty, Mary L. Marazita, and William L. Lowe for access to the GENEVA data for the analysis of parent-offspring transmission of anomalies. This work was supported by the following grants: U01-HG 005157, P01-GM099568, HD52953, HD57192, U01-DE-018993, R01-DE016148, R01-DE014899, U01-DE018903, U10-CA02115, P01-CA81538, R01-CA136591, CA21115, CA114737, R01-CA138461, U19-GM61388, R01-GM28157, CA132780, CA95241, and U01-HG005137. T. D. Shanafelt acknowledges support as a Clinical Scholar of the Leukemia and Lymphoma Society. NR 36 TC 4 Z9 4 U1 1 U2 6 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 2210-7762 EI 2210-7770 J9 CANCER GENET-NY JI Cancer Genet. PD JAN-FEB PY 2014 VL 207 IS 1-2 BP 19 EP 30 DI 10.1016/j.cancergen.2014.01.004 PG 12 WC Oncology; Genetics & Heredity SC Oncology; Genetics & Heredity GA AE0ME UT WOS:000333659600003 PM 24613276 ER PT S AU Swenson, ER AF Swenson, Erik R. BE Frost, SC McKenna, R TI Carbonic Anhydrase Inhibitors and High Altitude Illnesses SO CARBONIC ANHYDRASE: MECHANISM, REGULATION, LINKS TO DISEASE, AND INDUSTRIAL APPLICATIONS SE Subcellular Biochemistry LA English DT Article; Book Chapter DE Hypoxia; Acid-base; Pulmonary edema; Cerebral edema; Erythrocytosis; Carbonic anhydrase inhibitors ID ACUTE MOUNTAIN-SICKNESS; HYPOXIC PULMONARY VASOCONSTRICTION; ARTERIAL SMOOTH-MUSCLE; CEREBRAL-BLOOD-FLOW; VENTILATORY RESPONSE; EXERCISE CAPACITY; CHOROID-PLEXUS; GAS-EXCHANGE; CAROTID-BODY; NITRIC-OXIDE AB Carbonic anhydrase (CA) inhibitors, particularly acetazolamide, have been used at high altitude for decades to prevent or reduce acute mountain sickness (AMS), a syndrome of symptomatic intolerance to altitude characterized by headache, nausea, fatigue, anorexia and poor sleep. Principally CA inhibitors act to further augment ventilation over and above that stimulated by the hypoxia of high altitude by virtue of renal and endothelial cell CA inhibition which oppose the hypocapnic alkalosis resulting from the hypoxic ventilatory response (HVR), which acts to limit the full expression of the HVR. The result is even greater arterial oxygenation than that driven by hypoxia alone and greater altitude tolerance. The severity of several additional diseases of high attitude may also be reduced by acetazolamide, including high altitude cerebral edema (HACE), high altitude pulmonary edema (HAPE) and chronic mountain sickness (CMS), both by its CA-inhibiting action as described above, but also by more recently discovered non-CA inhibiting actions, that seem almost unique to this prototypical CA inhibitor and are of most relevance to HAPE. This chapter will relate the history of CA inhibitor use at high altitude, discuss what tissues and organs containing carbonic anhydrase play a role in adaptation and maladaptation to high altitude, explore the role of the enzyme and its inhibition at those sites for the prevention and/or treatment of the four major forms of illness at high altitude. C1 [Swenson, Erik R.] VA Puget Sound Hlth Care Syst, Seattle, WA 98108 USA. [Swenson, Erik R.] Univ Washington, Dept Med, Seattle, WA USA. RP Swenson, ER (reprint author), VA Puget Sound Hlth Care Syst, Seattle, WA 98108 USA. EM eswenson@u.washington.edu NR 119 TC 12 Z9 12 U1 0 U2 17 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013, UNITED STATES SN 0306-0225 BN 978-94-007-7359-2; 978-94-007-7358-5 J9 SUBCELL BIOCHEM JI Subcell. Biochem. PY 2014 VL 75 BP 361 EP 386 DI 10.1007/978-94-007-7359-2_18 D2 10.1007/978-94-007-7359-2 PG 26 WC Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA BA0QY UT WOS:000332111800018 PM 24146388 ER PT J AU Navarro-Alvarez, N Yang, YG AF Navarro-Alvarez, Nalu Yang, Yong-Guang TI Lack of CD47 on Donor Hepatocytes Promotes Innate Immune Cell Activation and Graft Loss: A Potential Barrier to Hepatocyte Xenotransplantation SO CELL TRANSPLANTATION LA English DT Article DE Hepatocyte; Hepatocyte transplantation (HTx); Innate immune cell activation; Graft rejection; Xenotransplantation ID MONOCYTE DIFFERENTIATION ANTIGEN; NECROSIS-FACTOR-ALPHA; LIVER-FAILURE; BINDING-PROTEIN; KUPFFER CELLS; UP-REGULATION; RECEPTOR-III; CD14; EXPRESSION; LIPOPOLYSACCHARIDE AB We have previously shown that interspecies incompatibility of CD47 plays an important role in triggering rejection of xenogeneic hematopoietic cells by macrophages. However, whether CD47 incompatibility also induces rejection of nonhematopoietic cellular xenografts remains unknown. Herein, we have addressed this question in a mouse model of hepatocyte transplantation in which CD47(-/-) hepatocytes were used to resemble xenografts for CD47 incompatibility. We show that intrasplenic transplantation of CD47(-/-), but not wild-type (WT) hepatocytes, into partially hepatectomized syngeneic WT mice resulted in a rapid increase in Mac-1(+) cells with an activation phenotype (i.e., Mac-1(+)CD(14+) and Mac-1(+)CD16/32(high)), compared to nontransplant controls. In addition, CD47 hepatocytes were more severely damaged than WT hepatocytes as indicated by the greater AST and ALT serum levels in these mice. Furthermore, long-term donor hepatocyte survival and liver repopulation were observed in mice receiving WT hepatocytes, whereas CD47(-/-) hepatocytes were completely rejected within 2 weeks. These results suggest that CD47 on donor hepatocytes prevents recipient myeloid innate immune cell activation, hence aiding in graft survival after hepatocyte transplantation. Thus, CD47 incompatibility is likely to present an additional barrier to hepatocyte xenotransplantation. C1 [Navarro-Alvarez, Nalu; Yang, Yong-Guang] Columbia Univ, Columbia Ctr Translat Immunol, Med Ctr, New York, NY 10032 USA. [Navarro-Alvarez, Nalu; Yang, Yong-Guang] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Transplantat Biol Res Ctr, Boston, MA USA. RP Yang, YG (reprint author), Columbia Univ, Columbia Ctr Translat Immunol, Black Bldg,650 W 168th St, New York, NY 10032 USA. EM yy2324@columbia.edu FU NIH [R01 AI064569, 2P01AI045897-11A]; Basic Science Fellowship from the American Society of Transplantation FX The authors thank Dr Hui Wang for the critical review of this manuscript. This work was supported by research grants from NIH (R01 AI064569, 2P01AI045897-11A). N. Navarro-Alvarez is partially supported by a Basic Science Fellowship from the American Society of Transplantation. The authors declare no conflict of interest. NR 40 TC 6 Z9 7 U1 1 U2 2 PU COGNIZANT COMMUNICATION CORP PI PUTNAM VALLEY PA 18 PEEKSKILL HOLLOW RD, PO BOX 37, PUTNAM VALLEY, NY 10579 USA SN 0963-6897 EI 1555-3892 J9 CELL TRANSPLANT JI Cell Transplant. PY 2014 VL 23 IS 3 BP 345 EP 354 DI 10.3727/096368913X663604 PG 10 WC Cell & Tissue Engineering; Medicine, Research & Experimental; Transplantation SC Cell Biology; Research & Experimental Medicine; Transplantation GA AD8FF UT WOS:000333501200007 PM 23394628 ER PT J AU Mannello, F Ligi, D Canale, M Raffetto, JD AF Mannello, Ferdinando Ligi, Daniela Canale, Matteo Raffetto, Joseph D. TI Sulodexide Down-Regulates the Release of Cytokines, Chemokines, and Leukocyte Colony Stimulating Factors from Human Macrophages: Role of Glycosaminoglycans in Inflammatory Pathways of Chronic Venous Disease SO CURRENT VASCULAR PHARMACOLOGY LA English DT Article DE Chronic venous disease; inflammation; glycosaminoglycan; pro-inflammatory cytokines; chemokines; sulodexide; U-937 macrophage-like cell line ID MONOCYTE CHEMOATTRACTANT PROTEIN-1; VARICOSE-VEIN FORMATION; LEG ULCERS; ENDOTHELIAL-CELLS; MATRIX METALLOPROTEINASES; MOLECULAR-MECHANISMS; VASCULAR DYSFUNCTION; COMPRESSION THERAPY; INSUFFICIENCY; PATHOGENESIS AB Chronic venous disease (CVeD) is a debilitating condition that affects millions of individuals worldwide. The condition can result in varicose veins, or advance to severe skin changes and venous ulceration. The fundamental basis for CVeD is inflammation within the venous circulation and that it is subjected to increased hydrostatic pressure resulting in increased ambulatory venous pressure. The inflammation involves leukocytes, in particular macrophages and monocytes, inflammatory modulators and chemokines, cytokine expression, growth factors, metalloproteinase (MMP) activity, and many regulatory pathways that perpetuate inflammation. Sulodexide (SDX) is a glycosaminoglycan with pro-fibrinolytic and anti-thrombotic properties. We have previously demonstrated that SDX inhibits the secretion of pro-zymogen MMP-9 from human leukocytes without displacing high molecular complexes of MMP-9. The anti-inflammatory properties of SDX on activated leukocytes have not been well established. We hypothesized that SDX will reduce the secretion of inflammatory mediators from lipopolysaccharide (LPS)-stimulated macrophages. Therefore, we evaluated the effects of SDX on LPS-stimulated macrophage secretion of various inflammatory and anti-inflammatory cytokines, chemokines, and colony stimulating factors. We used microplateb-ased multiplex immunoassays. LPS-stimulated macrophages in vitro caused a substantial increase of interleukins, tumor necrosis factor, interferon, chemokines and colony stimulating factors. The addition of SDX caused both a dose-dependent and dose-independent decrease in nearly all of the inflammatory cytokines, chemokines and colony stimulating factors. These findings suggest that SDX has a significant effect on the release of inflammatory mediators from macrophages, and may be useful in the treatment of early and advanced CVeD. C1 [Mannello, Ferdinando; Ligi, Daniela; Canale, Matteo] Univ Carlo Bo, Dept Biomol Sci, Sect Clin Biochem & Cell Biol, Urbino, PU, Italy. [Raffetto, Joseph D.] VA Boston Healthcare Syst, Div Vasc Surg, West Roxbury, MA USA. [Raffetto, Joseph D.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Boston, MA 02115 USA. RP Mannello, F (reprint author), Univ Carlo Bo, Dept Biomol Sci, Sect Clin Biochem & Cell Biol, Via O Ubaldini 7, Urbino, PU, Italy. EM ferdinando.mannello@uniurb.it NR 78 TC 16 Z9 18 U1 1 U2 4 PU BENTHAM SCIENCE PUBL LTD PI SHARJAH PA EXECUTIVE STE Y-2, PO BOX 7917, SAIF ZONE, 1200 BR SHARJAH, U ARAB EMIRATES SN 1570-1611 EI 1875-6212 J9 CURR VASC PHARMACOL JI Current Vascular Pharmacology PD JAN PY 2014 VL 12 IS 1 BP 173 EP 185 PG 13 WC Pharmacology & Pharmacy; Peripheral Vascular Disease SC Pharmacology & Pharmacy; Cardiovascular System & Cardiology GA AE1RY UT WOS:000333748600022 PM 24279420 ER PT J AU Bighamian, R Reisner, AT Hahn, JO AF Bighamian, Ramin Reisner, Andrew T. Hahn, Jin-Oh TI An Analytic Tool for Prediction of Hemodynamic Responses to Vasopressors SO IEEE TRANSACTIONS ON BIOMEDICAL ENGINEERING LA English DT Article DE Dose-response relationship; hemodynamics; prediction; vasopressor ID CARDIAC-OUTPUT; BLOOD-PRESSURE; CARDIOVASCULAR-RESPONSES; HEART-FAILURE; SEPTIC SHOCK; DOPAMINE; EPINEPHRINE; PERFUSION; SEPSIS; MODEL AB This paper presents a new analytic tool for automated control of vasopressor infusion, which uses measured changes in blood pressure to infer changes in the underlying cardiovascular system and then estimate dose-response relationships for the underlying cardinal cardiovascular parameters, i.e., those related to cardiac output (CO) and total peripheral resistance (TPR). Ultimately, blood pressure as a function of vasopressor dose is predicted based on the estimated underlying cardiovascular state by extrapolating the dose-response relationship. As well, this tool adapts to individual subjects with a minimum of individualized training data. In this report, proof-of-principle is provided using experimental epinephrine dose-response data from four different sets of subjects. Given two observations from different infusion rates, the analytic tool was able to accurately predict the groups' blood pressure, heart rate, TPR, stroke volume, and CO as a function of vasopressor dose levels: the root-mean-squared prediction error for the mean arterial pressure (MAP) was consistently smaller than 5% of the underlying MAP; the r(2) values for the TPR, stroke volume, and CO were consistently higher than 0.96; and the limits of agreement between actual versus predicted blood pressure (BP), TPR, stroke volume, and CO were consistently smaller than 8% of the respective underlying values. The proposed analytic tool may provide a meaningful step towards automated control of vasopressor therapy. C1 [Bighamian, Ramin; Hahn, Jin-Oh] Univ Maryland, Dept Mech Engn, College Pk, MD 20742 USA. [Reisner, Andrew T.] Massachusetts Gen Hosp, Dept Emergency Med, Boston, MA 02114 USA. [Reisner, Andrew T.] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Reisner, Andrew T.] MIT, Cambridge, MA 02139 USA. RP Hahn, JO (reprint author), Univ Maryland, Dept Mech Engn, College Pk, MD 20742 USA. EM rbighami@umd.edu; areisner@partners.org; jinoh.hahn@alum.mit.edu OI Bighamian, Ramin/0000-0002-2660-0851 NR 29 TC 2 Z9 2 U1 0 U2 0 PU IEEE-INST ELECTRICAL ELECTRONICS ENGINEERS INC PI PISCATAWAY PA 445 HOES LANE, PISCATAWAY, NJ 08855-4141 USA SN 0018-9294 EI 1558-2531 J9 IEEE T BIO-MED ENG JI IEEE Trans. Biomed. Eng. PD JAN PY 2014 VL 61 IS 1 BP 109 EP 118 DI 10.1109/TBME.2013.2277867 PG 10 WC Engineering, Biomedical SC Engineering GA AD5AI UT WOS:000333263300012 PM 23955691 ER PT J AU Zhang, L Xue, Y Jiang, BN Strouthos, C Duan, ZF Wu, YK Su, J Zhou, XB AF Zhang, Le Xue, Yao Jiang, Beini Strouthos, Costas Duan, Zhenfeng Wu, Yukun Su, Jing Zhou, Xiaobo TI Multiscale agent-based modelling of ovarian cancer progression under the stimulation of the STAT 3 pathway SO INTERNATIONAL JOURNAL OF DATA MINING AND BIOINFORMATICS LA English DT Article DE agent-based model; STAT 3 pathway; multiscale modelling; drug resistance; computational biology; IL-6; interleukin-6 ID EPIDERMAL-GROWTH-FACTOR; PACLITAXEL RESISTANCE; MULTIDRUG-RESISTANCE; CARCINOMA CELLS; TUMOR SYSTEMS; INTERLEUKIN-6; EXPRESSION; ACTIVATION; DYNAMICS; SURVIVAL AB This research is developed to simulate ovarian cancer progression with signal transducers and activators of the transcription 3 (STAT 3) pathway. The main focus is on studying how the STAT 3 pathway affects the cancer cells' biomechanical phenotype under the stimulation of the interleukin-6 (IL-6) cytokine and various well-known microscopic factors. The simulated results agreed with recent experimental evidence that ovarian cancer cells with a stimulated STAT 3 pathway have high survival rates and drug resistance. And we discussed how the IL6 and these well-known microscopic factors impacted the cancer progression. C1 [Zhang, Le] Southwest Univ, Coll Comp & Informat Sci, Chongqing 400715, Peoples R China. [Xue, Yao] Michigan Technol Univ, Dept Elect & Comp Engn, Houghton, MI 49931 USA. [Jiang, Beini] Michigan Technol Univ, Dept Computat Sci & Engn, Houghton, MI 49931 USA. [Strouthos, Costas] Cyprus Inst, Computat Based Sci & Technol Res Ctr, CY-1645 Nicosia, Cyprus. [Duan, Zhenfeng] Massachusetts Gen Hosp, Ctr Sarcoma & Connect Tissue Oncol, Sarcoma Biol Lab, Boston, MA 02114 USA. [Duan, Zhenfeng] Harvard Univ, Sch Med, Boston, MA USA. [Wu, Yukun] Univ Maryland, Sch Med, Ctr Vaccine Dev, Baltimore, MD 21201 USA. [Su, Jing; Zhou, Xiaobo] Methodist Hosp, Dept Pathol, Res Inst, Houston, TX 77030 USA. [Su, Jing; Zhou, Xiaobo] Weill Cornell Med Coll, Houston, TX USA. RP Zhang, L (reprint author), Southwest Univ, Coll Comp & Informat Sci, Chongqing 400715, Peoples R China. EM zhanglcq@swu.edu.cn; yaox@mtu.edu; beinij@mtu.edu; Strouthos@ucy.ac.cy; zduan@partners.org; wu@medicine.umaryland.edu; jsu@tmhs.org; xzhou@tmhs.org RI Strouthos, Costas/C-7086-2011; OI Strouthos, Costas/0000-0001-9972-6925; Su, Jing/0000-0003-4917-6173 FU Department of Mathematical Sciences of Michigan Technological University; Sarcoma Biology Laboratory, Center for Sarcoma and Connective Tissue Oncology, Massachusetts General Hospital, Boston, Massachusetts FX This work has been supported by a start-up grant from the Department of Mathematical Sciences of Michigan Technological University, and by the Sarcoma Biology Laboratory, Center for Sarcoma and Connective Tissue Oncology, Massachusetts General Hospital, Boston, Massachusetts. NR 44 TC 2 Z9 2 U1 2 U2 11 PU INDERSCIENCE ENTERPRISES LTD PI GENEVA PA WORLD TRADE CENTER BLDG, 29 ROUTE DE PRE-BOIS, CASE POSTALE 856, CH-1215 GENEVA, SWITZERLAND SN 1748-5673 EI 1748-5681 J9 INT J DATA MIN BIOIN JI Int. J. Data Min. Bioinform. PY 2014 VL 9 IS 3 BP 235 EP 253 DI 10.1504/IJDMB.2014.060050 PG 19 WC Mathematical & Computational Biology SC Mathematical & Computational Biology GA AE1RB UT WOS:000333745900002 PM 25163167 ER PT J AU Wharton, W Gleason, CE Dowling, NM Carlsson, CM Brinton, EA Santoro, MN Neal-Perry, G Taylor, H Naftolin, F Lobo, RA Merriam, G Manson, JE Cedars, MI Miller, VM Black, DM Budoff, M Hodis, HN Harman, SM Asthana, S AF Wharton, Whitney Gleason, Carey E. Dowling, N. Maritza Carlsson, Cynthia M. Brinton, Eliot A. Santoro, M. Nanette Neal-Perry, Genevieve Taylor, Hugh Naftolin, Frederick Lobo, Rogerio A. Merriam, George Manson, Joann E. Cedars, Marcelle I. Miller, Virginia M. Black, Dennis M. Budoff, Matthew Hodis, Howard N. Harman, S. Mitchell Asthana, Sanjay TI The KEEPS-Cognitive and Affective Study: Baseline Associations between Vascular Risk Factors and Cognition SO JOURNAL OF ALZHEIMERS DISEASE LA English DT Article DE Attention; blood pressure; clinical trial; cognition; estradiol; estrogen; hormone therapy; memory; vascular risk ID MIDLIFE BLOOD-PRESSURE; ALZHEIMERS-DISEASE; MENOPAUSAL TRANSITION; MEMORY PERFORMANCE; HYPERTENSION; DEMENTIA; LIFE; AGE; ESTROGEN; INDIVIDUALS AB Midlife vascular risk factors influence later cognitive decline and Alzheimer's disease (AD). The decrease in serum estradiol levels during menopause has been associated with cognitive impairment and increased vascular risk, such as high blood pressure (BP), which independently contributes to cognitive dysfunction and AD. We describe the extent to which vascular risk factors relate to cognition in healthy, middle-aged, recently postmenopausal women enrolled in the Kronos Early Estrogen Prevention Cognitive and Affective Study (KEEPS-Cog) at baseline. KEEPS-Cog is a double-blind, randomized, placebo-controlled, parallel group, clinical trial, investigating the efficacy of low-dose, transdermal 17 beta-estradiol and oral conjugated equine estrogen on cognition. All results are cross-sectional and represent baseline data only. Analyses confirm that the KEEPS-Cog cohort (n = 571) was middle aged (mean 52.7 years, range 42-59 years), healthy, and free of cognitive dysfunction. Higher systolic BP was weakly related to poorer performance in auditory working memory and attention (p = 0.004; adjusted for multiple comparisons p = 0.10). This relationship was not associated with endogenous hormone levels, and systolic BP was not related to any other cognitive domain. BP levels may be more sensitive than other vascular risk factors in detecting subtle differences in cognitive task performance in healthy, recently menopausal women. Lower BP early in menopause may affect cognitive domains known to be associated with AD. C1 [Wharton, Whitney] Emory Univ, Sch Med, Dept Neurol, Atlanta, GA 30329 USA. [Wharton, Whitney] Emory Alzheimers Dis Res Ctr, Adrc Atlanta, GA USA. [Gleason, Carey E.; Dowling, N. Maritza; Carlsson, Cynthia M.; Asthana, Sanjay] Univ Wisconsin, Dept Med, Sch Med & Publ Hlth, Madison, WI USA. [Gleason, Carey E.; Carlsson, Cynthia M.; Asthana, Sanjay] William S Middleton Mem Vet Adm Med Ctr, GRECC, Madison, WI USA. [Gleason, Carey E.; Dowling, N. Maritza; Carlsson, Cynthia M.; Asthana, Sanjay] Wisconsin Alzheimers Dis Res Ctr, Adrc Madison, WI USA. [Dowling, N. Maritza] Univ Wisconsin, Dept Biostat & Med Informat, Madison, WI USA. [Brinton, Eliot A.] Univ Utah, Sch Med, Salt Lake City, UT USA. [Santoro, M. Nanette] Univ Colorado, Sch Med, Aurora, CO USA. [Neal-Perry, Genevieve] Albert Einstein Coll Med, Bronx, NY 10467 USA. [Taylor, Hugh] Yale Univ, Sch Med, New Haven, CT USA. [Naftolin, Frederick] NYU, New York, NY USA. [Lobo, Rogerio A.] Columbia Univ, Sch Med, New York, NY USA. [Merriam, George] Univ Washington, VA Puget Sound Hlth Care Syst, Seattle, WA 98195 USA. [Merriam, George] Univ Washington, Div Metab Endocrinol & Nutr, Seattle, WA 98195 USA. [Manson, Joann E.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Boston, MA 02115 USA. [Cedars, Marcelle I.; Black, Dennis M.] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Miller, Virginia M.] Mayo Clin, Rochester, MN USA. [Budoff, Matthew] Los Angeles Biomed Res Inst, Torrance, CA USA. [Hodis, Howard N.] Univ So Calif, Atherosclerosis Res Unit, Los Angeles, CA USA. [Harman, S. Mitchell] Kronos Longev Res Inst, Phoenix, AZ USA. [Harman, S. Mitchell] Phoenix VA Med Ctr, Phoenix, AZ USA. RP Wharton, W (reprint author), Emory Univ, Wesley Woods Hlth Ctr, Emory Alzheimers Dis Res Ctr, Dept Neurol, 1841 Clifton Rd NE, Atlanta, GA 30329 USA. EM w.wharton@emory.edu FU Aurora Foundation; Bayer Health Care Pharmaceuticals, Inc. FX We gratefully acknowledge the dedicated efforts of all the investigators and staff at the KEEPS clinical centers, the KEEPS Data Coordinating Center at KLRI, and the NIH Institutes supporting ancillary studies. The KEEPS investigators would like to thank the Aurora Foundation for study support and Bayer Health Care Pharmaceuticals, Inc. and Abbott Laboratories for providing study medications. Above all, we recognize and thank the KEEPS participants for their dedication and commitment to the KEEPS research program. NR 52 TC 8 Z9 9 U1 1 U2 5 PU IOS PRESS PI AMSTERDAM PA NIEUWE HEMWEG 6B, 1013 BG AMSTERDAM, NETHERLANDS SN 1387-2877 EI 1875-8908 J9 J ALZHEIMERS DIS JI J. Alzheimers Dis. PY 2014 VL 40 IS 2 BP 331 EP 341 DI 10.3233/JAD-130245 PG 11 WC Neurosciences SC Neurosciences & Neurology GA AD9LX UT WOS:000333587700011 PM 24430001 ER PT J AU Gray, NE Morre, J Kelley, J Maier, CS Stevens, JF Quinn, JF Soumyanath, A AF Gray, Nora E. Morre, Jeff Kelley, Jeremiah Maier, Claudia S. Stevens, Jan F. Quinn, Joseph F. Soumyanath, Amala TI Caffeoylquinic Acids in Centella asiatica Protect against Amyloid-beta Toxicity SO JOURNAL OF ALZHEIMERS DISEASE LA English DT Article DE Amyloid-beta toxicity; caffeoylquinic acids; Centella asiatica; neuroprotection; tau ID ABNORMALLY PHOSPHORYLATED-TAU; ALZHEIMER-DISEASE BRAIN; OXIDATIVE STRESS; PRECURSOR PROTEIN; CORTICAL-NEURONS; CONDITIONAL EXPRESSION; INDUCED NEUROTOXICITY; SIGNALING PATHWAY; L. URBAN; IN-VITRO AB The accumulation of amyloid-beta (A beta) is a hallmark of Alzheimer's disease and is known to result in neurotoxicity both in vivo and in vitro. We previously demonstrated that treatment with the water extract of Centella asiatica (CAW) improves learning and memory deficits in Tg2576 mice, an animal model of A beta accumulation. However the active compounds in CAW remain unknown. Here we used two in vitro models of A beta toxicity to confirm this neuroprotective effect and identify several active constituents of the CAW extract. CAW reduced A beta-induced cell death and attenuated A beta-induced changes in tau expression and phosphorylation in both the MC65 and SH-SY5Y neuroblastoma cell lines. We confirmed and quantified the presence of several mono-and dicaffeoylquinic acids (CQAs) in CAW using chromatographic separation coupled to mass spectrometry and ultraviolet spectroscopy. Multiple dicaffeoylquinic acids showed efficacy in protecting MC65 cells against A beta-induced cytotoxicity. Isochlorogenic acid A and 1,5-dicaffeoylquinic acid were found to be the most abundant CQAs in CAW, and the most active in protecting MC65 cells from A beta-induced cell death. Both compounds showed neuroprotective activity in MC65 and SH-SY5Y cells at concentrations comparable to their levels in CAW. Each compound not only mitigated A beta-induced cell death, but was able to attenuate A beta-induced alterations in tau expression and phosphorylation in both cell lines, as seen with CAW. These data suggest that CQAs are active neuroprotective components in CAW, and therefore are important markers for future studies on CAW standardization, bioavailability, and dosing. C1 [Gray, Nora E.; Quinn, Joseph F.; Soumyanath, Amala] Oregon Hlth & Sci Univ, Dept Neurol, Portland, OR 97201 USA. [Morre, Jeff; Kelley, Jeremiah; Maier, Claudia S.] Oregon State Univ, Dept Chem, Corvallis, OR 97331 USA. [Stevens, Jan F.] Oregon State Univ, Dept Pharmaceut Sci, Corvallis, OR 97331 USA. [Stevens, Jan F.] Oregon State Univ, Linus Pauling Inst, Corvallis, OR 97331 USA. [Quinn, Joseph F.] Portland VA Med Ctr, Dept Neurol, Portland, OR USA. [Quinn, Joseph F.] Portland VA Med Ctr, Parkinsons Dis Res Educ & Clin Care Ctr PADRECC, Portland, OR USA. RP Soumyanath, A (reprint author), Oregon Hlth & Sci Univ, Dept Neurol, 3181 SW Sam Jackson Pk Rd, Portland, OR 97201 USA. EM soumyana@ohsu.edu OI Maier, Claudia S./0000-0003-0743-8956 FU NIH [P50 AT00066]; Oregon Alzheimer's Disease Center 5 [P30 AG008017 24]; T32 grant [NCCAM AT002688]; Department of Veterans Affairs Merit Review grant; Bio-Analytical Shared Resource/Pharmacokinetics Core in the Department of Physiology and Pharmacology at Oregon Health & Science University; Biomolecular Mass Spectrometry Core of the Environmental Health Sciences Core Center at Oregon State University (NIH) [P30ES000210, S10RR027878] FX This work was funded by a grant awarded to A. Soumyanath from NIH P50 AT00066 and to N. Gray from the Oregon Alzheimer's Disease Center 5 P30 AG008017 24, a T32 grant on which N. Gray is a trainee from NIH-NCCAM AT002688, and by a Department of Veterans Affairs Merit Review grant awarded to J. Quinn. HPLC and LCMS work was supported by the Bio-Analytical Shared Resource/Pharmacokinetics Core in the Department of Physiology and Pharmacology at Oregon Health & Science University. The authors also acknowledge the Biomolecular Mass Spectrometry Core of the Environmental Health Sciences Core Center at Oregon State University (NIH grant P30ES000210) for LC-HRMS and LC-MS analyses (NIH grant S10RR027878). NR 64 TC 13 Z9 13 U1 1 U2 12 PU IOS PRESS PI AMSTERDAM PA NIEUWE HEMWEG 6B, 1013 BG AMSTERDAM, NETHERLANDS SN 1387-2877 EI 1875-8908 J9 J ALZHEIMERS DIS JI J. Alzheimers Dis. PY 2014 VL 40 IS 2 BP 359 EP 373 DI 10.3233/JAD-131913 PG 15 WC Neurosciences SC Neurosciences & Neurology GA AD9LX UT WOS:000333587700014 PM 24448790 ER PT J AU Daniels, GH Vladic, A Brinar, V Zavalishin, I Valente, W Oyuela, P Palmer, J Margolin, DH AF Daniels, Gilbert H. Vladic, Anton Brinar, Vesna Zavalishin, Igor Valente, William Oyuela, Pedro Palmer, Jeffrey Margolin, David H. TI Alemtuzumab-Related Thyroid Dysfunction in a Phase 2 Trial of Patients With Relapsing-Remitting Multiple Sclerosis SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID ANTITHYROID DRUG-TREATMENT; GRAVES-DISEASE; SPONTANEOUS HYPOTHYROIDISM; RECEPTOR ANTIBODY; PREVALENCE; HYPERTHYROIDISM; AUTOANTIBODIES; MECHANISMS AB Context: Alemtuzumab, an anti-CD52 monoclonal antibody, increased the risk of thyroid dysfunction in CAMMS223, a phase 2 trial in relapsing-remitting multiple sclerosis. Objective: The objective of the study was a detailed description of thyroid dysfunction in CAMMS223. Design: Relapsing-remitting multiple sclerosis patients (n = 334) were randomized 1: 1: 1 to 44 mu g sc interferon-beta-1a (SC IFNB-1a, Rebif) or annual courses of 12 or 24 mg iv alemtuzumab. Thyroid function tests (TSH, free T-3, free T-4) and thyrotropin-binding inhibitory immunoglobulin (TBII) were assessed at screening, month 1, and quarterly thereafter; antithyroid peroxidase antibodies were assessed at screening and every 6 months. Thyroid dysfunction episodes were categorized post hoc by an endocrinologist. Results: During a median follow-up of 57.3 months, 34% of alemtuzumab and 6.5% of SC IFNB-1a patients had thyroid dysfunction (P < .0001). Ten percent of alemtuzumab and 3% of SC IFNB-1a patients had more than one episode of thyroid dysfunction. With alemtuzumab, Graves' hyperthyroidism occurred in 22%, hypothyroidism in 7%, and subacute thyroiditis in 4%. Of patients with overt Graves' hyperthyroidism, 23% spontaneously became euthyroid and an additional 15% spontaneously developed hypothyroidism. Of patients with overt hypothyroidism, 74% were TBII positive. The annual incidence of a first episode of thyroid dysfunction increased each year through year 3 and then decreased each subsequent study year. Conclusions: Thyroid dysfunction was more common with alemtuzumab than with SC IFNB-1a. There were few serious episodes. Regular monitoring facilitated early detection. Unique features of this population included high prevalence of Graves' hyperthyroidism, multiple episodes of thyroid dysfunction in individual patients, spontaneous hypothyroidism after overt Graves' hyperthyroidism, and a high prevalence of TBII-positive overt hypothyroidism. C1 [Daniels, Gilbert H.] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. [Daniels, Gilbert H.] Massachusetts Gen Hosp, Thyroid Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. [Vladic, Anton] Gen Hosp Sveti Duh, Dept Neurol, HR-10000 Zagreb, Croatia. [Brinar, Vesna] Zagreb Med Sch, Dept Neurol, HR-10000 Zagreb, Croatia. Univ Hosp Ctr, HR-10000 Zagreb, Croatia. [Zavalishin, Igor] Russian Acad Med Sci, Sci Res Inst Neurol, Moscow 123367, Russia. [Valente, William] Univ Maryland, Sch Med, Div Endocrinol Diabet & Nutr, Baltimore, MD 21201 USA. [Oyuela, Pedro; Palmer, Jeffrey; Margolin, David H.] Genzyme Corp, Cambridge, MA 02142 USA. RP Daniels, GH (reprint author), Massachusetts Gen Hosp, Thyroid Unit, ACC 730S, Boston, MA 02114 USA. EM gdaniels@partners.org FU Genzyme; Bayer Schering Pharma FX This work was supported by Genzyme and Bayer Schering Pharma, which provided financial support for the clinical trial and approved its design; only Genzyme participated in the data analysis, interpretation, and preparation of this report. G. H. D. reviewed all the data, wrote the manuscript, and had final responsibility, in consultation with Genzyme, for the decision to submit for publication. NR 27 TC 28 Z9 29 U1 1 U2 2 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 JAN PY 2014 VL 99 IS 1 BP 80 EP 89 DI 10.1210/jc.2013-2201 PG 10 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA AD6WP UT WOS:000333402200041 PM 24170099 ER PT J AU Makimura, H Murphy, CA Feldpausch, MN Grinspoon, SK AF Makimura, Hideo Murphy, Caitlin A. Feldpausch, Meghan N. Grinspoon, Steven K. TI The Effects of Tesamorelin on Phosphocreatine Recovery in Obese Subjects With Reduced GH SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID MAGNETIC-RESONANCE-SPECTROSCOPY; CARDIOVASCULAR RISK MARKERS; GROWTH-HORMONE-SECRETION; SKELETAL-MUSCLE; MITOCHONDRIAL-FUNCTION; ENDOGENOUS GH; HEALTHY-MEN; YOUNG; BODY; DEFICIENCY AB Context: Few studies have assessed the relationship between GH and mitochondrial function. Objective: The objective of this study was to determine the effects of improving IGF-I using a GHRH analog, tesamorelin, on mitochondrial function assessed by phosphocreatine (PCr) recovery using P-31 magnetic resonance spectroscopy in obese adults with reduced GH. Design: A total of 39 obese men and women with reduced GH secretion as determined by GHRH-arginine stimulation tests underwent magnetic resonance spectroscopy as part of a 12-month, double-blind, randomized, placebo-controlled trial comparing tesamorelin vs placebo. PCr recovery after submaximal exercise was assessed at baseline and at 12 months. Results: At baseline, there were no differences in age, sex, race/ethnicity, and GH or PCr parameters between tesamorelin and placebo. After 12 months, tesamorelin treatment led to a significantly greater increase in IGF-I than did placebo treatment (change, 102.9 +/- 31.8 mu g/L vs 22.8 +/- 8.9 mu g/L, tesamorelin vs placebo; P = .02). We demonstrated a significant positive relationship between increases in IGF-I and improvements in PCr recovery represented as Vi(PCr) (R = 0.56; P = .01). The association between IGF-I and PCr recovery was even stronger among subjects treated with tesamorelin only (Vi(PCr): R = 0.71; P = .03). This association remained significant after controlling for age, sex, race, ethnicity, and parameters of body composition and insulin sensitivity (all P < .05). Conclusions: Increases in IGF-I from 12 months of treatment with tesamorelin were significantly associated with improvements in PCr recovery parameters in obese men and women with reduced GH secretion, suggestive of improvements in mitochondrial function. C1 [Makimura, Hideo; Murphy, Caitlin A.; Feldpausch, Meghan N.; Grinspoon, Steven K.] Massachusetts Gen Hosp, Program Nutr Metab, Boston, MA 02114 USA. [Makimura, Hideo; Murphy, Caitlin A.; Feldpausch, Meghan N.; Grinspoon, Steven K.] Massachusetts Gen Hosp, Neuroendocrine Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Makimura, H (reprint author), Massachusetts Gen Hosp, Program Nutr Metab, Boston, MA 02114 USA. FU National Institutes of Health [K23DK087857, R01HL085268, P30DK040561, K24DK064545]; National Center for Research Resources [UL1RR025758]; Center for Functional Neuroimaging Technologies [P41RR14075]; Theratechnologies, Inc. FX This work was supported by the National Institutes of Health (Grants K23DK087857 to H. M., R01HL085268, P30DK040561, and K24DK064545 to S. K. G.), the National Center for Research Resources (UL1RR025758, Harvard Clinical and Translational Science Center), and the Center for Functional Neuroimaging Technologies (Grant P41RR14075 to the Athinoula A. Martinos Center for Biomedical Imaging where the 31P MRS imaging studies were conducted). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Center for Research Resources or the National Institutes of Health. Partial research funding and study drug was provided by Theratechnologies, Inc. NR 18 TC 4 Z9 4 U1 0 U2 2 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 JAN PY 2014 VL 99 IS 1 BP 338 EP 343 DI 10.1210/jc.2013-3436 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA AD6WP UT WOS:000333402200072 PM 24178787 ER PT J AU Smeekens, SP Huttenhower, C Riza, A van de Veerdonk, FL Zeeuwen, PLJM Schalkwijk, J van der Meer, JWM Xavier, RJ Netea, MG Gevers, D AF Smeekens, Sanne P. Huttenhower, Curtis Riza, Anca van de Veerdonk, Frank L. Zeeuwen, Patrick L. J. M. Schalkwijk, Joost van der Meer, Jos W. M. Xavier, Ramnik J. Netea, Mihai G. Gevers, Dirk TI Skin Microbiome Imbalance in Patients with STAT1/STAT3 Defects Impairs Innate Host Defense Responses SO JOURNAL OF INNATE IMMUNITY LA English DT Article DE Candida; Chronic mucocutaneous candidiasis; Immunodeficiency; Hyper-IgE syndrome; Microbiome ID CHRONIC MUCOCUTANEOUS CANDIDIASIS; HYPER-IGE SYNDROME; DNA-BINDING DOMAIN; GUT MICROBIOTA; STAT3 MUTATIONS; DISEASE; DIVERSITY; IL-17; IMMUNITY; IL-22 AB Background: Chronic mucocutaneous candidiasis (CMC) and hyper-IgE syndrome (HIES) are primary immunodeficiencies mainly caused by mutations in STAT1 and STAT3, respectively. CMC and HIES patients have an increased risk for skin and mucosal infections with fungal pathogens and Staphylococcus aureus. However, it is unknown whether the genetic defects in these patients also affect the skin and mucosal microbiome, which in turn may influence host defense mechanisms. Methods: The skin and oral microbiome of CMC and HIES patients was compared to that of healthy controls at five body sites using 165 rRNA sequencing. The influence of skin colonizers on the immune response was investigated using in vitro experiments. Results: The microbiome of CMC and HIES patients contained more Gram-negative bacteria, especially Acinetobacter spp., and less of the normal Corynebacterium spp. compared to healthy controls. Exposure of human primary leukocytes to Acinetobacter suppressed the cytokine response to Candida albicans and S. aureus, while the normal corynebacteria did not suppress cytokine responses. Discussion: These results demonstrate that central mediators of immune responses like STAT1 and STAT3 not only directly influence immune responses, but also result in changes in the skin microbiome that in turn can amplify the defective immune response against fungal and microbial pathogens. Copyright (C) 2013 S. Karger AG, Basel C1 [Smeekens, Sanne P.; Riza, Anca; van de Veerdonk, Frank L.; van der Meer, Jos W. M.; Netea, Mihai G.] Radboud Univ Nijmegen, Med Ctr, Dept Med, NL-6525 GA Nijmegen, Netherlands. [Riza, Anca; Zeeuwen, Patrick L. J. M.; Schalkwijk, Joost] Radboud Univ Nijmegen, Med Ctr, Dept Dermatol, NL-6525 GA Nijmegen, Netherlands. [Smeekens, Sanne P.; Riza, Anca; van de Veerdonk, Frank L.; van der Meer, Jos W. M.; Netea, Mihai G.] Nijmegen Inst Infect Inflammat & Immun N4i, Nijmegen, Netherlands. [Huttenhower, Curtis; Xavier, Ramnik J.; Gevers, Dirk] MIT, Broad Inst, Cambridge, MA 02139 USA. [Huttenhower, Curtis; Xavier, Ramnik J.; Gevers, Dirk] Harvard Univ, Cambridge, MA 02138 USA. [Xavier, Ramnik J.] Harvard Univ, Sch Med, Ctr Computat & Integrat Biol, Boston, MA USA. [Xavier, Ramnik J.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Gastrointestinal Unit, Boston, MA USA. [Huttenhower, Curtis] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. RP Netea, MG (reprint author), Radboud Univ Nijmegen, Med Ctr, Geert Grootepl Zuid 8, NL-6525 GA Nijmegen, Netherlands. EM M.Netea@aig.umcn.nl RI Schalkwijk, Joost/N-1774-2013; van de Veerdonk, Frank/C-7256-2008; Netea, Mihai/N-5155-2014; Zeeuwen, Patrick/N-1779-2013; Smeekens, Sanne/G-8307-2011; van der Meer, Jos/C-8521-2013; OI van de Veerdonk, Frank/0000-0002-1121-4894; Smeekens, Sanne/0000-0002-7835-914X; van der Meer, Jos/0000-0001-5120-3690; Huttenhower, Curtis/0000-0002-1110-0096 FU European Research Council [310372]; Dutch Ministry of Economic Affairs [PID082025]; National Institutes of Health [NIH 1R01HG005969]; Crohn's and Colitis Foundation of America FX This work was supported by an ERC Consolidator Grant from the European Research Council (310372 to M.G.N.); by the Dutch Ministry of Economic Affairs (PID082025 to J.S.); by the National Institutes of Health (NIH 1R01HG005969 to C.H.), and by a grant from the Crohn's and Colitis Foundation of America (to R.J.X, D.G., and C.H.). The authors declare no conflict of interest. NR 44 TC 21 Z9 22 U1 0 U2 20 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 1662-811X EI 1662-8128 J9 J INNATE IMMUN JI J. Innate Immun. PY 2014 VL 6 IS 3 BP 253 EP 262 DI 10.1159/000351912 PG 10 WC Immunology SC Immunology GA AE2AF UT WOS:000333775000002 PM 23796786 ER PT J AU Tanaka, S Miyagi, T Hide, I Shirafuji, T Chiocca, EA Sakai, N AF Tanaka, Shigeru Miyagi, Tatsuhiro Hide, Izumi Shirafuji, Toshihiko Chiocca, E. Antonio Sakai, Norio TI The expression of GPR3 protects cerebellar granular neurons from various apoptotic stimuli SO JOURNAL OF PHARMACOLOGICAL SCIENCES LA English DT Meeting Abstract CT 87th Annual Meeting of the Japanese-Pharmacological-Society CY MAR 19-21, 2014 CL Sendai, JAPAN SP Japanese Pharmacol Soc C1 [Tanaka, Shigeru; Miyagi, Tatsuhiro; Hide, Izumi; Shirafuji, Toshihiko; Sakai, Norio] Hiroshima Univ, Sch Biomed & Hlth Sci, Dept Pharmacol, Minami Ku, Hiroshima 7348551, Japan. [Chiocca, E. Antonio] Dana Farber Canc Inst, Dept Neurosurg, Boston, MA 02115 USA. RI Tanaka, Shigeru/O-3908-2015 NR 0 TC 0 Z9 0 U1 0 U2 3 PU JAPANESE PHARMACOLOGICAL SOC PI KYOTO PA EDITORIAL OFF, KANTOHYA BLDG GOKOMACHI-EBISUGAWA NAKAGYO-KU, KYOTO, 604, JAPAN SN 1347-8613 EI 1347-8648 J9 J PHARMACOL SCI JI J. Pharmacol. Sci. PY 2014 VL 124 SU 1 BP 113P EP 113P PG 1 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA AD8DZ UT WOS:000333498000364 ER PT J AU Russi, EG Raber-Durlacher, JE Sonis, ST AF Russi, Elvio G. Raber-Durlacher, Judith E. Sonis, Stephen T. TI Local and Systemic Pathogenesis and Consequences of Regimen-Induced Inflammatory Responses in Patients with Head and Neck Cancer Receiving Chemoradiation SO MEDIATORS OF INFLAMMATION LA English DT Review ID ALIMENTARY-TRACT MUCOSITIS; STEM-CELL TRANSPLANTATION; NF-KAPPA-B; QUALITY-OF-LIFE; CHOLINERGIC ANTIINFLAMMATORY PATHWAY; CYCLOOXYGENASE-2 COX-2 EXPRESSION; MOLECULAR-PATTERN MOLECULES; IONIZING-RADIATION INDUCE; INNATE IMMUNE-RESPONSES; GLYCATION END-PRODUCTS AB Treatment-related toxicities are common among patients with head and neck cancer, leading to poor clinical outcomes, reduced quality of life, and increased use of healthcare resources. Over the last decade, much has been learned about the pathogenesis of cancer regimen-related toxicities. Historically, toxicities were separated into those associated with tissue injury and those with behavioural or systemic changes. However, it is now clear that tissue-specific damage such as mucositis, dermatitis, or fibrosis is no longer the sole consequence of direct clonogenic cell death, and a relationship between toxicities that results in their presentation as symptom clusters has been documented and attributed to a common underlying pathobiology. In addition, the finding that patients commonly develop toxicities representing tissue injury outside radiation fields and side effects such as fatigue or cognitive dysfunction suggests the generation of systemic as well as local mediators. As a consequence, it might be appropriate to consider toxicity syndromes, rather than the traditional approach, in which each side effect was considered as an autonomous entity. In this paper, we propose a biologically based explanation which forms the basis for the diverse constellation of toxicities seen in response to current regimens used to treat cancers of the head and neck. C1 [Russi, Elvio G.] Univ Teaching Hosp AO S Croce & Carle, Dept Radiat Oncol, I-12100 Cuneo, Italy. [Raber-Durlacher, Judith E.] Univ Amsterdam, Acad Med Ctr, Dept Oral & Maxillofacial Surg, NL-1081 LA Amsterdam, Netherlands. [Sonis, Stephen T.] Brigham & Womens Hosp, Div Oral Med, Boston, MA 02115 USA. [Sonis, Stephen T.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Sonis, Stephen T.] Biomodels LLC, Boston, MA 02115 USA. RP Russi, EG (reprint author), Univ Teaching Hosp AO S Croce & Carle, Dept Radiat Oncol, Via M Coppino 26, I-12100 Cuneo, Italy. EM elviorussi@gmail.com FU Lega Italiana per la Lotta contro i Tumori Sez. di Cuneo FX The authors would like to thank "Lega Italiana per la Lotta contro i Tumori Sez. di Cuneo" for its grant. NR 196 TC 6 Z9 6 U1 1 U2 6 PU HINDAWI PUBLISHING CORP PI NEW YORK PA 410 PARK AVENUE, 15TH FLOOR, #287 PMB, NEW YORK, NY 10022 USA SN 0962-9351 EI 1466-1861 J9 MEDIAT INFLAMM JI Mediat. Inflamm. PY 2014 AR 518261 DI 10.1155/2014/518261 PG 14 WC Cell Biology; Immunology SC Cell Biology; Immunology GA AD9PJ UT WOS:000333596700001 ER PT S AU Lee, YK Cowan, CA AF Lee, Youn-Kyoung Cowan, Chad A. BE MacDougald, OA TI Differentiation of White and Brown Adipocytes from Human Pluripotent Stem Cells SO METHODS OF ADIPOSE TISSUE BIOLOGY, PT B SE Methods in Enzymology LA English DT Review; Book Chapter ID FAT; ADIPOGENESIS; INFLAMMATION; FIBROBLASTS; DERIVATION; DISEASE; TISSUE AB Given the rapid increase in the prevalence of obesity and related metabolic diseases, research to better understand adipose tissue biology and physiology has garnered considerable attention. Adipose has been studied using both cell culture systems and model organisms. However, the mechanisms of adipocyte regulation are not comprehensively understood, as currently available in vitro or in vivo systems do not fully recapitulate human metabolic processes. Human primary adipocytes are difficult to culture and expand, and current cell systems have limitations such as cell line-to-cell line variability for adipocyte differentiation, decreased proliferation, and differentiation potential upon continued passaging. To overcome these limitations, we developed and established an efficient and robust adipocyte differentiation protocol using human pluripotent stem cells (hPSCs) and inducible expression of key adipogenic transcriptional regulators. Here, we provide a simple and stepwise protocol for programming hPSCs into mature white or brown adipocytes. C1 [Lee, Youn-Kyoung; Cowan, Chad A.] Harvard Univ, Dept Stem Cell & Regenerat Biol, Cambridge, MA 02138 USA. [Lee, Youn-Kyoung; Cowan, Chad A.] Massachusetts Gen Hosp, Ctr Regenerat Med, Boston, MA 02114 USA. [Cowan, Chad A.] Harvard Stem Cell Inst, Cambridge, MA USA. RP Cowan, CA (reprint author), Harvard Univ, Dept Stem Cell & Regenerat Biol, Cambridge, MA 02138 USA. EM ccowan@fas.harvard.edu NR 21 TC 4 Z9 4 U1 1 U2 7 PU ELSEVIER ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA SN 0076-6879 BN 978-0-12-800280-3 J9 METHOD ENZYMOL JI Methods Enzymol. PY 2014 VL 538 BP 35 EP 47 DI 10.1016/B978-0-12-800280-3.00003-7 PG 13 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA BA2GT UT WOS:000333378700003 PM 24529432 ER PT J AU Yu, XQ Lin, J Yu, Q Kawai, T Taubman, MA Han, XZ AF Yu, Xiaoqian Lin, Jiang Yu, Qing Kawai, Toshihisa Taubman, Martin A. Han, Xiaozhe TI Activation of Toll-like receptor 9 inhibits lipopolysaccharide-induced receptor activator of nuclear factor kappa- B ligand expression in rat B lymphocytes SO MICROBIOLOGY AND IMMUNOLOGY LA English DT Article DE RANK ligand; Toll-like receptor; B lymphocytes; immune response ID RHEUMATOID SYNOVIAL FIBROBLASTS; CPG-OLIGODEOXYNUCLEOTIDES; OSTEOCLASTOGENIC ACTIVITY; PORPHYROMONAS-GINGIVALIS; PERIODONTAL-DISEASE; GROWTH-FACTOR; BONE-RESORPTION; T-CELLS; RANKL; APOPTOSIS AB B lymphocytes express multiple TLRs that regulate their cytokine production. We investigated the effect of TLR4 and TLR9 activation on receptor activator of NF-kappa B ligand (RANKL) expression by rat spleen B cells. Splenocytes or purified spleen B cells from Rowett rats were cultured with TLR4 ligand Escherichia coli LPS and/or TLR9 ligand CpG-oligodeoxynucleotide (CpG-ODN) for 2 days. RANKL mRNA expression and the percentage of RANKL-positive B cells were increased in rat splenocytes challenged by E. coli LPS alone. The increases were less pronounced when cells were treated with both CpG-ODN and E. coli LPS. Microarray analysis showed that expressions of multiple cyclin-dependent kinase (CDK) pathway-related genes were up-regulated only in cells treated with both E. coli LPS and CpG-ODN. This study suggests that CpG-ODN inhibits LPS-induced RANKL expression in rat B cells via regulation of the CDK pathway. C1 [Yu, Xiaoqian; Lin, Jiang; Yu, Qing; Kawai, Toshihisa; Taubman, Martin A.; Han, Xiaozhe] Forsyth Inst, Dept Immunol & Infect Dis, Cambridge, MA 02142 USA. [Yu, Xiaoqian] Peking Univ Sch & Hosp Stomatol, Dept Periodontol, Beijing 100081, Peoples R China. [Lin, Jiang] Harbin Med Univ, Hosp 4, Dept Stomatol, Harbin 150001, Peoples R China. RP Han, XZ (reprint author), Forsyth Inst, Dept Immunol & Infect Dis, 245 First St, Cambridge, MA 02142 USA. EM xhan@forsyth.org FU NIH from the National Institute of Dental and Craniofacial Research [DE-003420, DE-021837] FX Human OPG-Fc fusion protein was kindly provided by Dr. Colin Dunstan, Amgen, Thousand Oaks, CA, USA. This work was supported by NIH Grant DE-003420 and DE-021837 from the National Institute of Dental and Craniofacial Research. NR 44 TC 1 Z9 1 U1 0 U2 2 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0385-5600 EI 1348-0421 J9 MICROBIOL IMMUNOL JI Microbiol. Immunol. PD JAN PY 2014 VL 58 IS 1 BP 51 EP 60 DI 10.1111/1348-0421.12115 PG 10 WC Immunology; Microbiology SC Immunology; Microbiology GA AE0NR UT WOS:000333663500007 PM 24661200 ER PT J AU Ladinsky, MS Kieffer, C Olson, G Deruaz, M Vrbanac, V Tager, AM Kwon, DS Bjorkman, PJ AF Ladinsky, Mark S. Kieffer, Collin Olson, Gregory Deruaz, Maud Vrbanac, Vladimir Tager, Andrew M. Kwon, Douglas S. Bjorkman, Pamela J. TI Electron Tomography of HIV-1 Infection in GutAssociated Lymphoid Tissue SO PLOS PATHOGENS LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; T-CELL DEPLETION; DEFICIENCY SYNDROME AIDS; HUMANIZED BLT MICE; PLASMA-MEMBRANE; 3-DIMENSIONAL STRUCTURE; GASTROINTESTINAL-TRACT; VIRAL REPLICATION; HUMAN MACROPHAGES; IMMUNE-SYSTEM AB Critical aspects of HIV-1 infection occur in mucosal tissues, particularly in the gut, which contains large numbers of HIV-1 target cells that are depleted early in infection. We used electron tomography (ET) to image HIV-1 in gut-associated lymphoid tissue (GALT) of HIV-1-infected humanized mice, the first three-dimensional ultrastructural examination of HIV-1 infection in vivo. Human immune cells were successfully engrafted in the mice, and following infection with HIV-1, human T cells were reduced in GALT. Virions were found by ET at all stages of egress, including budding immature virions and free mature and immature viruses. Immuno-electron microscopy verified the virions were HIV-1 and showed CD4 sequestration in the endoplasmic reticulum of infected cells. Observation of HIV-1 in infected GALT tissue revealed that most HIV-1-infected cells, identified by immunolabeling and/or the presence of budding virions, were localized to intestinal crypts with pools of free virions concentrated in spaces between cells. Fewer infected cells were found in mucosal regions and the lamina propria. The preservation quality of reconstructed tissue volumes allowed details of budding virions, including structures interpreted as host-encoded scission machinery, to be resolved. Although HIV-1 virions released from infected cultured cells have been described as exclusively mature, we found pools of both immature and mature free virions within infected tissue. The pools could be classified as containing either mostly mature or mostly immature particles, and analyses of their proximities to the cell of origin supported a model of semi-synchronous waves of virion release. In addition to HIV-1 transmission by pools of free virus, we found evidence of transmission via virological synapses. Three-dimensional EM imaging of an active infection within tissue revealed important differences between cultured cell and tissue infection models and furthered the ultrastructural understanding of HIV-1 transmission within lymphoid tissue. Author Summary HIV/AIDS remains a global public health problem with over 33 million people infected worldwide. High-resolution imaging of infected tissues by three-dimensional electron microscopy can reveal details of the structure of HIV-1, the virus that causes AIDS, how it infects cells, and how and where the virus accumulates within different tissue sub-structures. Three-dimensional electron microscopy had previously only been performed to image infected cultured cells or purified virus. Here we used three-dimensional electron microscopy to examine an active infection in the gastrointestinal tract of HIV-1-infected mice with humanized immune systems, allowing visualization of the interplay between the virus and host immune cells. Recapitulating the course of infection in humans, immune cells were depleted in infected humanized mouse gut-associated lymphoid tissue, and individual HIV-1 particles were detected as they budded from host cells and accumulated in pools between cells. HIV-1 was mapped to different substructures and cell types within the gut, and free virions were found to accumulate in pools between cells and also to infect adjacent cells via regions of cell-to-cell contact called virological synapses. Our three-dimensional imaging of an HIV-1 infection in tissue uncovered differences between cultured cell and tissue models of HIV-1 infection and therefore furthered our understanding of HIV-1/AIDS as a disease of mucosal tissues. C1 [Ladinsky, Mark S.; Kieffer, Collin; Bjorkman, Pamela J.] CALTECH, Div Biol & Biol Engn 114 96, Pasadena, CA 91125 USA. [Olson, Gregory; Kwon, Douglas S.] Ragon Inst MGH MIT & Harvard, Cambridge, MA USA. [Deruaz, Maud; Vrbanac, Vladimir; Tager, Andrew M.] Massachusetts Gen Hosp, Ctr Immunol & Inflammatory Dis, Charlestown, MA USA. [Deruaz, Maud; Vrbanac, Vladimir; Tager, Andrew M.] Harvard Univ, Sch Med, Charlestown, MA USA. [Bjorkman, Pamela J.] CALTECH, Howard Hughes Med Inst, Pasadena, CA 91125 USA. RP Ladinsky, MS (reprint author), CALTECH, Div Biol & Biol Engn 114 96, Pasadena, CA 91125 USA. EM bjorkman@caltech.edu FU National Institutes of Health [2 P50 GM082545-06]; Ragon Institute post-doctoral fellowship; NIH K08 Award [K08 AI084546-04]; Burroughs Wellcome Fund; Harvard University Center for AIDS Research [P30 AI060354] FX This work was supported by the National Institutes of Health (2 P50 GM082545-06; WI Sundquist, PI), a Ragon Institute post-doctoral fellowship (CK), and gifts from the Gordon and Betty Moore Foundation and the Agouron Institute to support electron microscopy at Caltech. DSK is supported by an NIH K08 Award (K08 AI084546-04) and a fellowship from the Burroughs Wellcome Fund. The MGH Humanized Mouse Program is supported by the Harvard University Center for AIDS Research (P30 AI060354). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 71 TC 12 Z9 12 U1 0 U2 3 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1553-7366 EI 1553-7374 J9 PLOS PATHOG JI PLoS Pathog. PD JAN PY 2014 VL 10 IS 1 AR e1003899 DI 10.1371/journal.ppat.1003899 PG 15 WC Microbiology; Parasitology; Virology SC Microbiology; Parasitology; Virology GA AC6NQ UT WOS:000332640900015 PM 24497830 ER PT J AU Wo, JY Mamon, HJ Ferrone, CR Ryan, DP Blaszkowsky, LS Kwak, EL Tseng, YD Napolitano, BN Ancukiewicz, M Swanson, RS Lillemoe, KD Fernandez-del Castillo, C Hong, TS AF Wo, Jennifer Y. Mamon, Harvey J. Ferrone, Cristina R. Ryan, David P. Blaszkowsky, Lawrence S. Kwak, Eunice L. Tseng, Yolanda D. Napolitano, Brian N. Ancukiewicz, Marek Swanson, Richard S. Lillemoe, Keith D. Fernandez-del Castillo, Carlos Hong, Theodore S. TI Phase I study of neoadjuvant accelerated short course radiation therapy with photons and capecitabine for resectable pancreatic cancer SO RADIOTHERAPY AND ONCOLOGY LA English DT Article DE Short course; Pancreatic cancer ID ADENOCARCINOMA; RADIOTHERAPY; CHEMORADIATION; CHEMOTHERAPY; GEMCITABINE; TRIAL AB Purpose: In this phase I study, we sought to determine the feasibility and tolerability of neoadjuvant short course radiotherapy (SC-CRT) delivered with photon RT with concurrent capecitabine for resectable pancreatic adenocarcinoma. Materials and methods: Ten patients with localized, resectable pancreatic adenocarcinoma were enrolled from December 2009 to August 2011. In dose level I, patients received 3 Gy x 10. In dose level 2, patients received 5 Gy x 5 (every other day). In dose level 3, patients received 5 Gy x 5 (consecutive days). Capecitabine was given during weeks 1 and 2. Surgery was performed 1-3 weeks after completion of chemotherapy. Results: With an intended accrual of 12 patients, the study was closed early due to unexpected intraoperative complications. Compared to the companion phase I proton study, patients treated with photons had increased intraoperative RT fibrosis reported by surgeons (27% vs. 63%). Among those undergoing a Whipple resection, increased RT fibrosis translated to an increased mean OR time of 69 min. Dosimetric comparison revealed significantly increased low dose exposure to organs at risk for patients treated with photon RT. Conclusions: This phase) experience evaluating the tolerability of neoadjuvant SC-CRT with photon RT closed early due to unexpected intraoperative complications. (C) 2013 Elsevier Ireland Ltd. All rights reserved. Radiotherapy and Oncology 110 (2014) 160-164 C1 [Wo, Jennifer Y.; Napolitano, Brian N.; Ancukiewicz, Marek; Hong, Theodore S.] Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. [Ferrone, Cristina R.; Lillemoe, Keith D.; Fernandez-del Castillo, Carlos] Massachusetts Gen Hosp, Dept Gen Surg, Boston, MA 02114 USA. [Ryan, David P.; Blaszkowsky, Lawrence S.; Kwak, Eunice L.] Massachusetts Gen Hosp, Dept Med Oncol, Boston, MA 02114 USA. [Mamon, Harvey J.] Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Radiat Oncol, Boston, MA USA. [Swanson, Richard S.] Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Gen Surg, Boston, MA 02138 USA. [Tseng, Yolanda D.] Harvard Radiat Oncol Program, Boston, MA USA. RP Wo, JY (reprint author), Massachusetts Gen Hosp, 100 Blossom St,Cox 3, Boston, MA 02114 USA. EM jwo@partners.org NR 12 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 JAN PY 2014 VL 110 IS 1 BP 160 EP 164 DI 10.1016/j.radonc.2013.10.027 PG 5 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA AE2GU UT WOS:000333792100025 PM 24231241 ER PT J AU Xi, YZ Xia, JL Cauley, S Balakrishnan, V AF Xi, Yuanzhe Xia, Jianlin Cauley, Stephen Balakrishnan, Venkataramanan TI SUPERFAST AND STABLE STRUCTURED SOLVERS FOR TOEPLITZ LEAST SQUARES VIA RANDOMIZED SAMPLING SO SIAM JOURNAL ON MATRIX ANALYSIS AND APPLICATIONS LA English DT Article DE Toeplitz least squares; superfast and stable solvers; randomized sampling; rectangular HSS matrix; URV factorization; HSS error and stability analysis ID LINEAR-EQUATIONS; FAST ALGORITHMS; SEMISEPARABLE REPRESENTATIONS; EFFICIENT ALGORITHMS; MATRICES; FACTORIZATION; SYSTEMS; DECOMPOSITION; QR AB We present some superfast (O((m + n)log(2)(m + n)) complexity) and stable structured direct solvers for m x n Toeplitz least squares problems. Based on the displacement equation, a Toeplitz matrix T is first transformed into a Cauchy-like matrix C, which can be shown to have small off-diagonal numerical ranks when the diagonal blocks are rectangular. We generalize standard hierarchically semiseparable (HSS) matrix representations to rectangular ones, and construct a rectangular HSS approximation to C in nearly linear complexity with randomized sampling and fast multiplications of C with vectors. A new URV HSS factorization and a URV HSS solution are designed for the least squares solution. We also present two structured normal equation methods. Systematic error and stability analysis for our HSS methods is given, which is also useful for studying other HSS and rank structured methods. We derive the growth factors and the backward error bounds in the HSS factorizations, and show that the stability results are generally much better than those in dense LU factorizations with partial pivoting. Such analysis has not been done before for HSS matrices. The solvers are tested on various classical Toeplitz examples ranging from well-conditioned to highly ill-conditioned ones. Comparisons with some recent fast and superfast solvers are given. Our new methods are generally much faster, and give better (or at least comparable) accuracies, especially for ill-conditioned problems. C1 [Xi, Yuanzhe; Xia, Jianlin] Purdue Univ, Dept Math, W Lafayette, IN 47907 USA. [Cauley, Stephen] Harvard Univ, Massachusetts Gen Hosp, Dept Radiol, Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA 02129 USA. [Balakrishnan, Venkataramanan] Purdue Univ, Sch Elect & Comp Engn, W Lafayette, IN 47907 USA. RP Xi, YZ (reprint author), Purdue Univ, Dept Math, W Lafayette, IN 47907 USA. EM yxi@math.purdue.edu; xiaj@math.purdue.edu; stcauley@nmr.mgh.harvard.edu; ragu@ecn.purdue.edu RI xi, yuanzhe/O-5306-2015 OI xi, yuanzhe/0000-0002-6588-069X FU NSF [DMS-1255416, DMS-1115572, CHE-0957024] FX The research of the second author was supported in part by an NSF CAREER Award DMS-1255416 and NSF grants DMS-1115572 and CHE-0957024. NR 39 TC 13 Z9 13 U1 1 U2 4 PU SIAM PUBLICATIONS PI PHILADELPHIA PA 3600 UNIV CITY SCIENCE CENTER, PHILADELPHIA, PA 19104-2688 USA SN 0895-4798 EI 1095-7162 J9 SIAM J MATRIX ANAL A JI SIAM J. Matrix Anal. Appl. PY 2014 VL 35 IS 1 BP 44 EP 72 DI 10.1137/120895755 PG 29 WC Mathematics, Applied SC Mathematics GA AE0YW UT WOS:000333693300003 ER PT J AU Nusbaum, DM Antonsen, E Bockhorst, KH Easley, RB Clark, JB Brady, KM Kibler, KK Sutton, JP Kramer, L Sargsyan, AE AF Nusbaum, Derek M. Antonsen, Erik Bockhorst, Kurt H. Easley, R. Blaine Clark, Jonathan B. Brady, Kenneth M. Kibler, Kathleen K. Sutton, Jeffrey P. Kramer, Larry Sargsyan, Ashot E. TI Optic Nerve Sheath Diameter Measurement Techniques: Examination Using a Novel Ex-Vivo Porcine Model SO AVIATION SPACE AND ENVIRONMENTAL MEDICINE LA English DT Article DE ultrasound; magnetic resonance imaging; optic nerve sheath diameter; intracranial pressure ID INTRACRANIAL-PRESSURE AB Background: Ultrasound (U/S) and MRI measurements of the optic nerve sheath diameter (ONSD) have been proposed as intracranial pressure measurement surrogates, but these methods have not been fully evaluated or standardized. The purpose of this study was to develop an ex-vivo model for evaluating ONSD measurement techniques by comparing U/S and MRI measurements to physical measurements. Methods: The left eye of post mortem juvenile pigs (N = 3) was excised and the subdural space of the optic nerve cannulated. Caliper measurements and U/S imaging measurements of the ONSD were acquired at baseline and following 1 cc saline infusion into the sheath. The samples were then embedded in 0.5 % agarose and imaged in a 7 Tesla (7T) MRI. The ONSD was subsequently measured with digital calipers at locations and directions matching the U/S and direct measurements. Results: Both MRI and sonographic measurements were in agreement with direct measurements. U/S data, especially axial images, exhibited a positive bias and more variance (bias: 1.318, 95%. limit of agreement: 8.609) compared to MRI (bias: 0.3156, 95% limit of agreement: 2.773). In addition, U/S images were much more dependent on probe placement, distance between probe and target, and imaging plane. Conclusions: This model appears to be a valid test-bed for continued scrutiny of ONSD measurement techniques. In this model, 7T MRI was accurate and potentially useful for in-vivo measurements where direct measurements are not available. Current limitations with ultrasound imaging for ONSD measurement associated with image acquisition technique and equipment necessitate further standardization to improve its clinical utility. C1 [Nusbaum, Derek M.; Easley, R. Blaine; Clark, Jonathan B.; Brady, Kenneth M.; Kibler, Kathleen K.; Sutton, Jeffrey P.] Baylor Coll Med, Houston, TX 77030 USA. [Antonsen, Erik] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Clark, Jonathan B.; Sutton, Jeffrey P.] Natl Space Biomed Res Inst, Houston, TX USA. [Bockhorst, Kurt H.; Kramer, Larry] Univ Texas Hlth Sci Ctr Houston, Houston, TX 77030 USA. [Sargsyan, Ashot E.] Wyle Sci Technol & Engn Grp, Houston, TX USA. RP Nusbaum, DM (reprint author), Baylor Coll Med, Dept Internal Med, 1 Baylor Plaza, Houston, TX 77030 USA. EM nusbaum@bcm.edu OI Clark, Jonathan/0000-0002-1162-1238 FU NASA [NNX 10AK70G]; TCH Pediatric Anesthesiology Research Fund FX This work was supported by NASA Grant NNX 10AK70G and TCH Pediatric Anesthesiology Research Fund. NR 8 TC 1 Z9 1 U1 0 U2 1 PU AEROSPACE MEDICAL ASSOC PI ALEXANDRIA PA 320 S HENRY ST, ALEXANDRIA, VA 22314-3579 USA SN 0095-6562 EI 1943-4448 J9 AVIAT SPACE ENVIR MD JI Aviat. Space Environ. Med. PD JAN PY 2014 VL 85 IS 1 BP 50 EP 54 DI 10.3357/ASEM.3664.2014 PG 5 WC Public, Environmental & Occupational Health; Medicine, General & Internal; Sport Sciences SC Public, Environmental & Occupational Health; General & Internal Medicine; Sport Sciences GA AD1MA UT WOS:000332996900010 PM 24479259 ER PT J AU Kim, E Yang, KS Giedt, RJ Weissleder, R AF Kim, Eunha Yang, Katherine S. Giedt, Randy J. Weissleder, Ralph TI Red Si-rhodamine drug conjugates enable imaging in GFP cells SO CHEMICAL COMMUNICATIONS LA English DT Article ID LIVING CELLS; IN-VIVO; SINGLE-CELL; LOCALIZATION; MICROSCOPY; PROBE AB Here we evaluated a series of Si-derivatized rhodamine (SiR) dyes for their ability to visualize a model drug in live cells. We show that a charge neutral SiR derivative (but not others) can indeed be used to follow the intracellular location of the model therapeutic drug in GFP cells. C1 [Kim, Eunha; Yang, Katherine S.; Giedt, Randy J.; Weissleder, Ralph] Harvard Univ, Sch Med, Ctr Syst Biol, Massachusettes Gen Hosp, Boston, MA 02114 USA. [Weissleder, Ralph] Harvard Univ, Sch Med, Dept Syst Biol, Boston, MA 02115 USA. RP Weissleder, R (reprint author), Harvard Univ, Sch Med, Ctr Syst Biol, Massachusettes Gen Hosp, 185 Cambridge St, Boston, MA 02114 USA. EM rweissleder@mgh.harvard.edu RI Kim, Eunha/G-1242-2013 OI Kim, Eunha/0000-0002-0766-696X FU National Institutes of Health (NIH) [1R01CA164448, P01CA139980, P50CA086355]; NIH [T32CA079443] FX We thank Jenna Klubnick for synthesis of 4-(4-fluoro-3-(piperazine-1-carbonyl)benzyl)phthalazin-1(2H)-one and Alex Zaltsman for assistance in imaging. This work was supported in part by the National Institutes of Health (NIH) grants 1R01CA164448, P01CA139980 and P50CA086355 (R.W.). K. Y. and R. G. were supported by NIH grant T32CA079443. NR 16 TC 16 Z9 16 U1 2 U2 23 PU ROYAL SOC CHEMISTRY PI CAMBRIDGE PA THOMAS GRAHAM HOUSE, SCIENCE PARK, MILTON RD, CAMBRIDGE CB4 0WF, CAMBS, ENGLAND SN 1359-7345 EI 1364-548X J9 CHEM COMMUN JI Chem. Commun. PY 2014 VL 50 IS 34 BP 4504 EP 4507 DI 10.1039/c4cc00144c PG 4 WC Chemistry, Multidisciplinary SC Chemistry GA AD9JF UT WOS:000333580500026 PM 24663433 ER PT J AU Du, YPP Chu, RX Tregellas, JR AF Du, Yiping P. Chu, Renxin Tregellas, Jason R. TI Enhancing the Detection of BOLD Signal in fMRI by Reducing the Partial Volume Effect SO COMPUTATIONAL AND MATHEMATICAL METHODS IN MEDICINE LA English DT Article ID HIGH-RESOLUTION FMRI; HUMAN AUDITORY-CORTEX; HIGH MAGNETIC-FIELDS; SMOOTH-PURSUIT; ACTIVATION; BRAIN; ECHO; SENSITIVITY; ANGIOGRAPHY; CONTRAST AB Purpose. To investigate the advantages of reducing the partial volume effect (PVE) to enhance the detection of the BOLD signal in fMRI. Methods. A linear phase term was added in k-space to obtain half-voxel shifting of 64 x 64 T-2*-weighted echo-planar images. Three sets of image data shifted in the x, y, and diagonal direction, respectively, are combined with the original 64 x 64 data to form the 128 x 128 voxel-shifted interpolated data. Results. A simulation of a synthetic fMRI dataset shows that the voxel-shifted interpolation (VSI) can increase the t-score up to 50% in single-voxel activations. An fMRI study (n = 7) demonstrates that 20.4% of the interpolated voxels have higher t-scores than their nearest neighboring voxels in the original maps. The average increase of the t-score in these interpolated voxels is 13.3%. Conclusion. VSI yields increased sensitivity in detecting voxel-size BOLD activations, improved spatial accuracy of activated regions, and improved detection of the peak BOLD signal of an activated region. VSI can potentially be used as an alternative to the high-resolution fMRI studies in which reduction in SNR and increase in imaging time become prohibitive. C1 [Du, Yiping P.] Zhejiang Univ, Dept Biomed Engn, Hangzhou 310027, Peoples R China. [Du, Yiping P.] Educ Minist China, Key Lab Biomed Engn, Beijing, Peoples R China. [Du, Yiping P.; Chu, Renxin; Tregellas, Jason R.] Univ Colorado, Sch Med, Dept Psychiat, Brain Imaging Ctr, Aurora, CO USA. [Tregellas, Jason R.] Denver VA Med Ctr, Res Serv, Denver, CO 80220 USA. RP Du, YPP (reprint author), Zhejiang Univ, Dept Biomed Engn, Hangzhou 310027, Peoples R China. EM yipingdu@zju.edu.cn RI Tregellas, Jason/J-3637-2015 FU National Key Basic Research Program of China [2013CB329501]; National Natural Science Foundation of China [81371518, 81261120411]; Ministry of Science and Technology [2011BAI12B01] FX This work was partially supported by the National Key Basic Research Program of China (2013CB329501), the National Natural Science Foundation of China (81371518, 81261120411), and the Ministry of Science and Technology (2011BAI12B01). The Brain and Behavior Research Foundation, and the Blowitz-Ridgeway Foundation. NR 23 TC 0 Z9 0 U1 1 U2 9 PU HINDAWI PUBLISHING CORPORATION PI NEW YORK PA 410 PARK AVENUE, 15TH FLOOR, #287 PMB, NEW YORK, NY 10022 USA SN 1748-670X EI 1748-6718 J9 COMPUT MATH METHOD M JI Comput. Math. Method Med. PY 2014 AR 973972 DI 10.1155/2014/973972 PG 9 WC Mathematical & Computational Biology SC Mathematical & Computational Biology GA AD5LA UT WOS:000333293100001 ER PT J AU Wang, XG Robertson, AL Li, JY Chai, RJ Haishan, W Sadiku, P Ogryzko, NV Everett, M Yoganathan, K Luo, HR Renshaw, SA Ingham, PW AF Wang, Xingang Robertson, Anne L. Li, Jingyu Chai, Ruth Jinfen Haishan, Wang Sadiku, Pranvera Ogryzko, Nikolay V. Everett, Martin Yoganathan, Kanagasundaram Luo, Hongbo Robert Renshaw, Stephen A. Ingham, Philip W. TI Inhibitors of neutrophil recruitment identified using transgenic zebrafish to screen a natural product library SO DISEASE MODELS & MECHANISMS LA English DT Article DE Neutrophil; Recruitment; Migration; Drug screen; Zebrafish ID HYDROGEN-PEROXIDE; MOTILITY; INFLAMMATION; TISSUE; CHEMOTAXIS; RESOLUTION; POLARITY AB Cell migration is fundamental to the inflammatory response, but uncontrolled cell migration and excess recruitment of neutrophils and other leukocytes can cause damage to the tissue. Here we describe the use of an in vivo model - the Tg(mpx:GFP)(i114) zebrafish line, in which neutrophils are labelled by green fluorescent protein (GFP) - to screen a natural product library for compounds that can affect neutrophil migratory behaviour. Among 1040 fungal extracts screened, two were found to inhibit neutrophil migration completely. Subfractionation of these extracts identified sterigmatocystin and antibiotic PF1052 as the active components. Using the EZ-TAXIScan chemotaxis assay, both compounds were also found to have a dosage-dependent inhibitory effect on murine neutrophil migration. Furthermore, neutrophils treated with PF1052 failed to form pseudopods and appeared round in shape, suggesting a defect in PI3-kinase (PI3K) signalling. We generated a transgenic neutrophil-specific PtdIns(3,4,5)P-3 (PIP3) reporter zebrafish line, which revealed that PF1052 does not affect the activation of PI3K at the plasma membrane. In human neutrophils, PF1052 neither induced apoptosis nor blocked AKT phosphorylation. In conclusion, we have identified an antibiotic from a natural product library with potent antiinflammatory properties, and have established the utility of the mpx: GFP transgenic zebrafish for high-throughput in vivo screens for novel inhibitors of neutrophil migration. C1 [Wang, Xingang; Chai, Ruth Jinfen; Haishan, Wang; Ingham, Philip W.] Inst Mol & Cell Biol, Proteos 138673, Singapore. [Wang, Xingang] Tianjin Int Joint Acad Biotechnol & Med, High Throughput Mol Drug Discovery Ctr, Tianjin 300457, Peoples R China. [Robertson, Anne L.; Sadiku, Pranvera; Ogryzko, Nikolay V.; Renshaw, Stephen A.; Ingham, Philip W.] Univ Sheffield, MRC Ctr Dev & Biomed Genet, Western Bank, Sheffield S10 2TN, S Yorkshire, England. [Robertson, Anne L.; Sadiku, Pranvera; Renshaw, Stephen A.] Univ Sheffield, Dept Infect & Immun, Sheffield S10 2JF, S Yorkshire, England. [Li, Jingyu; Luo, Hongbo Robert] Harvard Univ, Dana Farber Harvard Canc Ctr, Sch Med, Dept Pathol, Boston, MA 02215 USA. [Li, Jingyu] Nankai Univ, Coll Life Sci, Dept Genet & Cell Biol, Tianjin Key Lab Prot Sci, Tianjin 300071, Peoples R China. [Everett, Martin; Yoganathan, Kanagasundaram] MerLion Pharmaceut Pte Ltd, Singapore 117610, Singapore. [Ingham, Philip W.] Natl Univ Singapore, Dept Biol Sci, Singapore 117543, Singapore. RP Ingham, PW (reprint author), Inst Mol & Cell Biol, 61 Biopolis Dr, Proteos 138673, Singapore. EM pingham@imcb.a-star.edu.sg RI Wang, Haishan/F-4763-2015; ASTAR, IMCB/E-2320-2012; Ingham, Philip/G-9903-2011; Renshaw, Stephen/E-6192-2010 OI Wang, Haishan/0000-0002-7959-7377; Ingham, Philip/0000-0001-8224-9958; Renshaw, Stephen/0000-0003-1790-1641 FU Agency for Science Technology and Research (A*STAR); Tianjin Municipal Science and Technology Commission [13ZCZDSY03300]; MRC [G0701932]; MRC Centre Grant [G0802527]; NIH [GM076084] FX This work was supported by the Agency for Science Technology and Research (A*STAR). X. W. was also supported by Tianjin Municipal Science and Technology Commission (13ZCZDSY03300). S. A. R. is supported by an MRC Senior Clinical Fellowship (G0701932) and A. L. R. by an MRC Centre Grant to P. W. I. (G0802527). H. R. L. is supported by NIH grant GM076084. NR 22 TC 13 Z9 13 U1 0 U2 15 PU COMPANY OF BIOLOGISTS LTD PI CAMBRIDGE PA BIDDER BUILDING CAMBRIDGE COMMERCIAL PARK COWLEY RD, CAMBRIDGE CB4 4DL, CAMBS, ENGLAND SN 1754-8403 EI 1754-8411 J9 DIS MODEL MECH JI Dis. Model. Mech. PD JAN PY 2014 VL 7 IS 1 BP 163 EP 169 DI 10.1242/dmm.012047 PG 7 WC Cell Biology; Pathology SC Cell Biology; Pathology GA AD7QB UT WOS:000333457700018 PM 24291762 ER PT J AU Bachireddy, C Soule, MC Izenberg, JM Dvoryak, S Dumchev, K Altice, FL AF Bachireddy, Chethan Soule, Michael C. Izenberg, Jacob M. Dvoryak, Sergey Dumchev, Konstantin Altice, Frederick L. TI Integration of health services improves multiple healthcare outcomes among HIV-infected people who inject drugs in Ukraine SO DRUG AND ALCOHOL DEPENDENCE LA English DT Article DE HIV/AIDS; Substance abuse; Quality healthcare indicators; Opioid substitution therapy; Health services delivery; International health; Integrated healthcare; Methadone; Buprenorphine ID METHADONE-MAINTENANCE TREATMENT; OUT-OF-TREATMENT; ANTIRETROVIRAL THERAPY; OPIOID DEPENDENCE; BUPRENORPHINE TREATMENT; SUBSTITUTION THERAPY; POLICY IMPLICATIONS; USERS; TUBERCULOSIS; HIV/AIDS AB Background: People who inject drugs (PWID) experience poor outcomes and fuel HIV epidemics in middleincome countries in Eastern Europe and Central Asia. We assess integrated/co-located (ICL) healthcare for HIV-infected PWID, which despite international recommendations, is neither widely available nor empirically examined. Methods:A 2010 cross-sectional study randomly sampled 296 HIV-infected opioid-dependent PWID from two representative HIV-endemic regions in Ukraine where ICL, non-co-located (NCL) and harm reduction/outreach (HRO) settings are available. ICL settings provide onsite HIV, addiction, and tuberculosis services, NCLs only treat addiction, and HROs provide counseling, needles/syringes, and referrals, but no opioid substitution therapy (OST). The primary outcome was receipt of quality healthcare, measured using a quality healthcare indicator (QHI) composite score representing percentage of eight guidelines-based recommended indicators Met for HIV, addiction and tuberculosis treatment. The secondary outcomes were individual QHIs and health-related quality-of-life (HRQoL). Results: On average, ICL-participants had significantly higher QHI composite scores compared to NCL- and HRO-participants (71.9% versus 54.8% versus 37.0%, p<0.001) even after controlling for potential confounders. Compared to NCL-participants, ICL-participants were significantly more likely to receive antiretroviral therapy (49.5% versus 19.2%,p<0.001), especially if CD4< 200(93.8% versus 62.5% p<0.05); guideline-recommended OST dosage (57.3% versus 41.4%, p<0.05); and isoniazid preventive therapy (423% versus 11.2%, p<0.001). Subjects receiving OST had significantly higher HRQoL than those not receiving it (p<0.001); however, HRQoL did not differ significantly between ICL- and NCL-participants. Conclusions: These findings suggest that OST alone improves quality-of-life, while receiving care in integrated settings collectively and individually improves healthcare quality indicators for PWID. (C) 2013 Elsevier Ireland Ltd. All rights reserved. C1 [Bachireddy, Chethan; Izenberg, Jacob M.; Altice, Frederick L.] Yale Univ, Sch Med, Dept Med, Infect Dis Sect,AIDS Program, New Haven, CT 06510 USA. [Soule, Michael C.] Massachussetts Gen Hosp, Dept Psychiat, Boston, MA USA. [Dvoryak, Sergey] Ukrainian Inst Publ Hlth Policy, Kiev, Ukraine. [Dumchev, Konstantin] Ctr Dis Control & Prevent, Kiev, Ukraine. [Altice, Frederick L.] Yale Univ, Sch Publ Hlth, Div Epidemiol Microbial Dis, New Haven, CT USA. RP Altice, FL (reprint author), 135 Coll St,Suite 323, New Haven, CT 06510 USA. EM frederick.altice@yale.edu FU National Institutes on Drug Abuse [K24 DA0170720, R01 DA029910, R01 DA33679]; National Institutes of Health Medical Science Training Program [GM07205]; International HIV/AIDS Alliance (Ukraine); Open Society Institute; World Health Organization FX The International HIV/AIDS Alliance (Ukraine), Open Society Institute, and World Health Organization provided funds for the completion of this study. Salary and research (R01 DA029910 and R01 DA33679) oversight as well as career development support for FLA (K24 DA0170720) was also provided by the National Institutes on Drug Abuse. Additional support was provided by the National Institutes of Health Medical Science Training Program (GM07205) for JMI and CB. JMI received funding from the Yale Global Health Institute, and MCS received funding from the Infectious Diseases Society of America. The funding sources had no role in the study design, data collection or analysis, manuscript writing or revision, or decision to submit this paper for publication. NR 83 TC 21 Z9 21 U1 1 U2 4 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0376-8716 EI 1879-0046 J9 DRUG ALCOHOL DEPEN JI Drug Alcohol Depend. PD JAN 1 PY 2014 VL 134 BP 106 EP 114 DI 10.1016/j.drugalcdep.2013.09.020 PG 9 WC Substance Abuse; Psychiatry SC Substance Abuse; Psychiatry GA AC3MI UT WOS:000332425500014 PM 24128379 ER PT J AU Santos, GM Emenyonu, NI Bajunirwe, F Mocello, AR Martin, JN Vittinghoff, E Bangsberg, DR Hahn, JA AF Santos, Glenn-Milo Emenyonu, Nneka I. Bajunirwe, Francis Mocello, A. Rain Martin, Jeffrey N. Vittinghoff, Eric Bangsberg, David R. Hahn, Judith A. TI Self-reported alcohol abstinence associated with ART initiation among HIV-infected persons in rural Uganda SO DRUG AND ALCOHOL DEPENDENCE LA English DT Article DE Alcohol; HIV; Alcohol abstinence; Hazardous drinking; ART-initiation; Antiretroviral treatment; Uganda; Africa ID RANDOMIZED CONTROLLED-TRIAL; PRIMARY MEDICAL-CARE; SUB-SAHARAN AFRICA; ANTIRETROVIRAL THERAPY; BRIEF INTERVENTIONS; PROBLEM DRINKING; FISHING COMMUNITIES; SOUTHWEST UGANDA; SEXUAL-BEHAVIOR; WESTERN KENYA AB Background: There is limited data on the impact of anti-retroviral treatment (ART) initiation on alcohol consumption. We characterized predictors of abstaining from alcohol among HIV-infected individuals following ART initiation. Methods: We analyzed data from a prospective cohort of HIV-infected adults in Mbarara, Uganda with quarterly measures of self-reported alcohol consumption, socio-demographics, health status, and blood draws. We used pooled logistic regression to evaluate predictors of becoming abstinent from alcohol for at least 90 days after baseline. Results: Among the 502 participants, 108(21.5%) were current drinkers who consumed alcohol within 90 days of baseline, 206(41.0%) were former drinkers, and 188 (37.5%) were lifetime abstainers at baseline. Among current drinkers, 67 (62.0%) drank at hazardous levels. 90 of current drinkers (83.3%) abstained from alcohol at least for 90 days over 3.6 median years of follow-up [IQR 2-4.8]; of those 69 (76.7%) remained abstinent for a median duration of follow-up of 3.25 years [1.6-4.5]. Becoming abstinent was independently associated with lower baseline AUDIT score (adjusted odds ratio [AOR] 0.95 [95%CI 0.91-0.99]), baseline physical health score (AOR 0.92 [0:87-0.97]), and decreases in physical health score at follow-up visits (AOR 0.92 [0.88-0.97)). Alcohol abstinence was most likely to start immediately after ART initiation (AORs for 6 month versus 3 month visit: 0.25 [0.10-0.61]; 9 month visit or later versus 3 month visit: 0.04 [0.02-0.09]). Conclusions: We found that a large majority of drinkers starting ART reported that they became and remained abstinent from alcohol. ART initiation may be an opportune time to implement interventions for alcohol consumption and other health behaviors. (C) 2013 Elsevier Ireland Ltd. All rights reserved. C1 [Santos, Glenn-Milo; Emenyonu, Nneka I.; Mocello, A. Rain; Martin, Jeffrey N.; Vittinghoff, Eric; Hahn, Judith A.] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Santos, Glenn-Milo] San Francisco Dept Publ Hlth, San Francisco, CA USA. [Bajunirwe, Francis] Mbarara Univ Sci & Technol, Mbarara, Uganda. [Bangsberg, David R.] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Hahn, JA (reprint author), Univ Calif San Francisco, Box 0886,50 Beale St,13th Floor 335, San Francisco, CA 94143 USA. EM Judy.hahn@ucsf.edu FU U.S. National Institutes of Health [U01 CA066529, R01 MH-054907, R01 AA-018631, R36 DA-035109A] FX The authors would like to thank the participants of UARTO for taking part in this study. The study was funded by U.S. National Institutes of Health U01 CA066529, R01 MH-054907 (PI: Bangsberg), and R01 AA-018631 (PI: Hahn). The authors acknowledge the following additional sources of support: R36 DA-035109A (Santos). NR 49 TC 6 Z9 6 U1 1 U2 2 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0376-8716 EI 1879-0046 J9 DRUG ALCOHOL DEPEN JI Drug Alcohol Depend. PD JAN 1 PY 2014 VL 134 BP 151 EP 157 DI 10.1016/j.drugalcdep.2013.09.025 PG 7 WC Substance Abuse; Psychiatry SC Substance Abuse; Psychiatry GA AC3MI UT WOS:000332425500020 PM 24169501 ER PT J AU Yao, XA Choudhury, AD Yamanaka, YJ Adalsteinsson, VA Gierahn, TM Williamson, CA Lamb, CR Taplin, ME Nakabayashi, M Chabot, MS Li, TT Lee, GSM Boehm, JS Kantoff, PW Hahn, WC Wittrup, KD Love, JC AF Yao, Xiaosai Choudhury, Atish D. Yamanaka, Yvonne J. Adalsteinsson, Viktor A. Gierahn, Todd M. Williamson, Christina A. Lamb, Carla R. Taplin, Mary-Ellen Nakabayashi, Mari Chabot, Matthew S. Li, Tiantian Lee, Gwo-Shu M. Boehm, Jesse S. Kantoff, Philip W. Hahn, William C. Wittrup, K. Dane Love, J. Christopher TI Functional analysis of single cells identifies a rare subset of circulating tumor cells with malignant traits SO INTEGRATIVE BIOLOGY LA English DT Article ID BREAST-CANCER PATIENTS; PROSTATE-CANCER; MICROMETASTASES; INVASION; CARCINOMAS; MECHANISMS; METASTASES; ANTIBODIES; DORMANCY; ANTIGEN AB Ample evidence supports genetic and functional heterogeneity in primary tumors, but it remains unclear whether circulating tumor cells (CTCs) also exhibit the same hierarchical organization. We examined the functional diversity of viable, single CTCs using an array of subnanoliter wells (nanowells). The compartmentalization of single cells by nanowells allowed clonal comparison and mapping of heterogeneity of single cells or preformed clusters of cells. By measuring the short-term viability, invasiveness and secretory profiles of individual CTCs, it was evident that only a rare subset of CTCs possessed malignant traits indicative of metastatic potential in late-stage, progressing metastatic castration-resistant prostate cancer (mCRPC) patients. These CTCs were resistant to anoikis after being in the circulation, were invasive in their epithelial state, or secreted proteases capable of cleaving peptide substrates. Every CTC observed, however, did not exhibit such metastatic potential, suggesting that enumeration of CTCs alone may be insufficient to understand metastasis or stratify patients. C1 [Yao, Xiaosai; Yamanaka, Yvonne J.; Adalsteinsson, Viktor A.; Gierahn, Todd M.; Wittrup, K. Dane; Love, J. Christopher] MIT, David H Koch Inst Integrat Canc Res, Cambridge, MA 02139 USA. [Yao, Xiaosai; Yamanaka, Yvonne J.; Wittrup, K. Dane] MIT, Dept Biol Engn, Cambridge, MA 02139 USA. [Choudhury, Atish D.; Taplin, Mary-Ellen; Nakabayashi, Mari; Chabot, Matthew S.; Li, Tiantian; Lee, Gwo-Shu M.; Kantoff, Philip W.; Hahn, William C.] Dana Farber Canc Inst, Boston, MA 02215 USA. [Choudhury, Atish D.; Taplin, Mary-Ellen; Kantoff, Philip W.; Hahn, William C.] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Choudhury, Atish D.; Adalsteinsson, Viktor A.; Boehm, Jesse S.; Hahn, William C.; Love, J. Christopher] Broad Inst Harvard & MIT, Cambridge, MA 02142 USA. [Adalsteinsson, Viktor A.; Wittrup, K. Dane; Love, J. Christopher] MIT, Dept Chem Engn, Cambridge, MA 02139 USA. [Williamson, Christina A.] Lahey Hosp & Med Ctr, Dept Thorac & Cardiovasc Surg, Burlington, MA 01803 USA. [Lamb, Carla R.] Lahey Hosp & Med Ctr, Dept Intervent Pulmonol, Burlington, MA 01803 USA. RP Yao, XA (reprint author), MIT, David H Koch Inst Integrat Canc Res, 77 Massachusetts Ave, Cambridge, MA 02139 USA. EM wittrup@mit.edu; clove@mit.edu OI Boehm, Jesse/0000-0002-6795-6336; /0000-0003-2398-5896 FU Janssen Pharmaceuticals; Koch Institute from the National Cancer Institute [P30-CA14051]; A*STAR, Singapore; Prostate Cancer Foundation Young Investigator Award; DoD Physician Scientist Training Award; National Science Foundation FX J.C.L. is a Camille Dreyfus Teacher-Scholar. This work was supported by Janssen Pharmaceuticals. This work was also supported in part by the Koch Institute Support (core) Grant P30-CA14051 from the National Cancer Institute. X.Y. was supported by a fellowship from A*STAR, Singapore. A.D.C is supported by the Prostate Cancer Foundation Young Investigator Award and the DoD Physician Scientist Training Award. V.A.A. was supported in part by a graduate fellowship from the National Science Foundation. The authors dedicate this paper to the memory of Officer Sean Collier, for his caring service to the MIT community and for his sacrifice. NR 34 TC 10 Z9 11 U1 2 U2 16 PU ROYAL SOC CHEMISTRY PI CAMBRIDGE PA THOMAS GRAHAM HOUSE, SCIENCE PARK, MILTON RD, CAMBRIDGE CB4 0WF, CAMBS, ENGLAND SN 1757-9694 EI 1757-9708 J9 INTEGR BIOL-UK JI Integr. Biol. PY 2014 VL 6 IS 4 BP 388 EP 398 DI 10.1039/c3ib40264a PG 11 WC Cell Biology SC Cell Biology GA AD5ZH UT WOS:000333331800002 PM 24522233 ER PT J AU Azzalini, L Sharma, UC Ghoshhajra, BB Elmariah, S Inglessis, I Palacios, IF Abbara, S AF Azzalini, Lorenzo Sharma, Umesh C. Ghoshhajra, Brian B. Elmariah, Sammy Inglessis, Ignacio Palacios, Igor F. Abbara, Suhny TI Feasibility of C-arm computed tomography for transcatheter aortic valve replacement planning SO JOURNAL OF CARDIOVASCULAR COMPUTED TOMOGRAPHY LA English DT Article DE Cone-beam CT; C-arm CT; Aortic annulus; Aortic root; Transcatheter aortic valve implantation; Transcatheter aortic valve replacement ID 3-DIMENSIONAL TRANSESOPHAGEAL ECHOCARDIOGRAPHY; PARAVALVULAR REGURGITATION; ROTATIONAL ANGIOGRAPHY; DYNA-CT; IMPLANTATION; ANNULUS; ROOT; IMPACT AB Background: The C-arm used for fluoroscopy during transcatheter aortic valve replacement (TAVR) may also be used to acquire 3-dimensional data sets similar to multidetector row CT (MDCT). Objective: The aim of this study was to evaluate the feasibility of C-arm CT (CACT) for aortic annulus and root (AoA/R) measurements in TAVR planning compared with MDCT. Methods: Twenty patients who were studied for TAVR underwent MDCT and CACT. Two independent observers measured predicted perpendicular projection to annular plane, diameters of the aortic annulus, sinus of Valsalva, sinotubular junction and ascending aorta, distance of coronary ostia to annular plane, sinus of Valsalva height, and leaflet length. Correlation between MDCT and CACT and interobserver variability were analyzed. Results: MDCT and CACT showed strong correlation for all the measurements of the AoA/R (r ranging from 0.62 to 0.94; P between <.001 and .042) and also for the predicted perpendicular projection (left/right anterior oblique: r = 0.96, P =.002; cranial/caudal: r = 0.83, P = .043). Interobserver variability analysis showed disagreement for the measurements of the aortic annulus structures with CACT (intraclass correlation coefficient [ICC], <0.25) but not for the rest of the variables (ICC between 0.47 and 0.97). MDCT showed no interobserver variability for all the measurements (ICC between 0.45 and 0.93). Conclusions: CACT showed strong correlation with MDCT for the measurement of all AoA/R structures. However, CACT showed also important interobserver variability for the assessment of the aortic annulus. Therefore, valve sizing may not be reliably performed on the basis of CACT measurements alone. (C) 2014 Society of Cardiovascular Computed Tomography. All rights reserved. C1 [Azzalini, Lorenzo; Sharma, Umesh C.; Ghoshhajra, Brian B.; Abbara, Suhny] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. [Azzalini, Lorenzo; Elmariah, Sammy; Inglessis, Ignacio; Palacios, Igor F.] Massachusetts Gen Hosp, Ctr Heart, Boston, MA 02114 USA. [Azzalini, Lorenzo] Univ Autonoma Barcelona, Dept Med, Barcelona, Spain. [Abbara, Suhny] Univ Texas SW Med Ctr Dallas, Dept Radiol, Dallas, TX 75390 USA. RP Abbara, S (reprint author), Massachusetts Gen Hosp, Dept Radiol, 55 Fruit St,GRB 295, Boston, MA 02114 USA. EM Suhny.Abbara@utsouthwestern.edu RI Ghoshhajra, Brian/J-2114-2016 OI Ghoshhajra, Brian/0000-0002-3865-3432 NR 28 TC 4 Z9 4 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1934-5925 J9 J CARDIOVASC COMPUT JI J. Cardiovasc. Comput. Tomogr. PD JAN-FEB PY 2014 VL 8 IS 1 BP 33 EP 43 DI 10.1016/j.jcct.2013.12.001 PG 11 WC Cardiac & Cardiovascular Systems; Radiology, Nuclear Medicine & Medical Imaging SC Cardiovascular System & Cardiology; Radiology, Nuclear Medicine & Medical Imaging GA AD3ME UT WOS:000333142400006 PM 24582041 ER PT S AU Irimia, D AF Irimia, Daniel BE Piel, M Thery, M TI Cell Migration in Confined Environments SO MICROPATTERNING IN CELL BIOLOGY, PT C SE Methods in Cell Biology LA English DT Review; Book Chapter ID CANCER-CELLS AB We describe a protocol for measuring the speed of human neutrophils migrating through small. channels, in conditions of mechanical confinement comparable to those experienced by neutrophils migrating through tissues. In such conditions, we find that neutrophils move persistently, at constant speed for tens of minutes, enabling precise measurements at single cells resolution, for large number of cells. The protocol relies on microfluidic devices with small channels in which a solution of chemoattractant and a suspension of isolated neutrophils are loaded in sequence. The migration of neutrophils can be observed for several hours, starting within minutes after loading the neutrophils in the devices. The protocol is divided into four main steps: the fabrication of the microfluidic devices, the separation of neutrophils from whole blood, the preparation of the assay and cell loading, and the analysis of data. We discuss the practical steps for the implementation of the migration assays in biology labs, the adaptation of the protocols to various cell types, including cancer cells, and the supplementary device features required for precise measurements of directionality and persistence during migration. C1 [Irimia, Daniel] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA 02130 USA. [Irimia, Daniel] Shirners Hosp Children, Boston, MA USA. RP Irimia, D (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA 02130 USA. OI Irimia, Daniel/0000-0001-7347-2082 FU NIBIB NIH HHS [P41 EB002503]; NIDCR NIH HHS [R01 DE019938]; NIGMS NIH HHS [R01 GM092804] NR 20 TC 6 Z9 6 U1 0 U2 19 PU ELSEVIER ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA SN 0091-679X BN 978-0-12-800281-0 J9 METHOD CELL BIOL JI Methods Cell Biol. PY 2014 VL 121 BP 141 EP + DI 10.1016/B978-0-12-800281-0.00010-5 D2 10.1007/978-3-8349-6619-3 PG 4 WC Cell Biology SC Cell Biology GA BA2GL UT WOS:000333375700010 PM 24560508 ER PT J AU Ross, SA Allen, DN Goldstein, G AF Ross, Sylvia An Allen, Daniel N. Goldstein, Gerald TI Factor Structure of the Halstead-Reitan Neuropsychological Battery for Children: A Brief Report Supplement SO APPLIED NEUROPSYCHOLOGY-CHILD LA English DT Article DE factor analysis; Halstead-Reitan Neuropsychological Battery for Older Children; neuropsychological assessment; Reitan-Indiana Neuropsychological Battery ID OLDER CHILDREN; TESTS; PLASTICITY; VALIDITY; MOTOR AB The Halstead-Reitan Neuropsychological Battery (HRNB) is the first factor-analyzed neuropsychological battery and consists of three batteries for young children, older children, and adults. Halstead's original factor analysis extracted four factors from the adult version of the battery, which were the basis for his theory of biological intelligence. These factors were called Central Integrative Field, Abstraction, Power, and Directional. Since this original analysis, Reitan's additions to the battery, and the development of the child versions of the test, this factor-analytic research continued. An introduction and the adult literature are reviewed in Ross, Allen, and Goldstein (in press). In this supplemental article, factor-analytic studies of the HRNB with children are reviewed. It is concluded that factor analysis of the HRNB or Reitan-Indiana Neuropsychological Battery with children does not replicate the extensiveness of the adult literature, although there is some evidence that when the traditional battery for older children is used, the factor structure is similar to what is found in adult studies. Reitan's changes to the battery appear to have added factors including language and sensory-perceptual factors. When other tests and scoring methods are used in addition to the core battery, differing solutions are produced. C1 [Ross, Sylvia An; Allen, Daniel N.] Univ Nevada, Dept Psychol, Las Vegas, NV 89154 USA. [Goldstein, Gerald] VA Pittsburgh Healthcare Syst, Mental Illness Res Educ & Clin Ctr, Pittsburgh, PA USA. RP Allen, DN (reprint author), Univ Nevada, Dept Psychol, 4505 Maryland Pkwy, Las Vegas, NV 89154 USA. EM Daniel.allen@unlv.edu FU Mental Illness Research, Education, and Clinical Center, VA Pittsburgh Healthcare System; Medical Research Service, Department of Veterans Affairs FX Indebtedness is expressed to the Mental Illness Research, Education, and Clinical Center, VA Pittsburgh Healthcare System, and the Medical Research Service, Department of Veterans Affairs, for support of this research. NR 30 TC 0 Z9 0 U1 1 U2 4 PU ROUTLEDGE JOURNALS, TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXFORDSHIRE, ENGLAND SN 2162-2965 EI 2162-2973 J9 APPL NEUROPSYCH-CHIL JI Appl. Neuropsychol.-Child PY 2014 VL 3 IS 1 BP 1 EP 9 DI 10.1080/21622965.2012.695882 PG 9 WC Clinical Neurology; Psychology SC Neurosciences & Neurology; Psychology GA AD0TI UT WOS:000332946600001 PM 24236936 ER PT J AU Song, SJ Pandolfi, PP AF Song, Su Jung Pandolfi, Pier Paolo TI miR-22 in tumorigenesis SO CELL CYCLE LA English DT Editorial Material DE microRNA; metastasis; cancer; epigenetics ID MICRORNA; CANCER C1 [Song, Su Jung; Pandolfi, Pier Paolo] Harvard Univ, Beth Israel Deaconess Med Ctr, Dept Med & Pathol, Canc Genet Program,Med Sch, Boston, MA 02215 USA. RP Pandolfi, PP (reprint author), Harvard Univ, Beth Israel Deaconess Med Ctr, Dept Med & Pathol, Canc Genet Program,Med Sch, Boston, MA 02215 USA. EM ppandolf@bidmc.harvard.edu FU NCI NIH HHS [R01 CA082328] NR 8 TC 12 Z9 13 U1 1 U2 4 PU LANDES BIOSCIENCE PI AUSTIN PA 1806 RIO GRANDE ST, AUSTIN, TX 78702 USA SN 1538-4101 EI 1551-4005 J9 CELL CYCLE JI Cell Cycle PD JAN 1 PY 2014 VL 13 IS 1 BP 11 EP 12 DI 10.4161/cc.27027 PG 2 WC Cell Biology SC Cell Biology GA AA9YS UT WOS:000331449600006 PM 24231768 ER PT J AU Papaspyridakos, P Chen, CJ Chuang, SK Weber, HP AF Papaspyridakos, Panos Chen, Chun-Jung Chuang, Sung-Kiang Weber, Hans-Peter TI Implant Loading Protocols for Edentulous Patients with Fixed Prostheses: A Systematic Review and Meta-Analysis SO INTERNATIONAL JOURNAL OF ORAL & MAXILLOFACIAL IMPLANTS LA English DT Article; Proceedings Paper CT 5th International-Team-Implantology Consensus Conference CY APR 23-25, 2013 CL Bern, SWITZERLAND SP Int Team Implantol DE dental implants; edentulous patients; fixed prosthesis; immediate loading; loading protocols ID IMMEDIATELY LOADED IMPLANTS; WELDED TITANIUM BAR; CONSECUTIVELY TREATED PATIENTS; TIOBLAST DENTAL IMPLANTS; FULL-ARCH REHABILITATION; 10-YEAR FOLLOW-UP; TILTED IMPLANTS; RETROSPECTIVE ANALYSIS; TECHNICAL COMPLICATIONS; COMPLETE DENTURES AB Purpose: To report on the effect of immediate implant loading with fixed prostheses compared to early and conventional loading on implant and prosthesis survival, failure, and complications. Materials and Methods: An electronic and manual search was conducted to identify randomized controlled clinical trials (RCTs) as well as prospective and retrospective studies involving rough surface implants and implant fixed complete dental prostheses for edentulous patients. Results: The 62 studies that fulfilled the inclusion criteria featured 4 RCTs, 2 prospective case-control studies, 34 prospective cohort studies, and 22 retrospective cohort studies. These studies yielded data from 2,695 patients (2,757 edentulous arches) with 13,653 implants. Studies were grouped according to the loading protocol applied; 45 studies reported on immediate loading, 8 on early loading, and 11 on conventional loading. For the immediate loading protocol with flap surgery, the implant and prosthesis survival rates ranged from 90.1% to 100% and 93.75% to 100%, respectively (range of follow-up, 1 to 10 years). When immediate loading was combined with guided flapless implant placement, the implant survival rates ranged from 90% to 99.4%. For the early loading protocol, the implant and prosthesis survival rates ranged from 94.74% to 100% and 93.75% to 100%, respectively (range of follow-up, 1 to 10 years). For the conventional loading protocol, the implant and prosthesis survival rates ranged from 94.95% to 100% and 87.5% to 100%, respectively (range of follow-up, 2 to 15 years). No difference was identified between maxilla and mandible. Conclusions: When selecting cases carefully and using dental implants with a rough surface, immediate loading with fixed prostheses in edentulous patients results in similar implant and prosthesis survival and failure rates as early and conventional loading. For immediate loading, most of the studies recommended a minimal insertion torque of 30 Ncm. The estimated 1-year implant survival was above 99% with all three loading protocols. Caution is necessary when interpreting these results, as there are many confounding factors that affect treatment outcomes with each of the loading protocols. C1 [Papaspyridakos, Panos] Tufts Univ, Sch Dent Med, Div Postdoctoral Prosthodont, Boston, MA 02111 USA. [Papaspyridakos, Panos] Univ Athens, Sch Dent, Dept Prosthodont, Athens 11528, Greece. [Chen, Chun-Jung] Chi Mei Med Ctr, Dept Dent, Tainan, Taiwan. [Chuang, Sung-Kiang] Harvard Univ, Sch Dent Med, Dept Oral & Maxillofacial Surg, Boston, MA 02115 USA. [Chuang, Sung-Kiang] Massachusetts Gen Hosp, Dept Oral & Maxillofacial Surg, Boston, MA 02114 USA. [Weber, Hans-Peter] Tufts Univ, Sch Dent Med, Dept Prosthodont, Boston, MA 02111 USA. RP Papaspyridakos, P (reprint author), Tufts Univ, Sch Dent Med, Div Postdoctoral Prosthodont, 1 Kneeland St, Boston, MA 02111 USA. EM panpapaspyridakos@gmail.com NR 76 TC 35 Z9 35 U1 2 U2 18 PU QUINTESSENCE PUBLISHING CO INC PI HANOVER PARK PA 4350 CHANDLER DRIVE, HANOVER PARK, IL 60133 USA SN 0882-2786 EI 1942-4434 J9 INT J ORAL MAX IMPL JI Int. J. Oral Maxillofac. Implants PY 2014 VL 29 SU S BP 256 EP 270 PG 15 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA AD2KR UT WOS:000333065100017 PM 24660202 ER PT J AU Karia, PS Schmults, CD AF Karia, Pritesh S. Schmults, Chrysalyne D. TI Screening for Nodal Metastasis and Its Challenges Nodal Needles in the SCC Haystack SO JAMA DERMATOLOGY LA English DT Editorial Material ID SQUAMOUS-CELL CARCINOMA; PRIMARY CUTANEOUS MELANOMA; COMPUTED-TOMOGRAPHY; BIOPSY; MANAGEMENT; ASPIRATION; UTILITY C1 [Karia, Pritesh S.; Schmults, Chrysalyne D.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Mohs & Dermatol Surg Ctr, Boston, MA 02115 USA. [Schmults, Chrysalyne D.] Dana Farber Brigham & Womens Canc Ctr, Boston, MA USA. [Schmults, Chrysalyne D.] Brigham & Womens Hosp, Dept Dermatol, Boston, MA 02115 USA. RP Schmults, CD (reprint author), Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Dermatol, 1153 Ctr St,Ste 4349, Jamaica Plain, MA 02130 USA. EM cschmults@partners.org NR 21 TC 0 Z9 0 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA SN 2168-6068 EI 2168-6084 J9 JAMA DERMATOL JI JAMA Dermatol. PD JAN PY 2014 VL 150 IS 1 BP 16 EP 17 DI 10.1001/jamadermatol.2013.6690 PG 3 WC Dermatology SC Dermatology GA AD2CV UT WOS:000333041600004 PM 24226031 ER PT J AU Niess, MA Prochazka, A AF Niess, Meredith A. Prochazka, Allan TI Preoperative Chest X-rays A Teachable Moment SO JAMA INTERNAL MEDICINE LA English DT Editorial Material C1 [Niess, Meredith A.] Univ Colorado, Sch Med, Aurora, CO 80045 USA. [Prochazka, Allan] Denver VA Med Ctr, Dept Ambulatory Care, Denver, CO USA. RP Niess, MA (reprint author), Univ Colorado, Sch Med, Internal Med Residency Program, 12631 E 17th Ave,B177, Aurora, CO 80045 USA. EM meredith.niess@ucdenver.edu NR 5 TC 1 Z9 1 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA SN 2168-6106 EI 2168-6114 J9 JAMA INTERN MED JI JAMA Intern. Med. PD JAN PY 2014 VL 174 IS 1 BP 12 EP 12 DI 10.1001/jamainternmed.2013.10531 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA AD2EM UT WOS:000333046500004 PM 24081219 ER PT J AU Stout, NK Nekhlyudov, L Li, LL Malin, ES Ross-Degnan, D Buist, DSM Rosenberg, MA Alfisher, M Fletcher, SW AF Stout, Natasha K. Nekhlyudov, Larissa Li, Lingling Malin, Elisabeth S. Ross-Degnan, Dennis Buist, Diana S. M. Rosenberg, Marjorie A. Alfisher, Marina Fletcher, Suzanne W. TI Rapid Increase in Breast Magnetic Resonance Imaging Use Trends From 2000 to 2011 SO JAMA INTERNAL MEDICINE LA English DT Article ID MUTATION CARRIERS; HIGH-RISK; COST-EFFECTIVENESS; BRCA MUTATIONS; CANCER; MRI; WOMEN; MAMMOGRAPHY; GUIDELINES; SOCIETY AB IMPORTANCE Breast magnetic resonance imaging (MRI) is highly sensitive for detecting breast cancer. Low specificity, cost, and little evidence regarding mortality benefits, however, limit recommendations for its use to high-risk women. How breast MRI is actually used in community settings is unknown. OBJECTIVE To describe breast MRI trends and indications in a community setting. DESIGN, SETTING, AND PARTICIPANTS Retrospective cohort study at a not-for-profit health plan and multispecialty group medical practice in New England of 10 518 women aged 20 years and older enrolled in the health plan for at least 1 year who had at least 1 breast MRI between January 1, 2000, and December 31, 2011. MAIN OUTCOMES AND MEASURES Breast MRI counts were obtained from claims data. Clinical indication (screening, diagnostic evaluation, staging or treatment, or surveillance) was determined using a prediction model developed from electronic medical records on a subset of participants. Breast cancer risk status was assessed using claims data and, for the subset, also through electronic medical record review. RESULTS Breast MRI use increased more than 20-fold from 6.5 per 10 000 women in 2000 to 130.7 per 10 000 in 2009. Use then declined and stabilized to 104.8 per 10 000 by 2011. Screening and surveillance, rare indications in 2000, together accounted for 57.6% of MRI use by 2011; 30.1% had a claims-documented personal history and 51.7% a family history of breast cancer, whereas 3.5% of women had a documented genetic mutation. In the subset of women with electronic medical records who received screening or surveillance MRIs, only 21.0% had evidence of meeting American Cancer Society (ACS) criteria for breast MRI. Conversely, only 48.4% of women with documented deleterious genetic mutations received breast MRI screening. CONCLUSIONS AND RELEVANCE Breast MRI use increased steeply over 10 years and then stabilized, especially for screening and surveillance among women with family or personal history of breast cancer; most women receiving screening and surveillance breast MRIs lacked documented evidence of meeting ACS criteria, and many women with mutations were not screened. Efforts are needed to ensure that breast MRI use and documentation are focused on those women who will benefit most. C1 [Stout, Natasha K.; Nekhlyudov, Larissa; Li, Lingling; Ross-Degnan, Dennis; Fletcher, Suzanne W.] Harvard Univ, Sch Med, Dept Populat Med, Boston, MA 02215 USA. [Stout, Natasha K.; Nekhlyudov, Larissa; Li, Lingling; Ross-Degnan, Dennis; Fletcher, Suzanne W.] Harvard Pilgrim Hlth Care Inst, Boston, MA USA. [Nekhlyudov, Larissa] Harvard Vanguard Med Associates, Dept Med, Boston, MA USA. [Malin, Elisabeth S.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Buist, Diana S. M.] Grp Hlth Res Inst, Seattle, WA USA. [Rosenberg, Marjorie A.] Univ Wisconsin, Dept Actuarial Sci Risk Management & Insurance, Madison, WI 53706 USA. [Rosenberg, Marjorie A.] Univ Wisconsin, Dept Biostat & Med Informat, Madison, WI 53706 USA. [Alfisher, Marina] Harvard Vanguard Med Associates, Dept Radiol, Boston, MA USA. RP Stout, NK (reprint author), Harvard Univ, Sch Med, Harvard Pilgrim Hlth Care Inst, Dept Populat Med, 133 Brookline Ave,6th Floor, Boston, MA 02215 USA. EM natasha_stout@hms.harvard.edu FU American Cancer Society [118223-MRSG-10-002-01-CPHPS]; Clinical and Translational Science Award program of the National Center for Research Resources, National Institutes of Health [1UL1RR025011] FX This research was supported by Mentored Research Scholar Grant 118223-MRSG-10-002-01-CPHPS from the American Cancer Society to Dr Stout and by grant 1UL1RR025011 from the Clinical and Translational Science Award program of the National Center for Research Resources, National Institutes of Health, to Dr Rosenberg. NR 42 TC 25 Z9 26 U1 0 U2 10 PU AMER MEDICAL ASSOC PI CHICAGO PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA SN 2168-6106 EI 2168-6114 J9 JAMA INTERN MED JI JAMA Intern. Med. PD JAN PY 2014 VL 174 IS 1 BP 114 EP 121 DI 10.1001/jamainternmed.2013.11958 PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA AD2EM UT WOS:000333046500026 PM 24247482 ER PT J AU Brownell, J Wang, J Smith, A Stephens, C Hsia, RY AF Brownell, Julia Wang, Joseph Smith, Alexander Stephens, Caroline Hsia, Renee Y. TI Trends in Emergency Department Visits for Ambulatory Care Sensitive Conditions by Elderly Nursing Home Residents, 2001 to 2010 SO JAMA INTERNAL MEDICINE LA English DT Letter C1 [Brownell, Julia; Hsia, Renee Y.] Univ Calif San Francisco, Dept Emergency Med, San Francisco, CA 94110 USA. [Wang, Joseph] Univ Calif San Francisco, Sch Med, San Francisco, CA 94110 USA. [Smith, Alexander] Univ Calif San Francisco, Dept Med, Div Geriatr, San Francisco, CA 94110 USA. [Smith, Alexander; Stephens, Caroline] Univ Calif San Francisco, San Francisco Vet Affairs Med Ctr, San Francisco, CA 94110 USA. [Stephens, Caroline] Univ Calif San Francisco, Dept Community Hlth Syst, San Francisco, CA 94110 USA. RP Brownell, J (reprint author), Univ Calif San Francisco, Dept Emergency Med, 1001 Potrero Ave,Room 1E2, San Francisco, CA 94110 USA. EM julia.brownell@emergency.ucsf.edu FU NCATS NIH HHS [KL2 TR000143] NR 5 TC 8 Z9 8 U1 2 U2 7 PU AMER MEDICAL ASSOC PI CHICAGO PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA SN 2168-6106 EI 2168-6114 J9 JAMA INTERN MED JI JAMA Intern. Med. PD JAN PY 2014 VL 174 IS 1 BP 156 EP 158 DI 10.1001/jamainternmed.2013.11821 PG 4 WC Medicine, General & Internal SC General & Internal Medicine GA AD2EM UT WOS:000333046500044 PM 24166099 ER PT J AU Stickrath, C Anderson, M AF Stickrath, Chad Anderson, Mel TI Considerations for Attending Rounds Reply SO JAMA INTERNAL MEDICINE LA English DT Letter C1 [Stickrath, Chad; Anderson, Mel] Univ Colorado, Sch Med, Dept Med, Denver, CO USA. [Stickrath, Chad; Anderson, Mel] Denver Vet Affairs Med Ctr, Med Serv, Denver, CO USA. RP Stickrath, C (reprint author), Univ Colorado, Sch Med, Denver VA Med Ctr, Med Serv, 1055 Clermont St,Box 111, Denver, CO 80220 USA. EM Chad.stickrath@va.gov NR 6 TC 0 Z9 0 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA SN 2168-6106 EI 2168-6114 J9 JAMA INTERN MED JI JAMA Intern. Med. PD JAN PY 2014 VL 174 IS 1 BP 162 EP 162 DI 10.1001/jamainternmed.2013.11085 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA AD2EM UT WOS:000333046500048 PM 24394927 ER PT J AU Clapp, JD Baker, AS Litwack, SD Sloan, DM Beck, JG AF Clapp, Joshua D. Baker, Aaron S. Litwack, Scott D. Sloan, Denise M. Beck, J. Gayle TI Properties of the Driving Behavior Survey among individuals with motor vehicle accident-related posttraumatic stress disorder SO JOURNAL OF ANXIETY DISORDERS LA English DT Article DE Driving anxiety; Driving behavior; Motor vehicle accident; Posttraumatic stress disorder; Assessment ID PTSD SYMPTOM SEVERITY; ANXIETY DISORDERS; COMBAT VETERANS; DRIVER STRESS; FOLLOW-UP; SURVIVORS; SAMPLE; SCALE; PERFORMANCE; ANGER AB Data suggest anxious drivers may engage in problematic behaviors that place themselves and others at increased risk of negative traffic events. Three domains of problematic behavior - exaggerated safety/caution, performance deficits, and hostile/aggressive behaviors - previously were identified during development of the Driving Behavior Survey (DBS), a novel measure of anxiety-related behavior. Extending this research, the current study examined the psychometric properties of DBS scores among individuals with posttraumatic stress disorder (PTSD) subsequent to motor vehicle trauma (N = 40). Internal consistencies and 12-week test-retest reliabilities for DBS scales ranged from good to excellent. Comparison of scores to normative student data indicated dose-response relationships for safety/caution and performance deficit subscales, with increased frequency of anxious behavior occurring within the PTSD sample. Associations With standard clinical measures provide additional evidence for anxiety-related driving behavior as a unique marker of functional impairment, distinct from both avoidance and disorder-specific symptoms. (C) 2013 Elsevier Ltd. All rights reserved. C1 [Clapp, Joshua D.] Univ Wyoming, Dept Psychol, Laramie, WY 82071 USA. [Baker, Aaron S.; Litwack, Scott D.; Sloan, Denise M.] VA Boston Healthcare Syst, Natl Ctr PTSD, Boston, MA 02130 USA. [Baker, Aaron S.; Litwack, Scott D.; Sloan, Denise M.] Boston Univ, Sch Med, Boston, MA 02130 USA. [Beck, J. Gayle] Univ Memphis, Dept Psychol, Memphis, TN 38152 USA. RP Clapp, JD (reprint author), Univ Wyoming, Dept Psychol, 1000 E Univ Ave, Laramie, WY 82071 USA. EM jclapp@uwyo.edu; Aaron.Baker2@va.gov; Scott.Litwack@va.gov; Denise.Sloan@va.gov; jgbeck@memphis.edu FU NIMH NIH HHS [R34 MH077658, T32 MH019836, R34MH077658-02, T32MH019836] NR 52 TC 3 Z9 4 U1 1 U2 11 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0887-6185 EI 1873-7897 J9 J ANXIETY DISORD JI J. Anxiety Disord. PD JAN PY 2014 VL 28 IS 1 BP 1 EP 7 DI 10.1016/j.janxdis.2013.10.008 PG 7 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA AD2MT UT WOS:000333070500001 PM 24325891 ER PT J AU Dutton, CE Adams, T Bujarski, S Badour, CL Feldner, MT AF Dutton, Courtney E. Adams, Thomas Bujarski, Sarah Badour, Christal L. Feldner, Matthew T. TI Posttraumatic stress disorder and alcohol dependence: Individual and combined associations with social network problems SO JOURNAL OF ANXIETY DISORDERS LA English DT Article DE PTSD; Alcohol dependence; Social support; Social conflict ID NATIONAL COMORBIDITY SURVEY; SUBSTANCE-ABUSE PATIENTS; REPLICATION NCS-R; AGGRESSION PERPETRATION; INTIMATE PARTNER; PTSD; SYMPTOMS; SUPPORT; TRAUMA; VETERANS AB People with either posttraumatic stress disorder (PTSD) or alcohol dependence (AD) are apt to report problems in their social networks, including low perceived support and elevated conflict. However, little research has examined social networks among people with comorbid PTSD/AD despite evidence suggesting these two conditions commonly co-occur and are linked to particularly severe problems. To test the hypothesis that people with comorbid PTSD/AD experience particularly elevated social network problems, individuals with lifetime diagnoses of PTSD, AD, comorbid PTSD/AD, or no lifetime history of Axis I psychopathology in the National Comorbidity Survey-Replication were compared on four dimensions of social networks: (I) Closeness, (2) Conflict, (3) Family Support, and (4) Apprehension. Persons with PTSD, AD, or comorbid PTSD/AD endorsed more problems with the Conflict, Family Support, and Apprehension factors compared to people with no history of Axis I psychopathology. Moreover, individuals with comorbid PTSD/AD endorsed greater Apprehension and significantly less Family Support compared to the other three groups. Results suggest people with comorbid PTSD/AD experience increased problems with their family as well as greater concerns about enlisting social support than even people with PTSD or AD alone. Treatments for people suffering from comorbid PTSD/AD should consider assessing for and possibly targeting family support and apprehension about being close to others. (C) 2013 Elsevier Ltd. All rights reserved. C1 [Dutton, Courtney E.; Adams, Thomas; Bujarski, Sarah; Badour, Christal L.; Feldner, Matthew T.] Univ Arkansas, Fayetteville, AR 72701 USA. [Adams, Thomas; Badour, Christal L.] Med Univ S Carolina, Charleston, SC 29425 USA. [Adams, Thomas; Badour, Christal L.] Ralph H Johnson Vet Affairs Med Ctr, Charleston, SC USA. [Feldner, Matthew T.] Laureate Inst Brain Res, Tulsa, OK 74136 USA. RP Dutton, CE (reprint author), Univ Arkansas, Dept Psychol Sci, 216 Mem Hall, Fayetteville, AR 72701 USA. EM cedutton@uark.edu; mfeldne@uark.edu NR 62 TC 6 Z9 6 U1 2 U2 11 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0887-6185 EI 1873-7897 J9 J ANXIETY DISORD JI J. Anxiety Disord. PD JAN PY 2014 VL 28 IS 1 BP 67 EP 74 DI 10.1016/j.janxdis.2013.11.010 PG 8 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA AD2MT UT WOS:000333070500009 PM 24462749 ER PT J AU Li, ZP Boyd, D Reindl, M Goldberg, MB AF Li, Zaoping Boyd, Dana Reindl, Martin Goldberg, Marcia B. TI Identification of YidC Residues That Define Interactions with the Sec Apparatus SO JOURNAL OF BACTERIOLOGY LA English DT Article ID MEMBRANE-PROTEIN INSERTION; ESCHERICHIA-COLI YIDC; F1F0 ATP SYNTHASE; TRANSLOCATION MACHINERY; ENDOPLASMIC-RETICULUM; TRANSLATING RIBOSOME; CYTOPLASMIC MEMBRANE; CONDUCTING CHANNEL; PERIPLASMIC DOMAIN; CATALYTIC CYCLE AB In bacteria, a subset of membrane proteins insert into the membrane via the Sec apparatus with the assistance of the widely conserved essential membrane protein insertase YidC. After threading into the SecYEG translocon, transmembrane segments of nascent proteins are thought to exit the translocon via a lateral gate in SecY, where YidC facilitates their transfer into the lipid bilayer. Interactions between YidC and components of the Sec apparatus are critical to its function. The first periplasmic loop of YidC interacts directly with SecF. We sought to identify the regions or residues of YidC that interact with SecY or with additional components of the Sec apparatus other than SecDF. Using a synthetic lethal screen, we identified residues of YidC that, when mutated, led to dependence on SecDF for viability. Each residue identified is highly conserved among YidC homologs; most lie within transmembrane domains. Overexpression of SecY in the presence of two YidC mutants partially rescued viability in the absence of SecDF, suggesting that the corresponding wild-type YidC residues (G355 and M471) participate in interactions, direct or indirect, with SecY. Staphylococcus aureus YidC complemented depletion of YidC, but not of SecDF, in Escherichia coli. G355 of E. coli YidC is invariant in S. aureus YidC, suggesting that this highly conserved glycine serves a conserved function in interactions with SecY. This study demonstrates that transmembrane residues are critical in YidC interactions with the Sec apparatus and provides guidance on YidC residues of interest for future structure-function analyses. C1 [Li, Zaoping; Goldberg, Marcia B.] Massachusetts Gen Hosp, Dept Med, Div Infect Dis, Cambridge, MA USA. [Boyd, Dana; Goldberg, Marcia B.] Harvard Univ, Sch Med, Dept Microbiol & Immunobiol, Boston, MA USA. [Reindl, Martin] Harvard Univ, Cambridge, MA 02138 USA. RP Goldberg, MB (reprint author), Massachusetts Gen Hosp, Dept Med, Div Infect Dis, Cambridge, MA USA. EM marcia.goldberg@mgh.harvard.edu FU NIH [R01 AI035817]; Executive Committee on Research, Massachusetts General Hospital FX We are grateful to J. Beckwith, T. Bernhardt, R. Dalbey, M. Mueller, and T. Rapoport for providing reagents. This work was supported by NIH R01 AI035817 (to M.B.G.) and funding from the Executive Committee on Research, Massachusetts General Hospital (to M.B.G.). NR 54 TC 3 Z9 3 U1 1 U2 5 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0021-9193 EI 1098-5530 J9 J BACTERIOL JI J. Bacteriol. PD JAN PY 2014 VL 196 IS 2 BP 367 EP 377 DI 10.1128/JB.01095-13 PG 11 WC Microbiology SC Microbiology GA AC6ID UT WOS:000332624300017 PM 24187090 ER PT J AU Folmer, RL Theodoroff, SM Martin, WH Shi, YB AF Folmer, Robert L. Theodoroff, Sarah M. Martin, William Hal Shi, Yongbing TI Experimental, Controversial, and Futuristic Treatments for Chronic Tinnitus SO JOURNAL OF THE AMERICAN ACADEMY OF AUDIOLOGY LA English DT Review DE Auditory rehabilitation; management; tinnitus; therapy; treatment ID TRANSCRANIAL MAGNETIC STIMULATION; PLACEBO-CONTROLLED TRIAL; DEEP BRAIN-STIMULATION; HAIR CELL REGENERATION; 8TH CRANIAL NERVE; LOW-LEVEL LASER; MICROVASCULAR DECOMPRESSION; DOUBLE-BLIND; SUBJECTIVE TINNITUS; AUDITORY-CORTEX AB Background: Because chronic tinnitus is a condition that negatively impacts the quality of life of millions of people worldwide, a safe and effective treatment for tinnitus has been sought for millennia. However, effective treatments for tinnitus are greatly outnumbered by ineffective strategies, medications, devices, and surgeries that continue to be developed and promoted for the condition. Purpose: This article describes and critiques experimental, controversial, and potential treatments for chronic tinnitus. The purpose of this review is to provide information that should help patients and clinicians to select tinnitus treatment and management strategies most likely to be effective for each set of symptoms and circumstances. Research Design: PubMed and MEDLINE databases (National Center for Biotechnology Information, U.S. National Library of Medicine) were searched for the term tinnitus in articles published from 1940 to 2012. Other historical documents and publications were also reviewed as needed for particular topics. Study Sample: Studies included in this review were selected to represent a sampling of treatment methodologies that have been used for tinnitus. Data Collection and Analysis: Due to the heterogeneity of the studies reviewed, it was not appropriate to perform a meta-analysis. A selective review of the literature was conducted to summarize and critique published research results. Results: Most invasive treatments for tinnitus should be avoided because (1) at best, there is scant evidence that any of these treatments is effective, and (2) the risk to patients for most invasive procedures is much greater than the risk posed by the tinnitus perception. Effective and non-invasive treatments for tinnitus include acoustic therapy (which includes hearing aids and other types of environmental sound enrichment); cognitive-behavioral therapy; psychological counseling; hypnosis; biofeedback; and relaxation training. Over-the-counter or prescription medications may be used as needed to facilitate sleep and to reduce anxiety, depression, or obsessive-compulsiveness. Conclusions: Patients and clinicians should be especially cautious when considering invasive (and potentially harmful) treatments for tinnitus, which is a non-life-threatening symptom. Unless well-designed clinical trials verify that a tinnitus therapy demonstrates effectiveness above and beyond the placebo effect, consumers should be wary of medications, devices, or procedures promoted as a "cure." Although a true cure for tinnitus has not yet been found, effective and noninvasive tinnitus management strategies are available now. If progress is made to medically (or genetically) treat sensorineural hearing loss in humans, this breakthrough should also help to simultaneously reduce the perception of tinnitus for many patients. C1 [Folmer, Robert L.; Theodoroff, Sarah M.] Portland VA Med Ctr, Natl Ctr Rehabil Auditory Res, Portland, OR 97239 USA. [Folmer, Robert L.; Theodoroff, Sarah M.; Martin, William Hal; Shi, Yongbing] Oregon Hlth & Sci Univ, Dept Otolaryngol, Portland, OR 97201 USA. RP Folmer, RL (reprint author), Portland VA Med Ctr, Natl Ctr Rehabil Auditory Res, 3710 SW US Vet Hosp Rd NCRAR, Portland, OR 97239 USA. EM Robert.Folmer@va.gov FU U.S. Department of Veterans Affairs Rehabilitation Research and Development (RR&D) Service (VA RRD) [C74481]; National Center for Rehabilitative Auditory Research; [C9230C] FX This research was supported by a grant from the U.S. Department of Veterans Affairs Rehabilitation Research and Development (RR&D) Service (VA RR&D grant #C74481). Additional support was provided by the National Center for Rehabilitative Auditory Research (funded by VA RR&D grant #C9230C) at Portland VA Medical Center. NR 145 TC 7 Z9 7 U1 3 U2 40 PU AMER ACAD AUDIOLOGY PI RESTON PA 11730 PLAZA DR, STE 300, RESTON, VA 20190 USA SN 1050-0545 EI 2157-3107 J9 J AM ACAD AUDIOL JI J. Am. Acad. Audiol. PD JAN PY 2014 VL 25 IS 1 SI SI BP 106 EP 125 DI 10.3766/jaaa.25.1.7 PG 20 WC Audiology & Speech-Language Pathology; Otorhinolaryngology SC Audiology & Speech-Language Pathology; Otorhinolaryngology GA AC7BX UT WOS:000332683100007 PM 24622863 ER PT J AU Nazar, H Al-Mutawa, S Ariga, J Soparkar, P Mascarenhas, AK AF Nazar, Huda Al-Mutawa, Sabiha Ariga, Jitendra Soparkar, Pramod Mascarenhas, Ana Karina TI Caries Prevalence, Oral Hygiene, and Oral Health Habits of Kuwaiti Infants and Toddlers SO MEDICAL PRINCIPLES AND PRACTICE LA English DT Article DE Dental caries; Oral hygiene; Tooth brushing; Night feeding; Bottle-feeding; Cavitated lesions; Noncavitated lesions ID PRIMARY TEETH AB Objective: The purpose of this study was to describe the oral health, oral hygiene, and oral health habits of Kuwaiti infants and toddlers. Subjects and Methods: This cross-sectional study of a convenience sample included 336 infants and toddlers (156 females and 180 males). The teeth of the infants and toddlers were examined using a mirror and a light source. Oral hygiene was recorded, and then all teeth were cleaned with gauze and examined for caries. Parents were interviewed regarding their children's feeding habits, brushing or tooth cleaning, and night feeding. The evaluation criteria for caries were sound teeth, noncavitated lesions, cavitated lesions, filled teeth, and missing teeth. Results: The mean age was 11.1 +/- 2.4 months (range 2-23). Of the 336 subjects, 247 (73%) had good oral hygiene, 64 (19%) had parents who brushed or cleaned their infants' and toddlers' teeth; 288 (86%) were bottle-fed, and 290 (86%) were also night fed. The mean number of teeth upon examination was 4.6 +/- 2.7 (range 2-8). Three percent of the infants and tod-dlers had caries. Cavitated lesions were present in 6 patients (1.8%), while 4 (1.2%) had noncavitated lesions. The mean d1d2t (caries teeth: noncavitated lesions and cavitated lesions) was 0.03 +/- 0.3, and the mean d1d2s (carious surfaces) was 0.07 +/- 0.5. Conclusion: The caries prevalence and severity was low in infants and toddlers. However, poor oral health practices and habits as well as unhealthy feeding practices that could affect the future caries prevalence were noted. (C) 2013 S. Karger AG, Basel C1 [Nazar, Huda; Al-Mutawa, Sabiha] Minist Hlth, Natl Sch Oral Hlth Program, Kuwait, Kuwait. [Al-Mutawa, Sabiha] Minist Hlth, Dept Dent, Kuwait, Kuwait. [Ariga, Jitendra] Natl Sch Oral Hlth Program, Kuwait, Kuwait. [Soparkar, Pramod] Forsyth Inst, Cambridge, MA USA. [Mascarenhas, Ana Karina] Nova SE Univ, Coll Dent Med, Ft Lauderdale, FL 33314 USA. RP Nazar, H (reprint author), Minist Hlth, Dept Dent, Sch Oral Hlth Program, POB 5338, Salmiya 22064, Kuwait. EM hudanazar@yahoo.com NR 12 TC 3 Z9 3 U1 0 U2 4 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 1011-7571 EI 1423-0151 J9 MED PRIN PRACT JI Med. Princ. Pract. PY 2014 VL 23 IS 2 BP 125 EP 128 DI 10.1159/000356866 PG 4 WC Medicine, General & Internal SC General & Internal Medicine GA AD1CG UT WOS:000332970800004 PM 24356643 ER PT J AU Hiddingh, L Tannous, BA Teng, J Tops, B Jeuken, J Hulleman, E Boots-Sprenger, SH Vandertop, WP Noske, DP Kaspers, GJL Wesseling, P Wurdinger, T AF Hiddingh, Lotte Tannous, Bakhos A. Teng, Jian Tops, Bas Jeuken, Judith Hulleman, Esther Boots-Sprenger, Sandra H. Vandertop, W. Peter Noske, David P. Kaspers, Gertjan J. L. Wesseling, Pieter Wurdinger, Thomas TI EFEMP1 induces gamma-secretase/Notch-mediated temozolomide resistance in glioblastoma SO ONCOTARGET LA English DT Article DE Temozolomide resistance; glioblastoma; EFEMP1; gamma-secretase; Notch; GSI ID MISMATCH REPAIR; IN-VIVO; O-6-METHYLGUANINE-DNA METHYLTRANSFERASE; ALKYLATING-AGENTS; GENE-EXPRESSION; ADJUVANT TEMOZOLOMIDE; TISSUE LOCALIZATION; TUMOR PROGRESSION; MALIGNANT GLIOMA; MSH6 MUTATIONS AB Glioblastoma is the most common malignant primary brain tumor. Temozolomide (TMZ) is the standard chemotherapeutic agent for this disease. However, intrinsic and acquired TMZ-resistance represents a major obstacle for this therapy. In order to identify factors involved in TMZ-resistance, we engineered different TMZ-resistant glioblastoma cell lines. Gene expression analysis demonstrated that EFEMP1, an extracellular matrix protein, is associated with TMZ-resistant phenotype. Silencing of EFEMP1 in glioblastoma cells resulted in decreased cell survival following TMZ treatment, whereas overexpression caused TMZ-resistance. EFEMP1 acts via multiple signaling pathways, including.-secretase-mediated activation of the Notch pathway. We show that inhibition of.-secretase by RO4929097 causes at least partial sensitization of glioblastoma cells to temozolomide in vitro and in vivo. In addition, we show that EFEMP1 expression levels correlate with survival in TMZ-treated glioblastoma patients. Altogether our results suggest EFEMP1 as a potential therapeutic target to overcome TMZ-resistance in glioblastoma. C1 [Hiddingh, Lotte; Vandertop, W. Peter; Noske, David P.; Wurdinger, Thomas] Vrije Univ Amsterdam Med Ctr, Dept Neurosurg, Amsterdam, Netherlands. [Hiddingh, Lotte; Hulleman, Esther; Kaspers, Gertjan J. L.] Vrije Univ Amsterdam Med Ctr, Dept Pediat Oncol, Amsterdam, Netherlands. [Hiddingh, Lotte; Hulleman, Esther; Noske, David P.; Wurdinger, Thomas] Vrije Univ Amsterdam Med Ctr, Neurooncol Res Grp, Canc Ctr Amsterdam, Amsterdam, Netherlands. [Tannous, Bakhos A.; Teng, Jian; Wurdinger, Thomas] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. [Tannous, Bakhos A.; Teng, Jian; Wurdinger, Thomas] Harvard Univ, Sch Med, Boston, MA USA. [Tops, Bas; Jeuken, Judith; Wesseling, Pieter] Radboud Univ Nijmegen, Med Ctr, Dept Pathol, Nijmegen, Netherlands. [Wesseling, Pieter] Vrije Univ Amsterdam Med Ctr, Dept Pathol, Amsterdam, Netherlands. [Jeuken, Judith] PAMM, Dept Pathol, Eindhoven, Netherlands. RP Wurdinger, T (reprint author), Vrije Univ Amsterdam Med Ctr, Dept Neurosurg, Amsterdam, Netherlands. EM t.wurdinger@vumc.nl RI Wesseling, P./H-8114-2014 OI Wesseling, P./0000-0001-5453-5201 FU NINDS NIH HHS [P30 NS045776] NR 57 TC 13 Z9 13 U1 0 U2 2 PU IMPACT JOURNALS LLC PI ALBANY PA 6211 TIPTON HOUSE, STE 6, ALBANY, NY 12203 USA SN 1949-2553 J9 ONCOTARGET JI Oncotarget PD JAN PY 2014 VL 5 IS 2 BP 363 EP 374 PG 12 WC Oncology; Cell Biology SC Oncology; Cell Biology GA AC7IC UT WOS:000332700400005 PM 24495907 ER PT J AU Gameiro, SR Jammeh, ML Wattenberg, MM Tsang, KY Ferrone, S Hodge, JW AF Gameiro, Sofia R. Jammeh, Momodou L. Wattenberg, Max M. Tsang, Kwong Y. Ferrone, Soldano Hodge, James W. TI Radiation-induced immunogenic modulation of tumor enhances antigen processing and calreticulin exposure, resulting in enhanced T-cell killing SO ONCOTARGET LA English DT Article DE radiation; immunogenic modulation; antigen-processing machinery; calreticulin; CTL; ER stress; PERK; TAP1; TAP2; calnexin; tapasin; LMP2; LMP7; LMP10 ID HUMAN CARCINOEMBRYONIC ANTIGEN; ENDOPLASMIC-RETICULUM; IMMUNE-SYSTEM; ANTICANCER CHEMOTHERAPY; MONOCLONAL-ANTIBODIES; FLOW-CYTOMETRY; DEATH; EXPRESSION; PHENOTYPE; THERAPY AB Radiation therapy (RT) is used for local tumor control through direct killing of tumor cells. Radiation-induced cell death can trigger tumor antigen-specific immune responses, but these are often noncurative. Radiation has been demonstrated to induce immunogenic modulation (IM) in various tumor types by altering the biology of surviving cells to render them more susceptible to T cell-mediated killing. Little is known about the mechanism(s) underlying IM elicited by sub-lethal radiation dosing. We have examined the molecular and immunogenic consequences of radiation exposure in breast, lung, and prostate human carcinoma cells. Radiation induced secretion of ATP and HMGB1 in both dying and surviving tumor cells. In vitro and in vivo tumor irradiation induced significant upregulation of multiple components of the antigen-processing machinery and calreticulin cell-surface expression. Augmented CTL lysis specific for several tumor-associated antigens was largely dictated by the presence of calreticulin on the surface of tumor cells and constituted an adaptive response to endoplasmic reticulum stress, mediated by activation of the unfolded protein response. This study provides evidence that radiation induces a continuum of immunogenic alterations in tumor biology, from immunogenic modulation to immunogenic cell death. We also expand the concept of immunogenic modulation, where surviving tumor cells recovering from radiation-induced endoplasmic reticulum stress become more sensitive to CTL killing. These observations offer a rationale for the combined use of radiation with immunotherapy, including for patients failing RT alone. C1 [Gameiro, Sofia R.; Jammeh, Momodou L.; Wattenberg, Max M.; Tsang, Kwong Y.; Hodge, James W.] NCI, Lab Tumor Immunol & Biol, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. [Ferrone, Soldano] Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. RP Hodge, JW (reprint author), NCI, Lab Tumor Immunol & Biol, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. EM jh241d@nih.gov RI Hodge, James/D-5518-2015 OI Hodge, James/0000-0001-5282-3154 FU Intramural Research Program of the Center for Cancer Research, National Cancer Institute, National Institutes of Health; PHS [R01 CA110249]; National Cancer Institute FX This research was supported by the Intramural Research Program of the Center for Cancer Research, National Cancer Institute, National Institutes of Health, and by the PHS grant R01 CA110249 (S.F.), awarded by the National Cancer Institute. NR 50 TC 72 Z9 75 U1 1 U2 8 PU IMPACT JOURNALS LLC PI ALBANY PA 6211 TIPTON HOUSE, STE 6, ALBANY, NY 12203 USA SN 1949-2553 J9 ONCOTARGET JI Oncotarget PD JAN PY 2014 VL 5 IS 2 BP 403 EP 416 PG 14 WC Oncology; Cell Biology SC Oncology; Cell Biology GA AC7IC UT WOS:000332700400008 PM 24480782 ER PT J AU Farrell, SR Sargoy, A Brecha, NC Barnes, S AF Farrell, Spring R. Sargoy, Allison Brecha, Nicholas C. Barnes, Steven TI Modulation of voltage-gated Ca2+ channels in rat retinal ganglion cells by gabapentin SO VISUAL NEUROSCIENCE LA English DT Article DE alpha(2)delta Ca channel subunit; Alpha2delta subunit; Cacna2d1; Retinal ganglion cell; Gabapentin ID CALCIUM-CHANNEL; ALPHA(2)DELTA SUBUNIT; PROTEIN-KINASE; NEURONS; CURRENTS; TRAFFICKING; PREGABALIN; LOCALIZATION; INHIBITION; RECEPTORS AB The alpha (2) delta auxiliary subunits of voltage-gated Ca2+ channels (VGCCs) are important modulators of VGCC function. Gabapentin interacts with alpha (2) delta (1) and alpha (2) delta (2) subunits and is reported to reduce Ca2+ channel current amplitude (I (Ca)). This study aimed to determine the effects of gabapentin on VGCCs in retinal ganglion cells (RGCs). Whole cell patch clamp was used to record I (Ca) in isolated RGCs, and calcium imaging was used to measure Ca2+ transients from RGCs in situ. Immunohistochemistry was used to detect the presence of alpha (2) delta (1)-containing VGCCs in isolated RGCs in the absence and presence of gabapentin pretreatment. Acute administration of gabapentin reduced I (Ca) and Ca2+ transients compared to control conditions. In isolated RGCs, pretreatment with gabapentin (4-18 h) reduced I (Ca), and cell surface alpha (2) delta (1) staining was reduced compared to nonpretreated cells. Acute administration of gabapentin to isolated RGCs that had been pretreated further reduced I (Ca). These results show that gabapentin has both short-term and long-term mechanisms to reduce I (Ca) in isolated RGCs. Some Ca2+ channel blockers have been shown to protect RGCs in retinal trauma suggesting that modulation of VGCCs by gabapentin may prevent the deleterious effects of elevated Ca2+ levels in RGCs in trauma and disease. C1 [Farrell, Spring R.; Barnes, Steven] Dalhousie Univ, Dept Physiol & Biophys, Halifax, NS B3H 4R2, Canada. [Sargoy, Allison; Brecha, Nicholas C.; Barnes, Steven] Univ Calif Los Angeles, David Geffen Sch Med, Dept Neurobiol, Los Angeles, CA 90095 USA. [Brecha, Nicholas C.] Univ Calif Los Angeles, David Geffen Sch Med, Jules Stein Eye Inst, Dept Med, Los Angeles, CA 90095 USA. [Brecha, Nicholas C.] Univ Calif Los Angeles, David Geffen Sch Med, CURE Digest Dis Res Ctr, Los Angeles, CA 90095 USA. [Brecha, Nicholas C.; Barnes, Steven] Vet Adm Greater Los Angeles Hlth Syst, Los Angeles, CA USA. [Barnes, Steven] Dalhousie Univ, Inst Neurosci, Halifax, NS B3H 4R2, Canada. [Barnes, Steven] Dalhousie Univ, Dept Ophthalmol & Visual Sci, Halifax, NS B3H 4R2, Canada. RP Farrell, SR (reprint author), Dalhousie Univ, Dept Physiol & Biophys, POB 15000, Halifax, NS B3H 4R2, Canada. EM sbarnes@dal.ca FU Canadian Institutes of Health Research; Nova Scotia Health Research Foundation; NIH [EY04067]; VA Merit Review; [W81XWH-10-2-0077] FX The authors would like to thank Dr. William Baldridge and Janette Nason for the preparation of postnatal retinal ganglion cell cultures. Funding for this work was provided by a Canadian Institutes of Health Research and Nova Scotia Health Research Foundation Regional Partnership Program grant to S.B. Part of this research and development project was conducted at the David Geffen School of Medicine at UCLA and is made possible by a contract agreement that was awarded to N.C.B. and administered by the U.S. Army Medical Research & Materiel Command (USAMRMC) and the Telemedicine & Advanced Technology Research Center (TATRC), at Fort Detrick, MD under Contract Number W81XWH-10-2-0077. Support for these studies also came from NIH EY04067, and a VA Merit Review was awarded to N.C.B. N.C.B. is a VA Career Research Scientist. NR 30 TC 2 Z9 2 U1 1 U2 3 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 32 AVENUE OF THE AMERICAS, NEW YORK, NY 10013-2473 USA SN 0952-5238 EI 1469-8714 J9 VISUAL NEUROSCI JI Visual Neurosci. PD JAN PY 2014 VL 31 IS 1 BP 47 EP 55 DI 10.1017/S0952523813000588 PG 9 WC Neurosciences; Ophthalmology SC Neurosciences & Neurology; Ophthalmology GA AD1DY UT WOS:000332975300005 PM 24801623 ER PT J AU Hanak, BW Walcott, BP Nahed, BV Muzikansky, A Mian, MK Kimberly, WT Curry, WT AF Hanak, Brian W. Walcott, Brian P. Nahed, Brian V. Muzikansky, Alona Mian, Matthew K. Kimberly, William T. Curry, William T. TI Postoperative Intensive Care Unit Requirements After Elective Craniotomy SO WORLD NEUROSURGERY LA English DT Article DE Craniotomy; Elective; ICU; Postoperative care ID TRAUMATIC BRAIN-INJURY; RESOURCE USE; TUMOR SURGERY; ICU CARE; COST; EXPERIENCE AB OBJECTIVE: Commonly, patients undergoing craniotomy are admitted to an intensive care setting postoperatively to allow for close monitoring. We aim to determine the frequency with which patients who have undergone elective craniotomies require intensive care unit (ICU) elevel interventions or experience significant complications during the postoperative period to identify a subset of patients for whom an alternative to ICU-level care may be appropriate. METHODS: Following Institutional Review Board approval, a prospective, consecutive cohort of adult patients undergoing elective craniotomy was established at the Massachusetts General Hospital between the dates of April 2010 and March 2011. Inclusion criteria were intradural operations requiring craniotomy performed on adults (18 years of age or older). Exclusion criteria were cases of an urgent or emergent nature, patients who remained intubated postoperatively, and patients who had a ventriculostomy drain in place at the conclusion of the case. RESULTS: Four hundred patients were analyzed. Univariate analysis revealed that patients with diabetes (P = 0.00047), those who required intraoperative blood product administration (P = 0.032), older patients (P < 0.0001), those with higher intraoperative blood losses (P = 0.041), and those who underwent longer surgical procedures (P = 0.021) were more likely to require ICU-level interventions or experience significant postoperative complications. Multivariate analysis only found diabetes (P = 0.0005) and age (P = 0.0091) to be predictive of a patient's need for postoperative ICU admission. CONCLUSIONS: Diabetes and older age predict the need for ICU-level intervention after elective craniotomy. Properly selected patients may not require postcraniotomy ICU monitoring. Further study of resource utilization is necessary to validate these preliminary findings, particularly in different hospital types. C1 [Hanak, Brian W.] Univ Washington, Harborview Med Ctr, Sch Med, Dept Neurosurg, Seattle, WA 98104 USA. [Walcott, Brian P.; Nahed, Brian V.; Mian, Matthew K.; Curry, William T.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Neurosurg, Boston, MA 02114 USA. [Muzikansky, Alona] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Biostat Unit, Boston, MA USA. [Kimberly, William T.] Harvard Univ, Sch Med, Dept Neurol, Massachusetts Gen Hosp, Boston, MA 02115 USA. RP Walcott, BP (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Neurosurg, Boston, MA 02114 USA. EM walcott.brian@mgh.harvard.edu FU Harvard Catalyst; Harvard Clinical and Translational Science Center (NIH) [UL1 RR 025758]; Harvard University; Council of State Neurosurgical Societiese-Congress of Neurological Surgeons (Medical Student Summer Fellowship in Socioeconomic Research); Council of State Neurological Societies Socioeconomic fellowship FX This work was conducted with support from Harvard Catalyst, The Harvard Clinical and Translational Science Center (NIH Award UL1 RR 025758 and financial contributions from Harvard University and its affiliated academic 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, the National Center for Research Resources, or the National Institutes of Health. Funding was also provided by the Council of State Neurosurgical Societiese-Congress of Neurological Surgeons (Medical Student Summer Fellowship in Socioeconomic Research). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Dr. Walcott is supported by the Council of State Neurological Societies Socioeconomic fellowship (2012-2013). NR 26 TC 7 Z9 8 U1 0 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1878-8750 EI 1878-8769 J9 WORLD NEUROSURG JI World Neurosurg. PD JAN PY 2014 VL 81 IS 1 BP 165 EP 172 DI 10.1016/j.wneu.2012.11.068 PG 8 WC Clinical Neurology; Surgery SC Neurosciences & Neurology; Surgery GA AC2DV UT WOS:000332309200048 PM 23182731 ER PT J AU Paruch, JL Ko, CY Bilimoria, KY AF Paruch, Jennifer L. Ko, Clifford Y. Bilimoria, Karl Y. TI An Opportunity to Improve Informed Consent and Shared Decision Making: The Role of the ACS NSQIP Surgical Risk Calculator in Oncology SO ANNALS OF SURGICAL ONCOLOGY LA English DT Editorial Material C1 [Paruch, Jennifer L.; Ko, Clifford Y.; Bilimoria, Karl Y.] Amer Coll Surg, Div Res & Optimal Patient Care, Chicago, IL USA. [Paruch, Jennifer L.] Univ Chicago, Pritzker Sch Med, Dept Surg, Chicago, IL 60637 USA. [Ko, Clifford Y.] Univ Calif Los Angeles, Los Angeles, CA USA. [Ko, Clifford Y.] VA Greater Angeles Healthcare Syst, Los Angeles, CA USA. [Bilimoria, Karl Y.] Northwestern Univ, Feinberg Sch Med, Robert H Lurie Comprehens Canc Ctr, Northwestern Inst Comparat Effectiveness Res Onco, Chicago, IL 60611 USA. [Bilimoria, Karl Y.] Northwestern Univ, Feinberg Sch Med, Dept Surg, Surg Outcomes & Qual Improvement Ctr, Chicago, IL 60611 USA. RP Bilimoria, KY (reprint author), Amer Coll Surg, Div Res & Optimal Patient Care, Chicago, IL USA. EM kbilimoria@facs.org NR 5 TC 21 Z9 21 U1 1 U2 3 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1068-9265 EI 1534-4681 J9 ANN SURG ONCOL JI Ann. Surg. Oncol. PD JAN PY 2014 VL 21 IS 1 BP 5 EP 7 DI 10.1245/s10434-013-3345-3 PG 3 WC Oncology; Surgery SC Oncology; Surgery GA AC6YE UT WOS:000332671700002 PM 24197763 ER PT J AU Mullen, JT Ryan, DP AF Mullen, John T. Ryan, David P. TI Neoadjuvant Chemotherapy for Gastric Cancer: What are we Trying to Accomplish? SO ANNALS OF SURGICAL ONCOLOGY LA English DT Editorial Material ID PHASE-II TRIAL; PERIOPERATIVE CHEMOTHERAPY; PATHOLOGICAL RESPONSE; SURGERY; CHEMORADIOTHERAPY; ADENOCARCINOMA; CISPLATIN; S-1; PACLITAXEL; CARCINOMA C1 [Mullen, John T.] Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. [Mullen, John T.; Ryan, David P.] Harvard Univ, Sch Med, Boston, MA USA. [Ryan, David P.] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. RP Mullen, JT (reprint author), Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. EM jmullen@partners.org NR 13 TC 4 Z9 4 U1 1 U2 5 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1068-9265 EI 1534-4681 J9 ANN SURG ONCOL JI Ann. Surg. Oncol. PD JAN PY 2014 VL 21 IS 1 BP 13 EP 15 DI 10.1245/s10434-013-3250-9 PG 3 WC Oncology; Surgery SC Oncology; Surgery GA AC6YE UT WOS:000332671700005 PM 24046112 ER PT J AU Selb, J Ogden, TM Dubb, J Fang, QQ Boas, DA AF Selb, Juliette Ogden, Tyler M. Dubb, Jay Fang, Qianqian Boas, David A. TI Comparison of a layered slab and an atlas head model for Monte Carlo fitting of time-domain near-infrared spectroscopy data of the adult head SO JOURNAL OF BIOMEDICAL OPTICS LA English DT Article DE near-infrared spectroscopy; time-domain; baseline optical properties; Monte Carlo simulations; brain imaging ID STRONGLY SCATTERING MEDIA; SURFACE-BASED ANALYSIS; OPTICAL-PROPERTIES; FREQUENCY-DOMAIN; RESOLVED REFLECTANCE; PHOTON MIGRATION; TURBID MEDIA; NONINVASIVE DETERMINATION; CONTINUOUS-WAVE; NEONATAL BRAIN AB Near-infrared spectroscopy (NIRS) estimations of the adult brain baseline optical properties based on a homogeneous model of the head are known to introduce significant contamination from extracerebral layers. More complex models have been proposed and occasionally applied to in vivo data, but their performances have never been characterized on realistic head structures. Here we implement a flexible fitting routine of time-domain NIRS data using graphics processing unit based Monte Carlo simulations. We compare the results for two different geometries: a two-layer slab with variable thickness of the first layer and a template atlas head registered to the subject's head surface. We characterize the performance of the Monte Carlo approaches for fitting the optical properties from simulated time-resolved data of the adult head. We show that both geometries provide better results than the commonly used homogeneous model, and we quantify the improvement in terms of accuracy, linearity, and cross-talk from extracerebral layers. (C) The Authors. Published by SPIE under a Creative Commons Attribution 3.0 Unported License. Distribution or reproduction of this work in whole or in part requires full attribution of the original publication, including its DOI. C1 [Selb, Juliette; Ogden, Tyler M.; Dubb, Jay; Fang, Qianqian; Boas, David A.] Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Opt Div, Charlestown, MA 02129 USA. RP Selb, J (reprint author), Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Opt Div, Bldg 149,13th St, Charlestown, MA 02129 USA. EM juliette@nmr.mgh.harvard.edu FU National Institute of Health [P41-RR14075] FX This work was supported by National Institute of Health grant P41-RR14075. NR 52 TC 13 Z9 14 U1 0 U2 7 PU SPIE-SOC PHOTO-OPTICAL INSTRUMENTATION ENGINEERS PI BELLINGHAM PA 1000 20TH ST, PO BOX 10, BELLINGHAM, WA 98225 USA SN 1083-3668 EI 1560-2281 J9 J BIOMED OPT JI J. Biomed. Opt. PD JAN PY 2014 VL 19 IS 1 AR 016010 DI 10.1117/1.JBO.19.1.016010 PG 10 WC Biochemical Research Methods; Optics; Radiology, Nuclear Medicine & Medical Imaging SC Biochemistry & Molecular Biology; Optics; Radiology, Nuclear Medicine & Medical Imaging GA AB6IZ UT WOS:000331892700042 PM 24407503 ER PT J AU Schuman-Olivier, Z Hoeppner, BB Evins, AE Brewer, JA AF Schuman-Olivier, Zev Hoeppner, Bettina B. Evins, A. Eden Brewer, Judson A. TI Finding the Right Match: Mindfulness Training May Potentiate the Therapeutic Effect of Nonjudgment of Inner Experience on Smoking Cessation SO SUBSTANCE USE & MISUSE LA English DT Article DE nicotine; tobacco; mindfulness; meditation; cognitive-behavioral therapy; clinical trial; cigarette smoking; smoking; nonjudgment; addiction ID SUBSTANCE USE DISORDERS; RELAPSE PREVENTION; DRUG-USERS; INTERVENTION; DEPENDENCE; FREEDOM; TRIAL; QUESTIONNAIRE; MEDITATION; DEPRESSION AB Mindfulness training (MT) is an emerging therapeutic modality for addictive disorders. Nonjudgment of inner experience, a component of mindfulness, may influence addiction treatment response. To test whether this component influences smoking cessation, tobacco smokers (n = 85) in a randomized control trial of MT vs. Freedom from Smoking (FFS), a standard cognitive-behaviorally-oriented treatment, were divided into split-half subgroups based on baseline Five Facet Mindfulness Questionnaire nonjudgment subscale. Smokers who rarely judge inner experience (nonjudgment > 30.5) smoked less during follow-up when randomized to MT (3.9 cigs/d) vs. FFS (11.1 cigs/d), p < .01. Measuring trait nonjudgment may help personalize treatment assignments, improving outcomes. C1 [Schuman-Olivier, Zev; Hoeppner, Bettina B.; Evins, A. Eden] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Addict Med, Boston, MA 02114 USA. [Brewer, Judson A.] Yale Univ, Sch Med, Ctr Therapeut Neurosci, New Haven, CT USA. RP Schuman-Olivier, Z (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Addict Med, Boston, MA 02114 USA. EM zschuman@cha.harvard.edu FU Mind & Life Varela Award; HMS Dupont-Warren Fellowship; [R03DA030899]; [K01DA027097]; [K12DA00167]; [K24DA030443]; [R03DA029163] FX This study was supported by several grants, including R03DA030899, Mind & Life Varela Award, and HMS Dupont-Warren Fellowship (Z. Schuman-Olivier), K01DA027097 (B. B. Hoeppner), K24DA030443 (A. E. Evins), and K12DA00167, R03DA029163 (J. Brewer). NR 42 TC 2 Z9 2 U1 3 U2 13 PU INFORMA HEALTHCARE PI LONDON PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND SN 1082-6084 EI 1532-2491 J9 SUBST USE MISUSE JI Subst. Use Misuse PY 2014 VL 49 IS 5 BP 586 EP 594 DI 10.3109/10826084.2014.850254 PG 9 WC Substance Abuse; Psychiatry; Psychology SC Substance Abuse; Psychiatry; Psychology GA AC9IR UT WOS:000332848400009 PM 24611853 ER PT J AU Ahveninen, J Kopco, N Jaaskelainen, IP AF Ahveninen, Jyrki Kopco, Norbert Jaaskelainen, Iiro P. TI Psychophysics and neuronal bases of sound localization in humans SO HEARING RESEARCH LA English DT Review ID HUMAN AUDITORY-CORTEX; INTERAURAL TIME DIFFERENCES; SHORT-TERM PLASTICITY; MONAURAL SPECTRAL CUES; HUMAN PLANUM TEMPORALE; HUMAN CEREBRAL-CORTEX; HUMAN BRAIN; MISMATCH NEGATIVITY; DISTANCE PERCEPTION; LEVEL DIFFERENCES AB Localization of sound sources is a considerable computational challenge for the human brain. Whereas the visual system can process basic spatial information in parallel, the auditory system lacks a straightforward correspondence between external spatial locations and sensory receptive fields. Consequently, the question how different acoustic features supporting spatial hearing are represented in the central nervous system is still open. Functional neuroimaging studies in humans have provided evidence for a posterior auditory "where" pathway that encompasses non-primary auditory cortex areas, including the planum temporale (PT) and posterior superior temporal gyrus (STG), which are strongly activated by horizontal sound direction changes, distance changes, and movement. However, these areas are also activated by a wide variety of other stimulus features, posing a challenge for the interpretation that the underlying areas are purely spatial. This review discusses behavioral and neuroimaging studies on sound localization, and some of the competing models of representation of auditory space in humans. This article is part of a Special Issue entitled . (C) 2013 Elsevier B.V. All rights reserved. C1 [Ahveninen, Jyrki; Kopco, Norbert] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Athinoula A Martinos Ctr Biomed Imaging,Dept Radi, Charlestown, MA USA. [Kopco, Norbert] Safarik Univ, Inst Comp Sci, Kosice, Slovakia. [Kopco, Norbert] Boston Univ, Heating Res Ctr, Boston, MA 02215 USA. [Jaaskelainen, Iiro P.] Aalto Univ, Dept Biomed Engn & Computat Sci BECS, Brain & Mind Lab, Espoo, Finland. RP Ahveninen, J (reprint author), MGH MIT HMS Martinos Ctr, Bldg 149,13th St, Charlestown, MA 02129 USA. EM jyrki@nmr.mgh.harvard.edu RI Jaaskelainen, Iiro/C-7392-2012; Kopco, Norbert/S-1447-2016 OI Jaaskelainen, Iiro/0000-0001-6001-6950; FU National Institutes of Health (NIH) [R21DC010060, R01MH083744, R01HD040712, R01NS037462, P41EB015896,]; Academy Of Finland [127624, 138145]; European Community [PIRSESGA-2009-247543]; Slovak Scientific Grant Agency [VEGA 1/0492/12] FX We thank Dr. Beata Tomoriova for her comments on the initial versions of the manuscript. This research was supported by the National Institutes of Health (NIH) grants R21DC010060, R01MH083744, R01HD040712, R01NS037462, and P41EB015896, as well as by the Academy Of Finland grants 127624 and 138145, the European Community's 7FP/2007-13 Grant PIRSESGA-2009-247543, and the Slovak Scientific Grant Agency Grant VEGA 1/0492/12. The content is solely the responsibility of the authors and does not necessarily represent the official views of the funding agencies. NR 206 TC 19 Z9 20 U1 3 U2 45 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0378-5955 EI 1878-5891 J9 HEARING RES JI Hear. Res. PD JAN PY 2014 VL 307 SI SI BP 86 EP 97 DI 10.1016/j.heares.2013.07.008 PG 12 WC Audiology & Speech-Language Pathology; Neurosciences; Otorhinolaryngology SC Audiology & Speech-Language Pathology; Neurosciences & Neurology; Otorhinolaryngology GA AA8LU UT WOS:000331347800009 PM 23886698 ER PT J AU Boland, TA McGuone, D Jindal, J Rocha, M Cumming, M Rupprecht, CE Barbosa, TFS Oliveira, RD Chu, CJ Cole, AJ Kotait, I Kuzmina, NA Yager, PA Kuzmin, IV Hedley-Whyte, ET Brown, CM Rosenthal, ES AF Boland, Torrey A. McGuone, Declan Jindal, Jenelle Rocha, Marcelo Cumming, Melissa Rupprecht, Charles E. Souza Barbosa, Taciana Fernandes Oliveira, Rafael de Novaes Chu, Catherine J. Cole, Andrew J. Kotait, Ivanete Kuzmina, Natalia A. Yager, Pamela A. Kuzmin, Ivan V. Hedley-Whyte, E. Tessa Brown, Catherine M. Rosenthal, Eric S. TI Phylogenetic and Epidemiologic Evidence of Multiyear Incubation in Human Rabies SO ANNALS OF NEUROLOGY LA English DT Article ID UNITED-STATES AB Eight years after emigrating from Brazil, an otherwise healthy man developed rabies. An exposure prior to immigration was reported. Genetic analysis revealed a canine rabies virus variant found only in the patient's home country, and the patient had not traveled internationally since immigrating to the United States. We describe how epidemiological, phylogenetic, and viral sequencing data provided confirmation that rabies encephalomyelitis may present after a long, multiyear incubation period, a consideration that previously has been hypothesized without the ability to exclude a more recent exposure. Accordingly, rabies should be considered in the diagnosis of any acute encephalitis, myelitis, or encephalomyelitis. C1 [Boland, Torrey A.] Rush Univ, Med Ctr, Dept Neurol Sci, Chicago, IL 60612 USA. [McGuone, Declan; Hedley-Whyte, E. Tessa] Harvard Univ, Massachusetts Gen Hosp, Sch Med, CS Kubik Lab Neuropathol,Dept Pathol, Boston, MA USA. [Jindal, Jenelle; Rocha, Marcelo; Chu, Catherine J.; Cole, Andrew J.; Rosenthal, Eric S.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Neurol, Boston, MA USA. [Cumming, Melissa; Brown, Catherine M.] Hinton State Lab, Massachusetts Dept Publ Hlth, Jamaica Plain, MA USA. [Rupprecht, Charles E.] Global Alliance Rabies Control, Manhattan, KS USA. [Souza Barbosa, Taciana Fernandes] Evandro Chagas Inst, Para, Brazil. [Oliveira, Rafael de Novaes; Kotait, Ivanete] Inst Pasteur, Sao Paulo, Brazil. [Kuzmina, Natalia A.; Yager, Pamela A.] Ctr Dis Control & Prevent, Atlanta, GA USA. [Kuzmin, Ivan V.] Aravan LLC, Lilburn, GA USA. RP Boland, TA (reprint author), Rush Univ, Med Ctr, Dept Neurol Sci, 1725 W Harrison St,Suite 1106, Chicago, IL 60612 USA. EM torrey_boland@rush.edu OI Rosenthal, Eric/0000-0003-3900-356X FU NIH National Institute of Neurological Diseases and Stroke FX A.J.C.: consultancy, Clarus Ventures, Concert Pharmaceuticals, Sage Pharmaceuticals, Eisai Pharmaceuticals; grants/grants pending, NIH National Institute of Neurological Diseases and Stroke. P. A. Y.: royalties, EMD Millipore (Chemicon International). NR 14 TC 2 Z9 2 U1 0 U2 5 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0364-5134 EI 1531-8249 J9 ANN NEUROL JI Ann. Neurol. PD JAN PY 2014 VL 75 IS 1 BP 155 EP 160 DI 10.1002/ana.24016 PG 6 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA AA3WQ UT WOS:000331026300017 PM 24038455 ER PT J AU Williams, FMK Carter, AM Hysi, PG Surdulescu, G Hodgkiss, D Soranzo, N Traylor, M Bevan, S Dichgans, M Rothwell, PMW Sudlow, C Farrall, M Silander, K Kaunisto, M Wagner, P Saarela, O Kuulasmaa, K Virtamo, J Salomaa, V Amouyel, P Arveiler, D Ferrieres, J Wiklund, PG Ikram, MA Hofman, A Boncoraglio, GB Parati, EA Helgadottir, A Gretarsdottir, S Thorsteinsdottir, U Thorleifsson, G Stefansson, K Seshadri, S DeStefano, A Gschwendtner, A Psaty, B Longstreth, W Mitchell, BD Cheng, YC Clarke, R Ferrario, M Bis, JC Levi, C Attia, J Holliday, EG Scott, RJ Fornage, M Sharma, P Furie, KL Rosand, J Nalls, M Meschia, J Mosely, TH Evans, A Palotie, A Markus, HS Grant, PJ Spector, TD AF Williams, Frances M. K. Carter, Angela M. Hysi, Pirro G. Surdulescu, Gabriela Hodgkiss, Dylan Soranzo, Nicole Traylor, Matthew Bevan, Steve Dichgans, Martin Rothwell, Peter M. W. Sudlow, Cathie Farrall, Martin Silander, Kaisa Kaunisto, Mari Wagner, Peter Saarela, Olli Kuulasmaa, Kari Virtamo, Jarmo Salomaa, Veikko Amouyel, Philippe Arveiler, Dominique Ferrieres, Jean Wiklund, Per-Gunnar Ikram, M. Arfan Hofman, Albert Boncoraglio, Giorgio B. Parati, Eugenio A. Helgadottir, Anna Gretarsdottir, Solveig Thorsteinsdottir, Unnur Thorleifsson, Gudmar Stefansson, Kari Seshadri, Sudha DeStefano, Anita Gschwendtner, Andreas Psaty, Bruce Longstreth, Will Mitchell, Braxton D. Cheng, Yu-Ching Clarke, Robert Ferrario, Marco Bis, Joshua C. Levi, Christopher Attia, John Holliday, Elizabeth G. Scott, Rodney J. Fornage, Myriam Sharma, Pankaj Furie, Karen L. Rosand, Jonathan Nalls, Mike Meschia, James Mosely, Thomas H. Evans, Alun Palotie, Aarno Markus, Hugh S. Grant, Peter J. Spector, Tim D. CA EuroCLOT Investigators Wellcome Trust Case Control Cons MOnica Risk Genetics Archiving Mon Int Stroke Genetics Consortium TI Ischemic stroke is associated with the ABO locus: The EuroCLOT study (vol 73, pg 16, 2013) SO ANNALS OF NEUROLOGY LA English DT Correction C1 [Williams, Frances M. K.; Hysi, Pirro G.; Surdulescu, Gabriela; Hodgkiss, Dylan; Spector, Tim D.] Kings Coll London, Dept Twin Res & Genet Epidemiol, London, England. [Carter, Angela M.; Grant, Peter J.] Univ Leeds, Div Cardiovasc & Diabet Res, Leeds, W Yorkshire, England. [Soranzo, Nicole; Palotie, Aarno] Wellcome Trust Sanger Inst, Hinxton, England. [Soranzo, Nicole; Palotie, Aarno] Broad Inst Massachusetts Inst Technol & Harvard, Program Med & Populat Genet & Genet Anal Platform, Cambridge, MA USA. [Soranzo, Nicole; Palotie, Aarno] Univ Helsinki, Dept Med Genet, Helsinki, Finland. [Soranzo, Nicole; Palotie, Aarno] Univ Cent Hosp, Helsinki, Finland. [Traylor, Matthew; Bevan, Steve; Markus, Hugh S.] St Georges Univ London, Stroke & Dementia Res Ctr, London, England. [Dichgans, Martin; Gschwendtner, Andreas] Univ Munich, Klinikum Univ Munich, Inst Stroke & Dementia Res, Munich, Germany. [Rothwell, Peter M. W.] Univ Oxford, Stroke Prevent Res Unit, Univ Dept Clin Neurol, Oxford, England. [Sudlow, Cathie] Univ Edinburgh, Div Clin Neurosci, Edinburgh, Midlothian, Scotland. [Farrall, Martin; Helgadottir, Anna] Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford, England. [Farrall, Martin; Helgadottir, Anna] Univ Oxford, Dept Cardiovasc Med, Oxford, England. [Silander, Kaisa; Kaunisto, Mari; Wagner, Peter; Palotie, Aarno] Univ Helsinki, Inst Mol Med Finland, Helsinki, Finland. [Saarela, Olli; Kuulasmaa, Kari; Virtamo, Jarmo; Salomaa, Veikko] Natl Inst Hlth & Welf, Chron Dis Epidemiol & Prevent Unit, Helsinki, Finland. [Amouyel, Philippe] Inst Pasteur, Dept Epidemiol & Publ Hlth, F-59019 Lille, France. [Arveiler, Dominique] Univ Strasbourg, Dept Epidemiol & Publ Hlth, Strasbourg, France. [Ferrieres, Jean] Fac Med Toulouse, Dept Epidemiol, Toulouse, France. [Wiklund, Per-Gunnar] Umea Univ, Dept Internal Med, Umea, Sweden. [Ikram, M. Arfan; Hofman, Albert] Erasmus MC, Dept Epidemiol, Rotterdam, Netherlands. [Boncoraglio, Giorgio B.; Parati, Eugenio A.] Neurol Inst Carlo Besta, Res Hosp, Dept Neurol, Milan, Italy. [Helgadottir, Anna; Gretarsdottir, Solveig; Thorsteinsdottir, Unnur; Thorleifsson, Gudmar; Stefansson, Kari] DeCODE Genet, Reykjavik, Iceland. [Seshadri, Sudha; DeStefano, Anita] Boston Univ, Sch Med, Boston, MA 02118 USA. [Seshadri, Sudha; DeStefano, Anita] Boston Univ, Sch Publ Hlth, Boston, MA USA. [Seshadri, Sudha; DeStefano, Anita] Framingham Heart Dis Epidemiol Study, Framingham, MA USA. [Psaty, Bruce; Longstreth, Will] Univ Washington, Dept Hlth Serv, Seattle, WA 98195 USA. [Psaty, Bruce; Longstreth, Will] Univ Washington, Hlth Serv, Seattle, WA 98195 USA. [Psaty, Bruce] Univ Washington, Med Serv, Seattle, WA 98195 USA. [Psaty, Bruce] Grp Hlth, Grp Hlth Res Inst, Seattle, WA USA. [Longstreth, Will] Univ Washington, Dept Neurol, Seattle, WA 98195 USA. [Mitchell, Braxton D.; Cheng, Yu-Ching] Univ Maryland, Dept Med, Baltimore, MD 21201 USA. [Clarke, Robert] Univ Oxford, Clin Trial Serv Unit, Oxford, England. [Ferrario, Marco] Univ Insubria, Res Ctr Epidemiol & Prevent Med, Varese, Italy. [Bis, Joshua C.] Univ Washington, Dept Med, Cardiovasc Hlth Res Unit, Seattle, WA USA. [Levi, Christopher; Attia, John; Holliday, Elizabeth G.; Scott, Rodney J.] Univ Newcastle, Callaghan, NSW 2308, Australia. [Levi, Christopher; Attia, John; Holliday, Elizabeth G.; Scott, Rodney J.] John Hunter Hosp, New Lambton Hts, Australia. [Levi, Christopher; Attia, John; Holliday, Elizabeth G.; Scott, Rodney J.] Hunter Med Res Inst, New Lambton, Australia. [Fornage, Myriam] Univ Texas Hlth Sci Ctr Houston, Ctr Human Genet, Houston, TX 77030 USA. [Fornage, Myriam] Univ Texas Hlth Sci Ctr Houston, Inst Mol Med, Houston, TX 77030 USA. [Sharma, Pankaj] Univ London Imperial Coll Sci Technol & Med, Imperial Coll Cerebrovasc Res Unit, London, England. [Furie, Karen L.; Rosand, Jonathan] Massachusetts Gen Hosp, Ctr Human Genet, Boston, MA 02114 USA. [Furie, Karen L.; Rosand, Jonathan] Harvard Univ, Sch Med, Boston, MA USA. [Nalls, Mike; Meschia, James] Mayo Clin, Dept Neurol, Jacksonville, FL 32224 USA. [Furie, Karen L.; Rosand, Jonathan] Univ Mississippi, Med Ctr, Jackson, MS 39216 USA. [Evans, Alun] Queens Univ Belfast, Belfast, Antrim, North Ireland. RP Williams, FMK (reprint author), Kings Coll London, Dept Twin Res & Genet Epidemiol, London, England. OI Williams, Frances/0000-0002-2998-2744 NR 1 TC 0 Z9 0 U1 1 U2 4 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0364-5134 EI 1531-8249 J9 ANN NEUROL JI Ann. Neurol. PD JAN PY 2014 VL 75 IS 1 BP 166 EP 167 DI 10.1002/ana.24105 PG 2 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA AA3WQ UT WOS:000331026300024 ER PT J AU Ben-Zvi, T Hueber, PA Valdivieso, R Azzizi, M Tholomier, C Bienz, M Bhojani, N Trinh, QD Zorn, KC AF Ben-Zvi, Tal Hueber, Pierre-Alain Valdivieso, Roger Azzizi, Mounsif Tholomier, Come Bienz, Marc Bhojani, Naeem Quoc-Dien Trinh Zorn, Kevin C. TI Urological resident exposure to transurethral: surgical options for BPH management in 2012-2013: A pan-Canadian survey SO CUAJ-CANADIAN UROLOGICAL ASSOCIATION JOURNAL LA English DT Editorial Material ID BENIGN PROSTATIC HYPERPLASIA; VIRTUAL-REALITY; PHOTOSELECTIVE VAPORIZATION; CONSTRUCT-VALIDITY; RESECTION TRAINER; 120-W LASER; METAANALYSIS; ENUCLEATION; SIMULATION; THERAPY C1 [Ben-Zvi, Tal] Univ Laval, Ctr Hosp, Dept Surg, Urol Sect, Quebec City, PQ, Canada. [Hueber, Pierre-Alain; Valdivieso, Roger; Azzizi, Mounsif; Zorn, Kevin C.] Univ Montreal, Ctr Hosp, Dept Surg, Urol Sect, Montreal, PQ, Canada. [Tholomier, Come; Bienz, Marc; Bhojani, Naeem] McGill Univ, Fac Med, Montreal, PQ, Canada. [Quoc-Dien Trinh] Brigham & Womens Hosp, Div Urol, Boston, MA 02115 USA. [Quoc-Dien Trinh] Harvard Univ, Sch Med, Dana Farber Canc Inst, Ctr Surg & Publ Hlth, Boston, MA 02115 USA. RP Zorn, KC (reprint author), 235 Rene Levesque Est,Suite 301, Montreal, PQ H2X 1N8, Canada. EM zorn.chumurology@gmail.com NR 22 TC 4 Z9 4 U1 0 U2 1 PU CANADIAN UROLOGICAL ASSOCIATION PI DORVAL PA 185 DORVAL AVENUE, STE 401, DORVAL, QC H9S 5J9, CANADA SN 1911-6470 EI 1920-1214 J9 CUAJ-CAN UROL ASSOC JI CUAJ-Can. Urol. Assoc. J. PD JAN-FEB PY 2014 VL 8 IS 1-2 BP 54 EP 60 DI 10.5489/cuaj.1647 PG 7 WC Urology & Nephrology SC Urology & Nephrology GA AC1NY UT WOS:000332264500020 PM 24578746 ER PT J AU Genco, RJ Schifferle, RE Dunford, RG Falkner, KL Hsu, WC Balukjian, J AF Genco, Robert J. Schifferle, Robert E. Dunford, Robert G. Falkner, Karen L. Hsu, William C. Balukjian, James TI Screening for diabetes mellitus in dental practices A field trial SO JOURNAL OF THE AMERICAN DENTAL ASSOCIATION LA English DT Article DE Diabetes screening; dental office; field trial; hemoglobin A(1c) ID PERIODONTAL-DISEASE; GLUCOSE CONTROL; TYPE-2; COMPLICATIONS; METAANALYSIS; PROGRESSION; REDUCTION AB Background. In this field trial, the authors assess the feasibility of screening for diabetes and prediabetes in dental practices and in a community health center. Methods. Dental patients 45 years and older who were not aware of their diabetic status underwent evaluation for diabetes risk with an American Diabetes Association Diabetes Risk Test and with hemoglobin (Hb) A(1c) measurement. Participants with an HbA(1c) level of 5.7 percent or greater were referred to their physicians for diagnosis. Results. Of the 1,022 patients screened, 416 (40.7 percent) had an HbA(1c) blood level of 5.7 percent or greater and were referred for diagnosis. The HbA(1c) and the American Diabetes Association Diabetes Risk Test were correlated (P<.001). Of the 416 participants who were referred, 35.1 percent received a diagnosis from their physicians within one year; 78.8 percent of these patients were seen in the community health center and 21.4 percent were seen in private dental offices. The diagnoses were diabetes (12.3 percent of patients), high risk of developing diabetes (that is, prediabetes) (23.3 percent) and no diabetes (64.4 percent). Conclusions. The study results show that screening for prediabetes and diabetes is feasible in a dental office, with acceptance by the dentist and dental office staff members, patients' physicians and patients. Patients from the community health center demonstrated good compliance with referrals to physicians; however, compliance was poor among those in the private dental offices. Practical Implications. Screening for diabetes and prediabetes in the dental office may provide an important benefit to patients and encourage interprofessional collaboration to achieve a chronic care model in which health care professionals work together to care for a panel of patients. C1 [Genco, Robert J.; Schifferle, Robert E.; Dunford, Robert G.; Falkner, Karen L.] SUNY Buffalo, Amherst 14228, NY USA. [Hsu, William C.] Asian Clin, Boston, MA USA. [Hsu, William C.] Joslin Diabet Ctr, Boston, MA 02215 USA. [Hsu, William C.] Joslin Clin, Boston, MA USA. [Hsu, William C.] Harvard Univ, Sch Med, Boston, MA USA. RP Genco, RJ (reprint author), SUNY Buffalo, Baird Res Pk,Suite 103,1576 Sweet Home Rd, Amherst 14228, NY USA. EM rjgenco@buffalo.edu FU Delta Dental of Rhode Island; School of Dental Medicine, State University of New York at Buffalo FX The authors thank Delta Dental of Rhode Island for its financial support of the study and thank Joseph A. Nagle, president and chief executive officer; Kathryn M. Shanley, vice president, External Affairs; and Debbie Abruzzi, Angela Santos, Mary Sommer and Monique Mitchell for their help with all aspects of the study. The authors also thank the School of Dental Medicine, State University of New York at Buffalo, for support of the study. NR 24 TC 12 Z9 12 U1 0 U2 9 PU AMER DENTAL ASSOC PI CHICAGO PA 211 E CHICAGO AVE, CHICAGO, IL 60611 USA SN 0002-8177 EI 1943-4723 J9 J AM DENT ASSOC JI J. Am. Dent. Assoc. PD JAN PY 2014 VL 145 IS 1 BP 57 EP 64 PG 8 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA AC0QT UT WOS:000332200500015 PM 24379330 ER PT J AU Karlin, BE Cross, G AF Karlin, Bradley E. Cross, Gerald TI From the Laboratory to the Therapy Room National Dissemination and Implementation of Evidence-Based Psychotherapies in the U.S. Department of Veterans Affairs Health Care System SO AMERICAN PSYCHOLOGIST LA English DT Article DE evidence-based psychotherapy; dissemination; implementation; sustainability; veterans ID COGNITIVE-BEHAVIORAL THERAPY; POSTTRAUMATIC-STRESS-DISORDER; PATIENT-LEVEL OUTCOMES; MENTAL-HEALTH; PRACTICE GUIDELINES; COMMITMENT THERAPY; DEPRESSION; KNOWLEDGE; ATTITUDES; IMPROVE AB Despite their established efficacy and recommendation-often as first-line treatments-in clinical practice guidelines, evidence-based psychotherapies (EBPs) have largely failed to make their way into mainstream clinical settings. Numerous attempts over the years to promote the translation of EBPs from science to practice, typically relying on one-dimensional dissemination approaches, have yielded limited success. As part of the transformation of its mental health care system, the Veterans Health Administration (VHA) of the U.S. Department of Veterans Affairs (VA) is working to disseminate and implement a number of EBPs for various mental and behavioral health conditions throughout the VA health care system. This article examines VHA's multidimensional model and specific strategies, involving policy, provider, local systems, patient, and accountability levels, for promoting the national dissemination and implementation of EBPs in VHA. In addition, the article identifies key lessons learned and next steps for further promoting EBP delivery and sustainability in the VA health care system. Beyond promoting the availability of effective treatments for veterans returning from Iraq and Afghanistan and for veterans of previous combat eras, VHA's EBP dissemination and implementation model and key lessons learned may help to inform other private and public health care systems interested in disseminating and implementing EBPs. C1 [Karlin, Bradley E.; Cross, Gerald] US Dept Vet Affairs, Cent Off, Washington, DC 20420 USA. [Karlin, Bradley E.] Johns Hopkins Univ, Baltimore, MD 21218 USA. RP Karlin, BE (reprint author), US Dept Vet Affairs, Natl Mental Hlth Director Psychotherapy & Psychog, Mental Hlth Serv 10P4M, Cent Off, 810 Vermont Ave NW, Washington, DC 20420 USA. EM bradley.karlin2@va.gov NR 88 TC 63 Z9 64 U1 1 U2 9 PU AMER PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 USA SN 0003-066X EI 1935-990X J9 AM PSYCHOL JI Am. Psychol. PD JAN PY 2014 VL 69 IS 1 BP 19 EP 33 DI 10.1037/a0033888 PG 15 WC Psychology, Multidisciplinary SC Psychology GA AB5AX UT WOS:000331802400002 PM 24001035 ER PT J AU Hinrichsen, GA Brickman, AM Edelstein, B Vacha-Haase, T Hiroto, K Zweig, R AF Hinrichsen, Gregory A. Brickman, Adam M. Edelstein, Barry Vacha-Haase, Tammi Hiroto, Kimberly Zweig, Richard CA Amer Psychological Assoc TI Guidelines for Psychological Practice With Older Adults SO AMERICAN PSYCHOLOGIST LA English DT Article ID PRIMARY-CARE PATIENTS; MENTAL-HEALTH-SERVICES; NURSING-HOME RESIDENTS; LONG-TERM-CARE; COMORBIDITY SURVEY REPLICATION; POSTTRAUMATIC-STRESS-DISORDER; RANDOMIZED CONTROLLED-TRIAL; PROBLEM-SOLVING THERAPY; LATE-LIFE DEPRESSION; ALZHEIMERS-DISEASE C1 [Hinrichsen, Gregory A.] Icahn Sch Med, Mt Sinai, NY USA. [Brickman, Adam M.] Columbia Univ, New York, NY 10027 USA. [Edelstein, Barry] W Virginia Univ, Morgantown, WV 26506 USA. [Vacha-Haase, Tammi] Colorado State Univ, Ft Collins, CO 80523 USA. [Hiroto, Kimberly] US Dept Vet Affairs, Puget Sound Hlth Care Syst, Washington, DC USA. [Zweig, Richard] Yeshiva Univ, New York, NY 10033 USA. RP Hinrichsen, GA (reprint author), Amer Psychol Assoc, Publ Interest Directorate, Off Aging, 750 First St NE, Washington, DC 20002 USA. NR 420 TC 11 Z9 12 U1 4 U2 22 PU AMER PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 USA SN 0003-066X EI 1935-990X J9 AM PSYCHOL JI Am. Psychol. PD JAN PY 2014 VL 69 IS 1 BP 34 EP 65 DI 10.1037/a0035063 PG 32 WC Psychology, Multidisciplinary SC Psychology GA AB5AX UT WOS:000331802400003 ER PT J AU Blaszkowsky, LS Ryan, DP Szymonifka, J Borger, DR Zhu, AX Clark, JW Kwak, EL Mamon, HJ Allen, JN Vasudev, E Shellito, PC Cusack, JC Berger, DL Hong, TS AF Blaszkowsky, L. S. Ryan, D. P. Szymonifka, J. Borger, D. R. Zhu, A. X. Clark, J. W. Kwak, E. L. Mamon, H. J. Allen, J. N. Vasudev, E. Shellito, P. C. Cusack, J. C. Berger, D. L. Hong, T. S. TI Phase I/II study of neoadjuvant bevacizumab, erlotinib and 5-fluorouracil with concurrent external beam radiation therapy in locally advanced rectal cancer SO ANNALS OF ONCOLOGY LA English DT Article DE rectal cancer; radiation; beyacizumab; erlotinib ID METASTATIC COLORECTAL-CANCER; III TRIAL; I TRIAL; PREOPERATIVE CETUXIMAB; NECK-CANCER; OXALIPLATIN; CHEMORADIATION; CAPECITABINE; CHEMORADIOTHERAPY; FLUOROURACIL AB Background: To determine the maximal tolerated dose of erlotinib when added to 5-fluorouracil (5-FU) chemoradiation and bevacizumab and safety and efficacy of this combination in patients with locally advanced rectal cancer. Patients and methods: Patients with Magnetic resonance imaging (MRI) or ultrasound defined 13 or 14 adenocarcinoma of the rectum and without evidence of metastatic disease were enrolled. Patients received infusional 5-FU 225 mg/M2/day continuously, along with bevacizumab 5 mg/kg days 14, 1, 15 and 29. Standard radiotherapy was administered to 50.4 Gy in 28 fractions. Erlotinib started at a dose of 50 mg orally daily and advanced by 50 mg increments in the subsequent cohort. Open total mesorectal excision was carried out 6-9 weeks following the completion of chemoradiation. Results: Thirty-two patients received one of three dose levels of erlotinib. Erlotinib dose level of 100 mg was determined to be the maximally tolerated dose. Thirty-one patients underwent resection of the primary tumor, one refused resection. Twenty-seven patients completed study therapy, all of whom underwent resection. At least one grade 3-4 toxicity occurred in 46.9% of patients. Grade 3-4 diarrhea occurred in 18.8%. The pathologic complete response (pCR) for all patients completing study therapy was 33%. With a median follow-up of 2.9 years, there are no documented local recurrences. Disease free survival at 3 years is 75.5% (confidence interval: 55.1-87.6%). Conclusions: Erlotinib added to infusional 5-FU, bevacizumab and radiation in patients with locally advanced rectal cancer is relatively well tolerated and associated with an encouraging pCR. Clinicaltrials.gov: NCT00307736. C1 [Blaszkowsky, L. S.; Ryan, D. P.; Zhu, A. X.; Clark, J. W.; Kwak, E. L.; Allen, J. N.; Vasudev, E.] Brigham & Womens Hosp, Dept Med, Dana Farber Canc Inst, Boston, MA 02115 USA. [Szymonifka, J.] Brigham & Womens Hosp, Dept Biostat, Dana Farber Canc Inst, Boston, MA 02115 USA. [Borger, D. R.] Brigham & Womens Hosp, Dept Pathol, Dana Farber Canc Inst, Boston, MA 02115 USA. [Mamon, H. J.] Brigham & Womens Hosp, Dept Radiat Oncol, Dana Farber Canc Inst, Boston, MA 02115 USA. [Shellito, P. C.; Cusack, J. C.; Berger, D. L.] Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. [Hong, T. S.] Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. RP Blaszkowsky, LS (reprint author), Massachusetts Gen Hosp, Dept Med, Div Hematol Oncol, Yawkey 7E,55 Fruit St, Boston, MA 02114 USA. EM lblaszkowsky@partners.org FU Genentech FX This study was funded by Genentech. NR 29 TC 10 Z9 10 U1 0 U2 1 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0923-7534 EI 1569-8041 J9 ANN ONCOL JI Ann. Oncol. PD JAN PY 2014 VL 25 IS 1 BP 121 EP 126 DI 10.1093/annonc/mdt516 PG 7 WC Oncology SC Oncology GA AA7HR UT WOS:000331268800018 PM 24356623 ER PT J AU Heng, DYC Choueiri, TK Rini, BI Lee, J Yuasa, T Pal, SK Srinivas, S Bjarnason, GA Knox, JJ MacKenzie, M Vaishampayan, UN Tan, MH Rha, SY Donskov, F Agarwal, N Kollmannsberger, C North, S Wood, LA AF Heng, D. Y. C. Choueiri, T. K. Rini, B. I. Lee, J. Yuasa, T. Pal, S. K. Srinivas, S. Bjarnason, G. A. Knox, J. J. MacKenzie, M. Vaishampayan, U. N. Tan, M. H. Rha, S. Y. Donskov, F. Agarwal, N. Kollmannsberger, C. North, S. Wood, L. A. TI Outcomes of patients with metastatic renal cell carcinoma that do not meet eligibility criteria for clinical trials SO ANNALS OF ONCOLOGY LA English DT Article DE metastatic renal cell cancer; outcomes; clinical trials; ineligible ID COLORECTAL-CANCER PATIENTS; PHASE-III TRIAL; INTERFERON-ALPHA; SUNITINIB; SORAFENIB; SURVIVAL; EFFICACY AB Background: Targeted therapies in metastatic renal cell carcinoma (mRCC) have been approved based on registration clinical trials that have strict eligibility criteria. The clinical outcomes of patients treated with targeted agents but are ineligible for trials are unknown. Patients and Methods: mRCC patients treated with vascular endothelial growth factor-targeted therapy were retrospectively deemed ineligible for clinical trials (according to commonly used inclusion/exclusion criteria) if they had a Karnofsky performance status (KPS) <70%, nonclear-cell histology, brain metastases, hemoglobin <= 9 g/dl, creatinine >2x the upper limit of normal, corrected calcium >= 12 mg/dl, platelet count of <100 x 10(3)/uL, or neutrophil count <1500/mm(3). Results: Overall, 768 of 2210 (35%) patients in the International Metastatic RCC Database Consortium (IMDC) were deemed ineligible for clinical trials by the above criteria. Between ineligible versus eligible patients, the response rate, median progression-free survival (PFS) and median overall survival of first-line targeted therapy were 22% versus 29% (P = 0.0005), 5.2 versus 8.6 months, and 12.5 versus 28.4 months (both P <0,0001), respectively. Second-line PFS (if applicable) was 2.8 months in the trial ineligible versus 4.3 months in the trial eligible patients (P = 0.0039). When adjusted by the IMDC prognostic categories, the HR for death between trial ineligible and trial eligible patients was 1.55 (95% confidence interval 1.378-1.751, P <0.0001). Conclusions: The number of patients that are ineligible for clinical trials is substantial and their outcomes are inferior. Specific trials addressing the unmet needs of protocol ineligible patients are warranted. C1 [Heng, D. Y. C.] Tom Baker Canc Clin, Calgary, AB, Canada. [Choueiri, T. K.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. [Rini, B. I.] Cleveland Clin, Taussig Canc Inst, Cleveland, OH 44106 USA. [Lee, J.] Univ Ulsan, Coll Med, Asan, South Korea. [Yuasa, T.] Japanese Fdn Canc Res, Canc Inst Hosp, Dept Urol, Tokyo, Japan. [Pal, S. K.] City Hope Comprehens Canc Ctr, Dept Med Oncol & Expt Therapeut, Duarte, CA USA. [Srinivas, S.] Stanford Univ, Sch Med, Stanford Canc Inst, Stanford, CA 94305 USA. [Bjarnason, G. A.] Sunnybrook Odette Canc Ctr, Toronto, ON, Canada. [Knox, J. J.] Univ Toronto, Princess Margaret Hosp, Toronto, ON, Canada. [MacKenzie, M.] London Hlth Sci Ctr, London, ON, Canada. [Vaishampayan, U. N.] Wayne State Univ, Karmanos Canc Inst, Detroit, MI USA. [Tan, M. H.] Natl Canc Ctr, Dept Med Oncol, Singapore, Singapore. [Tan, M. H.] Inst Bioengn & Nanotechnol, Singapore, Singapore. [Rha, S. Y.] Yonsei Univ, Coll Med, Yonsei Canc Ctr, Seoul, South Korea. [Donskov, F.] Aarhus Univ Hosp, Dept Oncol, DK-8000 Aarhus, Denmark. [Agarwal, N.] Univ Utah, Huntsman Canc Inst, Salt Lake City, UT USA. [Kollmannsberger, C.] British Columbia Canc Agcy, Vancouver Canc Ctr, Vancouver, BC V5Z 4E6, Canada. [North, S.] Univ Alberta, Cross Canc Ctr, Edmonton, AB, Canada. [Wood, L. A.] Queen Elizabeth 2 Hlth Sci Ctr, Halifax, NS, Canada. RP Heng, DYC (reprint author), Univ Calgary, Tom Baker Canc Ctr, 1331-29th St NW, Calgary, AB T2N 4N2, Canada. EM daniel.heng@albertahealthservices.ca OI Bjarnason, Georg Arnold/0000-0001-6903-5357; Donskov, Frede/0000-0002-8449-863X FU Pfizer; Bayer; Genentech/Roche; Novartis; GlaxoSmithKline FX DYCH: Consultant or Advisory Role-Bayer/Onyx; Novartis; Pfizer. TKC: Consultant or Advisory Role-AVEO; Bayer; Genentech; GlaxoSmithKline; Novartis; Pfizer, Research Funding-Pfizer. BIR: Consultant or Advisory Role-Pfizer, Research Funding-Pfizer. JLL: Honoraria-Bayer; Novartis; Pfizer, Research Funding-Bayer. GAB: Consultant or Advisory Role-Pfizer, Honoraria-Pfizer, Research Funding-Pfizer. JJK: Consultant or Advisory Role-AVEO, Research Funding-Pfizer. MJM: Honoraria-Novartis; Pfizer. UNV: Consultant or Advisory Role-Novartis; Pfizer. Research Funding-Genentech/Roche; Novartis, Other Remuneration-Genentech/Roche (Speakers Bureau); Novartis (Speakers Bureau); Pfizer (Educational Presentation Development); Pfizer (Speakers Bureau). FD: Research Funding-Novartis, CKK: Consultant or Advisory Role-Pfizer, Honoraria-Pfizer. LW: Consultant or Advisory Role-Pfizer, Research Funding - GlaxoSmithKline; Novartis; Pfizer. All remaining authors have declared no conflicts of interest. NR 15 TC 29 Z9 29 U1 0 U2 3 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0923-7534 EI 1569-8041 J9 ANN ONCOL JI Ann. Oncol. PD JAN PY 2014 VL 25 IS 1 BP 149 EP 154 DI 10.1093/annonc/mdt492 PG 6 WC Oncology SC Oncology GA AA7HR UT WOS:000331268800023 PM 24356626 ER PT J AU Ganjoo, KN Villalobos, VM Kamaya, A Fisher, GA Butrynski, JE Morgan, JA Wagner, AJ D'Adamo, D McMillan, A Demetri, GD George, S AF Ganjoo, K. N. Villalobos, V. M. Kamaya, A. Fisher, G. A. Butrynski, J. E. Morgan, J. A. Wagner, A. J. D'Adamo, D. McMillan, A. Demetri, G. D. George, S. TI A multicenter phase II study of pazopanib in patients with advanced gastrointestinal stromal tumors ( GIST) following failure of at least imatinib and sunitinib SO ANNALS OF ONCOLOGY LA English DT Article DE GIST; KIT; pazopanib; tyrosine kinase inhibitors ID ENDOTHELIAL GROWTH-FACTOR; EFFICACY; TRIAL; ANGIOGENESIS; REGORAFENIB; NILOTINIB; SAFETY AB Background: Advanced GISTs are incurable, but often treatable for years with tyrosine kinase inhibitors (TKIs). The majority of GISTs harbor an oncogenic activating mutation in KIT or PDGFRA. Inhibition of this activating mutation with TKIs most often leads to durable disease control for many patients. However, almost all patients develop resistance to these TKIs, typically due to the development of secondary mutations, heralding the need for new therapeutic options. We conducted a phase II study evaluating the efficacy and toxicity of pazopanib, a broad spectrum TKI inhibiting KIT, VEGFRs (-1, -2, and -3), and PDGFR (-alpha and-beta) in patients with advanced GIST following failure of at least imatinib and sunitinib. Methods: Patients received pazopanib 800 mg orally once daily. All patients were assessed for efficacy with CT scans every 8 weeks (two cycles). Patients continued pazopanib until progression or unacceptable toxicity. The primary end point was the 24-week nonprogression [complete response+partial response+stable disease (SD)] rate (NPR) per RECIST 1.1. Secondary end points included PFS, OS, and toxicity. Results: Between August 2011 and September 2012, a total of 25 patients were treated at two institutions. Median number of prior therapy was 3 (range 2-7). A total of 90 cycles of pazopanib were administered, with a median of two cycles (range 1 to 17+) per patient. Best response of SD at any time was observed in 12 (48%) patients. The NPR was 17% [95% confidence interval (CI) 4.5-37]. All but one patient discontinued protocol either due to PD (n = 19) or intolerance (n = 4). One patient with succinate dehydrogenase (SDH)-deficient GIST exhibited continuing disease control after 17 cycles. The median PFS for the entire cohort was 1.9 months (95% CI 1.6-5.2), and the median OS was 10.7 months (95% CI 3.9-NR). Conclusions: Pazopanib was reasonably well tolerated with no unexpected toxicities. Pazopanib as a single agent has marginal activity in unselected heavily pretreated patients with advanced GIST. C1 [Ganjoo, K. N.; Villalobos, V. M.; Kamaya, A.; Fisher, G. A.; McMillan, A.] Stanford Canc Inst, Stanford, CA USA. [Butrynski, J. E.; Morgan, J. A.; Wagner, A. J.; D'Adamo, D.; Demetri, G. D.; George, S.] Dana Farber Canc Inst, Ctr Sarcoma & Bone Oncol, Boston, MA 02115 USA. [Demetri, G. D.] Dana Farber Harvard Canc Ctr, Ludwig Ctr, Boston, MA USA. [Demetri, G. D.] Harvard Univ, Sch Med, Boston, MA USA. RP Ganjoo, KN (reprint author), 875 Blake Wilbur Dr, Stanford, CA 94305 USA. EM kganjoo@stanford.edu FU GlaxoSmithKline; Ludwig Center at Dana-Farber/Harvard Cancer Center FX This work was supported in part by GlaxoSmithKline investigator-initiated trial fund and by Ludwig Center at Dana-Farber/Harvard Cancer Center. NR 12 TC 25 Z9 28 U1 0 U2 3 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0923-7534 EI 1569-8041 J9 ANN ONCOL JI Ann. Oncol. PD JAN PY 2014 VL 25 IS 1 BP 236 EP 240 DI 10.1093/annonc/mdt484 PG 6 WC Oncology SC Oncology GA AA7HR UT WOS:000331268800038 PM 24356634 ER PT J AU Caballero, F Siniakowicz, K Jennifer-Hollister-Lock Duran, L Katsuta, H Yamada, T Lei, J Deng, SP Westermark, GT Markmann, J Bonner-Weir, S Weir, GC AF Caballero, Francisco Siniakowicz, Karolina Jennifer-Hollister-Lock Duran, Luisa Katsuta, Hitoshi Yamada, Takatsugu Lei, Ji Deng, Shaoping Westermark, Gunilla T. Markmann, James Bonner-Weir, Susan Weir, Gordon C. TI Birth and Death of Human beta-Cells in Pancreases From Cadaver Donors, Autopsies, Surgical Specimens, and Islets Transplanted Into Mice SO CELL TRANSPLANTATION LA English DT Article DE Diabetes; Turnover; beta-Cell neogenesis; beta-Cell replication ID EPIDERMAL-GROWTH-FACTOR; COMBINATION THERAPY; DUCT CELLS; IN-VIVO; GLUCOSE-TOLERANCE; KI-67 PROTEIN; REPLICATION; MASS; REGENERATION; GASTRIN AB There is great interest in the potential of the human endocrine pancreas for regeneration by beta-cell replication or neogenesis. Our aim was to explore this potential in adult human pancreases and in both islet and exocrine tissue transplanted into mice. The design was to examine pancreases obtained from cadaver donors, autopsies, and fresh surgical specimens and compare these findings with those obtained from islet and duct tissue grafted into the kidney. Islets and exocrine tissue were transplanted into normoglycemic ICR-SCID mice and studied 4 and 14 weeks later. beta-Cell replication, as assessed by double staining for insulin and Ki67, was 0.22 +/- 0.03% at 4 weeks and 0.13 +/- 0.03% at 14 weeks. In contrast, no evidence of beta-cell replication could be found in 11 cadaver donor and 10 autopsy pancreases. However, Ki67 staining of beta-cells in frozen sections obtained at surgery was comparable to that found in transplanted islets. Evidence for neogenesis in transplanted pancreatic exocrine tissue was supported by finding beta-cells within the duct epithelium and the presence of cells double stained for insulin and cytokeratin 19 (CK19). However, beta-cells within the ducts never constituted more than 1% of the CK19-positive cells. With confocal microscopy, 7 of 12 examined cells expressed both markers, consistent with a neogeneic process. Mice with grafts containing islet or exocrine tissue were treated with various combinations of exendin-4, gastrin, and epidermal growth factor; none increased beta-cell replication or stimulated neogenesis. In summary, human beta-cells replicate at a low level in islets transplanted into mice and in surgical pancreatic frozen sections, but rarely in cadaver donor or autopsy pancreases. The absence of beta-cell replication in many adult cadaver or autopsy pancreases could, in part, be an artifact of the postmortem state. Thus, it appears that adult human beta-cells maintain a low level of turnover through replication and neogenesis. C1 [Caballero, Francisco; Siniakowicz, Karolina; Jennifer-Hollister-Lock; Duran, Luisa; Katsuta, Hitoshi; Yamada, Takatsugu; Bonner-Weir, Susan; Weir, Gordon C.] Joslin Diabet Ctr, Sect Islet Cell & Regenerat Biol, Div Res, Boston, MA 02215 USA. [Lei, Ji; Deng, Shaoping; Markmann, James] Harvard Univ, Sch Med, Dept Surg, Div Transplantat,Massachusetts Gen Hosp, Boston, MA 02115 USA. [Westermark, Gunilla T.] Uppsala Univ, Dept Med Cell Biol, Uppsala, Sweden. RP Weir, GC (reprint author), Joslin Diabet Ctr, Sect Islet Cell & Regenerat Biol, 1 Joslin Pl, Boston, MA 02215 USA. EM gordon.weir@joslin.harvard.edu FU Juvenile Diabetes Research Foundation; National Institutes of Health NIH [R01 DK 66056, DK 93909]; Joslin Diabetes Research Center (DRC) Advanced Microscopy Core [P30 DK36836]; Diabetes Research and Wellness Foundation; Plan Nacional I-D+I FECYT-Ministerio de Ciencia e Innovacion, Spain (FCG); Swedish Research Council [GTW5343]; Swedish Diabetes Association; Family Ernfors Fund FX The authors thank Alevtina Pinkhasov and Chris Cahill for expert technical assistance. This study was supported by grants from the Juvenile Diabetes Research Foundation (G.C.W.) and the National Institutes of Health NIH R01 DK 66056 and DK 93909 (S.B.W.), P30 DK36836 Joslin Diabetes Research Center (DRC) Advanced Microscopy Core and the Diabetes Research and Wellness Foundation, and a fellowship from Plan Nacional I-D+I 2008-2011 FECYT-Ministerio de Ciencia e Innovacion, Spain (FCG), Swedish Research Council (GTW5343), the Swedish Diabetes Association, and the Family Ernfors Fund. The authors declare no conflicts of interest. NR 31 TC 9 Z9 10 U1 0 U2 2 PU COGNIZANT COMMUNICATION CORP PI PUTNAM VALLEY PA 18 PEEKSKILL HOLLOW RD, PO BOX 37, PUTNAM VALLEY, NY 10579 USA SN 0963-6897 EI 1555-3892 J9 CELL TRANSPLANT JI Cell Transplant. PY 2014 VL 23 IS 2 BP 139 EP 151 DI 10.3727/096368912X659916 PG 13 WC Cell & Tissue Engineering; Medicine, Research & Experimental; Transplantation SC Cell Biology; Research & Experimental Medicine; Transplantation GA AB3GW UT WOS:000331680300001 PM 23321263 ER PT J AU Lin, NU AF Lin, Nancy U. TI Targeted Therapies in Brain Metastases SO CURRENT TREATMENT OPTIONS IN NEUROLOGY LA English DT Review DE Brain metastases; Targeted therapies; Treatment; Breast cancer; Lung cancer; Melanoma; Renal cell carcinoma ID CELL LUNG-CANCER; LAPATINIB PLUS CAPECITABINE; NERVOUS-SYSTEM METASTASES; GRADED PROGNOSTIC ASSESSMENT; HER2-POSITIVE BREAST-CANCER; QUALITY-OF-LIFE; PHASE-II TRIAL; OPEN-LABEL; STEREOTACTIC RADIOSURGERY; RADIATION-THERAPY AB Brain metastases are a major clinical problem in patients with advanced breast cancer, lung cancer, melanoma, and renal cell carcinoma. Initial treatment for patients with brain metastases typically includes radiotherapy, either whole brain radiotherapy (WBRT), stereotactic radiosurgery (SRS), or both. Surgical resection is generally reserved for good prognosis patients with limited/controlled extracranial metastases and a single brain lesion. Once patients progress through upfront treatment, the treatment approach is quite variable and there is no clearly defined standard-of-care. Over the past decade, the role of systemic therapies and in particular, targeted therapies has been increasingly explored in patients with brain metastases from solid tumors. For example, lapatinib has been studied as monotherapy, and in combination with capecitabine, in patients with HER2-positive breast cancer, and activity has been observed in both the upfront and refractory settings. In patients with nonsmall cell lung cancer (NSCLC), central nervous system (CNS) activity has been reported with gefinitib and erlotinib. Finally, in melanoma, the B-raf inhibitors vemurafenib and dabrafenib, and the immunomodulator, ipilumimab, have reported CNS activity. Moving forward, the challenge will be to understand how to optimize the activity of targeted agents in the CNS and how to best incorporate them into the current treatment paradigms in order to improve outcomes for this patient population. C1 Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02215 USA. RP Lin, NU (reprint author), Dana Farber Canc Inst, Dept Med Oncol, 450 Brookline Ave, Boston, MA 02215 USA. EM nlin@partners.org FU Breast Cancer Research Foundation FX The author wishes to acknowledge support from the Breast Cancer Research Foundation. NR 64 TC 13 Z9 14 U1 2 U2 13 PU CURRENT MEDICINE GROUP PI PHILADELPHIA PA 400 MARKET STREET, STE 700, PHILADELPHIA, PA 19106 USA SN 1092-8480 EI 1534-3138 J9 CURR TREAT OPTION NE JI Curr. Treat. Options Neurol. PD JAN PY 2014 VL 16 IS 1 AR 276 DI 10.1007/s11940-013-0276-z PG 15 WC Clinical Neurology SC Neurosciences & Neurology GA AB6WK UT WOS:000331930000003 PM 24353011 ER PT J AU Wallis, TSA Taylor, CP Wallis, J Jackson, ML Bex, PJ AF Wallis, Thomas S. A. Taylor, Christopher Patrick Wallis, Jennifer Jackson, Mary Lou Bex, Peter J. TI Characterization of Field Loss Based on Microperimetry Is Predictive of Face Recognition Difficulties SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Article DE face recognition; central vision loss; low vision; perimetry; Bayesian inference ID CONTRAST-SENSITIVITY; MACULAR DEGENERATION; LOW-VISION; PERIPHERAL-VISION; VISUAL-FIELD; FIXATION STABILITY; IMAGE-ENHANCEMENT; T TEST; IDENTIFICATION; REHABILITATION AB PURPOSE. To determine how visual field loss as assessed by microperimetry is correlated with deficits in face recognition. METHODS. Twelve patients (age range, 26-70 years) with impaired visual sensitivity in the central visual field caused by a variety of pathologies and 12 normally sighted controls (control subject [CS] group; age range, 20-68 years) performed a face recognition task for blurred and unblurred faces. For patients, we assessed central visual field loss using microperimetry, fixation stability, Pelli-Robson contrast sensitivity, and letter acuity. RESULTS. Patients were divided into two groups by microperimetry: a low vision (LV) group (n = 8) had impaired sensitivity at the anatomical fovea and/or poor fixation stability, whereas a low vision that excluded the fovea (LV: F) group (n = 4) was characterized by at least some residual foveal sensitivity but insensitivity in other retinal regions. The LV group performed worse than the other groups at all blur levels, whereas the performance of the LV: F group was not credibly different from that of the CS group. The performance of the CS and LV: F groups deteriorated as blur increased, whereas the LV group showed consistently poor performance regardless of blur. Visual acuity and fixation stability were correlated with face recognition performance. CONCLUSIONS. Persons diagnosed as having disease affecting the central visual field can recognize faces as well as persons with no visual disease provided that they have residual sensitivity in the anatomical fovea and show stable fixation patterns. Performance in this task is limited by the upper resolution of nonfoveal vision or image blur, whichever is worse. C1 [Wallis, Thomas S. A.; Taylor, Christopher Patrick; Bex, Peter J.] Harvard Univ, Sch Med, Schepens Eye Res Inst, Boston, MA USA. [Wallis, Thomas S. A.] Univ Western Australia, Sch Psychol, Perth, WA 6009, Australia. [Wallis, Jennifer; Jackson, Mary Lou] Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Boston, MA USA. RP Wallis, TSA (reprint author), Univ Tubingen, Ctr Integrat Neurosci, Tubingen, Germany. EM thomas.wallis@uni-tuebingen.de FU National Health and Medical Research Council of Australia [634560]; National Institutes of Health [EY019281, EY018664] FX TSAW was supported by Fellowship 634560 from the National Health and Medical Research Council of Australia. PJB was supported by Grants EY019281 and EY018664 from the National Institutes of Health. NR 67 TC 3 Z9 3 U1 3 U2 15 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 EI 1552-5783 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD JAN PY 2014 VL 55 IS 1 BP 142 EP 153 DI 10.1167/iovs.13-12420 PG 12 WC Ophthalmology SC Ophthalmology GA AB6DG UT WOS:000331877200016 PM 24302589 ER PT J AU Low, BE Krebs, MP Joung, JK Tsai, SQ Nishina, PM Wiles, MV AF Low, Benjamin E. Krebs, Mark P. Joung, J. Keith Tsai, Shengdar Q. Nishina, Patsy M. Wiles, Michael V. TI Correction of the Crb1(rd8) Allele and Retinal Phenotype in C57BL/6N Mice Via TALEN-Mediated Homology-Directed Repair SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Article DE genetic engineering; TALEN; CRB1 associated disease; KOMP; gene therapy ID ZINC-FINGER TARGETER; EMBRYO MICROINJECTION; DROSOPHILA-CRUMBS; MOUSE STRAINS; GENE; MUTATIONS; DEGENERATION; MODEL; CRB1; CONSORTIUM AB PURPOSE. We directly corrected the mouse Crb1(rd8) gene mutation, which is present in many inbred laboratory strains derived from C57BL/6N and complicates genetic studies of retinal disease in mice. METHODS. Fertilized C57BL/6NJ oocytes were coinjected with mRNAs encoding a transcription activator-like effector nuclease (TALEN) targeting the Crb1(rd8) allele plus single-stranded oligonucleotides to correct the allele. The oligonucleotides included additional nucleotide changes to distinguish the corrected allele (Crb1(em1Mvw)) from wildtype Crb1 and to minimize TALEN recutting. Oligonucleotide length, concentration of injected oligonucleotides and TALEN mRNAs were varied to optimize homology-directed repair of the locus. Following microinjection, embryos were carried to term in pseudopregnant females. Correction efficiency was assessed by PCR analysis of the Crb1(em1Mvw) allele. Phenotypic correction was demonstrated by fundus imaging and optical coherence tomography of live mice, and by confocal fluorescence microscopy of retinal flat mounts. RESULTS. Under optimal conditions, homology-directed repair was observed in 27% (8/30) of live-born animals and showed minimal illegitimate recombination of donor DNA. However, extensive founder mosaicism was evident, emphasizing the need to analyze offspring of founder animals. Unlike C57BL/6NJ mice, which exhibited external limiting membrane fragmentation and regional retinal dysplasia, heterozygous Crb1(em1Mvw)/Crb1(rd8) mice showed a normal retinal phenotype. CONCLUSIONS. The C57BL/6NJ-Crb1(rd8) mutation and its associated retinal phenotypes were corrected efficiently by TALEN-mediated homology-directed repair. The C57BL/6NJCrb1(em1Mvw) mice generated by this strategy will enhance ocular phenotyping efforts based on the C57BL/6N background, such as those implemented by the International Mouse Phenotyping Consortium (IMPC) project. C1 [Low, Benjamin E.; Krebs, Mark P.; Nishina, Patsy M.; Wiles, Michael V.] Jackson Lab, Bar Harbor, ME 04609 USA. [Joung, J. Keith] Massachusetts Gen Hosp, Ctr Computat & Integrat Biol, Mol Pathol Unit, Charlestown, MA USA. [Joung, J. Keith] Massachusetts Gen Hosp, Ctr Canc Res, Charlestown, MA USA. [Tsai, Shengdar Q.] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. RP Wiles, MV (reprint author), Jackson Lab, 600 Main St, Bar Harbor, ME 04609 USA. EM mvwiles@jax.org FU National Institutes of Health [OD011190, EY011996]; National Institutes of Health Research Fellowship under Ruth L. Kirschstein National Research Service Award; National Institutes of Health Cancer Center Support (CORE) [5P30CA034196] FX Supported by National Institutes of Health Grant OD011190 (MVW), National Institutes of Health Grant EY011996 (PMN), National Institutes of Health Research Fellowship under the Ruth L. Kirschstein National Research Service Award 1F32GM105189 (SQT), and by National Institutes of Health Cancer Center Support (CORE) Grant 5P30CA034196 (The Jackson Laboratory). NR 32 TC 15 Z9 15 U1 0 U2 2 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 EI 1552-5783 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD JAN PY 2014 VL 55 IS 1 BP 387 EP 395 DI 10.1167/iovs.13-13278 PG 9 WC Ophthalmology SC Ophthalmology GA AB6DG UT WOS:000331877200044 PM 24346171 ER PT J AU Giovannetti, E Wang, QY Avan, A Funel, N Lagerweij, T Lee, JH Caretti, V van der Velde, A Boggi, U Wang, YS Vasile, E Peters, GJ Wurdinger, T Giaccone, G AF Giovannetti, Elisa Wang, Qiuyan Avan, Amir Funel, Niccola Lagerweij, Tonny Lee, Jih-Hsiang Caretti, Viola van der Velde, Arjan Boggi, Ugo Wang, Yisong Vasile, Enrico Peters, Godefridus J. Wurdinger, Thomas Giaccone, Giuseppe TI Role of CYB5A in Pancreatic Cancer Prognosis and Autophagy Modulation SO JNCI-JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Article ID DUCTAL ADENOCARCINOMA; SIGNALING PATHWAYS; LUNG-CANCER; CELL-DEATH; GENE; EXPRESSION; TRAF6; CHEMOTHERAPY; GEMCITABINE; GROWTH AB Background Loss of 18q22.3 is a prognostic marker in pancreatic ductal adenocarcinoma (PDAC). This study investigated genes encoded by this cytoband. Methods We studied mRNA/protein expression in radically resected (n = 130) and metastatic patients (n = 50). The role of CYB5A was tested in 11 PDAC cell lines and five primary cultures through retrovirus-mediated upregulation and small interfering RNA using wound-healing, invasion, annexin-V, electron microscopy, and autophagic assays, as well as autophagy genes and kinases arrays. CYB5A+ orthotopic models (n = 6 mice/group) were monitored by Firefly and Gaussia-luciferase bioluminescence, magnetic resonance imaging, and high-frequency ultrasound. Data were analyzed by t test, Fisher exact-test, log-rank test and Cox proportional hazards models. All statistical tests were two-sided. Results Both resected and metastatic patients with low mRNA or protein expression of CYB5A had statistically significantly shorter survival (eg, median = 16.7 months, 95% confidence interval [CI] = 13.5 to 19.9; vs median = 24.8 months, 95% CI = 12.8 to 36.9; P = .02, two-sided log-rank test; n = 82 radically resected PDACs), and multivariable analyses confirmed prognostic relevance. Moreover, we characterized a novel function to CYB5A, autophagy induction, concomitant with reduced proliferation and migration/invasion of PDAC cells. Network analysis of proautophagic pathways suggested CYB5A interaction with TRAF6, which was confirmed by TRAF6 downregulation after CYB5A reconstitution (-69% in SU.86.86-CYB5A+; P = .005, two-sided t test). CYB5A silencing had opposite effects, restoring TRAF6 expression and wound healing. In vivo studies showed that CYB5A induced autophagy while inhibiting tumor growth/metastasis and increasing survival (median = 57 days, 95% CI = 52 to 61; vs median = 44 days, 95% CI = 21 to 57; P = .03, two-sided log-rank test). Conclusions These results define CYB5A as a novel prognostic factor for PDAC that exerts its tumor-suppressor function through autophagy induction and TRAF6 modulation. C1 [Giovannetti, Elisa; Avan, Amir; Peters, Godefridus J.] Vrije Univ Amsterdam, Dept Med Oncol, Med Ctr, NL-1081 HV Amsterdam, Netherlands. [Lagerweij, Tonny; Caretti, Viola; Wurdinger, Thomas] Vrije Univ Amsterdam, Dept Neurosurg, Med Ctr, NL-1081 HV Amsterdam, Netherlands. [van der Velde, Arjan] Vrije Univ Amsterdam, Ctr Integrat Bioinformat, NL-1081 HV Amsterdam, Netherlands. [Funel, Niccola; Boggi, Ugo; Vasile, Enrico] Univ Pisa, Dept Ric Traslaz & Nuove Tecnol Med & Chirurg, Pisa, Italy. [Caretti, Viola] Stanford Univ, Dept Neurol, Stanford, CA 94305 USA. [Wurdinger, Thomas] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. [Wurdinger, Thomas] Harvard Univ, Sch Med, Program Neurosci, Boston, MA 02115 USA. [Wang, Qiuyan; Lee, Jih-Hsiang; Wang, Yisong; Giaccone, Giuseppe] NCI, Med Oncol Branch, NIH, Bethesda, MD 20892 USA. RP Giovannetti, E (reprint author), Vrije Univ Amsterdam, Dept Med Oncol, Canc Ctr Amsterdam, Med Ctr, CCA Rm 1-52,De Boelelaan 1117, NL-1081 HV Amsterdam, Netherlands. EM e.giovannetti@vumc.nl RI Giaccone, Giuseppe/E-8297-2017; OI Giaccone, Giuseppe/0000-0002-5023-7562; Lagerweij, Tonny/0000-0003-1043-7452; Giovannetti, Elisa/0000-0002-7565-7504; van der Velde, Arjan/0000-0003-1086-0859; Funel, Niccola/0000-0002-5028-2363 FU Netherlands Organization for Scientific Research; Marie Curie International Fellowship; CCA Foundation; Italian Minister of Research; Istituto Toscano Tumori; National Institutes of Health/National Cancer Institute intramural research funds; U.S. National Institute of General Medical Sciences [GM070743]; National Resource for Network Biology [P41 RR031228, GM103504]; Veni grant FX This work was partially supported by grants from Netherlands Organization for Scientific Research; Veni grant (to EG); Marie Curie International Fellowship (to EG); CCA Foundation 2012 (to EG, AA, GJP); Italian Minister of Research; PRIN-2009 (to UB, NF, EG); Istituto Toscano Tumori (to UB, NF, EV, EG), and National Institutes of Health/National Cancer Institute intramural research funds. Funding for continued development and maintenance of Cytoscape is provided by the U.S. National Institute of General Medical Sciences (GM070743). Cytoscape user support, education and new initiatives are supported by the National Resource for Network Biology (P41 RR031228 and GM103504). Further information is available at http://www.cytoscape.org/. NR 50 TC 9 Z9 9 U1 1 U2 8 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0027-8874 EI 1460-2105 J9 JNCI-J NATL CANCER I JI JNCI-. Natl. Cancer Inst. PD JAN PY 2014 VL 106 IS 1 AR djt346 DI 10.1093/jnci/djt346 PG 12 WC Oncology SC Oncology GA AB6IV UT WOS:000331891900006 PM 24301457 ER PT J AU Oxnard, GR Nguyen, KSH Costa, DB AF Oxnard, Geoffrey R. Nguyen, Kim-Son H. Costa, Daniel B. TI Germline Mutations in Driver Oncogenes and Inherited Lung Cancer Risk Independent of Smoking History SO JNCI-JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Editorial Material ID TYROSINE KINASE INHIBITORS; GENOME-WIDE ASSOCIATION; NEVER-SMOKERS; ACQUIRED-RESISTANCE; GENETIC-VARIANTS; EGFR; SUSCEPTIBILITY; ADENOCARCINOMAS; TUMORS; GEFITINIB C1 [Oxnard, Geoffrey R.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Nguyen, Kim-Son H.] Stanford Univ, Med Ctr, Dept Med, Div Med Oncol, Palo Alto, CA 94304 USA. [Costa, Daniel B.] Harvard Univ, Beth Israel Deaconess Med Ctr, Div Hematol Oncol, Dept Med,Med Sch, Boston, MA 02215 USA. RP Costa, DB (reprint author), Beth Israel Deaconess Med Ctr, Div Hematol Oncol, 330 Brookline Ave, Boston, MA 02215 USA. EM dbcosta@bidmc.harvard.edu OI Costa, Daniel/0000-0002-0689-395X NR 23 TC 3 Z9 4 U1 0 U2 5 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0027-8874 EI 1460-2105 J9 JNCI-J NATL CANCER I JI JNCI-. Natl. Cancer Inst. PD JAN PY 2014 VL 106 IS 1 AR djt361 DI 10.1093/jnci/djt361 PG 3 WC Oncology SC Oncology GA AB6IV UT WOS:000331891900015 PM 24317178 ER PT J AU Pierce, JP Patterson, RE Senger, CM Flatt, SW Caan, BJ Natarajan, L Nechuta, SJ Poole, EM Shu, XO Chen, WY AF Pierce, John P. Patterson, Ruth E. Senger, Carolyn M. Flatt, Shirley W. Caan, Bette J. Natarajan, Loki Nechuta, Sarah J. Poole, Elizabeth M. Shu, Xiao-Ou Chen, Wendy Y. TI Lifetime Cigarette Smoking and Breast Cancer Prognosis in the After Breast Cancer Pooling Project SO JNCI-JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Article ID PROSPECTIVE COHORT; RISK-FACTORS; SURVIVAL; WOMEN; MORTALITY; SMOKERS AB Background There is controversy on whether former smokers have increased risk for breast cancer recurrence or all-cause mortality, regardless of how much they smoked. Methods Data were from three US cohorts in the After Breast Cancer Pooling Project, with detailed information on smoking among 9975 breast cancer survivors. Smoking was assessed an average of 2 years after diagnosis. Delayed entry Cox proportional hazards models were used to examine the relationships of smoking status, cigarettes per day, years of smoking, and pack years with breast cancer prognosis. Endpoints included breast cancer recurrence (n = 1727), breast cancer mortality (n = 1059), and overall mortality (n = 1803). Results Compared with never smokers, former smokers with less than 20 pack-years of exposure had no increased risk of any outcome. However, former smokers with 20 to less than 34.9 pack-years of exposure had a 22% increased risk of breast cancer recurrence (hazard ratio [HR] = 1.22; 95% confidence interval [CI] = 1.01 to 1.48) and a 26% increased risk of all-cause mortality (HR = 1.26; 95% CI = 1.07 to 1.48). For former smokers with 35 or more pack-years of exposure, the probability of recurrence increased by 37% (HR = 1.37; 95% CI = 1.13 to 1.66), breast cancer mortality increased by 54% (HR = 1.54; 95% CI = 1.24 to 1.91), and all-cause mortality increased by 68% (HR = 1.68; 95% CI = 1.44 to 1.96). Current smoking increased the probability of recurrence by 41% (HR = 1.41; 95% CI = 1.16 to 1.71), increased breast cancer mortality by 60% (HR = 1.61; 95% CI = 1.28 to 2.03), and doubled the risk of all-cause mortality (HR = 2.17; 95% CI = 1.85 to 2.54). Conclusions Lifetime cigarette smoking was statistically significantly associated with a poor prognosis among women diagnosed with breast cancer, dose-dependent increased risks of recurrence, and breast cancer and all-cause mortality. C1 [Pierce, John P.; Patterson, Ruth E.; Senger, Carolyn M.; Flatt, Shirley W.; Natarajan, Loki] Univ Calif San Diego, Canc Prevent & Control Program, Moores UCSD Canc Ctr, La Jolla, CA 92093 USA. [Caan, Bette J.] Kaiser Permanente, Div Res, Oakland, CA USA. [Nechuta, Sarah J.; Shu, Xiao-Ou] Vanderbilt Univ, Sch Med, Div Epidemiol, Dept Med, Nashville, TN 37212 USA. [Poole, Elizabeth M.; Chen, Wendy Y.] Brigham & Womens Hosp, Dept Med, Channing Lab, Boston, MA USA. [Poole, Elizabeth M.; Chen, Wendy Y.] Harvard Univ, Sch Med, Boston, MA USA. [Chen, Wendy Y.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. RP Pierce, JP (reprint author), Univ Calif San Diego, Canc Prevent & Control Program, Moores UCSD Canc Ctr, La Jolla, CA 92093 USA. EM jppierce@ucsd.edu FU National Cancer Institute at the National Institutes of Health [3R01 CA118229-03S1, 1RO1CA166293-01A1]; Women's Healthy Eating & Living Study (Susan G. Komen Foundation) [KG100988]; Life After Cancer Epidemiology Study (National Cancer Institute) [R01 CA129059]; Nurses' Health Study [P01 CA87969] FX This Pooling Project was supported by the National Cancer Institute at the National Institutes of Health (3R01 CA118229-03S1 and 1RO1CA166293-01A1). Support for the individual cohorts came from Women's Healthy Eating & Living Study (Susan G. Komen Foundation, KG100988); Life After Cancer Epidemiology Study (National Cancer Institute, R01 CA129059); and the Nurses' Health Study (P01 CA87969). NR 26 TC 5 Z9 5 U1 0 U2 2 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0027-8874 EI 1460-2105 J9 JNCI-J NATL CANCER I JI JNCI-. Natl. Cancer Inst. PD JAN PY 2014 VL 106 IS 1 AR djt359 DI 10.1093/jnci/djt359 PG 8 WC Oncology SC Oncology GA AB6IV UT WOS:000331891900017 PM 24317179 ER PT J AU Murray, PS Kirkwood, CM Gray, MC Fish, KN Ikonomovic, MD Hamilton, RL Kofler, JK Klunk, WE Lopez, OL Sweet, RA AF Murray, Patrick S. Kirkwood, Caitlin M. Gray, Megan C. Fish, Kenneth N. Ikonomovic, Milos D. Hamilton, Ronald L. Kofler, Julia K. Klunk, William E. Lopez, Oscar L. Sweet, Robert A. TI Hyperphosphorylated Tau is Elevated in Alzheimer's Disease with Psychosis SO JOURNAL OF ALZHEIMERS DISEASE LA English DT Article DE Alzheimer's disease; Braak stage; Mini-Mental State Examination; psychosis; tau ID A-BETA OLIGOMERS; NEUROFIBRILLARY TANGLES; NATIONAL INSTITUTE; SYNAPSE LOSS; NEUROPATHOLOGIC ASSESSMENT; NEUROPSYCHIATRIC SYMPTOMS; COGNITIVE IMPAIRMENT; ENDOGENOUS TAU; RISK-FACTORS; LEWY BODIES AB Psychosis occurs in 40-60% of Alzheimer's disease (AD) subjects, is heritable, and indicates a more rapidly progressive disease phenotype. Neuroimaging and postmortem evidence support an exaggerated prefrontal cortical synaptic deficit in AD with psychosis. Microtubule-associated protein tau is a key mediator of amyloid-beta-induced synaptotoxicity in AD, and differential mechanisms of progressive intraneuronal phospho-tau accumulation and interneuronal spread of tau aggregates have recently been described. We hypothesized that psychosis in AD would be associated with greater intraneuronal concentration of phosphotau and greater spread of tau aggregates in prefrontal cortex. We therefore evaluated prefrontal cortex phospho-tau in a cohort of 45 AD cases with and without psychosis. Intraneuronal phospho-tau concentration was higher in subjects with psychosis, while a measure of phospho-tau spread, volume fraction, was not. Across groups both measures were associated with lower scores on the Mini-Mental State Examination and Digit Span Backwards test. These novel findings indicate that tau phosphorylation may be accelerated in AD with psychosis, indicating a more dynamic, exaggerated pathology in AD with psychosis. C1 [Murray, Patrick S.; Kirkwood, Caitlin M.; Gray, Megan C.; Fish, Kenneth N.; Ikonomovic, Milos D.; Klunk, William E.; Lopez, Oscar L.; Sweet, Robert A.] Univ Pittsburgh, Sch Med, Dept Psychiat, Pittsburgh, PA USA. [Murray, Patrick S.; Sweet, Robert A.] VA Pittsburgh Healthcare Syst, Educ & Clin Ctr, VISN Mental Illness Res 4, Pittsburgh, PA USA. [Ikonomovic, Milos D.; Klunk, William E.; Lopez, Oscar L.; Sweet, Robert A.] Univ Pittsburgh, Sch Med, Dept Neurol, Pittsburgh, PA 15261 USA. [Ikonomovic, Milos D.] VA Pittsburgh Healthcare Syst, Geriatr Res Educ & Clin Ctr, Pittsburgh, PA USA. [Hamilton, Ronald L.; Kofler, Julia K.] Univ Pittsburgh, Sch Med, Dept Pathol, Pittsburgh, PA USA. RP Sweet, RA (reprint author), Biomed Sci Tower,W1645,3811 OHara St, Pittsburgh, PA 15213 USA. EM sweetra@upmc.edu OI Murray, Patrick/0000-0002-6525-2888 FU Veterans Health Administration [BX000452]; National Institute of Mental Health [MH071533, MH019986]; National Institute on Aging [AG005133, AG027224] FX This work was supported by the Veterans Health Administration [BX000452 to R. A. S]; the National Institute of Mental Health [MH071533 to R. A. S.]; and the National Institute on Aging [AG005133 to O.L.L., AG027224 to R. A. S.]. P. S. M. is supported by the National Institute of Mental Health [MH019986] and seed grant funding from the National Institute on Aging [AG005133]. NR 70 TC 9 Z9 9 U1 4 U2 5 PU IOS PRESS PI AMSTERDAM PA NIEUWE HEMWEG 6B, 1013 BG AMSTERDAM, NETHERLANDS SN 1387-2877 EI 1875-8908 J9 J ALZHEIMERS DIS JI J. Alzheimers Dis. PY 2014 VL 39 IS 4 BP 759 EP 773 DI 10.3233/JAD-131166 PG 15 WC Neurosciences SC Neurosciences & Neurology GA AB5QD UT WOS:000331842500007 PM 24270207 ER PT J AU Kleinnijenhuis, J Quintin, J Preijers, F Benn, CS Joosten, LAB Jacobs, C van Loenhout, J Xavier, RJ Aaby, P van der Meer, JWM van Crevel, R Netea, MG AF Kleinnijenhuis, Johanneke Quintin, Jessica Preijers, Frank Benn, Christine Stabell Joosten, Leo A. B. Jacobs, Cor van Loenhout, Joke Xavier, Ramnik J. Aaby, Peter van der Meer, Jos W. M. van Crevel, Reinout Netea, Mihai G. TI Long-Lasting Effects of BCG Vaccination on Both Heterologous Th1/Th17 Responses and Innate Trained Immunity SO JOURNAL OF INNATE IMMUNITY LA English DT Article DE Innate immunity; BCG vaccination; Trained immunity ID CALMETTE-GUERIN VACCINATION; CANDIDA-ALBICANS; RANDOMIZED-TRIAL; CHILD SURVIVAL; GUINEA-BISSAU; WEST-AFRICA; RESISTANCE; MEMORY; PROTECTION; MORTALITY AB We have recently shown that BCG (Bacillus Calmette-Guerin) vaccination in healthy volunteers induces epigenetic reprogramming of monocytes, leading to increased cytokine production in response to nonrelated pathogens for up to 3 months after vaccination. This phenomenon was named 'trained immunity'. In the present study we assessed whether BCG was able to induce long-lasting effects on both trained immunity and heterologous T helper 1 (Th1) and Th17 immune responses 1 year after vaccination. The production of TNF alpha and IL-1 beta to mycobacteria or unrelated pathogens was higher after 2 weeks and 3 months postvaccination, but these effects were less pronounced 1 year after vaccination. However, monocytes recovered 1 year after vaccination had an increased expression of pattern recognition receptors such as CD14, Toll-like receptor 4 (TLR4) and mannose receptor, and this correlated with an increase in proinflammatory cytokine production after stimulation with the TLR4 ligand lipopolysaccharide. The heterologous production of Th1 (IFN-gamma) and Th17 (IL-17 and IL-22) immune responses to nonmycobacterial stimulation remained strongly elevated even 1 year after BCG vaccination. In conclusion, BCG induces sustained changes in the immune system associated with a nonspecific response to infections both at the level of innate trained immunity and at the level of heterologous Th1/Th17 responses. (C) 2013 S. Karger AG, Basel C1 [Kleinnijenhuis, Johanneke; Quintin, Jessica; Joosten, Leo A. B.; Jacobs, Cor; van der Meer, Jos W. M.; van Crevel, Reinout; Netea, Mihai G.] Radboud Univ Nijmegen, Med Ctr, Dept Med, NL-6525 GA Nijmegen, Netherlands. [Kleinnijenhuis, Johanneke; Quintin, Jessica; Joosten, Leo A. B.; Jacobs, Cor; van der Meer, Jos W. M.; van Crevel, Reinout; Netea, Mihai G.] Radboud Univ Nijmegen, Med Ctr, Nijmegen Inst Infect Inflammat & Immun N4i, NL-6525 GA Nijmegen, Netherlands. [Preijers, Frank] Radboud Univ Nijmegen, Med Ctr, Dept Lab Med, Hematol Lab, NL-6525 GA Nijmegen, Netherlands. [van Loenhout, Joke] Radboud Univ Nijmegen, Med Ctr, GGD, NL-6525 GA Nijmegen, Netherlands. [Benn, Christine Stabell; Aaby, Peter] Statens Serum Inst, Res Ctr Vitamins & Vaccines CVIVA, DK-2300 Copenhagen, Denmark. [Xavier, Ramnik J.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Computat & Integrat Biol, Boston, MA USA. [Xavier, Ramnik J.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Gastrointestinal Unit, Boston, MA USA. [Xavier, Ramnik J.] MIT, Broad Inst, Cambridge, MA 02139 USA. [Xavier, Ramnik J.] Harvard Univ, Cambridge, MA 02138 USA. RP Netea, MG (reprint author), Radboud Univ Nijmegen, Med Ctr, Dept Med 463, Geert Grooteplein Zuid 8, NL-6525 GA Nijmegen, Netherlands. EM m.netea@aig.umcn.nl RI van Crevel, reinout/A-6636-2010; Joosten, Leo/H-3138-2015; Netea, Mihai/N-5155-2014; Kleinnijenhuis, Johanneke/P-6309-2015; Preijers, F.W.M.B./L-4586-2015; kleinnijenhuis, johanneke/G-7978-2016; van der Meer, Jos/C-8521-2013 OI van der Meer, Jos/0000-0001-5120-3690 FU Vici Grant of the Netherlands Organization for Scientific Research; Vidi Grant of the Netherlands Organization for Scientific Research; US National Institutes of Health [AI 062773, DK 043351, DK 83756]; Helmsley Trust; Danish National Research Foundation [DNRF108]; ERC Starting Grant [ERC-2009-StG-243149] FX J.Q. and M.G.N. were supported by a Vici Grant of the Netherlands Organization for Scientific Research (to M.G.N.). R.V.C. was supported by a Vidi Grant of the Netherlands Organization for Scientific Research. R.J.X. was supported by grants (AI 062773, DK 043351, DK 83756) from the US National Institutes of Health and the Helmsley Trust. CVIVA is supported by the Danish National Research Foundation (DNRF108). CSB was funded by an ERC Starting Grant (through grant ERC-2009-StG-243149). NR 35 TC 44 Z9 44 U1 1 U2 12 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 1662-811X EI 1662-8128 J9 J INNATE IMMUN JI J. Innate Immun. PY 2014 VL 6 IS 2 BP 152 EP 158 DI 10.1159/000355628 PG 7 WC Immunology SC Immunology GA AB4QL UT WOS:000331774900005 PM 24192057 ER PT J AU Isenhart, C Dieperink, E Thuras, P Fuller, B Stull, L Koets, N Lenox, R AF Isenhart, Carl Dieperink, Eric Thuras, Paul Fuller, Bret Stull, Laura Koets, Nancy Lenox, Rebecca TI Training and maintaining motivational interviewing skills in a clinical trial SO JOURNAL OF SUBSTANCE USE LA English DT Article DE Consultation; training; motivational interviewing; implementation AB Motivational interviewing (MI) is an evidence-based practice that is being implemented in a wide range of settings. Research supports the importance of ongoing coaching and feedback sessions following initial training in MI to implement and sustain MI-adherent competencies. This article describes the development and preliminary testing of a group feedback and consultation process where clinicians code each others' clinical samples of MI sessions and provide feedback to each other regarding the level of adherence to MI fidelity measures. Preliminary results suggest that group feedback may help clinicians develop and sustain MI skills. C1 [Isenhart, Carl; Dieperink, Eric; Thuras, Paul] Minneapolis VA Hlth Care Syst, Mental Hlth Serv Line, Minneapolis, MN 55417 USA. [Isenhart, Carl] Univ Minnesota, Dept Psychol, Minneapolis, MN 55455 USA. [Isenhart, Carl; Dieperink, Eric; Thuras, Paul] Univ Minnesota, Dept Psychiat, Minneapolis, MN 55455 USA. [Fuller, Bret; Lenox, Rebecca] Portland VA Med Ctr, Portland, OR USA. [Stull, Laura] Anderson Univ, Dept Psychol, Indiana, PA USA. [Koets, Nancy] Wright Patterson Med Ctr, Fairborn, OH USA. RP Isenhart, C (reprint author), Minneapolis VA Hlth Care Syst, One Vet Dr, Minneapolis, MN 55417 USA. EM Carl.Isenhart@va.gov NR 12 TC 1 Z9 1 U1 2 U2 6 PU INFORMA HEALTHCARE PI NEW YORK PA 52 VANDERBILT AVE, NEW YORK, NY 10017 USA SN 1465-9891 EI 1475-9942 J9 J SUBST USE JI J. Subst. Use PY 2014 VL 19 IS 1-2 BP 164 EP 170 DI 10.3109/14659891.2013.765514 PG 7 WC Substance Abuse SC Substance Abuse GA AB6XM UT WOS:000331933000025 ER PT J AU Wan, JY Edwards, KL Hutter, CM Mata, IF Samii, A Roberts, JW Agarwal, P Checkoway, H Farin, FM Yearout, D Zabetian, CP AF Wan, Jia Y. Edwards, Karen L. Hutter, Carolyn M. Mata, Ignacio F. Samii, Ali Roberts, John W. Agarwal, Pinky Checkoway, Harvey Farin, Federico M. Yearout, Dora Zabetian, Cyrus P. TI Association mapping of the PARK10 region for Parkinson's disease susceptibility genes SO PARKINSONISM & RELATED DISORDERS LA English DT Article DE PARK10; Parkinson's disease; Replication; GWAS ID GENOME-WIDE ASSOCIATION; CANDIDATE GENES; RISK-FACTORS; ONSET; POPULATION; ELAVL4; AGE; IDENTIFICATION; GENETICS; LOCI AB Background: Previous studies indicate that as many as six genes within the PARK10 region (RNF11, UQCRH, HIVEP3, EIF2B3, USP24, ELAVL4) might modify susceptibility or age at onset in Parkinson's disease (PD). Methods: We sought to identify new PD susceptibility genes and to validate previously nominated candidate genes within the PARK10 region using a two-stage design. We used data from a large, publicly-available genome-wide association study (GWAS) in the discovery stage (n = 2000 cases and 1986 controls) and data from three independent studies for the replication stage (total n = 2113 cases and 2095 controls). Marker density was increased by imputation using HapMap 3 and 1000 Genomes reference panels, and over 40,000 single nucleotide polymorphisms (SNPs) were used in the final analysis. The association between each SNP and PD was modeled using logistic regression with an additive allele dosage effect and adjusted for sex, age, and axes of geographical variation. Results: Although the discovery stage yielded promising findings for SNPs in several novel genes, including DAB1, none of the results were validated in the replication stage. Furthermore, in meta-analyses across all datasets no genes within PARK10 reached significance after accounting for multiple testing. Conclusion: Our results suggest that common variation in the PARK10 region is not associated with PD risk. However, additional studies are needed to assess the role of PARK10 in modifying age at onset and to determine whether rare variants in this region might affect PD susceptibility. Published by Elsevier Ltd. C1 [Wan, Jia Y.; Edwards, Karen L.; Hutter, Carolyn M.; Checkoway, Harvey] Univ Washington, Sch Publ Hlth, Dept Epidemiol, Seattle, WA 98195 USA. [Mata, Ignacio F.; Samii, Ali; Yearout, Dora; Zabetian, Cyrus P.] Vet Affairs Puget Sound Hlth Care Syst, Seattle, WA USA. [Mata, Ignacio F.; Samii, Ali; Yearout, Dora; Zabetian, Cyrus P.] Univ Washington, Sch Med, Dept Neurol, Seattle, WA USA. [Roberts, John W.] Virginia Mason Med Ctr, Seattle, WA 98101 USA. [Agarwal, Pinky] Evergreen Hosp, Med Ctr, Booth Gardner Parkinsons Care Ctr, Kirkland, WA USA. [Checkoway, Harvey; Farin, Federico M.] Univ Washington, Sch Publ Hlth, Dept Environm & Occupat Hlth Sci, Seattle, WA 98195 USA. RP Zabetian, CP (reprint author), VA Puget Sound Hlth Care Syst, Geriatr Res Educ & Clin Ctr S 182, 1660 S Columbian Way, Seattle, WA 98108 USA. EM zabetian@u.washington.edu OI Zabetian, Cyrus/0000-0002-7739-4306 FU Allergan; Prana Biotechnology Limited; MERZ; NeuroSearch; Solstice Neurosciences; Ipsen; Adamas; CHDI; HP Therapeutics Foundation, Inc; Addex Therapeutics; NIH; Multiple Sclerosis Society; Department of Veterans Affairs; American Parkinson Disease Association; Parkinson's Disease Foundation FX Ms. Wan receives salary support from the NIH.; Dr. Edwards is funded by grants from the NIH.; Dr. Hutter received funding from University of Washington Royalty Research Fund and grants from the NIH.; Dr. Mata is funded by grants from the Department of Veterans Affairs, NIH, and Parkinson's Disease Foundation. Dr. Agarwal has received honoraria as a speaker for Teva, GSK, UCB, Impax, and consultancy for Merz and has been provided research support from Allergan, Prana Biotechnology Limited, MERZ, NeuroSearch, Solstice Neurosciences, Ipsen, Adamas, CHDI, HP Therapeutics Foundation, Inc., Addex Therapeutics, and the NIH.; Dr. Checkoway is funded by grants from the NIH and the Multiple Sclerosis Society. He also serves as a paid consultant for the Alcoa Co., Pittsburgh, PA, the Electric Power Research Institute, Palo Alto, CA, ENVIRON, Amherst, MA, and the University of Minnesota Dept. of Environmental Health, Minneapolis, MN.; Dr. Farin is funded by grants from the NIH.; Ms. Yearout receives salary support from the Department of Veterans Affairs and NIH.; Dr. Zabetian is funded by grants from the Department of Veterans Affairs, NIH, the American Parkinson Disease Association, Department of Veterans Affairs, NIH, and Parkinson's Disease Foundation. NR 30 TC 5 Z9 5 U1 0 U2 3 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 1353-8020 EI 1873-5126 J9 PARKINSONISM RELAT D JI Parkinsonism Relat. Disord. PD JAN PY 2014 VL 20 IS 1 BP 93 EP 98 DI 10.1016/j.parkreldis.2013.10.001 PG 6 WC Clinical Neurology SC Neurosciences & Neurology GA AB0VU UT WOS:000331511000018 PM 24156912 ER PT J AU Meserve, EE Lehmann, LE Perez-Atayde, AR Labelle, JL AF Meserve, Emily E. Lehmann, Leslie E. Perez-Atayde, Antonio R. Labelle, James L. TI Cyclophosphamide-Associated Cardiotoxicity in a Child After Stem Cell Transplantation for beta-Thalassemia Major: Case Report and Review of the Literature SO PEDIATRIC AND DEVELOPMENTAL PATHOLOGY LA English DT Review DE beta-thalassemia major; cyclophosphamide cardiotoxicity; endothelial cell; extracorporeal membrane oxygenation; hematopoietic stem cell transplantation; thrombotic microangiopathy ID BONE-MARROW-TRANSPLANTATION; CHEMOTHERAPY; THERAPY; UK AB We present a clinicopathologic study of the youngest reported child with lethal cyclophosphamide-induced cardiotoxicity after hematopoietic stem cell transplantation for beta-thalassemia major and the 1st pediatric report of the use of extracorporeal membrane oxygenation as a therapeutic modality to bridge the patient to myocardial recovery. Despite improvement in myocardial function while on extracorporeal membrane oxygenation, at autopsy 11 days after the onset of cardiac dysfunction, epicardial hemorrhage and extensive myocardial hemorrhagic infarction were revealed. Histopathologic and ultrastructural examination of the myocardium revealed extensive coagulative necrosis of cardiomyocytes, endothelial damage, fibrin thrombi, and subendothelial and interstitial fibrin. We review the literature on cyclophosphamide-induced cardiotoxicity and describe its clinicopathologic characteristics. Our findings point to endothelial damage leading to thrombotic microangiopathy and ischemic tissue injury as the most likely pathogenesis. C1 [Meserve, Emily E.; Perez-Atayde, Antonio R.] Boston Childrens Hosp, Dept Pathol, Boston, MA 02115 USA. [Lehmann, Leslie E.; Labelle, James L.] Dana Farber Canc Inst, Dept Pediat Hematol Oncol, Boston, MA 02115 USA. [Lehmann, Leslie E.; Labelle, James L.] Harvard Univ, Sch Med, Boston, MA USA. RP Perez-Atayde, AR (reprint author), Boston Childrens Hosp, Dept Pathol, Boston, MA 02115 USA. EM antonio.perezatayde@childrens.harvard.edu NR 19 TC 0 Z9 0 U1 0 U2 3 PU ALLIANCE COMMUNICATIONS GROUP DIVISION ALLEN PRESS PI LAWRENCE PA 810 EAST 10TH STREET, LAWRENCE, KS 66044 USA SN 1093-5266 EI 1615-5742 J9 PEDIATR DEVEL PATHOL JI Pediatr. Dev. Pathol. PD JAN-FEB PY 2014 VL 17 IS 1 BP 50 EP 54 DI 10.2350/13-04-1324-CR.1 PG 5 WC Pathology; Pediatrics SC Pathology; Pediatrics GA AB7AP UT WOS:000331942000007 PM 24144431 ER PT J AU Campos, GM Ziemelis, M Paparodis, R Ahmed, M Davis, DB AF Campos, Guilherme M. Ziemelis, Martynas Paparodis, Rodis Ahmed, Muhammed Davis, Dawn Belt TI Laparoscopic reversal of Roux-en-Y gastric bypass: Technique and utility for treatment of endocrine complications SO SURGERY FOR OBESITY AND RELATED DISEASES LA English DT Article DE Hypoglycemia; Hyperinsulinemic hypoglycemia; Hypocalcemia; Gastric bypass; Reversal; Sleeve gastrectomy; GLP-1; Hypoparathyroidism; Nesidioblastosis; Laparoscopic reversal; Bariatric surgery ID BARIATRIC SURGERY; HYPERINSULINEMIC HYPOGLYCEMIA; PANCREATIC RESECTION; ISLET HYPERPLASIA; MANAGEMENT; NESIDIOBLASTOSIS; MECHANISMS; RESOLUTION; RESPONSES; OBESITY AB Background: The anatomic and physiologic changes with Roux-en-Y gastric bypass (RYGB) may lead to uncommon but occasionally difficult to treat complications such as hyperinsulinemic hypoglycemia with neuroglycopenia and recalcitrant hypocalcemia associated to hypoparathyroidism. Medical management of these complications is challenging. Laparoscopic reversal of RYGB anatomy with restoration of pyloric function and duodenal continuity is a potential treatment. The objective of this study was to present the indications, surgical technique, and clinical outcomes of laparoscopic reversal of RYGB. Methods: Prospective study of consecutive patients offered laparoscopic reversal of RYGB. Results: Five patients with remote laparoscopic RYGB underwent laparoscopic reversal of RYGB to normal anatomy (n = 2) or modified sleeve gastrectomy (n = 3). Indications were medically refractory hyperinsulinemic hypoglycemia with neuroglycopenia (n = 3), recalcitrant hypocalcemia with hypoparathyroidism (n = 1), and both conditions simultaneously (n = 1). Before reversal, all patients had a gastrostomy tube placed in the excluded stomach to document improvement of symptom's. Laparoscopic reversal was accomplished successfully in all patients. Three postoperative complications occurred: bleeding that required transfusion, gallstone pancreatitis, and a superficial trocar site infection. Average length of stay was 3 days. At a mean follow-up of 12 months (range 3 to 22), no additional episodes of neuroglycopenia occurred, average number of hypoglycemic episodes per week decreased from 18.5 +/- 12.4 to 1.5 +/- 1.9 (P = .05), and hypocalcemia became responsive to oral replacement therapy in both patients. Conclusions: Laparoscopic reversal of RYGB to normal anatomy or modified sleeve gastrectomy is feasible and may be a therapeutic option for selected patients with medically refractory hyperinsulinemic hypoglycemia and/or recalcitrant hypocalcemia associated with hypoparathyroidism. (C) 2014 American Society for Metabolic and Bariatric Surgery. All rights reserved. C1 [Campos, Guilherme M.; Ziemelis, Martynas] Univ Wisconsin, Dept Surg, Sch Med & Publ Hlth, Div Gen Surg,Sect Foregut & Bariatr Surg, Madison, WI 53792 USA. [Paparodis, Rodis; Ahmed, Muhammed; Davis, Dawn Belt] Univ Wisconsin, Dept Med, Sch Med & Publ Hlth, Div Endocrinol Diabet & Metab, Madison, WI 53792 USA. [Davis, Dawn Belt] William S Middleton Mem Vet Adm Med Ctr, Madison, WI USA. RP Campos, GM (reprint author), Univ Wisconsin, Dept Surg, Sch Med & Publ Hlth, 600 Highland Av,K4-730 CSC, Madison, WI 53792 USA. EM campos@surgery.wisc.edu RI Davis, Dawn/B-1624-2013; OI Paparodis, Rodis/0000-0003-2804-0859 FU Clinical and Translational Science Award (CTSA) program, through the National Institutes of Health National Center for Advancing Translational Sciences (NCATS) [UL1TR000427] FX This study was supported by the Clinical and Translational Science Award (CTSA) program, through the National Institutes of Health National Center for Advancing Translational Sciences (NCATS), grant UL1TR000427. The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH or the federal government. NR 35 TC 21 Z9 21 U1 3 U2 6 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1550-7289 EI 1878-7533 J9 SURG OBES RELAT DIS JI Surg. Obes. Relat. Dis. PD JAN-FEB PY 2014 VL 10 IS 1 BP 36 EP 43 DI 10.1016/j.soard.2013.05.012 PG 8 WC Surgery SC Surgery GA AB4QA UT WOS:000331773800006 PM 24120983 ER PT J AU Sogg, S AF Sogg, Stephanie TI Comment on: Temperament and one-year outcome of gastric bypass for severe obesity SO SURGERY FOR OBESITY AND RELATED DISEASES LA English DT Editorial Material ID BARIATRIC SURGERY C1 [Sogg, Stephanie] Massachusetts Gen Hosp, Weight Ctr, Boston, MA 02114 USA. [Sogg, Stephanie] Harvard Univ, Sch Med, Boston, MA USA. RP Sogg, S (reprint author), Massachusetts Gen Hosp, Weight Ctr, Boston, MA 02114 USA. NR 13 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 1550-7289 EI 1878-7533 J9 SURG OBES RELAT DIS JI Surg. Obes. Relat. Dis. PD JAN-FEB PY 2014 VL 10 IS 1 BP 148 EP 150 PG 3 WC Surgery SC Surgery GA AB4QA UT WOS:000331773800027 PM 24507082 ER PT J AU Li, L Kim, HT Nellore, A Patsoukis, N Petkova, V McDonough, S Politikos, I Nikiforow, S Soiffer, R Antin, JH Ballen, K Cutler, C Ritz, J Boussiotis, VA AF Li, L. Kim, H. T. Nellore, A. Patsoukis, N. Petkova, V. McDonough, S. Politikos, I. Nikiforow, S. Soiffer, R. Antin, J. H. Ballen, K. Cutler, C. Ritz, J. Boussiotis, V. A. TI Prostaglandin E2 promotes survival of naive UCB T cells via the Wnt/beta-catenin pathway and alters immune reconstitution after UCBT SO BLOOD CANCER JOURNAL LA English DT Article DE umbilical cord blood transplantation; immune reconstitution; prostaglandin E2; Wnt/beta-catenin pathway ID CORD BLOOD TRANSPLANTATION; GLYCOGEN-SYNTHASE KINASE-3; EARLY ENGRAFTMENT KINETICS; CUTTING EDGE; BONE-MARROW; ANTITUMOR IMMUNITY; GENE-EXPRESSION; BETA-CATENIN; CYCLIC-AMP; STEM-CELLS AB The outcome of umbilical cord blood transplantation (UCBT) is compromised by low hematopoietic stem cell (HSC) doses leading to prolonged time to engraftment, delayed immunological reconstitution and late memory T-cell skewing. Exposure of UCB to dimethyl-prostaglandin E2 (dmPGE2) increases HSC in vivo. We determined that exposure of UCB T lymphocytes to dmPGE2 modified Wnt signaling resulting in T cell factor (TCF)-mediated transcription. Wnt signaling upregulated interleukin (IL)-7R and IL-2R beta, resulting in enhanced survival mediated by the homeostatic cytokines IL-7 and IL-15. dmPGE2 also induced components of the Wnt pathway and Wnt receptors, thereby priming UCB T cells to receive signals via Wnt ligands in vivo. We observed that the Wnt transcription factor TCF7 and its target EOMES were elevated in the T cells of patients who received PGE2-treated UCBs. Consistent with the role of Wnt/beta-catenin signaling to induce and maintain naive, memory precursors and long-lived central memory CD8(+) cells, these patients also had increased fractions of CD8(+)CD45RO(-)CD62L(+) plus CD8(+)CD45RO(+)CD62L(+) subsets encompassing these T-cell populations. These effects of the PGE2/Wnt/beta-catenin axis may have significant implications for harnessing immunity in the context of UCBT, where impaired immune reconstitution is associated with late memory T-cell skewing. C1 [Li, L.; Nellore, A.; Patsoukis, N.; Politikos, I.; Boussiotis, V. A.] Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Dept Med,Div Hematol Oncol & Canc Biol, Boston, MA 02215 USA. [Kim, H. T.] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA. [Petkova, V.] Beth Israel Deaconess Med Ctr, Dept Pathol, Boston, MA 02215 USA. [McDonough, S.; Nikiforow, S.; Soiffer, R.; Antin, J. H.; Cutler, C.; Ritz, J.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Ballen, K.] Massachusetts Gen Hosp, Dept Med, Div Hematol Oncol, Boston, MA 02114 USA. RP Boussiotis, VA (reprint author), Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Dept Med,Div Hematol Oncol & Canc Biol, 330 Brookline Ave, Boston, MA 02215 USA. EM vboussio@bidmc.harvard.edu OI Politikos, Ioannis/0000-0002-8925-2399 FU NIH [HL107997-01, R56AI43552, RO1CA183605-01, U54HL081030, T32AI07549]; Leukemia and Lymphoma Society Translational Research Program [TRP 6222-11]; HHV6 Foundation Award FX This work was supported by NIH Grants HL107997-01, R56AI43552, RO1CA183605-01, U54HL081030, T32AI07549, the Leukemia and Lymphoma Society Translational Research Program TRP 6222-11 and by the HHV6 Foundation Award. NR 52 TC 8 Z9 8 U1 2 U2 4 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 JAN PY 2014 VL 4 AR e178 DI 10.1038/bcj.2013.75 PG 10 WC Oncology SC Oncology GA AA9GU UT WOS:000331402600009 PM 24442207 ER PT J AU Yeh, RW Vasaiwala, S Forman, DE Silbaugh, TS Zelevinski, K Lovett, A Normand, SLT Mauri, L AF Yeh, Robert W. Vasaiwala, Samip Forman, Daniel E. Silbaugh, Treacy S. Zelevinski, Katya Lovett, Ann Normand, Sharon-Lise T. Mauri, Laura TI Instrumental Variable Analysis to Compare Effectiveness of Stents in the Extremely Elderly SO CIRCULATION-CARDIOVASCULAR QUALITY AND OUTCOMES LA English DT Article DE aged; drug-eluting stents; percutaneous coronary intervention; stents ID PERCUTANEOUS CORONARY INTERVENTION; DRUG-ELUTING STENTS; BARE-METAL STENTS; CARDIOVASCULAR DATA REGISTRY; AMERICAN-COLLEGE; SAFETY; BENEFIT; MANAGEMENT; EFFICACY; OUTCOMES AB Background Evaluating novel therapies is challenging in the extremely elderly. Instrumental variable methods identify variables associated with treatment allocation to perform adjusted comparisons that may overcome limitations of more traditional approaches. Methods and Results Among all patients aged 85 years undergoing percutaneous coronary intervention in nonfederal hospitals in Massachusetts between 2003 and 2009 (n=2690), we identified quarterly drug-eluting stent (DES) use rates as an instrumental variable. We estimated risk-adjusted differences in outcomes for DES versus bare metal stents using a 2-stage least squares instrumental variable analysis method. Quarterly DES use ranged from 15% to 88%. Unadjusted 1-year mortality rates were 14.5% for DES versus 23.0% for bare metal stents (risk difference, -8.5%; P<0.001), an implausible finding compared with randomized trial results. Using instrumental variable analysis, DES were associated with no difference in 1-year mortality (risk difference, -0.8%; P=0.76) or bleeding (risk difference, 2.3%; P=0.33) and with significant reduction in target vessel revascularization (risk difference, -8.3%; P<0.0001). Conclusions Using an instrumental variable analysis, DES were associated with similar mortality and bleeding and a significant reduction in target vessel revascularization compared with bare metal stents in the extremely elderly. Variation in use rates may be useful as an instrumental variable to facilitate comparative effectiveness in groups underrepresented in randomized trials. C1 [Yeh, Robert W.] Massachusetts Gen Hosp, Dept Med, Div Cardiol, Boston, MA 02114 USA. [Vasaiwala, Samip] Maine Med Ctr, Dept Cardiol, Portland, OR USA. [Forman, Daniel E.; Mauri, Laura] Brigham & Womens Hosp, Dept Med, Div Cardiovasc Med, Boston, MA 02115 USA. [Yeh, Robert W.; Forman, Daniel E.; Silbaugh, Treacy S.; Zelevinski, Katya; Lovett, Ann; Normand, Sharon-Lise T.; Mauri, Laura] Harvard Univ, Sch Med, Dept Hlth Care Policy, Boston, MA 02115 USA. [Normand, Sharon-Lise T.] Harvard Univ, Sch Med, Dept Hlth Care Policy Biostat, Boston, MA USA. [Normand, Sharon-Lise T.] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. RP Mauri, L (reprint author), Brigham & Womens Hosp, 75 Francis St, Boston, MA 02115 USA. EM lmauri1@partners.org FU Agency for Healthcare Research and Quality [F32HS020130]; National Heart, Lung, and Blood Institute [1 K23 HL118138-01] FX This project was supported by grant number F32HS020130 from the Agency for Healthcare Research and Quality (Dr Vasaiwala). Dr Yeh is supported by career development award (1 K23 HL118138-01) from the National Heart, Lung, and Blood Institute. NR 25 TC 6 Z9 6 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1941-7705 EI 1941-7713 J9 CIRC-CARDIOVASC QUAL JI Circ.-Cardiovasc. Qual. Outcomes PD JAN PY 2014 VL 7 IS 1 BP 118 EP 124 DI 10.1161/CIRCOUTCOMES.113.000476 PG 7 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA AA4MY UT WOS:000331071200017 PM 24254887 ER PT J AU Givertz, MM Postmus, D Hillege, HL Mansoor, GA Massie, BM Davison, BA Ponikowski, P Metra, M Teerlink, JR Cleland, JGF Dittrich, HC O'Connor, CM Cotter, G Voors, AA AF Givertz, Michael M. Postmus, Douwe Hillege, Hans L. Mansoor, George A. Massie, Barry M. Davison, Beth A. Ponikowski, Piotr Metra, Marco Teerlink, John R. Cleland, John G. F. Dittrich, Howard C. O'Connor, Christopher M. Cotter, Gad Voors, Adriaan A. TI Renal Function Trajectories and Clinical Outcomes in Acute Heart Failure SO CIRCULATION-HEART FAILURE LA English DT Article DE cardiorenal syndrome; heart failure; hospitalization; mortality ID IN-HOSPITAL MORTALITY; MEDICARE BENEFICIARIES; ROLOFYLLINE; PROTECT; DYSFUNCTION; ANTAGONIST; PRESSURE; IMPACT; MODEL; TRIAL AB Background Prior studies have demonstrated adverse risk associated with baseline and worsening renal function in acute heart failure, but none has modeled the trajectories of change in renal function and their impact on outcomes. Methods and Results We used linear mixed models of serial measurements of blood urea nitrogen and creatinine to describe trajectories of renal function in 1962 patients with acute heart failure and renal dysfunction enrolled in the Placebo-Controlled Randomized Study of the Selective A(1) Adenosine Receptor Antagonist Rolofylline for Patients Hospitalized with Acute Decompensated Heart Failure and Volume Overload to Assess Treatment Effect on Congestion and Renal Function study. We assessed risk of 180-day mortality and 60-day cardiovascular or renal readmission and used Cox regression to determine association between renal trajectories and outcomes. Compared with patients alive at 180 days, patients who died were older, had lower blood pressure and ejection fraction, and higher creatinine levels at baseline. On average for the entire cohort, creatinine rose from days 1 to 3 and increased further after discharge, with the trajectory dependent on the day of discharge. Blood urea nitrogen, creatinine, and the rate of change in creatinine from baseline were the strongest independent predictors of 180-day mortality and 60-day readmission, whereas the rate of change of blood urea nitrogen from baseline was not predictive of outcomes. Baseline blood urea nitrogen >35 mg/dL and increase in creatinine >0.1 mg/dL per day increased the risk of mortality, whereas stable or decreasing creatinine was associated with reduced risk. Conclusions Patients with acute heart failure and renal dysfunction demonstrate variable rise and fall in renal indices during and immediately after hospitalization. Risk of morbidity and mortality can be predicted based on baseline renal function and creatinine trajectory during the first 7 days. Clinical Trial Registration URL: http://www.clinicaltrials.gov. Unique identifiers: NCT00328692 and NCT00354458. C1 [Givertz, Michael M.] Harvard Univ, Sch Med, Brigham & Womens Hosp, Div Cardiovasc,Dept Med, Boston, MA 02115 USA. [Postmus, Douwe; Hillege, Hans L.; Voors, Adriaan A.] Univ Groningen, Univ Med Ctr Groningen, Groningen, Netherlands. [Mansoor, George A.] Merck Res Labs, Rahway, NJ USA. [Massie, Barry M.; Teerlink, John R.] Univ Calif San Francisco, San Francisco VAMC, San Francisco, CA 94143 USA. [Davison, Beth A.; Cotter, Gad] Momentum Res Inc, Durham, NC USA. [Ponikowski, Piotr] Med Univ, Clin Mil Hosp, Wroclaw, Poland. [Metra, Marco] Univ Brescia, Brescia, Italy. [Cleland, John G. F.] Univ Hull, Kingston Upon Hull, Yorks, England. [Dittrich, Howard C.] Univ Iowa, Dept Med, Iowa City, IA 52242 USA. [O'Connor, Christopher M.] Duke Univ, Med Ctr, Durham, NC USA. RP Givertz, MM (reprint author), Harvard Univ, Sch Med, Brigham & Womens Hosp, Div Cardiovasc, 75 Francis St, Boston, MA 02115 USA. EM mgivertz@partners.org RI Ponikowski, Piotr/O-6454-2015; OI Ponikowski, Piotr/0000-0002-3391-7064; Metra, Marco/0000-0001-6691-8568; Davison, Beth/0000-0003-2374-6449; Cleland, John/0000-0002-1471-7016 FU NovaCardia, Inc. FX This study was originally funded by NovaCardia, Inc. In September 2007, NovaCardia became a wholly owned subsidiary of Merck & Co, Inc. NR 44 TC 22 Z9 22 U1 0 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1941-3289 EI 1941-3297 J9 CIRC-HEART FAIL JI Circ.-Heart Fail. PD JAN PY 2014 VL 7 IS 1 BP 59 EP 67 DI 10.1161/CIRCHEARTFAILURE.113.000556 PG 9 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA AA4ND UT WOS:000331071800009 PM 24281137 ER PT J AU Cleland, JG Chiswell, K Teerlink, JR Stevens, S Fiuzat, M Givertz, MM Davison, BA Mansoor, GA Ponikowski, P Voors, AA Cotter, G Metra, M Massie, BM O'Connor, CM AF Cleland, John G. Chiswell, Karen Teerlink, John R. Stevens, Susanna Fiuzat, Mona Givertz, Michael M. Davison, Beth A. Mansoor, George A. Ponikowski, Piotr Voors, Adriaan A. Cotter, Gad Metra, Marco Massie, Barry M. O'Connor, Christopher M. TI Predictors of Postdischarge Outcomes From Information Acquired Shortly After Admission for Acute Heart Failure A Report From the Placebo-Controlled Randomized Study of the Selective A1 Adenosine Receptor Antagonist Rolofylline for Patients Hospitalized With Acute Decompensated Heart Failure and Volume Overload to Assess Treatment Effect on Congestion and Renal Function (PROTECT) Study SO CIRCULATION-HEART FAILURE LA English DT Article DE acute heart failure; mortality; randomized controlled trial ID BLOOD UREA NITROGEN; INITIATE LIFESAVING TREATMENT; BRAIN NATRIURETIC PEPTIDE; PROGNOSTIC VALUE; OPTIMIZE-HF; VASOPRESSIN ANTAGONIST; INTRAVENOUS MILRINONE; SYSTOLIC DYSFUNCTION; RISK STRATIFICATION; ORGANIZED PROGRAM AB Background Acute heart failure is a common reason for admission, and outcome is often poor. Improved prognostic risk stratification may assist in the design of future trials and in patient management. Using data from a large randomized trial, we explored the prognostic value of clinical variables, measured at hospital admission for acute heart failure, to determine whether a few selected variables were inferior to an extended data set. Methods and Results The prognostic model included 37 clinical characteristics collected at baseline in PROTECT, a study comparing rolofylline and placebo in 2033 patients admitted with acute heart failure. Prespecified outcomes at 30 days were death or rehospitalization for any reason; death or rehospitalization for cardiovascular or renal reasons; and, at both 30 and 180 days, all-cause mortality. No variable had a c-index >0.70, and few had values >0.60; c-indices were lower for composite outcomes than for mortality. Blood urea was generally the strongest single predictor. Eighteen variables contributed independent prognostic information, but a reduced model using only 8 items (age, previous heart failure hospitalization, peripheral edema, systolic blood pressure, serum sodium, urea, creatinine, and albumin) performed similarly. For prediction of all-cause mortality at 180 days, the model c-index using all variables was 0.72 and for the simplified model, also 0.72. Conclusions A few simple clinical variables measured on admission in patients with acute heart failure predict a variety of adverse outcomes with accuracy similar to more complex models. However, predictive models were of only moderate accuracy, especially for outcomes that included nonfatal events. Better methods of risk stratification are required. Clinical Trial Registration URL: http://www.clinicaltrials.gov. Unique identifiers: NCT00328692 and NCT00354458. C1 [Cleland, John G.] Univ Hull, Kingston Upon Hull, Yorks, England. [Cleland, John G.] Univ London Imperial Coll Sci Technol & Med, Natl Heart & Lung Inst, London, England. [Chiswell, Karen; Stevens, Susanna; Fiuzat, Mona; O'Connor, Christopher M.] Duke Univ, Med Ctr, Duke Clin Res Inst, Durham, NC USA. [Teerlink, John R.; Massie, Barry M.] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Teerlink, John R.; Massie, Barry M.] San Francisco VA Med Ctr, San Francisco, CA USA. [Givertz, Michael M.] Brigham & Womens Hosp, Boston, MA 02115 USA. [Ponikowski, Piotr] Kardiol Klin, Wroclaw, Poland. [Voors, Adriaan A.] Univ Groningen, Univ Med Ctr Groningen, Groningen, Netherlands. [Davison, Beth A.; Cotter, Gad] Momentum Res Inc, Durham, NC USA. [Metra, Marco] Univ Brescia, Pzza Spedali Civili, Brescia, Italy. [Mansoor, George A.] Merck Res Labs, Rahway, NJ USA. RP Cleland, JG (reprint author), Univ London Imperial Coll Sci Technol & Med, Royal Brompton Hosp, Natl Heart & Lung Inst, London, England. EM j.cleland@imperial.ac.uk RI Ponikowski, Piotr/O-6454-2015; OI Ponikowski, Piotr/0000-0002-3391-7064; Cleland, John/0000-0002-1471-7016 FU Merck Research Laboratories, Rahway, NJ FX The study and analyses were funded by Merck Research Laboratories, Rahway, NJ. NR 45 TC 44 Z9 44 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1941-3289 EI 1941-3297 J9 CIRC-HEART FAIL JI Circ.-Heart Fail. PD JAN PY 2014 VL 7 IS 1 BP 76 EP 87 DI 10.1161/CIRCHEARTFAILURE.113.000284 PG 12 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA AA4ND UT WOS:000331071800011 PM 24281134 ER PT J AU Zakeri, R Borlaug, BA McNulty, SE Mohammed, SF Lewis, GD Semigran, MJ Deswal, A LeWinter, M Hernandez, AF Braunwald, E Redfield, MM AF Zakeri, Rosita Borlaug, Barry A. McNulty, Steven E. Mohammed, Selma F. Lewis, Gregory D. Semigran, Marc J. Deswal, Anita LeWinter, Martin Hernandez, Adrian F. Braunwald, Eugene Redfield, Margaret M. TI Impact of Atrial Fibrillation on Exercise Capacity in Heart Failure With Preserved Ejection Fraction A RELAX Trial Ancillary Study SO CIRCULATION-HEART FAILURE LA English DT Article DE atrial fibrillation; exercise; heart failure ID VENTRICULAR SYSTOLIC DYSFUNCTION; STRICT RATE CONTROL; RHYTHM CONTROL; VENTILATORY RESPONSE; ENERGY-EXPENDITURE; CATHETER ABLATION; CLINICAL STATUS; OF-CARDIOLOGY; CARDIOVERSION; MORTALITY AB Background Atrial fibrillation (AF) is common among patients with heart failure and preserved ejection fraction (HFpEF), but its clinical profile and impact on exercise capacity remain unclear. RELAX (Phosphodiesterase-5 Inhibition to Improve Clinical Status and Exercise Capacity in HFpEF) was a multicenter randomized trial testing the impact of sildenafil on peak VO2 in stable outpatients with chronic HFpEF. We sought to compare clinical features and exercise capacity among patients with HFpEF who were in sinus rhythm (SR) or AF. Methods and Results RELAX enrolled 216 patients with HFpEF, of whom 79 (37%) were in AF, 124 (57%) in SR, and 13 in other rhythms. Participants underwent baseline cardiopulmonary exercise testing, echocardiogram, biomarker assessment, and rhythm status assessment before randomization. Patients with AF were older than those in SR but had similar symptom severity, comorbidities, and renal function. -blocker use and chronotropic indices were also similar. Despite comparable left ventricular size and mass, AF was associated with worse systolic (lower EF, stroke volume, and cardiac index) and diastolic (shorter deceleration time and larger left atria) function compared with SR. Pulmonary artery systolic pressure was higher in AF. Patients with AF had higher N-terminal pro-B-type natriuretic peptide, aldosterone, endothelin-1, troponin I, and C-telopeptide for type I collagen levels, suggesting more severe neurohumoral activation, myocyte necrosis, and fibrosis. Peak VO2 was lower in AF, even after adjustment for age, sex, and chronotropic response, and V-E/VCO2 was higher. Conclusions AF identifies an HFpEF cohort with more advanced disease and significantly reduced exercise capacity. These data suggest that evaluation of the impact of different rate or rhythm control strategies on exercise tolerance in patients with HFpEF and AF is warranted. Clinical Trial Registration URL: http://www.clinicaltrials.gov. Unique identifier: NCT00763867. C1 [Zakeri, Rosita; Borlaug, Barry A.; Mohammed, Selma F.; Redfield, Margaret M.] Mayo Clin, Div Cardiol, Rochester, MN 55905 USA. [McNulty, Steven E.] Duke Clin Res Inst, Durham, NC USA. [Lewis, Gregory D.; Semigran, Marc J.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Deswal, Anita] Baylor Coll Med, Michael E DeBakey VA Med Ctr, Houston, TX 77030 USA. [Deswal, Anita] Baylor Coll Med, Dept Med, Houston, TX 77030 USA. [LeWinter, Martin] Univ Vermont, Coll Med, Cardiol Unit, Burlington, VT 05405 USA. [Braunwald, Eugene] Brigham & Womens Hosp, Dept Med, Div Cardiovasc, Boston, MA 02115 USA. RP Zakeri, R (reprint author), Mayo Clin, Guggenheim 9,200 First St SW, Rochester, MN 55905 USA. EM zakeri.rosita@mayo.edu RI Hernandez, Adrian F./A-7818-2016 OI Hernandez, Adrian F./0000-0003-3387-9616 FU NHLBI [U01HL084904, U01HL084861, U01HL084875, U01HL084877, U01HL084889, U01HL084890, U01HL084891, U01HL084899, U01HL084907, U01HL084931]; National Center for Advancing Translational Sciences (NCATS): [UL1TR000454]; National Institute on Minority Health and Health Disparities (NIMHD) [U54 MD007588]; Mayo Clinic Center for Clinical and Translational Science from the National Center for Advancing Translational Science [UL1TR000135]; [U10HL110262]; [T32 HL007111] FX This study was supported by grants from the NHLBI: U01HL084904 (for the data coordinating center), and U01HL084861, U01HL084875, U01HL084877, U01HL084889, U01HL084890, U01HL084891, U01HL084899, U01HL084907, and U01HL084931 (for the clinical centers). This work is also supported by the National Center for Advancing Translational Sciences (NCATS): UL1TR000454; and the National Institute on Minority Health and Health Disparities (NIMHD): U54 MD007588. R. Zakeri is supported by the Mayo Clinic Center for Clinical and Translational Science (Grant UL1TR000135) from the National Center for Advancing Translational Science). R. Zakeri and S. F. Mohammed are Heart Failure Network Clinical Research Skills Development Fellows, and support for mentoring R. Zakeri and S. F. Mohammed is provided by U01HL084907and U10HL110262. Support for S. F. Mohammed was provided by T32 HL007111. NR 47 TC 30 Z9 37 U1 2 U2 8 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1941-3289 EI 1941-3297 J9 CIRC-HEART FAIL JI Circ.-Heart Fail. PD JAN PY 2014 VL 7 IS 1 BP 123 EP 130 DI 10.1161/CIRCHEARTFAILURE.113.000568 PG 8 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA AA4ND UT WOS:000331071800016 PM 24162898 ER PT J AU Dai, J Matsui, T Abel, ED Dedhar, S Gerszten, RE Seidman, CE Seidman, JG Rosenzweig, A AF Dai, Jing Matsui, Takashi Abel, E. Dale Dedhar, Shoukat Gerszten, Robert E. Seidman, Christine E. Seidman, J. G. Rosenzweig, Anthony TI Deep Sequence Analysis of Gene Expression Identifies Osteopontin as a Downstream Effector of Integrin-Linked Kinase (ILK) in Cardiac-Specific ILK Knockout Mice SO CIRCULATION-HEART FAILURE LA English DT Article DE cardiomyopathy; dilated; gene expression profiling; integrin-linked kinase; osteopontin ID DILATED CARDIOMYOPATHY; HEART-FAILURE; ENDOTHELIAL-CELLS; TARGETED ABLATION; PROTEIN-KINASE; HYPERTROPHY; ACTIVATION; GROWTH; CARDIOMYOCYTES; FIBROSIS AB Background Integrin-linked kinase (ILK) is a serine/threonine kinase that has been linked to human and experimental heart failure, but its role in the heart is not fully understood. Methods and Results To define the role of cardiomyocyte ILK, we generated cardiac-specific ILK knockout mice using -myosin heavy chain-driven Cre expression. Cardiac-specific ILK knockout mice spontaneously developed lethal dilated cardiomyopathy and heart failure with an early increase in apoptosis, fibrosis, and cardiac inflammation. To identify downstream effectors, we used deep sequence analysis of gene expression to compare comprehensive transcriptional profiles of cardiac-specific ILK knockout and wild-type hearts from 10-day-old mice before the development of cardiac dysfunction. Approximately 2x10(6) cDNA clones from each genotype were sequenced, corresponding to 33 274 independent transcripts. A total of 93 genes were altered, using nominal thresholds of >1.4-fold change and P<0.001. The most highly upregulated gene was osteopontin (47-fold increase; P=9.6x10(-45)), an inflammatory chemokine implicated in heart failure pathophysiology. ILK also regulated osteopontin expression in cardiomyocytes in vitro. Importantly, blocking antibodies to osteopontin mitigated but did not fully rescue the functional decline in cardiac-specific ILK knockout mice. Conclusions Cardiomyocyte-specific ILK deletion leads to a lethal cardiomyopathy characterized by cardiomyocyte death, fibrosis, and inflammation. Comprehensive profiling identifies ILK-dependent transcriptional effects and implicates osteopontin as a contributor to these phenotypes. C1 [Dai, Jing; Rosenzweig, Anthony] Beth Israel Deaconess Med Ctr, Div Cardiovasc, Boston, MA 02215 USA. [Dai, Jing; Gerszten, Robert E.] Harvard Univ, Sch Med, Boston, MA USA. [Matsui, Takashi] Univ Hawaii, Ctr Cardiovasc Res, John A Burns Sch Med, Honolulu, HI USA. [Abel, E. Dale] Univ Utah, Div Endocrinol, Salt Lake City, UT USA. [Abel, E. Dale] Univ Utah, Program Mol Med, Salt Lake City, UT USA. [Dedhar, Shoukat] British Columbia Canc Res Ctr, Vancouver, BC, Canada. [Gerszten, Robert E.] Massachusetts Gen Hosp, Boston, MA USA. [Seidman, Christine E.] Brigham & Womens Hosp, Boston, MA USA. [Seidman, Christine E.; Seidman, J. G.] Harvard Univ, Sch Med, Dept Genet, Boston, MA USA. RP Rosenzweig, A (reprint author), Beth Israel Deaconess Med Ctr, Div Cardiovasc, 3 Blackfan Circle,CLS-947, Boston, MA 02215 USA. EM arosenzw@bidmc.harvard.edu FU Leducq Foundation Network of Research Excellence; National Institutes of Health [HL059521, HL094677, HL098423, T32 HL073734]; Canadian Institutes for Health Research; Canadian Cancer Society Research Institute FX This research was supported by a Leducq Foundation Network of Research Excellence (A. Rosenzweig, J.G. Seidman, and C. E. Seidman) and grants from the National Institutes of Health (J.G. Seidman [The National Heart, Lung, and Blood Institute], A. Rosenzweig [HL059521, HL094677], T. Matsui [HL098423], and J. Dai [T32 HL073734]). A. Rosenzweig also gratefully acknowledges support from Judith and David Ganz. S. Dedhar was supported by grants from the Canadian Institutes for Health Research and the Canadian Cancer Society Research Institute. NR 42 TC 5 Z9 6 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1941-3289 EI 1941-3297 J9 CIRC-HEART FAIL JI Circ.-Heart Fail. PD JAN PY 2014 VL 7 IS 1 BP 184 EP 193 DI 10.1161/CIRCHEARTFAILURE.113.000649 PG 10 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA AA4ND UT WOS:000331071800023 PM 24319095 ER PT J AU Zheng, JY Yancey, DM Ahmed, MI Wei, CC Powell, PC Shanmugam, M Gupta, H Lloyd, SG McGiffin, DC Schiros, CG Denney, TS Babu, GJ Dell'Italia, LJ AF Zheng, Junying Yancey, Danielle M. Ahmed, Mustafa I. Wei, Chih-Chang Powell, Pamela C. Shanmugam, Mayilvahanan Gupta, Himanshu Lloyd, Steven G. McGiffin, David C. Schiros, Chun G. Denney, Thomas S., Jr. Babu, Gopal J. Dell'Italia, Louis J. TI Increased Sarcolipin Expression and Adrenergic Drive in Humans With Preserved Left Ventricular Ejection Fraction and Chronic Isolated Mitral Regurgitation SO CIRCULATION-HEART FAILURE LA English DT Article DE heart ventricles; mitral valve insufficiency ID CARDIAC-SPECIFIC OVEREXPRESSION; RETICULUM CALCIUM-TRANSPORT; DILATED CARDIOMYOPATHY; EXTRACELLULAR-MATRIX; RECEPTOR BLOCKADE; VOLUME OVERLOAD; HEART-FAILURE; CONTRACTILITY; PROTEIN; ABNORMALITIES AB Background There is currently no therapy proven to attenuate left ventricular (LV) dilatation and dysfunction in volume overload induced by isolated mitral regurgitation (MR). To better understand molecular signatures underlying isolated MR, we performed LV gene expression analyses and overlaid regulated genes into ingenuity pathway analysis in patients with isolated MR. Methods and Results Gene arrays from LV tissue of 35 patients, taken at the time of surgical repair for isolated MR, were compared with 13 normal controls. Cine-MRI was performed in 31 patients before surgery to measure LV function and volume from serial short-axis summation. LV end-diastolic volume was 2-fold (P=0.005) higher in MR patients than in normal controls, and LV ejection fraction was 647% (50%-79%) in MR patients. Ingenuity pathway analysis identified significant activation of pathways involved in -adrenergic, cAMP, and G-protein-coupled signaling, whereas there was downregulation of pathways associated with complement activation and acute phase response. SERCA2a and phospholamban protein were unchanged in MR versus control left ventricles. However, mRNA and protein levels of the sarcoplasmic reticulum Ca2+ ATPase (SERCA) regulatory protein sarcolipin, which is predominantly expressed in normal atria, were increased 12- and 6-fold, respectively. Immunofluorescence analysis confirmed the absence of sarcolipin in normal left ventricles and its marked upregulation in MR left ventricles. Conclusions These results demonstrate alterations in multiple pathways associated with -adrenergic signaling and sarcolipin in the left ventricles of patients with isolated MR and LV ejection fraction >50%, suggesting a beneficial role for -adrenergic blockade in isolated MR. C1 [Wei, Chih-Chang; Gupta, Himanshu; Lloyd, Steven G.; Dell'Italia, Louis J.] Univ Alabama Birmingham, Birmingham Vet Affairs Med Ctr, Birmingham, AL 35294 USA. [Zheng, Junying; Yancey, Danielle M.; Ahmed, Mustafa I.; Wei, Chih-Chang; Powell, Pamela C.; Gupta, Himanshu; Lloyd, Steven G.; Dell'Italia, Louis J.] Univ Alabama Birmingham, Dept Med, Div Cardiovasc Dis, Birmingham, AL 35294 USA. [McGiffin, David C.] Univ Alabama Birmingham, Div Cardiovasc Surg, Birmingham, AL 35294 USA. [Schiros, Chun G.; Denney, Thomas S., Jr.] Auburn Univ, Dept Elect & Comp Engn, Auburn, AL 36849 USA. [Shanmugam, Mayilvahanan; Babu, Gopal J.] Univ Med & Dent New Jersey NJMS, Dept Cell Biol & Mol Med, Newark, NJ USA. RP Dell'Italia, LJ (reprint author), Univ Alabama Birmingham, UAB Comprehens Cardiovasc Ctr, Dept Med, Div Cardiol, 434 BMR2,901 19th St S, Birmingham, AL 35294 USA. EM loudell@uab.edu FU National Institutes of Health Specialized Center of Clinically Oriented Research in Cardiac Dysfunction [50-HL077100] FX This work was supported by National Institutes of Health Specialized Center of Clinically Oriented Research in Cardiac Dysfunction 50-HL077100. NR 33 TC 9 Z9 9 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1941-3289 EI 1941-3297 J9 CIRC-HEART FAIL JI Circ.-Heart Fail. PD JAN PY 2014 VL 7 IS 1 BP 194 EP 202 DI 10.1161/CIRCHEARTFAILURE.113.000519 PG 9 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA AA4ND UT WOS:000331071800024 PM 24297688 ER PT J AU Melman, YF Shah, R Das, S AF Melman, Yonathan F. Shah, Ravi Das, Saumya TI MicroRNAs in Heart Failure Is the Picture Becoming Less miRky? SO CIRCULATION-HEART FAILURE LA English DT Article DE biomarker; cardiac resynchronization therapy; dyssynchrony; heart failure; miRNA ID SMALL INTERFERING RNA; CONTROLS CARDIAC-HYPERTROPHY; MYOCARDIAL-INFARCTION; CIRCULATING MICRORNAS; CARDIOVASCULAR-DISEASES; VENTRICULAR COMPLIANCE; ENRICHED MICRORNA; IN-VIVO; EXPRESSION; FIBROSIS C1 [Melman, Yonathan F.; Das, Saumya] Beth Israel Deaconess Med Ctr, Cardiovasc Inst, Boston, MA 02215 USA. [Shah, Ravi] Massachusetts Gen Hosp, Dept Med, Div Cardiol, Boston, MA 02114 USA. RP Das, S (reprint author), Beth Israel Deaconess Med Ctr, Cardiovasc Inst, CLS 907,330 Brookline Ave, Boston, MA 02215 USA. EM sdas@bidmc.harvard.edu FU Klarman Foundation FX Dr Das is funded by a grant from the Klarman Foundation. NR 110 TC 24 Z9 24 U1 2 U2 11 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1941-3289 EI 1941-3297 J9 CIRC-HEART FAIL JI Circ.-Heart Fail. PD JAN PY 2014 VL 7 IS 1 BP 203 EP 214 DI 10.1161/CIRCHEARTFAILURE.113.000266 PG 12 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA AA4ND UT WOS:000331071800025 PM 24449811 ER PT J AU Johnson, JM Minson, CT Kellogg, DL AF Johnson, John M. Minson, Christopher T. Kellogg, Dean L., Jr. TI Cutaneous Vasodilator and Vasoconstrictor Mechanisms in Temperature Regulation SO COMPREHENSIVE PHYSIOLOGY LA English DT Article ID SKIN BLOOD-FLOW; NITRIC-OXIDE SYNTHASE; AGED HUMAN SKIN; VASOACTIVE-INTESTINAL-PEPTIDE; ACTIVE THERMOREGULATORY VASODILATION; CYCLASE-ACTIVATING POLYPEPTIDE; TYPE-2 DIABETES-MELLITUS; LASER-DOPPLER FLOWMETRY; HUMAN FINGER SKIN; POSTURAL TACHYCARDIA SYNDROME AB In this review, we focus on significant developments in our understanding of the mechanisms that control the cutaneous vasculature in humans, with emphasis on the literature of the last half-century. To provide a background for subsequent sections, we review methods of measurement and techniques of importance in elucidating control mechanisms for studying skin blood flow. In addition, the anatomy of the skin relevant to its thermoregulatory function is outlined. The mechanisms by which sympathetic nerves mediate cutaneous active vasodilation during whole body heating and cutaneous vasoconstriction during whole body cooling are reviewed, including discussions of mechanisms involving cotransmission, NO, and other effectors. Current concepts for the mechanisms that effect local cutaneous vascular responses to local skin warming and cooling are examined, including the roles of temperature sensitive afferent neurons as well as NO and other mediators. Factors that can modulate control mechanisms of the cutaneous vasculature, such as gender, aging, and clinical conditions, are discussed, as are nonthermoregulatory reflex modifiers of thermoregulatory cutaneous vascular responses. (C) 2014 American Physiological Society. C1 [Johnson, John M.; Kellogg, Dean L., Jr.] Univ Texas Hlth Sci Ctr San Antonio, Dept Physiol, San Antonio, TX 78229 USA. [Minson, Christopher T.] Univ Oregon, Dept Human Physiol, Eugene, OR 97403 USA. [Kellogg, Dean L., Jr.] Univ Texas Hlth Sci Ctr San Antonio, Geriatr Res Educ & Clin Ctr, South Texas Vet Hlth Care Syst, San Antonio, TX 78229 USA. [Kellogg, Dean L., Jr.] Univ Texas Hlth Sci Ctr San Antonio, Dept Med, San Antonio, TX 78229 USA. RP Minson, CT (reprint author), Univ Oregon, Dept Human Physiol, Eugene, OR 97403 USA. EM minson@uoregon.edu FU National Institutes of Health FX The authors acknowledge the contributions of colleagues world-wide whose research contributed to this synthesis. This includes those who provided the important groundwork (John Shepherd and Loring Rowell among many others) and those who made many of the more recent contributions (Lacy Holowatz, Larry Kenney, Craig Crandall, Gary Hodges, and Nicholas Flavahan also among many others). We also acknowledge our colleagues who participated in research in our laboratories. We acknowledge Vienna Brunt and Molly Geiger for their invaluable assistance in the preparation of this review. We also gratefully acknowledge support for the research in our laboratories from the National Institutes of Health. NR 460 TC 51 Z9 51 U1 10 U2 45 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 2040-4603 J9 COMPR PHYSIOL JI Compr. Physiol. PD JAN PY 2014 VL 4 IS 1 BP 33 EP 89 DI 10.1002/cphy.c130015 PG 57 WC Physiology SC Physiology GA AA6HL UT WOS:000331199300002 PM 24692134 ER PT J AU Gandaglia, G Becker, A Trinh, QD Abdollah, F Schiffmann, J Roghmann, F Tian, Z Montorsi, F Briganti, A Karakiewicz, PI Sun, M AF Gandaglia, G. Becker, A. Trinh, Q-D Abdollah, F. Schiffmann, J. Roghmann, F. Tian, Z. Montorsi, F. Briganti, A. Karakiewicz, P. I. Sun, M. TI Long-term survival in patients with germ cell testicular cancer: A population-based competing-risks regression analysis SO EJSO LA English DT Article DE Testicular germ cell tumor; Secondary malignancy; Long-term survival; Other-cancer mortality; Cancer-specific mortality ID FOLLOW-UP; CARDIOVASCULAR-DISEASE; 2ND MALIGNANCIES; 5-YEAR SURVIVORS; MORTALITY; SUSCEPTIBILITY; LEUKEMIA; SEMINOMA; TUMORS AB Backgrounds: Incidence of secondary malignancies and cardiovascular diseases among testicular germ cell tumor (TGCT) survivors is higher compared to the general population. We sought to describe the rates of other-cancer (OCM), non-cancer related (NCRM), and cancer-specific mortality (CSM) among men with TGCT. Methods: Using the Surveillance, Epidemiology, and End Results (SEER) database, 31,330 patients with a primary diagnosis of TGCT between 1973 and 2009 were identified. The primary endpoints comprised of 15-year CSM, OCM, and NCRM rates. Survival rates were stratified according to histology (seminoma vs. non-seminoma), median age (<34 vs. >= 34 years old), and disease stage (localized vs. regional vs. distant). Competing-risks Poisson regression methodologies were performed. Results: For seminoma patients, the rates of CSM at 15 years increased with advancing stage (0.4-12.6%; P < 0.001), but varies little with age. In contrast, the rates of OCM (0.4-7.9%) and NCRM (2.9-8.9%) at 15 years increased with advancing stage and age (all P < 0.001). For non-seminoma patients, the 15-year CSM rates increased with advancing stage and age (1.9-24.4%; all P < 0.001). For the same time point, the rates of OCM (0.3-11.4%) and NCRM (2.4-8.0%) also increased with age and stage (all P < 0.001). Conclusions: The risk of dying from secondary malignancies or other causes significantly increases with advancing stage and age at diagnosis among TGCT survivors. Such information can help provide patients and physicians with better screening strategies, follow-up protocols, and mental preparedness for such undesirable effects. (C) 2013 Elsevier Ltd. All rights reserved. C1 [Gandaglia, G.; Becker, A.; Trinh, Q-D; Schiffmann, J.; Roghmann, F.; Tian, Z.; Karakiewicz, P. I.; Sun, M.] Univ Montreal, Ctr Hlth, Canc Prognost & Hlth Outcomes Unit, Montreal, PQ, Canada. [Gandaglia, G.; Abdollah, F.; Montorsi, F.; Briganti, A.] Univ Vita Salute San Raffaele, Urol Res Inst, San Raffaele Res Inst, Dept Urol, I-20132 Milan, Italy. [Becker, A.; Schiffmann, J.] Univ Med Ctr Hamburg Eppendolf, Martiniclin, Hamburg, Germany. [Trinh, Q-D] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Surg,Div Urol,Brigham & Womens Hosp, Boston, MA 02115 USA. [Roghmann, F.] Ruhr Univ Bochum, Dept Urol, Bochum, Germany. [Karakiewicz, P. I.] Univ Montreal, Ctr Hlth, Dept Urol, Montreal, PQ, Canada. RP Gandaglia, G (reprint author), Univ Vita Salute San Raffaele, Urol Res Inst, San Raffaele Res Inst, I-20132 Milan, Italy. EM giorgan10@libero.it OI , Jonas/0000-0002-0654-5920 NR 28 TC 4 Z9 4 U1 1 U2 5 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0748-7983 EI 1532-2157 J9 EJSO-EUR J SURG ONC JI EJSO PD JAN PY 2014 VL 40 IS 1 BP 103 EP 112 DI 10.1016/j.ejso.2013.09.019 PG 10 WC Oncology; Surgery SC Oncology; Surgery GA AA9LH UT WOS:000331414500016 PM 24099755 ER PT J AU Rieken, M Xylinas, E Kluth, L Trinh, QD Lee, RK Fajkovic, H Novara, G Margulis, V Lotan, Y Martinez-Salamanca, JI Matsumoto, K Seitz, C Remzi, M Karakiewicz, PI Scherr, DS Briganti, A Kautzky-Willer, A Bachmann, A Shariat, SF AF Rieken, M. Xylinas, E. Kluth, L. Trinh, Q-D Lee, R. K. Fajkovic, H. Novara, G. Margulis, V. Lotan, Y. Martinez-Salamanca, J. I. Matsumoto, K. Seitz, C. Remzi, M. Karakiewicz, P. I. Scherr, D. S. Briganti, A. Kautzky-Willer, A. Bachmann, A. Shariat, S. F. CA UTUC Collaboration TI Diabetes mellitus without metformin intake is associated with worse oncologic outcomes after radical nephroureterectomy for upper tract urothelial carcinoma SO EJSO LA English DT Article DE Upper tract urothelial carcinoma; Diabetes mellitus; Metformin; Surgery ID BLADDER-CANCER; HEPATOCELLULAR-CARCINOMA; MORTALITY; RISK; RECURRENCE; COHORT; THERAPY; DISEASE; IMPACT AB Aims: Evidence suggests a detrimental effect of diabetes. mellitus (DM) on cancer incidence and outcomes. To date, the effect of DM and its treatment on prognosis in upper tract urothelial carcinoma (UTUC) remains uninvestigated. We tested the hypothesis that DM and metformin use impact oncologic outcomes of patients treated with radical nephroureterectomy (RNU) for UTUC. Methods: Retrospective analysis of 2492 patients with UTUC treated at 23 institutions with RNU without neoadjuvant therapy. Cox regression models addressed the association of DM and metformin use with disease recurrence, cancer-specific mortality and any-cause mortality. Results: A total of 365 (14.3%) patients had DM and 194 (7.8%) patients used metformin. Within a median follow-up of 36 months, 663 (26.6%) patients experienced disease recurrence, 545 patients (21.9%) died of UTUC and 884 (35.5%) patients died from any cause. Diabetic patients who did not use metformin were at significantly higher risk of disease recurrence and cancer-specific death compared to nondiabetic patients and diabetic patients who used metformin. In multivariable Cox regression analyses, DM treated without metformin was associated with worse recurrence-free survival (HR: 1.44, 95% CI 1.10-1.90, p = 0.009) and cancer-specific mortality (HR: 1.49, 95% CI 1.11-2.00, p = 0.008). Conclusions: Diabetic UTUC patients without metformin use have significantly worse oncologic outcomes than diabetics who used metformin and non-diabetics. The possible mechanism behind the impact of DM on UTUC biology and the potentially protective effect of metformin need further elucidation. (C) 2013 Elsevier Ltd. All rights reserved. C1 [Rieken, M.; Xylinas, E.; Kluth, L.; Lee, R. K.; Scherr, D. S.; Shariat, S. F.] Weill Cornell Med Coll, New York Presbyterian Hosp, Dept Urol, New York, NY USA. [Rieken, M.; Bachmann, A.] Univ Basel Hosp, Dept Urol, CH-4031 Basel, Switzerland. [Xylinas, E.] Paris Descartes Univ, Cochin Hosp, APHP, Dept Urol, Paris, France. [Kluth, L.] Univ Med Ctr Hamburg Eppendorf, Dept Urol, Hamburg, Germany. [Briganti, A.] Univ Vita Salute San Raffaele, Dept Urol, Milan, Italy. [Karakiewicz, P. I.] Univ Montreal, Dept Urol, Montreal, PQ, Canada. [Novara, G.] Univ Padua, Urol Clin, Dept Surg Oncol & Gastroenterol Sci, I-35100 Padua, Italy. [Margulis, V.; Lotan, Y.] Univ Texas SW Med Ctr Dallas, Dept Urol, Dallas, TX 75390 USA. [Martinez-Salamanca, J. I.] Univ Autonoma Madrid, Dept Urol, Hosp Univ Puerta de Hierro Majadahonda, Madrid, Spain. [Matsumoto, K.] Kitasato Univ, Sch Med, Dept Urol, Sagamihara, Kanagawa 228, Japan. [Remzi, M.] Landesklinikum Korneuburg, Dept Urol, Korneuburg, Austria. [Kautzky-Willer, A.] Med Univ Vienna, Unit Gender Med, Div Endocrinol & Metab, Dept Internal Med 3, Vienna, Austria. [Fajkovic, H.; Seitz, C.; Shariat, S. F.] Med Univ Vienna, Dept Urol, Vienna, Austria. [Trinh, Q-D] Harvard Univ, Sch Med, Div Urol Surg, Boston, MA USA. [Trinh, Q-D] Harvard Univ, Sch Med, Dana Farber Canc Inst, Ctr Surg & Publ Hlth,Brigham & Womens Hosp, Boston, MA 02115 USA. RP Shariat, SF (reprint author), Med Univ Vienna, Dept Urol, Wahringer Gurtel 18-20, A-1090 Vienna, Austria. EM sfshariat@gmail.com OI JUAN IGNACIO, MARTINEZ SALAMANCA/0000-0001-5586-6838 FU Swiss National Science Foundation FX M. Rieken: Grant support from Swiss National Science Foundation. NR 31 TC 11 Z9 13 U1 0 U2 5 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0748-7983 EI 1532-2157 J9 EJSO-EUR J SURG ONC JI EJSO PD JAN PY 2014 VL 40 IS 1 BP 113 EP 120 DI 10.1016/j.ejso.2013.09.016 PG 8 WC Oncology; Surgery SC Oncology; Surgery GA AA9LH UT WOS:000331414500017 PM 24113620 ER PT J AU Schmidt, EJ Fung, MM Ciris, PA Song, T Shankaranarayanan, A Holmvang, G Gupta, SN Chaput, M Levine, RA Ruskin, J Reddy, VY D'avila, A Aletras, AH Danik, SB AF Schmidt, Ehud J. Fung, Maggie M. Ciris, Pelin Aksit Song, Ting Shankaranarayanan, Ajit Holmvang, Godtfred Gupta, Sandeep N. Chaput, Miguel Levine, Robert A. Ruskin, Jeremy Reddy, Vivek Y. D'avila, Andre Aletras, Anthony H. Danik, Stephan B. TI Navigated DENSE strain imaging for post-radiofrequency ablation lesion assessment in the swine left atria SO EUROPACE LA English DT Article DE Magnetic resonance imaging ablation; Atrial fibrillation; Porcine model ID CHRONIC MYOCARDIAL-INFARCTION; PULMONARY VEIN CONTRACTION; CATHETER ABLATION; INTRACARDIAC ECHOCARDIOGRAPHY; STIMULATED ECHOES; FIBRILLATION; MRI; TRACKING; MOTION; HEART AB Aims Prior work has demonstrated that magnetic resonance imaging (MRI) strain can separate necrotic/stunned myocardium from healthy myocardium in the left ventricle (LV). We surmised that high-resolution MRI strain, using navigator-echo-triggered DENSE, could differentiate radiofrequency ablated tissue around the pulmonary vein (PV) from tissue that had not been damaged by radiofrequency energy, similarly to navigated 3D myocardial delayed enhancement (3D-MDE). Methods and results A respiratory-navigated 2D-DENSE sequence was developed, providing strain encoding in two spatial directions with 1.2 x 1.0 x 4 mm(3) resolution. It was tested in the LV of infarcted sheep. In four swine, incomplete circumferential lesions were created around the right superior pulmonary vein (RSPV) using ablation catheters, recorded with electro-anatomic mapping, and imaged 1 h later using atrial-diastolic DENSE and 3D-MDE at the left atrium/RSPV junction. DENSE detected ablation gaps (regions with >12% strain) in similar positions to 3D-MDE (2D cross-correlation 0.89 +/- 0.05). Low-strain (<8%) areas were, on average, 33% larger than equivalent MDE regions, so they include both injured and necrotic regions. Optimal DENSE orientation was perpendicular to the PV trunk, with high shear strain in adjacent viable tissue appearing as a sensitive marker of ablation lesions. Conclusions Magnetic resonance imaging strain may be a non-contrast alternative to 3D-MDE in intra-procedural monitoring of atrial ablation lesions. C1 [Schmidt, Ehud J.] Brigham & Womens Hosp, Dept Radiol, Boston, MA 02115 USA. [Fung, Maggie M.] GE Healthcare MR, Waukesha, WI 53051 USA. [Ciris, Pelin Aksit] Yale Univ, Dept Biomed Engn, New Haven, CT 06520 USA. [Song, Ting; Shankaranarayanan, Ajit] GE Healthcare Appl Sci Lab, Bethesda, MD 20892 USA. [Holmvang, Godtfred; Chaput, Miguel; Levine, Robert A.; Ruskin, Jeremy; Danik, Stephan B.] Massachusetts Gen Hosp, Dept Cardiol, Boston, MA 02104 USA. [Gupta, Sandeep N.] GE Global Res, Niskayuna, NY 12309 USA. [Reddy, Vivek Y.; D'avila, Andre] Mt Sinai Sch Med, Dept Cardiol, New York, NY 10029 USA. [Aletras, Anthony H.] Univ Cent Greece, Dept Biomed Informat, Lamia 35100, Greece. RP Danik, SB (reprint author), Massachusetts Gen Hosp, Dept Cardiol, 55 Fruit St,GRB109, Boston, MA 02104 USA. EM sdanik@partners.org RI Ciris, Pelin/A-2796-2016; d'Avila, Andre/F-8009-2010; OI Ciris, Pelin/0000-0002-6405-2462; d'Avila, Andre/0000-0001-8769-1411; Aletras, Anthony/0000-0002-3786-3817 FU NCRR NIH HHS [1U41RR019703-01A2, U41 RR019703]; NHLBI NIH HHS [K23 HL068064, K23 HL68064, K24 HL067434, R01 HL072265, R01 HL109506]; NIBIB NIH HHS [P41 EB015898] NR 43 TC 2 Z9 2 U1 0 U2 1 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1099-5129 EI 1532-2092 J9 EUROPACE JI Europace PD JAN PY 2014 VL 16 IS 1 BP 133 EP 141 DI 10.1093/europace/eut229 PG 9 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA AA5EH UT WOS:000331118400025 PM 24014803 ER PT J AU Bhama, P Gliklich, RE Weinberg, JS Hadlock, TA Lindsay, R AF Bhama, Prabhat Gliklich, Richard E. Weinberg, Julie S. Hadlock, Tessa A. Lindsay, RobinW. TI Optimizing Total Facial Nerve Patient Management for Effective Clinical Outcomes Research SO JAMA FACIAL PLASTIC SURGERY LA English DT Article ID VALIDATION; SCALE AB IMPORTANCE Assessment of outcomes in patients with facial paralysis is challenging owing to the lack of objective tools to evaluate facial function and suboptimal data collection. OBJECTIVE To describe a methodology for prospective evaluation of patients with facial paralysis that permits optimal assessment of clinical outcomes. DESIGN, SETTING, AND PARTICIPANTS At the Massachusetts Eye and Ear Infirmary, we have treated over 2000 patients with facial nerve injury since 2002. To better quantify and improve our outcomes, we have developed what we now believe represents a systematic method for the previsit evaluation, intake, management, and follow-up of our facial nerve patients to optimize data collection for the purposes of clinical outcome studies, as detailed in this retrospective descriptive study. RESULTS Data collection is often poor if there is not a specific individual delegated to the task and is particularly challenging in the intraoperative setting. Retrospective acquisition of data are inherently less accurate and time consuming. A user-friendly searchable database is required to use the collected data. CONCLUSIONS AND RELEVANCE Clinical outcomes research in the field of facial paralysis requires meticulous attention to comprehensive data collection at appropriate time points, precision photography, and the use of available quality of life and objective measurement tools. Ideally, a standardized approach for data collection would be adopted that would permit multi-institutional data analysis to improve the quality of outcomes research currently available. C1 [Bhama, Prabhat; Gliklich, Richard E.; Weinberg, Julie S.; Hadlock, Tessa A.; Lindsay, RobinW.] Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Div Facial Plast & Reconstruct Surg,Dept Otol & L, Boston, MA USA. [Bhama, Prabhat] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. [Gliklich, Richard E.] Harvard Univ, Sch Med, Clin Outcomes Res Unit, Boston, MA USA. [Bhama, Prabhat; Gliklich, Richard E.; Weinberg, Julie S.; Hadlock, Tessa A.; Lindsay, RobinW.] Massachusetts Eye & Ear Infirm, Facial Nerve Ctr, Boston, MA 02114 USA. RP Bhama, P (reprint author), Massachusetts Eye & Ear Infirm, 243 Charles St, Boston, MA 02114 USA. EM pbhama@gmail.com NR 10 TC 12 Z9 12 U1 0 U2 3 PU AMER MEDICAL ASSOC PI CHICAGO PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA SN 2168-6076 EI 2168-6092 J9 JAMA FACIAL PLAST SU JI JAMA Facial Plast. Surg. PD JAN-FEB PY 2014 VL 16 IS 1 BP 9 EP 14 DI 10.1001/jamafacial.2013.1382 PG 6 WC Surgery SC Surgery GA AA8UR UT WOS:000331371000003 PM 24136326 ER PT J AU Hohman, MH Kleiss, IJ Knox, CJ Weinberg, JS Heaton, JT Hadlock, TA AF Hohman, Marc H. Kleiss, Ingrid J. Knox, Christopher J. Weinberg, Julie S. Heaton, James T. Hadlock, Tessa A. TI Functional Recovery After Facial Nerve Cable Grafting in a Rodent Model SO JAMA FACIAL PLASTIC SURGERY LA English DT Article ID WHISKER MOVEMENTS; RATS; CONDUIT; MOTOR; REPAIR AB IMPORTANCE Cable grafting is widely considered to be the preferred alternative to primary repair of the injured facial nerve; however, quantitative comparison of the 2 techniques has not been previously undertaken in a rodent model. OBJECTIVE To establish functional recovery parameters after interposition autografting in a rodent facial nerve model. DESIGN, SETTING, AND PARTICIPANTS Prospective randomized animal study at a tertiary care facial nerve center using 16 female Wistar Hannover rats. INTERVENTION The experimental group received reversed autograft reconstruction of a 20-mm neural gap, and the control group received facial nerve transection and primary repair. MAIN OUTCOME AND MEASURE Whisker excursion was measured weekly for 70 postoperative days using laser micrometers. RESULTS The control group exhibited the most rapid recovery, with substantial return of whisker movement occurring during the third postoperative week. The experimental group demonstrated return of function beginning in the fourth postoperative week, eventually achieving a degree of function comparable to that of the control group by the sixth postoperative week (P = .68). CONCLUSIONS AND RELEVANCE Recovery of facial function after cable grafting seems to be slower than, but eventually similar to, recovery after primary neurorrhaphy in a rodent model. In the present study we have established a benchmark for recovery of whisker movement across a 20-mm rodent facial nerve gap, which will be used for comparison of different facial nerve gap bridging materials in future studies. C1 [Hohman, Marc H.; Hadlock, Tessa A.] Harvard Univ, Sch Med, Dept Otol & Laryngol, Boston, MA 02115 USA. [Hohman, Marc H.; Kleiss, Ingrid J.; Knox, Christopher J.; Weinberg, Julie S.; Hadlock, Tessa A.] Massachusetts Eye & Ear Infirm, Div Facial Plast Surg, Boston, MA 02114 USA. [Kleiss, Ingrid J.] Radboud Univ Nijmegen, Dept Otolaryngol Head & Neck Surg, NL-6525 ED Nijmegen, Netherlands. [Heaton, James T.] Massachusetts Gen Hosp, Dept Surg, Div Laryngeal Surg, Boston, MA 02114 USA. RP Hohman, MH (reprint author), Massachusetts Eye & Ear Infirm, Facial Nerve Ctr, 243 Charles St, Boston, MA 02114 USA. EM marc_hohman@meei.harvard.edu FU National Institutes of Health FX The work of Drs Heaton and Hadlock was facilitated by a grant from the National Institutes of Health, which provided funding for the use of laboratory and animal care facilities. NR 15 TC 3 Z9 3 U1 0 U2 5 PU AMER MEDICAL ASSOC PI CHICAGO PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA SN 2168-6076 EI 2168-6092 J9 JAMA FACIAL PLAST SU JI JAMA Facial Plast. Surg. PD JAN-FEB PY 2014 VL 16 IS 1 BP 20 EP 24 DI 10.1001/jamafacial.2013.1431 PG 5 WC Surgery SC Surgery GA AA8UR UT WOS:000331371000005 PM 24232003 ER PT J AU Ojha, S Ashland, JE Hersh, C Ramakrishna, J Maurer, R Hartnick, CJ AF Ojha, Shilpa Ashland, Jean E. Hersh, Cheryl Ramakrishna, Jyoti Maurer, Rie Hartnick, Christopher J. TI Type 1 Laryngeal Cleft A Multidimensional Management Algorithm SO JAMA OTOLARYNGOLOGY-HEAD & NECK SURGERY LA English DT Article ID POSTERIOR LARYNGEAL; DIAGNOSIS AB IMPORTANCE Early diagnosis and assessment in children with type 1 laryngeal cleft are essential in preventing aspiration and associated comorbidity. Appropriate use of conservative and surgical interventions in an evidence-based management strategy can improve overall outcome. OBJECTIVE To evaluate the management of care for children with type 1 laryngeal cleft in our practice and develop an updated management algorithm. DESIGN, SETTING, AND PARTICIPANTS We performed a review of medical records at a tertiary pediatric aerodigestive center. During a period of 7 years (July 18, 2005, to July 18, 2012), 1014 children younger than 18 years were evaluated for aspiration, choking, cough, or recurrent pneumonia. Of these, 44 children (4.3%) had a type 1 laryngeal cleft. Two were lost to follow-up; thus, 42 children were included in our final sample (28 males, 14 females). INTERVENTIONS The care of 15 patients (36%) was managed conservatively, and 27 patients (64%) underwent endoscopic surgical repair of their laryngeal cleft. MAIN OUTCOME AND MEASURE Assessment of our current management strategy. RESULTS Success was defined as improving when a child was able to tolerate a feeding without aspirating or resolved when the child had transitioned to tolerating thin liquids. All patients received a trial of conservative therapy. Fifteen of the 42 patients (36%) had an anatomic cleft and were able to maintain the feeding regimen; thus, conservative treatment was successful in this group. The remaining 27 patients (64%) received surgical intervention. Overall operative success rate was 21 of the 27 patients (78%). The age of the child (P < .01) and comorbid conditions (P < .001) affected the outcomes of conservative measures and surgical repair. Only 6 patients did not demonstrate resolution, 5 of whom had significant comorbidities. CONCLUSIONS AND RELEVANCE Age, comorbidity status, severity of aspiration, and the ability to tolerate a feeding regimen should be taken into account when deciding on conservative or surgical management for children with a type 1 laryngeal cleft. A clinical pathway for conservative and surgical management is presented. C1 [Ojha, Shilpa; Maurer, Rie] Massachusetts Eye & Ear Infirm, Dept Otolaryngol, Boston, MA 02114 USA. [Ashland, Jean E.; Hartnick, Christopher J.] Harvard Univ, Sch Med, Dept Otol & Laryngol, Boston, MA 02115 USA. [Ashland, Jean E.] Massachusetts Gen Hosp, Dept Gastroenterol, Boston, MA 02114 USA. [Hersh, Cheryl] Massachusetts Gen Hosp, Dept Pediat, Boston, MA 02114 USA. [Hersh, Cheryl] Massachusetts Eye & Ear Infirm, Pediat Airway Voice & Swallowing Ctr, Boston, MA 02114 USA. [Ramakrishna, Jyoti] Massachusetts Gen Hosp, Dept Speech Language & Swallowing Disorders, Boston, MA 02114 USA. [Ramakrishna, Jyoti] Harvard Univ, Sch Med, Dept Pediat, Massachusetts Gen Hosp Children, Boston, MA 02115 USA. RP Hartnick, CJ (reprint author), Massachusetts Eye & Ear Infirm, Dept Otol & Laryngol, 243 Charles St, Boston, MA 02114 USA. EM Christopher_Hartnick@meei.harvard.edu NR 17 TC 9 Z9 10 U1 0 U2 1 PU AMER MEDICAL ASSOC PI CHICAGO PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA SN 2168-6181 EI 2168-619X J9 JAMA OTOLARYNGOL JI JAMA Otolaryngol-Head Neck Surg. PD JAN PY 2014 VL 140 IS 1 BP 34 EP 40 DI 10.1001/jamaoto.2013.5739 PG 7 WC Otorhinolaryngology; Surgery SC Otorhinolaryngology; Surgery GA AA8UE UT WOS:000331369700006 PM 24263209 ER PT J AU Simon, LS Strand, V Bingham, CO Singh, JA AF Simon, Lee S. Strand, Vibeke Bingham, Clifton O., III Singh, Jasvinder A. TI OMERACT 11-International Consensus Conference on Outcome Measures in Rheumatology Clinical Trials Introduction SO JOURNAL OF RHEUMATOLOGY LA English DT Editorial Material C1 [Strand, Vibeke] Stanford Univ, Portola Valley, CA USA. [Bingham, Clifton O., III] Johns Hopkins Univ, Baltimore, MD USA. [Singh, Jasvinder A.] Univ Birmingham, Birmingham VA Med Ctr, Birmingham, MD USA. [Singh, Jasvinder A.] Univ Birmingham, Birmingham VA Med Ctr, Birmingham, MD USA. [Singh, Jasvinder A.] Univ Birmingham, Div Rheumatol, Dept Med, Birmingham, MD USA. [Singh, Jasvinder A.] Univ Birmingham, Div Epidemiol, Birmingham, MD USA. EM lssconsult@aol.com NR 0 TC 1 Z9 1 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 EI 1499-2752 J9 J RHEUMATOL JI J. Rheumatol. PD JAN PY 2014 VL 41 IS 1 BP 147 EP 149 DI 10.3899/jrheum.130937 PG 3 WC Rheumatology SC Rheumatology GA AA5QF UT WOS:000331154000024 PM 24382928 ER PT J AU O'Neill, J Rader, T Guillemin, F Boonen, A Christensen, R Lyddiatt, A Pardo, JP Welch, V Singh, JA Tugwell, P AF O'Neill, Jennifer Rader, Tamara Guillemin, Francis Boonen, Annelies Christensen, Robin Lyddiatt, Anne Pardo, Jordi Pardo Welch, Vivian Singh, Jasvinder A. Tugwell, Peter TI Including Health Equity Considerations in Development of Instruments for Rheumatology Research: An Introduction to a Novel OMERACT Paradigm SO JOURNAL OF RHEUMATOLOGY LA English DT Article DE HEALTH EQUITY; MUSCULOSKELETAL CONDITIONS; RHEUMATOLOGY ID CROSS-CULTURAL ADAPTATION; ASSESSMENT QUESTIONNAIRE; ARTHRITIS; GUIDELINES; QUALITY; GOUT; CARE AB The Outcome Measures in Rheumatology (OMERACT) Equity Special Interest Group (SIG) was established in 2008 to create a preliminary core set of outcome measures for clinical trials that can assess equity gaps in healthcare and the effectiveness of interventions to close or narrow gaps between advantaged and disadvantaged populations with musculoskeletal (MSK) conditions. At the OMERACT 11 meeting in 2012, the Equity SIG workshop focused on health assessment scales and their applicability for disadvantaged patients with MSK conditions. The intent was to determine whether the items and domains in 2 common questionnaires, the Health Assessment Questionnaire and the Medical Outcome Study Short Form-36 Survey, are appropriate for the activities and life experiences of certain disadvantaged populations, and whether completion of any of the scales would present a challenge to disadvantaged persons. To generate discussion, we considered the reading level of items in these questionnaires and whether they would be accessible to people with different levels of literacy. The group concluded that the choice of measurement instrument may contribute to "outcome measure generated inequalities" because disadvantaged groups might have difficulty understanding some of the questions. The future work of the Equity SIG will explore the appropriateness of different measurement scales as they relate to inequities in arthritis as well as the risk of exacerbating disadvantages for patients with low literacy. C1 [O'Neill, Jennifer] Univ Ottawa, Inst Populat Hlth, Ottawa, ON K1N 6N5, Canada. Univ Lorraine, Nancy, France. Maastricht Univ, Med Ctr, Maastricht, Netherlands. Copenhagen Univ Hosp, Parker Inst, Dept Rheumatol, Copenhagen, Denmark. Birmingham VA Med Ctr, Birmingham, MD USA. [Singh, Jasvinder A.] Univ Alabama Birmingham, Birmingham, AL USA. Univ Ottawa, Inst Populat Hlth, Clin Epidemiol Program,Dept Med, Ottawa Hosp,Res Inst,Fac Med,Dept Epidemiol & Com, Ottawa, ON K1N 6N5, Canada. RP O'Neill, J (reprint author), Univ Ottawa, Inst Populat Hlth, 1 Stewart St, Ottawa, ON K1N 6N5, Canada. EM Jennifer.ONeill@uottawa.ca OI Tugwell, Peter/0000-0001-5062-0556 FU Canadian Institutes of Health Research; Allergan; Ardea; Savient; Novartis; Takeda FX P. Tugwell is supported in part by the Canadian Institutes of Health Research. J. Singh has received consultant fees, speaking fees, and/or honoraria (less than $10,000 each) from Allergan, Ardea, Savient, and Novartis; and (more than $10,000) from Takeda; and an investigator-initiated grant from Savient and Takeda. NR 21 TC 3 Z9 3 U1 0 U2 6 PU J RHEUMATOL PUBL CO PI TORONTO PA 365 BLOOR ST E, STE 901, TORONTO, ONTARIO M4W 3L4, CANADA SN 0315-162X EI 1499-2752 J9 J RHEUMATOL JI J. Rheumatol. PD JAN PY 2014 VL 41 IS 1 BP 150 EP 152 DI 10.3899/jrheum.130812 PG 3 WC Rheumatology SC Rheumatology GA AA5QF UT WOS:000331154000025 PM 24128775 ER PT J AU Ahmad, M Mahajan, VS Matto, H Stone, JH Pillai, S AF Ahmad, Maimuna Mahajan, Vinay S. Matto, Hamid Stone, John H. Pillai, Shiv TI Individuals with IgG4-related Disease Do Not Have an Increased Frequency of the K409 Variant of IgG4 that Compromises Fab-arm Exchange SO JOURNAL OF RHEUMATOLOGY LA English DT Letter ID IMMUNOGLOBULIN G4 C1 [Ahmad, Maimuna; Mahajan, Vinay S.; Matto, Hamid] Massachusetts Gen Hosp, Ctr Canc Res, Boston, MA 02129 USA. [Stone, John H.] Harvard Univ, Sch Med, Cambridge, MA 02138 USA. [Stone, John H.; Pillai, Shiv] Massachusetts Gen Hosp, Boston, MA 02129 USA. [Pillai, Shiv] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Canc Res, Boston, MA USA. RP Pillai, S (reprint author), Massachusetts Gen Hosp, 149 13th St, Boston, MA 02129 USA. EM pillai@helix.mgh.harvard.edu FU NHLBI NIH HHS [T32 HL007627]; NIAID NIH HHS [AI 076505, AI064930] NR 10 TC 3 Z9 4 U1 0 U2 0 PU J RHEUMATOL PUBL CO PI TORONTO PA 365 BLOOR ST E, STE 901, TORONTO, ONTARIO M4W 3L4, CANADA SN 0315-162X EI 1499-2752 J9 J RHEUMATOL JI J. Rheumatol. PD JAN PY 2014 VL 41 IS 1 BP 185 EP 187 DI 10.3899/jrheum.131017 PG 3 WC Rheumatology SC Rheumatology GA AA5QF UT WOS:000331154000030 PM 24382929 ER PT J AU Duivenvoorden, R Tang, J Cormode, DP Mieszawska, AJ Izquierdo-Garcia, D Ozcan, C Otten, MJ Zaidi, N Lobatto, ME van Rijs, SM Priem, B Kuan, EL Martel, C Hewing, B Sager, H Nahrendorf, M Randolph, GJ Stroes, ESG Fuster, V Fisher, EA Fayad, ZA Mulder, WJM AF Duivenvoorden, Raphael Tang, Jun Cormode, David P. Mieszawska, Aneta J. Izquierdo-Garcia, David Ozcan, Canturk Otten, Maarten J. Zaidi, Neeha Lobatto, Mark E. van Rijs, Sarian M. Priem, Bram Kuan, Emma L. Martel, Catherine Hewing, Bernd Sager, Hendrik Nahrendorf, Matthias Randolph, Gwendalyn J. Stroes, Erik S. G. Fuster, Valentin Fisher, Edward A. Fayad, Zahi A. Mulder, Willem J. M. TI A statin-loaded reconstituted high-density lipoprotein nanoparticle inhibits atherosclerotic plaque inflammation SO NATURE COMMUNICATIONS LA English DT Article ID APOLIPOPROTEIN E-DEFICIENT; RANDOMIZED CONTROLLED-TRIAL; A-I-MILANO; CORONARY ATHEROSCLEROSIS; CHOLESTEROL; MICE; PLASMA; HDL; SIMVASTATIN; MACROPHAGES AB Inflammation is a key feature of atherosclerosis and a target for therapy. Statins have potent anti-inflammatory properties but these cannot be fully exploited with oral statin therapy due to low systemic bioavailability. Here we present an injectable reconstituted high-density lipoprotein (rHDL) nanoparticle carrier vehicle that delivers statins to atherosclerotic plaques. We demonstrate the anti-inflammatory effect of statin-rHDL in vitro and show that this effect is mediated through the inhibition of the mevalonate pathway. We also apply statin-rHDL nanoparticles in vivo in an apolipoprotein E-knockout mouse model of atherosclerosis and show that they accumulate in atherosclerotic lesions in which they directly affect plaque macrophages. Finally, we demonstrate that a 3-month low-dose statin-rHDL treatment regimen inhibits plaque inflammation progression, while a 1-week high-dose regimen markedly decreases inflammation in advanced atherosclerotic plaques. Statin-rHDL represents a novel potent atherosclerosis nanotherapy that directly affects plaque inflammation. C1 [Duivenvoorden, Raphael; Tang, Jun; Cormode, David P.; Mieszawska, Aneta J.; Izquierdo-Garcia, David; Ozcan, Canturk; Otten, Maarten J.; Zaidi, Neeha; Lobatto, Mark E.; van Rijs, Sarian M.; Priem, Bram; Fayad, Zahi A.; Mulder, Willem J. M.] Icahn Sch Med Mt Sinai, Translat & Mol Imaging Inst, New York, NY 10029 USA. [Duivenvoorden, Raphael; Lobatto, Mark E.; Stroes, Erik S. G.; Mulder, Willem J. M.] Univ Amsterdam, Acad Med Ctr, Dept Vasc Med, NL-1105 AZ Amsterdam, Netherlands. [Tang, Jun] Icahn Sch Med Mt Sinai, Grad Sch Biomed Sci, New York, NY 10029 USA. [Kuan, Emma L.] Icahn Sch Med Mt Sinai, Dept Gene & Cell Med, Inst Immunol, New York, NY 10029 USA. [Martel, Catherine; Randolph, Gwendalyn J.] Washington Univ, Dept Pathol & Immunol, St Louis, MO 63110 USA. [Hewing, Bernd] NYU, Sch Med, Dept Med Cardiol & Cell Biol, Marc & Ruti Bell Program Vasc Biol, New York, NY 10016 USA. [Hewing, Bernd; Fisher, Edward A.] Charite, Med Klin Kardiol & Angiol, D-13353 Berlin, Germany. [Sager, Hendrik; Nahrendorf, Matthias] Massachusetts Gen Hosp, Ctr Syst Biol, Boston, MA 02114 USA. [Sager, Hendrik; Nahrendorf, Matthias] Harvard Univ, Sch Med, Boston, MA 02114 USA. [Fuster, Valentin] Icahn Sch Med Mt Sinai, Dept Cardiol, Marie Jose & Henry R Kravis Cardiovasc Hlth Ctr, Zena & Michael Weiner Cardiovasc Inst, New York, NY 10029 USA. [Fuster, Valentin] Ctr Nacl Invest Cardiovasc, Madrid 28029, Spain. RP Mulder, WJM (reprint author), Icahn Sch Med Mt Sinai, Translat & Mol Imaging Inst, New York, NY 10029 USA. EM willem.mulder@mssm.edu RI Fuster, Valentin/H-4319-2015; OI Fuster, Valentin/0000-0002-9043-9986; Cormode, David/0000-0002-8391-9500; Tang, Jun/0000-0002-8285-5111; Fisher, Edward/0000-0001-9802-143X FU NHLBI, NIH [HHSN268201000045C]; NIH [R01 EB009638, K99 EB012165, R01 CA155432, P01HL098055, R01HL084312, 1 S10 RR0 9145-01]; NWO grant ZonMW Vidi [91713324]; American Heart Association [13PRE14350020]; Deutsche Forschungsgemeinschaft [SA 1668/2-1]; German Research Foundation DFG [HE 6092/1-1]; International Atherosclerosis Society; Foundation 'De Drie Lichten' in The Netherlands; NIH-NCI [5R24 CA095823-04]; NSF [DBI-9724504] FX We would like to thank S. Russell for helping with the FPLC experiments and Wei Chen for his contribution to the flow cytometry experiments. R. Nolasco is gratefully acknowledged for his help in cryosectioning the aorta specimens and CSL (Parkville, Australia) for their kind gift of ApoAI. This work was supported by the NHLBI, NIH, as a Program of Excellence in Nanotechnology (PEN) Award, Contract number HHSN268201000045C as well as the NIH grants R01 EB009638 (Z.A.F.), K99 EB012165 (D. P. C.), R01 CA155432 (W.J.M.M.), P01HL098055 (E. A. F.), R01HL084312 (E. A. F.) and the NWO grant ZonMW Vidi 91713324 (W.J.M.M.). Additional support was provided by the American Heart Association Award number 13PRE14350020-Founders (J.T.), the Deutsche Forschungsgemeinschaft number SA 1668/2-1 (H. S.), the German Research Foundation DFG number HE 6092/1-1 (B. H.) as well as by the International Atherosclerosis Society and by the Foundation 'De Drie Lichten' in The Netherlands (M. E. L). Flow cytometry was performed at the MSSM-Flow Cytometry Shared Resource Facility and RT-PCR at the Quantitative PCR Shared Resource Facility. Fluorescence microscopy was performed at the MSSM-Microscopy Shared Resource Facility, supported with funding from NIH-NCI shared resources grant (5R24 CA095823-04), NSF Major Research Instrumentation grant (DBI-9724504) and NIH shared instrumentation grant (1 S10 RR0 9145-01). NR 36 TC 76 Z9 76 U1 3 U2 57 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 JAN PY 2014 VL 5 AR 3065 DI 10.1038/ncomms4065 PG 11 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA AA4RQ UT WOS:000331084200007 PM 24445279 ER PT J AU Zhou, CK Wu, LM Ni, FM Ji, W Wu, J Zhang, HL AF Zhou, Chunkui Wu, Limin Ni, Fengming Ji, Wei Wu, Jiang Zhang, Hongliang TI Critical illness polyneuropathy- and myopathy: a systematic reviewu SO NEURAL REGENERATION RESEARCH LA English DT Review DE nerve regeneration; neurodegenerative diseases; critical illness polyneuropathy; critical illness myopathy; intensive care unit; sepsis; multiple organ failure; Guillain-Barre syndrome; NSFC grant; neural regeneration ID INTENSIVE-CARE-UNIT; GUILLAIN-BARRE-SYNDROME; ACUTE QUADRIPLEGIC MYOPATHY; NEUROMUSCULAR ELECTRICAL-STIMULATION; MULTIPLE ORGAN FAILURE; OBSTRUCTIVE PULMONARY-DISEASE; ITALIAN MULTICENTER CRIMYNE; DIRECT MUSCLE STIMULATION; INSULIN THERAPY PROTECTS; HUMAN SKELETAL-MUSCLE AB Critical illness polyneuropathy and critical illness myopathy are frequent complications of severe illness that involve sensorimotor axons and skeletal muscles, respectively. Clinically, they manifest as limb and respiratory muscle weakness. Critical illness polyneuropathy/myopathy in isolation or combination increases intensive care unit morbidity via the inability or difficulty in weaning these patients off mechanical ventilation. Many patients continue to suffer from decreased exercise capacity and compromised quality of life for months to years after the acute event. Substantial progress has been made lately in the understanding of the pathophysiology of critical illness polyneuropathy and myopathy. Clinical and ancillary test results should be carefully interpreted to differentiate critical illness polyneuropathy/myopathy from similar weaknesses in this patient population. The present review is aimed at providing the latest knowledge concerning the pathophysiology of critical illness polyneuropathy/myopathy along with relevant clinical, diagnostic, differentiating, and treatment information for this debilitating neurological disease. C1 [Zhou, Chunkui; Wu, Limin; Wu, Jiang; Zhang, Hongliang] Jilin Univ, Bethune Hosp 1, Dept Neurol, Changchun 130021, Jilin Province, Peoples R China. [Wu, Limin] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Neuroprotect Res Lab, Charlestown, MA 02129 USA. [Ni, Fengming] Jilin Univ, Bethune Hosp 1, Ctr Oncol, Dept Radiotherapy, Changchun 130021, Jilin Province, Peoples R China. [Ji, Wei] Peoples Hosp Jilin Prov, Dept Vasc Surg, Changchun 130000, Jilin Province, Peoples R China. RP Zhang, HL (reprint author), Jilin Univ, Bethune Hosp 1, Dept Neurol, Xinmin St 71, Changchun 130021, Jilin Province, Peoples R China. EM drzhl@hotmail.com FU China Scholarship Council [2008102056]; National Natural Science Foundation of China [81241147] FX This work was supported by grants from China Scholarship Council, No. 2008102056; the National Natural Science Foundation of China, No. 81241147. NR 110 TC 9 Z9 9 U1 2 U2 14 PU SHENYANG EDITORIAL DEPT NEURAL REGENERATION RES PI SHENYANG PA PO BOX 1234, SHENYANG, LIAONING 110004, PEOPLES R CHINA SN 1673-5374 J9 NEURAL REGEN RES JI Neural Regen. Res. PD JAN PY 2014 VL 9 IS 1 BP 101 EP 110 DI 10.4103/1673-5374.125337 PG 10 WC Cell Biology; Neurosciences SC Cell Biology; Neurosciences & Neurology GA AB0MV UT WOS:000331487500015 PM 25206749 ER PT J AU Kozlenkov, A Roussos, P Timashpolsky, A Barbu, M Rudchenko, S Bibikova, M Klotzle, B Byne, W Lyddon, R Di Narzo, AF Hurd, YL Koonin, EV Dracheva, S AF Kozlenkov, Alexey Roussos, Panos Timashpolsky, Alisa Barbu, Mihaela Rudchenko, Sergei Bibikova, Marina Klotzle, Brandy Byne, William Lyddon, Rebecca Di Narzo, Antonio Fabio Hurd, Yasmin L. Koonin, Eugene V. Dracheva, Stella TI Differences in DNA methylation between human neuronal and glial cells are concentrated in enhancers and non-CpG sites SO NUCLEIC ACIDS RESEARCH LA English DT Article ID BODY-SPECIFIC METHYLATION; GENOME BROWSER DATABASE; HUMAN PREFRONTAL CORTEX; CENTRAL-NERVOUS-SYSTEM; HUMAN BRAIN; GENE-EXPRESSION; EPIGENETIC MECHANISMS; HISTONE MODIFICATIONS; MAMMALIAN DEVELOPMENT; NETWORK ANALYSIS AB We applied Illumina Human Methylation450K array to perform a genomic-scale single-site resolution DNA methylation analysis in neuronal and nonneuronal (primarily glial) nuclei separated from the orbitofrontal cortex of postmortem human brain. The findings were validated using enhanced reduced representation bisulfite sequencing. We identified thousands of sites differentially methylated (DM) between neuronal and nonneuronal cells. The DM sites were depleted within CpG-island-containing promoters but enriched in predicted enhancers. Classification of the DM sites into those undermethylated in neurons (neuronal type) and those undermethylated in nonneuronal cells (glial type), combined with findings of others that methylation within control elements typically negatively correlates with gene expression, yielded large sets of predicted neuron-specific and nonneuron-specific genes. These sets of predicted genes were in excellent agreement with the available direct measurements of gene expression in human and mouse. We also found a distinct set of DNA methylation patterns that were unique for neuronal cells. In particular, neuronal-type differential methylation was overrepresented in CpG island shores, enriched within gene bodies but not in intergenic regions, and preferentially harbored binding motifs for a distinct set of transcription factors, including neuron-specific activity-dependent factors. Finally, non-CpG methylation was substantially more prevalent in neurons than in nonneuronal cells. C1 [Kozlenkov, Alexey; Roussos, Panos; Timashpolsky, Alisa; Byne, William; Lyddon, Rebecca; Dracheva, Stella] James J Peters VA Med Ctr, Educ & Clin Ctr MIRECC, VISN Mental Illness Res 3, Bronx, NY 10468 USA. [Kozlenkov, Alexey; Roussos, Panos; Byne, William; Lyddon, Rebecca; Hurd, Yasmin L.; Dracheva, Stella] Icahn Sch Med Mt Sinai, Friedman Brain Inst, New York, NY USA. [Kozlenkov, Alexey; Roussos, Panos; Byne, William; Lyddon, Rebecca; Hurd, Yasmin L.; Dracheva, Stella] Icahn Sch Med Mt Sinai, Dept Psychiat, New York, NY USA. [Roussos, Panos; Di Narzo, Antonio Fabio] Icahn Sch Med Mt Sinai, Dept Genet & Genom Sci, New York, NY USA. [Barbu, Mihaela; Rudchenko, Sergei] Hosp Special Surg, Div Res, New York, NY 10021 USA. [Bibikova, Marina; Klotzle, Brandy] Illumina Inc, San Diego, CA USA. [Koonin, Eugene V.] NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20892 USA. RP Dracheva, S (reprint author), James J Peters VA Med Ctr, Educ & Clin Ctr MIRECC, VISN Mental Illness Res 3, Bronx, NY 10468 USA. EM Stella.Dracheva@mssm.edu RI Roussos, Panos/J-7090-2013 OI Roussos, Panos/0000-0002-4640-6239 FU National Institute on Drug Abuse [R21DA031557]; National Institute of Mental Health [R21MH090352]; Hope for Depression Research Foundation; VISN 3 Mental Illness Research, Education and Clinical Center (MIRECC); US Department of Health and Human Services FX National Institute on Drug Abuse [R21DA031557 to S. D.]; National Institute of Mental Health [R21MH090352 to S. D.]; Hope for Depression Research Foundation grants (to S. D.); VISN 3 Mental Illness Research, Education and Clinical Center (MIRECC) (to S. D.). The work was also supported with resources and the use of facilities at the James J Peters VA Medical Center, Bronx, NY; Supported by intramural funds of the US Department of Health and Human Services (to National Library of Medicine) (to E. V. K.). Funding for open access charge: Authors' funding. NR 107 TC 41 Z9 41 U1 3 U2 17 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0305-1048 EI 1362-4962 J9 NUCLEIC ACIDS RES JI Nucleic Acids Res. PD JAN PY 2014 VL 42 IS 1 BP 109 EP 127 DI 10.1093/nar/gkt838 PG 19 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA AA5KF UT WOS:000331136000016 PM 24057217 ER PT J AU McCall, MN Jaffee, HA Zelisko, SJ Sinha, N Hooiveld, G Irizarry, RA Zilliox, MJ AF McCall, Matthew N. Jaffee, Harris A. Zelisko, Susan J. Sinha, Neeraj Hooiveld, Guido Irizarry, Rafael A. Zilliox, Michael J. TI The Gene Expression Barcode 3.0: improved data processing and mining tools SO NUCLEIC ACIDS RESEARCH LA English DT Article ID ROBUST MULTIARRAY ANALYSIS; MICROARRAY QUALITY; FRMA AB The Gene Expression Barcode project, http://barcode.luhs.org, seeks to determine the genes expressed for every tissue and cell type in humans and mice. Understanding the absolute expression of genes across tissues and cell types has applications in basic cell biology, hypothesis generation for gene function and clinical predictions using gene expression signatures. In its current version, this project uses the abundant publicly available microarray data sets combined with a suite of single-array preprocessing, quality control and analysis methods. In this article, we present the improvements that have been made since the previous version of the Gene Expression Barcode in 2011. These include a variety of new data mining tools and summaries, estimated transcriptomes and curated annotations. C1 [McCall, Matthew N.] Univ Rochester, Med Ctr, Dept Biostat & Computat Biol, Rochester, NY 14642 USA. [Jaffee, Harris A.] Johns Hopkins Univ, Dept Biostat, Baltimore, MD 21205 USA. [Zelisko, Susan J.] Loyola Univ, Stritch Sch Med, Maywood, IL 60153 USA. [Sinha, Neeraj; Hooiveld, Guido] Wageningen Univ, Div Human Nutr, Nutr Metab & Genom Grp, NL-6700 AP Wageningen, Netherlands. [Irizarry, Rafael A.] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02215 USA. [Zilliox, Michael J.] Loyola Univ, Stritch Sch Med, Dept Pharmacol & Mol Therapeut, Ctr Biomed Informat, Maywood, IL 60153 USA. RP Zilliox, MJ (reprint author), Loyola Univ, Stritch Sch Med, Dept Pharmacol & Mol Therapeut, Ctr Biomed Informat, 2160 S 1st Ave, Maywood, IL 60153 USA. EM mizilliox@lumc.edu RI Hooiveld, Guido/F-4912-2010 OI Hooiveld, Guido/0000-0003-1954-3542 FU National Institutes of Health [CA132480, CA009363, GM083084, GM103552, 1G20RR030939]; Loyola Institutional funds FX National Institutes of Health [CA132480 to M.J.Z., CA009363 to M.N.M., GM083084 and GM103552 to R. A. I. and 1G20RR030939]; and Loyola Institutional funds. Funding for open access charge: Loyola Institutional Funds. NR 13 TC 22 Z9 22 U1 1 U2 6 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0305-1048 EI 1362-4962 J9 NUCLEIC ACIDS RES JI Nucleic Acids Res. PD JAN PY 2014 VL 42 IS D1 BP D938 EP D943 DI 10.1093/nar/gkt1204 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA AA5LF UT WOS:000331139800138 PM 24271388 ER PT J AU Wang, QX Huang, JY Sun, HF Liu, J Wang, J Wang, Q Qin, Q Mei, SL Zhao, CC Yang, XQ Liu, XS Zhang, Y AF Wang, Qixuan Huang, Jinyan Sun, Hanfei Liu, Jing Wang, Juan Wang, Qian Qin, Qian Mei, Shenglin Zhao, Chengchen Yang, Xiaoqin Liu, X. Shirley Zhang, Yong TI CR Cistrome: a ChIP-Seq database for chromatin regulators and histone modification linkages in human and mouse SO NUCLEIC ACIDS RESEARCH LA English DT Article ID AGGRESSIVE BREAST-CANCER; PROSTATE-CANCER; TRANSCRIPTIONAL REGULATION; H3 VARIANTS; GENOME; EZH2; ACETYLATION; POLYCOMB; CELLS; GENES AB Diversified histone modifications (HMs) are essential epigenetic features. They play important roles in fundamental biological processes including transcription, DNA repair and DNA replication. Chromatin regulators (CRs), which are indispensable in epigenetics, can mediate HMs to adjust chromatin structures and functions. With the development of ChIP-Seq technology, there is an opportunity to study CR and HM profiles at the whole-genome scale. However, no specific resource for the integration of CR ChIP-Seq data or CR-HM ChIP-Seq linkage pairs is currently available. Therefore, we constructed the CR Cistrome database, available online at http://compbio.tongji.edu.cn/cr and http://cistrome.org/cr/, to further elucidate CR functions and CR-HM linkages. Within this database, we collected all publicly available ChIP-Seq data on CRs in human and mouse and categorized the data into four cohorts: the reader, writer, eraser and remodeler cohorts, together with curated introductions and ChIP-Seq data analysis results. For the HM readers, writers and erasers, we provided further ChIP-Seq analysis data for the targeted HMs and schematized the relationships between them. We believe CR Cistrome is a valuable resource for the epigenetics community. C1 [Wang, Qixuan; Huang, Jinyan; Sun, Hanfei; Liu, Jing; Wang, Juan; Wang, Qian; Qin, Qian; Mei, Shenglin; Zhao, Chengchen; Yang, Xiaoqin; Zhang, Yong] Tongji Univ, Sch Life Sci & Technol, Shanghai Key Lab Signaling & Dis Res, Shanghai 200092, Peoples R China. [Liu, X. Shirley] Harvard Univ, Sch Publ Hlth, Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02215 USA. RP Zhang, Y (reprint author), Tongji Univ, Sch Life Sci & Technol, Shanghai Key Lab Signaling & Dis Res, Shanghai 200092, Peoples R China. EM xsliu@jimmy.harvard.edu; yzhang@tongji.edu.cn RI Zhang, Yong/B-4838-2011 OI Zhang, Yong/0000-0001-6316-2734 FU National Basic Research Program of China [973 Program] [2010CB944904, 2011CB965104]; National Natural Science Foundation of China [31071114, 31371288, 31329003]; New Century Excellent Talents in the University of China [NCET-11-0389]; Innovative Research Team Program Ministry of Education of China [IRT1168]; National Institutes of Health [HG4069]; National Basic Research Program of China [2010CB944904] FX The National Basic Research Program of China [973 Program; 2010CB944904 and 2011CB965104]; National Natural Science Foundation of China [31071114, 31371288 and 31329003]; New Century Excellent Talents in the University of China [NCET-11-0389]; Innovative Research Team Program Ministry of Education of China [IRT1168]; National Institutes of Health [HG4069]. Funding for open access charge: The National Basic Research Program of China [2010CB944904]. NR 54 TC 16 Z9 16 U1 6 U2 10 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0305-1048 EI 1362-4962 J9 NUCLEIC ACIDS RES JI Nucleic Acids Res. PD JAN PY 2014 VL 42 IS D1 BP D450 EP D458 DI 10.1093/nar/gkt1151 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA AA5LF UT WOS:000331139800068 PM 24253304 ER PT J AU Scarpati, GD Fusciello, C Perri, F Sabbatino, F Ferrone, S Carlomagno, C Pepe, S AF Scarpati, Giuseppina Della Vittoria Fusciello, Celeste Perri, Francesco Sabbatino, Francesco Ferrone, Soldano Carlomagno, Chiara Pepe, Stefano TI Ipilimumab in the treatment of metastatic melanoma: management of adverse events SO ONCOTARGETS AND THERAPY LA English DT Review DE melanoma; T-cells; CTLA-4; autoimmunity; adverse events ID ANTIBODY THERAPY; REGRESSION; ANTIGEN-4; BLOCKADE; PROFILE; SAFETY AB Recently, "ipilimumab," an anti-cytotoxic T-lymphocyte antigen-4 (CTLA-4) monoclonal antibody, has been demonstrated to improve overall survival in metastatic melanoma. "CTLA-4" is an immune-checkpoint molecule that downregulates pathways of T-cell activation. Ipilimumab, by targeting CTLA-4, is able to remove the CTLA-4 inhibitory signal, allowing the immune system to react to cancer cells. Due to its immune-based mechanism of action, ipilimumab causes the inhibition of CTLA-4-mediated immunomodulatory effects, the enhancement of antitumor specific immune response mediated by the weakening of self-tolerance mechanisms while exacerbating the development of autoimmune diseases and immune-related adverse events, including dermatitis, hepatitis, enterocolitis, hypophysitis, and uveitis. C1 [Scarpati, Giuseppina Della Vittoria; Pepe, Stefano] Univ Salerno, Dept Med, I-84100 Salerno, Italy. [Scarpati, Giuseppina Della Vittoria; Pepe, Stefano] AOU San Giovanni Dio & Ruggi Aragona, Div Oncol, Salerno, Italy. [Fusciello, Celeste; Carlomagno, Chiara] Univ Naples Federico II, Dept Clin Med & Surg, Naples, Italy. [Perri, Francesco] Natl Tumor Inst, Head & Neck Med Oncol Unit, Naples, Italy. [Sabbatino, Francesco; Ferrone, Soldano] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Surg, Boston, MA USA. RP Scarpati, GD (reprint author), AOU San Giovanni Dio & Ruggi Aragona, Salerno, Italy. EM giuseppina.dellavittoria@alice.it OI Sabbatino, Francesco/0000-0001-6431-8278 NR 29 TC 24 Z9 24 U1 5 U2 8 PU DOVE MEDICAL PRESS LTD PI ALBANY PA PO BOX 300-008, ALBANY, AUCKLAND 0752, NEW ZEALAND SN 1178-6930 J9 ONCOTARGETS THER JI OncoTargets Ther. PY 2014 VL 7 BP 203 EP 209 DI 10.2147/OTT.S57335 PG 7 WC Biotechnology & Applied Microbiology; Oncology SC Biotechnology & Applied Microbiology; Oncology GA AB5PF UT WOS:000331840100001 ER PT J AU Castillo, JJ Iyengar, M Kuritzky, B Bishop, KD AF Castillo, Jorge J. Iyengar, Meera Kuritzky, Benjamin Bishop, Kenneth D. TI Isotype-specific inhibition of the phosphatidylinositol-3-kinase pathway in hematologic malignancies SO ONCOTARGETS AND THERAPY LA English DT Review DE phosphatidylinositol-3-kinase pathway; inhibitors; leukemia; lymphoma; myeloma ID CHRONIC LYMPHOCYTIC-LEUKEMIA; B-CELL LYMPHOMA; ACUTE MYELOID-LEUKEMIA; MULTIPLE-MYELOMA; IN-VIVO; PHOSPHOINOSITIDE 3-KINASES; 3-KINASE/MAMMALIAN TARGET; RAPAMYCIN INHIBITOR; P110-DELTA ISOFORM; HODGKIN LYMPHOMA AB In the last decade, the advent of biological targeted therapies has revolutionized the management of several types of cancer, especially in the realm of hematologic malignancies. One of these pathways, and the center of this review, is the phosphatidylinositol-3-kinase (PI3K) pathway. The PI3K pathway seems to play an important role in the pathogenesis and survival advantage in hematologic malignancies, such as leukemia, lymphoma, and myeloma. The objectives of the present review, hence, are to describe the current knowledge on the PI3K pathway and its isoforms, and to summarize preclinical and clinical studies using PI3K inhibitors, focusing on the advances made in hematologic malignancies. C1 [Castillo, Jorge J.] Dana Farber Canc Inst, Div Hematol Malignancies, Boston, MA 02115 USA. [Iyengar, Meera; Kuritzky, Benjamin; Bishop, Kenneth D.] Rhode Isl Hosp, Div Hematol & Oncol, Providence, RI USA. RP Castillo, JJ (reprint author), 450 Brookline Ave,M221, Boston, MA 02215 USA. EM jorgej_castillo@dfci.harvard.edu OI Castillo, Jorge/0000-0001-9490-7532 NR 54 TC 5 Z9 5 U1 0 U2 2 PU DOVE MEDICAL PRESS LTD PI ALBANY PA PO BOX 300-008, ALBANY, AUCKLAND 0752, NEW ZEALAND SN 1178-6930 J9 ONCOTARGETS THER JI OncoTargets Ther. PY 2014 VL 7 BP 333 EP 342 DI 10.2147/OTT.S34641 PG 10 WC Biotechnology & Applied Microbiology; Oncology SC Biotechnology & Applied Microbiology; Oncology GA AB5PZ UT WOS:000331842100001 PM 24591840 ER PT J AU Berhane, H Epperly, MW Goff, J Kalash, R Cao, SN Franicola, D Zhang, XC Shields, D Houghton, F Wang, H Wipf, P Parmar, K Greenberger, JS AF Berhane, Hebist Epperly, Michael W. Goff, Julie Kalash, Ronny Cao, Shaonan Franicola, Darcy Zhang, Xichen Shields, Donna Houghton, Frank Wang, Hong Wipf, Peter Parmar, Kalindi Greenberger, Joel S. TI Radiologic Differences between Bone Marrow Stromal and Hematopoietic Progenitor Cell Lines from Fanconi Anemia (Fancd2(-/-)) Mice SO RADIATION RESEARCH LA English DT Article ID DNA-DAMAGE; SUPEROXIDE-DISMUTASE; IONIZING-RADIATION; SENSITIVITY; PATHWAY; STEM; FIBROBLASTS; CULTURES AB FancD2 plays a central role in the human Fanconi anemia DNA damage response (DDR) pathway. Fancd2(-/-) mice exhibit many features of human Fanconi anemia including cellular DNA repair defects. Whether the DNA repair defect in Fancd2(-/-) mice results in radiologic changes in all cell lineages is unknown. We measured stress of hematopoiesis in long-term marrow cultures and radiosensitivity in clonogenic survival curves, as well as comet tail intensity, total antioxidant stores and radiation-induced gene expression in hematopoietic progenitor compared to bone marrow stromal cell lines. We further evaluated radioprotection by a mitochondrial-targeted antioxidant GS-nitroxide, JP4-039. Hematopoiesis longevity in Fancd2(-/-) mouse long-term marrow cultures was diminished and bone marrow stromal cell lines were radiosensitive compared to Fancd2(+/+) stromal cells (Fancd2(-/-) D-0 = 1.4 +/- 0.1 Gy, n = 5.0 +/- 0.6 vs. Fancd2(+/+) D-0 = 1.6 +/- 0.1 Gy, n = 6.7 +/- 1.6), P = 0.0124 for D-0 and P = 0.0023 for n, respectively). In contrast, Fancd2(-/-) IL-3-dependent hematopoietic progenitor cells were radioresistant (D-0 = 1.71 +/- 0.04 Gy and n = 5.07 +/- 0.52) compared to Fancd2(+/+) (D-0 = 1.39 +/- 0.09 Gy and n = 2.31 +/- 0.85, P = 0.001 for D-0). CFU-GM from freshly explanted Fancd2(-/-) marrow was also radioresistant. Consistent with radiosensitivity, irradiated Fancd2(-/-) stromal cells had higher DNA damage by comet tail intensity assay compared to Fancd2(+/+) cells (P < 0.0001), slower DNA damage recovery, lower baseline total antioxidant capacity, enhanced radiation-induced depletion of antioxidants, and increased CDKN1A-p21 gene transcripts and protein. Consistent with radioresistance, Fancd2(-/-) IL-3-dependent hematopoietic cells had higher baseline and post irradiation total antioxidant capacity. While, there was no detectable alteration of radiation-induced cell cycle arrest with Fancd2(-/-) stromal cells, hematopoietic progenitor cells showed reduced G(2)/M cell cycle arrest. The absence of the mouse Fancd2 gene product confers radiosensitivity to bone marrow stromal but not hematopoietic progenitor cells. (C) 2014 by Radiation Research Society C1 [Berhane, Hebist; Epperly, Michael W.; Goff, Julie; Kalash, Ronny; Cao, Shaonan; Franicola, Darcy; Zhang, Xichen; Shields, Donna; Houghton, Frank; Wang, Hong; Greenberger, Joel S.] Univ Pittsburgh, Inst Canc, Dept Radiat Oncol, Pittsburgh, PA 15232 USA. [Wipf, Peter] Univ Pittsburgh, Dept Chem, Pittsburgh, PA 15260 USA. [Parmar, Kalindi] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. RP Greenberger, JS (reprint author), Univ Pittsburgh, Inst Canc, Dept Radiat Oncol, UPMC Canc Pavil,Rm 533,5150 Ctr Ave, Pittsburgh, PA 15232 USA. EM greenbergerjs@upmc.edu OI Wang, Hong/0000-0003-0477-2908 FU NIH [U19-A1068021]; FA Research Foundation; [P30CA047904] FX This manuscript is supported by NIH grant U19-A1068021 and the FA Research Foundation. This project used the UPCI animal facility that is supported in part by award P30CA047904. NR 29 TC 15 Z9 15 U1 0 U2 2 PU RADIATION RESEARCH SOC PI LAWRENCE PA 810 E TENTH STREET, LAWRENCE, KS 66044 USA SN 0033-7587 EI 1938-5404 J9 RADIAT RES JI Radiat. Res. PD JAN PY 2014 VL 181 IS 1 BP 76 EP 89 DI 10.1667/RR13405.1 PG 14 WC Biology; Biophysics; Radiology, Nuclear Medicine & Medical Imaging SC Life Sciences & Biomedicine - Other Topics; Biophysics; Radiology, Nuclear Medicine & Medical Imaging GA AB1CZ UT WOS:000331530200008 PM 24397476 ER PT S AU Vaine, CA Soberman, RJ AF Vaine, Christine A. Soberman, Roy J. BE Alt, FW TI The CD200-CD200R1 Inhibitory Signaling Pathway: Immune Regulation and Host-Pathogen Interactions SO ADVANCES IN IMMUNOLOGY, VOL 121 SE Advances in Immunology LA English DT Review; Book Chapter ID NATURAL-KILLER-CELLS; IMMUNOGLOBULIN-LIKE RECEPTORS; ACTIVATION IN-VIVO; CD200 RECEPTOR; MACROPHAGE ACTIVATION; DOWN-REGULATION; HLA-E; CYTOKINE PRODUCTION; TYROSINE KINASE; MYELOID CELLS AB The CD200:CD200R1 inhibitory signaling pathway has been implicated in playing a prominent role in limiting inflammation in a wide range of inflammatory diseases. CD200R1 signaling inhibits the expression of proinflammatory molecules including tumor necrosis factor, interferons, and inducible nitric oxide synthase in response to selected stimuli. Unsurprisingly, due to the regulatory role that CD200R1 plays in multiple inflammatory pathways, an increasing number of parasitic, bacterial, and viral pathogens exploit this pathway to suppress host defenses. A complete understanding of the pathways regulated by CD200R1 signaling and the diverse mechanisms that pathogens have evolved to manipulate the CD200:CD200R1 pathway can help identify clinical situations where targeting this interaction can be of therapeutic benefit. In this review, we compare CD200R1 to other pathogen-targeted inhibitory receptors and highlight how this signaling pathway is utilized by a diverse number of pathogens and, therefore, may represent a novel targeting strategy for the treatment of infectious diseases. C1 [Vaine, Christine A.; Soberman, Roy J.] Massachusetts Gen Hosp, Dept Med, Div Nephrol, Boston, MA 02114 USA. RP Soberman, RJ (reprint author), Massachusetts Gen Hosp, Dept Med, Div Nephrol, Boston, MA 02114 USA. EM soberman@helix.mgh.harvard.edu OI Vaine, Christine/0000-0003-2645-8223 FU NHLBI NIH HHS [R01 HL097796, R01HL097796]; NIAID NIH HHS [R01 AI068871, R01AI068871, R01AI068871-04S1]; NIDDK NIH HHS [T32 DK007540] NR 73 TC 7 Z9 9 U1 2 U2 19 PU ELSEVIER ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA SN 0065-2776 BN 978-0-12-800100-4 J9 ADV IMMUNOL JI Adv.Immunol. PY 2014 VL 121 BP 191 EP 211 DI 10.1016/B978-0-12-800100-4.00005-2 PG 21 WC Immunology SC Immunology GA BA0CR UT WOS:000331017400005 PM 24388216 ER PT J AU Heyworth, L Bitton, A Lipsitz, SR Schilling, T Schiff, GD Bates, DW Simon, SR AF Heyworth, Leonie Bitton, Asaf Lipsitz, Stuart R. Schilling, Thad Schiff, Gordon D. Bates, David W. Simon, Steven R. TI Patient-Centered Medical Home Transformation With Payment Reform: Patient Experience Outcomes SO AMERICAN JOURNAL OF MANAGED CARE LA English DT Article ID PRIMARY-CARE; HEALTH; COST AB Objective: To examine changes in patient experience across key domains of the patient-centered medical home (PCMH) following practice transformation with Lean quality improvement methodology inclusive of payment reform. Study Design: Pre-intervention/postintervention analysis of intervention with a comparison group, a quasi-experimental design. We surveyed patients following office visits at the intervention (n = 2502) and control (n = 1622) practices during the 15-month period before and 14-month period after PCMH Lean transformation (April-October 2009). Methods: We measured and compared pre-intervention and postintervention levels of patient satisfaction and other indicators of patient-centered care. Propensity weights adjusted for potential case-mix differences in intervention and control groups; propensity-adjusted proportions accounted for physician-level clustering. Results: More intervention patients were very satisfied with their care after the PCMH Lean intervention (68%) compared with pre-intervention (62%). Among control patients, there was no corresponding increase in satisfaction (63% very satisfied pre-intervention vs 64% very satisfied postintervention). This comparison resulted in a statistical trend (P=.10) toward greater overall satisfaction attributable to the intervention. Post-intervention, patients in the intervention practice consistently rated indicators of patient-centered care higher than patients in the control practice, particularly in the personal physician and communication domain. In this domain, intervention patients reported superior provider explanations, time spent, provider concern, and follow-up instructions compared with control participants, whereas control group ratings fell in the postintervention period (P for difference <=.05). Conclusions: In a pilot PCMH transformation including Lean enhancement with payment reform, patient experience was sustained or improved across key PCMH domains. C1 [Heyworth, Leonie; Simon, Steven R.] Dept Vet Affairs Med Ctr, Boston, MA USA. [Heyworth, Leonie; Bitton, Asaf; Lipsitz, Stuart R.; Schiff, Gordon D.; Bates, David W.; Simon, Steven R.] Brigham & Womens Hosp, Boston, MA 02115 USA. [Schilling, Thad] Harvard Vanguard Med Associates, Boston, MA USA. [Bitton, Asaf] Harvard Univ, Sch Med, Ctr Primary Care, Boston, MA USA. RP Heyworth, L (reprint author), VA Boston Healthcare Syst, 150 South Huntington Ave,Bldg 9 152G, Boston, MA 02130 USA. FU Health Resources and Services Administration [T32 HP10251]; Department of Veterans Affairs, Veterans Health Administration, Office of Research and Development; Commonwealth Fund, a national, private foundation based in New York City FX This study was supported by The Commonwealth Fund, a national, private foundation based in New York City that supports independent research on healthcare issues and makes grants to improve healthcare practice and policy. The views presented here are those of the authors and not necessarily those of The Commonwealth Fund, its directors, officers, or staff. Dr Heyworth is supported by Health Resources and Services Administration grant T32 HP10251 and by the Department of Veterans Affairs, Veterans Health Administration, Office of Research and Development. Dr Bitton is a special advisor to the Center for Medicare and Medicaid Innovation Comprehensive Primary Care initiative. The Centers for Medicare & Medicaid Services (CMS) had no role in this study, and this study in no way reflects any official positions CMS may have. NR 19 TC 8 Z9 8 U1 3 U2 10 PU MANAGED CARE & HEALTHCARE COMMUNICATIONS LLC PI PLAINSBORO PA 666 PLAINSBORO RD, STE 300, PLAINSBORO, NJ 08536 USA SN 1088-0224 J9 AM J MANAG CARE JI Am. J. Manag. Care PD JAN PY 2014 VL 20 IS 1 BP 26 EP 33 PG 8 WC Health Care Sciences & Services; Health Policy & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 302IV UT WOS:000330599000003 PM 24512168 ER PT J AU Sedaghat, AR Cunningham, MJ Ishman, SL AF Sedaghat, Ahmad R. Cunningham, Michael J. Ishman, Stacey L. TI Regional and socioeconomic disparities in emergency department use of radiographic imaging for acute pediatric sinusitis SO AMERICAN JOURNAL OF RHINOLOGY & ALLERGY LA English DT Article ID CLINICAL-PRACTICE GUIDELINE; INTRACRANIAL COMPLICATIONS; CHILDREN; MANAGEMENT; RHINOSINUSITIS; DIAGNOSIS AB Background: Acute pediatric sinusitis (APS) is a common complication of pediatric upper respiratory tract infections. Children with all degrees of APS severity may present to emergency departments (EDs) for evaluation and management. This study was designed to analyze the use of imaging in APS presenting to U.S. EDs. Methods: A cross-sectional analysis of the 2008 National Emergency Department Sample database was performed. One hundred one thousand six hundred sixty children, aged <= 18 years, assigned at least one ICD9 code for APS were identified. Current procedural terminology codes for sinus plain film radiographs, computed tomography (CT), and magnetic resonance imaging identified children who underwent sinus imaging. Association of performance of sinus imaging was sought with multiple predictor variables including clinicodemographic and hospital characteristics. Results: The use of any imaging was associated with older age (odds ratio [OR] = 1.07; p < 0.001), male gender (OR = 1.57; p < 0.001), and diagnosis of chronic rhinosinusitis (OR = 2.46; p < 0.001). Imaging was more common in metropolitan teaching (OR = 1.40; 0 p < 0.001) and nonteaching (OR = 5.64; p < 0.001) hospitals. Markers of higher socioeconomic status-private health insurance (OR = 1.37; p < 0.001) and higher income level (OR = 1.96; p < 0.001)-were associated with greater use of imaging, especially CT scans. Conclusion: The use of ED imaging in APS is appropriately associated with factors known to be associated with APS complications. However, additional disparities with respect to regional and socioeconomic factors exist. Interventions to eliminate these health care disparities in use of imaging resources may lead to quality improvement in care and outcomes for APS. C1 [Sedaghat, Ahmad R.] Massachusetts Eye & Ear Infirm, Dept Otolaryngol Head & Neck Surg, Boston, MA 02114 USA. [Sedaghat, Ahmad R.; Cunningham, Michael J.] Harvard Univ, Sch Med, Dept Otol & Laryngol, Boston, MA 02115 USA. [Cunningham, Michael J.] Childrens Hosp Boston, Dept Otolaryngol & Commun Enhancement, Boston, MA USA. [Ishman, Stacey L.] Cincinnati Childrens Hosp Med Ctr, Div Otolaryngol Head & Neck Surg, Cincinnati, OH 45229 USA. [Ishman, Stacey L.] Cincinnati Childrens Hosp Med Ctr, Div Pulm Med, Cincinnati, OH 45229 USA. RP Sedaghat, AR (reprint author), Massachusetts Eye & Ear Infirm, Dept Otolaryngol Head & Neck Surg, 243 Charles St, Boston, MA 02114 USA. EM ahmad_sedaghat@meei.harvard.edu OI Ishman, Stacey/0000-0003-0997-9692 NR 23 TC 8 Z9 8 U1 0 U2 2 PU OCEAN SIDE PUBLICATIONS INC PI PROVIDENCE PA 95 PITMAN ST, PROVIDENCE, RI 02906 USA SN 1945-8924 EI 1945-8932 J9 AM J RHINOL ALLERGY JI Am. J. Rhinol. Allergy PD JAN-FEB PY 2014 VL 28 IS 1 BP 23 EP 28 DI 10.2500/ajra.2014.28.3992 PG 6 WC Otorhinolaryngology SC Otorhinolaryngology GA AA2WC UT WOS:000330953900020 PM 24717874 ER PT J AU Parikh, NG Junaid, I Sheinkopf, L Randhawa, I Santiago, SM Klaustermeyer, WB AF Parikh, Neil G. Junaid, Imran Sheinkopf, Lee Randhawa, Inderpal Santiago, Silverio M. Klaustermeyer, William B. TI Clinical control in the dual diagnosis of obstructive sleep apnea syndrome and rhinitis: A prospective analysis SO AMERICAN JOURNAL OF RHINOLOGY & ALLERGY LA English DT Article ID PERENNIAL ALLERGIC RHINITIS; NASAL OBSTRUCTION; INFLAMMATION; PREVALENCE; RESISTANCE; SURGERY AB Background: Obstructive sleep apnea syndrome (OSAS) and allergic rhinitis (AR) are common coexisting disorders. Upper airway, specifically nasal resistance, is thought to increase during exacerbations of AR and nonallergic rhinitis (NAR), as well as in OSAS. The study objective was to determine if a correlation exists between clinical control of rhinitis and OSAS. Methods: This prospective study followed 43 patients with concurrent OSAS and AR or NAR. OSAS was diagnosed by polysomnography, and AR or NAR was diagnosed by history, skin testing, serum-specific IgE, and total IgE levels. Measurements of control of OSAS included the Epworth Sleepiness Scale (ESS) survey and compliance with continuous positive airway pressure (CPAP) device. Measurements of rhinitis control included Assessment of Nasal Symptom Severity and Assessment of Nonnasal Symptom Severity (NSS refers to both) and Global Assessment of Nasal and Nonnasal Symptom Severity surveys (GSS). Higher NSS scores correlate with more rhinitis symptoms, whereas higher GSS scores correlate with less symptoms. Results: All patients completed the study. There was a positive correlation between ESS and NSS scores (p < 0.001), inverse correlation between ESS and GSS scores (p < 0.001), inverse correlation between CPAP compliance and NSS scores (p < 0.001), and positive correlation between CPAP compliance and GSS scores (p < 0.001). There was no statistically significant difference between the AR, NAR, and AR/NAR groups. Conclusion: Our study showed a statistically significant positive correlation between clinical control of rhinitis symptoms and clinical control of OSAS. This study emphasizes the importance of achieving concurrent optimal control of both OSAS and AR/NAR. C1 [Parikh, Neil G.; Junaid, Imran; Sheinkopf, Lee; Randhawa, Inderpal; Santiago, Silverio M.; Klaustermeyer, William B.] Univ Calif Los Angeles, David Geffen Sch Med, Vet Affairs Greater Los Angeles Healthcare Syst, Div Allergy & Immunol, Los Angeles, CA 90073 USA. RP Parikh, NG (reprint author), Univ Calif Los Angeles, Vet Affairs Greater Los Angeles Healthcare Syst, 11301 Wilshire Blvd,Allergy Immunol 111R, Los Angeles, CA 90073 USA. EM nparikh2009@gmail.com NR 25 TC 5 Z9 5 U1 3 U2 13 PU OCEAN SIDE PUBLICATIONS INC PI PROVIDENCE PA 95 PITMAN ST, PROVIDENCE, RI 02906 USA SN 1945-8924 EI 1945-8932 J9 AM J RHINOL ALLERGY JI Am. J. Rhinol. Allergy PD JAN-FEB PY 2014 VL 28 IS 1 BP E52 EP E55 DI 10.2500/ajra.2014.28.3977 PG 4 WC Otorhinolaryngology SC Otorhinolaryngology GA AA2WC UT WOS:000330953900010 PM 24717883 ER PT J AU Cox, AG Saunders, DC Kelsey, PB Conway, AA Tesmenitsky, Y Marchini, JF Brown, KK Stamler, JS Colagiovanni, DB Rosenthal, GJ Croce, KJ North, TE Goessling, W AF Cox, Andrew G. Saunders, Diane C. Kelsey, Peter B., Jr. Conway, Allie A. Tesmenitsky, Yevgenia Marchini, Julio F. Brown, Kristin K. Stamler, Jonathan S. Colagiovanni, Dorothy B. Rosenthal, Gary J. Croce, Kevin J. North, Trista E. Goessling, Wolfram TI S-Nitrosothiol Signaling Regulates Liver Development and Improves Outcome following Toxic Liver Injury SO CELL REPORTS LA English DT Article ID NITRIC-OXIDE SYNTHASE; ACETAMINOPHEN-INDUCED HEPATOTOXICITY; NRF2 KNOCKOUT MICE; NF-KAPPA-B; PARTIAL-HEPATECTOMY; OXIDATIVE STRESS; IN-VIVO; REGENERATION; ZEBRAFISH; NITROSYLATION AB Toxic liver injury is a leading cause of liver failure and death because of the organ's inability to regenerate amidst massive cell death, and few therapeutic options exist. The mechanisms coordinating damage protection and repair are poorly understood. Here, we show that S-nitrosothiols regulate liver growth during development and after injury in vivo; in zebrafish, nitric-oxide (NO) enhanced liver formation independently of cGMP-mediated vasoactive effects. After acetaminophen (APAP) exposure, inhibition of the enzymatic regulator S-nitrosoglutathione reductase (GSNOR) minimized toxic liver damage, increased cell proliferation, and improved survival through sustained activation of the cytoprotective Nrf2 pathway. Preclinical studies of APAP injury in GSNOR-deficient mice confirmed conservation of hepatoprotective properties of S-nitrosothiol signaling across vertebrates; a GSNOR-specific inhibitor improved liver histology and acted with the approved therapy N-acetylcysteine to expand the therapeutic time window and improve outcome. These studies demonstrate that GSNOR inhibitors will be beneficial therapeutic candidates for treating liver injury. C1 [Cox, Andrew G.; Saunders, Diane C.; Kelsey, Peter B., Jr.; Conway, Allie A.; Goessling, Wolfram] Harvard Univ, Brigham & Womens Hosp, Sch Med, Div Genet, Boston, MA 02115 USA. [Tesmenitsky, Yevgenia; Marchini, Julio F.; Croce, Kevin J.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Div Cardiovasc Med, Boston, MA 02115 USA. [Brown, Kristin K.; North, Trista E.] Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Dept Pathol, Boston, MA 02115 USA. [Stamler, Jonathan S.] Case Western Reserve Univ, Harrington Discovery Inst, Inst Transformat Mol Med, Cleveland, OH 44106 USA. [Stamler, Jonathan S.] Case Western Reserve Univ, Harrington Discovery Inst, Dept Med, Cleveland, OH 44106 USA. [Colagiovanni, Dorothy B.; Rosenthal, Gary J.] N30 Pharmaceut, Boulder, CO 80301 USA. [North, Trista E.; Goessling, Wolfram] Harvard Stem Cell Inst, Cambridge, MA 02138 USA. [Goessling, Wolfram] Harvard Univ, Brigham & Womens Hosp, Sch Med, Div Gastroenterol, Boston, MA 02115 USA. [Goessling, Wolfram] Dana Farber Canc Inst, Gastrointestinal Canc Ctr, Boston, MA 02115 USA. [Goessling, Wolfram] MIT, Broad Inst, Cambridge, MA 02142 USA. [Goessling, Wolfram] Harvard Univ, Cambridge, MA 02142 USA. RP North, TE (reprint author), Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Dept Pathol, Boston, MA 02115 USA. EM tnorth@bidmc.harvard.edu; wgoessling@partners.org RI Marchini, Julio/H-4034-2014; OI Marchini, Julio/0000-0002-2279-1945; Goessling, Wolfram/0000-0001-9972-1569 FU Public Health Service [DK090311]; Harvard Stem Cell Institute; Pew Charitable Trusts; American Liver Foundation FX We would like to thank N30 pharmaceuticals for providing the GSNOR inhibitor (N6547). We thank members of the Goessling and North laboratories for helpful discussions. This work was supported by Public Health Service Grant DK090311 (W.G.), a junior faculty grant from the Harvard Stem Cell Institute (W.G. and T.E.N.), and the Pew Charitable Trusts (W.G.). A.G.C. is the recipient of an American Liver Foundation Postdoctoral Research Fellowship Award. D.B.C. and G.J.R. are employees of N30 Pharmaceutical. NR 48 TC 14 Z9 15 U1 0 U2 5 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 2211-1247 J9 CELL REP JI Cell Reports PD JAN PY 2014 VL 6 IS 1 BP 56 EP 69 DI 10.1016/j.celrep.2013.12.007 PG 14 WC Cell Biology SC Cell Biology GA AA5PX UT WOS:000331153200007 PM 24388745 ER PT J AU Wang, Y Zhang, Y AF Wang, Yu Zhang, Yi TI Regulation of TET Protein Stability by Calpains SO CELL REPORTS LA English DT Article ID EMBRYONIC STEM-CELLS; CXXC DOMAIN; 5-METHYLCYTOSINE OXIDATION; MAMMALIAN DNA; SELF-RENEWAL; 5-HYDROXYMETHYLCYTOSINE; 5-CARBOXYLCYTOSINE; DIFFERENTIATION; SPECIFICATION; MECHANISMS AB DNA methylation at the fifth position of cytosine (5mC) is an important epigenetic modification that affects chromatin structure and gene expression. Recent studies have established a critical function of the Ten-eleven translocation (Tet) family of proteins in regulating DNA methylation dynamics. Three Tet genes have been identified in mammals, and they all encode for proteins capable of oxidizing 5mC as part of the DNA demethylation process. Although regulation of Tet expression at the transcriptional level is well documented, how TET proteins are regulated at posttranslational level is poorly understood. In this study, we report that all three TET proteins are direct substrates of calpains, a family of calcium-dependent proteases. Specifically, calpain1 mediates TET1 and TET2 turnover in mouse ESCs, and calpain2 regulates TET3 level during differentiation. This study provides evidence that TET proteins are subject to calpain-mediated degradation. C1 [Wang, Yu; Zhang, Yi] Harvard Univ, Sch Med, Howard Hughes Med Inst, Boston, MA 02115 USA. [Wang, Yu; Zhang, Yi] Harvard Univ, Sch Med, Boston Childrens Hosp, Program Cellular & Mol Med, Boston, MA 02115 USA. [Wang, Yu; Zhang, Yi] Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA. [Zhang, Yi] Harvard Univ, Sch Med, Harvard Stem Cell Inst, Boston, MA 02115 USA. RP Zhang, Y (reprint author), Harvard Univ, Sch Med, Howard Hughes Med Inst, WAB 149G,200 Longwood Ave, Boston, MA 02115 USA. EM yzhang@genetics.med.harvard.edu FU NIH [GM68804, U01DK089565] FX We thank Drs. Feng Zhang for the px330 vector, Li Shen and Hao Wu for Tet1 and Tet3 shRNA lentiviral vectors, and Hao Wu and Damian Sendler for critical reading of the manuscript. This study is supported by GM68804 and U01DK089565 from NIH. Y.Z. is an Investigator of the Howard Hughes Medical Institute. NR 30 TC 24 Z9 24 U1 1 U2 12 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 2211-1247 J9 CELL REP JI Cell Reports PD JAN PY 2014 VL 6 IS 2 BP 278 EP 284 DI 10.1016/j.celrep.2013.12.031 PG 7 WC Cell Biology SC Cell Biology GA AA5VD UT WOS:000331166800006 PM 24412366 ER PT J AU Chudnovsky, Y Kim, D Zheng, SY Whyte, WA Bansal, M Bray, MA Gopal, S Theisen, MA Bilodeau, S Thiru, P Muffat, J Yilmaz, OH Mitalipova, M Woolard, K Lee, J Nishimura, R Sakata, N Fine, HA Carpenter, AE Silver, SJ Verhaak, RGW Califano, A Young, RA Ligon, KL Mellinghoff, IK Root, DE Sabatini, DM Hahn, WC Chheda, MG AF Chudnovsky, Yakov Kim, Dohoon Zheng, Siyuan Whyte, Warren A. Bansal, Mukesh Bray, Mark-Anthony Gopal, Shuba Theisen, Matthew A. Bilodeau, Steve Thiru, Prathapan Muffat, Julien Yilmaz, Omer H. Mitalipova, Maya Woolard, Kevin Lee, Jeongwu Nishimura, Riko Sakata, Nobuo Fine, Howard A. Carpenter, Anne E. Silver, Serena J. Verhaak, Roel G. W. Califano, Andrea Young, Richard A. Ligon, Keith L. Mellinghoff, Ingo K. Root, David E. Sabatini, David M. Hahn, William C. Chheda, Milan G. TI ZFHX4 Interacts with the NuRD Core Member CHD4 and Regulates the Glioblastoma Tumor-Initiating Cell State SO CELL REPORTS LA English DT Article ID GLIOMA STEM-CELLS; BRAIN-TUMORS; MESENCHYMAL TRANSFORMATION; TRANSCRIPTIONAL NETWORK; PEDIATRIC GLIOBLASTOMA; MALIGNANT GLIOMA; GENE-EXPRESSION; RNAI SCREEN; C-MYC; DIFFERENTIATION AB Glioblastoma (GBM) harbors subpopulations of therapy-resistant tumor-initiating cells (TICs) that are self-renewing and multipotent. To understand the regulation of the TIC state, we performed an image-based screen for genes regulating GBM TIC maintenance and identified ZFHX4, a 397 kDa transcription factor. ZFHX4 is required to maintain TIC-associated and normal human neural precursor cell phenotypes in vitro, suggesting that ZFHX4 regulates differentiation, and its suppression increases glioma-free survival in intracranial xenografts. ZFHX4 interacts with CHD4, a core member of the nucleosome remodeling and deacetylase (NuRD) complex. ZFHX4 and CHD4 bind to overlapping sets of genomic loci and control similar gene expression programs. Using expression data derived from GBM patients, we found that ZFHX4 significantly affects CHD4-mediated gene expression perturbations, which defines ZFHX4 as a master regulator of CHD4. These observations define ZFHX4 as a regulatory factor that links the chromatin-remodeling NuRD complex and the GBM TIC state. C1 [Chudnovsky, Yakov; Kim, Dohoon; Whyte, Warren A.; Thiru, Prathapan; Muffat, Julien; Yilmaz, Omer H.; Mitalipova, Maya; Young, Richard A.; Sabatini, David M.] Whitehead Inst Biomed Res, Cambridge, MA 02142 USA. [Chudnovsky, Yakov; Kim, Dohoon; Yilmaz, Omer H.; Young, Richard A.; Sabatini, David M.] MIT, Dept Biol, Cambridge, MA 02139 USA. [Chudnovsky, Yakov; Bray, Mark-Anthony; Gopal, Shuba; Carpenter, Anne E.; Silver, Serena J.; Root, David E.; Sabatini, David M.; Hahn, William C.; Chheda, Milan G.] Broad Inst Harvard & MIT, Cambridge, MA 02142 USA. [Zheng, Siyuan; Verhaak, Roel G. W.] Univ Texas Houston, MD Anderson Canc Ctr, Dept Bioinformat & Computat Biol, Houston, TX 77030 USA. [Bansal, Mukesh; Califano, Andrea] Columbia Univ, Dept Syst Biol, New York, NY 10032 USA. [Bansal, Mukesh; Califano, Andrea] Columbia Univ, Ctr Computat Biol & Bioinformat, New York, NY 10032 USA. [Theisen, Matthew A.; Ligon, Keith L.] Dana Farber Canc Inst, Ctr Mol Oncol Pathol, Dept Med Oncol, Boston, MA 02115 USA. [Bilodeau, Steve] Univ Laval, Hotel Dieu Quebec, CHU Quebec, Ctr Rech Canc, Quebec City, PQ G1R 2J6, Canada. [Bilodeau, Steve] Univ Laval, Hotel Dieu Quebec, CHU Quebec, Ctr Rech, Quebec City, PQ G1R 2J6, Canada. [Bilodeau, Steve] Univ Laval, Fac Med, Dept Biol Mol Biochim Med & Pathol, Quebec City, PQ G1R 2J6, Canada. [Yilmaz, Omer H.; Sabatini, David M.] MIT, David H Koch Inst Integrat Canc Res, Cambridge, MA 02139 USA. [Woolard, Kevin] Univ Calif Davis, Sch Vet Med, Dept Pathol Microbiol & Immunol, Davis, CA 95616 USA. [Lee, Jeongwu] Lerner Res Inst, Dept Stem Cell Biol & Regenerat Med, Cleveland, OH 44195 USA. [Nishimura, Riko] Osaka Univ, Grad Sch Dent, Dept Mol & Cellular Biochem, Suita, Osaka 5650871, Japan. [Sakata, Nobuo] Showa Pharmaceut Univ, Dept Biochem, Machida, Tokyo 1948543, Japan. [Fine, Howard A.] NYU, Langone Med Ctr, Inst Canc, Div Hematol & Med Oncol, New York, NY 10016 USA. [Fine, Howard A.] NYU, Langone Med Ctr, Inst Canc, Brain Tumor Ctr, New York, NY 10016 USA. [Verhaak, Roel G. W.] Univ Texas Houston, MD Anderson Canc Ctr, Dept Genom Med, Houston, TX 77030 USA. [Califano, Andrea] Columbia Univ, Dept Biomed Informat, New York, NY 10032 USA. [Califano, Andrea] Columbia Univ, Dept Biochem & Mol Biophys, New York, NY 10032 USA. [Califano, Andrea] Columbia Univ, Inst Canc Genet, New York, NY 10032 USA. [Califano, Andrea] Columbia Univ, Herbert Irving Comprehens Canc Ctr, New York, NY 10032 USA. [Ligon, Keith L.] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. [Ligon, Keith L.] Boston Childrens Hosp, Dept Pathol, Boston, MA 02115 USA. [Mellinghoff, Ingo K.; Chheda, Milan G.] Mem Sloan Kettering Canc Ctr, Dept Neurol, New York, NY 10065 USA. [Mellinghoff, Ingo K.; Chheda, Milan G.] Mem Sloan Kettering Canc Ctr, Human Oncol & Pathogenesis Program, New York, NY 10065 USA. [Mellinghoff, Ingo K.] Weill Cornell Grad Sch Biomed Sci, Dept Pharmacol, New York, NY 10021 USA. [Sabatini, David M.] Howard Hughes Med Inst, Cambridge, MA 02139 USA. [Hahn, William C.; Chheda, Milan G.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Hahn, William C.] Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. RP Sabatini, DM (reprint author), Whitehead Inst Biomed Res, 9 Cambridge Ctr, Cambridge, MA 02142 USA. EM sabatini@wi.mit.edu; william_hahn@dfci.harvard.edu RI Muffat, Julien/P-2298-2014; Bray, Mark/C-5973-2008; Carpenter, Anne/C-4982-2008; Sakata, Nobuo/L-9753-2015; Young, Richard/F-6495-2012; OI Bray, Mark/0000-0002-9748-3592; Carpenter, Anne/0000-0003-1555-8261; Sakata, Nobuo/0000-0001-9967-8409; Young, Richard/0000-0001-8855-8647; Muffat, Julien/0000-0003-1889-7023 FU American Cancer Society postdoctoral fellowship; American Brain Tumor Association Discovery Grant; National Institutes of Health (NIH) [P30CA016672, U24CA143883, U01CA168426, U54CA121852, R01HG002668, R01CA146455, R01CA170592, P01CA095616, R01NS080944, R01CA129105, P01CA142536, U01CA176058, K08NS062907, K12CA090354]; European Leukodystrophy Association; MEXT/JSPS [KAKENHI 25670168]; Sontag Foundation; Goldhirsh Foundation; Starr Foundation; Koch Institute Research Program; National Brain Tumor Foundation; American Brain Tumor Association fellowship, an American Association for Cancer Research/National Brain Tumor Foundation fellowship; Dana-Farber Cancer Institute Pediatric Low Grade Astrocytoma Program; Broad Institute FX We thank members of the D.M.S., W.C.H., and I.K.M. laboratories for advice; members of the H.A.F., Kornblum, and K.L.L. laboratories for advice on work with GBM TICs; C. Maire for technical assistance; L. Solomon, L. Gaffney, and T. DiCesare for extensive graphical help preparing manuscript figures; E. Spooner for mass spectrometric analysis; and H. Le, S. Ponduru, M. Vokes, V. Ljosa, A. Papallo, and other members of the RNAi and Imaging Platforms at the Broad Institute for assistance with RNAi screening and analysis. This work was supported in part by an American Cancer Society postdoctoral fellowship and an American Brain Tumor Association Discovery Grant to Y.C.; grants from the National Institutes of Health (NIH; P30CA016672 and U24CA143883) to S.Z. and R.G.W.V.; a grant from the European Leukodystrophy Association to J.M.; a grant from MEXT/JSPS (KAKENHI 25670168) to N.S.; a grant from the NIH (R01GM089652) and funding from the Broad Institute to A. E.C.; grants from the NIH (U01CA168426 and U54CA121852) to A.C. and M.B.; grants from the NIH (R01HG002668 and R01CA146455) to R.A.Y.; grants from the NIH (R01CA170592 and P01CA095616), Sontag Foundation, and Goldhirsh Foundation to K.L.L.; a grant from the NIH (R01NS080944) to I.K.M.; a grant from the NIH (R01CA129105) and awards from the Starr Foundation, Koch Institute Research Program, Goldhirsh Foundation, and National Brain Tumor Foundation to D.M.S.; grants from the NIH (P01CA095616, P01CA142536, and U01CA176058) to W.C.H.; career development grants from the NIH (K08NS062907 and K12CA090354), an American Brain Tumor Association fellowship, an American Association for Cancer Research/National Brain Tumor Foundation fellowship, and a grant from the Dana-Farber Cancer Institute Pediatric Low Grade Astrocytoma Program to M.G.C.; and a SPARC award from the Broad Institute to D.M.S., W.C.H., and D.E.R. D.M.S. is an investigator of the Howard Hughes Medical Institute. S.J.S. is currently an employee of Novartis. R.A.Y. is a founder of Syros Pharmaceuticals and a member of its board of directors. NR 56 TC 29 Z9 29 U1 0 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 JAN PY 2014 VL 6 IS 2 BP 313 EP 324 DI 10.1016/j.celrep.2013.12.032 PG 12 WC Cell Biology SC Cell Biology GA AA5VD UT WOS:000331166800010 PM 24440720 ER PT J AU Lewandrowski, K Sluss, P AF Lewandrowski, Kent Sluss, Patrick TI Preface to the special edition of Clin Chem Acta: Utilization management in the clinical laboratory SO CLINICA CHIMICA ACTA LA English DT Editorial Material DE Utilization management; overutilization; clinical laboratory utilization; utilization management incentives C1 [Lewandrowski, Kent; Sluss, Patrick] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Lewandrowski, K (reprint author), Massachusetts Gen Hosp, Gray 5 Chem Fruit St, Boston, MA 02114 USA. EM klewandrowski@partners.org NR 0 TC 0 Z9 0 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0009-8981 EI 1873-3492 J9 CLIN CHIM ACTA JI Clin. Chim. Acta PD JAN 1 PY 2014 VL 427 SI SI BP 107 EP 108 DI 10.1016/j.cca.2013.11.011 PG 2 WC Medical Laboratory Technology SC Medical Laboratory Technology GA AA0WX UT WOS:000330819200020 PM 24309229 ER PT J AU Rao, SK AF Rao, Sandhya K. TI Utilization management in the changing health-care environment SO CLINICA CHIMICA ACTA LA English DT Article DE Utilization management; Health-care policy; Health-care costs; Health-care reform AB US health-care costs are growing at an alarming rate. "Value-based" payment models that hold providers accountable for outcomes and costs of care are becoming more prevalent. In these arrangements, provider groups will be accountable for the costs of lab tests, many of which have traditionally been revenue-generating. "Stewardship" programs aimed at newer, high-cost specialized tests, decision support on more routine tests, variation reporting, and incentives are familiar tactics that will need to be deployed in this new context. (C) 2013 Elsevier B.V. All rights reserved. C1 [Rao, Sandhya K.] Massachusetts Gen Hosp, Div Gen Med, Boston, MA 02114 USA. RP Rao, SK (reprint author), Massachusetts Gen Hosp, Bulfinch 205,55 Fruit Str, Boston, MA 02114 USA. EM skrao@partners.org NR 10 TC 2 Z9 2 U1 0 U2 3 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0009-8981 EI 1873-3492 J9 CLIN CHIM ACTA JI Clin. Chim. Acta PD JAN 1 PY 2014 VL 427 SI SI BP 109 EP 110 DI 10.1016/j.cca.2013.09.036 PG 2 WC Medical Laboratory Technology SC Medical Laboratory Technology GA AA0WX UT WOS:000330819200021 PM 24084508 ER PT J AU Huck, A Lewandrowski, K AF Huck, Amelia Lewandrowski, Kent TI Utilization management in the clinical laboratory: An introduction and overview of the literature SO CLINICA CHIMICA ACTA LA English DT Article DE Utilization management; Literature review; Clinical laboratory ID ACUTE MYOCARDIAL-INFARCTION; HOSPITAL-ACQUIRED ANEMIA; ACADEMIC-MEDICAL-CENTER; INTENSIVE-CARE-UNIT; DEMAND MANAGEMENT; DIAGNOSTIC-TESTS; INTERVENTION; PHYSICIANS; RECOMMENDATION; PROGRAM AB There is a broad literature addressing the need for improving utilization management in medical care. Numerous review articles and case studies have described approaches to utilization management challenges in the laboratory. This article will present an overview of the literature on laboratory utilization management and will compile a "toolbox" of strategies that can be used to address specific utilization management initiatives. A clear theme among successful utilization management programs is the need to recruit institutional champions both for the overall utilization management program and for ad hoc assistance with specific utilization challenges. It is important that these individuals represent a cross section of laboratory and clinical specialties and that the group be organized as a committee that has been established by the administrative and physician leadership of the organization. The changing nature of healthcare reimbursement will likely provide increased motivation to control laboratory testing and costs. Clinical pathologists are in a unique position to observe testing behavior patterns, suggest alternatives, implement order entry changes, manage testing algorithms and provide interpretive services for laboratory testing. For these reasons, clinical pathologists have a major opportunity to become institutional leaders in utilization management. (C) 2013 Elsevier B.V. All rights reserved. C1 [Huck, Amelia] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Cambridge, MA 02138 USA. RP Lewandrowski, K (reprint author), Massachusetts Gen Hosp, Dept Pathol, Gray 5,Fruit St, Boston, MA 02114 USA. EM klewandrowski@partners.org NR 41 TC 11 Z9 11 U1 1 U2 8 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0009-8981 EI 1873-3492 J9 CLIN CHIM ACTA JI Clin. Chim. Acta PD JAN 1 PY 2014 VL 427 SI SI BP 111 EP 117 DI 10.1016/j.cca.2013.09.021 PG 7 WC Medical Laboratory Technology SC Medical Laboratory Technology GA AA0WX UT WOS:000330819200022 PM 24080430 ER PT J AU MacMillan, D AF MacMillan, Donna TI Calculating cost savings in utilization management SO CLINICA CHIMICA ACTA LA English DT Article DE Cost accounting; Utilization management; Job order; Process accounting; Clinical laboratories AB A major motivation for managing the utilization of laboratory testing is to reduce the cost of medical care. For this reason it is important to understand the basic principles of cost accounting in the clinical laboratory. The process of laboratory testing includes three distinct components termed the pre-analytic, analytic and post-analytic phases. Utilization management efforts may impact the cost structure of these three phases in different ways depending on the specific details of the initiative. Estimates of cost savings resulting from utilization management programs reported in the literature have often been fundamentally flawed due to a failure to understand basic concepts such as the difference between laboratory costs versus charges and the impact of reducing laboratory test volumes on the average versus marginal cost structure in the laboratory. This article will provide an overview of basic cost accounting principles in the clinical laboratory including both job order and process cost accounting. Specific examples will be presented to illustrate these concepts in various different scenarios. (C) 2013 Published by Elsevier B.V. C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. RP MacMillan, D (reprint author), Massachusetts Gen Hosp, Fruit St,Gray 504, Boston, MA 02114 USA. EM DMACMILIAN@PARTNERS.ORG NR 1 TC 5 Z9 5 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0009-8981 EI 1873-3492 J9 CLIN CHIM ACTA JI Clin. Chim. Acta PD JAN 1 PY 2014 VL 427 SI SI BP 123 EP 126 DI 10.1016/j.cca.2013.09.024 PG 4 WC Medical Laboratory Technology SC Medical Laboratory Technology GA AA0WX UT WOS:000330819200024 PM 24084505 ER PT J AU Yeh, DD AF Yeh, D. Dante TI A clinician's perspective on laboratory utilization management SO CLINICA CHIMICA ACTA LA English DT Review DE Utilization management; Clinician perspective; Laboratory test utilization; Utilization interventions ID INTENSIVE-CARE-UNIT; ANCILLARY COST REDUCTION; SURGICAL CRITICAL-CARE; DIAGNOSTIC-TESTS; PHYSICIAN BEHAVIOR; TRAUMA PATIENTS; D-DIMER; CONTAINMENT; STRATEGIES; CHEMISTRY AB Background: Excessive laboratory utilization is a common problem in the hospital setting. Physicians control up to 80% of healthcare costs and wield great influence. Methods: This review article describes reasons for overutilization of labs and recommends interventional strategies to change clinician ordering behavior. Results: Powerful factors exist that encourage overutilization, including fear of missing a diagnosis, provider inexperience, peer pressure, financial rewards, practice inertia, and fear of legal punishment. Features of automated order entry, such as bundling and "daily until discontinued" options contribute to wasteful ordering behavior. Conclusion: The most successful and long-lasting interventions are multi-faceted and have included a combination of education, feedback and audit, and administrative changes. The support of senior physicians and top administration is critical to the success of any initiative and ideally, interventions should be original from a multi-disciplinary committee of respected individuals. (C) 2013 Elsevier B.V. All rights reserved. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA 02114 USA. RP Yeh, DD (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, 165 Cambridge St 810, Boston, MA 02114 USA. EM dyeh2@partners.org NR 47 TC 7 Z9 7 U1 2 U2 6 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0009-8981 EI 1873-3492 J9 CLIN CHIM ACTA JI Clin. Chim. Acta PD JAN 1 PY 2014 VL 427 SI SI BP 145 EP 150 DI 10.1016/j.cca.2013.09.023 PG 6 WC Medical Laboratory Technology SC Medical Laboratory Technology GA AA0WX UT WOS:000330819200029 PM 24084504 ER PT J AU Sluss, PM AF Sluss, Patrick M. TI Reference laboratory utilization management SO CLINICA CHIMICA ACTA LA English DT Article DE Reference laboratory; Utilization management; Performance parameters; Informatic tools; Implementation strategies ID ACADEMIC-MEDICAL-CENTER; TESTS; IMPACT; INTERVENTION; INFORMATION; PROGRAM AB This chapter describes the unique challenges of managing reference laboratory utilization. The nature of reference laboratory testing and how it differs from routine hospital clinical laboratory testing is discussed. The vast majority of reference laboratory testing is high complexity, low volume testing to support specialized care. In contrast the hospital clinical laboratory is most effective at performing rapid turn-around, routine, high volume testing. The implication of these differences with respect to identifying utilization issues and interventions to manage utilization is presented along with examples. (C) 2013 Elsevier B.V. All rights reserved. C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Sluss, PM (reprint author), Massachusetts Gen Hosp, GRB554,55 Fruit St, Boston, MA 02114 USA. EM PSLUSS@PARTNERS.ORG NR 38 TC 2 Z9 2 U1 1 U2 4 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0009-8981 EI 1873-3492 J9 CLIN CHIM ACTA JI Clin. Chim. Acta PD JAN 1 PY 2014 VL 427 SI SI BP 167 EP 172 DI 10.1016/j.cca.2013.09.035 PG 6 WC Medical Laboratory Technology SC Medical Laboratory Technology GA AA0WX UT WOS:000330819200033 PM 24140173 ER PT J AU Branda, JA Lewandrowski, K AF Branda, John A. Lewandrowski, Kent TI Utilization management in microbiology SO CLINICA CHIMICA ACTA LA English DT Review DE Utilization management; Microbiology; Antimicrobial stewardship; Decision support; MALDI-TOF mass spectroscopy ID DESORPTION IONIZATION-TIME; URINARY-TRACT-INFECTIONS; FLIGHT MASS-SPECTROMETRY; BLOOD CULTURES; CLINICAL MICROBIOLOGY; RESOURCE UTILIZATION; NOSOCOMIAL DIARRHEA; COST-EFFECTIVENESS; CONTROLLED-TRIAL; DIAGNOSIS AB The available literature concerning utilization management in the clinical microbiology laboratory is relatively limited compared with that for high-volume, automated testing in the central Core Laboratory. However, the same strategies employed elsewhere in the clinical laboratory operation can be applied to utilization management challenges in microbiology, including decision support systems, application of evidence-based medicine, screening algorithms and gatekeeper functions. The results of testing in the microbiology laboratory have significant effects on the cost of clinical care, especially costs related to antimicrobial agents and infection control practices. Consequently many of the successful utilization management interventions described in clinical microbiology have targeted not just the volume of tests performed in the laboratory, but also the downstream costs of care. This article will review utilization management strategies in clinical microbiology, including specific examples from our institution and other healthcare organizations. (C) 2013 Elsevier B.V. All rights reserved. C1 [Lewandrowski, Kent] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Cambridge, MA 02138 USA. RP Lewandrowski, K (reprint author), Massachusetts Gen Hosp, Dept Pathol, Gray 5,Fruit St, Boston, MA 02114 USA. EM klewandrowski@partners.org NR 26 TC 0 Z9 0 U1 1 U2 8 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0009-8981 EI 1873-3492 J9 CLIN CHIM ACTA JI Clin. Chim. Acta PD JAN 1 PY 2014 VL 427 SI SI BP 173 EP 177 DI 10.1016/j.cca.2013.09.031 PG 5 WC Medical Laboratory Technology SC Medical Laboratory Technology GA AA0WX UT WOS:000330819200034 PM 24080434 ER PT J AU Pena, JRA Dzik, W AF Pena, Jeremy Ryan Andrew Dzik, Walter Sunny TI Utilization management in the blood transfusion service SO CLINICA CHIMICA ACTA LA English DT Article DE Blood transfusion; Transfusion medicine; Utilization management ID RANDOMIZED CONTROLLED-TRIAL; BIRTH-WEIGHT INFANTS; RED-CELL TRANSFUSION; INTENSIVE-CARE-UNIT; CARDIAC-SURGERY; ADVERSE EVENTS; CLINICAL-TRIAL; COST-BENEFIT; DOUBLE-BLIND; LEUKOREDUCTION AB The scope of activity of the Blood Transfusion Service (BTS) makes it unique among the clinical laboratories. The combination of therapeutic and diagnostic roles necessitates a multi-faceted approach to utilization management in the BTS. We present our experience in utilization management in large academic medical center. (C) 2013 Elsevier B.V. All rights reserved. C1 [Pena, Jeremy Ryan Andrew; Dzik, Walter Sunny] Massachusetts Gen Hosp, Dept Pathol, Blood Transfus Serv, Boston, MA 02114 USA. RP Pena, JRA (reprint author), Beth Israel Deaconess Med Ctr, Dept Pathol, Div Lab & Transfus Med, 330 Brookline Ave, Boston, MA 02215 USA. EM jrpena@bidmc.harvard.edu; sdzik@partners.org FU NHLBI NIH HHS [K12 HL087164] NR 38 TC 0 Z9 0 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0009-8981 EI 1873-3492 J9 CLIN CHIM ACTA JI Clin. Chim. Acta PD JAN 1 PY 2014 VL 427 SI SI BP 178 EP 182 DI 10.1016/j.cca.2013.09.030 PG 5 WC Medical Laboratory Technology SC Medical Laboratory Technology GA AA0WX UT WOS:000330819200035 PM 24080431 ER PT J AU Lewandrowski, K Black-Schaffer, S AF Lewandrowski, Kent Black-Schaffer, Steven TI Utilization management in anatomic pathology SO CLINICA CHIMICA ACTA LA English DT Article DE Utilization management; Anatomic pathology; Surgical pathology; Reimbursement ID IMPACT AB There is relatively little published literature concerning utilization management in anatomic pathology. Nonetheless there are many utilization management opportunities that currently exist and are well recognized. Some of these impact only the cost structure within the pathology department itself whereas others reduce charges for third party payers. Utilization management may result in medical legal liabilities for breaching the standard of care. For this reason it will be important for pathology professional societies to develop national utilization guidelines to assist individual practices in implementing a medically sound approach to utilization management. (C) 2013 Elsevier B.V. All rights reserved. C1 [Lewandrowski, Kent; Black-Schaffer, Steven] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. RP Lewandrowski, K (reprint author), Massachusetts Gen Hosp, Dept Pathol, Gray 5,Fruit St, Boston, MA 02114 USA. EM klewandrowski@partners.org NR 4 TC 1 Z9 1 U1 1 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0009-8981 EI 1873-3492 J9 CLIN CHIM ACTA JI Clin. Chim. Acta PD JAN 1 PY 2014 VL 427 SI SI BP 183 EP 187 DI 10.1016/j.cca.2013.09.032 PG 5 WC Medical Laboratory Technology SC Medical Laboratory Technology GA AA0WX UT WOS:000330819200036 PM 24140174 ER PT J AU Van Cott, EM AF Van Cott, Elizabeth M. TI Laboratory test interpretations and algorithms in utilization management SO CLINICA CHIMICA ACTA LA English DT Article DE Laboratory test; Interpretation; Algorithm ID EXTERNAL QUALITY ASSESSMENT; DEFICIENCY; AGGREGOMETRY AB Appropriate assimilation of laboratory test results into patient care is enhanced when pathologist interpretations of the laboratory tests are provided for clinicians, and when reflex algorithm testing is utilized. Benefits of algorithms and interpretations include avoidance of misdiagnoses, reducing the number of laboratory tests needed, reducing the number of procedures, transfusions and admissions, shortening the amount of time needed to reach a diagnosis, reducing errors in test ordering, and providing additional information about how the laboratory results might affect other aspects of a patient's care. Providing interpretations can be challenging for pathologists, therefore mechanisms to facilitate the successful implementation of an interpretation service are described. These include algorithm-based testing and interpretation, optimizing laboratory requisitions and/or order entry systems, proficiency testing programs that assess interpretations and provide constructive feedback, utilization of a collection of interpretive sentences or paragraphs that can be building blocks ("coded comments") for constructing preliminary interpretations, middleware, and pathology resident participation and education. In conclusion, the combination of algorithms and interpretations for laboratory testing has multiple benefits for the medical care for the patient. (C) 2013 Elsevier B.V. All rights reserved. C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Van Cott, EM (reprint author), Massachusetts Gen Hosp, GRJ235,55 Fruit St, Boston, MA 02114 USA. NR 20 TC 3 Z9 3 U1 1 U2 5 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0009-8981 EI 1873-3492 J9 CLIN CHIM ACTA JI Clin. Chim. Acta PD JAN 1 PY 2014 VL 427 SI SI BP 188 EP 192 DI 10.1016/j.cca.2013.09.025 PG 5 WC Medical Laboratory Technology SC Medical Laboratory Technology GA AA0WX UT WOS:000330819200037 PM 24080245 ER PT J AU Baron, JM Dighe, AS AF Baron, Jason M. Dighe, Anand S. TI The role of informatics and decision support in utilization management SO CLINICA CHIMICA ACTA LA English DT Review DE Provider order entry; Laboratory utilization; Clinical decision support; Analytics ID PHYSICIAN ORDER ENTRY; ACADEMIC-MEDICAL-CENTER; RANDOMIZED-TRIAL; DIAGNOSTIC-TESTS; CARE-UNIT; INTERVENTION; SERVICE; IMPACT; ERRORS AB Information systems provide a critical link between clinical laboratories and the clinicians and patients they serve. Strategic deployment of informatics resources can enable a wide array of utilization initiatives and can substantially improve the appropriateness of test selection and results interpretation. In this article, we review information systems including computerized provider order entry (CPOE) systems, laboratory information systems (LISs), electronic health records (EHRs), laboratory middleware, knowledge management systems and systems for data extraction and analysis, and describe the role that each can play in utilization management. We also discuss specific utilization strategies that laboratories can employ within these systems, citing examples both from our own institution and from the literature. Finally, we review how emerging applications of decision support technologies may help to further refine test utilization, "personalize" laboratory diagnosis, and enhance the diagnostic value of laboratory testing. (C) 2013 Elsevier B.V. All rights reserved. C1 [Baron, Jason M.; Dighe, Anand S.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. RP Dighe, AS (reprint author), Massachusetts Gen Hosp, Dept Pathol, 55 Fruit St, Boston, MA 02114 USA. EM jmbaron@partners.org; asdighe@partners.org NR 32 TC 7 Z9 7 U1 1 U2 21 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0009-8981 EI 1873-3492 J9 CLIN CHIM ACTA JI Clin. Chim. Acta PD JAN 1 PY 2014 VL 427 SI SI BP 196 EP 201 DI 10.1016/j.cca.2013.09.027 PG 6 WC Medical Laboratory Technology SC Medical Laboratory Technology GA AA0WX UT WOS:000330819200039 PM 24084507 ER PT J AU Arvold, ND Reardon, DA AF Arvold, Nils D. Reardon, David A. TI Treatment options and outcomes for glioblastoma in the elderly patient SO CLINICAL INTERVENTIONS IN AGING LA English DT Review DE glioblastoma; elderly; radiotherapy; hypofractionated; temozolomide; MGMT ID RADIOTHERAPY PLUS CONCOMITANT; RECURSIVE PARTITIONING ANALYSIS; NEWLY-DIAGNOSED GLIOBLASTOMA; ADJUVANT TEMOZOLOMIDE; RADIATION-THERAPY; OLDER PATIENTS; PROGNOSTIC BIOMARKER; MULTIFORME SURVIVAL; GENETIC ALTERATIONS; ABBREVIATED COURSE AB Age remains the most powerful prognostic factor among glioblastoma (GBM) patients. Half of all patients with GBM are aged 65 years or older at the time of diagnosis, and the incidence rate of GBM in patients aged over 65 years is increasing rapidly. Median survival for elderly GBM patients is less than 6 months and reflects less favorable tumor biologic factors, receipt of less aggressive care, and comorbid disease. The standard of care for elderly GBM patients remains controversial. Based on limited data, extensive resection appears to be more beneficial than biopsy. For patients with favorable Karnofsky performance status (KPS), adjuvant radiotherapy (RT) has a demonstrated survival benefit with no observed decrement in quality of life. Concurrent and adjuvant temozolomide (TMZ) along with RT to 60 Gy have not been prospectively studied among patients aged over 70 years but should be considered for patients aged 65-70 years with excellent KPS. Based on the recent NOA-08 and Nordic randomized trials, testing for O-6-methylguanine-DNA-methyltransferase (MGMT) promoter methylation should be performed routinely immediately after surgery to aid in adjuvant treatment decisions. Patients aged over 70 years with favorable KPS, or patients aged 60-70 years with borderline KPS, should be considered for monotherapy utilizing standard TMZ dosing for patients with MGMT-methylated tumors, and hypofractionated RT (34 Gy in ten fractions or 40 Gy in 15 fractions) for patients with MGMT-unmethylated tumors. The ongoing European Organisation for Research and Treatment of Cancer/National Cancer Institute of Canada trial will help clarify the role for concurrent TMZ with hypofractionated RT. For elderly patients with poor KPS, reasonable options include best supportive care, TMZ alone, hypofractionated RT alone, or whole brain RT for symptomatic patients needing to start treatment urgently. Given the balance between short survival and quality of life in this patient population, optimal management of elderly GBM patients must be made individually according to patient age, MGMT methylation status, performance score, and patient preferences. C1 [Arvold, Nils D.] Dana Farber Brigham & Womens Canc Ctr, Dept Radiat Oncol, Boston, MA USA. [Reardon, David A.] Dana Farber Brigham & Womens Canc Ctr, Ctr Neurooncol, Boston, MA USA. RP Arvold, ND (reprint author), Brigham & Womens Hosp, Dept Radiat Oncol, ASB1 Level L2,75 Francis St, Boston, MA 02215 USA. EM narvold@partners.org NR 45 TC 13 Z9 14 U1 1 U2 6 PU DOVE MEDICAL PRESS LTD PI ALBANY PA PO BOX 300-008, ALBANY, AUCKLAND 0752, NEW ZEALAND SN 1176-9092 EI 1178-1998 J9 CLIN INTERV AGING JI Clin. Interv. Aging PY 2014 VL 9 BP 357 EP 367 DI 10.2147/CIA.S44259 PG 11 WC Geriatrics & Gerontology SC Geriatrics & Gerontology GA AB5RT UT WOS:000331846900001 PM 24591820 ER PT J AU Palmer, SC Navaneethan, SD Craig, JC Perkovic, V Johnson, DW Nigwekar, SU Hegbrant, J Strippoli, GFM AF Palmer, Suetonia C. Navaneethan, Sankar D. Craig, Jonathan C. Perkovic, Vlado Johnson, David W. Nigwekar, Sagar U. Hegbrant, Jorgen Strippoli, Giovanni F. M. TI HMG CoA reductase inhibitors (statins) for kidney transplant recipients SO COCHRANE DATABASE OF SYSTEMATIC REVIEWS LA English DT Review DE Cardiovascular Diseases [mortality; prevention & control] Cholesterol [blood]; Graft Rejection [prevention & control]; Hydroxymethylglutaryl-CoA Reductase Inhibitors [adverse effects; therapeutic use]; Hypolipidemic Agents [therapeutic use]; Kidney Transplantation [mortality]; Randomized Controlled Trials as Topic; Triglycerides [blood]; Humans ID PLACEBO-CONTROLLED TRIAL; RENAL-ALLOGRAFT REJECTION; ALL-CAUSE MORTALITY; PATIENTS RECEIVING CYCLOSPORINE; LIPID-LOWERING THERAPY; LOW-DOSE SIMVASTATIN; CARDIAC END-POINTS; LONG-TERM EFFICACY; ALERT TRIAL; RISK-FACTORS AB Background People with chronic kidney disease (CKD) have higher risks of cardiovascular disease compared to the general population. Specifically, cardiovascular deaths account most deaths in kidney transplant recipients. Statins are a potentially beneficial intervention for kidney transplant patients given their established benefits in patients at risk of cardiovascular disease in the general population. This is an update of a review first published in 2009. Objectives We aimed to evaluate the benefits (reductions in all-cause and cardiovascular mortality, major cardiovascular events, myocardial infarction and stroke, and progression of CKD to requiring dialysis) and harms (muscle or liver dysfunction, withdrawal, cancer) of statins compared to placebo, no treatment, standard care, or another statin in adults with CKD who have a functioning kidney transplant. Search methods We searched the Cochrane Renal Group's Specialised Register to 29 February 2012 through contact with the Trials Search Co-ordinator using search terms relevant to this review. Selection criteria We included randomised controlled trials (RCTs) and quasi-RCTs that compared the effects of statins with placebo, no treatment, standard care, or statins on mortality, cardiovascular events, kidney function and toxicity in kidney transplant recipients. Data collection and analysis Two authors independently extracted data and assessed risk of bias. Treatment effects were expressed as mean difference (MD) for continuous outcomes (lipids, glomerular filtration rate (GFR), proteinuria) and relative risk (RR) for dichotomous outcomes (major cardiovascular events, mortality, fatal or non-fatal myocardial infarction, fatal or non-fatal stroke, elevated muscle or liver enzymes, withdrawal due to adverse events, cancer, end-stage kidney disease (ESKD), acute allograft rejection) together with 95% confidence intervals (CI). Main results We identified 22 studies (3465 participants); 17 studies (3282 participants) compared statin with placebo or no treatment, and five studies (183 participants) compared two different statin regimens. From data generally derived from a single high-quality study, it was found that statins may reduce major cardiovascular events (1 study, 2102 participants: RR 0.84, CI 0.66 to 1.06), cardiovascular mortality (4 studies, 2322 participants: RR 0.68, CI 0.45 to 1.01), and fatal or non-fatal myocardial infarction (1 study, 2102 participants: RR 0.70, CI 0.48 to 1.01); although effect estimates lack precision and include the possibility of no effect. Statins had uncertain effects on all-cause mortality (6 studies, 2760 participants: RR 1.08, CI 0.63 to 1.83); fatal or non-fatal stroke (1 study, 2102 participants: RR 1.18, CI 0.85 to 1.63); creatine kinase elevation (3 studies, 2233 participants: RR 0.86, CI 0.39 to 1.89); liver enzyme elevation (4 studies, 608 participants: RR 0.62, CI 0.33 to 1.19); withdrawal due to adverse events (9 studies, 2810 participants: RR 0.89, CI 0.74 to 1.06); and cancer (1 study, 2094 participants: RR 0.94, CI 0.82 to 1.07). Statins significantly reduced serum total cholesterol (12 studies, 3070 participants: MD -42.43 mg/dL, CI -51.22 to -33.65); low-density lipoprotein cholesterol (11 studies, 3004 participants: MD-43.19 mg/dL, CI -52.59 to -33.78); serum triglycerides (11 studies, 3012 participants: MD -27.28 mg/dL, CI -34.29 to -20.27); and lowered high-density lipoprotein cholesterol (11 studies, 3005 participants: MD -5.69 mg/dL, CI -10.35 to -1.03). Statins had uncertain effects on kidney function: ESKD(6 studies, 2740 participants: RR 1.14, CI 0.94 to 1.37); proteinuria (2 studies, 136 participants: MD -0.04 g/24 h, CI -0.17 to 0.25); acute allograft rejection (4 studies, 582 participants: RR 0.88, CI 0.61 to 1.28); and GFR (1 study, 62 participants: MD -1.00 mL/min, CI -9.96 to 7.96). Due to heterogeneity in comparisons, data directly comparing differing statin regimens could not be meta-analysed. Evidence for statins in people who have had a kidney transplant were sparse and lower quality due to imprecise effect estimates and provided limited systematic evaluation of treatment harm. Authors' conclusions Statins may reduce cardiovascular events in kidney transplant recipients, although treatment effects are imprecise. Statin treatment has uncertain effects on overall mortality, stroke, kidney function, and toxicity outcomes in kidney transplant recipients. Additional studies would improve our confidence in the treatment benefits and harms of statins on cardiovascular events in this clinical setting. C1 [Palmer, Suetonia C.] Univ Otago, Dept Med, Christchurch, New Zealand. [Navaneethan, Sankar D.] Cleveland Clin, Glickman Urol & Kidney Inst, Dept Nephrol & Hypertens, Cleveland, OH 44106 USA. [Craig, Jonathan C.; Strippoli, Giovanni F. M.] Univ Sydney, Sydney Sch Publ Hlth, Sydney, NSW 2006, Australia. [Craig, Jonathan C.; Strippoli, Giovanni F. M.] Childrens Hosp, Ctr Kidney Res, Cochrane Renal Grp, Westmead, NSW, Australia. [Perkovic, Vlado] George Inst Global Hlth, Renal & Metab Div, Camperdown, NSW, Australia. [Johnson, David W.] Princess Alexandra Hosp, Dept Nephrol, Woolloongabba, Qld 4102, Australia. [Nigwekar, Sagar U.] Harvard Univ, Brigham & Womens Hosp, Massachusetts Gen Hosp, Sch Med, Boston, MA 02115 USA. [Hegbrant, Jorgen] Diaverum Renal Serv Grp, Med Off, Lund, Sweden. [Strippoli, Giovanni F. M.] Mario Negri Sud Consortium, Dept Clin Pharmacol & Epidemiol, Santa Maria Imbaro, Italy. [Strippoli, Giovanni F. M.] Diaverum, Med Sci Off, Lund, Sweden. RP Strippoli, GFM (reprint author), Univ Sydney, Sydney Sch Publ Hlth, Sydney, NSW 2006, Australia. EM strippoli@negrisud.it RI Craig, Jonathan/E-2813-2013 OI Craig, Jonathan/0000-0002-2548-4035 FU Consorzio Mario Negri Sud; Amgen Dompe, Italy FX Internal sources; No sources of support supplied; External sources; Suetonia Palmer received a fellowship from the Consorzio Mario Negri Sud from an unrestricted grant by Amgen Dompe, Italy. NR 183 TC 4 Z9 4 U1 0 U2 116 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1469-493X EI 1361-6137 J9 COCHRANE DB SYST REV JI Cochrane Database Syst Rev. PY 2014 IS 1 AR CD005019 DI 10.1002/14651858.CD005019.pub4 PG 73 WC Medicine, General & Internal SC General & Internal Medicine GA 301BQ UT WOS:000330508100023 PM 24470059 ER PT J AU O'Keefe, VM Wingate, LR Tucker, RP Rhoades-Kerswill, S Slish, ML Davidson, CL AF O'Keefe, Victoria M. Wingate, LaRicka R. Tucker, Raymond P. Rhoades-Kerswill, Sarah Slish, Meredith L. Davidson, Collin L. TI Interpersonal Suicide Risk for American Indians: Investigating Thwarted Belongingness and Perceived Burdensomeness SO CULTURAL DIVERSITY & ETHNIC MINORITY PSYCHOLOGY LA English DT Article DE American Indian; Native American; suicide; interpersonal ID PSYCHOLOGICAL THEORY; SOCIAL NETWORKS; SCREENING TOOL; YOUNG-ADULTS; OLDER-ADULTS; IDEATION; ADOLESCENTS; VALIDITY; BEHAVIOR; QUESTIONNAIRE AB American Indians (AIs) experience increased suicide rates compared with other groups in the United States. However, no past studies have examined AI suicide by way of a recent empirically supported theoretical model of suicide. The current study investigated whether AI suicidal ideation can be predicted by two components: thwarted belongingness and perceived burdensomeness, from the Interpersonal-Psychological Theory of Suicide (T. E. Joiner, 2005, Why people die by suicide. Cambridge, MA: Harvard University Press). One hundred seventy-one AIs representing 27 different tribes participated in an online survey. Hierarchical regression analyses showed that perceived burdensomeness significantly predicted suicidal ideation above and beyond demographic variables and depressive symptoms; however, thwarted belongingness did not. Additionally, the two-way interaction between thwarted belongingness and perceived burdensomeness significantly predicted suicidal ideation. These results provide initial support for continued research on the components of the Interpersonal-Psychological Theory of Suicide, an empirically supported theoretical model of suicide, to predict suicidal ideation among AI populations. C1 [O'Keefe, Victoria M.; Wingate, LaRicka R.; Tucker, Raymond P.; Rhoades-Kerswill, Sarah; Slish, Meredith L.] Oklahoma State Univ, Dept Psychol, Stillwater, OK 74078 USA. [Davidson, Collin L.] Denver VA Med Ctr, VISN MIRECC 19, Denver, CO USA. RP Wingate, LR (reprint author), Oklahoma State Univ, Dept Psychol, 116 North Murray Hall, Stillwater, OK 74078 USA. EM laricka.wingate@okstate.edu NR 39 TC 14 Z9 14 U1 1 U2 10 PU EDUCATIONAL PUBLISHING FOUNDATION-AMERICAN PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST, NE, WASHINGTON, DC 20002-4242 USA SN 1099-9809 EI 1939-0106 J9 CULT DIVERS ETHN MIN JI Cult. Divers. Ethn. Minor. Psychol. PD JAN PY 2014 VL 20 IS 1 BP 61 EP 67 DI 10.1037/a0033540 PG 7 WC Ethnic Studies; Psychology, Social SC Ethnic Studies; Psychology GA AA1SN UT WOS:000330876100008 PM 24041264 ER PT J AU Iezzoni, LI AF Iezzoni, Lisa I. TI Policy concerns raised by the growing US population aging with disability SO DISABILITY AND HEALTH JOURNAL LA English DT Editorial Material DE Disability; Aging; Health policy AB The number of Americans aging with disabilities will grow substantially in coming decades. Promulgating policies and practices to improve their independent functioning within communities and participation in daily life are therefore imperative, but the most effective approaches for meeting various needs are generally unknown. Historically, research addressing approaches targeting elderly individuals have differed in important ways (e.g., underlying models of disability) from studies involving younger persons aging with disabilities. Participants in a conference addressing this discordance identified, six major areas requiring study: (1) resources to support independent living; (2) improving quality of life and participation in daily activities; (3) performing activities of daily living (ADL) and instrumental ADLs; :(4) role of families; (5) medical care; and (6) concerns transcending sectors. As these investigations move forward, bridging the divide between approaches addressing elderly individuals versus persons with disabilities will be critical. (C) 2014 Elsevier Inc. All rights reserved. C1 Harvard Univ, Sch Med, Mongan Inst Hlth Policy, Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Iezzoni, LI (reprint author), Harvard Univ, Sch Med, Mongan Inst Hlth Policy, Massachusetts Gen Hosp, Room 901B,50 Staniford St, Boston, MA 02114 USA. EM liezzoni@partners.org FU NIA NIH HHS [P30 AG012846, P30 AG034464] NR 6 TC 7 Z9 7 U1 0 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1936-6574 EI 1876-7583 J9 DISABIL HEALTH J JI Disabil. Health J. PD JAN PY 2014 VL 7 SU 1 BP S64 EP S68 DI 10.1016/j.dhjo.2013.06.004 PG 5 WC Health Care Sciences & Services; Health Policy & Services; Public, Environmental & Occupational Health; Rehabilitation SC Health Care Sciences & Services; Public, Environmental & Occupational Health; Rehabilitation GA AA2IO UT WOS:000330918500010 PM 24456688 ER PT J AU Vila, PM Kingsley, MJ Polydorides, AD Protano, MA Pierce, MC Sauk, J Kim, MK Patel, K Godbold, JH Waye, JD Richards-Kortum, R Anandasabapathy, S AF Vila, P. M. Kingsley, M. J. Polydorides, A. D. Protano, M. -A. Pierce, M. C. Sauk, J. Kim, M. K. Patel, K. Godbold, J. H. Waye, J. D. Richards-Kortum, R. Anandasabapathy, S. TI Accuracy and interrater reliability for the diagnosis of Barrett's neoplasia among users of a novel, portable high-resolution microendoscope SO DISEASES OF THE ESOPHAGUS LA English DT Article DE cancer; diagnostic imaging; esophagogastroduodenoscopy; optical device ID CONFOCAL LASER ENDOMICROSCOPY; IN-VIVO; METHYLENE-BLUE; GI TRACT; ESOPHAGUS; SURVEILLANCE; CHROMOENDOSCOPY; MICROSCOPY; ENDOSCOPY; DYSPLASIA AB The high-resolution microendoscope (HRME) is a novel imaging modality that may be useful in the surveillance of Barrett's esophagus in low-resource or community-based settings. In order to assess accuracy and interrater reliability of microendoscopists in identifying Barrett's-associated neoplasia using HRME images, we recruited 20 gastroenterologists with no microendoscopic experience and three expert microendoscopists in a large academic hospital in New York City to interpret HRME images. They prospectively reviewed 40 HRME images from 28 consecutive patients undergoing surveillance for metaplasia and low-grade dysplasia and/or evaluation for high-grade dysplasia or cancer. Images were reviewed in a blinded fashion, after a 4-minute training with 11 representative images. All imaged sites were biopsied and interpreted by an expert pathologist. Sensitivity of all endoscopists for identification of high-grade dysplasia or cancer was 0.90 (95% confidence interval [CI]: 0.88-0.92) and specificity was 0.82 (95% CI: 0.79-0.85). Positive and negative predictive values were 0.72 (95% CI: 0.68-0.77) and 0.94 (95% CI: 0.92-0.96), respectively. No significant differences in accuracy were observed between experts and novices (0.90 vs. 0.84). The kappa statistic for all raters was 0.56 (95% CI: 0.54-0.58), and the difference between groups was not significant (0.64 vs. 0.55). These data suggest that gastroenterologists can diagnose Barrett's-related neoplasia on HRME images with high sensitivity and specificity, without the aid of prior microendoscopy experience. C1 [Polydorides, A. D.] Mt Sinai Sch Med, Dept Pathol, New York, NY 10029 USA. [Protano, M. -A.; Kim, M. K.; Patel, K.; Waye, J. D.; Anandasabapathy, S.] Mt Sinai Sch Med, Div Gastroenterol, New York, NY 10029 USA. [Kingsley, M. J.] Mt Sinai Sch Med, Dept Med, New York, NY 10029 USA. [Godbold, J. H.] Mt Sinai Sch Med, Dept Prevent Med, New York, NY 10029 USA. [Vila, P. M.] Mt Sinai Sch Med, New York, NY 10029 USA. [Pierce, M. C.] Rutgers State Univ, Dept Bioengn, Piscataway, NJ USA. [Sauk, J.] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. [Richards-Kortum, R.] Rice Univ, Dept Bioengn, Houston, TX USA. RP Anandasabapathy, S (reprint author), Mt Sinai Sch Med, Div Gastroenterol, 1 Gustave L Levy Pl,Box 1069, New York, NY 10029 USA. EM sharmila.anandasabapathy@mountsinai.org RI Richards-Kortum, Rebecca/P-4074-2014; OI Richards-Kortum, Rebecca/0000-0003-2347-9467; Vila, Peter/0000-0003-3639-2432 FU Doris Duke Charitable Research Foundation FX This project was funded in part by the Doris Duke Charitable Research Foundation. NR 34 TC 10 Z9 11 U1 0 U2 5 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1120-8694 EI 1442-2050 J9 DIS ESOPHAGUS JI Dis. Esophagus PD JAN PY 2014 VL 27 IS 1 BP 55 EP 62 DI 10.1111/dote.12040 PG 8 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA AA1IE UT WOS:000330849000010 PM 23442220 ER PT J AU Murphy, SA Giugliano, RP AF Murphy, Sabina A. Giugliano, Robert P. TI Atrial fibrillation and prior MI: searching for balance in ischaemic and bleeding events in patients treated with factor-specific anticoagulants SO EUROPEAN HEART JOURNAL LA English DT Editorial Material ID THERAPY C1 [Murphy, Sabina A.; Giugliano, Robert P.] Brigham & Womens Hosp, TIMI Study Grp, Boston, MA 01760 USA. RP Murphy, SA (reprint author), Brigham & Womens Hosp, TIMI Study Grp, 350 Longwood Ave, Boston, MA 01760 USA. EM smurphy15@partners.org NR 9 TC 0 Z9 0 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 JAN PY 2014 VL 35 IS 4 BP 207 EP 208 DI 10.1093/eurheartj/eht480 PG 2 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA AA1DU UT WOS:000330837300004 PM 24282188 ER PT J AU Mahaffey, KW Stevens, SR White, HD Nessel, CC Goodman, SG Piccini, JP Patel, MR Becker, RC Halperin, JL Hacke, W Singer, DE Hankey, GJ Califf, RM Fox, KAA Breithardt, G AF Mahaffey, Kenneth W. Stevens, Susanna R. White, Harvey D. Nessel, Christopher C. Goodman, Shaun G. Piccini, Jonathan P. Patel, Manesh R. Becker, Richard C. Halperin, Jonathan L. Hacke, Werner Singer, Daniel E. Hankey, Graeme J. Califf, Robert M. Fox, Keith A. A. Breithardt, Guenter CA ROCKET AF Investigators TI Ischaemic cardiac outcomes in patients with atrial fibrillation treated with vitamin K antagonism or factor Xa inhibition: results from the ROCKET AF trial SO EUROPEAN HEART JOURNAL LA English DT Article DE Atrial fibrillation; Myocardial infarction; Coronary artery disease; Outcomes; Factor Xa; Rivaroxaban; Warfarin AB Aims We investigated the prevalence of prior myocardial infarction (MI) and incidence of ischaemic cardiovascular (CV) events among atrial fibrillation (AF) patients. Methods and results In ROCKET AF, 14 264 patients with nonvalvular AF were randomized to rivaroxaban or warfarin. The key efficacy outcome for these analyses was CV death, MI, and unstable angina (UA). This pre-specified analysis was performed on patients while on treatment. Rates are per 100 patient-years. Overall, 2468 (17%) patients had prior MI at enrollment. Compared with patients without prior MI, these patients were more likely to be male (75 vs. 57%), on aspirin at baseline (47 vs. 34%), have prior congestive heart failure (78 vs. 59%), diabetes (47 vs. 39%), hypertension (94 vs. 90%), higher mean CHADS(2) score (3.64 vs. 3.43), and fewer prior strokes or transient ischaemic attacks (46 vs. 54%). CV death, MI, or UA rates tended to be lower in patients assigned rivaroxaban compared with warfarin [2.70 vs. 3.15; hazard ratio (HR) 0.86, 95% confidence interval (CI) 0.731.00; P = 0.0509]. CV death, MI, or UA rates were higher in those with prior MI compared with no prior MI (6.68 vs. 2.19; HR 3.04, 95% CI 2.59-3.56) with consistent results for CV death, MI, or UA for rivaroxaban compared with warfarin in prior MI compared with no prior MI (P interaction = 0.10). Conclusion Prior MI was common and associated with substantial risk for subsequent cardiac events. Patients with prior MI assigned rivaroxaban compared with warfarin had a non-significant 14% reduction of ischaemic cardiac events. C1 [Mahaffey, Kenneth W.] Stanford Univ, Dept Med, Stanford, CA 94305 USA. [Stevens, Susanna R.; Piccini, Jonathan P.; Patel, Manesh R.; Becker, Richard C.] Duke Univ, Med Ctr, Duke Clin Res Inst, Durham, NC USA. [White, Harvey D.] Auckland City Hosp, Green Lane Cardiovasc Serv, Auckland, New Zealand. [Nessel, Christopher C.] Johnson & Johnson Pharmaceut Res & Dev, Raritan, NJ USA. [Goodman, Shaun G.] Univ Toronto, St Michaels Hosp, Canadian Heart Res Ctr, Toronto, ON, Canada. [Goodman, Shaun G.] Univ Toronto, St Michaels Hosp, Terrence Donnelly Heart Ctr, Div Cardiol, Toronto, ON, Canada. [Halperin, Jonathan L.] Mt Sinai Med Ctr, Cardiovasc Inst, New York, NY 10029 USA. [Hacke, Werner] Heidelberg Univ, Heidelberg, Germany. [Singer, Daniel E.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Singer, Daniel E.] Harvard Univ, Sch Med, Boston, MA USA. [Hankey, Graeme J.] Royal Perth Hosp, Perth, WA 6001, Australia. [Califf, Robert M.] Duke Univ, Med Ctr, Duke Translat Med Inst, Durham, NC USA. [Fox, Keith A. A.] Univ Edinburgh, Edinburgh, Midlothian, Scotland. [Fox, Keith A. A.] Royal Infirm Edinburgh NHS Trust, Edinburgh, Midlothian, Scotland. [Breithardt, Guenter] Hosp Univ Munster, Munster, Germany. RP Mahaffey, KW (reprint author), Stanford Univ, Dept Med, Stanford, CA 94305 USA. EM kenneth.mahaffey@stanford.edu RI Hankey, Graeme /H-4968-2014 OI Hankey, Graeme /0000-0002-6044-7328 FU Johnson & Johnson Pharmaceutical Research & Development, Raritan, NJ; Bayer HealthCare AG, Leverkusen, Germany FX This work was supported by Johnson & Johnson Pharmaceutical Research & Development, Raritan, NJ and Bayer HealthCare AG, Leverkusen, Germany. NR 0 TC 19 Z9 19 U1 0 U2 3 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 JAN PY 2014 VL 35 IS 4 BP 233 EP 241 DI 10.1093/eurheartj/eht428 PG 9 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA AA1DU UT WOS:000330837300008 PM 24132190 ER PT J AU Jones, WS Hellkamp, AS Halperin, J Piccini, JP Breithardt, G Singer, DE Fox, KAA Hankey, GJ Mahaffey, KW Califf, RM Patel, MR AF Jones, William Schuyler Hellkamp, Anne S. Halperin, Jonathan Piccini, Jonathan P. Breithardt, Gunter Singer, Daniel E. Fox, Keith A. A. Hankey, Graeme J. Mahaffey, Kenneth W. Califf, Robert M. Patel, Manesh R. TI Efficacy and safety of rivaroxaban compared with warfarin in patients with peripheral artery disease and non-valvular atrial fibrillation: insights from ROCKET AF SO EUROPEAN HEART JOURNAL LA English DT Article DE Peripheral artery disease; Atrial fibrillation; Rivaroxaban; Stroke; Systemic embolism; Bleeding ID RISK STRATIFICATION; PREDICTING STROKE; PREVENTION; ASPIRIN AB Aims Vascular disease is included in a risk scoring system to predict stroke in patients with non-valvular atrial fibrillation (AF). This post hoc analysis of ROCKET AF aimed to determine the absolute rates of stroke and bleeding, and the relative effectiveness and safety of rivaroxaban vs. warfarin in patients with and without peripheral artery disease (PAD). Peripheral artery disease was defined on the case-report form as the presences of intermittent claudication, amputation for arterial insufficiency, vascular reconstruction, bypass surgery, or percutaneous intervention to the extremities, or previously documented abdominal aortic aneurysm. Methods and results ROCKET AF was a double-blind, double-dummy, randomized-controlled trial comparing rivaroxaban and warfarin for the prevention of stroke or systemic embolism. A total of 839 (5.9%) patients in ROCKET AF had PAD. Patients with and without PAD had similar rates of stroke or systemic embolism [HR: 1.04, 95 CI (0.72, 1.50), P = 0.84] and major or non-major clinically relevant (NMCR) bleeding [HR: 1.11, 95% CI (0.96, 1.28), P = 0.17], respectively. The efficacy of rivaroxaban when compared with warfarin for the prevention of stroke or systemic embolism was similar in patients with PAD (HR: 1.19, 95% CI: 0.63-2.22) and without PAD (HR: 0.86, 95% CI: 0.73-1.02; interaction P = 0.34). There was a significant interaction for major or NMCR bleeding in patients with PAD treated with rivaroxaban compared with warfarin (HR: 1.40, 95% CI: 1.06-1.86) compared with those without PAD (HR: 1.03, 95% CI: 0.95-1.11; interaction P = 0.037). Conclusion Patients with PAD in ROCKET AF did not have a statistically significant higher risk of stroke or systemic embolism than patients without PAD, and there were similar efficacy outcomes in patients treated with rivaroxaban and warfarin. In PAD patients, there was a higher risk of major bleeding or NMCR bleeding with rivaroxaban when compared with warfarin (interaction P = 0.037). Further investigation is warranted to validate this subgroup analysis and determine the optimal treatment in this high-risk cohort of AF patients with PAD. C1 [Jones, William Schuyler; Hellkamp, Anne S.; Piccini, Jonathan P.; Mahaffey, Kenneth W.; Califf, Robert M.; Patel, Manesh R.] Duke Univ, Med Ctr, Duke Clin Res Inst, Durham, NC 27708 USA. [Halperin, Jonathan] Mt Sinai Med Ctr, New York, NY 10029 USA. [Breithardt, Gunter] Hosp Univ Munster, Dept Cardiovasc Med, Munster, Germany. [Singer, Daniel E.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Singer, Daniel E.] Harvard Univ, Sch Med, Boston, MA USA. [Fox, Keith A. A.] Univ Edinburgh, Edinburgh EH8 9YL, Midlothian, Scotland. [Hankey, Graeme J.] Univ Western Australia, Sch Med & Pharmacol, Crawley, Australia. RP Jones, WS (reprint author), Duke Univ, Med Ctr, Duke Clin Res Inst, Box 3126, Durham, NC 27708 USA. EM schuyler.jones@dm.duke.edu RI Hankey, Graeme /H-4968-2014 OI Hankey, Graeme /0000-0002-6044-7328 FU Johnson and Johnson Pharmaceutical Research and Development; Bayer HealthCare FX Johnson and Johnson Pharmaceutical Research and Development and Bayer HealthCare sponsored the ROCKET AF trial. The Duke Clinical Research Institute coordinated the trial, managed the database, and undertook the primary analysis independent of the sponsors. The authors had complete access to the data and were responsible for writing and submitting the manuscript for publication. NR 12 TC 15 Z9 16 U1 1 U2 3 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 JAN PY 2014 VL 35 IS 4 BP 242 EP 249 DI 10.1093/eurheartj/eht492 PG 8 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA AA1DU UT WOS:000330837300010 PM 24302273 ER PT J AU Liu, CZ Litscher, G Liang, FR Kong, J Wang, LP Wang, L AF Liu, Cun-Zhi Litscher, Gerhard Liang, Fan-Rong Kong, Jian Wang, Lin-Peng Wang, Lu TI Deqi Sensation in Different Kinds of Acupuncture SO EVIDENCE-BASED COMPLEMENTARY AND ALTERNATIVE MEDICINE LA English DT Editorial Material C1 [Liu, Cun-Zhi] Capital Med Univ, Beijing Hosp Tradit Chinese Med, Acupuncture & Moxibust Dept, Beijing 100010, Peoples R China. [Litscher, Gerhard; Wang, Lu] Med Univ Graz, TCM Res Ctr Graz, Res Unit Biomed Engn Anesthesia & Intens Care Med, Stronach Res Unit Complementary & Integrat Laser, A-8036 Graz, Austria. [Liang, Fan-Rong] Chengdu Univ Tradit Chinese Med, Coll Acupuncture & Massage, Chengdu 610075, Sichuan, Peoples R China. [Kong, Jian] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02129 USA. [Wang, Lin-Peng] Capital Med Univ, Sch Tradit Chinese Med, Beijing 100069, Peoples R China. RP Liu, CZ (reprint author), Capital Med Univ, Beijing Hosp Tradit Chinese Med, Acupuncture & Moxibust Dept, 23 Meishuguanhou St, Beijing 100010, Peoples R China. EM lcz623780@126.com OI Litscher, Gerhard/0000-0001-6287-0130 NR 0 TC 1 Z9 1 U1 0 U2 8 PU HINDAWI PUBLISHING CORPORATION PI NEW YORK PA 410 PARK AVENUE, 15TH FLOOR, #287 PMB, NEW YORK, NY 10022 USA SN 1741-427X EI 1741-4288 J9 EVID-BASED COMPL ALT JI Evid.-based Complement Altern. Med. PY 2014 AR 121573 DI 10.1155/2014/121573 PG 1 WC Integrative & Complementary Medicine SC Integrative & Complementary Medicine GA AB4LB UT WOS:000331760100001 ER PT J AU Viswanathan, AN Lee, H Berkowitz, R Berlin, S Campos, S Feltmate, C Horowitz, N Muto, M Sadow, CA Matulonis, U AF Viswanathan, Akila N. Lee, Hang Berkowitz, Ross Berlin, Suzanne Campos, Susanna Feltmate, Colleen Horowitz, Neil Muto, Michael Sadow, Cheryl A. Matulonis, Ursula TI A prospective feasibility study of radiation and concurrent bevacizumab for recurrent endometrial cancer SO GYNECOLOGIC ONCOLOGY LA English DT Article DE Radiation; Bevacizumab; Gynecologic malignancies ID ENDOTHELIAL GROWTH-FACTOR; DEFINITIVE RADIOTHERAPY; TUMOR ANGIOGENESIS; OVARIAN-CANCER; PHASE-II; CARCINOMA; THERAPY; VEGF; TRIAL; EXPRESSION AB Objectives. To determine the toxicity and survival rates in a trial of concurrent bevacizumab and external beam radiation (EB) for patients with recurrent endometrial or ovarian cancer. Methods. Nineteen women with recurrent endometrial (n = 15) or ovarian (n = 4) cancer with gross disease involving the vaginal cuff, and/or pelvic nodes and/or para-aortic nodes, cancer were enrolled between 2008 and 2010. All patients received bevacizumab during radiation. Toxicity was assessed at baseline, weekly during treatment and every 3 months for at least 1 year after treatment. Results. All patients completed EB on schedule. For the 15 patients with recurrent endometrial cancer, the land 3-year progression-free survival (PFS was) 80%/67% and overall survival (OS) was 93%/80%. Patients that had a vaginal cuff recurrence alone had a 1- and 3-year PFS of 75%/63% and OS of 100%/75%. Two patients with pelvic node involvement did not recur throughout the entire follow-up period. The 5 patients with para-aortic node involvement had a 1- and 3-year PFS of 80%/60% and OS of 80%/80%. Of the 4 ovarian cancer patients 3 relapsed with 1- and 3-year PFS of 80%/40% and OS of 100%/60%. Toxicities included thrombosis and 1 embolic event in the setting of metastastic disease. No gastrointestinal perforations were noted. Conclusions. Delivering bevacizumab with concurrent radiation provides excellent local tumor control and survival for women with recurrent endometrioid endometrial cancer, particularly those with unresectable nodes. Caution must be used in those at highest risk of developing metastatic disease given the increased risk of thromboembolic events. This regimen may be considered for recurrent gynecologic malignancies in future trials. (C) 2013 Elsevier Inc. All right's reserved. C1 [Viswanathan, Akila N.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Radiat Oncol,Brigham & Womens Hosp, Boston, MA 02115 USA. [Lee, Hang] Massachusetts Gen Hosp, Dept Biostat Med, Boston, MA 02114 USA. [Berkowitz, Ross; Feltmate, Colleen; Horowitz, Neil; Muto, Michael] Harvard Univ, Sch Med, Dana Farber Canc Inst, Div Gynecol Oncol,Brigham & Womens Hosp, Boston, MA 02115 USA. [Berlin, Suzanne; Campos, Susanna; Matulonis, Ursula] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Sadow, Cheryl A.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Radiol, Boston, MA 02115 USA. RP Viswanathan, AN (reprint author), Brigham & Womens Hosp, Dept Radiat Oncol, 75 Francis St,ASB 1,L2, Boston, MA 02115 USA. EM aviswanathan@lroc.harvard.edu NR 21 TC 6 Z9 6 U1 1 U2 2 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0090-8258 EI 1095-6859 J9 GYNECOL ONCOL JI Gynecol. Oncol. PD JAN PY 2014 VL 132 IS 1 BP 55 EP 60 DI 10.1016/j.ygyno.2013.10.031 PG 6 WC Oncology; Obstetrics & Gynecology SC Oncology; Obstetrics & Gynecology GA AA2GJ UT WOS:000330912800011 PM 24201015 ER PT J AU Lee, LJ De Maria, R Berkowitz, R Matulonis, U Viswanathan, AN AF Lee, Larissa J. De Maria, Rebecca Berkowitz, Ross Matulonis, Ursula Viswanathan, Akila N. TI Clinical predictors of long-term survival for stage IVB uterine papillary serous carcinoma confined to the abdomen SO GYNECOLOGIC ONCOLOGY LA English DT Article DE Uterine papillary serous carcinoma; FIGO Stage IVB; Endometrial cancer; Non-endometrioid endometrial cancer; Optimal cytoreductive surgery ID PLATINUM-BASED CHEMOTHERAPY; GYNECOLOGIC-ONCOLOGY-GROUP; CLEAR-CELL; CYTOREDUCTIVE SURGERY; CANCER; ENDOMETRIUM; PACLITAXEL; MANAGEMENT; DEBULKING AB Objective. To identify clinical predictors of long-term survival in women with FIGO Stage IVB uterine papillary serous carcinoma (UPSC) confined to the abdomen Methods. Records were reviewed for 48 patients with Stage IVB UPSC diagnosed from 1/1980 to 12/2011. Study inclusion required hysterectomy, salpingo-oophorectomy and negative chest imaging. Disease-free (DFS) and overall (OS) survival rates were calculated using the Kaplan-Meier method. Multivariate analysis (MVA) was performed using Cox proportional hazards. Results. Median age at diagnosis was 70 years (range, 53-87). Optimal cytoreduction (Opt) to <1 cm residual disease was performed in 36 patients (75%). With a median follow-up of 21 months for all patients and 99 months for survivors, 36 (75%) experienced disease progression or relapse, most commonly intraperitoneal (16, 44%). At 5 years, DFS and OS rates were 12% and 19%, respectively. Five patients (10%) were long-term survivors without relapse at a median of 124 months. All 5 had Opt and carboplatin/paclitaxel chemotherapy, and 4 received radiotherapy (2 pelvic, 1 whole-abdominal, 1 brachytherapy). On MVA in the chemotherapy-treated population, Opt (HR 0.09, 95% CI 0.02-0.35) and radiotherapy (HR 036, 0.15-0.80) were associated with decreased rates of recurrence or progression. Opt (HR 0.09, 0.02-038) was prognostic for OS when adjusted for age. Conclusions. Clinical predictors of long-term survival for Stage IVB UPSC confined to the abdomen include optimal cytoreduction and adjuvant platinum and paclitaxel chemotherapy. Radiotherapy may decrease rates of recurrence or progression. Despite intra-abdominal involvement, disease remission and long-term survival may be achieved in some patients. (C) 2013 Elsevier Inc. All rights reserved. C1 [Lee, Larissa J.; De Maria, Rebecca; Viswanathan, Akila N.] Brigham & Womens Hosp, Dept Radiat Oncol, Boston, MA 02115 USA. [Berkowitz, Ross] Brigham & Womens Hosp, Dept Gynecol Oncol, Boston, MA 02115 USA. [Matulonis, Ursula] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Lee, Larissa J.; Berkowitz, Ross; Matulonis, Ursula; Viswanathan, Akila N.] Harvard Univ, Sch Med, Boston, MA USA. RP Lee, LJ (reprint author), Brigham & Womens Hosp, Dept Radiat Oncol, 75 Francis St,ASB1-L2, Boston, MA 02115 USA. EM llee@lroc.harvard.edu NR 23 TC 6 Z9 6 U1 0 U2 0 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0090-8258 EI 1095-6859 J9 GYNECOL ONCOL JI Gynecol. Oncol. PD JAN PY 2014 VL 132 IS 1 BP 65 EP 69 DI 10.1016/j.ygyno.2013.10.035 PG 5 WC Oncology; Obstetrics & Gynecology SC Oncology; Obstetrics & Gynecology GA AA2GJ UT WOS:000330912800013 PM 24211401 ER PT J AU Fauci, JM Sabbatino, F Wang, YY Londono-Joshi, AI Straughn, JM Landen, CN Ferrone, S Buchsbaum, DJ AF Fauci, Janelle M. Sabbatino, Francesco Wang, YangYang Londono-Joshi, Angelina I. Straughn, J. Michael, Jr. Landen, Charles N. Ferrone, Soldano Buchsbaum, Donald J. TI Monoclonal antibody-based immunotherapy of ovarian cancer: Targeting ovarian cancer cells with the B7-H3-specific mAb 376.96 SO GYNECOLOGIC ONCOLOGY LA English DT Article DE Ovarian cancer; lmmunotherapy; Chemoresistance; Cancer initiating cells; B7-H3; Sunitinib ID STEM-CELLS; ALDEHYDE DEHYDROGENASE; BREAST-CANCER; PANCREATIC-CANCER; EXPRESSION; CARCINOMA; SURVIVAL; B7-H3; IDENTIFICATION; CD133 AB Objective. The high rate of relapse in patients with advanced ovarian cancer likely reflects the chemoresistance of cancer initiating cells (CICs). We evaluated the anti-tumor activity of monoclonal antibody (mAb) 376.96, which recognizes a B7-H3 epitope expressed on ovarian carcinoma cells (OCCs), in combination with the tyrosine kinase inhibitor Sunitinib and chemotherapy on chemosensitive and chemoresistant cells and CICs. Methods. Eight ovarian cancer cell lines including platinum- and taxane-resistant cell lines were analyzed by flow cytometry to establish expression of the mAb 376.96-defined-B7-H3-epitope on differentiated ovarian cancer cells and CICs. Samples from 10 ovarian cancer patients were analyzed via immunohistochemistry for mAb 376.96-defined-B7-H3-epitope expression. In vitro studies assessed mAb 376.96 alone and in combination With Sunitinib on the growth of chemosensitive and chemoresistant cell lines and on the content of CICs. Results. The mAb-376.96-defined-B7-H3 epitope is expressed on both differentiated cells and CICs in chemosensitive and chemoresistant ovarian cancer cell lines and 10 patient derived ovarian cancer tumors. In vitro treatment of chemoresistant cell lines with mAb 376.96 resulted in decreased cell viability. mAb 376.96 enhanced the cytotoxicity of Sunitinib and reduced the content of CICs. Conclusion. The mAb-376.96-defined-B7-H3-epitope was found to be expressed on both differentiated ovarian cancer cells and CICs in chemosensitive and chemoresistant ovarian cancer cell lines. mAb 376.96 inhibited the in vitro growth of chemosensitive and chemoresistant OCCs and reduced the content of CICs when used with Sunitinib. Further studies examining B7-H3 as a potential target of mAb-based immunotherapy for this type of malignancy are warranted. (C) 2013 Elsevier Inc. All rights reserved. C1 [Fauci, Janelle M.; Straughn, J. Michael, Jr.; Landen, Charles N.] Univ Alabama Birmingham, Dept Obstet & Gynecol, Birmingham, AL 35233 USA. [Sabbatino, Francesco; Wang, YangYang; Ferrone, Soldano] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Cambridge, MA 02138 USA. [Londono-Joshi, Angelina I.] Univ Alabama Birmingham, Div Mol & Cellular Pathol, Birmingham, AL 35233 USA. [Buchsbaum, Donald J.] Univ Alabama Birmingham, Dept Radiat Oncol, Birmingham, AL 35233 USA. RP Fauci, JM (reprint author), Univ Alabama Birmingham, Dept Obstet & Gynecol, Div Gynecol Oncol, 1700 6th Ave South, Birmingham, AL 35233 USA. EM janelle.fauci@gmail.com RI Sabbatino, Francesco/F-4992-2014 OI Sabbatino, Francesco/0000-0001-6431-8278 FU NCI NIH HHS [R01CA110249, R01CA138188, R21 CA164756] NR 38 TC 9 Z9 13 U1 1 U2 7 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0090-8258 EI 1095-6859 J9 GYNECOL ONCOL JI Gynecol. Oncol. PD JAN PY 2014 VL 132 IS 1 BP 203 EP 210 DI 10.1016/j.ygyno.2013.10.038 PG 8 WC Oncology; Obstetrics & Gynecology SC Oncology; Obstetrics & Gynecology GA AA2GJ UT WOS:000330912800036 PM 24216048 ER PT J AU Mendonca, PRS Lamb, P Sahani, DV AF Mendonca, Paulo R. S. Lamb, Peter Sahani, Dushyant V. TI A Flexible Method for Multi-Material Decomposition of Dual-Energy CT Images SO IEEE TRANSACTIONS ON MEDICAL IMAGING LA English DT Article DE Computed tomography (CT); dual-energy CT; liver-fat quantification; material decomposition; virtual un-enhancement ID FATTY LIVER-DISEASE; COMPUTED-TOMOGRAPHY; RENAL MASSES; MAGNETIC-RESONANCE; MULTIDETECTOR CT; SINGLE-ENERGY; QUANTIFICATION; STEATOSIS; INFILTRATION; FEASIBILITY AB The ability of dual-energy computed-tomographic (CT) systems to determine the concentration of constituent materials in a mixture, known as material decomposition, is the basis for many of dual-energy CT's clinical applications. However, the complex composition of tissues and organs in the human body poses a challenge for many material decomposition methods, which assume the presence of only two, or at most three, materials in the mixture. We developed a flexible, model-based method that extends dual-energy CT's core material decomposition capability to handle more complex situations, in which it is necessary to disambiguate among and quantify the concentration of a larger number of materials. The proposed method, named multi-material decomposition (MMD), was used to develop two image analysis algorithms. The first was virtual unenhancement (VUE), which digitally removes the effect of contrast agents from contrast-enhanced dual-energy CT exams. VUE has the ability to reduce patient dose and improve clinical workflow, and can be used in a number of clinical applications such as CT urography and CT angiography. The second algorithm developed was liver-fat quantification (LFQ), which accurately quantifies the fat concentration in the liver from dual-energy CT exams. LFQ can form the basis of a clinical application targeting the diagnosis and treatment of fatty liver disease. Using image data collected from a cohort consisting of 50 patients and from phantoms, the application of MMD to VUE and LFQ yielded quantitatively accurate results when compared against gold standards. Furthermore, consistent results were obtained across all phases of imaging (contrast-free and contrast-enhanced). This is of particular importance since most clinical protocols for abdominal imaging with CT call for multi-phase imaging. We conclude that MMD can successfully form the basis of a number of dual-energy CT image analysis algorithms, and has the potential to improve the clinical utility of dual-energy CT in disease management. C1 [Mendonca, Paulo R. S.; Lamb, Peter] GE Global Res, Niskayuna, NY 12309 USA. [Sahani, Dushyant V.] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Mendonca, PRS (reprint author), GE Global Res, Niskayuna, NY 12309 USA. EM mendonca@ge.com; peter.lamb@ge.com; dsahani@partners.org NR 86 TC 21 Z9 21 U1 1 U2 14 PU IEEE-INST ELECTRICAL ELECTRONICS ENGINEERS INC PI PISCATAWAY PA 445 HOES LANE, PISCATAWAY, NJ 08855-4141 USA SN 0278-0062 EI 1558-254X J9 IEEE T MED IMAGING JI IEEE Trans. Med. Imaging PD JAN PY 2014 VL 33 IS 1 BP 99 EP 116 DI 10.1109/TMI.2013.2281719 PG 18 WC Computer Science, Interdisciplinary Applications; Engineering, Biomedical; Engineering, Electrical & Electronic; Imaging Science & Photographic Technology; Radiology, Nuclear Medicine & Medical Imaging SC Computer Science; Engineering; Imaging Science & Photographic Technology; Radiology, Nuclear Medicine & Medical Imaging GA AA7SI UT WOS:000331296800009 PM 24058018 ER PT J AU Lin, YG Haldar, JP Li, QZ Conti, PS Leahy, RM AF Lin, Yanguang Haldar, Justin P. Li, Quanzheng Conti, Peter S. Leahy, Richard M. TI Sparsity Constrained Mixture Modeling for the Estimation of Kinetic Parameters in Dynamic PET SO IEEE TRANSACTIONS ON MEDICAL IMAGING LA English DT Article DE Compartment model; dynamic positron emission tomography (PET); kinetic parameter estimation; mixture modeling; sparsity ID POSITRON-EMISSION-TOMOGRAPHY; INDEPENDENT COMPONENT ANALYSIS; PENALIZED-LIKELIHOOD; COMPARTMENTAL-MODELS; IMAGE-RECONSTRUCTION; RESOLUTION; BRAIN; TUMOR; EXTRACTION; REGRESSION AB The estimation and analysis of kinetic parameters in dynamic positron emission tomography (PET) is frequently confounded by tissue heterogeneity and partial volume effects. We propose a new constrained model of dynamic PET to address these limitations. The proposed formulation incorporates an explicit mixture model in which each image voxel is represented as a mixture of different pure tissue types with distinct temporal dynamics. We use Cramer-Rao lower bounds to demonstrate that the use of prior information is important to stabilize parameter estimation with this model. As a result, we propose a constrained formulation of the estimation problem that we solve using a two-stage algorithm. In the first stage, a sparse signal processing method is applied to estimate the rate parameters for the different tissue compartments from the noisy PET time series. In the second stage, tissue fractions and the linear parameters of different time activity curves are estimated using a combination of spatial-regularity and fractional mixture constraints. A block coordinate descent algorithm is combined with a manifold search to robustly estimate these parameters. The method is evaluated with both simulated and experimental dynamic PET data. C1 [Lin, Yanguang; Haldar, Justin P.; Leahy, Richard M.] Univ So Calif, Signal & Image Proc Inst, Los Angeles, CA 90089 USA. [Li, Quanzheng] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. [Conti, Peter S.] Univ So Calif, Dept Radiol, Los Angeles, CA 90033 USA. RP Leahy, RM (reprint author), Univ So Calif, Signal & Image Proc Inst, Los Angeles, CA 90089 USA. RI Haldar, Justin/B-4983-2008 OI Haldar, Justin/0000-0002-1838-0211 FU National Institutes of Health (NIH) [R21-CA149587, R01-EB013293, R01-EB010197] FX This work is supported by the National Institutes of Health (NIH) under Grant R21-CA149587, Grant R01-EB013293, and Grant R01-EB010197. Asterisk indicates corresponding author. NR 43 TC 4 Z9 4 U1 0 U2 5 PU IEEE-INST ELECTRICAL ELECTRONICS ENGINEERS INC PI PISCATAWAY PA 445 HOES LANE, PISCATAWAY, NJ 08855-4141 USA SN 0278-0062 EI 1558-254X J9 IEEE T MED IMAGING JI IEEE Trans. Med. Imaging PD JAN PY 2014 VL 33 IS 1 BP 173 EP 185 DI 10.1109/TMI.2013.2283229 PG 13 WC Computer Science, Interdisciplinary Applications; Engineering, Biomedical; Engineering, Electrical & Electronic; Imaging Science & Photographic Technology; Radiology, Nuclear Medicine & Medical Imaging SC Computer Science; Engineering; Imaging Science & Photographic Technology; Radiology, Nuclear Medicine & Medical Imaging GA AA7SI UT WOS:000331296800014 PM 24216681 ER PT J AU Hamza, B Wong, E Patel, S Cho, HS Martel, J Irimia, D AF Hamza, Bashar Wong, Elisabeth Patel, Sachin Cho, Hansang Martel, Joseph Irimia, Daniel TI Retrotaxis of human neutrophils during mechanical confinement inside microfluidic channels SO INTEGRATIVE BIOLOGY LA English DT Article ID REVERSE MIGRATION; IN-VIVO; CHEMOTAXIS; INFLAMMATION; GRADIENTS; RESOLUTION; ACTIVATION; ZEBRAFISH; APOPTOSIS; ADHESION AB The current paradigm of unidirectional migration of neutrophils from circulation to sites of injury in tissues has been recently challenged by observations in zebrafish showing that neutrophils can return from tissues back into the circulation. However, the relevance of these observations to human neutrophils remains unclear, the forward and reverse migration of neutrophils is difficult to quantify, and the precise conditions modulating the reverse migration cannot be isolated. Here, we designed a microfluidic platform inside which we observed human neutrophil migration in response to chemoattractant sources inside channels, simulating the biochemical and mechanical confinement conditions at sites of injury in tissues. We observed that, after initially following the direction of chemoattractant gradients, more than 90% of human neutrophils can reverse their direction and migrate persistently and for distances longer than one thousand micrometers away from chemoattractant sources (retrotaxis). Retrotaxis is enhanced in the presence of lipoxin A4 (LXA(4)), a well-established mediator of inflammation resolution, or Tempol, a standard antioxidant. Retrotaxis stops after neutrophils encounter targets which they phagocytise or on surfaces presenting high concentrations of fibronectin. Our microfluidic model suggests a new paradigm for neutrophil accumulation at sites of inflammation, which depends on the balance of three simultaneous processes: chemotaxis along diffusion gradients, retrotaxis following mechanical guides, and stopping triggered by phagocytosis. C1 [Irimia, Daniel] Harvard Univ, Sch Med, Massachusetts Gen Hosp, BioMEMS Resource Ctr, Charlestown, MA 02129 USA. Shriners Hosp Children, Charlestown, MA 02129 USA. RP Irimia, D (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, BioMEMS Resource Ctr, Charlestown, MA 02129 USA. EM dirimia@hms.harvard.edu OI Irimia, Daniel/0000-0001-7347-2082 FU National Institutes of Health [GM092804, EB0025003] FX We thank Dr A. J. Aranyosi and Mr Octavio Hurtado for assistance with device fabrication at the BioMEMS Resource Center, Mr Harrison Prentice-Mott for helpful discussions and Dr Jagesh Shah for sharing of various HL-60 cell lines. This work was supported by the National Institutes of Health (GM092804, EB0025003). NR 31 TC 12 Z9 12 U1 1 U2 11 PU ROYAL SOC CHEMISTRY PI CAMBRIDGE PA THOMAS GRAHAM HOUSE, SCIENCE PARK, MILTON RD, CAMBRIDGE CB4 0WF, CAMBS, ENGLAND SN 1757-9694 EI 1757-9708 J9 INTEGR BIOL-UK JI Integr. Biol. PY 2014 VL 6 IS 2 BP 175 EP 183 DI 10.1039/c3ib40175h PG 9 WC Cell Biology SC Cell Biology GA AA0OU UT WOS:000330795500006 PM 24419464 ER PT J AU Wojnar, DM Katzenmeyer, A AF Wojnar, Danuta M. Katzenmeyer, Amy TI Experiences of Preconception, Pregnancy, and New Motherhood for Lesbian Nonbiological Mothers SO JOGNN-JOURNAL OF OBSTETRIC GYNECOLOGIC AND NEONATAL NURSING LA English DT Article DE nonbiological lesbian mothers; pregnancy; descriptive phenomenology ID POSTPARTUM DEPRESSION; CO-MOTHERS; PARENTHOOD; FAMILIES; COUPLES; CHILDBEARING; NEEDS; ADOLESCENTS; TRANSITION; INTERVIEWS AB ObjectiveTo describe the experiences of preconception, pregnancy, and new motherhood from the perspective of lesbian nonbiological mothers. DesignDescriptive phenomenology. SettingA private room at the study site and participants' homes. ParticipantsTwenty-four self-identified lesbian nonbiological mothers in a committed relationship and whose partner gave birth within the past 2years participated. All of the participants were from urban or suburban areas in the Pacific Northwest. MethodsWomen participated in semistructured in person interviews that were audio recorded and transcribed verbatim for analysis. Coliazzi's method guided the process. ResultsAn overarching theme of feeling different permeated the experiences of preconception, pregnancy, and new motherhood for the participants. The women's narratives revealed seven themes that illustrated their experiences: (a) Launching pregnancy: A roller coaster ride; (b) Having legal and biological concerns: Biology prevails; (c) There is a little person in there: Dealing with pregnancy issues; (d) Losing relationships over pregnancy: The elephant in the room; (e) Feeling incomplete as a mother; (f) Carving a unique role: There are very few of us out there; and (g) Sadness and regret: Nonbiological mothers get the postpartum blues, too. ConclusionsThe experience of preconception, pregnancy, and new motherhood for nonbiological lesbian mothers is complicated by the lack of biological and legal substantiation to the infant, few role models, and limited social support. Nurses and health care providers cognizant of these issues can play an important role in facilitating a positive transition to motherhood for this population. C1 [Wojnar, Danuta M.] Seattle Univ, Coll Nursing, Dept Maternal Child & Family Nursing, Seattle, WA 98122 USA. [Katzenmeyer, Amy] VA Puget Sound Hlth Care Syst, Dept Orthoped, Seattle, WA USA. RP Wojnar, DM (reprint author), Seattle Univ, Coll Nursing, 901 12th Ave,POB 222000, Seattle, WA 98122 USA. EM wojnard@seattleu.edu NR 42 TC 6 Z9 6 U1 2 U2 16 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0884-2175 EI 1552-6909 J9 JOGNN-J OBST GYN NEO JI JOGNN PD JAN PY 2014 VL 43 IS 1 BP 50 EP 60 DI 10.1111/1552-6909.12270 PG 11 WC Nursing; Obstetrics & Gynecology SC Nursing; Obstetrics & Gynecology GA AA1GI UT WOS:000330844200007 PM 24354595 ER PT J AU Imudia, AN Goldman, RH Awonuga, AO Wright, DL Styer, AK Toth, TL AF Imudia, Anthony N. Goldman, Randi H. Awonuga, Awoniyi O. Wright, Diane L. Styer, Aaron K. Toth, Thomas L. TI The impact of supraphysiologic serum estradiol levels on peri-implantation embryo development and early pregnancy outcome following in vitro fertilization cycles SO JOURNAL OF ASSISTED REPRODUCTION AND GENETICS LA English DT Article DE Fertilization; Implantation; Hyperstimulation; Oocyte quality; Estradiol; Pregnancy outcome ID CONTROLLED OVARIAN HYPERSTIMULATION; ASSISTED REPRODUCTIVE TECHNOLOGY; GONADOTROPIN-RELEASING HORMONE; INVITRO FERTILIZATION; UTERINE RECEPTIVITY; IMPLANTATION; STIMULATION; RISK; RESPONDER; DISEASE AB To determine the impact of elevated serum estradiol levels (EE2-defined as levels > 90th percentile) on the day of hCG administration during IVF on oocyte fertilization, embryo development, implantation, clinical pregnancy and miscarriage rates. A total of 2,995 consecutive IVF cycles in 1,889 patients with non-donor oocyte retrieval resulting in fresh embryo transfer between 1/1/2005 and 12/31/2011 were analyzed. Cycles were stratified by serum E-2 level on the day of hCG administration into those with levels > 90th percentile and a parts per thousand currency signaEuro parts per thousand 90th percentile. Rates of normal fertilization, embryo development, positive pregnancy test, implantation, clinical pregnancy and spontaneous miscarriage were compared. Serum estradiol above the 90th percentile on the day of hCG administration was associated with a significantly lower rate of normal fertilization (68.6 +/- 20 vs. 71.6 +/- 21, p = 0.02) when compared with patients with a lower serum estradiol threshold. The proportion of embryos that progressed from 2PN to 6-8 cell on day 3 was not different between the two groups. Although rates of positive pregnancy test (55.2 % vs. 57 %), implantation (26.4 % vs. 28.5 %) and clinical pregnancy (45.5 % vs. 49.4 %) were lower in patients with a higher estradiol threshold, these differences were not statistically significant. Similarly, there was no difference in the spontaneous miscarriage rates between the two groups (8.4 % vs. 7.1 %). Serum estradiol levels above the 90th percentile on the day of hCG administration is associated with lower oocyte fertilization rate; however, such levels do not impact embryo development, implantation, clinical pregnancy or spontaneous miscarriage rates. C1 [Imudia, Anthony N.] Univ S Florida, Morsani Sch Med, Dept Obstet & Gynecol, Div Reprod Endocrinol & Infertil, Tampa, FL 33606 USA. [Goldman, Randi H.; Wright, Diane L.; Styer, Aaron K.; Toth, Thomas L.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Vincent Dept Obstet & Gynecol, Boston, MA USA. [Awonuga, Awoniyi O.] Wayne State Univ, Sch Med, Dept Obstet & Gynecol, Div Reprod Endocrinol & Infertil, Detroit, MI 48201 USA. [Wright, Diane L.; Styer, Aaron K.; Toth, Thomas L.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Massachusetts Gen Hosp Fertil Ctr,Vincent Dept Ob, Boston, MA USA. [Imudia, Anthony N.] Univ S Florida, Tampa, FL 33606 USA. RP Imudia, AN (reprint author), Univ S Florida, 2 Tampa Gen Circle,Suite 6022, Tampa, FL 33606 USA. EM aimudia@health.usf.edu NR 36 TC 10 Z9 11 U1 0 U2 2 PU SPRINGER/PLENUM PUBLISHERS PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1058-0468 EI 1573-7330 J9 J ASSIST REPROD GEN JI J. Assist. Reprod. Genet. PD JAN PY 2014 VL 31 IS 1 BP 65 EP 71 DI 10.1007/s10815-013-0117-8 PG 7 WC Genetics & Heredity; Obstetrics & Gynecology; Reproductive Biology SC Genetics & Heredity; Obstetrics & Gynecology; Reproductive Biology GA AA3JB UT WOS:000330987600009 PM 24193696 ER PT J AU Papakostas, GI AF Papakostas, George I. TI Cognitive Symptoms in Patients With Major Depressive Disorder and Their Implications for Clinical Practice SO JOURNAL OF CLINICAL PSYCHIATRY LA English DT Review ID POPULATION-BASED SAMPLE; ANTIDEPRESSANT-TREATMENT; EXECUTIVE DYSFUNCTION; SEROTONIN-REUPTAKE; DOUBLE-BLIND; ELDERLY-PATIENTS; REMITTED STATE; YOUNG-ADULTS; TRIAL; METAANALYSIS AB Context: The literature regarding cognitive symptoms in major depressive disorder (MDD) is vast and often contradictory. To provide clinicians with a concise understanding of these prevalent and disabling symptoms, this overview describes what is known regarding cognitive symptoms in patients with MDD, the limitations of the current literature, and the implications of these data for current and future clinical practice. Evidence Acquisition: PubMed searches were conducted to identify studies, meta-analyses, and systematic reviews evaluating cognitive function (not cognitive bias) in patients with MDD. Search terms used in combination with MDD were cognition, cognitive dysfunction, memory, psychomotor processing, and executive function. Searches were limited to articles available in the English language and those published between April 2007 and March 2012. Additional studies and those describing screening tools were identified using reference lists and PubMed "related citations." Ongoing trials were identified by searching for cognitive dysfunction and MDD at www.ClinicalTrials.gov. Relevant articles were obtained and reviewed by the author. Results: Small sample size and inconsistent assessment tools were identified as major limitations of studies assessing clinical characteristics and risk factors for cognitive symptoms. Meta-analyses and systematic reviews were used to mitigate this limitation. Conclusions: Cognitive symptoms of depression are prevalent and associated with earlier illness onset and longer episode duration. They can have an adverse impact on the treatment course of MDD as well as on functional recovery in depression. Further studies are needed to help determine whether certain treatments can be more effective than others at targeting these symptoms. (C) Copyright 2013 Physicians Postgraduate Press, Inc. C1 [Papakostas, George I.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Papakostas, George I.] Harvard Univ, Sch Med, Boston, MA USA. RP Papakostas, GI (reprint author), Massachusetts Gen Hosp, One Bowdoin Sq,6th Floor, Boston, MA 02114 USA. EM gpapakostas@partners.org FU Takeda Pharmaceutical Company, Ltd; H. Lundbeck A/S FX This study was supported by the Takeda Pharmaceutical Company, Ltd, and H. Lundbeck A/S. NR 39 TC 35 Z9 37 U1 1 U2 28 PU PHYSICIANS POSTGRADUATE PRESS PI MEMPHIS PA P O BOX 752870, MEMPHIS, TN 38175-2870 USA SN 0160-6689 EI 1555-2101 J9 J CLIN PSYCHIAT JI J. Clin. Psychiatry PY 2014 VL 75 IS 1 BP 8 EP 14 DI 10.4088/JCP.13r08710 PG 7 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA AA0FO UT WOS:000330771200004 PM 24345473 ER PT J AU Kisiel, C Fehrenbach, T Torgersen, E Stolbach, B McClelland, G Griffin, G Burkman, K AF Kisiel, Cassandra L. Fehrenbach, Tracy Torgersen, Elizabeth Stolbach, Brad McClelland, Gary Griffin, Gene Burkman, Kristine TI Constellations of Interpersonal Trauma and Symptoms in Child Welfare: Implications for a Developmental Trauma Framework SO JOURNAL OF FAMILY VIOLENCE LA English DT Article DE Complex trauma; Developmental trauma disorder; Posttraumatic stress; Child; Youth; Caregiver ID POLY-VICTIMIZATION; COMPLEX TRAUMA; POSTTRAUMATIC-STRESS; NATIONAL SAMPLE; YOUNG-CHILDREN; MALTREATMENT; ADOLESCENTS; DISORDER; EXPERIENCES; PREVALENCE AB Patterns of trauma exposure and symptoms were examined in a sample of 16,212 children in Illinois child welfare. Data were collected on trauma histories, child and caregiver needs and strengths, and analyzed in light of the proposed Developmental Trauma Disorder diagnostic criteria. Youth exposed to both interpersonal violence and attachment-based ("non-violent") traumas within the caregiving system had significantly higher levels of affective/physiological, attentional/behavioral, and self/relational dysregulation in addition to posttraumatic stress symptoms compared to youth with either type of trauma alone or in relation to other trauma experiences. These complexly traumatized children exhibited higher levels of functional impairment and were more likely to have placement disruptions and psychiatric hospitalizations. Findings suggest a developmental trauma framework can more adequately capture the spectrum of needs of these multiply traumatized youth than existing diagnostic formulations. Utilizing this framework for assessment, treatment planning, and intervention can lead to more targeted and effective services for these children. C1 [Kisiel, Cassandra L.; Fehrenbach, Tracy; Torgersen, Elizabeth; McClelland, Gary; Griffin, Gene] Northwestern Univ, Dept Psychiat & Behav Sci, Feinberg Sch Med, Chicago, IL 60611 USA. [Stolbach, Brad] Univ Chicago, Pritzker Sch Med, Dept Pediat, Chicago, IL 60637 USA. [Burkman, Kristine] San Francisco VA Med Ctr, Dept Psychol, San Francisco, CA USA. RP Kisiel, C (reprint author), Northwestern Univ, Dept Psychiat & Behav Sci, Feinberg Sch Med, 710 N Lake Shore Dr,12th Floor, Chicago, IL 60611 USA. EM c-kisiel@northwestern.edu NR 55 TC 8 Z9 8 U1 2 U2 21 PU SPRINGER/PLENUM PUBLISHERS PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0885-7482 EI 1573-2851 J9 J FAM VIOLENCE JI J. Fam. Violence PD JAN PY 2014 VL 29 IS 1 BP 1 EP 14 DI 10.1007/s10896-013-9559-0 PG 14 WC Psychology, Clinical; Family Studies SC Psychology; Family Studies GA AA4QU UT WOS:000331081800001 ER PT J AU Vu, JP Million, M Larauche, M Luong, L Norris, J Waschek, JA Pothoulakis, C Pisegna, JR Germano, PM AF Vu, John P. Million, Mulugeta Larauche, Muriel Luong, Leon Norris, Joshua Waschek, James A. Pothoulakis, Charalabos Pisegna, Joseph R. Germano, Patrizia M. TI Inhibition of Vasoactive Intestinal Polypeptide (VIP) Induces Resistance to Dextran Sodium Sulfate (DSS)-Induced Colitis in Mice SO JOURNAL OF MOLECULAR NEUROSCIENCE LA English DT Article DE VIP; Colitis; VIP antagonist: IBD ID INFLAMMATORY-BOWEL-DISEASE; EXPERIMENTAL AUTOIMMUNE ENCEPHALOMYELITIS; DIFFERENTIAL EXPRESSION; CROHNS-DISEASE; RECEPTOR ANTAGONIST; ULCERATIVE-COLITIS; CANCER GROWTH; PEPTIDE VIP; IN-VIVO; CELLS AB VIP is highly expressed in the colon and regulates motility, vasodilatation, and sphincter relaxation. However, its role in the development and progress of colitis is still controversial. Our aim was to determine the participation of VIP on dextran sodium sulfate (DSS)-induced colonic mucosal inflammation using VIP-/- and WT mice treated with VIP antagonists. Colitis was induced in 32 adult VIP-/- and 14 age-matched WT litter-mates by giving 2.5 % DSS in the drinking water. DSS-treated WT mice were injected daily with VIP antagonists, VIPHyb (n = 22), PG 97-269 (n = 9), or vehicle (n = 31). After euthanasia, colons were examined; colonic cytokines mRNA were quantified. VIP-/- mice were remarkably resistant to DSS-induced colitis compared to WT. Similarly, DSS-treated WT mice injected with VIPHyb (1 mu M) or PG 97-269 (1 nM) had significantly reduced clinical signs of colitis. Furthermore, colonic expression of IL-1I, TNF-alpha, and IL-6 was significantly lower in VIP-/- and VIPHyb or PG 97-269 compared to vehicle-treated WT. Genetic deletion of VIP or pharmacological inhibition of VIP receptors resulted in resistance to colitis. These data demonstrate a pro-inflammatory role for VIP in murine colitis and suggest that VIP antagonists may be an effective clinical treatment for human inflammatory bowel diseases. C1 [Vu, John P.; Million, Mulugeta; Larauche, Muriel; Luong, Leon; Norris, Joshua; Waschek, James A.; Pothoulakis, Charalabos; Pisegna, Joseph R.; Germano, Patrizia M.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Med, CURE Digest Dis Res Ctr, Los Angeles, CA 90095 USA. [Vu, John P.; Million, Mulugeta; Larauche, Muriel; Luong, Leon; Norris, Joshua; Waschek, James A.; Pothoulakis, Charalabos; Pisegna, Joseph R.; Germano, Patrizia M.] VA Greater Los Angeles Hlth Care Syst, Los Angeles, CA USA. [Waschek, James A.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Psychiat, Los Angeles, CA 90095 USA. [Germano, Patrizia M.] VA Greater Los Angeles Healthcare Syst, Div Pulm & Crit Care, Dept Med, Los Angeles, CA USA. [Pothoulakis, Charalabos] Univ Calif Los Angeles, David Geffen Sch Med, Div Digest Dis, Ctr Inflammatory Bowel Dis, Los Angeles, CA 90095 USA. [Pisegna, Joseph R.] VA Greater Los Angeles Healthcare Syst, Div Gastroenterol & Hepatol, Dept Med, Los Angeles, CA USA. [Germano, Patrizia M.] CURE UCLA West Los Angeles VA Healthcare Syst, Los Angeles, CA USA. RP Germano, PM (reprint author), CURE UCLA West Los Angeles VA Healthcare Syst, Bldg 115,Rm 313, Los Angeles, CA USA. EM pgermano@ucla.edu OI Larauche, Muriel/0000-0003-3320-3675 FU Department of Veterans Affairs Merit Review; NIH [DK-41301]; RO1 [DK-078676] FX Department of Veterans Affairs Merit Review (PG, JP) NIH DK-41301 & RO1 DK-078676 (MM) NR 46 TC 7 Z9 7 U1 0 U2 5 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DRIVE SUITE 208, TOTOWA, NJ 07512 USA SN 0895-8696 EI 1559-1166 J9 J MOL NEUROSCI JI J. Mol. Neurosci. PD JAN PY 2014 VL 52 IS 1 BP 37 EP 47 DI 10.1007/s12031-013-0205-3 PG 11 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA AA1LN UT WOS:000330857900005 PM 24395090 ER PT J AU Cho, H Hamza, B Wong, EA Irimia, D AF Cho, Hansang Hamza, Bashar Wong, Elisabeth A. Irimia, Daniel TI On-demand, competing gradient arrays for neutrophil chemotaxis SO LAB ON A CHIP LA English DT Article ID MULTIPLE CHEMICALS; INFLAMMATION; GENERATION; NAVIGATION; SIGNALS; SYSTEM AB Neutrophils are the most abundant type of white blood cells in the circulation, protecting the body against pathogens and responding early to inflammation. Although we understand how neutrophils respond to individual stimuli, we know less about how they prioritize between competing signals or respond to combinational signals. This situation is due in part to the lack of adequate experimental systems to provide signals in controlled spatial and temporal fashion. To address these limitations, we designed a platform for generating on-demand, competing chemical gradients and for monitoring neutrophil migration. On this platform, we implemented forty-eight assays generating independent gradients and employed synchronized valves to control the timing of these gradients. We observed faster activation of neutrophils in response to fMLP than to LTB4 and unveiled for the first time a potentiating effect for fMLP during migration towards LTB4. Our observations, enabled by the new tools, challenge the current paradigm of inhibitory competition between distinct chemoattractant gradients and suggest that human neutrophils are capable of complex integration of chemical signals in their environment. C1 [Irimia, Daniel] Harvard Univ, Massachusetts Gen Hosp, Sch Med, BioMEMS Resource Ctr, Charlestown, MA 02129 USA. Shriners Hosp Children, Charlestown, MA 02129 USA. RP Irimia, D (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, BioMEMS Resource Ctr, Charlestown, MA 02129 USA. EM dirimia@hms.harvard.edu OI Irimia, Daniel/0000-0001-7347-2082 FU National Institutes of Health [GM092804, DE019938, EB002503] FX This work was supported in part by funding from the National Institutes of Health, grants GM092804, DE019938, and EB002503. NR 35 TC 6 Z9 7 U1 0 U2 17 PU ROYAL SOC CHEMISTRY PI CAMBRIDGE PA THOMAS GRAHAM HOUSE, SCIENCE PARK, MILTON RD, CAMBRIDGE CB4 0WF, CAMBS, ENGLAND SN 1473-0197 EI 1473-0189 J9 LAB CHIP JI Lab Chip PY 2014 VL 14 IS 5 BP 972 EP 978 DI 10.1039/c3lc50959a PG 7 WC Biochemical Research Methods; Chemistry, Multidisciplinary; Nanoscience & Nanotechnology SC Biochemistry & Molecular Biology; Chemistry; Science & Technology - Other Topics GA AA0KQ UT WOS:000330784400018 PM 24430002 ER PT J AU Parikh, S Goldstein, A Koenig, MK Scaglia, F Enns, GM Saneto, R Anselm, I Collins, A Cohen, BH DeBrosse, SD Dimmock, D Falk, MJ Ganesh, J Greene, C Gropman, AL Haas, R Kahler, SG Kamholz, J Kendall, F Korson, MS Mattman, A Milone, M Niyazov, D Pearl, PL Reimschisel, T Salvarinova-Zivkovic, R Sims, K Tarnopolsky, M Tsao, CY van Hove, J Walsh, L Wolfe, LA AF Parikh, Sumit Goldstein, Amy Koenig, Mary Kay Scaglia, Fernando Enns, Gregory M. Saneto, Russell Anselm, Irina Collins, Abigail Cohen, Bruce H. DeBrosse, Suzanne D. Dimmock, David Falk, Marni J. Ganesh, Jaya Greene, Carol Gropman, Andrea L. Haas, Richard Kahler, Stephen G. Kamholz, John Kendall, Fran Korson, Mark S. Mattman, Andre Milone, Margherita Niyazov, Dmitriy Pearl, Phillip L. Reimschisel, Tyler Salvarinova-Zivkovic, Ramona Sims, Katherine Tarnopolsky, Mark Tsao, Chang-Yong van Hove, Johan Walsh, Laurence Wolfe, Lynne A. CA Mitochondrial Med Soc Clinical Dir MMS Clinical Director's Work Grp TI Practice patterns of mitochondrial disease physicians in North America. Part 1: Diagnostic and clinical challenges SO MITOCHONDRION LA English DT Article DE Mitochondrial disease; Mitochondrial medicine; Clinical guidelines ID POLYACRYLAMIDE-GEL ELECTROPHORESIS; RESPIRATORY-CHAIN DEFICIENCIES; OXIDATIVE-PHOSPHORYLATION; DISORDERS; CRITERIA; CHILDREN; AUTISM; TOOL; DNA AB Mitochondrial medicine is a young subspecialty. Clinicians have a limited evidence base on which to formulate clinical decisions regarding diagnosis, treatment and patient management. Mitochondrial medicine specialists have cobbled together an informal set of rules and paradigms for preventive care and management based in part on anecdotal experience. The Mitochondrial Medicine Society (MMS) assessed the current state of clinical practice from diagnosis, to preventive care and treatment as provided by various mitochondrial disease specialists in North America. We hope that by obtaining this information we can begin moving towards formulating a set of consensus criteria and establishing standards of care. (C) 2013 Elsevier B.V. and Mitochondria Research Society. All rights reserved. C1 [Anselm, Irina] Boston Childrens Hosp, Boston, MA USA. [Collins, Abigail] Univ Colorado, Sch Med, Denver, CO USA. [Cohen, Bruce H.] Childrens Hosp, Med Ctr Akron, NeuroDev Sci Ctr, Akron, OH USA. [DeBrosse, Suzanne D.] Univ Hosp Case Med Ctr, Ctr Human Genet, Cleveland, OH USA. [DeBrosse, Suzanne D.] Case Western Reserve Univ, Cleveland, OH 44106 USA. [Dimmock, David] Med Coll Wisconsin, Dept Pediat, Div Genet, Milwaukee, WI 53226 USA. [Falk, Marni J.] Childrens Hosp Philadelphia, Dept Pediat, Div Human Genet, Philadelphia, PA 19104 USA. [Falk, Marni J.] Univ Penn, Perelman Sch Med, Philadelphia, PA 19104 USA. [Ganesh, Jaya] Childrens Hosp Philadelphia, Sect Metab Dis, Philadelphia, PA 19104 USA. [Greene, Carol] Univ Maryland, Med Ctr, Baltimore, MD 21201 USA. [Gropman, Andrea L.; Pearl, Phillip L.] Childrens Natl Med Ctr, Dept Neurol, Washington, DC 20010 USA. [Gropman, Andrea L.] George Washington Univ Hlth Sci, Washington, DC USA. [Haas, Richard] UCSD Med Ctr, La Jolla, CA USA. [Haas, Richard] Rady Childrens Hosp San Diego, La Jolla, CA USA. [Kahler, Stephen G.] Univ Arkansas Med Sci, Dept Pediat, Little Rock, AR 72205 USA. [Kahler, Stephen G.] Arkansas Childrens Hosp, Little Rock, AR 72202 USA. [Kamholz, John] Wayne State Univ, Detroit, MI USA. [Kendall, Fran] Virtual Med Practice LLC, Atlanta, GA USA. [Korson, Mark S.] Tufts Med Ctr, Boston, MA USA. [Mattman, Andre] Vancouver Gen Hosp, Adult Metab Dis Clin, Vancouver, BC, Canada. [Milone, Margherita] Mayo Med Ctr, Rochester, MN USA. [Niyazov, Dmitriy] Ochsner Clin Fdn, Dept Pediat, New Orleans, IA USA. [Reimschisel, Tyler] Vanderbilt Univ, Sch Med, Nashville, TN 37212 USA. [Salvarinova-Zivkovic, Ramona] Univ British Columbia, BC Childrens Hosp, Dept Pediat, Div Biochem Dis, Vancouver, BC V5Z 1M9, Canada. [Sims, Katherine] Harvard Univ, Sch Med, Boston, MA USA. [Sims, Katherine] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Tarnopolsky, Mark] McMaster Univ, Hamilton, ON, Canada. [Tsao, Chang-Yong] Nationwide Childrens Hosp, Columbus, OH USA. [van Hove, Johan] Childrens Hosp Colorado, Denver, CO USA. [Walsh, Laurence] Indiana Univ Sch Med, Indianapolis, IN 46202 USA. [Walsh, Laurence] James Whitcomb Riley Hosp Children, Indianapolis, IN 46202 USA. [Wolfe, Lynne A.] NIH, Bethesda, MD 20892 USA. [Parikh, Sumit] Cleveland Clin, Childrens Hosp, Ctr Child Neurol, Cleveland, OH 44195 USA. [Goldstein, Amy] Childrens Hosp Pittsburgh, Div Child Neurol, Pittsburgh, PA 15213 USA. [Koenig, Mary Kay] Univ Texas Houston, Sch Med, Div Child & Adolescent Neurol, Houston, TX USA. [Scaglia, Fernando] Baylor Coll Med, Dept Mol & Human Genet, Houston, TX 77030 USA. [Scaglia, Fernando] Texas Childrens Hosp, Houston, TX 77030 USA. [Enns, Gregory M.] Stanford Univ, Dept Pediat, Div Med Genet, Lucile Packard Childrens Hosp, Palo Alto, CA 94304 USA. [Saneto, Russell] Univ Washington, Seattle Childrens Hosp, Seattle, WA 98195 USA. RP Parikh, S (reprint author), Cleveland Clin, 9500 Euclid Ave,S60, Cleveland, OH 44195 USA. EM parikhs@ccf.org RI Falk, Marni/K-1997-2014; Dimmock, David/I-7913-2015 OI Dimmock, David/0000-0001-6690-2523 NR 21 TC 8 Z9 8 U1 2 U2 7 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 1567-7249 EI 1872-8278 J9 MITOCHONDRION JI Mitochondrion PD JAN PY 2014 VL 14 BP 26 EP 33 DI 10.1016/j.mito.2013.07.116 PG 8 WC Cell Biology; Genetics & Heredity SC Cell Biology; Genetics & Heredity GA AA2GD UT WOS:000330912200004 PM 23891656 ER PT J AU Annese, J Schenker-Ahmed, NM Bartsch, H Maechler, P Sheh, C Thomas, N Kayano, J Ghatan, A Bresler, N Frosch, MP Klaming, R Corkin, S AF Annese, Jacopo Schenker-Ahmed, Natalie M. Bartsch, Hauke Maechler, Paul Sheh, Colleen Thomas, Natasha Kayano, Junya Ghatan, Alexander Bresler, Noah Frosch, Matthew P. Klaming, Ruth Corkin, Suzanne TI Postmortem examination of patient HM's brain based on histological sectioning and digital 3D reconstruction SO NATURE COMMUNICATIONS LA English DT Article ID MEDIAL TEMPORAL-LOBE; AMNESIC SYNDROME; PROFOUND AMNESIA; FOLLOW-UP; HIPPOCAMPUS; MEMORY; DISSOCIATION; PHENYTOIN; RESECTION; EXCISION AB Modern scientific knowledge of how memory functions are organized in the human brain originated from the case of Henry G. Molaison (H.M.), an epileptic patient whose amnesia ensued unexpectedly following a bilateral surgical ablation of medial temporal lobe structures, including the hippocampus. The neuroanatomical extent of the 1953 operation could not be assessed definitively during H.M.'s life. Here we describe the results of a procedure designed to reconstruct a microscopic anatomical model of the whole brain and conduct detailed 3D measurements in the medial temporal lobe region. This approach, combined with cellular-level imaging of stained histological slices, demonstrates a significant amount of residual hippocampal tissue with distinctive cytoarchitecture. Our study also reveals diffuse pathology in the deep white matter and a small, circumscribed lesion in the left orbitofrontal cortex. The findings constitute new evidence that may help elucidate the consequences of H.M.'s operation in the context of the brain's overall pathology. C1 [Annese, Jacopo; Schenker-Ahmed, Natalie M.; Bartsch, Hauke; Maechler, Paul; Sheh, Colleen; Thomas, Natasha; Kayano, Junya; Ghatan, Alexander; Bresler, Noah; Klaming, Ruth] Brain Observ, San Diego, CA 92101 USA. [Annese, Jacopo; Schenker-Ahmed, Natalie M.; Bartsch, Hauke; Maechler, Paul; Sheh, Colleen; Klaming, Ruth] Univ Calif San Diego, Dept Radiol, San Diego, CA 92093 USA. [Frosch, Matthew P.] Massachusetts Gen Hosp, CS Kubik Lab Neuropathol, Boston, MA 02114 USA. [Frosch, Matthew P.] Harvard Univ, Sch Med, Boston, MA 02114 USA. [Corkin, Suzanne] MIT, Dept Brain & Cognit Sci, Cambridge, MA 02139 USA. RP Annese, J (reprint author), Brain Observ, San Diego, CA 92101 USA. EM drjannese@gmail.com RI Schenker-Ahmed, Natalie/B-7470-2011 OI Schenker-Ahmed, Natalie/0000-0002-2651-1576 FU National Science Foundation [NSF-SGER 0714660]; Dana Foundation [2007-4234]; National Eye Institute [R01 EY018359-02, ARRA R01 EY018359-02S1]; National Institute of Mental Health [R01MH084756] FX The work was supported by grants from the National Science Foundation (NSF-SGER 0714660, J.A., Principal Investigator), the Dana Foundation (Brain and Immuno-Imaging Award, 2007-4234, J.A., Principal Investigator) and by private contributions from viewers of the web broadcast of the dissection. In the course of the study, Dr. Annese was in part supported by two research grants from the National Eye Institute, R01 EY018359-02 and ARRA R01 EY018359-02S1 (J.A., Principal Investigator) and the National Institute of Mental Health, R01MH084756 (J.A., Principal Investigator). The authors would like to thank Herbert and Sharon Lurie, M.S., for their generous contribution towards publishing the article on an open access basis. We would like to dedicate the project and this publication to H.M. He transformed his difficult experience into a lifelong contribution to scientific research on the mechanisms supporting human memory. This study also honours all the researchers who conducted studies with H.M. when he was alive, and Brenda Milner, in particular, who first demonstrated the importance of his case. The authors would like to acknowledge the critical contribution of David Malmberg in the development of the instrumentation and thank Dr. Elizabeth Murphy for editorial assistance. NR 46 TC 28 Z9 29 U1 4 U2 30 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 JAN PY 2014 VL 5 AR 3122 DI 10.1038/ncomms4122 PG 9 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA AA4RS UT WOS:000331084400031 PM 24473151 ER PT J AU Nilsson, R Jain, M Madhusudhan, N Sheppard, NG Strittmatter, L Kampf, C Huang, J Asplund, A Mootha, VK AF Nilsson, Roland Jain, Mohit Madhusudhan, Nikhil Sheppard, Nina Gustafsson Strittmatter, Laura Kampf, Caroline Huang, Jenny Asplund, Anna Mootha, Vamsi K. TI Metabolic enzyme expression highlights a key role for MTHFD2 and the mitochondrial folate pathway in cancer SO NATURE COMMUNICATIONS LA English DT Article ID DEPENDENT METHYLENETETRAHYDROFOLATE DEHYDROGENASE; HUMAN CELL-CYCLE; BREAST-CANCER; GENE-EXPRESSION; MEMORIAL-LECTURE; SIGNATURE; PROLINE; GLYCINE; CYCLOHYDROLASE; TRANSFORMATION AB Metabolic remodeling is now widely regarded as a hallmark of cancer, but it is not clear whether individual metabolic strategies are frequently exploited by many tumours. Here we compare messenger RNA profiles of 1,454 metabolic enzymes across 1,981 tumours spanning 19 cancer types to identify enzymes that are consistently differentially expressed. Our meta-analysis recovers established targets of some of the most widely used chemotherapeutics, including dihydrofolate reductase, thymidylate synthase and ribonucleotide reductase, while also spotlighting new enzymes, such as the mitochondrial proline biosynthetic enzyme PYCR1. The highest scoring pathway is mitochondrial one-carbon metabolism and is centred on MTHFD2. MTHFD2 RNA and protein are markedly elevated in many cancers and correlated with poor survival in breast cancer. MTHFD2 is expressed in the developing embryo, but is absent in most healthy adult tissues, even those that are proliferating. Our study highlights the importance of mitochondrial compartmentalization of one-carbon metabolism in cancer and raises important therapeutic hypotheses. C1 [Nilsson, Roland; Sheppard, Nina Gustafsson] Karolinska Inst, Dept Med, Unit Computat Med, S-17176 Stockholm, Sweden. [Nilsson, Roland; Sheppard, Nina Gustafsson] Karolinska Inst, Ctr Mol Med, S-17176 Stockholm, Sweden. [Jain, Mohit; Madhusudhan, Nikhil; Strittmatter, Laura; Mootha, Vamsi K.] Broad Inst, Cambridge, MA 02142 USA. [Jain, Mohit; Madhusudhan, Nikhil; Strittmatter, Laura; Mootha, Vamsi K.] Harvard Univ, Sch Med, Dept Syst Biol, Boston, MA 02115 USA. [Jain, Mohit; Madhusudhan, Nikhil; Strittmatter, Laura; Mootha, Vamsi K.] Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. [Jain, Mohit; Madhusudhan, Nikhil; Strittmatter, Laura; Mootha, Vamsi K.] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA. [Jain, Mohit] Brigham & Womens Hosp, Dept Med, Div Cardiovasc Med, Boston, MA USA. [Kampf, Caroline; Asplund, Anna] Uppsala Univ, Sci Life Lab, Dept Immunol Genet & Pathol, S-75185 Uppsala, Sweden. [Huang, Jenny] La Jolla Inst Allergy & Immunol, San Diego, CA 92037 USA. RP Mootha, VK (reprint author), Broad Inst, Cambridge, MA 02142 USA. EM vamsi@hms.harvard.edu OI Gustafsson Sheppard, Nina/0000-0001-6401-0548 FU Swedish Research Council [K2012-99X-22007-01-3]; Foundation for Strategic Research [ICA10-0023]; NIH [K08HL107451, R01DK081457] FX We acknowledge the National Cancer Institute for cellular reagents. We acknowledge Joseph White (Dana-Farber Cancer Institute) for assistance with the GCOD database. R.N. and N.G.S. were supported by grants from the Swedish Research Council (K2012-99X-22007-01-3) and Foundation for Strategic Research (ICA10-0023). M.J. was supported by NIH K08HL107451. This work was funded by grants from the NIH (R01DK081457) V.K.M. is an Investigator of the Howard Hughes Medical Institute. NR 46 TC 68 Z9 69 U1 4 U2 28 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 JAN PY 2014 VL 5 AR 3128 DI 10.1038/ncomms4128 PG 10 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA AA4RS UT WOS:000331084400037 PM 24451681 ER PT J AU Galovski, TE Elwood, LS Blain, LM Resick, PA AF Galovski, Tara E. Elwood, Lisa S. Blain, Leah M. Resick, Patricia A. TI Changes in Anger in Relationship to Responsivity to PTSD Treatment SO PSYCHOLOGICAL TRAUMA-THEORY RESEARCH PRACTICE AND POLICY LA English DT Article DE anger; PTSD; psychotherapy outcomes; cognitive therapy; sexual assault ID POSTTRAUMATIC-STRESS-DISORDER; EXPOSURE THERAPY; CRIME VICTIMS; METAANALYSIS; HOSTILITY; EFFICACY; TRIAL; SCALE; FEAR AB This study examined the clinical course of different dimensions of anger and their relationship to change in posttraumatic stress disorder (PTSD) in a sample of 139 female survivors of interpersonal violence suffering from PTSD. Specifically, this study evaluated differences in the rates of change in anger dimensions by responsivity to treatment status (responders, nonresponders, and dropouts). Responders and nonresponders did not differ in rate of change on state anger and anger directed inward, suggesting that treatment led to improvements in these dimensions of anger regardless of final PTSD diagnosis. Responders did evidence statistically significantly more change in trait anger and control over one's anger than did the nonresponders, suggesting that changes in these dimensions of anger may be related to recovery from PTSD. Individuals who terminated therapy prematurely did not experience the same gains in state anger, trait anger, or anger-in as those who completed treatment. Differences in rates of change (linear vs. quadratic growth patterns), particularly with respect to continued improvement in anger following treatment completion, are discussed. C1 [Galovski, Tara E.; Elwood, Lisa S.; Blain, Leah M.] Univ Missouri, Dept Psychol, St Louis, MO 63121 USA. [Resick, Patricia A.] Vet Affairs Boston Healthcare Syst, Natl Ctr PTSD, Boston, MA USA. [Resick, Patricia A.] Boston Univ, Boston, MA 02215 USA. RP Galovski, TE (reprint author), Univ Missouri, Ctr Trauma Recovery, 1 Univ Blvd, St Louis, MO 63121 USA. EM galovskit@umsl.edu FU NIMH NIH HHS [R01 MH051509] NR 35 TC 2 Z9 2 U1 6 U2 13 PU EDUCATIONAL PUBLISHING FOUNDATION-AMERICAN PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST, NE, WASHINGTON, DC 20002-4242 USA SN 1942-9681 EI 1942-969X J9 PSYCHOL TRAUMA-US JI Psychol. Trauma PD JAN PY 2014 VL 6 IS 1 BP 56 EP 64 DI 10.1037/a0031364 PG 9 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA AA1HN UT WOS:000330847300007 PM 25045416 ER PT J AU Stappenbeck, CA Hellmuth, JC Simpson, T Jakupcak, M AF Stappenbeck, Cynthia A. Hellmuth, Julianne C. Simpson, Tracy Jakupcak, Matthew TI The Effects of Alcohol Problems, PTSD, and Combat Exposure on Nonphysical and Physical Aggression Among Iraq and Afghanistan War Veterans SO PSYCHOLOGICAL TRAUMA-THEORY RESEARCH PRACTICE AND POLICY LA English DT Article DE Iraq and Afghanistan war veterans; aggression; PTSD; combat exposure; alcohol problems ID POSTTRAUMATIC-STRESS-DISORDER; INTIMATE PARTNER VIOLENCE; MILITARY VETERANS; VIETNAM VETERANS; UNITED-STATES; INTERPERSONAL VIOLENCE; CONCEPTUAL-FRAMEWORK; HISPANIC COUPLES; CONDUCT PROBLEMS; PERPETRATION AB Aggression among combat veterans is of great concern. Although some studies have found an association between combat exposure and aggressive behavior following deployment, others conclude that aggression is more strongly associated with symptoms of posttraumatic stress disorder (PTSD), and that alcohol misuse may influence this association. Many of these studies have assessed aggression as a single construct, whereas the current study explored both nonphysical aggression only and physical aggression in a sample of Iraq and Afghanistan war veterans (N = 337; 91% male). We found that alcohol problems interacted with PTSD symptom severity to predict nonphysical aggression only. At low levels of PTSD symptoms, veterans with alcohol problems were more likely to perpetrate nonphysical aggression only, as compared with no aggression, than veterans without an alcohol problem. There was no difference in the likelihood of nonphysical aggression only between those with and without alcohol problems at high levels of PTSD symptoms. The likelihood of nonphysical aggression only, as compared with no aggression, was also greater among younger veterans. Greater combat exposure and PTSD symptom severity were associated with an increased likelihood of perpetrating physical aggression, as compared with no aggression. Ethnic minority status and younger age were also associated with physical aggression, as compared with no aggression. Findings suggest that a more detailed assessment of veterans' aggressive behavior, as well as their alcohol problems and PTSD symptoms, by researchers and clinicians is needed in order to determine how best to intervene. C1 [Stappenbeck, Cynthia A.; Hellmuth, Julianne C.; Simpson, Tracy; Jakupcak, Matthew] VA Puget Sound Hlth Care Syst, Seattle Div, Seattle, WA USA. [Stappenbeck, Cynthia A.; Simpson, Tracy; Jakupcak, Matthew] Univ Washington, Dept Psychiat & Behav Sci, Seattle, WA 98105 USA. RP Stappenbeck, CA (reprint author), Univ Washington, Dept Psychiat & Behav Sci, 1107 NE 45th St Suite 201, Seattle, WA 98105 USA. EM cstappen@uw.edu FU NIDA NIH HHS [T32 DA019426] NR 66 TC 6 Z9 6 U1 3 U2 13 PU EDUCATIONAL PUBLISHING FOUNDATION-AMERICAN PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST, NE, WASHINGTON, DC 20002-4242 USA SN 1942-9681 EI 1942-969X J9 PSYCHOL TRAUMA-US JI Psychol. Trauma PD JAN PY 2014 VL 6 IS 1 BP 65 EP 72 DI 10.1037/a0031468 PG 8 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA AA1HN UT WOS:000330847300008 PM 25225593 ER PT J AU Jakupcak, M Blais, RK Grossbard, J Garcia, H Okiishi, J AF Jakupcak, Matthew Blais, Rebecca K. Grossbard, Joel Garcia, Hector Okiishi, John TI "Toughness" in Association With Mental Health Symptoms Among Iraq and Afghanistan War Veterans Seeking Veterans Affairs Health Care SO PSYCHOLOGY OF MEN & MASCULINITY LA English DT Article DE Iraq/Afghanistan Veterans; emotional toughness; gender norms ID HELP-SEEKING; SELF-REPORT; MASCULINITY; COMBAT; PTSD; STRESS; NORMS AB The association between endorsement of emotional "toughness" (i.e., extreme self-reliance and the suppression of outward displays of emotional distress) and likelihood for screening positive for mental health conditions was examined in a male sample of 198 Iraq and Afghanistan veterans presenting for postdeployment Veteran Affairs health care. After accounting for relevant covariates, veterans endorsing higher levels of emotional toughness were more likely to screen positive for posttraumatic stress disorder and depression. There was also a nonsignificant trend (p = .08) associated with a positive relationship between toughness and likelihood of self-reported alcohol abuse. Results are discussed in terms of identifying and addressing toughness norms among returning veterans to promote effective use of mental health services. C1 [Jakupcak, Matthew; Blais, Rebecca K.; Grossbard, Joel] Vet Affairs Puget Sound Hlth Care Syst, Seattle Div, Seattle, WA USA. [Jakupcak, Matthew] Univ Washington, Dept Psychiat & Behav Sci, Seattle, WA 98195 USA. [Blais, Rebecca K.] Univ Utah, Dept Psychol, Salt Lake City, UT 84112 USA. [Grossbard, Joel] Univ Washington, Dept Psychiat & Behav Sci, Seattle, WA 98195 USA. [Garcia, Hector] South Texas Vet Hlth Care Syst, San Antonio, TX USA. [Garcia, Hector] Univ Texas Hlth Sci Ctr San Antonio, Dept Psychiat, San Antonio, TX USA. [Okiishi, John] Joint Base Lewis McCord, Tacoma, WA USA. RP Jakupcak, M (reprint author), VA Puget Sound Hlth Care Syst, Deployment Hlth Clin, 1660 South Columbia Way, Seattle, WA 98108 USA. EM matthew.jakupcak@va.gov NR 29 TC 5 Z9 5 U1 0 U2 2 PU EDUCATIONAL PUBLISHING FOUNDATION-AMERICAN PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST, NE, WASHINGTON, DC 20002-4242 USA SN 1524-9220 EI 1939-151X J9 PSYCHOL MEN MASCULIN JI Psychol. Men Masculinity PD JAN PY 2014 VL 15 IS 1 BP 100 EP 104 DI 10.1037/a0031508 PG 5 WC Psychology, Social SC Psychology GA AA1GW UT WOS:000330845600013 ER PT J AU McLoud, TC AF McLoud, Theresa C. TI Lung cancer screening: current status SO RADIOLOGIA MEDICA LA English DT Editorial Material ID DOSE SPIRAL CT; BASE-LINE; TRIAL; DESIGN; PREVALENCE C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA 02114 USA. RP McLoud, TC (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, 55 Fruit St, Boston, MA 02114 USA. EM tmcloud@partners.org NR 19 TC 0 Z9 0 U1 0 U2 2 PU SPRINGER-VERLAG ITALIA SRL PI MILAN PA VIA DECEMBRIO, 28, MILAN, 20137, ITALY SN 0033-8362 EI 1826-6983 J9 RADIOL MED JI Radiol. Med. PD JAN PY 2014 VL 119 IS 1 SI SI BP 1 EP 3 DI 10.1007/s11547-013-0313-8 PG 3 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA AA3BG UT WOS:000330967300001 PM 24263456 ER PT J AU Golberg, A Vitkin, E Linshiz, G Khan, SA Hillson, NJ Yakhini, Z Yarmush, ML AF Golberg, Alexander Vitkin, Edward Linshiz, Gregory Khan, Sabaa Ahmad Hillson, Nathan J. Yakhini, Zohar Yarmush, Martin L. TI Proposed design of distributed macroalgal biorefineries: thermodynamics, bioconversion technology, and sustainability implications for developing economies SO BIOFUELS BIOPRODUCTS & BIOREFINING-BIOFPR LA English DT Article DE biorefinery design; thermodynamic modeling; biorefinery optimization; fermentation modeling; metabolic modeling; biofuel sustainability; biofuel policy ID SEAWEED ULVA-LACTUCA; METABOLIC NETWORK; LIGNOCELLULOSIC BIOMASS; FUNCTIONAL-PROPERTIES; MICROBIAL-PRODUCTION; CONSTRUCTAL DESIGN; ESCHERICHIA-COLI; RECONSTRUCTION; BIOENERGY; BIOFUELS AB Biomass to fuel programs are under research and development worldwide. The largest biomass programs are underway in industrialized countries. In the coming decades, however, developing countries will be responsible for the major increase in transportation fuel demand. Although the lack of existing large-scale infrastructure and primary resources preclude oil refining in developing countries, this provides an opportunity for the rapid implementation of small-scale distributed biorefineries to serve multiple communities locally. The principles for biorefinery design, however, are still in their infancy. This review sets a precedent in combining thermodynamic, metabolic, and sustainability analyses for biorefinery design. We exemplify this approach through the design and optimization of a marine biorefinery for an average town in rural India. In this combined model, we include sustainability and legislation factors, intensive macro algae Ulva farming, and metabolic modeling of the biological two-step conversion of Ulva feedstock by a yeast (Saccharomyces cerevisiae), and then by a bacterium (Escherichia coli), into bioethanol. We hope that the model presented here will be useful in considering practical aspects of biorefinery design. (c) 2013 Society of Chemical Industry and John Wiley & Sons, Ltd C1 [Golberg, Alexander; Yarmush, Martin L.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Engn Med, Boston, MA 02114 USA. [Vitkin, Edward; Yakhini, Zohar] Technion Israel Inst Technol, Dept Comp Sci, IL-32000 Haifa, Israel. [Linshiz, Gregory] Joint BioEnergy Inst, Emeryville, CA USA. [Linshiz, Gregory; Hillson, Nathan J.] Lawrence Berkeley Natl Labs, Berkeley, CA USA. [Khan, Sabaa Ahmad] McGill Univ, Fac Law, Montreal, PQ, Canada. [Hillson, Nathan J.] Joint BioEnergy Inst, Berkeley Lab, Emeryville, CA USA. [Hillson, Nathan J.] DOE Joint Genome Inst, Walnut Creek, CA USA. [Yakhini, Zohar] Technion Israel Inst Technol, Agilent Labs, Haifa, Israel. [Yarmush, Martin L.] Rutgers State Univ, Pisacataway, NJ USA. RP Yarmush, ML (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Engn Med,Dept Surg, Boston, MA 02114 USA. EM ireis@sbi.org OI Golberg, Alexander/0000-0001-8782-8879 FU MGH Fund for Medical Discovery; Technion; Office of Science, Office of Biological and Environmental Research of the U.S. Department of Energy [DE-AC02-05CH11231] FX AG acknowledges MGH Fund for Medical Discovery for an ECOR postdoctoral fellowship. The Technion's generous support for EV's work is also acknowledged. The work conducted by the Joint BioEnergy Institute and the U.S. Department of Energy Joint Genome Institute was supported by the Office of Science, Office of Biological and Environmental Research of the U.S. Department of Energy (Contract No. DE-AC02-05CH11231). NR 78 TC 12 Z9 12 U1 3 U2 23 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1932-104X EI 1932-1031 J9 BIOFUEL BIOPROD BIOR JI Biofuels Bioprod. Biorefining PD JAN PY 2014 VL 8 IS 1 BP 67 EP 82 DI 10.1002/bbb.1438 PG 16 WC Biotechnology & Applied Microbiology; Energy & Fuels SC Biotechnology & Applied Microbiology; Energy & Fuels GA AA0QK UT WOS:000330801200008 ER PT J AU Buyyounouski, MK Viswanathan, AN Prestidge, BR AF Buyyounouski, Mark K. Viswanathan, Akila N. Prestidge, Bradley R. CA Amer Brachytherapy Soc Comm Eviden TI Examining the evidence in pursuit of the highest possible brachytherapy standards SO BRACHYTHERAPY LA English DT Editorial Material ID AMERICAN BRACHYTHERAPY; CONSENSUS STATEMENT; GUIDELINES; SOCIETY; QUALITY C1 [Buyyounouski, Mark K.] Stanford Univ, Dept Radiat Oncol, Stanford, CA 94305 USA. [Viswanathan, Akila N.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dana Farber Canc Inst,Dept Radiat Oncol, Boston, MA 02115 USA. [Prestidge, Bradley R.] Mem Hermann Southwest Hosp, Dept Radiat Therapy, Houston, TX USA. RP Buyyounouski, MK (reprint author), Stanford Univ, Dept Radiat Oncol, Stanford, CA 94305 USA. EM mark.buyyounouski@stanford.edu NR 13 TC 0 Z9 0 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1538-4721 EI 1873-1449 J9 BRACHYTHERAPY JI Brachytherapy PD JAN-FEB PY 2014 VL 13 IS 1 BP 15 EP 16 DI 10.1016/j.brachy.2013.07.003 PG 2 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA AA2IY UT WOS:000330919500002 PM 24055009 ER PT J AU Hsu, ICJ Yamada, Y Assimos, DG D'Amico, AV Davis, BJ Frank, SJ Gottschalk, AR Gustafson, GS McLaughlin, PW Nguyen, PL Rosenthal, SA Taira, A Vapiwala, N Merrick, G AF Hsu, I-Chow Joe Yamada, Yoshiya Assimos, Dean G. D'Amico, Anthony V. Davis, Brian J. Frank, Steven J. Gottschalk, Alexander R. Gustafson, Gary S. McLaughlin, Patrick W. Nguyen, Paul L. Rosenthal, Seth A. Taira, Al V. Vapiwala, Neha Merrick, Gregory TI ACR Appropriateness Criteria high-dose-rate brachytherapy for prostate cancer SO BRACHYTHERAPY LA English DT Article DE Appropriateness criteria; Prostate cancer; HDR; Brachytherapy ID RATE INTERSTITIAL BRACHYTHERAPY; RATE AFTERLOADING BRACHYTHERAPY; EXTERNAL-BEAM RADIOTHERAPY; PHASE-II; SALVAGE BRACHYTHERAPY; RADIATION-THERAPY; CATHETER MOVEMENT; MONOTHERAPY; FRACTIONS; TOXICITY AB PURPOSE: High-dose-rate (HDR) brachytherapy plays a potential curative role in the treatment of prostate cancer. An expert panel was convened to review the recent literature and reach a consensus on its appropriate clinical applications. METHODS AND MATERIALS: 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. RESULTS: A summary of HDR brachytherapy's clinical applications and recent literature review was completed. Three clinical variants were developed to address common HDR dose, fractionations, and indications for its use in definitive therapy for primary and local recurrent prostate cancer. The panel reached a consensus on the specific treatment approaches with numerical rating and commentary. CONCLUSIONS: In combining available medical literature and expert opinion, this manuscript may serve as an aid for other practitioners in the appropriate application of HDR brachytherapy for prostate cancer. (C) 2014 American College of Radiology. Published by Elsevier Inc. on behalf of American Brachytherapy Society. All rights reserved. C1 [Hsu, I-Chow Joe; Gottschalk, Alexander R.] Univ Calif San Francisco, Dept Radiat Oncol, San Francisco, CA USA. [Yamada, Yoshiya] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. [Assimos, Dean G.] Univ Alabama Birmingham, Sch Med, Amer Urol Assoc, Birmingham, AL USA. [D'Amico, Anthony V.] Amer Soc Clin Oncol, Joint Ctr Radiat Therapy, Boston, MA USA. [Davis, Brian J.] Mayo Clin, Rochester, MN USA. [Frank, Steven J.] Univ Texas Houston, MD Anderson Canc Ctr, Houston, TX 77030 USA. [Gustafson, Gary S.] William Beaumont Hosp, Troy, MI USA. [McLaughlin, Patrick W.] Univ Michigan, Novi, MI USA. [Nguyen, Paul L.] Brigham & Womens Hosp, Dana Farber Canc Inst, Boston, MA 02115 USA. [Rosenthal, Seth A.] Radiol Associates Sacramento, Sacramento, CA USA. [Rosenthal, Seth A.] Sutter Canc Ctr, Sacramento, CA USA. [Taira, Al V.] Mt View Oncol, Westen Radiat Oncol, Mountain View, CA USA. [Vapiwala, Neha] Univ Penn, Med Ctr, Philadelphia, PA 19104 USA. [Merrick, Gregory] Schiffler Canc Ctr, Wheeling, WV USA. [Merrick, Gregory] Wheeling Jesuit Univ, Wheeling, WV USA. RP Hsu, ICJ (reprint author), Amer Coll Radiol, 1891 Preston White Dr, Reston, VA 20191 USA. EM IHsu@radonc.ucsf.edu OI Davis, Brian/0000-0002-8288-1096 NR 34 TC 5 Z9 5 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1538-4721 EI 1873-1449 J9 BRACHYTHERAPY JI Brachytherapy PD JAN-FEB PY 2014 VL 13 IS 1 BP 27 EP 31 DI 10.1016/j.brachy.2013.11.007 PG 5 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA AA2IY UT WOS:000330919500005 PM 24368283 ER PT J AU Damato, AL Cormack, RA Viswanathan, AN AF Damato, Antonio L. Cormack, Robert A. Viswanathan, Akila N. TI Characterization of implant displacement and deformation in gynecologic interstitial brachytherapy SO BRACHYTHERAPY LA English DT Article DE Brachytherapy; Gynecologic; Interstitial; Displacement; Uncertainty; Catheter ID DOSE-RATE BRACHYTHERAPY; PROSTATE-CANCER; CATHETER MOVEMENT; HDR BRACHYTHERAPY; MALIGNANCIES; FRACTIONS AB PURPOSE: To determine the uncertainties in implant position during multifraction gynecologic interstitial brachytherapy, we analyzed the interfraction displacements and deformations of gynecologic interstitial implants. METHODS AND MATERIALS: Fourteen gynecologic patients treated with multifraction high-dose-rate interstitial brachytherapy received two CT scans each at the time of implantation and 48-72 h later. Rigid fusions on the pubic symphysis were performed. This analysis included catheter shifts in the cranial (CR), caudal (CA), anterior, posterior, left, and right directions; template shifts; the change in the catheter length measured along the path from catheter tip to catheter connector (offset); the change in relative distances between catheters (deformations); and changes in rectum and bladder D-2cc and tumor D-90. RESULTS: Of the 198 catheters analyzed, the number of catheter shifts (%) and mean +/- standard deviation were 43% CA (5.0 +/- 2.0 mm), 22% CR (7.9 +/- 4.0 mm), 14% anterior (6.3 +/- 2.1 mm), 48% posterior (8.7 +/- 3.1 mm), 7% left (4.8 +/- 0.4 mm), and 9% right (5.4 +/- 0.9 mm). Catheter offsets were 3% CA (7.2 +/- 6.3 mm) and 11% CR (6.1 +/- 2.6 mm). Template shifts were 43% CA (5.2 +/- 1.6 mm) and 14% CR (6.6 +/- 4.0 mm). Deformations were 10 shrinkages (4.7 +/- 0.9 mm) and 32 expansions (4.7 +/- 0.5 mm). Dosimetric changes were 5.2% +/- 10.8% for rectum D-2cc -1.1% +/- 18.5% for bladder D-2cc, and -5.1% +/- 6.7% for tumor D-90. CONCLUSIONS: On average, less than 1 cm displacements and deformations of the implant occurred over the course of treatment. Proper quality assurance methodologies should be in place to detect shifts that can potentially result in inadvertent insertion into normal tissue. (C) 2014 American Brachytherapy Society. Published by Elsevier Inc. All rights reserved. C1 Brigham & Womens Hosp, Dept Radiat Oncol, Boston, MA 02115 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. RP Damato, AL (reprint author), Brigham & Womens Hosp, Dana Farber Canc Inst, Dept Radiat Oncol, 75 Francis St,ASB1-L2, Boston, MA 02115 USA. EM adamato@lroc.harvard.edu OI Cormack, Robert/0000-0001-5553-9984 NR 21 TC 11 Z9 11 U1 2 U2 7 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1538-4721 EI 1873-1449 J9 BRACHYTHERAPY JI Brachytherapy PD JAN-FEB PY 2014 VL 13 IS 1 BP 100 EP 109 DI 10.1016/j.brachy.2013.09.010 PG 10 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA AA2IY UT WOS:000330919500017 PM 24269145 ER PT J AU Forde, CT Karri, SK Young, AMH Ogilvy, CS AF Forde, Cillian T. Karri, Surya K. Young, Adam M. H. Ogilvy, Christopher S. TI Predictive markers in traumatic brain injury: opportunities for a serum biosignature SO BRITISH JOURNAL OF NEUROSURGERY LA English DT Review DE biomarker; brain; traumatic; injury ID NEURON-SPECIFIC ENOLASE; SPECTRIN BREAKDOWN PRODUCTS; FIBRILLARY ACIDIC PROTEIN; SEVERE HEAD-INJURY; INTRACRANIAL-PRESSURE; CEREBROSPINAL-FLUID; S100B; CHILDREN; BIOMARKERS; DIAGNOSIS AB The current diagnostic criteria for traumatic brain injury (TBI) are heavily reliant on an accurate clinical history of events. Diagnosis of mild injury relies on one or more of the following: confusion or disorientation, loss of consciousness (LOC) for 30 min or less, post-ictus amnesia for less than 24 h and/or other transient neurological abnormalities and a Glasgow Coma Score (GCS). Given the nature of the condition it is obvious that significant clinical challenges remain to identify in the cases of mild TBI, and additionally to grade more severe forms so that appropriate treatment is received. The lack of clinically useful biomarkers in the serum of TBI patients is a significant barrier to improving their outlook. Discovery of such markers would aid the timely diagnosis of novel and recurrent disease in a minimally invasive manner. A PubMed search was performed to identify studies reporting serum biomarkers in traumatic brain injury. Details regarding the biomarkers analysed, specificity, indications for outcome and statistical significance were recorded. A total of 40 manuscripts reporting 11 biomarkers were identified in the literature. All but a few studies reported statistically significant differences in biomarker expression between groups. We conclude that serum biomarkers of TBI are an effective means for investigating the condition. However, the lack of novel markers identified in this mass of studies highlights the need to adopt new measure of biomarker identification. C1 [Forde, Cillian T.; Young, Adam M. H.] Univ Cambridge, Addenbrookes Hosp, Sch Clin Med, Cambridge CB2 0SP, England. [Karri, Surya K.; Young, Adam M. H.; Ogilvy, Christopher S.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Neurosurg, Boston, MA USA. RP Forde, CT (reprint author), Univ Cambridge, Addenbrookes Hosp, Sch Clin Med, Hills Rd, Cambridge CB2 0SP, England. EM cf337@cam.ac.uk NR 52 TC 15 Z9 16 U1 2 U2 19 PU INFORMA HEALTHCARE PI LONDON PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND SN 0268-8697 EI 1360-046X J9 BRIT J NEUROSURG JI Br. J. Neurosurg. PD JAN PY 2014 VL 28 IS 1 BP 8 EP 15 DI 10.3109/02688697.2013.815317 PG 8 WC Clinical Neurology; Surgery SC Neurosciences & Neurology; Surgery GA 304FB UT WOS:000330731400003 PM 23855389 ER PT J AU Lee, KM Yeh, HD Zhao, GP Wei, LL O'Connor, M Stott, RT Soohoo, J Dunussi, K Fiorina, P Deng, SP Markmann, JF Kim, JI AF Lee, Kang Mi Yeh, Heidi Zhao, Gaoping Wei, Lingling O'Connor, Matthew Stott, Ryan T. Soohoo, Julie Dunussi, Kyri Fiorina, Paolo Deng, Shaoping Markmann, James F. Kim, James I. TI B-Cell Depletion Improves Islet Allograft Survival With Anti-CD45RB SO CELL TRANSPLANTATION LA English DT Article DE B-cells; Anti-CD45RB; Anti-CD22; Islet transplantation; Tolerance ID INCOMPATIBLE KIDNEY-TRANSPLANTATION; ANTIGEN-PRESENTING CELLS; ACUTE HUMORAL REJECTION; MEMORY T-CELLS; RITUXIMAB THERAPY; IN-VIVO; OPERATIONAL TOLERANCE; MEDIATED REJECTION; GRAFT ACCEPTANCE; LIVER AB A short course of anti-CD45RB leads to long-term islet allograft survival and donor-specific tolerance in approximately half of immunocompetent mice. We have previously demonstrated that anti-CD45RB antibodymediated tolerance requires B-cells for cardiac allograft survival. We therefore asked whether B-cells were also required for anti-CD45RB antibody-mediated survival of islets. Unexpectedly, we found that nearly 100% of islet allografts survive long term in B-cell-deficient mice. Similarly, B-cell depletion by anti-CD22/cal augmented anti-CD45RB-mediated tolerance when administered pretransplant, although it had no effect on tolerance induction when administered posttransplant. Our results demonstrate that the role of B-cells in promoting tolerance with anti-CD45RB is graft specific, promoting tolerance in cardiac grafts but resisting tolerance in islet transplantation. These findings may help elucidate the varied action of B-cells in promoting tolerance versus rejection. C1 [Lee, Kang Mi; Yeh, Heidi; Zhao, Gaoping; Wei, Lingling; O'Connor, Matthew; Stott, Ryan T.; Soohoo, Julie; Deng, Shaoping; Markmann, James F.; Kim, James I.] Harvard Univ, Sch Med, Dept Surg, Massachusetts Gen Hosp,Transplantat Unit, Boston, MA 02115 USA. [Zhao, Gaoping; Wei, Lingling; Deng, Shaoping] Sichuan Prov Peoples Hosp, Dept Surg, Chengdu, Sichuan Provinc, Peoples R China. [Zhao, Gaoping; Wei, Lingling; Deng, Shaoping] Sichuan Acad Med Sci, Chengdu, Sichuan Provinc, Peoples R China. [Dunussi, Kyri; Fiorina, Paolo] Harvard Univ, Sch Med, Childrens Hosp Boston, Transplantat Res Ctr, Boston, MA USA. [Dunussi, Kyri] Pfizer Res, Cambridge, MA USA. [Fiorina, Paolo] Ist Sci San Raffaele, I-20132 Milan, Italy. RP Markmann, JF (reprint author), Massachusetts Gen Hosp, 55 Fruit St 5 White, Boston, MA 02114 USA. EM jmarkmann@partners.org FU NIH [RO1AI057851-05, K01DK079207, 5T32AI7529, 5K08DK094965-02] FX This work was supported in part by NIH grants RO1AI057851-05 (J.F.M.), K01DK079207 (J.I.K.), 5T32AI7529 (K.M.L.), and 5K08DK094965-02 (H.Y.). The authors declare no conflict of interest. NR 33 TC 3 Z9 3 U1 0 U2 4 PU COGNIZANT COMMUNICATION CORP PI PUTNAM VALLEY PA 18 PEEKSKILL HOLLOW RD, PO BOX 37, PUTNAM VALLEY, NY 10579 USA SN 0963-6897 EI 1555-3892 J9 CELL TRANSPLANT JI Cell Transplant. PY 2014 VL 23 IS 1 BP 51 EP 58 DI 10.3727/096368912X658962 PG 8 WC Cell & Tissue Engineering; Medicine, Research & Experimental; Transplantation SC Cell Biology; Research & Experimental Medicine; Transplantation GA 302KV UT WOS:000330604300005 PM 23192154 ER PT J AU Lee, HY Wei, D Loeken, MR AF Lee, Hyung-yul Wei, Dan Loeken, Mary R. TI Lack of metformin effect on mouse embryo AMPK activity: implications for metformin treatment during pregnancy SO DIABETES-METABOLISM RESEARCH AND REVIEWS LA English DT Article DE metformin; AMP kinase; diabetic pregnancy; diabetic embryopathy; oral hypoglycaemics; Pax3 ID POLYCYSTIC-OVARY-SYNDROME; ACTIVATED PROTEIN-KINASE; TRANSPORTER 3 OCT3/SLC22A3; NEURAL-TUBE DEFECTS; DIABETIC PREGNANCY; GENE-EXPRESSION; STEM-CELLS; WOMEN; PLACENTA; MODEL AB BackgroundAdenosine monophosphate-activated protein kinase (AMPK) is stimulated in embryos during diabetic pregnancy by maternal hyperglycaemia-induced embryo oxidative stress. Stimulation of AMPK disrupts embryo gene expression and causes neural tube defects. Metformin, which may be taken during early pregnancy, has been reported to stimulate AMPK activity. Thus, the benefits of improved glycaemic control could be offset by stimulated embryo AMPK activity. Here, we investigated whether metformin can stimulate AMPK activity in mouse embryos and can adversely affect embryo gene expression and neural tube defects. MethodsPregnant nondiabetic mice were administered metformin beginning on the first day of pregnancy. Activation of maternal and embryo AMPK [phospho-AMPK (Thr172) relative to total AMPK], expression of Pax3, a gene required for neural tube closure, and neural tube defects were studied. Mouse embryonic stem cells were used as a cell culture model of embryonic neuroepithelium to study metformin effects on AMPK and Pax3 expression. ResultsMetformin had no effect on AMPK in embryos or maternal skeletal muscle but increased activated AMPK in maternal liver. Metformin did not inhibit Pax3 expression or increase neural tube defects. However, metformin increased activated AMPK and inhibited Pax3 expression by mouse embryonic stem cells. Mate1/Slc47a1 and Oct3/Slc22a, which encode metformin transporters, were expressed at barely detectable levels by embryos. ConclusionsAlthough metformin can have effects associated with diabetic embryopathy in vitro, the lack of effects on mouse embryos in vivo may be due to lack of metformin transporters and indicates that the benefits of metformin on glycaemic control are not counteracted by stimulation of embryo AMPK activity and consequent embryopathy. Copyright (c) 2013 John Wiley & Sons, Ltd. C1 [Lee, Hyung-yul; Wei, Dan; Loeken, Mary R.] Joslin Diabet Ctr, Sect Islet Cell & Regenerat Biol, Boston, MA 02215 USA. [Lee, Hyung-yul; Wei, Dan; Loeken, Mary R.] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. RP Loeken, MR (reprint author), Joslin Diabet Ctr, Sect Islet Cell & Regenerat Biol, One Pl, Boston, MA 02215 USA. EM mary.loeken@joslin.harvard.edu OI Loeken, Mary/0000-0002-8056-9816 FU Diabetes Endocrine Research Center from the National Institute of Diabetes and Digestive and Kidney Diseases [P30DK036836]; [RO1 DK58300] FX We are grateful to Dr Florence Brown (Joslin Diabetes Center) for the helpful discussion and critical review of the manuscript. We appreciate the help of Eric B. Taylor from the Goodyear lab (Joslin Diabetes Center) for the advice in the assay of AMPK. We are thankful to Kaitlyn Sanders for assistance with mouse mating and to Jin Hyuk Jung for assistance with real-time PCR (members of the Loeken lab, Joslin Diabetes Center). This project was supported by RO1 DK58300 (to MRL) and was assisted by core facilities supported by a Diabetes Endocrine Research Center grant, P30DK036836, from the National Institute of Diabetes and Digestive and Kidney Diseases. NR 34 TC 6 Z9 6 U1 0 U2 6 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1520-7560 J9 DIABETES-METAB RES JI Diabetes-Metab. Res. Rev. PD JAN PY 2014 VL 30 IS 1 BP 23 EP 30 DI 10.1002/dmrr.2451 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA AA0IO UT WOS:000330779000004 PM 23983188 ER PT J AU Kaunitz, JD AF Kaunitz, Jonathan D. TI Introduction to the 80th Anniversary Issue SO DIGESTIVE DISEASES AND SCIENCES LA English DT Editorial Material C1 Univ Calif Los Angeles, David Geffen Sch Med, Greater Los Angeles VA Hlth Care Syst, Los Angeles, CA 90095 USA. RP Kaunitz, JD (reprint author), Univ Calif Los Angeles, David Geffen Sch Med, Greater Los Angeles VA Hlth Care Syst, Los Angeles, CA 90095 USA. EM Jonathan.Kaunitz@va.gov NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0163-2116 EI 1573-2568 J9 DIGEST DIS SCI JI Dig. Dis. Sci. PD JAN PY 2014 VL 59 IS 1 BP 1 EP 1 DI 10.1007/s10620-013-3009-y PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 302ES UT WOS:000330585500001 ER PT J AU Wang, HH Xie, NN Li, QY Hu, YQ Ren, JL Guleng, B AF Wang, Huan-Huan Xie, Na-Na Li, Qi-Yuan Hu, Yi-Qun Ren, Jian-Lin Guleng, Bayasi TI Exome Sequencing Revealed Novel Germline Mutations in Chinese Peutz-Jeghers Syndrome Patients SO DIGESTIVE DISEASES AND SCIENCES LA English DT Article DE Peutz-Jeghers syndrome; Whole-exome sequencing; Causative mutation; Candidate gene ID HAMARTOMATOUS POLYPOSIS SYNDROMES; COLORECTAL-CANCER; LKB1/STK11 GENE; INCREASED RISK; CELL-DEATH; VARIANTS; FAMILIES; KINASE; LKB1; MAP AB Background and Aims Peutz-Jeghers Syndrome (PJS) is an autosomal dominant disorder which predisposes to the development of various cancers. Germline mutation in the serine/threonine kinase 11 gene (STK11) is known as one of the major causes of PJS. However, a notable proportion of PJS samples do not carry any mutation in STK11, suggesting possible genetic heterogeneity in the disease and the existence of other causative variants. In order to identify other germline variants in the coding regions of the genome that are associated with PJS, we performed exome sequencing in three Chinese individuals with PJS and identified 16 common germline variants (12 protein-coding including STK11, 4 in pre-microRNAs). We further validated protein-coding variants in six PJS individuals (three with wild-type STK11) and predicted the functional impact. As result, we found that 7 coding variants are likely to have functional impacts. Especially, we identified 2 new germline variants which are represented in all six PJS samples and are independent of STK11 mutation. Our study provided an exomic view of PJS. The germline variants identified in our analysis may help to resolve the complex genetic background of the disease and thus lead to the discovery of novel causative variants of PJS. C1 [Wang, Huan-Huan; Xie, Na-Na; Hu, Yi-Qun; Ren, Jian-Lin; Guleng, Bayasi] Xiamen Univ, Zhongshan Hosp, Dept Gastroenterol, Xiamen 361004, Fujian, Peoples R China. [Li, Qi-Yuan; Guleng, Bayasi] Xiamen Univ, Coll Med, Fac Clin Med, Xiamen 361005, Fujian, Peoples R China. [Li, Qi-Yuan] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. RP Ren, JL (reprint author), Xiamen Univ, Zhongshan Hosp, Dept Gastroenterol, 201 Hubin South Rd, Xiamen 361004, Fujian, Peoples R China. EM renjianl@xmu.edu.cn; bayasi8@gmail.com FU National Natural Science Foundation of China [81370505, 81072013, 91229201]; Fundamental Research Funds for the Central Universities in China [2010111082]; Foundations of Health Bureau of Xiamen in China [3502Z200940010] FX We are grateful to all the patients and their family members for their generous participation in this work. This work was supported by National Natural Science Foundation of China (No. 81370505, 81072013 & 91229201), Fundamental Research Funds for the Central Universities in China (No. 2010111082) and Foundations of Health Bureau of Xiamen in China (No. 3502Z200940010). NR 48 TC 5 Z9 5 U1 3 U2 7 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0163-2116 EI 1573-2568 J9 DIGEST DIS SCI JI Dig. Dis. Sci. PD JAN PY 2014 VL 59 IS 1 BP 64 EP 71 DI 10.1007/s10620-013-2875-7 PG 8 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 302ES UT WOS:000330585500015 PM 24154639 ER PT J AU Johnson, KB Campbell, EJ Chi, H Zheng, H King, LY Wu, Y DeLemos, A Hurairah, A Corey, K Richter, JM Chung, RT AF Johnson, Kara B. Campbell, Emily J. Chi, Heng Zheng, Hui King, Lindsay Y. Wu, Ying DeLemos, Andrew Hurairah, Abu Corey, Kathleen Richter, James M. Chung, Raymond T. TI Advanced Disease, Diuretic Use, and Marital Status Predict Hospital Admissions in an Ambulatory Cirrhosis Cohort SO DIGESTIVE DISEASES AND SCIENCES LA English DT Article DE Liver cirrhosis; Ascites; Hospitalization; Quality Improvement ID LIVER-DISEASE; UNITED-STATES; ASCITES AB Hospital admissions in cirrhotic patients are a source of significant health care expenditure. Most studies to date have focused on readmissions in patients with decompensated cirrhosis. We sought to describe predictors of hospital admissions in an ambulatory cirrhosis cohort consisting of both compensated and decompensated patients to identify patients who could benefit from intensified outpatient chronic disease management. We performed a retrospective cohort study of 395 cirrhotic patients followed at an academic medical center liver clinic. Inclusion criteria were documented cirrhosis and longitudinal care at our center during 2006-2008. Patients were followed until December 2011, death, or liver transplantation. The primary outcomes were non-elective cirrhosis-related hospital admissions within 1 year and time to admission. The secondary outcome was 2-year cirrhosis-related mortality. The study was approved by the Partners Human Research Committee (protocol 2012P001912). Seventy-eight patients (19.7 %) had at least one cirrhosis-related hospital admission within 1 year. The following were significant predictors in the multivariable model: model for end-stage liver disease score a parts per thousand yen15 [OR 2.22, 95 % CI (1.21-4.07), p = 0.01], diagnosis of hepatocellular carcinoma [3.64 (1.42-9.35), 0.007], diuretic use [2.27 (1.23-4.17), 0.008], at least one cirrhosis-related admission during the baseline year [2.17 (1.21-3.89), 0.01], and being unmarried [1.92 (1.10-3.35), 0.02]. Advanced disease, diuretic use, and marital status were associated with cirrhosis-related hospital admissions in patients followed at an academic medical center liver clinic. Our findings suggest that patients with inadequately or overzealously treated ascites, as well as those with limited social supports, could benefit from intensified outpatient management. C1 [Johnson, Kara B.; Zheng, Hui] Harvard Univ, Sch Med, Boston, MA USA. [Johnson, Kara B.; Campbell, Emily J.; King, Lindsay Y.; Wu, Ying; DeLemos, Andrew; Corey, Kathleen; Richter, James M.; Chung, Raymond T.] Massachusetts Gen Hosp, Div Gastroenterol, Dept Med, Boston, MA 02114 USA. [Chi, Heng] Univ Med Ctr Rotterdam, Erasmus MC, Dept Gastroenterol & Hepatol, NL-3015 CE Rotterdam, Netherlands. [Zheng, Hui] Massachusetts Gen Hosp, Biostat Ctr, Boston, MA 02114 USA. [Hurairah, Abu] Mt Auburn Hosp, Dept Med, Cambridge, MA USA. RP Chung, RT (reprint author), Massachusetts Gen Hosp, Div Gastroenterol, Dept Med, 55 Fruit St, Boston, MA 02114 USA. EM kara_johnson@hms.harvard.edu; ejcampbell@partners.org; h.chi@erasmusmc.nl; hzheng1@partners.org; lyking@partners.org; dywu@partners.org; adelemos@partners.org; ahurairah@partners.org; kcorey@partners.org; jrichter@partners.org; rtchung@partners.org FU National Institutes of Health [NIH K24 DK078772, NIH T32 DK007191] FX The authors would like to thank Eric Braun for his technical assistance and Amy Nash for her administrative support. This study was funded in part by research grants from the National Institutes of Health (NIH K24 DK078772, NIH T32 DK007191). NR 14 TC 4 Z9 4 U1 0 U2 2 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0163-2116 EI 1573-2568 J9 DIGEST DIS SCI JI Dig. Dis. Sci. PD JAN PY 2014 VL 59 IS 1 BP 174 EP 182 DI 10.1007/s10620-013-2832-5 PG 9 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 302ES UT WOS:000330585500028 PM 23990035 ER PT J AU Tan, Y Tamayo, P Nakaya, H Pulendran, B Mesirov, JP Haining, WN AF Tan, Yan Tamayo, Pablo Nakaya, Helder Pulendran, Bali Mesirov, Jill P. Haining, W. Nicholas TI Gene signatures related to B-cell proliferation predict influenza vaccine-induced antibody response SO EUROPEAN JOURNAL OF IMMUNOLOGY LA English DT Article ID YELLOW-FEVER VACCINE; SYSTEMS VACCINOLOGY; T-CELLS; EXPRESSION; IMMUNITY; BIOLOGY; HUMANS C1 [Tan, Yan; Tamayo, Pablo; Mesirov, Jill P.; Haining, W. Nicholas] Broad Inst MIT & Harvard, Cambridge, MA 02142 USA. [Tan, Yan; Mesirov, Jill P.] Boston Univ, Bioinformat Program, Boston, MA 02215 USA. [Nakaya, Helder; Pulendran, Bali] Yerkes Natl Primate Ctr, Dept Pathol, Emory Vaccine Ctr, Atlanta, GA USA. [Haining, W. Nicholas] Harvard Univ, Sch Med, Dept Pediat Oncol, Dana Farber Canc Inst, Boston, MA 02115 USA. [Haining, W. Nicholas] Harvard Univ, Sch Med, Div Hematol Oncol, Childrens Hosp, Boston, MA 02115 USA. RP Haining, WN (reprint author), Harvard Univ, Sch Med, Dept Pediat Oncol, Dana Farber Canc Inst, 44 Binney St,Dana 640, Boston, MA 02115 USA. EM mesirov@broad.mit.edu; nicholas_haining@dfci.harvard.edu RI Nakaya, Helder/A-1397-2010 OI Nakaya, Helder/0000-0001-5297-9108 FU Infrastructure and Opportunity Fund Grant from the Human Immune Phenotyping Consortium; Bill and Melinda Gates Foundation [OPP50092]; [R01AI091493]; [U19AI090023] FX Supported by R01AI091493 to W.N.H.; U19AI090023 to B.P. and W.N.H, by an Infrastructure and Opportunity Fund Grant from the Human Immune Phenotyping Consortium to W.N.H. and J.M.; and by the Bill and Melinda Gates Foundation OPP50092 to J.M. NR 31 TC 25 Z9 25 U1 0 U2 8 PU WILEY PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0014-2980 EI 1521-4141 J9 EUR J IMMUNOL JI Eur. J. Immunol. PD JAN PY 2014 VL 44 IS 1 BP 285 EP 295 PG 11 WC Immunology SC Immunology GA AA0RA UT WOS:000330803400028 PM 24136404 ER PT J AU Oh, B Kim, J Lu, WD Rosenthal, D AF Oh, Byeongsang Kim, Jihun Lu, Weidong Rosenthal, David TI Anticancer Effect of Fucoidan in Combination with Tyrosine Kinase Inhibitor Lapatinib SO EVIDENCE-BASED COMPLEMENTARY AND ALTERNATIVE MEDICINE LA English DT Article ID ALTERNATIVE MEDICINE USE; BREAST-CANCER; CLADOSIPHON-OKAMURANUS; ANTITUMOR-ACTIVITY; DOWN-REGULATION; UNITED-STATES; BROWN ALGA; CELLS; APOPTOSIS; SEAWEED AB Background. Despite a number of in vitro and in vivo studies reporting the efficacy of fucoidan in treating various cancers, few studies have measured the efficacy of dietary fucoidan (DF) in combination with cancer drugs. Thus, we examined the sensitivity of DF in combination with the EGFR/ERBB2-targeting reagent lapatinib on cancer cells. Method. We selected six EGFR/ERBB2-amplified cancer cell lines (OE19, NCI-N87, OE33, ESO26, MKN7, and BT474) as an in vitro model and tested their sensitivity to DF alone and to DF in combination with the well-known EGFR/ERBB2-targeting reagent lapatinib. Result. Overall, in drug independent sensitivity test, DF alone did not significantly inhibit the growth of EGFR/ERBB2-amplified cancer cells in vitro. When DF was given in combination with lapatinib, however, it tended to synergistically inhibit cell growth in OE33 but antagonized the action of lapatinib in ESO26, NCI-N87, and OE19. Conclusion. This study suggests that DF has the potential to increase or decrease the effects of certain anticancer drugs on certain cancer cell types. Further study is needed to explore the mechanism of interaction and synergistic antitumor activity of DF in combination with chemotherapy and targeted therapy. C1 [Oh, Byeongsang; Kim, Jihun; Lu, Weidong; Rosenthal, David] Harvard Univ, Sch Med, Dana Faber Canc Inst, Boston, MA 02215 USA. [Oh, Byeongsang] Univ Sydney, Sydney Med Sch, Sydney, NSW 2006, Australia. [Kim, Jihun] Univ Ulsan, Coll Med, Asan Med Ctr, Seoul, South Korea. RP Oh, B (reprint author), Harvard Univ, Sch Med, Dana Faber Canc Inst, Boston, MA 02215 USA. EM byeongsang_oh@dfci.harvard.edu RI Lu, Weidong/C-3844-2008 OI Lu, Weidong/0000-0003-2838-6307 FU Comprehensive and Integrative Medicine Institute (CIMI), Daegu, Republic of Korea FX This study was supported by the Comprehensive and Integrative Medicine Institute (CIMI), Daegu, Republic of Korea. The authors would like to acknowledge that dietary fucoidan samples (Sulfoidan) were donated by EnzAlg Bio Sciences (New Zealand). NR 30 TC 4 Z9 4 U1 5 U2 14 PU HINDAWI PUBLISHING CORPORATION PI NEW YORK PA 410 PARK AVENUE, 15TH FLOOR, #287 PMB, NEW YORK, NY 10022 USA SN 1741-427X EI 1741-4288 J9 EVID-BASED COMPL ALT JI Evid.-based Complement Altern. Med. PY 2014 AR 865375 DI 10.1155/2014/865375 PG 6 WC Integrative & Complementary Medicine SC Integrative & Complementary Medicine GA 304IC UT WOS:000330739300001 ER PT J AU Voulgarelis, M Mavragani, CP Xu, L Treon, SP Moutsopoulos, HM AF Voulgarelis, M. Mavragani, C. P. Xu, L. Treon, S. P. Moutsopoulos, H. M. TI Absence of somatic MYD88 L265P mutations in patients with primary Sjogren's syndrome SO GENES AND IMMUNITY LA English DT Article DE Sjogren's syndrome (SS); lymphoproliferation; MYD88 L265P ID TOLL-LIKE RECEPTORS; WALDENSTROM MACROGLOBULINEMIA; LYMPHOMA DEVELOPMENT; EXPRESSION; CELLS; RISK AB Sjogren's syndrome (SS) is a chronic autoimmune disorder with the highest risk for lymphoma development among all autoimmune diseases. In order to evaluate whether the presence of the recently described MYD88 L265P mutation in patients with Waldenstrom's macroglobulinemia (WM) is contributory to SS-associated lymphomagenesis, a quantitative allele-specific PCR method was performed in peripheral blood derived from 90 SS patients as well as in minor salivary gland tissues derived from 12 primary SS patients with or without lymphoma. MYD88 L265P was not detected in either of the samples tested. Although the absence of the MyD88 L265P somatic mutation in our SS cohort does not exclude a common germline susceptibility gene in SS, it might suggest a distinct operating pathogenetic mechanism in SS-related lymphoma compared with WM and other hematological malignancies. C1 [Voulgarelis, M.; Moutsopoulos, H. M.] Univ Athens, Dept Pathophysiol, Sch Med, Athens 11527, Greece. [Mavragani, C. P.] Univ Athens, Dept Physiol, Sch Med, Athens 11527, Greece. [Xu, L.; Treon, S. P.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Bing Ctr Waldenstroms Macroglobulinemia, Boston, MA 02115 USA. RP Voulgarelis, M (reprint author), Univ Athens, Dept Pathophysiol, Sch Med, M Asias 75, Athens 11527, Greece. EM mvoulgar@med.uoa.gr FU S Niarchos Foundation FX We would like to thank Aristea Papageorgiou, MD for helping in the recruitment of SS patients, Adrianos Nezos, PhD and Efstathia Kapsogeorgou, PhD for performing DNA extractions of peripheral blood and minor salivary gland tissues, respectively, and S Niarchos Foundation for financial support. NR 16 TC 1 Z9 1 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1466-4879 EI 1476-5470 J9 GENES IMMUN JI Genes Immun. PD JAN-FEB PY 2014 VL 15 IS 1 BP 54 EP 56 DI 10.1038/gene.2013.54 PG 3 WC Genetics & Heredity; Immunology SC Genetics & Heredity; Immunology GA 304LG UT WOS:000330747800008 PM 24153350 ER PT J AU Stone, GS Tarus, T Shikanga, M Biwott, B Ngetich, T Andale, T Cheriro, B Aruasa, W AF Stone, Geren S. Tarus, Titus Shikanga, Mainard Biwott, Benson Ngetich, Thomas Andale, Thomas Cheriro, Betsy Aruasa, Wilson TI The association between insurance status and in-hospital mortality on the public medical wards of a Kenyan referral hospital SO GLOBAL HEALTH ACTION LA English DT Article DE health insurance; disparities; hospital medicine; Africa ID HEALTH-INSURANCE; UNITED-STATES; COVERAGE; CARE; SERVICES; OUTCOMES; ADULTS; SECTOR; DEATH; RISK AB Background: Observational data in the United States suggests that those without health insurance have a higher mortality and worse health outcomes. A linkage between insurance coverage and outcomes in hospitalized patients has yet to be demonstrated in resource-poor settings. Methods: To determine whether uninsured patients admitted to the public medical wards at a Kenyan referral hospital have any difference in in-hospital mortality rates compared to patients with insurance, we performed a retrospective observational study of all inpatients discharged from the public medical wards at Moi Teaching and Referral Hospital in Eldoret, Kenya, over a 3-month study period from October through December 2012. The primary outcome of interest was in-hospital death, and the primary explanatory variable of interest was health insurance status. Results: During the study period, 201 (21.3%) of 956 patients discharged had insurance. The National Hospital Insurance Fund was the only insurance scheme noted. Overall, 211 patients (22.1%) died. The proportion who died was greater among the uninsured compared to the insured (24.7% vs. 11.4%, Chi-square = 15.6, p<0.001). This equates to an absolute risk reduction of 13.3% (95% CI 7.9-18.7%) and a relative risk reduction of 53.8% (95% CI 30.8-69.2%) of in-hospital mortality with insurance. After adjusting for comorbid illness, employment status, age, HIV status, and gender, the association between insurance status and mortality remained statistically significant (adjusted odds ratio (AOR) = 0.40, 95% CI 0.24-0.66) and similar in magnitude to the association between HIV status and mortality (AOR = 2.45, 95% CI 1.56-3.86). Conclusions: Among adult patients hospitalized in a public referral hospital in Kenya, insurance coverage was associated with decreased in-hospital mortality. This association was comparable to the relationship between HIV and mortality. Extension of insurance coverage may yield substantial benefits for population health. C1 [Stone, Geren S.] Massachusetts Gen Hosp, Ctr Global Hlth, Dept Med, Boston, MA 02114 USA. [Stone, Geren S.] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. [Stone, Geren S.] Indiana Univ Sch Med, Dept Med, Indianapolis, IN 46202 USA. [Stone, Geren S.] Moi Univ, Dept Med, Eldoret, Kenya. [Tarus, Titus; Shikanga, Mainard; Biwott, Benson; Ngetich, Thomas; Andale, Thomas; Cheriro, Betsy; Aruasa, Wilson] Moi Teaching & Referral Hosp, Eldoret, Kenya. RP Stone, GS (reprint author), Massachusetts Gen Hosp, Ctr Global Hlth, 100 Cambridge St,15th Floor, Boston, MA 02114 USA. EM gstone@partners.org NR 26 TC 3 Z9 3 U1 0 U2 3 PU CO-ACTION PUBLISHING PI JARFALLA PA RIPVAGEN 7, JARFALLA, SE-175 64, SWEDEN SN 1654-9880 J9 GLOBAL HEALTH ACTION JI Glob. Health Action PY 2014 VL 7 AR 23137 DI 10.3402/gha.v7.23137 PG 6 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA AA4OR UT WOS:000331076000001 PM 24560256 ER PT S AU Nadkarni, P Chepurny, OG Holz, GG AF Nadkarni, Prashant Chepurny, Oleg G. Holz, George G. BE Tao, YX TI Regulation of Glucose Homeostasis by GLP-1 SO GLUCOSE HOMEOSTATIS AND THE PATHOGENESIS OF DIABETES MELLITUS SE Progress in Molecular Biology and Translational Science LA English DT Review; Book Chapter ID GLUCAGON-LIKE PEPTIDE-1; PANCREATIC BETA-CELLS; GASTRIC-BYPASS-SURGERY; TYPE-2 DIABETES-MELLITUS; PROTEIN-KINASE-A; DEPENDENT INSULINOTROPIC POLYPEPTIDE; INCRETIN-BASED THERAPIES; CA2+-INDUCED CA2+ RELEASE; SMALL-MOLECULE AGONISTS; CAMP SENSOR EPAC AB Glucagon-like peptide-1(7-36)amide (GLP-1) is a secreted peptide that acts as a key determinant of blood glucose homeostasis by virtue of its abilities to slow gastric emptying, to enhance pancreatic insulin secretion, and to suppress pancreatic glucagon secretion. GLP-1 is secreted from L cells of the gastrointestinal mucosa in response to a meal, and the blood glucose-lowering action of GLP-1 is terminated due to its enzymatic degradation by dipeptidyl-peptidase-IV (DPP-IV). Released GLP-1 activates enteric and autonomic reflexes while also circulating as an incretin hormone to control endocrine pancreas function. The GLP-1 receptor (GLP-1R) is a G protein-coupled receptor that is activated directly or indirectly by blood glucose-lowering agents currently in use for the treatment of type 2 diabetes mellitus (T2DM). These therapeutic agents include GLP-1R agonists (exenatide, liraglutide, lixisenatide, albiglutide, dulaglutide, and langlenatide) and DPP-IV inhibitors (sitagliptin, vildagliptin, saxagliptin, linagliptin, and alogliptin). Investigational agents for use in the treatment of T2DM include GPR119 and GPR40 receptor agonists that stimulate the release of GLP-1 from L cells. Summarized here is the role of GLP-1 to control blood glucose homeostasis, with special emphasis on the advantages and limitations of GLP-1-based therapeutics. C1 [Nadkarni, Prashant; Chepurny, Oleg G.; Holz, George G.] SUNY Upstate Med Univ, Dept Med, Syracuse, NY 13210 USA. [Nadkarni, Prashant] SUNY Upstate Med Univ, Joslin Diabet Ctr, Syracuse, NY 13210 USA. [Holz, George G.] SUNY Upstate Med Univ, Dept Pharmacol, Syracuse, NY 13210 USA. RP Holz, GG (reprint author), SUNY Upstate Med Univ, Dept Med, Syracuse, NY 13210 USA. EM holzg@upstate.edu FU NIDDK NIH HHS [R01 DK045817, R01 DK069575] NR 274 TC 29 Z9 40 U1 1 U2 15 PU ELSEVIER ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA SN 1877-1173 BN 978-0-12-800101-1 J9 PROG MOL BIOL TRANSL JI Prog. Molec. Biol. Transl. Sci. PY 2014 VL 121 BP 23 EP 65 DI 10.1016/B978-0-12-800101-1.00002-8 PG 43 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA BA0CU UT WOS:000331017900002 PM 24373234 ER PT J AU Oh, WK McDermott, D Porta, C Levy, A Elaidi, R Scotte, F Hawkins, R Castellano, D Bellmunt, J Rha, SY Sun, JM Nathan, P Feinberg, BA Scott, J McDermott, R Ahn, JH Wagstaff, J Chang, YH Ou, YC Donnellan, P Huang, CY McCaffrey, J Chiang, PH Chuang, CK Korves, C Neary, MP Diaz, JR Mehmud, F Duh, MS AF Oh, William K. McDermott, David Porta, Camillo Levy, Antonin Elaidi, Reza Scotte, Florian Hawkins, Robert Castellano, Daniel Bellmunt, Joaquim Rha, Sun Young Sun, Jong-Mu Nathan, Paul Feinberg, Bruce A. Scott, Jeffrey McDermott, Ray Ahn, Jin-Hee Wagstaff, John Chang, Yen-Hwa Ou, Yen-Chuan Donnellan, Paul Huang, Chao-Yuan McCaffrey, John Chiang, Po-Hui Chuang, Cheng-Keng Korves, Caroline Neary, Maureen P. Diaz, Jose R. Mehmud, Faisal Duh, Mei Sheng TI Angiogenesis inhibitor therapies for advanced renal cell carcinoma: Toxicity and treatment patterns in clinical practice from a global medical chart review SO INTERNATIONAL JOURNAL OF ONCOLOGY LA English DT Article DE renal cell carcinoma; angiogenesis inhibitors; safety; treatment patterns; interruption; dose reduction ID TREATMENT OUTCOMES; SAFETY; SUNITINIB; EFFICACY; SORAFENIB; CANCER; TRIAL; EXPERIENCE; SURVIVAL AB The aim of this study was to assess the treatment patterns and safety of sunitinib, sorafenib and bevacizumab in real-world clinical settings in US, Europe and Asia. Medical records were abstracted at 18 community oncology clinics in the US and at 21 tertiary oncology centers in US, Europe and Asia for 883 patients 18 years who had histologically/cytologically confirmed diagnosis of advanced RCC and received sunitinib (n=631), sorafenib (n=207) or bevacizumab (n=45) as first-line treatment. No prior treatment was permitted. Data were collected on all adverse events (AEs) and treatment modifications, including discontinuation, interruption and dose reduction. Treatment duration was estimated using Kaplan-Meier analysis. Demographics were similar across treatment groups and regions. Median treatment duration ranged from 6.1 to 10.7 months, 5.1 to 8.5 months and 7.5 to 9.8 months for sunitinib, sorafenib and bevacizumab patients, respectively. Grade 3/4 AEs were experienced by 26.0, 28.0 and 15.6% of sunitinib, sorafenib and bevacizumab patients, respectively. Treatment discontinuations occurred in 62.4 (Asia) to 63.1% (US) sunitinib, 68.8 (Asia) to 90.0% (Europe) sorafenib, and 66.7 (Asia) to 81.8% (US) bevacizumab patients. Globally, treatment modifications due to AEs occurred in 55.1, 54.2 and 50.0% sunitinib, sorafenib and bevacizumab patients, respectively. This study in a large, global cohort of advanced RCC patients found that angiogenesis inhibitors are associated with high rates of AEs and treatment modifications. Findings suggest an unmet need for more tolerable agents for RCC treatment. C1 [Oh, William K.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Oh, William K.] Mt Sinai Sch Med, Tisch Canc Inst, New York, NY USA. [McDermott, David] Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. [Porta, Camillo] IRCCS San Matteo Univ Hosp Fdn, Pavia, Italy. [Levy, Antonin] Inst Gustave Roussy, Paris, France. [Elaidi, Reza; Scotte, Florian] Hop Europeen Georges Pompidou, Paris, France. [Hawkins, Robert] The Christie, Manchester, Lancs, England. [Hawkins, Robert] Univ Manchester, Manchester, Lancs, England. [Castellano, Daniel] 12 Octubre Univ Hosp, Res Inst I 12, Dept Med Oncol, Unit Urooncol, Madrid, Spain. [Bellmunt, Joaquim] Hosp del Mar, IMIM, Barcelona, Spain. [Rha, Sun Young] Yonsei Univ, Coll Med, Yonsei Canc Ctr, Severance Hosp, Seoul, South Korea. [Sun, Jong-Mu] Sungkyunkwan Univ, Sch Med, Samsung Med Ctr, Seoul, South Korea. [Nathan, Paul] Mt Vernon Canc Ctr, Northwood, Middx, England. [Feinberg, Bruce A.; Scott, Jeffrey] P4 Healthcare, Ellicott City, MD USA. [McDermott, Ray] Adelaide & Meath Hosp, Tallaght, Ireland. [Ahn, Jin-Hee] Asan Med Ctr, Seoul, South Korea. [Wagstaff, John] Singleton Hosp, South West Wales Canc Inst, Swansea SA2 8QA, W Glam, Wales. [Chang, Yen-Hwa] Taipei Vet Gen Hosp, Taipei, Taiwan. [Ou, Yen-Chuan] Taichung Vet Gen Hosp, Taichung, Taiwan. [Donnellan, Paul] Univ Coll Hosp Galway, Galway, Ireland. [Huang, Chao-Yuan] Natl Taiwan Univ Hosp, Taipei, Taiwan. [McCaffrey, John] Mater Misericordiae Univ Hosp, Dublin 7, Ireland. [Chiang, Po-Hui] Chang Gung Mem Hosp, Kaohsiung, Taiwan. [Chuang, Cheng-Keng] Chang Gung Mem Hosp, Linkuo, Taiwan. [Korves, Caroline; Duh, Mei Sheng] Anal Grp Inc, Boston, MA 02199 USA. [Neary, Maureen P.; Diaz, Jose R.; Mehmud, Faisal] GlaxoSmithKline, Collegeville, PA USA. RP Duh, MS (reprint author), Anal Grp Inc, 111 Huntington Ave,Tenth Floor, Boston, MA 02199 USA. EM mduh@analysisgroup.com RI sun, jm/O-5938-2014; OI Porta, Camillo/0000-0003-2412-1563; HUANG, CHAO-YUAN/0000-0002-9322-6062; McDermott, Ray/0000-0002-8952-4315; , Antonin/0000-0003-4798-8899 FU GlaxoSmithKline (GSK), Collegeville, PA; GSK; Analysis Group Inc. FX This study was funded by GlaxoSmithKline (GSK), Collegeville, PA. The funding from GSK was not contingent upon the study results. GSK participated in the study design, results interpretation and manuscript preparation as reflected in the authorship by GSK employees, M.P.N., J.R.D. and F.M.. A molecule with similar mechanism of action developed by GSK (pazopanib) was recently approved by the United States Food and Drug Administration and European Medical Agency for treatment of patients with advanced renal cell carcinoma. The institutions where W.K.O., D.M., C.P., A.L., R.E., F.S., R.H., D.C., J.B., S.Y.R., J.-M.S., P.N., B.A.F., J.S., R.M., J.-H.A., J.W., Y.-H.C., Y.-C.O., P.D., C.-Y.H., J.M., P.-H.C. and C.-K.C. are, have received research funds from Analysis Group Inc. M.S.D. and C.K. are employees of Analysis Group Inc., which has received research grants from GSK. NR 20 TC 17 Z9 18 U1 0 U2 9 PU SPANDIDOS PUBL LTD PI ATHENS PA POB 18179, ATHENS, 116 10, GREECE SN 1019-6439 EI 1791-2423 J9 INT J ONCOL JI Int. J. Oncol. PD JAN PY 2014 VL 44 IS 1 BP 5 EP 16 DI 10.3892/ijo.2013.2181 PG 12 WC Oncology SC Oncology GA AA0LI UT WOS:000330786200001 PM 24247547 ER PT J AU Friedlander, AH AF Friedlander, Arthur H. TI Dental Implant Cone Beam Scans of Older Individuals Often Reveal Potentially Life-Threatening Atherosclerotic Disease SO INTERNATIONAL JOURNAL OF ORAL & MAXILLOFACIAL IMPLANTS LA English DT Editorial Material ID STROKE C1 [Friedlander, Arthur H.] VA Greater Los Angeles Healthcare Syst, Los Angeles, CA 90073 USA. [Friedlander, Arthur H.] Ronald Reagan UCLA Med Ctr, Hosp Dent Serv, Los Angeles, CA USA. [Friedlander, Arthur H.] Univ Calif Los Angeles, Sch Dent, Los Angeles, CA 90024 USA. RP Friedlander, AH (reprint author), VA Greater Los Angeles Healthcare Syst, Los Angeles, CA 90073 USA. EM arthur.friedlander@va.gov NR 7 TC 0 Z9 0 U1 0 U2 1 PU QUINTESSENCE PUBLISHING CO INC PI HANOVER PARK PA 4350 CHANDLER DRIVE, HANOVER PARK, IL 60133 USA SN 0882-2786 EI 1942-4434 J9 INT J ORAL MAX IMPL JI Int. J. Oral Maxillofac. Implants PD JAN-FEB PY 2014 VL 29 IS 1 BP 19 EP 20 PG 2 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 304ME UT WOS:000330750200001 PM 24451850 ER PT J AU Tsai, TT Patel, UD Chang, TI Kennedy, KF Masoudi, FA Matheny, ME Kosiborod, M Amin, AP Messenger, JC Rumsfeld, JS Spertus, JA AF Tsai, Thomas T. Patel, Uptal D. Chang, Tara I. Kennedy, Kevin F. Masoudi, Frederick A. Matheny, Michael E. Kosiborod, Mikhail Amin, Amit P. Messenger, John C. Rumsfeld, John S. Spertus, John A. TI Contemporary Incidence, Predictors, and Outcomes of Acute Kidney Injury in Patients Undergoing Percutaneous Coronary Interventions SO JACC-CARDIOVASCULAR INTERVENTIONS LA English DT Article DE acute kidney injury; PCI; stent(s) ID CONTRAST-INDUCED NEPHROPATHY; ACUTE MYOCARDIAL-INFARCTION; ACUTE-RENAL-FAILURE; CARDIOVASCULAR DATA REGISTRY; INTENSIVE-CARE-UNIT; SERUM CREATININE; REQUIRING DIALYSIS; HOSPITALIZED-PATIENTS; REPLACEMENT THERAPY; RISK-FACTORS AB Objectives This study sought to examine the contemporary incidence, predictors and outcomes of acute kidney injury in patients undergoing percutaneous coronary interventions. Background Acute kidney injury (AKI) is a serious and potentially preventable complication of percutaneous coronary interventions (PCIs) that is associated with adverse outcomes. The contemporary incidence, predictors, and outcomes of AKI are not well defined, and clarifying these can help identify high-risk patients for proactive prevention. Methods A total of 985,737 consecutive patients underwent PCIs at 1,253 sites participating in the National Cardiovascular Data Registry Cath-PCI registry from June 2009 through June 2011. AKI was defined on the basis of changes in serum creatinine level in the hospital according to the Acute Kidney Injury Network (AKIN) criteria. Using multivariable regression analyses with generalized estimating equations, we identified patient characteristics associated with AKI. Results Overall, 69,658 (7.1%) patients experienced AKI, with 3,005 (0.3%) requiring new dialysis. On multivariable analyses, the factors most strongly associated with development of AKI included ST-segment elevation myocardial infarction (STEMI) presentation (odds ratio [OR]: 2.60; 95% confidence interval [CI]: 2.53 to 2.67), severe chronic kidney disease (OR: 3.59; 95% CI: 3.47 to 3.71), and cardiogenic shock (OR: 2.92; 95% CI: 2.80 to 3.04). The in-hospital mortality rate was 9.7% for patients with AKI and 34% for those requiring dialysis compared with 0.5% for patients without AKI (p < 0.001). After multivariable adjustment, AKI (OR: 7.8; 95% CI: 7.4 to 8.1, p< 0.001) and dialysis (OR: 21.7; 95% CI: 19.6 to 24.1; p< 0.001) remained independent predictors of in-hospital mortality. Conclusions Approximately 7% of patients undergoing a PCI experience AKI, which is strongly associated with in-hospital mortality. Defining strategies to minimize the risk of AKI in patients undergoing PCI are needed to improve the safety and outcomes of the procedure. (C) 2014 by the American College of Cardiology Foundation C1 [Tsai, Thomas T.; Masoudi, Frederick A.; Messenger, John C.; Rumsfeld, John S.] Kaiser Permanente Colorado, Inst Hlth Res, Denver, CO USA. [Tsai, Thomas T.] Univ Colorado, Denver, CO 80202 USA. [Patel, Uptal D.] Duke Univ, Med Ctr, Duke Clin Res Inst, Durham, NC USA. [Chang, Tara I.] Stanford Sch Med, Palo Alto, CA USA. [Kennedy, Kevin F.; Kosiborod, Mikhail; Amin, Amit P.; Spertus, John A.] St Lukes Hosp, Mid Amer Heart Inst, Kansas City, MO 64111 USA. [Kennedy, Kevin F.; Kosiborod, Mikhail; Amin, Amit P.; Spertus, John A.] Univ Missouri, Sch Med, Kansas City, MO 64108 USA. [Rumsfeld, John S.] Denver VA Med Ctr, Denver, CO USA. [Matheny, Michael E.] Tennesse Vallry Hlth Syst VA, Nashville, TN USA. [Matheny, Michael E.] Vanderbilt Univ, Med Ctr, Nashville, TN USA. RP Tsai, TT (reprint author), Univ Colorado Denver, Kaiser Permanente Colorado, Inst Hlth Res, 280 Exempla Circle, Lafayette, CO 80026 USA. EM thomas.tsai@coloradooutcomes.org FU NIDDK NIH HHS [T32 DK007357] NR 45 TC 75 Z9 80 U1 0 U2 4 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1936-8798 EI 1876-7605 J9 JACC-CARDIOVASC INTE JI JACC-Cardiovasc. Interv. PD JAN PY 2014 VL 7 IS 1 BP 1 EP 9 DI 10.1016/j.jcin.2013.06.016 PG 9 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA AA2VU UT WOS:000330953100003 PM 24456715 ER PT J AU Scheinert, D Scheinert, D Duda, S Zeller, T Krankenberg, H Ricke, J Bosiers, M Tepe, G Naisbitt, S Rosenfield, K AF Scheinert, Dierk Scheinert, Dierk Duda, Stephan Zeller, Thomas Krankenberg, Hans Ricke, Jens Bosiers, Marc Tepe, Gunnar Naisbitt, Scott Rosenfield, Kenneth TI The LEVANT I (Lutonix Paclitaxel-Coated Balloon for the Prevention of Femoropopliteal Restenosis) Trial for Femoropopliteal Revascularization First-in-Human Randomized Trial of Low-Dose Drug-Coated Balloon Versus Uncoated Balloon Angioplasty SO JACC-CARDIOVASCULAR INTERVENTIONS LA English DT Article DE angioplasty; drug-coated balloon; drug-eluting balloon; paclitaxel; peripheral vascular disease; restenosis ID PERIPHERAL ARTERIAL-DISEASE; SUPERFICIAL FEMORAL-ARTERY; NITINOL STENT IMPLANTATION; ELUTING STENT; CORONARY; LESIONS; PROLIFERATION; INHIBITION; MANAGEMENT; CATHETER AB Objectives This study sought to evaluate the safety and efficacy of the Lutonix drug-coated balloon (DCB) coated with 2 mu g/mm(2) paclitaxel and a polysorbate/sorbitol carrier for treatment of femoropopliteal lesions. Background Percutaneous treatment of peripheral vascular disease is associated with a high recurrence. Paclitaxel-coated balloons at 3 mu g/mm(2) formulated differently have shown promising results with reduced restenosis. Methods Subjects at 9 centers with Rutherford class 2 to 5 femoropopliteal lesions were randomized between June 2009 and December 2009 to treatment with Lutonix DCB (n = 49) versus uncoated balloons (control group [n = 52]), stratified by whether balloon-only treatment (n = 75) or stenting (n = 26) was intended. The primary endpoint was angiographic late lumen loss at 6 months. Secondary outcomes included adjudicated major adverse events (death, amputation, target lesion thrombosis, reintervention), functional outcomes, and pharmacokinetics. Results Demographic, peripheral vascular disease, and lesion characteristics were matched, with mean lesion length of 8.1 +/- 3.8 cm and 42% total occlusions. At 6 months, late lumen loss was 58% lower for the Lutonix DCB group (0.46 +/- 1.13 mm) than for the control group (1.09 +/- 1.07 mm; p = 0.016). Composite 24-month major adverse events were 39% for the DCB group, including 15 target lesion revascularizations, 1 amputation, and 4 deaths versus 46% for uncoated balloon group, with 20 target lesion revascularizations, 1 thrombosis, and 5 deaths. Pharmacokinetics showed biexponential decay with peak concentration (C-max) of 59 ng/ml and total observed exposure (AUC(all)) of 73 ng h/ml. For successful DCB deployment excluding 8 malfunctions, 6-month late lumen loss was 0.39 mm and the 24-month target lesion revascularization rate was 24%. Conclusions Treatment of femoropopliteal lesions with the low-dose Lutonix DCB reduced late lumen loss with safety comparable to that of control angioplasty. (C) 2014 by the American College of Cardiology Foundation C1 Pk Hosp Leipzig, Ctr Vasc Med Angiol Cardiol & Vasc Surg, D-04289 Leipzig, Germany. St Blasius Hosp, Dept Vasc Surg, Dendermonde, Belgium. RoMed Acad Hosp Rosenheim, Dept Diagnost & Intervent Radiol, Rosenheim, Germany. Lutonix Inc, New Hope, MN USA. Massachusetts Gen Hosp, Dept Med Cardiol, Cambridge, MA USA. RP Scheinert, D (reprint author), Pk Hosp Leipzig, Ctr Vasc Med Angiol Cardiol & Vasc Surg, Strumpellstr 41, D-04289 Leipzig, Germany. EM dierk.scheinert@gmx.de NR 27 TC 30 Z9 32 U1 0 U2 6 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1936-8798 EI 1876-7605 J9 JACC-CARDIOVASC INTE JI JACC-Cardiovasc. Interv. PD JAN PY 2014 VL 7 IS 1 BP 11 EP 19 PG 9 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA AA2VU UT WOS:000330953100004 ER PT J AU Growdon, JH Hyman, BT AF Growdon, John H. Hyman, Bradley T. TI APOE Genotype and Brain Development SO JAMA NEUROLOGY LA English DT Editorial Material ID APOLIPOPROTEIN-E; ALZHEIMERS-DISEASE; SYNAPTIC PLASTICITY; RECEPTOR; MICE C1 [Growdon, John H.; Hyman, Bradley T.] Massachusetts Gen Hosp, Neurol Serv, Boston, MA 02114 USA. RP Growdon, JH (reprint author), Massachusetts Gen Hosp, Neurol Serv, 42 Fruit St, Boston, MA 02114 USA. EM jgrowdon@partners.org FU NIA NIH HHS [P50 AG005134] NR 10 TC 0 Z9 0 U1 0 U2 2 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60654-0946 USA SN 2168-6149 EI 2168-6157 J9 JAMA NEUROL JI JAMA Neurol. PD JAN PY 2014 VL 71 IS 1 BP 7 EP 8 DI 10.1001/jamaneurol.2013.5200 PG 2 WC Clinical Neurology SC Neurosciences & Neurology GA 301YH UT WOS:000330567700002 PM 24276019 ER PT J AU Alcalay, RN Caccappolo, E Mejia-Santana, H Tang, MX Rosado, L Reilly, MO Ruiz, D Louis, ED Comella, CL Nance, MA Bressman, SB Scott, WK Tanner, CM Mickel, SF Waters, CH Fahn, S Cote, LJ Frucht, SJ Ford, B Rezak, M Novak, KE Friedman, JH Pfeiffer, RF Marsh, L Hiner, B Payami, H Molho, E Factor, SA Nutt, JG Serrano, C Arroyo, M Ottman, R Pauciulo, MW Nichols, WC Clark, LN Marder, KS AF Alcalay, Roy N. Caccappolo, Elise Mejia-Santana, Helen Tang, Ming Xin Rosado, Llency Reilly, Martha Orbe Ruiz, Diana Louis, Elan D. Comella, Cynthia L. Nance, Martha A. Bressman, Susan B. Scott, William K. Tanner, Caroline M. Mickel, Susan F. Waters, Cheryl H. Fahn, Stanley Cote, Lucien J. Frucht, Steven J. Ford, Blair Rezak, Michael Novak, Kevin E. Friedman, Joseph H. Pfeiffer, Ronald F. Marsh, Laura Hiner, Bradley Payami, Haydeh Molho, Eric Factor, Stewart A. Nutt, John G. Serrano, Carmen Arroyo, Maritza Ottman, Ruth Pauciulo, Michael W. Nichols, William C. Clark, Lorraine N. Marder, Karen S. TI Cognitive and Motor Function in Long-Duration PARKIN-Associated Parkinson Disease SO JAMA NEUROLOGY LA English DT Article ID EARLY-ONSET PD; MUTATIONS; FREQUENCY; DEMENTIA; DECLINE; ENTITY; GENE AB IMPORTANCE Data on the long-term cognitive outcomes of patients with PARKIN-associated Parkinson disease (PD) are unknown but may be useful when counseling these patients. OBJECTIVE Among patients with early-onset PD of long duration, we assessed cognitive and motor performances, comparing homozygotes and compound heterozygotes who carry 2 PARKIN mutations with noncarriers. DESIGN, SETTING, AND PARTICIPANTS Cross-sectional study of 44 participants at 17 different movement disorder centers who were in the Consortium on Risk for Early-Onset PD study with a duration of PD greater than the median duration (>14 years): 4 homozygotes and 17 compound heterozygotes (hereafter referred to as carriers) and 23 noncarriers. MAIN OUTCOMES AND MEASURES Unified Parkinson Disease Rating Scale Part III (UPDRS-III) and Clinical Dementia Rating scores and neuropsychological performance. Linear regression models were applied to assess the association between PARKIN mutation status and cognitive domain scores and UPDRS-III scores. Models were adjusted for age, education, disease duration, language, and levodopa equivalent daily dose. RESULTS Carriers had an earlier age at onset of PD (P < .001) and were younger (P = .004) at time of examination than noncarriers. They performed better than noncarriers on the Mini-Mental State Examination (P = .010) and were more likely to receive lower scores on the Clinical Dementia Rating (P = .003). In multivariate analyses, carriers performed better than noncarriers on the UPDRS-III (P = .02) and on tests of attention (P = .03), memory (P = .03), and visuospatial (P = .02) cognitive domains. CONCLUSIONS AND RELEVANCE In cross-sectional analyses, carriers demonstrated better cognitive and motor performance than did noncarriers with long disease duration, suggesting slower disease progression. A longitudinal follow-up study is required to confirm these findings. C1 [Alcalay, Roy N.; Caccappolo, Elise; Mejia-Santana, Helen; Tang, Ming Xin; Rosado, Llency; Reilly, Martha Orbe; Ruiz, Diana; Louis, Elan D.; Waters, Cheryl H.; Fahn, Stanley; Cote, Lucien J.; Frucht, Steven J.; Ford, Blair; Ottman, Ruth; Marder, Karen S.] Columbia Univ, Dept Neurol, Coll Phys & Surg, New York, NY 10032 USA. [Alcalay, Roy N.; Tang, Ming Xin; Louis, Elan D.; Clark, Lorraine N.; Marder, Karen S.] Columbia Univ, Taub Inst Res Alzheimers Dis & Aging Brain, Coll Phys & Surg, New York, NY 10032 USA. [Louis, Elan D.; Cote, Lucien J.; Ottman, Ruth; Marder, Karen S.] Columbia Univ, Gertrude H Sergievsky Ctr, Coll Phys & Surg, New York, NY 10032 USA. [Louis, Elan D.; Ottman, Ruth] Columbia Univ, Dept Epidemiol, Mailman Sch Publ Hlth, New York, NY 10032 USA. [Comella, Cynthia L.] Rush Univ, Dept Neurol Sci, Med Ctr, Chicago, IL 60612 USA. [Nance, Martha A.] Struthers Parkinsons Ctr, Pk Nicollet Clin, Golden Valley, MN USA. [Bressman, Susan B.] Beth Israel Deaconess Med Ctr, Alan & Barbara Mirken Dept Neurol, New York, NY 10003 USA. [Bressman, Susan B.] Albert Einstein Coll Med, Dept Neurol, Bronx, NY 10467 USA. [Scott, William K.] Univ Miami, Miller Sch Med, Dr John T Macdonald Fdn, Dept Human Genet,Miami Inst Human Genom, Miami, FL 33136 USA. [Tanner, Caroline M.] Parkinsons Inst, Sunnyvale, CA USA. [Tanner, Caroline M.] Stanford Univ, Dept Hlth Res & Policy, Palo Alto, CA 94304 USA. [Mickel, Susan F.] Marshfield Clin Fdn Med Res & Educ, Dept Neurol, Marshfield Clin, Marshfield, WI 54449 USA. [Rezak, Michael] Cent DuPage Hosp, Inst Neurosci, Movement Disorders Ctr, Winfield, IL USA. [Novak, Kevin E.] NorthShore Univ Hlth Syst, Dept Neurol, Evanston, IL USA. [Novak, Kevin E.] Univ Chicago, Dept Neurol, Pritzker Sch Med, Chicago, IL 60637 USA. [Friedman, Joseph H.] Butler Hosp, Dept Neurol, Providence, RI 02906 USA. [Friedman, Joseph H.] Brown Univ, Alpert Med Sch, Dept Neurol, Providence, RI 02912 USA. [Pfeiffer, Ronald F.] Univ Tennessee, Ctr Hlth Sci, Dept Neurol, Coll Med, Memphis, TN USA. [Marsh, Laura] Johns Hopkins Univ, Sch Med, Morris K Udall Parkinsons Dis Res Ctr Excellence, Baltimore, MD USA. [Marsh, Laura] Johns Hopkins Univ, Sch Med, Dept Psychiat & Behav Sci, Baltimore, MD 21205 USA. [Marsh, Laura] Johns Hopkins Univ, Sch Med, Dept Neurol & Neurol Sci, Baltimore, MD USA. [Hiner, Bradley] Med Coll Wisconsin, Dept Neurol, Milwaukee, WI 53226 USA. [Payami, Haydeh] New York State Dept Hlth, Wadsworth Ctr, Albany, NY USA. [Molho, Eric] Albany Med Ctr, Parkinsons Dis & Movement Disorders Ctr, Albany, NY USA. [Factor, Stewart A.] Emory Univ, Dept Neurol, Atlanta, GA USA. [Nutt, John G.] Parkinson Dis Res Educ & Clin Ctr, Portland VA Med Ctr, Portland, OR USA. [Nutt, John G.] Oregon Hlth & Sci Univ, Portland, OR 97201 USA. [Serrano, Carmen; Arroyo, Maritza] Univ Puerto Rico, Dept Neurol, San Juan, PR 00936 USA. [Ottman, Ruth] New York State Psychiat Inst & Hosp, Div Epidemiol, New York, NY 10032 USA. [Pauciulo, Michael W.; Nichols, William C.] Univ Cincinnati, Coll Med, Div Human Genet, Cincinnati Childrens Hosp Med Ctr, Cincinnati, OH 45221 USA. [Pauciulo, Michael W.; Nichols, William C.] Univ Cincinnati, Coll Med, Dept Pediat, Cincinnati, OH 45221 USA. [Clark, Lorraine N.] Columbia Univ, Dept Pathol & Cell Biol, Coll Phys & Surg, New York, NY 10032 USA. [Clark, Lorraine N.] Columbia Univ, Ctr Human Genet, Coll Phys & Surg, New York, NY 10032 USA. [Marder, Karen S.] Columbia Univ, Dept Psychiat, Med Ctr, New York, NY 10032 USA. RP Alcalay, RN (reprint author), Columbia Univ, Dept Neurol, Coll Phys & Surg, 710 W 168th St, New York, NY 10032 USA. EM rna2104@columbia.edu RI Ottman, Ruth/O-2371-2013 FU Scott; Marder; Clark; Payami; Fahn FX Obtained funding: Scott, Fahn, Payami, Clark, Marder. NR 28 TC 14 Z9 15 U1 1 U2 3 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60654-0946 USA SN 2168-6149 EI 2168-6157 J9 JAMA NEUROL JI JAMA Neurol. PD JAN PY 2014 VL 71 IS 1 BP 62 EP 67 DI 10.1001/jamaneurol.2013.4498 PG 6 WC Clinical Neurology SC Neurosciences & Neurology GA 301YH UT WOS:000330567700010 PM 24190026 ER PT J AU Lu, PH Lee, GJ Shapira, J Jimenez, E Mather, MJ Thompson, PM Bartzokis, G Mendez, MF AF Lu, Po H. Lee, Grace J. Shapira, Jill Jimenez, Elvira Mather, Michelle J. Thompson, Paul M. Bartzokis, George Mendez, Mario F. TI Regional Differences in White Matter Breakdown Between Frontotemporal Dementia and Early-Onset Alzheimer's Disease SO JOURNAL OF ALZHEIMERS DISEASE LA English DT Article DE Alzheimer's disease; behavioral variant; diffusion tensor imaging; early onset; frontotemporal dementia; magnetic resonance imaging; myelin; white matter ID MYELINATED NERVE-FIBERS; MILD COGNITIVE IMPAIRMENT; DIFFUSION TENSOR MRI; LOBAR DEGENERATION; HUMAN BRAIN; RHESUS-MONKEY; AGE; ATROPHY; CORTEX; HUMANS AB Background: White matter abnormalities have been associated with both behavioral variant frontotemporal dementia (bvFTD) and Alzheimer's disease (AD). Objective: Using MRI diffusion tensor imaging (DTI) measures, we compared white matter integrity between patients with bvFTD and those with early-onset AD and correlated these biomarkers with behavioral symptoms involving emotional blunting. Methods: We studied 8 bvFTD and 12 AD patients as well as 12 demographically-matched healthy controls (NCs). Using four DTI metrics (fractional anisotropy, axial diffusivity, radial diffusivity, and mean diffusivity), we assessed the frontal lobes (FWM) and genu of the corpus callosum (GWM), which are vulnerable late-myelinating regions, and a contrasting early-myelinating region (splenium of the corpus callosum). The Scale for Emotional Blunting Scale (SEB) was used to assess emotional functioning of the study participants. Results: Compared to AD patients and NCs, the bvFTD subjects exhibited significantly worse FWM and GWM integrity on all four DTI metrics sensitive to myelin and axonal integrity. In contrast, AD patients showed a numerical trend toward worse splenium of the corpus callosum integrity than bvFTD and NC groups. Significant associations between SEB ratings and GWM DTI measures were demonstrated in the combined bvFTD and AD sample. When examined separately, these relationships remained robust for the bvFTD group but not the AD group. Conclusions: The regional DTI alterations suggest that FTD and AD are each associated with a characteristic distribution of white matter degradation. White matter breakdown in late-myelinating regions was associated with symptoms of emotional blunting, particularly within the bvFTD group. C1 [Lu, Po H.; Shapira, Jill; Jimenez, Elvira; Thompson, Paul M.; Mendez, Mario F.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Neurol, Los Angeles, CA 90095 USA. [Lee, Grace J.] Loma Linda Univ, Sch Behav Hlth, Dept Psychol, Loma Linda, CA 92350 USA. [Shapira, Jill; Jimenez, Elvira; Mather, Michelle J.; Mendez, Mario F.] Greater Los Angeles VA Healthcare Syst, West Los Angeles, CA USA. [Thompson, Paul M.; Bartzokis, George] Univ Calif Los Angeles, David Geffen Sch Med, Dept Neurol, Lab Neuroimaging, Los Angeles, CA 90095 USA. [Bartzokis, George] Univ Calif Los Angeles, David Geffen Sch Med, Dept Psychiat & Biobehav Sci, Los Angeles, CA 90095 USA. RP Lu, PH (reprint author), 710 Westwood Plaza,RNRC 2-258, Los Angeles, CA 90095 USA. EM plu@mednet.ucla.edu FU NIH from the National Institute of Aging (NIA) [K23-AG028727, R01-AG034499]; Alzheimer's Disease Research Center [P50 AG-16570]; California Alzheimer's Disease Centers; Department of Veterans Affairs FX This work was supported by NIH grants K23-AG028727 and R01-AG034499 from the National Institute of Aging (NIA), the Alzheimer's Disease Research Center grant P50 AG-16570, California Alzheimer's Disease Centers, and the Department of Veterans Affairs. NR 59 TC 7 Z9 7 U1 0 U2 4 PU IOS PRESS PI AMSTERDAM PA NIEUWE HEMWEG 6B, 1013 BG AMSTERDAM, NETHERLANDS SN 1387-2877 EI 1875-8908 J9 J ALZHEIMERS DIS JI J. Alzheimers Dis. PY 2014 VL 39 IS 2 BP 261 EP 269 DI 10.3233/JAD-131481 PG 9 WC Neurosciences SC Neurosciences & Neurology GA 304HZ UT WOS:000330739000006 PM 24150110 ER PT J AU Freedman, RA Muss, HB AF Freedman, Rachel A. Muss, Hyman B. TI Managing metastatic human epidermal growth factor receptor 2 (HER2)-positive breast cancer in the older patient SO JOURNAL OF GERIATRIC ONCOLOGY LA English DT Article DE Older-women; Breast cancer; Metastatic; Human Epidermal Growth Factor; Receptor 2 ID PHASE-III TRIAL; ADJUVANT CHEMOTHERAPY; CLINICAL-OUTCOMES; ELDERLY-PATIENTS; FOLLOW-UP; 1ST-LINE CHEMOTHERAPY; PLUS TRASTUZUMAB; WEEKLY DOCETAXEL; HEART-FAILURE; SINGLE-AGENT AB Treating older patients with metastatic human epidermal growth factor receptor 2 (HER2)-positive breast cancer is often challenging. This is largely due to the issues providers face in making decisions in the setting of limited efficacy and toxicity data specific to older women in addition to the competing challenges of managing comorbidity and preserving functional status. Here, we discuss currently available treatment regimens and other important issues to consider when treating older patients with metastatic, HER2-positive disease. (C) 2013 Elsevier Ltd. All rights reserved. C1 [Freedman, Rachel A.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02215 USA. [Muss, Hyman B.] Univ N Carolina, Lineberger Comprehens Canc Ctr, Dept Med, Chapel Hill, NC 27514 USA. RP Freedman, RA (reprint author), Dana Farber Canc Inst, 450 Brookline Ave, Boston, MA 02215 USA. EM rafreedman@partners.org; hyman_muss@med.unc.edu NR 57 TC 2 Z9 2 U1 1 U2 4 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1879-4068 EI 1879-4076 J9 J GERIATR ONCOL JI J. Geriatr. Oncol. PD JAN PY 2014 VL 5 IS 1 BP 2 EP 7 DI 10.1016/j.jgo.2013.10.001 PG 6 WC Oncology; Geriatrics & Gerontology SC Oncology; Geriatrics & Gerontology GA AA0XJ UT WOS:000330820400001 PM 24484711 ER PT J AU Maggiore, RJ Gorawara-Bhat, R Levine, SK Dale, W AF Maggiore, Ronald J. Gorawara-Bhat, Rita Levine, Stacie K. Dale, William TI Perceptions, attitudes, and experiences of hematology/oncology fellows toward incorporating geriatrics in their training SO JOURNAL OF GERIATRIC ONCOLOGY LA English DT Article DE Geriatrics; Education; Training; Hematology/Oncology; Fellowship ID INTERNAL-MEDICINE-RESIDENTS; CANCER; KNOWLEDGE; COMPETENCES; CURRICULUM; CONSENSUS; OLDER AB The aging of the U.S. population continues to highlight emerging issues in providing care generally for older adults and specifically for older adults with cancer. The majority of patients with cancer in the U.S. are currently 65 years of age or older; therefore, training and research in geriatrics and geriatric oncology are viewed to be integral in meeting the needs of this vulnerable population. Yet, the ways to develop and integrate best geriatrics training within the context of hematology/oncology fellowship remain unclear. Toward this end, the current study seeks to evaluate the prior and current geriatric experiences and perspectives of hematology/oncology fellows. To gain insight into these experiences, focus groups of hematology/oncology fellows were conducted. Emergent themes included: 1) perceived lack of formal geriatric oncology didactics among fellows; 2) a considerable amount of variability exists in pre-fellowship geriatric experiences; 3) shared desire to participate in a geriatric oncology-based clinic; 4) differences across training levels in confidence in managing older adults with cancer; and 5) identification of specific criteria on how best to approach older adults with cancer in a particular clinical scenario. The present findings will help guide future studies in evaluating geriatrics among hematology/oncology fellows across institutions. They will also have implications in the development of geriatrics curricula and competencies specific to hematology/oncology training. Published by Elsevier Ltd. C1 [Maggiore, Ronald J.; Gorawara-Bhat, Rita; Levine, Stacie K.; Dale, William] Univ Chicago, Sect Geriatr & Palliat Med, Chicago, IL 60637 USA. [Maggiore, Ronald J.; Dale, William] Univ Chicago, Dept Med, Hematol Oncol Sect, Chicago, IL 60637 USA. RP Maggiore, RJ (reprint author), Portland VA Med Ctr, 3710 US Vet Hosp Rd,P3MED, Portland, OR 97239 USA. EM maggiore@ohsu.edu; stacie.levine@uchospitals.edu FU John A. Hartford Foundation of Center of Excellence in Geriatrics FX Supported by the auspices from the John A. Hartford Foundation of Center of Excellence in Geriatrics. NR 18 TC 3 Z9 3 U1 1 U2 4 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1879-4068 EI 1879-4076 J9 J GERIATR ONCOL JI J. Geriatr. Oncol. PD JAN PY 2014 VL 5 IS 1 BP 106 EP 115 DI 10.1016/j.jgo.2013.10.003 PG 10 WC Oncology; Geriatrics & Gerontology SC Oncology; Geriatrics & Gerontology GA AA0XJ UT WOS:000330820400014 PM 24484724 ER PT J AU Gardner, A Iverson, GL Stanwell, P AF Gardner, Andrew Iverson, Grant L. Stanwell, Peter TI A Systematic Review of Proton Magnetic Resonance Spectroscopy Findings in Sport-Related Concussion SO JOURNAL OF NEUROTRAUMA LA English DT Review DE athlete; concussion; magnetic resonance spectroscopy ID TRAUMATIC BRAIN-INJURY; TENSOR IMAGING FINDINGS; MR SPECTROSCOPY; TEMPORAL WINDOW; METABOLITE CONCENTRATIONS; FOOTBALL PLAYERS; QUANTIFICATION; GENDER; LACTATE; VULNERABILITY AB Traditional structural neuroimaging techniques are normal in athletes who sustain sport-related concussions and are only considered to be clinically helpful in ruling out a more serious brain injury. There is a clinical need for more sophisticated, non-invasive imaging techniques capable of detecting changes in neurophysiology after injury. Concussion is associated with neurometabolic changes including neuronal depolarization, release of excitatory neurotransmitters, ionic shifts, changes in glucose metabolism, altered cerebral blood flow, and impaired axonal function. Proton magnetic resonance spectroscopy (H-1-MRS, or simply MRS) is capable of measuring brain biochemistry and has the potential to identify and quantify physiologic changes after concussion. The focus of the current review is to provide an overview of research findings using MRS in sport-related concussion. A systematic review of articles published in the English language, up to February 2013, was conducted. Articles were retrieved via the databases: PsychINFO, Medline, Embase, SportDiscus, Scopus, Web of Science, and Informit using key terms: magnetic resonance spectroscopy, nuclear magnetic resonance spectroscopy, neurospectroscopy, spectroscopy, two-dimensional nuclear magnetic resonance spectroscopy, correlation spectroscopy, J-spectroscopy, exchange spectroscopy, nuclear overhauser effect spectroscopy, NMR, MRS, COSY, EXSY, NOESY, 2D NMR, craniocerebral trauma, mild traumatic brain injury, mTBI, traumatic brain injury, brain concussion, concussion, brain damage, sport, athletic, and athlete. Observational, cohort, correlational, cross-sectional, and longitudinal studies were all included in the current review. The review identified 11 publications that met criteria for inclusion, comprised of data on 200 athletes and 116 controls. Nine of 11 studies reported a MRS abnormality consistent with an alteration in neurochemistry. The results support the use of MRS as a research tool for identifying altered neurophysiology and monitoring recovery in adult athletes, even beyond the resolution of post-concussive symptoms and other investigation techniques returning to normative levels. Larger cross-sectional, prospective, and longitudinal studies are needed to understand the sensitivity and prognostic value of MRS within the field of sport-related concussion. C1 [Gardner, Andrew; Stanwell, Peter] Univ Newcastle, Ctr Translat Neurosci & Mental Hlth, Sch Med & Publ Hlth, Fac Hlth, Callaghan, NSW 2308, Australia. [Iverson, Grant L.] Harvard Univ, Sch Med, Dept Phys Med & Rehabil, Boston, MA USA. [Iverson, Grant L.] Red Sox Fdn, Boston, MA USA. [Iverson, Grant L.] Massachusetts Gen Hosp, Home Base Program, Boston, MA 02114 USA. RP Gardner, A (reprint author), Univ Newcastle, Ctr Translat Neurosci & Mental Hlth, Sch Med & Publ Hlth, Fac Hlth, Bowman Bldg, Callaghan, NSW 2308, Australia. EM gardner_andrew@hotmail.com RI Gardner, Andrew/J-5162-2013; Stanwell, Peter/F-9136-2012; OI Stanwell, Peter/0000-0002-4780-0393 NR 68 TC 16 Z9 17 U1 5 U2 20 PU MARY ANN LIEBERT, INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 0897-7151 EI 1557-9042 J9 J NEUROTRAUM JI J. Neurotrauma PD JAN 1 PY 2014 VL 31 IS 1 BP 1 EP 18 DI 10.1089/neu.2013.3079 PG 18 WC Critical Care Medicine; Clinical Neurology; Neurosciences SC General & Internal Medicine; Neurosciences & Neurology GA 302WJ UT WOS:000330635500001 PM 24047225 ER PT J AU Waljas, M Lange, RT Hakulinen, U Huhtala, H Dastidar, P Hartikainen, K Ohman, J Iverson, GL AF Waeljas, Minna Lange, Rael T. Hakulinen, Ullamari Huhtala, Heini Dastidar, Prasun Hartikainen, Kaisa Oehman, Juha Iverson, Grant L. TI Biopsychosocial Outcome after Uncomplicated Mild Traumatic Brain Injury SO JOURNAL OF NEUROTRAUMA LA English DT Review DE cognition; diffusion tensor imaging; mild traumatic brain injury; postconcussion syndrome ID SPORTS-RELATED CONCUSSION; TENSOR IMAGING FINDINGS; POSTTRAUMATIC-STRESS-DISORDER; WHITE-MATTER ABNORMALITIES; DIFFUSE AXONAL INJURY; MINOR HEAD-INJURY; GOOD OLD DAYS; POSTCONCUSSION-SYNDROME; CORPUS-CALLOSUM; NEUROPSYCHOLOGICAL OUTCOMES AB The purpose of this study was to examine the biopsychosocial outcome from uncomplicated mild traumatic brain injury (MTBI) within the first 3 weeks post injury. Participants were 48 prospectively enrolled patients from the Emergency Department of Tampere University Hospital, Finland, who sustained an uncomplicated MTBI. At 3 weeks post injury, diffusion tensor imaging (DTI) of the whole brain was undertaken using a Siemens 3T scanner. Measures of fractional anisotropy (FA) were calculated for 16 regions of interest (ROIs) and measures of apparent diffusion coefficient (ADC) were calculated for 10 ROIs. Twenty-four healthy control participants also completed DTI of the whole brain for comparison. Participants were administered a brief battery of self-report (e.g., postconcussion symptoms, depression, and fatigue) and neurocognitive measures (e.g., verbal learning and memory). There were no significant differences between the uncomplicated MTBI and healthy control group on any measures of learning and memory. Compared to the control group, the uncomplicated MTBI group reported a greater number of postconcussion symptoms and fatigue, but not depression. When considering all DTI ROIs simultaneously, the MTBI group had a significantly larger number of low DTI measures (FA values) compared to the healthy controls. MTBI patients with multifocal white matter changes did not show evidence of worse symptoms, cognitive impairment, or slower return to work compared to MTBI patients with broadly normal white matter. C1 [Waeljas, Minna; Oehman, Juha] Tampere Univ Hosp, Dept Neurosci & Rehabil, Tampere 33521, Finland. [Hakulinen, Ullamari; Dastidar, Prasun] Tampere Univ Hosp, Dept Radiol, Med Imaging Ctr, Tampere 33521, Finland. [Hakulinen, Ullamari; Dastidar, Prasun] Tampere Univ Hosp, Dept Hosp Pharm, Tampere 33521, Finland. [Waeljas, Minna; Dastidar, Prasun; Oehman, Juha] Univ Tampere, Sch Med, FIN-33101 Tampere, Finland. [Lange, Rael T.] Univ British Columbia, Vancouver, BC V5Z 1M9, Canada. [Lange, Rael T.] Def & Vet Brain Injury Ctr, Bethesda, MD USA. [Lange, Rael T.] Walter Reed Natl Mil Med Ctr, Bethesda, MD USA. [Hakulinen, Ullamari] Tampere Univ Technol, Dept Elect & Commun Engn, FIN-33101 Tampere, Finland. [Huhtala, Heini] Univ Tampere, Sch Hlth Sci, FIN-33101 Tampere, Finland. [Hartikainen, Kaisa] Pirkanmaa Hosp Dist, Behav Neurol Res Unit, Tampere, Finland. [Iverson, Grant L.] Harvard Univ, Sch Med, Dept Phys Med & Rehabil, Boston, MA USA. [Iverson, Grant L.] Red Sox Fdn, Boston, MA USA. [Iverson, Grant L.] Massachusetts Gen Hosp, Home Base Program, Boston, MA 02114 USA. RP Waljas, M (reprint author), Tampere Univ Hosp, Dept Neurosci & Rehabil, POB 2000, Tampere 33521, Finland. EM minna.waljas@gmail.com OI Ohman, Juha/0000-0002-6592-1367 FU Pirkanmaa Hospital District, Tampere University Hospital FX This research was funded by Competitive Research Funding of the Pirkanmaa Hospital District, Tampere University Hospital. This study was done as part of the first author's PhD thesis research program. The authors thank Suvi Liimatainen (MD, PhD) and Pasi Jolma (MD, PhD) for recruiting the patients and conducting neurological examinations, Antti Brander, MD, PhD, and Pertti Ryymin, PhLic for their helpful assistance with the DTI image analyses, and Annika Vuorinen (MSc) for assistance in recruitment and assessment of the control sample. Dr. Lange notes that the views expressed in this article are those of the authors and do not reflect the official policy of the Department of Defense or U.S. Government. Preliminary results of this study have been presented at the 8th World Congress on Brain Injury, International Brain Injury Association, Washington, DC, USA, March 2010. NR 136 TC 10 Z9 11 U1 2 U2 24 PU MARY ANN LIEBERT, INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 0897-7151 EI 1557-9042 J9 J NEUROTRAUM JI J. Neurotrauma PD JAN 1 PY 2014 VL 31 IS 1 BP 108 EP 124 DI 10.1089/neu.2013.2941 PG 17 WC Critical Care Medicine; Clinical Neurology; Neurosciences SC General & Internal Medicine; Neurosciences & Neurology GA 302WJ UT WOS:000330635500010 PM 23978227 ER PT J AU Schaefer, KG Griffin, L Smith, C May, CW Stevenson, LW AF Schaefer, Kristen G. Griffin, Leslie Smith, Colleen May, Christopher W. Stevenson, Lynne W. TI An Interdisciplinary Checklist for Left Ventricular Assist Device Deactivation SO JOURNAL OF PALLIATIVE MEDICINE LA English DT Letter ID LIFE; END C1 [Schaefer, Kristen G.] Dana Farber Canc Inst, Div Adult Palliat Care, Boston, MA 02215 USA. [Griffin, Leslie; Smith, Colleen; Stevenson, Lynne W.] Brigham & Womens Hosp, Adv Heart Dis Sect, Boston, MA 02115 USA. [May, Christopher W.] Inova Fairfax Hosp, Adv Heart Failure & Transplant Program, Falls Church, VA USA. RP Schaefer, KG (reprint author), Dana Farber Canc Inst, D2-016A 450 Brookline Ave, Boston, MA 02215 USA. EM Kristen_Schaefer@dfci.harvard.edu NR 5 TC 4 Z9 4 U1 0 U2 1 PU MARY ANN LIEBERT, INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1096-6218 EI 1557-7740 J9 J PALLIAT MED JI J. Palliat. Med. PD JAN 1 PY 2014 VL 17 IS 1 BP 4 EP 5 DI 10.1089/jpm.2013.0450 PG 2 WC Health Care Sciences & Services SC Health Care Sciences & Services GA 302VW UT WOS:000330634100002 PM 24286202 ER PT J AU Sadasivam, RS Luger, TM Coley, HL Taylor, BB Padir, T Ritchie, CS Houston, TK AF Sadasivam, Rajani S. Luger, Tana M. Coley, Heather L. Taylor, Benjamin B. Padir, Taskin Ritchie, Christine S. Houston, Thomas K. TI Robot-assisted home hazard assessment for fall prevention: a feasibility study SO JOURNAL OF TELEMEDICINE AND TELECARE LA English DT Article ID OLDER-ADULTS; CARE; TECHNOLOGY; IMPAIRMENT; SIMULATION; MOBILITY; DESIGN AB We examined the feasibility of using a remotely manoeuverable robot to make home hazard assessments for fall prevention. We employed use-case simulations to compare robot assessments with in-person assessments. We screened the homes of nine elderly patients (aged 65 years or more) for fall risks using the HEROS screening assessment. We also assessed the participants' perspectives of the remotely-operated robot in a survey. The nine patients had a median Short Blessed Test score of 8 (interquartile range, IQR 2-20) and a median Life-Space Assessment score of 46 (IQR 27-75). Compared to the in-person assessment (mean = 4.2 hazards identified per participant), significantly more home hazards were perceived in the robot video assessment (mean = 7.0). Only two checklist items (adequate bedroom lighting and a clear path from bed to bathroom) had more than 60% agreement between in-person and robot video assessment. Participants were enthusiastic about the robot and did not think it violated their privacy. The study found little agreement between the in-person and robot video hazard assessments. However, it identified several research questions about how to best use remotely-operated robots. C1 [Sadasivam, Rajani S.; Houston, Thomas K.] Univ Massachusetts, Sch Med, Div Hlth Informat & Implementat Sci, Worcester, MA 01655 USA. [Sadasivam, Rajani S.; Luger, Tana M.; Houston, Thomas K.] Bedford VAMC, VA E Hlth Qual Enhancement Res Initiat, Bedford, MA USA. [Luger, Tana M.; Houston, Thomas K.] Bedford VAMC, Ctr Healthcare Org & Implementat Res, Bedford, MA USA. [Coley, Heather L.] Univ Alabama Birmingham, Div Infect Dis, Dept Med, Birmingham, AL USA. [Taylor, Benjamin B.] Univ Alabama Birmingham, Div Gen Internal Med, Dept Med, Birmingham, AL USA. [Padir, Taskin] Worcester Polytech Inst, Dept Elect & Comp Engn, Worcester, MA USA. [Ritchie, Christine S.] Univ Calif San Francisco, Div Geriatr, Dept Med, San Francisco, CA 94143 USA. [Ritchie, Christine S.] San Francisco VA Med Ctr, San Francisco, CA USA. RP Sadasivam, RS (reprint author), Univ Massachusetts, Sch Med, Div Hlth Informat & Implementat Sci, 368 Plantat St, Worcester, MA 01655 USA. EM Rajani.Sadasivam@umassmed.edu FU National Institute on Aging [P30AG031054]; National Center for Advancing Translational Sciences of the National Institutes of Health [UL1TR000161]; National Cancer Institute Career Development Award [K07CA172677] FX The work was supported by the National Institute on Aging (award number P30AG031054) and the National Center for Advancing Translational Sciences of the National Institutes of Health (award number UL1TR000161). Dr Sadasivam is also funded by a National Cancer Institute Career Development Award (K07CA172677). The paper does not necessarily represent the official views of the National Institute on Aging or the National Institutes of Health, or the Department of Veterans Affairs or the United States government. NR 19 TC 2 Z9 2 U1 4 U2 9 PU SAGE PUBLICATIONS LTD PI LONDON PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND SN 1357-633X EI 1758-1109 J9 J TELEMED TELECARE JI J. Telemed. Telecare PD JAN PY 2014 VL 20 IS 1 BP 3 EP 10 DI 10.1177/1357633X13517350 PG 8 WC Health Care Sciences & Services SC Health Care Sciences & Services GA 302OE UT WOS:000330613200001 PM 24352900 ER PT J AU Karavan, M Compton, N Knezevich, S Raugi, G Kodama, S Taylor, L Reiber, GE AF Karavan, Mahsa Compton, Nicholas Knezevich, Stevan Raugi, Gregory Kodama, Samantha Taylor, Leslie Reiber, Gayle E. TI Teledermatology in the diagnosis of melanoma SO JOURNAL OF TELEMEDICINE AND TELECARE LA English DT Article ID CUTANEOUS MALIGNANT-MELANOMA; FORWARD TELEDERMATOLOGY; MANAGEMENT; DERMATOLOGISTS; LESIONS; TRIAGE AB We conducted a retrospective chart review of US Veterans in the Pacific Northwest area to compute melanoma incidence and Breslow depth at diagnosis. We compared Veterans with access to teledermatology (TD) and those without (non-TD). We identified pathology-confirmed primary melanomas in Veterans who had had at least one encounter at a VA facility during a 3-year study period. The age-adjusted melanoma incidence for all, TD and non-TD Veterans was 36, 15 and 57 per 100,000, respectively. The mean Breslow depth was significantly greater in the TD group (P = 0.03). Although a higher proportion of thin (Breslow depth <= 1 mm) TD melanomas were mitotically active, this difference was not significant. We also found that 180 (40%) of the non-TD (face-to-face) diagnosed melanomas were from Veterans living in areas where TD was available. This suggests that the higher melanoma incidence in the non-TD group was mainly due to under-utilization of TD services. The study demonstrated that the TD service was not fully utilized in the VISN20 region, although the reasons for this are not clear. Where TD was utilized it tended to diagnose more advanced melanomas with worse initial prognosis. C1 [Karavan, Mahsa; Kodama, Samantha; Taylor, Leslie; Reiber, Gayle E.] VA Puget Sound Hlth Care Syst, Dept Vet Affairs, Hlth Serv Res & Dev, Seattle, WA USA. [Compton, Nicholas; Raugi, Gregory] VA Puget Sound Hlth Care Syst, Dept Vet Affairs, Div Dermatol, Specialty Care Serv, Seattle, WA USA. [Knezevich, Stevan] VA Puget Sound Hlth Care Syst, Dept Vet Affairs, Div Pathol, Seattle, WA USA. [Karavan, Mahsa; Compton, Nicholas; Raugi, Gregory] Univ Washington, Sch Med, Seattle, WA USA. [Knezevich, Stevan] Univ Washington, Dept Pathol, Seattle, WA 98195 USA. [Reiber, Gayle E.] Univ Washington, Dept Hlth Serv, Seattle, WA 98195 USA. RP Reiber, GE (reprint author), 1100 Olive Way 1400, Seattle, WA 98101 USA. EM Gayle.Reiber@va.gov FU US Department of Veterans Affairs; VISN20 Office of Rural Health Services; Health Services Research and Development Center of Excellence; VA Puget Sound Health Care System; Career Scientist Award of Dr Gayle Reiber [RCS 98-353] FX The work was supported by the US Department of Veterans Affairs, VISN20 Office of Rural Health Services, Health Services Research and Development Center of Excellence, VA Puget Sound Health Care System, and the Career Scientist Award of Dr Gayle Reiber (RCS 98-353). NR 21 TC 2 Z9 2 U1 0 U2 5 PU SAGE PUBLICATIONS LTD PI LONDON PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND SN 1357-633X EI 1758-1109 J9 J TELEMED TELECARE JI J. Telemed. Telecare PD JAN PY 2014 VL 20 IS 1 BP 18 EP 23 DI 10.1177/1357633X13517354 PG 6 WC Health Care Sciences & Services SC Health Care Sciences & Services GA 302OE UT WOS:000330613200003 PM 24352898 ER PT J AU Boland, GW Duszak, R McGinty, G Allen, B AF Boland, Giles W. Duszak, Richard, Jr. McGinty, Geraldine Allen, Bibb, Jr. TI Delivery of Appropriateness, Quality, Safety, Efficiency and Patient Satisfaction SO JOURNAL OF THE AMERICAN COLLEGE OF RADIOLOGY LA English DT Editorial Material ID RADIOLOGYS VALUE; WORK PROCESS; HEALTH-CARE; SYSTEM C1 [Boland, Giles W.] Harvard Univ, Sch Med, Dept Radiol, Massachusetts Gen Hosp, Boston, MA 02115 USA. [Duszak, Richard, Jr.] Harvey L Neiman Hlth Policy Inst, Reston, VA USA. [McGinty, Geraldine] NRAD Med Associates PC, Garden City, NY USA. [Allen, Bibb, Jr.] Trinity Med Ctr, Birmingham, AL USA. RP Boland, GW (reprint author), Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. EM Boland.Giles@mgh.harvard.edu RI Duszak, Richard/L-1811-2016; OI Duszak, Richard/0000-0003-0425-3008; McGinty, Geraldine/0000-0001-6111-2514 NR 18 TC 21 Z9 21 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 JAN PY 2014 VL 11 IS 1 BP 7 EP 11 DI 10.1016/j.jacr.2013.07.016 PG 5 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 303NS UT WOS:000330681800005 PM 24387963 ER PT J AU Earls, JP Woodard, PK Abbara, S Akers, SR Araoz, PA Cummings, K Cury, RC Dorbala, S Hoffmann, U Hsu, JY Jacobs, JE Min, JK AF Earls, James P. Woodard, Pamela K. Abbara, Suhny Akers, Scott R. Araoz, Philip A. Cummings, Kristopher Cury, Ricardo C. Dorbala, Sharmila Hoffmann, Udo Hsu, Joe Y. Jacobs, Jill E. Min, James K. TI ACR Appropriateness Criteria Asymptomatic Patient at Risk for Coronary Artery Disease SO JOURNAL OF THE AMERICAN COLLEGE OF RADIOLOGY LA English DT Article DE Appropriateness criteria; coronary artery calcium score; coronary artery disease; asymptomatic; multidetector CT (MDCT) ID CARDIAC COMPUTED-TOMOGRAPHY; AMERICAN-HEART-ASSOCIATION; CARDIOVASCULAR MAGNETIC-RESONANCE; INCREMENTAL PROGNOSTIC VALUE; SILENT-MYOCARDIAL-ISCHEMIA; STRESS ECHOCARDIOGRAPHY; CT ANGIOGRAPHY; TASK-FORCE; DIAGNOSTIC PERFORMANCE; PRACTICE GUIDELINES AB Atherosclerotic cardiovascular disease is the leading cause of death for both men and women in the United States. Coronary artery disease has a long asymptomatic latent period and early targeted preventive measures can reduce mortality and morbidity. It is important to accurately classify individuals at elevated risk in order to identify those who might benefit from early intervention. Imaging advances have made it possible to detect subclinical coronary atherosclerosis. Coronary artery calcium score correlates closely with overall atherosclerotic burden and provides useful prognostic information for patient management. Our purpose is to discuss use of diagnostic imaging in asymptomatic patients at elevated risk for future cardiovascular events. The goal for these patients is to further refine targeted preventative efforts based on risk. The following imaging modalities are available for evaluating asymptomatic patients at elevated risk: radiography, fluoroscopy, multidetector CT, ultrasound, MRI, cardiac perfusion scintigraphy, echocardiography, and PET. The ACR Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed every 2 years by a multidisciplinary expert panel. The guideline development and review include an extensive analysis of current medical literature from peer-reviewed journals and the application of a well-established consensus methodology (modified Delphi) to rate the appropriateness of imaging and treatment procedures by the panel. In those instances where evidence is lacking or not definitive, expert opinion may be used to recommend imaging or treatment. C1 [Earls, James P.] Fairfax Radiol Consultants, Fairfax, VA USA. [Woodard, Pamela K.; Cummings, Kristopher] Washington Univ, Sch Med, Mallinckrodt Inst Radiol, St Louis, MO USA. [Abbara, Suhny] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Akers, Scott R.] VA Med Ctr, Philadelphia, PA USA. [Araoz, Philip A.] Mayo Clin, Rochester, MN USA. [Cury, Ricardo C.] Baptist Hosp Miami, Kendall, FL USA. [Dorbala, Sharmila] Brigham & Womens Hosp, Soc Nucl Med, Boston, MA 02115 USA. [Hoffmann, Udo] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Hoffmann, Udo] Harvard Univ, Sch Med, Boston, MA USA. [Hsu, Joe Y.] Kaiser Permanente, Los Angeles, CA USA. [Jacobs, Jill E.] NYU Med Ctr, New York, NY 10016 USA. [Min, James K.] Cedars Sinai Med Ctr, Amer Coll Cardiol, Los Angeles, CA 90048 USA. RP Earls, JP (reprint author), Amer Coll Radiol, 1891 Preston White Dr, Reston, VA 20191 USA. EM jpearls@yahoo.com FU Astellas Pharma US Inc.; NIH K23 grant FX Dr Dorbala is the recipient of a research grant from Astellas Pharma US Inc. and is funded by an NIH K23 grant. NR 73 TC 4 Z9 5 U1 0 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 JAN PY 2014 VL 11 IS 1 BP 12 EP 19 DI 10.1016/j.jacr.2013.09.021 PG 8 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 303NS UT WOS:000330681800006 PM 24316232 ER PT J AU Sierzenski, PR Linton, OW Amis, ES Courtney, DM Larson, PA Mahesh, M Novelline, RA Frush, DP Mettler, FA Timins, JK Tenforde, TS Boice, JD Brink, JA Bushberg, JT Schauer, DA AF Sierzenski, Paul R. Linton, Otha W. Amis, E. Stephen, Jr. Courtney, D. Mark Larson, Paul A. Mahesh, Mahadevappa Novelline, Robert A. Frush, Donald P. Mettler, Fred A. Timins, Julie K. Tenforde, Thomas S. Boice, John D., Jr. Brink, James A. Bushberg, Jerrold T. Schauer, David A. TI Applications of Justification and Optimization in Medical Imaging: Examples of Clinical Guidance for Computed Tomography Use in Emergency Medicine SO JOURNAL OF THE AMERICAN COLLEGE OF RADIOLOGY LA English DT Article ID MINOR HEAD-INJURY; DECISION-SUPPORT; UNITED-STATES; CRITICAL-ISSUES; CT; TRAUMA; POLICY; RULE; PERFORMANCE; MANAGEMENT AB Availability, reliability, and technical improvements have led to continued expansion of computed tomography (CT) imaging. During a CT scan, there is substantially more exposure to ionizing radiation than with conventional radiography. This has led to questions and critical conclusions about whether the continuous growth of CT scans should be subjected to review and potentially restraints or, at a minimum, closer investigation. This is particularly pertinent to populations in emergency departments, such as children and patients who receive repeated CT scans for benign diagnoses. During the last several decades, among national medical specialty organizations; the American College of Emergency Physicians and the American College of Radiology have each formed membership working groups to consider value, access, and expedience and to promote broad acceptance of CT protocols and procedures within their disciplines. Those efforts have had positive effects on the use criteria for CT by other physician groups, health insurance carriers, regulators, and legislators. C1 [Sierzenski, Paul R.] Christiana Care Hlth Syst, Dept Emergency Med, Sect Emergency Ultrasound, Newark, DE 19716 USA. [Amis, E. Stephen, Jr.] Albert Einstein Coll Med, Dept Radiol, Bronx, NY 10467 USA. [Amis, E. Stephen, Jr.] Montefiore Med Ctr, Bronx, NY 10467 USA. [Courtney, D. Mark] Northwestern Univ, Dept Emergency Med, Chicago, IL 60611 USA. [Larson, Paul A.] Radiol Associates Fox Valley, Neenah, WI USA. [Mahesh, Mahadevappa] Johns Hopkins Univ, Sch Med, Russell H Morgan Dept Radiol & Radiol Sci, Baltimore, MD USA. [Novelline, Robert A.] Harvard Univ, Sch Med, Boston, MA USA. [Novelline, Robert A.] Massachusetts Gen Hosp, Emergency Radiol Div, Boston, MA 02114 USA. [Frush, Donald P.] Duke Univ, Med Ctr, Div Pediat Radiol, Durham, NC USA. [Mettler, Fred A.] New Mexico VAHCS, Dept Radiol, Albuquerque, NM USA. [Tenforde, Thomas S.; Boice, John D., Jr.; Schauer, David A.] Natl Council Radiat Protect & Measurements, Bethesda, MD USA. [Brink, James A.] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. [Bushberg, Jerrold T.] Univ Calif Davis, Dept Radiol, Sacramento, CA 95817 USA. RP Sierzenski, PR (reprint author), Christiana Care Hlth Syst, Dept Emergency Med, Sect Emergency Ultrasound, Newark, DE 19716 USA. EM psierzenski@christianacare.org NR 50 TC 9 Z9 9 U1 0 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 JAN PY 2014 VL 11 IS 1 BP 36 EP 44 DI 10.1016/j.jacr.2013.09.023 PG 9 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 303NS UT WOS:000330681800010 PM 24135540 ER PT J AU Iyer, RS Lam, DL Bhargava, P Stern, EJ Wood, BP Paladin, AM AF Iyer, Ramesh S. Lam, Diana L. Bhargava, Puneet Stern, Eric J. Wood, Beverly P. Paladin, Angelisa M. TI Implementing and Refining a Faculty-Resident Mentorship Program SO JOURNAL OF THE AMERICAN COLLEGE OF RADIOLOGY LA English DT Editorial Material ID ACADEMIC MEDICINE; RADIOLOGY C1 [Iyer, Ramesh S.; Paladin, Angelisa M.] Seattle Childrens Hosp, Dept Radiol, Seattle, WA USA. [Lam, Diana L.; Stern, Eric J.] Univ Washington, Sch Med, Dept Radiol, Seattle, WA 98195 USA. [Bhargava, Puneet] VA Puget Sound Hlth Care Syst, Dept Radiol, Seattle, WA USA. [Wood, Beverly P.] Univ So Calif, Dept Radiol, Keck Sch Med, Los Angeles, CA USA. RP Iyer, RS (reprint author), Univ Washington, Sch Med, Seattle Childrens Hosp, 4800 Sand Point Way NE, Seattle, WA 98105 USA. EM riyer@uw.edu OI Bhargava, Puneet/0000-0002-3849-9666 NR 14 TC 0 Z9 0 U1 0 U2 7 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 JAN PY 2014 VL 11 IS 1 BP 85 EP 87 DI 10.1016/j.jacr.2013.02.006 PG 3 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 303NS UT WOS:000330681800020 PM 23583083 ER PT J AU Moldt, B Saye-Francisco, K Schultz, N Burton, DR Hessen, AJ AF Moldt, Brian Saye-Francisco, Karen Schultz, Niccole Burton, Dennis R. Hessen, Ann J. TI Simplifying the synthesis of SIgA: Combination of dIgA and rhSC using affinity chromatography SO METHODS LA English DT Article DE IgA; Secretory IgA; Mucosal IgA; Affinity chromatography; Antibody ID POLYMERIC IG RECEPTOR; MEDIATED EPITHELIAL TRANSPORT; SECRETORY COMPONENT; J-CHAIN; IMMUNOGLOBULIN-A; IN-VITRO; IMMUNODEFICIENCY-VIRUS; MONOCLONAL-ANTIBODY; ANTIGEN-BINDING; DIMERIC IGA AB The mucosal epithelia together with adaptive immune responses, such as local production and secretion of dimeric and polymeric immunoglobulin A (IgA), are a crucial part of the first line of defense against invading pathogens. IgA is primarily secreted as SIgA and plays multiple roles in mucosal defense. The study of SIgA-mediated protection is an important area of research in mucosal immunity but an easy, fast and reproducible method to generate pathogen-specific SIgA in vitro has not been available. We report here a new method to produce SIgA by co-purification of dimeric IgA, containing J chain, and recombinant human SC expressed in CHO cells. We previously reported the generation, production and characterization of the human recombinant monoclonal antibody IgA2 b12. This antibody, derived from the variable regions of the neutralizing anti-HIV-1 mAb IgG1 b12, blocked viral attachment and uptake by epithelial cells in vitro. We used a cloned CHO cell line that expresses monomeric, dimeric and polymeric species of IgA2 b12 for large-scale production of dIgA2 b12. Subsequently, we generated a CHO cell line to express recombinant human secretory component (rhSC). Here, we combined dIgA2 b12 and CHO-expressed rhSC via column chromatography to produce SIgA2 b12 that remains fully intact upon elution with 0.1 M citric acid, pH 3.0. We have performed biochemical analysis of the synthesized SIgA to confirm the species is of the expected size and retains the functional properties previously described for IgA2 b12. We show that SIgA2 b12 binds to the HIV-1 gp120 glycoprotein with similar apparent affinity to that of monomeric and dimeric forms of IgA2 b12 and neutralizes HIV-1 isolates with similar potency. An average yield of 6 mg of SIgA2 b12 was achieved from the combination of 20 mg of purified dIgA2 b12 and 2 L of rhSC-containing CHO cell supernatant. We conclude that synthesized production of stable SIgA can be generated by co-purification. This process introduces a simplified means of generating a variety of pathogen-specific SIgA antibodies for research and clinical applications. (C) 2013 Elsevier Inc. All rights reserved. C1 [Moldt, Brian; Saye-Francisco, Karen; Schultz, Niccole; Burton, Dennis R.; Hessen, Ann J.] Scripps Res Inst, Dept Immunol & Microbial Sci, La Jolla, CA 92037 USA. [Moldt, Brian; Saye-Francisco, Karen; Schultz, Niccole; Burton, Dennis R.; Hessen, Ann J.] Scripps Res Inst, IAVI Neutralizing Antibody Ctr, La Jolla, CA 92037 USA. [Moldt, Brian; Saye-Francisco, Karen; Schultz, Niccole; Burton, Dennis R.] Scripps Res Inst, Ctr HIV AIDS Vaccine Immunol & Immunogen Discover, La Jolla, CA 92037 USA. [Burton, Dennis R.] MIT, Massachusetts Gen Hosp, Ragon Inst, Boston, MA USA. RP Hessen, AJ (reprint author), Oregon Hlth & Sci Univ, Oregon Natl Primate Res Ctr, Beaverton, OR 97006 USA. EM hessell@ohsu.edu FU National Institutes of Allergy and Infectious Diseases [R01 AI33292]; Center for HIV/AIDS Vaccine Immunology and Immunogen Discovery Grant [UM1AI100663]; Lundbeck Foundation FX We thank Diane Kubitz and staff at the Antibody Production Core at The Scripps Research Institute for purification of dIgA2 b12. We thank Christina Corbaci for graphic design and artwork. This work was supported by the National Institutes of Allergy and Infectious Diseases Grant R01 AI33292 (DRB), Center for HIV/AIDS Vaccine Immunology and Immunogen Discovery Grant UM1AI100663 (DRB), and the Lundbeck Foundation (BM). NR 35 TC 7 Z9 9 U1 0 U2 8 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1046-2023 EI 1095-9130 J9 METHODS JI Methods PD JAN 1 PY 2014 VL 65 IS 1 BP 127 EP 132 DI 10.1016/j.ymeth.2013.06.022 PG 6 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 302LM UT WOS:000330606000014 PM 23811333 ER PT J AU Bolli, N Avet-Loiseau, H Wedge, DC Van Loo, P Alexandrov, LB Martincorena, I Dawson, KJ Iorio, F Nik-Zainal, S Bignell, GR Hinton, JW Li, YL Tubio, JMC McLaren, S Meara, SO Butler, AP Teague, JW Mudie, L Anderson, E Rashid, N Tai, YT Shammas, MA Sperling, AS Fulciniti, M Richardson, PG Parmigiani, G Magrangeas, F Minvielle, S Moreau, P Attal, M Facon, T Futreal, PA Anderson, KC Campbell, PJ Munshi, NC AF Bolli, Niccolo Avet-Loiseau, Herve Wedge, David C. Van Loo, Peter Alexandrov, Ludmil B. Martincorena, Inigo Dawson, Kevin J. Iorio, Francesco Nik-Zainal, Serena Bignell, Graham R. Hinton, Jonathan W. Li, Yilong Tubio, Jose M. C. McLaren, Stuart Meara, Sarah O' Butler, Adam P. Teague, Jon W. Mudie, Laura Anderson, Elizabeth Rashid, Naim Tai, Yu-Tzu Shammas, Masood A. Sperling, Adam S. Fulciniti, Mariateresa Richardson, Paul G. Parmigiani, Giovanni Magrangeas, Florence Minvielle, Stephane Moreau, Philippe Attal, Michel Facon, Thierry Futreal, P. Andrew Anderson, Kenneth C. Campbell, Peter J. Munshi, Nikhil C. TI Heterogeneity of genomic evolution and mutational profiles in multiple myeloma SO NATURE COMMUNICATIONS LA English DT Article ID CHRONIC LYMPHOCYTIC-LEUKEMIA; 21 BREAST CANCERS; KAPPA-B PATHWAY; INTRACLONAL HETEROGENEITY; PANCREATIC-CANCER; SOMATIC MUTATIONS; FREQUENT MUTATION; CELL LYMPHOMA; GENES; ACTIVATION AB Multiple myeloma is an incurable plasma cell malignancy with a complex and incompletely understood molecular pathogenesis. Here we use whole-exome sequencing, copy-number profiling and cytogenetics to analyse 84 myeloma samples. Most cases have a complex subclonal structure and show clusters of subclonal variants, including subclonal driver mutations. Serial sampling reveals diverse patterns of clonal evolution, including linear evolution, differential clonal response and branching evolution. Diverse processes contribute to the mutational repertoire, including kataegis and somatic hypermutation, and their relative contribution changes over time. We find heterogeneity of mutational spectrum across samples, with few recurrent genes. We identify new candidate genes, including truncations of SP140, LTB, ROBO1 and clustered missense mutations in EGR1. The myeloma genome is heterogeneous across the cohort, and exhibits diversity in clonal admixture and in dynamics of evolution, which may impact prognostic stratification, therapeutic approaches and assessment of disease response to treatment. C1 [Bolli, Niccolo; Wedge, David C.; Van Loo, Peter; Alexandrov, Ludmil B.; Martincorena, Inigo; Dawson, Kevin J.; Iorio, Francesco; Nik-Zainal, Serena; Bignell, Graham R.; Hinton, Jonathan W.; Li, Yilong; Tubio, Jose M. C.; McLaren, Stuart; Meara, Sarah O'; Butler, Adam P.; Teague, Jon W.; Mudie, Laura; Anderson, Elizabeth; Futreal, P. Andrew; Campbell, Peter J.] Wellcome Trust Sanger Inst, Canc Genome Project, Hinxton CB10 1SA, England. [Bolli, Niccolo; Campbell, Peter J.] Univ Cambridge, CIMR, Dept Haematol, Cambridge CB2 0XY, England. [Avet-Loiseau, Herve] CHU Rangueil, Unite Genom Myelome, F-31059 Toulouse, France. [Avet-Loiseau, Herve] INSERM, U1037, CRCT, F-31400 Toulouse, France. [Van Loo, Peter] VIB, Dept Human Genet, B-3000 Louvain, Belgium. [Van Loo, Peter] Univ Leuven, B-3000 Louvain, Belgium. [Iorio, Francesco] European Bioinformat Inst, European Mol Biol Lab, Hinxton CB10 1SA, England. [Nik-Zainal, Serena] Addenbrookes Hosp NHS Trust, Dept Med Genet, Cambridge CB2 0QQ, England. [Rashid, Naim; Tai, Yu-Tzu; Shammas, Masood A.; Sperling, Adam S.; Fulciniti, Mariateresa; Richardson, Paul G.; Anderson, Kenneth C.; Munshi, Nikhil C.] Harvard Univ, Sch Med, Lebow Inst Myeloma Therapeut, Boston, MA 02115 USA. [Rashid, Naim; Tai, Yu-Tzu; Shammas, Masood A.; Sperling, Adam S.; Fulciniti, Mariateresa; Richardson, Paul G.; Anderson, Kenneth C.; Munshi, Nikhil C.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Jerome Lipper Multiple Myeloma Ctr, Boston, MA 02115 USA. [Shammas, Masood A.; Munshi, Nikhil C.] Boston Vet Adm Healthcare Syst, West Roxbury, MA 02132 USA. [Parmigiani, Giovanni] Dana Farber Canc Inst, Boston, MA 02115 USA. [Parmigiani, Giovanni] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. [Magrangeas, Florence; Minvielle, Stephane] Univ Nantes, IRS UN, Inserm CNRS 6299, Ctr Canc Res Nantes Angers,UMR 892, F-44072 Nantes, France. [Magrangeas, Florence; Minvielle, Stephane] Univ Hosp, UMGC, F-44093 Nantes, France. [Moreau, Philippe] Univ Hosp, Dept Hematol, F-44093 Nantes, France. [Attal, Michel] Univ Hosp, Dept Hematol, F-31400 Toulouse, France. [Attal, Michel] INSERM, CRCT, U1037, F-31400 Toulouse, France. [Facon, Thierry] Univ Hosp, Dept Hematol, F-59045 Lille, France. RP Campbell, PJ (reprint author), Wellcome Trust Sanger Inst, Canc Genome Project, Hinxton CB10 1SA, England. EM pc8@sanger.ac.uk; nikhil_munshi@dfci.harvard.edu RI FACON, THIERRY/M-9736-2014; Tubio, Jose/H-5076-2015; richard, chrystelle/K-8595-2015; Magrangeas, Florence/L-3080-2015; Minvielle, Stephane/K-8251-2015; Bolli, Niccolo/D-4057-2011; OI FACON, THIERRY/0000-0001-7705-8460; Tubio, Jose/0000-0003-3540-2459; Bolli, Niccolo/0000-0002-1018-5139; Van Loo, Peter/0000-0003-0292-1949; Iorio, Francesco/0000-0001-7063-8913; Wedge, David/0000-0002-7572-3196; Alexandrov, Ludmil/0000-0003-3596-4515 FU NIH [PO1-155258, RO1-124929, P50-100007, PO1-78378, RCA125711C]; Veterans Administration grant [I01-BX001584]; Wellcome Trust [077012/Z/05/Z]; Lady Tata Memorial Trust FX This work was supported by a grant from NIH PO1-155258 (N.C.M., P.J.C., K. C. A., H. A.-L. and S. M.), RO1-124929 (N.C.M.) P50-100007 (K. C. A. and N.C.M.) PO1-78378 (K. C. A. and N.C.M.) NIH RCA125711C (M. A. S.), by a Veterans Administration grant I01-BX001584 (N.C.M.), and by the Wellcome Trust (grant reference 077012/Z/05/Z). P.J.C. is personally funded through a Wellcome Trust Senior Clinical Research Fellowship. K. C. A. is an American Cancer Society Clinical Research Professor N.B. is an EHA fellow and has been supported by a grant from the Lady Tata Memorial Trust. P. V. L. is a postdoctoral researcher of the Research Foundation-Flanders. S.N.-Z. is funded through a Wellcome Trust Intermediate Clinical Fellowship. We thank the Intergroupe Francophone du Myelome for providing patient samples and scientific support. NR 60 TC 155 Z9 156 U1 6 U2 40 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 2041-1723 J9 NAT COMMUN JI Nat. Commun. PD JAN PY 2014 VL 5 AR 2997 DI 10.1038/ncomms3997 PG 13 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA AA4QV UT WOS:000331081900001 PM 24429703 ER PT J AU Rodin, S Antonsson, L Niaudet, C Simonson, OE Salmela, E Hansson, EM Domogatskaya, A Xiao, ZJ Damdimopoulou, P Sheikhi, M Inzunza, J Nilsson, AS Baker, D Kuiper, R Sun, Y Blennow, E Nordenskjold, M Grinnemo, KH Kere, J Betsholtz, C Hovatta, O Tryggvason, K AF Rodin, Sergey Antonsson, Liselotte Niaudet, Colin Simonson, Oscar E. Salmela, Elina Hansson, Emil M. Domogatskaya, Anna Xiao, Zhijie Damdimopoulou, Pauliina Sheikhi, Mona Inzunza, Jose Nilsson, Ann-Sofie Baker, Duncan Kuiper, Raoul Sun, Yi Blennow, Elisabeth Nordenskjold, Magnus Grinnemo, Karl-Henrik Kere, Juha Betsholtz, Christer Hovatta, Outi Tryggvason, Karl TI Clonal culturing of human embryonic stem cells on laminin-521/E-cadherin matrix in defined and xeno-free environment SO NATURE COMMUNICATIONS LA English DT Article ID LAMININ LAMININ BETA-2; TERM SELF-RENEWAL; E-CADHERIN; FEEDER CELLS; SERUM REMOVAL; LINES; GROWTH; DERIVATION; EXPRESSION; EXPANSION AB Lack of robust methods for establishment and expansion of pluripotent human embryonic stem (hES) cells still hampers development of cell therapy. Laminins (LN) are a family of highly cell-type specific basement membrane proteins important for cell adhesion, differentiation, migration and phenotype stability. Here we produce and isolate a human recombinant LN-521 isoform and develop a cell culture matrix containing LN-521 and E-cadherin, which both localize to stem cell niches in vivo. This matrix allows clonal derivation, clonal survival and long-term self-renewal of hES cells under completely chemically defined and xeno-free conditions without ROCK inhibitors. Neither LN-521 nor E-cadherin alone enable clonal survival of hES cells. The LN-521/E-cadherin matrix allows hES cell line derivation from blastocyst inner cell mass and single blastomere cells without a need to destroy the embryo. This method can facilitate the generation of hES cell lines for development of different cell types for regenerative medicine purposes. C1 [Rodin, Sergey; Domogatskaya, Anna; Xiao, Zhijie; Nilsson, Ann-Sofie; Tryggvason, Karl] Karolinska Inst, Dept Med Biochem & Biophys, Div Matrix Biol, SE-17177 Stockholm, Sweden. [Antonsson, Liselotte; Damdimopoulou, Pauliina; Sheikhi, Mona; Inzunza, Jose; Hovatta, Outi] Karolinska Inst, Dept Clin Sci Intervent & Technol, Div Obstet & Gynecol, SE-14186 Huddinge, Sweden. [Antonsson, Liselotte; Damdimopoulou, Pauliina; Sheikhi, Mona; Inzunza, Jose; Hovatta, Outi] Karolinska Univ Hosp, SE-14186 Huddinge, Sweden. [Niaudet, Colin; Betsholtz, Christer] Karolinska Inst, Dept Med Biochem & Biophys, SE-17177 Stockholm, Sweden. [Simonson, Oscar E.; Grinnemo, Karl-Henrik] Karolinska Inst, Adv Ctr Translat Regenerat Med ACTREM, Dept Mol Med & Surg, Div Cardiothorac Surg & Anaesthesiol, SE-17177 Stockholm, Sweden. [Simonson, Oscar E.; Grinnemo, Karl-Henrik] Karolinska Univ Hosp, SE-17177 Stockholm, Sweden. [Salmela, Elina; Kere, Juha] Univ Helsinki, Res Programs Unit, FI-00014 Helsinki, Finland. [Salmela, Elina; Kere, Juha] Folkhalsan Inst Genet, FI-00014 Helsinki, Finland. [Hansson, Emil M.] Massachusetts Gen Hosp, Cardiovasc Res Ctr, Boston, MA 02114 USA. [Baker, Duncan] Sheffield Childrens NHS Trust, Sheffield Diagnost Genet Serv, Sheffield S10 2TH, S Yorkshire, England. [Kuiper, Raoul] Karolinska Hosp, Karolinska Inst, FENO, Dept Lab Med, SE-14186 Stockholm, Sweden. [Sun, Yi] BioLamina AB, S-17266 Sundbyberg, Sweden. [Blennow, Elisabeth; Nordenskjold, Magnus] Karolinska Univ Hosp, Dept Mol Med & Surg, S-17176 Stockholm, Sweden. [Blennow, Elisabeth; Nordenskjold, Magnus] Karolinska Univ Hosp, Karolinska Inst, Ctr Mol Med, S-17176 Stockholm, Sweden. [Kere, Juha] Karolinska Inst, Dept Biosci & Nutr, SE-14183 Stockholm, Sweden. [Kere, Juha] Karolinska Inst, Sci Life Lab, SE-14183 Stockholm, Sweden. [Tryggvason, Karl] Duke NUS, Cardiovasc & Metab Disorders Program, Singapore 169857, Singapore. RP Tryggvason, K (reprint author), Karolinska Inst, Dept Med Biochem & Biophys, Div Matrix Biol, SE-17177 Stockholm, Sweden. EM karl.tryggvason@ki.se RI Domogatskaya, Anna/F-5794-2012; OI Domogatskaya, Anna/0000-0002-6468-1963; Kere, Juha/0000-0003-1974-0271; Kuiper, Raoul/0000-0001-5645-2389; Grinnemo, Karl-Henrik/0000-0001-6717-3393; Damdimopoulou, Pauliina/0000-0001-8458-0855; Nordenskjold, Magnus/0000-0002-4974-425X; Rodin, Sergey/0000-0002-6954-1986; Salmela, Elina/0000-0003-1326-4462 FU Swedish Research Council; Knut and Alice Wallenberg Foundation; AFA Insurance Foundation; Soderberg's Foundation; European Commission; Sigrid Juselius Foundation; Leducq Foundation; National Medical Research Council, Singapore; Roche FX This work was supported in part by grants from the Swedish Research Council (K.T., O.H. and C.B.), the Knut and Alice Wallenberg Foundation (K.T. and C.B.), AFA Insurance Foundation.(K. T. and O.H.), Soderberg's Foundation (K.T. and C.B.), European Commission (O.H.), Sigrid Juselius Foundation (J.K.), the Leducq Foundation (C.B.), and National Medical Research Council, Singapore. E.M.H. is a Wenner-Gren Foundation fellow and performed the derivation of iPS cells as part of a project funded by Roche. Frank Lau and the Brigham and Women's Hospital's Specialized Histopathology Core performed the teratoma analysis of CVTB1.2 cells. We thank Myriam Peyrard-Janvid for the CNV analysis reference data and Ingela Forsberg for excellent technical assistance with karyotyping of human ES cells. NR 48 TC 67 Z9 67 U1 1 U2 29 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 JAN PY 2014 VL 5 AR 3195 DI 10.1038/ncomms4195 PG 13 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA AA5FX UT WOS:000331122600003 PM 24463987 ER PT J AU Kim, DY Wertz, MH Gautam, V D'Avanzo, C Bhattacharyya, R Kovacs, DM AF Kim, Doo Yeon Wertz, Mary H. Gautam, Vivek D'Avanzo, Carla Bhattacharyya, Raja Kovacs, Dora M. TI The E280A Presenilin Mutation Reduces Voltage. Gated Sodium Channel Levels in Neuronal Cells SO NEURODEGENERATIVE DISEASES LA English DT Article; Proceedings Paper CT 11th International Conference on Alzheimer's and Parkinson's Diseases (AD/PD) CY MAR 06-10, 2013 CL Florence, ITALY SP Covance, GE Healthcare, Greenberg Family, Nutricia Adv Med Nutr, Pfizer & Janssen Alzheimers Alliance, Prothena DE Alzheimer's disease; Presenilin; Voltage-gated sodium channel ID ALZHEIMERS-DISEASE; SECRETASE; BACE1; CLEAVAGE; EPILEPSY AB Background: Familial Alzheimer's disease (FAD) mutations in presenilin (PS) modulate PS/gamma-secretase activity and therefore contribute to AD pathogenesis. Previously, we found that PS/gamma-secretase cleaves voltage-gated sodium channel beta(2)-subunits (Na-v beta(2)), releases the intracellular domain of Na-v beta(2) (beta(2)-ICD), and thereby, increases intracellular sodium channel a-subunit Na(v)1.1 levels. Here, we tested whether FAD-linked PS1 mutations modulate Na-v beta(2) cleavages and Nav1.1 levels. Objective: It was the aim of this study to analyze the effects of PS1-linked FAD mutations on Na-v beta(2) processing and Nav1.1 levels in neuronal cells. Methods: We first generated B104 rat neuroblastoma cells stably expressing NavB2 and wild-type PS1 (wtPS1), PS1 with one of three FAD mutations (E280A, M146L or Delta E9), or PS1 with a non-FAD mutation (D333G). Na-v beta(2) processing and Nav1.1 protein and nnRNA levels were then analyzed by Western blot and real-time RT-PCR, respectively. Results: The FAD-linked E280A mutation significantly decreased PS/gamma-secretase-mediated processing of Na-v beta(2) as compared to wtPS1 controls, both in cells and in a cell-free system. Nav1.1 mRNA and protein levels , as well as the surface levels of Na-v channel alpha-subunits, were also significantly reduced in PS1 (E280A) cells. Conclusion: Our data indicate that the FAD-linked PS1(E280A) mutation decreases Nav channel levels by partially inhibiting the PS/gamma-secretase-mediated cleavage of Na-v beta(2) in neuronal cells. (C) 2013 S. Karger AG, Basel C1 [Kim, Doo Yeon; Wertz, Mary H.; Gautam, Vivek; D'Avanzo, Carla; Bhattacharyya, Raja; Kovacs, Dora M.] Harvard Univ, MassGen Inst Neurodegenerat Dis, Neurobiol Dis Lab, Genet & Aging Res Unit,Massachusetts Gen Hosp, Charlestown, MA 02129 USA. RP Kovacs, DM (reprint author), Massachusetts Gen Hosp, Neurobiol Dis Lab, Genet & Aging Res Unit, MassGen Inst Neurodegenerat Dis, Charlestown, MA 02129 USA. EM dora_kovacs@hms.harvard.edu FU NIA NIH HHS [R21 AG031483, P01 AG015379, R01 AG014713]; NINDS NIH HHS [R01 NS045860] NR 18 TC 2 Z9 2 U1 0 U2 0 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 1660-2854 EI 1660-2862 J9 NEURODEGENER DIS JI Neurodegener. Dis. PY 2014 VL 13 IS 2-3 BP 64 EP 68 DI 10.1159/000354669 PG 5 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 304MY UT WOS:000330752200004 PM 24217025 ER PT J AU Hung, AY Schwarzschild, MA AF Hung, Albert Y. Schwarzschild, Michael A. TI Treatment of Parkinson's Disease: What's in the Non-dopaminergic Pipeline? SO NEUROTHERAPEUTICS LA English DT Review DE Parkinson's disease; Non-dopaminergic; Dyskinesias; Motor fluctuations; Glutamate; Adenosine ID LEVODOPA-INDUCED DYSKINESIA; DOPA-INDUCED DYSKINESIA; ADENOSINE A(2A) RECEPTORS; ADRENOCEPTOR ANTAGONIST IDAZOXAN; METABOTROPIC GLUTAMATE RECEPTORS; RANDOMIZED CLINICAL-TRIAL; PLACEBO-CONTROLLED TRIAL; LESIONED MARMOSET MODEL; ON-OFF PHENOMENA; MOTOR FLUCTUATIONS AB Dopamine depletion resulting from degeneration of nigrostriatal dopaminergic neurons is the primary neurochemical basis of the motor symptoms of Parkinson's disease (PD). While dopaminergic replacement strategies are effective in ameliorating these symptoms early in the disease process, more advanced stages of PD are associated with the development of treatment-related motor complications and dopamine-resistant symptoms. Other neurotransmitter and neuromodulator systems are expressed in the basal ganglia and contribute to the extrapyramidal refinement of motor function. Furthermore, neuropathological studies suggest that they are also affected by the neurodegenerative process. These non-dopaminergic systems provide potential targets for treatment of motor fluctuations, levodopa-induced dyskinesias, and difficulty with gait and balance. This review summarizes recent advances in the clinical development of novel pharmacological approaches for treatment of PD motor symptoms. Although the non-dopaminergic pipeline has been slow to yield new drugs, further development will likely result in improved treatments for PD symptoms that are induced by or resistant to dopamine replacement. C1 [Hung, Albert Y.; Schwarzschild, Michael A.] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. [Schwarzschild, Michael A.] MassGen Inst Neurodegenerat Dis, Charlestown, MA 02129 USA. RP Hung, AY (reprint author), Massachusetts Gen Hosp, Dept Neurol, 55 Fruit St, Boston, MA 02114 USA. EM ahung@partners.org FU NIH [5K24NS060991]; DoD [W81XWH-11-1-0150] FX Work on this review was supported by NIH (5K24NS060991) and DoD (W81XWH-11-1-0150) (M.A.S.). NR 130 TC 10 Z9 11 U1 0 U2 8 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1933-7213 EI 1878-7479 J9 NEUROTHERAPEUTICS JI Neurotherapeutics PD JAN PY 2014 VL 11 IS 1 BP 34 EP 46 DI 10.1007/s13311-013-0239-9 PG 13 WC Clinical Neurology; Neurosciences; Pharmacology & Pharmacy SC Neurosciences & Neurology; Pharmacology & Pharmacy GA 302TC UT WOS:000330626800006 PM 24310604 ER PT J AU Bianchi, G Anderson, KC Harris, NL Sohani, AR AF Bianchi, Giada Anderson, Kenneth C. Harris, Nancy Lee Sohani, Aliyah R. TI The Heavy Chain Diseases: Clinical and Pathologic Features SO ONCOLOGY-NEW YORK LA English DT Article ID SMALL-INTESTINAL DISEASE; MEDITERRANEAN LYMPHOMA; CAMPYLOBACTER-JEJUNI; MACROGLOBULINEMIA; FLUDARABINE; INVOLVEMENT; GAMMOPATHY AB Heavy chain diseases are a family of rare, systemic syndromes typically associated with or representing a variant of a B-cell neoplasm. Their characteristic feature is production of a mutated imnnunoglobulin heavy chain incapable of either partnering with light chains in the formation of a full immunoglobulin molecule or of being degraded by the proteasonne. The abnormal heavy Chain is detected in urine and/or serum without an associated light chain, a pathognomonic finding. Depending on the subtype of the altered heavy chain, these conditions can be subclassified as alpha, gamma, or mu heavy chain disease. We discuss the clinical presentation; epidemiology; laboratory, radiologic, and pathologic features; and treatment options for each of the heavy chain diseases, emphasising the importance of an accurate pathologic diagnosis and correct interpretation of immunologic studies in their identification. C1 [Bianchi, Giada; Anderson, Kenneth C.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Bianchi, Giada; Anderson, Kenneth C.] Harvard Univ, Sch Med, Boston, MA USA. [Harris, Nancy Lee; Sohani, Aliyah R.] Harvard Univ, Massachusetts Gen Hosp, James Homer Wright Pathol Labs, Cambridge, MA 02138 USA. [Harris, Nancy Lee; Sohani, Aliyah R.] Harvard Univ, Sch Med, Dept Pathol, Cambridge, MA 02138 USA. RP Bianchi, G (reprint author), Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. NR 44 TC 5 Z9 5 U1 1 U2 2 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 JAN PY 2014 VL 28 IS 1 BP 45 EP 53 PG 9 WC Oncology SC Oncology GA 301QQ UT WOS:000330547400006 PM 24683718 ER PT J AU Daskalakis, NP Diamantopoulou, A Claessens, SEF Remmers, E Tjalve, M Oitzl, MS Champagne, DL de Kloet, ER AF Daskalakis, Nikolaos P. Diamantopoulou, Anastasia Claessens, Sanne E. F. Remmers, Elisa Tjalve, Marika Oitzl, Melly S. Champagne, Danielle L. de Kloet, E. Ronald TI Early experience of a novel-environment in isolation primes a fearful phenotype characterized by persistent amygdala activation SO PSYCHONEUROENDOCRINOLOGY LA English DT Article DE Maternal separation; Novelty stress; Amygdala; c-Fos; ACTH; Corticosterone; Social play; Short-term memory; Fear-conditioning ID PITUITARY-ADRENAL AXIS; EARLY-LIFE STRESS; MATERNAL-CARE; SPATIAL MEMORY; POSTNATAL-DEVELOPMENT; NATURAL VARIATIONS; NEONATAL-RATS; BRAIN-REGIONS; SOCIAL PLAY; ADULT RATS AB Prolonged maternal separation (MS) activates the neonate's hypothalamus-pituitary-adrenal axis causing elevated basal and stress-induced corticosterone levels that may initiate amygdala-dependent fear learning. Here we test the hypothesis that the adult fearful phenotype is programmed by the pup's stressful experience during prolonged MS rather than by prolonged maternal absence per se. For this purpose, Wistar rat pups were exposed, on postnatalday (pnd) 3, to: (i) repeated-MS in home-environment (HOME-SEP), 8h-MS daily for three days with the pups remaining together in the home-cage; (ii) repeated-MS in a novel-environment (NOVEL-SEP), with the same separation procedure, but now the pups were individually housed in a novel-environment during the 8 h dam's absence; (iii) repeated handling, which consisted of daily brief (15 min instead of 8 h) MS in the home-altogether or in a novel-environment individually (HOME-HAN and NOVEL-HAN, respectively); (iv) no-separation/no-handling (NON-SEP/NON-HAN) control condition, in which pups were left undisturbed in their home-cage. Compared to HOME-SEP rats, the NOVEL-SEP rats showed one day after the last MS enhanced stress-induced amygdala c-Fos expression and ACTH-release, despite of reduced adrenal corticosterone secretion. The higher amygdala c-Fos expression, ACTH-release and reduced corticosterone output observed postnatally, persisted into adulthood of the NOVEL-SEP animals. Behaviorally, NOVEL-SEP juvenile rats displayed deficits in social play, had intact spatial memory in the pen-pubertal period and showed more contextual fear memory compared to HOME-SEP in adulthood. Finally, NOVEL-HAN, compared to HOME-HAN, displayed increased stress-induced corticosterone output, no deficits in social play and reduced contextual fear. In conclusion, programming of an adult fearful phenotype linked to amygdala priming develops if pups are repeatedly isolated from peers in a novel-environment, while away from the dam for a prolonged period of time. (C) 2013 Elsevier Ltd. All rights reserved. C1 [Daskalakis, Nikolaos P.; Diamantopoulou, Anastasia; Claessens, Sanne E. F.; Remmers, Elisa; Tjalve, Marika; Oitzl, Melly S.; Champagne, Danielle L.; de Kloet, E. Ronald] Leiden Univ, Leiden Univ Med Ctr, Leiden Acad Ctr Drug Res, Div Med Pharmacol, Leiden, Netherlands. [Daskalakis, Nikolaos P.; de Kloet, E. Ronald] Leiden Univ, Leiden Univ Med Ctr, Dept Endocrinol & Metab, Leiden, Netherlands. [Daskalakis, Nikolaos P.] Icahn Sch Med Mt Sinai, Dept Psychiat, Traumat Stress Studies Div, New York, NY 10029 USA. [Daskalakis, Nikolaos P.] Icahn Sch Med Mt Sinai, Dept Psychiat, Lab Mol Neuropsychiat, New York, NY 10029 USA. [Daskalakis, Nikolaos P.] James J Peters Vet Affairs Med Ctr, Mental Hlth Care Ctr, PTSD Clin Res Program, Bronx, NY USA. [Daskalakis, Nikolaos P.] James J Peters Vet Affairs Med Ctr, Lab Clin Neuroendocrinol & Neurochem, Bronx, NY USA. [Diamantopoulou, Anastasia] Univ Athens, Sch Hlth Sci, Fac Nursing, Lab Biol Biochem, GR-10679 Athens, Greece. [Diamantopoulou, Anastasia] Columbia Univ, Dept Psychiat, New York, NY USA. RP Daskalakis, NP (reprint author), Icahn Sch Med Mt Sinai, Dept Psychiat, 1 Gustave L Levy Pl,Box 1668, New York, NY 10029 USA. EM nikolaos.daskalakis@mssm.edu RI Daskalakis, Nikolaos/B-7930-2014 OI Daskalakis, Nikolaos/0000-0003-1660-9112 FU Dutch TI-Pharma [T5-209]; Royal Netherlands Academy of Sciences FX The support by Dutch TI-Pharma T5-209 grant (to NPD and ERdK) and the Royal Netherlands Academy of Sciences (to ERdK) is gratefully acknowledged. We would like to thank Servane Lachize and Maaike van der Mark for the technical assistance with RIA; Wesley Fung, Marjolein Koller and Jasper Laboyrie for help in brain cryosectioning and/or in situ hybridization; Wout Meelis for the technical assistance with animal sampling and decapitation; Ricardo Llorente and Rixt van der Veen for help with maternal care observations; Rixt van der Veen for scientific input; the anonymous reviewers of this manuscript for their fruitful suggestions on the interpretation of the data. NR 88 TC 15 Z9 15 U1 1 U2 7 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0306-4530 J9 PSYCHONEUROENDOCRINO JI Psychoneuroendocrinology PD JAN PY 2014 VL 39 BP 39 EP 57 DI 10.1016/j.psyneuen.2013.09.021 PG 19 WC Endocrinology & Metabolism; Neurosciences; Psychiatry SC Endocrinology & Metabolism; Neurosciences & Neurology; Psychiatry GA AA0WM UT WOS:000330818100005 PM 24275003 ER PT J AU Nakao, M Takeuchi, T Fricchione, G AF Nakao, Mutsuhiro Takeuchi, Takeaki Fricchione, Gregory TI Definition of Psychosomatic Medicine and the Applicability of DSM-IV-TR to Outpatients Visiting a Japanese Psychosomatic Clinic SO PSYCHOTHERAPY AND PSYCHOSOMATICS LA English DT Letter ID DISORDERS C1 [Nakao, Mutsuhiro; Takeuchi, Takeaki] Teikyo Univ Hosp, Dept Psychosomat Med, Tokyo 1738605, Japan. [Fricchione, Gregory] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Int Psychiat, Boston, MA USA. [Fricchione, Gregory] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Benson Henry Inst Mind Body Med, Boston, MA USA. RP Nakao, M (reprint author), Teikyo Univ Hosp, Dept Psychosomat Med, Itabashi Ku, 2-11-1 Kaga, Tokyo 1738605, Japan. EM mnakao@med.teikyo-u.ac.jp NR 10 TC 2 Z9 2 U1 0 U2 1 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0033-3190 EI 1423-0348 J9 PSYCHOTHER PSYCHOSOM JI Psychother. Psychosom. PY 2014 VL 83 IS 2 BP 120 EP 121 DI 10.1159/000354182 PG 2 WC Psychiatry; Psychology SC Psychiatry; Psychology GA 302WH UT WOS:000330635300007 PM 24457266 ER PT J AU Jung, HS Kong, WH Sung, DK Lee, MY Beack, SE Keum, DH Kim, KS Yun, SH Hahn, SK AF Jung, Ho Sang Kong, Won Ho Sung, Dong Kyung Lee, Min-Young Beack, Song Eun Keum, Do Hee Kim, Ki Su Yun, Seok Hyun Hahn, Sei Kwang TI Nanographene Oxide-Hyaluronic Acid Conjugate for Photothermal Ablation Therapy of Skin Cancer SO ACS NANO LA English DT Article DE nanographene oxide; hyaluronic acid; photothermal therapy; skin cancer ID GRAPHENE OXIDE; DELIVERY; COMPLEX; TUMOR; NANOPARTICLES; APOPTOSIS AB Melanoma skin cancer is one of the most dangerous skin cancers and the main cause of skin-cancer-related mortality. Hyaluronic acid (HA) has been used as an effective transdermal delivery carrier of chemical drugs and biopharmaceuticals. In this work, a nanographene oxide-HA conjugate (NGO-HA) was synthesized for photothermal ablation therapy of melanoma skin cancer using a near-infrared (NIR) laser. Confocal microscopy and ex vivo bioimaging clearly visualized the remarkable transdermal delivery of NGO-HA to tumor tissues in the skin of mice, which might be ascribed to highly expressed HA receptors and relatively leaky structures around tumor tissues, enabling the enhanced permeation and retention of nanoparticles. The NIR irradiation resulted in complete ablation of tumor tissues with no recurrence of tumorigenesis. The antitumor effect was confirmed by ELISA for caspase-3 activity and histological and immunohistochemical analyses with TUNEL assay for tumor apoptosis. Taken together, we could confirm the feasibility of transdermal NGO-HA for photothermal ablation therapy of melanoma skin cancers. C1 [Jung, Ho Sang; Kong, Won Ho; Lee, Min-Young; Beack, Song Eun; Keum, Do Hee; Hahn, Sei Kwang] Pohang Univ Sci & Technol POSTECH, Dept Mat Sci & Engn, Pohang 790784, Kyungbuk, South Korea. [Sung, Dong Kyung] Sungkyunkwan Univ, Samsung Med Ctr, Sch Med, Dept Pediat, Seoul 135710, South Korea. [Kim, Ki Su; Yun, Seok Hyun; Hahn, Sei Kwang] Harvard Univ, Sch Med, Dept Dermatol, Wellman Ctr Photomed, Cambridge, MA 02139 USA. [Kim, Ki Su; Yun, Seok Hyun; Hahn, Sei Kwang] Massachusetts Gen Hosp, Cambridge, MA 02139 USA. RP Hahn, SK (reprint author), Pohang Univ Sci & Technol POSTECH, Dept Mat Sci & Engn, San 31, Pohang 790784, Kyungbuk, South Korea. EM skhanb@postech.ac.kr FU Converging Research Center Program through the National Research Foundation of Korea (NRF); Ministry of Education, Science and Technology [2009-0081871]; Midcareer Researcher Program through NRF grant; MEST [2012R1A2A2A06045773] FX This work was financially supported by the Converging Research Center Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education, Science and Technology (2009-0081871). This study was also supported by Midcareer Researcher Program through NRF grant funded by the MEST (No. 2012R1A2A2A06045773). We would like to thank In Tec Song and Prof. Hee Cheul Choi for the Raman spectroscopic analysis. NR 31 TC 48 Z9 51 U1 10 U2 137 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 1936-0851 EI 1936-086X J9 ACS NANO JI ACS Nano PD JAN PY 2014 VL 8 IS 1 BP 260 EP 268 DI 10.1021/nn405383a PG 9 WC Chemistry, Multidisciplinary; Chemistry, Physical; Nanoscience & Nanotechnology; Materials Science, Multidisciplinary SC Chemistry; Science & Technology - Other Topics; Materials Science GA 301OX UT WOS:000330542900025 ER PT J AU Lai, CP Mardini, O Ericsson, M Prabhakar, S Maguire, CA Chen, JW Tannous, BA Breakefield, XO AF Lai, Charles P. Mardini, Osama Ericsson, Maria Prabhakar, Shilpa Maguire, Casey A. Chen, John W. Tannous, Bakhos A. Breakefield, Xandra O. TI Dynamic Biodistribution of Extracellular Vesicles in Vivo Using a Multimodal Imaging Reporter SO ACS NANO LA English DT Article DE exosomes; microvesicles; bioluminescence; fluorescence; biotin; biodistribution; delivery ID DELIVERY-SYSTEM; CANCER CELLS; EXOSOMES; MICROVESICLES; INJECTION; LIPOSOMES; RECEPTOR; BRAIN; MICE; RNA AB Extracellular vesicles (EVs) are nanosized vesicles released by normal and diseased cells as a novel form of intercellular communication and can serve as an effective therapeutic vehicle for genes and drugs. Yet, much remains unknown about the in vivo properties of EVs such as tissue distribution, blood levels, and urine clearance, important parameters that will define their therapeutic effectiveness and potential toxicity. Here we combined Gaussia luciferase and metabolic biotinylation to create a sensitive EV reporter (EV-GlucB) for multimodal imaging in vivo, as well as monitoring of EV levels in the organs and biofluids ex vivo after administration of EVs. Bioluminescence and fluorescence-mediated tomography imaging on mice displayed a predominant localization of intravenously administered EVs in the spleen followed by the liver. Monitoring EV signal in the organs, blood, and urine further revealed that the EVs first undergo a rapid distribution phase followed by a longer elimination phase via hepatic and renal routes within six hours, which are both faster than previously reported using dye-labeled EVs. Moreover, we demonstrate systemically injected EVs can be delivered to tumor sites within an hour following injection. Altogether, we show the EVs are dynamically processed in vivo with accurate spatiotemporal resolution and target a number of normal organs as well as tumors with implications for disease pathology and therapeutic design. C1 [Lai, Charles P.; Mardini, Osama; Prabhakar, Shilpa; Maguire, Casey A.; Tannous, Bakhos A.; Breakefield, Xandra O.] Massachusetts Gen Hosp, Dept Neurol, Charlestown, MA 02129 USA. [Tannous, Bakhos A.; Breakefield, Xandra O.] Massachusetts Gen Hosp, Dept Radiol, Charlestown, MA 02129 USA. [Chen, John W.] Massachusetts Gen Hosp, Ctr Syst Biol, Charlestown, MA 02129 USA. [Chen, John W.] Massachusetts Gen Hosp, Ctr Mol Imaging Res, Charlestown, MA 02129 USA. [Lai, Charles P.; Tannous, Bakhos A.; Breakefield, Xandra O.] Harvard Univ, Sch Med, Program Neurosci, Boston, MA 02115 USA. [Ericsson, Maria] Harvard Univ, Sch Med, Convent Electron Microscopy Core, Boston, MA 02115 USA. RP Lai, CP (reprint author), Massachusetts Gen Hosp, Dept Neurol, Charlestown, MA 02129 USA. EM lai.charles@mgh.harvard.edu; breakefield@hms.harvard.edu RI Lai, Charles/D-5442-2017 FU NIH/NCI [CA141150, CA069246, U19CA179563]; Voices Against Brain Cancer (VABC); Canadian Institute of Health Research (CIHR); NIH/NINDS [P30NS045776] FX This work was supported by grants from NIH/NCI CA141150, CA069246, U19CA179563, and Voices Against Brain Cancer (VABC) (X.O.B.). C.P.L was supported by the Canadian Institute of Health Research (CIHR). We would like to thank R. Amante for his suggestions and discussion, P. Waterman for his help with FMT imaging, G. Lewandroski and D. Morse for the production of lentiviruses (MGH Vector Core, Boston, MA, USA, supported by NIH/NINDS P30NS045776 [BAT., X.O.B.]), Ran C. for IVIS Spectrum imaging assistance (Martinos Center for Biomedical Imaging, Boston, MA), and T. Diefenbach for microscope assistance (Ragon Institute Microscopy Core, Boston, MA). NR 40 TC 58 Z9 58 U1 4 U2 39 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 1936-0851 EI 1936-086X J9 ACS NANO JI ACS Nano PD JAN PY 2014 VL 8 IS 1 BP 483 EP 494 DI 10.1021/nn404945r PG 12 WC Chemistry, Multidisciplinary; Chemistry, Physical; Nanoscience & Nanotechnology; Materials Science, Multidisciplinary SC Chemistry; Science & Technology - Other Topics; Materials Science GA 301OX UT WOS:000330542900048 PM 24383518 ER PT J AU Bryant, A Nakagawa, S Norton, M Pena, S Bishop, J Kuppermann, M AF Bryant, Allison Nakagawa, Sanae Norton, Mary Pena, Sherri Bishop, Judith Kuppermann, Miriam TI Prenatal testing results: what do women understand? SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Meeting Abstract CT 34th Annual Scientific Pregnancy Meeting of the Society-for-Maternal-Fetal-Medicine CY FEB 03-08, 2014 CL New Orleans, LA SP Soc Maternal Fetal Med C1 [Bryant, Allison] Massachusetts Gen Hosp, Div Maternal Fetal Med, Vincent Obstet & Gynecol Dept, Boston, MA 02114 USA. [Nakagawa, Sanae; Norton, Mary; Pena, Sherri; Bishop, Judith; Kuppermann, Miriam] Univ Calif San Francisco, Dept Obstet Gynecol & Reprod Sci, Div Maternal Fetal Med, San Francisco, CA 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 0002-9378 EI 1097-6868 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD JAN PY 2014 VL 210 IS 1 SU S BP S236 EP S236 PG 1 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 298KK UT WOS:000330322600472 ER PT J AU Croft, D Bryant, A Nakagawa, S Norton, M Kuppermann, M AF Croft, Damien Bryant, Allison Nakagawa, Sanae Norton, Mary Kuppermann, Miriam TI Prenatal screening for aneuploidy: do women know what's been done? SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Meeting Abstract CT 34th Annual Scientific Pregnancy Meeting of the Society-for-Maternal-Fetal-Medicine CY FEB 03-08, 2014 CL New Orleans, LA SP Soc Maternal Fetal Med C1 [Croft, Damien; Bryant, Allison] Massachusetts Gen Hosp, Div Maternal Fetal Med Vincent Obstet & Gynecol, Boston, MA 02114 USA. [Nakagawa, Sanae; Norton, Mary; Kuppermann, Miriam] Univ Calif San Francisco, Div Maternal Fetal Med, Dept Obstet Gynecol & Reprod Sci, San Francisco, CA 94143 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 0002-9378 EI 1097-6868 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD JAN PY 2014 VL 210 IS 1 SU S BP S243 EP S243 PG 1 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 298KK UT WOS:000330322600488 ER PT J AU Darney, B Snowden, J Dublin, S Nicholson, J Kaimal, A Getahun, D Cheng, Y Caughey, A AF Darney, Blair Snowden, Jonathan Dublin, Sascha Nicholson, James Kaimal, Anjali Getahun, Darios Cheng, Yvonne Caughey, Aaron TI Does maternal age moderate the relationship between elective induction of labor at 39 weeks and primary cesarean delivery? SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Meeting Abstract CT 34th Annual Scientific Pregnancy Meeting of the Society-for-Maternal-Fetal-Medicine CY FEB 03-08, 2014 CL New Orleans, LA SP Soc Maternal Fetal Med C1 [Darney, Blair] Oregon Hlth & Sci Univ, Dept Med Informat & Clin Epidemiol, Portland, OR 97201 USA. [Snowden, Jonathan; Caughey, Aaron] Oregon Hlth & Sci Univ, Portland, OR 97201 USA. [Dublin, Sascha] Grp Hlth Res Inst, Seattle, WA USA. [Getahun, Darios] Kaiser Permanente So Calif, Dept Res & Evaluat, Pasadena, CA 91101 USA. [Cheng, Yvonne] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Nicholson, James] Penn State Univ, Coll Med, Hershey, PA USA. [Kaimal, Anjali] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Cambridge, MA 02138 USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9378 EI 1097-6868 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD JAN PY 2014 VL 210 IS 1 SU S BP S313 EP S314 PG 2 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 298KK UT WOS:000330322600640 ER PT J AU Dukhovny, S Louik, C Kerr, S Werler, M Lin, A Mitchell, A AF Dukhovny, Stephanie Louik, Carol Kerr, Stephen Werler, Martha Lin, Angela Mitchell, Allen TI Risk factors for anophthalmia/microphthalmia SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Meeting Abstract CT 34th Annual Scientific Pregnancy Meeting of the Society-for-Maternal-Fetal-Medicine CY FEB 03-08, 2014 CL New Orleans, LA SP Soc Maternal Fetal Med C1 [Dukhovny, Stephanie] Brigham & Womens Hosp, Boston, MA 02115 USA. [Louik, Carol; Kerr, Stephen; Werler, Martha; Mitchell, Allen] Boston Univ, Slone Epidemiol Ctr, Boston, MA 02215 USA. [Lin, Angela] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 3 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9378 EI 1097-6868 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD JAN PY 2014 VL 210 IS 1 SU S BP S105 EP S105 PG 1 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 298KK UT WOS:000330322600192 ER EF