FN Thomson Reuters Web of Science™ VR 1.0 PT J AU Peterson, MJ Kahn, JA Kerrigan, MV Gutmann, JM Harrow, JJ AF Peterson, Matthew J. Kahn, Julie A. Kerrigan, Michael V. Gutmann, Joseph M. Harrow, Jeffrey J. TI Pressure ulcer risk of patient handling sling use SO JOURNAL OF REHABILITATION RESEARCH AND DEVELOPMENT LA English DT Article DE decubitus ulcer; interface pressure; patient handling; patient handling sling; patient lifting; patient moving and lifting; patient repositioning; pressure sore; pressure ulcer; pressure ulcer risk; spinal cord injury ID INJURIES AB Patient handling slings and lifts reduce the risk of musculoskeletal injuries for healthcare providers. However, no published evidence exists of their safety with respect to pressure ulceration for vulnerable populations, specifically persons with spinal cord injury, nor do any studies compare slings for pressure distribution. High-resolution interface pressure mapping was used to describe and quantify risks associated with pressure ulceration due to normal forces and identify at-risk anatomical locations. We evaluated 23 patient handling slings with 4 non-disabled adults. Sling-participant interface pressures were recorded while participants lay supine on a hospital bed and while they were suspended during typical patient transfers. Sling-participant interface pressures were greatest while participants were suspended for all seated and supine slings and exceeded 200 mm Hg for all seated slings. Interface pressures were greatest along the sling seams (edges), regardless of position or sling type. The anatomical areas most at risk while participants were suspended in seated slings were the posterior upper and lower thighs. For supine slings, the perisacral area, ischial tuberosities, and greater trochanters were most at risk. The duration of time spent in slings, especially while suspended, should be limited. C1 [Peterson, Matthew J.; Gutmann, Joseph M.] James A Haley Vet Hosp, Dept Vet Affairs, Hlth Serv Res & Dev Ctr Innovat Disabil & Rehabil, Tampa, FL USA. [Kahn, Julie A.] Univ S Florida, Dept Chem & Biomed Engn, Tampa, FL USA. [Kerrigan, Michael V.] US Patent & Trademark Off, Alexandria, VA USA. [Harrow, Jeffrey J.] Audie L Murphy Mem Vet Adm Med Ctr, San Antonio, TX 78284 USA. RP Peterson, MJ (reprint author), James A Haley Vet Hosp 151R, HSR&D Ctr Innovat Disabil & Rehabil Res CINDRR, 8900 Grand Oak Cir, Tampa, FL 33637 USA. EM Matthew.Peterson1@va.gov FU VA Central Office Occupational Health Strategic Healthcare Group [SPTOF00A1] FX This work was supported by the VA Central Office Occupational Health Strategic Healthcare Group (no. SPTOF00A1). NR 16 TC 0 Z9 0 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 2015 VL 52 IS 3 BP 291 EP 300 DI 10.1682/JRRD.2014.06.0140 PG 10 WC Rehabilitation SC Rehabilitation GA CN0NR UT WOS:000358111100004 PM 26237005 ER PT J AU Danilack, VA Okunbor, O Richardson, CR Teylan, M Moy, ML AF Danilack, Valery A. Okunbor, Osarenoma Richardson, Caroline R. Teylan, Merilee Moy, Marilyn L. TI Performance of a pedometer to measure physical activity in a US cohort with chronic obstructive pulmonary disease SO JOURNAL OF REHABILITATION RESEARCH AND DEVELOPMENT LA English DT Article DE continuous walking; COPD; exercise; functional capacity; intermittent steps; Omron; pedometer; physical activity; pulmonary disease; StepWatch Activity Monitor ID DAILY STEP COUNT; RESPIRATORY SOCIETY STATEMENT; ACTIVITY MONITORS; WALKING PROGRAM; DAILY-LIFE; COPD; VALIDITY; REHABILITATION; MORTALITY; PATTERNS AB Objective assessment of physical activity (PA) in chronic obstructive pulmonary disease (COPD) is important. We examined the performance of the Omron HJ-720ITC pedometer. A sample of 176 persons with stable COPD wore the Omron and the StepWatch Activity Monitor (SAM) in the clinic and the community. A 4 s step filter in the Omron screens out erroneous intermittent steps; it captures continuous walking that lasts >4 s. The SAM captures all intermittent and continuous steps walked. Omron-steps were compared with manually counted steps in the clinic and with SAM-steps in the community. We calculated the intraclass correlation coefficient for the first 2 d, the first 3 d, etc., up to 14 d. The Omron registered >/= 90% of the manually counted steps from the in-clinic walk in 155 of 176 subjects (88%). In the community, 47 +/-16% of SAM-steps were continuous ones that were captured by the Omron. For the Omron and the SAM, at least 7 d of monitoring should be used to capture decreases in PA on weekend days and obtain optimum reliability for all Global Initiative for Chronic Obstructive Lung Disease stages. The Omron accurately and reliably measures continuous walking in COPD. The Omron may be ideal for use in PA interventions that promote continuous walking as exercise. C1 [Danilack, Valery A.] Brown Univ, Sch Publ Hlth, Dept Epidemiol, Providence, RI 02912 USA. [Danilack, Valery A.; Okunbor, Osarenoma; Teylan, Merilee; Moy, Marilyn L.] VA Boston Healthcare Syst, Pulm & Crit Care Med Sect, Dept Vet Affairs, Boston, MA USA. [Richardson, Caroline R.] VA Ctr Clin Management Res, Ann Arbor, MI USA. [Richardson, Caroline R.] Univ Michigan, Dept Family Med, Ann Arbor, MI 48109 USA. [Moy, Marilyn L.] VA Rehabil Res & Dev Serv, Washington, DC USA. [Moy, Marilyn L.] Harvard Univ, Sch Med, Boston, MA USA. RP Moy, ML (reprint author), VA Boston Healthcare Syst, Pulm & Crit Care Sect, 1400 VFW Pkwy,Mail Code 111PI, West Roxbury, MA 02132 USA. EM marilyn.moy@va.gov FU VA, Veterans Health Administration; Rehabilitation Research and Development Service through VA Career Development [F6847W] FX This material was based on work supported by the VA, Veterans Health Administration, Rehabilitation Research and Development Service through a VA Career Development Award (F6847W) to Dr. Moy. NR 44 TC 3 Z9 3 U1 1 U2 4 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 2015 VL 52 IS 3 BP 333 EP 342 DI 10.1682/JRRD.2014.11.0282 PG 10 WC Rehabilitation SC Rehabilitation GA CN0NR UT WOS:000358111100008 PM 26230737 ER PT J AU Ghodbane, M Stucky, EC Maguire, TJ Schloss, RS Shreiber, DI Zahn, JD Yarmush, ML AF Ghodbane, Mehdi Stucky, Elizabeth C. Maguire, Tim J. Schloss, Rene S. Shreiber, David I. Zahn, Jeffrey D. Yarmush, Martin L. TI Development and validation of a microfluidic immunoassay capable of multiplexing parallel samples in microliter volumes SO LAB ON A CHIP LA English DT Article ID RAT HIPPOCAMPAL SLICES; TUMOR-NECROSIS-FACTOR; SPINAL-CORD-INJURY; INFLAMMATORY CYTOKINES; PROTEIN BIOMARKERS; CHIP; DIAGNOSTICS; SYSTEM; CELLS; LIPOPOLYSACCHARIDE AB Immunoassays are widely utilized due to their ability to quantify a vast assortment of biomolecules relevant to biological research and clinical diagnostics. Recently, immunoassay capabilities have been improved by the development of multiplex assays that simultaneously measure multiple analytes in a single sample. However, these assays are hindered by high costs of reagents and relatively large sample requirements. For example, in vitro screening systems currently dedicate individual wells to each time point of interest and this limitation is amplified in screening studies when the investigation of many experimental conditions is necessary; resulting in large volumes for analysis, a correspondingly high cost and a limited temporal experimental design. Microfluidics based immunoassays have been developed in order to overcome these drawbacks. Together, previous studies have demonstrated on-chip assays with either a large dynamic range, high performance sensitivity, and/or the ability to process samples in parallel on a single chip. In this report, we develop a multiplex immunoassay possessing all of these parallel characteristics using commercially available reagents, which allows the analytes of interest to be easily changed. The device presented can measure 6 proteins in 32 samples simultaneously using only 4.2 mu L of sample volume. High quality standard curves are generated for all 6 analytes included in the analysis, and spiked samples are quantified throughout the working range of the assay. In addition, we demonstrate a strong correlation (R-2 = 0.8999) between in vitro supernatant measurements using our device and those obtained from a bench-top multiplex immunoassay. Finally, we describe cytokine secretion in an in vitro inflammatory hippocampus culture system, establishing proof-of-concept of the ability to use this platform as an in vitro screening tool. The low-volume, multiplexing abilities of the microdevice described in this report could be broadly applied to numerous situations where sample volumes and costs are limiting. C1 [Ghodbane, Mehdi; Maguire, Tim J.; Schloss, Rene S.; Shreiber, David I.; Zahn, Jeffrey D.; Yarmush, Martin L.] Rutgers State Univ, Dept Biomed Engn, Piscataway, NJ 08854 USA. [Stucky, Elizabeth C.] Rutgers State Univ, Dept Chem & Biochem Engn, Piscataway, NJ 08854 USA. [Yarmush, Martin L.] Massachusetts Gen Hosp, Ctr Engn Med Surg Serv, Boston, MA 02114 USA. RP Yarmush, ML (reprint author), Rutgers State Univ, Dept Biomed Engn, 599 Taylor Rd, Piscataway, NJ 08854 USA. EM yarmush@rci.rutgers.edu OI Stucky Hunter, Elizabeth/0000-0003-0797-9453 FU National Institute of Health [P41EB002503, UH2TR000503]; National Institute of Health Rutgers Biotechnology Training Program [T32GM008339]; National Science Foundation Integrated Science and Engineering of Stem Cells Program [DGE0801620]; New Jersey Commission on Brain Injury Research [CBIR12IRG019] FX This work was partially funded by the National Institute of Health grants P41EB002503 and UH2TR000503, the National Institute of Health Rutgers Biotechnology Training Program (T32GM008339), the National Science Foundation Integrated Science and Engineering of Stem Cells Program (DGE0801620), The New Jersey Commission on Brain Injury Research grant CBIR12IRG019, and Corning Inc. The authors would like to thank Dr. Bhaskar Mitra and Henry Yu for support in developing the fabrication protocols, and Prof. Lawrence Williams for productive discussion in designing the experiments. NR 57 TC 4 Z9 4 U1 2 U2 18 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 2015 VL 15 IS 15 BP 3211 EP 3221 DI 10.1039/c5lc00398a PG 11 WC Biochemical Research Methods; Chemistry, Multidisciplinary; Nanoscience & Nanotechnology SC Biochemistry & Molecular Biology; Chemistry; Science & Technology - Other Topics GA CM9IU UT WOS:000358022900014 PM 26130452 ER PT S AU Galarreta-Valverde, MA Zoghbi, JM Pereira, F Beregi, JP Mekkaoui, C Jackowski, MP AF Galarreta-Valverde, Miguel A. Zoghbi, Jihan M. Pereira, Fabricio Beregi, Jean-Paul Mekkaoui, Choukri Jackowski, Marcel P. BE Hadjiiski, LM Tourassi, GD TI Characterization of Vascular Tree Architecture using the Tokunaga Taxonomy SO MEDICAL IMAGING 2015: COMPUTER-AIDED DIAGNOSIS SE Proceedings of SPIE LA English DT Proceedings Paper CT Computer-Aided Diagnosis (CAD) Conference at the SPIE Medical Imaging Symposium CY FEB 22-25, 2015 CL Orlando, FL SP SPIE, ALIO Ind, Alpin Med Syst, Modus Med Dev Inc, Bruker DE Magnetic resonance imaging; computed tomography angiography; vascular architecture; 3D blood vessel; Tokunaga taxonomy AB The diagnosis of cardiovascular disease is usually assisted by resonance angiography (MRA) or computed tomography angiography (CTA) imaging. The identification of abnormal vascular architecture from angiographic three-dimensional images is therefore crucial to the diagnosis of cardiovascular disease. Automated detection and quantification of vascular structure and architecture thus holds significant clinical value. In this work, we employ a Lindenmayer system to represent vascular trees from angiographic images and describe a quantitative measure based on the Tokunaga taxonomy to differentiate vascular architectures. Synthetic vessel architectures with varying bifurcation patterns were compared and results showed that this architectural measure is proportional to the level of branching. In real MRA images, this measure was able to differentiate between normal and abnormal intracerebral vasculature containing an aneurysm. Hence, this methodology not only allows for compact representation of vascular architectures but also provides a quantitative metric of bifurcation complexity, which has the potential to characterize different types of vascular abnormalities. C1 [Galarreta-Valverde, Miguel A.; Zoghbi, Jihan M.; Jackowski, Marcel P.] Univ Sao Paulo, Inst Math & Stat, Dept Comp Sci, Sao Paulo, Brazil. [Pereira, Fabricio; Beregi, Jean-Paul; Mekkaoui, Choukri] Univ Hosp Ctr Nimes, Dept Radiol, Nimes, France. [Pereira, Fabricio; Beregi, Jean-Paul; Mekkaoui, Choukri] Res Team EA 2415, Nimes, France. [Beregi, Jean-Paul; Mekkaoui, Choukri] Univ Montpellier, Fac Med, F-34059 Montpellier, France. [Mekkaoui, Choukri] Harvard Univ, Sch Med, Dept Radiol, Massachusetts Gen Hosp,Athinoula A Martinos Ctr B, Boston, MA 02115 USA. RP Galarreta-Valverde, MA (reprint author), Univ Sao Paulo, Inst Math & Stat, Dept Comp Sci, Sao Paulo, Brazil. EM mjack@ime.usp.br RI Jackowski, Marcel/G-7602-2012 NR 5 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 978-1-62841-504-9 J9 PROC SPIE PY 2015 VL 9414 AR 941438 DI 10.1117/12.2080854 PG 6 WC Optics; Radiology, Nuclear Medicine & Medical Imaging SC Optics; Radiology, Nuclear Medicine & Medical Imaging GA BD0US UT WOS:000357728600109 ER PT S AU Nappi, JJ Regge, D Yoshida, H AF Naeppi, Janne J. Regge, Daniele Yoshida, Hiroyuki BE Hadjiiski, LM Tourassi, GD TI Context-specific method for detection of soft-tissue lesions in non-cathartic low-dose dual-energy CT colonography SO MEDICAL IMAGING 2015: COMPUTER-AIDED DIAGNOSIS SE Proceedings of SPIE LA English DT Proceedings Paper CT Computer-Aided Diagnosis (CAD) Conference at the SPIE Medical Imaging Symposium CY FEB 22-25, 2015 CL Orlando, FL SP SPIE, ALIO Ind, Alpin Med Syst, Modus Med Dev Inc, Bruker DE Computer-aided detection; polyp detection; false-positive reduction; dual-energy CT; noncathartic preparation; virtual colonoscopy ID ADENOMATOUS POLYPS; PSEUDO-ENHANCEMENT; REDUCTION AB In computed tomographic colonography (CTC), orally administered fecal-tagging agents can be used to indicate residual feces and fluid that could otherwise hide or imitate lesions on CTC images of the colon. Although the use of fecal tagging improves the detection accuracy of CTC, it can introduce image artifacts that may cause lesions that are covered by fecal tagging to have a different visual appearance than those not covered by fecal tagging. This can distort the values of image-based computational features, thereby reducing the accuracy of computer-aided detection (CADe). We developed a context-specific method that performs the detection of lesions separately on lumen regions covered by air and on those covered by fecal tagging, thereby facilitating the optimization of detection parameters separately for these regions and their detected lesion candidates to improve the detection accuracy of CADe. For pilot evaluation, the method was integrated into a dual-energy CADe (DE-CADe) scheme and evaluated by use of leave-one-patient-out evaluation on 66 clinical non-cathartic low-dose dual-energy CTC (DE-CTC) cases that were acquired at a low effective radiation dose and reconstructed by use of iterative image reconstruction. There were 22 colonoscopy-confirmed lesions >= 6 mm in size in 21 patients. The DE-CADe scheme detected 96% of the lesions at a median of 6 FP detections per patient. These preliminary results indicate that the use of context-specific detection can yield high detection accuracy of CADe in non-cathartic low-dose DE-CTC examinations. C1 [Naeppi, Janne J.; Yoshida, Hiroyuki] Massachusetts Gen Hosp, Dept Radiol, Imaging Res 3D, Boston, MA 02114 USA. [Naeppi, Janne J.; Yoshida, Hiroyuki] Harvard Univ, Sch Med, Boston, MA 02114 USA. [Regge, Daniele] Inst Canc Res & Treatment, IT-10060 Turin, Italy. 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 OI Nappi, Janne/0000-0002-0108-0992 FU NCI NIH HHS [R01 CA166816, R03 CA156664, R03 CA182107, R01 CA095279] NR 22 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 978-1-62841-504-9 J9 PROC SPIE PY 2015 VL 9414 AR 94142Y DI 10.1117/12.2081284 PG 7 WC Optics; Radiology, Nuclear Medicine & Medical Imaging SC Optics; Radiology, Nuclear Medicine & Medical Imaging GA BD0US UT WOS:000357728600102 PM 25964710 ER PT S AU Tachibana, R Nappi, JJ Kim, SH Yoshida, H AF Tachibana, Rie Naeppi, Janne J. Kim, Se Hyung Yoshida, Hiroyuki BE Hadjiiski, LM Tourassi, GD TI Electronic cleansing for dual-energy CT colonography based on material decomposition and virtual monochromatic imaging SO MEDICAL IMAGING 2015: COMPUTER-AIDED DIAGNOSIS SE Proceedings of SPIE LA English DT Proceedings Paper CT Computer-Aided Diagnosis (CAD) Conference at the SPIE Medical Imaging Symposium CY FEB 22-25, 2015 CL Orlando, FL SP SPIE, ALIO Ind, Alpin Med Syst, Modus Med Dev Inc, Bruker DE Colon; virtual cleansing; dual-energy CT; random forest; virtual colonoscopy ID TOMOGRAPHY AB CT colonography (CTC) uses orally administered fecal-tagging agents to enhance retained fluid and feces that would otherwise obscure or imitate polyps on CTC images. To visualize the complete region of colon without residual materials, electronic cleansing (EC) can be used to perform virtual subtraction of the tagged materials from CTC images. However, current EC methods produce subtraction artifacts and they can fail to subtract unclearly tagged feces. We developed a novel multi-material EC (MUMA-EC) method that uses dual-energy CTC (DE-CTC) and machine-learning methods to improve the performance of EC. In our method, material decomposition is performed to calculate water-iodine decomposition images and virtual monochromatic (VIM) images. Using the images, a random forest classifier is used to label the regions of lumen air, soft tissue, fecal tagging, and their partial-volume boundaries. The electronically cleansed images are synthesized from the multi-material and VIM image volumes. For pilot evaluation, we acquired the clinical DE-CTC data of 7 patients. Preliminary results suggest that the proposed MUMA-EC method is effective and that it minimizes the three types of image artifacts that were present in previous EC methods. C1 [Tachibana, Rie; Naeppi, Janne J.; Yoshida, Hiroyuki] Massachusetts Gen Hosp, Dept Radiol, Imaging Res 3D, Boston, MA 02114 USA. [Tachibana, Rie; Naeppi, Janne J.; Yoshida, Hiroyuki] Harvard Univ, Sch Med, Boston, MA 02114 USA. [Kim, Se Hyung] Seoul Natl Univ Hosp, Seoul 110744, South Korea. RP Yoshida, H (reprint author), Massachusetts Gen Hosp, Dept Radiol, Imaging Res 3D, 25 New Chardon St,Suite 400C, Boston, MA 02114 USA. EM rtachibana@mgh.harvard.edu; janne.nappi@mgh.harvard.edu; yoshida.hiro@mgh.harvard.edu FU NCI NIH HHS [R01 CA095279, R03 CA156664, R01 CA166816] NR 12 TC 1 Z9 1 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 978-1-62841-504-9 J9 PROC SPIE PY 2015 VL 9414 AR 94140Q DI 10.1117/12.2082375 PG 7 WC Optics; Radiology, Nuclear Medicine & Medical Imaging SC Optics; Radiology, Nuclear Medicine & Medical Imaging GA BD0US UT WOS:000357728600025 PM 25844029 ER PT S AU Wu, J Ou, YM Weinstein, SP Conant, EF Yu, N Hoshmand, V Keller, B Ashraf, AB Rosen, M DeMichele, A Davatzikos, C Kontos, D AF Wu, Jia Ou, Yangming Weinstein, Susan P. Conant, Emily F. Yu, Ning Hoshmand, Vahid Keller, Brad Ashraf, Ahmed B. Rosen, Mark DeMichele, Angela Davatzikos, Christos Kontos, Despina BE Hadjiiski, LM Tourassi, GD TI Quantification of Tumor Changes during Neoadjuvant Chemotherapy with Longitudinal Breast DCE-MRI Registration SO MEDICAL IMAGING 2015: COMPUTER-AIDED DIAGNOSIS SE Proceedings of SPIE LA English DT Proceedings Paper CT Computer-Aided Diagnosis (CAD) Conference at the SPIE Medical Imaging Symposium CY FEB 22-25, 2015 CL Orlando, FL SP SPIE, ALIO Ind, Alpin Med Syst, Modus Med Dev Inc, Bruker DE Deformable Registration; Breast Tumor; DCE-MRI; Tumor Response; Neoadjuvant Chemotherapy ID CANCER-TREATMENT RESPONSE; PARAMETRIC RESPONSE; PATHOLOGICAL RESPONSE; IMAGE REGISTRATION; SURVIVAL; PREDICTION; RECIST; ADENOCARCINOMA; CRITERIA; MAPS AB Imaging plays a central role in the evaluation of breast tumor response to neoadjuvant chemotherapy. Image-based assessment of tumor change via deformable registration is a powerful, quantitative method potentially to explore novel information of tumor heterogeneity, structure, function, and treatment response. In this study, we continued a previous pilot study to further validate the feasibility of an open source deformable registration algorithm DRAMMS developed within our group as a means to analyze spatio-temporal tumor changes for a set of 14 patients with DCE-MR imaging. Two experienced breast imaging radiologists marked landmarks according to their anatomical meaning on image sets acquired before and during chemotherapy. Yet, chemotherapy remarkably changed the anatomical structure of both tumor and normal breast tissue, leading to significant discrepancies between both raters for landmarks in certain areas. Therefore, we proposed a novel method to grade the manually denoted landmarks into different challenge levels based on the inter-rater agreement, where a high level indicates significant discrepancies and considerable amounts of anatomical structure changes, which would indeed impose giant problem for the following registration algorithm. It is interesting to observe that DRAMMS performed in a similar manner as the human raters: landmark errors increased as inter-rater differences rose. Among all selected six deformable registration algorithms, DRAMMS achieves the highest overall accuracy, which is around 5.5 mm, while the average difference between human raters is 3 mm. Moreover, DRAMMS performed consistently well within both tumor and normal tissue regions. Lastly, we comprehensively tuned the fundamental parameters of DRAMMS to better understand DRAMMS to guide similar works in the future. Overall, we further validated that DRAMMS is a powerful registration tool to accurately quantify tumor changes and potentially predict early tumor response to chemotherapy. Therefore, future studies that aim at examining if DRAMMS can generate valuable biomarkers for tumor response prediction during chemotherapy become feasible. C1 [Wu, Jia; Weinstein, Susan P.; Conant, Emily F.; Keller, Brad; Ashraf, Ahmed B.; Rosen, Mark; DeMichele, Angela; Davatzikos, Christos; Kontos, Despina] Univ Penn, Dept Radiol, Philadelphia, PA 19104 USA. [Ou, Yangming] Harvard Univ, Massachusetts Gen Hosp, Cambridge, MA 02138 USA. [Yu, Ning; Hoshmand, Vahid] Univ Penn, Sch Engn & Appl Sci, Philadelphia, PA 19104 USA. RP Kontos, D (reprint author), Univ Penn, Dept Radiol, Philadelphia, PA 19104 USA. EM Despina.Kontos@uphs.upenn.edu OI Ou, Yangming/0000-0002-7726-6208; Weinstein, Susan/0000-0001-6159-1500 NR 25 TC 0 Z9 0 U1 1 U2 16 PU SPIE-INT SOC OPTICAL ENGINEERING PI BELLINGHAM PA 1000 20TH ST, PO BOX 10, BELLINGHAM, WA 98227-0010 USA SN 0277-786X BN 978-1-62841-504-9 J9 PROC SPIE PY 2015 VL 9414 AR 94141Z DI 10.1117/12.2081938 PG 7 WC Optics; Radiology, Nuclear Medicine & Medical Imaging SC Optics; Radiology, Nuclear Medicine & Medical Imaging GA BD0US UT WOS:000357728600069 ER PT S AU Naeser, MA Martin, PI Ho, MD Krengel, MH Bogdanova, Y Knight, JA Yee, MK Zafonte, R Frazier, J Hamblin, MR Koo, BB AF Naeser, Margaret A. Martin, Paula I. Ho, Michael D. Krengel, Maxine H. Bogdanova, Yelena Knight, Jeffrey A. Yee, Megan K. Zafonte, Ross Frazier, Judith Hamblin, Michael R. Koo, Bang-Bon BE George, T Dutta, AK Islam, MS TI Red/near-infrared light-emitting diode therapy for traumatic brain injury SO MICRO- AND NANOTECHNOLOGY SENSORS, SYSTEMS, AND APPLICATIONS VII SE Proceedings of SPIE LA English DT Proceedings Paper CT Conference on Micro- and Nanotechnology Sensors, Systems, and Applications VII CY APR 20-24, 2015 CL Baltimore, MD SP SPIE DE Traumatic brain injury; TBI; photobiomodulation therapy; TBI treatment; cognitive dysfunction; light emitting diodes LED; post-concussion syndrome; sports head injury; PTSD; LLLT ID POSTTRAUMATIC-STRESS-DISORDER; DEFAULT MODE NETWORK; LEVEL LASER THERAPY; COLLEGIATE FOOTBALL PLAYERS; INTRINSIC CONNECTIVITY NETWORKS; CONTROLLED CORTICAL IMPACT; ALTERED WORKING-MEMORY; DIFFUSE AXONAL INJURY; FUNCTIONAL CONNECTIVITY; HEAD-INJURY AB This invited paper reviews our research with scalp application of red/near-infrared (NIR) light-emitting diodes (LED) to improve cognition in chronic, traumatic brain injury(1). Application of red/NIR light improves mitochondrial function (especially hypoxic/compromised cells) promoting increased ATP, important for cellular metabolism. Nitric oxide is released locally, increasing regional cerebral blood flow. Eleven chronic, mTBI participants with closed-head injury and cognitive dysfunction received 18 outpatient treatments (MWF, 6 Wks) starting at 10 Mo. to 8 Yr. post-mTBI (MVA, sports-related, IED blast injury). LED therapy is non-invasive, painless, non-thermal (FDA-cleared, non-significant risk device). Each LED cluster head (2.1 '' diameter, 500mW, 22.2mW/cm(2)) was applied 10 min (13J/cm(2)) to 11 scalp placements: midline, from front-to-back hairline; and bilaterally on dorsolateral prefrontal cortex, temporal, and parietal areas. Testing performed pre- and post-LED (+ 1 Wk, 1 and 2 Mo post-18th treatment) showed significant linear trend for LED effect over time, on improved executive function and verbal memory. Fewer PTSD symptoms were reported. New studies at VA Boston include TBI patients treated with transcranial LED (26J/cm(2)); or treated with only intranasal red, 633nm and NIR, 810nm diodes placed into the nostrils (25 min, 6.5mW, 11.4J/cm(2)). Intranasal LEDs are hypothesized to deliver photons to hippocampus. Results are similar to Naeser et al. (2014). Actigraphy sleep data show increased sleep time (average, + 1 Hr/night) post-18th transcranial or intranasal LED treatment. LED treatments may be self-administered at home (Naeser et al., 2011). A sham-controlled study with Gulf War Illness Veterans is underway. C1 [Naeser, Margaret A.; Martin, Paula I.; Ho, Michael D.; Krengel, Maxine H.; Bogdanova, Yelena; Knight, Jeffrey A.; Yee, Megan K.] VA Boston Healthcare Syst 12A, Boston, MA 02130 USA. [Naeser, Margaret A.; Martin, Paula I.; Ho, Michael D.; Krengel, Maxine H.; Yee, Megan K.] Boston Univ, Dept Neurol, Sch Med, Boston, MA 02118 USA. [Bogdanova, Yelena; Knight, Jeffrey A.] Boston Univ, Dept Psychiat, Sch Med, Boston, MA 02118 USA. [Knight, Jeffrey A.] VA Boston Healthcare Syst, Natl Ctr PTSD, Behav Sci Div, Boston, MA USA. [Zafonte, Ross] Harvard Univ, Sch Med, Dept Phys Med & Rehabil, Cambridge, MA 02138 USA. [Zafonte, Ross] Spaulding Rehabil Hosp, Charlestown, MA 02129 USA. [Zafonte, Ross] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Zafonte, Ross] Brigham & Womens Hosp, Boston, MA 02114 USA. [Frazier, Judith] Spaulding Rehabil Hosp, TBI Res Program, Charlestown, MA 02129 USA. [Hamblin, Michael R.] Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA. [Hamblin, Michael R.] Harvard Univ, Sch Med, Dept Dermatol, Boston, MA 02115 USA. [Hamblin, Michael R.] MIT, Harvard Mit Div Hlth Sci & Technol, Cambridge, MA 02139 USA. [Koo, Bang-Bon] Boston Univ, Ctr Biomed Imaging, Boston, MA 02118 USA. RP Naeser, MA (reprint author), VA Boston Healthcare Syst 12A, 150 So Huntington Ave, Boston, MA 02130 USA. EM mnaeser@bu.edu OI Koo, Bang-bon/0000-0001-7423-5572 NR 129 TC 0 Z9 0 U1 1 U2 11 PU SPIE-INT SOC OPTICAL ENGINEERING PI BELLINGHAM PA 1000 20TH ST, PO BOX 10, BELLINGHAM, WA 98227-0010 USA SN 0277-786X BN 978-1-62841-583-4 J9 PROC SPIE PY 2015 VL 9467 AR 94670M DI 10.1117/12.2176345 PG 21 WC Engineering, Electrical & Electronic; Nanoscience & Nanotechnology; Optics; Physics, Applied SC Engineering; Science & Technology - Other Topics; Optics; Physics GA BD0IX UT WOS:000357259000015 ER PT S AU Zhang, YS Wang, YC Murray, CK Hamblin, MR Gu, Y Dai, TH AF Zhang, Yunsong Wang, Yucheng Murray, Clinton K. Hamblin, Michael R. Gu, Ying Dai, Tianhong BE George, T Dutta, AK Islam, MS TI Antimicrobial blue light therapy for Candida albicans burn infection in mice SO MICRO- AND NANOTECHNOLOGY SENSORS, SYSTEMS, AND APPLICATIONS VII SE Proceedings of SPIE LA English DT Proceedings Paper CT Conference on Micro- and Nanotechnology Sensors, Systems, and Applications VII CY APR 20-24, 2015 CL Baltimore, MD SP SPIE DE Photodynamic inactivation; endogenous porphyrins; fungus; animal model; bioluminescence imagining ID MRSA IN-VITRO; PHOTODYNAMIC THERAPY; PSEUDOMONAS-AERUGINOSA; STREPTOCOCCUS-MUTANS; BACTERIA; INACTIVATION; RESISTANCE; BIOFILM; EPIDEMIOLOGY; MECHANISMS AB In this preclinical study, we investigated the utility of antimicrobial blue light therapy for Candida albicans infection in acutely burned mice. A bioluminescent strain of C. albicans was used. The susceptibilities to blue light inactivation were compared between C. albicans and human keratinocyte. In vitro serial passaging of C. albicans on blue light exposure was performed to evaluate the potential development of resistance to blue light inactivation. A mouse model of acute thermal burn injury infected with the bioluminescent strain of C. albicans was developed. Blue light (415 nm) was delivered to mouse burns for decolonization of C. albicans. Bioluminescence imaging was used to monitor in real time the extent of fungal infection in mouse burns. Experimental results showed that C. albicans was approximately 42-fold more susceptible to blue light inactivation in vitro than human keratinocyte (P=0.0022). Serial passaging of C. albicans on blue light exposure implied a tendency for the fungal susceptibility to blue light inactivation to decrease with the numbers of passages. Blue light reduced fungal burden by over 4-log10 (99.99%) in acute mouse burns infected with C. albicans in comparison to infected mouse burns without blue light therapy (P=0.015). C1 [Zhang, Yunsong] Jinan Univ, Guangzhou Red Cross Hosp, Dept Burn & Plast Surg, Guangzhou 510760, Guangdong, Peoples R China. [Zhang, Yunsong; Wang, Yucheng; Hamblin, Michael R.; Dai, Tianhong] Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA. [Zhang, Yunsong; Wang, Yucheng; Hamblin, Michael R.; Dai, Tianhong] Harvard Univ, Sch Med, Dept Dermatol, Boston, MA 02115 USA. [Wang, Yucheng; Gu, Ying] Chinese Peoples Liberat Army Gen Hosp, Dept Laser Med, Beijing 100853, Peoples R China. [Wang, Yucheng] Nankai Univ, Coll Med, Tianjin 300071, Peoples R China. [Murray, Clinton K.] Brooke Army Med Ctr, Infect Dis Serv, Ft Sam Houston, TX 78234 USA. RP Zhang, YS (reprint author), Jinan Univ, Guangzhou Red Cross Hosp, Dept Burn & Plast Surg, Guangzhou 510760, Guangdong, Peoples R China. NR 43 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 978-1-62841-583-4 J9 PROC SPIE PY 2015 VL 9467 AR 94670K DI 10.1117/12.2178232 PG 13 WC Engineering, Electrical & Electronic; Nanoscience & Nanotechnology; Optics; Physics, Applied SC Engineering; Science & Technology - Other Topics; Optics; Physics GA BD0IX UT WOS:000357259000014 ER PT J AU Koumarianou, A Kaltsas, G Kulke, MH Oberg, K Strosberg, JR Spada, F Galdy, S Barberis, M Fumagalli, C Berruti, A Fazio, N AF Koumarianou, Anna Kaltsas, Gregory Kulke, Matthew H. Oberg, Kjell Strosberg, Jonathan R. Spada, Francesca Galdy, Salvatore Barberis, Massimo Fumagalli, Caterina Berruti, Alfredo Fazio, Nicola TI Temozolomide in Advanced Neuroendocrine Neoplasms: Pharmacological and Clinical Aspects SO NEUROENDOCRINOLOGY LA English DT Article DE Neuroendocrine neoplasms; Pancreatic neuroendocrine neoplasms; Neuroendocrine carcinomas; Ki-67 labelling index; Progression-free survival ID ISLET-CELL-CARCINOMA; PHASE-II TRIAL; O-6-ALKYLGUANINE-DNA ALKYLTRANSFERASE ACTIVITY; METHYLGUANINE-DNA METHYLTRANSFERASE; PANCREATIC ENDOCRINE CARCINOMAS; O-6-METHYLGUANINE-DNA METHYLTRANSFERASE; GLIOBLASTOMA-MULTIFORME; ALKYLATING-AGENTS; MALIGNANT PARAGANGLIOMA; APLASTIC-ANEMIA AB Alkylating agents, such as streptozocin and dacarbazine, have been reported as active in neuroendocrine neoplasms (NENs). Temozolomide (TMZ) is an oral, potentially less toxic derivative of dacarbazine, which has shown activity both as a single agent and in combination with other drugs. Nevertheless, its role in NENs has not been well defined. Several retrospective and prospective phase I-II studies have been published describing its use in a variety of NENs. In a retrospective series, the combination of capecitabine and TMZ was reported to be associated with a particularly high tumour response in pancreatic NENs as a first-line treatment. Although in NENs, determination of the CP-nnethylguanineDNA methyltransferase (MGMT) status has been suggested as a predictive biomarker of response, its role still remains investigational, awaiting validation along with the establishment of the optimal detection method. Metronomic schedules have been reported to potentially overcome MGMT-related drug resistance. Toxicity is manageable if well monitored. We reviewed the literature regarding pharmacological and clinical aspects of TMZ, focusing on specific settings of NENs, different schedules, toxicity and safety profiles, and potential predictive biomarkers of response. (C) 2015 S. Karger AG, Basel C1 [Koumarianou, Anna] Attikon Univ Hosp, Hematol Oncol Unit, Dept Internal Med 4, GR-12462 Athens, Greece. [Kaltsas, Gregory] Natl Tech Univ Athens, Dept Pathophysiol, Endocrine Unit, Athens, Greece. [Kulke, Matthew H.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Strosberg, Jonathan R.] Univ S Florida, Coll Med, H Lee Moffitt Canc Ctr & Res Inst, Tampa, FL 33612 USA. [Oberg, Kjell] Univ Uppsala Hosp, Dept Endocrine Oncol, Uppsala, Sweden. [Spada, Francesca; Galdy, Salvatore; Fazio, Nicola] European Inst Oncol, Gastrointestinal Med Oncol & Neuroendocrine Tumor, IT-20141 Milan, Italy. [Barberis, Massimo; Fumagalli, Caterina] European Inst Oncol, Div Pathol, IT-20141 Milan, Italy. [Berruti, Alfredo] Univ Brescia, Dipartimento Specialita Med Chirurg Sci Radiol &, Azienda Osped Spedali Civili, Brescia, Italy. RP Koumarianou, A (reprint author), Attikon Univ Hosp, Hematol Oncol Unit, Dept Internal Med 4, Rimini 1, GR-12462 Athens, Greece. EM akoumari@yahoo.com; nicola.fazio@ieo.it OI Koumarianou, Anna/0000-0002-4159-2511; fazio, nicola/0000-0001-6869-0704 NR 86 TC 8 Z9 8 U1 1 U2 3 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0028-3835 EI 1423-0194 J9 NEUROENDOCRINOLOGY JI Neuroendocrinology PY 2015 VL 101 IS 4 BP 274 EP 288 DI 10.1159/000430816 PG 15 WC Endocrinology & Metabolism; Neurosciences SC Endocrinology & Metabolism; Neurosciences & Neurology GA CN0KV UT WOS:000358103400002 PM 25924937 ER PT J AU Mirzakhani, H van Noorden, MS Swen, J Nozari, A Guchelaar, HJ AF Mirzakhani, Hooman van Noorden, Martijn S. Swen, Jesse Nozari, Ala Guchelaar, Henk-Jan TI Pharmacogenetics in electroconvulsive therapy and adjunctive medications SO PHARMACOGENOMICS LA English DT Review DE depression; ECT; efficacy; pharmacogenetics; safety ID MAJOR DEPRESSIVE DISORDER; NEUROLEPTIC MALIGNANT SYNDROME; TREATMENT-RESISTANT DEPRESSION; APOLIPOPROTEIN-E POLYMORPHISM; POSITRON-EMISSION-TOMOGRAPHY; WHITE-MATTER ABNORMALITIES; 5-HT1A RECEPTOR-BINDING; ADD-ON TRIAL; NEUROTROPHIC FACTOR; TREATMENT RESPONSE AB Electroconvulsive therapy (ECT) has shown apparent efficacy in treatment of patients with depression and other mental illnesses who do not respond to psychotropic medications or need urgent control of their symptoms. Pharmacogenetics contributes to an individual's sensitivity and response to a variety of drugs. Clinical insights into pharmacogenetics of ECT and adjunctive medications not only improves its safety and efficacy in the indicated patients, but can also lead to the identification of novel treatments in psychiatric disorders through understanding of potential molecular and biological mechanisms involved. In this review, we explore the indications of pharmacogenetics role in safety and efficacy of ECT and present the evidence for its role in patients with psychiatric disorders undergoing ECT. C1 [Mirzakhani, Hooman] Brigham & Womens Hosp, Channing Div Network Med, Dept Med, Boston, MA 02115 USA. [Mirzakhani, Hooman] Harvard Univ, Sch Med, Div Biomed Informat, Boston, MA USA. [Mirzakhani, Hooman; Swen, Jesse; Guchelaar, Henk-Jan] Leiden Univ, Med Ctr, Dept Clin Pharm & Toxicol, Leiden, Netherlands. [van Noorden, Martijn S.] Leiden Univ, Med Ctr, Dept Psychiat, Leiden, Netherlands. [Nozari, Ala] Massachusetts Gen Hosp, Dept Anesthesia, Orthoped Anesthesia Div, Boston, MA 02114 USA. [Nozari, Ala] Harvard Univ, Sch Med, Boston, MA USA. RP Guchelaar, HJ (reprint author), Leiden Univ, Med Ctr, Dept Clin Pharm & Toxicol, Leiden, Netherlands. EM h.j.guchelaar@lumc.nl OI Mirzakhani, Hooman/0000-0002-2290-4436 NR 113 TC 1 Z9 1 U1 2 U2 4 PU FUTURE MEDICINE LTD PI LONDON PA UNITEC HOUSE, 3RD FLOOR, 2 ALBERT PLACE, FINCHLEY CENTRAL, LONDON, N3 1QB, ENGLAND SN 1462-2416 EI 1744-8042 J9 PHARMACOGENOMICS JI Pharmacogenomics PY 2015 VL 16 IS 9 BP 1015 EP 1031 DI 10.2217/pgs.15.57 PG 17 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA CM7IJ UT WOS:000357864700010 PM 26115083 ER PT J AU Diamond, SJ Sonnenberg, A AF Diamond, Sarah J. Sonnenberg, Amnon TI A game theoretic approach to repeated foreign body ingestion SO ENDOSCOPY LA English DT Editorial Material ID ENDOSCOPY; BODIES C1 Portland VA Med Ctr, Portland, OR USA. [Diamond, Sarah J.; Sonnenberg, Amnon] Oregon Hlth & Sci Univ, Div Gastroenterol Hepatol, Portland, OR 97201 USA. RP Sonnenberg, A (reprint author), Portland VA Med Ctr P3 GI, 3710 SW US Vet Hosp Rd, Portland, OR 97239 USA. EM sonnenbe@ohsu.edu NR 5 TC 1 Z9 1 U1 0 U2 0 PU GEORG THIEME VERLAG KG PI STUTTGART PA RUDIGERSTR 14, D-70469 STUTTGART, GERMANY SN 0013-726X EI 1438-8812 J9 ENDOSCOPY JI Endoscopy PY 2015 VL 47 SU 1 BP E79 EP E80 DI 10.1055/s-0034-1390920 PG 2 WC Gastroenterology & Hepatology; Surgery SC Gastroenterology & Hepatology; Surgery GA CL2RC UT WOS:000356791200021 PM 25926224 ER PT J AU Hashash, JG Habib-Bein, N Khalid, A Francis, FF AF Hashash, Jana G. Habib-Bein, Nadia Khalid, Asif Francis, Fadi F. TI Recurrent bladder cancer presenting as rectal linitis plastica SO ENDOSCOPY LA English DT Editorial Material C1 [Hashash, Jana G.; Khalid, Asif; Francis, Fadi F.] Univ Pittsburgh, Div Gastroenterol Hepatol & Nutr, Pittsburgh, PA 15213 USA. [Habib-Bein, Nadia] Univ Pittsburgh, Dept Microbiol, Vet Affairs Pittsburgh Healthcare Syst, Pittsburgh, PA 15213 USA. RP Hashash, JG (reprint author), Univ Pittsburgh, Div Gastroenterol Hepatol & Nutr, 200 Lothrop St,M2,C Wing, Pittsburgh, PA 15213 USA. EM alhashashj@upmc.edu NR 2 TC 0 Z9 0 U1 0 U2 1 PU GEORG THIEME VERLAG KG PI STUTTGART PA RUDIGERSTR 14, D-70469 STUTTGART, GERMANY SN 0013-726X EI 1438-8812 J9 ENDOSCOPY JI Endoscopy PY 2015 VL 47 SU 1 BP E102 EP E103 DI 10.1055/s-0034-1391300 PG 2 WC Gastroenterology & Hepatology; Surgery SC Gastroenterology & Hepatology; Surgery GA CL2RC UT WOS:000356791200032 PM 25734804 ER PT J AU Logan, DE Koo, KH Kilmer, JR Blayney, JA Lewis, MA AF Logan, Diane E. Koo, Kelly H. Kilmer, Jason R. Blayney, Jessica A. Lewis, Melissa A. TI Use of Drinking Protective Behavioral Strategies and Sexual Perceptions and Behaviors in US College Students SO JOURNAL OF SEX RESEARCH LA English DT Article ID ALCOHOL-RELATED CONSEQUENCES; NEGATIVE CONSEQUENCES; CONDOM USE; HEAVY-DRINKING; 1ST YEAR; EXPECTANCIES; CONSUMPTION; ADOLESCENTS; RISK; GENDER AB Alcohol use among college students is linked to an increased likelihood of engaging in risky sexual behaviors, including casual sex and unprotected sex. These behaviors increase college students' risks for negative social and health-related consequences. This study examined the relationship between drinking behaviors and protective behavioral strategies (PBS), expectancies and perceptions of sexual risk, and actual alcohol-related sexual behaviors and consequences. Sexually active college students completed Web-based self-report measures of drinking behaviors and use of PBS, alcohol expectancies and perceptions of risk, and sexual behaviors and related consequences (n = 524; 57.1% women). Findings indicated that PBS were related to lower expectancies of sexual risk and sexual disinhibition, and among lighter drinkers, lower expectancies of sexual enhancement from alcohol. PBS were also related to decreased perceptions of sexual-related risks, some alcohol-related sexual behaviors, including number of drinks before/during sex, and number of sexual consequences, but were not related to abstaining during sex, frequency of alcohol-related sexual behaviors, or general condom use. These findings demonstrate a disconnect between perceived and actual risks among college students, such that decreased perceptions of risk may not be associated with protective behaviors. Prevention and intervention implications are discussed. C1 [Logan, Diane E.] Brown Univ, Dept Behav & Social Sci, Providence, RI 02912 USA. [Koo, Kelly H.] San Francisco VA Med Ctr, Dept Mental Hlth, San Francisco, CA USA. [Koo, Kelly H.] Univ Calif San Francisco, Dept Psychiat, San Francisco, CA 94143 USA. [Kilmer, Jason R.; Lewis, Melissa A.] Univ Washington, Dept Psychiat & Behav Sci, Seattle, WA 98195 USA. [Kilmer, Jason R.] Univ Washington, Div Student Life, Hlth & Wellness, Seattle, WA 98195 USA. [Blayney, Jessica A.] SUNY Buffalo, Dept Psychol, Buffalo, NY 14260 USA. RP Logan, DE (reprint author), Brown Univ, Sch Publ Hlth, Dept Behav & Social Sci, Ctr Alcohol & Addict Studies, Box G-S121-4, Providence, RI 02912 USA. EM diane_logan@brown.edu FU National Institute on Alcohol Abuse and Alcoholism [K01AA016966, 1F31AA018238-01A1, 2T32AA007459] FX Data collection and manuscript preparation was supported by National Institute on Alcohol Abuse and Alcoholism Grant K01AA016966 awarded to M. A. Lewis. Manuscript preparation was supported by National Institute on Alcohol Abuse and Alcoholism Grant 1F31AA018238-01A1 awarded to D. E. Logan and National Institute on Alcohol Abuse and Alcoholism Grant 2T32AA007459 awarded to P. Monti. NR 66 TC 1 Z9 1 U1 6 U2 13 PU ROUTLEDGE JOURNALS, TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXFORDSHIRE, ENGLAND SN 0022-4499 EI 1559-8519 J9 J SEX RES JI J. Sex Res. PY 2015 VL 52 IS 5 BP 558 EP 569 DI 10.1080/00224499.2014.964167 PG 12 WC Psychology, Clinical; Social Sciences, Interdisciplinary SC Psychology; Social Sciences - Other Topics GA CM1FA UT WOS:000357425100007 PM 25350078 ER PT J AU Sawatsky, AP Zickmund, SL Berlacher, K Lesky, D Granieri, R AF Sawatsky, Adam P. Zickmund, Susan L. Berlacher, Kathryn Lesky, Dan Granieri, Rosanne TI Understanding the challenges to facilitating active learning in the resident conferences: a qualitative study of internal medicine faculty and resident perspectives SO MEDICAL EDUCATION ONLINE LA English DT Article DE medical education; graduate medical education; conference; lecture; active learning; lifelong learning ID TRAINING EXAMINATION SCORES; CONFERENCE ATTENDANCE; NOON CONFERENCE; EDUCATION.; PROGRAMS AB Background: In the Next Accreditation System, the Accreditation Council for Graduate Medical Education outlines milestones for medical knowledge and requires regular didactic sessions in residency training. There are many challenges to facilitating active learning in resident conferences, and we need to better understand resident learning preferences and faculty perspectives on facilitating active learning. The goal of this study was to identify challenges to facilitating active learning in resident conferences, both through identifying specific implementation barriers and identifying differences in perspective between faculty and residents on effective teaching and learning strategies. Methods: The investigators invited core residency faculty to participate in focus groups. The investigators used a semistructured guide to facilitate discussion about learning preferences and teaching perspectives in the conference setting and used an 'editing approach' within a grounded theory framework to qualitative analysis to code the transcripts and analyze the results. Data were compared to previously collected data from seven resident focus groups. Results: Three focus groups with 20 core faculty were conducted. We identified three domains pertaining to facilitating active learning in resident conferences: barriers to facilitating active learning formats, similarities and differences in faculty and resident learning preferences, and divergence between faculty and resident opinions about effective teaching strategies. Faculty identified several setting, faculty, and resident barriers to facilitating active learning in resident conferences. When compared to residents, faculty expressed similar learning preferences; the main differences were in motivations for conference attendance and type of content. Resident preferences and faculty perspectives differed on the amount of information appropriate for lecture and the role of active participation in resident conferences. Conclusion: This study highlights several challenges to facilitating active learning in resident conferences and provides insights for residency faculty who seek to transform the conference learning environment within their residency program. C1 [Sawatsky, Adam P.] Mayo Clin, Div Gen Internal Med, Rochester, MN 55905 USA. [Zickmund, Susan L.] VA Pittsburgh Healthcare Syst, Ctr Hlth Equ Res & Promot, Pittsburgh, PA USA. [Berlacher, Kathryn] Univ Pittsburgh, Sch Med, Div Cardiol, Pittsburgh, PA USA. [Lesky, Dan] Univ Pittsburgh, Sch Med, Pittsburgh, PA USA. [Granieri, Rosanne] Univ Pittsburgh, Sch Med, Div Gen Internal Med, Pittsburgh, PA USA. RP Sawatsky, AP (reprint author), Mayo Clin, Div Gen Internal Med, 200 1st St SW, Rochester, MN 55905 USA. EM sawatsky.adam@mayo.edu FU Division of General Internal Medicine; Faculty Award at the University of Pittsburgh FX The authors thank the Division of General Internal Medicine Fellow and Faculty Award at the University of Pittsburgh for funding this project. NR 28 TC 0 Z9 0 U1 1 U2 6 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 2015 VL 20 AR 27289 DI 10.3402/meo.v20.27289 PG 7 WC Education & Educational Research SC Education & Educational Research GA CM3MN UT WOS:000357586500001 PM 26160805 ER PT J AU Madigan, MC McEnaney, RM Shukla, AJ Hong, GY Kelley, EE Tarpey, MM Gladwin, M Zuckerbraun, BS Tzeng, E AF Madigan, Michael C. McEnaney, Ryan M. Shukla, Ankur J. Hong, Guiying Kelley, Eric E. Tarpey, Margaret M. Gladwin, Mark Zuckerbraun, Brian S. Tzeng, Edith TI Xanthine Oxidoreductase Function Contributes to Normal Wound Healing SO MOLECULAR MEDICINE LA English DT Article ID NITRIC-OXIDE SYNTHASE; EGF-RECEPTOR PHOSPHORYLATION; ISCHEMIA-REPERFUSION INJURY; ENDOTHELIAL GROWTH-FACTOR; IMPAIRED SKIN REPAIR; MIGRATION IN-VITRO; OXIDATIVE STRESS; HYDROGEN-PEROXIDE; DEFICIENT MICE; REDOX CONTROL AB Chronic, nonhealing wounds result in patient morbidity and disability. Reactive oxygen species (ROS) and nitric oxide (NO) are both required for normal wound repair, and derangements of these result in impaired healing. Xanthine oxidoreductase (XOR) has the unique capacity to produce both ROS and NO. We hypothesize that XOR contributes to normal wound healing. Cutaneous wounds were created in C57Bl6 mice. XOR was inhibited with dietary tungsten or allopurinol. Topical hydrogen peroxide (H2O2, 0.15%) or allopurinol (30 mu g) was applied to wounds every other day. Wounds were monitored until closure or collected at d 5 to assess XOR expression and activity, cell proliferation and histology. The effects of XOR, nitrite, H2O2 and allopurinol on keratinocyte cell (KC) and endothelial cell (EC) behavior were assessed. We identified XOR expression and activity in the skin and wound edges as well as granulation tissue. Cultured human KCs also expressed XOR. Tungsten significantly inhibited XOR activity and impaired healing with reduced ROS production with reduced angiogenesis and KC proliferation. The expression and activity of other tungsten-sensitive enzymes were minimal in the wound tissues. Oral allopurinol did not reduce XOR activity or alter wound healing but topical allopurinol significantly reduced XOR activity and delayed healing. Topical H2O2 restored wound healing in tungsten-fed mice. In vitro, nitrite and H2O2 both stimulated KC and EC proliferation and EC migration. These studies demonstrate for the first time that XOR is abundant in wounds and participates in normal wound healing through effects on ROS production. C1 [Madigan, Michael C.; McEnaney, Ryan M.; Shukla, Ankur J.; Hong, Guiying; Tarpey, Margaret M.; Zuckerbraun, Brian S.; Tzeng, Edith] Dept Vet Affairs Med Ctr, Surg Serv, Pittsburgh, PA USA. [Madigan, Michael C.; McEnaney, Ryan M.; Shukla, Ankur J.; Hong, Guiying; Zuckerbraun, Brian S.; Tzeng, Edith] Univ Pittsburgh, Dept Surg, Pittsburgh, PA USA. [Kelley, Eric E.; Tarpey, Margaret M.] Univ Pittsburgh, Dept Anesthesia, Pittsburgh, PA USA. [Gladwin, Mark] Univ Pittsburgh, Dept Med, Pittsburgh, PA USA. RP Tzeng, E (reprint author), VA Pittsburgh Healthcare Syst, Vasc Surg, A1010 PUH,200 Lothrop St, Pittsburgh, PA 15213 USA. EM tzenge@upmc.edu FU Department of Veterans Affairs, Veterans Health Administration; Office of Biomedical Laboratory Research and Development - National Institutes of Health (NIH) [NIH T32 HL098036, NIH R01 HL058115]; NIH [R01HL098032, R01HL096973, PO1HL103455]; Institute for Transfusion Medicine; Hemophilia Center of Western Pennsylvania FX We gratefully acknowledge the excellent technical assistance provided by NJ Hundley, SI Zharikov and N Cantu-Medellin. This material is based on work supported in part by the Department of Veterans Affairs, Veterans Health Administration and Office of Biomedical Laboratory Research and Development (ET), through funding from the National Institutes of Health (NIH) (NIH T32 HL098036 to MC Madigan, RM McEnaney and AJ Shukla and NIH R01 HL058115 to MM Tarpey). M Gladwin received research support from NIH grants R01HL098032, R01HL096973 and PO1HL103455 as well as from the Institute for Transfusion Medicine and the Hemophilia Center of Western Pennsylvania. NR 51 TC 4 Z9 4 U1 2 U2 8 PU FEINSTEIN INST MED RES PI MANHASSET PA 350 COMMUNITY DR, MANHASSET, NY 11030 USA SN 1076-1551 EI 1528-3658 J9 MOL MED JI Mol. Med. PY 2015 VL 21 BP 313 EP 322 DI 10.2119/molmed.2014.00191 PG 10 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA CM4JW UT WOS:000357651800008 PM 25879627 ER PT S AU Schwartz, E Jakab, A Kasprian, G Zollei, L Langs, G AF Schwartz, Ernst Jakab, Andras Kasprian, Gregor Zoellei, Lilla Langs, Georg BE Durrleman, S Fletcher, T Gerig, G Niethammer, M Pennec, X TI A Locally Linear Method for Enforcing Temporal Smoothness in Serial Image Registration SO SPATIO-TEMPORAL IMAGE ANALYSIS FOR LONGITUDINAL AND TIME-SERIES IMAGE DATA SE Lecture Notes in Computer Science LA English DT Proceedings Paper CT 3rd International Workshop on Spatiotemporal Image Analysis for Longitudinal and Time-Series Image Data (STIA) CY SEP 18, 2014 CL Boston, MA SP Sci Comp & Imaging Inst, Natl Alliance Med Image Comp, Ctr Rech, Inst Cerveau Moelle Epiniere ID IN-UTERO; BRAIN; ATLAS; DIFFEOMORPHISMS; DEFORMATION; TEMPLATE AB Deformation fields obtained from image registration are commonly used for deriving measurements of morphological changes between reference and follow-up images. As the underlying image matching problem is ill-posed, the exact shape of these deformation fields is often dependent on the regularization method. In longitudinal and cross-sectional studies this effect is amplified if time between acquisitions varies and smoothness between serial deformations is neglected. Existing solutions suffer from high computational costs, strong modeling assumptions and the bias towards a single reference image. In this paper, we propose a computationally efficient solution to this problem via a temporal smoothing formulation in the one-parameter subgroup of diffeomorphisms parametrized by stationary velocity fields. When applied to modeling fetal brain development, the proposed regularization results in smooth deformation fields over time and high data fidelity. C1 [Schwartz, Ernst; Jakab, Andras; Langs, Georg] Med Univ Vienna, CIR Lab, Dept Biomed Imaging & Image Guided Therapy, Vienna, Austria. [Schwartz, Ernst; Jakab, Andras; Kasprian, Gregor; Langs, Georg] Med Univ Vienna, Dept Biomed Imaging & Image Guided Therapy, Vienna, Austria. [Zoellei, Lilla] Massachusetts Gen Hosp, Lab Computat Neuroimaging, Martinos Ctr Biomed Imaging, Boston, MA 02114 USA. RP Schwartz, E (reprint author), Med Univ Vienna, CIR Lab, Dept Biomed Imaging & Image Guided Therapy, Vienna, Austria. EM ernst.schwartz@meduniwien.ac.at OI Kasprian, Gregor/0000-0003-3858-3347 NR 29 TC 2 Z9 2 U1 2 U2 2 PU SPRINGER-VERLAG BERLIN PI BERLIN PA HEIDELBERGER PLATZ 3, D-14197 BERLIN, GERMANY SN 0302-9743 BN 978-3-319-14905-9; 978-3-319-14904-2 J9 LECT NOTES COMPUT SC PY 2015 VL 8682 BP 13 EP 24 DI 10.1007/978-3-319-14905-9_2 PG 12 WC Computer Science, Artificial Intelligence; Computer Science, Theory & Methods SC Computer Science GA BD0SU UT WOS:000357678700002 ER PT J AU Yang, AM Xiao, X Zhao, MF LaRue, AC Schulte, BA Wang, GY AF Yang, Aimin Xiao, Xia Zhao, Mingfeng LaRue, Amanda C. Schulte, Bradley A. Wang, Gavin Y. TI Differential Reponses of Hematopoietic Stem and Progenitor Cells to mTOR Inhibition SO STEM CELLS INTERNATIONAL LA English DT Article ID ACUTE MYELOID-LEUKEMIA; MAMMALIAN TARGET; ANTITUMOR-ACTIVITY; RAPAMYCIN; PTEN; PATHWAY; AZD8055; CANCER; LEUKEMOGENESIS; SENESCENCE AB Abnormal activation of the mammalian target of rapamycin (mTOR) signaling pathway has been observed in a variety of human cancers. Therefore, targeting of the mTOR pathway is an attractive strategy for cancer treatment and several mTOR inhibitors, including AZD8055 (AZD), a novel dual mTORC1/2 inhibitor, are currently in clinical trials. Although bone marrow (BM) suppression is one of the primary side effects of anticancer drugs, it is not known if pharmacological inhibition of dual mTORC1/2 affects BM hematopoietic stem and progenitor cells (HSPCs) function and plasticity. Here we report that dual inhibition of mTORC1/2 by AZD or its analogue (KU-63794) depletes mouse BM Lin(-)Sca-1(+)c-Kit(+) cells in cultures via the induction of apoptotic cell death. Subsequent colony-forming unit (CFU) assays revealed that inhibition of mTORC1/2 suppresses the clonogenic function of hematopoietic progenitor cells (HPCs) in a dose-dependent manner. Surprisingly, we found that dual inhibition of mTORC1/2 markedly inhibits the growth of day-14 cobblestone area-forming cells (CAFCs) but enhances the generation of day-35 CAFCs. Given the fact that day-14 and day-35 CAFCs are functional surrogates of HPCs and hematopoietic stem cells (HSCs), respectively, these results suggest that dual inhibition of mTORC1/2 may have distinct effects on HPCs versus HSCs. C1 [Yang, Aimin; Xiao, Xia; LaRue, Amanda C.; Schulte, Bradley A.; Wang, Gavin Y.] Med Univ S Carolina, Dept Pathol & Lab Med, Charleston, SC 29425 USA. [Xiao, Xia; Zhao, Mingfeng] Tianjin First Ctr Hosp, Dept Hematol, Tianjin 300192, Peoples R China. [LaRue, Amanda C.] Ralph H Johnson VAMC, Res Serv, Charleston, SC USA. [LaRue, Amanda C.; Wang, Gavin Y.] Med Univ S Carolina, Hollings Canc Ctr, Canc Genes & Mol Regulat Program, Charleston, SC 29425 USA. RP Wang, GY (reprint author), Med Univ S Carolina, Dept Pathol & Lab Med, Charleston, SC 29425 USA. EM wangy@musc.edu FU National Heart, Lung and Blood Institute (NHLBI) [HL106451]; Hollings Cancer Center [P30 CA138313]; South Carolina Clinical & Translational Research (SCTR) Institute; Medical University of South Carolina CTSA, NIH/NCATS Grant [UL1TR000062] FX This study was supported, in part, by a Grant from the National Heart, Lung and Blood Institute (NHLBI) no. HL106451 (Gavin Y. Wang) and a pilot grant from the Hollings Cancer Center (Gavin Y. Wang) via P30 CA138313. This work was also supported in part by the South Carolina Clinical & Translational Research (SCTR) Institute, with an academic home at the Medical University of South Carolina CTSA, NIH/NCATS Grant no. UL1TR000062. NR 31 TC 1 Z9 1 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 1687-966X EI 1687-9678 J9 STEM CELLS INT JI Stem Cells Int. PY 2015 AR 561404 DI 10.1155/2015/561404 PG 9 WC Cell & Tissue Engineering SC Cell Biology GA CM6QG UT WOS:000357813000001 ER PT J AU Nadol, JB Marshall, JD Bronson, RT AF Nadol, Joseph B., Jr. Marshall, Jan D. Bronson, Roderick T. TI Histopathology of the Human Inner Ear in Alstrom's Syndrome SO AUDIOLOGY AND NEURO-OTOLOGY LA English DT Article DE Alstrom's syndrome; ALMS1; Human; Histopathology; Inner ear ID ALMS1; DEAFNESS AB Alstrom's syndrome is an autosomal recessive syndromic genetic disorder caused by mutations in the ALMS1 gene. Sensorineural hearing loss occurs in greater than 85% of patients. Histopathology of the inner ear abnormalities in the human has not previously been fully described. Histopathology of the inner ear in Alstrom's syndrome is presented in 2 genetically confirmed cases. The predominant histopathologic correlates of the sensorineural loss were degeneration of the organ of Corti, both inner and outer hair cells, degeneration of spiral ganglion cells, and atrophy of the stria vascularis and spiral ligament. (C) 2015 S. Karger AG, Basel C1 [Nadol, Joseph B., Jr.] Massachusetts Eye & Ear Infirm, Dept Otolaryngol, Otopathol Lab, Boston, MA 02115 USA. [Nadol, Joseph B., Jr.; Bronson, Roderick T.] Harvard Univ, Sch Med, Boston, MA USA. [Marshall, Jan D.; Bronson, Roderick T.] Jackson Lab, Bar Harbor, ME 04609 USA. RP Nadol, JB (reprint author), Massachusetts Eye & Ear Infirm, Dept Otolaryngol, 243 Charles St, Boston, MA 02115 USA. EM joseph_nadol@meei.harvard.edu FU NIH grant [HD036878, U24DC011943] FX Supported by: NIH grant HD036878 (J.D.M.) and NIH grant U24DC011943 (J.B.N.). NR 15 TC 1 Z9 1 U1 0 U2 1 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 2015 VL 20 IS 4 BP 267 EP 272 DI 10.1159/000381935 PG 6 WC Audiology & Speech-Language Pathology; Neurosciences; Otorhinolaryngology SC Audiology & Speech-Language Pathology; Neurosciences & Neurology; Otorhinolaryngology GA CM3PV UT WOS:000357596100008 PM 26111748 ER PT B AU Silva, GV Palacios, IF AF Silva, Guilherme V. Palacios, Igor F. BE Sievert, H Qureshi, SA Wilson, N Hijazi, ZM TI Transseptal left heart catheterization SO INTERVENTIONS IN STRUCTURAL, VALVULAR, AND CONGENITAL HEART DISEASE LA English DT Article; Book Chapter ID TRANS-SEPTAL CATHETERIZATION; CARDIAC-CATHETERIZATION; LEFT ATRIAL; COMPLICATIONS; EXPERIENCE; DISEASE; SAFETY C1 [Silva, Guilherme V.] Texas Heart Inst, Houston, TX 77025 USA. [Palacios, Igor F.] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. RP Silva, GV (reprint author), Texas Heart Inst, Houston, TX 77025 USA. NR 34 TC 0 Z9 0 U1 0 U2 0 PU CRC PRESS-TAYLOR & FRANCIS GROUP PI BOCA RATON PA 6000 BROKEN SOUND PARKWAY NW, STE 300, BOCA RATON, FL 33487-2742 USA BN 978-1-4822-1564-9; 978-1-4822-1563-2 PY 2015 BP 145 EP 152 PG 8 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA BC7ZN UT WOS:000355441100016 ER PT B AU Palacios, IF Silva, GV AF Palacios, Igor F. Silva, Guilherme V. BE Sievert, H Qureshi, SA Wilson, N Hijazi, ZM TI Mitral and tricuspid valve stenosis: Percutaneous mitral valvuloplasty SO INTERVENTIONS IN STRUCTURAL, VALVULAR, AND CONGENITAL HEART DISEASE LA English DT Article; Book Chapter ID LEFT-HEART CATHETERIZATION; PREVIOUS SURGICAL COMMISSUROTOMY; TRANS-SEPTAL CATHETERIZATION; BALLOON VALVOTOMY; FOLLOW-UP; TRANSSEPTAL CATHETERIZATION; CARDIAC-CATHETERIZATION; LEFT ATRIAL; RANDOMIZED-TRIAL; ADULT PATIENTS C1 [Palacios, Igor F.] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. [Silva, Guilherme V.] Texas Heart Inst, Houston, TX 77025 USA. RP Palacios, IF (reprint author), Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. NR 70 TC 0 Z9 0 U1 0 U2 0 PU CRC PRESS-TAYLOR & FRANCIS GROUP PI BOCA RATON PA 6000 BROKEN SOUND PARKWAY NW, STE 300, BOCA RATON, FL 33487-2742 USA BN 978-1-4822-1564-9; 978-1-4822-1563-2 PY 2015 BP 349 EP 360 PG 12 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA BC7ZN UT WOS:000355441100039 ER PT J AU Gustafson, DR Morris, MC Scarmeas, N Shah, RC Sijben, J Yaffe, K Zhu, XW AF Gustafson, Deborah R. Morris, Martha Clare Scarmeas, Nikolaos Shah, Raj C. Sijben, John Yaffe, Kristine Zhu, Xiongwei TI New Perspectives on Alzheimer's Disease and Nutrition SO JOURNAL OF ALZHEIMERS DISEASE LA English DT Article DE Alzheimer's disease; cognition disorders; diet therapy; neuronal membrane; nutrition ID MILD COGNITIVE IMPAIRMENT; BODY-MASS INDEX; POLYUNSATURATED FATTY-ACID; DOCOSAHEXAENOIC ACID; MEDITERRANEAN DIET; OXIDATIVE STRESS; VITAMIN-E; CONTROLLED-TRIAL; OLDER-ADULTS; CARDIOVASCULAR-DISEASE AB Accumulating evidence shows nutritional factors influence the risk of developing Alzheimer's disease (AD) and its rate of clinical progression. Dietary and lifestyle guidelines to help adults reduce their risk have been developed. However, the clinical dementia picture remains complex, and further evidence is required to demonstrate that modifying nutritional status can protect the brain and prevent, delay, or reduce pathophysiological consequences of AD. Moreover, there is a pressing need for further research because of the global epidemic of overweight and obesity combined with longer life expectancy of the general population and generally observed decreases in body weight with aging and AD. A new research approach is needed, incorporating more sophisticated models to account for complex scenarios influencing the relationship between nutritional status and AD. Systematic research should identify and address evidence gaps. Integrating longitudinal epidemiological data with biomarkers of disease, including brain imaging technology, and randomized controlled interventions may provide greater insights into progressive and subtle neurological changes associated with dietary factors in individuals at risk for or living with AD. In addition, greater understanding of mechanisms involved in nutritional influences on AD risk and progression, such as oxidative stress and loss of neuronal membrane integrity, will better inform possible interventional strategies. There is consensus among the authors that nutritional deficits, and even states of excess, are associated with AD, but more work is needed to determine cause and effect. Appropriately designed diets or nutritional interventions may play a role, but additional research is needed on their clinical-cognitive effectiveness. C1 [Gustafson, Deborah R.] Suny Downstate Med Ctr, Dept Neurol, Brooklyn, NY 11203 USA. [Gustafson, Deborah R.] Univ Gothenburg, Sect Psychiat & Neurochem, NeuroPsychiat Epidemiol Unit, Inst Neurosci & Physiol,Sahlgrenska Acad, Gothenburg, Sweden. [Morris, Martha Clare] Rush Univ, Med Ctr, Dept Internal Med, Sect Nutr & Nutr Epidemiol, Chicago, IL 60612 USA. [Scarmeas, Nikolaos] Columbia Univ, Gertrude H Sergievsky Ctr, Dept Neurol, Taub Inst Res Alzheimers Dis & Aging Brain, New York, NY 10027 USA. [Scarmeas, Nikolaos] Univ Athens, Dept Social Med Psychiat & Neurol, Athens 11528, Greece. [Shah, Raj C.] Rush Univ, Med Ctr, Dept Family Med, Chicago, IL 60612 USA. [Shah, Raj C.] Rush Univ, Med Ctr, Rush Alzheimers Dis Ctr, Chicago, IL 60612 USA. [Sijben, John] Nutricia Res, Nutricia Adv Med Nutr, Utrecht, Netherlands. [Yaffe, Kristine] Univ Calif San Francisco, Dept Psychiat, San Francisco, CA 94121 USA. [Yaffe, Kristine] Univ Calif San Francisco, Dept Neurol, San Francisco, CA 94121 USA. [Yaffe, Kristine] San Francisco VA Med Ctr, San Francisco, CA USA. [Zhu, Xiongwei] Case Western Reserve Univ, Dept Pathol, Cleveland, OH 44106 USA. RP Yaffe, K (reprint author), Univ Calif San Francisco, Psychiat, 4150 Clement St, San Francisco, CA 94121 USA. EM kristine.yaffe@ucsf.edu FU Swedish Research Council for Health, Working Life and Welfare [AGECAP 2013-2300]; EU [211696]; ESPA-EU program Excellence Grant (ARISTEIA) [189 10276/8/9/2011]; European Social Fund; Greek National resources; Ministry for Health and Social Solidarity (Greece) [DeltaY2beta/oiotakappa.51657/14.4.2009]; Illinois Department of Public Health; National Institute on Aging; National Institute on Environmental Health Sciences FX The authors received the following support: Deborah R. Gustafson: Swedish Research Council for Health, Working Life and Welfare (AGECAP 2013-2300) and EU 7th framework LipiDiDiet project (FP7/2007-2015) under grant agreement no. 211696; Nikolaos Scarmeas: 189 10276/8/9/2011 from the ESPA-EU program Excellence Grant (ARISTEIA) which is co-funded by the European Social Fund and Greek National resources; and Delta Y2 beta/o iota kappa.51657/14.4.2009 from the Ministry for Health and Social Solidarity (Greece); Raj C Shah: The Illinois Department of Public Health; Morris MC: National Institute on Aging and National Institute on Environmental Health Sciences. NR 143 TC 7 Z9 7 U1 4 U2 16 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 2015 VL 46 IS 4 BP 1111 EP 1127 DI 10.3233/JAD-150084 PG 17 WC Neurosciences SC Neurosciences & Neurology GA CM1GM UT WOS:000357429300026 PM 26402637 ER PT S AU Davis, CP West, JA AF Davis, Christopher P. West, Jason A. BE Nakagawa, S Hirose, T TI Purification of Specific Chromatin Regions Using Oligonucleotides: Capture Hybridization Analysis of RNA Targets (CHART) SO NUCLEAR BODIES AND NONCODING RNAS: METHODS AND PROTOCOLS SE Methods in Molecular Biology LA English DT Article; Book Chapter DE CHART; RNA; lncRNA; lincRNA; ncRNA; Chromatin ID NONCODING RNA; MAPS AB cation of genomic binding sites and proteins associated with noncoding RNAs will lead to more complete mechanistic characterization of the regulatory activities of noncoding RNAs. Capture hybridization analysis of RNA targets (CHART) is a powerful technique wherein specific RNA molecules are isolated from cross-linked nuclear extracts using complementary, biotinylated capture oligonucleotides, allowing subsequent identification of genomic DNA and proteins cross-linked to the RNA of interest. Here, we describe the procedure for CHART and list strategies to optimize nuclear extract preparation, capture oligonucleotide design, and isolation of nucleic acids and proteins enriched through CHART. C1 [Davis, Christopher P.; West, Jason A.] Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. [Davis, Christopher P.; West, Jason A.] Harvard Univ, Sch Med, Dept Genet, Boston, MA USA. [West, Jason A.] Amgen Inc, Therapeut Innovat Unit, Cambridge, MA USA. RP Davis, CP (reprint author), Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. RI West, Jason/I-4445-2014 OI West, Jason/0000-0002-7252-8651 NR 5 TC 3 Z9 3 U1 1 U2 9 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DR, STE 208, TOTOWA, NJ 07512-1165 USA SN 1064-3745 BN 978-1-4939-2253-6; 978-1-4939-2252-9 J9 METHODS MOL BIOL JI Methods Mol. Biol. PY 2015 VL 1262 BP 167 EP 182 DI 10.1007/978-1-4939-2253-6_10 D2 10.1007/978-1-4939-2253-6 PG 16 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA BD0TO UT WOS:000357692500011 PM 25555581 ER PT J AU McDonald, LT Mehrotra, M LaRue, AC AF McDonald, Lindsay T. Mehrotra, Meenal LaRue, Amanda C. TI Hematopoietic Origin of Murine Lung Fibroblasts SO STEM CELLS INTERNATIONAL LA English DT Article ID INDUCED PULMONARY-FIBROSIS; MESENCHYMAL STEM-CELLS; BONE-MARROW; CIRCULATING FIBROCYTES; IN-VITRO; MYOFIBROBLASTS; IDENTIFICATION; RECONSTITUTION; PROLIFERATION; PRECURSORS AB Multiple origins, including the bone marrow, have been suggested to contribute to fibroblast populations in the lung. Using bone marrow reconstitution strategies, the present study tested the hypothesis that the bone marrow hematopoietic stem cell (HSC) gives rise to lung tissue fibroblasts in vivo. Data demonstrate that the nonadherent bone marrow fraction is enriched for CD45(+) HSC-derived cells and was able to reconstitute hematopoiesis in lethally irradiated animals. Analysis of peripheral blood and lung tissues from engrafted mice demonstrated the ability of this population to give rise to CD45(+)/Discoidin-Domain Receptor-2(+) (DDR2) circulating fibroblast precursors (CFPs) in blood and fibroblast populations in lung. An HSC origin for lung fibroblasts was confirmed using a novel clonal cell transplantation method in which the bone marrow is reconstituted by a clonal population derived from a single HSC. Together, these findings provide evidence for an HSC contribution to lung fibroblasts and demonstrate a circulating intermediate through the CD45(+)/DDR2(+) HSC-derived CFP. C1 [McDonald, Lindsay T.; LaRue, Amanda C.] Ralph H Johnson Dept Vet Affairs Med Ctr, Res Serv, Charleston, SC 29401 USA. [McDonald, Lindsay T.; Mehrotra, Meenal; LaRue, Amanda C.] Med Univ S Carolina, Dept Pathol & Lab Med, Charleston, SC 29425 USA. [LaRue, Amanda C.] Med Univ S Carolina, Hollings Canc Ctr, Charleston, SC 29425 USA. RP LaRue, AC (reprint author), Ralph H Johnson Dept Vet Affairs Med Ctr, Res Serv, Charleston, SC 29401 USA. EM laruerc@musc.edu FU VA [BX-12-011] FX This work was supported by a VA merit awarded to Amanda C. LaRue (BX-12-011). The authors thank the staff of the Radiation Oncology Department of the Medical University of South Carolina in irradiation of mice, and the animal care staff of the Ralph H. Johnson VAMC. They also acknowledge the Hollings Cancer Center Flow Cytometry Core P30 CA138313. NR 41 TC 0 Z9 0 U1 0 U2 0 PU HINDAWI PUBLISHING CORPORATION PI NEW YORK PA 410 PARK AVENUE, 15TH FLOOR, #287 PMB, NEW YORK, NY 10022 USA SN 1687-966X EI 1687-9678 J9 STEM CELLS INT JI Stem Cells Int. PY 2015 AR 159713 DI 10.1155/2015/159713 PG 11 WC Cell & Tissue Engineering SC Cell Biology GA CM2EY UT WOS:000357493800001 ER PT J AU Yin, R Hamblin, MR AF Yin, Rui Hamblin, Michael R. TI Antimicrobial Photosensitizers: Drug Discovery Under the Spotlight SO CURRENT MEDICINAL CHEMISTRY LA English DT Article DE Antimicrobial photodynamic therapy; bacteria; bacteriochlorin; chlorin; fullerene; fungi; infection; natural product; phenothiazinium salt; phthalocyanine; porphyrin; titania photocatalysis; xanthene dye ID MEDIATED PHOTODYNAMIC THERAPY; STAPHYLOCOCCUS-EPIDERMIDIS BIOFILMS; TOLUIDINE-BLUE-O; RESISTANT PSEUDOMONAS-AERUGINOSA; HELICOBACTER-PYLORI INFECTION; SINGLET OXYGEN GENERATION; GRAM-NEGATIVE BACTERIA; N-METHYL-PYRIDYL; IN-VITRO; CANDIDA-ALBICANS AB Although photodynamic therapy (PDT) was discovered over a hundred years ago by its ability to destroy microorganisms, it has been developed mainly as a cancer therapy. In recent years, due to the inexorable rise in multi-antibiotic resistant strains of pathogens, PDT is being considered as a versatile antimicrobial approach to which microbial cells will not be able to develop resistance. The goal of this review is to survey the different classes of chemical compounds that have been tested as antimicrobial . Some of these compounds have been known for many years, while others have been rationally designed based on recently discovered structural principles. Tetrapyrrole-based compounds (some of which are approved as cancer therapies) that efficiently generate singlet oxygen are more efficient and broad-spectrum when they bear cationic charges, As the macrocycle structure moves from porphyrins to chlorins to phthalocyanines to bacteriochlorins the long wavelength absorption moves to the near-infrared where tissue penetration is better. Four main types of natural products have been tested: curcumin, riboflavin, hypericin and psoralens. Phenothiazinium dyes, such as methylene blue and toluidine blue, have been tested, and some are clinically approved. A variety of non-phenothiazinium dyes with xanthene, triarylmethane and indocyanine structures have also been tested. New ring structures based on BODIPY, squaraine and fullerene cages can also mediate antimicrobial PDT. Finally the process of photocatalysis using titanium dioxide can also have medical uses. Designing new antimicrobial photosensitizers is likely to keep chemists engaged for a long time to come. C1 [Yin, Rui] Third Mil Med Univ, Southwest Hosp, Dept Dermatol, Chongqing 40038, Peoples R China. [Yin, Rui; Hamblin, Michael R.] Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA. [Yin, Rui; Hamblin, Michael R.] Harvard Univ, Sch Med, Dept Dermatol, Boston, MA 02115 USA. [Hamblin, Michael R.] MIT, Harvard Mit Div Hlth Sci & Technol, Cambridge, MA 02139 USA. RP Hamblin, MR (reprint author), Massachusetts Gen Hosp, Wellman Ctr Photomed, 40 Blossom St, Boston, MA 02114 USA. EM Hamblin@helix.mgh.harvard.edu FU NIH [R01AI050875] FX Michael R Hamblin is supported by NIH grant R01AI050875. NR 235 TC 11 Z9 11 U1 15 U2 71 PU BENTHAM SCIENCE PUBL LTD PI SHARJAH PA EXECUTIVE STE Y-2, PO BOX 7917, SAIF ZONE, 1200 BR SHARJAH, U ARAB EMIRATES SN 0929-8673 EI 1875-533X J9 CURR MED CHEM JI Curr. Med. Chem. PY 2015 VL 22 IS 18 BP 2159 EP 2185 PG 27 WC Biochemistry & Molecular Biology; Chemistry, Medicinal; Pharmacology & Pharmacy SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy GA CL5ZL UT WOS:000357044400005 PM 25787964 ER PT S AU Jordan, JT Wen, PY AF Jordan, Justin T. Wen, Patrick Y. BE Raizer, J Parsa, A TI Novel Chemotherapeutic Approaches in Adult High-Grade Gliomas SO CURRENT UNDERSTANDING AND TREATMENT OF GLIOMAS SE Cancer Treatment and Research LA English DT Article; Book Chapter DE Glioma; Glioblastoma; Targeted therapy; Chemotherapy ID RECURRENT MALIGNANT GLIOMA; PHASE-II TRIAL; NEWLY-DIAGNOSED GLIOBLASTOMA; BRAIN-TUMOR CONSORTIUM; GROWTH-FACTOR RECEPTOR; EGFR KINASE INHIBITORS; ADVANCED SOLID TUMORS; RADIATION-THERAPY; IMATINIB MESYLATE; I/II TRIAL AB Despite decades of advancing science and clinical trials, average survival remains dismal for individuals with high-grade gliomas. Our understanding of the genetic and molecular aberrations that contribute to the aggressive nature of these tumors is continually growing, as is our ability to target such specific traits. Herein, we review the major classes of such targeted therapies, as well as the relevant clinical trial outcomes regarding their efficacy. C1 [Jordan, Justin T.; Wen, Patrick Y.] Dana Farber Brigham & Womens Canc Ctr, Ctr Neurooncol, Boston, MA 02215 USA. [Wen, Patrick Y.] Harvard Univ, Sch Med, Brigham & Womens Hosp, Div Neurooncol,Dept Neurol, Boston, MA 02115 USA. RP Wen, PY (reprint author), Dana Farber Brigham & Womens Canc Ctr, Ctr Neurooncol, 450 Brookline Ave, Boston, MA 02215 USA. EM pwen@partners.org NR 121 TC 4 Z9 4 U1 0 U2 1 PU SPRINGER PI DORDRECHT PA PO BOX 17, 3300 AA DORDRECHT, NETHERLANDS SN 0927-3042 BN 978-3-319-12048-5; 978-3-319-12047-8 J9 CANCER TREAT RES JI Canc. Treat. Res. PY 2015 VL 163 BP 117 EP 142 D2 10.1007/978-3-319-12048-5 PG 26 WC Oncology; Clinical Neurology SC Oncology; Neurosciences & Neurology GA BD0KN UT WOS:000357285600008 PM 25468229 ER PT J AU Hoggatt, KJ Jamison, AL Lehavot, K Cucciare, MA Timko, C Simpson, TL AF Hoggatt, Katherine J. Jamison, Andrea L. Lehavot, Keren Cucciare, Michael A. Timko, Christine Simpson, Tracy L. TI Alcohol and Drug Misuse, Abuse, and Dependence in Women Veterans SO EPIDEMIOLOGIC REVIEWS LA English DT Article DE alcohol; drugs; gender; military; substance-related disorders; veterans; women ID SUBSTANCE USE DISORDERS; POSTTRAUMATIC-STRESS-DISORDER; VA HEALTH-CARE; NURSING-HOME RESIDENTS; FEMALE VETERANS; MENTAL-HEALTH; AFGHANISTAN VETERANS; GENDER-DIFFERENCES; UNITED-STATES; MILITARY SERVICE AB We conducted a systematic literature review on substance misuse, abuse, and dependence in women veterans, including National Guard/reserve members. We identified 837 articles published between 1980 and 2013. Of 56 included studies, 32 reported rates of alcohol misuse, binge drinking, or other unhealthy alcohol use not meeting diagnostic criteria for abuse or dependence, and 33 reported rates of drug misuse or diagnosed alcohol or drug use disorders. Rates ranged from 4% to 37% for alcohol misuse and from 7% to 25% for binge drinking; among Veterans Health Administration (VA) health-care system outpatients, rates ranged from 3% to 16% for substance use disorder. Studies comparing women veterans and civilians reported no clear differences in binge or heavy drinking. Substance misuse rates were generally lower among women veterans than men veterans. Substance misuse was associated with higher rates of trauma, psychiatric and medical conditions, and increased mortality and suicide rates. Most studies included only VA patients, and many used only VA medical record data; therefore, the reported substance misuse rates likely do not reflect true prevalence. Rates also varied by assessment method, source of data, and the subgroups studied. Further efforts to develop epidemiologically valid prevalence estimates are needed to capture the true health burden of substance misuse in women veterans, particularly those not using VA care. C1 [Hoggatt, Katherine J.] VA Greater Los Angeles, Hlth Serv Res & Dev Ctr, Study Healthcare Innovat Implementat & Policy, Sepulveda, CA 91343 USA. RP Hoggatt, KJ (reprint author), VA Greater Los Angeles, Hlth Serv Res & Dev Ctr, Study Healthcare Innovat Implementat & Policy, 16111 Plummer St Mailstop 152, Sepulveda, CA 91343 USA. EM khoggatt@ucla.edu FU VA HSRD [SDR 10-012, CX 000867, CDA 08-004-3, RCS 00-001]; VA HSRD/QUERI [CDA 11-261] FX This work was supported by VA HSR&D (SDR 10-012), with excerpts presented at the VA Substance Use Disorder Workgroup of the Women's Health Research Consortium. Funding was also provided through a VA HSR&D/QUERI Career Development Award (CDA 11-261) to K. J. H., a VA CSR&D Career Development Award (CX 000867) to K. L., a VA HSR&D Career Development Award (CDA 08-004-3) to M. A. C., and a VA HSR&D Senior Research Career Scientist Award (RCS 00-001) to C. T. NR 119 TC 8 Z9 8 U1 3 U2 16 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0193-936X EI 1478-6729 J9 EPIDEMIOL REV JI Epidemiol. Rev. PY 2015 VL 37 IS 1 BP 23 EP 37 DI 10.1093/epirev/mxu010 PG 15 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA CL3ZX UT WOS:000356892800003 PM 25608962 ER PT J AU Theodoroff, SM Lewis, MS Folmer, RL Henry, JA Carlson, KF AF Theodoroff, Sarah M. Lewis, M. Samantha Folmer, Robert L. Henry, James A. Carlson, Kathleen F. TI Hearing Impairment and Tinnitus: Prevalence, Risk Factors, and Outcomes in US Service Members and Veterans Deployed to the Iraq and Afghanistan Wars SO EPIDEMIOLOGIC REVIEWS LA English DT Article DE hearing loss; prevalence; risk factors; tinnitus; veterans' health ID TRAUMATIC BRAIN-INJURY; OPERATION ENDURING FREEDOM; COMBAT WOUNDS; BLAST INJURY; GLOBAL WAR; MECHANISM; TERROR; AIDS AB Hearing loss and tinnitus are the 2 most prevalent service-connected disabilities among veterans in the United States. Veterans of Operations Enduring Freedom, Iraqi Freedom, and New Dawn have been exposed to multiple hazards associated with these conditions, such as blasts/explosions, ototoxic chemicals, and most notably high levels of noise. We conducted a systematic literature review of evidence on 1) prevalence of, 2) risk and protective factors for, and 3) functional and quality-of-life outcomes of hearing impairment and tinnitus in US Operations Enduring Freedom, Iraqi Freedom, and New Dawn veterans and military personnel. We identified studies published from 2001 through 2013 using PubMed, PsycINFO, REHABDATA, Cochrane Library, pearling, and expert recommendation. Peer-reviewed English language articles describing studies of 30 or more adults were included if they informed one or more key questions. A total of 839 titles/abstracts were reviewed for relevance by investigators trained in critical analysis of literature; 14 studies met inclusion criteria. Of these, 13 studies presented data on prevalence and 4 on risk/protective factors, respectively. There were no included studies reporting on outcomes. Findings from this systematic review will help inform clinicians, researchers, and policy makers on future resource and research needs pertaining to hearing impairment and tinnitus in this newest generation of veterans. C1 [Theodoroff, Sarah M.] Portland VA Med Ctr, Natl Ctr Rehabilitat Auditory Res, Portland, OR 97239 USA. RP Theodoroff, SM (reprint author), Portland VA Med Ctr, Natl Ctr Rehabilitat Auditory Res, 3710 Southwest US Vet Hosp Rd, Portland, OR 97239 USA. EM sarah.theodoroff@va.gov FU Department of Defense Congressionally Directed Medical Research Programs [PR121146]; Veterans Health Administration Health Services Research and Development Service [CDA 08-025]; National Center for Rehabilitative Auditory Research - VA RR&D at the Portland VA Medical Center [C9230C] FX This work was supported, in part, by the Department of Defense Congressionally Directed Medical Research Programs (PR121146 to J. A. H.) and a career development grant from the Veterans Health Administration Health Services Research and Development Service (CDA 08-025 to K. F. C.). Additional support was provided by the National Center for Rehabilitative Auditory Research (funded by VA RR&D grant C9230C) at the Portland VA Medical Center. NR 46 TC 4 Z9 4 U1 2 U2 15 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0193-936X EI 1478-6729 J9 EPIDEMIOL REV JI Epidemiol. Rev. PY 2015 VL 37 IS 1 BP 71 EP 85 DI 10.1093/epirev/mxu005 PG 15 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA CL3ZX UT WOS:000356892800006 PM 25600417 ER PT J AU Beste, LA Ioannou, GN AF Beste, Lauren A. Ioannou, George N. TI Prevalence and Treatment of Chronic Hepatitis C Virus Infection in the US Department of Veterans Affairs SO EPIDEMIOLOGIC REVIEWS LA English DT Article DE epidemiology; hepatitis C virus; United States; veterans ID SUSTAINED VIROLOGICAL RESPONSE; UNITED-STATES VETERANS; GENOTYPE 1 INFECTION; TREATMENT ELIGIBILITY; ANTIVIRAL THERAPY; VIRAL-HEPATITIS; PLUS RIBAVIRIN; RISK-FACTORS; COHORT; CARE AB Chronic hepatitis C virus (HCV) is the most common blood-borne pathogen in the United States. HCV disproportionately affects Veterans Affairs (VA) health-care users: 174,302 HCV-infected veterans were in VA care in 2013, making the VA the world's largest HCV care provider. This systematic review identified 546 articles related to HCV in the VA. After assessment by 2 independent reviewers, 28 articles describing prevalence and treatment of HCV in VA users ultimately met inclusion criteria. Most VA patients currently living with HCV infection were born between 1945 and 1965 and were infected with HCV between 1970 and 1990. To prevent HCV-related complications such as cirrhosis, hepatocellular carcinoma, and death, medical personnel must identify and treat HCV. However, antiviral therapy has historically been limited by medication side effects, contraindications, and patient acceptance. Although treatment initiation rates are higher in the VA than in the general United States, only 23% of VA HCV patients have received treatment and, of those, only a minority were cured. Recent development of more effective and tolerable antiviral agents represents a major pharmacological breakthrough. Eradication of HCV is theoretically possible for the majority of HCV patients for the first time, although new barriers, such as high drug costs, may limit future uptake. C1 [Beste, Lauren A.] Vet Affairs Puget Sound Hlth Care Syst, Seattle, WA 98108 USA. RP Beste, LA (reprint author), Vet Affairs Puget Sound Hlth Care Syst, 1660 South Columbian Way,S-111 GI, Seattle, WA 98108 USA. EM lauren.beste@va.gov NR 60 TC 15 Z9 15 U1 2 U2 8 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0193-936X EI 1478-6729 J9 EPIDEMIOL REV JI Epidemiol. Rev. PY 2015 VL 37 IS 1 BP 131 EP 143 DI 10.1093/epirev/mxu002 PG 13 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA CL3ZX UT WOS:000356892800010 PM 25600415 ER PT J AU Sun, GB Haining, R Lin, H Oreskovic, NM He, J AF Sun, Guibo Haining, Robert Lin, Hui Oreskovic, Nicolas M. He, Jie TI Comparing the perception with the reality of walking in a hilly environment: an accessibility method applied to a University campus in Hong Kong SO GEOSPATIAL HEALTH LA English DT Article DE walking; hilly environment; accessibility; perception; geographic information system ID PHYSICAL-ACTIVITY; DISTANCE; SPACE; TIME AB The influence of hilliness on walking behavior could be a consequence of the real effect of the local topography, but individual perception of the difficulties associated with walking in a hilly environment may also be important. Previous studies have found that people's perceptions do not necessarily match well with the realities of walking in hilly environments. There are a few methods that can be used to visualize the geography of that difference for use by urban planners and public health practitioners. A walking accessibility measure that allows comparison of perception and reality is proposed and implemented in this study. We note that difficulties in calculating accessibility measures in the present context arise primarily from problems with data quality, three-dimensional pedestrian network modelling and the adequacy of accessibility methods for describing and predicting walking behavior. We present practical strategies for addressing these issues using geographic information systems. Our method is illustrated by calculating accessibility for a hilly university campus in Hong Kong. Walking behaviors on, and people's perceptions of, this hilly environment were obtained through walking diaries and a survey. The article concludes with suggested directions for the future development of walking accessibility measures along with some ideas about their applicability to the practice of planning and designing a walkable environment. C1 [Sun, Guibo; Lin, Hui] Chinese Univ Hong Kong, Inst Space & Earth Informat Sci, Shatin, Hong Kong, Peoples R China. [Haining, Robert] Univ Cambridge, Dept Geog, Cambridge CB2 1TN, England. [Lin, Hui] Chinese Univ Hong Kong, Dept Geog & Resource Management, Shatin, Hong Kong, Peoples R China. [Oreskovic, Nicolas M.] Massachusetts Gen Hosp, Dept Internal Med, Boston, MA 02114 USA. [Oreskovic, Nicolas M.] Massachusetts Gen Hosp, Dept Pediat, Boston, MA 02114 USA. [He, Jie] Harvard Univ, Sch Med, Boston, MA USA. [He, Jie] Tianjin Univ, Sch Architecture, Tianjin, Peoples R China. RP Lin, H (reprint author), Chinese Univ Hong Kong, Inst Space & Earth Informat Sci, Fok Ying Tung Remote Sensing Sci Bldg, Shatin, Hong Kong, Peoples R China. EM huilin@cuhk.edu.hk FU program Introducing Talents of Discipline to Universities [B13011]; National Natural Science Foundation of China [51478300]; National Heart, Lung, and Blood Institute [K23HL103841] FX Funding: this study is partially supported by program Introducing Talents of Discipline to Universities (B13011). Guibo Sun and Jie He are supported by a National Natural Science Foundation of China (51478300). Nicolas Oreskovic is supported by a grant from the National Heart, Lung, and Blood Institute (K23HL103841). NR 24 TC 0 Z9 0 U1 1 U2 9 PU UNIV NAPLES FEDERICO II PI NAPLES PA FAC VET MED, DEP PATHOLOGY & ANIMAL HEALTH, VET PARASITOLOGY, VIA DELLA VETERINARIA 1, NAPLES, 80137, ITALY SN 1827-1987 EI 1970-7096 J9 GEOSPATIAL HEALTH JI Geospatial Health PY 2015 VL 10 IS 1 BP 32 EP 39 DI 10.4081/gh.2015.340 PG 8 WC Health Care Sciences & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA CL0FJ UT WOS:000356615300006 ER PT J AU Amalakuhan, B Adams, SG AF Amalakuhan, Bravein Adams, Sandra G. TI Improving outcomes in chronic obstructive pulmonary disease: the role of the interprofessional approach SO INTERNATIONAL JOURNAL OF CHRONIC OBSTRUCTIVE PULMONARY DISEASE LA English DT Review DE optimal care; shared decision-making; co-morbidities ID RANDOMIZED CONTROLLED-TRIAL; SMOKING-CESSATION; LUNG TRANSPLANTATION; INTERNATIONAL SOCIETY; MANAGEMENT PROGRAM; PHYSICAL-ACTIVITY; SLEEP-APNEA; ADULT LUNG; COPD; REHABILITATION AB Chronic obstructive pulmonary disease (COPD) is associated with significant morbidity, places substantial time and cost burden on the health care system, and is now the third leading cause of death in the US. Many interventions are available to appropriately manage patients with COPD; however, fully implementing these strategies to help improve outcomes may be difficult. Collaboration between an interprofessional team of health care professionals (which includes physicians, nurses, respiratory therapists, physical therapists, dietitians, pharmacists, and many others) and COPD patients and caregivers is necessary to optimally manage these patients and to truly impact outcomes in this devastating disease. Prescribing evidence-based non-pharmacological and pharmacological therapies is an important start, but a true team-based approach is critical to successfully implement comprehensive care in patients with COPD. The goal of this review is to employ a case-based approach to provide practical information regarding the roles of the interprofessional team in implementing strategies to optimally manage COPD patients. C1 [Amalakuhan, Bravein; Adams, Sandra G.] Univ Texas Hlth Sci Ctr San Antonio, Dept Med, Div Pulm Dis Crit Care Med, San Antonio, TX 78229 USA. [Amalakuhan, Bravein; Adams, Sandra G.] South Texas Vet Hlth Care Syst, Audie L Murphy Div, San Antonio, TX USA. RP Adams, SG (reprint author), Audie L Murphy Mem Vet Adm Med Ctr, South Texas Vet Hlth Care Syst, Pulm Dis Sect 111E,7400 Merton Minter Blvd, San Antonio, TX 78229 USA. EM adamssg@uthscsa.edu FU National Institute of Health; Veterans Affairs Cooperative Studies Program; CHEST Foundation; University of Texas System Patient Safety Grant; AstraZeneca Pharmaceuticals LP; Boehringer Ingelheim Pharmaceuticals, Inc; GlaxoSmithKline; Novartis Pharmaceuticals AG FX Sandra Adams has funded research by National Institute of Health, Veterans Affairs Cooperative Studies Program, CHEST Foundation, University of Texas System Patient Safety Grant, AstraZeneca Pharmaceuticals LP, Boehringer Ingelheim Pharmaceuticals, Inc, GlaxoSmithKline, and Novartis Pharmaceuticals AG, and is the President of a not-for-profit organization entitled WipeDiseases Foundation. Bravein Amalakuhan reports no conflict of interest in this work. NR 66 TC 4 Z9 4 U1 0 U2 4 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 2015 VL 10 BP 1225 EP 1232 DI 10.2147/COPD.S71450 PG 8 WC Respiratory System SC Respiratory System GA CL5VV UT WOS:000357031300003 PM 26170651 ER PT J AU O'Day, DH Eshak, K Myre, MA AF O'Day, Danton H. Eshak, Kristeen Myre, Michael A. TI Calmodulin Binding Proteins and Alzheimer's Disease SO JOURNAL OF ALZHEIMERS DISEASE LA English DT Review DE Alzheimer's disease; calcium; calcium channels; calmodulin; calmodulin binding proteins; cholesterol metabolism; endocytosis; genome wide association studies; neuroinflammation ID AMYLOID-PRECURSOR-PROTEIN; TANDEM MASS-SPECTROMETRY; NEURONAL CELL-DEATH; KINASE-II; TAU-PROTEIN; NMDA RECEPTORS; CALCIUM HYPOTHESIS; MUTANT PRESENILIN; COMMON VARIANTS; CYCLE REENTRY AB The small, calcium-sensor protein, calmodulin, is ubiquitously expressed and central to cell function in all cell types. Here the literature linking calmodulin to Alzheimer's disease is reviewed. Several experimentally-verified calmodulin-binding proteins are involved in the formation of amyloid-beta plaques including amyloid-beta protein precursor, beta-secretase, presenilin-1, and ADAM10. Many others possess potential calmodulin-binding domains that remain to be verified. Three calmodulin binding proteins are associated with the formation of neurofibrillary tangles: two kinases (CaMKII, CDK5) and one protein phosphatase (PP2B or calcineurin). Many of the genes recently identified by genome wide association studies and other studies encode proteins that contain putative calmodulin-binding domains but only a couple (e.g., APOE, BIN1) have been experimentally confirmed as calmodulin binding proteins. At least two receptors involved in calcium metabolism and linked to Alzheimer's disease (mAchR; NMDAR) have also been identified as calmodulin-binding proteins. In addition to this, many proteins that are involved in other cellular events intimately associated with Alzheimer's disease including calcium channel function, cholesterol metabolism, neuroinflammation, endocytosis, cell cycle events, and apoptosis have been tentatively or experimentally verified as calmodulin binding proteins. The use of calmodulin as a potential biomarker and as a therapeutic target is discussed. C1 [O'Day, Danton H.] Univ Toronto, Dept Biol, Mississauga, ON L5L 1C6, Canada. [O'Day, Danton H.] Univ Toronto, Dept Cell & Syst Biol, Toronto, ON, Canada. [Eshak, Kristeen] McMaster Univ, Dept Biochem & Biomed Sci, Hamilton, ON L8N 3Z5, Canada. [Myre, Michael A.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Human Genet Res,Richard B Simches Res Ctr, Boston, MA USA. RP O'Day, DH (reprint author), Univ Toronto, Dept Biol, 3359 Mississauga Rd North, Mississauga, ON L5L 1C6, Canada. EM danton.oday@utoronto.ca FU Natural Sciences and Engineering Research Council of Canada [A6807] FX Robert J. Huber is thanked for his constructive comments on a draft of this manuscript. This work was supported by the Natural Sciences and Engineering Research Council of Canada (DHO'D; A6807). NR 138 TC 2 Z9 2 U1 2 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 2015 VL 46 IS 3 BP 553 EP 569 DI 10.3233/JAD-142772 PG 17 WC Neurosciences SC Neurosciences & Neurology GA CL4ZJ UT WOS:000356967200001 PM 25812852 ER PT J AU Munro, CE Donovan, NJ Guercio, BJ Wigman, SE Schultz, AP Amariglio, RE Rentz, DM Johnson, KA Sperling, RA Marshall, GA AF Munro, Catherine E. Donovan, Nancy J. Guercio, Brendan J. Wigman, Sarah E. Schultz, Aaron P. Amariglio, Rebecca E. Rentz, Dorene M. Johnson, Keith A. Sperling, Reisa A. Marshall, Gad A. TI Neuropsychiatric Symptoms and Functional Connectivity in Mild Cognitive Impairment SO JOURNAL OF ALZHEIMERS DISEASE LA English DT Article DE Alzheimer's disease; apathy; functional magnetic resonance imaging; mild cognitive impairment; neuropsychiatric symptoms ID DEFAULT MODE NETWORK; LATE-LIFE DEPRESSION; ALZHEIMERS-DISEASE; EXECUTIVE FUNCTION; APATHY; DEMENTIA; SPECTRUM; FMRI; PROGRESSION; TOMOGRAPHY AB Background: Neuropsychiatric symptoms (NPS), such as apathy and depression, commonly accompany cognitive and functional decline in early Alzheimer's disease (AD). Prior studies have shown associations between affective NPS and neurodegeneration of medial frontal and inferior temporal regions in mild cognitive impairment (MCI) and AD dementia. Objective: To investigate the association between functional connectivity in four brain networks and NPS in elderly with MCI. Methods: NPS were assessed using the Neuropsychiatric Inventory in 42 subjects with MCI. Resting-state functional connectivity in four networks (default mode network, fronto-parietal control network (FPCN), dorsal attention network, and ventral attention network) was assessed using seed-based magnetic resonance imaging. Factor analysis was used to identify two factors of NPS: Affective and Hyperactivity. Linear regression models were utilized with the neuropsychiatric factors as the dependent variable and the four networks as the predictors of interest. Covariates included age, gender, premorbid intelligence, processing speed, memory, head movement, and signal-to-noise ratio. These analyses were repeated with the individual items of the affective factor, using the same predictors. Results: There was a significant association between greater Affective factor symptoms and reduced FPCN connectivity (p = 0.03). There was no association between the Hyperactivity factor and any of the networks. Secondary analyses revealed an association between greater apathy and reduced FPCN connectivity (p = 0.005), but none in other networks. Conclusions: Decreased connectivity in the FPCN may be associated with greater affective symptoms, particularly apathy, early in AD. These findings extend prior studies, using different functional imaging modalities in individuals with greater disease severity. C1 [Munro, Catherine E.; Wigman, Sarah E.; Schultz, Aaron P.; Amariglio, Rebecca E.; Rentz, Dorene M.; Sperling, Reisa A.; Marshall, Gad A.] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. [Johnson, Keith A.] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. [Johnson, Keith A.] Harvard Univ, Sch Med, Boston, MA USA. [Donovan, Nancy J.; Amariglio, Rebecca E.; Rentz, Dorene M.; Johnson, Keith A.; Sperling, Reisa A.; Marshall, Gad A.] Harvard Univ, Sch Med, Brigham & Womens Hosp, Ctr Alzheimer Res & Treatment, Boston, MA USA. [Donovan, Nancy J.; Wigman, Sarah E.; Amariglio, Rebecca E.; Rentz, Dorene M.; Johnson, Keith A.; Sperling, Reisa A.; Marshall, Gad A.] Harvard Univ, Sch Med, Dept Neurol, Brigham & Womens Hosp, Boston, MA 02115 USA. [Donovan, Nancy J.; Amariglio, Rebecca E.; Rentz, Dorene M.] Harvard Univ, Sch Med, Dept Psychiat, Brigham & Womens Hosp, Boston, MA 02115 USA. RP Marshall, GA (reprint author), Brigham & Womens Hosp, Ctr Alzheimer Res & Treatment, 221 Longwood Ave,BL-104 H, 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, K24AG035007, R03AG045080]; Massachusetts Alzheimer's Disease Research Center [P50 AG005134]; Harvard Aging Brain Study [P01 AGO36694, R01 AG037497]; Harvard Medical School Department of Psychiatry; Harvard Medical School Scholars in Medicine Office; Janssen Alzheimer Immunotherapy; Wyeth/Pfizer Pharmaceuticals; Eisai Inc.; Eli Lilly and Company; Avid Radiopharmaceuticals; Bristol-Myers-Squibb FX This study was supported by R01 AG027435, K23 AG033634, K24AG035007, R03AG045080, the Rosalinde and Arthur Gilbert Foundation/AFAR New Investigator Awards in Alzheimer's Disease, the Massachusetts Alzheimer's Disease Research Center (P50 AG005134), and the Harvard Aging Brain Study (P01 AGO36694, R01 AG037497). The authors have also received research salary support from the Harvard Medical School Department of Psychiatry Dupont-Warren Fellowship and Livingston Award and the Harvard Medical School Scholars in Medicine Office.; The authors have received research salary support from Janssen Alzheimer Immunotherapy (GAM, REA), Wyeth/Pfizer Pharmaceuticals (GAM, REA), Eisai Inc. (GAM), Eli Lilly and Company (GAM), Avid Radiopharmaceuticals (KAJ), and Bristol-Myers-Squibb (GAM, RAS). NR 59 TC 3 Z9 3 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 2015 VL 46 IS 3 BP 727 EP 735 DI 10.3233/JAD-150017 PG 9 WC Neurosciences SC Neurosciences & Neurology GA CL4ZJ UT WOS:000356967200016 PM 25854929 ER PT J AU Dhimolea, E Groen, R Aedin, C Nicholas, M Kornelia, P Constantine, M AF Dhimolea, Eugen Groen, Richard Aedin, Culhane Nicholas, Mitsiades Kornelia, Polyak Constantine, Mitsiades TI Non-malignant cells from metastatic niches induce estrogen receptor-positive breast cancer cell resistance to therapy SO CANCER RESEARCH LA English DT Meeting Abstract CT AACR Special Conference on Cellular Heterogeneity in the Tumor Microenvironment CY FEB 26-MAR 01, 2014 CL San Diego, CA SP AACR C1 [Dhimolea, Eugen; Groen, Richard; Aedin, Culhane; Kornelia, Polyak; Constantine, Mitsiades] Dana Farber Canc Inst, Boston, MA 02115 USA. [Nicholas, Mitsiades] Baylor Coll Med, Houston, TX 77030 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD JAN 1 PY 2015 VL 75 IS 1 SU S MA B54 DI 10.1158/1538-7445.CHTME14-B54 PG 2 WC Oncology SC Oncology GA CL0JZ UT WOS:000356630300103 ER PT J AU Eisinger-Mathason, TSK Zhang, MS Qiong, Q Skuli, N Nakazawa, MS Karakasheva, T Mucaj, V Shay, JES Stangenberg, L Pure, E Yoon, SS Kirsch, DG Simon, MC AF Eisinger-Mathason, T. S. Karin Zhang, Minsi Qiong, Qiu Skuli, Nicolas Nakazawa, Michael S. Karakasheva, Tatiana Mucaj, Vera Shay, Jessica E. S. Stangenberg, Lars Pure, Ellen Yoon, Sam S. Kirsch, David G. Simon, M. Celeste TI Hypoxia-dependent modification of collagen networks promotes sarcoma metastasis SO CANCER RESEARCH LA English DT Meeting Abstract CT AACR Special Conference on Cellular Heterogeneity in the Tumor Microenvironment CY FEB 26-MAR 01, 2014 CL San Diego, CA SP AACR C1 [Eisinger-Mathason, T. S. Karin; Skuli, Nicolas; Nakazawa, Michael S.; Karakasheva, Tatiana; Mucaj, Vera; Shay, Jessica E. S.; Pure, Ellen; Simon, M. Celeste] Univ Penn, Philadelphia, PA 19104 USA. [Zhang, Minsi; Qiong, Qiu; Kirsch, David G.] Duke Univ, Durham, NC USA. [Stangenberg, Lars] Massachusets Gen Hosp, Boston, MA USA. [Yoon, Sam S.] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. NR 0 TC 0 Z9 0 U1 1 U2 2 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD JAN 1 PY 2015 VL 75 IS 1 SU S MA A41 DI 10.1158/1538-7445.CHTME14-A41 PG 1 WC Oncology SC Oncology GA CL0JZ UT WOS:000356630300029 ER PT J AU Guerriero, JL Letai, A AF Guerriero, Jennifer L. Letai, Anthony TI Modulation of tumor-associated macrophages towards an antitumor phenotype SO CANCER RESEARCH LA English DT Meeting Abstract CT AACR Special Conference on Cellular Heterogeneity in the Tumor Microenvironment CY FEB 26-MAR 01, 2014 CL San Diego, CA SP AACR C1 [Guerriero, Jennifer L.; Letai, Anthony] Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD JAN 1 PY 2015 VL 75 IS 1 SU S MA A17 DI 10.1158/1538-7445.CHTME14-A17 PG 1 WC Oncology SC Oncology GA CL0JZ UT WOS:000356630300014 ER PT J AU Kozono, D Li, J Nitta, M Sampetrean, O Ng, K Gonda, D Kushwaha, D Hiroko, M Harismendy, O Becher, O Kwon, CH Ligon, KL Saya, H Carter, BS Pizzo, D Vandenberg, S Chen, CC AF Kozono, David Li, Jie Nitta, Masayuki Sampetrean, Oltea Ng, Kimberly Gonda, David Kushwaha, Deepa Hiroko, Matsui Harismendy, Olivier Becher, Oren Kwon, Chang-Hyuk Ligon, Keith L. Saya, Hideyuki Carter, Bob S. Pizzo, Donald Vandenberg, Scott Chen, Clark C. TI Epigenetic regulation of MYC drives dynamic transition between tumor initiating states in glioblastoma SO CANCER RESEARCH LA English DT Meeting Abstract CT AACR Special Conference on Cellular Heterogeneity in the Tumor Microenvironment CY FEB 26-MAR 01, 2014 CL San Diego, CA SP AACR C1 [Kozono, David; Nitta, Masayuki; Ng, Kimberly; Kushwaha, Deepa; Ligon, Keith L.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Li, Jie; Gonda, David; Hiroko, Matsui; Harismendy, Olivier; Carter, Bob S.; Pizzo, Donald; Vandenberg, Scott; Chen, Clark C.] Univ Calif San Diego, La Jolla, CA 92093 USA. [Sampetrean, Oltea] Div Gene Regulat, Tokyo, Japan. [Becher, Oren] Duke Univ, Med Ctr, Durham, NC USA. [Kwon, Chang-Hyuk] Ohio State Univ, Columbus, OH 43210 USA. [Saya, Hideyuki] Keio Univ, Tokyo, Japan. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD JAN 1 PY 2015 VL 75 IS 1 SU S MA PR13 DI 10.1158/1538-7445.CHTME14-PR13 PG 2 WC Oncology SC Oncology GA CL0JZ UT WOS:000356630300149 ER PT J AU Laws, DA Kraft, AS Leddy, LR LaRue, AC AF Laws, Dayvia A. Kraft, Andrew S. Leddy, Lee R. LaRue, Amanda C. TI The role of circulating fibroblast precursors in promoting metastatic sarcoma SO CANCER RESEARCH LA English DT Meeting Abstract CT AACR Special Conference on Cellular Heterogeneity in the Tumor Microenvironment CY FEB 26-MAR 01, 2014 CL San Diego, CA SP AACR C1 [Laws, Dayvia A.; Kraft, Andrew S.; Leddy, Lee R.] Med Univ S Carolina, Charleston, SC 29425 USA. [LaRue, Amanda C.] Ralph H Johnson VAMC, Charleston, SC USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD JAN 1 PY 2015 VL 75 IS 1 SU S MA A46 DI 10.1158/1538-7445.CHTME14-A46 PG 1 WC Oncology SC Oncology GA CL0JZ UT WOS:000356630300031 ER PT J AU Mumenthaler, S Foo, J Choi, N Pao, W Agus, D Michor, F Mallick, P AF Mumenthaler, Shannon Foo, Jasmine Choi, Nathan Pao, William Agus, David Michor, Franziska Mallick, Parag TI Spatio-temporal heterogeneity in the tumor microenvironment influences the evolutionary dynamics of drug resistance SO CANCER RESEARCH LA English DT Meeting Abstract CT AACR Special Conference on Cellular Heterogeneity in the Tumor Microenvironment CY FEB 26-MAR 01, 2014 CL San Diego, CA SP AACR C1 [Mumenthaler, Shannon; Choi, Nathan; Agus, David] Univ So Calif, Los Angeles, CA USA. [Foo, Jasmine] Univ Minnesota, Minneapolis, MN USA. [Pao, William] Vanderbilt Ingram Canc Ctr, Nashville, TN USA. [Michor, Franziska] Dana Farber Canc Inst, Boston, MA 02115 USA. [Mallick, Parag] Stanford Univ, Palo Alto, CA 94304 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD JAN 1 PY 2015 VL 75 IS 1 SU S MA PR16 DI 10.1158/1538-7445.CHTME14-PR16 PG 1 WC Oncology SC Oncology GA CL0JZ UT WOS:000356630300152 ER PT J AU Pittet, M AF Pittet, Mikael TI Cancer-promoting immunity SO CANCER RESEARCH LA English DT Meeting Abstract CT AACR Special Conference on Cellular Heterogeneity in the Tumor Microenvironment CY FEB 26-MAR 01, 2014 CL San Diego, CA SP AACR C1 [Pittet, Mikael] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD JAN 1 PY 2015 VL 75 IS 1 SU S MA IA04 DI 10.1158/1538-7445.CHTME14-IA04 PG 1 WC Oncology SC Oncology GA CL0JZ UT WOS:000356630300127 ER PT J AU Roccaro, AM Sacco, A Moschetta, M Maiso, P Mishima, Y Aljawai, Y Facchetti, F Kruschinski, A Rossi, G Ghobrial, IM AF Roccaro, Aldo M. Sacco, Antonio Moschetta, Michele Maiso, Patricia Mishima, Yuji Aljawai, Yosra Facchetti, Fabio Kruschinski, Anna Rossi, Giuseppe Ghobrial, Irene M. TI In vivo targeting of stromal-derived factor-1 as a strategy to prevent myeloma cell dissemination to distant bone marrow niches SO CANCER RESEARCH LA English DT Meeting Abstract CT AACR Special Conference on Cellular Heterogeneity in the Tumor Microenvironment CY FEB 26-MAR 01, 2014 CL San Diego, CA SP AACR C1 [Roccaro, Aldo M.; Sacco, Antonio; Moschetta, Michele; Maiso, Patricia; Mishima, Yuji; Aljawai, Yosra; Ghobrial, Irene M.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Facchetti, Fabio; Rossi, Giuseppe] Spedali Civil Brescia, I-25125 Brescia, Italy. [Kruschinski, Anna] NOXXON Pharma, Berlin, Germany. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD JAN 1 PY 2015 VL 75 IS 1 SU S MA PR14 DI 10.1158/1538-7445.CHTME14-PR14 PG 2 WC Oncology SC Oncology GA CL0JZ UT WOS:000356630300150 ER PT J AU Roccaro, AM Sacco, A Maiso, P Moschetta, M Manier, S Mishima, Y Reagan, M Aljawai, Y Ghobrial, IM AF Roccaro, Aldo M. Sacco, Antonio Maiso, Patricia Moschetta, Michele Manier, Salomon Mishima, Yuji Reagan, Michaela Aljawai, Yosra Ghobrial, Irene M. TI Stroma-derived exosomes mediate progression in multiple meyloma SO CANCER RESEARCH LA English DT Meeting Abstract CT AACR Special Conference on Cellular Heterogeneity in the Tumor Microenvironment CY FEB 26-MAR 01, 2014 CL San Diego, CA SP AACR C1 [Roccaro, Aldo M.; Sacco, Antonio; Maiso, Patricia; Moschetta, Michele; Manier, Salomon; Mishima, Yuji; Reagan, Michaela; Aljawai, Yosra; Ghobrial, Irene M.] Dana Farber Canc Inst, Boston, MA 02115 USA. RI Reagan, Michaela/E-3549-2017 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD JAN 1 PY 2015 VL 75 IS 1 SU S MA B62 DI 10.1158/1538-7445.CHTME14-B62 PG 2 WC Oncology SC Oncology GA CL0JZ UT WOS:000356630300108 ER PT J AU Sevenich, L Bowman, R Mason, S Quail, D Rapaport, F Elie, B Brogi, E Brastianos, P Hahn, W Holsinger, L Massague, J Leslie, C Joyce, JA AF Sevenich, Lisa Bowman, Robert Mason, Steve Quail, Daniela Rapaport, Franck Elie, Benelita Brogi, Edi Brastianos, Priscilla Hahn, William Holsinger, Leslie Massague, Joan Leslie, Christina Joyce, Johanna A. TI A brain metastasis-promoting role for cathepsin S identified from analysis of tumor- and stroma-supplied proteolytic networks SO CANCER RESEARCH LA English DT Meeting Abstract CT AACR Special Conference on Cellular Heterogeneity in the Tumor Microenvironment CY FEB 26-MAR 01, 2014 CL San Diego, CA SP AACR C1 [Sevenich, Lisa; Bowman, Robert; Mason, Steve; Quail, Daniela; Rapaport, Franck; Elie, Benelita; Brogi, Edi; Massague, Joan; Leslie, Christina; Joyce, Johanna A.] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. [Brastianos, Priscilla; Hahn, William] Dana Farber Canc Inst, Boston, MA 02115 USA. [Holsinger, Leslie] Virobay Inc, Menlo Pk, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD JAN 1 PY 2015 VL 75 IS 1 SU S MA IA18 DI 10.1158/1538-7445.CHTME14-IA18 PG 1 WC Oncology SC Oncology GA CL0JZ UT WOS:000356630300136 ER PT J AU Sigmans, J Noort, W Lindsley, C Pan, L Aalders, L Bariteau, M Ebert, B Aster, J Steidl, U Schuringa, J Yuan, HP de Bruijn, J Raymakers, R Lokhorst, H Mutis, T Martens, A Mitsiades, C Groen, R AF Sigmans, Jessica Noort, Willy Lindsley, Coleman Pan, Li Aalders, Linda Bariteau, Megan Ebert, Benjamin Aster, Jon Steidl, Uli Schuringa, Jan Yuan, Huipin de Bruijn, Joost Raymakers, Reinier Lokhorst, Henk Mutis, Tuna Martens, Anton Mitsiades, Constantine Groen, Richard TI Biological insights into tumor-bone marrow microenvironment interactions derived from a humanized murine model SO CANCER RESEARCH LA English DT Meeting Abstract CT AACR Special Conference on Cellular Heterogeneity in the Tumor Microenvironment CY FEB 26-MAR 01, 2014 CL San Diego, CA SP AACR C1 [Sigmans, Jessica; Noort, Willy; Aalders, Linda; Raymakers, Reinier; Lokhorst, Henk; Mutis, Tuna; Martens, Anton; Groen, Richard] Univ Med Ctr Utrecht, Utrecht, Netherlands. [Lindsley, Coleman; Bariteau, Megan; Ebert, Benjamin; Mitsiades, Constantine] Dana Farber Canc Inst, Boston, MA 02115 USA. [Pan, Li; Aster, Jon] Brigham & Womens Hosp, Boston, MA 02115 USA. [Steidl, Uli] Albert Einstein Coll Med, New York, NY USA. [Schuringa, Jan] Univ Med Ctr Groningen, NL-9713 AV Groningen, Netherlands. [Yuan, Huipin; de Bruijn, Joost] Xpand Biotechnol BV, Bilthoven, Netherlands. NR 0 TC 1 Z9 1 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD JAN 1 PY 2015 VL 75 IS 1 SU S MA PR12 DI 10.1158/1538-7445.CHTME14-PR12 PG 1 WC Oncology SC Oncology GA CL0JZ UT WOS:000356630300148 ER PT J AU Xiong, Y Laws, DA LaRue, AC AF Xiong, Ying Laws, Dayvia A. LaRue, Amanda C. TI Hematopoietic stem cell-derived adipocytes promote tumor progression SO CANCER RESEARCH LA English DT Meeting Abstract CT AACR Special Conference on Cellular Heterogeneity in the Tumor Microenvironment CY FEB 26-MAR 01, 2014 CL San Diego, CA SP AACR C1 [Xiong, Ying; Laws, Dayvia A.] Med Univ S Carolina, Charleston, SC 29425 USA. [LaRue, Amanda C.] Ralph H Johnson VAMC, Charleston, SC USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD JAN 1 PY 2015 VL 75 IS 1 SU S MA A77 DI 10.1158/1538-7445.CHTME14-A77 PG 1 WC Oncology SC Oncology GA CL0JZ UT WOS:000356630300057 ER PT J AU Hatef, E Sena, DF Fallano, KA Crews, J Do, DV AF Hatef, Elham Sena, Dayse F. Fallano, Katherine A. Crews, Jonathan Do, Diana V. TI Pneumatic retinopexy versus scleral buckle for repairing simple rhegmatogenous retinal detachments SO COCHRANE DATABASE OF SYSTEMATIC REVIEWS LA English DT Review ID CLINICAL-TRIAL; MANAGEMENT; SURGERY AB Background Rhegmatogenous retinal detachment (RRD) is a full-thickness break in the sensory retina, caused by vitreous traction on the retina. While pneumatic retinopexy, scleral buckle, and vitrectomy are the accepted surgical interventions for eyes with RRD, their relative effectiveness has remained controversial. Objectives The objectives of this review were to assess the effectiveness and safety of pneumatic retinopexy versus scleral buckle or pneumatic retinopexy versus a combination treatment of scleral buckle and vitrectomy for people with RRD. The secondary objectives were to summarize any data on economic measures and quality of life. Search methods We searchedCENTRAL (which contains theCochrane Eyes andVisionGroupTrialsRegister) (2014, Issue 12), OvidMEDLINE, Ovid MEDLINE In-Process and Other Non-Indexed Citations, Ovid MEDLINE Daily, Ovid OLDMEDLINE (January 1946 to January 2015), EMBASE (January 1980 to January 2015), Latin American and Caribbean Health Sciences Literature Database (LILACS) (January 1982 to January 2015), the ISRCTN registry (www.isrctn.com/editAdvancedSearch), ClinicalTrials.gov (www.clinicaltrials.gov) and theWorld Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP) (www.who.int/ictrp/search/en). We did not use any date or language restrictions in the electronic searches for trials. We last searched the electronic databases on 13 January 2015. Selection criteria We included all randomized or quasi-randomized controlled trials comparing the effectiveness of pneumatic retinopexy versus scleral buckle (with or without vitrectomy) for eyes with RRD. Data collection and analysis After screening for eligibility, two review authors independently extracted study characteristics, methods, and outcomes. We followed systematic review standards as set forth by The Cochrane Collaboration. Main results We included two randomized controlled trials (218 eyes of 216 participants) comparing the effectiveness of pneumatic retinopexy versus scleral buckle for eyes with RRD. We identified no studies investigating the comparison of pneumatic retinopexy versus a combination treatment of scleral buckle and vitrectomy. Of the two included studies, one was a small study with 20 participants enrolled in Ireland and followed for an average of 16 months. The second study was larger with 196 participants (198 eyes) enrolled in the United States and followed for at least 6 months. Cautious interpretation of the results is warranted, since we graded the evidence as low to moderate quality due to insufficient reporting of study methods and imprecision and inconsistency among study results. Both studies showed fewer eyes achieving retinal reattachment in the pneumatic retinopexy group compared with the scleral buckle group by six-months follow-up (risk ratio (RR) 0.89, 95% confidence interval (CI) 0.77 to 1.02, 218 eyes); however, we are uncertain as to whether the intervention has an important effect on reattachment because the results are imprecise. Eyes in the pneumatic retinopexy group also were more likely to have had a recurrence of retinal detachment by six-months follow-up (RR 1.80, 95% CI 1.00 to 3.24, 218 eyes); however, we are uncertain as to whether the intervention has an important effect on recurrence because the lower CI equals no difference. Neither study reported mean change in visual acuity, quality of life data, or economic measures. Differences between the pneumatic retinopexy group and scleral buckle group were uncertain due to small numbers of events with respect to operative ocular adverse events (RR 0.67, 95% CI 0.32 to 1.42, 218 eyes), development of cataract (RR 0.92, 95% CI 0.06 to 14.54, 198 eyes), glaucoma (RR 0.31, 95% CI 0.03 to 2.91, 198 eyes), macular pucker (RR 0.74, 95% CI 0.20 to 2.67, 198 eyes), and proliferative vitreoretinopathy (RR 0.94, 95% CI 0.30 to 2.96, 218 eyes). Fewer eyes in the pneumatic retinopexy group compared with the scleral buckle group experienced choroidal detachment (RR 0.17, 95% CI 0.05 to 0.57, 198 eyes) or myopic shift equal to or greater than 1 diopter spherical equivalent (RR 0.04, 95% CI 0.01 to 0.13, 198 eyes). Authors' conclusions The evidence suggests that pneumatic retinopexy may result in lower rates of reattachment and higher rates of recurrence than scleral buckle for eyes with RRD, but does not rule out no difference between procedures. The relative safety of the procedures is uncertain and the relative effects of these procedures in terms of other patient-important outcomes, such as visual acuity and quality of life, is unknown. Due to the limited information available between pneumatic retinopexy and scleral buckle procedures, future research addressing these evidence gaps are warranted. C1 [Hatef, Elham] Johns Hopkins Univ, Sch Med, Wilmer Eye Inst, Baltimore, MD 21287 USA. [Sena, Dayse F.] Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. [Fallano, Katherine A.] Univ Rochester, Sch Med, Flaum Eye Inst, Rochester, NY USA. [Crews, Jonathan; Do, Diana V.] Univ Nebraska Med Ctr, Stanley M Truhlsen Eye Inst, Omaha, NE USA. RP Hatef, E (reprint author), Johns Hopkins Univ, Sch Med, Wilmer Eye Inst, 600 North Wolfe St,Wilmer B-43, Baltimore, MD 21287 USA. EM ehatef@jhsph.edu FU National Eye Institute, National Institutes of Health, USA; National Institute for Health Research (NIHR), UK; Department of Health through National Institute for Health Research; NIHR; [1 U01 EY020522] FX National Eye Institute, National Institutes of Health, USA.; Methodological support provided by the Cochrane Eyes and Vision Group, US Project funded by grant 1 U01 EY020522; National Institute for Health Research (NIHR), UK.; Richard Wormald, Co-ordinating Editor for the Cochrane Eyes and Vision Group (CEVG) acknowledges financial support for his CEVG research sessions from the Department of Health through the award made by the National Institute for Health Research to Moorfields Eye Hospital NHS Foundation Trust and UCL Institute of Ophthalmology for a Specialist Biomedical Research Centre for Ophthalmology.; The NIHR also funds the CEVG Editorial Base in London. NR 32 TC 0 Z9 0 U1 0 U2 2 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 2015 IS 5 AR CD008350 DI 10.1002/14651858.CD008350.pub2 PG 33 WC Medicine, General & Internal SC General & Internal Medicine GA CK1UR UT WOS:000355993600029 PM 25950286 ER PT J AU Kang, A Nigwekar, SU Perkovic, V Kulshrestha, S Zoungas, S Navaneethan, SD Cass, A Gallagher, MP Ninomiya, T Strippoli, GFM Jardine, MJ AF Kang, Amy Nigwekar, Sagar U. Perkovic, Vlado Kulshrestha, Satyarth Zoungas, Sophia Navaneethan, Sankar D. Cass, Alan Gallagher, Martin P. Ninomiya, Toshiharu Strippoli, Giovanni F. M. Jardine, Meg J. TI Interventions for lowering plasma homocysteine levels in kidney transplant recipients SO COCHRANE DATABASE OF SYSTEMATIC REVIEWS LA English DT Review ID VASCULAR OUTCOME REDUCTION; FOLIC-ACID SUPPLEMENTATION; INTIMA-MEDIA THICKNESS; STAGE RENAL-DISEASE; RANDOMIZED CONTROLLED-TRIAL; PLACEBO-CONTROLLED TRIAL; CARDIOVASCULAR-DISEASE; B-VITAMINS; FAVORIT TRIAL; MYOCARDIAL-INFARCTION AB Background Elevated homocysteine levels have been shown to be an independent risk factor for cardiovascular disease. However studies of homocysteine lowering in general and end-stage kidney disease (ESKD) populations have not demonstrated a reduction in cardiovascular event rates. Kidney transplant recipients have high homocysteine levels, high cardiovascular event rates and, unlike the ESKD population, may achieve normalisation of homocysteine levels with homocysteine lowering therapies. Thus may benefit from homocysteine lowering therapy. Objectives To evaluate the effects of established homocysteine lowering therapy on cardiovascular mortality in patients with functioning kidney transplants. Search methods We searched the Cochrane Renal Group's Specialised Register to 16 March 2015 through contact with the Trials' Search Co-ordinator using search terms relevant to this review. Selection criteria Randomised controlled trials of any therapy that has been shown to significantly lower homocysteine levels conducted in people with functioning kidney transplants. Studies were to be included if they compared homocysteine lowering therapy with placebo or usual care, or compare higher versus lower doses of homocysteine lowering therapy. Data collection and analysis Two authors independently assessed study quality and extracted data. Results were to be expressed as the risk ratio (RR) for dichotomous outcomes or mean difference (MD) for continuous outcomes with 95% confidence intervals (CI). Data was to be pooled using the random effects model. Main results The literature search yielded 359 reports of which only one study was identified that met our inclusion criteria and reported relevant clinical endpoints. This study randomised 4110 adult participants with a functioning kidney transplant and elevated homocysteine levels to folic acid plus high dose B multivitamins or low dose multivitamins who were followed for amean 4.0 years. Despite effectively lowering homocysteine levels) in homocysteine levels at follow-up (MD -4.40 mu mol/L, 95% CI -5.98 to -2.82) there was no evidence the intervention impacted on any of the outcomes reported including cardiovascular mortality (RR 0.91, 95% CI 0.69 to 1.20), allcause mortality (RR 1.04, 95% CI 0.88 to 1.22), myocardial infarction (RR 1.02, 95% CI 0.77 to 1.35), stroke (RR 1.08, 95% CI 0.69 to 1.71), commencement of renal replacement therapy (RR 1.12, 95% CI 0.91 to 1.37) or all reported adverse events (RR 1.02, 95% CI 0.87 to 1.20). There was no evidence the intervention impacted on the primary endpoint of the study, a cardiovascular event composite (RR 0.99, 95% CI 0.85 to 1.15). The study was of high quality. Authors' conclusions There is no current evidence to support the use of homocysteine lowering therapy for cardiovascular disease prevention in kidney transplant recipients. C1 [Kang, Amy] Univ Sydney, Sydney Med Sch, Camperdown, NSW, Australia. [Nigwekar, Sagar U.] Harvard Univ, Brigham & Womens Hosp, Massachusetts Gen Hosp, Scholars Clin Sci Program,Med Sch, Boston, MA 02115 USA. [Perkovic, Vlado] George Inst Global Hlth, Camperdown, NSW, Australia. [Kulshrestha, Satyarth] Univ Iowa, Carver Coll Med, Nephrol, Iowa City, IA USA. [Zoungas, Sophia] Monash Univ, Sch Publ Hlth & Prevent Med, Monash Ctr Hlth Res & Implementat, Diabet & Vasc Res Program, Clayton, Vic, Australia. [Navaneethan, Sankar D.] Cleveland Clin, Glickman Urol & Kidney Inst, Dept Nephrol & Hypertens, Cleveland, OH 44106 USA. [Cass, Alan] Menzies Sch Hlth Res, Casuarina, Australia. [Gallagher, Martin P.; Ninomiya, Toshiharu] George Inst Global Hlth, Renal & Metab Div, Camperdown, NSW, Australia. [Strippoli, Giovanni F. M.] Childrens Hosp Westmead, Ctr Kidney Res, Cochrane Renal Grp, Westmead, NSW, Australia. [Strippoli, Giovanni F. M.] Univ Bari, Dept Emergency & Organ Transplantat, Bari, Italy. [Strippoli, Giovanni F. M.] Diaverum Med Sci Off, Lund, Sweden. [Strippoli, Giovanni F. M.] Diaverum Acad, Bari, Italy. [Jardine, Meg J.] Univ Sydney, George Inst Global Hlth, Camperdown, NSW 2050, Australia. [Jardine, Meg J.] Concord Repatriat Gen Hosp, Dept Renal Med, Concord, Australia. RP Jardine, MJ (reprint author), Univ Sydney, George Inst Global Hlth, POB M201,Missenden Rd, Camperdown, NSW 2050, Australia. EM mjardine@georgeinstitute.org.au FU George Institute for Global Health, Australia FX Internal sources; The George Institute for Global Health, Australia. NR 82 TC 0 Z9 0 U1 1 U2 2 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 2015 IS 5 AR UNSP CD007910 DI 10.1002/14651858.CD007910.pub2 PG 29 WC Medicine, General & Internal SC General & Internal Medicine GA CK1UR UT WOS:000355993600026 PM 25938479 ER PT J AU Maxwell, LJ Zochling, J Boonen, A Singh, JA Veras, MMS Ghogomu, ET Jandu, MB Tugwell, P Wells, GA AF Maxwell, Lara J. Zochling, Jane Boonen, Annelies Singh, Jasvinder A. Veras, Mirella M. S. Ghogomu, Elizabeth Tanjong Jandu, Maria Benkhalti Tugwell, Peter Wells, George A. TI TNF-alpha inhibitors for ankylosing spondylitis SO COCHRANE DATABASE OF SYSTEMATIC REVIEWS LA English DT Review ID PLACEBO-CONTROLLED TRIAL; NECROSIS-FACTOR-ALPHA; LOW-DOSE INFLIXIMAB; SOCIETY CLASSIFICATION CRITERIA; REDUCES SPINAL INFLAMMATION; PATIENT-REPORTED OUTCOMES; SHORT-TERM IMPROVEMENT; ETANERCEPT 50 MG; PHASE-III TRIAL; DOUBLE-BLIND AB Background TNF (tumor necrosis factor)-alpha inhibitors block a key protein in the inflammatory chain reaction responsible for joint inflammation, pain, and damage in ankylosing spondylitis. Objectives To assess the benefit and harms of adalimumab, etanercept, golimumab, and infliximab (TNF-alpha inhibitors) in peoplewith ankylosing spondylitis. Search methods We searched the following databases to January 26, 2009: MEDLINE (from 1966); EMBASE (from 1980); the Cochrane Central Register of Controlled Trials (CENTRAL; 2008, Issue 4); ACP Journal Club; CINAHL (from1982); and ISIWeb of Knowledge (from 1900). We ran updated searches in May 2012, October 2013, and in June 2014 for McMaster PLUS. We searched major regulatory agencies for safety warnings and clinicaltrials. gov for registered trials. Selection criteria Randomized controlled trials (RCTs) comparing adalimumab, etanercept, golimumab and infliximab to placebo, other drugs or usual care in patients with ankylosing spondylitis, reported in abstract or full-text. Data collection and analysis Two authors independently assessed search results, risk of bias, and extracted data. We conducted Bayesian mixed treatment comparison (MTC) meta-analyses using WinBUGS software. To investigate a class-effect of harms across biologics, we pooled harms data using Review Manager 5. Main results We included twenty-one, short-term(24 weeks or less) RCTs with a total of 3308 participants; 18 contributed data to the MTC analysis: adalimumab (4 studies), etanercept (8 studies), golimumab (2 studies), infliximab (3 studies), and one head-to-head study (etanercept versus infliximab) which was unblinded and considered at a higher risk of bias. The risk of selection and detection bias was low or unclear for most of the studies. The risk of selective outcome reporting was low for most studies as they reported on outcomes recommended by the Assessment of SpondyloArthritis international Society. We found little heterogeneity and no significant inconsistency in the MTC analyses. The majority of the studies were funded by pharmaceutical companies. Most studies permitted concomitant therapy of stable doses of disease-modifying anti-rheumatic drugs, non-steroidal anti-inflammatory drugs, or corticosteroids, but allowances varied across studies. Compared with placebo, there was high quality evidence that patients on an anti-TNF agent were three to four times more likely to achieve an ASAS40 response (assessing spinal pain, function, and inflammation, as measured by the mean of intensity and duration of morning stiffness, and patient global assessment) by six months (adalimumab: risk ratio (RR) 3.53, 95% credible interval (Crl) 2.49 to 4.91; etanercept: RR 3.31, 95% Crl 2.38 to 4.53; golimumab: RR 2.90, 95% Crl 1.90 to 4.23; infliximab: RR 4.07, 95% Crl 2.80 to 5.74, with a 25% to 40% absolute difference between treatment and placebo groups. The number needed to treat (NNT) to achieve an ASAS 40 response ranged from 3 to 5. There was high quality evidence of improvement in physical function on a 0 to 10 scale (adalimumab: mean difference (MD) -1.6, 95% Crl -2.2 to -0.9; etanercept: MD -1.1, 95% CrI -1.6 to -0.6; golimumab: MD -1.5, 95% Crl -2.3 to -0.7; infliximab: MD 2.1, 95% Crl -2.7 to -1.4, with an 11% to 21% absolute difference between treatment and placebo groups. The NNT to achieve the minimally clinically important difference of 0.7 points ranged from 2 to 4. Compared with placebo, there was moderate quality evidence (downgraded for imprecision) that patients on an anti-TNF agent were more likely to achieve an ASAS partial remission by six months (adalimumab: RR 6.28, 95% Crl 3.13 to 12.78; etanercept: RR 4.24, 95% Crl 2.31 to 8.09; golimumab: RR 5.18, 95% Crl 1.90 to 14.79; infliximab: RR 15.41, 95% Crl 5.09 to 47.98 with a 10% to 44% absolute difference between treatment and placebo groups. The NNT to achieve an ASAS partial remission response ranged from 3 to 11. There was low to moderate level evidence of a greater reduction in spinal inflammation as measured by magnetic resonance imaging though the absolute differences were small and the clinical relevance of the difference was unclear: adalimumab (1 trial; -6% (95% confidence interval (CI) -12% to 0.05%); 1 trial: 53.6% mean decrease from baseline versus 9.4% mean increase in the placebo group), golimumab (1 trial; -2.5%, (95% CI -5.6% to -0.7%)), and infliximab (1 trial; -3% (95% CI -4% to -2.4%)). Radiographic progression was measured in one trial (N = 60) of etanercept versus placebo and it found that radiologic changes were similar in both groups (detailed data not provided). There were few events of withdrawals due to adverse events leading to imprecision around the estimates. When all the anti-TNF agents were combined against placebo, there was moderate quality evidence from 16 studies of an increased risk of withdrawals due to adverse events in the anti-TNF group (Peto odds ratio (OR) 2.44, 95% CI 1.26 to 4.72; total events: 38/1637 in biologic group; 7/986 in placebo) though the absolute increase in harm was small (1%; 95% CI 0% to 2%). Due to low event rates, evidence of the effect of individual TNF-inhibitors against placebo or for all four biologics pooled together versus placebo on serious adverse events is inconclusive (moderate quality; downgraded for imprecision). For all anti-TNF pooled versus placebo based on 16 studies: Peto OR 1.45, 95% CI 0.85 to 2.48; 51/1530 in biologic group; 18/878 in placebo; absolute difference: 1% (95% CI 0% to 2%). Using indirect comparison methodology, and one head-to-head study of etanercept versus infliximab, wide confidence intervals meant that results were inconclusive for evidence of differences in themajor outcomes between different anti-TNF agents. Regulatory agencies have published warnings about rare adverse events of serious infections, including tuberculosis, malignancies and lymphoma. Authors' conclusions There is moderate to high quality evidence that anti-TNF agents improve clinical symptoms in the treatment of ankylosing spondylitis. More participants withdrew due to adverse events when on an anti-TNF agent but we did not find evidence of an increase in serious adverse events, though event rates were low and trials had a short duration. The short-term toxicity profile appears acceptable. Based on indirect comparison methodology, we are uncertain whether there are differences between anti-TNF agents in terms of the key benefit or harm outcomes. C1 [Maxwell, Lara J.] Ottawa Hosp Res Inst, Ctr Practice Changing Res, Ottawa, ON K1H 8L6, Canada. [Zochling, Jane] Menzies Res Inst, Hobart, Tas, Australia. [Boonen, Annelies] Caphri Res Inst, Dept Rheumatol, NL-6202 AZ Maastricht, Netherlands. [Singh, Jasvinder A.] Birmingham VA Med Ctr, Dept Med, Birmingham, AL USA. [Veras, Mirella M. S.] Univ Montreal, Ecole Readaptac, Montreal, PQ, Canada. [Ghogomu, Elizabeth Tanjong] Univ Ottawa, Bruyere Res Inst, Ottawa, ON, Canada. [Jandu, Maria Benkhalti] Univ Ottawa, Inst Populat Hlth, Ctr Global Hlth, Ottawa, ON, Canada. [Tugwell, Peter] Univ Ottawa, Dept Med, Fac Med, Ottawa, ON, Canada. [Wells, George A.] Univ Ottawa, Dept Epidemiol & Community Med, Ottawa, ON, Canada. RP Maxwell, LJ (reprint author), Ottawa Hosp Res Inst, Ctr Practice Changing Res, Ottawa Hosp Gen Campus,501 Smyth Rd,Box 711, Ottawa, ON K1H 8L6, Canada. EM lmaxwell@uottawa.ca OI Tugwell, Peter/0000-0001-5062-0556 FU Institute of Population Health, University of Ottawa, Canada; Rheumazentrum Ruhrgebiet, Germany; NIHR Cochrane Incentive Award, UK FX Internal sources; Institute of Population Health, University of Ottawa, Canada.; Rheumazentrum Ruhrgebiet, Germany.; External sources; NIHR Cochrane Incentive Award 2013, UK.; Award to assist with completion of the review. NR 109 TC 11 Z9 12 U1 0 U2 5 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 2015 IS 4 AR CD005468 DI 10.1002/14651858.CD005468.pub2 PG 144 WC Medicine, General & Internal SC General & Internal Medicine GA CK1UQ UT WOS:000355993500018 PM 25887212 ER PT J AU Guex, AA Vachicouras, N Hight, AE Brown, MC Lee, DJ Lacour, SP AF Guex, Amelie A. Vachicouras, Nicolas Hight, Ariel Edward Brown, M. Christian Lee, Daniel J. Lacour, Stephanie P. TI Conducting polymer electrodes for auditory brainstem implants SO JOURNAL OF MATERIALS CHEMISTRY B LA English DT Article ID POLY(3,4-ETHYLENEDIOXYTHIOPHENE) PEDOT; ELECTRICAL-STIMULATION; MICROELECTRODE ARRAYS; NEURAL STIMULATION; RECORDINGS; CHARGE; RAT AB The auditory brainstem implant (ABI) restores hearing in patients with damaged auditory nerves. One of the main ideas to improve the efficacy of ABIs is to increase spatial specificity of stimulation, in order to minimize extra-auditory side-effects and to maximize the tonotopy of stimulation. This study reports on the development of a microfabricated conformable electrode array with small (100 mm diameter) electrode sites. The latter are coated with a conducting polymer, PEDOT: PSS, to offer high charge injection properties and to safely stimulate the auditory system with small stimulation sites. We report on the design and fabrication of the polymer implant, and characterize the coatings in physiological conditions in vitro and under mechanical deformation. We characterize the coating electrochemically and during bending tests. We present a proof of principle experiment where the auditory system is efficiently activated by the flexible polymeric interface in a rat model in vivo. These results demonstrate the potential of using conducting polymer coatings on small electrode sites for electrochemically safe and efficient stimulation of the central auditory system. C1 [Guex, Amelie A.; Vachicouras, Nicolas; Lacour, Stephanie P.] Ecole Polytech Fed Lausanne, Ctr Neuroprosthet, Lausanne, Switzerland. [Hight, Ariel Edward; Brown, M. Christian; Lee, Daniel J.] Harvard Univ, Sch Med, Eaton Peabody Labs, Boston, MA 02115 USA. [Hight, Ariel Edward; Brown, M. Christian; Lee, Daniel J.] Harvard Univ, Sch Med, Dept Otolaryngol Head & Neck Surg, Massachusetts Eye & Ear Infirm,Dept Otol & Laryng, Boston, MA 02115 USA. RP Lacour, SP (reprint author), Ecole Polytech Fed Lausanne, Ctr Neuroprosthet, Lausanne, Switzerland. EM stephanie.lacour@epfl.ch RI Lacour, Stephanie/E-6375-2010 FU Fondation Bertarelli; National Institute of Health [DC01089] FX This work was supported by the Fondation Bertarelli and the National Institute of Health (grant DC01089). NR 23 TC 1 Z9 1 U1 5 U2 19 PU ROYAL SOC CHEMISTRY PI CAMBRIDGE PA THOMAS GRAHAM HOUSE, SCIENCE PARK, MILTON RD, CAMBRIDGE CB4 0WF, CAMBS, ENGLAND SN 2050-750X EI 2050-7518 J9 J MATER CHEM B JI J. Mat. Chem. B PY 2015 VL 3 IS 25 BP 5021 EP 5027 DI 10.1039/c5tb00099h PG 7 WC Materials Science, Biomaterials SC Materials Science GA CK6YS UT WOS:000356375800012 PM 26207184 ER PT J AU Williams, DA Kogan, JR Hauer, KE Yamashita, T Aagaard, EM AF Williams, David A. Kogan, Jennifer R. Hauer, Karen E. Yamashita, Traci Aagaard, Eva M. TI The impact of exposure to shift-based schedules on medical students SO MEDICAL EDUCATION ONLINE LA English DT Article DE duty-hour reform; shift-based schedules; medical students; internal medicine clerkship; team fragmentation ID SURGICAL RESIDENTS; ROLE-MODELS; DUTY HOURS; CONTINUITY; EXPERIENCE; CLERKSHIP; TEACHERS; DESCRIBE; REFORM; CARE AB Background: With new resident duty-hour regulations, resident work schedules have progressively transitioned towards shift-based systems, sometimes resulting in increased team fragmentation. We hypothesized that exposure to shift-based schedules and subsequent team fragmentation would negatively affect medical student experiences during their third-year internal medicine clerkship. Design: As part of a larger national study on duty-hour reform, 67 of 150 eligible third-year medical students completed surveys about career choice, teaching and supervision, assessment, patient care, well-being, and attractiveness of a career in internal medicine after completing their internal medicine clerkship. Students who rotated to hospitals with shift-based systems were compared to those who did not. Non-demographic variables used a five-point Likert scale. Chi-squared and Fisher's exact tests were used to assess the relationships between exposure to shift-based schedules and student responses. Questions with univariate p50.1 were included in multivariable logistic regression models. Results: Thirty-six students (54%) were exposed to shift-based schedules. Students exposed to shift-based schedules were less likely to perceive that their attendings were committed to teaching (odds ratio [OR] 0.35, 95% confidence interval [CI]: 0.13-0.90, p = 0.01) or perceive that residents had sufficient exposure to assess their performance (OR 0.29, 95% CI: 0.09-0.91, p = 0.03). However, those students were more likely to feel their interns were able to observe them at the bedside (OR 1.89, 95% CI: 1.08-3.13, p = 0.02) and had sufficient exposure to assess their performance (OR 3.00, 95% CI: 1.01-8.86, p = 0.05). Conclusions: These findings suggest that shift-based schedules designed in response to duty-hour reform may have important broader implications for the teaching environment. C1 [Williams, David A.] Univ Colorado, Sch Med, Dept Internal Med, Denver Vet Affairs Med Ctr, Aurora, CO USA. [Kogan, Jennifer R.] Univ Penn, Dept Med, Perleman Sch Med, Philadelphia, PA 19104 USA. [Hauer, Karen E.] Univ Calif San Francisco, Sch Med, Dept Med, San Francisco, CA USA. [Yamashita, Traci; Aagaard, Eva M.] Univ Colorado, Sch Med, Dept Med, Aurora, CO USA. RP Williams, DA (reprint author), Denver Vet Affairs Med Ctr, 1055 Clermont St, Denver, CO 80220 USA. EM david.williams18@va.gov NR 27 TC 0 Z9 0 U1 0 U2 2 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 2015 VL 20 AR 27434 DI 10.3402/meo.v20.27434 PG 6 WC Education & Educational Research SC Education & Educational Research GA CK9ZG UT WOS:000356597500001 PM 26095587 ER PT B AU Fenves, AZ Shchelochkov, OA AF Fenves, Andrew Z. Shchelochkov, Oleg A. BE Rothkopf, MM Nusbaum, MJ Haverstick, LP TI Hyperammonemic Encephalopathy after Roux-en-Y Gastric Bypass Surgery SO METABOLIC MEDICINE AND SURGERY LA English DT Article; Book Chapter ID BARIATRIC-SURGERY C1 [Fenves, Andrew Z.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA 02114 USA. [Shchelochkov, Oleg A.] Univ Iowa Hosp & Clin, Dept Pediat, Div Genet, Iowa City, IA 52242 USA. RP Fenves, AZ (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA 02114 USA. NR 12 TC 0 Z9 0 U1 0 U2 0 PU CRC PRESS-TAYLOR & FRANCIS GROUP PI BOCA RATON PA 6000 BROKEN SOUND PARKWAY NW, STE 300, BOCA RATON, FL 33487-2742 USA BN 978-1-4665-6712-2; 978-1-4665-6711-5 PY 2015 BP 373 EP 381 PG 9 WC Endocrinology & Metabolism; Nutrition & Dietetics; Surgery SC Endocrinology & Metabolism; Nutrition & Dietetics; Surgery GA BC6XI UT WOS:000354561800023 ER PT B AU Kudsk, KA Pierre, JF AF Kudsk, Kenneth A. Pierre, Joseph F. BE Rothkopf, MM Nusbaum, MJ Haverstick, LP TI Nutrition and Immunity of the Gut SO METABOLIC MEDICINE AND SURGERY LA English DT Article; Book Chapter ID RESPIRATORY-TRACT IMMUNITY; MAJOR ABDOMINAL-TRAUMA; LYMPHOID-TISSUE; PARENTERAL-NUTRITION; MUCOSAL IMMUNITY; ENTERAL NUTRITION; BACTERIAL PNEUMONIA; SEPTIC MORBIDITY; INNATE IMMUNITY; SMALL-INTESTINE C1 [Kudsk, Kenneth A.] Univ Wisconsin, Sch Med & Publ Hlth, Madison, WI 53706 USA. [Kudsk, Kenneth A.] William S Middleton Mem Vet Adm Med Ctr, Vet Adm Surg Serv, Madison, WI USA. [Pierre, Joseph F.] Univ Chicago, Dept Med, Sect Gastroenterol Hepatol & Nutr, Chicago, IL 60637 USA. RP Kudsk, KA (reprint author), Univ Wisconsin, Sch Med & Publ Hlth, Madison, WI 53706 USA. NR 55 TC 0 Z9 0 U1 0 U2 1 PU CRC PRESS-TAYLOR & FRANCIS GROUP PI BOCA RATON PA 6000 BROKEN SOUND PARKWAY NW, STE 300, BOCA RATON, FL 33487-2742 USA BN 978-1-4665-6712-2; 978-1-4665-6711-5 PY 2015 BP 457 EP 468 PG 12 WC Endocrinology & Metabolism; Nutrition & Dietetics; Surgery SC Endocrinology & Metabolism; Nutrition & Dietetics; Surgery GA BC6XI UT WOS:000354561800027 ER PT J AU Xu, AJ Niciu, MJ Lundin, NB Luckenbaugh, DA Ionescu, DF Richards, EM Voort, JLV Ballard, ED Brutsche, NE Machado-Vieira, R Zarate, CA AF Xu, Annie J. Niciu, Mark J. Lundin, Nancy B. Luckenbaugh, David A. Ionescu, Dawn F. Richards, Erica M. Voort, Jennifer L. Vande Ballard, Elizabeth D. Brutsche, Nancy E. Machado-Vieira, Rodrigo Zarate, Carlos A., Jr. TI Lithium and Valproate Levels Do Not Correlate with Ketamine's Antidepressant Efficacy in Treatment-Resistant Bipolar Depression SO NEURAL PLASTICITY LA English DT Article ID GLYCOGEN-SYNTHASE KINASE-3; ADD-ON TRIAL; MAJOR DEPRESSION; NEUROTROPHIC FACTOR; MOOD STABILIZERS; DISORDER; INHIBITION; ALPHA; CARBAMAZEPINE; ANTAGONISTS AB Ketamine and lithium both inhibit glycogen synthase kinase 3. In addition, lithium and ketamine have synergistic antidepressant-like effects at individually subeffective doses in rodents. We hypothesized that ketamine's antidepressant effects would be improved by therapeutic doses of lithium versus valproate and that serum lithium levels would positively correlate with ketamine's antidepressant efficacy. Thirty-six patients with treatment-resistant bipolar depression maintained on therapeutic-dose lithium (n = 23, 0.79 +/- 0.15 mEq/L) or valproate (n = 13, 79.6 +/- 12.4 mg/mL) received 0.5 mg/kg ketamine infusion in a randomized, double-blind, placebo-controlled, crossover trial. The primary depression outcome measure-the Montgomery-Asberg Depression Rating Scale (MADRS)-was assessed before infusion and at numerous postinfusion time points. Both lithium (F-1,F-118 = 152.08, p < 0.001, and d = 2.27) and valproate (F-1,F-128 = 20.12, p < 0.001, and d = 0.79) significantly improved depressive symptoms, but no statistically significant difference was observed between mood stabilizer groups (F-1,F-28 = 2.51, p = 0.12, and d = 0.60). Serum lithium and valproate levels did not correlate with ketamine's antidepressant efficacy. Although the study was potentially underpowered, our results suggest that lithiummay not potentiate ketamine's antidepressant efficacy in treatment-resistant bipolar depression. C1 [Xu, Annie J.] New York Med Coll, Valhalla, NY 10595 USA. [Niciu, Mark J.; Lundin, Nancy B.; Luckenbaugh, David A.; Richards, Erica M.; Ballard, Elizabeth D.; Brutsche, Nancy E.; Machado-Vieira, Rodrigo; Zarate, Carlos A., Jr.] NIMH, NIH, Expt Therapeut & Pathophysiol Branch, Bethesda, MD 20892 USA. [Ionescu, Dawn F.] Massachusetts Gen Hosp, Depress Clin & Res Program, Boston, MA 02114 USA. [Voort, Jennifer L. Vande] Mayo Clin, Dept Psychiat, Rochester, MN 55905 USA. [Voort, Jennifer L. Vande] Mayo Clin, Psychol Serv, Rochester, MN 55905 USA. RP Zarate, CA (reprint author), NIMH, NIH, Expt Therapeut & Pathophysiol Branch, 10 Ctr Dr,Bldg 10-CRC, Bethesda, MD 20892 USA. EM zaratec@mail.nih.gov RI Ionescu, Dawn/K-5675-2015; OI MACHADO-VIEIRA, RODRIGO/0000-0002-4830-1190 FU Intramural Research Program of the National Institute of Mental Health, National Institutes of Health (IRP-NIMH-NIH; Bethesda, MD, USA); 7SE Inpatient Mood and Anxiety Disorders Research Unit of the IRP-NIMH-NIH FX The authors gratefully acknowledge the support of the Intramural Research Program of the National Institute of Mental Health, National Institutes of Health (IRP-NIMH-NIH; Bethesda, MD, USA), and thank the 7SE Inpatient Mood and Anxiety Disorders Research Unit of the IRP-NIMH-NIH for their support. Ioline Henter (NIMH) provided excellent editorial assistance. NR 40 TC 2 Z9 2 U1 1 U2 2 PU HINDAWI PUBLISHING CORPORATION PI NEW YORK PA 410 PARK AVENUE, 15TH FLOOR, #287 PMB, NEW YORK, NY 10022 USA SN 2090-5904 EI 1687-5443 J9 NEURAL PLAST JI Neural. Plast. PY 2015 AR 858251 DI 10.1155/2015/858251 PG 7 WC Neurosciences SC Neurosciences & Neurology GA CL1PD UT WOS:000356715100001 ER PT J AU George, S AF George, Suzanne TI Fifteen Years of Kinase Inhibition in Gastrointestinal Stromal Tumor: Clinical Implications of Tumor Genotyping SO ONCOLOGIST LA English DT Meeting Abstract C1 [George, Suzanne] Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU ALPHAMED PRESS PI DURHAM PA 318 BLACKWELL ST, STE 260, DURHAM, NC 27701-2884 USA SN 1083-7159 EI 1549-490X J9 ONCOLOGIST JI Oncologist PY 2015 VL 20 SU 1 MA 8 BP S4 EP S4 PG 1 WC Oncology SC Oncology GA CL1BR UT WOS:000356677900009 ER PT J AU Johnson, BE AF Johnson, Bruce E. TI Implications of Genomic Diversity in Lung Cancers SO ONCOLOGIST LA English DT Meeting Abstract C1 [Johnson, Bruce E.] Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ALPHAMED PRESS PI DURHAM PA 318 BLACKWELL ST, STE 260, DURHAM, NC 27701-2884 USA SN 1083-7159 EI 1549-490X J9 ONCOLOGIST JI Oncologist PY 2015 VL 20 SU 1 MA 9 BP S5 EP S5 PG 1 WC Oncology SC Oncology GA CL1BR UT WOS:000356677900010 ER PT J AU Stahlman, S Javanbakht, M Cochran, S Shoptaw, S Hamilton, AB Gorbach, PM AF Stahlman, Shauna Javanbakht, Marjan Cochran, Susan Shoptaw, Steven Hamilton, Alison B. Gorbach, Pamina M. TI A comparison of self-reported sexual risk behaviours between US civilian and active duty military women SO SEXUAL HEALTH LA English DT Article ID TRANSMITTED INFECTIONS; UNITED-STATES; SUBSTANCE USE; RECRUITS; TRENDS AB Women in the US military report a high prevalence of sexual risk behaviours, such as binge drinking and new or multiple sexual partnerships. However, demographical differences pose challenges to making comparisons with civilians. Two public-use datasets were used to compare prevalence of sexual risk behaviours between sexually active military and civilian women, after adjusting for demographic factors. It was found that women in the military reported a higher prevalence of binge drinking and new/multiple sexual partners as compared with civilians, which suggests that military women are a high-risk group and the military environment may at least partially facilitate these risk behaviours. C1 [Stahlman, Shauna; Javanbakht, Marjan; Cochran, Susan; Gorbach, Pamina M.] Univ Calif Los Angeles, Dept Epidemiol, Fielding Sch Publ Hlth, Los Angeles, CA 90095 USA. [Hamilton, Alison B.] Univ Calif Los Angeles, Dept Psychiat & Biobehav Sci, Los Angeles, CA 90095 USA. [Hamilton, Alison B.] VA Greater Los Angeles Healthcare Syst, Los Angeles, CA 90073 USA. [Shoptaw, Steven] Univ Calif Los Angeles, Dept Family Med, Los Angeles, CA 90095 USA. RP Stahlman, S (reprint author), Univ Calif Los Angeles, Dept Epidemiol, Fielding Sch Publ Hlth, Los Angeles, CA 90095 USA. EM sstahlman@ucla.edu OI Shoptaw, Steven/0000-0002-3583-0026 FU NIMH NIH HHS [P30 MH058107] NR 16 TC 1 Z9 1 U1 0 U2 3 PU CSIRO PUBLISHING PI CLAYTON PA UNIPARK, BLDG 1, LEVEL 1, 195 WELLINGTON RD, LOCKED BAG 10, CLAYTON, VIC 3168, AUSTRALIA SN 1448-5028 EI 1449-8987 J9 SEX HEALTH JI Sex Health PY 2015 VL 12 IS 3 BP 272 EP 275 DI 10.1071/SH14211 PG 4 WC Public, Environmental & Occupational Health; Infectious Diseases SC Public, Environmental & Occupational Health; Infectious Diseases GA CK7EV UT WOS:000356395300015 PM 25844558 ER PT J AU Matteucci, E Giampietro, O Covolan, V Giustarini, D Fanti, P Rossi, R AF Matteucci, Elena Giampietro, Ottavio Covolan, Vera Giustarini, Daniela Fanti, Paolo Rossi, Ranieri TI Insulin administration: present strategies and future directions for a noninvasive (possibly more physiological) delivery SO DRUG DESIGN DEVELOPMENT AND THERAPY LA English DT Review DE type 1 diabetes mellitus; drug formulations; drug administration routes; insulin; portal system; nanoparticles; biodegradable polymers ID TRANSDERMAL DRUG-DELIVERY; TIME-ACTION PROFILE; SUBCUTANEOUSLY INJECTED INSULIN; INHALED TECHNOSPHERE INSULIN; RANDOMIZED CONTROLLED-TRIAL; SOLID LIPID NANOPARTICLES; REGULAR HUMAN INSULIN; ORAL INSULIN; DIABETES-MELLITUS; IN-VIVO AB Insulin is a life-saving medication for people with type 1 diabetes, but traditional insulin replacement therapy is based on multiple daily subcutaneous injections or continuous subcutaneous pump-regulated infusion. Nonphysiologic delivery of subcutaneous insulin implies a rapid and sustained increase in systemic insulin levels due to the loss of concentration gradient between portal and systemic circulations. In fact, the liver degrades about half of the endogenous insulin secreted by the pancreas into the venous portal system. The reverse insulin distribution has short- and long-term effects on glucose metabolism. Thus, researchers have explored less-invasive administration routes based on innovative pharmaceutical formulations, which preserve hormone stability and ensure the therapeutic effectiveness. This review examines some of the recent proposals from clinical and material chemistry point of view, giving particular attention to patients' (and diabetologists') ideal requirements that organic chemistry could meet. C1 [Matteucci, Elena; Giampietro, Ottavio] Univ Pisa, Dept Clin & Expt Med, I-56100 Pisa, Italy. [Covolan, Vera] Univ Pisa, Dept Chem & Ind Chem, I-56100 Pisa, Italy. [Giustarini, Daniela; Rossi, Ranieri] Univ Siena, Lab Pharmacol & Toxicol, Dept Life Sci, I-53100 Siena, Italy. [Fanti, Paolo] Univ Texas Hlth Sci Ctr San Antonio, Div Nephrol, South Texas Vet Hlth Care Syst, San Antonio, TX 78229 USA. RP Matteucci, E (reprint author), Dipartimento Med Clin & Sperimentale, Via Roma 67, I-56126 Pisa, Italy. EM elena.matteucci@med.unipi.it NR 75 TC 4 Z9 4 U1 3 U2 24 PU DOVE MEDICAL PRESS LTD PI ALBANY PA PO BOX 300-008, ALBANY, AUCKLAND 0752, NEW ZEALAND SN 1177-8881 J9 DRUG DES DEV THER JI Drug Des. Dev. Ther. PY 2015 VL 9 BP 3109 EP 3118 DI 10.2147/DDDT.S79322 PG 10 WC Chemistry, Medicinal; Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA CK6RA UT WOS:000356354100001 PM 26124635 ER PT J AU Mottalib, A Sakr, M Shehabeldin, M Hamdy, O AF Mottalib, Adham Sakr, Mahmoud Shehabeldin, Mohamed Hamdy, Osama TI Diabetes Remission after Nonsurgical Intensive Lifestyle Intervention in Obese Patients with Type 2 Diabetes SO JOURNAL OF DIABETES RESEARCH LA English DT Article ID BETA-CELL FUNCTION; CARDIOVASCULAR RISK-FACTORS; BARIATRIC SURGERY; INSULIN SENSITIVITY; GLUCOSE-TOLERANCE; WEIGHT MANAGEMENT; MELLITUS; RESISTANCE; THERAPY; METAANALYSIS AB Partial or complete remission from type 2 diabetes was recently observed after bariatric surgeries. Limited data is available about the possibility of inducing diabetes remission through intensive weight reduction. We retrospectively evaluated diabetes remissions after one year of the Weight Achievement and Intensive Treatment (Why WAIT) program, a 12-week intensive program for diabetes weight management in real-world clinical practice. Among 120 obese patients with type 2 diabetes who completed the program, 88 patients returned for follow-up at one year. Nineteen patients (21.6%) had major improvement in their glycemic control, defined as achieving an A1C < 6.5% after one year. Four patients (4.5%) achieved either partial or complete diabetes remission defined as A1C < 6.5% and < 5.7%, respectively, on no antihyperglycemic medications for one year; 2 achieved partial remission (2.3%) and 2 achieved complete remission (2.3%). At the time of intervention, patients who achieved diabetes remission had shorter diabetes duration (< 5 years) and lower A1C (< 8%) and were treated with fewer than 2 oral medications. They achieved a weight reduction of > 7% after 12 weeks. These results indicate that a subset of obese patients with type 2 diabetes is appropriate for intensive lifestyle intervention with the aim of inducing diabetes remission. C1 [Mottalib, Adham; Sakr, Mahmoud; Shehabeldin, Mohamed; Hamdy, Osama] Joslin Diabet Ctr, Boston, MA 02215 USA. RP Hamdy, O (reprint author), Joslin Diabet Ctr, One Joslin Pl, Boston, MA 02215 USA. EM osama.hamdy@joslin.harvard.edu OI Mottalib, Adham/0000-0002-8573-6329 FU Metagenics, Inc.; Neurometrix, Inc. FX Osama Hamdy is a Consultant for Abbott Nutrition, Merck & Co., Inc. Research Support was received from Metagenics, Inc., and Neurometrix, Inc. NR 27 TC 1 Z9 1 U1 1 U2 3 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 2015 AR 468704 DI 10.1155/2015/468704 PG 4 WC Endocrinology & Metabolism; Medicine, Research & Experimental SC Endocrinology & Metabolism; Research & Experimental Medicine GA CK5JB UT WOS:000356258800001 ER PT J AU Asselin, P Knezevic, S Kornfeld, S Cirnigliaro, C Agranova-Breyter, I Bauman, WA Spungen, AM AF Asselin, Pierre Knezevic, Steven Kornfeld, Stephen Cirnigliaro, Christopher Agranova-Breyter, Irina Bauman, William A. Spungen, Ann M. TI Heart rate and oxygen demand of powered exoskeleton-assisted walking in persons with paraplegia SO JOURNAL OF REHABILITATION RESEARCH AND DEVELOPMENT LA English DT Article DE 6MWT; ambulatory device; energy expenditure; metabolic; overground walking; oxygen uptake; paraplegia; powered exoskeleton; reciprocating gait orthosis; RGO; spinal cord injury ID SPINAL-CORD-INJURY; RECIPROCATING-GAIT ORTHOSIS; QUALITY-OF-LIFE; ELECTRICAL-STIMULATION; ENERGY-EXPENDITURE; HYBRID ORTHOSIS; EXERCISE; INDIVIDUALS; PERFORMANCE; COST AB Historically, persons with paralysis have limited options for overground ambulation. Recently, powered exoskeletons, which are systems that translate the user's body movements to activate motors that move the lower limbs through a predetermined gait pattern, have become available. As part of an ongoing clinical study (NCT01454570), eight nonambulatory persons with paraplegia were trained to ambulate with a powered exoskeleton. Measurements of oxygen uptake (VO2) and heart rate (HR) were recorded for 6 mm each during each maneuver while sitting, standing, and walking. The average value of VO2 during walking (11.2 +/- 1.7 mL/kg/min) was significantly higher than for sitting and standing (3.5 +/- 0.4 and 4.3 +/- 0.9 mL/kg/min, respectively; p < 0.001). The HR response during walking was significantly greater than that of either sitting or standing (118 +/- 21 vs 70 +/- 10 and 81 +/- 12 beats per minute, respectively; p < 0.001). Persons with paraplegia were able to ambulate efficiently using the powered exoskeleton for overground ambulation, providing the potential for functional gain and improved fitness. C1 [Asselin, Pierre; Knezevic, Steven; Kornfeld, Stephen; Cirnigliaro, Christopher; Bauman, William A.; Spungen, Ann M.] Natl Ctr Excellence Med Consequences Spinal Cord, Dept Vet Affairs VA Rehabil Res & Dev, Bronx, NY USA. [Kornfeld, Stephen] Spinal Cord Injury Patient Care Ctr, Bronx, NY USA. [Agranova-Breyter, Irina] James J Peters VA Med Ctr, Rehabil Med, Bronx, NY USA. [Bauman, William A.; Spungen, Ann M.] Icahn Sch Med Mt Sinai, Dept Med, New York, NY 10029 USA. [Bauman, William A.; Spungen, Ann M.] Icahn Sch Med Mt Sinai, Dept Rehabil Med, New York, NY 10029 USA. RP Spungen, AM (reprint author), 130 W Kingsbridge Rd,Rm 7A-13, Bronx, NY 10468 USA. EM Ann.spungen@va.gov FU VA Rehabilitation Research & Development National Center of Excellence for the Medical Consequences of Spinal Cord Injury [VA RRD B9212C] FX Funding/Support: This material was based on work supported by the VA Rehabilitation Research & Development National Center of Excellence for the Medical Consequences of Spinal Cord Injury (VA RR&D B9212C). Two of the four ReWalk devices were obtained on a loaner basis at no cost from Argo Medical Technologies (Marlborough, Massachusetts). Orthopedic shoes used in this trial were donated by Aetrex Worldwide Inc. (Teaneck, New Jersey). NR 55 TC 5 Z9 5 U1 0 U2 10 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 2015 VL 52 IS 2 BP 147 EP 158 DI 10.1682/JRRD.2014.02.0060 PG 12 WC Rehabilitation SC Rehabilitation GA CK6DB UT WOS:000356317600003 PM 26230182 ER PT J AU Littman, AJ Thompson, ML Arterburn, DE Bouldin, E Haselkorn, JK Sangeorzan, BJ Boyko, EJ AF Littman, Alyson J. Thompson, Mary Lou Arterburn, David E. Bouldin, Erin Haselkorn, Jodie K. Sangeorzan, Bruce J. Boyko, Edward J. TI Lower-limb amputation and body weight changes in men SO JOURNAL OF REHABILITATION RESEARCH AND DEVELOPMENT LA English DT Article DE adult; lower-limb amputation; men; obesity; partial foot amputation; toe amputation; transfemoral amputation; transtibial amputation; Veterans; weight change ID CARDIOVASCULAR-DISEASE; UNITED-STATES; PSYCHOSOCIAL ADJUSTMENT; RISK-ADJUSTMENT; PREVALENCE; MORTALITY; VETERANS; AMPUTEES; OBESITY; HEALTH AB Little is known about the relationship between lower-limb amputation (LLA) and subsequent changes in body weight. We conducted a retrospective cohort study using clinical and administrative databases to identify and follow weight changes in 759 males with amputation (partial foot amputation [PFA], n = 396; transtibial amputation [TTA], n = 267; and transfemoral amputation [TFA], n = 96) and 3,790 men without amputation frequency-matched (5:1) on age, body mass index, diabetes, and calendar year from eight Department of Veterans Affairs medical care facilities in the Pacific Northwest. We estimated and compared longitudinal percent weight change from baseline up to 39 mo of follow-up in men with and without amputation. Weight gain in the 2 yr after amputation was significantly more in men with an amputation than without, and in men with a TTA or TFA (8%-9% increase) than in men with a PFA (3%-6% increase). Generally, percent weight gain peaked at 2 yr and was followed by some weight loss in the third year. These findings indicate that LLA is often followed by clinically important weight gain. Future studies are needed to better understand the reasons for weight gain and to identify intervention strategies to prevent excess weight gain and the deleterious consequences that may ensue. C1 [Littman, Alyson J.; Thompson, Mary Lou; Bouldin, Erin; Boyko, Edward J.] Dept Vet Affairs VA Puget Sound Hlth Care Syst, Seattle Epidemiol Res & Informat Ctr, Seattle, WA USA. [Littman, Alyson J.; Bouldin, Erin; Haselkorn, Jodie K.] Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA. [Thompson, Mary Lou] Univ Washington, Dept Biostat, Seattle, WA 98195 USA. [Arterburn, David E.] Grp Hlth Res Inst, Seattle, WA USA. [Haselkorn, Jodie K.] Univ Washington, VA Puget Sound Hlth Care Syst, Multiple Sclerosis Ctr Excellence West, Seattle, WA 98195 USA. [Haselkorn, Jodie K.] Univ Washington, Dept Rehabil, Seattle, WA 98195 USA. [Haselkorn, Jodie K.; Sangeorzan, Bruce J.] Univ Washington, Harborview Med Ctr, VA Puget Sound Hlth Care Syst, VA Ctr Excellence Limb Loss Prevent & Prosthet En, Seattle, WA 98104 USA. [Haselkorn, Jodie K.; Sangeorzan, Bruce J.] Univ Washington, Harborview Med Ctr, Dept Orthopaed & Sports Med, Seattle, WA 98104 USA. RP Littman, AJ (reprint author), VA Puget Sound Med Ctr, Seattle Epidemiol Res & Informat Ctr, 1100 Olive Way,Metropolitan Pk West,Suite 1400, Seattle, WA 98101 USA. EM alyson.littman@va.gov OI Bouldin, Erin/0000-0001-7550-309X FU VA Office of Research and Development Cooperative Studies Program; Seattle Epidemiologic Research and Information Center of the VA; VA Rehabilitation Research and Development Career Development Award [6982] FX Funding/Support: This material was based on work supported in part by the VA Office of Research and Development Cooperative Studies Program. The Seattle Epidemiologic Research and Information Center of the VA provided support for this research. Dr. Littman's time was also supported by a VA Rehabilitation Research and Development Career Development Award (grant 6982). NR 20 TC 2 Z9 2 U1 1 U2 6 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 2015 VL 52 IS 2 BP 159 EP 169 DI 10.1682/JRRD.2014.07.0166 PG 11 WC Rehabilitation SC Rehabilitation GA CK6DB UT WOS:000356317600004 PM 26244755 ER PT J AU Barks, L Luther, SL Brown, LM Schulz, B Bowen, ME Powell-Cope, G AF Barks, Lelia Luther, Stephen L. Brown, Lisa M. Schulz, Brian Bowen, Mary Elizabeth Powell-Cope, Gail TI Development and initial validation of the Seated Posture Scale SO JOURNAL OF REHABILITATION RESEARCH AND DEVELOPMENT LA English DT Article DE elder; geriatric; long-term care; posture; reliability; seat; SPS; validity; Veteran; wheelchair ID WHEELCHAIR; RELIABILITY; RESIDENTS; PERFUSION; PRESSURE; CHILDREN AB Literature shows that some health outcomes (e.g., eating, breathing, and speaking) are directly related to posture. Evidence of outcomes mediated by wheelchair seated posture is limited to interface pressure, physical function, and wheelchair skills and safety. This study's purpose was to develop and validate a rapid, low-burden, paper-pencil assessment of wheelchair seated posture for research use and to test feasibility of its use with a sample of older adults. We used a prospective design and a convenience sample of older adults who were receiving rehabilitation services in a community living center. Forty-nine older wheelchair users participated. Main measures were the Seated Posture Scale (SPS), Modified Ashworth Scale, Barthel Index, Visual Descriptor Scale, scale-content validity index (S-CVI), Cronbach alpha, and test-retest reliability. Rating by six experts yielded the overall content validity score (S-CVI) of 0.744. Total SPS score correlated positively with physical function (Barthel Index, r = 0.46, p < 0.001) and negatively with muscle tone (Modified Ashworth Scale, r = -0.44, p = 0.001), supporting SPS construct validity. Internal consistency was 0.66 (Cronbach alpha). Test-retest reliability yielded Pearson product-moment correlations of 0.89 to 0.99. We conclude that the SPS has sufficient preliminary validity and reliability to support its use as an evaluation of wheelchair seated posture in outcomes research. C1 [Barks, Lelia; Luther, Stephen L.; Brown, Lisa M.; Bowen, Mary Elizabeth; Powell-Cope, Gail] James A Haley Vet Hosp, Ctr Innovat Disabil & Rehabil Res, Tampa, FL 33612 USA. [Barks, Lelia; Luther, Stephen L.; Brown, Lisa M.; Bowen, Mary Elizabeth; Powell-Cope, Gail] Dept Vet Affairs VA, Rehabil Res & Dev Serv, Washington, DC USA. [Brown, Lisa M.; Schulz, Brian] Univ S Florida, Sch Aging Studies, Tampa, FL USA. [Bowen, Mary Elizabeth] Philadelphia VA Med Ctr, Philadelphia, PA USA. [Bowen, Mary Elizabeth] Ctr West Chester Univ, W Chester, PA USA. RP Barks, L (reprint author), Hlth Serv Res & Dev Rehabil Res & Dev Ctr Innovat, 8900 Grand Oak Cir, Tampa, FL 33637 USA. EM Lelia.Barks@va.gov OI Powell-Cope, Gail/0000-0002-4608-0128 FU VA Office of Academic Affiliations; VA Office of Research and Development, Rehabilitation Research and Development Service (Career Development Award) [07646-W, 2] FX Funding/Support: This material was based on work supported initially by the VA Office of Academic Affiliations (postdoctoral fellowship) and later by the VA Office of Research and Development, Rehabilitation Research and Development Service (Career Development Award 2 No. 07646-W). NR 27 TC 0 Z9 0 U1 0 U2 0 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 2015 VL 52 IS 2 BP 201 EP 210 DI 10.1682/JRRD.2014.04.0100 PG 10 WC Rehabilitation SC Rehabilitation GA CK6DB UT WOS:000356317600008 PM 26230339 ER PT S AU Jin, YN Yin, ZY Yao, YY Wang, H Wu, MY Kalra, M De Man, B AF Jin, Yannan Yin, Zhye Yao, Yangyang Wang, Hui Wu, Mingye Kalra, Mannudeep De Man, Bruno BE Hoeschen, C Kontos, D TI Patient Specific Tube Current Modulation for CT Dose Reduction SO MEDICAL IMAGING 2015: PHYSICS OF MEDICAL IMAGING SE Proceedings of SPIE LA English DT Proceedings Paper CT Conference on Medical Imaging - Physics of Medical Imaging CY FEB 22-25, 2015 CL Orlando, FL SP SPIE, ALIO Ind, Alpin Med Syst, Modus Med Devices Inc, Bruker, Carestream Health Inc, GE Healthcare, American Assoc Physicists Med, American Physiolog Soc, Comp Assisted Radiol & Surg, Med Image Percept Soc, Radiolog Soc N America, Soc Imaging Informat Med, World Mol Imaging Soc, DICOM Stand Comm DE Computed Tomography; dose reduction; mA modulation; patient-specific dose optimization ID IMAGE QUALITY; STRATEGIES; PHANTOM AB Radiation exposure during CT imaging has drawn growing concern from academia, industry as well as the general public. Sinusoidal tube current modulation has been available in most commercial products and used routinely in clinical practice. To further exploit the potential of tube current modulation, Sperl et al. proposed a Computer-Assisted Scan Protocol and Reconstruction (CASPAR) scheme [6] that modulates the tube current based on the clinical applications and patient specific information. The purpose of this study is to accelerate the CASPAR scheme to make it more practical for clinical use and investigate its dose benefit for different clinical applications. The Monte Carlo simulation in the original CASPAR scheme was substituted by the dose reconstruction to accelerate the optimization process. To demonstrate the dose benefit, we used the CATSIM package generate the projection data and perform standard FDK reconstruction. The NCAT phantom at thorax position was used in the simulation. We chose three clinical cases (routine chest scan, coronary CT angiography with and without breast avoidance) and compared the dose level with different mA modulation schemes (patient specific, sinusoidal and constant mA) with matched image quality. The simulation study of three clinical cases demonstrated that the patient specific mA modulation could significantly reduce the radiation dose compared to sinusoidal modulation. The dose benefits depend on the clinical application and object shape. With matched image quality, for chest scan the patient specific mA profile reduced the dose by about 15% compared to the sinusoid mA modulation; for the organ avoidance scan the dose reduction to the breast was over 50% compared to the constant mA baseline. C1 [Jin, Yannan; Yin, Zhye; De Man, Bruno] GE Global Res Ctr, CT Syst & Applicat Lab, Niskayuna, NY 12309 USA. [Yao, Yangyang; Wang, Hui; Wu, Mingye] GE Global Res Ctr, CT & Xray Lab, Shanghai, Peoples R China. [Kalra, Mannudeep] Harvard Univ, Sch Med, Dept Radiol, Massachusetts Gen Hosp, Boston, MA 02115 USA. RP Jin, YN (reprint author), GE Global Res Ctr, CT Syst & Applicat Lab, Niskayuna, NY 12309 USA. NR 13 TC 1 Z9 1 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 978-1-62841-502-5 J9 PROC SPIE PY 2015 VL 9412 AR 94122Z DI 10.1117/12.2081486 PG 6 WC Optics; Physics, Applied; Radiology, Nuclear Medicine & Medical Imaging SC Optics; Physics; Radiology, Nuclear Medicine & Medical Imaging GA BC8EX UT WOS:000355581700096 ER PT S AU Nasirudin, RA Tachibana, R Nappi, JJ Mei, K Kopp, FK Rummeny, EJ Yoshida, H Noel, PB AF Nasirudin, Radin A. Tachibana, Rie Naeppi, Janne J. Mei, Kai Kopp, Felix K. Rummeny, Ernst J. Yoshida, Hiroyuki Noel, Peter B. BE Hoeschen, C Kontos, D TI A comparison of material decomposition techniques for dual-energy CT colonography SO MEDICAL IMAGING 2015: PHYSICS OF MEDICAL IMAGING SE Proceedings of SPIE LA English DT Proceedings Paper CT Conference on Medical Imaging - Physics of Medical Imaging CY FEB 22-25, 2015 CL Orlando, FL SP SPIE, ALIO Ind, Alpin Med Syst, Modus Med Devices Inc, Bruker, Carestream Health Inc, GE Healthcare, American Assoc Physicists Med, American Physiolog Soc, Comp Assisted Radiol & Surg, Med Image Percept Soc, Radiolog Soc N America, Soc Imaging Informat Med, World Mol Imaging Soc, DICOM Stand Comm DE Dual-Energy CT; CT Colonography; Computer-Aided Design; Material Decomposition ID POLYPS; PERFORMANCE; EXPERIENCE; CAD AB In recent years, dual-energy computed tomography (DECT) has been widely used in the clinical routine due to improved diagnostics capability from additional spectral information. One promising application for DECT is CT colonography (CTC) in combination with computer-aided diagnosis (CAD) for detection of lesions and polyps. While CAD has demonstrated in the past that it is able to detect small polyps, its performance is highly dependent on the quality of the input data. The presence of artifacts such as beam-hardening and noise in ultra-low-dose CTC may severely degrade detection performances of small polyps. In this work, we investigate and compare virtual monochromatic images, generated by image-based decomposition and projection-based decomposition, with respect to CAD performance. In the image-based method, reconstructed images are firstly decomposed into water and iodine before the virtual monochromatic images are calculated. On the contrary, in the projection-based method, the projection data are first decomposed before calculation of virtual monochromatic projection and reconstruction. Both material decomposition methods are evaluated with regards to the accuracy of iodine detection. Further, the performance of the virtual monochromatic images is qualitatively and quantitatively assessed. Preliminary results show that the projection-based method does not only have a more accurate detection of iodine, but also delivers virtual monochromatic images with reduced beam hardening artifacts in comparison with the image-based method. With regards to the CAD performance, the projection-based method yields an improved detection performance of polyps in comparison with that of the image-based method. C1 [Nasirudin, Radin A.; Mei, Kai; Kopp, Felix K.; Rummeny, Ernst J.; Noel, Peter B.] Tech Univ Munich, Dept Diagnost & Intervent Radiol, D-80290 Munich, Germany. [Tachibana, Rie; Naeppi, Janne J.; Yoshida, Hiroyuki] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiol,Imaging Res D3, Boston, MA USA. RP Nasirudin, RA (reprint author), Tech Univ Munich, Dept Diagnost & Intervent Radiol, D-80290 Munich, Germany. OI Noel, Peter/0000-0002-9671-6171 NR 10 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 978-1-62841-502-5 J9 PROC SPIE PY 2015 VL 9412 AR 94124F DI 10.1117/12.2081982 PG 6 WC Optics; Physics, Applied; Radiology, Nuclear Medicine & Medical Imaging SC Optics; Physics; Radiology, Nuclear Medicine & Medical Imaging GA BC8EX UT WOS:000355581700145 ER PT S AU Viana, RS Galarreta-Valverde, MA Mekkaoui, C Yoriyaz, H Jackowski, MP AF Viana, Rodrigo S. Galarreta-Valverde, Miguel A. Mekkaoui, Choukri Yoriyaz, Helio Jackowski, Marcel P. BE Hoeschen, C Kontos, D TI NSECT sinogram sampling optimization by normalized mutual information SO MEDICAL IMAGING 2015: PHYSICS OF MEDICAL IMAGING SE Proceedings of SPIE LA English DT Proceedings Paper CT Conference on Medical Imaging - Physics of Medical Imaging CY FEB 22-25, 2015 CL Orlando, FL SP SPIE, ALIO Ind, Alpin Med Syst, Modus Med Devices Inc, Bruker, Carestream Health Inc, GE Healthcare, American Assoc Physicists Med, American Physiolog Soc, Comp Assisted Radiol & Surg, Med Image Percept Soc, Radiolog Soc N America, Soc Imaging Informat Med, World Mol Imaging Soc, DICOM Stand Comm DE Neutron stimulated emission computed tomography; mutual information; MCNP5; radon transform; image reconstruction ID CANCER AB Neutron Stimulated Emission Computed Tomography (NSECT) is an emerging noninvasive imaging technique that measures the distribution of isotopes from biological tissue using fast-neutron inelastic scattering reaction. As a high-energy neutron beam illuminates the sample, the excited nuclei emit gamma rays whose energies are unique to the emitting nuclei. Tomographic images of each element in the spectrum can then be reconstructed to represent the spatial distribution of elements within the sample using a first generation tomographic scan. NSECT's high radiation dose deposition, however, requires a sampling strategy that can yield maximum image quality under a reasonable radiation dose. In this work, we introduce an NSECT sinogram sampling technique based on the Normalized Mutual Information (NMI) of the reconstructed images. By applying the Radon Transform on the ground-truth image obtained from a carbon-based synthetic phantom, different NSECT sinogram configurations were simulated and compared by using the NMI as a similarity measure. The proposed methodology was also applied on NSECT images acquired using MCNP5 Monte Carlo simulations of the same phantom to validate our strategy. Results show that NMI can be used to robustly predict the quality of the reconstructed NSECT images, leading to an optimal NSECT acquisition and a minimal absorbed dose by the patient. C1 [Viana, Rodrigo S.; Yoriyaz, Helio] IPEN CEN, Inst Nucl Energy Res, Nucl Engn Ctr, Sao Paulo, SP, Brazil. [Galarreta-Valverde, Miguel A.; Jackowski, Marcel P.] Univ Sao Paulo, Dept Comp Sci, Inst Math & Stat, Sao Paulo, SP, Brazil. [Mekkaoui, Choukri] Univ Hosp Ctr Nimes, Dept Radiol, Nimes, France. [Mekkaoui, Choukri] Res Team EA 2415, Nimes, France. [Mekkaoui, Choukri] Univ Montpellier, Fac Med, F-34059 Montpellier, France. [Mekkaoui, Choukri] Harvard Univ, Sch Med, Dept Radiol, Massachusetts Gen Hosp,Athinoula A Martinos Ctr B, Boston, MA 02115 USA. RP Viana, RS (reprint author), IPEN CEN, Inst Nucl Energy Res, Nucl Engn Ctr, Sao Paulo, SP, Brazil. EM mjack@ime.usp.br RI Jackowski, Marcel/G-7602-2012; Yoriyaz, Helio/K-1874-2012 OI Yoriyaz, Helio/0000-0003-4023-236X NR 11 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 978-1-62841-502-5 J9 PROC SPIE PY 2015 VL 9412 AR 94122B DI 10.1117/12.2082496 PG 6 WC Optics; Physics, Applied; Radiology, Nuclear Medicine & Medical Imaging SC Optics; Physics; Radiology, Nuclear Medicine & Medical Imaging GA BC8EX UT WOS:000355581700076 ER PT J AU Li, J Ji, L Chen, JP Zhang, WG Ye, ZJ AF Li, Jing Ji, Ling Chen, Jieping Zhang, Wengeng Ye, Zhijia TI Wnt/beta-Catenin Signaling Pathway in Skin Carcinogenesis and Therapy SO BIOMED RESEARCH INTERNATIONAL LA English DT Review ID NEURAL CREST STEM; NONSTEROIDAL ANTIINFLAMMATORY DRUGS; HAIR FOLLICLE MORPHOGENESIS; BETA-CATENIN; CUTANEOUS MELANOMA; MALIGNANT-MELANOMA; CELL CARCINOMA; ADULT SKIN; VITAMIN-D; WNT AB Cooperating with other signaling pathways, Wnt signaling controls cell proliferation, morphology, motility, and embryonic development destination and maintains the homeostasis of tissues including skin, blood, intestine, and brain by regulating somatic stem cells and their niches throughout adult life. Abnormal regulation of Wnt pathways leads to neoplastic proliferation in these tissues. Recent research shows that Wnt signaling is also associated with the regulation of cancer stem cells (CSCs) through a similar mechanism to that observed in normal adult stem cells. Thus, the Wnt/beta-catenin signaling pathway has been intensively studied and characterized. For this review, we will focus on the regulation of the Wnt/beta-catenin signaling pathway in skin cancer. With the important role in stemness and skin CSC proliferation, the Wnt/beta-catenin signaling pathway and its elements have the potential to be targets for skin cancer therapy. C1 [Li, Jing; Ji, Ling; Ye, Zhijia] Third Mil Med Univ, Inst Trop Med, Chongqing 400038, Peoples R China. [Ji, Ling] Third Mil Med Univ, Southwest Hosp, Dept Hematol, Chongqing 400038, Peoples R China. [Zhang, Wengeng] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Engn Med,Dept Surg, Boston, MA 02114 USA. RP Zhang, WG (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Engn Med,Dept Surg, 51 Blossom St, Boston, MA 02114 USA. EM wengeng.zhang@mgh.harvard.edu; zjye@tmmu.edu.cn FU National Natural Science Foundation of China [81170471, 31371393]; Natural Science Foundation of Chongqing Science & Technology Commission [cstc2013jjB10027] FX This research was supported by the National Natural Science Foundation of China (81170471, 31371393) and the Natural Science Foundation of Chongqing Science & Technology Commission (cstc2013jjB10027). NR 73 TC 0 Z9 0 U1 1 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 2015 AR 964842 DI 10.1155/2015/964842 PG 8 WC Biotechnology & Applied Microbiology; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Research & Experimental Medicine GA CJ5JG UT WOS:000355523000001 ER PT J AU Huang, YY Luo, DZ Hamblin, MR AF Huang, Ying-Ying Luo, Dianzhong Hamblin, Michael R. TI Stable Synthetic Bacteriochlorins: Potent Light-Activated Anti-Cancer Drugs SO CURRENT ORGANIC CHEMISTRY LA English DT Article DE Anti-cancer drugs; near-infrared light; photodynamic therapy; reactive oxygen species; stable synthetic bacteriochlorins; structure-function relationship ID PHOTODYNAMIC THERAPY ROLE; IN-VITRO; CREMOPHOR EL; 2ND-GENERATION PHOTOSENSITIZER; CENTRAL METAL; CANCER-CELLS; FLUORESCENCE; DELIVERY; DERIVATIVES; MECHANISMS AB Photodynamic therapy (PDT) uses non-toxic dyes called photosensitizers (PS) to absorb light of visible or near-infrared wavelengths at non-thermal power densities that (in the presence of oxygen) combine together to produce reactive oxygen species (ROS). The main ROS formed are singlet oxygen and hydroxyl radicals that can both have cytotoxic effects. PDT has two separate mechanisms of specificity due to specific accumulation in the tumor coupled with spatially confined illumination. The first-generation PS were porphyrins, but due to the need for long-wavelength activation to improve tissue penetration, second-generation chlorins (far red) and bacteriochlorins (BC) (near infrared [NIR]) have been investigated. This review covers quantitative structure-function relationship with charge and lipophilicity, the effect the central metal atom has on determining the photochemical mechanism, the effect that electron withdrawing di-cyano groups have on preventing photobleaching, the improvement in activity found when micellar nanocarriers are employed, and the relative superiority of mono-substitution over symmetrical di-substitution. Finally, the necessity for long-wavelength (730 nm) activation is underlined by looking at PDT of pigmented melanoma in vitro and in a mouse model of melanoma. C1 [Huang, Ying-Ying; Luo, Dianzhong] Guangxi Med Univ, Affiliated Hosp 1, Dept Pathol, Nanning 530021, Guangxi Zhuang, Peoples R China. [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. [Hamblin, Michael R.] Harvard Mit Div Hlth Sci & Technol, Cambridge, MA 02139 USA. RP Hamblin, MR (reprint author), BAR414,40 Blossom St, Boston, MA 02114 USA. EM Hamblin@helix.mgh.harvard.edu FU US NIH [R01AI050875]; National Science Foundation of China [81060200] FX YYH and MRH were supported by US NIH grant R01AI050875. DL was supported by National Science Foundation of China (81060200). NR 43 TC 5 Z9 5 U1 2 U2 23 PU BENTHAM SCIENCE PUBL LTD PI SHARJAH PA EXECUTIVE STE Y-2, PO BOX 7917, SAIF ZONE, 1200 BR SHARJAH, U ARAB EMIRATES SN 1385-2728 EI 1875-5348 J9 CURR ORG CHEM JI Curr. Org. Chem. PY 2015 VL 19 IS 10 BP 948 EP 957 PG 10 WC Chemistry, Organic SC Chemistry GA CJ3IT UT WOS:000355377300007 ER PT J AU Devkota, S Chang, EB AF Devkota, Suzanne Chang, Eugene B. TI Interactions between Diet, Bile Acid Metabolism, Gut Microbiota, and Inflammatory Bowel Diseases SO DIGESTIVE DISEASES LA English DT Article DE Bile acids; Diet; Inflammatory bowel disease; Microbiome; Pathobiont ID SULFATE-REDUCING BACTERIA; BILOPHILA-WADSWORTHIA; ULCERATIVE-COLITIS; HYDROGEN-SULFIDE; EPIDEMIOLOGY; PATHOGENESIS; PREVALENCE; HEALTHY; FAT AB The composite human gut microbiomes of Western populations have changed over the past century, brought on by new environmental triggers that often have a negative impact on human health. Diets high in saturated fats and refined sugars and low in fiber are leading candidates for these events and for triggering the increased prevalence of immune-mediated diseases like inflammatory bowel disease (IBD). Our studies have shown that consumption of a 'Western' diet high in saturated (milk-derived) fat (MF) or n-6 polyunsaturated (safflower oil) fat have similar effects on the structure of the colonic microbiome of wild-type and IL-1 10(-/-) mice, characterized by increased Bacteroidetes and decreased Firmicutes. However, the MF diet uniquely promotes the expansion of an immunogenic sulfite-reducing pathobiont, Bilophila wadsworthia, a member of the Deltaproteo-bacteria and minor component of the gut microbiome. This bacterial bloom results from a ME diet-induced shift in hepatic conjugation of bile acids, from glycocholic to taurocholic (TC) acid, which is important for solubilizing the more hydrophobic ME diet. However, it is also responsible for delivery of taurine-derived sulfur to the distal bowel, promoting the assemblage of bile-tolerant microbes such as B. wadsworthia. The bloom of this species promotes a Th1-mediated immune response and the development of colitis in IL-10(-/-) mice. A similar bloom of B. wadsworthia is seen when IL-10(-/-) mice are fed a low-fat diet supplemented with TC. B. wadsworthia colonization of monoassociated germ-free IL-10(-/-) mice was dependent on the host consuming either a high-saturated ME diet or the gavage with TC. Together, these data provide a plausible explanation for the link between diseases such as IBD and dietary-mediated selection of gut microbial pathobionts in genetically susceptible hosts. With this knowledge, it may be possible to mitigate the bloom of these types of pathobionts by modifying the conjugation states of bile acids. (C) 2015 S. Karger AG, Basel C1 [Devkota, Suzanne] Harvard Univ, Sch Med, Joslin Diabet Ctr, Boston, MA 02115 USA. [Devkota, Suzanne] Harvard Univ, Sch Med, Boston, MA USA. [Chang, Eugene B.] Univ Chicago, Dept Med, Chicago, IL 60637 USA. RP Chang, EB (reprint author), Knapp Ctr Biomed Discovery, 900 E 57th St, Chicago, IL 60637 USA. EM echang@medicine.bsd.uchicago.edu FU National Institutes of Health [P30 DK42086, R37 DK47722, R01 DK097268, T32 DK07074, F32 DK09025]; Leona M. and Harry B. Helmsley Charitable Trust; Gastro-Intestinal Research Foundation of Chicago FX The authors received funding from the National Institutes of Health grants P30 DK42086, R37 DK47722, R01 DK097268, T32 DK07074 to E.B.C and F32 DK09025 (to S.D.), the Leona M. and Harry B. Helmsley Charitable Trust, and the Gastro-Intestinal Research Foundation of Chicago. NR 20 TC 9 Z9 9 U1 8 U2 32 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0257-2753 EI 1421-9875 J9 DIGEST DIS JI Dig. Dis. PY 2015 VL 33 IS 3 BP 351 EP 356 DI 10.1159/000371687 PG 6 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA CJ6XN UT WOS:000355638600010 PM 26045269 ER PT J AU Chen, KJ Lee, MS Xu, H Zhang, QH AF Chen, Ke-Ji Lee, Myeong Soo Xu, Hao Zhang, Qunhao TI Complementary/Alternative Medicine in Cardiovascular Diseases 2014 SO EVIDENCE-BASED COMPLEMENTARY AND ALTERNATIVE MEDICINE LA English DT Editorial Material C1 [Chen, Ke-Ji; Xu, Hao] China Acad Chinese Med Sci, Xiyuan Hosp, Ctr Cardiovasc, Beijing 100091, Peoples R China. [Lee, Myeong Soo] Korea Inst Oriental Med, Div Clin Res, Taejon 305811, South Korea. [Zhang, Qunhao] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Med, Boston, MA 02114 USA. RP Chen, KJ (reprint author), China Acad Chinese Med Sci, Xiyuan Hosp, Ctr Cardiovasc, Beijing 100091, Peoples R China. EM kjchenvip@163.com RI Lee, Myeong Soo/C-8147-2013 OI Lee, Myeong Soo/0000-0001-6651-7641 NR 0 TC 0 Z9 0 U1 0 U2 0 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 2015 AR 349375 DI 10.1155/2015/349375 PG 2 WC Integrative & Complementary Medicine SC Integrative & Complementary Medicine GA CJ9DZ UT WOS:000355804000001 ER PT J AU Wilson, R Anzueto, A Miravitlles, M Arvis, P Haverstock, D Trajanovic, M Sethi, S AF Wilson, Robert Anzueto, Antonio Miravitlles, Marc Arvis, Pierre Haverstock, Daniel Trajanovic, Mila Sethi, Sanjay TI Prognostic factors for clinical failure of exacerbations in elderly outpatients with moderate-to-severe COPD SO INTERNATIONAL JOURNAL OF CHRONIC OBSTRUCTIVE PULMONARY DISEASE LA English DT Article DE AECOPD; clinical failure; prognostic factor; long-term outcome; poor outcome ID OBSTRUCTIVE PULMONARY-DISEASE; RANDOMIZED CONTROLLED-TRIAL; LONG-TERM OUTCOMES; CHRONIC-BRONCHITIS; ANTIBIOTIC-TREATMENT; ORAL PREDNISONE; MORTALITY; RISK; CARE; CORTICOSTEROIDS AB Background: Acute exacerbations represent a significant burden for patients with moderate-to-severe chronic obstructive pulmonary disease. Each exacerbation episode is frequently associated with a lengthy recovery and impaired quality of life. Prognostic factors for outpatients that may predict poor outcome after treatment with antibiotics recommended in the guidelines, are not fully understood. We aimed to identify pretherapy factors predictive of clinical failure in elderly (>= 60 years old) outpatients with acute Anthonisen type 1 exacerbations. Trial registration: NCT00656747. Methods: Based on the moxifloxacin in AECOPDs (acute exacerbations of chronic obstructive pulmonary disease) trial (MAESTRAL) database, this study evaluated pretherapy demographic, clinical, sputum bacteriological factors using multivariate logistic regression analysis, with internal validation by bootstrap replicates, to investigate their possible association with clinical failure at end of therapy (EOT) and 8 weeks posttherapy. Results: The analyses found that the independent factors predicting clinical failure at EOT were more frequent exacerbations, increased respiratory rate and lower body temperature at exacerbation, treatment with long-acting anticholinergic drugs, and in vitro bacterial resistance to study drug. The independent factors predicting poor outcome at 8 weeks posttherapy included wheezing at preexacerbation, mild or moderate (vs extreme) sleep disturbances, lower body temperature at exacerbation, forced expiratory volume in 1 second <30%, lower body mass index, concomitant systemic corticosteroids for the current exacerbation, maintenance long-acting beta(2)-agonist and long-acting anticholinergic treatments, and positive sputum culture at EOT. Conclusion: Several bacteriological, historical, treatment-related factors were identified as predictors of early (EOT) and later (8 weeks posttherapy) clinical failure in this older outpatient population with moderate-to-severe chronic obstructive pulmonary disease. These patients should be closely monitored and sputum cultures considered before and after treatment. C1 [Wilson, Robert] Royal Brompton Hosp, Host Def Unit, London SW3 6NP, England. [Anzueto, Antonio] Univ Texas Hlth Sci Ctr San Antonio, South Texas Vet Hlth Care Syst, San Antonio, TX 78229 USA. [Miravitlles, Marc] Hosp Univ Vall dHebron, CIBER Enfermedades Resp CIBERES, Pneumol Dept, Barcelona, Spain. [Arvis, Pierre] Bayer HealthCare Pharmaceut, Loos, France. [Haverstock, Daniel] Bayer HealthCare Pharmaceut, Whippany, NJ USA. [Trajanovic, Mila] Bayer HealthCare Pharmaceut, Toronto, ON, Canada. [Sethi, Sanjay] SUNY Buffalo, Buffalo, NY 14260 USA. RP Wilson, R (reprint author), Royal Brompton Hosp, Host Def Unit, Sydney St, London SW3 6NP, England. EM r.wilson@rbht.nhs.uk OI Miravitlles, Marc/0000-0002-9850-9520 FU Bayer HealthCare, Germany; Bayer HealthCare FX This study was supported by Bayer HealthCare, Germany. Editorial assistance was provided by Highfield Communication, Oxford, UK, sponsored by Bayer HealthCare. The authors thank Mr Feng Zhan, inVentive Health, US, for his invaluable support in the bootstrapping and logistic regression analyses. NR 38 TC 0 Z9 0 U1 0 U2 2 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 2015 VL 10 DI 10.2147/COPD.S80926 PG 9 WC Respiratory System SC Respiratory System GA CJ9VG UT WOS:000355850700001 ER PT J AU Steinhauer, SR Condray, R Pless, ML AF Steinhauer, Stuart R. Condray, Ruth Pless, Misha L. TI Pharmacological Isolation of Cognitive Components Influencing the Pupillary Light Reflex SO JOURNAL OF OPHTHALMOLOGY LA English DT Article ID NORADRENERGIC LOCUS-COERULEUS; FUNCTIONAL NEUROANATOMY; SCHIZOPHRENIC-PATIENTS; DAPIPRAZOLE; MODULATION; AROUSAL; ROLES AB Cognitive operations can be detected by reduction of the pupillary light response. Neurophysiological pathways mediating this reduction have not been distinguished. We utilized selective blockade of pupillary sphincter or dilator muscles to isolate parasympathetic or sympathetic activity during cognition, without modifying central processes. Pupil diameter was measured during the light reaction in 29 normal adults under three processing levels: No Task, during an easy task (Add 1), or a difficult task (Subtract 7). At three separate sessions, the pupil was treated with placebo, tropicamide (blocking the muscarinic sphincter receptor), or dapiprazole (blocking the adrenergic dilator receptor). With placebo, pupil diameter increased with increasing task difficulty. The light reaction was reduced only in the Subtract 7 condition. Dapiprazole (which decreased overall diameter) showed similar task-related changes in diameter and light reflex as for placebo. Following tropicamide (which increased overall diameter), there was a further increase in diameter only in the difficult task. Findings suggest two separate inhibitory components at the parasympathetic oculomotor center. Changes in baseline diameter are likely related to reticular activation. Inhibition of the light reaction in the difficult task is likely associated with cortical afferents. Sustained sympathetic activity also was present during the difficult task. C1 [Steinhauer, Stuart R.; Condray, Ruth] VA Pittsburgh Healthcare Syst, Biometr Res Program, Pittsburgh, PA 15240 USA. [Steinhauer, Stuart R.] Univ Pittsburgh, Dept Psychiat, Sch Med, Pittsburgh, PA 15260 USA. [Pless, Misha L.] Luzerner Kantonsspital, Zentrum Neurol & Neurorehabil, Leitender Arzt Neuroophthalmol & Neurol Augenklin, CH-6000 Luzern 16, Switzerland. RP Steinhauer, SR (reprint author), VA Pittsburgh Healthcare Syst, Biometr Res Program, 151R,Univ Dr C, Pittsburgh, PA 15240 USA. EM sthauer@pitt.edu FU USPHS Grant [MH55762]; Medical Research Service of the United States Department of Veterans Affairs FX This work was supported by USPHS Grant MH55762 and by the Medical Research Service of the United States Department of Veterans Affairs. The authors thank Dr. Richard Rosen for additional ophthalmological screening, and the nursing and pharmacy services of the VA Pittsburgh Healthcare System for valuable assistance. NR 24 TC 0 Z9 0 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 2090-004X EI 2090-0058 J9 J OPHTHALMOL JI J. Ophthalmol. PY 2015 AR 179542 DI 10.1155/2015/179542 PG 7 WC Medicine, Research & Experimental; Ophthalmology SC Research & Experimental Medicine; Ophthalmology GA CJ9EZ UT WOS:000355806600001 ER PT J AU Hamza, B Irimia, D AF Hamza, Bashar Irimia, Daniel TI Whole blood human neutrophil trafficking in a microfluidic model of infection and inflammation SO LAB ON A CHIP LA English DT Article ID LEUKOCYTE MIGRATION; LIPID MEDIATORS; IN-VIVO; RESOLUTION; MECHANISMS; ZEBRAFISH; DISEASES; SITES; DROP AB Appropriate inflammatory responses to wounds and infections require adequate numbers of neutrophils arriving at injury sites. Both insufficient and excessive neutrophil recruitment can be detrimental, favouring systemic spread of microbes or triggering severe tissue damage. Despite its importance in health and disease, the trafficking of neutrophils through tissues remains difficult to control and the mechanisms regulating it are insufficiently understood. These mechanisms are also complex and difficult to isolate using traditional in vivo models. Here we designed a microfluidic model of tissue infection/inflammation, in which human neutrophils emerge from a droplet-size samples of whole blood and display bi-directional traffic between this and micro-chambers containing chemoattractant and microbe-like particles. Two geometrical barriers restrict the entrance of red blood cells from the blood to the micro-chambers and simulate the mechanical function of the endothelial barrier separating the cells in blood from cells in tissues. We found that in the presence of chemoattractant, the number of neutrophils departing the chambers by retrotaxis is in dynamic equilibrium with the neutrophils recruited by chemotaxis. We also found that in the presence of microbe-like particles, the number of neutrophils trapped in the chambers is proportional to the number of particles. Together, the dynamic equilibrium between migration, reversed-migration and trapping processes determine the optimal number of neutrophils at a site. These neutrophils are continuously refreshed and responsive to the number of microbes. Further studies using this infection-inflammationon- a-chip-model could help study the processes of inflammation resolution. The new in vitro experimental tools may also eventually help testing new therapeutic strategies to limit neutrophil accumulation in tissues during chronic inflammation, without increasing the risk for infections. C1 [Hamza, Bashar] Massachusetts Gen Hosp, BioMEMS Resource Ctr, Dept Surg, Boston, MA 02129 USA. [Irimia, Daniel] Harvard Univ, Sch Med, Boston, MA 02129 USA. [Irimia, Daniel] MGH, CNY, Charlestown, MA 02129 USA. RP Irimia, D (reprint author), Harvard Univ, Sch Med, Boston, MA 02129 USA. EM dirimia@hms.harvard.edu FU National Institutes of Health [GM092804, EB0025003] FX We thank Drs. Anna Robertson and Steven Renshaw at the University of Sheffield for the helpful discussions and Dr. Joseph Martel and Mr. Robert Kimmerling for their assistance with COMSOL-based simulations. Moreover, we thank Mr. Octavio Hurtado for assistance with device fabrication at the BioMEMS Resource Center Clean room. This work was supported by the National Institutes of Health (GM092804, EB0025003). NR 36 TC 8 Z9 8 U1 3 U2 16 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 2015 VL 15 IS 12 BP 2625 EP 2633 DI 10.1039/c5lc00245a PG 9 WC Biochemical Research Methods; Chemistry, Multidisciplinary; Nanoscience & Nanotechnology SC Biochemistry & Molecular Biology; Chemistry; Science & Technology - Other Topics GA CJ6WF UT WOS:000355635200011 PM 25987163 ER PT S AU Sun, PZ Zhou, IY Igarashi, T Guo, YK Xiao, G Wu, RH AF Sun, Phillip Zhe Zhou, Iris Yuewen Igarashi, Takahiro Guo, Yingkun Xiao, Gang Wu, Renhua BE Gimi, B Molthen, RC TI Simplified correction of B-1 inhomogeneity for chemical exchange saturation transfer (CEST) MRI measurement with surface transceiver coil SO MEDICAL IMAGING 2015: BIOMEDICAL APPLICATIONS IN MOLECULAR, STRUCTURAL, AND FUNCTIONAL IMAGING SE Proceedings of SPIE LA English DT Proceedings Paper CT Conference on Medical Imaging - Biomedical Applications in Molecular, Structural, and Functional Imaging CY FEB 24-26, 2015 CL Orlando, FL SP SPIE, ALIO Ind, Alpin Med Syst, Modus Med Devices Inc, Bruker ID PH; ACIDOSIS; STROKE AB Chemical exchange saturation transfer (CEST) MRI is sensitive to dilute exchangeable protons and local properties such as pH and temperate, yet its susceptibility to field inhomogeneity limits its in vivo applications. Particularly, CEST measurement varies with RF irradiation power, the dependence of which is complex due to concomitant direct RF saturation (RF spillover) effect. Because the volume transmitters provide relatively homogeneous RF field, they have been conventionally used for CEST imaging despite of their elevated specific absorption rate (SAR) and relatively low sensitivity than surface coils. To address this limitation, we developed an efficient B-1 inhomogeneity correction algorithm that enables CEST MRI using surface transceiver coils. This is built on recent work that showed the inverse CEST asymmetry analysis (CESTRind) is not susceptible to confounding RF spillover effect. We here postulated that the linear relationship between RF power level and CESTRind can be extended for correcting B-1 inhomogeneity induced CEST MRI artifacts. Briefly, we prepared a tissue-like Creatine gel pH phantom and collected multi-parametric MRI including relaxation, field map and CEST MRI under multiple RF power levels, using a conventional surface transceiver coil. The raw CEST images showed substantial heterogeneity due to B-1 inhomogeneity, with pH contrast to noise ratio (CNR) being 8.8. In comparison, pH MRI CNR of the field-inhomogeneity corrected CEST MRI was found to be 17.2, substantially higher than that without correction. To summarize, our study validated an efficient field inhomogeneity correction that enables sensitive CEST MRI with surface transceiver, promising for in vivo translation. C1 [Sun, Phillip Zhe; Zhou, Iris Yuewen; Igarashi, Takahiro; Xiao, Gang] Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Dept Radiol, Charlestown, MA 02129 USA. [Sun, Phillip Zhe; Zhou, Iris Yuewen; Igarashi, Takahiro; Xiao, Gang] Harvard Univ, Sch Med, Charlestown, MA USA. [Guo, Yingkun] Sichuan Univ, West China Univ Hosp 2, Dept Radiol, Chengdu 610064, Peoples R China. [Wu, Renhua] Shantou Univ, Affiliated Hosp 2, Coll Med, Dept Radiol, Shantou, Guangdong, Peoples R China. RP Sun, PZ (reprint author), Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Dept Radiol, Charlestown, MA 02129 USA. RI Zhou, Iris Yuwen/A-2089-2017 OI Zhou, Iris Yuwen/0000-0002-4351-7398 NR 8 TC 0 Z9 0 U1 3 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 978-1-62841-507-0 J9 PROC SPIE PY 2015 VL 9417 AR 94171H DI 10.1117/12.2082653 PG 6 WC Optics; Radiology, Nuclear Medicine & Medical Imaging SC Optics; Radiology, Nuclear Medicine & Medical Imaging GA BC8GL UT WOS:000355665600049 ER PT S AU Zhou, IY Igarashi, T Guo, Y Sun, PZ AF Zhou, Iris Yuewen Igarashi, Takahiro Guo, Yingkun Sun, Phillip Zhe BE Gimi, B Molthen, RC TI Quantification of in vivo pH-weighted amide proton transfer (APT) MRI in acute ischemic stroke SO MEDICAL IMAGING 2015: BIOMEDICAL APPLICATIONS IN MOLECULAR, STRUCTURAL, AND FUNCTIONAL IMAGING SE Proceedings of SPIE LA English DT Proceedings Paper CT Conference on Medical Imaging - Biomedical Applications in Molecular, Structural, and Functional Imaging CY FEB 24-26, 2015 CL Orlando, FL SP SPIE, ALIO Ind, Alpin Med Syst, Modus Med Devices Inc, Bruker DE CEST; Amide proton transfer (APT) imaging; MRI; Acute ischemic stroke; pH ID SATURATION-TRANSFER CEST; TRANSFER RATIO MEASUREMENTS; ACUTE CEREBRAL-ISCHEMIA; MAGNETIZATION-TRANSFER; CHEMICAL-EXCHANGE; INTRACELLULAR PH; CONTRAST AGENTS; PENUMBRA; LACTATE; ERRORS AB Amide proton transfer (APT) imaging is a specific form of chemical exchange saturation transfer (CEST) MRI that probes the pH-dependent amide proton exchange. The endogenous APT MRI is sensitive to tissue acidosis, which may complement the commonly used perfusion and diffusion scans for characterizing heterogeneous ischemic tissue damage. Whereas the saturation transfer asymmetry analysis (MTRasym) may reasonably compensate for direct RF saturation, in vivo MTRasym is however, susceptible to an intrinsically asymmetric shift (MTR'(asym)). Specifically, the reference scan for the endogenous APT MRI is 7 ppm upfield from that of the label scan, and subjects to concomitant RF irradiation effects, including nuclear overhauser effect (NOE)-mediated saturation transfer and semisolid macromolecular magnetization transfer. As such, the commonly used asymmetry analysis could not fully compensate for such slightly asymmetric concomitant RF irradiation effects, and MTRasym has to be delineated in order to properly characterize the pH-weighted APT MRI contrast. Given that there is very little change in relaxation time immediately after ischemia and the concomitant RF irradiation effects only minimally depends on pH, the APT contrast can be obtained as the difference of MTRasym between the normal and ischemic regions. Thereby, the endogenous amide proton concentration and exchange rate can be solved using a dual 2-pool model, and the in vivo MTR'(asym) can be calculated by subtracting the solved APT contrast from asymmetry analysis (i.e., MTR'(asym) = MTRasym-APTR). In addition, MTR'(asym) can be quantified using the classical 2-pool exchange model. In sum, our study delineated the conventional in vivo pH-sensitive MTRasym contrast so that pH-specific contrast can be obtained for imaging ischemic tissue acidosis. SUMMARY Amide proton transfer (APT) imaging is pH sensitive, and has been shown promising to complement perfusion and diffusion MRI for stratifying heterogeneous ischemic tissue injury. Whereas conventional asymmetry analysis (MTRasym) reasonably compensates for the direct RF saturation effect, it is susceptible to an intrinsically asymmetric shift (MTR'(asym)). To improve tissue acidosis mapping, we delineated pH-sensitive APT effect from confounding factors using an animal model of stroke. We quantified concentration and exchange rate for both APT and nuclear overhauser effects (NOE). Our study elucidated conventional pH-weighted MTRasym contrast so that more specific pH-sensitive images can be obtained for characterizing ischemic acidosis. C1 [Zhou, Iris Yuewen] Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Dept Radiol, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Charlestown, MA USA. RP Zhou, IY (reprint author), Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Dept Radiol, Charlestown, MA 02129 USA. RI Zhou, Iris Yuwen/A-2089-2017 OI Zhou, Iris Yuwen/0000-0002-4351-7398 NR 22 TC 0 Z9 0 U1 1 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 978-1-62841-507-0 J9 PROC SPIE PY 2015 VL 9417 AR 94170E DI 10.1117/12.2082683 PG 6 WC Optics; Radiology, Nuclear Medicine & Medical Imaging SC Optics; Radiology, Nuclear Medicine & Medical Imaging GA BC8GL UT WOS:000355665600012 ER PT S AU Zhou, IY Igarashi, T Guo, Y Sun, PZ AF Zhou, Iris Yuewen Igarashi, Takahiro Guo, Yingkun Sun, Phillip Zhe BE Gimi, B Molthen, RC TI Susceptibility weighted imaging of stroke brain in response to normobaric oxygen (NBO) therapy SO MEDICAL IMAGING 2015: BIOMEDICAL APPLICATIONS IN MOLECULAR, STRUCTURAL, AND FUNCTIONAL IMAGING SE Proceedings of SPIE LA English DT Proceedings Paper CT Conference on Medical Imaging - Biomedical Applications in Molecular, Structural, and Functional Imaging CY FEB 24-26, 2015 CL Orlando, FL SP SPIE, ALIO Ind, Alpin Med Syst, Modus Med Devices Inc, Bruker DE Normobaric oxygen (NBO) therapy; Acute ischemic stroke; Susceptibility weighted imaging; MRI ID FOCAL CEREBRAL-ISCHEMIA; RAT MODEL; HYPEROXIA AB The neuroprotective effect of oxygen leads to recent interest in normobaric oxygen (NBO) therapy after acute ischemic stroke. However, the mechanism remains unclear and inconsistent outcomes were reported in human studies. Because NBO aims to improve brain tissue oxygenation by enhancing oxygen delivery to ischemic tissue, monitoring the oxygenation level changes in response to NBO becomes necessary to elucidate the mechanism and to assess the efficacy. Susceptibility weighted imaging (SWI) which provides a new MRI contrast by combining the magnitude and phase images is fit for purpose. SWI is sensitive to deoxyhemoglobin level changes and thus can be used to evaluate the cerebral metabolic rate of oxygen. In this study, SWI was used for in vivo monitoring of oxygenation changes in a rat model of permanent middle cerebral artery occlusion (MCAO) before, during and after 30 min of NBO treatment. Regions of interest in ischemic core, penumbra and contralateral normal area were generated based on diffusion-weighted imaging and perfusion imaging. Significant differences in SWI indicating different oxygenation levels were generally found: contralateral normal > penumbra > ischemic core. Ischemic core showed insignificant increase in oxygenation during NBO and returned to pre-treatment level after termination of NBO. Meanwhile, the oxygenation levels slightly increased in contralateral normal and penumbra regions during NBO and significantly decreased to a level lower than pre-treatment after termination of NBO, indicating secondary metabolic disruption upon the termination of transient metabolic support from oxygen. Further investigation of NBO effect combined with reperfusion is necessary while SWI can be used to detect hemorrhagic transformation after reperfusion. SUMMARY Normobaric oxygen (NBO) is under investigation as a neuroprotective therapy for acute ischemic stroke. However, the mechanism remains unclear and inconsistent outcomes were reported. We used susceptibility weighted imaging (SWI) to monitor the oxygenation response to NBO in rat stroke model. The oxygenation levels slightly increased in contralateral normal and penumbra regions during NBO and significantly decreased to a level lower than pre-treatment after NBO stopped, indicating secondary metabolic disruption upon the termination of transient metabolic support from oxygen. Further investigation of NBO effect combined with reperfusion is necessary while SWI can be used to detect hemorrhagic transformation after reperfusion. C1 [Zhou, Iris Yuewen] Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Dept Radiol, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Charlestown, MA USA. RP Zhou, IY (reprint author), Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Dept Radiol, Charlestown, MA 02129 USA. RI Zhou, Iris Yuwen/A-2089-2017 OI Zhou, Iris Yuwen/0000-0002-4351-7398 NR 11 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 978-1-62841-507-0 J9 PROC SPIE PY 2015 VL 9417 AR 94170D DI 10.1117/12.2082655 PG 6 WC Optics; Radiology, Nuclear Medicine & Medical Imaging SC Optics; Radiology, Nuclear Medicine & Medical Imaging GA BC8GL UT WOS:000355665600011 ER PT S AU Xing, FX Ye, CY Woo, J Stone, M Prince, JL AF Xing, Fangxu Ye, Chuyang Woo, Jonghye Stone, Maureen Prince, Jerry L. BE Ourselin, S Styner, MA TI Relating Speech Production to Tongue Muscle Compressions Using Tagged and High-resolution Magnetic Resonance Imaging SO MEDICAL IMAGING 2015: IMAGE PROCESSING SE Proceedings of SPIE LA English DT Proceedings Paper CT Conference on Medical Imaging - Image Processing CY FEB 24-26, 2015 CL Orlando, FL SP SPIE, ALIO Ind, Alpin Med Syst, Modus Med Devices Inc, Bruker, American Assoc Physicists Med, American Physiolog Soc, Comp Assisted Radiol & Surg, Med Image Percept Soc, Radiolog Soc N America, Soc Imaging Informat Med, World Mol Imaging Soc, DICOM Stand Comm DE Speech; tongue; muscle; MRI; tagged; motion; strain; fiber; compression ID CANCER; MOTION; MRI AB The human tongue is composed of multiple internal muscles that work collaboratively during the production of speech. Assessment of muscle mechanics can help understand the creation of tongue motion, interpret clinical observations, and predict surgical outcomes. Although various methods have been proposed for computing the tongue's motion, associating motion with muscle activity in an interdigitated fiber framework has not been studied. In this work, we aim to develop a method that reveals different tongue muscles' activities in different time phases during speech. We use four-dimensional tagged magnetic resonance (MR) images and static high-resolution MR images to obtain tongue motion and muscle anatomy, respectively. Then we compute strain tensors and local tissue compression along the muscle fiber directions in order to reveal their shortening pattern. This process relies on the support from multiple image analysis methods, including super-resolution volume reconstruction from MR image slices, segmentation of internal muscles, tracking the incompressible motion of tissue points using tagged images, propagation of muscle fiber directions over time, and calculation of strain in the line of action, etc. We evaluated the method on a control subject and two post-glossectomy patients in a controlled speech task. The normal subject's tongue muscle activity shows high correspondence with the production of speech in different time instants, while both patients' muscle activities show different patterns from the control due to their resected tongues. This method shows potential for relating overall tongue motion to particular muscle activity, which may provide novel information for future clinical and scientific studies. C1 [Xing, Fangxu; Ye, Chuyang; Prince, Jerry L.] Johns Hopkins Univ, Dept Elect & Comp Engn, Baltimore, MD 21218 USA. [Woo, Jonghye] Massachusetts Gen Hosp, Ctr Adv Med Imaging Sci, Boston, MA 02114 USA. [Stone, Maureen] Univ Maryland, Sch Dent, Dept Neural & Pain Sci, Baltimore, MD 21201 USA. RP Xing, FX (reprint author), Johns Hopkins Univ, Dept Elect & Comp Engn, Image Anal & Commun Lab, Baltimore, MD 21218 USA. EM fxing1@jhu.edu NR 13 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 978-1-62841-503-2 J9 PROC SPIE PY 2015 VL 9413 AR 94131L DI 10.1117/12.2081652 PG 6 WC Optics; Radiology, Nuclear Medicine & Medical Imaging SC Optics; Radiology, Nuclear Medicine & Medical Imaging GA BC8GE UT WOS:000355653800055 ER PT J AU Marzec, LN Carey, EP Lambert-Kerzner, AC Del Giacco, EJ Melnyk, SD Bryson, CL Fahdi, IE Bosworth, HB Fiocchi, F Ho, PM AF Marzec, Lucas N. Carey, Evan P. Lambert-Kerzner, Anne C. Del Giacco, Eric J. Melnyk, Stephanie D. Bryson, Chris L. Fahdi, Ibrahim E. Bosworth, Hayden B. Fiocchi, Fran Ho, P. Michael TI Cognitive dysfunction and poor health literacy are common in veterans presenting with acute coronary syndrome: insights from the MEDICATION study SO PATIENT PREFERENCE AND ADHERENCE LA English DT Article DE medication adherence ID UNIVERSITY MENTAL STATUS; MYOCARDIAL-INFARCTION; HOSPITAL DISCHARGE; HEART-FAILURE; ADHERENCE; INTERVENTION; DEMENTIA; DISCONTINUATION; PREVALENCE; MORTALITY AB Background: Patient nonadherence to cardiac medications following acute coronary syndrome (ACS) is associated with increased risk of recurrent events. However, the prevalence of cognitive dysfunction and poor health literacy among ACS patients and their association with medication nonadherence are poorly understood. Methods: We assessed rates of cognitive dysfunction and poor health literacy among participants of a clinical trial that tested the effectiveness of an intervention to improve medication adherence in patients hospitalized with ACS. Of 254 patients, 249 completed the Rapid Estimate of Adult Literacy in Medicine, Revised (REALM-R) survey, an assessment of risk for poor literacy, and the St Louis University Mental Status (SLUMS) exam, a tool assessing for neurocognitive deficits, during ACS hospitalization. We assessed if SLUMS or REALM-R scores were associated with medication adherence. Results: Based on SLUMS score, 14% of patients were categorized as having dementia, and 52% with mild neurocognitive disorder (MNCD). Based on REALM-R score of. 6, 34% of patients were categorized as at risk for poor health literacy. There was no association between poor health literacy and medication nonadherence. Of those with MNCD, 35.5% were nonadherent, compared to 17.5% with normal cognitive function and 6.7% with dementia. In multivariable analysis, cognitive dysfunction was associated with medication nonadherence (P=0.007), mainly due to an association between MNCD and nonadherence (odds ratio = 12.2, 95% confidence interval = 1.9 to 243; P= 0.007). Cognitive status was not associated with adherence in patients randomized to the intervention. Conclusion: Cognitive dysfunction and risk for poor health literacy are common in patients hospitalized with ACS. We found an association between MNCD and medication nonadherence in the usual care group but not in the intervention group. These findings suggest efforts to screen for MNCD are needed during ACS hospitalization to identify patients at risk for nonadherence and who may benefit from an adherence intervention. C1 [Marzec, Lucas N.; Carey, Evan P.; Lambert-Kerzner, Anne C.; Ho, P. Michael] Denver VA Med Ctr, Div Cardiol, Denver, CO USA. [Del Giacco, Eric J.; Fahdi, Ibrahim E.] Little Rock VA Med Ctr, Dept Med, Little Rock, AR USA. [Melnyk, Stephanie D.; Bosworth, Hayden B.] Durham VA Med Ctr, Dept Med, Durham, NC USA. [Bryson, Chris L.] Puget Sound VA Med Ctr, Dept Med, Seattle, WA USA. [Fiocchi, Fran] Amer Coll Cardiol, Washington, DC USA. RP Marzec, LN (reprint author), Acad Off 1, Room 7104,12631 E 17th Ave,Campus Box B-130, Aurora, CO 80045 USA. EM lucas.marzec@ucdenver.edu NR 22 TC 0 Z9 0 U1 2 U2 2 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 2015 VL 9 BP 745 EP 751 DI 10.2147/PPA.S75110 PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA CJ9WW UT WOS:000355855000001 PM 26089651 ER PT J AU Kim, KS Hong, SW Kim, H Cho, M Kim, S Hur, W Yun, SH Yoon, SK Hahn, SK AF Kim, Ki Su Hong, Sung Woo Kim, Hyemin Cho, Minsoo Kim, Seonghoon Hur, Wonhee Yun, Seok Hyun Yoon, Seung Kew Hahn, Sei Kwang TI Hyaluronate-Flt1 peptide conjugate/epirubicin micelles for theranostic application to liver cancers SO RSC ADVANCES LA English DT Article ID HYALURONIC-ACID DERIVATIVES; DRUG-DELIVERY SYSTEMS; POLYMERIC MICELLES; ANTI-FLT1 PEPTIDE; CONJUGATE; DOXORUBICIN; NEOVASCULARIZATION; NANOPARTICLES; EPIRUBICIN; RECEPTOR AB Cancer theranostic systems using polymeric micelles are emerging for simultaneous diagnosis and therapy. In this work, we have developed hyaluronate (HA)-Flt1 peptide conjugate micelles encapsulating epirubicin for theranostic treatment of hepatocellular carcinoma. Intravital bioimaging without labelling and in vivo anti-tumor therapeutic effect clearly confirmed the feasibility of HA-Flt1 peptide conjugate/epirubicin micelles for target-specific theranostic treatment of liver cancers. C1 [Kim, Ki Su; Yun, Seok Hyun] Massachusetts Gen Hosp, Wellman Ctr Photomed, Cambridge, MA 02139 USA. [Kim, Ki Su; Yun, Seok Hyun] Harvard Univ, Sch Med, Cambridge, MA 02139 USA. [Hong, Sung Woo; Hur, Wonhee; Yoon, Seung Kew] Catholic Univ Korea, Liver Res Ctr, Seoul 137701, South Korea. [Hong, Sung Woo; Hur, Wonhee; Yoon, Seung Kew] Catholic Univ Korea, WHO Collaborating Ctr Viral Hepatitis, Seoul 137701, South Korea. [Kim, Hyemin; Cho, Minsoo; Hahn, Sei Kwang] Pohang Univ Sci & Technol POSTECH, Dept Mat Sci & Engn, Pohang 790784, Gyeongbuk, South Korea. [Kim, Seonghoon] Korea Adv Inst Sci & Technol, Grad Sch Nanosci & Technol, Taejon 305338, South Korea. RP Hahn, SK (reprint author), Pohang Univ Sci & Technol POSTECH, Dept Mat Sci & Engn, 77 Cheongam Ro, Pohang 790784, Gyeongbuk, South Korea. EM skhanb@postech.ac.kr FU Korean Health Technology R&D Project, Ministry of Health and Welfare, Korea [HI14C1658]; Bio & Medical Technology Development Program of the National Research Foundation (NRF) - Korean government (MEST) [2012M3A9C6049791] FX This research was supported by a grant of the Korean Health Technology R&D Project, Ministry of Health and Welfare, Korea (HI14C1658) and the Bio & Medical Technology Development Program (no. 2012M3A9C6049791) of the National Research Foundation (NRF) funded by the Korean government (MEST). NR 23 TC 3 Z9 3 U1 0 U2 14 PU ROYAL SOC CHEMISTRY PI CAMBRIDGE PA THOMAS GRAHAM HOUSE, SCIENCE PARK, MILTON RD, CAMBRIDGE CB4 0WF, CAMBS, ENGLAND SN 2046-2069 J9 RSC ADV JI RSC Adv. PY 2015 VL 5 IS 60 BP 48615 EP 48618 DI 10.1039/c5ra07464a PG 4 WC Chemistry, Multidisciplinary SC Chemistry GA CJ8GN UT WOS:000355738300056 ER PT J AU Eswara, JR Heney, NM Wu, CL McDougal, WS AF Eswara, Jairam R. Heney, Niall M. Wu, Chin-Lee McDougal, W. Scott TI Long-Term Outcomes of Organ Preservation in Patients with Small Cell Carcinoma of the Bladder SO UROLOGIA INTERNATIONALIS LA English DT Article DE Small cell carcinoma; Bladder; Cystectomy; Chemotherapy; Radiation ID URINARY-BLADDER; CLINICOPATHOLOGICAL ANALYSIS; UROTHELIAL CANCER; CHEMOTHERAPY; EXPERIENCE; SURVIVAL; TRACT AB Background: Small cell carcinoma of the bladder is an uncommon but clinically aggressive disease. There is no standard surgical or medical management for the disease. Methods: Between 1995 and 2009, 28 patients underwent transurethral resection (TUR) and/or cystectomy, chemotherapy, and/or radiation for small cell carcinoma of the bladder at our institution. Results: The median follow-up for survivors was 34 months. Patients presented most often with muscle-invasive disease (T2-4 - 89%), and 21% had lymph node/ distant metastases. Tobacco use and chemical exposure were noted in 64 and 4% of patients, respectively. Patients with T1-2N0M0 had a median survival of 22 months compared to 8 months for those with more advanced disease (p = 0.03). Patients with T3-4 or nodal/metastatic disease who were given chemotherapy had an improved survival compared to those with T3-4 or nodal/metastatic disease who did not undergo chemotherapy (13 vs. 4 months, p =0.005). The median time to recurrence of the entire cohort was 8 months, overall and cancer-specific survival was 14 months, and 5-year survival was 11%. Conclusions: Small cell carcinoma of the bladder is an aggressive disease with poor outcomes. Patients with T1-2N0M0 disease survived longer than those with advanced disease. Patients with T3-4 or nodal/metastatic disease had improved survival with chemotherapy. (C) 2015 S. Karger AG, Basel C1 [Eswara, Jairam R.; Heney, Niall M.; McDougal, W. Scott] Massachusetts Gen Hosp, Dept Urol, Boston, MA 02114 USA. [Wu, Chin-Lee] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. RP Eswara, JR (reprint author), Massachusetts Gen Hosp, Dept Urol, 55 Fruit St, Boston, MA 02114 USA. EM jeswara@partners.org NR 15 TC 3 Z9 3 U1 1 U2 2 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0042-1138 EI 1423-0399 J9 UROL INT JI Urol.Int. PY 2015 VL 94 IS 4 BP 401 EP 405 DI 10.1159/000366522 PG 5 WC Urology & Nephrology SC Urology & Nephrology GA CK0GZ UT WOS:000355885000005 PM 25660255 ER PT J AU Geiger-Gritsch, S Oberaigner, W Muhlberger, N Siebert, U Ladurner, M Klocker, H Horninger, W AF Geiger-Gritsch, Sabine Oberaigner, Wilhelm Muehlberger, Nikolai Siebert, Uwe Ladurner, Michael Klocker, Helmut Horninger, Wolfgang TI Patient-Reported Urinary Incontinence and Erectile Dysfunction Following Radical Prostatectomy: Results from the European Prostate Centre Innsbruck SO UROLOGIA INTERNATIONALIS LA English DT Article DE Erectile dysfunction; Prostatectomy; Prostatic neoplasms; Urinary incontinence ID QUALITY-OF-LIFE; SURGICAL APPROACH; CANCER MORTALITY; CONTINENCE; METAANALYSIS; POTENCY; OUTCOMES; IMPACT; TRIAL; INDEX AB Introduction: Urinary and erectile functions were assessed by using self-administered validated questionnaires in patients undergoing radical prostatectomy. Materials and Methods: In a prospective observational study, a total of 253 consecutive patients diagnosed with clinically localised prostate cancer between 2008 and 2009 at the European Prostate Centre Innsbruck were included. Patient-reported outcomes were assessed before radical prostatectomy and 12 months postoperatively using the validated International Consultation on Incontinence Questionnaire (ICIQ) and the International Index of Erectile Function (IIEF). The Wilcoxon signed-rank test and Chi square statistics were used for analysis. Results: The study showed that before radical prostatectomy, urinary incontinence of various severity grades was reported in 18.8, postoperatively in 63.0% (p < 0.001) and erectile dysfunction of various degrees was reported in 39.6 at baseline compared to 80.1% 12 months postoperatively (p < 0.001). Conclusions: This study suggests that radical prostatectomy is associated with a significantly increased risk of urinary incontinence and erectile dysfunction 12 months postoperatively. (C) 2015 S. Karger AG, Basel C1 [Geiger-Gritsch, Sabine; Oberaigner, Wilhelm] Canc Registry Tyrol, Tyrolean State Hosp Ltd, Dept Clin Epidemiol, A-6020 Innsbruck, Austria. [Geiger-Gritsch, Sabine; Oberaigner, Wilhelm; Muehlberger, Nikolai; Siebert, Uwe] UMIT Univ Hlth Sci Med Informat & Technol, Dept Publ Hlth & Hlth Technol Assessment, Hall In Tirol, Austria. [Muehlberger, Nikolai; Siebert, Uwe] Med Univ Innsbruck, Oncotyrol Ctr Personalised Canc Med, Area Hlth Technol Assessment & Bioinformat 4, A-6020 Innsbruck, Austria. [Ladurner, Michael; Klocker, Helmut; Horninger, Wolfgang] Med Univ Innsbruck, Dept Urol, A-6020 Innsbruck, Austria. [Siebert, Uwe] Harvard Univ, Sch Publ Hlth, Massachusetts Gen Hosp, Inst Technol Assessment, Boston, MA 02115 USA. [Siebert, Uwe] Harvard Univ, Sch Publ Hlth, Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02115 USA. [Siebert, Uwe] Harvard Univ, Sch Publ Hlth, Dept Hlth Policy & Management, Ctr Hlth Decis Sci, Boston, MA 02115 USA. RP Geiger-Gritsch, S (reprint author), Canc Registry Tyrol, Tyrolean State Hosp Ltd, Dept Clin Epidemiol, Anichstr 35, A-6020 Innsbruck, Austria. EM Sabine.Geiger-Gritsch@tilak.at FU COMET Center ONCOTYROL - Austrian Federal Ministries BMVIT/BMWFJ (via FFG); Tiroler Zukunftsstiftung/Standortagentur Tirol (SAT) FX This work was supported by the COMET Center ONCOTYROL, which is funded by the Austrian Federal Ministries BMVIT/BMWFJ (via FFG) and the Tiroler Zukunftsstiftung/Standortagentur Tirol (SAT). NR 37 TC 5 Z9 5 U1 1 U2 1 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0042-1138 EI 1423-0399 J9 UROL INT JI Urol.Int. PY 2015 VL 94 IS 4 BP 419 EP 427 DI 10.1159/000369475 PG 9 WC Urology & Nephrology SC Urology & Nephrology GA CK0GZ UT WOS:000355885000008 PM 25662301 ER PT J AU Patel, V Zhang, XL Tautiva, NA Nyabera, AN Owa, OO Baidya, M Sung, HC Taunk, PS Abdollahi, S Charles, S Gonnella, RA Gadi, N Duong, KT Fawver, JN Ran, CZ Jalonen, TO Murray, IVJ AF Patel, Viharkumar Zhang, Xueli Tautiva, Nicolas A. Nyabera, Akwe N. Owa, Opeyemi O. Baidya, Melvin Sung, Hee Chang Taunk, Pardeep S. Abdollahi, Shahrzad Charles, Stacey Gonnella, Rachel A. Gadi, Nikhita Duong, Karen T. Fawver, Janelle N. Ran, Chongzhao Jalonen, Tuula O. Murray, Ian V. J. TI Small Molecules and Alzheimer's Disease: Misfolding, Metabolism and Imaging SO CURRENT ALZHEIMER RESEARCH LA English DT Article DE Alzheimer's disease; amyloid binding; animal models; ATP; brain imaging; near infrared fluorescence; small compounds ID IN-VIVO DETECTION; A-BETA OLIGOMERS; MILD COGNITIVE IMPAIRMENT; UNFOLDED PROTEIN RESPONSE; TRANSGENIC MOUSE MODEL; POSITRON-EMISSION-TOMOGRAPHY; AMYLOID PRECURSOR PROTEIN; OXIDATIVE STRESS; METHYLENE-BLUE; ENDOPLASMIC-RETICULUM AB Small molecule interactions with amyloid proteins have had a huge impact in Alzheimer's disease (AD), especially in three specific areas: amyloid folding, metabolism and brain imaging. Amyloid plaque amelioration or prevention have, until recently, driven drug development, and only a few drugs have been advanced for use in AD. Amyloid proteins undergo misfolding and oligomerization via intermediates, eventually forming protease resistant amyloid fibrils. These fibrils accumulate to form the hallmark amyloid plaques and tangles of AD. Amyloid binding compounds can be grouped into three categories, those that: i) prevent or reverse misfolding, ii) halt misfolding or trap intermediates, and iii) accelerate the formation of stable and inert amyloid fibrils. Such compounds include hydralazine, glycosaminoglycans, curcumin, beta sheet breakers, catecholamines, and ATP. The versatility of amyloid binding compounds suggests that the amyloid structure may serve as a scaffold for the future development of sensors to detect such compounds. Metabolic dysfunction is one of the earliest pathological features of AD. In fact, AD is often referred to as type 3 diabetes due to the presence of insulin resistance in the brain. A recent study indicates that altering metabolism improves cognitive function. While metabolic reprogramming is one therapeutic avenue for AD, it is more widely used in some cancer therapies. FDA approved drugs such as metformin, dichloroacetic acid (DCA), and methylene blue can alter metabolism. These drugs can therefore be potentially applied in alleviating metabolic dysfunction in AD. Brain imaging has made enormous strides over the past decade, offering a new window to the mind. Recently, there has been remarkable development of compounds that have the ability to image both types of pathological amyloids: tau and amyloid beta. We have focused on the low cost, simple to use, near infrared fluorescence (NIRF) imaging probes for amyloid beta (A beta), with specific attention on recent developments to further improve contrast, specificity, and sensitivity. With advances in imaging technologies, such fluorescent imaging probes will open new diagnostic avenues. C1 [Patel, Viharkumar; Tautiva, Nicolas A.; Nyabera, Akwe N.; Owa, Opeyemi O.; Baidya, Melvin; Sung, Hee Chang; Taunk, Pardeep S.; Abdollahi, Shahrzad; Charles, Stacey; Gonnella, Rachel A.; Gadi, Nikhita; Jalonen, Tuula O.; Murray, Ian V. J.] St Georges Univ, Sch Med, Dept Physiol & Neurosci, St Georges, Grenada. [Zhang, Xueli] Southeast Univ, ZhongDa Hosp, Dept Pharm, Nanjing 210009, Jiangsu, Peoples R China. [Ran, Chongzhao] Harvard Univ, Massachusetts Gen Hosp, Sch Med,Dept Radiol,Mol Imaging Lab, MGH MIT HMS Athinoula Martinos Ctr Biomed Imaging, Charlestown, MA USA. RP Murray, IVJ (reprint author), St Georges Univ, Dept Physiol & Neurosci, POB 7, St Georges, Grenada. EM imurray@sgu.edu NR 230 TC 9 Z9 9 U1 4 U2 41 PU BENTHAM SCIENCE PUBL LTD PI SHARJAH PA EXECUTIVE STE Y-2, PO BOX 7917, SAIF ZONE, 1200 BR SHARJAH, U ARAB EMIRATES SN 1567-2050 EI 1875-5828 J9 CURR ALZHEIMER RES JI Curr. Alzheimer Res. PY 2015 VL 12 IS 5 BP 445 EP 461 PG 17 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA CJ0ST UT WOS:000355189000007 PM 25938871 ER PT J AU Marshall, GA Zoller, AS Lorius, N Amariglio, RE Locascio, JJ Johnson, KA Sperling, RA Rentz, DM AF Marshall, Gad A. Zoller, Amy S. Lorius, Natacha Amariglio, Rebecca E. Locascio, Joseph J. Johnson, Keith A. Sperling, Reisa A. Rentz, Dorene M. CA Alzheimer's Dis Neuroimaging Initi TI Functional Activities Questionnaire Items that Best Discriminate and Predict Progression from Clinically Normal to Mild Cognitive Impairment SO CURRENT ALZHEIMER RESEARCH LA English DT Article DE Activities of daily living; Alzheimer's disease; clinical assessment; clinically normal elderly; daily functioning; mild cognitive impairment ID ALZHEIMERS-DISEASE SPECTRUM; DATA SET UDS; INSTRUMENTAL ACTIVITIES; EVERYDAY FUNCTION; DEMENTIA; COMMUNITY; ASSOCIATION; CENTERS; DECLINE; SELF AB Background: Impairment in instrumental activities of daily living (IADL) emerges in the transition from mild cognitive impairment (MCI) to Alzheimer's disease (AD) dementia. Some IADL scales are sensitive to early deficits in MCI, but none have been validated for detecting subtle functional changes in clinically normal (CN) elderly at risk for AD. Methods: Data from 624 subjects participating in the Alzheimer's Disease Neuroimaging Initiative and 524 subjects participating in the Massachusetts Alzheimer's Disease Research Center, which are two large cohorts including CN elderly and MCI subjects, were used to determine which Functional Activities Questionnaire items best discriminate between and predict progression from CN to MCI. Results: We found that "Remembering appointments" and "assembling tax records" best discriminated between CN and MCI subjects, while worse performance on "paying attention and understanding a TV program", "paying bills/balancing checkbook", and "heating water and turning off the stove" predicted greater hazard of progressing from a diagnosis of CN to MCI. Conclusions: These results demonstrate that certain questions are especially sensitive in detecting the earliest functional changes in CN elderly at risk for AD. As the field moves toward earlier intervention in preclinical AD, it is important to determine which IADL changes can be detected at that stage and track decline over time. C1 [Marshall, Gad A.; Lorius, Natacha; Amariglio, Rebecca E.; Johnson, Keith A.; Sperling, Reisa A.; Rentz, Dorene M.] Harvard Univ, Sch Med, Brigham & Womens Hosp, Ctr Alzheimer Res & Treatment, Boston, MA 02115 USA. [Marshall, Gad A.; Lorius, Natacha; Amariglio, Rebecca E.; Johnson, Keith A.; Sperling, Reisa A.; Rentz, Dorene M.] Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Neurol, Boston, MA 02115 USA. [Marshall, Gad A.; Zoller, Amy S.; Lorius, Natacha; Amariglio, Rebecca E.; Locascio, Joseph J.; Johnson, Keith A.; Sperling, Reisa A.; Rentz, Dorene M.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Massachusetts Alzheimers Dis Res Ctr, Boston, MA 02114 USA. [Marshall, Gad A.; Lorius, Natacha; Amariglio, Rebecca E.; Locascio, Joseph J.; Sperling, Reisa A.; Rentz, Dorene M.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Neurol, Boston, MA 02114 USA. [Zoller, Amy S.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Psychiat, Boston, MA 02114 USA. [Johnson, Keith A.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiol, Boston, MA 02114 USA. RP Marshall, GA (reprint author), Brigham & Womens Hosp, Ctr Alzheimer Res & Treatment, 221 Longwood Ave,BL-104H, Boston, MA 02115 USA. EM gamarshall@partners.org FU ADNI [U01 AG024904]; DOD ADNI [W81XWH-12-2-0012]; MADRC [P50 AG005134, R01 AG027435, K23 AG033634, K24 AG035007]; Harvard Aging Brain Study [P01 AGO36694]; National Institute on Aging; National Institute of Biomedical Imaging and Bioengineering; Canadian Institutes of Health Research FX This study was supported by ADNI (U01 AG024904), DOD ADNI (W81XWH-12-2-0012), the MADRC (P50 AG005134), R01 AG027435, K23 AG033634, K24 AG035007, and the Harvard Aging Brain Study (P01 AGO36694). ADNI is funded by the National Institute on Aging, the National Institute of Biomedical Imaging and Bioengineering, and through generous contributions from the following: Alzheimer's Association; Alzheimer's Drug Discovery Foundation; BioClinica, Inc.; Biogen Idec Inc.; Bristol- Myers Squibb Company; Eisai Inc.; Elan Pharmaceuticals, Inc.; Eli Lilly and Company; F. Hoffmann-La Roche Ltd and its affiliated company Genentech, Inc.; GE Healthcare; Innogenetics, N. V.; IXICO Ltd.; Janssen Alzheimer Immunotherapy Research & Development, LLC.; Johnson & Johnson Pharmaceutical Research & Development LLC.; Medpace, Inc.; Merck & Co., Inc.; Meso Scale Diagnostics, LLC.; NeuroRx Research; Novartis Pharmaceuticals Corporation; Pfizer Inc.; Piramal Imaging; Servier; Synarc Inc.; and Takeda Pharmaceutical Company. The Canadian Institutes of Health Research is providing funds to support ADNI clinical sites in Canada. Private sector contributions are facilitated by the Foundation for the National Institutes of Health (www.fnih.org). The grantee organization is the Northern California Institute for Research and Education, and the study is coordinated by the Alzheimer's Disease Cooperative Study at the University of California, San Diego. ADNI data are disseminated by the Laboratory for Neuro Imaging at the University of Southern California. NR 41 TC 0 Z9 0 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 1567-2050 EI 1875-5828 J9 CURR ALZHEIMER RES JI Curr. Alzheimer Res. PY 2015 VL 12 IS 5 BP 493 EP 502 PG 10 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA CJ0ST UT WOS:000355189000010 PM 26017560 ER PT J AU Dording, CM Schettler, PJ Dalton, ED Parkin, SR Walker, RSW Fehling, KB Fava, M Mischoulon, D AF Dording, Christina M. Schettler, Pamela J. Dalton, Elizabeth D. Parkin, Susannah R. Walker, Rosemary S. W. Fehling, Kara B. Fava, Maurizio Mischoulon, David TI A Double-Blind Placebo-Controlled Trial of Maca Root as Treatment for Antidepressant-Induced Sexual Dysfunction in Women SO EVIDENCE-BASED COMPLEMENTARY AND ALTERNATIVE MEDICINE LA English DT Article ID LEPIDIUM-MEYENII MACA; ADULT HEALTHY-MEN; DESIRE DISORDER; EXTRACT; RATS; QUESTIONNAIRE; BUPROPION; SYMPTOMS; VALIDITY; BEHAVIOR AB Objective. We sought to demonstrate that maca root may be an effective treatment for antidepressant-induced sexual dysfunction (AISD) in women. Method. We conducted a 12-week, double-blind, placebo-controlled trial of maca root (3.0 g/day) in 45 female outpatients (mean age of 41.5 +/- 12.5 years) with SSRI/SNRI-induced sexual dysfunction whose depression remitted. Endpoints were improvement in sexual functioning as per the Arizona Sexual Experience Scale (ASEX) and the Massachusetts General Hospital Sexual Function Questionnaire (MGH-SFQ). Results. 45 of 57 consented females were randomized, and 42 (30 premenopausal and 12 postmenopausal women) were eligible for a modified intent-to-treat analysis based on having had at least one postmedication visit. Remission rates by the end of treatment were higher for the maca than the placebo group, based on attainment of an ASEX total score <= 10 (9.5% for maca versus 4.8% for placebo), attaining an MGH-SFQ score <= 12 (30.0% for maca versus 20.0% for placebo) and reaching an MGH-SFQ score <= 8 (9.5% for maca versus 5.0% for placebo). Higher remission rates for the maca versus placebo group were associated with postmenopausal status. Maca was well tolerated. Conclusion. Maca root may alleviate SSRI-induced sexual dysfunction in postmenopausal women. This trial is registered with NCT00568126. C1 [Dording, Christina M.; Dalton, Elizabeth D.; Parkin, Susannah R.; Walker, Rosemary S. W.; Fehling, Kara B.; Fava, Maurizio; Mischoulon, David] Massachusetts Gen Hosp, Dept Psychiat, Depress Clin & Res Program, Boston, MA 02114 USA. [Schettler, Pamela J.] Emory Univ, Dept Psychiat & Behav Sci, Atlanta, GA 30322 USA. RP Dording, CM (reprint author), Massachusetts Gen Hosp, Dept Psychiat, Depress Clin & Res Program, Boston, MA 02114 USA. EM cdording@partners.org FU National Center of Complementary and Alternative Medicine (NCCAM) FX Dr. Christina M. Dording was supported by an R21 grant from the National Center of Complementary and Alternative Medicine (NCCAM). NR 35 TC 1 Z9 1 U1 3 U2 18 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 2015 AR 949036 DI 10.1155/2015/949036 PG 9 WC Integrative & Complementary Medicine SC Integrative & Complementary Medicine GA CJ4TQ UT WOS:000355480200001 ER PT J AU Fleming, JT Clark, S Camargo, CA Rudders, SA AF Fleming, Jude T. Clark, Sunday Camargo, Carlos A., Jr. Rudders, Susan A. TI Early Treatment of Food-Induced Anaphylaxis with Epinephrine Is Associated with a Lower Risk of Hospitalization SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY-IN PRACTICE LA English DT Article DE Food allergy; Epinephrine; Early treatment; Pediatrics; Emergency department; Anaphylaxis; Hospitalization ID EMERGENCY-DEPARTMENT; INJECTABLE EPINEPHRINE; UNITED-STATES; ALLERGY; MANAGEMENT; CHILDREN; UPDATE; GUIDELINES; EPIPEN AB BACKGROUND: Food-induced anaphylaxis (FIA) is potentially life threatening. Prompt administration of epinephrine is universally recommended by current treatment guidelines. OBJECTIVE: To identify factors associated with early epinephrine treatment for FIA and to specifically examine the association between early epinephrine treatment and hospitalization. METHODS: A chart review study conducted at Hasbro Children's Hospital/Rhode Island Hospital. By using the International Classification of Diseases, Ninth Revision codes, we identified all patients who presented to the emergency department with FIA between January 1, 2004, and December 31, 2009. Early epinephrine treatment was defined as receipt of epinephrine before arrival to the emergency department. The independent association between early epinephrine treatment and hospitalization was assessed using logistic regression. RESULTS: Among the 384 emergency department visits for FIA identified during the study period, 234 patients received epinephrine (61%). Among this subset, most (164 [70%]) received early epinephrine treatment, whereas a smaller number of patients (70 [30%]) first received epinephrine in the emergency department (late treatment). Patients who received early epinephrine treatment were older (7.4 vs 4.3 years; P = .008), were more likely to have a known food allergy (66% vs 34%; P < .001), and were more likely to own an epinephrine autoinjector (80% vs 23%; P < .001). Patients treated early were less likely to be hospitalized (17% vs 43%; P < .001). After adjusting for age, sex, and race, the patients who received early epinephrine treatment remained at significantly decreased risk of hospitalization compared with those who received late epinephrine treatment (odds ratio 0.25 [95% CI, 0.12-0.49]). CONCLUSIONS: In this population, early treatment of FIA with epinephrine was associated with significantly lower risk of hospitalization. Accordingly, this study supports the benefit of prompt administration of epinephrine for the treatment of FIA. (C) 2014 American Academy of Allergy, Asthma & Immunology C1 [Fleming, Jude T.; Rudders, Susan A.] Brown Univ, Hasbro Childrens Hosp, Rhode Isl Hosp, Div Asthma & Allergy,Dept Pediat,Alpert Med Sch, Providence, RI 02912 USA. [Clark, Sunday] Weill Cornell Med Coll, Dept Emergency Med, New York, NY USA. [Camargo, Carlos A., Jr.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Emergency Med, Boston, MA USA. [Camargo, Carlos A., Jr.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Allergy Immunol,Dept Med, Boston, MA USA. RP Rudders, SA (reprint author), Rhode Isl Hosp, Hasbro Childrens Hosp, 593 Eddy St, Providence, RI 02906 USA. EM srudders@lifespan.org FU Department of Pediatrics at Hasbro Children's Hospital/Rhode Island Hospital FX The study was supported, in part, by institutional funding from the Department of Pediatrics at Hasbro Children's Hospital/Rhode Island Hospital. NR 26 TC 17 Z9 17 U1 5 U2 9 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 2213-2198 EI 2213-2201 J9 J ALLER CL IMM-PRACT JI J. Allergy Clin. Immunol.-Pract. PD JAN-FEB PY 2015 VL 3 IS 1 BP 57 EP 62 DI 10.1016/j.jaip.2014.07.004 PG 6 WC Allergy; Immunology SC Allergy; Immunology GA CH7IS UT WOS:000354210100008 PM 25577619 ER PT J AU Guyer, AC Saff, RR Conroy, M Blumenthal, KG Camargo, CA Long, AA Banerji, A AF Guyer, Autumn C. Saff, Rebecca R. Conroy, Michelle Blumenthal, Kimberly G. Camargo, Carlos A., Jr. Long, Aidan A. Banerji, Aleena TI Comprehensive Allergy Evaluation Is Useful in the Subsequent Care of Patients with Drug Hypersensitivity Reactions During Anesthesia SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY-IN PRACTICE LA English DT Article DE Allergic reactions during anesthesia; Drug allergy; Drug hypersensitivity reaction; General anesthetics; Hypersensitivity reactions during anesthesia; Intraoperative anaphylaxis; Perioperative anaphylaxis; Tryptase ID ANAPHYLACTOID REACTIONS; RISK STRATIFICATION; CLINICAL-FEATURES; MASTOCYTOSIS; FRANCE; ANTIBIOTICS; GRANISETRON; ONDANSETRON; GUIDELINES; MANAGEMENT AB BACKGROUND: For patients with a history of drug hypersensitivity reaction (HSR) during anesthesia, strategies to minimize risk with subsequent anesthesia are unclear. Identification of the cause of HSR during anesthesia remains challenging. OBJECTIVE: To determine the success of a comprehensive allergy evaluation and management plan for patients with HSR during anesthesia, including identification of the causative agent and review of outcomes during subsequent anesthesia exposure. METHODS: We performed chart reviews of patients referred for the evaluation of HSR during anesthesia between 2003 and 2012. Data collection included patient characteristics, signs/symptoms of HSR during anesthesia, and subsequent outcomes. Patients underwent comprehensive allergy evaluation including skin testing for identifying potential culprit agents, and the results were used to provide recommendations for any subsequent anesthesia. RESULTS: Over the 10-year study period, 73 patients with HSR during anesthesia were referred for further evaluation. Thirteen patients (18%) had positive skin test results to a drug received during anesthesia. One patient with a positive skin test result was diagnosed with mastocytosis. The causative agents identified in these 13 patients included latex, beta-lactam antibiotics, neuromuscular blockers, tetracaine, odansetron, and fentanyl. On follow-up, 47 of the 73 patients (64%) subsequently underwent procedures requiring anesthesia. Using our recommendations from evaluation and testing, 45 of these 47 patients (96%) successfully tolerated subsequent anesthesia. The 2 patients who developed recurrent HSR during anesthesia were later diagnosed with mast cell disorders. CONCLUSIONS: Our comprehensive evaluation and management plan minimizes risk with subsequent anesthesia even when the cause of HSR could not be identified. Baseline tryptase levels may be helpful in this patient population to diagnose mast cell disorders. (C) 2014 American Academy of Allergy, Asthma & Immunology C1 [Guyer, Autumn C.] Beth Israel Deaconess Med Ctr, Div Allergy & Inflammat, Dept Med, Brookline, MA 02445 USA. [Saff, Rebecca R.; Conroy, Michelle; Blumenthal, Kimberly G.; Camargo, Carlos A., Jr.; Long, Aidan A.; Banerji, Aleena] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Div Rheumatol Allergy & Immunol,Dept Med, Boston, MA USA. [Camargo, Carlos A., Jr.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Emergency Med, Boston, MA USA. RP Guyer, AC (reprint author), Beth Israel Deaconess Med Ctr, Div Allergy & Inflammat, Dept Med, One Brookline Pl,Ste 623, Brookline, MA 02445 USA. EM aguyer@bidmc.harvard.edu FU First Consult FX A. Guyer has received payment for manuscript development from First Consult and receives royalties from UpToDate. The rest of the authors declare that they have no relevant conflicts of interest. NR 35 TC 10 Z9 10 U1 1 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 2213-2198 EI 2213-2201 J9 J ALLER CL IMM-PRACT JI J. Allergy Clin. Immunol.-Pract. PD JAN-FEB PY 2015 VL 3 IS 1 BP 94 EP 100 DI 10.1016/j.jaip.2014.11.011 PG 7 WC Allergy; Immunology SC Allergy; Immunology GA CH7IS UT WOS:000354210100014 PM 25577625 ER PT J AU Donovan, NJ Hsu, DC Dagley, AS Schultz, AP Amariglio, RE Mormino, EC Okereke, OI Rentz, DM Johnson, KA Sperling, RA Marshall, GA AF Donovan, Nancy J. Hsu, David C. Dagley, Alexander S. Schultz, Aaron P. Amariglio, Rebecca E. Mormino, Elizabeth C. Okereke, Olivia I. Rentz, Dorene M. Johnson, Keith A. Sperling, Reisa A. Marshall, Gad A. TI Depressive Symptoms and Biomarkers of Alzheimer's Disease in Cognitively Normal Older Adults SO JOURNAL OF ALZHEIMERS DISEASE LA English DT Article DE Alzheimer's disease; biomarkers; neurodegeneration; normal cognition; preclinical; subthreshold depressive symptoms ID LATE-LIFE DEPRESSION; PRIMARY-CARE PATIENTS; RECURRENT MAJOR DEPRESSION; PITTSBURGH COMPOUND-B; GERIATRIC DEPRESSION; SUBSYNDROMAL DEPRESSION; HIPPOCAMPAL VOLUME; AMYLOID BURDEN; NEUROPSYCHIATRIC PREDICTORS; LATE-ONSET AB Even low levels of depressive symptoms are associated with an increased risk of cognitive decline in older adults without overt cognitive impairment (CN). Our objective was to examine whether very low, "subthreshold symptoms of depression" are associated with Alzheimer's disease (AD) biomarkers of neurodegeneration in CN adults and whether these associations are specific to particular depressive symptoms. We analyzed data from 248 community-dwelling CN older adults, including measurements of cortical amyloid burden, neurodegeneration markers of hippocampal volume (HV) and cerebral F-18-fluorodeoxyglucose (FDG) metabolism in a composite of AD-related regions and the 30-item Geriatric Depression Scale (GDS). Participants with GDS > 10 were excluded. General linear regression models evaluated the cross-sectional relations of GDS to HV or FDG in separate backward elimination models. Predictors included GDS total score, age, gender, premorbid intelligence, a binary amyloid variable and its interaction with GDS. Principal component analyses of GDS item scores revealed three factors (the Dysphoria, Apathy-Anhedonia, and Anxiety-Concentration Factors). In secondary analyses, GDS total score was replaced with the three factor scores in repeated models. Higher GDS score (p = 0.03) was significantly associated with lower HV and was marginally related (p = 0.06) to FDG hypometabolism. In secondary models, higher Dysphoria (p = 0.02) and Apathy-Anhedonia (p = 0.05) were related to lower HV while higher Apathy-Anhedonia (p = 0.003) was the sole factor related to FDG hypometabolism. Amyloid was not a significant predictor in any model. In conclusion, very low-level dysphoria, apathy and anhedonia may point to neurodegeneration in AD-related regions but this association appears to be independent of amyloid burden. C1 [Donovan, Nancy J.; Amariglio, Rebecca E.; Rentz, Dorene M.; Johnson, Keith A.; Sperling, Reisa A.; Marshall, Gad A.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Ctr Alzheimer Res & Treatment, Boston, MA 02115 USA. [Donovan, Nancy J.; Amariglio, Rebecca E.; Rentz, Dorene M.; Johnson, Keith A.; Sperling, Reisa A.; Marshall, Gad A.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Neurol, Boston, MA 02115 USA. [Donovan, Nancy J.; Hsu, David C.; Dagley, Alexander S.; Amariglio, Rebecca E.; Okereke, Olivia I.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Psychiat, Boston, MA 02115 USA. [Dagley, Alexander S.; Schultz, Aaron P.; Amariglio, Rebecca E.; Mormino, Elizabeth C.; Marshall, Gad A.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Neurol, Boston, MA USA. [Hsu, David C.; Dagley, Alexander S.; Schultz, Aaron P.; Okereke, Olivia I.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Psychiat, Boston, MA USA. [Johnson, Keith A.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiol, Boston, MA USA. RP Donovan, NJ (reprint author), Brigham & Womens Hosp, Ctr Alzheimer Res & Treatment, 221 Longwood Ave,BL-104H, Boston, MA 02115 USA. EM njdonovan@partners.org RI Okereke, Olivia/R-9934-2016 FU Harvard Medical School Department of Psychiatry Dupont-Warren Fellowship [R03 AG045080, R01 AG027435, K23 AG033634, K24 AG035007]; Massachusetts Alzheimer's Disease Research Center [P50 AG005134]; Harvard Aging Brain Study [P01 AGO36694, R01 AG037497] FX This study was supported by R03 AG045080, R01 AG027435, K23 AG033634, K24 AG035007, the Harvard Medical School Department of Psychiatry Dupont-Warren Fellowship and Livingston Award, the Massachusetts Alzheimer's Disease Research Center (P50 AG005134) and the Harvard Aging Brain Study (P01 AGO36694, R01 AG037497). NR 64 TC 9 Z9 9 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 2015 VL 46 IS 1 BP 63 EP 73 DI 10.3233/JAD-142940 PG 11 WC Neurosciences SC Neurosciences & Neurology GA CI5HO UT WOS:000354786000007 PM 25697700 ER PT J AU Martinez, J Harris, C Jalali, C Tung, J Meyer, R AF Martinez, Johanna Harris, Christina Jalali, Cathy Tung, Judy Meyer, Robert TI Using peer-assisted learning to teach and evaluate residents' musculoskeletal skills SO MEDICAL EDUCATION ONLINE LA English DT Article DE medical education; clinical skills; OSCE; peer learning; physical exam ID MEDICAL-STUDENTS; EDUCATION; IMPLEMENTATION; RHEUMATOLOGY; KNOWLEDGE; FACULTY; EXAM AB Although direct observation and corrective feedback are established methods of increasing select aspects of residents' musculoskeletal (MSK) clinical skills, the evaluation and management of patients with MSK complaints remains an underemphasized part of internal medicine training. This paper reports on the development of an innovative peer-assisted learning (PAL) model to teach five MSK areas (back, knee, shoulder, neck, or hip pain). Based on data from 42 participating interns and 44 senior residents from an urban US academic medical center, results from an objective structured clinical exam (OSCE) demonstrate gains in both knowledge and self-reported confidence in MSK skills. Moreover, subsequent focus group results reveal a strong preference for the PAL model. In conclusion, an educational module that utilizes the OSCE format holds much promise for teaching MSK skills to both intern and senior residents. C1 [Martinez, Johanna; Jalali, Cathy; Tung, Judy; Meyer, Robert] New York Presbyterian Weill Cornell Med Ctr, New York, NY 10021 USA. [Harris, Christina] Univ Calif Los Angeles, David Geffen Sch Med, VA Greater Los Angeles Healthcare Syst, Los Angeles, CA 90095 USA. RP Martinez, J (reprint author), New York Presbyterian Weill Cornell Med Ctr, 505 East 70th St,HT 4, New York, NY 10021 USA. EM jom9050@med.cornell.edu NR 21 TC 1 Z9 1 U1 2 U2 5 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 2015 VL 20 AR 27255 DI 10.3402/meo.v20.27255 PG 4 WC Education & Educational Research SC Education & Educational Research GA CJ3SP UT WOS:000355404500001 PM 26028495 ER PT J AU Han, JF Alvarez-Breckenridge, CA Wang, QE Yu, JH AF Han, Jianfeng Alvarez-Breckenridge, Christopher A. Wang, Qi-En Yu, Jianhua TI TGF-beta signaling and its targeting for glioma treatment SO AMERICAN JOURNAL OF CANCER RESEARCH LA English DT Review DE TGF-beta; TGF-beta signaling; glioma; gliomagenesis; glioma treatment ID GROWTH-FACTOR-BETA; I KINASE INHIBITOR; CENTRAL-NERVOUS-SYSTEM; NATURAL-KILLER-CELLS; HUMAN GLIOBLASTOMA; STEM-CELLS; MALIGNANT GLIOMAS; NK CELLS; IMMUNE SURVEILLANCE; INITIATING CELLS AB Transforming growth factor-beta (TGF-beta) is a pleiotropic cytokine, secreted by a variety of cells including immune cells, tumor cells, and stromal cells. TGF-beta signaling is dysregulated in cancer patients, and this aberrant signaling at least in part contributes to initiation and progression of many cancers including glioma. The dysregulated signaling components provide molecular targets for the treatment of glioma. In this article, we review TGF-beta signaling and its targeting in glioma. C1 [Han, Jianfeng; Yu, Jianhua] Ohio State Univ, Coll Med, Dept Internal Med, Div Hematol, Columbus, OH 43210 USA. [Han, Jianfeng; Wang, Qi-En; Yu, Jianhua] Ohio State Univ, Ctr Comprehens Canc, Columbus, OH 43210 USA. [Alvarez-Breckenridge, Christopher A.] Massachusetts Gen Hosp, Dept Neurosurg, Boston, MA 02114 USA. RP Yu, JH (reprint author), Ohio State Univ, Dept Internal Med, Div Hematol, Biomed Res Tower 816,460 West 12th Ave, Columbus, OH 43210 USA. EM jianhua.yu@osumc.edu FU National Institutes of Health [CA155521] FX This review was supported by the grant CA155521 from the National Institutes of Health. The authors sincerely thank David M. Lucas for his careful and critical reading of this manuscript. NR 78 TC 21 Z9 22 U1 1 U2 5 PU E-CENTURY PUBLISHING CORP PI MADISON PA 40 WHITE OAKS LN, MADISON, WI 53711 USA SN 2156-6976 J9 AM J CANCER RES JI Am. J. Cancer Res. PY 2015 VL 5 IS 3 BP 945 EP 955 PG 11 WC Oncology SC Oncology GA CI5DJ UT WOS:000354772800006 PM 26045979 ER PT J AU Zhang, RC Zhang, YH An, T Guo, X Yin, SJ Wang, YH Januzzi, JL Cappola, TP Zhang, J AF Zhang, Rongcheng Zhang, Yuhui An, Tao Guo, Xiao Yin, Shijie Wang, Yunhong Januzzi, James L. Cappola, Thomas P. Zhang, Jian TI Prognostic value of sST2 and galectin-3 for death relative to renal function in patients hospitalized for heart failure SO BIOMARKERS IN MEDICINE LA English DT Article DE biomarker; cardiac remodeling; death; eGFR; galectin-3; heart failure; NT-proBNP; prognosis; renal function; sST2 ID SOLUBLE ST2; FIBROSIS; STRATIFICATION; EXPRESSION; PLASMA AB Aim: To evaluate the associations of soluble ST2 (sST2) and galectin-3 with death relative to renal function in patients with heart failure (HF). Methods: Eleven-hundred-and-sixty-one patients hospitalized for HF with 1-year follow up were enrolled for biomarkers analysis. Results: Patients were divided into two groups based on eGFR of either > or 60 ml/min/1.73 m(2). sST2 was independently associated with death in both categories of renal function, while galectin-3 lost this significance after addition of NT-proBNP to the model of patients with eGFR 60 ml/min/1.73 m(2). Conclusion: In patients with HF, sST2 improved prediction for death beyond risk factors without being influenced by renal function, however, the prognostic value of galectin-3 is less clear below an eGFR of 60 ml/min/1.73 m(2). C1 [Zhang, Rongcheng; Zhang, Yuhui; An, Tao; Guo, Xiao; Yin, Shijie; Wang, Yunhong; Zhang, Jian] Chinese Acad Med Sci, Natl Ctr Cardiovasc Dis, State Key Lab Cardiovasc Dis, Heart Failure Ctr,Fuwai Hosp, Beijing 100037, Peoples R China. [Zhang, Rongcheng; Zhang, Yuhui; An, Tao; Guo, Xiao; Yin, Shijie; Wang, Yunhong; Zhang, Jian] Peking Union Med Coll, Beijing 100037, Peoples R China. [Januzzi, James L.] Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. [Cappola, Thomas P.] Univ Penn, Sch Med, Penn Cardiovasc Inst, Philadelphia, PA 19104 USA. RP Zhang, J (reprint author), Chinese Acad Med Sci, Natl Ctr Cardiovasc Dis, State Key Lab Cardiovasc Dis, Heart Failure Ctr,Fuwai Hosp, Beijing 100037, Peoples R China. EM fwzhangjian62@126.com FU Critical Diagnostics; Key Projects in the National Science & Technology Pillar Program of the 12th Five-year Plan Period, Beijing, China [2011BAI11B02] FX JL Januzzi has received grant support and consulting income from Critical Diagnostics. This study was supported by grants from the Key Projects in the National Science & Technology Pillar Program of the 12th Five-year Plan Period (no. 2011BAI11B02, project for heart failure), Beijing, China. ST2 assays were provided by Critical Diagnostics, and NT-proBNP assays were provided by Alere, Inc. Neither of these companies had role in study design, data collection and analysis, decision to publish or preparation of the manuscript. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed. NR 25 TC 1 Z9 3 U1 1 U2 6 PU FUTURE MEDICINE LTD PI LONDON PA UNITEC HOUSE, 3RD FLOOR, 2 ALBERT PLACE, FINCHLEY CENTRAL, LONDON, N3 1QB, ENGLAND SN 1752-0363 EI 1752-0371 J9 BIOMARK MED JI Biomark. Med. PY 2015 VL 9 IS 5 BP 433 EP 441 DI 10.2217/bmm.15.12 PG 9 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA CI3KX UT WOS:000354647700005 PM 25985174 ER PT J AU Drain, PK Gounder, L Grobler, A Sahid, F Bassett, IV Moosa, MYS AF Drain, Paul K. Gounder, Lilishia Grobler, Anneke Sahid, Faieza Bassett, Ingrid V. Moosa, Mahomed-Yunus S. TI Urine lipoarabinomannan to monitor antituberculosis therapy response and predict mortality in an HIV-endemic region: a prospective cohort study SO BMJ OPEN LA English DT Article ID PULMONARY TUBERCULOSIS; MYCOBACTERIUM-TUBERCULOSIS; SPUTUM; DIAGNOSIS AB Objective: To determine if urinary lipoarabinomannan (LAM) may serve as a biomarker to monitor antituberculosis (TB) therapy response, and whether LAM results before and after treatment are predictive of patient outcomes. Design: Prospective cohort. Setting: Outpatient referral clinic and tertiary hospital in South Africa. Participants: Adults (>= 18 years) with >= 2 TB-related symptoms (cough, fever, weight loss, night sweats) for >= 2 weeks being initiated on anti-TB therapy. Interventions: On enrolment, we obtained urine and nebulised sputum specimens, offered HIV testing and started participants on anti-TB therapy for >= 6 months. We collected urine samples after the 2-month intensive treatment phase and at the completion of anti-TB therapy. Positive LAM results were graded from 1 (low) to 5 (high). Participants were followed for >3 years. Outcome measures: The primary outcome was change in urine LAM results during anti-TB therapy. The secondary outcome was all-cause mortality. Results: Among 90 participants, 57 (63%) had culture-confirmed pulmonary TB. Among the 88 participants tested, 82 (93%) were HIV-infected with median CD4 168/mm(3) (IQR 89-256/mm(3)). During anti-TB therapy, the percentage of LAM-positive participants decreased from baseline to 2 months (32% to 16%), and from baseline to 6-months (32% to 10%) (p values <0.005). In multivariate longitudinal analyses, urine LAM positivity and grade decreased among those with culture-confirmed pulmonary TB (p<0.0001), and had no change in sputum culture-negative participants. At the 2-month visit, participants with positive laboratory-based LAM or rapid LAM with >= 2+ grade had a significantly greater risk of mortality. In analyses adjusted for age, sex, baseline Karnofsky score and HIV status, participants with a rapid LAM >= 2+ grade after 2 months of anti-TB therapy had a 5.6-fold (95% CI 1.2 to 25.2) greater risk of mortality. Conclusions: Rapid urine LAM testing may be a valuable tool to monitor anti-TB therapy response and to assess prognosis of patients being treated for pulmonary TB in HIV-endemic regions. C1 [Drain, Paul K.; Bassett, Ingrid V.] Med Practice Evaluat Ctr, Boston, MA 02117 USA. [Drain, Paul K.; Bassett, Ingrid V.] Massachusetts Gen Hosp, Dept Med, Div Infect Dis, Boston, MA 02114 USA. [Gounder, Lilishia] Inkosi Albert Luthuli Cent Hosp, Natl Hlth Lab Serv, Dept Virol, Durban, South Africa. [Grobler, Anneke] Ctr AIDS Programme Res South Africa, Durban, South Africa. [Sahid, Faieza] Univ Witwatersrand, Johannesburg, South Africa. [Moosa, Mahomed-Yunus S.] Univ KwaZulu Natal, Nelson R Mandela Sch Med, Dept Infect Dis, Durban, South Africa. RP Drain, PK (reprint author), Med Practice Evaluat Ctr, Boston, MA 02117 USA. EM pdrain@partners.org FU Medical Research Council of South Africa; Howard Hughes Medical Institute; KwaZulu-Natal Research Institute for TB and HIV (K-RITH); UK's Department for International Development; Harvard Global Health Institute; Fogarty International Clinical Research Scholars and Fellows Program at Vanderbilt University [R24 TW007988]; Infectious Disease Society of America Education & Research Foundation (IDSA ERF); National Foundation for Infectious Diseases (NFID); Program in AIDS Clinical Research Training Grant [T32 AI007433]; National Institute of Allergy and Infectious Disease [K23 AI108293]; Harvard University Center for AIDS Research [P30 AI060354]; Massachusetts General Hospital Executive Committee on Research; National Institute of Mental Health [R01 MH090326]; Claflin Distinguished Scholar Award FX This study was funded by the Medical Research Council of South Africa, the Howard Hughes Medical Institute, the KwaZulu-Natal Research Institute for TB and HIV (K-RITH), and the UK's Department for International Development. Dr Drain was supported by the Harvard Global Health Institute, the Fogarty International Clinical Research Scholars and Fellows Program at Vanderbilt University (R24 TW007988), the Infectious Disease Society of America Education & Research Foundation (IDSA ERF) and National Foundation for Infectious Diseases (NFID), The Program in AIDS Clinical Research Training Grant (T32 AI007433), the National Institute of Allergy and Infectious Disease (K23 AI108293), the Harvard University Center for AIDS Research (P30 AI060354) and the Massachusetts General Hospital Executive Committee on Research. Dr Bassett was supported by the National Institute of Mental Health R01 MH090326 (IVB) and the Claflin Distinguished Scholar Award (IVB). NR 29 TC 7 Z9 7 U1 0 U2 4 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 2015 VL 5 IS 4 AR e006833 DI 10.1136/bmjopen-2014-006833 PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA CI4GB UT WOS:000354705000036 PM 25877271 ER PT J AU Scott, J Rouhani, S Greiner, A Albutt, K Kuwert, P Hacker, MR VanRooyen, M Bartels, S AF Scott, Jennifer Rouhani, Shada Greiner, Ashley Albutt, Katherine Kuwert, Philipp Hacker, Michele R. VanRooyen, Michael Bartels, Susan TI Respondent-driven sampling to assess mental health outcomes, stigma and acceptance among women raising children born from sexual violence-related pregnancies in eastern Democratic Republic of Congo SO BMJ OPEN LA English DT Article ID HIDDEN POPULATIONS; CONTROLLED-TRIAL; PRIMARY-CARE; SURVIVORS; STIGMATIZATION; REJECTION; ATTITUDES; THERAPY; VICTIMS; ASSAULT AB Objectives: Assess mental health outcomes among women raising children from sexual violence-related pregnancies (SVRPs) in eastern Democratic Republic of Congo and stigma toward and acceptance of women and their children. Design: Participants were recruited using respondent-driven sampling. Setting: Bukavu, Democratic Republic of Congo in 2012. Participants: 757 adult women raising children from SVRPs were interviewed. A woman aged 18 and older was eligible for the study if she self-identified as a sexual violence survivor since the start of the conflict (similar to 1996), conceived an SVRP, delivered a liveborn child and was currently raising the child. A woman was ineligible for the study if the SVRP ended with a spontaneous abortion or fetal demise or the child was not currently living or in the care of the biological mother. Intervention: Trained female Congolese interviewers verbally administered a quantitative survey after obtaining verbal informed consent. Outcome measures: Symptom criteria for major depressive disorder, post-traumatic stress disorder, anxiety and suicidality were assessed, as well as stigma toward the woman and her child. Acceptance of the woman and child from the spouse, family and community were analysed. Results: 48.6% met symptom criteria for major depressive disorder, 57.9% for post-traumatic stress disorder, 43.3% for anxiety and 34.2% reported suicidality. Women who reported stigma from the community (38.4%) or who reported stigma toward the child from the spouse (42.9%), family (31.8%) or community (38.1%) were significantly more likely to meet symptom criteria for most mental health disorders. Although not statistically significant, participants who reported acceptance and acceptance of their children from the spouse, family and community were less likely to meet symptom criteria. Conclusions: Women raising children from SVRPs experience symptoms of mental health disorders. Programming addressing stigma and acceptance following sexual violence may improve mental health outcomes in this population. C1 [Scott, Jennifer; Hacker, Michele R.] Beth Israel Deaconess Med Ctr, Dept Obstet & Gynecol, Boston, MA 02215 USA. [Scott, Jennifer] Brigham & Womens Hosp, Div Womens Hlth, Boston, MA 02115 USA. [Scott, Jennifer; Rouhani, Shada; Greiner, Ashley; Albutt, Katherine; VanRooyen, Michael; Bartels, Susan] Harvard Humanitarian Initiat, Cambridge, MA 02138 USA. [Scott, Jennifer; Rouhani, Shada; Greiner, Ashley; Albutt, Katherine; Hacker, Michele R.; VanRooyen, Michael; Bartels, Susan] Harvard Univ, Sch Med, Boston, MA USA. [Rouhani, Shada; VanRooyen, Michael] Brigham & Womens Hosp, Dept Emergency Med, Boston, MA 02115 USA. [Greiner, Ashley; Bartels, Susan] Beth Israel Deaconess Med Ctr, Dept Emergency Med, Boston, MA 02215 USA. [Albutt, Katherine] Massachusetts Gen Hosp, Dept Gen Surg, Boston, MA 02114 USA. [Kuwert, Philipp] HELIOS Hansehosp Stralsund, Univ Med Greifswald, Dept Psychiat & Psychotherapy, Stralsund, Germany. [Hacker, Michele R.] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. [VanRooyen, Michael; Bartels, Susan] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. RP Bartels, S (reprint author), Harvard Humanitarian Initiat, Cambridge, MA 02138 USA. EM susanabartels@gmail.com FU Harvard Medical School; Harvard Humanitarian Initiative; Harvard Catalyst\The Harvard Clinical and Translational Science Center (National Institutes of Health) [8UL1TR000170-05]; Harvard University FX The study was funded by the Eleanor and Miles Shore Fellowship from Harvard Medical School and funding from Harvard Humanitarian Initiative. Data analysis was supported by Harvard Catalyst vertical bar The Harvard Clinical and Translational Science Center (National Institutes of Health Award 8UL1TR000170-05 and financial contributions from Harvard University and affiliated academic health centers). NR 43 TC 2 Z9 2 U1 2 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 2015 VL 5 IS 4 AR e007057 DI 10.1136/bmjopen-2014-007057 PG 11 WC Medicine, General & Internal SC General & Internal Medicine GA CI4GB UT WOS:000354705000053 PM 25854968 ER PT J AU Watase, H Hagiwara, Y Chiba, T Camargo, CA Hasegawa, K AF Watase, Hiroko Hagiwara, Yusuke Chiba, Takuyo Camargo, Carlos A., Jr. Hasegawa, Kohei CA Japanese Emergency Med Network TI Multicentre observational study of adults with asthma exacerbations: who are the frequent users of the emergency department in Japan? SO BMJ OPEN LA English DT Article ID FOLLOW-UP; CARE; PREDICTORS; SMOKING; RISK AB Objectives: Emergency department (ED) visits for asthma exacerbation reflect a failure of longitudinal asthma management. However, little is known about the characteristics of patients with frequent ED visits (>= 2 visits in a 1-year period). We aimed to characterise the adult patients who frequently presented to the ED for asthma exacerbation in Japan. Design: A multicentre chart review study of 23 EDs across Japan. Participants: Adults aged 18-54 years who presented to the ED with asthma exacerbation from 2009 to 2011. Outcome measures: Frequency of ED visits for asthma exacerbation in a 1-year period, including the index ED visit. Results: Of the 1002 eligible patients, 218 (22%) had frequent ED visits, accounting for 48% of total ED visits for asthma exacerbation in the 1-year period. Specifically, 12% had 2 ED visits and 10% had >= 3 visits. In these patients, guideline-recommended chronic management was suboptimal. For example, among patients with >= 3 ED visits, only 63% were treated with inhaled corticosteroids and 49% were current smokers. In a multinomial logistic regression model, markers of chronic asthma severity (history of hospitalisation for asthma and use of inhaled corticosteroids) were significantly associated with a higher frequency of ED visits (both p<0.05). Conclusions: This multicentre study in Japan demonstrated that many patients are frequent ED users for asthma exacerbation. We also found that their asthma control management is suboptimal, most likely contributing to worse chronic severity and more frequent ED visits. Further dissemination and adoption of evidence-based guidelines are required to reduce asthma morbidity in this high-risk population. C1 [Watase, Hiroko; Hagiwara, Yusuke; Chiba, Takuyo; Hasegawa, Kohei] Univ Washington, Dept Radiol, Seattle, WA 98195 USA. [Hagiwara, Yusuke] Tokyo Metropolitan Childrens Med Ctr, Dept Emergency Med, Tokyo, Japan. [Chiba, Takuyo] Univ Massachusetts, Sch Med, Dept Emergency Med, Worcester, MA USA. [Camargo, Carlos A., Jr.; Hasegawa, Kohei] Harvard Univ, Massachusetts Gen Hosp, Dept Emergency Med, Sch Med, Boston, MA USA. RP Watase, H (reprint author), Univ Washington, Dept Radiol, Seattle, WA 98195 USA. EM hiroko7@uw.edu FU St. Luke's Life Science Institute (Tokyo, Japan) FX This study was supported by a grant from St. Luke's Life Science Institute (Tokyo, Japan). NR 24 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 2044-6055 J9 BMJ OPEN JI BMJ Open PY 2015 VL 5 IS 4 AR e007435 DI 10.1136/bmjopen-2014-007435 PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA CI4GB UT WOS:000354705000098 PM 25922104 ER PT J AU Zulman, DM Chee, CP Wagner, TH Yoon, J Cohen, DM Holmes, TH Ritchie, C Asch, SM AF Zulman, Donna M. Chee, Christine Pal Wagner, Todd H. Yoon, Jean Cohen, Danielle M. Holmes, Tyson H. Ritchie, Christine Asch, Steven M. TI Multimorbidity and healthcare utilisation among high-cost patients in the US Veterans Affairs Health Care System SO BMJ OPEN LA English DT Article ID COMORBID MENTAL-DISORDERS; AVERAGE COST; VA; BENEFICIARIES; PREVALENCE; DEPRESSION; PRINCIPLES; MANAGEMENT; STAYS AB Objectives: To investigate the relationship between multimorbidity and healthcare utilisation patterns among the highest cost patients in a large, integrated healthcare system. Design: In this retrospective cross-sectional study of all patients in the U.S. Veterans Affairs (VA) Health Care System, we aggregated costs of individuals' outpatient and inpatient care, pharmacy services and VA-sponsored contract care received in 2010. We assessed chronic condition prevalence, multimorbidity as measured by comorbidity count, and multisystem multimorbidity (number of body systems affected by chronic conditions) among the 5% highest cost patients. Using multivariate regression, we examined the association between multimorbidity and healthcare utilisation and costs, adjusting for age, sex, race/ethnicity, marital status, homelessness and health insurance status. Setting: USAVA Health Care System. Participants: 5.2 million VA patients. Measures: Annual total costs; absolute and share of costs generated through outpatient, inpatient, pharmacy and VA-sponsored contract care; number of visits to primary, specialty and mental healthcare; number of emergency department visits and hospitalisations. Results: The 5% highest cost patients (n=261 699) accounted for 47% of total VA costs. Approximately two-thirds of these patients had chronic conditions affecting >= 3 body systems. Patients with cancer and schizophrenia were less likely to have documented comorbid conditions than other high-cost patients. Multimorbidity was generally associated with greater outpatient and inpatient utilisation. However, increased multisystem multimorbidity was associated with a higher outpatient share of total costs (1.6 percentage points per affected body system, p<0.01) but a lower inpatient share of total costs (-0.6 percentage points per affected body system, p<0.01). Conclusions: Multisystem multimorbidity is common among high-cost VA patients. While some patients might benefit from disease-specific programmes, for most patients with multimorbidity there is a need for interventions that coordinate and maximise efficiency of outpatient services across multiple conditions. C1 [Zulman, Donna M.; Chee, Christine Pal; Wagner, Todd H.; Yoon, Jean; Asch, Steven M.] VA Palo Alto Hlth Care Syst, Ctr Innovat Implementat, Menlo Pk, CA 94025 USA. [Zulman, Donna M.; Cohen, Danielle M.; Asch, Steven M.] Stanford Univ, Div Gen Med Disciplines, Stanford, CA 94305 USA. [Chee, Christine Pal; Wagner, Todd H.; Yoon, Jean] VA Palo Alto Hlth Care Syst, Hlth Econ Resource Ctr, Menlo Pk, CA USA. [Wagner, Todd H.] Stanford Univ, Hlth Res & Policy, Stanford, CA 94305 USA. [Holmes, Tyson H.] Stanford Univ, Dept Psychiat & Behav Sci, Stanford, CA 94305 USA. [Ritchie, Christine] Univ Calif San Francisco, Div Geriatr, San Francisco, CA 94143 USA. [Ritchie, Christine] San Francisco VA Med Ctr, San Francisco, CA USA. RP Zulman, DM (reprint author), VA Palo Alto Hlth Care Syst, Ctr Innovat Implementat, Menlo Pk, CA 94025 USA. EM dzulman@stanford.edu FU U.S. Department of Veterans Affairs (VA) HSR&D Career Development Award [CDA 12-173]; VA Office of Specialty Care Services (Specialty/Surgical Care Neighborhood Team Based Model Pilot Program); Advanced Illness and Multimorbidity Geriatric Academic Leadership Award [1K07AG31779]; [SDR-ECN-99017-1] FX DMZ is supported by a U.S. Department of Veterans Affairs (VA) HSR&D Career Development Award (CDA 12-173). CPC, THW, and JY received core funding SDR-ECN-99017-1 to the VA Health Economics Resource Center. THH and DMC are supported in part by the VA Office of Specialty Care Services (Specialty/Surgical Care Neighborhood Team Based Model Pilot Program). CR is supported by the Advanced Illness and Multimorbidity Geriatric Academic Leadership Award (1K07AG31779). NR 34 TC 12 Z9 12 U1 0 U2 3 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 2015 VL 5 IS 4 AR e007771 DI 10.1136/bmjopen-2015-007771 PG 9 WC Medicine, General & Internal SC General & Internal Medicine GA CI4GB UT WOS:000354705000122 PM 25882486 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 2014 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, Res Unit Complementary & Integrat Laser Med, Res Unit Biomed Engn Anesthesia & Intens Care Med, TCM Res Ctr Graz, 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 0 Z9 0 U1 1 U2 4 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 2015 AR 306138 DI 10.1155/2015/306138 PG 1 WC Integrative & Complementary Medicine SC Integrative & Complementary Medicine GA CJ0RJ UT WOS:000355185000001 ER PT J AU Toi, M Winer, EP Benson, JR Inamoto, T Forbes, JF von Minckwitz, G Robertson, JFR Grobmyer, SR Jatoi, I Sasano, H Kunkler, I Ho, AY Yamauchi, C Chow, LWC Huang, CS Han, W Noguchi, S Pegram, MD Yamauchi, H Lee, ES Larionov, AA Bevilacqua, JLB Yoshimura, M Sugie, T Yamauchi, A Krop, IE Noh, DY Klimberg, VS AF Toi, Masakazu Winer, Eric P. Benson, John R. Inamoto, Takashi Forbes, John F. von Minckwitz, Gunter Robertson, John F. R. Grobmyer, Stephen R. Jatoi, Ismail Sasano, Hironobu Kunkler, Ian Ho, Alice Y. Yamauchi, Chikako Chow, Louis W. C. Huang, Chiun-Sheng Han, Wonshik Noguchi, Shinzaburo Pegram, Mark D. Yamauchi, Hideko Lee, Eun-Sook Larionov, Alexey A. Bevilacqua, Jose L. B. Yoshimura, Michio Sugie, Tomoharu Yamauchi, Akira Krop, Ian E. Noh, Dong Young Klimberg, V. Suzanne CA 2014 Kyoto Breast Canc Consensus C TI Personalization of loco-regional care for primary breast cancer patients (part 1) SO FUTURE ONCOLOGY LA English DT Article DE axillary conserving therapy; breast cancer; loco-regional care; preoperative systemic therapy; sentinel lymph node biopsy ID LYMPH-NODE BIOPSY; SURGICAL ADJUVANT BREAST; AXILLARY DISSECTION; SENTINEL-NODE; NEOADJUVANT CHEMOTHERAPY; CLINICAL-TRIAL; SURGERY; FLUORESCENCE; MULTICENTER AB Kyoto Breast Cancer Consensus Conference, Kyoto, Japan, 18-20 February 2014 The loco-regional management of breast cancer is increasingly complex with application of primary systemic therapies, oncoplastic techniques and genetic testing for breast cancer susceptibility. Personalization of loco-regional treatment is integral to optimization of breast cancer care. Clinical and pathological tumor stage, biological features and host factors influence loco-regional treatment strategies and extent of surgical procedures. Key issues including axillary staging, axillary treatment, radiation therapy, primary systemic therapy (PST), preoperative hormonal therapy and genetic predisposition were identified and discussed at the Kyoto Breast Cancer Consensus Conference (KBCCC2014). In the first of a two part conference scene, consensus recommendations for axillary management are presented and focus on the following topics: indications for completion axillary lymph node dissection in primary surgical patients with 2 macrometastases or any sentinel nodal deposits after PST; the timing of sentinel lymph node biopsy in the context of PST; use of axillary irradiation as a component of primary treatment plans and the role of intraoperative node assessment in the post-Z0011 era. C1 [Toi, Masakazu] Kyoto Univ, Grad Sch Med, Breast Surg, Sakyo Ku, Kyoto 6068507, Japan. [Winer, Eric P.; Krop, Ian E.] Harvard Univ, Sch Med, Breast Oncol Ctr, Dana Farber Canc Inst,Brigham & Womens Canc Ctr, Boston, MA 02215 USA. [Benson, John R.] Addenbrookes Hosp, Cambridge Breast Unit, Cambridge, England. [Benson, John R.] Univ Cambridge, Cambridge, England. [Inamoto, Takashi] Tenri Hlth Care Univ, Fac Hlth Care, Nara, Japan. [Forbes, John F.] Univ Newcastle, Surg Oncol, Newcastle, NSW 2300, Australia. [von Minckwitz, Gunter] German Breast Grp, Frankfurt, Germany. [Robertson, John F. R.] Univ Nottingham, Breast Surg, Royal Derby Hosp, Nottingham NG7 2RD, England. [Grobmyer, Stephen R.] Case Western Reserve Univ, Cleveland Clin, Cleveland, OH 44195 USA. [Grobmyer, Stephen R.] Case Western Reserve Univ, Lerner Coll Med, Cleveland, OH 44195 USA. [Jatoi, Ismail] Univ Texas Hlth Sci Ctr San Antonio, San Antonio, TX 78229 USA. [Sasano, Hironobu] Tohoku Univ, Sch Med, Pathol, Sendai, Miyagi 980, Japan. [Kunkler, Ian] Univ Edinburgh, Edinburgh Canc Res UK Ctr, Edinburgh EH8 9YL, Midlothian, Scotland. [Ho, Alice Y.] Mem Sloan Kettering Canc Ctr, Radiat Oncol, New York, NY 10065 USA. [Yamauchi, Chikako] Shiga Med Ctr Adults, Radiat Oncol, Moriyama, Japan. [Chow, Louis W. C.] Univ Hong Kong, UNIMED Med Inst, Hong Kong, Hong Kong, Peoples R China. [Huang, Chiun-Sheng] Natl Taiwan Univ, Natl Taiwan Univ Hosp, Coll Med, Surg, Taipei 10764, Taiwan. [Han, Wonshik; Lee, Eun-Sook; Noh, Dong Young] Seoul Natl Univ Hosp, Surg, Seoul 110744, South Korea. [Noguchi, Shinzaburo] Osaka Univ, Breast & Endocrine Surg, Grad Sch Med, Osaka, Japan. [Pegram, Mark D.] Stanford Univ, Stanford Canc Inst, Sch Med, Stanford, CA 94305 USA. [Yamauchi, Hideko] St Lukes Hosp, Dept Surg, Tokyo, Japan. [Larionov, Alexey A.] Univ Cambridge, Stat & Computat Biol Lab, Canc Res UK Cambridge Inst, Cambridge CB2 1TN, England. [Bevilacqua, Jose L. B.] AC Camargo Canc Ctr, Dept Breast Surg, Sao Paulo, Brazil. [Yoshimura, Michio] Kyoto Univ, Grad Sch Med, Radiat Oncol, Kyoto, Japan. [Sugie, Tomoharu] Kansai Med Univ, Beast Surg, Osaka, Japan. [Yamauchi, Akira] Kitano Hosp, Breast Ctr, Tazuke Kofukai Med Res Inst, Osaka, Japan. [Klimberg, V. Suzanne] Univ Arkansas Med Sci, Surg, Rockefeller Canc Inst, Little Rock, AR 72205 USA. RP Toi, M (reprint author), Kyoto Univ, Grad Sch Med, Breast Surg, Sakyo Ku, 54 Shogoin Kawara Cho, Kyoto 6068507, Japan. EM toi@kuhp.kyoto-u.ac.jp RI Bevilacqua, Jose Luiz/J-7739-2012; Larionov, Alexey/A-5088-2010; Han, Wonshik/B-3699-2008; OI Larionov, Alexey/0000-0001-6374-9391; Huang, Chiun-Sheng/0000-0002-6557-211X NR 17 TC 3 Z9 3 U1 0 U2 1 PU FUTURE MEDICINE LTD PI LONDON PA UNITEC HOUSE, 3RD FLOOR, 2 ALBERT PLACE, FINCHLEY CENTRAL, LONDON, N3 1QB, ENGLAND SN 1479-6694 EI 1744-8301 J9 FUTURE ONCOL JI Future Oncol. PY 2015 VL 11 IS 9 BP 1297 EP 1300 DI 10.2217/fon.15.65 PG 4 WC Oncology SC Oncology GA CH9XR UT WOS:000354390500002 PM 25952777 ER PT J AU Toi, M Winer, EP Benson, JR Inamoto, T Forbes, JF von Minckwitz, G Robertson, JFR Grobmyer, SR Jatoi, I Sasano, H Kunkler, I Ho, AY Yamauchi, C Chow, LWC Huang, CS Han, W Noguchi, S Pegram, MD Yamauchi, H Lee, ES Larionov, AA Bevilacqua, JLB Yoshimura, M Sugie, T Yamauchi, A Krop, IE Noh, DY Klimberg, VS AF Toi, Masakazu Winer, Eric P. Benson, John R. Inamoto, Takashi Forbes, John F. von Minckwitz, Gunter Robertson, John F. R. Grobmyer, Stephen R. Jatoi, Ismail Sasano, Hironobu Kunkler, Ian Ho, Alice Y. Yamauchi, Chikako Chow, Louis W. C. Huang, Chiun-Sheng Han, Wonshik Noguchi, Shinzaburo Pegram, Mark D. Yamauchi, Hideko Lee, Eun-Sook Larionov, Alexey A. Bevilacqua, Jose L. B. Yoshimura, Michio Sugie, Tomoharu Yamauchi, Akira Krop, Ian E. Noh, Dong Young Klimberg, V. Suzanne CA 2014 Kyoto Breast Canc Consensus C TI Personalization of loco-regional care for primary breast cancer patients (part 2) SO FUTURE ONCOLOGY LA English DT Article DE breast cancer; BRCA1/2; luminal type; postmastectomy radiation therapy ID NEOADJUVANT CHEMOTHERAPY; RANDOMIZED-TRIALS; SENTINEL-NODE; RADIOTHERAPY; METAANALYSIS; RECURRENCE; SURGERY; DISSECTION; MASTECTOMY; THERAPY AB Kyoto Breast Cancer Consensus Conference, Kyoto, Japan, 18-20 February 2014 The loco-regional management of breast cancer is increasingly complex with application of primary systemic therapies, oncoplastic techniques and genetic testing for breast cancer susceptibility. Personalization of loco-regional treatment is integral to optimization of breast cancer care. Clinical and pathological tumor stage, biological features and host factors influence loco-regional treatment strategies and extent of surgical procedures. Key issues including axillary staging, axillary treatment, radiation therapy, primary systemic therapy (PST), preoperative hormonal therapy and genetic predisposition were identified and discussed at the Kyoto Breast Cancer Consensus Conference (KBCCC2014). In the second of a two part conference scene, consensus recommendations for radiation treatment, primary systemic therapies and management of genetic predisposition are reported and focus on the following topics: influence of both clinical response to PST and stage at presentation on recommendations for postmastectomy radiotherapy; use of regional nodal irradiation in selected node-positive patients and those with adverse pathological factors; extent of surgical resection following downstaging of tumors with PST; use of preoperative hormonal therapy in premenopausal women with larger, node-negative luminal A-like tumors and managing increasing demands for contralateral prophylactic mastectomy in patients with a unilateral sporadic breast cancer. C1 [Toi, Masakazu] Kyoto Univ, Grad Sch Med, Breast Surg, Sakyo Ku, Kyoto 6068507, Japan. [Winer, Eric P.; Krop, Ian E.] Harvard Univ, Sch Med, Breast Oncol Ctr, Dana Farber Canc Inst,Brigham & Womens Canc Ctr, Boston, MA 02215 USA. [Benson, John R.] Addenbrookes Hosp, Cambridge Breast Unit, Cambridge, England. [Benson, John R.] Univ Cambridge, Cambridge, England. [Inamoto, Takashi] Tenri Hlth Care Univ, Fac Hlth Care, Nara, Japan. [Forbes, John F.] Univ Newcastle, Surg Oncol, Newcastle, NSW 2300, Australia. [von Minckwitz, Gunter] German Breast Grp, Frankfurt, Germany. [Robertson, John F. R.] Univ Nottingham, Breast Surg, Royal Derby Hosp, Nottingham NG7 2RD, England. [Grobmyer, Stephen R.] Case Western Reserve Univ, Cleveland Clin, Cleveland, OH 44195 USA. [Grobmyer, Stephen R.] Case Western Reserve Univ, Lerner Coll Med, Cleveland, OH 44195 USA. [Jatoi, Ismail] Univ Texas Hlth Sci Ctr San Antonio, San Antonio, TX 78229 USA. [Sasano, Hironobu] Tohoku Univ, Sch Med, Pathol, Sendai, Miyagi 980, Japan. [Kunkler, Ian] Univ Edinburgh, Edinburgh Canc Res UK Ctr, Edinburgh EH8 9YL, Midlothian, Scotland. [Ho, Alice Y.] Mem Sloan Kettering Canc Ctr, Radiat Oncol, New York, NY 10065 USA. [Yamauchi, Chikako] Shiga Med Ctr Adults, Radiat Oncol, Moriyama, Japan. [Chow, Louis W. C.] Univ Hong Kong, UNIMED Med Inst, Hong Kong, Hong Kong, Peoples R China. [Huang, Chiun-Sheng] Natl Taiwan Univ, Natl Taiwan Univ Hosp, Coll Med, Surg, Taipei 10764, Taiwan. [Han, Wonshik; Lee, Eun-Sook; Noh, Dong Young] Seoul Natl Univ Hosp, Surg, Seoul 110744, South Korea. [Noguchi, Shinzaburo] Osaka Univ, Breast & Endocrine Surg, Grad Sch Med, Osaka, Japan. [Pegram, Mark D.] Stanford Univ, Stanford Canc Inst, Sch Med, Stanford, CA 94305 USA. [Yamauchi, Hideko] St Lukes Hosp, Dept Surg, Tokyo, Japan. [Larionov, Alexey A.] Univ Cambridge, Stat & Computat Biol Lab, Canc Res UK Cambridge Inst, Cambridge CB2 1TN, England. [Bevilacqua, Jose L. B.] AC Camargo Canc Ctr, Dept Breast Surg, Sao Paulo, Brazil. [Yoshimura, Michio] Kyoto Univ, Grad Sch Med, Radiat Oncol, Kyoto, Japan. [Sugie, Tomoharu] Kansai Med Univ, Beast Surg, Osaka, Japan. [Yamauchi, Akira] Kitano Hosp, Breast Ctr, Tazuke Kofukai Med Res Inst, Osaka, Japan. Univ Arkansas Med Sci, Surg, Rockefeller Canc Inst, Little Rock, AR 72205 USA. RP Toi, M (reprint author), Kyoto Univ, Grad Sch Med, Breast Surg, Sakyo Ku, 54 Shogoin Kawara Cho, Kyoto 6068507, Japan. EM toi@kuhp.kyoto-u.ac.jp RI Bevilacqua, Jose Luiz/J-7739-2012; Larionov, Alexey/A-5088-2010; Han, Wonshik/B-3699-2008; OI Larionov, Alexey/0000-0001-6374-9391; Huang, Chiun-Sheng/0000-0002-6557-211X NR 20 TC 0 Z9 0 U1 0 U2 2 PU FUTURE MEDICINE LTD PI LONDON PA UNITEC HOUSE, 3RD FLOOR, 2 ALBERT PLACE, FINCHLEY CENTRAL, LONDON, N3 1QB, ENGLAND SN 1479-6694 EI 1744-8301 J9 FUTURE ONCOL JI Future Oncol. PY 2015 VL 11 IS 9 BP 1301 EP 1305 DI 10.2217/fon.15.66 PG 5 WC Oncology SC Oncology GA CH9XR UT WOS:000354390500003 PM 25952778 ER PT J AU Wahlstrom, LC Scott, JP Tuliao, AP DiLillo, D McChargue, DE AF Wahlstrom, Laura C. Scott, Jillian Panuzio Tuliao, Antover P. DiLillo, David McChargue, Dennis E. TI Posttraumatic Stress Disorder Symptoms, Emotion Dysregulation, and Aggressive Behavior Among Incarcerated Methamphetamine Users SO JOURNAL OF DUAL DIAGNOSIS LA English DT Article DE PTSD; methamphetamine; aggression; emotion regulation; incarceration ID INTIMATE PARTNER VIOLENCE; MILITARY VETERANS; COMBAT VETERANS; ANGER; TRAUMA; PTSD; MEN; PERPETRATION; ABUSE; DIFFICULTIES AB Objective: Methamphetamine use remains a prevalent problem in the United States and is linked to numerous deleterious outcomes, including aggressive behavior, criminal activity, and incarceration. Given these associations, a greater understanding of factors that contribute to aggression among users of methamphetamine is needed, particularly within criminal justice settings, where users of this drug are overrepresented. Methods: The present study examined the relationships between posttraumatic stress disorder (PTSD) symptoms and emotion dysregulation and in-prison physical aggression among incarcerated males who identified as methamphetamine users (N = 60). Results: Participants' average age was 34.4years (SD = 7.9), and they were predominantly European American (n = 48, 80%), had spent an average of 6.53years incarcerated (SD = 4.64), and perpetrated about 1.54 acts of aggression (SD = 6.74) during the past three months. Bivariate correlations found that greater PTSD symptoms (p <.001), greater impulse control difficulties (p <.001), and limited access to emotion regulation strategies (p <.05) were associated with aggression perpetrated in prison. However, results from multiple regression analyses indicated that only PTSD symptoms (p <.001) and nonacceptance of emotional responses (p <.03) were predictive of aggression. Regression analyses also suggested that impulse control difficulties (p <.001), limited access to emotion regulation strategies (p <.04), and nonacceptance of emotional responses (p <.001) interacted with PTSD symptoms to predict increased aggressive behavior. The first interaction ran counter to study hypotheses: At greater levels of PTSD symptoms, those with greater acceptance of emotional responses reported greater aggression perpetration than those with lesser acceptance of emotional responses. The other two interactions were in line with hypotheses, showing that at greater levels of PTSD symptoms, those with greater impulse control difficulties (or lesser access to emotion regulation strategies) reported more aggressive behaviors. Conclusions: Consistent with theories of aggression, study findings suggest that PTSD symptoms bolster the risk of aggression via various forms emotion dysregulation. Results shed light on potential mechanisms that promote in-prison aggression and violent recidivism among this population. C1 [Wahlstrom, Laura C.] Cent Texas VA Hlth Care Syst, Temple, TX USA. [Scott, Jillian Panuzio] VA Boston Healthcare Syst, Boston, MA USA. [Scott, Jillian Panuzio] Boston Univ, Sch Med, Boston, MA 02118 USA. [Tuliao, Antover P.; DiLillo, David; McChargue, Dennis E.] Univ Nebraska, Dept Psychol, Lincoln, NE 68588 USA. RP McChargue, DE (reprint author), Univ Nebraska, Dept Psychol, 238 Burnett Hall, Lincoln, NE 68588 USA. EM dmcchargue2@unl.edu FU Nebraska State Penitentiary; Nebraska Crime Commission FX The authors thank the Nebraska State Penitentiary and the Nebraska Crime Commission for their support in accomplishing this project. NR 61 TC 2 Z9 2 U1 4 U2 17 PU ROUTLEDGE JOURNALS, TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXFORDSHIRE, ENGLAND SN 1550-4263 EI 1550-4271 J9 J DUAL DIAGN JI J. Dual Diagn. PY 2015 VL 11 IS 2 BP 118 EP 127 DI 10.1080/15504263.2015.1025026 PG 10 WC Psychology, Clinical; Substance Abuse; Psychiatry SC Psychology; Substance Abuse; Psychiatry GA CI5GP UT WOS:000354782900004 PM 25781457 ER PT J AU Morgan, P Embry, A Perry, L Holthaus, K Gregory, CM AF Morgan, Patrick Embry, Aaron Perry, Lindsay Holthaus, Katy Gregory, Chris M. TI Feasibility of lower-limb muscle power training to enhance locomotor function poststroke SO JOURNAL OF REHABILITATION RESEARCH AND DEVELOPMENT LA English DT Article DE exercise; locomotion; locomotor function; muscle; optimization of walking; poststroke; rehabilitation; strengthening; stroke; walking ID LEG POWER; CHRONIC STROKE; GAIT SPEED; PHYSICAL PERFORMANCE; KNEE EXTENSION; OLDER WOMEN; REHABILITATION; STRENGTH; MOBILITY; INDIVIDUALS AB Poststroke motor control is characterized by greatly reduced muscle power generation. To date, the extent to which muscle power limits walking performance or whether its remediation should be a primary component of locomotor rehabilitation has yet to be established. The purpose of this study was to examine the feasibility and the effects of Poststroke Optimization of Walking using Explosive Resistance training, an intervention aimed at improving poststroke muscular and locomotor function. Twelve subjects (6-60 mo poststroke) participated in 24 training sessions (3 sessions/wk for 8 wk). Exercises included leg press, calf raises, and jump training, all performed at high concentric velocity, as well as trials of fast walking. We measured self-selected and fastest comfortable walking speeds as well as knee extensor and plantar flexor strength and power at pretraining, posttraining, and 8 wk follow-up time points. In addition, we also performed a number of clinical assessments commonly used in poststroke rehabilitation trials. Following training, significant improvements in lower-limb muscle strength and power were realized and accompanied by improvements in self-selected as well as fastest comfortable walking speeds. No changes in clinical assessments resulted from training. C1 [Morgan, Patrick; Embry, Aaron; Perry, Lindsay; Holthaus, Katy; Gregory, Chris M.] Med Univ S Carolina, Dept Hlth Sci & Res, Charleston, SC 29425 USA. [Embry, Aaron; Perry, Lindsay; Gregory, Chris M.] Med Univ S Carolina, Div Phys Therapy, Charleston, SC 29425 USA. [Gregory, Chris M.] Vet Affairs Med Ctr, Ralph H Johnson Dept, Charleston, SC 29403 USA. RP Gregory, CM (reprint author), Med Univ S Carolina, Dept Hlth Sci & Res, 77 President St,MSC 700, Charleston, SC 29425 USA. EM gregoryc@musc.edu FU Department of Veterans Affairs (VA), Office of Research and Development, Rehabilitation Research and Development Service [AHA-11BGIA7450016]; Ralph H. Johnson VA Medical Center, Charleston, South Carolina FX Funding/Support: This material was based on work supported by the Department of Veterans Affairs (VA), Office of Research and Development, Rehabilitation Research and Development Service (grant AHA-11BGIA7450016) and the Ralph H. Johnson VA Medical Center, Charleston, South Carolina. NR 31 TC 2 Z9 2 U1 1 U2 7 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 2015 VL 52 IS 1 BP 77 EP 84 DI 10.1682/JRRD.2014.04.0109 PG 8 WC Rehabilitation SC Rehabilitation GA CI8YI UT WOS:000355057200008 PM 26186176 ER PT J AU Udemba, A Smith, G Nguyen, QD Kaliszczak, M Carroll, L Fortt, R Fuchter, MJ Aboagye, EO AF Udemba, A. Smith, G. Nguyen, Q. -D. Kaliszczak, M. Carroll, L. Fortt, R. Fuchter, M. J. Aboagye, E. O. TI Design, synthesis and initial characterisation of a radiolabelled [F-18]pyrimidoindolone probe for detecting activated caspase-3/7 SO ORGANIC & BIOMOLECULAR CHEMISTRY LA English DT Article ID POSITRON-EMISSION-TOMOGRAPHY; PET TRACER; APOPTOSIS; CANCER; TUMORS AB Evasion of apoptosis is one of the six initially proposed hallmarks of cancer, and as such, a method to detect apoptosis in a tumour would be of considerable interest in both clinical trials of new cancer therapeutics, as well as for routine patient management. Activation of caspase-3/7 is a key biomarker of cellular apoptosis. Herein we describe the design, synthesis and initial characterisation of the first pyrimidoindolone compound for detection of caspase-3/7 activation using positron emission tomography. C1 [Udemba, A.; Kaliszczak, M.; Carroll, L.; Aboagye, E. O.] Univ London Imperial Coll Sci Technol & Med, Dept Surg & Canc, Comprehens Canc Imaging Ctr, London W12 0NN, England. [Smith, G.] Inst Canc Res, London SW7 3RP, England. [Nguyen, Q. -D.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Lurie Family Imaging Ctr,Ctr Biomed Imaging Oncol, Boston, MA 02215 USA. [Fortt, R.] St Thomas Hosp, Kings Coll London, Div Imaging Sci & Biomed Engn, London SE1 7EH, England. [Fuchter, M. J.] Univ London Imperial Coll Sci Technol & Med, Dept Chem, London SW7 2AY, England. RP Aboagye, EO (reprint author), Univ London Imperial Coll Sci Technol & Med, Dept Surg & Canc, Comprehens Canc Imaging Ctr, Hammersmith Campus,Du Cane Rd, London W12 0NN, England. EM e.aboagye@imperial.ac.uk OI Smith, Graham/0000-0002-0762-3812 FU CRUK/EPSRC.MRC/DoH (England) [C2536/A10337] FX We thank CRUK/EPSRC.MRC/DoH (England) for funding (grant C2536/A10337). NR 22 TC 0 Z9 0 U1 3 U2 15 PU ROYAL SOC CHEMISTRY PI CAMBRIDGE PA THOMAS GRAHAM HOUSE, SCIENCE PARK, MILTON RD, CAMBRIDGE CB4 0WF, CAMBS, ENGLAND SN 1477-0520 EI 1477-0539 J9 ORG BIOMOL CHEM JI Org. Biomol. Chem. PY 2015 VL 13 IS 19 BP 5418 EP 5423 DI 10.1039/c5ob00058k PG 6 WC Chemistry, Organic SC Chemistry GA CH7HC UT WOS:000354205600016 PM 25865735 ER PT S AU Olson, ES Nakajima, HH AF Olson, Elizabeth S. Nakajima, Hideko H. BE Choi, B Kollias, N Zeng, H Kang, HW Wong, BJF Ilgner, JF Nuttal, A Richter, CP Skala, MC Dewhirst, MW Tearney, GJ Gregory, KW Marcu, L Mandelis, A TI A family of fiber-optic based pressure sensors for intracochlear measurements SO PHOTONIC THERAPEUTICS AND DIAGNOSTICS XI SE Proceedings of SPIE LA English DT Proceedings Paper CT Conference on Photonic Therapeutics and Diagnostics XI CY FEB 07-08, 2015 CL San Francisco, CA SP SPIE, Assoc Res Otolaryngol DE pressure sensor; fiber optic; cochlea; middle ear ID ROUND-WINDOW STIMULATION; HUMAN TEMPORAL BONES; MIDDLE-EAR; SOUND PRESSURES; COCHLEAR PARTITION; TYMPANIC MEMBRANE; CANAL DEHISCENCE; GERBIL; TRANSMISSION; CHINCHILLA AB Fiber-optic pressure sensors have been developed for measurements of intracochlear pressure. The present family of transducers includes an 81 mu m diameter sensor employing a SLED light source and single-mode optic fiber, and LED/multi-mode sensors with 126 and 202 mu m diameter. The 126 mu m diameter pressure sensor also has been constructed with an electrode adhered to its side, for coincident pressure and voltage measurements. These sensors have been used for quantifying cochlear mechanical impedances, informing our understanding of conductive hearing loss and its remediation, and probing the operation of the cochlear amplifier. C1 [Olson, Elizabeth S.] Columbia Univ, Dept Otolaryngol Head & Neck Surg & Biomed Engn, New York, NY 10027 USA. [Nakajima, Hideko H.] Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Otol & Laryngol, Boston, MA USA. RP Olson, ES (reprint author), Columbia Univ, Dept Otolaryngol Head & Neck Surg & Biomed Engn, New York, NY 10027 USA. NR 30 TC 1 Z9 1 U1 0 U2 7 PU SPIE-INT SOC OPTICAL ENGINEERING PI BELLINGHAM PA 1000 20TH ST, PO BOX 10, BELLINGHAM, WA 98227-0010 USA SN 0277-786X BN 978-1-62841-393-9 J9 PROC SPIE PY 2015 VL 9303 AR 93031O DI 10.1117/12.2178056 PG 7 WC Engineering, Biomedical; Optics SC Engineering; Optics GA BC6PW UT WOS:000354366400029 ER PT J AU Turetsky, A Lee, K Song, J Giedt, RJ Kim, E Kovach, AE Hochberg, EP Castro, CM Lee, H Weissleder, R AF Turetsky, Anna Lee, Kyungheon Song, Jun Giedt, Randy J. Kim, Eunha Kovach, Alexandra E. Hochberg, Ephraim P. Castro, Cesar M. Lee, Hakho Weissleder, Ralph TI On Chip Analysis of CNS Lymphoma in Cerebrospinal Fluid SO THERANOSTICS LA English DT Article DE lymphoma; microfluidics; point-of-care; cerebrospinal fluid; drug testing ID B-CELL LYMPHOMA; CENTRAL-NERVOUS-SYSTEM; NON-HODGKINS-LYMPHOMA; OCCULT LEPTOMENINGEAL DISEASE; BRUTONS TYROSINE KINASE; FLOW-CYTOMETRY; CD20 EXPRESSION; GENE-EXPRESSION; RISK-FACTORS; INVOLVEMENT AB Molecular profiling of central nervous system lymphomas in cerebrospinal fluid (CSF) samples can be challenging due to the paucicellular and limited nature of the samples. Presented herein is a microfluidic platform for complete CSF lymphoid cell analysis, including single cell capture in sub-nanoliter traps, and molecular and chemotherapeutic response profiling via on-chip imaging, all in less than one hour. The system can detect scant lymphoma cells and quantitate their kappa/lambda immunoglobulin light chain restriction patterns. The approach can be further customized for measurement of additional biomarkers, such as those for differential diagnosis of lymphoma subtypes or for prognosis, as well as for imaging exposure to experimental drugs. C1 [Turetsky, Anna; Lee, Kyungheon; Song, Jun; Giedt, Randy J.; Kim, Eunha; Castro, Cesar M.; Lee, Hakho; Weissleder, Ralph] Massachusetts Gen Hosp, Ctr Syst Biol, Boston, MA 02114 USA. [Song, Jun] Harvard Univ, Sch Engn & Appl Sci, Cambridge, MA 02138 USA. [Kovach, Alexandra E.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Hochberg, Ephraim P.; Castro, Cesar M.] Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA. [Weissleder, Ralph] Harvard Univ, Sch Med, Dept Syst Biol, Boston, MA 02115 USA. RP Weissleder, R (reprint author), Massachusetts Gen Hosp, Ctr Syst Biol, 185 Cambridge St,CPZN 5206, Boston, MA 02114 USA. EM rweissleder@mgh.harvard.edu FU Harvard Biophysics Graduate Program under NIH training grant [T32008313]; NSF Graduate Research Fellowship [DGE0946799, DGE1144152] FX Authors 1, 2, and 3 contributed equally to this work. We thank A. Letai, T. Gilmore, and R. Ryan for cell lines, and the Harvard Center for Nanoscale Systems for use of their Nanofabrication cleanroom facility. A.T. was supported by the Harvard Biophysics Graduate Program under NIH training grant T32008313 and by an NSF Graduate Research Fellowship under grant numbers DGE0946799 and DGE1144152. NR 40 TC 2 Z9 2 U1 0 U2 7 PU IVYSPRING INT PUBL PI LAKE HAVEN PA PO BOX 4546, LAKE HAVEN, NSW 2263, AUSTRALIA SN 1838-7640 J9 THERANOSTICS JI Theranostics PY 2015 VL 5 IS 8 BP 796 EP 804 DI 10.7150/thno.11220 PG 9 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA CI7QT UT WOS:000354959900002 PM 26000053 ER PT J AU Kim, YR Kim, S Choi, JW Choi, SY Lee, SH Kim, H Hahn, SK Koh, GY Yun, SH AF Kim, Yi Rang Kim, Seonghoon Choi, Jin Woo Choi, Sung Yong Lee, Sang-Hee Kim, Homin Hahn, Sei Kwang Koh, Gou Young Yun, Seok Hyun TI Bioluminescence-Activated Deep-Tissue Photodynamic Therapy of Cancer SO THERANOSTICS LA English DT Article DE Photodynamic Therapy; Bioluminescence; Photosensitizers; Resonance Energy Transfer; Cancer; Photobiology; Photomedicine ID ENERGY-TRANSFER BRET; IN-VIVO; BREAST-CANCER; MULTIDRUG-RESISTANCE; IONIZING-RADIATION; CELLULAR UPTAKE; CHLORIN E6; EX-VIVO; LIGHT; PHOTOIMMUNOTHERAPY AB Optical energy can trigger a variety of photochemical processes useful for therapies. Owing to the shallow penetration of light in tissues, however, the clinical applications of light-activated therapies have been limited. Bioluminescence resonant energy transfer (BRET) may provide a new way of inducing photochemical activation. Here, we show that efficient bioluminescence energy-induced photodynamic therapy (PDT) of macroscopic tumors and metastases in deep tissue. For monolayer cell culture in vitro incubated with Chlorin e6, BRET energy of about 1 nJ per cell generated as strong cytotoxicity as red laser light irradiation at 2.2 mW/cm(2) for 180 s. Regional delivery of bioluminescence agents via draining lymphatic vessels killed tumor cells spread to the sentinel and secondary lymph nodes, reduced distant metastases in the lung and improved animal survival. Our results show the promising potential of novel bioluminescence-activated PDT. C1 [Kim, Yi Rang; Kim, Seonghoon; Koh, Gou Young; Yun, Seok Hyun] Korea Adv Inst Sci & Technol, Grad Sch Nanosci & Technol WCU, Taejon 305701, South Korea. [Kim, Yi Rang; Choi, Sung Yong; Lee, Sang-Hee; Kim, Homin; Koh, Gou Young] Korea Adv Inst Sci & Technol, Grad Sch Med Sci & Engn, Taejon 305701, South Korea. [Kim, Yi Rang] Univ Ulsan, Coll Med, Asan Med Ctr, Dept Oncol, Seoul, South Korea. [Choi, Jin Woo] Wonkwang Univ, Sch Dent, Wonkwang Inst Dent Res, Dept Pharmacol, Iksan 570749, Chonbuk, South Korea. [Choi, Jin Woo; Yun, Seok Hyun] Massachusetts Gen Hosp, Wellman Ctr Photomed, Cambridge, MA 02139 USA. [Hahn, Sei Kwang] Pohang Univ Sci & Technol POSTECH, Dept Mat Sci & Engn, Pohang 790784, Gyeongbuk, South Korea. [Yun, Seok Hyun] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Dermatol, Boston, MA 02114 USA. RP Yun, SH (reprint author), Korea Adv Inst Sci & Technol, Grad Sch Nanosci & Technol WCU, 291 Daehak Ro, Taejon 305701, South Korea. EM syun@hms.harvard.edu RI Koh, Gou Young /C-1615-2011 FU Korea National Research Foundation of Korea [R31-2008-000-10071-0]; Bio & Medical Technology Development Program [2012M3A9C6049791]; Mid-career Researcher Program of the National Research Foundation (NRF) - Korean government (MEST) [2012R1A2A2A06045773]; MGH ECOR Fund for Medical Discovery; US National Institutes of Health [U54CA143837, P41EB015903] FX We thank S. Kim for technical help on TEM, and Dr. Tayyaba Hasan at Wellman Center and Drs. Myung-Gyu Choi and Jae-Myung Park at Seoul St. Mary's Hospital for discussions. This work was funded by the Korea National Research Foundation of Korea (R31-2008-000-10071-0), the Bio & Medical Technology Development Program (2012M3A9C6049791), and Mid-career Researcher Program (2012R1A2A2A06045773) of the National Research Foundation (NRF) funded by the Korean government (MEST), and also by MGH ECOR Fund for Medical Discovery and the US National Institutes of Health (U54CA143837, P41EB015903). NR 73 TC 7 Z9 7 U1 10 U2 57 PU IVYSPRING INT PUBL PI LAKE HAVEN PA PO BOX 4546, LAKE HAVEN, NSW 2263, AUSTRALIA SN 1838-7640 J9 THERANOSTICS JI Theranostics PY 2015 VL 5 IS 8 BP 805 EP 817 DI 10.7150/thno.11520 PG 13 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA CI7QT UT WOS:000354959900003 PM 26000054 ER PT S AU Dhou, S Hurwitz, M Mishra, P Berbeco, R Lewis, J AF Dhou, Salam Hurwitz, Martina Mishra, Pankaj Berbeco, Ross Lewis, John BE Yaniv, ZR Webster, RJ TI 4DCBCT-based motion modeling and 3D fluoroscopic image generation for lung cancer radiotherapy SO MEDICAL IMAGING 2015: IMAGE-GUIDED PROCEDURES, ROBOTIC INTERVENTIONS, AND MODELING SE Proceedings of SPIE LA English DT Proceedings Paper CT Conference on Medical Imaging - Image-Guided Procedures, Robotic Interventions, and Modeling CY FEB 22-24, 2015 CL Orlando, FL SP SPIE, ALIO Ind, Alpin Med Syst, Modus Med Devices Inc, Bruker, Siemens, Natl Diagnost Imaging ID RESPIRATORY MOTION; XCAT PHANTOM; ARTIFACTS AB A method is developed to build patient-specific motion models based on 4DCBCT images taken at treatment time and use them to generate 3D time-varying images (referred to as 3D fluoroscopic images). Motion models are built by applying Principal Component Analysis (PCA) on the displacement vector fields (DVFs) estimated by performing deformable image registration on each phase of 4DCBCT relative to a reference phase. The resulting PCA coefficients are optimized iteratively by comparing 2D projections captured at treatment time with projections estimated using the motion model. The optimized coefficients are used to generate 3D fluoroscopic images. The method is evaluated using anthropomorphic physical and digital phantoms reproducing real patient trajectories. For physical phantom datasets, the average tumor localization error (TLE) and (95th percentile) in two datasets were 0.95 (2.2) mm. For digital phantoms assuming superior image quality of 4DCT and no anatomic or positioning disparities between 4DCT and treatment time, the average TLE and the image intensity error (TIE) in six datasets were smaller using 4DCT-based motion models. When simulating positioning disparities and tumor baseline shifts at treatment time compared to planning 4DCT, the average TLE (95th percentile) and TIE were 4.2 (5.4) mm and 0.15 using 4DCT-based models, while they were 1.2 (2.2) mm and 0.10 using 4DCBCT-based ones, respectively. 4DCBCT-based models were shown to perform better when there are positioning and tumor baseline shift uncertainties at treatment time. Thus, generating 3D fluoroscopic images based on 4DCBCT-based motion models can capture both inter- and intra- fraction anatomical changes during treatment. C1 [Dhou, Salam; Hurwitz, Martina; Berbeco, Ross; Lewis, John] Brigham & Womens Hosp, Dana Farber Canc Inst, Boston, MA 02115 USA. [Dhou, Salam; Hurwitz, Martina; Berbeco, Ross; Lewis, John] Harvard Univ, Sch Med, Boston, MA USA. [Mishra, Pankaj] Varian Med Syst, Palo Alto, CA USA. RP Dhou, S (reprint author), Brigham & Womens Hosp, Dana Farber Canc Inst, 75 Francis St, Boston, MA 02115 USA. NR 19 TC 0 Z9 0 U1 1 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 978-1-62841-505-6 J9 PROC SPIE PY 2015 VL 9415 AR 941510 DI 10.1117/12.2082291 PG 8 WC Optics; Radiology, Nuclear Medicine & Medical Imaging SC Optics; Radiology, Nuclear Medicine & Medical Imaging GA BC6PU UT WOS:000354365300034 ER PT S AU Hamblin, MR AF Hamblin, Michael R. BE Chen, WR TI Strategies to potentiate immune response after photodynamic therapy SO BIOPHOTONICS AND IMMUNE RESPONSES X SE Proceedings of SPIE LA English DT Proceedings Paper CT Conference on Biophotonics and Immune Responses X CY FEB 09-10, 2015 CL San Francisco, CA SP SPIE DE Photodynamic therapy; anti-tumor immunity; dendritic cells; cytotoxic T cells; tumor antigens; T-regulatory cells; immunostimulants ID COLONY-STIMULATING FACTOR; LOW-DOSE CYCLOPHOSPHAMIDE; MHC-CLASS-I; VULVAL INTRAEPITHELIAL NEOPLASIA; TRANSITIONAL CELL-CARCINOMA; REGULATORY T-CELLS; ANTITUMOR IMMUNITY; DENDRITIC CELLS; TUMOR-IMMUNITY; STREPTOCOCCAL PREPARATION AB Photodynamic therapy (PDT) has been used as a cancer therapy for forty years but has not yet advanced to a mainstream cancer treatment. Although PDT has been shown to be an efficient photochemical way to destroy local tumors by a combination of non-toxic dyes and harmless visible light, it is its additional effects in mediating the stimulation of the host immune system that gives PDT a great potential to become more widely used. Although the stimulation of tumor-specific cytotoxic T-cells that can destroy distant tumor deposits after PDT has been reported in some animal models, it remains the exception rather than the rule. This realization has prompted several investigators to test various combination approaches that could potentiate the immune recognition of tumor antigens that have been released after PDT. Some of these combination approaches use immunostimulants including various microbial preparations that activate Toll-like receptors and other receptors for pathogen associated molecular patterns. Other approaches use cytokines and growth factors whether directly administered or genetically encoded. Other promising approaches involve depleting regulatory T-cells and epigenetic reversal agents. We believe that by understanding the methods employed by tumors to evade immune response and neutralizing them, more precise ways of potentiating PDT-induced immunity can be devised. C1 [Hamblin, Michael R.] Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA. [Hamblin, Michael R.] Harvard Univ, Sch Med, Dept Dermatol, Boston, MA 02115 USA. [Hamblin, Michael R.] Harvard MIT Div Hlth Sci & Technol, Cambridge, MA USA. RP Hamblin, MR (reprint author), Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA. NR 94 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 978-1-62841-414-1 J9 PROC SPIE PY 2015 VL 9324 AR 932405 DI 10.1117/12.2081029 PG 15 WC Immunology; Optics; Radiology, Nuclear Medicine & Medical Imaging SC Immunology; Optics; Radiology, Nuclear Medicine & Medical Imaging GA BC5XU UT WOS:000353632200001 ER PT S AU Wang, J Li, B Wu, MX AF Wang, Ji Li, Bo Wu, Mei X. BE Chen, WR TI Non-ablative fractional laser in conjunction with microneedle arrays for improved cutaneous vaccination SO BIOPHOTONICS AND IMMUNE RESPONSES X SE Proceedings of SPIE LA English DT Proceedings Paper CT Conference on Biophotonics and Immune Responses X CY FEB 09-10, 2015 CL San Francisco, CA SP SPIE DE Biodegradable micro-needle; non-ablative fractional laser; double-stranded DNA ID CYCLIC GMP-AMP; DENDRITIC CELLS; CYTOSOLIC DNA; INTRADERMAL DELIVERY; SKIN VACCINATION; ANTIMICROBIAL PEPTIDE; ANTIGEN PRESENTATION; IMMUNE-RESPONSES; INFLUENZA-VIRUS; INNATE IMMUNITY AB Skin is more potent than the muscle for vaccination, but it is not a common site for immunization to date, in part, owing to a relatively high rate of pains and skin irritation and difficulty of administration. Here, we show effective and lesion-free cutaneous vaccination by a combination of a biodegradable microneedle array (MNs) and a FDA-approved non-ablative fractional laser (NAFL). Delivering a vaccine into many micropores, instead of a single "big" pore, in the skin effectively segregated vaccine-induced inflammation into many microzones and resulted in quick resolution of the inflammation, provided that distances between any two micropores were far enough. When the inoculation site was treated by NAFL, prior to insertion of the MNs comprised of PR8 model influenza vaccine, the mice displayed vigorous antigen-uptake, giving rise to strong, Th1-biased immunity. The mice were protected from a challenge of homologous influenza virus at a high dose as well as heterologous H1N1 and H3N2 viruses. The adjuvant effect of NAFL was ascribed primarily to activation of the dsDNA sensing pathway by dsDNA released from laser-damaged skin cells. Thus, mice deficient in the dsDNA sensing pathway, but not Toll like receptor (TLR) or inflammasome pathways, showed poor response to NAFL. Importantly, both mice and swine exhibited strong, protective immunity, but no overt skin reactions with this approach, in sharp contrast to intradermal injections that caused severe, overt skin reactions. The effective lesion-free transcutaneous vaccination merits further clinical studies. C1 [Wu, Mei X.] Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Dermatol, Boston, MA 02114 USA. RP Wu, MX (reprint author), Massachusetts Gen Hosp, Wellman Ctr Photomed, 50 Blossom St,Edwards 222, Boston, MA 02114 USA. EM mwu5@mgh.harvard.org NR 53 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 978-1-62841-414-1 J9 PROC SPIE PY 2015 VL 9324 AR 932409 DI 10.1117/12.2079304 PG 17 WC Immunology; Optics; Radiology, Nuclear Medicine & Medical Imaging SC Immunology; Optics; Radiology, Nuclear Medicine & Medical Imaging GA BC5XU UT WOS:000353632200003 ER PT J AU Luoto, TM Iverson, GL Losoi, H Waljas, M Tenovuo, O Kataja, A Brander, A Ohman, J AF Luoto, Teemu M. Iverson, Grant L. Losoi, Heidi Waljas, Minna Tenovuo, Olli Kataja, Anneli Brander, Antti Ohman, Juha TI Clinical correlates of retrograde amnesia in mild traumatic brain injury SO BRAIN INJURY LA English DT Article DE Concussion; head injury; post-concussion syndrome; retrograde amnesia; return to work; traumatic brain injury ID CLOSED-HEAD-INJURY; POST-CONCUSSION SYMPTOMS; POSTTRAUMATIC AMNESIA; TEMPORAL-LOBE; SCANDINAVIAN GUIDELINES; INITIAL MANAGEMENT; PRACTICAL SCALE; MEMORY; IMPAIRMENT; PREDICTORS AB Primary objective: The purpose of this study was to examine the clinical significance of retrograde amnesia (RA) in patients with acute mild traumatic brain injuries (MTBI). Methods and procedures: An emergency department sample of patients (n = 75), aged 18-60 years, with no pre-morbid medical or psychiatric conditions, who met the WHO criteria for MTBI were enrolled in this prospective, descriptive, follow-up study. This study examined the presence and duration of RA in relation to socio-demographics, MTBI severity markers including neuroimaging (CT, MRI) and clinical outcomes (Rivermead post-concussion symptoms questionnaire, post-concussion syndrome (PCS) diagnosis and return to work (RTW) status) at 2 weeks, 1 month and 6 months post-injury. Main outcomes and results: GCS scores and duration of post-traumatic amnesia (PTA) were related to RA. Those with GCS scores of 14 vs. 15 were more likely to have RA (chi(2) (1) = 13.70, p<0.0001) and a longer duration (Mann-Whitney U = 56.0, p<0.0001, d = 1.15) of RA. The duration of RA and PTA correlated positively (Spearman rho(75) = 0.42, p<0.0001) and those with RA had longer durations of PTA (Mann-Whitney U = 228.5, p = 0.001, d = 1.21). During the follow-up, the presence and duration of RA were not significantly associated with PCS diagnosis or time to RTW. Conclusions: In this study, the presence and duration of RA was not associated with outcome. C1 [Luoto, Teemu M.; Losoi, Heidi; Waljas, Minna; Ohman, Juha] Tampere Univ Hosp, Dept Neurosci & Rehabil, FI-33521 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. [Tenovuo, Olli] Univ Turku, Dept Rehabil & Brain Trauma, Turku, Finland. [Tenovuo, Olli] Univ Turku, Cent Hosp, FIN-20520 Turku, Finland. [Kataja, Anneli; Brander, Antti] Tampere Univ Hosp, Dept Radiol, Med Imaging Ctr, FI-33521 Tampere, Finland. RP Luoto, TM (reprint author), Tampere Univ Hosp, P Box 2000, FI-33521 Tampere, Finland. EM teemu.luoto@pshp.fi OI Ohman, Juha/0000-0002-6592-1367; Luoto, Teemu/0000-0002-7329-3284 FU Medical Research Fund of Tampere University Hospital FX The authors thank research assistants Anne Simi and Marika Suopanki-Ervasti for their contribution in data collection. This study was done as part of the first author's PhD thesis research program. A portion of this study was presented at the 9th World Congress on Brain Injury in Edinburgh, Scotland, in March 2012. This study has been supported by the Medical Research Fund of Tampere University Hospital. NR 56 TC 2 Z9 2 U1 2 U2 9 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 530 WALNUT STREET, STE 850, PHILADELPHIA, PA 19106 USA SN 0269-9052 EI 1362-301X J9 BRAIN INJURY JI Brain Inj. PY 2015 VL 29 IS 5 BP 565 EP 572 DI 10.3109/02699052.2014.1002421 PG 8 WC Neurosciences; Rehabilitation SC Neurosciences & Neurology; Rehabilitation GA CH3GL UT WOS:000353917000004 PM 25789824 ER PT J AU Negraes, PD Trujillo, CA Pillat, MM Teng, YD Ulrich, H AF Negraes, Priscilla D. Trujillo, Cleber A. Pillat, Micheli M. Teng, Yang D. Ulrich, Henning TI Roles of Kinins in the Nervous System SO CELL TRANSPLANTATION LA English DT Review DE Bradykinin; B1BKR and B2BKR; Neural differentiation; Neuroprotection; Inflammation ID SPINAL-CORD-INJURY; TRAUMATIC BRAIN-INJURY; BRADYKININ B-1 RECEPTOR; NEURAL STEM-CELLS; TISSUE KALLIKREIN; B2 RECEPTOR; ALZHEIMERS-DISEASE; ISCHEMIC-STROKE; INHIBITING APOPTOSIS; KINASE ACTIVATION AB The kallikrein kinin system (KKS) is an endogenous pathway involved in many biological processes. Although primarily related to blood pressure control and inflammation, its activation goes beyond these effects. Neurogenesis and neuroprotection might be stimulated by bradykinin being of great interest for clinical applications following brain injury. This peptide is also an important player in spinal cord injury pathophysiology and recovery, in which bradykinin receptor blockers represent substantial therapeutic potential. Here, we highlight the participation of kinin receptors and especially bradykinin in mediating ischemia pathophysiology in the central and peripheral nervous systems. Moreover, we explore the recent advances on mechanistic and therapeutic targets for biological, pathological, and neural repair processes involving kinins. C1 [Negraes, Priscilla D.; Pillat, Micheli M.; Ulrich, Henning] Univ Sao Paulo, Inst Quim, Dept Bioquim, BR-05508900 Sao Paulo, Brazil. [Trujillo, Cleber A.] Univ Calif San Diego, Sch Med, Dept Pediat, Rady Childrens Hosp San Diego,Stem Cell Program, La Jolla, CA 92093 USA. [Teng, Yang D.] Harvard Univ, Sch Med, Dept Neurosurg, Boston, MA USA. [Teng, Yang D.] Harvard Univ, Sch Med, Dept Phys Med & Rehabil, Boston, MA USA. [Teng, Yang D.] VABHS, Div SCI Res, Boston, MA USA. RP Ulrich, H (reprint author), Univ Sao Paulo, Inst Quim, Dept Bioquim, Ave Prof Linen Prestes 748, BR-05508900 Sao Paulo, Brazil. EM henning@iq.usp.br RI Ulrich, Henning/C-5245-2013 OI Ulrich, Henning/0000-0002-2114-3815 FU Fundacao de Amparo a Pesquisa do Estado de Sao Paulo (FAPESP); Conselho Nacional de Desenvolvimento Cientifico e Tecnologico (CNPq), Brazil FX This work was supported by research grants from Fundacao de Amparo a Pesquisa do Estado de Sao Paulo (FAPESP) and Conselho Nacional de Desenvolvimento Cientifico e Tecnologico (CNPq), Brazil. The authors declare no conflict of interest. NR 101 TC 5 Z9 6 U1 0 U2 5 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 2015 VL 24 IS 4 SI SI BP 613 EP 623 DI 10.3727/096368915X687778 PG 11 WC Cell & Tissue Engineering; Medicine, Research & Experimental; Transplantation SC Cell Biology; Research & Experimental Medicine; Transplantation GA CH3KD UT WOS:000353928700004 PM 25839228 ER PT J AU Koh, SH Liang, AC Takahashi, Y Maki, T Shindo, A Osumi, N Zhao, J Lin, H Holder, JC Chuang, TT McNeish, JD Arai, K Lo, EH AF Koh, S. H. Liang, A. C. Takahashi, Y. Maki, T. Shindo, A. Osumi, N. Zhao, J. Lin, H. Holder, J. C. Chuang, T. T. McNeish, J. D. Arai, K. Lo, E. H. TI Differential Effects of Isoxazole-9 on Neural Stein/Progenitor Cells, Oligodendrocyte Precursor Cells, and Endothelial Progenitor Cells in Primary Culture SO CELL TRANSPLANTATION LA English DT Meeting Abstract CT 22nd Annual Meeting of the American-Society-for-Neural-Therapy-and-Repair (ASNTR) CY APR 30-MAY 02, 2015 CL Clearwater, FL SP Amer Soc Neural Therapy & Repair C1 [Koh, S. H.; Liang, A. C.; Takahashi, Y.; Maki, T.; Shindo, A.; Arai, K.; Lo, E. H.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Radiol,Neuroprotect Res Lab, Cambridge, MA 02138 USA. [Koh, S. H.; Liang, A. C.; Takahashi, Y.; Maki, T.; Shindo, A.; Arai, K.; Lo, E. H.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Neurol,Neuroprotect Res Lab, Cambridge, MA 02138 USA. [Koh, S. H.] Hanyang Univ, Coll Med, Dept Neurol, Seoul 133791, South Korea. [Takahashi, Y.; Osumi, N.] Tohoku Univ, Grad Sch Med, United Ctr Adv Res & Translat Med, Div Dev Neurosci, Sendai, Miyagi 980, Japan. 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 2015 VL 24 IS 4 SI SI BP 763 EP 763 PG 1 WC Cell & Tissue Engineering; Medicine, Research & Experimental; Transplantation SC Cell Biology; Research & Experimental Medicine; Transplantation GA CH3KD UT WOS:000353928700052 ER PT J AU Liang, AC Maki, T Shindo, A Mandeville, ET Som, AT Chuang, TT McNeish, JD Holder, JC Lo, EH Arai, K AF Liang, A. C. Maki, T. Shindo, A. Mandeville, E. T. Som, A. T. Chuang, T. T. McNeish, J. D. Holder, J. C. Lo, E. H. Arai, K. TI Aging Disturbs Regenerative Responses in Neural Stein/Progenitor Cells and Oligodendrocyte Precursor Cells in Spontaneous Hypertensive Rats SO CELL TRANSPLANTATION LA English DT Meeting Abstract CT 22nd Annual Meeting of the American-Society-for-Neural-Therapy-and-Repair (ASNTR) CY APR 30-MAY 02, 2015 CL Clearwater, FL SP Amer Soc Neural Therapy & Repair C1 [Liang, A. C.; Maki, T.; Shindo, A.; Mandeville, E. T.; Som, A. T.; Lo, E. H.; Arai, K.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Neuroprotect Res Lab,Dept Radiol, Cambridge, MA 02138 USA. [Liang, A. C.; Maki, T.; Shindo, A.; Mandeville, E. T.; Som, A. T.; Lo, E. H.; Arai, K.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Neuroprotect Res Lab,Dept Neurol, Cambridge, MA 02138 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 2015 VL 24 IS 4 SI SI BP 764 EP 764 PG 1 WC Cell & Tissue Engineering; Medicine, Research & Experimental; Transplantation SC Cell Biology; Research & Experimental Medicine; Transplantation GA CH3KD UT WOS:000353928700054 ER PT J AU Miyamoto, N Maki, T Liang, AC Shindo, A Itoh, K Lo, EK Lok, J Arai, K AF Miyamoto, N. Maki, T. Liang, A. C. Shindo, A. Itoh, K. Lo, E. K. Lok, J. Arai, K. TI Endogenous Brain-Derived Neurotrophic Factor Promotes Oligodendrogenesis by Mediating Signals From Astrocytes to Oligodendrocyte Precursor Cells SO CELL TRANSPLANTATION LA English DT Meeting Abstract CT 22nd Annual Meeting of the American-Society-for-Neural-Therapy-and-Repair (ASNTR) CY APR 30-MAY 02, 2015 CL Clearwater, FL SP Amer Soc Neural Therapy & Repair C1 [Miyamoto, N.; Maki, T.; Liang, A. C.; Shindo, A.; Itoh, K.; Lo, E. K.; Lok, J.; Arai, K.] Massachusetts Gen Hosp, Dept Radiol, Neuroprotect Res Lab, Cambridge, MA USA. [Miyamoto, N.; Maki, T.; Liang, A. C.; Shindo, A.; Itoh, K.; Lo, E. K.; Lok, J.; Arai, K.] Massachusetts Gen Hosp, Dept Neurol, Neuroprotect Res Lab, Cambridge, MA USA. [Miyamoto, N.; Maki, T.; Liang, A. C.; Shindo, A.; Itoh, K.; Lo, E. K.; Lok, J.; Arai, K.] Harvard Univ, Sch Med, Cambridge, MA 02138 USA. [Lok, J.] Massachusetts Gen Hosp, Dept Pediat, Cambridge, 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 2015 VL 24 IS 4 SI SI BP 766 EP 766 PG 1 WC Cell & Tissue Engineering; Medicine, Research & Experimental; Transplantation SC Cell Biology; Research & Experimental Medicine; Transplantation GA CH3KD UT WOS:000353928700060 ER PT J AU Huffman, JC DuBois, CM Millstein, RA Celano, CM Wexler, D AF Huffman, Jeff C. DuBois, Christina M. Millstein, Rachel A. Celano, Christopher M. Wexler, Deborah TI Positive Psychological Interventions for Patients with Type 2 Diabetes: Rationale, Theoretical Model, and Intervention Development SO JOURNAL OF DIABETES RESEARCH LA English DT Review ID RANDOMIZED-CONTROLLED-TRIAL; PROMOTE PHYSICAL-ACTIVITY; MOTIVATIONAL ENHANCEMENT THERAPY; COGNITIVE-BEHAVIORAL THERAPY; SELF-DETERMINATION THEORY; CORONARY-HEART-DISEASE; GLYCEMIC CONTROL; WEIGHT-LOSS; LIFE-STYLE; DISPOSITIONAL OPTIMISM AB Most patients with type 2 diabetes (T2D) have suboptimal adherence to recommended diet, physical activity, and/or medication. Current approaches to improve health behaviors in T2D have been variably effective, and successful interventions are often complex and intensive. It is therefore vital to develop interventions that are simple, well-accepted, and applicable to a wide range of patients who suffer from T2D. One approach may be to boost positive psychological states, such as positive affect or optimism, as these constructs have been prospectively and independently linked to improvements in health behaviors. Positive psychology (PP) interventions, which utilize systematic exercises to increase optimism, well-being, and positive affect, consistently increase positive states and are easily delivered to patients with chronic illnesses. However, to our knowledge, PP interventions have not been formally tested in T2D. In this paper, we review a theoretical model for the use of PP interventions to target health behaviors in T2D, describe the structure and content of a PP intervention for T2D patients, and describe baseline data from a single-arm proof-of-concept (N = 15) intervention study in T2D patients with or without depression. We also discuss how PP interventions could be combined with motivational interviewing (MI) interventions to provide a blended psychological-behavioral approach. C1 [Huffman, Jeff C.; DuBois, Christina M.; Millstein, Rachel A.; Celano, Christopher M.; Wexler, Deborah] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. [Huffman, Jeff C.; Millstein, Rachel A.; Celano, Christopher M.] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Wexler, Deborah] Massachusetts Gen Hosp, Dept Med, MGH Diabet Ctr, Boston, MA 02114 USA. RP Huffman, JC (reprint author), Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. EM jhuffman@partners.org FU NIH Grant [R01HL113272] FX This work was supported in part by NIH Grant R01HL113272 to Dr. Jeff Huffman. NR 151 TC 0 Z9 0 U1 9 U2 25 PU HINDAWI PUBLISHING CORP 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 2015 AR 428349 DI 10.1155/2015/428349 PG 18 WC Endocrinology & Metabolism; Medicine, Research & Experimental SC Endocrinology & Metabolism; Research & Experimental Medicine GA CH8ZO UT WOS:000354325900001 ER PT J AU Hou, HW Bhattacharyya, RP Hung, DT Han, J AF Hou, Han Wei Bhattacharyya, Roby P. Hung, Deborah T. Han, Jongyoon TI Direct detection and drug-resistance profiling of bacteremias using inertial microfluidics SO LAB ON A CHIP LA English DT Article ID STAPHYLOCOCCUS-AUREUS; CLINICAL MICROBIOLOGY; RAPID IDENTIFICATION; INFECTIOUS-DISEASES; SEQUENCE-ANALYSIS; SEPTIC SHOCK; WHOLE-BLOOD; SEPARATION; BACTERIAL; PCR AB Detection of bacteria in bloodstream infections and their antibiotic susceptibility patterns is critical to guide therapeutic decision-making for optimal patient care. Current culture-based assays are too slow (> 48 h), leading to excessive up-front use of broad-spectrum antibiotics and/or incorrect antibiotic choices due to resistant bacteria, each with deleterious consequences for patient care and public health. To approach this problem, we describe a method to rapidly isolate bacteria from whole blood using inertial microfluidics and directly determine pathogen identity and antibiotic susceptibility with hybridization-based RNA detection. Using the principle of Dean flow fractionation, bacteria are separated from host blood cells in a label-free separation method with efficient recovery of even low abundance bacteria. Ribosomal RNA detection can then be applied for direct identification of low abundance pathogens (similar to 100 per mL) from blood without culturing or enzymatic amplification. Messenger RNA detection of antibiotic-responsive transcripts after brief drug exposure permits rapid susceptibility determination from bacteria with minimal culturing (similar to 10(5) per mL). This unique coupling of microfluidic cell separation with RNA-based molecular detection techniques represents significant progress towards faster diagnostics (similar to 8 hours) to guide antibiotic therapy. C1 [Hou, Han Wei; Han, Jongyoon] MIT, Dept Elect Engn & Comp Sci, Cambridge, MA 02139 USA. [Bhattacharyya, Roby P.; Hung, Deborah T.] Broad Inst, Cambridge, MA 02142 USA. [Bhattacharyya, Roby P.] Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA. [Hung, Deborah T.] Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. [Hung, Deborah T.] Massachusetts Gen Hosp, Ctr Computat & Integrat Biol, Boston, MA 02114 USA. [Hung, Deborah T.] Harvard Univ, Sch Med, Dept Microbiol & Immunol, Boston, MA 02115 USA. [Han, Jongyoon] MIT, Dept Biol Engn, Cambridge, MA 02139 USA. RP Hung, DT (reprint author), Broad Inst, Cambridge, MA 02142 USA. EM hung@molbio.mgh.harvard.edu; jyhan@mit.edu FU MIT's Microsystems Technology Laboratories; DARPA DLT (Dialysis-Like Therapeutics) program under SSC Pacific [N66001-11-1-4182]; KL2/Catalyst Medical Research Investigator Training award from Harvard Catalyst \ The Harvard Clinical Translational Science Center (National Center for Research Resources); KL2/Catalyst Medical Research Investigator Training award from Harvard Catalyst \ The Harvard Clinical Translational Science Center (National Center for Advancing Translational Sciences, National Institutes of Health) [1KL2TR001100-01]; Lee Kong Chian School of Medicine (LKCMedicine, Singapore) Postdoctoral Fellowship FX This work is supported by the use of MIT's Microsystems Technology Laboratories, as well as the financial support by DARPA DLT (Dialysis-Like Therapeutics) program, under SSC Pacific grant N66001-11-1-4182. This work was also conducted with the support of a KL2/Catalyst Medical Research Investigator Training award (an appointed KL2 award, to R.P.B.) from Harvard Catalyst vertical bar The Harvard Clinical Translational Science Center (National Center for Research Resources and the National Center for Advancing Translational Sciences, National Institutes of Health Award 1KL2TR001100-01). The content is solely the responsibility of the authors and does not represent the official views of Harvard Catalyst, Harvard University and its affiliated academic health care centers, the National Institutes of Health, or DARPA. H.W.H. is supported by Lee Kong Chian School of Medicine (LKCMedicine, Singapore) Postdoctoral Fellowship. NR 57 TC 16 Z9 16 U1 8 U2 55 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 2015 VL 15 IS 10 BP 2297 EP 2307 DI 10.1039/c5lc00311c PG 11 WC Biochemical Research Methods; Chemistry, Multidisciplinary; Nanoscience & Nanotechnology SC Biochemistry & Molecular Biology; Chemistry; Science & Technology - Other Topics GA CH7DU UT WOS:000354196600016 PM 25882432 ER PT S AU Dong, TT Zhang, Q Hamblin, MR Wu, MX AF Dong, Tingting Zhang, Qi Hamblin, Michael R. Wu, Mei X. BE Hamblin, MR Carroll, JD Arany, P TI Low level light in combination with metabolic modulators for effective therapy SO MECHANISMS FOR LOW-LIGHT THERAPY X SE Proceedings of SPIE LA English DT Proceedings Paper CT Conference on Mechanisms for Low-Light Therapy X CY FEB 07-08, 2015 CL San Francisco, CA SP SPIE, THOR Photomedicine Ltd DE TBI; hypoxia; Low Level Light; Lactate/Pyruvate; mitochondrial function ID TRAUMATIC BRAIN-INJURY; RAT-LIVER MITOCHONDRIA; TREATMENT STRATEGIES; TRANSCRANIAL LASER; ENERGY-METABOLISM; UNITED-STATES; SPINAL-CORD; IN-VITRO; HYPOXIA; LACTATE AB Vascular damage occurs frequently at the injured brain causing hypoxia and is associated with poor outcomes in the clinics. We found high levels of glycolysis, reduced ATP generation, and increased formation of reactive oxygen species (ROS) and apoptosis in neurons under hypoxia. Strikingly, these adverse events were reversed significantly by noninvasive exposure of injured brain to low-level light (LLL). LLL illumination sustained the mitochondrial membrane potential, constrained cytochrome C leakage in hypoxic cells, and protected them from apoptosis, underscoring a unique property of LLL. The effect of LLL was further bolstered by combination with metabolic substrates such as pyruvate or lactate both in vivo and in vitro. The combinational treatment retained memory and learning activities of injured mice to a normal level, whereas those treated with LLL or pyruvate alone, or sham light displayed partial or severe deficiency in these cognitive functions. In accordance with well-protected learning and memory function, the hippocampal region primarily responsible for learning and memory was completely protected by a combination of LLL and pyruvate, in marked contrast to the severe loss of hippocampal tissue due to secondary damage in control mice. These data clearly suggest that energy metabolic modulators can additively or synergistically enhance the therapeutic effect of LLL in energy-producing insufficient tissues like injured brain. C1 [Dong, Tingting; Zhang, Qi; Hamblin, Michael R.; Wu, Mei X.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Wellman Ctr Photomed,Dept Dermatol, Boston, MA 02114 USA. RP Wu, MX (reprint author), 50 Blossom St, Boston, MA 02114 USA. EM mwu5@mgh.harvard.edu NR 49 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 978-1-62841-399-1 J9 PROC SPIE PY 2015 VL 9309 AR 93090A DI 10.1117/12.2079363 PG 22 WC Optics; Radiology, Nuclear Medicine & Medical Imaging SC Optics; Radiology, Nuclear Medicine & Medical Imaging GA BC6EU UT WOS:000353877400009 ER PT S AU Hamblin, MR de Sousa, MVP Arany, PR Carroll, JD Patthoff, D AF Hamblin, Michael R. Pires de Sousa, Marcelo Victor Arany, Praveen R. Carroll, James D. Patthoff, Donald BE Hamblin, MR Carroll, JD Arany, P TI Low Level Laser (Light) Therapy and Photobiomodulation: The Path Forward SO MECHANISMS FOR LOW-LIGHT THERAPY X SE Proceedings of SPIE LA English DT Proceedings Paper CT Conference on Mechanisms for Low-Light Therapy X CY FEB 07-08, 2015 CL San Francisco, CA SP SPIE, THOR Photomedicine Ltd DE low level laser (light) therapy; LLLT; photobiomodulation; mechanism of action; mitochondria; TRP ion channels; new indications; new light sources ID NEAR-INFRARED LIGHT; POTENTIAL TRP CHANNELS; BIPHASIC DOSE-RESPONSE; MPTP-TREATED MICE; BONE-MARROW; MOUSE MODEL; STEM-CELLS; NEUROPROTECTION; DEGENERATION; INFLAMMATION AB Low level laser (light) therapy (LLLT) also known as photobiomodulation (PBM) therapy has been practiced for almost fifty years, and hundreds of positive clinical trials and thousands of laboratory studies have been published. Despite these impressive accomplishments LLLT has still not reached the stage of acceptance by mainstream medicine. The reasons for this were discussed at a recent Optical Society of America (OSA) Incubator meeting in Washington DC in 2014. Uncertainty about mechanisms was highlighted, and this paper will describe the current thinking. To drive LLLT towards mainstream medicine, we need better guidelines with standardized protocols and consistent parameters. Studies should be published in higher impact scientific and medical journals. Companies should avoid false promises and deceptive marketing, and physicians should receive a clearly defined return on investment with insurance reimbursement. C1 [Hamblin, Michael R.] Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA. [Hamblin, Michael R.] Harvard Univ, Sch Med, Dept Dermatol, Boston, MA 02115 USA. [Hamblin, Michael R.] Harvard Mit Div Hlth Sci & Technol, Cambridge, MA USA. [Pires de Sousa, Marcelo Victor] Univ Sao Paulo, Inst Phys, Lab Radiat Dosimetry & Med Phys, Sao Paulo, Brazil. [Arany, Praveen R.] NIDCR, NIH, Bethesda, MD USA. [Carroll, James D.] THOR Photomed Ltd, Chesham, England. [Patthoff, Donald] Gen Dent, Martinsburg, WV USA. RP Hamblin, MR (reprint author), Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA. NR 58 TC 2 Z9 2 U1 3 U2 10 PU SPIE-INT SOC OPTICAL ENGINEERING PI BELLINGHAM PA 1000 20TH ST, PO BOX 10, BELLINGHAM, WA 98227-0010 USA SN 0277-786X BN 978-1-62841-399-1 J9 PROC SPIE PY 2015 VL 9309 AR 930902 DI 10.1117/12.2084049 PG 11 WC Optics; Radiology, Nuclear Medicine & Medical Imaging SC Optics; Radiology, Nuclear Medicine & Medical Imaging GA BC6EU UT WOS:000353877400002 ER PT S AU Xuan, WJ Huang, LY Vatansever, F Agrawal, T Hamblin, MR AF Xuan, Weijun Huang, Liyi Vatansever, Fatma Agrawal, Tanupriya Hamblin, Michael R. BE Hamblin, MR Carroll, JD Arany, P TI Transcranial low-level laser therapy increases memory, learning, neuroprogenitor cells, BDNF and synaptogenesis in mice with traumatic brain injury. SO MECHANISMS FOR LOW-LIGHT THERAPY X SE Proceedings of SPIE LA English DT Proceedings Paper CT Conference on Mechanisms for Low-Light Therapy X CY FEB 07-08, 2015 CL San Francisco, CA SP SPIE, THOR Photomedicine Ltd DE traumatic brain injury; LLLT; neurogenesis; synaptogenesis; BDNF; dentate gyrus ID ADULT NEUROGENESIS; NEUROTROPHIC FACTOR; ALZHEIMERS-DISEASE; DENTATE GYRUS; LIGHT THERAPY; ISCHEMIA; EXERCISE; STROKE; RAT; NEUROPROTECTION AB Increasing concern is evident over the epidemic of traumatic brain injury in both civilian and military medicine, and the lack of approved treatments. Transcranial low level laser therapy tLLLT) is a new approach in which near infrared laser is delivered to the head, penetrates the scalp and skull to reach the brain. We asked whether tLLLT at 810-nm could improve memory and learning in mice with controlled cortical impact traumatic brain injury. We investigated the mechanism of action by immunofluorescence studies in sections from brains of mice sacrificed at different times. Mice with TBI treated with 1 or 3 daily laser applications performed better on Morris Water Maze test at 28 days. Laser treated mice had increased BrdU incorporation into NeuN positive cells in the dentate gyrus and subventricular zone indicating formation of neuroprogenitor cells at 7 days and less at 28 days. Markers of neuron migration (DCX and Tuj1) were also increased, as was the neurotrophin, brain derived neurotrophic factor (BDNF) at 7 days. Markers of synaptogenesis (formation of new connections between existing neurons) were increased in the perilesional cortex at 28 days. tLLLT is proposed to be able to induce the brain to repair itself after injury. However its ability to induce neurogenesis and synaptogenesis suggests that tLLLT may have much wider applications to neurodegenerative and psychiatric disorders. C1 [Xuan, Weijun; Huang, Liyi; Vatansever, Fatma; Agrawal, Tanupriya; Hamblin, Michael R.] Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA. [Xuan, Weijun; Huang, Liyi; Vatansever, Fatma; Agrawal, Tanupriya; Hamblin, Michael R.] Harvard Univ, Sch Med, Dept Dermatol, Boston, MA 02115 USA. [Xuan, Weijun] Tradit Chinese Med Univ Guangxi, Dept Otolaryngol, Nanning, Peoples R China. [Huang, Liyi] Guangxi Med Univ, Dept Infect Dis, Affiliated Coll & Hosp 1, Nanning, Peoples R China. [Hamblin, Michael R.] Harvard Mit Div Hlth Sci & Technol, Cambridge, MA USA. RP Xuan, WJ (reprint author), Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA. NR 46 TC 0 Z9 0 U1 2 U2 7 PU SPIE-INT SOC OPTICAL ENGINEERING PI BELLINGHAM PA 1000 20TH ST, PO BOX 10, BELLINGHAM, WA 98227-0010 USA SN 0277-786X BN 978-1-62841-399-1 J9 PROC SPIE PY 2015 VL 9309 AR 93090C DI 10.1117/12.2081022 PG 10 WC Optics; Radiology, Nuclear Medicine & Medical Imaging SC Optics; Radiology, Nuclear Medicine & Medical Imaging GA BC6EU UT WOS:000353877400010 ER PT J AU Yang, YF Hou, LF El Ouaamari, A Xin, LJ AF Yang, Yifu Hou, Lifei El Ouaamari, Abdelfattah Xin, Lijun TI Anti-Inflammatory Natural Products SO MEDIATORS OF INFLAMMATION LA English DT Editorial Material C1 [Yang, Yifu] Shanghai Univ Tradit Chinese Med, Lab Immunol & Virol, Shanghai 201203, Peoples R China. [Hou, Lifei] Harvard Univ, Sch Med, Boston Childrens Hosp, Program Cellular & Mol Med, Boston, MA 02115 USA. [Hou, Lifei] Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. [El Ouaamari, Abdelfattah] Harvard Univ, Sch Med, Joslin Diabet Ctr, Boston, MA 02115 USA. [Xin, Lijun] Cincinnati Childrens Hosp Med Ctr, Div Infect Dis, Cincinnati, OH 45229 USA. RP Yang, YF (reprint author), Shanghai Univ Tradit Chinese Med, Lab Immunol & Virol, Shanghai 201203, Peoples R China. EM yangyifu@mail.shcnc.ac.cn NR 2 TC 0 Z9 0 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 2015 AR 608613 DI 10.1155/2015/608613 PG 1 WC Cell Biology; Immunology SC Cell Biology; Immunology GA CH9BW UT WOS:000354332000001 ER PT J AU Apetoh, L Smyth, MJ Drake, CG Abastado, JP Apte, RN Ayyoub, M Blay, JY Bonneville, M Butterfield, LH Caignard, A Castelli, C Cavallo, F Celis, E Chen, LP Colombo, MP Comin-Anduix, B Coukos, G Dhodapkar, MV Dranoff, G Frazer, IH Fridman, WH Gabrilovich, DI Gilboa, E Gnjatic, S Jager, D Kalinski, P Kaufman, HL Kiessling, R Kirkwood, J Knuth, A Liblau, R Lotze, MT Lugli, E Marincola, F Melero, I Melief, CJ Mempel, TR Mittendorf, EA Odun, K Overwijk, WW Palucka, AK Parmiani, G Ribas, A Romero, P Schreiber, RD Schuler, G Srivastava, PK Tartour, E Valmori, D van der Burg, SH van der Bruggen, P van den Eynde, BJ Wang, E Zou, WP Whiteside, TL Speiser, DE Pardoll, DM Restifo, NP Anderson, AC AF Apetoh, Lionel Smyth, Mark J. Drake, Charles G. Abastado, Jean-Pierre Apte, Ron N. Ayyoub, Maha Blay, Jean-Yves Bonneville, Marc Butterfield, Lisa H. Caignard, Anne Castelli, Chiara Cavallo, Federica Celis, Esteban Chen, Lieping Colombo, Mario P. Comin-Anduix, Begona Coukos, Georges Dhodapkar, Madhav V. Dranoff, Glenn Frazer, Ian H. Fridman, Wolf-Herve Gabrilovich, Dmitry I. Gilboa, Eli Gnjatic, Sacha Jaeger, Dirk Kalinski, Pawel Kaufman, Howard L. Kiessling, Rolf Kirkwood, John Knuth, Alexander Liblau, Roland Lotze, Michael T. Lugli, Enrico Marincola, Francesco Melero, Ignacio Melief, Cornelis J. Mempel, Thorsten R. Mittendorf, Elizabeth A. Odun, Kunle Overwijk, Willem W. Palucka, Anna Karolina Parmiani, Giorgio Ribas, Antoni Romero, Pedro Schreiber, Robert D. Schuler, Gerold Srivastava, Pramod K. Tartour, Eric Valmori, Danila van der Burg, Sjoerd H. van der Bruggen, Pierre van den Eynde, Benoit J. Wang, Ena Zou, Weiping Whiteside, Theresa L. Speiser, Daniel E. Pardoll, Drew M. Restifo, Nicholas P. Anderson, Ana C. TI Consensus nomenclature for CD8(+) T cell phenotypes in cancer SO ONCOIMMUNOLOGY LA English DT Article DE anergy; anticancer immunity; CD8(+) T cells; cytotoxicity; exhaustion; effector; IFN gamma; senescence; stemness ID CHRONIC VIRAL-INFECTION; ANTIGEN-LOSS VARIANTS; TUMOR-SPECIFIC CTL; ANTITUMOR IMMUNITY; REPLICATIVE SENESCENCE; MELANOMA PATIENTS; INTERFERON-GAMMA; DENDRITIC CELLS; IN-VITRO; INHIBITORY RECEPTORS C1 [Apetoh, Lionel] INSERM, UMR 866, Dijon, France. [Apetoh, Lionel] Ctr Georges Francois Leclerc, Dijon, France. [Apetoh, Lionel] Univ Bourgogne, Dijon, France. [Smyth, Mark J.] QIMR Berghofer Med Res Inst, Herston, Qld, Australia. [Drake, Charles G.; Pardoll, Drew M.] Johns Hopkins Univ, Sch Med, Sidney Kimmel Comprehens Canc Ctr, Baltimore, MD USA. [Abastado, Jean-Pierre] Inst Rech Int Servier, Suresnes, France. [Apte, Ron N.] Ben Gurion Univ Negev, Fac Hlth Sci, Shraga Segal Dept Microbiol, Immunol & Genet, Beer Sheva, Israel. [Ayyoub, Maha; Valmori, Danila] INSERM, U1102, Equipe Labellisee Ligue Canc, Inst Cancerol Ouest, Nantes St Hreblain, France. [Blay, Jean-Yves] Canc Res Ctr Lyon, INSERM UMR 1052, CNRS UMR 5286, Ctr Leon Berard, Lyon, France. [Blay, Jean-Yves] Dept Med Oncol, Lyon, France. [Bonneville, Marc] CRCNA, INSERM U892, CNRS UMR 6299, Nantes, France. [Bonneville, Marc] Inst Merienx, Lyon, France. [Butterfield, Lisa H.] Univ Pittsburgh, Inst Canc, Dept Med, Pittsburgh, PA USA. [Butterfield, Lisa H.] Univ Pittsburgh, Inst Canc, Dept Surg, Pittsburgh, PA USA. [Butterfield, Lisa H.] Univ Pittsburgh, Inst Canc, Dept Immunol, Pittsburgh, PA USA. [Caignard, Anne] INSERM UMR 1116, Paris, France. [Castelli, Chiara] Fdn IRCCS Ist Nazl Tumori, Dept Expt Oncol & Mol Med, Unit Immunotherapy Human Tumor, Milan, Italy. [Cavallo, Federica] Univ Turin, Ctr Mol Biotechnol, Dept Mol Biotechnol & Hlth Sci, I-10124 Turin, Italy. [Celis, Esteban] Georgia Regents Univ, Ctr Canc, Canc Immunol, Inflammat & Tolerance Program, Augusta, GA USA. [Chen, Lieping] Yale Univ, Sch Med, Dept Immunobiol, New Haven, CT USA. [Chen, Lieping] Yale Univ, Sch Med, Yale Canc Ctr, New Haven, CT USA. [Colombo, Mario P.] Fdn IRCCS Ist Nazl Tumori, Mol Immunol Unit, Dept Expt Oncol & Mol Med, Milan, Italy. [Comin-Anduix, Begona; Ribas, Antoni] Univ Calif Los Angeles, Sch Med, Jonsson Comprehens Canc Ctr Los Angels, Los Angeles, CA 90024 USA. [Coukos, Georges; Romero, Pedro; Speiser, Daniel E.] Univ Lausanne, Dept Oncol, Ludwig Ctr Canc Res, CH-1015 Lausanne, Switzerland. [Dranoff, Glenn] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Dranoff, Glenn] Dana Farber Canc Inst, Canc Vaccine Ctr, Boston, MA 02115 USA. [Dranoff, Glenn] Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. [Dranoff, Glenn; Anderson, Ana C.] Harvard Univ, Sch Med, Boston, MA USA. [Frazer, Ian H.] Univ Queensland, Brisbane, Qld 4072, Australia. [Fridman, Wolf-Herve] Univ Paris 05, Cordeliers Res Ctr, Paris, France. [Gabrilovich, Dmitry I.] Wistar Inst Anat & Biol, Translat Tumor Immunol, Philadelphia, PA 19104 USA. [Gilboa, Eli] Univ Miami, Miller Sch Med, Dodson Interdisciplinary Immunotherapy Inst, Dept Microbiol & Immunol,Sylvester Comprehens Can, Miami, FL USA. [Gnjatic, Sacha] Icahn Sch Med Mt Sinai, Tisch Canc Inst, New York, NY 10029 USA. [Jaeger, Dirk] Univ Heidelberg Hosp, Internal Med 4, Natl Ctr Tumor Dis, Dept Med Oncol, Heidelberg, Germany. [Kalinski, Pawel] Univ Pittsburgh, Dept Surg, Pittsburgh, PA USA. [Kaufman, Howard L.] Rutgers Canc Inst New Jersey, New Brunswick, NJ USA. [Kiessling, Rolf] Karolinska Inst, Dept Oncol Pathol, Stockholm, Sweden. [Kirkwood, John] Univ Pittsburgh, Dept Med, Sch Med, Div Hematol Oncol, Pittsburgh, PA USA. [Kirkwood, John] Univ Pittsburgh, Inst Canc, Melanoma & Skin Canc Program, Pittsburgh, PA USA. [Knuth, Alexander] Natl Ctr Canc Care & Res, Doha, Qatar. [Liblau, Roland] INSERM UMR 1043, Toulouse, France. [Liblau, Roland] CNRS, U5282, Toulouse, France. [Liblau, Roland] Univ Toulouse, UPS, Ctr Physiopathol Toulouse Purpan, Toulouse, France. [Liblau, Roland] CHU Toulouse Purpan, Toulouse, France. [Lotze, Michael T.] Univ Pittsburgh, Sch Hlth Sci, Hillman Canc Ctr, Pittsburgh, PA USA. [Lugli, Enrico] Humanitas Clin & Res Ctr, Unit Clin & Expt Immunol, Rozzano, Italy. [Marincola, Francesco; Wang, Ena] Sidra Med & Res Ctr, Res Branch, Doha, Qatar. [Melero, Ignacio] Univ Navarra, Div Oncol, Ctr Appl Med Res & Clin, E-31080 Pamplona, Spain. [Melief, Cornelis J.] Leiden Univ, ISA Pharmaceut, NL-2300 RA Leiden, Netherlands. [Mempel, Thorsten R.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Immunol & Inflammatory Dis, Boston, MA USA. [Mittendorf, Elizabeth A.] Univ Texas MD Anderson Canc Ctr, Dept Surg Oncol, Houston, TX 77030 USA. [Odun, Kunle] Roswell Pk Canc Inst, Dept Gynecol Oncol, Buffalo, NY 14263 USA. [Odun, Kunle] Roswell Pk Canc Inst, Dept Immunol, Buffalo, NY 14263 USA. [Overwijk, Willem W.] Univ Texas MD Anderson Canc Ctr, Dept Melanoma Med Oncol, Houston, TX 77030 USA. [Palucka, Anna Karolina] Jackson Lab Genom Med, Farmington, CT USA. [Parmiani, Giorgio] Univ Hosp, Div Med Oncol & Immunotherapy, Siena, Italy. [Schreiber, Robert D.] Washington Univ, Sch Med, Dept Pathol & Immunol, St Louis, MO USA. [Schuler, Gerold] Univ Klinikum Erlangen, Dept Dermatol, Erlangen, Germany. [Srivastava, Pramod K.] Univ Connecticut, Ctr Hlth, Carole & Ray Neag Comprehens Canc Ctr, Ctr Immunotherapy Canc & Infect Dis, Farmington, CT USA. [Tartour, Eric] Univ Paris 05, Sorbonne Paris Cite, INSERM U970, Dept Clin Oncol, Paris, France. [Tartour, Eric] Serv Immunol Biol, Hop Europeen Georges Pompidou, Paris, France. [Valmori, Danila] Univ Nantes, Fac Med, F-44035 Nantes, France. [van der Burg, Sjoerd H.] Leiden Univ, Med Ctr, Leiden, Netherlands. [van der Bruggen, Pierre; van den Eynde, Benoit J.] Catholic Univ Louvain, Brussels Branch, Ludwig Inst Canc Res, Duve Inst, B-1200 Brussels, Belgium. [Zou, Weiping] Univ Michigan, Sch Med, Dept Surg, Ann Arbor, MI USA. [Whiteside, Theresa L.] Univ Pittsburgh, Dept Pathol, Inst Canc, Immunol & Otolaryngol, Pittsburgh, PA USA. [Restifo, Nicholas P.] Natl Canc Inst, NIH, Bethesda, MD USA. [Anderson, Ana C.] Brigham & Womens Hosp, Ann Romney Ctr Neurol Dis, Evergrande Ctr Immunol Dis, Boston, MA 02115 USA. RP Apetoh, L (reprint author), INSERM, UMR 866, Dijon, France. EM lionel.apetoh@inserm.fr; acanderson@partners.org RI Caignard, Anne/F-8159-2013; Valmori, Danila/K-2439-2015; Smyth, Mark/H-8709-2014; Apetoh, Lionel/G-3310-2014; Blay, Jean-Yves/N-3966-2016; Ayyoub, Maha/A-2074-2017; castelli, chiara/K-6899-2012; Cavallo, Federica/C-5666-2011; OI Smyth, Mark/0000-0001-7098-7240; Apetoh, Lionel/0000-0002-2774-438X; Blay, Jean-Yves/0000-0001-7190-120X; castelli, chiara/0000-0001-6891-8350; Colombo, Mario Paolo/0000-0003-0042-7955; Cavallo, Federica/0000-0003-4571-1060; MELERO BERMEJO, IGNACIO/0000-0002-1360-348X FU American Cancer Society [RSG-11-057-02-LIB]; National Health and Medical Research Council of Australia [628623]; French National Research Agency [ANR-13-JSV3-0001] FX Work in the author's laboratories is supported by grants from the American Cancer Society (RSG-11-057-02-LIB to A.C.A.), the National Health and Medical Research Council of Australia (628623 to MJS), and the French National Research Agency (ANR-13-JSV3-0001 to L.A.). Due to space and other limitations, it is not possible to include all other sources of financial support. NR 97 TC 14 Z9 14 U1 2 U2 20 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 530 WALNUT STREET, STE 850, PHILADELPHIA, PA 19106 USA SN 2162-402X J9 ONCOIMMUNOLOGY JI OncoImmunology PY 2015 VL 4 IS 4 AR e998538 DI 10.1080/2162402X.2014.998538 PG 10 WC Oncology; Immunology SC Oncology; Immunology GA CH7NS UT WOS:000354224400020 PM 26137416 ER PT J AU Zhu, LX Davoodi, M Srivastava, MK Kachroo, P Lee, JM John, MS Harris-White, M Huang, M Strieter, RM Dubinett, S Sharma, S AF Zhu, Li X. Davoodi, Michael Srivastava, Minu K. Kachroo, Puja Lee, Jay M. John, Maie St. Harris-White, Marni Huang, Min Strieter, Robert M. Dubinett, Steven Sharma, Sherven TI GITR agonist enhances vaccination responses in lung cancer SO ONCOIMMUNOLOGY LA English DT Article DE APC; lung cancer; NK; T cell activation; vaccination responses ID INDUCED TNF RECEPTOR; T-CELLS; COSTIMULATORY RECEPTOR; TUMOR; SUPERFAMILY; ACTIVATION; IPILIMUMAB; CARCINOMA; MELANOMA; SURVIVAL AB An immune tolerant tumor microenvironment promotes immune evasion of lung cancer. Agents that antagonize immune tolerance will thus aid the fight against this devastating disease. Members of the tumor necrosis factor receptor (TNFR) family modulate the magnitude, duration and phenotype of immune responsiveness to antigens. Among these, GITR expressed on immune cells functions as a key regulator in inflammatory and immune responses. Here, we evaluate the GITR agonistic antibody (DTA-1) as a mono-therapy and in combination with therapeutic vaccination in murine lung cancer models. We found that DTA-1 treatment of tumor-bearing mice increased: (i) the frequency and activation of intratumoral natural killer (NK) cells and T lymphocytes, (ii) the antigen presenting cell (APC) activity in the tumor, and (iii) systemic T-cell specific tumor cell cytolysis. DTA-1 treatment enhanced tumor cell apoptosis as quantified by cleaved caspase-3 staining in the tumors. DTA-1 treatment increased expression of IFN gamma, TNF alpha and IL-12 but reduced IL-10 levels in tumors. Furthermore, increased anti-angiogenic chemokines corresponding with decreased pro-angiogenic chemokine levels correlated with reduced expression of the endothelial cell marker Meca 32 in the tumors of DTA-1 treated mice. In accordance, there was reduced tumor growth (8-fold by weight) in the DTA-1 treatment group. NK cell depletion markedly inhibited the antitumor response elicited by DTA-1. DTA-1 combined with therapeutic vaccination caused tumor rejection in 38% of mice and a 20-fold reduction in tumor burden in the remaining mice relative to control. Mice that rejected tumors following therapy developed immunological memory against subsequent re-challenge. Our data demonstrates GITR agonist antibody activated NK cell and T lymphocyte activity, and enhanced therapeutic vaccination responses against lung cancer. C1 [Zhu, Li X.; Srivastava, Minu K.; Kachroo, Puja; Lee, Jay M.; John, Maie St.; Huang, Min; Dubinett, Steven; Sharma, Sherven] Univ Calif Los Angeles, David Geffen Sch Med, UCLA Lung Canc Res Program, Dept Med, Los Angeles, CA 90095 USA. [Zhu, Li X.; Davoodi, Michael; Srivastava, Minu K.; Lee, Jay M.; Harris-White, Marni; Huang, Min; Dubinett, Steven; Sharma, Sherven] Vet Affairs Greater Los Angeles Healthcare Syst, Mol Gene Med Lab, Los Angeles, CA USA. [Kachroo, Puja; Lee, Jay M.; John, Maie St.; Dubinett, Steven; Sharma, Sherven] Univ Calif Los Angeles, David Geffen Sch Med, Jonsson Comprehens Canc Ctr, Los Angeles, CA 90095 USA. [Strieter, Robert M.] Univ Virginia, Dept Med, Charlottesville, VA USA. RP Sharma, S (reprint author), Univ Calif Los Angeles, David Geffen Sch Med, UCLA Lung Canc Res Program, Dept Med, Los Angeles, CA 90095 USA. EM ssharma@mednet.ucla.edu FU University of California Los Angeles Lung Cancer Program, Department of Veterans Affairs Medical Research Funds, NIH [RO1 CA95686, RO1 CA126944, P50 CA90388]; National Center for Research Resources [UL1RR033176]; National Center for Advancing Translational Sciences [UL1TR000124]; Tobacco Related Disease Program Award Program of University of California [15RT-0207, 20FT0082] FX This work was supported by the: University of California Los Angeles Lung Cancer Program, Department of Veterans Affairs Medical Research Funds, NIH Grants (RO1 CA95686, RO1 CA126944 and P50 CA90388), National Center for Research Resources, Grant UL1RR033176, and is now at the National Center for Advancing Translational Sciences, Grant UL1TR000124 and Tobacco Related Disease Program Award Program of University of California (15RT-0207 and 20FT0082). The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH. NR 23 TC 1 Z9 1 U1 2 U2 3 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 530 WALNUT STREET, STE 850, PHILADELPHIA, PA 19106 USA SN 2162-402X J9 ONCOIMMUNOLOGY JI OncoImmunology PY 2015 VL 4 IS 4 AR e992237 DI 10.4161/2162402X.2014.992237 PG 12 WC Oncology; Immunology SC Oncology; Immunology GA CH7NS UT WOS:000354224400011 ER PT J AU Wright, DL Afeiche, MC Ehrlich, S Smith, K Williams, PL Chavarro, JE Batsis, M Toth, TL Hauser, R AF Wright, Diane L. Afeiche, Myriam C. Ehrlich, Shelley Smith, Kristen Williams, Paige L. Chavarro, Jorge E. Batsis, Maria Toth, Thomas L. Hauser, Russ TI Hair mercury concentrations and in vitro fertilization (IVF) outcomes among women from a fertility clinic SO REPRODUCTIVE TOXICOLOGY LA English DT Article DE Mercury (Hg); Oocyte; Fertilization; In vitro fertilization (IVF); Implantation; Human ID BISPHENOL-A CONCENTRATIONS; LIVE-BIRTH-RATES; OCCUPATIONAL EXPOSURE; REPRODUCTIVE HEALTH; SEAFOOD CONSUMPTION; HEAVY-METALS; TOXIC METALS; CADMIUM; BLOOD; FISH AB Total hair mercury (Hg) was measured among 205 women undergoing in vitro fertilization (IVF) treatment and the association with prospectively collected IVF outcomes (229 IVF cycles) was evaluated. Hair Hg levels (median = 0.62 ppm, range: 0.03-5.66 ppm) correlated with fish intake (r = 0.59), and exceeded the recommended EPA reference of 1 ppm in 33% of women. Generalized linear mixed models with random intercepts accounting for within-woman correlations across treatment cycles were used to evaluate the association of hair Hg with IVF outcomes adjusted for age, body mass index, race, smoking status, infertility diagnosis, and protocol type. Hair Hg levels were not related to ovarian stimulation outcomes (peak estradiol levels, total and mature oocyte yields) or to fertilization rate, embryo quality, clinical pregnancy rate or live birth rate. (C) 2015 Elsevier Inc. All rights reserved. C1 [Wright, Diane L.; Batsis, Maria; Toth, Thomas L.; Hauser, Russ] Harvard Univ, Sch Med, Vincent Dept Obstet & Gynecol Serv, Div Reprod Med & IVF,Massachusetts Gen Hosp,Ferti, Boston, MA USA. [Afeiche, Myriam C.; Smith, Kristen; Hauser, Russ] Harvard Univ, Sch Publ Hlth, Dept Environm Hlth, Boston, MA 02115 USA. [Ehrlich, Shelley] Cincinnati Childrens Hosp Med Ctr, Div Biostat & Epidemiol, Cincinnati, OH 45229 USA. [Williams, Paige L.] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. [Williams, Paige L.; Chavarro, Jorge E.; Hauser, Russ] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. [Chavarro, Jorge E.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Channing Div Network Med, Boston, MA 02115 USA. [Chavarro, Jorge E.] Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA. [Batsis, Maria] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Sect Endocrinol & Genet, Program Dev Endocrinol & Genet, NIH, Bethesda, MD 20892 USA. [Batsis, Maria] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Sect Endocrinol & Genet, Pediat Endocrinol Interinst Training Program, NIH, Bethesda, MD 20892 USA. RP Wright, DL (reprint author), Massachusetts Gen Hosp, Vincent Mem Obstet & Gynecol Serv, Boston, MA 02114 USA. EM dwright4@mgh.harvard.edu RI Ehrlich , Shelley/L-6991-2015 FU National Institutes of Health (NIH) [ES009718, ES000002, T32ES007069] FX Work supported by grants ES009718, ES000002, and T32ES007069 from the National Institutes of Health (NIH). NR 38 TC 2 Z9 2 U1 2 U2 6 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0890-6238 J9 REPROD TOXICOL JI Reprod. Toxicol. PD JAN PY 2015 VL 51 BP 125 EP 132 DI 10.1016/j.reprotox.2015.01.003 PG 8 WC Reproductive Biology; Toxicology SC Reproductive Biology; Toxicology GA CH6NH UT WOS:000354152800015 PM 25601638 ER PT S AU Guimaraes, C An, J Humar, M Goth, W Yun, A AF Guimaraes, Caio An, Jeesoo Humar, Matjaz Goth, Will Yun, Andy BE Lee, LP Rogers, JA Yun, SHA TI Biocompatible optical needle array for antibacterial blue light therapy SO BIOINSPIRED BIOINTEGRATED BIOENGINEERED PHOTONIC DEVICES III SE Proceedings of SPIE LA English DT Proceedings Paper CT Conference on Bioinspired, Biointegrated, Bioengineered Photonic Devices III CY FEB 07-08, 2015 CL San Francisco, CA SP SPIE DE biocompatible optical needle array; BONA; antibacterial blue light therapy; waveguide AB Biocompatible Optical Needle Array (BONA) is showing to be a powerful tool complementing the novel antibacterial blue light therapy. BONA is able to deliver light to deeper skin tissue layers successfully as shown in experiments. In this study, we will discuss BONA's design, mechanical and optical properties, production method, plus propose improvements to optimize it all. A special skin phantom with photosensitizer was developed in order to investigate how light is delivered inside the tissue. The phantom shows the light scattering pattern through photobleach, allowing us to determine length, thickness and spacing between needles. Other quantitative optical properties as penetration depth were determined using a different phantom (using PDMS). Mechanical properties as needle resistance were determined using one axis of a custom biaxial tensile strain device. The results led us to conclude that besides the great results, there is still room for improvements regarding tip sharpness and manufacturing time and cost, which would be solved with the enhanced fabrication method proposed. C1 [Guimaraes, Caio] POLI UPE Polytech Sch Pernambuco, Recife, PE, Brazil. [Guimaraes, Caio] Univ Pernambuco, Recife, PE, Brazil. [An, Jeesoo; Humar, Matjaz; Yun, Andy] Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA. [An, Jeesoo; Humar, Matjaz; Yun, Andy] Harvard Univ, Sch Med, Cambridge, MA 02138 USA. [Humar, Matjaz] J Stefan Inst, Condensed Matter Dept, Ljubljana, Slovenia. [Goth, Will] Univ Texas Austin, Dept Biomed Engn, Austin, TX 78712 USA. RP Guimaraes, C (reprint author), POLI UPE Polytech Sch Pernambuco, Recife, PE, Brazil. RI Humar, Matjaz/I-8862-2012 OI Humar, Matjaz/0000-0003-3338-6723 NR 2 TC 0 Z9 0 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 978-1-62841-431-8 J9 PROC SPIE PY 2015 VL 9341 AR 93410R DI 10.1117/12.2083384 PG 7 WC Engineering, Biomedical; Optics SC Engineering; Optics GA BC6FE UT WOS:000353890300007 ER PT J AU Perez, DL Dworetzky, BA Dickerson, BC Leung, L Cohn, R Baslet, G Silbersweig, DA AF Perez, David L. Dworetzky, Barbara A. Dickerson, Bradford C. Leung, Lorene Cohn, Rachel Baslet, Gaston Silbersweig, David A. TI An Integrative Neurocircuit Perspective on Psychogenic Nonepileptic Seizures and Functional Movement Disorders: Neural Functional Unawareness SO CLINICAL EEG AND NEUROSCIENCE LA English DT Review DE psychogenic nonepileptic seizures; functional movement disorder; conversion disorder; dissociation; fMRI ID POSTTRAUMATIC-STRESS-DISORDER; MOTOR CONVERSION DISORDER; DISSOCIATIVE IDENTITY DISORDER; MEDICALLY UNEXPLAINED SYMPTOMS; PREDICTS TREATMENT RESPONSE; HUMAN CEREBRAL-CORTEX; EPILEPTIC SEIZURES; PARIETAL CORTEX; ANTERIOR INSULA; PANIC-ATTACKS AB Functional neurological disorder (conversion disorder) is a neurobehavioral condition frequently encountered by neurologists. Psychogenic nonepileptic seizure (PNES) and functional movement disorder (FMD) patients present to epileptologists and movement disorder specialists respectively, yet neurologists lack a neurobiological perspective through which to understand these enigmatic groups. Observational research studies suggest that PNES and FMD may represent variants of similar (or the same) conditions given that both groups exhibit a female predominance, have increased prevalence of mood-anxiety disorders, frequently endorse prior abuse, and share phenotypic characteristics. In this perspective article, neuroimaging studies in PNES and FMD are reviewed, and discussed using studies of emotional dysregulation, dissociation and psychological trauma in the context of motor control. Convergent neuroimaging findings implicate alterations in brain circuits mediating emotional expression, regulation and awareness (anterior cingulate and ventromedial prefrontal cortices, insula, amygdala, vermis), cognitive control and motor inhibition (dorsal anterior cingulate, dorsolateral prefrontal, inferior frontal cortices), self-referential processing and perceptual awareness (posterior parietal cortex, temporoparietal junction), and motor planning and coordination (supplementary motor area, cerebellum). Striatal-thalamic components of prefrontal-parietal networks may also play a role in pathophysiology. Aberrant medial prefrontal and amygdalar neuroplastic changes mediated by chronic stress may facilitate the development of functional neurological symptoms in a subset of patients. Improved biological understanding of PNES and FMD will likely reduce stigma and aid the identification of neuroimaging biomarkers guiding treatment development, selection, and prognosis. Additional research should investigate neurocircuit abnormalities within and across functional neurological disorder subtypes, as well as compare PNES and FMD with mood-anxiety-dissociative disorders. C1 [Perez, David L.; Dickerson, Bradford C.] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. [Perez, David L.] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. [Perez, David L.; Leung, Lorene; Cohn, Rachel; Baslet, Gaston; Silbersweig, David A.] Brigham & Womens Hosp, Dept Psychiat, Boston, MA 02115 USA. [Dworetzky, Barbara A.; Silbersweig, David A.] Brigham & Womens Hosp, Dept Neurol, Boston, MA 02115 USA. RP Perez, DL (reprint author), Massachusetts Gen Hosp, Dept Neurol, 149 13th St, Charlestown, MA 02129 USA. EM david.lperez@gmail.com OI Dworetzky, Barbara/0000-0002-3364-2347 FU NINDS [R25NS065743-05S1] FX The author(s) disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: Dr David L. Perez was funded by a NINDS R25NS065743-05S1 grant. NR 135 TC 10 Z9 10 U1 11 U2 19 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 1550-0594 EI 2169-5202 J9 CLIN EEG NEUROSCI JI Clin. EEG Neurosci. PD JAN PY 2015 VL 46 IS 1 SI SI BP 4 EP 15 DI 10.1177/1550059414555905 PG 12 WC Clinical Neurology; Neurosciences; Neuroimaging; Psychiatry; Psychology SC Neurosciences & Neurology; Psychiatry; Psychology GA CH3IM UT WOS:000353924200002 PM 25432161 ER PT J AU Reinsberger, C Sarkis, R Papadelis, C Doshi, C Perez, DL Baslet, G Loddenkemper, T Dworetzky, BA AF Reinsberger, Claus Sarkis, Rani Papadelis, Christos Doshi, Chiran Perez, David L. Baslet, Gaston Loddenkemper, Tobias Dworetzky, Barbara A. TI Autonomic Changes in Psychogenic Nonepileptic Seizures: Toward a Potential Diagnostic Biomarker? SO CLINICAL EEG AND NEUROSCIENCE LA English DT Article DE psychogenic nonepileptic seizures (PNES); autonomic nervous system (ANS); electrodermal activity (EDA); heart rate variability (HRV) ID POSTTRAUMATIC-STRESS-DISORDER; HEART-RATE-VARIABILITY; BORDERLINE PERSONALITY-DISORDER; CARDIAC VAGAL CONTROL; ELECTRODERMAL ACTIVITY; DEPRESSIVE PATIENTS; SPECTRAL-ANALYSIS; PANIC DISORDER; MODULATION; SCHIZOPHRENIA AB Disturbances of the autonomic nervous system (ANS) are common in neuropsychiatric disorders. Disease specific alterations of both sympathetic and parasympathetic activity can be assessed by heart rate variability (HRV), whereas electrodermal activity (EDA) can assess sympathetic activity. In posttraumatic stress disorder (PTSD), parasympathetic HRV parameters are typically decreased and EDA is increased, whereas in major depressive disorder (MDD) and dissociation, both parasympathetic and sympathetic markers are decreased. ANS abnormalities have also been identified in psychogenic nonepileptic seizures (PNES) by using HRV, indicating lower parasympathetic activity at baseline. In addition to reviewing the current literature on ANS abnormalities in PTSD, MDD, and disorders with prominent dissociation, including borderline personality disorder (BPD), this article also presents data from a pilot study on EDA in patients with PNES. Eleven patients with PNES, during an admission to our epilepsy monitoring unit (EMU), were compared with 9 with generalized tonic-clonic seizures (GTCS). The area under the EDA curve, the number of EDA responses lasting longer than 2 seconds, and the number of EDA surges during sleep (sympathetic sleep storms) were calculated on ictal and interictal days by an automated algorithm. EDA changes in PNES patients did not follow a systematic pattern of sympathetic hyperarousal (like EDA after GTCS) but were more variable. How specific PNES semiologies, and/or underlying neuropsychiatric disorders, may influence ictal and interictal EDA patterns, and lead to a novel diagnostic biomarker remains to be evaluated in future larger studies. C1 [Reinsberger, Claus; Sarkis, Rani; Baslet, Gaston; Dworetzky, Barbara A.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Edward B Bromfield Epilepsy Ctr, Boston, MA 02115 USA. [Reinsberger, Claus] Univ Paderborn, Inst Sports Med, D-33098 Paderborn, Germany. [Papadelis, Christos; Doshi, Chiran; Loddenkemper, Tobias] Harvard Univ, Sch Med, Dept Neurol, Div Epilepsy & Clin Neurophysiol,Boston Childrens, Boston, MA 02115 USA. [Perez, David L.; Baslet, Gaston] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Psychiat, Boston, MA 02115 USA. [Perez, David L.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Neurol, Boston, MA USA. [Perez, David L.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Psychiat, Boston, MA USA. RP Reinsberger, C (reprint author), Univ Paderborn, Inst Sports Med, Warburger Str 100, D-33098 Paderborn, Germany. EM reinsberger@sportmed.upb.de OI Sarkis, Rani/0000-0001-8291-7864; Dworetzky, Barbara/0000-0002-3364-2347 NR 71 TC 6 Z9 6 U1 0 U2 7 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 1550-0594 EI 2169-5202 J9 CLIN EEG NEUROSCI JI Clin. EEG Neurosci. PD JAN PY 2015 VL 46 IS 1 SI SI BP 16 EP 25 DI 10.1177/1550059414567739 PG 10 WC Clinical Neurology; Neurosciences; Neuroimaging; Psychiatry; Psychology SC Neurosciences & Neurology; Psychiatry; Psychology GA CH3IM UT WOS:000353924200003 PM 25780264 ER PT J AU Dworetzky, BA Weisholtz, DS Perez, DL Baslet, G AF Dworetzky, Barbara A. Weisholtz, Daniel S. Perez, David L. Baslet, Gaston TI A Clinically Oriented Perspective on Psychogenic Nonepileptic Seizure-Related Emergencies SO CLINICAL EEG AND NEUROSCIENCE LA English DT Article DE nonepileptic psychogenic status; pseudostatus; pregnancy; suicide; accidents ID EPILEPSY MONITORING UNIT; STATUS EPILEPTICUS; PSEUDOSTATUS EPILEPTICUS; CONVERSION DISORDER; PSYCHIATRIC-DISORDERS; SAFETY CONSIDERATIONS; ANTIEPILEPTIC DRUGS; PREGNANCY; INJURY; MISDIAGNOSIS AB Psychogenic nonepileptic seizures (PNES) can present emergently and are often mistaken for epileptic seizures. PNES emergencies have not been well studied, and yet there are associated serious morbidities, particularly when patients are seen in an emergency setting and are misdiagnosed. PNES may be prolonged, mimicking status epilepticus, a condition we refer to as nonepileptic psychogenic status (NEPS), and patients may receive aggressive and unnecessary medical treatments that can lead to serious iatrogenic complications, including death. NEPS is also associated with an increased risk of self-harm, including suicide attempts, and may indicate a serious comorbid psychiatric illness. In addition to iatrogenic complications of PNES, accidents and injuries are an underrecognized source of morbidity. PNES may also present during medical procedures, which may not only interfere with their completion, but may alarm practitioners who, fearing liability, may initiate further medical evaluations and treatments. When PNES occur during pregnancy, patients may be misdiagnosed with eclampsia and their offspring delivered prematurely. They also risk being placed on medications that are harmful to the fetus. Increased awareness of PNES is necessary to prevent iatrogenic harm and to identify underlying psychiatric illnesses that carry their own risks. As yet, data available to guide treatment are scant, and further study is needed. C1 [Dworetzky, Barbara A.; Weisholtz, Daniel S.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Neurol, Boston, MA 02115 USA. [Perez, David L.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Neurol, Boston, MA USA. [Perez, David L.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Psychiat, Boston, MA USA. [Perez, David L.; Baslet, Gaston] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Psychiat, Boston, MA 02115 USA. RP Dworetzky, BA (reprint author), Brigham & Womens Hosp, Div Epilepsy, Dept Neurol, 75 Francis St, Boston, MA 02115 USA. EM bdworetzky@partners.org OI Dworetzky, Barbara/0000-0002-3364-2347 NR 74 TC 2 Z9 2 U1 2 U2 7 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 1550-0594 EI 2169-5202 J9 CLIN EEG NEUROSCI JI Clin. EEG Neurosci. PD JAN PY 2015 VL 46 IS 1 SI SI BP 26 EP 33 DI 10.1177/1550059414566880 PG 8 WC Clinical Neurology; Neurosciences; Neuroimaging; Psychiatry; Psychology SC Neurosciences & Neurology; Psychiatry; Psychology GA CH3IM UT WOS:000353924200004 PM 25780265 ER PT J AU Baslet, G Dworetzky, B Perez, DL Oser, M AF Baslet, Gaston Dworetzky, Barbara Perez, David L. Oser, Megan TI Treatment of Psychogenic Nonepileptic Seizures: Updated Review and Findings From a Mindfulness-Based Intervention Case Series SO CLINICAL EEG AND NEUROSCIENCE LA English DT Article DE psychogenic nonepileptic seizures; treatment; therapeutics; mindfulness-based psychotherapy ID CONTROLLED CLINICAL-TRIAL; CONVERSION DISORDER; PSEUDOSEIZURE PATIENTS; NEUROLOGICAL SYMPTOMS; GROUP PSYCHOEDUCATION; MOVEMENT-DISORDERS; CARE UTILIZATION; GROUP-THERAPY; MOTOR TYPE; DIAGNOSIS AB Psychogenic nonepileptic seizures (PNES) were first described in the medical literature in the 19th century, as seizure-like attacks not related to an identified central nervous system lesion, and are currently classified as a conversion disorder, according to the Diagnostic and Statistical Manual of Mental Disorders, fifth edition (DSM-5). While a universally accepted and unifying etiological model does not yet exist, several risk factors have been identified. Management of PNES should be based on interdisciplinary collaboration, targeting modifiable risk factors. The first treatment phase in PNES is patient engagement, which is challenging given the demonstrated low rates of treatment retention. Acute interventions constitute the next phase in treatment, and most research studies focus on short-term evidence-based interventions. Randomized controlled pilot trials support cognitive-behavioral therapy. Other psychotherapeutic and psychopharmacological interventions have been less well-studied using controlled and uncontrolled trials. Within the discussion of acute interventions, we present a preliminary evaluation for feasibility of a mindfulness-based psychotherapy protocol in a very small sample of PNES patients. We demonstrated in 6 subjects that this intervention is feasible in real-life clinical scenarios and warrants further investigation in larger scale studies. The final treatment phase is long-term follow-up. Long-term outcome studies in PNES show that a significant proportion of patients remains symptomatic and experiences continued impairments in quality of life and functionality. We believe that PNES should be understood as a disease that requires different types of intervention during the various phases of treatment. C1 [Baslet, Gaston; Perez, David L.; Oser, Megan] Brigham & Womens Hosp, Dept Psychiat, Boston, MA 02115 USA. [Baslet, Gaston; Dworetzky, Barbara; Perez, David L.; Oser, Megan] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Dworetzky, Barbara] Brigham & Womens Hosp, Dept Neurol, Boston, MA 02115 USA. [Perez, David L.] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. [Perez, David L.] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. RP Baslet, G (reprint author), Harvard Univ, Sch Med, Dept Psychiat, Brigham & Womens Hosp, 221 Longwood Ave, Boston, MA 02115 USA. EM gbaslet@partners.org OI Dworetzky, Barbara/0000-0002-3364-2347 FU NINDS [R25 NS065743-05S1] FX Dr. David L. Perez was funded by a NINDS R25 NS065743-05S1 grant. NR 59 TC 9 Z9 9 U1 2 U2 7 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 1550-0594 EI 2169-5202 J9 CLIN EEG NEUROSCI JI Clin. EEG Neurosci. PD JAN PY 2015 VL 46 IS 1 SI SI BP 54 EP 64 DI 10.1177/1550059414557025 PG 11 WC Clinical Neurology; Neurosciences; Neuroimaging; Psychiatry; Psychology SC Neurosciences & Neurology; Psychiatry; Psychology GA CH3IM UT WOS:000353924200007 PM 25465435 ER PT J AU Shad, MU Prasad, K Forman, SD Haas, GL Walker, JD Pisarov, LA Goldstein, G AF Shad, Mujeeb U. Prasad, Konasale Forman, Steven D. Haas, Gretchen L. Walker, Jon D. Pisarov, Liubomir A. Goldstein, Gerald TI Insight and neurocognitive functioning in bipolar subjects SO COMPREHENSIVE PSYCHIATRY LA English DT Article ID MOOD DISORDERS; CHRONIC-ALCOHOLICS; CORPUS-CALLOSUM; EXECUTIVE FUNCTION; GRAY-MATTER; SCHIZOPHRENIA; ABNORMALITIES; PSYCHOSIS; ILLNESS; WHITE AB Background: Insight concerning having a mental illness has been found to influence outcome and effectiveness of treatment. It has been studied mainly in the area of schizophrenia with few studies addressing other disorders. This study evaluates insight in individuals with bipolar disorder using the Scale to Assess Unawareness of Mental Disorder (SUMD), a comprehensive interview for evaluation of awareness of illness and attribution of symptoms. The hypothesis was that in bipolar disorder level of awareness may be associated with numerous factors including neurocognitive function, structural changes in the frontal lobes and hippocampus evaluated by MRI, neurocognitive status, severity of mania and other psychiatric symptoms and comorbid alcoholism. Method: In order to evaluate this hypothesis 33 individuals with DSM-IV diagnosed bipolar disorder, some with and some without comorbid alcoholism, were administered the SUMD and a number of other procedures including a quantitative MR' measuring volume of the frontal lobes and hippocampus, a brief battery of neurocognitive tests, the Brief Psychiatric Rating Scale, and the Young Mania Rating Scale. The data were analyzed by comparing participants with and without alcoholism on these procedures using t tests and by linear multiple regression, with SUMD ratings of awareness and attribution as the dependent variables and variable sets from the other procedures administered as multivariate independent variables. Results: The median score obtained from the SUMD for current awareness was in a range between full awareness and uncertainty concerning presence of a mental disorder. For attribution, the median score indicated that attribution was usually made to the illness itself. None of the differences between participants with and without comorbid alcoholism were significant for the SUMD awareness and attribution scores, neurocognitive or MRI variables. The multiple regression analyses only showed a significant degree of association between the SUMD awareness score and the Young Mania Rating Scale (r(2) = .632, p < .05). A stepwise analysis indicated that items assessing degree of insight, irritability, and sleep disturbance met criteria for entry into the regression equation. None of the regression analyses for the SUMD attribution item were significant. Conclusions: Apparently unlike the case for schizophrenia, most of the participants, all of whom had bipolar disorder, were aware of their symptoms and correctly related them to a mental disorder. Hypotheses concerning the relationships between degree of unawareness and possible contributors to its development including comorbid alcoholism, cognitive dysfunction and structural reduction of gray matter in the frontal region and hippocampus, were not associated with degree of unawareness but symptoms of mania were significantly associated. The apparent reason for this result is that the sample obtained a SUMD modal awareness score of 1 or 2, reflecting the area between full awareness and uncertainty about having a mental disorder. None of the participants were rated as having a 5 response reflecting the belief that s/he does not have a mental disorder. Published by Elsevier Inc. C1 [Shad, Mujeeb U.] VA Pittsburgh Healthcare Syst, Mental Illness Res Educ & Clin Ctr, Pittsburgh, PA 15206 USA. [Prasad, Konasale; Forman, Steven D.; Haas, Gretchen L.; Goldstein, Gerald] Univ Pittsburgh, Sch Med, Dept Psychiat, Educ & Clin Ctr,VA Pittsburgh Healthcare Syst, Pittsburgh, PA USA. [Forman, Steven D.; Haas, Gretchen L.; Walker, Jon D.; Pisarov, Liubomir A.; Goldstein, Gerald] VA Pittsburgh Healthcare Syst, VISN Mental Illness Res Educ & Clin Ctr 4, Pittsburgh, PA 15206 USA. RP Goldstein, G (reprint author), VA Pittsburgh Healthcare Syst, 7180 Highland Dr 151R, Pittsburgh, PA 15206 USA. EM ggold@nb.net OI Prasad, Konasale/0000-0003-0245-1393 FU Department of Veterans Affairs, Veterans Health Administration, Office of Research and Development; VISN 4 Mental Illness Research, Education, and Clinical Center (MIRECC), VA Pittsburgh Healthcare System FX This material is based upon work supported by the Department of Veterans Affairs, Veterans Health Administration, Office of Research and Development. The project was funded by infrastructure support funding from the VISN 4 Mental Illness Research, Education, and Clinical Center (MIRECC, Director: D. Oslin; Pittsburgh Site Director: G. Haas), VA Pittsburgh Healthcare System. NR 39 TC 0 Z9 0 U1 1 U2 7 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0010-440X EI 1532-8384 J9 COMPR PSYCHIAT JI Compr. Psychiat. PY 2015 VL 56 BP 112 EP 120 DI 10.1016/j.comppsych.2014.04.016 PG 9 WC Psychiatry SC Psychiatry GA CH2PM UT WOS:000353867100014 PM 25439524 ER PT J AU Tung, ES Flessner, CA Grant, JE Keuthen, NJ AF Tung, Esther S. Flessner, Christopher A. Grant, Jon E. Keuthen, Nancy J. TI Predictors of life disability in trichotillomania SO COMPREHENSIVE PSYCHIATRY LA English DT Article ID HAIRPULLING SCALE; PRIMARY-CARE; IMPACT; PHENOMENOLOGY; IMPAIRMENT; DISORDER AB Background: Limited research has investigated disability and functional impairment in trichotillomania (TTM) subjects. This study examined the relationships between hair pulling (HP) style and severity and disability while controlling for mood severity. Disability was measured in individual life areas (work, social, and family/home life) instead of as a total disability score as in previous studies. Methods: One hundred fifty three adult hair pullers completed several structured interviews and self-report instruments. HP style and severity, as well as depression, anxiety, and stress were correlated with work, social, and family/home life impairment on the Sheehan Disability Scale (SDS). Multiple regression analyses were performed to determine significant predictors of life impairment. Results: Depressive severity was a significant predictor for all SDS life areas. In addition, interference/avoidance associated with HP was a predictor for work and social life disability. Distress from HP was a significant predictor of social and family/home life disability. Focused HP score and anxiety were significant predictors of family/home life disability. Conclusions: As expected, depression in hair pullers predicted disability across life domains. Avoiding work and social situations can seriously impair functioning in those life domains. Severity of distress and worry about HP may be most elevated in social situations with friends and family and thus predict impairment in those areas. Finally, since HP often occurs at home, time spent in focused hair pulling would have a greater negative impact on family and home responsibilities than social and work life. (C) 2014 Elsevier Inc. All rights reserved. C1 [Tung, Esther S.; Keuthen, Nancy J.] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. [Flessner, Christopher A.] Kent State Univ, Dept Psychol, Kent, OH 44242 USA. [Grant, Jon E.] Univ Chicago, Dept Psychiat & Behav Neurosci, Chicago, IL 60637 USA. RP Keuthen, NJ (reprint author), Massachusetts Gen Hosp, OCD & Related Disorders Program, 185 Cambridge St,Suite 2200, Boston, MA 02114 USA. EM etung2@partners.org; cflessne@kent.edu; jgrant4@bsd.uchicago.edu; nkeuthen@partners.org RI Flessner, Christopher/K-1483-2015 FU Trichotillomania Learning Center; Greater Kansas City Foundation FX This research was financially supported by grants from the Trichotillomania Learning Center and the Greater Kansas City Foundation. The funding sponsors had no role in study design, data collection, data analysis or interpretation, manuscript preparation or the decision to submit the manuscript for publication. NR 23 TC 3 Z9 3 U1 0 U2 8 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0010-440X EI 1532-8384 J9 COMPR PSYCHIAT JI Compr. Psychiat. PY 2015 VL 56 BP 239 EP 244 DI 10.1016/j.comppsych.2014.09.018 PG 6 WC Psychiatry SC Psychiatry GA CH2PM UT WOS:000353867100029 PM 25281991 ER PT J AU Tegos, GP AF Tegos, George P. TI Versatile Approaches to Target Staphylococcal Infections SO CURRENT PHARMACEUTICAL DESIGN LA English DT Editorial Material DE multidrug resistance staphylococci; biocides; target based discovery; antimicrobial peptides; quorum-sensing inhibitors; drug repurposing; photoantimicrobials; pathogen-innate immunity dynamics; vaccines C1 [Tegos, George P.] Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA. [Tegos, George P.] Harvard Univ, Sch Med, Dept Dermatol, Boston, MA 02115 USA. [Tegos, George P.] Torrey Pines Inst Mol Studies, Port St Lucie, FL 34987 USA. RP Tegos, GP (reprint author), Torrey Pines Inst Mol Studies, Port St Lucie, FL 34987 USA. EM gtegos@tpims.org NR 12 TC 0 Z9 0 U1 0 U2 2 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 2015 VL 21 IS 16 BP 2046 EP 2047 PG 2 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA CG9RK UT WOS:000353655700001 PM 25760333 ER PT J AU Magana, M Ioannidis, A Magiorkinis, E Ursu, O Bologa, CG Chatzipanagiotou, S Hamblin, MR Tegos, GP AF Magana, Maria Ioannidis, Anastasios Magiorkinis, Emmanouil Ursu, Oleg Bologa, Cristian G. Chatzipanagiotou, Stylianos Hamblin, Michael R. Tegos, George P. TI Therapeutic Options and Emerging Alternatives for Multidrug Resistant Staphylococcal Infections SO CURRENT PHARMACEUTICAL DESIGN LA English DT Article DE MRSA; multidrug resistance; staphylococcal infections; drug discovery ID PANTON-VALENTINE LEUKOCIDIN; SOFT-TISSUE INFECTIONS; INDUCIBLE CLINDAMYCIN RESISTANCE; VENTILATOR-ASSOCIATED PNEUMONIA; EVALUATING CEFTAROLINE FOSAMIL; SKIN-STRUCTURE INFECTIONS; AUREUS STRAIN USA300; PHAGE LYTIC ENZYME; METHICILLIN-RESISTANT; EFFLUX PUMPS AB Methicillin-resistant Staphylococcus aureus (MRSA) remains the single biggest challenge in infectious disease in the civilized world. Moreover, vancomycin resistance is also spreading, leading to fears of untreatable infections as were common in ancient times. Molecular microbiology and bioinformatics have revealed many of the mechanisms involved in resistance development. Mobile genetic elements, up-regulated virulence factors and multi-drug efflux pumps have been implicated. A range of approved antibiotics from the glycopeptide, lipopeptide, pleuromutilin, macrolide, oxazolidinone, lincosamide, aminoglycoside, tetracycline, steptogramin, and cephalosporin classes has been employed to treat MRSA infections. The upcoming pipeline of drugs for MRSA includes some new compounds from the above classes, together with fluoroquinolones, antibacterial peptide mimetics, aminomethylciclines, porphyrins, peptide deformylase inhibitors, oxadiazoles, and diaminopyrimidines. A range of non-drug alternative approaches has emerged for MRSA treatment. Bacteriophage-therapy including purified lysins has made a comeback after being discovered in the 1930s. Quorum-sensing inhibitors are under investigation. Small molecule inhibitors of multi-drug efflux pumps may potentiate existing antibiotics. The relative failure of staphylococcal vaccines is being revisited by efforts with multi-valent vaccines and improved adjuvants. Photodynamic therapy uses non-toxic photosensitizers and harmless visible light to produce reactive oxygen species that can nonspecifically destroy bacteria while preserving host cells. Preparation of nanoparticles can kill bacteria themselves, as well as improve the delivery of anti-bacterial drugs. Anti-MRSA drug discovery remains an exciting field with great promise for the future. C1 [Magana, Maria; Ioannidis, Anastasios] Univ Peloponnese, Fac Human Movement & Qual Life Sci, Dept Nursing, Sparta, Greece. [Ioannidis, Anastasios; Chatzipanagiotou, Stylianos] Aeginit Hosp, Athens Med Sch, Dept Clin Microbiol, Athens, Greece. [Magiorkinis, Emmanouil] Univ Athens, Sch Med, Dept Hyg Epidemiol & Med Stat, GR-11527 Athens, Greece. [Ursu, Oleg; Bologa, Cristian G.] Univ New Mexico, Hlth Sci Ctr, Dept Internal Med, Translat Informat Div, Albuquerque, NM 87131 USA. [Ursu, Oleg; Bologa, Cristian G.] Univ New Mexico, Ctr Mol Discovery, Albuquerque, NM 87131 USA. [Hamblin, Michael R.] Harvard MIT Div Hlth Sci & Technol, Cambridge, MA USA. [Hamblin, Michael R.; Tegos, George P.] Harvard Univ, Sch Med, Dept Dermatol, Boston, MA 02115 USA. [Hamblin, Michael R.; Tegos, George P.] Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA. [Tegos, George P.] Torrey Pines Inst Mol Studies, Port St Lucie, FL 34987 USA. RP Tegos, GP (reprint author), Torrey Pines Inst Mol Studies, Port St Lucie, FL 34987 USA. EM gtegos@mgh.harvard.edu FU US NIH [5U54MH084690-02, R01AI050875]; US DTRA [HDTRA1-13-C-0005] FX George P Tegos was supported by the US NIH grant 5U54MH084690-02 (CDP1) and by the US DTRA contract HDTRA1-13-C-0005 and Michael R Hamblin was supported by US NIH grant R01AI050875. NR 180 TC 4 Z9 5 U1 10 U2 39 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 2015 VL 21 IS 16 BP 2058 EP 2072 PG 15 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA CG9RK UT WOS:000353655700004 PM 25760340 ER PT J AU Agrawal, T Avci, P Gupta, GK Rineh, A Lakshmanan, S Batwala, V Tegos, GP Hamblin, MR AF Agrawal, Tanupriya Avci, Pinar Gupta, Gaurav K. Rineh, Ardeshir Lakshmanan, Shanmugamurthy Batwala, Vincent Tegos, George P. Hamblin, Michael R. TI Harnessing the Power of Light to Treat Staphylococcal Infections Focusing on MRSA SO CURRENT PHARMACEUTICAL DESIGN LA English DT Article DE Photodynamic therapy; MRSA; PDI; blue light; UV light; photosensitizer; multi-drug efflux pump ID ACTIVATED ANTIMICROBIAL AGENT; MULTIDRUG-RESISTANCE PUMPS; ULTRAVIOLET C IRRADIATION; STRAIN-DEPENDENT RESPONSE; GENE REGULATOR AGR; INDUCED DNA-DAMAGE; PHOTODYNAMIC THERAPY; BLUE-LIGHT; IN-VITRO; HELICOBACTER-PYLORI AB Methicillin-resistant Staphylococcus aureus (MRSA) has become the most important drug-resistant microbial pathogen in countries throughout the world. Morbidity and mortality due to MRSA infections continue to increase despite efforts to improve infection control measures and to develop new antibiotics. Therefore alternative antimicrobial strategies that do not give rise to development of resistance are urgently required. A group of therapeutic interventions has been developed in the field of photomedicine with the common theme that they rely on electromagnetic radiation with wavelengths between 200 and 1000 nm broadly called "light". These techniques all use simple absorption of photons by specific chromophores to deliver the killing blow to microbial cells while leaving the surrounding host mammalian cells relatively unharmed. Photodynamic inactivation uses dyes called photosensitizers (PS) that bind specifically to MRSA cells and not host cells, and generate reactive oxygen species including singlet oxygen and singlet oxygen upon illumination. Sophisticated molecular strategies to target the PS to MRSA cells have been designed. Ultraviolet C radiation can damage microbial DNA without unduly harming host DNA. Blue light can excite endogenous porphyrins and flavins in MRSA cells that are not present in host cells. Near-infrared lasers can interfere with microbial membrane potentials without raising the temperature of the tissue. Taken together these innovative approaches towards harnessing the power of light suggest that the ongoing threat of MRSA may eventually be defeated. C1 [Agrawal, Tanupriya; Avci, Pinar; Gupta, Gaurav K.; Rineh, Ardeshir; Lakshmanan, Shanmugamurthy; Tegos, George P.; Hamblin, Michael R.] Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA. [Agrawal, Tanupriya; Avci, Pinar; Gupta, Gaurav K.; Lakshmanan, Shanmugamurthy; Tegos, George P.] Harvard Univ, Sch Med, Dept Dermatol, Boston, MA 02115 USA. [Avci, Pinar] Semmelweis Univ, Sch Med, Dept Dermatol, H-1085 Budapest, Hungary. [Rineh, Ardeshir] Univ Wollongong, Sch Chem, Wollongong, NSW 2522, Australia. [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.] Harvard Mit Div Hlth Sci & Technol, Cambridge, MA 02139 USA. [Batwala, Vincent] Harvard Univ, Sch Publ Hlth, Dept Immunol & Infect Dis, Boston, MA 02115 USA. RP Hamblin, MR (reprint author), Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA. EM hamblin@helix.mgh.harvard.edu FU US NIH [R01AI050875] FX Research in The Hamblin laboratory is supported by US NIH grant R01AI050875. NR 139 TC 0 Z9 0 U1 2 U2 13 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 2015 VL 21 IS 16 BP 2109 EP 2121 PG 13 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA CG9RK UT WOS:000353655700008 PM 25760339 ER PT J AU Bledsoe, JR Christiani, DC Kradin, RL AF Bledsoe, Jacob R. Christiani, David C. Kradin, Richard L. TI Pleural plaques in smoking-associated fibrosis and pulmonary asbestosis Reply SO INTERNATIONAL JOURNAL OF CHRONIC OBSTRUCTIVE PULMONARY DISEASE LA English DT Letter ID PATHOLOGY; DISEASES C1 [Bledsoe, Jacob R.; Kradin, Richard L.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Christiani, David C.; Kradin, Richard L.] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. RP Kradin, RL (reprint author), Massachusetts Gen Hosp, Dept Pathol, Warren Bldg 253,55 Fruit St, Boston, MA 02114 USA. EM rkradin@partners.org NR 6 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 2015 VL 10 BP 871 EP 871 PG 1 WC Respiratory System SC Respiratory System GA CH2XD UT WOS:000353887500002 PM 26080463 ER PT J AU Sasase, T Yokoi, N Pezzolesi, MG Shinohara, M AF Sasase, Tomohiko Yokoi, Norihide Pezzolesi, Marcus G. Shinohara, Masami TI Animal Models of Diabetes and Metabolic Disease 2014 SO JOURNAL OF DIABETES RESEARCH LA English DT Editorial Material C1 [Sasase, Tomohiko] Japan Tobacco Inc, Cent Pharmaceut Res Inst, Biol Pharmacol Res Labs, Osaka 5691125, Japan. [Yokoi, Norihide] Kobe Univ, Grad Sch Med, Dept Physiol & Cell Biol, Div Mol & Metab Med, Kobe, Hyogo 6500017, Japan. [Pezzolesi, Marcus G.] Harvard Univ, Sch Med, Joslin Diabet Ctr, Sect Genet & Epidemiol, Boston, MA 02215 USA. [Shinohara, Masami] CLEA Japan Inc, Tokyo Anim & Diet Dept, Tokyo 1538533, Japan. RP Sasase, T (reprint author), Japan Tobacco Inc, Cent Pharmaceut Res Inst, Biol Pharmacol Res Labs, Osaka 5691125, Japan. EM tomohiko.sasase@jt.com NR 0 TC 1 Z9 1 U1 0 U2 0 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 2015 AR 571809 DI 10.1155/2015/571809 PG 2 WC Endocrinology & Metabolism; Medicine, Research & Experimental SC Endocrinology & Metabolism; Research & Experimental Medicine GA CH1MQ UT WOS:000353786200001 ER PT J AU Chandler, PD Scott, JB Drake, BF Ng, K Chan, AT Hollis, BW Emmons, KM Giovannucci, EL Fuchs, CS Bennett, GG AF Chandler, P. D. Scott, J. B. Drake, B. F. Ng, K. Chan, A. T. Hollis, B. W. Emmons, K. M. Giovannucci, E. L. Fuchs, C. S. Bennett, G. G. TI Impact of vitamin D supplementation on adiposity in African-Americans SO NUTRITION & DIABETES LA English DT Article ID FOOD FREQUENCY QUESTIONNAIRE; RANDOMIZED CONTROLLED-TRIALS; NUTRITION EXAMINATION SURVEY; 3RD NATIONAL-HEALTH; 25-HYDROXYVITAMIN D; OBESE SUBJECTS; BODY-WEIGHT; CALCIUM; WOMEN; REPRODUCIBILITY AB BACKGROUND: African-Americans have higher rates of obesity-associated chronic diseases. Serum 25-hydroxyvitamin D (25(OH) D) shows an inverse association with obesity status. We investigated whether vitamin D supplementation changes body mass index (BMI). SUBJECTS: In total, 328 overweight African-Americans were enrolled over three consecutive winter periods (2007-2010) into a randomized, double-blind, placebo-controlled trial to receive cholecalciferol supplementation (0, 1000 international units (IU), 2000 IU or 4000 IU per day) for 3 months. Plasma concentrations of 25(OH) D and anthropometric measurements were done at baseline, 3 and 6 months. RESULTS: At 3 months, vitamin D supplementation in three dose groups (1000 IU, 2000 IU or 4000 IU per day) did not cause any significant changes in BMI as compared with placebo group 3-month change in BMI per 1000 IU per day estimate (SE): 0.01 (0.039); P = 0.78. CONCLUSIONS: In overweight African-Americans, short-term high-dose vitamin D supplementation did not alter BMI. C1 [Chandler, P. D.] Brigham & Womens Hosp, Div Prevent Med, Dept Med, Boston, MA 02215 USA. [Chandler, P. D.; Ng, K.; Chan, A. T.; Emmons, K. M.; Giovannucci, E. L.; Fuchs, C. S.] Harvard Univ, Sch Med, Boston, MA USA. [Scott, J. B.] Michigan State Univ, Dept Epidemiol & Biostat, E Lansing, MI 48824 USA. [Drake, B. F.] Washington Univ, Sch Med, Dept Surg, Div Publ Hlth Sci, St Louis, MO 63110 USA. [Ng, K.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Chan, A. T.] Massachusetts Gen Hosp, Dept Gastroenterol, Boston, MA 02114 USA. [Hollis, B. W.] Med Univ S Carolina, Div Pediat, Charleston, SC 29425 USA. [Emmons, K. M.] Dana Farber Canc Inst, Ctr Community Based Res, Boston, MA 02115 USA. [Giovannucci, E. L.] Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA. [Giovannucci, E. L.] Brigham & Womens Hosp, Channing Div Network Med, Boston, MA 02115 USA. [Bennett, G. G.] Duke Univ, Dept Psychol & Neurosci, Durham, NC USA. RP Chandler, PD (reprint author), Brigham & Womens Hosp, Div Prevent Med, 900 Commonwealth Ave,Third Floor, Boston, MA 02215 USA. EM pchandler@partners.org OI Drake, Bettina/0000-0001-9340-5848 FU National Cancer Institute [P50CA127003, K07CA148894, K22CA126992, 5K05CA124415, U01CA138962]; Department of Defense Prostate Cancer Research Program [PC081669]; American Society of Clinical Oncology Career Development Award; Pharmavite LLC FX We would like to thank Cara Marcus, MSLIS, AHIP, Director of Library Services, Brigham and Women's Faulkner Hospital for facilitating access to reference articles and Harvard Catalyst for statistical support. The authors' responsibilities were as follows-CSF, ELG, KME, BFD, GGB: conceived and designed the study; PDC CSF ELG: analyzed the study; and all authors contributed to the manuscript. This trial was funded by the National Cancer Institute (P50CA127003; K07CA148894 [Ng]; K22CA126992; 5K05CA124415 [Emmons]; U01CA138962 [Chandler]), the Department of Defense Prostate Cancer Research Program (PC081669 [Drake]), the American Society of Clinical Oncology Career Development Award (Ng) and Pharmavite LLC. The sponsor had no role in designing, developing the protocol, or conducting the trial; in data collection, analysis, management, or interpretation of the data; or in preparing the manuscript. NR 32 TC 2 Z9 2 U1 2 U2 3 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 2044-4052 J9 NUTR DIABETES JI Nutr. Diabetes PD JAN PY 2015 VL 5 AR e147 DI 10.1038/nutd.2014.44 PG 7 WC Endocrinology & Metabolism; Nutrition & Dietetics SC Endocrinology & Metabolism; Nutrition & Dietetics GA CH0EC UT WOS:000353690900001 PM 25599559 ER PT S AU Sinha, L Elliott, JT Hasan, T Pogue, BW Samkoe, KS Tichauer, KM AF Sinha, Lagnojita Elliott, Jonathan T. Hasan, Tayyaba Pogue, Brian W. Samkoe, Kimberley S. Tichauer, Kenneth M. BE Kessel, DH Hasan, T TI Early photosensitizer uptake kinetics predict optimum drug-light interval for photodynamic therapy SO OPTICAL METHODS FOR TUMOR TREATMENT AND DETECTION: MECHANISMS AND TECHNIQUES IN PHOTODYNAMIC THERAPY XXIV 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 XXIV CY FEB 07-09, 2015 CL San Francisco, CA SP SPIE DE cancer; Photo dynamic therapy; tracer kinetics for PDT; optimum drug-light interval; photosensitizer uptake kinetics; molecular imaging; early uptake Prediction; compartment model ID VASCULAR-PERMEABILITY; AGENTS; TUMORS; DELIVERY; BARRIERS; DAMAGE AB Photodynamic therapy (PDT) has shown promising results in targeted treatment of cancerous cells by developing localized toxicity with the help of light induced generation of reactive molecular species. The efficiency of this therapy depends on the product of the intensity of light dose and the concentration of photosensitizer (PS) in the region of interest (ROI). On account of this, the dynamic and variable nature of PS delivery and retention depends on many physiological factors that are known to be heterogeneous within and amongst tumors (e.g., blood flow, blood volume, vascular permeability, and lymph drainage rate). This presents a major challenge with respect to how the optimal time and interval of light delivery is chosen, which ideally would be when the concentration of PS molecule is at its maximum in the ROI. In this paper, a predictive algorithm is developed that takes into consideration the variability and dynamic nature of PS distribution in the body on a region-by-region basis and provides an estimate of the optimum time when the PS concentration will be maximum in the ROI. The advantage of the algorithm lies in the fact that it predicts the time in advance as it takes only a sample of initial data points (similar to 12 min) as input. The optimum time calculated using the algorithm estimated a maximum dose that was only 0.58 +/- 1.92% under the true maximum dose compared to a mean dose error of 39.85 +/- 6.45% if a 1 h optimal light deliver time was assumed for patients with different efflux rate constants of the PS, assuming they have the same plasma function. Therefore, if the uptake values of PS for the blood and the ROI is known for only first 12 minutes, the entire curve along with the optimum time of light radiation can be predicted with the help of this algorithm. C1 [Sinha, Lagnojita; Tichauer, Kenneth M.] IIT, Biomed Engn, Chicago, IL 60616 USA. [Elliott, Jonathan T.; Pogue, Brian W.; Samkoe, Kimberley S.] Dartmouth Coll, Thayer Sch Engn, Hanover, NH 03755 USA. [Hasan, Tayyaba] Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA. RP Sinha, L (reprint author), IIT, Biomed Engn, Chicago, IL 60616 USA. NR 19 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 978-1-62841-398-4 J9 PROC SPIE PY 2015 VL 9308 AR 930811 DI 10.1117/12.2077842 PG 8 WC Engineering, Biomedical; Optics; Radiology, Nuclear Medicine & Medical Imaging SC Engineering; Optics; Radiology, Nuclear Medicine & Medical Imaging GA BC6CO UT WOS:000353802500003 ER PT S AU Abdallah, CG Averill, LA Krystal, JH AF Abdallah, Chadi G. Averill, Lynnette A. Krystal, John H. GP New York Acad Sci TI Ketamine as a promising prototype for a new generation of rapid-acting antidepressants SO TRANSLATIONAL NEUROSCIENCE IN PSYCHIATRY SE Annals of the New York Academy of Sciences LA English DT Article; Proceedings Paper CT Conference on Translational Psychiatry - Light at the End of the Tunnel CY APR 08, 2014 CL New York Acad Sci, New York, NY HO New York Acad Sci DE ketamine; depression; antidepressant; treatment mechanisms; neurobiology ID TREATMENT-RESISTANT DEPRESSION; D-ASPARTATE ANTAGONIST; POSTTRAUMATIC-STRESS-DISORDER; NMDA RECEPTOR BLOCKADE; LOW-DOSE KETAMINE; ADD-ON TRIAL; MAJOR DEPRESSION; ELECTROCONVULSIVE-THERAPY; INTRAVENOUS KETAMINE; BIPOLAR DEPRESSION AB The discovery of ketamine's rapid and robust antidepressant effects opened a window into a new generation of antidepressants. Multiple controlled trials and open-label studies have demonstrated these effects across a variety of patient populations known to often achieve little to no response from traditional antidepressants. Ketamine has been generally well tolerated across patient groups, with transient mild-to-moderate adverse effects during infusion. However, the optimal dosing and route of administration and the safety of chronic treatment are not fully known. This review summarizes the clinical effects of ketamine and its neurobiological underpinnings and mechanisms of action, which may provide insight into the neurobiology of depression, relevant biomarkers, and treatment targets. Moreover, we offer suggestions for future research that may continue to advance the field forward and ultimately improve the psychopharmacologic interventions available for those individuals struggling with depressive and trauma-related disorders. C1 [Abdallah, Chadi G.; Averill, Lynnette A.; Krystal, John H.] US Dept Vet Affairs, Clin Neurosci Div, Natl Ctr Posttraumat Stress Disorder, VA Connecticut Healthcare Syst, West Haven, CT USA. [Abdallah, Chadi G.; Averill, Lynnette A.; Krystal, John H.] Yale Univ, Sch Med, Dept Psychiat, New Haven, CT USA. RP Abdallah, CG (reprint author), US Dept Vet Affairs, Clin Neurosci Div, Natl Ctr Posttraumat Stress Disorder, VA Natl Ctr PTSD, 950 Campbell Ave 151E, West Haven, CT 06516 USA. EM chadi.abdallah@yale.edu OI Abdallah, Chadi/0000-0001-5783-6181 FU Brain and Behavior Research Foundation (NARSAD); American Psychiatric Foundation; Genentech FX Dr. Averill declares no conflicts of interest. Dr. Abdallah has received research funding or consultation fees from the Brain and Behavior Research Foundation (NARSAD), the American Psychiatric Foundation, and Genentech. Dr. Krystal has served as a scientific consultant to the following companies (the individual consultant agreements listed are less than $10000/year): Aisling Capital, Astellas Pharma Global Development, AstraZeneca Pharmaceuticals, Biocortech, Brintnall & Nicolini, Easton Associates, Gilead Sciences, GlaxoSmithKline, Janssen Pharmaceuticals, Lundbeck Research USA, Medivation, Merz Pharmaceuticals, MK Medical Communications, Hoffmann-La Roche, SK Holdings, Sunovion Pharmaceuticals, Takeda Industries, and Teva Pharmaceutical Industries. He is on the Scientific Advisory Board for the following companies: Abbott Laboratories, Bristol-Myers Squibb, Eisai, Eli Lilly, Forest Laboratories, Lohocla Research Corporation, Mnemosyne Pharmaceuticals, Naurex, Pfizer Pharmaceuticals, and Shire Pharmaceuticals. He holds less than $150 in exercisable warrant options with Tetragenex Pharmaceuticals. He is also on the Board of Directors of the Coalition for Translational Research in Alcohol and Substance Use Disorders and was the principal investigator of a multicenter study in which Janssen Research Foundation provided drug and some support to the Department of Veterans Affairs. He is Editor of Biological Psychiatry. In addition, he has a patent on dopamine and noradrenergic reuptake inhibitors in the treatment of schizophrenia (patent number 5447948) and is a coinventor with Dr. Gerard Sanacora on a filed patent application by Yale University related to targeting the glutamatergic system for the treatment of neuropsychiatric disorders (PCTWO06108055A1). He has a patent pending on intranasal administration of ketamine to treat depression. NR 88 TC 28 Z9 28 U1 6 U2 13 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 2015 VL 1344 BP 66 EP 77 DI 10.1111/nyas.12718 PG 12 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA BC5PU UT WOS:000353469600006 PM 25727103 ER PT J AU Arthur, R Rodriguez-Vida, A Zadra, G Moller, H Van Hemelrijck, M AF Arthur, Rhonda Rodriguez-Vida, Alejo Zadra, Giorgia Moller, Henrik Van Hemelrijck, Mieke TI Serum lipids as markers of prostate cancer occurrence and prognosis? SO CLINICAL LIPIDOLOGY LA English DT Review DE apoA-1; apoB; cholesterol; HDL; LDL; prostate cancer; triglycerides ID HIGH-DENSITY-LIPOPROTEIN; INHIBIT TUMOR-DEVELOPMENT; METABOLIC SYNDROME; HDL CHOLESTEROL; UNITED-STATES; MOUSE MODEL; RISK; CELLS; PROLIFERATION; PROGRESSION AB With the current epidemic of lipid-related disorders and prostate cancer (PCa) in western countries, there is growing interest in the potential causal relationship between lipids and PCa. PCa is a heterogeneous disease, which undermines researchers' ability to determine the mechanistic pathways responsible for its development and progression. Currently, detection and progression of PCa is mainly determined by prostate specific antigen, but this biomarker lacks specificity and is unable to discriminate between indolent and aggressive cancer. Nonetheless, there is evidence to suggest that lipid markers might potentially be useful in conjunction with other markers such as prostate specific antigen in improving detection and management of this disease. This review aims to highlight findings from epidemiological studies which examined the role of serum lipids in PCa occurrence and prognosis. C1 [Arthur, Rhonda; Moller, Henrik; Van Hemelrijck, Mieke] Kings Coll London, Guys Hosp, Canc Epidemiol Grp, Div Canc Studies,Res Oncol, London SE1 9RT, England. [Rodriguez-Vida, Alejo] Guys & St Thomas NHS Fdn Trust, Dept Med Oncol, London, England. [Zadra, Giorgia] Dana Farber Canc Inst, Ctr Mol Oncol Pathol, Boston, MA 02215 USA. RP Arthur, R (reprint author), Kings Coll London, Guys Hosp, Canc Epidemiol Grp, Div Canc Studies,Res Oncol, 3rd Floor,Bermondsey Wing, London SE1 9RT, England. EM rhonda.arthur@kcl.ac.uk OI Moller, Henrik/0000-0001-8200-5929 FU Experimental Cancer Medicine Centre at King's College London; National Institute for Health Research (NIHR) Biomedical Research Centre based at Guy's and St Thomas' NHS Foundation Trust; King's College London FX This research was supported by the Experimental Cancer Medicine Centre at King's College London and also by the National Institute for Health Research (NIHR) Biomedical Research Centre based at Guy's and St Thomas' NHS Foundation Trust and King's College London. 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 81 TC 1 Z9 1 U1 3 U2 5 PU FUTURE MEDICINE LTD PI LONDON PA UNITEC HOUSE, 3RD FLOOR, 2 ALBERT PLACE, FINCHLEY CENTRAL, LONDON, N3 1QB, ENGLAND SN 1758-4299 EI 1758-4302 J9 CLIN LIPIDOL JI Clin. Lipidol. PY 2015 VL 10 IS 2 BP 145 EP 165 DI 10.2217/CLP.14.69 PG 21 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA CG6LJ UT WOS:000353412100005 ER PT J AU Costine, BA Missios, S Taylor, SR McGuone, D Smith, CM Dodge, CP Harris, BT Duhaime, AC AF Costine, Beth A. Missios, Symeon Taylor, Sabrina R. McGuone, Declan Smith, Colin M. Dodge, Carter P. Harris, Brent T. Duhaime, Ann-Christine TI The Subventricular Zone in the Immature Piglet Brain: Anatomy and Exodus of Neuroblasts into White Matter after Traumatic Brain Injury SO DEVELOPMENTAL NEUROSCIENCE LA English DT Article DE Traumatic brain injury; Subventricular zone; Neurogenesis; Neuroblasts ID MATURATION-DEPENDENT RESPONSE; CENTRAL-NERVOUS-SYSTEM; CELL-PROLIFERATION; POSTNATAL NEUROGENESIS; OLFACTORY-BULB; DENTATE GYRUS; IN-VITRO; FOREBRAIN; MIGRATION; MICE AB Stimulation of postnatal neurogenesis in the subventricular zone (SVZ) and robust migration of neuroblasts to the lesion site in response to traumatic brain injury (TBI) is well established in rodent species; however, it is not yet known whether postnatal neurogenesis plays a role in repair after TBI in gyrencephalic species. Here we describe the anatomy of the SVZ in the piglet for the first time and initiate an investigation into the effect of TBI on the SVZ architecture and the number of neuroblasts in the white matter. Among all ages of immaturity examined the SVZ contained a dense mesh network of neurogenic precursor cells (doublecortin+) positioned directly adjacent to the ependymal cells (ventricular SVZ, Vsvz) and neuroblasts organized into chains that were distinct from the Vsvz (abventricular SVZ, Asvz). Though the architecture of the SVZ was similar among ages, the areas of Vsvz and Asvz neuroblast chains declined with age. At postnatal day (PND) 14 the white matter tracts have a tremendous number of individual neuroblasts. In our scaled corticalimpact model, lesion size increased with age. Similarly, the response of the SVZ to injury was also age dependent. The younger age groups that sustained the proportionately smallest lesions had the largest SVZ areas, which further increased in response to injury. In piglets that were injured at 4 months of age and had the largest lesions, the SVZ did not increase in response to injury. Similar to humans, swine have abundant gyri and gyral white matter, providing a unique platform to study neuroblasts potentially migrating from the SVZ to the lesioned cortex along these white matter tracts. In piglets injured at PND 7, TBI did not increase the total number of neuroblasts in the white matter compared to uninjured piglets, but redistribution occurred with a greater number of neuroblasts in the white matter of the hemisphere ipsilateral to the injury compared to the contralateral hemisphere. At 7 days after injury, less than 1% of neuroblasts in the white matter were born in the 2 days following injury. These data show that the SVZ in the piglet shares many anatomical similarities with the SVZ in the human infant, and that TBI had only modest effects on the SVZ and the number of neuroblasts in the white matter. Piglets at an equivalent developmental stage to human infants were equipped with the largest SVZ and a tremendous number of neuroblasts in the white matter, which may be sufficient in lesion repair without the dramatic stimulation of neurogenic machinery. It has yet to be determined whether neurogenesis and migrating neuroblasts play a role in repair after TBI and/or whether an alteration of normal migration during active postnatal population of brain regions is beneficial in species with gyrencephalic brains. (C) 2015 S. Karger AG, Basel C1 [Costine, Beth A.; Smith, Colin M.; Duhaime, Ann-Christine] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Neurosurg, Charlestown, MA 02114 USA. [McGuone, Declan] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Pathol, Charlestown, MA 02114 USA. [Costine, Beth A.; Duhaime, Ann-Christine] Harvard Univ, Sch Med, Dept Neurosurg, Charlestown, MA 02114 USA. [Missios, Symeon] Cleveland Clin, Dept Neurosurg, Cleveland, OH 44106 USA. [Taylor, Sabrina R.] Spaulding Rehabil Hosp, Dept Phys Med & Rehabil, Charlestown, MA USA. [Dodge, Carter P.] Childrens Hosp Dartmouth, Dartmouth Med Sch, Dept Anesthesiol, Lebanon, NH USA. [Harris, Brent T.] Georgetown Med Sch, Dept Neurol, Washington, DC USA. [Harris, Brent T.] Georgetown Med Sch, Dept Pathol, Washington, DC USA. RP Costine, BA (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Bldg 149,13th St,Room 3-405, Charlestown, MA 02114 USA. EM bcostine@mgh.harvard.edu FU NIH National Institute of Child Health and Human Development [R01 HD45364-5]; Pediatric Neuroscience Fund of the Children's Hospital at Dartmouth; Nicholas T. Zervas Chair of Harvard Medical School; Joel Alan Viktor Research Fund at Massachusetts General Hospital; NINDS [5P30NS045776] FX This work was supported by R01 HD45364-5 from the NIH National Institute of Child Health and Human Development, the Pediatric Neuroscience Fund of the Children's Hospital at Dartmouth, the Nicholas T. Zervas Chair of Harvard Medical School, and the Joel Alan Viktor Research Fund at Massachusetts General Hospital. The authors express their gratitude to Leslie Adams, Kate Hillier, Ijeoma Chinwuba, Michael Simoni, and Kristen Saliga for their assistance with animal handling, immunohistochemistry and quantification. The authors also wish to thank Kenneth Orndorff (Dartmouth Optical Cellular Imaging Shared Resource Center) and Igor Bagayev (MGH Neuroscience Center Imaging Core supported by NINDS grant 5P30NS045776) for their assistance with confocal microscopy and Emily Belli for proofreading the manuscript. NR 43 TC 5 Z9 5 U1 0 U2 0 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 2015 VL 37 IS 2 BP 115 EP 130 DI 10.1159/000369091 PG 16 WC Developmental Biology; Neurosciences SC Developmental Biology; Neurosciences & Neurology GA CG8LB UT WOS:000353558000003 PM 25678047 ER PT J AU Connelly, KJ Larson, EA Marks, DL Klein, RF AF Connelly, Kara J. Larson, Emily A. Marks, Daniel L. Klein, Robert F. TI Neonatal Estrogen Exposure Results in Biphasic Age-Dependent Effects on the Skeletal Development of Male Mice SO ENDOCRINOLOGY LA English DT Article ID HORMONE-RELEASING-HORMONE; SOMATOSTATIN GENE-EXPRESSION; PEAK BONE MASS; GROWTH-HORMONE; SEX STEROIDS; ANDROGEN INSENSITIVITY; SECRETORY PATTERNS; GONADAL-STEROIDS; CORTICAL BONE; MALE-RATS AB Peak bone mass, one of the most important predictors for fracture risk later in life, is attained during puberty and adolescence and influenced by neonatal and pubertal sex-specific gonadal hormones and GH-IGF-I secretion patterns. This study examined the effects of brief neonatal estrogen (NE) exposure on growth and skeletal development in C57BL/6J mice. A single injection of 100-mu g estradiol or vehicle was administered on the first day of life. Growth parameters were monitored and skeletal phenotyping performed at 16 weeks in female mice and at 4 and 16 weeks in male mice. NE exposure negatively impacted adult femoral length in both sexes, but adult body weight, areal bone density, and bone strength in female mice were unaffected. In contrast, somatic growth was attenuated in estrogen-exposed male mice throughout the study period. At the prepubertal time point, the estrogen-exposed males exhibited higher bone mineral density, cortical volume, and cortical thickness compared with controls. However, by the time of peak bone mass acquisition, the early skeletal findings had reversed; estrogen-exposed mice had lower bone density with reduced cross-sectional area, cortical volume, and cortical thickness, resulting in cortical bones that were less resistant to fracture. NE exposure also resulted in reduced testicular volume and lower circulating IGF-I. Male mice exposed to estrogen on the first day of life experience age-dependent changes in skeletal development. Prepubertal animals experience greater endocortical bone acquisition as a result of estrogen exposure. However, by adulthood, continued developmental changes result in overall reduced skeletal integrity. C1 [Connelly, Kara J.; Marks, Daniel L.] Oregon Hlth & Sci Univ, Doernbecher Childrens Hosp, Div Pediat Endocrinol, Dept Pediat, Portland, OR 97239 USA. [Larson, Emily A.; Klein, Robert F.] Oregon Hlth & Sci Univ, Bone & Mineral Res Unit, Dept Med, Portland, OR 97239 USA. [Marks, Daniel L.] Oregon Hlth & Sci Univ, Pape Pediat Res Inst, Portland, OR 97239 USA. [Klein, Robert F.] Portland VA Med Ctr, Portland, OR 97239 USA. RP Connelly, KJ (reprint author), Oregon Hlth & Sci Univ, Doernbecher Childrens Hosp, Child Dev & Rehabil Ctr Pediat CDRC P, 707 Southwest Gaines St, Portland, OR 97239 USA. EM connellk@ohsu.edu FU National Institutes of Health Grant [R01 AR44659, R01 DK070333, T32 DK7674-19]; Veterans Affairs Medical Research Service FX This work was supported by National Institutes of Health Grants R01 AR44659 (to R.F.K.) and R01 DK070333 (to D.L.M.), T32 DK7674-19 (to K.J.C.), and by the Veterans Affairs Medical Research Service (R.F.K.). NR 42 TC 2 Z9 2 U1 0 U2 1 PU ENDOCRINE SOC PI WASHINGTON PA 2055 L ST NW, SUITE 600, WASHINGTON, DC 20036 USA SN 0013-7227 EI 1945-7170 J9 ENDOCRINOLOGY JI Endocrinology PD JAN PY 2015 VL 156 IS 1 BP 193 EP 202 DI 10.1210/en.2014-1324 PG 10 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA CG2TA UT WOS:000353126800021 PM 25330099 ER PT J AU Rosenquist, KJ Massaro, JM Pedley, A Long, MT Kreger, BE Vasan, RS Murabito, JM Hoffmann, U Fox, CS AF Rosenquist, Klara J. Massaro, Joseph M. Pedley, Alison Long, Michelle T. Kreger, Bernard E. Vasan, Ramachandran S. Murabito, Joanne M. Hoffmann, Udo Fox, Caroline S. TI Fat Quality and Incident Cardiovascular Disease, All-Cause Mortality, and Cancer Mortality SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID BODY-MASS INDEX; ADIPOSE-TISSUE; INSULIN-RESISTANCE; EXTRACELLULAR-MATRIX; RISK-FACTORS; US ADULTS; OBESITY; ASSOCIATION; OVERWEIGHT; SENSITIVITY AB Context: Cellular characteristics of fat quality have been associated with cardiometabolic risk and can be estimated by computed tomography (CT) attenuation. Objective: The aim was to determine the association between CT attenuation (measured in Hounsfield units [ HU]) and clinical outcomes. Methods: This was a prospective community-based cohort study using data from the Framingham Heart Study (n = 3324, 48% women, mean age 51 years) and Cox proportional hazard models. Main Outcomes: The primary outcomes of interest were incident cardiovascular disease (CVD) and all-cause mortality. The secondary outcomes of interest were incident cancer, non-CVD death, and cancer death. Results: There were 111 incident CVD events, 137 incident cancers, 85 deaths including 69 non-CVD deaths, and 45 cancer deaths in up to 23 047 person-years of follow-up. A1-SD increment in visceral adipose tissue (VAT) HU was inversely associated with incident CVD in the age-and sex-adjusted model (hazard ratio [HR] 0.78, P = .02) but not after multivariable adjustment (HR 0.83, P = .11). VAT HU was directly associated with all-cause mortality (multivariable HR 1.40, P = .003), which maintained significance after additional adjustment for body mass index (HR 1.53, P < .001) and VAT volume (HR 1.99, P < .001). Non-CVDdeath remained significant in all 3 models, including after adjustment for VAT volume (HR 1.97, P < .001). VAT HU was also associated with cancer mortality (HR 1.93, P = .002). Similar results were obtained for sc adipose tissue HU. Conclusions: Fat quality, as estimated by CT attenuation, is associated with all-cause mortality, non-CVD death, and cancer death. These associations highlight how indirect indices of fat quality can potentially add to a better understanding of obesity-related complications. C1 [Rosenquist, Klara J.; Fox, Caroline S.] Brigham & Womens Hosp, Div Endocrinol & Metab, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA USA. [Rosenquist, Klara J.; Long, Michelle T.; Kreger, Bernard E.; Vasan, Ramachandran S.; Murabito, Joanne M.; Fox, Caroline S.] NHLBI, Framingham Heart Study, Framingham, MA 01702 USA. [Rosenquist, Klara J.; Pedley, Alison; Long, Michelle T.; Fox, Caroline S.] Div Intramural Res, Framingham, MA 01702 USA. [Rosenquist, Klara J.; Pedley, Alison; Long, Michelle T.; Fox, Caroline S.] Ctr Populat Studies, Framingham, MA 01702 USA. [Massaro, Joseph M.] Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02118 USA. [Long, Michelle T.] Boston Med Ctr, Sect Gastroenterol, Dept Med, Boston, MA 02118 USA. [Kreger, Bernard E.; Murabito, Joanne M.] Boston Med Ctr, Sect Gen Internal Med, Dept Med, Boston, MA 02118 USA. [Vasan, Ramachandran S.; Hoffmann, Udo] Boston Med Ctr, Sect Prevent Med & Epidemiol & Cardiol, Dept Med, Boston, MA 02118 USA. Boston Univ, Sch Med, Boston, MA 02118 USA. Massachusetts Gen Hosp, Dept Med, Boston, MA USA. Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Fox, CS (reprint author), 73 Mt Wayte Ave Suite 2, Framingham, MA 01702 USA. EM foxca@nhlbi.nih.gov OI Long, Michelle/0000-0001-6131-3981; Ramachandran, Vasan/0000-0001-7357-5970 FU NHLBI's FHS [N01-HC-25195, ROI-HL-077477]; Whitaker Cardiovascular Institute [T32 HL007224] FX This research was conducted in part using data and resources from the Framingham Heart Study (FHS) of the National Heart, Lung, and Blood Institute (NHLBI) of the National Institutes of Health and Boston University School of Medicine. This work was supported by the NHLBI's FHS (Contract N01-HC-25195) and ROI-HL-077477 (to R.S.V.). K.J. R. is supported through funding from the Whitaker Cardiovascular Institute (T32 HL007224). NR 40 TC 17 Z9 17 U1 0 U2 4 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 2015 VL 100 IS 1 BP 227 EP 234 DI 10.1210/jc.2013-4296 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA CG4UA UT WOS:000353281300072 PM 25226289 ER PT J AU Karaca, E Buyukkaya, R Pehlivan, D Charng, WL Yaykasli, KO Bayram, Y Gambin, T Withers, M Atik, MM Arslanoglu, I Bolu, S Erdin, S Buyukkaya, A Yaykasli, E Jhangiani, SN Muzny, DM Gibbs, RA Lupski, JR AF Karaca, Ender Buyukkaya, Ramazan Pehlivan, Davut Charng, Wu-Lin Yaykasli, Kursat O. Bayram, Yavuz Gambin, Tomasz Withers, Marjorie Atik, Mehmed M. Arslanoglu, Ilknur Bolu, Semih Erdin, Serkan Buyukkaya, Ayla Yaykasli, Emine Jhangiani, Shalini N. Muzny, Donna M. Gibbs, Richard A. Lupski, James R. TI Whole-Exome Sequencing Identifies Homozygous GPR161 Mutation in a Family with Pituitary Stalk Interruption Syndrome SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID PROTEIN-COUPLED RECEPTOR; HEDGEHOG; PHENOTYPE; GLI3; HYPOPITUITARISM; MECHANISMS; VARIANTS; GENES; ALPHA; GLAND AB Context: Pituitary stalk interruption syndrome (PSIS) is a rare, congenital anomaly of the pituitary gland characterized by pituitary gland insufficiency, thin or discontinuous pituitary stalk, anterior pituitary hypoplasia, and ectopic positioning of the posterior pituitary gland (neurohypophysis). The clinical presentation of patients with PSIS varies from isolated growth hormone (GH) deficiency to combined pituitary insufficiency and accompanying extrapituitary findings. Mutations in HESX1, LHX4, OTX2, SOX3, and PROKR2 have been associated with PSIS in less than 5% of cases; thus, the underlying genetic etiology for the vast majority of cases remains to be determined. Objective: We applied whole-exome sequencing (WES) to a consanguineous family with two affected siblings who have pituitary gland insufficiency and radiographic findings of hypoplastic (thin) pituitary gland, empty sella, ectopic neurohypophysis, and interrupted pitiutary stalk-characteristic clinical diagnostic findings of PSIS. Design and Participants: WES was applied to two affected and one unaffected siblings. Results: WES of two affected and one unaffected sibling revealed a unique homozygous missense mutation in GPR161, which encodes the orphan G protein-coupled receptor 161, a protein responsible for transducing extracellular signals across the plasma membrane into the cell. Conclusion: Mutations of GPR161 may be implicated as a potential novel cause of PSIS. C1 [Karaca, Ender; Pehlivan, Davut; Charng, Wu-Lin; Bayram, Yavuz; Gambin, Tomasz; Withers, Marjorie; Atik, Mehmed M.; Gibbs, Richard A.; Lupski, James R.] Baylor Coll Med, Dept Mol & Human Genet, Houston, TX 77030 USA. [Buyukkaya, Ramazan] Duzce Univ, Sch Med, Dept Radiol, TR-81620 Duzce, Turkey. [Yaykasli, Kursat O.] Kahramanmaras Sutcu Imam Univ, Sch Med, Dept Med Biol, TR-46100 Kahramanmaras, Turkey. [Arslanoglu, Ilknur; Bolu, Semih] Duzce Univ, Sch Med, Dept Pediat Endocrinol, TR-81620 Duzce, Turkey. [Erdin, Serkan] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA. [Buyukkaya, Ayla] Duzce Ataturk Community Hosp, Dept Radiol, TR-81620 Duzce, Turkey. [Yaykasli, Emine] Duzce Univ, Inst Hlth Sci, Dept Med Biol & Genet, TR-81620 Duzce, Turkey. [Jhangiani, Shalini N.; Muzny, Donna M.; Gibbs, Richard A.] Baylor Coll Med, Human Genome Sequencing Ctr, Houston, TX 77030 USA. [Lupski, James R.] Baylor Coll Med, Dept Pediat, Houston, TX 77030 USA. [Lupski, James R.] Texas Childrens Hosp, Houston, TX 77030 USA. RP Lupski, JR (reprint author), Baylor Coll Med, Dept Mol & Human Genet, One Baylor Plaza,Room 604B, Houston, TX 77030 USA. EM jlupski@bcm.edu RI Erdin, Serkan/B-4988-2008; OI Erdin, Serkan/0000-0001-6587-2625; Gambin, Tomasz/0000-0002-0941-4571 FU US National Human Genome Research Institute (NHGRI)/National Heart Lung and Blood Institute (NHLBI) [U54HG006542] FX This work was supported by the US National Human Genome Research Institute (NHGRI)/National Heart Lung and Blood Institute (NHLBI) Grant No. U54HG006542 to the Baylor-Hopkins Center for Mendelian Genomics. NR 29 TC 14 Z9 16 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 2015 VL 100 IS 1 BP E140 EP E147 DI 10.1210/jc.2014-1984 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA CG4UA UT WOS:000353281300033 PM 25322266 ER PT J AU Lombardi, A Inabnet, WB Owen, R Farenholtz, KE Tomer, Y AF Lombardi, Angela Inabnet, William Barlow, III Owen, Randall Farenholtz, Kaitlyn Ellen Tomer, Yaron TI Endoplasmic Reticulum Stress as a Novel Mechanism in Amiodarone-Induced Destructive Thyroiditis SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID UNFOLDED PROTEIN RESPONSE; ATRIAL-FIBRILLATION; ER STRESS; INDUCED THYROTOXICOSIS; RHEUMATOID-ARTHRITIS; HEART-FAILURE; MESSENGER-RNA; DISEASE; DEGRADATION; CHAPERONES AB Context: Amiodarone (AMIO) is one of the most effective antiarrhythmic drugs available; however, its use is limited by a serious side effect profile, including thyroiditis. The mechanisms underlying AMIO thyroid toxicity have been elusive; thus, identification of novel approaches in order to prevent thyroiditis is essential in patients treated with AMIO. Objective: Our aim was to evaluate whether AMIO treatment could induce endoplasmic reticulum (ER) stress in human thyroid cells and the possible implications of this effect in AMIO-induced destructive thyroiditis. Results: Here we report that AMIO, but not iodine, significantly induced the expression of ER stress markers including Ig heavy chain-binding protein (BiP), phosphoeukaryotic translation initiation factor 2 alpha (eIF2 alpha), CCAAT/enhancer-binding protein homologous protein (CHOP) and spliced X-box binding protein-1 (XBP-1) in human thyroid ML-1 cells and human primary thyrocytes. In both experimental systems AMIO down-regulated thyroglobulin (Tg) protein but had little effect on Tg mRNA levels, suggesting a mechanism involving Tg protein degradation. Indeed, pretreatment with the specific proteasome inhibitor MG132 reversed AMIO-induced down-regulation of Tg protein levels, confirming a proteasome-dependent degradation of Tg protein. Corroborating our findings, pretreatment of ML-1 cells and human primary thyrocytes with the chemical chaperone 4-phenylbutyric acid completely prevented the effect of AMIO on both ER stress induction and Tg down-regulation. Conclusions: We identified ER stress as a novel mechanism contributing to AMIO-induced destructive thyroiditis. Our data establish that AMIO-induced ER stress impairs Tg expression via proteasome activation, providing a valuable therapeutic avenue for the treatment of AMIO-induced destructive thyroiditis. C1 [Lombardi, Angela; Farenholtz, Kaitlyn Ellen; Tomer, Yaron] Icahn Sch Med Mt Sinai, Div Endocrinol, New York, NY 10029 USA. [Inabnet, William Barlow, III; Owen, Randall] Icahn Sch Med Mt Sinai, Dept Surg, New York, NY 10029 USA. [Tomer, Yaron] James J Peters Vet Affairs Med Ctr, Bronx, NY 10468 USA. RP Lombardi, A (reprint author), Icahn Sch Med Mt Sinai, Div Endocrinol, Box 1055,One Gustave L Levy Pl, New York, NY 10029 USA. EM angela.lombardi@mssm.edu; yaron.tomer@mssm.edu FU NIH from the National Institute of Diabetes and Digestive and Kidney Diseases [DK061659, DK067555, DK073681]; Department of Veterans Affairs FX This work was supported by NIH Grants DK061659, DK067555, and DK073681 from the National Institute of Diabetes and Digestive and Kidney Diseases In addition, this material is based upon work supported in part by the Department of Veterans Affairs. NR 51 TC 2 Z9 2 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 2015 VL 100 IS 1 BP E1 EP E10 DI 10.1210/jc.2014-2745 PG 10 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA CG4UA UT WOS:000353281300014 PM 25295624 ER PT J AU Giavina-Bianchi, M Giavina-Bianchi, P Sotto, MN Muzikansky, A Kalil, J Festa-Neto, C Duncan, LM AF Giavina-Bianchi, Mara Giavina-Bianchi, Pedro Sotto, Mirian Nacagami Muzikansky, Alona Kalil, Jorge Festa-Neto, Cyro Duncan, Lyn M. TI Increased NY-ESO-1 Expression and Reduced Infiltrating CD3+T Cells in Cutaneous Melanoma SO JOURNAL OF IMMUNOLOGY RESEARCH LA English DT Article ID CANCER-TESTIS ANTIGENS; VERTICAL GROWTH-PHASE; METASTATIC MELANOMA; LYMPHOCYTE GRADE; OVARIAN-CANCER; STAGE; SURVIVAL; RESPONSES; IMMUNOGENICITY; IMMUNOTHERAPY AB NY-ESO-1 is a cancer-testis antigen aberrantly expressed in melanomas, which may serve as a robust and specific target in immunotherapy. NY-ESO-1 antigen expression, tumor features, and the immune profile of tumor infiltrating lymphocytes were assessed in primary cutaneous melanoma. NY-ESO-1 protein was detected in 20% of invasive melanomas (16/79), rarely in in situ melanoma (1/10) and not in benign nevi (0/20). Marked intratumoral heterogeneity of NY-ESO-1 protein expression was observed. NY-ESO-1 expression was associated with increased primary tumor thickness (P = 0.007) and inversely correlated with superficial spreading melanoma (P < 0.02). NY-ESO-1 expression was also associated with reduced numbers and density of CD3+ tumor infiltrating lymphocytes (P = 0.017). When NY-ESO-1 protein was expressed, CD3+ T cells were less diffusely infiltrating the tumor and were more often arranged in small clusters (P = 0.010) or as isolated cells (P = 0.002) than in large clusters of more than five lymphocytes. No correlation of NY-ESO-1 expression with gender, age, tumor site, ulceration, lymph node sentinel status, or survival was observed. NY-ESO-1 expression in melanoma was associated with tumor progression, including increased tumor thickness, and with reduced tumor infiltrating lymphocytes. C1 [Giavina-Bianchi, Mara; Sotto, Mirian Nacagami; Festa-Neto, Cyro] Univ Sao Paulo, Dept Dermatol, BR-05403900 Sao Paulo, SP, Brazil. [Giavina-Bianchi, Pedro; Kalil, Jorge] Univ Sao Paulo, Div Clin Immunol & Allergy, BR-05403900 Sao Paulo, SP, Brazil. [Muzikansky, Alona] MGH Biostat Ctr, Boston, MA 02114 USA. [Duncan, Lyn M.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dermatopathol Unit,Pathol Serv, Boston, MA 02114 USA. RP Giavina-Bianchi, M (reprint author), Univ Sao Paulo, Dept Dermatol, Ave Dr Eneas de Carvalho Aguiar 255,3 Andar, BR-05403900 Sao Paulo, SP, Brazil. EM clinicadermato@ig.com.br RI Sotto, Mirian/C-3475-2013 FU FAPESP (Fundacao de Amparo a Pesquisa do Estado de Sao Paulo); CNPQ (Conselho Nacional de Pesquisa), Brazil FX The authors acknowledge Ludwig Institute for Cancer Research, Brazil, for the donation of antibody E978 and also recognized the expert technical support of the Laboratorio Diagnostika, Brazil, for performing immunohistochemical stains and controls. They want to thank Patricia Della Pelle for T cell immunohistochemical staining. This study was supported by grants from FAPESP (Fundacao de Amparo a Pesquisa do Estado de Sao Paulo), and CNPQ (Conselho Nacional de Pesquisa), Brazil, and the consultative funds of one of the authors (Lyn M. Duncan). NR 49 TC 0 Z9 0 U1 0 U2 1 PU HINDAWI PUBLISHING CORP PI NEW YORK PA 410 PARK AVENUE, 15TH FLOOR, #287 PMB, NEW YORK, NY 10022 USA SN 2314-8861 EI 2314-7156 J9 J IMMUNOL RES JI J Immunol. Res. PY 2015 AR 761378 DI 10.1155/2015/761378 PG 8 WC Immunology SC Immunology GA CG7JR UT WOS:000353479700001 ER PT J AU Russell, SJ AF Russell, Steven J. TI When you come to a fork in the road, take it! SO LANCET DIABETES & ENDOCRINOLOGY LA English DT Editorial Material ID ARTIFICIAL PANCREAS; GLUCAGON; HYPOGLYCEMIA C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Russell, SJ (reprint author), Massachusetts Gen Hosp, Boston, MA 02114 USA. EM sjrussell@mgh.harvard.edu NR 10 TC 1 Z9 1 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 2213-8587 J9 LANCET DIABETES ENDO JI Lancet Diabetes Endocrinol. PD JAN PY 2015 VL 3 IS 1 BP 2 EP 3 DI 10.1016/S2213-8587(14)70195-0 PG 2 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA CG1KB UT WOS:000353030400005 PM 25434966 ER PT J AU Shi, CC Li, HP Yang, YF Hou, LF AF Shi, Chenchen Li, Haipeng Yang, Yifu Hou, Lifei TI Anti-Inflammatory and Immunoregulatory Functions of Artemisinin and Its Derivatives SO MEDIATORS OF INFLAMMATION LA English DT Review ID NF-KAPPA-B; T-CELL-ACTIVATION; IMMUNOSUPPRESSIVE ACTIVITY; RHEUMATOID-ARTHRITIS; PLASMODIUM-FALCIPARUM; QINGHAOSU ARTEMISININ; TH17 RESPONSES; TNF-ALPHA; IN-VITRO; ARTESUNATE AB Artemisinin and its derivatives are widely used in the world as the first-line antimalarial drug. Recently, growing evidences reveal that artemisinin and its derivatives also possess potent anti-inflammatory and immunoregulatory properties. Meanwhile, researchers around the world are still exploring the unknown bioactivities of artemisinin derivatives. In this review, we provide a comprehensive discussion on recent advances of artemisinin derivatives affecting inflammation and autoimmunity, the underlying molecular mechanisms, and also drug development of artemisinins beyond antimalarial functions. C1 [Shi, Chenchen; Yang, Yifu] Shanghai Univ Tradit Chinese Med, Lab Immunol & Virol, Shanghai, Peoples R China. [Li, Haipeng] Beijing Army Gen Hosp, Dept Orthoped, Beijing, Peoples R China. [Hou, Lifei] Harvard Univ, Sch Med, Boston Childrens Hosp, Program Cellular & Mol Med, Boston, MA 02115 USA. [Hou, Lifei] Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. RP Yang, YF (reprint author), Shanghai Univ Tradit Chinese Med, Lab Immunol & Virol, Shanghai, Peoples R China. EM yangyifu@mail.shcnc.ac.cn; lifei.hou@childrens.harvard.edu NR 41 TC 1 Z9 2 U1 2 U2 14 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 2015 AR 435713 DI 10.1155/2015/435713 PG 7 WC Cell Biology; Immunology SC Cell Biology; Immunology GA CG7OE UT WOS:000353492400001 ER PT S AU Eisen, HN Schlesinger, S AF Eisen, Herman N. Schlesinger, Sondra BE Littman, DR Yokoyama, WM TI Remembrance of Immunology Past: Conversations with Herman Eisen SO ANNUAL REVIEW OF IMMUNOLOGY VOL 33 SE Annual Review of Immunology LA English DT Review; Book Chapter DE antibodies; affinity maturation; myeloma proteins; CD8(+) T cells ID PIG T-LYMPHOCYTES; ANTIGEN RECOGNITION; RELATIVE AFFINITY; IMMUNE-RESPONSE; INFLUENZA-VIRUS; ANTIBODIES; HETEROGENEITY; SPECIFICITY; MACROPHAGES; MATURATION AB Herman Eisen and Sondra Schlesinger spent several days together in September 2007 in Woods Hole, Massachusetts, talking about immunology, focusing on his remembrances of the field over the more than 60 years of his involvement. This article is an abridged version of those discussions (the full version is available on the Annual Reviews website). It is both an oral history and a written memory of some important but selected areas of immunology. C1 [Eisen, Herman N.] MIT, Koch Inst Integrat Canc Res, Cambridge, MA 02139 USA. [Eisen, Herman N.] MIT, Dept Biol, Cambridge, MA 02139 USA. [Eisen, Herman N.] MIT, Massachusetts Gen Hosp, Ragon Inst, Boston, MA 02129 USA. [Eisen, Herman N.] Harvard Univ, Boston, MA 02129 USA. [Schlesinger, Sondra] Washington Univ, Sch Med, Dept Mol Microbiol, St Louis, MO 63110 USA. RP Eisen, HN (reprint author), MIT, Koch Inst Integrat Canc Res, 77 Massachusetts Ave, Cambridge, MA 02139 USA. EM sondra@wusm.wustl.edu NR 32 TC 1 Z9 1 U1 0 U2 5 PU ANNUAL REVIEWS PI PALO ALTO PA 4139 EL CAMINO WAY, PO BOX 10139, PALO ALTO, CA 94303-0897 USA SN 0732-0582 BN 978-0-8243-3033-0 J9 ANNU REV IMMUNOL JI Annu. Rev. Immunol. PY 2015 VL 33 BP 1 EP + DI 10.1146/annurev-immunol-111214-122349 PG 116 WC Immunology SC Immunology GA BC4TF UT WOS:000352911900001 PM 25581308 ER PT S AU Yin, Q Fu, TM Li, JX Wu, H AF Yin, Qian Fu, Tian-Min Li, Jixi Wu, Hao BE Littman, DR Yokoyama, WM TI Structural Biology of Innate Immunity SO ANNUAL REVIEW OF IMMUNOLOGY VOL 33 SE Annual Review of Immunology LA English DT Review; Book Chapter DE Toll-like receptor; RIG-I-like receptor; intlammasome; cGAS; STING; death domain superfamily; higher-order assembly ID CYCLIC DI-GMP; DOUBLE-STRANDED-RNA; TOLL-LIKE RECEPTORS; SENSOR RIG-I; NF-KAPPA-B; ANTIVIRAL SIGNAL ACTIVATION; CRYSTAL-STRUCTURE; ADAPTER PROTEIN; CYTOSOLIC DNA; PYRIN DOMAIN AB Innate immune responses depend on timely recognition of pathogenic or danger signals by multiple cell surface or cytoplasmic receptors and transmission of signals for proper counteractions through adaptor and effector molecules. At the forefront of innate immunity are four major signaling pathways, including those elicited by Toll-like receptors, RIG-I-like receptors, inflammasomes, or cGAS, each with its own cellular localization, ligand specificity, and signal relay mechanism. They collectively engage a number of overlapping signaling outcomes, such as NF-kappa B activation, interferon response, cvtokine maturation, and cell death. Several proteins often assemble into a supramolecular complex to enable signal transduction and amplification. In this article, we review the recent progress in mechanistic delineation of proteins in these pathways, their structural features, modes of ligand recognition, conformational changes, and homo- and hetero-oligomeric interactions within the supramolecular complexes. Regardless of seemingly distinct interactions and mechanisms, the recurring themes appear to consist of autoinhibited resting-state receptors, ligand-induced conformational changes, and higher-order assemblies of activated receptors, adaptors, and signaling enzymes through conserved protein-protein interactions. C1 [Yin, Qian; Fu, Tian-Min; Li, Jixi; Wu, Hao] Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA. [Yin, Qian; Fu, Tian-Min; Li, Jixi; Wu, Hao] Boston Childrens Hosp, Program Cellular & Mol Med, Boston, MA 02115 USA. [Li, Jixi] Fudan Univ, State Key Lab Genet Engn, Shanghai 200438, Peoples R China. [Li, Jixi] Fudan Univ, Sch Life Sci, Shanghai 200438, Peoples R China. RP Yin, Q (reprint author), Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA. EM lijixi@fudan.edu.cn; hao.wu@childrens.harvard.edu FU NIAID NIH HHS [R01 AI045937, AI045937, AI089882, K99 AI108793, R01 AI050872, R01 AI089882, R37 AI050872] NR 142 TC 11 Z9 11 U1 3 U2 36 PU ANNUAL REVIEWS PI PALO ALTO PA 4139 EL CAMINO WAY, PO BOX 10139, PALO ALTO, CA 94303-0897 USA SN 0732-0582 BN 978-0-8243-3033-0 J9 ANNU REV IMMUNOL JI Annu. Rev. Immunol. PY 2015 VL 33 BP 393 EP 416 DI 10.1146/annurev-immunol-032414-112258 PG 24 WC Immunology SC Immunology GA BC4TF UT WOS:000352911900013 PM 25622194 ER PT J AU Koontz, AM Ding, D Jan, YK de Groot, S Hansen, A AF Koontz, Alicia M. Ding, Dan Jan, Yih-Kuen de Groot, Sonja Hansen, Andrew TI Wheeled Mobility SO BIOMED RESEARCH INTERNATIONAL LA English DT Editorial Material C1 [Koontz, Alicia M.; Ding, Dan] VA Pittsburgh Healthcare Syst, Human Engn Res Labs, Pittsburgh, PA 15206 USA. [Koontz, Alicia M.; Ding, Dan] Univ Pittsburgh, Dept Rehabil Sci & Technol, Pittsburgh, PA 15260 USA. [Jan, Yih-Kuen] Univ Illinois, Dept Kinesiol & Community Hlth, Champaign, IL 61820 USA. [de Groot, Sonja] Reade, Amsterdam Rehabil Res Ctr, NL-1040 HG Amsterdam, Netherlands. [de Groot, Sonja] Univ Groningen, Univ Med Ctr Groningen, Ctr Human Movement Sci, NL-9700 AB Groningen, Netherlands. [Hansen, Andrew] Minneapolis VA Healthcare Syst, Rehabil Engn Res Program, Minneapolis, MN 55417 USA. [Hansen, Andrew] Univ Minnesota, Program Rehabil Sci, Dept Phys Med & Rehabil, Minneapolis, MN 55455 USA. RP Koontz, AM (reprint author), VA Pittsburgh Healthcare Syst, Human Engn Res Labs, Pittsburgh, PA 15206 USA. EM akoontz@pitt.edu OI Jan, Yih-Kuen/0000-0001-7149-4034 NR 3 TC 0 Z9 0 U1 1 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 2015 AR 138176 DI 10.1155/2015/138176 PG 2 WC Biotechnology & Applied Microbiology; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Research & Experimental Medicine GA CF9LK UT WOS:000352886000001 ER PT B AU Felsenfeld, AJ Levine, BS AF Felsenfeld, Arnold J. Levine, Barton S. BE Kimmel, PL Rosenberg, ME TI Pathophysiology of Calcium, Phosphorus, and Magnesium in Chronic Kidney Disease SO CHRONIC RENAL DISEASE LA English DT Article; Book Chapter ID CHRONIC-RENAL-FAILURE; PARATHYROID-HORMONE LEVELS; GROWTH-FACTOR 23; LEFT-VENTRICULAR HYPERTROPHY; SERUM PHOSPHATE LEVELS; TRADE-OFF HYPOTHESIS; INTACT PTH LEVELS; HEMODIALYSIS-PATIENTS; VITAMIN-D; MINERAL METABOLISM C1 [Felsenfeld, Arnold J.; Levine, Barton S.] VA Greater Los Angeles Healthcare Syst, Dept Med, Los Angeles, CA 90073 USA. [Felsenfeld, Arnold J.; Levine, Barton S.] Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90095 USA. RP Felsenfeld, AJ (reprint author), VA Greater Los Angeles Healthcare Syst, Dept Med, Los Angeles, CA 90073 USA. NR 139 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS LTD-ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL ROAD, LONDON NW1 7DX, ENGLAND BN 978-0-12-411616-0; 978-0-12-411602-3 PY 2015 BP 391 EP 405 DI 10.1016/B978-0-12-411602-3.00033-0 PG 15 WC Primary Health Care; Urology & Nephrology SC General & Internal Medicine; Urology & Nephrology GA BC2OW UT WOS:000351158600033 ER PT B AU Maynard, SI Thadhani, RE AF Maynard, Sharon I. Thadhani, Ravi E. BE Kimmel, PL Rosenberg, ME TI Pregnancy and Chronic Kidney Disease SO CHRONIC RENAL DISEASE LA English DT Article; Book Chapter ID SYSTEMIC-LUPUS-ERYTHEMATOSUS; GLOMERULAR-FILTRATION-RATE; CONVERTING ENZYME-INHIBITORS; TYPE-1 DIABETIC WOMEN; SIGNIFICANT PROTEINURIA; RENAL-DISEASE; ANTIHYPERTENSIVE MEDICATION; PRETERM DELIVERY; GLYCEMIC CONTROL; IGA NEPHROPATHY C1 [Maynard, Sharon I.] Univ S Florida, Morsani Coll Med, Lehigh Valley Hlth Network, Allentown, PA 18069 USA. [Thadhani, Ravi E.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. RP Maynard, SI (reprint author), Univ S Florida, Morsani Coll Med, Lehigh Valley Hlth Network, Allentown, PA 18069 USA. NR 110 TC 0 Z9 0 U1 1 U2 5 PU ACADEMIC PRESS LTD-ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL ROAD, LONDON NW1 7DX, ENGLAND BN 978-0-12-411616-0; 978-0-12-411602-3 PY 2015 BP 800 EP 812 DI 10.1016/B978-0-12-411602-3.00066-4 PG 13 WC Primary Health Care; Urology & Nephrology SC General & Internal Medicine; Urology & Nephrology GA BC2OW UT WOS:000351158600066 ER PT J AU Khan, M Dhammu, TS Matsuda, F Baarine, M Dhindsa, TS Singh, I Singh, AK AF Khan, Mushfiquddin Dhammu, Tajinder S. Matsuda, Fumiyo Baarine, Mauhammad Dhindsa, Tejbir Singh Singh, Inderjit Singh, Avtar K. TI Promoting endothelial function by S-nitrosoglutathione through the HIF-1 alpha/VEGF pathway stimulates neurorepair and functional recovery following experimental stroke in rats SO DRUG DESIGN DEVELOPMENT AND THERAPY LA English DT Article DE GSNO; IR; HIF-1 alpha; VEGF; motor function; subtle behavior; neuroprotection; neurorepair; angiogenesis; S-nitrosylation; stroke ID TRAUMATIC BRAIN-INJURY; INDUCIBLE FACTOR-I; AMERICAN-HEART-ASSOCIATION; FOCAL CEREBRAL-ISCHEMIA; NITRIC-OXIDE DONORS; NEUROVASCULAR UNIT; LIQUID-CHROMATOGRAPHY; COGNITIVE IMPAIRMENT; PROTECTS BRAIN; CELL MIGRATION AB Background: For stroke patients, stimulating neurorepair mechanisms is necessary to reduce morbidity and disability. Our previous studies on brain and spinal cord trauma show that exogenous treatment with the S-nitrosylating agent S-nitrosoglutathione (GSNO) - a nitric oxide and glutathione metabolite of the human body - stimulates neurorepair and aids functional recovery. Using a rat model of cerebral ischemia and reperfusion (IR) in this study, we tested the hypothesis that GSNO invokes the neurorepair process and improves neurobehavioral functions through the angiogenic HIF-1 alpha/VEGF pathway. Methods: Stroke was induced by middle cerebral artery occlusion for 60 minutes followed by reperfusion in adult male rats. The injured animals were treated with saline (IR group, n=7), GSNO (0.25 mg/kg, GSNO group, n=7), and GSNO plus the HIF-1 alpha inhibitor 2-methoxyestradiol (2-ME) (0.25 mg/kg GSNO + 5.0 mg/kg 2-ME, GSNO + 2-ME group, n=7). The groups were studied for either 7 or 14 days to determine neurorepair mediators and functional recovery. Brain capillary endothelial cells were used to show that GSNO promotes angiogenesis and that GSNO-mediated induction of VEGF and the stimulation of angiogenesis are dependent on HIF-1 alpha activity. Results: IR injury increased the expression of neurorepair mediators HIF-1 alpha, VEGF, and PECAM-1 and vessel markers to a limited degree that correlate well with significantly compromised neurobehavioral functions compared with sham animals. GSNO treatment of IR not only remarkably enhanced further the expression of HIF-1 alpha, VEGF, and PECAM-1 but also improved functioning compared with IR. The GSNO group also had a higher degree of vessel density than the IR group. Increased expression of VEGF and the degree of tube formation (angiogenesis) by GSNO were reduced after the inhibition of HIF-1 alpha by 2-ME in an endothelial cell culture model. 2-ME treatment of the GSNO group also blocked not only GSNO's effect of reduced infarct volume, decreased neuronal loss, and enhanced expression of PECAM-1 (P<0.001), but also its improvement of motor and neurological functions (P<0.001). Conclusion: GSNO stimulates the process of neurorepair, promotes angiogenesis, and aids functional recovery through the HIF-1 alpha-dependent pathway, showing therapeutic and translational promise for stroke. C1 [Khan, Mushfiquddin; Dhammu, Tajinder S.; Matsuda, Fumiyo; Dhindsa, Tejbir Singh; Singh, Inderjit] Med Univ S Carolina, Dept Pediat, Charleston, SC 29425 USA. [Matsuda, Fumiyo] Kagoshima Univ, Sch Hlth Sci, Kagoshima 890, Japan. [Baarine, Mauhammad; Singh, Avtar K.] Med Univ S Carolina, Dept Pathol & Lab Med, Charleston, SC 29425 USA. [Singh, Avtar K.] Ralph H Johnson VA Med Ctr, Charleston, SC USA. RP Singh, AK (reprint author), Med Univ S Carolina, Dept Pathol & Lab Med, 513 Childrens Res Inst,173 Ashley Ave, Charleston, SC 29425 USA. EM khanm@musc.edu; singha@musc.edu FU NIH [NS-72511]; VA merit award [BX001062]; NIH from the Extramural Research Facilities Program of the National Center for Research Resources [C06 RR018823, C06 RR015455] FX This work was supported by grants from NIH (NS-72511) and VA merit award (BX001062). This work was also supported by the NIH, Grants C06 RR018823 and No C06 RR015455 from the Extramural Research Facilities Program of the National Center for Research Resources. We thank Ms Joyce Bryan and Ms Terry Hope for their technical help and secretarial assistance. We are grateful to Dr Harutoshi Sakakima and Dr Yoshihiro Yoshida for their valuable input. We also acknowledge Dr Tom Smith and Dr Lisa Kerr from the MUSC Writing Center for their valuable editing of the manuscript. NR 76 TC 5 Z9 5 U1 2 U2 9 PU DOVE MEDICAL PRESS LTD PI ALBANY PA PO BOX 300-008, ALBANY, AUCKLAND 0752, NEW ZEALAND SN 1177-8881 J9 DRUG DES DEV THER JI Drug Des. Dev. Ther. PY 2015 VL 9 BP 2233 EP 2247 DI 10.2147/DDDT.S77115 PG 15 WC Chemistry, Medicinal; Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA CG1SN UT WOS:000353054400001 PM 25945035 ER PT J AU Richardson, PG Moreau, P Laubach, JP Gupta, N Hui, AM Anderson, KC Miguel, JFS Kumar, S AF Richardson, Paul G. Moreau, Philippe Laubach, Jacob P. Gupta, Neeraj Hui, Ai-Min Anderson, Kenneth C. Miguel, Jesus F. San Kumar, Shaji TI The investigational proteasome inhibitor ixazomib for the treatment of multiple myeloma SO FUTURE ONCOLOGY LA English DT Article DE continuous therapy; induction; multiple myeloma; newly diagnosed; oral administration; proteasome inhibition; refractory; relapsed ID SINGLE-AGENT CARFILZOMIB; STEM-CELL TRANSPLANTATION; LOW-DOSE DEXAMETHASONE; MLN9708 PLUS LENALIDOMIDE; ADVANCED SOLID TUMORS; CITRATE MLN9708; COMBINATION THERAPY; PRECLINICAL MODELS; REFRACTORY MYELOMA; ANTITUMOR-ACTIVITY AB Ixazomib is an investigational, reversible 20S proteasome inhibitor. It is the first oral proteasome inhibitor under clinical investigation in multiple myeloma (MM). Under physiological conditions, the stable citrate ester drug substance, ixazomib citrate (MLN9708), rapidly hydrolyzes to the biologically active boronic acid, ixazomib (MLN2238). Preclinical studies have demonstrated antitumor activity in MM cell lines and xenograft models. In Phase I/II clinical studies ixazomib has had generally manageable toxicities, with limited peripheral neuropathy observed to date. Preliminary data from these studies indicate ixazomib is active as a single agent in relapsed/refractory MM and as part of combination regimens in newly diagnosed patients. Phase III studies in combination with lenalidomide-dexamethasone are ongoing. C1 [Richardson, Paul G.; Laubach, Jacob P.; Anderson, Kenneth C.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Jerome Lipper Multiple Myeloma Ctr,Div Hematol Ma, Boston, MA 02215 USA. [Moreau, Philippe] Univ Hosp Hotel Dieu, Hematol Dept, Nantes, France. [Gupta, Neeraj; Hui, Ai-Min] Millennium Pharmaceut Inc, Cambridge, MA USA. [Miguel, Jesus F. San] Univ Navarra Clin, CIMA, Pamplona, Spain. [Kumar, Shaji] Mayo Clin, Div Hematol, Rochester, MN USA. RP Richardson, PG (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Jerome Lipper Multiple Myeloma Ctr,Div Hematol Ma, 450 Brookline Ave, Boston, MA 02215 USA. EM paul_richardson@dfci.harvard.edu RI richard, chrystelle/K-8595-2015 FU Celgene; Millennium Pharmaceuticals, Inc.; Novartis; Onyx; Genzyme; Cephalon FX PG Richardson is an advisory committee member for Celgene, Janssen Pharmaceuticals and Millennium Pharmaceuticals, Inc., and has received research funding from Celgene and Millennium Pharmaceuticals, Inc. P Moreau is a consultant for and has received honoraria from Millennium Pharmaceuticals, Inc. JP Laubach has received research funding from Novartis and Onyx. N Gupta and A-M Hui are employees of Millennium Pharmaceuticals, Inc., a wholly owned subsidiary of Takeda Pharmaceutical Company Ltd. KC Anderson is a consultant for Celgene Corporation, Onyx Pharmaceuticals, Sanofi-Aventis and Gilead, and has equity ownership in Acetylon Pharmaceuticals and Oncopep. JF San Miguel serves on advisory boards for Janssen, Celgene, Millennium Pharmaceuticals, Inc., Novartis and Onyx Pharmaceuticals. S Kumar is a consultant for Merck, Celgene, Millennium Pharmaceuticals, Inc., and Onyx, and receives research funding from Millennium Pharmaceuticals, Inc., Celgene, Novartis, Genzyme, Onyx and Cephalon. 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 82 TC 6 Z9 6 U1 2 U2 5 PU FUTURE MEDICINE LTD PI LONDON PA UNITEC HOUSE, 3RD FLOOR, 2 ALBERT PLACE, FINCHLEY CENTRAL, LONDON, N3 1QB, ENGLAND SN 1479-6694 EI 1744-8301 J9 FUTURE ONCOL JI Future Oncol. PY 2015 VL 11 IS 8 BP 1153 EP 1168 DI 10.2217/fon.15.9 PG 16 WC Oncology SC Oncology GA CF4IS UT WOS:000352512900005 PM 25832873 ER PT J AU Sun, Q Cai, HR Mark, EJ Miao, LY Wu, HY Zhou, Q Chen, J Zhang, W Meng, FQ AF Sun, Qi Cai, Hou-Rong Mark, Eugene J. Miao, Li-Yun Wu, Hong-Yan Zhou, Qiang Chen, Jun Zhang, Wei Meng, Fan-Qing TI Multfocal micronodular pneumocyte hyperplasia in a Chinese man masquerading as miliary tuberculosis SO INTERNATIONAL JOURNAL OF CLINICAL AND EXPERIMENTAL PATHOLOGY LA English DT Article DE Tuberous sclerosis complex; multifocal micronodular pneumocyte hyperplasia ID TUBEROUS SCLEROSIS AB Multifocal Micronodular Pneumocyte Hyperplasia (MMPH) is a rare and histologically, distinctive pulmonary manifestation of tuberous sclerosis complex (TSC) characterized by numerous and extensive proliferative lesions of type II pneumocytes similar to atypical adenomatous hyperplasia (AAH) or non-mucinous adenocarcinoma in situ (AIS). We reported MMPH in a 38-year-old Chinese man with TSC masquerading for 16 months as miliary tuberculosis and discussed the differential diagnosis. C1 [Sun, Qi; Wu, Hong-Yan; Zhou, Qiang; Chen, Jun; Meng, Fan-Qing] Nanjing Univ, Sch Med, Affiliated Hosp 1, Nanjing Drum Tower Hosp,Dept Pathol, Nanjing 210008, Jiangsu, Peoples R China. [Cai, Hou-Rong; Miao, Li-Yun] Nanjing Univ, Sch Med, Affiliated Hosp 1, Nanjing Drum Tower Hosp,Dept Resp Med, Nanjing 210008, Jiangsu, Peoples R China. [Mark, Eugene J.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Mark, Eugene J.] Harvard Univ, Sch Med, Boston, MA USA. [Zhang, Wei] Chinese Acad Med Sci, Inst Dermatol, Nanjing, Jiangsu, Peoples R China. [Zhang, Wei] Peking Union Med Coll, Nanjing, Jiangsu, Peoples R China. RP Meng, FQ (reprint author), Nanjing Univ, Sch Med, Affiliated Hosp 1, Nanjing Drum Tower Hosp,Dept Pathol, 321 Zhongshan Rd, Nanjing 210008, Jiangsu, Peoples R China. EM fqmeng2004@126.com NR 14 TC 0 Z9 1 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 2015 VL 8 IS 2 BP 2165 EP 2170 PG 6 WC Oncology; Pathology SC Oncology; Pathology GA CF2IU UT WOS:000352371800126 PM 25973120 ER PT J AU Zhang, LL Iyer, AK Yang, XQ Kobayashi, E Guo, YQ Mankin, H Hornicek, FJ Amiji, MM Duan, ZF AF Zhang, Linlin Iyer, Arun K. Yang, Xiaoqian Kobayashi, Eisuke Guo, Yuqi Mankin, Henry Hornicek, Francis J. Amiji, Mansoor M. Duan, Zhenfeng TI Polymeric nanoparticle-based delivery of microRNA-199a-3p inhibits proliferation and growth of osteosarcoma cells SO INTERNATIONAL JOURNAL OF NANOMEDICINE LA English DT Article DE bone tumor; dextran nanoparticles; miR-199a-3p; let-7a; RNAi ID DOWN-REGULATION; CANCER-THERAPY; MIRNA; SIRNA; EXPRESSION; RNA; RESISTANCE; MIGRATION; TARGETS; MTOR AB Our prior screening of microRNAs (miRs) identified that miR-199a-3p expression is reduced in osteosarcoma cells, one of the most common types of bone tumor. miR-199a-3p exhibited functions of tumor cell growth inhibition, suggesting the potential application of miR-199a-3p as an anticancer agent. In the study reported here, we designed and developed a lipid-modified dextran-based polymeric nanoparticle platform for encapsulation of miRs, and determined the efficiency and efficacy of delivering miR-199a-3p into osteosarcoma cells. In addition, another potent miR, let-7a, which also displayed tumor suppressive ability, was selected as a candidate miR for evaluation. Fluorescence microscopy studies and real-time polymerase chain reaction results showed that dextran nanoparticles could deliver both miR199a-3p and let-7a into osteosarcoma cell lines (KHOS and U-2OS) successfully. Western blotting analysis and 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assays demonstrated that dextran nanoparticles loaded with miRs could efficiently downregulate the expression of target proteins and effectively inhibit the growth and proliferation of osteosarcoma cells. These results demonstrate that a lipid-modified dextran-based polymeric nanoparticle platform may be an effective nonviral carrier for potential miR-based anticancer therapeutics. C1 [Zhang, Linlin; Yang, Xiaoqian; Kobayashi, Eisuke; Guo, Yuqi; Mankin, Henry; Hornicek, Francis J.; Duan, Zhenfeng] Massachusetts Gen Hosp, Sarcoma Biol Lab, Ctr Sarcoma & Connect Tissue Oncol, Boston, MA 02114 USA. [Zhang, Linlin; Guo, Yuqi] Zhengzhou Univ, Affiliated Hosp 3, Dept Pathol, Zhengzhou 450052, Peoples R China. [Iyer, Arun K.; Amiji, Mansoor M.] Northeastern Univ, Dept Pharmaceut Sci, Sch Pharm, Boston, MA 02115 USA. [Iyer, Arun K.] Wayne State Univ, Dept Pharmaceut Sci, Eugene Applebaum Coll Pharm & Hlth Sci, Detroit, MI USA. RP Duan, ZF (reprint author), Massachusetts Gen Hosp, Sarcoma Biol Lab, Ctr Sarcoma & Connect Tissue Oncol, 100 Blossom St,Jackson 1115, Boston, MA 02114 USA. EM zduan@mgh.harvard.edu FU National Cancer Institute's Alliance for Nanotechnology in Cancer through the Cancer Nanotechnology Platform Partnership [U01-CA15145]; Gattegno and Wechsler funds; Sarcoma Foundation of America FX This study was supported in part by the National Cancer Institute's Alliance for Nanotechnology in Cancer through the Cancer Nanotechnology Platform Partnership (grant number U01-CA15145). Support was also received from the Gattegno and Wechsler funds, and in the form of a grant from the Sarcoma Foundation of America. NR 41 TC 6 Z9 6 U1 0 U2 15 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 2015 VL 10 BP 2913 EP 2924 DI 10.2147/IJN.S79143 PG 12 WC Nanoscience & Nanotechnology; Pharmacology & Pharmacy SC Science & Technology - Other Topics; Pharmacology & Pharmacy GA CG0HQ UT WOS:000352947800001 PM 25931818 ER PT J AU Dougherty, DD Corse, AK Chou, T Duffy, A Arulpragasam, AR Deckersbach, T Jenike, MA Keuthen, NJ AF Dougherty, Darin D. Corse, Andrew K. Chou, Tina Duffy, Amanda Arulpragasam, Amanda R. Deckersbach, Thilo Jenike, Michael A. Keuthen, Nancy J. TI Open-Label Study of Duloxetine for the Treatment of Obsessive-Compulsive Disorder SO INTERNATIONAL JOURNAL OF NEUROPSYCHOPHARMACOLOGY LA English DT Article DE duloxetine; obsessive-compulsive disorder; serotonin-norepinephrine reuptake inhibitors; compulsions; obsessions ID DOUBLE-BLIND; VENLAFAXINE; PLACEBO; FLUVOXAMINE; MULTICENTER; DEPRESSION; SERTRALINE; INVENTORY AB Background: This study sought to investigate the efficacy of duloxetine for the treatment of obsessive-compulsive disorder (DSM-IV). Methods: Twenty individuals were enrolled in a 17-week, open-label trial of duloxetine at Massachusetts General Hospital. Data were collected between March 2007 and September 2012. Study measures assessing obsessive-compulsive disorder symptoms, quality of life, depression, and anxiety were administered at baseline and weeks 1, 5, 9, 13, and 17. The primary outcome measures were the Yale-Brown Obsessive Compulsive Scale and Clinical Global Improvement scale. Results: For the 12 study completers, pre- and posttreatment analyses revealed significant improvements (P < .05) on clinician- and self-rated measures of obsessive-compulsive disorder symptoms and quality of life. Among the 12 completers, more than one-half (n = 7) satisfied full medication response criteria. Intention-to-treat analyses (n = 20) showed similar improvements (P < .05) on primary and secondary study outcome measures. Conclusion: The results of this study suggest that duloxetine may provide a significant reduction in symptoms for patients with obsessive-compulsive disorder. C1 [Dougherty, Darin D.; Corse, Andrew K.; Chou, Tina; Duffy, Amanda; Arulpragasam, Amanda R.; Deckersbach, Thilo] Massachusetts Gen Hosp, Div Neurotherapeut, Dept Psychiat, Charlestown, MA USA. [Dougherty, Darin D.; Jenike, Michael A.; Keuthen, Nancy J.] Massachusetts Gen Hosp, OCD, Boston, MA 02114 USA. [Dougherty, Darin D.; Jenike, Michael A.; Keuthen, Nancy J.] Massachusetts Gen Hosp, Related Disorders Program, Boston, MA 02114 USA. [Chou, Tina] Harvard Univ, Dept Psychol, Cambridge, MA 02138 USA. [Duffy, Amanda] Brown Univ, Dept Neurosci, Providence, RI 02912 USA. RP Dougherty, DD (reprint author), Massachusetts Gen Hosp, Div Neurotherapeut, 149 13th St,Room 2612, Charlestown, MA 02129 USA. EM ddougherty@partners.org FU Eli Lilly and Company FX This study was supported by a research grant from Eli Lilly and Company. NR 21 TC 1 Z9 1 U1 1 U2 4 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1461-1457 EI 1469-5111 J9 INT J NEUROPSYCHOPH JI Int. J. Neuropsychopharmacol. PD JAN PY 2015 VL 18 IS 2 DI 10.1093/ijnp/pyu062 PG 4 WC Clinical Neurology; Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA CF4OS UT WOS:000352530300017 ER PT J AU Wisse, LEM Reijmer, YD ter Telgte, A Kuijf, HJ Leemans, A Luijten, PR Koek, HL Geerlings, MI Biessels, GJ AF Wisse, Laura E. M. Reijmer, Yael D. ter Telgte, Annemieke Kuijf, Hugo J. Leemans, Alexander Luijten, Peter R. Koek, Huiberdina L. Geerlings, Mirjam I. Biessels, Geert Jan CA Utrecht Vasc Cognitive Impairment TI Hippocampal Disconnection in Early Alzheimer's Disease: A 7 Tesla MRI Study SO JOURNAL OF ALZHEIMERS DISEASE LA English DT Article DE Alzheimer's disease; diffusion magnetic resonance imaging; fornix; hippocampus; mild cognitive impairment; subiculum ID MILD COGNITIVE IMPAIRMENT; TENSOR IMAGING TRACTOGRAPHY; ASSOCIATION WORKGROUPS; DIAGNOSTIC GUIDELINES; NATIONAL INSTITUTE; CINGULUM BUNDLE; RHESUS-MONKEY; DIFFUSION MRI; MATTER; VOLUME AB Background: In patients with Alzheimer's disease (AD), atrophy of the entorhinal cortex (ERC) and hippocampal formation may induce degeneration of connecting white matter tracts. Objective: We examined the association of hippocampal subfield and ERC atrophy at 7 tesla MRI with fornix and parahippocampal cingulum (PHC) microstructure in patients with early AD. Methods: Twenty-five patients with amnestic mild cognitive impairment (aMCI) (n = 15) or early AD (n = 10) and 17 controls underwent 3 tesla diffusion MRI to obtain fractional anisotropy (FA) of the fornix and PHC and 7 tesla MRI to obtain ERC and hippocampal subfield volumes. Linear regression analyses were performed, adjusted for age, gender, and intracranial volume. Results: Fornix FA was significantly lower and subiculum, cornu ammonis (CA) 1, and dentate gyrus & CA4 volume were significantly smaller in patients with MCI or AD as compared to controls. In patients with MCI or AD, fornix FA was positively associated with subiculum volume (beta = 0.53, 95% CI 0.10; 0.96), but not with ERC/other subfield volumes. PHC FA was not associated with ERC/subfield volumes. Conclusion: These findings indicate that in early AD subiculum atrophy is associated with lower FA of the fornix, which primarily consists of axons originating in the subiculum. This suggests that degeneration of subicular cell bodies and their axons are related processes in early AD. C1 [Wisse, Laura E. M.; Reijmer, Yael D.; ter Telgte, Annemieke; Biessels, Geert Jan] Univ Med Ctr Utrecht, Dept Neurol, Brain Ctr Rudolf Magnus, NL-3508 GA Utrecht, Netherlands. [Wisse, Laura E. M.; Geerlings, Mirjam I.] Univ Med Ctr Utrecht, Julius Ctr Hlth Sci & Primary Care, NL-3508 GA Utrecht, Netherlands. [Reijmer, Yael D.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, J Philip Kistler Stroke Ctr, Boston, MA USA. [Kuijf, Hugo J.; Leemans, Alexander] Univ Med Ctr Utrecht, Image Sci Inst, NL-3508 GA Utrecht, Netherlands. [Luijten, Peter R.] Univ Med Ctr Utrecht, Dept Radiol, NL-3508 GA Utrecht, Netherlands. [Koek, Huiberdina L.] Univ Med Ctr Utrecht, Dept Geriatr, NL-3508 GA Utrecht, Netherlands. RP Biessels, GJ (reprint author), Univ Med Ctr Utrecht, Dept Neurol, G03-232,POB 85500, NL-3508 GA Utrecht, Netherlands. EM g.j.biessels@umcutrecht.nl RI Leemans, Alexander/A-1784-2011; OI de Bresser, Jeroen/0000-0003-0759-8407 FU VIDI grant from ZonMw [91711384]; Netherlands Organisation for Health Research and Development; Netherlands Heart Foundation [2010T073]; VIDI grant from the Netherlands Organization for Scientific Research (NWO) [917-66-311, 639.072.411] FX The research of GJB was supported by a VIDI grant 91711384 from ZonMw, The Netherlands Organisation for Health Research and Development and grant 2010T073 from the Netherlands Heart Foundation. The research of MIG was supported by a VIDI grant from the Netherlands Organization for Scientific Research (NWO: project no. 917-66-311). The research of AL is supported by a VIDI grant 639.072.411 from the Netherlands Organization for Scientific Research (NWO). NR 55 TC 10 Z9 10 U1 1 U2 9 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 2015 VL 45 IS 4 BP 1247 EP 1256 DI 10.3233/JAD-142994 PG 10 WC Neurosciences SC Neurosciences & Neurology GA CF8NQ UT WOS:000352819200023 PM 25697703 ER PT B AU Bilezikian, JP Marcus, R Levine, MA Marcocci, C Potts, JT Silverberg, SJ AF Bilezikian, John P. Marcus, Robert Levine, Michael A. Marcocci, Claudio Potts, John T. Silverberg, Shonni J. BE Bilezikian, JP TI THE PARATHYROIDS BASIC AND CLINICAL CONCEPTS Preface to the Third Edition SO PARATHYROIDS: BASIC AND CLINICAL CONCEPTS, 3RD EDITION LA English DT Editorial Material; Book Chapter C1 [Bilezikian, John P.] Columbia Univ, Coll Phys & Surg, Dept Med, Metab Bone Dis Unit,Div Endocrinol, New York, NY 10027 USA. [Marcus, Robert] Stanford Univ, Dept Med, Stanford, CA 94305 USA. [Levine, Michael A.] Childrens Hosp Philadelphia, Div Endocrinol & Diabet, Philadelphia, PA 19104 USA. [Levine, Michael A.] Univ Penn, Perelman Sch Med, Dept Pediat, Philadelphia, PA 19104 USA. [Marcocci, Claudio] Univ Pisa, Dept Clin & Expt Med, Univ Hosp Pisa, Pisa, Italy. [Potts, John T.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Silverberg, Shonni J.] Columbia Univ, Coll Phys & Surg, Dept Med, New York, NY USA. RP Bilezikian, JP (reprint author), Columbia Univ, Coll Phys & Surg, Dept Med, Metab Bone Dis Unit,Div Endocrinol, New York, NY 10027 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS LTD-ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL ROAD, LONDON NW1 7DX, ENGLAND BN 978-0-12-397790-8; 978-0-12-397166-1 PY 2015 BP XIX EP XX PG 2 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA BC2OR UT WOS:000351154500001 ER PT B AU Mannstadt, M Kronenberg, HM AF Mannstadt, Michael Kronenberg, Henry M. BE Bilezikian, JP TI Parathyroid Hormone Gene Structure, Evolution, and Regulation SO PARATHYROIDS: BASIC AND CLINICAL CONCEPTS, 3RD EDITION LA English DT Article; Book Chapter ID FAMILIAL ISOLATED HYPOPARATHYROIDISM; MESSENGER-RIBONUCLEIC-ACID; PROTEIN-COUPLED-RECEPTORS; PREPROPARATHYROID HORMONE; NUCLEOTIDE-SEQUENCE; RNA STABILITY; VITAMIN-D; IN-VITRO; TRANSCRIPTIONAL REGULATION; 3'-UNTRANSLATED REGION C1 [Mannstadt, Michael; Kronenberg, Henry M.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Endocrine Unit, Boston, MA 02163 USA. RP Mannstadt, M (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Endocrine Unit, Boston, MA 02163 USA. NR 72 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS LTD-ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL ROAD, LONDON NW1 7DX, ENGLAND BN 978-0-12-397790-8; 978-0-12-397166-1 PY 2015 BP 37 EP 44 DI 10.1016/B978-0-12-397166-1.00002-3 PG 8 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA BC2OR UT WOS:000351154500006 ER PT B AU Gardella, TJ AF Gardella, Thomas J. BE Bilezikian, JP TI Interactions of PTH with Receptors and Signaling SO PARATHYROIDS: BASIC AND CLINICAL CONCEPTS, 3RD EDITION LA English DT Article; Book Chapter ID PARATHYROID-HORMONE-RECEPTOR; PROTEIN-COUPLED-RECEPTOR; (PTH)/PTH-RELATED PEPTIDE RECEPTOR; CORTICOTROPIN-RELEASING-FACTOR; PHOTOAFFINITY CROSS-LINKING; N-TERMINAL REGION; JANSENS METAPHYSEAL CHONDRODYSPLASIA; EXTRACELLULAR LOOP REGIONS; AMINO ACID SEQUENCE; CLASS-B GPCRS C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Endocrine Unit, Boston, MA 02163 USA. RP Gardella, TJ (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Endocrine Unit, Boston, MA 02163 USA. NR 141 TC 3 Z9 3 U1 0 U2 0 PU ACADEMIC PRESS LTD-ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL ROAD, LONDON NW1 7DX, ENGLAND BN 978-0-12-397790-8; 978-0-12-397166-1 PY 2015 BP 65 EP 80 DI 10.1016/B978-0-12-397166-1.00004-7 PG 16 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA BC2OR UT WOS:000351154500008 ER PT B AU Bilezikian, JP Brandi, ML Eastell, R Silverberg, SJ Udelsman, R Marcocci, C Potts, JT AF Bilezikian, John P. Brandi, Maria Luisa Eastell, Richard Silverberg, Shonni J. Udelsman, Robert Marcocci, Claudio Potts, John T., Jr. BE Bilezikian, JP TI Guidelines for the Management of Asymptomatic Primary Hyperparathyroidism SO PARATHYROIDS: BASIC AND CLINICAL CONCEPTS, 3RD EDITION LA English DT Article; Book Chapter ID MILD PRIMARY HYPERPARATHYROIDISM; NORMOCALCEMIC PRIMARY HYPERPARATHYROIDISM; VITAMIN-D DEFICIENCY; POSTMENOPAUSAL WOMEN; PARATHYROID-HORMONE; NEUROPSYCHOLOGICAL SYMPTOMS; IMMUNORADIOMETRIC ASSAY; CLINICAL UTILITY; ORAL ALENDRONATE; BONE C1 [Bilezikian, John P.; Silverberg, Shonni J.] Columbia Univ, Coll Phys & Surg, New York, NY 10027 USA. [Brandi, Maria Luisa] Univ Florence, Dept Surg & Translat Med, Bone Metab Dis Unit, Florence, Italy. [Eastell, Richard] Univ Sheffield, Sheffield, S Yorkshire, England. [Udelsman, Robert] Yale Univ, Sch Med, Dept Surg, Sect Endocrine Surg, New Haven, CT 06510 USA. [Marcocci, Claudio] Univ Pisa, Univ Hosp Pisa, Dept Clin & Expt Med, Pisa, Italy. [Potts, John T., Jr.] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Bilezikian, JP (reprint author), Columbia Univ, Coll Phys & Surg, New York, NY 10027 USA. NR 60 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS LTD-ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL ROAD, LONDON NW1 7DX, ENGLAND BN 978-0-12-397790-8; 978-0-12-397166-1 PY 2015 BP 489 EP 497 DI 10.1016/B978-0-12-397166-1.00034-5 PG 9 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA BC2OR UT WOS:000351154500037 ER PT B AU Silve, C Juppner, H AF Silve, Caroline Jueppner, Harald BE Bilezikian, JP TI Genetic Disorders Caused by Mutations in the PTH/PTHrP Receptor and Downstream Effector Molecules SO PARATHYROIDS: BASIC AND CLINICAL CONCEPTS, 3RD EDITION LA English DT Article; Book Chapter ID (PTH)/PTH-RELATED PEPTIDE RECEPTOR; HORMONE-RELATED PEPTIDE; JANSENS METAPHYSEAL CHONDRODYSPLASIA; FAMILIAL ISOLATED HYPOPARATHYROIDISM; BLOMSTRAND LETHAL OSTEOCHONDRODYSPLASIA; DEPENDENT PROTEIN-KINASE; AUTOSOMAL-DOMINANT HYPOPARATHYROIDISM; ALBRIGHTS HEREDITARY OSTEODYSTROPHY; EXTRACELLULAR CA2+-SENSING RECEPTOR; ADVANCED SKELETAL MATURATION C1 [Silve, Caroline] Hop Bicetre, INSERM, U986, Paris, France. [Silve, Caroline] Hop Bicetre, Ctr Reference Malad Rares Calcium & Phosphore, Paris, France. [Silve, Caroline] Hop Bichat Claude Bernard, Lab Biochim Hormonale & Genet, F-75877 Paris 18, France. [Jueppner, Harald] Massachusetts Gen Hosp, Dept Med, Endocrine Unit, Boston, MA 02114 USA. [Jueppner, Harald] Harvard Univ, Sch Med, Boston, MA USA. [Jueppner, Harald] Massachusetts Gen Hosp, MassGen Hosp Children, Pediat Nephrol, Boston, MA 02114 USA. RP Silve, C (reprint author), Hop Bicetre, INSERM, U986, Paris, France. NR 156 TC 1 Z9 1 U1 0 U2 0 PU ACADEMIC PRESS LTD-ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL ROAD, LONDON NW1 7DX, ENGLAND BN 978-0-12-397790-8; 978-0-12-397166-1 PY 2015 BP 587 EP 605 DI 10.1016/B978-0-12-397166-1.00040-0 PG 19 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA BC2OR UT WOS:000351154500043 ER PT B AU Mannstadt, M Mitchell, DM AF Mannstadt, Michael Mitchell, Deborah M. BE Bilezikian, JP TI Clinical Manifestations of Hypoparathyroidism SO PARATHYROIDS: BASIC AND CLINICAL CONCEPTS, 3RD EDITION LA English DT Article; Book Chapter ID BASAL GANGLIA CALCIFICATION; CALCIUM-SENSING RECEPTOR; HORMONE 2 RECEPTOR; BONE GLA-PROTEIN; IDIOPATHIC HYPOPARATHYROIDISM; PARATHYROID-HORMONE; HYPOCALCEMIC MYOPATHY; VITAMIN-D; NEUROLOGICAL MANIFESTATIONS; SURGICAL HYPOPARATHYROIDISM C1 [Mannstadt, Michael; Mitchell, Deborah M.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Endocrine Unit, Boston, MA 02138 USA. [Mitchell, Deborah M.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Pediat Endocrine Unit, Boston, MA USA. RP Mannstadt, M (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Endocrine Unit, Boston, MA 02138 USA. OI Mitchell, Deborah/0000-0003-0364-9107 NR 128 TC 2 Z9 2 U1 0 U2 0 PU ACADEMIC PRESS LTD-ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL ROAD, LONDON NW1 7DX, ENGLAND BN 978-0-12-397790-8; 978-0-12-397166-1 PY 2015 BP 761 EP 770 DI 10.1016/B978-0-12-397166-1.00053-9 PG 10 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA BC2OR UT WOS:000351154500056 ER PT B AU Leder, BZ AF Leder, Benjamin Z. BE Bilezikian, JP TI Combination Osteoporosis Therapy with Parathyroid Hormone SO PARATHYROIDS: BASIC AND CLINICAL CONCEPTS, 3RD EDITION LA English DT Article; Book Chapter ID BONE-MINERAL DENSITY; RANDOMIZED CONTROLLED-TRIAL; FRACTURE RISK REDUCTION; POSTMENOPAUSAL WOMEN; OVARIECTOMIZED RATS; TERIPARATIDE TREATMENT; REPLACEMENT THERAPY; VERTEBRAL FRACTURE; ZOLEDRONIC ACID; OSTEOCLAST DIFFERENTIATION C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Med,Endocrine Unit, Boston, MA 02138 USA. RP Leder, BZ (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Med,Endocrine Unit, Boston, MA 02138 USA. NR 75 TC 0 Z9 0 U1 0 U2 1 PU ACADEMIC PRESS LTD-ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL ROAD, LONDON NW1 7DX, ENGLAND BN 978-0-12-397790-8; 978-0-12-397166-1 PY 2015 BP 853 EP 863 DI 10.1016/B978-0-12-397166-1.00061-8 PG 11 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA BC2OR UT WOS:000351154500064 ER PT J AU Choi, JW Kim, P Kim, JK Kim, YR Fukumura, D Yun, SH AF Choi, Jin Woo Kim, Pilhan Kim, Jun Ki Kim, Yi Rang Fukumura, Dai Yun, Seok Hyun TI Longitudinal Tracing of Spontaneous Regression and Anti-angiogenic Response of Individual Microadenomas during Colon Tumorigenesis SO THERANOSTICS LA English DT Article DE Angiogenesis; tumorigenesis; colon tumor ID HEREDITARY COLORECTAL-CANCER; GROWTH-FACTOR RECEPTOR-2; ABERRANT CRYPT FOCI; IN-VIVO; MOUSE MODEL; SURVIVAL; THERAPY; ENDOMICROSCOPY; CARCINOGENESIS; CARCINOMATOSIS AB Angiogenesis is essential for the progression of cancer, but its involvement in the initial phase of colon tumorigenesis is not well understood. Using intravital endomicroscopy, we visualized the natural history of early pre-tumorous lesions and adenomas in the colon of conditional Apc-knockout and Apc/Kras double mutant mouse models. Early lesions emerged about 4 weeks after the onset of somatic mutations, accompanying vascular dilation when the size of lesions reached about 200 mu m, but most lesions regressed spontaneously and cleared within 10 weeks after their emergence. Anti-angiogenic treatments with vascular endothelial growth factor receptor (VEGFR) antagonists reduced the size of the early lesions and the number of polyps. We found surprisingly that anti-angiogenic treatments delayed the natural clearance of transient lesions by up to several weeks in both genetic models. The results represent the previously unexpected role of early angiogenesis on the spontaneous regression of early-stage colon tumors. C1 [Choi, Jin Woo; Yun, Seok Hyun] Harvard Univ, Sch Med, Boston, MA 02114 USA. [Choi, Jin Woo; Yun, Seok Hyun] Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA. [Choi, Jin Woo] Wonkwang Univ, Dept Pharmacol, Iksan 570749, Chonbuk, South Korea. [Choi, Jin Woo] Wonkwang Univ, Dent Res Inst, Sch Dent, Grad Sch,Dept Smart Life Care Convergence, Iksan 570749, Chonbuk, South Korea. [Choi, Jin Woo] Seoul Natl Univ, Adv Inst Convergence Technol, Suwon 443270, Gyeonggi Do, South Korea. [Kim, Pilhan; Kim, Yi Rang; Yun, Seok Hyun] Korea Adv Inst Sci & Technol, Grad Sch Nanosci & Technol, Taejon 305701, South Korea. [Kim, Jun Ki] Korea Adv Inst Sci & Technol, Grad Sch Med Sci & Engn, Taejon 305701, South Korea. [Kim, Yi Rang] Asan Med Ctr, Asan Inst Life Sci, Biomed Engn Res Ctr, Seoul 138736, South Korea. [Kim, Yi Rang] Univ Ulsan, Coll Med, Seoul 138736, South Korea. [Kim, Yi Rang] Univ Ulsan, Coll Med, Asan Med Ctr, Dept Oncol, Seoul 138736, South Korea. [Fukumura, Dai] Massachusetts Gen Hosp, Dept Radiat Oncol, Edwin L Steele Lab Tumor Biol, Boston, MA 02114 USA. RP Choi, JW (reprint author), Harvard Univ, Sch Med, 40 Blossom St, Boston, MA 02114 USA. EM jinwoochoi@wku.ac.kr; syun@hms.harvard.edu RI Kim, Pilhan/C-1836-2011 OI Kim, Pilhan/0000-0001-8388-1840 FU National Institutes of Health [U54CA143837, P01CA080124, P01HL120839, P41-EB015903]; National Research Foundation of Korea [2008-0062484, 2011K000864, 2012M3A6A4054261, 2013M3A6A4072626, 2014R1A1A1002431] FX This work was supported by grants from the National Institutes of Health (U54CA143837, P01CA080124, P01HL120839, P41-EB015903) and the National Research Foundation of Korea (2008-0062484, 2011K000864, 2012M3A6A4054261, 2013M3A6A4072626 and 2014R1A1A1002431) NR 31 TC 0 Z9 0 U1 0 U2 0 PU IVYSPRING INT PUBL PI LAKE HAVEN PA PO BOX 4546, LAKE HAVEN, NSW 2263, AUSTRALIA SN 1838-7640 J9 THERANOSTICS JI Theranostics PY 2015 VL 5 IS 7 BP 724 EP 732 DI 10.7150/thno.10734 PG 9 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA CG1VX UT WOS:000353064500006 PM 25897337 ER PT J AU Mathew, AR Cook, JW Japuntich, SJ Leventhal, AM AF Mathew, Amanda R. Cook, Jessica W. Japuntich, Sandra J. Leventhal, Adam M. TI Post-Traumatic Stress Disorder Symptoms, Underlying Affective Vulnerabilities, and Smoking for Affect Regulation SO AMERICAN JOURNAL ON ADDICTIONS LA English DT Article AB Background and ObjectivesOpioid dependent patients are hospitalized frequently. We aimed to determine if initiation of buprenorphine treatment during hospitalization facilitates entry into treatment following discharge. MethodsRetrospective case series (n=47). ResultsTwenty-two (46.8%) patients successfully initiated buprenorphine treatment within 2 months of discharge. Those patients obtaining a referral to a specific program were more successful in continuing treatment, but this difference did not reach statistical significance (59.1% vs 39.1%, p=0.18). Discussion and ConclusionsHospitalization may be an important opportunity to engage opioid dependent patients to initiate buprenorphine treatment. Scientific SignificanceThis study provides provisional support for utilizing buprenorphine for hospitalized patients. (Am J Addict 2015;24:10-14) C1 [Mathew, Amanda R.] Med Univ S Carolina, Dept Neurosci, Charleston, SC 29425 USA. [Mathew, Amanda R.] Med Univ S Carolina, Dept Psychiat & Behav Sci, Charleston, SC 29425 USA. [Cook, Jessica W.] Univ Wisconsin, Sch Med & Publ Hlth, Madison, WI USA. [Japuntich, Sandra J.] VA Boston Healthcare Syst, Natl Ctr PTSD, Boston, MA USA. [Leventhal, Adam M.] Univ So Calif, Keck Sch Med, Dept Prevent Med, Los Angeles, CA 90033 USA. [Leventhal, Adam M.] Univ So Calif, Keck Sch Med, Dept Psychol, Los Angeles, CA 90033 USA. RP Mathew, AR (reprint author), Med Univ S Carolina, Dept Neurosci, 67 President St,Room 565 North,MSC 861, Charleston, SC 29425 USA. EM mathea@musc.edu FU National Institute on Drug Abuse, Bethesda, MD [R01-DA026831, K08-DA025041]; National Institute on Drug Abuse [T32 DA007288]; United States Department of Veterans Affairs Clinical Sciences Research and Development Service [1IK2CX000918-01A1] FX This work was supported by grants R01-DA026831 and K08-DA025041 to Dr. Leventhal from the National Institute on Drug Abuse, Bethesda, MD. Dr Mathew is supported by National Institute on Drug Abuse grant T32 DA007288. This work was supported in part by Career Development Award (Japuntich) # 1IK2CX000918-01A1 from the United States Department of Veterans Affairs Clinical Sciences Research and Development Service. The contents do not represent the views of the Department of Veterans Affairs or the United States Government. NR 0 TC 2 Z9 2 U1 1 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1055-0496 EI 1521-0391 J9 AM J ADDICTION JI Am. J. Addict. PD JAN PY 2015 VL 24 IS 1 BP 39 EP 46 DI 10.1111/ajad.12170 PG 8 WC Substance Abuse SC Substance Abuse GA CE7NZ UT WOS:000352029900007 PM 25823634 ER PT J AU Batki, SL Schmeling, B Lasher, B Pennington, D Herbst, E Plaut, Z Striebel, J Vrana, S Straznickas, J AF Batki, Steven L. Schmeling, Brandi Lasher, Brooke Pennington, David Herbst, Ellen Plaut, Zachary Striebel, Joan Vrana, Sally Straznickas, John TI Combined Naltrexone and Topiramate Treatment of Veterans with Alcohol Use Disorder: A Case Series SO AMERICAN JOURNAL ON ADDICTIONS LA English DT Meeting Abstract C1 Univ Calif San Francisco, San Francisco, CA 94143 USA. San Francisco VA Med Ctr, San Francisco, CA USA. NR 0 TC 0 Z9 0 U1 2 U2 2 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1055-0496 EI 1521-0391 J9 AM J ADDICTION JI Am. J. Addict. PD JAN PY 2015 VL 24 IS 1 BP 63 EP 64 PG 2 WC Substance Abuse SC Substance Abuse GA CE7NZ UT WOS:000352029900027 ER PT J AU Wilens, T Zulauf, C Martelon, M AF Wilens, Timothy Zulauf, Courtney Martelon, Marykate TI Characteristics of Young Adults Who Misuse Stimulant Medications SO AMERICAN JOURNAL ON ADDICTIONS LA English DT Meeting Abstract C1 [Wilens, Timothy; Zulauf, Courtney; Martelon, Marykate] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Wilens, Timothy] Harvard Univ, Sch Med, Cambridge, MA 02138 USA. FU NIH [K24 DA016264, R01 DA12945] FX NIH grants K24 DA016264 and R01 DA12945. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1055-0496 EI 1521-0391 J9 AM J ADDICTION JI Am. J. Addict. PD JAN PY 2015 VL 24 IS 1 BP 68 EP 69 PG 2 WC Substance Abuse SC Substance Abuse GA CE7NZ UT WOS:000352029900038 ER PT J AU Wilens, TE Zulauf, C Ryland, D Carrellas, N Catalina-Wellington, I AF Wilens, Timothy E. Zulauf, Courtney Ryland, Denece Carrellas, Nicholas Catalina-Wellington, Isela TI Prescription Medication Misuse among Opioid Abusers SO AMERICAN JOURNAL ON ADDICTIONS LA English DT Meeting Abstract C1 [Wilens, Timothy E.; Zulauf, Courtney; Carrellas, Nicholas] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Wilens, Timothy E.] Harvard Univ, Sch Med, Cambridge, MA 02138 USA. [Ryland, Denece; Catalina-Wellington, Isela] Andrew House Detox Ctr, North Quincy, MA USA. FU NIDA FX Dr. Zulauf, Ms. Ryland, Mr. Carrellas, and Ms. Catalina-Wellington have nothing to disclose. Dr. Wilens has received grant support from NIDA and has served as a consultant for Ethymics/Neurovance, NIDA, Theravance, the U.S. National Football League, and TRIS. Dr. Wilens provided clinical services to U.S. Minor/Major League Baseball, and Bay Cove Human Services. Dr. Wilens has published a book with Guilford Press. Dr. Wilens currently serves as the Director of the Center for Addiction Medicine at Massachusetts General Hospital. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1055-0496 EI 1521-0391 J9 AM J ADDICTION JI Am. J. Addict. PD JAN PY 2015 VL 24 IS 1 BP 68 EP 68 PG 1 WC Substance Abuse SC Substance Abuse GA CE7NZ UT WOS:000352029900037 ER PT J AU Wilens, T Zulauf, C Martelon, M AF Wilens, Timothy Zulauf, Courtney Martelon, Marykate TI Substance and Nicotine Use in Young Adults with Bipolar Disorder: Initial Findings of a Controlled Longitudinal Study SO AMERICAN JOURNAL ON ADDICTIONS LA English DT Meeting Abstract C1 [Wilens, Timothy; Zulauf, Courtney; Martelon, Marykate] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Wilens, Timothy] Harvard Univ, Sch Med, Cambridge, MA 02138 USA. FU [R01DA12945] FX R01DA12945 NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1055-0496 EI 1521-0391 J9 AM J ADDICTION JI Am. J. Addict. PD JAN PY 2015 VL 24 IS 1 BP 69 EP 69 PG 1 WC Substance Abuse SC Substance Abuse GA CE7NZ UT WOS:000352029900039 ER PT J AU Jha, MK Abele, M Brown, J AF Jha, Manish K. Abele, Misoo Brown, Julie TI Motivational Interviewing Education of General Psychiatry Residents SO AMERICAN JOURNAL ON ADDICTIONS LA English DT Meeting Abstract C1 [Jha, Manish K.] North Texas State Hosp, BMT Program, Vernon, TX USA. [Abele, Misoo] Portland VA Med Ctr, Portland, OR USA. [Brown, Julie] VA North Texas Med Ctr, Dallas, TX USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1055-0496 EI 1521-0391 J9 AM J ADDICTION JI Am. J. Addict. PD JAN PY 2015 VL 24 IS 1 BP 73 EP 73 PG 1 WC Substance Abuse SC Substance Abuse GA CE7NZ UT WOS:000352029900046 ER PT J AU Lache, D Ascher, M Wassef, T Dhopesh, V AF Lache, Daniel Ascher, Michael Wassef, Tamer Dhopesh, Vasant TI Prognosis of Cerebellar Ataxia in Alcohol Dependent Patients: A Case Report SO AMERICAN JOURNAL ON ADDICTIONS LA English DT Meeting Abstract C1 Univ Penn, Philadelphia, PA 19104 USA. Philadelphia VA Med Ctr, Philadelphia, PA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1055-0496 EI 1521-0391 J9 AM J ADDICTION JI Am. J. Addict. PD JAN PY 2015 VL 24 IS 1 BP 75 EP 76 PG 2 WC Substance Abuse SC Substance Abuse GA CE7NZ UT WOS:000352029900051 ER PT J AU Santa Ana, E LaRowe, S Lamb, K Tompkins, M Hartwell, K AF Santa Ana, Elizabeth LaRowe, Steve Lamb, Kayla Tompkins, Michelle Hartwell, Karen TI Impact of Group Motivational Interviewing on Enhancing Treatment Engagement for Homeless Veterans with Nicotine Dependence and other Substance Use Disorders: A Pilot Investigation SO AMERICAN JOURNAL ON ADDICTIONS LA English DT Meeting Abstract C1 Ralph H Johnson VA Med Ctr, Charleston, SC USA. Med Univ S Carolina, Charleston, SC USA. FU American Cancer Society, Institutional Research Grant [IRG-97-219-14] FX American Cancer Society, Institutional Research Grant #IRG-97-219-14. NR 0 TC 0 Z9 0 U1 3 U2 3 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1055-0496 EI 1521-0391 J9 AM J ADDICTION JI Am. J. Addict. PD JAN PY 2015 VL 24 IS 1 BP 81 EP 82 PG 2 WC Substance Abuse SC Substance Abuse GA CE7NZ UT WOS:000352029900063 ER PT S AU Fang, A Wilhelm, S AF Fang, Angela Wilhelm, Sabine BE Cannon, TD Widiger, T TI Clinical Features, Cognitive Biases, and Treatment of Body Dysmorphic Disorder SO ANNUAL REVIEW OF CLINICAL PSYCHOLOGY, VOL 11 SE Annual Review of Clinical Psychology LA English DT Article; Book Chapter DE body image; cognitive bias; cognitive-behavioral model; cognitive-behavioral therapy ID OBSESSIVE-COMPULSIVE DISORDER; RANDOMIZED CONTROLLED-TRIAL; SOCIAL ANXIETY DISORDER; EMOTION RECOGNITION DEFICITS; POPULATION-BASED SURVEY; DOMAIN CRITERIA RDOC; BEHAVIORAL THERAPY; D-CYCLOSERINE; RESPONSE PREVENTION; IMAGINED UGLINESS AB In the past two decades, research advances have enhanced our understanding of the clinical features, cognitive biases, and treatment of body dysmorphic disorder (BDD). In this review, we critically examine the current state of the evidence on the proposed cognitive and emotional processing mechanisms of BDD. We describe how major findings in these areas made unique contributions to the development of an empirically informed cognitive-behavioral model of BDD, which in turn facilitated the translation of research to treatment strategies. Finally, we outline important areas of future research. C1 [Fang, Angela; Wilhelm, Sabine] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Psychiat, Boston, MA 02114 USA. RP Fang, A (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Psychiat, Boston, MA 02114 USA. EM swilhelm@mgh.harvard.edu NR 120 TC 7 Z9 7 U1 5 U2 23 PU ANNUAL REVIEWS PI PALO ALTO PA 4139 EL CAMINO WAY, PO BOX 10139, PALO ALTO, CA 94303-0897 USA SN 1548-5943 BN 978-0-8243-3911-1 J9 ANNU REV CLIN PSYCHO JI Annu. Rev. Clin. Psychol. PY 2015 VL 11 BP 187 EP 212 DI 10.1146/annurev-clinpsy-032814-112849 PG 26 WC Psychology, Clinical; Psychology SC Psychology GA BC3WH UT WOS:000352014000009 PM 25581240 ER PT J AU Castellanos-Rizaldos, E Richardson, K Lin, R Wu, G Makrigiorgos, MG AF Castellanos-Rizaldos, Elena Richardson, Katherine Lin, Rui Wu, Grant Makrigiorgos, Mike G. TI Single-Tube, Highly Parallel Mutation Enrichment in Cancer Gene Panels by Use of Temperature-Tolerant COLD-PCR SO CLINICAL CHEMISTRY LA English DT Article ID CIRCULATING TUMOR DNA; KRAS MUTATIONS; RARE MUTATIONS; MOLECULAR DIAGNOSTICS; ACQUIRED-RESISTANCE; COLORECTAL-CANCER; SENSITIVITY; IDENTIFICATION; AMPLIFICATION; PRODUCTS AB BACKGROUND: Multiplexed detection of low-level mutations presents a technical challenge for many technologies, including cancer gene panels used for targeted-resequencing. Analysis of mutations below approximately 2%-5% abundance in tumors with heterogeneity, samples with stromal contamination, or biofluids is problematic owing to increased noise from sequencing errors. Technologies that reduce noise via deep sequencing unavoidably reduce throughput and increase cost. Here we provide proof of principle that coamplification at lower denaturation temperature (COLD)-PCR technology enables multiplex low-level mutation detection in cancer gene panels while retaining throughput. METHODS: We have developed a multiplex temperature-tolerant COLD-PCR (fast-TT-COLD-PCR) approach that uses cancer gene panels developed for massively parallel sequencing. After multiplex preamplification from genomic DNA, we attach tails to all amplicons and perform fast-TT-COLD-PCR. This approach gradually increases denaturation temperatures in a step-wise fashion, such that all possible denaturation temperatures are encompassed. By introducing modified nucleotides, fast-COLD-PCR is adapted to enrich for melting temperature (T-m)-increasing mutations over all amplicons, in a single tube. Therefore, in separate reactions, both T-m-decreasing and T-m-increasing mutations are enriched. RESULTS: Using custom-made and commercial gene panels containing 8, 50, 190, or 16 000 amplicons, we demonstrate that fast-TT-COLD-PCR enriches mutations on all examined targets simultaneously. Incorporation of deoxyinosine triphosphate (dITP)/2,6-diaminopurine triphosphate (dDTP) in place of deoxyguanosine triphosphate (dGTP)/deoxyadenosine triphosphate (dATP) enables enrichment of T-m-increasing mutations. Serial dilution experiments demonstrate a limit of detection of approximately 0.01%-0.1% mutation abundance by use of Ion-Torrent and 0.1%-0.3% by use of Sanger sequencing. CONCLUSIONS: Fast-TT-COLD-PCR improves the limit of detection of cancer gene panels by enabling mutation enrichment in multiplex, single-tube reactions. This novel adaptation of COLD-PCR converts subclonal mutations to clonal, thereby facilitating detection and subsequent mutation sequencing. (C) 2014 American Association for Clinical Chemistry C1 [Castellanos-Rizaldos, Elena; Makrigiorgos, Mike G.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Radiat Oncol,Div DNA Repair & Genome Stabil, Boston, MA 02115 USA. [Makrigiorgos, Mike G.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Radiat Oncol,Div Med Phys & Biophys, Boston, MA 02115 USA. [Richardson, Katherine; Lin, Rui; Wu, Grant] Transgenomic Inc, Omaha, NE USA. RP Makrigiorgos, MG (reprint author), Brigham & Womens Hosp, Dana Farber Brigham & Womens Canc Ctr, Radiat Therapy, Level L2,75 Francis St, Boston, MA 02115 USA. EM mmakrigiorgos@lroc.harvard.edu FU National Cancer Institute [1 R41 CA180389-01, 1 R21 CA175542-01A1] FX K. Richardson, National Cancer Institute grant 1 R41 CA180389-01; G.M. Makrigiorgos, National Cancer Institute grants 1 R41 CA180389-01 and 1 R21 CA175542-01A1. NR 38 TC 1 Z9 2 U1 8 U2 19 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 2015 VL 61 IS 1 BP 267 EP 277 DI 10.1373/clinchem.2014.228361 PG 11 WC Medical Laboratory Technology SC Medical Laboratory Technology GA CE8ZS UT WOS:000352133500037 PM 25297854 ER PT J AU Yeo, S An, KS Hong, YM Choi, YG Rosen, B Kim, SH Lim, S AF Yeo, Sujung An, Keon Sang Hong, Yeon-Mi Choi, Yeong-Gon Rosen, Bruce Kim, Sung-Hoon Lim, Sabina TI Neuroprotective changes in degeneration-related gene expression in the substantia nigra following acupuncture in an MPTP mouse model of Parkinsonism: Microarray analysis SO GENETICS AND MOLECULAR BIOLOGY LA English DT Article DE Parkinson's disease; gene array; differentially expressed genes; neurodegeneration; acupoints ID V-LIKE ANTIGEN; TRYPTOPHAN-HYDROXYLASE; GABA TRANSPORTER; DISEASE; SEROTONIN; PROLINE; NEURONS; CELLS; MICE; INHIBITOR AB Parkinson's disease (PD) is a neurodegenerative disorder characterized by the death of dopamine-generating cells in the substantia nigra (SN). Acupuncture stimulation results in an enhanced survival of dopaminergic neurons in the SN in Parkinsonism animal models. The present study investigated changes in gene expression profiles measured using whole transcript array in the SN region related to the inhibitory effects of acupuncture in a chronic 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) Parkinsonism model. In this model, acupuncture stimulation at GB34 and LR3 attenuated the decrease in tyrosine hydroxylase in the SN region; stimulation at non-acupoints did not suppress this decrease. Gene array analysis revealed that 22 (10 annotated genes: Cdh1, Itih2, Mpzl2, Rdh9, Serping1, Slc6a13, Slc6a20a, Slc6a4, Tph2, and Ucma) probes that were up-regulated in MPTP animals relative to controls were exclusively down-regulated by acupuncture stimulation. In addition, 17 (two annotated genes: 4921530L21Rik and Gm13931) probes that were down-regulated in MPTP animals compared to controls were exclusively up-regulated by acupuncture stimulation. These findings indicate that the 39 probes (12 annotated genes) affected by MPTP and acupuncture may be responsible for the inhibitory effects of acupuncture on degeneration-related gene expression in the SN following damage induced by MPTP intoxication. C1 [Yeo, Sujung; Hong, Yeon-Mi; Choi, Yeong-Gon; Lim, Sabina] Kyung Hee Univ, East West Med Res Inst, Res Grp Pain & Neurosci, WHO Collaborating Ctr Tradit Med, Seoul 130701, South Korea. [Yeo, Sujung; An, Keon Sang; Hong, Yeon-Mi; Choi, Yeong-Gon; Rosen, Bruce; Kim, Sung-Hoon; Lim, Sabina] Kyung Hee Univ, Coll Korean Med, Dept Basic Korean Med Sci, Seoul 130701, South Korea. [Rosen, Bruce] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Radiol,Athinoula A Martinos Ctr Biomed Imagi, Boston, MA 02115 USA. RP Lim, S (reprint author), Kyung Hee Univ, East West Med Res Inst, Res Grp Pain & Neurosci, WHO Collaborating Ctr Tradit Med, Seoul 130701, South Korea. EM lims@khu.ac.kr FU National Research Foundation of Korea - Korean Government [MEST] [2007-0054931, NRF-2014R1A1A1004100] FX This work was supported by a National Research Foundation of Korea grant funded by the Korean Government [MEST] (No. 2007-0054931, NRF-2014R1A1A1004100). The funders had no role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 68 TC 2 Z9 2 U1 1 U2 6 PU SOC BRASIL GENETICA PI RIBEIRAO PRET PA RUA CAP ADELMIO NORBET DA SILVA, 736, ALTO DA BOA VISTA, 14025-670 RIBEIRAO PRET, BRAZIL SN 1415-4757 EI 1678-4685 J9 GENET MOL BIOL JI Genet. Mol. Biol. PY 2015 VL 38 IS 1 BP 115 EP 127 DI 10.1590/S1415-475738120140137 PG 13 WC Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA CF3KY UT WOS:000352448600017 PM 25983633 ER PT J AU Alameddine, Y Ellenbogen, JM Bianchi, MT AF Alameddine, Yvonne Ellenbogen, Jeffrey M. Bianchi, Matt T. TI Sleep-Wake Time Perception Varies by Direct or Indirect Query SO JOURNAL OF CLINICAL SLEEP MEDICINE LA English DT Article DE time perception; inconsistency; subjective; self-report ID STATE MISPERCEPTION; DISORDER PATIENTS; CHRONIC INSOMNIA; MEDICAL-CENTER; DURATION; APNEA AB Study Objectives: The diagnosis of insomnia rests on self-report of difficulty initiating or maintaining sleep. However, subjective reports may be unreliable, and possibly may vary by the method of inquiry. We investigated this possibility by comparing within-individual response to direct versus indirect time queries after overnight polysomnography. Methods: We obtained self-reported sleep-wake times via morning questionnaires in 879 consecutive adult diagnostic polysomnograms. Responses were compared within subjects (direct versus indirect query) and across groups defined by apnea-hypopnea index and by self-reported insomnia symptoms in presleep questionnaires. Direct queries required a time duration response, while indirect queries required clock times from which we calculated time durations. Results: Direct and indirect queries of sleep latency were the same in only 41% of cases, and total sleep time queries matched in only 5.4%. For both latency and total sleep, the most common discrepancy involved the indirect value being larger than the direct response. The discrepancy between direct and indirect queries was not related to objective sleep metrics. The degree of discrepancy was not related to the presence of insomnia symptoms, although patients reporting insomnia symptoms showed underestimation of total sleep duration by direct response. Conclusions: Self-reported sleep latency and total sleep time are often internally inconsistent when comparing direct and indirect survey queries of each measure. These discrepancies represent substantive challenges to effective clinical practice, particularly when diagnosis and management depends on self-reported sleep patterns, as with insomnia. Although self-reported sleep-wake times remains fundamental to clinical practice, objective measures provide clinically relevant adjunctive information. C1 [Alameddine, Yvonne; Bianchi, Matt T.] Massachusetts Gen Hosp, Dept Neurol, Sleep Div, Boston, MA 02114 USA. [Ellenbogen, Jeffrey M.] Johns Hopkins Univ, Dept Neurol, Baltimore, MD 21218 USA. [Bianchi, Matt T.] Harvard Univ, Sch Med, Div Sleep Med, Boston, MA USA. RP Bianchi, MT (reprint author), Massachusetts Gen Hosp, Dept Neurol, 55 Fruit St,Wing 739, Boston, MA 02114 USA. EM mtbianchi@partners.org FU Department of Neurology, Massachusetts General Hospital; Young Clinician Award, Center for Integration of Medicine and Innovative Technology; Harvard Catalyst KL2 Medical Research Investigator Fellowship; Center for Integration of Medicine and Innovative Technology FX Support for this study was provided by the Department of Neurology, Massachusetts General Hospital; Young Clinician Award, Center for Integration of Medicine and Innovative Technology; Harvard Catalyst KL2 Medical Research Investigator Fellowship. Dr. Bianchi has consulting agreement with Sunovion, is on the advisory board of Foramis and is a co-inventor on a pending patent for a sleep monitoring device. Dr. Bianchi receives funding from the Department of Neurology, Massachusetts General Hospital, and a Young Clinician Award from the Center for Integration of Medicine and Innovative Technology. The other authors have indicated no financial conflicts of interest. NR 25 TC 2 Z9 2 U1 1 U2 4 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 2015 VL 11 IS 2 BP 123 EP U151 DI 10.5664/jcsm.4456 PG 9 WC Clinical Neurology SC Neurosciences & Neurology GA CE9CI UT WOS:000352140800007 PM 25406269 ER PT J AU Bianchi, MT AF Bianchi, Matt T. TI Evidence that Home Apnea Testing does not Follow AASM Practice Guidelines or Bayes' Theorem SO JOURNAL OF CLINICAL SLEEP MEDICINE LA English DT Letter C1 [Bianchi, Matt T.] Massachusetts Gen Hosp, Dept Neurol, Sleep Div, Boston, MA 02114 USA. RP Bianchi, MT (reprint author), Massachusetts Gen Hosp, Wang Neurol 7, 55 Fruit St, Boston, MA 02114 USA. EM mtbianchi@partners.org NR 3 TC 3 Z9 3 U1 0 U2 0 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 2015 VL 11 IS 2 BP 189 EP 189 DI 10.5664/jcsm.4476 PG 1 WC Clinical Neurology SC Neurosciences & Neurology GA CE9CI UT WOS:000352140800017 PM 25580609 ER PT J AU Wu, XJ Wu, W Pan, W Wu, LM Liu, KD Zhang, HL AF Wu, Xiujuan Wu, Wei Pan, Wei Wu, Limin Liu, Kangding Zhang, Hong-Liang TI Acute Necrotizing Encephalopathy: An Underrecognized Clinicoradiologic Disorder SO MEDIATORS OF INFLAMMATION LA English DT Review ID CEREBROSPINAL-FLUID; THALAMIC LESIONS; IMAGING FINDINGS; COMBINED THERAPY; VIRUS-INFECTION; INFLUENZA; CHILDHOOD; CHILDREN; HYPOTHERMIA; DIPHTHERIA AB Acute necrotizing encephalopathy (ANE) is a rare but distinctive type of acute encephalopathy with global distribution. Occurrence of ANE is usually preceded by a virus-associated febrile illness and ensued by rapid deterioration. However, the causal relationship between viral infections and ANE and the exact pathogenesis of ANE remain unclear; both environmental and host factors might be involved. Most cases of ANE are sporadic and nonrecurrent, namely, isolated or sporadic ANE; however, few cases are recurrent and with familial episodes. The recurrent and familial forms of ANE were found to be incompletely autosomal-dominant. Further the missense mutations in the gene encoding the nuclear pore protein Ran Binding Protein 2 (RANBP2) were identified. Although the clinical course and the prognosis of ANE are diverse, the hallmark of neuroradiologic manifestation of ANE is multifocal symmetric brain lesions which are demonstrated by computed tomography (CT) or magnetic resonance imaging (MRI). The treatment of ANE is still under investigation. We summarize the up-to-date knowledge on ANE, with emphasis on prompt diagnosis and better treatment of this rare but fatal disease. C1 [Wu, Xiujuan; Wu, Limin; Liu, Kangding; Zhang, Hong-Liang] Jilin Univ, Neurosci Ctr, Dept Neurol, Hosp 1, Changchun 130021, Peoples R China. [Wu, Wei] Jilin Univ, Dept Neurovasc Surg, Hosp 1, Changchun 130021, Peoples R China. [Pan, Wei] Jilin Univ, Sch Publ Hlth, Changchun 130021, Peoples R China. [Wu, Limin] Harvard Univ, Sch Med, Neuroprotect Res Lab, Massachusetts Gen Hosp, Charlestown, MA 02129 USA. RP Zhang, HL (reprint author), Jilin Univ, Neurosci Ctr, Dept Neurol, Hosp 1, Xinmin St 71, Changchun 130021, Peoples R China. EM hongliang.zhang@ki.se FU Young Scholars Program of Norman Bethune Health Science Center of Jilin University [2013205035]; Young Scholars Program of the First Hospital of Jilin University [JDYY42013003]; Scientific Research Foundation for the Returned Overseas Chinese Scholars [3C113BK73428]; State Education Ministry; National Natural Science Foundation of China [81241147] FX The work was supported by grants from Young Scholars Program of Norman Bethune Health Science Center of Jilin University (no. 2013205035), Young Scholars Program of the First Hospital of Jilin University (no. JDYY42013003), the Scientific Research Foundation for the Returned Overseas Chinese Scholars (3C113BK73428), State Education Ministry, and the National Natural Science Foundation of China (no. 81241147). NR 73 TC 2 Z9 2 U1 1 U2 2 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 2015 AR 792578 DI 10.1155/2015/792578 PG 10 WC Cell Biology; Immunology SC Cell Biology; Immunology GA CF3KG UT WOS:000352446800001 ER PT J AU Liu, G Sprenger, C Wu, PJ Sun, SH Uo, T Haugk, K Epilepsia, KS Plymate, S AF Liu, Gang Sprenger, Cynthia Wu, Pin-Jou Sun, Shihua Uo, Takuma Haugk, Kathleen Epilepsia, Kathryn Soriano Plymate, Stephen TI MED1 mediates androgen receptor splice variant induced gene expression in the absence of ligand SO ONCOTARGET LA English DT Article ID RESISTANT PROSTATE-CANCER; ACTIVATED PROTEIN-KINASE; CELL-PROLIFERATION; COREGULATORY ROLE; BREAST-CANCER; T-ANTIGEN; CASTRATION; OVEREXPRESSION; PROGRESSION; GROWTH AB The appearance of constitutively active androgen receptor splice variants (AR-Vs) has been proposed as one of the causes of castration-resistant prostate cancer (CRPC). However, the underlying mechanism of AR-Vs in CRPC transcriptional regulation has not been defined. A distinct transcriptome enriched with cell cycle genes, e.g. UBE2C, has been associated with AR-Vs, which indicates the possibility of an altered transcriptional mechanism when compared to full-length wild-type AR (AR(fl)). Importantly, a recent study reported the critical role of p-MED1 in enhancing UBE2C expression through a locus looping pattern, which only occurs in CRPC but not in androgen-dependent prostate cancer (ADPC). To investigate the potential correlation between AR-V and MED1, in the present study we performed protein co-immunoprecipitation, chromatin immunoprecipitation, and cell proliferation assays and found that MED1 is necessary for AR(v567es) induced UBE2C up-regulation and subsequent prostate cancer cell growth. Furthermore, p-MED1 is bound to AR(v567es) independent of full-length AR; p-MED1 has higher recruitment to UBE2C promoter and enhancer regions in the presence of AR(v567es). Our data indicate that p-MED1 serves as a key mediator in AR(v567es) induced gene expression and suggests a mechanism by which AR-Vs promote the development and progression of CRPC. C1 [Liu, Gang; Sprenger, Cynthia; Wu, Pin-Jou; Sun, Shihua; Uo, Takuma; Epilepsia, Kathryn Soriano; Plymate, Stephen] Univ Washington, Dept Med, Seattle, WA 98104 USA. [Sprenger, Cynthia; Haugk, Kathleen; Plymate, Stephen] Vet Affairs Puget Sound Hlth Care Syst, Seattle, WA 98104 USA. RP Plymate, S (reprint author), Univ Washington, Dept Med, Seattle, WA 98104 USA. EM splymate@u.washington.edu FU National Cancer Institute Pacific Northwest Prostate Cancer Specialized Program of Research Excellence (SPORE) [2 P50 CA 097186-07]; US Army Medical Research and Materiel Command Prostate Cancer Research Programs [W81XWH-11-1-0551, W81XWH-13-2-0093]; Department of Veterans Affairs; [PO1 CA85859]; [P01 CA163227] FX We would like to thank Dr. Qianben Wang for providing the UBE2C luciferase reporter constructs and p-MED1 antibody. This work was supported by the National Cancer Institute Pacific Northwest Prostate Cancer Specialized Program of Research Excellence (SPORE; 2 P50 CA 097186-07 Project 5), PO1 CA85859, P01 CA163227, US Army Medical Research and Materiel Command Prostate Cancer Research Programs (W81XWH-11-1-0551 and W81XWH-13-2-0093), and Department of Veterans Affairs, to S.R.P. NR 55 TC 8 Z9 9 U1 0 U2 1 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 1 PY 2015 VL 6 IS 1 BP 288 EP 304 PG 17 WC Oncology; Cell Biology SC Oncology; Cell Biology GA CE8BE UT WOS:000352065200024 PM 25481872 ER PT J AU Budczies, J von Winterfeld, M Klauschen, F Bockmayr, M Lennerz, JK Denkert, C Wolf, T Warth, A Dietel, M Anagnostopoulos, I Weichert, W Wittschieber, D Stenzinger, A AF Budczies, Jan von Winterfeld, Moritz Klauschen, Frederick Bockmayr, Michael Lennerz, Jochen K. Denkert, Carsten Wolf, Thomas Warth, Arne Dietel, Manfred Anagnostopoulos, Ioannis Weichert, Wilko Wittschieber, Daniel Stenzinger, Albrecht TI The landscape of metastatic progression patterns across major human cancers SO ONCOTARGET LA English DT Article DE autopsy; metastasis; systemic disease; carcinoma; solid tumor; cancer; survival ID BREAST-CANCER; CONSECUTIVE PATIENTS; TUMOR-CELLS; AUTOPSY; ADENOCARCINOMA; CARCINOMA; LUNG; EVOLUTION; NETWORKS; MELANOMA AB The majority of patients with solid malignancies die from metastatic burden. However, our current understanding of the mechanisms and resulting patterns of dissemination is limited. Here, we analyzed patterns of metastatic progression across 16 major cancer types in a cohort of 1008 patients with metastatic cancer autopsied between 2000 and 2013 to assess cancer specific progression patterns of disease and related risk predictions. The frequency and location of metastases were evaluated in and across 1) 16 major cancers, 2) smoking- and non-smoking-related cancers and 3) adeno- and squamous cell carcinoma. Associations between primary and secondary sites were analyzed by the fractional and the relative risk methods. We detected significantly different cancer specific patterns of metastatic progression with specific relative risk profiles for secondary site involvement. Histology and smoking etiology influenced these patterns. Backward analysis showed that metastatic patterns help to predict unknown primary sites. Solid malignancies maintain a unique and recurrent organ tropism to specific secondary sites which does not appear to be strongly influenced by advances in cancer medicine as shown by comparison with previous data sets. The delineated landscape of metastatic progression patterns is a comprehensive data resource to both clinical and basic scientists which aids fostering new hypotheses for cancer research and cancer therapies. C1 [Budczies, Jan; von Winterfeld, Moritz; Klauschen, Frederick; Bockmayr, Michael; Denkert, Carsten; Dietel, Manfred; Anagnostopoulos, Ioannis] Charite, Inst Pathol, Berlin, Germany. [Budczies, Jan] German Canc Res Ctr, Heidelberg, Germany. [Lennerz, Jochen K.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Pathol, Boston, MA USA. [Wolf, Thomas; Warth, Arne; Weichert, Wilko; Stenzinger, Albrecht] Univ Heidelberg Hosp, Inst Pathol, Heidelberg, Germany. [Wittschieber, Daniel] Univ Hosp Munster, Inst Legal Med, Munster, Germany. [Budczies, Jan; Denkert, Carsten; Wolf, Thomas; Weichert, Wilko] German Consortium Translat Canc Res DKTK, Heidelberg, Germany. [Weichert, Wilko] Natl Ctr Tumor Dis NCT, Heidelberg, Germany. RP Stenzinger, A (reprint author), Univ Heidelberg Hosp, Inst Pathol, Heidelberg, Germany. EM jan.budczies@charite.de; albrecht.stenzinger@med.uni-heidelberg.de RI Klauschen, Frederick/C-5637-2015 NR 50 TC 14 Z9 14 U1 0 U2 1 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 1 PY 2015 VL 6 IS 1 BP 570 EP 583 PG 14 WC Oncology; Cell Biology SC Oncology; Cell Biology GA CE8BE UT WOS:000352065200045 PM 25402435 ER PT J AU Almario, CV Chey, W Kaung, A Whitman, C Fuller, G Reid, M Nguyen, K Bolus, R Dennis, B Encarnacion, R Martinez, B Talley, J Modi, R Agarwal, N Lee, A Kubomoto, S Sharma, G Bolus, S Chang, L Spiegel, BMR AF Almario, Christopher V. Chey, William Kaung, Aung Whitman, Cynthia Fuller, Garth Reid, Mark Nguyen, Ken Bolus, Roger Dennis, Buddy Encarnacion, Rey Martinez, Bibiana Talley, Jennifer Modi, Rushaba Agarwal, Nikhil Lee, Aaron Kubomoto, Scott Sharma, Gobind Bolus, Sally Chang, Lin Spiegel, Brennan M. R. TI Computer-Generated Vs. Physician-Documented History of Present Illness (HPI): Results of a Blinded Comparison SO AMERICAN JOURNAL OF GASTROENTEROLOGY LA English DT Article ID PATIENT-REPORTED OUTCOMES; GASTROINTESTINAL SYMPTOM SCALES; RECORDS AB OBJECTIVES: Healthcare delivery now mandates shorter visits with higher documentation requirements, undermining the patient-provider interaction. To improve clinic visit efficiency, we developed a patient-provider portal that systematically collects patient symptoms using a computer algorithm called Automated Evaluation of Gastrointestinal Symptoms (AEGIS). AEGIS also automatically "translates" the patient report into a full narrative history of present illness (HPI). We aimed to compare the quality of computer-generated vs. physician-documented HPIs. METHODS: We performed a cross-sectional study with a paired sample design among individuals visiting outpatient adult gastrointestinal (GI) clinics for evaluation of active GI symptoms. Participants first underwent usual care and then subsequently completed AEGIS. Each individual thereby had both a physician-documented and a computer-generated HPI. Forty-eight blinded physicians assessed HPI quality across six domains using 5-point scales: (i) overall impression, (ii) thoroughness, (iii) usefulness, (iv) organization, (v) succinctness, and (vi) comprehensibility. We compared HPI scores within patient using a repeated measures model. RESULTS: Seventy-five patients had both computer-generated and physician-documented HPIs. The mean overall impression score for computer-generated HPIs was higher than physician HPIs (3.68 vs. 2.80; P < 0.001), even after adjusting for physician and visit type, location, mode of transcription, and demographics. Computer-generated HPIs were also judged more complete (3.70 vs. 2.73; P < 0.001), more useful (3.82 vs. 3.04; P < 0.001), better organized (3.66 vs. 2.80; P < 0.001), more succinct (3.55 vs. 3.17; P < 0.001), and more comprehensible (3.66 vs. 2.97; P < 0.001). CONCLUSIONS: Computer-generated HPIs were of higher overall quality, better organized, and more succinct, comprehensible, complete, and useful compared with HPIs written by physicians during usual care in GI clinics. C1 [Almario, Christopher V.; Kaung, Aung; Whitman, Cynthia; Fuller, Garth; Nguyen, Ken; Martinez, Bibiana; Talley, Jennifer; Modi, Rushaba; Agarwal, Nikhil; Lee, Aaron; Kubomoto, Scott; Sharma, Gobind; Spiegel, Brennan M. R.] Cedars Sinai Med Ctr, Div Gastroenterol, Los Angeles, CA 90048 USA. [Almario, Christopher V.; Kaung, Aung; Reid, Mark; Martinez, Bibiana; Talley, Jennifer; Modi, Rushaba; Agarwal, Nikhil; Spiegel, Brennan M. R.] VA Greater Angeles Healthcare Syst, Div Gastroenterol, Los Angeles, CA USA. [Almario, Christopher V.; Modi, Rushaba; Agarwal, Nikhil; Chang, Lin] Univ Calif Los Angeles, Div Digest Dis, Los Angeles, CA USA. [Almario, Christopher V.; Whitman, Cynthia; Fuller, Garth; Reid, Mark; Nguyen, Ken; Bolus, Roger; Martinez, Bibiana; Talley, Jennifer; Bolus, Sally; Spiegel, Brennan M. R.] Cedars Sinai Ctr Outcomes Res & Educ, Los Angeles, CA 90048 USA. [Chey, William] Univ Michigan, Div Gastroenterol, Ann Arbor, MI 48109 USA. [Dennis, Buddy; Encarnacion, Rey] Univ Calif Los Angeles, Comp Technol Res Lab, Los Angeles, CA USA. RP Spiegel, BMR (reprint author), Cedars Sinai Ctr Outcomes Res & Educ, Cedars Sinai Hlth Syst, Hlth Serv Res, Pacific Theaters Bldg,116 North Robertson Blvd, Los Angeles, CA 90048 USA. EM brennan.spiegel@cshs.org FU NIH/NIAMS [U01 AR057936A]; National Institutes of Health through the NIH Roadmap for Medical Research Grant [AR052177]; National Institutes of Health [NIH T32DK07180-39]; Ironwood Pharmaceuticals FX This study was supported by NIH/NIAMS U01 AR057936A, the National Institutes of Health through the NIH Roadmap for Medical Research Grant (AR052177). Dr Almario was supported by a National Institutes of Health T32 training grant (NIH T32DK07180-39) during his gastroenterology and health services research training at UCLA. Support for the My GI Health portal used in this study was obtained from Ironwood Pharmaceuticals. NR 23 TC 5 Z9 5 U1 1 U2 3 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0002-9270 EI 1572-0241 J9 AM J GASTROENTEROL JI Am. J. Gastroenterol. PD JAN PY 2015 VL 110 IS 1 BP 170 EP 179 DI 10.1038/ajg.2014.356 PG 10 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA CE5ZJ UT WOS:000351914700017 PM 25461620 ER PT J AU Anaya, HD Butler, JN Knapp, H Chan, K Conners, EE Rumanes, SF AF Anaya, Henry D. Butler, Jaimi N. Knapp, Herschel Chan, Kee Conners, Erin E. Rumanes, Sophia F. TI Implementing an HIV Rapid Testing-Linkage-to-Care Project Among Homeless Individuals in Los Angeles County: A Collaborative Effort Between Federal, County, and City Government SO AMERICAN JOURNAL OF PUBLIC HEALTH LA English DT Article ID NEW-YORK-CITY; INJECTION-DRUG USERS; TUBERCULOSIS INFECTION; EMERGENCY-DEPARTMENT; SAN-FRANCISCO; UNITED-STATES; SEROPREVALENCE; ADULTS; RISK; PREVALENCE AB Objectives. We developed and implemented an HIV rapid testing-linkage-to-care initiative between federal and local government. Methods. We used mixed methodology; HIV testing data were collected on-site, and qualitative data were collected via telephone. We used postintervention stakeholder and staff interviews to evaluate barriers and facilitators to this initiative. Results. We tested 817 individuals. We identified and confirmed 7 preliminary HIV positive individuals (0.86% seropositivity), 5 of whom were linked to care. Mean testing cost was $ 48.95 per client; cost per positive result was $ 5714. Conclusions. This initiative can be used as a template for other health departments and research teams focusing on homelessness and mitigation of the HIV/ AIDS epidemic. C1 [Anaya, Henry D.; Butler, Jaimi N.; Knapp, Herschel; Conners, Erin E.] VA Greater Los Angeles Healthcare Syst, VA Greater Los Angeles Hlth Serv Res & Dev IISR&D, Vet Affairs VA Qual Enhancement Res Initiat HIV &, Los Angeles, CA USA. [Anaya, Henry D.; Butler, Jaimi N.; Knapp, Herschel; Conners, Erin E.] VA Greater Los Angeles Healthcare Syst, VA Greater Los Angeles Hlth Serv Res & Dev IISR&D, Ctr Study Healthcare Provider Behav, Los Angeles, CA USA. [Chan, Kee] Boston Univ, Dept Hlth Sci, Coll Hlth & Rehabil Sci, Sargent Coll, Boston, MA 02215 USA. [Rumanes, Sophia F.] Cty Los Angeles Dept Publ Hlth, Div HIV & STD Programs, Los Angeles, CA USA. RP Anaya, HD (reprint author), 11301 Wilshire Blvd 111G, Los Angeles, CA 90073 USA. EM hanaya@ucla.edu FU Gilead Sciences; David Geffen School of Medicine at the University of California, Los Angeles; University of California FX This research was funded by a Gilead Sciences grant awarded to H. D. Anaya and supported by the David Geffen School of Medicine at the University of California, Los Angeles.; The views and opinions expressed in this article are those of the authors and do not necessarily represent the views of Gilead Sciences or the University of California. Gilead Sciences and the University of California supported this study but had no input in the design or reporting or in the decision to submit this article for publication. NR 36 TC 2 Z9 2 U1 1 U2 2 PU AMER PUBLIC HEALTH ASSOC INC PI WASHINGTON PA 800 I STREET, NW, WASHINGTON, DC 20001-3710 USA SN 0090-0036 EI 1541-0048 J9 AM J PUBLIC HEALTH JI Am. J. Public Health PD JAN PY 2015 VL 105 IS 1 BP 85 EP 90 DI 10.2105/AJPH.2014.302213 PG 6 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA CE6BG UT WOS:000351920100031 PM 25393202 ER PT J AU Wang, XL Zhou, XH AF Wang, Xueli Zhou, Xiao-Hua TI Some Results About Standardization for a Non Confounder in Estimators of (log) Relative Risk SO COMMUNICATIONS IN STATISTICS-THEORY AND METHODS LA English DT Article DE Confounding; Non confounder; Precision; Relative risk; Standardization ID COLLAPSIBILITY; HOMOGENEITY AB Confounding is very fundamental to the design and analysis of studies of causal effects. A variable is not a confounder if it is not a risk factor to disease or if it has the same distribution in the exposed and unexposed population. Whether or not to adjust for a non confounder to improve the precision of estimation has been argued by many authors. This article shows that if C is a non confounder, the pooled and standardized (log) relative risk estimators are asymptotic normal distributions with the mean being the true (log) relative risk, and that the asymptotic variance of the pooled (log) relative risk estimator is less than that of the stratified estimator. C1 [Wang, Xueli] Beijing Univ Posts & Telecommun, Sch Sci, Beijing 100876, Peoples R China. [Wang, Xueli; Zhou, Xiao-Hua] VA Puget Sound Hlth Care Syst, HSR&D, Seattle, WA USA. [Wang, Xueli; Zhou, Xiao-Hua] Univ Washington, Dept Biostat, Washington, DC USA. [Zhou, Xiao-Hua] Peking Univ, Beijing Int Ctr Math Res, Beijing 100871, Peoples R China. RP Wang, XL (reprint author), Beijing Univ Posts & Telecommun, Sch Sci, Beijing 100876, Peoples R China. EM wangxl@bupt.edu.cn FU National Natural Science Foundation of China [NSFC 10801019, 11471053, 11401037]; Fundamental Research Funds for the Central Universities [BUPT 2012RC0708, 2014RC0905] FX This research was supported by the National Natural Science Foundation of China (NSFC 10801019, 11471053, and 11401037) and the Fundamental Research Funds for the Central Universities (BUPT 2012RC0708 and 2014RC0905). NR 21 TC 0 Z9 0 U1 1 U2 2 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 530 WALNUT STREET, STE 850, PHILADELPHIA, PA 19106 USA SN 0361-0926 EI 1532-415X J9 COMMUN STAT-THEOR M JI Commun. Stat.-Theory Methods PY 2015 VL 44 IS 7 BP 1497 EP 1507 DI 10.1080/03610926.2013.769599 PG 11 WC Statistics & Probability SC Mathematics GA CE7GF UT WOS:000352005700013 ER PT J AU Gao, Y Shen, JK Milane, L Hornicek, FJ Amiji, MM Duan, ZF AF Gao, Yan Shen, Jacson K. Milane, Lara Hornicek, Francis J. Amiji, Mansoor M. Duan, Zhenfeng TI Targeted Cancer Therapy; Nanotechnology Approaches for Overcoming Drug Resistance SO CURRENT MEDICINAL CHEMISTRY LA English DT Article DE Drug resistance; nanotechnology; targeted cancer therapy ID TYROSINE KINASE INHIBITORS; TRANS-RETINOIC ACID; HUMAN BREAST-CANCER; CELL LUNG-CANCER; GASTROINTESTINAL STROMAL TUMORS; MANGANESE SUPEROXIDE-DISMUTASE; HISTONE DEACETYLASE INHIBITORS; CHRONIC MYELOGENOUS LEUKEMIA; CHRONIC LYMPHOCYTIC-LEUKEMIA; ACUTE PROMYELOCYTIC LEUKEMIA AB Recent advances in cancer molecular biology have resulted in parallel and unprecedented progress in the development of targeted cancer therapy. Targeted therapy can provide higher efficacy and lower toxicity than conventional chemotherapy for cancer. However, like traditional chemotherapy, molecularly targeted cancer therapy also faces the challenge of drug resistance. Multiple mechanisms are responsible for chemotherapy resistance in tumors, including over-expression of efflux transporters, somatic alterations of drug targets, deregulation of apoptosis, and numerous pharmacokinetic issues. Nanotechnology based approaches are proving to be efficacious in overcoming drug resistance in cancer. Combination of targeted therapies with nanotechnology approaches is a promising strategy to overcome targeted therapy drug resistance in cancer treatment. This review discusses the mechanisms of targeted drug resistance in cancer and discusses nanotechnology approaches to circumvent this resistance. C1 [Gao, Yan; Shen, Jacson K.; Hornicek, Francis J.; Duan, Zhenfeng] Massachusetts Gen Hosp, Ctr Sarcoma & Connect Tissue Oncol, Sarcoma Biol Lab, Boston, MA 02114 USA. [Gao, Yan] Zhengzhou Univ, Affiliated Hosp 3, Dept Clin Lab, Zhengzhou 450052, Henan, Peoples R China. [Milane, Lara; Amiji, Mansoor M.] Northeastern Univ, Bouve Coll Hlth Sci, Sch Pharm, Dept Pharmaceut Sci, Boston, MA 02115 USA. RP Duan, ZF (reprint author), Massachusetts Gen Hosp, 55 Fruit St,Jackson Bldg Room 1115, Boston, MA 02114 USA. EM zduan@mgh.harvard.edu FU National Cancer Institute's Alliance for Nanotechnology in Cancer through the Platform Partnership grant [U01- CA151452]; China Scholarship Council; Excellent Doctorial Dissertations Grant of Zhengzhou University FX Our work on the development of nanotechnology-based therapeutics is partially supported by the National Cancer Institute's Alliance for Nanotechnology in Cancer through the Platform Partnership grant U01- CA151452. Dr. Gao is supported by scholarship from the China Scholarship Council and Excellent Doctorial Dissertations Grant of Zhengzhou University. NR 137 TC 5 Z9 5 U1 3 U2 16 PU BENTHAM SCIENCE PUBL LTD PI SHARJAH PA EXECUTIVE STE Y-2, PO BOX 7917, SAIF ZONE, 1200 BR SHARJAH, U ARAB EMIRATES SN 0929-8673 EI 1875-533X J9 CURR MED CHEM JI Curr. Med. Chem. PY 2015 VL 22 IS 11 BP 1335 EP 1347 PG 13 WC Biochemistry & Molecular Biology; Chemistry, Medicinal; Pharmacology & Pharmacy SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy GA CE5HY UT WOS:000351863400004 PM 25666804 ER PT J AU Rinaldi, CA Burri, H Thibault, B Curnis, A Raos, A Gras, D Sperzel, J Singh, JP Biffi, M Bordachar, P Leclercq, C AF Rinaldi, Christopher Aldo Burri, Haran Thibault, Bernard Curnis, Antonio Raos, Archana Gras, Daniel Sperzel, Johannes Singh, Jagmeet P. Biffi, Mauro Bordachar, Pierre Leclercq, Christophe TI A review of multisite pacing to achieve cardiac resynchronization therapy SO EUROPACE LA English DT Review DE Cardiac resynchronization therapy; Dyssynchrony; Heart failure; Pacemaker; Multisite pacing ID LEFT-VENTRICULAR LEAD; PHRENIC-NERVE STIMULATION; ACUTE HEMODYNAMIC-RESPONSE; CHRONIC HEART-FAILURE; SINGLE-CENTER EXPERIENCE; BUNDLE-BRANCH BLOCK; QUADRIPOLAR LEAD; BIVENTRICULAR STIMULATION; ACTIVATION PATTERN; RANDOMIZED-TRIAL AB Non-response to cardiac resynchronization therapy remains a significant problem in up to 30% of patients. Multisite stimulation has emerged as a way of potentially overcoming non-response. This may be achieved by the use of multiple leads placed within the coronary sinus and its tributaries (dual-vein pacing) or more recently by the use of multipolar (quadripolar) left ventricular pacing leads which can deliver pacing stimuli at multiple sites within the same vein. This review covers the role of multisite pacing including the interaction with the underlying pathophysiology, the current and planned studies, and the potential pitfalls of this technology. C1 [Rinaldi, Christopher Aldo] Guys & St Thomas Hosp, Dept Cardiac, London SE1 7EH, England. [Burri, Haran] Univ Hosp Geneva, Serv Cardiol, CH-1205 Geneva, Switzerland. [Thibault, Bernard] Montreal Heart Inst, Dept Med, Montreal, PQ H1T 1C8, Canada. [Thibault, Bernard] Montreal Heart Inst, Res Ctr, Montreal, PQ H1T 1C8, Canada. [Thibault, Bernard] Univ Montreal, Montreal, PQ, Canada. [Curnis, Antonio] Univ Brescia, Sect Cardiovasc Dis, Dept Expt & Appl Med, Brescia, Italy. [Raos, Archana] Liverpool Heart & Chest Hosp, Liverpool L14 3PE, Merseyside, England. [Gras, Daniel] Nouvelles Clin Nantaises, Nantes, France. [Sperzel, Johannes] Kerckhoff Klin GmbH, Dept Cardiol & Electrophysiol, D-61231 Bad Nauheim, Germany. [Singh, Jagmeet P.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Heart, Boston, MA 02114 USA. [Biffi, Mauro] Univ Bologna, Inst Cardiol, I-40138 Bologna, Italy. [Bordachar, Pierre] Univ Bordeaux 2, Hop Cardiol Haut Leveque, Serv Rythmol, F-33604 Bordeaux, France. [Leclercq, Christophe] CHU Pontchaillou 2, Dept Cardiol & Malad Vasc, F-35033 Rennes 09, France. RP Rinaldi, CA (reprint author), Guys & St Thomas Hosp, Dept Cardiac, London SE1 7EH, England. EM c.rinaldi@virgin.net FU St Jude Medical FX This review was prepared by a writing group which was invited on behalf of the European Heart Rhythm Association Education Committee. This document was supported by a grant from St Jude Medical; however, the content has not been influenced in any way by its sponsor. NR 85 TC 15 Z9 16 U1 0 U2 8 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 1 PY 2015 VL 17 IS 1 BP 7 EP 17 DI 10.1093/europace/euu197 PG 11 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA CE1WP UT WOS:000351603900004 PM 25214507 ER PT J AU Scirica, BM Belardinelli, L Chaitman, BR Waks, JW Volo, S Karwatowska-Prokopczuk, E Murphy, SA Cheng, ML Braunwald, E Morrow, DA AF Scirica, Benjamin M. Belardinelli, Luiz Chaitman, Bernard R. Waks, Jonathan W. Volo, Samuel Karwatowska-Prokopczuk, Ewa Murphy, Sabina A. Cheng, Mei L. Braunwald, Eugene Morrow, David A. TI Effect of ranolazine on at a fibrilla on in patients with non-ST eleva on acute coronary syndromes: observations from the MERLIN-TIMI 36 trial SO EUROPACE LA English DT Article DE Atrial fibrillation; Ranolazine; Anti-arrhythmic therapy; Acute coronary syndromes ID ONSET ATRIAL-FIBRILLATION; LATE SODIUM CURRENT; MYOCARDIAL-INFARCTION; SEGMENT-ELEVATION; ANTIANGINAL AGENT; AMIODARONE; THROMBOLYSIS; MANAGEMENT; CONVERSION; OUTCOMES AB Aims To determine the effect of ranolazine, an anti-ischaemic agent with anti-arrhythmic properties, on the overall burden of atrial fibrillation (AF) in acute coronary syndromes (ACS) and determine whether ranolazine reduces the long-term incidence of clinical AF after ACS. Methods and results MERLIN-TIMI 36 randomized patients with non-ST elevation ACS to ranotazine or placebo. Atrial fibrillation episodes detected on continuous electrocardiogram (cECG) monitoring were reviewed in 6351 patients (97% of trial). Atrial fibrillation burden was categorized according to the time in AF: clinically insignificant AF (<0.01% of time), paroxysmal AF (>0.01-98%), or predominantly persistent AF (>98%). Clinical AF events were identified through adverse event reporting for a median 1-year follow-up. Overall, patients assigned to ranolazine had a trend towards fewer episodes of AF [75 (2.4%) vs. 55 (1.7%) patients, P = 0.08] detected on cECG during the first 7 days after randomization. The pattern of new-onset AF differed between ranotazine vs. placebo: clinically insignificant AF (five patients in ranolazine vs. seven in placebo), paroxysmal AF (18 vs. 48 patients), and predominantly chronic AF (28 vs. 20 patients, three-way P < 0.01). Among patients with a paroxysmal AF pattern, the overall burden was lower with ranolazine than with placebo (median 4.4 vs .16.1%, P = 0.015). Over the median 1-year follow-up, fewer patients treated with ranolazine experienced an AF event compared with placebo (2.9 vs. 4.1%, RR 0.71, P = 0.01). Conclusion Ranolazine, an anti-anginal agent with electrophysiological effects, may reduce the frequency of paroxysmal AF in patients with non-ST elevation ACS with a pattern of tower overall AF burden in this group. Ranolazine reduced the overall 1-year incidence of clinical AF events. These atrial-specific anti-arrhythmic properties of ranolazine may be of clinical interest and warrant additional investigation. C1 [Scirica, Benjamin M.; Waks, Jonathan W.; Volo, Samuel; Murphy, Sabina A.; Braunwald, Eugene; Morrow, David A.] Brigham & Womens Hosp, Dept Med, Div Cardiovasc, TIMI Study Grp, Boston, MA 02115 USA. [Scirica, Benjamin M.; Waks, Jonathan W.; Volo, Samuel; Murphy, Sabina A.; Braunwald, Eugene; Morrow, David A.] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Belardinelli, Luiz; Karwatowska-Prokopczuk, Ewa; Cheng, Mei L.] Gilead Sci Inc, Foster City, CA USA. [Chaitman, Bernard R.] St Louis Univ, Sch Med, St Louis, MO USA. RP Scirica, BM (reprint author), Brigham & Womens Hosp, Dept Med, Div Cardiovasc, TIMI Study Grp, 75 Francis St, Boston, MA 02115 USA. EM bscirica@partners.org FU Gilead FX MERLIN-TIMI 36 was funded by CV Therapeutics (now Gilead). NR 23 TC 19 Z9 20 U1 0 U2 2 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 1 PY 2015 VL 17 IS 1 BP 32 EP 37 DI 10.1093/europace/euu217 PG 6 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA CE1WP UT WOS:000351603900008 PM 25210025 ER PT J AU Leff, B Carlson, CM Saliba, D Ritchie, C AF Leff, Bruce Carlson, Charlotte M. Saliba, Debra Ritchie, Christine TI The Invisible Homebound: Setting Quality-Of-Care Standards For Home-Based Primary And Palliative Care SO HEALTH AFFAIRS LA English DT Article ID OLDER-ADULTS; HOUSE CALLS; HEALTH; BENEFICIARIES; POPULATION; MANAGEMENT; VETERANS; DEATH; COST AB Approximately four million adults in the United States are homebound, and many of them cannot access office-based primary care. Home-based medical care can improve outcomes and reduce health care costs, but this care operates in a quality measurement desert, having been largely left out of the national conversation on care quality. To address this shortcoming, two of the authors created the National Home-Based Primary and Palliative Care Network, an organization whose members include exemplary home-based medical practices, professional societies, and patient advocacy groups. This article describes the current status of home-based medical care in the United States and offers a brief narrative of a fictional homebound patient and the health events and fragmented care she faces. The article then describes the network's quality-of-care framework, which includes ten quality-of-care domains, thirty-two standards, and twenty quality indicators that are being tested in the field. The same two authors also developed a practice-based registry that will be used for quality-of-care benchmarking, practice-based quality improvement, performance reporting, and comparative effectiveness research. Together, these steps should help bring home-based medical care further into the mainstream of US health care. C1 [Leff, Bruce] Johns Hopkins Univ, Sch Med, Med, Baltimore, MD 21205 USA. [Carlson, Charlotte M.] On Lok Senior Hlth Serv, San Francisco, CA USA. [Saliba, Debra] Univ Calif Los Angeles, Borun Ctr, Los Angeles, CA 90024 USA. [Saliba, Debra] Vet Affairs Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. [Ritchie, Christine] Univ Calif San Francisco, Dept Med, San Francisco, CA USA. RP Leff, B (reprint author), Johns Hopkins Univ, Sch Med, Med, Baltimore, MD 21205 USA. EM bleff@jhmi.edu FU Retirement Research Foundation; Commonwealth Fund; California HealthCare Foundation; National Institutes of Health; Agency for Healthcare Research and Quality; John A. Hartford Foundation FX Portions of this work were presented at the annual meeting of the American Academy of Home Care Medicine, in Orlando, Florida, May 14, 2014. This work was supported by the Retirement Research Foundation, the Commonwealth Fund, and the California HealthCare Foundation. The views presented here are those of the authors and not necessarily those of the Commonwealth Fund, its directors, officers, or staff. Bruce Leff is a current member of the board of directors and past president of the American Academy of Home Care Medicine. He and Debra Saliba are members of the PostAcute Care/Long-Term Care Workgroup of the Measure Application Partnership at the National Quality Forum. Christine Ritchie is president-elect of the American Academy of Hospice and Palliative Medicine. She is a section editor for UpToDate, Inc. Leff and Ritchie have received grant funding from the Commonwealth Fund, the Retirement Research Foundation, the California HealthCare Foundation, the National Institutes of Health, and the Agency for Healthcare Research and Quality. Leff has also received funding from the John A. Hartford Foundation. The authors thank Diane Meier for her thoughtful review of the manuscript and Debbie Statom for her assistance in preparing the manuscript. NR 35 TC 13 Z9 13 U1 0 U2 7 PU PROJECT HOPE PI BETHESDA PA 7500 OLD GEORGETOWN RD, STE 600, BETHESDA, MD 20814-6133 USA SN 0278-2715 J9 HEALTH AFFAIR JI Health Aff. PD JAN PY 2015 VL 34 IS 1 BP 21 EP 29 DI 10.1377/hlthaff.2014.1008 PG 9 WC Health Care Sciences & Services; Health Policy & Services SC Health Care Sciences & Services GA CE3GZ UT WOS:000351716000005 PM 25561640 ER PT J AU Scott, JW Sommers, BD Tsai, TC Scott, KW Schwartz, AL Song, ZR AF Scott, John W. Sommers, Benjamin D. Tsai, Thomas C. Scott, Kirstin W. Schwartz, Aaron L. Song, Zirui TI Dependent Coverage Provision Led To Uneven Insurance Gains And Unchanged Mortality Rates In Young Adult Trauma Patients SO HEALTH AFFAIRS LA English DT Article ID AFFORDABLE CARE ACT; SAFETY-NET HOSPITALS; DATA-BANK; HEALTH-INSURANCE; PENETRATING TRAUMA; VEHICULAR INJURY; STATUS MATTER; OUTCOMES; DISPARITIES; RACE AB Insurance coverage has increased among young adults as a result of the Affordable Care Act (ACA) provision that allows young adults to remain covered under their parents' plans until age twenty-six. However, little is known about the provision's effects on the clinical outcomes and insurance coverage of patients with trauma-the most frequent cause of death and physical disability among young adults. Using 2007-12 data from the National Trauma Data Bank, we conducted a difference-in-differences analysis of coverage rates among trauma patients ages 19-25 (compared to patients ages 26-34, who served as the control group), and we examined trauma-relevant outcomes by patient, injury, and hospital characteristics. We found a 3.4-percentage-point decrease in uninsurance status among younger trauma patients following the policy change. The decrease was concentrated among men, non-Hispanic whites, those with relatively less severe injuries, and those who presented to nonteaching hospitals. We did not detect significant changes in the use of intensive care or in overall mortality. The heterogeneous coverage impact of the ACA dependent coverage provision on high- versus low-risk trauma patients has implications for future efforts to expand coverage. C1 [Scott, John W.] Brigham & Womens Hosp, Ctr Surg & Publ Hlth, Boston, MA 02115 USA. [Sommers, Benjamin D.] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. [Sommers, Benjamin D.] Brigham & Womens Hosp, Med, Boston, MA 02115 USA. [Tsai, Thomas C.] Brigham & Womens Hosp, Gen Surg, Boston, MA 02115 USA. [Tsai, Thomas C.] Harvard Univ, Sch Publ Health, Dept Hlth Policy & Management, Cambridge, MA 02138 USA. [Scott, Kirstin W.] Harvard Univ, Interfac Initiat Hlth Policy, Cambridge, MA 02138 USA. [Schwartz, Aaron L.] Harvard Univ, Dept Hlth Care, Cambridge, MA 02138 USA. [Song, Zirui] Massachusetts Gen Hosp, Internal Med, Boston, MA 02114 USA. [Song, Zirui] Harvard Univ, Sch Med, Boston, MA USA. RP Scott, JW (reprint author), Brigham & Womens Hosp, Ctr Surg & Publ Hlth, 75 Francis St, Boston, MA 02115 USA. EM jwscott@partners.org OI Scott, John/0000-0002-9916-6523 FU Henry Ellis Warren Fellowship; Center for Surgery and Public Health at Brigham and Women's Hospital; Agency for Healthcare Research and Quality (AHRQ) [T32HS000055]; National Science Foundation Graduate Research Fellowship [NSF 13-584]; National Institute on Aging of the National Institutes of Health [F30 AG044106]; National Institute on Aging [NIA F30 AG039175-2]; National Cancer Institute's Program in Cancer Outcomes Research Training [R25CA92203] FX Preliminary data from this analysis were presented at the AcademyHealth Annual Research Meeting in San Diego, California, June 9, 2014. The authors acknowledge John Orav and Jennifer Polinski for their assistance in early analyses of these data. John Scott is funded by the Henry Ellis Warren Fellowship and the Center for Surgery and Public Health at Brigham and Women's Hospital. Kirstin Scott is funded by the Agency for Healthcare Research and Quality (AHRQ; Grant No. T32HS000055) and the National Science Foundation Graduate Research Fellowship (Grant No. NSF 13-584) Aaron Schwartz was supported by the National Institute on Aging of the National Institutes of Health (Grant No. F30 AG044106). Zirui Song was supported by the National Institute on Aging (Grant No. NIA F30 AG039175-2). Thomas Tsai was supported by the National Cancer Institute's Program in Cancer Outcomes Research Training (Grant No. R25CA92203). Tsai serves as an adviser and Benjamin Sommers serves part time as an adviser in the Office of the Assistant Secretary for Planning and Evaluation at the Department of Health and Human Services (HHS). The content of this article is solely the responsibility of the authors and does not necessarily represent the official views of AHRQ or HHS. NR 42 TC 7 Z9 7 U1 1 U2 3 PU PROJECT HOPE PI BETHESDA PA 7500 OLD GEORGETOWN RD, STE 600, BETHESDA, MD 20814-6133 USA SN 0278-2715 J9 HEALTH AFFAIR JI Health Aff. PD JAN PY 2015 VL 34 IS 1 BP 125 EP 133 DI 10.1377/hlthaff.2014.0880 PG 9 WC Health Care Sciences & Services; Health Policy & Services SC Health Care Sciences & Services GA CE3GZ UT WOS:000351716000019 PM 25561653 ER PT J AU Lee, SW Fried, SI AF Lee, Seung Woo Fried, Shelley I. TI Suppression of Subthalamic Nucleus Activity by Micromagnetic Stimulation SO IEEE TRANSACTIONS ON NEURAL SYSTEMS AND REHABILITATION ENGINEERING LA English DT Article DE Deep brain stimulation (DBS); magnetic stimulation; neural prosthesis; Parkinson's disease (PD); repetitive transcranial magnetic stimulation (rTMS); subthalamic nucleus (STN) ID DEEP BRAIN-STIMULATION; TRANSCRANIAL MAGNETIC STIMULATION; HIGH-FREQUENCY STIMULATION; OBSESSIVE-COMPULSIVE DISORDER; LIQUID-CRYSTAL POLYMERS; RETINAL GANGLION-CELLS; ELECTRICAL-STIMULATION; PARKINSONS-DISEASE; MICROELECTRODE ARRAYS; COCHLEAR IMPLANTS AB Magnetic stimulation delivered via 0.5-mm diameter coils was recently shown to activate retinal neurons; the small coil size raises the possibility that micromagnetic stimulation (mu MS) could underlie a new generation of implanted neural prosthetics. Such an approach has several inherent advantages over conventional electric stimulation, including the potential for selective activation of neuronal targets as well as less susceptibility to inflammatory responses. The viability of mu MS for some applications, e.g., deep brain stimulation (DBS), may require suppression (rather than creation) of neuronal activity, however, and therefore we explore here whether (mu MS) could, in fact, suppress activity. While single pulses elicited weak and inconsistent spiking in neurons of the mouse subthalamic nucleus (in vitro), repetitive stimulation effectively suppressed activity in similar to 70% of targeted neurons. This is the same percentage suppressed by conventional electric stimulation; with both modalities, suppression occurred only after an initial increase in spiking. The latency to the onset of suppression was inversely correlated to the energy of the stimulus waveform: larger amplitudes and lower frequencies had the fastest onset of suppression. These findings continue to support the viability of mu MS as a next-generation implantable neural prosthetic. C1 [Lee, Seung Woo] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Neurol, Boston, MA 02114 USA. [Fried, Shelley I.] Boston Vet Adm Healthcare Syst, Rehabil Res & Dev, Boston, MA 01230 USA. [Fried, Shelley I.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Neurosurg, Boston, MA 02114 USA. RP Lee, SW (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Neurol, Boston, MA 02114 USA. EM Lee.Se-ungwoo@mgh.harvard.edu; Fried.Shelley@mgh.harvard.edu FU Veterans Administration [MR 1I01RX000350-01A1]; National Eye Institute [R01EY019967, R01EY023651] FX This work was supported by the Veterans Administration under Grant MR 1I01RX000350-01A1 and by the National Eye Institute under Grant R01EY019967 and Grant R01EY023651. NR 68 TC 5 Z9 5 U1 3 U2 6 PU IEEE-INST ELECTRICAL ELECTRONICS ENGINEERS INC PI PISCATAWAY PA 445 HOES LANE, PISCATAWAY, NJ 08855-4141 USA SN 1534-4320 EI 1558-0210 J9 IEEE T NEUR SYS REH JI IEEE Trans. Neural Syst. Rehabil. Eng. PD JAN PY 2015 VL 23 IS 1 BP 116 EP 127 DI 10.1109/TNSRE.2014.2348415 PG 12 WC Engineering, Biomedical; Rehabilitation SC Engineering; Rehabilitation GA AZ0CG UT WOS:000347913400012 PM 25163063 ER PT J AU Gaffney, A AF Gaffney, Adam TI THE NEOLIBERAL TURN IN AMERICAN HEALTH CARE SO INTERNATIONAL JOURNAL OF HEALTH SERVICES LA English DT Article AB Leaving millions both uninsured and underinsured, the Affordable Care Act does not create a system of universal health care in the United States. To understand its shortcomings, we have to understand it as part of a historic shift in the political economy of American health care. This "neoliberal turn" began as a reaction against the welfare state as it expanded during the New Deal and post-World War II period. What began as a movement associated with philosophers like Friedrich Hayek ultimately had a powerful impact via the attraction of powerful corporate sponsors and political supporters, and it was to historically transform American health care thought and organization. In health policy circles, for example, it can be seen in a rising emphasis on "moral hazard," overuse, and cost sharing above a concern with universalism and equity. It was likewise manifested by the corporatization of the health maintenance organization and the rise of the "consumer-driven" health care movement. By the time of the health care reform debate, the influence of corporate "stakeholders" was to prove predominant. These developments, however, must be construed as connected parts of a much larger political transformation, reflected in rising inequality and privatization, occurring both domestically and internationally. C1 [Gaffney, Adam] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Gaffney, Adam] Columbia Univ, Med Ctr, New York, NY 10027 USA. RP Gaffney, A (reprint author), 84 Willow St 2, Cambridge, 02141, England. EM agaffney@mgh.harvard.edu NR 0 TC 4 Z9 4 U1 0 U2 1 PU SAGE PUBLICATIONS LTD PI LONDON PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND SN 0020-7314 EI 1541-4469 J9 INT J HEALTH SERV JI Int. J. Health Serv. PD JAN PY 2015 VL 45 IS 1 BP 33 EP 52 DI 10.2190/HS.45.1.d PG 20 WC Health Care Sciences & Services; Health Policy & Services SC Health Care Sciences & Services GA CE6JT UT WOS:000351943400004 PM 26460446 ER PT J AU Hoggatt, J Tate, TA Pelus, LM AF Hoggatt, Jonathan Tate, Tiffany A. Pelus, Louis M. TI Role of lipegfilgrastim in the management of chemotherapy-induced neutropenia SO INTERNATIONAL JOURNAL OF NANOMEDICINE LA English DT Review DE granulocyte-colony stimulating factor; biosimilar; filgrastim; neutrophil; XM22; cancer ID COLONY-STIMULATING FACTOR; TRANSITIONAL-CELL-CARCINOMA; CANCER-PATIENTS; G-CSF; DAILY FILGRASTIM; ACTIVE-CONTROL; DOUBLE-BLIND; STEM-CELLS; PROLIFERATION; MULTICENTER AB Chemotherapy, irradiation, and other agents are widely used to target the process of cell division in neoplastic cells. However, while these therapies are effective against most cancers, the high proliferative rate of the cells of the hematopoietic system that produce billions of blood cells needed daily throughout life is extremely sensitive to these agents, resulting in loss of blood cell populations, which can be life threatening. Neutropenia is the most serious hematologic toxicity of chemotherapy, which can result in patient morbidity and mortality due to opportunistic infection and often is the limiting factor in dose escalation or duration of chemotherapeutic administration. Neutropenic patients often require hospitalization and incur substantial medical costs associated with anti-infective therapy. Treatment of iatrogenic and congenic neutropenia was changed in the early 1990s with the introduction of filgrastim (Neupogen (R)) and pegfilgrastim (Neulasta (R)). With the expiration of patent lives of both of these drugs, biosimilars have begun to emerge. In this review, we will summarize the chemical characteristics, pharmacokinetics, safety and efficacy of lipegfilgrastim (Lonquex (R)), the first long-acting biosimilar filgrastim to receive regulatory approval and enter the marketplace. C1 [Hoggatt, Jonathan; Tate, Tiffany A.] Harvard Univ, Dept Stem Cell & Regenerat Biol, Cambridge, MA 02115 USA. [Pelus, Louis M.] Indiana Univ, Sch Med, Dept Microbiol & Immunol, Indianapolis, IN 46202 USA. RP Hoggatt, J (reprint author), Harvard Univ, Massachusetts Gen Hosp, Ctr Regenerat Med, Dept Stem Cell & Regenerat Biol, 185 Cambridge St,CPZN 4400, Boston, MA 02114 USA. EM hoggatt.jonathan@mgh.harvard.edu; ipelus@iupui.edu FU NCATS NIH HHS [UL1 TR001108] NR 36 TC 7 Z9 7 U1 1 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 2015 VL 10 BP 2647 EP 2652 DI 10.2147/IJN.S55796 PG 6 WC Nanoscience & Nanotechnology; Pharmacology & Pharmacy SC Science & Technology - Other Topics; Pharmacology & Pharmacy GA CE7IS UT WOS:000352013200003 PM 25878498 ER PT J AU Brommelhoff, JA Sultzer, DL AF Brommelhoff, Jessica A. Sultzer, David L. TI Brain Structure and Function Related to Depression in Alzheimer's Disease: Contributions from Neuroimaging Research SO JOURNAL OF ALZHEIMERS DISEASE LA English DT Review DE Alzheimer's disease; depression; late-life depression; neuroimaging ID LATE-LIFE DEPRESSION; MILD COGNITIVE IMPAIRMENT; DORSOLATERAL PREFRONTAL CORTEX; EMISSION COMPUTED-TOMOGRAPHY; VOXEL-BASED MORPHOMETRY; DEFAULT-MODE NETWORK; WHITE-MATTER CHANGES; GERIATRIC DEPRESSION; RATING-SCALE; HIPPOCAMPAL VOLUME AB The development of minimally invasive in vivo methods for imaging the brain has allowed for unprecedented advancement in our understanding of brain-behavior relationships. Structural, functional, and multimodal neuroimaging techniques have become more sophisticated in detecting structural and physiological abnormalities that may underlie various affective disorders and neurological illnesses such as depression in Alzheimer's disease (AD). In general, neuroimaging studies of depression in AD investigate whether depression is associated with damage to structures in specific neural networks involving frontal and subcortical structures or with functional disruption of cortical neural systems. This review provides an overview of how various imaging modalities have contributed to our understanding of the neurobiology of depression in AD. At present, the literature does not conclusively support any specific pathogenesis for depression, and it is not clear whether patients with AD and depression have histopathological and neurochemical characteristics that contribute to mood symptoms that are different from cognitively intact individuals with depression. Neuroimaging studies suggest that atrophy of temporal or frontal structures, white matter lesions in frontal lobe or subcortical systems, reduced activity in dorsolateral frontal cortex, or small vessel cerebrovascular disease may be associated with depression in AD. Conceptual, clinical, and methodological challenges in studying this relationship are discussed. Further work is needed to understand the specific brain structures, relevant white matter tracts, and interactions among them that are most important. This review concludes with potential directions for future research. C1 [Brommelhoff, Jessica A.; Sultzer, David L.] Univ Calif Los Angeles, David Geffen Sch Med, Mental Hlth Serv, VA Greater Los Angeles Hlth Care Syst, Los Angeles, CA 90095 USA. [Brommelhoff, Jessica A.; Sultzer, David L.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Psychiat & Biobehav Sci, Los Angeles, CA 90095 USA. RP Sultzer, DL (reprint author), VA Greater Los Angeles Hlth Care Syst, 11301 Wilshire Blvd,Bldg 401,116AE, Los Angeles, CA 90073 USA. EM dsultzer@ucla.edu FU Department of Veteran Affairs (MIRECC Advanced Fellowship); Department of Veteran Affairs (Merit Review Research Grant) FX Supported in part by the Department of Veteran Affairs (MIRECC Advanced Fellowship, Dr. Brommelhoff; Merit Review Research Grant, Dr. Sultzer). NR 96 TC 5 Z9 6 U1 4 U2 11 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 2015 VL 45 IS 3 BP 689 EP 703 DI 10.3233/JAD-148007 PG 15 WC Neurosciences SC Neurosciences & Neurology GA CE1YK UT WOS:000351608700002 PM 25633682 ER PT J AU Pan, C Korff, A Galasko, D Ginghina, C Peskind, E Li, G Quinn, J Montine, TJ Cain, K Shi, M Zhang, J AF Pan, Catherine Korff, Ane Galasko, Douglas Ginghina, Carmen Peskind, Elaine Li, Ge Quinn, Joseph Montine, Thomas J. Cain, Kevin Shi, Min Zhang, Jing TI Diagnostic Values of Cerebrospinal Fluid T-Tau and A beta(42) using Meso Scale Discovery Assays for Alzheimer's Disease SO JOURNAL OF ALZHEIMERS DISEASE LA English DT Article DE A beta(42); Alzheimer's disease; cerebrospinal fluid; Meso Scale Discovery; tau ID QUALITY-CONTROL PROGRAM; CSF ALPHA-SYNUCLEIN; BETA-AMYLOID 1-42; APOLIPOPROTEIN-E; ASSOCIATION WORKGROUPS; ANALYTICAL PLATFORMS; PARKINSONS-DISEASE; NATIONAL INSTITUTE; CONFIRMED DEMENTIA; VASCULAR DEMENTIA AB Background: Meso Scale Discovery (MSD) recently established electrochemiluminescence-based assays to measure cerebrospinal fluid (CSF) levels of total tau (t-tau) and amyloid-beta 1-42 peptide (A beta(42)) that can aid in the diagnosis of Alzheimer's disease (AD). The goal of this investigation is to independently evaluate this platform and establish cut-off values of these biomarkers for AD diagnosis. Objective: To validate the analytical and clinical performance of the MSD t-tau and A beta(42) kits and propose diagnostic cut-off values for the field. Methods: The analytical performance of the CSF t-tau and A beta(42) assays was determined, followed by assessment of diagnostic performance of CSF t-tau, A beta(42), and t-tau/A beta(42) in three clinically characterized cohorts. Results: Both MSD assays demonstrated consistent and stable analytical performance, as well as resistance to several important pre-analytic variables. Diagnostically, t-tau/A beta(42) performed the best. Conclusions: Our results independently confirm the analytical and clinical performance of the MSD CSF t-tau and A beta(42) assays. Based on a large, multi-center, clinically-diagnosed cohort, we propose for the first time candidate diagnostic cut-offs for MSD measured CSF t-tau, A beta(42), and t-tau/A beta(42). However, these values needs to be refined as more subjects are included and the assays are tested by other laboratories. C1 [Pan, Catherine; Korff, Ane; Ginghina, Carmen; Montine, Thomas J.; Shi, Min; Zhang, Jing] Univ Washington, Sch Med, Dept Pathol, Seattle, WA 98104 USA. [Galasko, Douglas] Univ Calif San Diego, Dept Neurosci, San Diego, CA 92103 USA. [Peskind, Elaine] VA Puget Sound Hlth Care Syst, Northwest Network VISN 20, Mental Illness Res Educ & Clin Ctr, Seattle, WA USA. [Peskind, Elaine; Li, Ge] Univ Washington, Dept Psychiat & Behav Sci, Seattle, WA 98195 USA. [Li, Ge] Vet Affairs Puget Sound Hlth Care Syst, Geriatr Res Educ & Clin Ctr, Seattle, WA USA. [Quinn, Joseph] Oregon Hlth & Sci Univ, Dept Neurol, Portland, OR 97201 USA. [Quinn, Joseph] Portland VA Med Ctr, Portland, OR USA. [Cain, Kevin] Univ Washington, Sch Med, Dept Biostat, Seattle, WA 98195 USA. RP Zhang, J (reprint author), Univ Washington, Sch Med, Dept Pathol, HMC Box 359635,325 9th Ave, Seattle, WA 98104 USA. EM zhangj@uw.edu RI Shi, Min/G-6165-2012 OI Shi, Min/0000-0002-6901-2558 FU [NINDS: U01 NS082137 03]; [NIA: P50 AG005131 31]; [NIA: P30 AG008017 25]; [NIA: P50 AG005136 31] FX The authors' efforts were supported by the NINDS: U01 NS082137 03 and NIA: P50 AG005131 31, P30 AG008017 25, and P50 AG005136 31. The authors would also like to thank the Friends of Alzheimer's research and the Department of Veterans Affairs. MSD had no role in the design, conduct, or analysis of results of the current study. NR 52 TC 2 Z9 3 U1 0 U2 3 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 2015 VL 45 IS 3 BP 709 EP 719 DI 10.3233/JAD-143099 PG 11 WC Neurosciences SC Neurosciences & Neurology GA CE1YK UT WOS:000351608700004 PM 25613100 ER PT J AU Gray, NE Sampath, H Zweig, JA Quinn, JF Soumyanath, A AF Gray, Nora E. Sampath, Harini Zweig, Jonathan A. Quinn, Joseph F. Soumyanath, Amala TI Centella asiatica Attenuates Amyloid-beta-Induced Oxidative Stress and Mitochondrial Dysfunction SO JOURNAL OF ALZHEIMERS DISEASE LA English DT Article DE Amyloid-beta toxicity; calcium homeostasis; Centella asiatica; mitochondrial dysfunction; neuroprotection; reactive oxygen species ID ALZHEIMERS-DISEASE; SH-SY5Y CELLS; MOUSE MODEL; INDUCED NEUROTOXICITY; CAFFEOYLQUINIC ACIDS; CEREBRAL-CORTEX; IN-VIVO; NEURONS; PROTEIN; RATS AB Background: We previously showed that a water extract of the medicinal plant Centella asiatica (CAW) attenuates amyloid-beta (A beta)-induced cognitive deficits in vivo, and prevents A beta-induced cytotoxicity in vitro. Yet the neuroprotective mechanism of CAW is unknown. Objective: The goal of this study was to identify biochemical pathways altered by CAW using in vitro models of A beta toxicity. Methods: The effects of CAW on aberrations in antioxidant response, calcium homeostasis, and mitochondrial function induced by A beta were evaluated in MC65 and SH-SY5Y neuroblastoma cells. Results: CAW decreased intracellular reactive oxygen species and calcium levels elevated in response to A beta, and induced the expression of antioxidant response genes in both cell lines. In SH-SY5Y cells, CAW increased basal and maximal oxygen consumption without altering spare capacity, and attenuated A beta-induced decreases in mitochondrial respiration. CAW also prevented A beta-induced decreases in ATP and induced the expression of mitochondrial genes and proteins in both cell types. Caffeoylquinic acids from CAW were shown to have a similar effect on antioxidant and mitochondrial gene expression in neuroblastoma cells. Primary rat hippocampal neurons treated with CAW also showed an increase in mitochondrial and antioxidant gene expression. Conclusions: These data suggest an effect of CAW on mitochondrial biogenesis, which in conjunction with activation of antioxidant response genes and normalizing calcium homeostasis, likely contributes to its neuroprotective action against A beta toxicity. C1 [Gray, Nora E.; Quinn, Joseph F.; Soumyanath, Amala] Oregon Hlth & Sci Univ, Dept Neurol, Portland, OR 97201 USA. [Sampath, Harini] Oregon Hlth & Sci Univ, Oregon Inst Occupat Hlth Sci, Portland, OR 97201 USA. [Zweig, Jonathan A.] Oregon Hlth & Sci Univ, Dept Cell Dev & Canc Biol, Portland, OR 97201 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 Gray, NE (reprint author), Oregon Hlth & Sci Univ, Dept Neurol, 3181 SW Sam Jackson Pk Rd, Portland, OR 97201 USA. EM grayn@ohsu.edu FU NIH-NCCAM grant [R01AT008099]; Oregon Alzheimer's Disease Center (OADC) [3P30-AG008017 24 S1]; OADC [5 P30 AG008017 24]; T32 grant from NIH-NCCAM [AT002688]; K99 grant [K99DK100640]; Department of Veterans Affairs Merit Review grant FX This work was funded by NIH-NCCAM grant R01AT008099, a grant awarded to A. Soumyanath from the Oregon Alzheimer's Disease Center (OADC) 3P30-AG008017 24 S1 and one to N. Gray from the OADC 5 P30 AG008017 24, a T32 grant on which N. Gray was a trainee from NIH-NCCAM AT002688, a K99 grant to H. Sampath K99DK100640 and by a Department of Veterans Affairs Merit Review grant awarded to J. Quinn. The authors acknowledge Dr. Stephen Lloyd for his assistance with the Seahorse XF Analyzer experiments and Barbara Smoody for her help with the primary neuron experiments. MC65 cells were generously provided by Randy Woltjer, MD, PhD. NR 53 TC 8 Z9 9 U1 1 U2 8 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 2015 VL 45 IS 3 BP 933 EP 946 DI 10.3233/JAD-142217 PG 14 WC Neurosciences SC Neurosciences & Neurology GA CE1YK UT WOS:000351608700022 PM 25633675 ER PT J AU Sikov, WM Berry, DA Perou, CM Singh, B Cirrincione, CT Tolaney, SM Kuzma, CS Pluard, TJ Somlo, G Port, ER Golshan, M Bellon, JR Collyar, D Hahn, OM Carey, LA Hudis, CA Winer, EP AF Sikov, William M. Berry, Donald A. Perou, Charles M. Singh, Baljit Cirrincione, Constance T. Tolaney, Sara M. Kuzma, Charles S. Pluard, Timothy J. Somlo, George Port, Elisa R. Golshan, Mehra Bellon, Jennifer R. Collyar, Deborah Hahn, Olwen M. Carey, Lisa A. Hudis, Clifford A. Winer, Eric P. TI Impact of the Addition of Carboplatin and/or Bevacizumab to Neoadjuvant Once-per-Week Paclitaxel Followed by Dose-Dense Doxorubicin and Cyclophosphamide on Pathologic Complete Response Rates in Stage II to III Triple-Negative Breast Cancer: CALGB 40603 (Alliance) SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID CHEMOTHERAPY; TRIAL; CISPLATIN; SURVIVAL; SUBTYPES; THERAPY AB Purpose One third of patients with triple-negative breast cancer (TNBC) achieve pathologic complete response (pCR) with standard neoadjuvant chemotherapy (NACT). CALGB 40603 (Alliance), a 2 x 2 factorial, open-label, randomized phase II trial, evaluated the impact of adding carboplatin and/or bevacizumab. Patients and Methods Patients (N = 443) with stage II to III TNBC received paclitaxel 80 mg/m(2) once per week (wP) for 12 weeks, followed by doxorubicin plus cyclophosphamide once every 2 weeks (ddAC) for four cycles, and were randomly assigned to concurrent carboplatin (area under curve 6) once every 3 weeks for four cycles and/or bevacizumab 10 mg/kg once every 2 weeks for nine cycles. Effects of adding these agents on pCR breast (ypT0/is), pCR breast/axilla (ypT0/isN0), treatment delivery, and toxicities were analyzed. Results Patients assigned to either carboplatin or bevacizumab were less likely to complete wP and ddAC without skipped doses, dose modification, or early discontinuation resulting from toxicity. Grade >= 3 neutropenia and thrombocytopenia were more common with carboplatin, as were hypertension, infection, thromboembolic events, bleeding, and postoperative complications with bevacizumab. Employing one-sided P values, addition of either carboplatin (60% v 44%; P = .0018) or bevacizumab (59% v 48%; P = .0089) significantly increased pCR breast, whereas only carboplatin (54% v 41%; P = .0029) significantly raised pCR breast/axilla. More-than-additive interactions between the two agents could not be demonstrated. Conclusion In stage II to III TNBC, addition of either carboplatin or bevacizumab to NACT increased pCR rates, but whether this will improve relapse-free or overall survival is unknown. Given results from recently reported adjuvant trials, further investigation of bevacizumab in this setting is unlikely, but the role of carboplatin could be evaluated in definitive studies, ideally limited to biologically defined patient subsets most likely to benefit from this agent. (C) 2014 by American Society of Clinical Oncology C1 [Sikov, William M.] Brown Univ, Miriam Hosp, Providence, RI USA. [Sikov, William M.] Brown Univ, Alpert Med Sch, Providence, RI 02912 USA. [Berry, Donald A.] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. [Perou, Charles M.; Carey, Lisa A.] Univ N Carolina, Lineberger Comprehens Canc Ctr, Chapel Hill, NC 27599 USA. [Cirrincione, Constance T.] Alliance Stat Ctr, Durham, NC USA. [Kuzma, Charles S.] Southeast Canc Control Consortium, Winston Salem, NC USA. [Singh, Baljit] NYU, Med Ctr, New York, NY 10016 USA. [Port, Elisa R.] Mt Sinai Med Ctr, New York, NY 10029 USA. [Hudis, Clifford A.] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. [Tolaney, Sara M.; Golshan, Mehra; Bellon, Jennifer R.; Winer, Eric P.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Pluard, Timothy J.] Washington Univ, Med Ctr, St Louis, MO USA. [Somlo, George] City Hope Comprehens Canc Ctr, Duarte, CA USA. [Collyar, Deborah] Patient Advocates Res, Danville, CA USA. [Hahn, Olwen M.] Univ Chicago, Med Ctr, Chicago, IL 60637 USA. RP Sikov, WM (reprint author), Women & Infants Hosp Rhode Isl, Breast Hlth Ctr, 101 Dudley St, Providence, RI 02905 USA. EM wsikov@wihri.org FU National Cancer Institute [CA31946, CA33601, CA076001, CA025224, CA32102, CA46368]; Genentech, a division of F. Hoffman-La Roche; Breast Cancer Research Foundation; American Recovery and Reinvestment Act FX Supported in part by National Cancer Institute Grants No. CA31946 to the Alliance for Clinical Trials in Oncology, CA33601 to the Alliance Statistics and Data Center, CA076001 to the American College of Surgeons Oncology Group, CA025224 to the North Central Cancer Treatment Group, and CA32102 and CA46368 to the Southwest Oncology Group; by Genentech, a division of F. Hoffman-La Roche; by the Breast Cancer Research Foundation; and by funding provided by the American Recovery and Reinvestment Act to the Coalition for Cancer Cooperative Groups. NR 26 TC 122 Z9 131 U1 6 U2 25 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD JAN 1 PY 2015 VL 33 IS 1 BP 13 EP U34 DI 10.1200/JCO.2014.57.0572 PG 11 WC Oncology SC Oncology GA CE2DP UT WOS:000351624300006 PM 25092775 ER PT J AU Shi, Q de Gramont, A Grothey, A Zalcberg, J Chibaudel, B Schmoll, HJ Seymour, MT Adams, R Saltz, L Goldberg, RM Punt, CJA Douillard, JY Hoff, PM Hecht, JR Hurwitz, H Diaz-Rubio, E Porschen, R Tebbutt, NC Fuchs, C Souglakos, J Falcone, A Tournigand, C Kabbinavar, FF Heinemann, V Van Cutsem, E Bokemeyer, C Buyse, M Sargent, DJ AF Shi, Qian de Gramont, Aimery Grothey, Axel Zalcberg, John Chibaudel, Benoist Schmoll, Hans-Joachim Seymour, Matthew T. Adams, Richard Saltz, Leonard Goldberg, Richard M. Punt, Cornelis J. A. Douillard, Jean-Yves Hoff, Paulo M. Hecht, Joel Randolph Hurwitz, Herbert Diaz-Rubio, Eduardo Porschen, Rainer Tebbutt, Niall C. Fuchs, Charles Souglakos, John Falcone, Alfredo Tournigand, Christophe Kabbinavar, Fairooz F. Heinemann, Volker Van Cutsem, Eric Bokemeyer, Carsten Buyse, Marc Sargent, Daniel J. TI Individual Patient Data Analysis of Progression-Free Survival Versus Overall Survival As a First-Line End Point for Metastatic Colorectal Cancer in Modern Randomized Trials: Findings From the Analysis and Research in Cancers of the Digestive System Database SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID PHASE-III TRIAL; COMBINATION CHEMOTHERAPY; INFUSIONAL FLUOROURACIL; PLUS OXALIPLATIN; CLINICAL-TRIALS; MUTATION STATUS; DOUBLE-BLIND; FINAL REPORT; LEUCOVORIN; CETUXIMAB AB Purpose Progression-free survival (PFS) has previously been established as a surrogate for overall survival (OS) for first-line metastatic colorectal cancer (mCRC). Because mCRC treatment has advanced in the last decade with extended OS, this surrogacy requires re-examination. Methods Individual patient data from 16,762 patients were available from 22 first-line mCRC studies conducted from 1997 to 2006; 12 of those studies tested antiangiogenic and/or anti-epidermal growth factor receptor agents. The relationship between PFS (first event of progression or death) and OS was evaluated by using R-2 statistics (the closer the value is to 1, the stronger the correlation) from weighted least squares regression of trial-specific hazard ratios estimated by using Cox and Copula models. Results Forty-four percent of patients received a regimen that included biologic agents. Median first-line PFS was 8.3 months, and median OS was 18.2 months. The correlation between PFS and OS was modest (R-2, 0.45 to 0.69). Analyses limited to trials that tested treatments with biologic agents, nonstrategy trials, or superiority trials did not improve surrogacy. Conclusion In modern mCRC trials, in which survival after the first progression exceeds time to first progression, a positive but modest correlation was observed between OS and PFS at both the patient and trial levels. This finding demonstrates the substantial variability in OS introduced by the number of lines of therapy and types of effective subsequent treatments and the associated challenge to the use of OS as an end point to assess the benefit attributable to a single line of therapy. PFS remains an appropriate primary end point for first-line mCRC trials to detect the direct treatment effect of new agents. (C) 2014 by American Society of Clinical Oncology C1 [Shi, Qian; Grothey, Axel] Mayo Clin, Rochester, MN 55905 USA. [de Gramont, Aimery; Chibaudel, Benoist] Hosp St Antoine, Paris, France. [Tournigand, Christophe] Univ Paris Est Creteil, Paris, France. [Douillard, Jean-Yves] Inst Canc Res Western, St Herblain, France. [Zalcberg, John] Monash Univ, Melbourne, Vic 3004, Australia. [Tebbutt, Niall C.] Austin Hlth, Melbourne, Vic, Australia. [Schmoll, Hans-Joachim] Univ Halle Wittenberg, D-06108 Halle, Germany. [Porschen, Rainer] Klinikum Bremen Ost, Bremen, Germany. [Heinemann, Volker] Univ Munich, Munich, Germany. [Bokemeyer, Carsten] Univ Hamburg Hosp, Hamburg, Germany. [Seymour, Matthew T.] Canc Res UK Clincal Ctr, Leeds, W Yorkshire, England. [Adams, Richard] Cardiff Univ, Cardiff CF10 3AX, S Glam, Wales. [Saltz, Leonard] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. [Goldberg, Richard M.] Ohio State Univ, Columbus, OH 43210 USA. [Punt, Cornelis J. A.] Univ Amsterdam, Acad Med Ctr, NL-1105 AZ Amsterdam, Netherlands. [Hoff, Paulo M.] Hosp Sirio Libanes, Sao Paulo, Brazil. [Hecht, Joel Randolph; Kabbinavar, Fairooz F.] Univ Calif Los Angeles, Los Angeles, CA USA. [Hurwitz, Herbert] Duke Univ, Durham, NC USA. [Diaz-Rubio, Eduardo] Hosp Clin San Carlos, Madrid, Spain. [Fuchs, Charles] Dana Farber Canc Inst, Boston, MA 02115 USA. [Souglakos, John] Univ Crete, Iraklion, Greece. [Falcone, Alfredo] Univ Pisa, Pisa, Italy. [Van Cutsem, Eric] Univ Hosp Gasthuisberg, Leuven, Belgium. [Buyse, Marc] Int Inst Drug Dev, Louvain La Neuve, Belgium. RP Sargent, DJ (reprint author), Mayo Clin, 200 First St SW,Harwick 8-27, Rochester, MN 55905 USA. EM sargent.daniel@mayo.edu FU Analysis and Research in Cancers of the Digestive System Foundation FX Supported by the Analysis and Research in Cancers of the Digestive System Foundation. NR 43 TC 25 Z9 25 U1 2 U2 16 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD JAN 1 PY 2015 VL 33 IS 1 BP 22 EP U47 DI 10.1200/JCO.2014.56.5887 PG 13 WC Oncology SC Oncology GA CE2DP UT WOS:000351624300007 PM 25385741 ER PT J AU Yuan, C Rubinson, DA Qian, ZR Wu, C Kraft, P Bao, Y Ogino, S Ng, K Clancy, TE Swanson, RS Gorman, MJ Brais, LK Li, TT Stampfer, MJ Hu, FB Giovannucci, EL Kulke, MH Fuchs, CS Wolpin, BM AF Yuan, Chen Rubinson, Douglas A. Qian, Zhi Rong Wu, Chen Kraft, Peter Bao, Ying Ogino, Shuji Ng, Kimmie Clancy, Thomas E. Swanson, Richard S. Gorman, Megan J. Brais, Lauren K. Li, Tingting Stampfer, Meir J. Hu, Frank B. Giovannucci, Edward L. Kulke, Matthew H. Fuchs, Charles S. Wolpin, Brian M. TI Survival Among Patients With Pancreatic Cancer and Long-Standing or Recent-Onset Diabetes Mellitus SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID PHYSICAL-ACTIVITY; TEMPORAL ASSOCIATION; RISK; GLUCOSE; ADENOCARCINOMA; INSULIN; OBESITY; METAANALYSIS; DIAGNOSIS; WOMEN AB Purpose Long-standing diabetes is a risk factor for pancreatic cancer, and recent-onset diabetes in the several years before diagnosis is a consequence of subclinical pancreatic malignancy. However, the impact of diabetes on survival is largely unknown. Patients and Methods We analyzed survival by diabetes status among 1,006 patients diagnosed from 1986 to 2010 from two prospective cohort studies: the Nurses' Health Study (NHS) and Health Professionals Follow-Up Study (HPFS). We validated our results among 386 patients diagnosed from 2004 to 2013 from a clinic-based case series at Dana-Farber Cancer Institute (DFCI). We estimated hazard ratios (HRs) for death using Cox proportional hazards models, with adjustment for age, sex, race/ethnicity, smoking, diagnosis year, and cancer stage. Results In NHS and HPFS, HR for death was 1.40 (95% CI, 1.15 to 1.69) for patients with long-term diabetes (> 4 years) compared with those without diabetes (P < .001), with median survival times of 3 months for long-term diabetics and 5 months for nondiabetics. Adjustment for a propensity score to reduce confounding by comorbidities did not change the results. Among DFCI patient cases, HR for death was 1.53 (95% CI, 1.07 to 2.20) for those with long-term diabetes compared with those without diabetes (P = .02), with median survival times of 9 months for long-term diabetics and 13 months for nondiabetics. Compared with nondiabetics, survival times were shorter for long-term diabetics who used oral hypoglycemics or insulin. We observed no statistically significant association of recent-onset diabetes (< 4 years) with survival. Conclusion Long-standing diabetes was associated with statistically significantly decreased survival among patients with pancreatic cancer enrolled onto three longitudinal studies. (C) 2014 by American Society of Clinical Oncology C1 [Yuan, Chen; Rubinson, Douglas A.; Qian, Zhi Rong; Ogino, Shuji; Ng, Kimmie; Gorman, Megan J.; Brais, Lauren K.; Li, Tingting; Kulke, Matthew H.; Fuchs, Charles S.; Wolpin, Brian M.] Dana Farber Canc Inst, Boston, MA 02215 USA. [Wu, Chen; Kraft, Peter; Ogino, Shuji; Stampfer, Meir J.; Hu, Frank B.; Giovannucci, Edward L.] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. [Bao, Ying; Ogino, Shuji; Ng, Kimmie; Clancy, Thomas E.; Swanson, Richard S.; Stampfer, Meir J.; Hu, Frank B.; Giovannucci, Edward L.; Kulke, Matthew H.; Fuchs, Charles S.; Wolpin, Brian M.] Brigham & Womens Hosp, Boston, MA 02115 USA. [Bao, Ying; Ogino, Shuji; Ng, Kimmie; Clancy, Thomas E.; Swanson, Richard S.; Stampfer, Meir J.; Hu, Frank B.; Giovannucci, Edward L.; Kulke, Matthew H.; Fuchs, Charles S.; Wolpin, Brian M.] Harvard Univ, Sch Med, Boston, MA USA. RP Wolpin, BM (reprint author), Dana Farber Canc Inst, 450 Brookline Ave, Boston, MA 02215 USA. EM bwolpin@partners.org FU National Cancer Institute (NCI; National Institutes of Health [NIH]) [P01 CA87969, P01 CA55075, U54 CA155626, P50 CA127003, R01 CA124908, R01 CA49449, 1UM1 CA167552]; NCI NIH [P50 CA127003, K07 CA140790]; Robert T. and Judith B. Hale Fund for Pancreatic Cancer Research; Lustgarten Foundation for the Dana-Farber Cancer Institute; American Society of Clinical Oncology Conquer Cancer Foundation; Howard Hughes Medical Institute; Lustgarten Foundation; Promises for Purple; NIH/NCI [K07 CA148894] FX Supported by National Cancer Institute (NCI; National Institutes of Health [NIH]) Grants No. P01 CA87969, P01 CA55075, U54 CA155626, P50 CA127003, R01 CA124908, R01 CA49449, and 1UM1 CA167552 for the Nurses' Health Study and Health Professionals Follow-up Study; in part by NCI NIH Grant No. P50 CA127003, the Robert T. and Judith B. Hale Fund for Pancreatic Cancer Research, and the Lustgarten Foundation for the Dana-Farber Cancer Institute; in part by NCI NIH Grant No. K07 CA140790, the American Society of Clinical Oncology Conquer Cancer Foundation, the Howard Hughes Medical Institute, the Lustgarten Foundation, and Promises for Purple (B.M.W.); and in part by NIH/NCI Grant No. K07 CA148894 and the American Society of Clinical Oncology Conquer Cancer Foundation (K.N.). NR 43 TC 14 Z9 17 U1 0 U2 11 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD JAN 1 PY 2015 VL 33 IS 1 BP 29 EP U58 DI 10.1200/JCO.2014.57.5688 PG 11 WC Oncology SC Oncology GA CE2DP UT WOS:000351624300008 PM 25403204 ER PT J AU Vaz-Luis, I Lin, NU AF Vaz-Luis, Ines Lin, Nancy U. TI Combination Trastuzumab and Chemotherapy May Have a Role in Women With Small, Node-Negative, Human Epidermal Growth Factor Receptor 2-Positive Breast Cancer Reply SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Letter C1 [Vaz-Luis, Ines; Lin, Nancy U.] Dana Farber Canc Inst, Boston, MA 02115 USA. RP Vaz-Luis, I (reprint author), Dana Farber Canc Inst, Boston, MA 02115 USA. NR 4 TC 1 Z9 1 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD JAN 1 PY 2015 VL 33 IS 1 BP 125 EP U183 DI 10.1200/JCO.2014.58.9655 PG 2 WC Oncology SC Oncology GA CE2DP UT WOS:000351624300021 PM 25403214 ER PT J AU Adams, JM Alexander, GA Chisari, RG Banister, G McAuley, ME Whitney, KB Erickson, JI AF Adams, Jeffrey M. Alexander, Gail A. Chisari, R. Gino Banister, Gaurdia McAuley, Mary Elizabeth Whitney, Kevin B. Erickson, Jeanette Ives TI Strengthening New Graduate Nurse Residency Programs in Critical Care: Recommendations From Nurse Residents and Organizational Stakeholders SO JOURNAL OF CONTINUING EDUCATION IN NURSING LA English DT Article ID SATISFACTION AB Background: Thirty-four new graduate nurses participated in a critical care nurse residency program in preparation for opening a new intensive care unit. At the end of the program, multi-constituent focus groups were held to assess program effectiveness. Method: Participants included 34 new graduate nurses, 18 preceptors and staff nurse partners, five clinical nurse specialists, and five nurse directors. Twelve focus groups were held; groups included four to eight nurses from the same role group. Two independent reviewers analyzed recordings and transcripts of focus group content to identify themes. Results: Five themes were identified: program design, developing nursing expertise, program impact on the unit, future expectations, and communication. Comments were used to guide program improvements and offer new insights for residency programs in acute and critical care. Conclusion: Obtaining structured input from multiple program stakeholders is beneficial in evaluating a program's impact and identifying areas for improvement. C1 [Adams, Jeffrey M.] Massachusetts Gen Hosp, Ctr Innovat Care Delivery, Inst Patient Care, Robert Wood Johnson Fdn, Boston, MA 02114 USA. [Adams, Jeffrey M.] Massachusetts Gen Hosp, Ctr Innovat Care Delivery, Inst Patient Care, Boston, MA 02114 USA. [Alexander, Gail A.; Banister, Gaurdia] Massachusetts Gen Hosp, Inst Patient Care, Boston, MA 02114 USA. [Chisari, R. Gino] Massachusetts Gen Hosp, Inst Patient Care, Norman Knight Nursing Ctr Clin & Profess Dev, Boston, MA 02114 USA. [McAuley, Mary Elizabeth] Massachusetts Gen Hosp, Intens Care Unit, Boston, MA 02114 USA. [Whitney, Kevin B.] Massachusetts Gen Hosp, Nurse Surg Orthoped & Neurosci, Boston, MA 02114 USA. [Erickson, Jeanette Ives] Massachusetts Gen Hosp, Patient Care, Boston, MA 02114 USA. RP Adams, JM (reprint author), Massachusetts Gen Hosp, Ctr Innovat Care Delivery, Inst Patient Care, Robert Wood Johnson Fdn, Profess Off Bldg Room 432,275 Cambridge St, Boston, MA 02114 USA. EM jeff.adams@mgh.harvard.edu NR 20 TC 2 Z9 2 U1 2 U2 9 PU SLACK INC PI THOROFARE PA 6900 GROVE RD, THOROFARE, NJ 08086 USA SN 0022-0124 EI 1938-2472 J9 J CONTIN EDUC NURS JI J. Contin. Educ. Nursing PD JAN PY 2015 VL 46 IS 1 BP 41 EP 48 DI 10.3928/00220124-20151217-01 PG 8 WC Nursing SC Nursing GA CE7DT UT WOS:000351998200010 PM 25522374 ER PT J AU Trygstad, LN Buccheri, RK Buffum, MD Ju, DS Dowling, GA AF Trygstad, Louise Nigh Buccheri, Robin K. Buffum, Martha D. Ju, Dau-shen Dowling, Glenna A. TI Auditory Hallucinations Interview Guide Promoting Recovery with an Interactive Assessment Tool SO JOURNAL OF PSYCHOSOCIAL NURSING AND MENTAL HEALTH SERVICES LA English DT Article ID COMMAND HALLUCINATIONS; BEHAVIORAL-MANAGEMENT; SELF-MANAGEMENT; HARM AB The Auditory Hallucinations Interview Guide (AHIG) is a 32-item tool that helps psychiatric-mental health (PMH) nurses assess past and current experiences of voice hearers so they can provide more individualized care. The AHIG was developed as a research tool but has also been found to be clinically useful in both inpatient and outpatient settings to help voice hearers and nurses develop a shared terminology of auditory hallucinations (AH). Using the AHIG, voice hearers are able to tell their stories in a structured and safe environment, thus encouraging recovery. Through respect and active listening, PMH nurses can communicate unconditional acceptance, caring, and hope for recovery, which helps develop rapport and promote trust in the nurse-patient relationship. Once trust is developed, voice hearers and PMH nurses can work together to find effective strategies for managing AH, including commands to harm self and others. C1 [Trygstad, Louise Nigh; Buccheri, Robin K.] Univ San Francisco, DNP Dept, Sch Nursing & Hlth Profess, San Francisco, CA 94117 USA. [Buffum, Martha D.] Univ Calif San Francisco, Sch Nursing, Dept Community Hlth Syst, San Francisco, CA 94143 USA. [Dowling, Glenna A.] Univ Calif San Francisco, Sch Nursing, Dept Physiol Nursing, San Francisco, CA 94143 USA. [Ju, Dau-shen] Iowa City Vet Affairs Hlth Care Syst, Mental Hlth Serv Line, Iowa City, IA USA. [Buffum, Martha D.] San Francisco VA Med Ctr, San Francisco, CA USA. RP Buccheri, RK (reprint author), Univ San Francisco, DNP Dept, Sch Nursing & Hlth Profess, Cowell Hall 222,2130 Fulton St, San Francisco, CA 94117 USA. EM buccherir@usfca.edu FU University of San Francisco Faculty Development Funds FX The authors have disclosed no potential conflicts of interest, financial or otherwise. This project was funded by a grant from the University of San Francisco Faculty Development Funds. This material is the result of work supported with resources and the use of facilities at the San Francisco Veterans Affairs Medical Center, San Francisco, California, and Iowa City Veterans Affairs Health Care System, Iowa City, Iowa. This article is dedicated to all of the psychiatric-mental health nurses and other mental health clinicians who work diligently to help their patients learn how to manage their auditory hallucinations and stay safe. NR 16 TC 0 Z9 0 U1 2 U2 3 PU SLACK INC PI THOROFARE PA 6900 GROVE RD, THOROFARE, NJ 08086 USA SN 0279-3695 EI 1938-2413 J9 J PSYCHOSOC NURS MEN JI J. Psychosoc. Nurs. Ment. Health Serv. PD JAN PY 2015 VL 53 IS 1 BP 20 EP 28 DI 10.3928/02793695-20141203-01 PG 9 WC Nursing SC Nursing GA CE7IL UT WOS:000352012500009 PM 25490776 ER PT J AU Gettinger, SN Bazhenova, L Salgia, R Langer, CJ Gold, KA Rosell, R Shaw, AT Weiss, GJ Narasimhan, NI Dorer, DJ Rivera, VM Clackson, T Haluska, FG Camidge, DR AF Gettinger, S. N. Bazhenova, L. Salgia, R. Langer, C. J. Gold, K. A. Rosell, R. Shaw, A. T. Weiss, G. J. Narasimhan, N. I. Dorer, D. J. Rivera, V. M. Clackson, T. Haluska, F. G. Camidge, D. R. TI Efficacy and safety of AP26113 in ALK+ non-small cell lung cancer (NSCLC), including patients with brain metastases SO LUNG CANCER LA English DT Meeting Abstract C1 [Gettinger, S. N.] Yale Canc Ctr, Thorac Oncol Program, New Haven, CT USA. [Bazhenova, L.] Univ Calif San Diego, Div Hematol Oncol, Moores Canc Ctr, San Diego, CA 92103 USA. [Salgia, R.] Univ Chicago Med, Pathol & Dermatol Dept, Chicago, IL USA. [Langer, C. J.] Univ Penn, Abramson Canc, Dept Med, Philadelphia, PA 19104 USA. [Gold, K. A.] Univ Texas MD Anderson Canc Ctr, Thorac Head & Neck Med Oncol, Houston, TX 77030 USA. [Rosell, R.] Hosp Badalona Germans Trias & Pujol, Canc Biol & Precis Med Program, Catalan Inst Oncol, Barcelona, Spain. [Shaw, A. T.] Massachusetts Gen Hosp, Ctr Canc, Hematol Oncol, Boston, MA USA. [Weiss, G. J.] Canc Treatment Ctr Amer, Western Reg Med Ctr, Scottsdale, AZ USA. [Narasimhan, N. I.; Rivera, V. M.] ARIAD Pharmaceut Inc, Preclin & Translat Res, Cambridge, MA USA. [Dorer, D. J.; Clackson, T.] ARIAD Pharmaceut Inc, Res & Dev, Cambridge, MA USA. [Haluska, F. G.] ARIAD Pharmaceut Inc, Cambridge, MA USA. [Camidge, D. R.] Univ Colorado, Sch Med, Div Oncol, Denver, CO 80202 USA. NR 0 TC 0 Z9 0 U1 1 U2 3 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0169-5002 EI 1872-8332 J9 LUNG CANCER JI Lung Cancer PD JAN PY 2015 VL 87 SU 1 MA 81 BP S32 EP S32 PG 1 WC Oncology; Respiratory System SC Oncology; Respiratory System GA CE4IQ UT WOS:000351794700081 ER PT J AU Mackie, S Winkelman, JW AF Mackie, Susan Winkelman, John W. TI Insomnia SO PSYCHIATRIC ANNALS LA English DT Article ID MAJOR DEPRESSIVE DISORDER; SLEEP; PTSD AB Insomnia is frequently present in patients with a variety of psychiatric conditions. Both the Diagnostic and Statistical Manual of Mental Disorders, fifth edition and the International Classification of Sleep Disorders, third edition include definitions that emphasize symptoms of difficulty initiating or maintaining sleep in the face of adequate opportunity for sleep. Although insomnia has historically been thought of as merely a symptom of various psychiatric conditions, more recent research indicates that psychiatric patients with comorbid insomnia benefit from identification and specific treatment of the sleep disorder. This review provides an introduction to the changing definitions of insomnia disorder, discusses the complex relationship with psychiatric conditions, and outlines the most effective available treatment options for insomnia, including cognitive behavioral therapy and hypnotic agents. C1 [Mackie, Susan] Harvard Univ, Sch Med, Brigham & Womens Hosp, Med, Boston, MA 02138 USA. [Winkelman, John W.] Massachusetts Gen Hosp, Dept Psychiat, Sleep Disorders Clin Res Program, Boston, MA 02114 USA. [Winkelman, John W.] Harvard Univ, Sch Med, Cambridge, MA 02138 USA. RP Winkelman, JW (reprint author), Sleep Disorders Clin Res Program, 1 Bowdoin Sq,9th Floor, Boston, MA 02114 USA. EM jwwinkelman@partners.org FU UCB Pharma; Insys; FlexPharma; Merck Co. FX John W. Winkelman discloses consulting fees from UCB Pharma, Insys, FlexPharma, and Merck & Co.; contracted research for UCB Pharma and Purdue; and expert testimony for Cantor Colburn. The remaining author has no relevant financial relationships to disclose. NR 17 TC 0 Z9 0 U1 1 U2 10 PU SLACK INC PI THOROFARE PA 6900 GROVE RD, THOROFARE, NJ 08086 USA SN 0048-5713 EI 1938-2456 J9 PSYCHIAT ANN JI Psychiatr. Ann. PD JAN PY 2015 VL 45 IS 1 DI 10.3928/00485713-20150106-04 PG 9 WC Psychiatry SC Psychiatry GA CE6JG UT WOS:000351942100004 ER PT J AU Pusztaszeri, MP Faquin, WC AF Pusztaszeri, Marc P. Faquin, William C. TI Cytologic evaluation of cervical lymph node metastases from cancers of unknown primary origin SO SEMINARS IN DIAGNOSTIC PATHOLOGY LA English DT Article DE HPV; EBV; Oropharynx; Squamous cell carcinoma; Fine-needle aspiration; Cervical lymph node metastases ID FINE-NEEDLE-ASPIRATION; SQUAMOUS-CELL CARCINOMA; EPSTEIN-BARR-VIRUS; IN-SITU HYBRIDIZATION; PAPILLARY THYROID-CARCINOMA; HYBRID CAPTURE 2; HIGH-RISK HPV; HUMAN-PAPILLOMAVIRUS; NASOPHARYNGEAL CARCINOMA; NECK-CANCER AB Fine-needle aspiration biopsy (FNAB) is often the first diagnostic procedure performed in patients with head and neck (RN) masses. Metastatic squamous cell carcinoma (SCC) to cervical lymph nodes is by far the most common malignancy aspirated in the RN, but in approximately 3-10% of patients, a primary tumor will not be found even after complete clinico-radiological workup. Several HN cancers are associated with oncogenic viruses, including HPV-associated SCC and EBV-associated nasopharyngeal carcinoma (NPC). While the primary tumor is sometimes small or undetectable, patients often present initially with cervical lymph node metastases. HPV-associated SCC and EBV-associated NPC are typically non-keratinizing carcinomas that can mimic several other poorly differentiated HN cancers by FNAB but have a significantly better prognosis. Therefore, the precise classification of the metastatic disease in the FNAB material is very useful since it can facilitate the subsequent location of the primary tumor, and it can provide prognostic and therapeutic information as well. In this review, we discuss the major entities that can present as a metastatic cancer of unknown primary in cervical lymph node other than supraclavicular, including their cytologic features and the role of ancillary studies. (C) 2014 Elsevier Inc. All rights reserved. C1 [Pusztaszeri, Marc P.] Univ Hosp Geneva, Dept Pathol, CH-1211 Geneva 14, Switzerland. [Faquin, William C.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Faquin, William C.] Harvard Univ, Sch Med, Boston, MA USA. RP Pusztaszeri, MP (reprint author), Univ Hosp Geneva, Dept Pathol, 1 Rue Michel Servet, CH-1211 Geneva 14, Switzerland. EM Marc.Pusztaszeri@hcuge.ch NR 52 TC 6 Z9 6 U1 1 U2 4 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0740-2570 EI 1930-1111 J9 SEMIN DIAGN PATHOL JI Semin. Diagn. Pathol. PD JAN PY 2015 VL 32 IS 1 BP 32 EP 41 DI 10.1053/j.semdp.2014.12.002 PG 10 WC Medical Laboratory Technology; Pathology SC Medical Laboratory Technology; Pathology GA CE5PD UT WOS:000351886700005 PM 25618223 ER PT J AU Amgarten, B Rajan, R Martinez-Saez, N Oliveira, BL Albuquerque, IS Brooks, RA Reid, DG Duer, MJ Bernardes, GJL AF Amgarten, Beatrice Rajan, Rakesh Martinez-Saez, Nuria Oliveira, Bruno L. Albuquerque, Ines S. Brooks, Roger A. Reid, David G. Duer, Melinda J. Bernardes, Goncalo J. L. TI Collagen labelling with an azide-proline chemical reporter in live cells SO CHEMICAL COMMUNICATIONS LA English DT Article ID NEWLY SYNTHESIZED PROTEINS; CONFORMATIONAL STABILITY; MAMMALIAN-CELLS; CLICK CHEMISTRY; TRIPLE HELICES; LIVING CELLS; COPPER-FREE; VISUALIZATION AB We have developed a strategy for selective imaging of collagen in live foetal ovine osteoblasts. Our approach involves the incorporation of an azide-tagged proline in the biosynthesis of collagen followed by labelling using a strain-promoted [3+2] azide-alkyne cycloaddition reaction. C1 [Amgarten, Beatrice; Martinez-Saez, Nuria; Reid, David G.; Duer, Melinda J.; Bernardes, Goncalo J. L.] Univ Cambridge, Dept Chem, Cambridge CB2 1EW, England. [Rajan, Rakesh; Brooks, Roger A.] Univ Cambridge, Addenbrookes Hosp, Div Trauma & Orthopaed Surg, Cambridge CB2 0QQ, England. [Oliveira, Bruno L.] Harvard Univ, Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Sch Med,Dept Radiol, Charlestown, MA USA. [Albuquerque, Ines S.; Bernardes, Goncalo J. L.] Univ Lisbon, Fac Med, Inst Mol Med, P-1649028 Lisbon, Portugal. RP Bernardes, GJL (reprint author), Univ Cambridge, Dept Chem, Lensfield Rd, Cambridge CB2 1EW, England. EM gb453@cam.ac.uk RI Martinez-Saez, Nuria/L-1955-2016; Albuquerque, Ines/P-5325-2016; OI Albuquerque, Ines/0000-0002-1108-0961; Oliveira, Bruno/0000-0002-7687-4746; Bernardes, Goncalo/0000-0001-6594-8917 FU EU; FCT Portugal; EPSRC; National Institute of Health Research FX We thank the EU (Erasmus studentship to B.A.; Marie Curie CIG to G.J.L.B.), FCT Portugal (FCT Investigator to G.J.L.B.), the EPSRC and the National Institute of Health Research for funding. We also thank Karin Muller for help with confocal microscopy and SEM and Dr Filipa Cruz for critical reading of the manuscript. G.J.L.B. is a Royal Society University Research Fellow. NR 24 TC 1 Z9 1 U1 5 U2 16 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 2015 VL 51 IS 25 BP 5250 EP 5252 DI 10.1039/c4cc07974d PG 3 WC Chemistry, Multidisciplinary SC Chemistry GA CD9CG UT WOS:000351393600009 PM 25415185 ER PT J AU Yonekawa, Y Kim, IK AF Yonekawa, Yoshihiro Kim, Ivana K. TI Clinical Characteristics and Current Treatment of Age-Related Macular Degeneration SO COLD SPRING HARBOR PERSPECTIVES IN MEDICINE LA English DT Article ID POLYPOIDAL CHOROIDAL VASCULOPATHY; TISSUE-PLASMINOGEN ACTIVATOR; OPTICAL-COHERENCE-TOMOGRAPHY; RETINAL ANGIOMATOUS PROLIFERATION; VERTEPORFIN PHOTODYNAMIC THERAPY; THICK SUBMACULAR HEMORRHAGE; ENDOTHELIAL GROWTH-FACTOR; BEAVER DAM EYE; VEGF TRAP-EYE; GEOGRAPHIC ATROPHY AB Age-related macular degeneration (AMD) is a multifactorial degeneration of photoreceptors and retinal pigment epithelium. The societal impact is significant, with more than 2 million individuals in the United States alone affected by advanced stages of AMD. Recent progress in our understanding of this complex disease and parallel developments in therapeutics and imaging have translated into new management paradigms in recent years. However, there are many unanswered questions, and diagnostic and prognostic precision and treatment outcomes can still be improved. In this article, we discuss the clinical features of AMD, provide correlations with modern imaging and histopathology, and present an overview of treatment strategies. C1 [Yonekawa, Yoshihiro; Kim, Ivana K.] Harvard Univ, Sch Med, Massachusetts Eye & Ear Infirm, Dept Ophthalmol,Retina Serv, Boston, MA 02114 USA. RP Kim, IK (reprint author), Harvard Univ, Sch Med, Massachusetts Eye & Ear Infirm, Dept Ophthalmol,Retina Serv, Boston, MA 02114 USA. EM Ivana_Kim@meei.harvard.edu NR 124 TC 2 Z9 2 U1 1 U2 3 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 2015 VL 5 IS 1 AR a017178 DI 10.1101/cshperspect.a017178 PG 18 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA CD6YM UT WOS:000351236900004 ER PT J AU Puchner, SB Ferencik, M Maurovich-Horvat, P Nakano, M Otsuka, F Kauczor, HU Virmani, R Hoffmann, U Schlett, CL AF Puchner, Stefan B. Ferencik, Maros Maurovich-Horvat, Pal Nakano, Masataka Otsuka, Fumiyuki Kauczor, Hans-Ulrich Virmani, Renu Hoffmann, Udo Schlett, Christopher L. TI Iterative image reconstruction algorithms in coronary CT angiography improve the detection of lipid-core plaque - a comparison with histology SO EUROPEAN RADIOLOGY LA English DT Article DE Coronary CT angiography; Iterative reconstruction algorithm; Vulnerable plaque; Low attenuation plaque; Diagnostic accuracy ID 64-SLICE COMPUTED-TOMOGRAPHY; FILTERED BACK-PROJECTION; INTRAVASCULAR ULTRASOUND; ATHEROSCLEROTIC LESIONS; VULNERABLE PLAQUE; ARTERY CALCIUM; CARDIAC CT; QUANTIFICATION; STENOSIS; MODEL AB Objectives To evaluate whether iterative reconstruction algorithms improve the diagnostic accuracy of coronary CT angiography (CCTA) for detection of lipid-core plaque (LCP) compared to histology. Methods and materials CCTA and histological data were acquired from three ex vivo hearts. CCTA images were reconstructed using filtered back projection (FBP), adaptivestatistical (ASIR) and model-based (MBIR) iterative algorithms. Vessel cross-sections were co-registered between FBP/ASIR/MBIR and histology. Plaque area <60 HU was semiautomatically quantified in CCTA. LCP was defined by histology as fibroatheroma with a large lipid/necrotic core. Area under the curve (AUC) was derived from logistic regression analysis as a measure of diagnostic accuracy. Results Overall, 173 CCTA triplets (FBP/ASIR/MBIR) were co-registered with histology. LCP was present in 26 crosssections. Average measured plaque area <60 HU was significantly larger in LCP compared to non-LCP cross-sections (mm(2): 5.78 +/- 2.29 vs. 3.39 +/- 1.68 FBP; 5.92 +/- 1.87 vs. 3.43 +/- 1.62 ASIR; 6.40 +/- 1.55 vs. 3.49 +/- 1.50 MBIR; all p<0.0001). AUC for detecting LCP was 0.803/0.850/0.903 for FBP/ASIR/MBIR and was significantly higher for MBIR compared to FBP (p=0.01). MBIR increased sensitivity for detection of LCP by CCTA. Conclusion Plaque area <60 HU in CCTA was associated with LCP in histology regardless of the reconstruction algorithm. However, MBIR demonstrated higher accuracy for detecting LCP, which may improve vulnerable plaque detection by CCTA. C1 [Puchner, Stefan B.; Ferencik, Maros; Maurovich-Horvat, Pal; Hoffmann, Udo; Schlett, Christopher L.] Harvard Univ, Sch Med, Dept Radiol, Cardiac MR PET CT Program,Massachusetts Gen Hosp, Boston, MA 02115 USA. [Puchner, Stefan B.] Med Univ Vienna, Dept Biomed Imaging & Image Guided Therapy, Vienna, Austria. [Ferencik, Maros] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Cardiol, Boston, MA 02115 USA. [Maurovich-Horvat, Pal] Semmelweis Univ, MTA SE Lendulet Cardiovasc Imaging Res Grp, Heart & Vasc Ctr, H-1085 Budapest, Hungary. [Nakano, Masataka; Otsuka, Fumiyuki; Virmani, Renu] CV Path Inst Inc, Gaithersburg, MD USA. [Kauczor, Hans-Ulrich; Schlett, Christopher L.] Heidelberg Univ, Dept Diagnost & Intervent Radiol, Univ Heidelberg Hosp, Heidelberg, Germany. RP Schlett, CL (reprint author), Harvard Univ, Sch Med, Dept Radiol, Cardiac MR PET CT Program,Massachusetts Gen Hosp, Boston, MA 02115 USA. EM christopher.schlett@post.harvard.edu FU GE Healthcare, Milwaukee WI FX The scientific guarantor of this publication is Prof. Dr. Udo Hoffmann, Division Head of Cardiac and Vascular Imaging, Massachusetts General Hospital/Harvard Medical School, Boston, MA. The authors of this manuscript declare relationships with the following companies: This work was supported by an unrestricted grant from GE Healthcare, Milwaukee WI. The authors had access to pre-commercial image reconstruction algorithms as developed by GE Healthcare. Commercially available software for the (semi-) automated plaque assessment was provided free of charge by Vital Images, Minnetonka, MN. One of the authors has significant statistical expertise. Institutional Review Board approval was obtained. Written informed consent was waived by the Institutional Review Board. Some study subjects or cohorts have been previously reported as part of the MGH Multi-Modality Coronary Plaque Imaging Database [Maurovich-Horvat P, Schlett CL, Alkadhi H, et al. Differentiation of early from advanced coronary atherosclerotic lesions: systematic comparison of CT, intravascular US, and optical frequency domain imaging with histopathologic examination in ex vivo human hearts. Radiology. 2012 Nov; 265(2): 393-401]. Methodology: prospective, experimental (ex vivo), performed at one institution. NR 52 TC 9 Z9 9 U1 2 U2 7 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0938-7994 EI 1432-1084 J9 EUR RADIOL JI Eur. Radiol. PD JAN PY 2015 VL 25 IS 1 BP 15 EP 23 DI 10.1007/s00330-014-3404-6 PG 9 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA CD6UQ UT WOS:000351225500003 PM 25182630 ER PT J AU Kwon, JY Zurakowski, D Ellington, JK AF Kwon, John Y. Zurakowski, David Ellington, J. Kent TI Influence of Contralateral Radiographs on Accuracy of Anatomic Reduction in Surgically Treated Calcaneus Fractures SO FOOT & ANKLE INTERNATIONAL LA English DT Article DE calcaneus; fracture; template; contralateral X-ray ID ANGLES; BOHLERS; RELIABILITY; POPULATION AB Background: The purpose of this study was to determine whether obtaining a radiograph of the uninjured contralateral calcaneus (template) before surgery allowed for more precise restoration of Bohler's angle and calcaneal length when performing open reduction internal fixation (ORIF) of intra-articular calcaneus fractures. Methods: Patients who sustained an intra-articular calcaneus fracture requiring surgery who met inclusion criteria were prospectively randomized into those who had a preoperative template obtained for review at the time of ORIF (group 1) versus those who had the contralateral radiograph obtained after surgery (group 2). Results: There was no benefit of the preoperative template in allowing for more anatomic restoration of Bohler's angle or calcaneal length. Operative time was decreased with the use of a preoperative template when using the extensile lateral or percutaneous approaches. Conclusion: Preoperative templating of the uninjured contralateral calcaneus did not allow for more anatomic reduction or restoration of pre-injury morphology of the calcaneus undergoing operative fixation as based on Bohler's angle and calcaneal length. Templating may be of benefit by reducing operative time. C1 [Kwon, John Y.] Massachusetts Gen Hosp, Dept Orthopaed Surg, Boston, MA 02115 USA. [Zurakowski, David] Boston Childrens Hosp, Boston, MA USA. [Ellington, J. Kent] Foot & Ankle Inst, OrthoCarolina, Charlotte, NC USA. RP Kwon, JY (reprint author), Massachusetts Gen Hosp, Dept Orthopaed Surg, Boston, MA 02115 USA. EM johnkwonmd@gmail.com NR 23 TC 5 Z9 5 U1 0 U2 0 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 1071-1007 EI 1944-7876 J9 FOOT ANKLE INT JI Foot Ankle Int. PD JAN PY 2015 VL 36 IS 1 BP 75 EP 82 DI 10.1177/1071100714552483 PG 8 WC Orthopedics SC Orthopedics GA CD7BD UT WOS:000351244300013 PM 25301892 ER PT J AU Chamberlain, D Sweeney, CJ AF Chamberlain, Dominic Sweeney, Christopher J. TI Insights into E3805: the CHAARTED trial SO FUTURE ONCOLOGY LA English DT Editorial Material DE androgen-deprivation therapy; docetaxel; hormone-sensitive metastatic prostate cancer C1 [Chamberlain, Dominic] Dana Farber Canc Inst, Boston, MA 02215 USA. [Sweeney, Christopher J.] Indiana Univ, Med Ctr, Bloomington, IN 47405 USA. [Sweeney, Christopher J.] Simon Canc Ctr, Indianapolis, IN USA. [Sweeney, Christopher J.] Dana Farber Canc Inst, Lank Ctr Genitourinary Oncol, Boston, MA USA. [Sweeney, Christopher J.] Harvard Univ, Sch Med, Cambridge, MA 02138 USA. RP Chamberlain, D (reprint author), Dana Farber Canc Inst, Boston, MA 02215 USA. NR 0 TC 2 Z9 2 U1 1 U2 2 PU FUTURE MEDICINE LTD PI LONDON PA UNITEC HOUSE, 3RD FLOOR, 2 ALBERT PLACE, FINCHLEY CENTRAL, LONDON, N3 1QB, ENGLAND SN 1479-6694 EI 1744-8301 J9 FUTURE ONCOL JI Future Oncol. PY 2015 VL 11 IS 6 BP 897 EP 899 DI 10.2217/FON.14.310 PG 3 WC Oncology SC Oncology GA CD7ON UT WOS:000351280200005 ER PT J AU Zhang, MY Keel, SB Walsh, T Lee, MK Gulsuner, S Watts, AC Pritchard, CC Salipante, SJ Jeng, MR Hofmann, I Williams, DA Fleming, MD Abkowitz, JL King, MC Shimamura, A AF Zhang, Michael Y. Keel, Sioban B. Walsh, Tom Lee, Ming K. Gulsuner, Suleyman Watts, Amanda C. Pritchard, Colin C. Salipante, Stephen J. Jeng, Michael R. Hofmann, Inga Williams, David A. Fleming, Mark D. Abkowitz, Janis L. King, Mary-Claire Shimamura, Akiko TI Genomic analysis of bone marrow failure and myelodysplastic syndromes reveals phenotypic and diagnostic complexity SO HAEMATOLOGICA LA English DT Article ID DNA-LIGASE-IV; SHWACHMAN-DIAMOND-SYNDROME; PROTEIN GENE DELETIONS; ACUTE MYELOID-LEUKEMIA; B-CELL LYMPHOMA; DYSKERATOSIS-CONGENITA; MONOMAC SYNDROME; FANCONI-ANEMIA; GATA2 MUTATIONS; HIGH-FREQUENCY AB Accurate and timely diagnosis of inherited bone marrow failure and inherited myelodysplastic syndromes is essential to guide clinical management. Distinguishing inherited from acquired bone marrow failure/myelodysplastic syndrome poses a significant clinical challenge. At present, diagnostic genetic testing for inherited bone marrow failure/myelodysplastic syndrome is performed gene-by-gene, guided by clinical and laboratory evaluation. We hypothesized that standard clinically-directed genetic testing misses patients with cryptic or atypical presentations of inherited bone marrow failure/myelodysplastic syndrome. In order to screen simultaneously for mutations of all classes in bone marrow failure/myelodysplastic syndrome genes, we developed and validated a panel of 85 genes for targeted capture and multiplexed massively parallel sequencing. In patients with clinical diagnoses of Fanconi anemia, genomic analysis resolved subtype assignment, including those of patients with inconclusive complementation test results. Eight out of 71 patients with idiopathic bone marrow failure or myelodysplastic syndrome were found to harbor damaging germline mutations in GATA2, RUNX1, DKC1, or LIG4. All 8 of these patients lacked classical clinical stigmata or laboratory findings of these syndromes and only 4 had a family history suggestive of inherited disease. These results reflect the extensive genetic heterogeneity and phenotypic complexity of bone marrow failure/myelodysplastic syndrome phenotypes. This study supports the integration of broad unbiased genetic screening into the diagnostic workup of children and young adults with bone marrow failure and myelodysplastic syndromes. C1 [Zhang, Michael Y.; Shimamura, Akiko] Fred Hutchinson Canc Res Ctr, Clin Res Div, Seattle, WA 98104 USA. [Keel, Sioban B.; Abkowitz, Janis L.] Univ Washington, Dept Med, Div Hematol, Seattle, WA 98195 USA. [Walsh, Tom; Lee, Ming K.; Gulsuner, Suleyman; Watts, Amanda C.; King, Mary-Claire] Univ Washington, Dept Med, Seattle, WA 98195 USA. [Walsh, Tom; Lee, Ming K.; Gulsuner, Suleyman; Watts, Amanda C.; King, Mary-Claire] Univ Washington, Dept Genome Sci, Seattle, WA 98195 USA. [Pritchard, Colin C.; Salipante, Stephen J.] Univ Washington, Dept Lab Med, Seattle, WA 98195 USA. [Jeng, Michael R.] Stanford Univ, Sch Med, Dept Pediat, Stanford, CA 94305 USA. [Hofmann, Inga; Williams, David A.] Childrens Hosp, Dana Farber Canc Inst, Div Hematol Oncol, Boston, MA 02115 USA. [Hofmann, Inga; Williams, David A.] Harvard Univ, Sch Med, Boston, MA USA. [Williams, David A.] Harvard Stem Cell Inst, Boston, MA USA. [Fleming, Mark D.] Boston Childrens Hosp, Dept Pathol, Boston, MA USA. [Shimamura, Akiko] Seattle Childrens Hosp, Dept Pediat Hematol Oncol, Seattle, WA USA. [Shimamura, Akiko] Univ Washington, Dept Pediat, Seattle, WA 98195 USA. RP Shimamura, A (reprint author), Fred Hutchinson Canc Res Ctr, Clin Res Div, 1124 Columbia St, Seattle, WA 98104 USA. EM ashimamu@fhcrc.org OI Walsh, Tom/0000-0002-8875-0310 FU NIH/NIDDK [R24DK093425, R24DK099808, R24DK094746, T32AG000057]; Ghiglione Aplastic Anemia Fund; Julian's Dinosaur Guild at Seattle Children's Hospital FX This work was supported by NIH/NIDDK grants R24DK093425 and R24DK099808 (A.S., M.C.K., J.A.), R24DK094746 (M.D.F., D.A.W.), T32AG000057 (M.Y.Z.), and the Ghiglione Aplastic Anemia Fund and the Julian's Dinosaur Guild at Seattle Children's Hospital (A.S.). M.C.K. is an American Cancer Society professor. NR 48 TC 24 Z9 24 U1 1 U2 5 PU FERRATA STORTI FOUNDATION PI PAVIA PA VIA GIUSEPPE BELLI 4, 27100 PAVIA, ITALY SN 0390-6078 J9 HAEMATOLOGICA JI Haematologica PD JAN PY 2015 VL 100 IS 1 BP 42 EP 48 DI 10.3324/haematol.2014.113456 PG 7 WC Hematology SC Hematology GA CD7NX UT WOS:000351278500021 PM 25239263 ER PT J AU Dimopoulos, MA Orlowski, RZ Facon, T Sonneveld, P Anderson, KC Beksac, M Benboubker, L Roddie, H Potamianou, A Couturier, C Feng, H Ataman, O de Velde, HV Richardson, PG AF Dimopoulos, Meletios A. Orlowski, Robert Z. Facon, Thierry Sonneveld, Pieter Anderson, Kenneth C. Beksac, Meral Benboubker, Lotfi Roddie, Huw Potamianou, Anna Couturier, Catherine Feng, Huaibao Ataman, Ozlem de Velde, Helgi van Richardson, Paul G. TI Retrospective matched-pairs analysis of bortezomib plus dexamethasone versus bortezomib monotherapy in relapsed multiple myeloma SO HAEMATOLOGICA LA English DT Article ID RANDOMIZED PHASE-III; EXTENDED FOLLOW-UP; REFRACTORY MYELOMA; COMBINATION; SURVIVAL; MULTICENTER; TRIAL; TIME; PROGRAM; DISEASE AB Bortezomib-dexamethasone is widely used for relapsed myeloma in routine clinical practice, but comparative data versus single-agent bortezomib are lacking. This retrospective analysis compared second-line treatment with bortezomib-dexamethasone and bortezomib using 109 propensity score-matched pairs of patients treated in three clinical trials: MMY-2045, APEX, and DOXIL-MMY-3001. Propensity scores were estimated using logistic regression analyses incorporating 13 clinical variables related to drug exposure or clinical outcome. Patients received intravenous bortezomib 1.3 mg/m(2) on days 1, 4, 8, and 11, in 21-day cycles, alone or with oral dexamethasone 20 mg on the days of/after bortezomib dosing. Median bortezomib cumulative dose (27.02 and 28.60 mg/m2) and treatment duration (19.6 and 17.6 weeks) were similar with bortezomib-dexamethasone and bortezomib, respectively. The overall response rate was higher (75% vs. 41%; odds ratio=3.467; P<0.001), and median time-to-progression (13.6 vs. 7.0 months; hazard ratio [HR]=0.394; P=0.003) and progression-free survival (11.9 vs. 6.4 months; HR=0.595; P=0.051) were longer with bortezomib-dexamethasone versus bortezomib, respectively. Rates of any-grade adverse events, most common grade 3 or higher adverse events, and discontinuations due to adverse events appeared similar between the groups. Two patients per group died of treatment-related adverse events. These data indicate the potential benefit of bortezomib-dexamethasone compared with single-agent bortezomib at first relapse in myeloma. The MMY-2045, APEX, and DOXIL-MMY-3001 clinical trials were registered at, respectively, clinicaltrials.govidentifier: 00908232, 00048230, and 00103506. C1 [Dimopoulos, Meletios A.] Univ Athens, Sch Med, Dept Clin Therapeut, GR-10679 Athens, Greece. [Orlowski, Robert Z.] Univ Texas Houston, MD Anderson Canc Ctr, Houston, TX 77030 USA. [Facon, Thierry] Hop Claude Huriez, Lille, France. [Sonneveld, Pieter] Univ Rotterdam Hosp, Erasmus Med Ctr, Dept Hematol, Rotterdam, Netherlands. [Anderson, Kenneth C.; Richardson, Paul G.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Beksac, Meral] Ankara Univ, Sch Med, Dept Hematol, TR-06100 Ankara, Turkey. [Benboubker, Lotfi] CHRU, Ctr Reg Cancerol Henry Kaplan, Tours, France. [Benboubker, Lotfi] Hop Bretonneau, Tours, France. [Roddie, Huw] Western Gen Hosp, Dept Haematol, Edinburgh EH4 2XU, Midlothian, Scotland. [Potamianou, Anna] Janssen Cilag Pharmaceut SACI, Athens, Greece. [Couturier, Catherine] Janssen Cilag, Issy Les Moulineaux, France. [Feng, Huaibao] Janssen Res & Dev LLC, Raritan, NJ USA. [Ataman, Ozlem] Janssen Cilag UK, High Wycombe, Bucks, England. [de Velde, Helgi van] Div Janssen Pharmaceut NV, Janssen Res & Dev, Beerse, Belgium. RP Dimopoulos, MA (reprint author), Univ Athens, Sch Med, Dept Clin Therapeut, GR-10679 Athens, Greece. EM mdimop@med.uoa.gr RI FACON, THIERRY/M-9736-2014 OI FACON, THIERRY/0000-0001-7705-8460 FU Janssen Research Development FX This work was supported by Janssen Research & Development. NR 43 TC 19 Z9 20 U1 0 U2 1 PU FERRATA STORTI FOUNDATION PI PAVIA PA VIA GIUSEPPE BELLI 4, 27100 PAVIA, ITALY SN 0390-6078 J9 HAEMATOLOGICA JI Haematologica PD JAN PY 2015 VL 100 IS 1 BP 100 EP 106 DI 10.3324/haematol.2014.112037 PG 7 WC Hematology SC Hematology GA CD7NX UT WOS:000351278500029 PM 25261096 ER PT J AU Ehret, PJ LaBrie, JW Santerre, C Sherman, DK AF Ehret, Phillip J. LaBrie, Joseph W. Santerre, Craig Sherman, David K. TI Self-affirmation and motivational interviewing: integrating perspectives to reduce resistance and increase efficacy of alcohol interventions SO HEALTH PSYCHOLOGY REVIEW LA English DT Article DE message processing; intervention efficacy; self-affirmation theory; resistance; alcohol interventions; motivational interviewing ID HEALTH-RISK INFORMATION; RANDOMIZED CONTROLLED-TRIAL; POSITIVE-AFFECT; PHYSICAL-ACTIVITY; BEHAVIOR-CHANGE; DISSONANCE; STRESS; DEFENSIVENESS; VULNERABILITY; CONSEQUENCES AB To promote efforts at reducing problematic alcohol use and improving health outcomes, the present review proposes an integration of a social psychological approach - self-affirmation theory - with a clinical psychology intervention - motivational interviewing. Motivational interviewing (MI) is a popular empirically-designed treatment approach that has shown moderate success at reducing drinking and improving health, especially with resistant drinkers. Experiments informed by self-affirmation theory have found that people exhibit reduced defensiveness to threatening health messages and increased intentions to reduce alcohol consumption when affirmed. This review focuses on the mechanisms by which self-affirmation reduces resistance and how these mechanisms are complementary to the MI approach. Further, the review outlines suggestions for conducting and integrating self-affirmation into a MI intervention and provides recommendations for future empirical research. C1 [Ehret, Phillip J.; Sherman, David K.] Univ Calif Santa Barbara, Dept Psychol & Brain Sci, Santa Barbara, CA 93106 USA. [LaBrie, Joseph W.] Loyola Marymount Univ, Dept Psychol, Los Angeles, CA 90045 USA. [Santerre, Craig] Vet Affairs Puget Sound Hlth Care Syst, Seattle Div, Seattle, WA 98108 USA. RP Ehret, PJ (reprint author), Univ Calif Santa Barbara, Dept Psychol & Brain Sci, Santa Barbara, CA 93106 USA. EM ehret@psych.ucsb.edu NR 80 TC 2 Z9 2 U1 3 U2 16 PU ROUTLEDGE JOURNALS, TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXFORDSHIRE, ENGLAND SN 1743-7199 EI 1743-7202 J9 HEALTH PSYCHOL REV JI Health Psychol. Rev. PD JAN 1 PY 2015 VL 9 IS 1 BP 83 EP 102 DI 10.1080/17437199.2013.840953 PG 20 WC Psychology, Clinical SC Psychology GA CE3SJ UT WOS:000351748500010 PM 25793492 ER PT J AU Cummings, J Mintzer, J Brodaty, H Sano, M Banerjee, S Devanand, DP Gauthier, S Howard, R Lanctot, K Lyketsos, CG Peskind, E Porsteinsson, AP Reich, E Sampaio, C Steffens, D Wortmann, M Zhong, K AF Cummings, Jeffrey Mintzer, Jacobo Brodaty, Henry Sano, Mary Banerjee, Sube Devanand, D. P. Gauthier, Serge Howard, Robert Lanctot, Krista Lyketsos, Constantine G. Peskind, Elaine Porsteinsson, Anton P. Reich, Edgardo Sampaio, Cristina Steffens, David Wortmann, Marc Zhong, Kate TI Agitation in cognitive disorders: International Psychogeriatric Association provisional consensus clinical and research definition SO INTERNATIONAL PSYCHOGERIATRICS LA English DT Article DE Alzheimer's disease; agitation; cognitive impairment; aggression; International Psychogeriatric Association; Food and Drug Administration; clinical trials; intervention; epidemiology ID NEUROPSYCHIATRIC SYMPTOMS; ALZHEIMERS-DISEASE; BEHAVIORAL SYMPTOMS; NURSING-HOME; DEMENTIA; MANAGEMENT; EFFICACY; MEMORY AB Background: Agitation is common across neuropsychiatric disorders and contributes to disability, institutionalization, and diminished quality of life for patients and their caregivers. There is no consensus definition of agitation and no widespread agreement on what elements should be included in the syndrome. The International Psychogeriatric Association formed an Agitation Definition Work Group (ADWG) to develop a provisional consensus definition of agitation in patients with cognitive disorders that can be applied in epidemiologic, non-interventional clinical, pharmacologic, non-pharmacologic interventional, and neurobiological studies. A consensus definition will facilitate communication and cross-study comparison and may have regulatory applications in drug development programs. Methods: The ADWG developed a transparent process using a combination of electronic, face-to-face, and survey-based strategies to develop a consensus based on agreement of a majority of participants. Nine-hundred twenty-eight respondents participated in the different phases of the process. Results: Agitation was defined broadly as: (1) occurring in patients with a cognitive impairment or dementia syndrome; (2) exhibiting behavior consistent with emotional distress; (3) manifesting excessive motor activity, verbal aggression, or physical aggression; and (4) evidencing behaviors that cause excess disability and are not solely attributable to another disorder (psychiatric, medical, or substance-related). A majority of the respondents rated all surveyed elements of the definition as "strongly agree" or "somewhat agree" (68-88% across elements). A majority of the respondents agreed that the definition is appropriate for clinical and research applications. Conclusions: A provisional consensus definition of agitation has been developed. This definition can be used to advance interventional and non-interventional research of agitation in patients with cognitive impairment. C1 [Cummings, Jeffrey; Zhong, Kate] Cleveland Clin, Lou Ruvo Ctr Brain Hlth, Las Vegas, NV 89106 USA. [Mintzer, Jacobo] Roper St Francis Hosp, Clin Biotechnol Res Inst, Charleston, SC USA. [Brodaty, Henry] Univ New S Wales, Ctr Hlth Brain Ageing, Sydney, NSW, Australia. [Sano, Mary] Mt Sinai Sch Med, New York, NY USA. [Banerjee, Sube] Univ Sussex, Trafford Ctr Med Res, Brighton & Sussex Med Sch, Brighton, E Sussex, England. [Devanand, D. P.] New York State Psychiat Inst & Hosp, New York, NY 10032 USA. [Gauthier, Serge] Douglas Mental Hlth Univ Inst Montreal, McGill Ctr Studies Aging, Montreal, PQ, Canada. [Howard, Robert] Kings Coll London, Inst Psychiat, London WC2R 2LS, England. [Lanctot, Krista] Univ Toronto, Sunnybrook Res Inst, Toronto, ON, Canada. [Lyketsos, Constantine G.] Johns Hopkins Bayview Med Ctr, Johns Hopkins Memory & Alzheimers Treatment Ctr, Baltimore, MD USA. [Peskind, Elaine] VA Puget Sound Hlth Care Syst, Seattle, WA USA. [Porsteinsson, Anton P.] Monroe Community Hosp, Rochester, NY USA. [Reich, Edgardo] Univ Buenos Aires, Hosp Julio Mendez, Dept Neurosci, Buenos Aires, DF, Argentina. [Sampaio, Cristina] CHDI Fdn, Princeton, NJ USA. [Steffens, David] Univ Connecticut, Ctr Hlth, Dept Psychiat, Farmington, CT 06032 USA. [Wortmann, Marc] Alzheimers Dis Int, London, England. RP Cummings, J (reprint author), Cleveland Clin, Lou Ruvo Ctr Brain Hlth, 888 W Bonneville Ave, Las Vegas, NV 89106 USA. EM cumminj@ccf.org FU Otsuka and Avanir Pharmaceutricals; Eli Lilly; Associated Jewish Federation of Baltimore; Weinberg Foundation; Forest; GlaxoSmithKline; Eisai; Pfizer; Astra-Zeneca; Lilly; Ortho-McNeil; Bristol-Myers; Novartis; National Football League; Elan; Functional Neuromodulation; Takeda Global Research and Development Center; Genentech; Merck; Accera; Avanir; F. Hoffmann-La Roche; Baxter; Wyeth; Janssen Alzheimer Initiative; Genentech/Roche; Toyama; Bayer; MerckSerono; Mertz; Teva; National Institute of Mental Health; American Psychiatric Press FX The sponsors, Otsuka and Avanir Pharmaceutricals, gave unrestricted education grants to help support the international meeting that was part of the definition-building process.; Dr. Jeffrey Cummings has provided consultation to Acadia, ADAMAS, Anavex, Avanir, Boehinger-Ingelheim, Eisai, EnVivo, GE Healthcare, Genentech, Lilly, Lundbeck, Medavante, Merck, Novartis, Otsuka, Pfizer, Prana, QR Pharma, Resverlogix, Roche, Sonexa, Suven, Takeda, and Toyoma companies. Dr. Cummings owns the copyright of the Neuropsychiatric Inventory.; Professor Sube Banerjee has received consultancy fees, honoraria for speaking, and support in attending conferences from the makers of anti-dementia medication and other psychotropics, including Abbvie, Eisai, Pfizer, Novartis, Lilly, and Shire.; Professor Henry Brodaty has served as investigator for Janssen, Lilly, Medivation, Merck, Sanofi, Servier, and Tau Therapeutics, and has been on the advisory boards of Pfizer, Novartis, Janssen, Lundbeck, and Nutricia. Dr. Brodaty has provided consultation to Baxter, Lilly, Merck, and Nutricia.; D.P. Devanand has received research support from Eli Lilly, and has provided consultation to AbbVie.; Dr. Serge Gauthier has been on the scientific advisory board or investigator with Abbvie, Affiris, Eisai, Lilly, Navidea, Novartis, Pfizer, Sanofi-Synthelabo, Servier, and TauRx.; Professor Robert Howard reports that he has no relevant disclosures to make.; Dr. Krista Lanctot has had research support and/or speaker's honoraria from Abbvie Canada, Lundbeck Canada Inc., Pfizer Canada Inc., Janssen Ortho, and Rocheand Wyeth.; Dr. Constantine Lyketsos has received grant support (research or CME) from Associated Jewish Federation of Baltimore, Weinberg Foundation, Forest, GlaxoSmithKline, Eisai, Pfizer, Astra-Zeneca, Lilly, Ortho-McNeil, Bristol-Myers, Novartis, National Football League, Elan, and Functional Neuromodulation. Dr. Lyketsos has been a consultant or advisor to Astra-Zeneca, GlaxoSmithKline, Eisai, Novartis, Forest, Supernus, Adlyfe, Takeda, Wyeth, Lundbeck, Merz, Lilly, Pfizer, Genentech, Elan, NFL Players Association, NFL Benefits Office, Avanir, Zinfandel, BMS, Abvie, Janssen, and Orion. Honorarium or travel support has been received from Pfizer, Forest, GlaxoSmithKline, and Health Monitor.; Dr. Jacobo Mintzer reports receipt of grants to his institution from Takeda Global Research and Development Center, Pfizer, Genentech, Merck, Accera, Elan, Avanir, F. Hoffmann-La Roche, Novartis, Baxter, Eli Lilly, Wyeth, and Janssen Alzheimer Initiative; and employment with NeuroQuest, and BioPharma Connex.; Dr. Elaine Peskind has been on the speakers' bureau for Forest Pharmaceuticals and on the Advisory Committee for Avanir. Dr. Peskind served on the Adjudication Committee for Takeda Pharmaceuticals.; Dr. Anton Porsteinsson has received a grant for his institution from Avanir, Eisai, Elan, Genentech/Roche, Janssen Alzheimer Initiative, Merck, Pfizer, and Toyama. He has provided consultation for Elan, Janssen Alzheimer Initiative, and TransTech Pharma. Dr. Porsteinsson has membership on data safety and monitoring boards for Quintiles.; Dr. Edgardo Reich has participated as investigator in different pharmaceutical-sponsored trials for Ely Lilly, Glaxo, Forest, Mertz. Astra Zeneca, Novartis, Roche, and Janssen. He has received travel grants from Bayer, MerckSerono, Novartis, Mertz, and Teva.; Dr. Cristina Sampaio has been a consultant for Abbvie, Alkermes, AstraZeneca, Avanir, Biogen, BMS, Chelsea, Genzyme, Lilly, Lundbeck, Otsuka, Pfizer, Roche, Sanofi, Servier, Takeda, and Teva.; Dr. Mary Sano has been on the Scientific Advisory Board for Medication and as a consultant for Bayer Schering Pharma, Bristol-Meyers Squibb, Elan, Genentech, Medivation, Medpace, Pfizer, Janssen, Takeda, and United Biosource.; Dr. David Steffens is supported through grants from the National Institute of Mental Health, and he receives textbook royalties from the American Psychiatric Press.; Dr. Marc Wortmann reports no other salaries than from Alzheimer's Disease International.; Dr. Kate Zhong has provided consultation to Avanir, Pfizer, Janssen, and Wyeth Pharmaceuticals. NR 31 TC 24 Z9 24 U1 5 U2 12 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 32 AVENUE OF THE AMERICAS, NEW YORK, NY 10013-2473 USA SN 1041-6102 EI 1741-203X J9 INT PSYCHOGERIATR JI Int. Psychogeriatr. PD JAN PY 2015 VL 27 IS 1 BP 7 EP 17 DI 10.1017/S1041610214001963 PG 11 WC Psychology, Clinical; Geriatrics & Gerontology; Gerontology; Psychiatry; Psychology SC Psychology; Geriatrics & Gerontology; Psychiatry GA CD4LX UT WOS:000351055400003 PM 25311499 ER PT J AU Crnej, A Omoto, M Dohlman, TH Dohlman, CH Dana, R AF Crnej, Alja Omoto, Masahiro Dohlman, Thomas H. Dohlman, Claes H. Dana, Reza TI Corneal Inflammation After Miniature Keratoprosthesis Implantation SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Article DE Boston Keratoprosthesis; penetrating keratoplasty; cornea inflammation; syngeneic; allogeneic ID REPEAT PENETRATING KERATOPLASTY; LONG-TERM OUTCOMES; BOSTON KERATOPROSTHESIS; I KERATOPROSTHESIS; CROSS-LINKING; GRAFT FAILURE; DONOR CORNEAS; RISK-FACTORS; TRANSPLANTATION; MULTICENTER AB PURPOSE. To compare corneal inflammation after syngeneic and allogeneic penetrating keratoplasty (PK) with miniature Keratoprosthesis (m-KPro) implantation in mice. METHODS. BALB/C (syngeneic) or C57BL/6 (allogeneic) corneas were transplanted onto BALB/C host beds as part of PK or m-KPro implantation. Corneal inflammation was assessed by determining the frequencies of CD45(+) leukocytes, CD4(+) T cells, CD11b(+) cells, and Gr-1(+) granulocytes/monocytes by flow cytometry at 2, 4, and 8 weeks post transplantation. In addition, expression levels of the proinflammatory cytokines TNF-alpha and IL-1 beta were analyzed using real-time qPCR at 8 weeks post transplantation. RESULTS. Cell frequencies in the syngeneic (syn) and allogeneic (allo) m-KPro groups were higher compared with the syngeneic and allogeneic PK groups, respectively, at all time points. However, after week 4, frequencies of all analyzed immune cells were higher in the alloPK group as compared with synKPro group. At 8 weeks, the expression of TNF-alpha was higher in synKPro, alloPK, and alloKPro groups compared with the naive and synPK groups. The expression of IL-1 beta was significantly higher in both KPro groups as compared with PK groups. CONCLUSIONS. Although the m-KPro device augments the inflammatory response in the cornea after its implantation, allogenicity (of the carrier tissue) is also a significant contributor to corneal inflammation. These data suggest that using syngeneic or decellularized corneal tissue as a Boston-KPro carrier could reduce the postoperative inflammation response. C1 Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Boston, MA USA. Harvard Univ, Sch Med, Schepens Eye Res Inst, Boston, MA USA. RP Dana, R (reprint author), Schepens Eye Res Inst, 20 Staniford St, Boston, MA 02114 USA. EM reza_dana@meei.harvard.edu FU Boston-KPro research fund (Boston, MA, USA); National Institutes of Health (Bethesda, MD, USA) [R01-EY 12963] FX Supported by grants from the Boston-KPro research fund (Boston, MA, USA) and the National Institutes of Health (Grant R01-EY 12963; Bethesda, MD, USA). NR 36 TC 1 Z9 1 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 2015 VL 56 IS 1 BP 185 EP 189 DI 10.1167/iovs.14-15884 PG 5 WC Ophthalmology SC Ophthalmology GA CE0TQ UT WOS:000351519800021 ER PT J AU Mukherjee, S Zhou, XH Rajaiya, J Chodosh, J AF Mukherjee, Santanu Zhou, Xiaohong Rajaiya, Jaya Chodosh, James TI Ultrastructure of Adenovirus Keratitis SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Article DE adenovirus; keratitis; mouse; electron microscopy ID NUCLEAR-PORE COMPLEX; EPIDEMIC KERATOCONJUNCTIVITIS; BIOINFORMATICS ANALYSIS; CELL ENTRY; IN-VITRO; MACROPINOCYTOSIS; RECEPTOR; DNA; ENDOCYTOSIS; ACTIVATION AB PURPOSE. We determined the ultrastructure of mouse adenovirus keratitis, a model for human adenovirus keratitis. METHODS. Adenovirus keratitis was induced in C57Bl/6j mice by intrastromal injection of human adenovirus species D type 37 (HAdV-D37) with a heat-pulled, glass, micropipette needle under compressed air. At select time points after infection, mice were euthanized and their corneas removed, fixed, and sectioned at 70-nm thickness for electron microscopy. RESULTS. Injection of HAdV-D37 into the mouse corneal stroma placed virus predominantly in the pericellular corneal stromal matrix. Virus was seen bound to and entering stromal cells at 1 and 2 hours after infection, respectively. Cell membrane transit by virus was seen to involve two distinct structures resembling caveolae and macropinosomes. However, later during infection intracellular virus was not seen within membrane-bound organelles. By 8 hours after infection, intracellular virus had accumulated into densely packed, perinuclear arrays. Virus disassembly was not obvious at any time point after infection. Infiltrating neutrophils seen by one day after infection had engulfed degraded stromal cells by 4 days after infection. CONCLUSIONS. By transmission electron microscopy, injected HAdV-D37 readily enters stromal cells in the C57Bl/6j mouse cornea and induces stromal inflammation, as was shown previously by light microscopy. However, electron microscopy also revealed dense, static arrays of intracytoplasmic virus, suggesting a block in viral capsid disassembly and viral DNA nuclear entry. These findings may explain why human adenoviruses do not replicate in the mouse corneal stroma. C1 [Mukherjee, Santanu; Zhou, Xiaohong; Rajaiya, Jaya; Chodosh, James] Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Ophthalmol,Howe Lab, Boston, MA USA. RP Chodosh, J (reprint author), Massachusetts Eye & Ear, 243 Charles St, Boston, MA 02114 USA. EM jaya_rajaiya@meei.harvard.edu; James_Chodosh@meei.harvard.edu FU National Institutes of Health (Bethesda, MD, USA) [EY013124, EY021558, P30EY014104]; Research to Prevent Blindness, Inc., New York, NY; Massachusetts Lions Eye Research Fund; Falk Foundation FX Supported by National Institutes of Health (Bethesda, MD, USA) Grants EY013124, EY021558, and P30EY014104, a Senior Scientific Investigator Award (JC) from Research to Prevent Blindness, Inc., New York, NY, the Massachusetts Lions Eye Research Fund, and the Falk Foundation. NR 39 TC 3 Z9 3 U1 0 U2 3 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 2015 VL 56 IS 1 BP 472 EP 477 DI 10.1167/iovs.14-15635 PG 6 WC Ophthalmology SC Ophthalmology GA CE0TQ UT WOS:000351519800053 PM 25564451 ER PT J AU Meeker, KD Meabon, JS Cook, DG AF Meeker, Kole D. Meabon, James S. Cook, David G. TI Partial Loss of the Glutamate Transporter GLT-1 Alters Brain Akt and Insulin Signaling in a Mouse Model of Alzheimer's Disease SO JOURNAL OF ALZHEIMERS DISEASE LA English DT Article DE Amyloid-beta; EAAT2; excitotoxicity; GLT1; metabolism; SLC1A2 ID SYNAPTICALLY RELEASED GLUTAMATE; AMYOTROPHIC-LATERAL-SCLEROSIS; DEGRADING ENZYME; NEURODEGENERATIVE DISORDERS; HUNTINGTONS-DISEASE; COGNITIVE DECLINE; BETA-PEPTIDE; MICE LACKING; S6 KINASE; IN-VIVO AB The glutamate transporter GLT-1 (also called EAAT2 in humans) plays a critical role in regulating extracellular glutamate levels in the central nervous system (CNS). In Alzheimer's disease (AD), EAAT2 loss is associated with neuropathology and cognitive impairment. In keeping with this, we have reported that partial GLT-1 loss (GLT-1+/-) causes early-occurring cognitive deficits in mice harboring familial AD A beta PPswe/PS1 Delta E9 mutations. GLT-1 plays important roles in several molecular pathways that regulate brain metabolism, including Akt and insulin signaling in astrocytes. Significantly, AD pathogenesis also involves chronic Akt activation and reduced insulin signaling in the CNS. In this report we tested the hypothesis that GLT-1 heterozygosity (which reduces GLT-1 to levels that are comparable to losses in AD patients) in A beta PPswe/PS1 Delta E9 mice would induce sustained activation of Akt and disturb components of the CNS insulin signaling cascade. We found that partial GLT-1 loss chronically increased Akt activation (reflected by increased phosphorylation at serine 473), impaired insulin signaling (reflected by decreased IR beta phosphorylation of tyrosines 1150/1151 and increased IRS-1 phosphorylation at serines 632/635 - denoted as 636/639 in humans), and reduced insulin degrading enzyme (IDE) activity in brains of mice expressing familial A beta PPswe/PS1 Delta E9 AD mutations. GLT-1 loss also caused an apparent compensatory increase in IDE activity in the liver, an organ that has been shown to regulate peripheral amyloid-beta levels and expresses GLT-1. Taken together, these findings demonstrate that partial GLT-1 loss can cause insulin/Akt signaling abnormalities that are in keeping with those observed in AD. C1 [Meeker, Kole D.; Cook, David G.] Univ Washington, Sch Med, Dept Pharmacol, Seattle, WA 98195 USA. [Meeker, Kole D.; Cook, David G.] Vet Affairs Puget Sound Hlth Care Syst, Geriatr Res Educ & Clin Ctr, Seattle, WA 98108 USA. [Meabon, James S.] Vet Affairs Puget Sound Hlth Care Syst, Mental Illness Res Educ & Clin Ctr, Seattle, WA 98108 USA. [Meabon, James S.] Univ Washington, Sch Med, Dept Psychiat & Behav Sci, Seattle, WA 98195 USA. [Cook, David G.] Univ Washington, Sch Med, Dept Med, Div Gerontol, Seattle, WA 98195 USA. RP Cook, DG (reprint author), Vet Affairs Puget Sound Hlth Care Syst, Geriatr Res Educ & Clin Ctr, 1660 S Columbian Way, Seattle, WA 98108 USA. EM dgcook@u.washington.edu FU Veteran's Affairs Office of Research and Development Medical Research Service; NIH Pharmacological Sciences training grant [5T32GM00775033]; NIH [T32 AG000258]; Cellular Functional Analysis Core of the University of Washington Diabetes Research Center [PO1 DK17047] FX This work was supported by funding from the Veteran's Affairs Office of Research and Development Medical Research Service (DGC), an NIH Pharmacological Sciences training grant [5T32GM00775033] (KDM), an NIH institutional fellowship [T32 AG000258] (JSM), and services by the Cellular Functional Analysis Core of the University of Washington Diabetes Research Center (PO1 DK17047). Original GLT-1 (+/-) mice were graciously made availabe by Kohichi Tanaka (Tokyo Medical and Dental University). NR 75 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 2015 VL 45 IS 2 BP 509 EP 520 DI 10.3233/JAD-142304 PG 12 WC Neurosciences SC Neurosciences & Neurology GA CE1PL UT WOS:000351583900017 PM 25589729 ER PT J AU Wang, XB Lopez, O Sweet, RA Becker, JT DeKosky, ST Barmada, MM Feingold, E Demirci, FY Kamboh, MI AF Wang, Xingbin Lopez, Oscar Sweet, Robert A. Becker, James T. DeKosky, Steven T. Barmada, Mahmud M. Feingold, Eleanor Demirci, F. Yesim Kamboh, M. Ilyas TI Genetic Determinants of Survival in Patients with Alzheimer's Disease SO JOURNAL OF ALZHEIMERS DISEASE LA English DT Article DE Gene-based analysis; genome-wide association studies; late-onset Alzheimer's disease; survival ID GENOME-WIDE ASSOCIATION; APOLIPOPROTEIN-E; INCREASED RISK; PROMOTER POLYMORPHISM; INTERLEUKIN-10 GENE; IDENTIFIES VARIANTS; COMMON VARIANTS; POPULATION; DEMENTIA; MORTALITY AB There is a strong genetic basis for late-onset of Alzheimer's disease (LOAD), and thus far >20 genes/loci have been identified that affect the risk of LOAD. In addition to disease risk, genetic variation at these loci may also affect components of the natural history of AD, such as survival in AD. In this study, we first examined the role of known LOAD genes with survival time in 983 AD patients. We then performed genome-wide single-nucleotide polymorphism (SNP) and gene-based association analyses to identify novel loci that may influence survival of AD. Survival analysis was conducted using Cox proportional hazards regression under an additive genetics model. We found multiple nominally significant associations (p < 0.01) either within or adjacent to known LOAD genes. Genome-wide SNP analysis identified multiple suggestive novel loci and two of them were also significant in gene-based analysis (CCDC85C and NARS2) that survived after controlling for false-discovery rate at 0.05. In summary, we have identified two novel genes for survival in AD that need to be replicated in independent samples. Our findings highlight the importance of focusing on AD-related phenotypes that may help to identify additional genes relevant to AD. C1 [Wang, Xingbin; Barmada, Mahmud M.; Feingold, Eleanor; Demirci, F. Yesim; Kamboh, M. Ilyas] Univ Pittsburgh, Dept Human Genet, Pittsburgh, PA 15261 USA. [Wang, Xingbin; Feingold, Eleanor] Univ Pittsburgh, Dept Biostat, Pittsburgh, PA 15261 USA. [Lopez, Oscar; Sweet, Robert A.; Becker, James T.] Univ Pittsburgh, Dept Neurol, Pittsburgh, PA 15261 USA. [Lopez, Oscar; Sweet, Robert A.; Becker, James T.; Kamboh, M. Ilyas] Univ Pittsburgh, Alzheimers Dis Res Ctr, Pittsburgh, PA 15261 USA. [Sweet, Robert A.; Kamboh, M. Ilyas] Univ Pittsburgh, Dept Psychiat, Pittsburgh, PA 15261 USA. [DeKosky, Steven T.] Univ Virginia, Sch Med, Dept Neurol, Charlottesville, VA 22908 USA. [Sweet, Robert A.] VA Pittsburgh Healthcare Syst, VISN Mental Illness Res Educ & Clin Ctr MIRECC 4, Pittsburgh, PA 15261 USA. RP Kamboh, MI (reprint author), Univ Pittsburgh, Grad Sch Publ Hlth, Dept Human Genet, Pittsburgh, PA 15261 USA. EM kamboh@pitt.edu OI Feingold, Eleanor/0000-0003-2898-6484; Demirci, F. Yesim/0000-0001-6907-9843; Kamboh, M. Ilyas/0000-0002-3453-1438; Barmada, M Michael/0000-0002-3604-6460 FU National Institutes of Health [AG030653, AG041718, AG005133, AG027224] FX This study was supported by the National Institutes of Health grants AG030653, AG041718, AG005133, and AG027224. The content is solely the responsibility of the authors and does not necessarily represent the official views of the Department of Veterans Affairs, the National Institutes of Health, or the United States Government. NR 51 TC 0 Z9 0 U1 1 U2 3 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 2015 VL 45 IS 2 BP 651 EP 658 DI 10.3233/JAD-142442 PG 8 WC Neurosciences SC Neurosciences & Neurology GA CE1PL UT WOS:000351583900029 PM 25649651 ER PT J AU Seda, G Sanchez-Ortuno, MM Welsh, CH Halbower, AC Edinger, JD AF Seda, Gilbert Sanchez-Ortuno, Maria M. Welsh, Carolyn H. Halbower, Ann C. Edinger, Jack D. TI Comparative Meta-Analysis of Prazosin and Imagery Rehearsal Therapy for Nightmare Frequency, Sleep Quality, and Posttraumatic Stress SO JOURNAL OF CLINICAL SLEEP MEDICINE LA English DT Article DE posttraumatic stress disorder; nightmares; prazosin; imagery rehearsal therapy; cognitive behavior therapy; insomnia ID RANDOMIZED CONTROLLED-TRIAL; SEXUAL ASSAULT SURVIVORS; BEHAVIORAL TREATMENT; COMBAT VETERANS; CLINICAL-TRIAL; PTSD; DISORDER; TRAUMA; DISTURBANCES; SYMPTOMS AB Study Objective: In this meta-analysis, we compare the short-term efficacy of prazosin vs. IRT on nightmares, sleep quality, and posttraumatic stress symptoms (PTSS). Methods: Reference databases were searched for randomized controlled trials using IRT or prazosin for nightmares, sleep disturbance, and/or PTSS. Effect sizes were calculated by subtracting the mean posttest score in the control group from the mean posttest score in the treatment group, and dividing the result by the pooled standard deviation of both groups. Mixed effects models were performed to evaluate effects of treatment characteristics, as well as sample characteristics (veteran vs. civilian) on treatment efficacy. Results: Four studies used prazosin, 10 used IRT alone or in combination with another psychological treatment, and 1 included a group receiving prazosin and another group receiving IRT. Overall effect sizes of both treatments were of moderate magnitude for nightmare frequency, sleep quality, and PTSS (p < 0.01). Effect size was not significantly different with type of treatment (psychological vs. pharmacological) on nightmare frequency (p = 0.79), sleep quality (p = 0.65), or PTSS, (p = 0.52). IRT combined with CBT for insomnia showed more improvement in sleep quality compared to prazosin (p = 0.03), IRT alone (p = 0.03), or IRT combined with another psychological intervention, (p < 0.01). Conclusion: Although IRT interventions and prazosin yield comparable acute effects for the treatment of nightmares, adding CBT for insomnia to IRT seems to enhance treatment outcomes pertaining to sleep quality and PTSS. More randomized clinical trials with long-term follow-up are warranted. Commentary: A commentary on this article appears in this issue on page 9. C1 [Seda, Gilbert] Naval Med Ctr, Dept Pulm & Sleep Med, San Diego, CA USA. [Sanchez-Ortuno, Maria M.] Univ Murcia, Sch Nursing, Murcia, Spain. [Welsh, Carolyn H.] Univ Colorado, Dept Med, Div Pulm Sci & Crit Care Med, Denver, CO USA. [Halbower, Ann C.] Childrens Hosp Colorado, Dept Pulm Med, Denver, CO USA. [Halbower, Ann C.] Univ Colorado, Denver, CO 80202 USA. [Sanchez-Ortuno, Maria M.; Edinger, Jack D.] Natl Jewish Hlth, Dept Med, Denver, CO USA. [Welsh, Carolyn H.] Denver Vet Affairs Med Ctr, Denver, CO USA. [Edinger, Jack D.] Duke Univ, Med Ctr, Durham, NC USA. RP Seda, G (reprint author), 8546 Chevy Chase Dr, La Mesa, CA 91941 USA. EM gilbert.seda@gmail.com FU Fundacion Seneca, Murcia, Spain FX This was not an industry supported study. The authors have indicated no financial conflicts of interest. Dr. Sanchez-Ortuno was supported by a research fellowship award from Fundacion Seneca, Murcia, Spain. The opinions expressed herein are those of the authors and do not necessarily reflect those of the Department of the Navy, Department of Defense, the U.S. Government, or any of its agencies. NR 51 TC 5 Z9 5 U1 5 U2 16 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 2015 VL 11 IS 1 BP 11 EP 22 DI 10.5664/jcsm.4354 PG 12 WC Clinical Neurology SC Neurosciences & Neurology GA CD5ZN UT WOS:000351167800004 PM 25325592 ER PT J AU Dzierzewski, JM Mitchell, M Rodriguez, JC Fung, CH Jouldjian, S Alessi, CA Martin, JL AF Dzierzewski, Joseph M. Mitchell, Michael Rodriguez, Juan Carlos Fung, Constance H. Jouldjian, Stella Alessi, Cathy A. Martin, Jennifer L. TI Patterns and Predictors of Sleep Quality Before, During, and After Hospitalization in Older Adults SO JOURNAL OF CLINICAL SLEEP MEDICINE LA English DT Article DE sleep; hospitalization; aging; latent class analysis; clinical cutoffs ID POST-ACUTE REHABILITATION; LATENT CLASS ANALYSIS; ILLNESS RATING-SCALE; CLINICAL-OUTCOMES; POOR SLEEP; INDEX; PAIN; DEPRESSION; INSOMNIA; PEOPLE AB Study Objectives: The impact of hospitalization on sleep in late-life is underexplored. The current study examined patterns of sleep quality before, during, and following hospitalization, investigated predictors of sleep quality patterns, and examined predictors of classification discordance between two suggested clinical cutoffs used to demarcate poor/good sleep. Methods: This study included older adults (n = 163; mean age 79.7 +/- 6.9 years, 31% female) undergoing inpatient post-acute rehabilitation. Upon admission to inpatient postacute rehabilitation, patients completed the Pittsburgh Sleep Quality Index (PSQI) retrospectively regarding their sleep prior to hospitalization. They subsequently completed the PSQI at discharge, and 3 months, 6 months, 9 months, and 1 year post discharge. Patient demographic and clinical characteristics (pain, depression, cognition, comorbidity) were collected upon admission. Results: Using latent class analysis methods, older adults could be classified into (1) Consistently Good Sleepers and (2) Chronically Poor Sleepers based on patterns of self-reported sleep quality pre-illness, during, and up to 1 year following inpatient rehabilitation. This pattern was maintained regardless of the clinical cutoff employed (> 5 or > 8). Logistic regression analyses indicated that higher pain and depressive symptoms were consistently associated with an increased likelihood of being classified as a chronic poor sleeper. While there was substantial classifi cation discordance based on clinical cutoff employed, no significant predictors of this discordance emerged. Conclusions: Clinicians should exercise caution in assessing sleep quality in inpatient settings. Alterations in the cutoffs employed may result in discordant clinical classifi cations of older adults. Pain and depression warrant detailed considerations when working with older adults on inpatient units when poor sleep is a concern. C1 [Dzierzewski, Joseph M.; Rodriguez, Juan Carlos; Fung, Constance H.; Alessi, Cathy A.; Martin, Jennifer L.] Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90095 USA. [Dzierzewski, Joseph M.; Mitchell, Michael; Rodriguez, Juan Carlos; Fung, Constance H.; Jouldjian, Stella; Alessi, Cathy A.; Martin, Jennifer L.] VA Greater Los Angeles Healthcare Syst, Geriatr Res Educ & Clin Ctr, Los Angeles, CA USA. [Rodriguez, Juan Carlos] Pontificia Univ Catolica Chile, Sch Med, Santiago, Chile. RP Martin, JL (reprint author), VA GRECC 11E,16111 Plummer St, North Hills, CA 91343 USA. EM jennifer.martin@va.gov FU UCLA Claude Pepper Older Americans Independence Center by NIA [5P30AG028748, AG-10415]; NIH/NCATS UCLA CTSI [UL1TR000124]; NIA [K23 AG028452]; VA Health Services Research Development [IIR-01-053-1, IIR 04-321-2, AIA-03-047]; VA Advanced Geriatrics Fellowship Program; VA Greater Los Angeles Healthcare System Geriatric Research, Education and Clinical Center; National Institute on Aging [K23AG045937] FX This work was performed at the University of California, Los Angeles and the VA Greater Los Angeles Healthcare System. This work was supported by UCLA Claude Pepper Older Americans Independence Center by NIA (5P30AG028748 & AG-10415), NIH/NCATS UCLA CTSI (UL1TR000124), NIA K23 AG028452, VA Health Services Research & Development IIR-01-053-1, IIR 04-321-2, and AIA-03-047, VA Advanced Geriatrics Fellowship Program, and VA Greater Los Angeles Healthcare System Geriatric Research, Education and Clinical Center. CHF was supported by National Institute on Aging (K23AG045937). The content is solely the responsibility of the authors and not necessarily the responsibility of the funding agencies (VA or NIH). The authors have indicated no financial conflicts of interest. NR 40 TC 0 Z9 0 U1 2 U2 10 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 2015 VL 11 IS 1 BP 45 EP 51 DI 10.5664/jcsm.4362 PG 7 WC Clinical Neurology SC Neurosciences & Neurology GA CD5ZN UT WOS:000351167800008 PM 25325580 ER PT J AU Domoto, AL Cormock, RA Viswanothon, AN AF Domoto, Antonio L. Cormock, Robert A. Viswanothon, Akilo N. TI A novel intracavitary applicator design for the treatment of deep vaginal fornices: preliminary dose metrics and geometric analysis SO JOURNAL OF CONTEMPORARY BRACHYTHERAPY LA English DT Article ID SOCIETY CONSENSUS GUIDELINES; ENDOMETRIAL CANCER; RATE BRACHYTHERAPY; CUFF BRACHYTHERAPY; OPTIMIZATION; HYSTERECTOMY; RECURRENCES; CYLINDER C1 [Domoto, Antonio L.; Cormock, Robert A.; Viswanothon, Akilo N.] Brigham & Womens Hosp, Dana Farber Canc Inst, Boston, MA 02115 USA. RP Domoto, AL (reprint author), Brigham & Womens Hosp, Dept Radiat Oncol, ASB1,L2,75 Francis St, Boston, MA 02115 USA. EM adamato@lroc.harvard.edu NR 20 TC 0 Z9 0 U1 0 U2 0 PU TERMEDIA PUBLISHING HOUSE LTD PI POZNAN PA WENEDOW ST 9-1, POZNAN, 61-614, POLAND SN 1689-832X EI 2081-2841 J9 J CONTEMP BRACHYTHER JI J. Contemp. Brachytherapy PD JAN-FEB PY 2015 VL 7 IS 1 BP 48 EP 54 PG 7 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA CD6IH UT WOS:000351192300009 ER PT J AU Akhigbe, T Chin, AS Svircev, JN Hoenig, H Burns, SP Weaver, FM Bailey, L Carbone, L AF Akhigbe, Titilola Chin, Amy S. Svircev, Jelena N. Hoenig, Helen Burns, Stephen P. Weaver, Frances M. Bailey, Lauren Carbone, Laura TI A retrospective review of lower extremity fracture care in patients with spinal cord injury SO JOURNAL OF SPINAL CORD MEDICINE LA English DT Article DE Lower extremity fractures; Spinal cord injury; Wheelchairs; Osteoporosis therapies ID ANKLE FRACTURES; OSTEOPOROTIC FRACTURES; HIP FRACTURE; RISK-FACTORS; WHEELCHAIR; WOMEN; PARAPLEGIA; COHORT AB Context/Objective: To identify circumstances surrounding incident lower extremity fractures (ILEFs) in patients with spinal cord injury (SCI) and to describe the impact of these fractures on service needs and provision of pharmacological therapies for osteoporosis. Design: Retrospective medical record review. Setting: Four Veterans Affairs Medical Centers in the USA. Participants: One hundred and forty patients with traumatic SCI who sustained an ILEF from 2002 to 2007. Outcome measures: Fracture circumstances and use of assistive devices were described using percentages, means, and standard deviations. Fisher's exact test was used to determine the relationship between fracture site, and patient age and duration of SCI. Differences in pharmacological provision of therapies for osteoporosis pre- and post-fracture were examined using exact McNemar's test. Results: One hundred and fifty-five ILEFs were identified in 140 patients. Tibia/fibula and femur fractures were the most common fractures. Fracture site was not related to patient's age or duration of SCI. Almost one-third of all fractures occurred during transfers to and from wheelchairs. Post-fracture, the provision of new or modified assistive devices, primarily wheelchairs, was frequent, occurring in 83% of patients in the year post-fracture. Few patients transferred residence to a nursing home following the fracture. There was a significant difference in the use of pharmacological therapies for osteoporosis in the first year post-fracture compared with the year prior to the fracture (P < 0.01), with significant differences in the volume of prescriptions for calcium supplements (P < 0.01) and bisphosphonates (P = 0.02). Overall, the amount of prescriptions for osteoporosis increased the year post-fracture (56%) from the year pre-fracture (39%); this increase was secondary to increases in prescriptions for calcium supplements (pre = 13%; post = 30%) and bisphosphonates (pre = 2%; post = 7%). Conclusions: We have identified that wheelchair and other transfer activities are a key area that could be a focus of fracture prevention in SCI. The need for new or modified assistive devices and/or wheelchair skills retraining post-fracture should be anticipated. Examination of whether treatments for osteoporosis following a fracture can prevent future osteoporotic fractures is warranted. C1 [Akhigbe, Titilola; Carbone, Laura] Dept Vet Affairs Med Ctr, Memphis, TN USA. [Akhigbe, Titilola; Carbone, Laura] Univ Tennessee, Ctr Hlth Sci, Dept Med, Memphis, TN 38163 USA. [Chin, Amy S.; Weaver, Frances M.; Bailey, Lauren] Edward J Hines Jr Vet Affairs Hosp, Hines, IL USA. [Svircev, Jelena N.; Burns, Stephen P.] Vet Affairs Puget Sound Hlth Care Syst, Seattle, WA USA. [Hoenig, Helen] Durham Vet Affairs Med Ctr, Durham, NC USA. [Weaver, Frances M.] Loyola Univ, Stritch Sch Med, Maywood, IL 60153 USA. RP Carbone, L (reprint author), Univ Tennessee, Ctr Hlth Sci, Dept Med, Div Rheumatol, 956 Court Ave,Room G326, Memphis, TN 38163 USA. EM lcarbone@uthsc.edu FU Department of Veterans Affairs, Veterans Health Administration, Health Services Research and Development [IIR 08-033] FX This work was supported by the Department of Veterans Affairs, Veterans Health Administration, Health Services Research and Development #IIR 08-033. NR 36 TC 5 Z9 5 U1 0 U2 1 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 2015 VL 38 IS 1 BP 2 EP 9 DI 10.1179/2045772313Y.0000000156 PG 8 WC Clinical Neurology SC Neurosciences & Neurology GA CD4RJ UT WOS:000351070900001 PM 24621029 ER PT J AU Bauman, WA La Fountaine, MF Cirnigliaro, CM Kirshblum, SC Spungen, AM AF Bauman, William A. La Fountaine, Michael F. Cirnigliaro, Christopher M. Kirshblum, Steven C. Spungen, Ann M. TI Lean tissue mass and energy expenditure are retained in hypogonadal men with spinal cord injury after discontinuation of testosterone replacement therapy SO JOURNAL OF SPINAL CORD MEDICINE LA English DT Article DE Spinal cord injury; Lean tissue mass; Hypogonadism; Testosterone ID DENSITY LIPOPROTEIN CHOLESTEROL; ANDROGEN DEFICIENCY SYNDROMES; CLINICAL-PRACTICE GUIDELINE; BODY-COMPOSITION; CARDIOVASCULAR-DISEASE; MUSCLE STRENGTH; ADULT MEN; INDIVIDUALS; PLASMA; RISK AB Objective: To determine whether favorable changes to lean tissue mass (LTM), resting energy expenditure (REE), and testosterone (T) that occurred with 12 months of physiological testosterone replacement therapy (TRT) were retained 6 months after discontinuing treatment. Design: Prospective, open-label, controlled drug intervention trial. Setting: Metropolitan area hospitals. Subjects: Eugonadal (n = 11) and hypogonadal (n = 13) men with chronic spinal cord injury (SCI). Interventions: Hypogonadal subjects received a 5 or 10 mg transdermal T patch daily for 12 months, with adjustment of the dose to normalize the serum T concentration; TRT was discontinued after 12 months (TRT-12M) and subjects were followed for an additional 6 months and re-evaluated (Post-TRT). Total body dual energy X-ray absorptiometry and blood draws were performed at baseline (BL) prior to TRT, TRT-12M, and Post-TRT. Eugonadal subjects did not receive treatment and were evaluated at comparable time points. Results: There were no significant differences between groups prior to TRT at BL for any of the study endpoints. In the hypogonadal group, a significant increase in LTM was observed from BL to TRT-12M (50.2 +/- 7.4 vs. 52.9 +/- 6.8 kg, P < 0.01), which persisted Post-TRT compared to BL (52.2 +/- 7.8 kg, P < 0.05). The increase in REE from BL to TRT-12M (1283 +/- 246 vs. 1410 +/- 250 kcal/day) was also retained at Post-TRT (1393 +/- 220 kcal/day). These sustained improvements in LTM and REE after termination of anabolic hormonal therapy may be associated with persistent beneficial effects on health and physical function of hypogonadal men with chronic SCI. C1 [Bauman, William A.; La Fountaine, Michael F.; Cirnigliaro, Christopher M.; Spungen, Ann M.] James J Peters VA Med Ctr, VA RR&D Natl Ctr Excellence Med Consequences Spin, Bronx, NY 10468 USA. [Bauman, William A.; Spungen, Ann M.] James J Peters VA Med Ctr, Med Serv, Bronx, NY 10468 USA. [Bauman, William A.; Spungen, Ann M.] Icahn Sch Med Mt Sinai, Dept Med, New York, NY 10029 USA. [Bauman, William A.; Spungen, Ann M.] Icahn Sch Med Mt Sinai, Dept Rehabil Med, New York, NY 10029 USA. [La Fountaine, Michael F.] Seton Hall Univ, Sch Hlth & Med Sci, Dept Phys Therapy, S Orange, NJ 07079 USA. [Kirshblum, Steven C.] Kessler Inst Rehabil, W Orange, NJ USA. [Kirshblum, Steven C.] Rutgers New Jersey Med Sch, Dept Phys Med & Rehabil, Newark, NJ USA. RP Bauman, WA (reprint author), James J Peters VA Med Ctr, Ctr Excellence Med Consequences Spinal Cord Injur, 130 West Kingsbridge Rd, Bronx, NY 10468 USA. EM william.bauman@va.gov FU Veteran Affairs Rehabilitation Research and Development Service [B9212-C, B4162-C, B2468-C]; James J. Peters VA Medical Center FX Veteran Affairs Rehabilitation Research and Development Service (#B9212-C, #B4162-C, and #B2468-C) and the James J. Peters VA Medical Center. NR 41 TC 3 Z9 3 U1 0 U2 3 PU TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND SN 1079-0268 EI 2045-7723 J9 J SPINAL CORD MED JI J. Spinal Cord. Med. PD JAN PY 2015 VL 38 IS 1 BP 38 EP 47 DI 10.1179/2045772314Y.0000000206 PG 10 WC Clinical Neurology SC Neurosciences & Neurology GA CD4RJ UT WOS:000351070900005 PM 24968251 ER PT J AU Hausmann, LRM Myaskovsky, L Niyonkuru, C Oyster, ML Switzer, GE Burkitt, KH Fine, MJ Gao, SS Boninger, ML AF Hausmann, Leslie R. M. Myaskovsky, Larissa Niyonkuru, Christian Oyster, Michelle L. Switzer, Galen E. Burkitt, Kelly H. Fine, Michael J. Gao, Shasha Boninger, Michael L. TI Examining implicit bias of physicians who care for individuals with spinal cord injury: A pilot study and future directions SO JOURNAL OF SPINAL CORD MEDICINE LA English DT Article DE Racism; Social discrimination; Spinal cord injuries; Wheelchair ID ASSOCIATION TEST; HEALTH-STATUS; MEDICAL-CARE; RACIAL/ETHNIC DISCRIMINATION; RACIAL-DISCRIMINATION; ETHNIC IDENTIFICATION; UNFAIR TREATMENT; NATIONAL LATINO; ASIAN-AMERICANS; ATTITUDES AB Context: Despite evidence that healthcare providers have implicit biases that can impact clinical interactions and decisions, implicit bias among physicians caring for individuals with spinal cord injury (SCI) has not been examined. Objective: Conduct a pilot study to examine implicit racial bias of SCI physicians and its association with functioning and wellbeing for individuals with SCI. Design: Combined data from cross-sectional surveys of individuals with SCI and their SCI physicians. Setting: Four national SCI Model Systems sites. Participants: Individuals with SCI (N = 162) and their SCI physicians (N = 14). Outcome measures: SCI physicians completed online surveys measuring implicit racial (pro-white/anti-black) bias. Individuals with SCI completed questionnaires assessing mobility, physical independence, occupational functioning, social integration, self-reported health, depression, and life satisfaction. We used multilevel regression analyses to examine the associations of physician bias and outcomes of individuals with SCI. Results: Physicians had a mean bias score of 0.62 (SD = 0.35), indicating a strong pro-white/anti-black bias. Greater physician bias was associated with disability among individuals with SCI in the domain of social integration (odds ratio = 4.80, 95% confidence interval (CI) = 1.44, 16.04), as well as higher depression (B = 3.24, 95% CI = 1.06, 5.41) and lower life satisfaction (B = -4.54, 95% CI= -8.79, -0.28). Conclusion: This pilot study indicates that SCI providers are susceptible to implicit racial bias and provides preliminary evidence that greater implicit racial bias of physicians is associated with poorer psychosocial health outcomes for individuals with SCI. It demonstrates the feasibility of studying implicit bias among SCI providers and provides guidance for future research on physician bias and patient outcomes. C1 [Hausmann, Leslie R. M.; Myaskovsky, Larissa; Switzer, Galen E.; Burkitt, Kelly H.; Fine, Michael J.; Gao, Shasha] VA Pittsburgh Healthcare Syst, Ctr Hlth Equ Res & Promot, Pittsburgh, PA 15240 USA. [Hausmann, Leslie R. M.; Myaskovsky, Larissa; Switzer, Galen E.; Fine, Michael J.] Univ Pittsburgh, Sch Med, Dept Med, Pittsburgh, PA 15213 USA. [Niyonkuru, Christian; Oyster, Michelle L.; Boninger, Michael L.] Univ Pittsburgh, Sch Med, Dept Phys Med & Rehabil, Pittsburgh, PA USA. [Oyster, Michelle L.; Boninger, Michael L.] VA Pittsburgh Healthcare Syst, Ctr Excellence Wheelchairs & Associated Rehabil E, Pittsburgh, PA 15240 USA. RP Hausmann, LRM (reprint author), VA Pittsburgh Healthcare Syst, Ctr Hlth Equ Res & Promot, Bldg 30,Univ Dr 151C, Pittsburgh, PA 15240 USA. EM leslie.hausmann@gmail.com OI Boninger, Michael/0000-0001-6966-919X FU Veterans Affairs Health Services Research and Development Career Development Program [RCD 06-287]; National Institute on Disability and Rehabilitation Research, Office of Special Education and Rehabilitation Services, U.S. Department of Education [H133N060019] FX This research was funded by the National Institute on Disability and Rehabilitation Research, Office of Special Education and Rehabilitation Services, U.S. Department of Education (grant no. H133N060019; PI: M.L.B.). Dr L.R.M.H.'s effort was supported by the Veterans Affairs Health Services Research and Development Career Development Program (RCD 06-287). NR 46 TC 10 Z9 10 U1 5 U2 8 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 2015 VL 38 IS 1 BP 102 EP 110 DI 10.1179/2045772313Y.0000000184 PG 9 WC Clinical Neurology SC Neurosciences & Neurology GA CD4RJ UT WOS:000351070900013 PM 24621034 ER PT S AU Hove, MJ Keller, PE AF Hove, Michael J. Keller, Peter E. BE Bigand, E Tillmann, B Peretz, I Zatorre, RJ Lopez, L Majno, M TI Impaired movement timing in neurological disorders: rehabilitation and treatment strategies SO NEUROSCIENCES AND MUSIC V: COGNITIVE STIMULATION AND REHABILITATION SE Annals of the New York Academy of Sciences LA English DT Article; Proceedings Paper CT Conference on Neurosciences and Music V CY MAY 29-JUN 01, 2014 CL Dijon, FRANCE DE gait rehabilitation; Parkinson's disease; rhythmic auditory stimulation; adaptive timing; groove ID RHYTHMIC AUDITORY-STIMULATION; PARKINSONS-DISEASE PATIENTS; SENSORIMOTOR SYNCHRONIZATION; PHASE CORRECTION; VISUOMOTOR SYNCHRONIZATION; FRACTAL DYNAMICS; TIME PERCEPTION; MOTOR TEMPO; HUMAN GAIT; MUSIC AB Timing abnormalities have been reported in many neurological disorders, including Parkinson's disease (PD). In PD, motor-timing impairments are especially debilitating in gait. Despite impaired audiomotor synchronization, PD patients' gait improves when they walk with an auditory metronome or with music. Building on that research, we make recommendations for optimizing sensory cues to improve the efficacy of rhythmic cuing in gait rehabilitation. Adaptive rhythmic metronomes (that synchronize with the patient's walking) might be especially effective. In a recent study we showed that adaptive metronomes synchronized consistently with PD patients' footsteps without requiring attention; this improved stability and reinstated healthy gait dynamics. Other strategies could help optimize sensory cues for gait rehabilitation. Groove music strongly engages the motor system and induces movement; bass-frequency tones are associated with movement and provide strong timing cues. Thus, groove and bass-frequency pulses could deliver potent rhythmic cues. These strategies capitalize on the close neural connections between auditory and motor networks; and auditory cues are typically preferred. However, moving visual cues greatly improve visuomotor synchronization and could warrant examination in gait rehabilitation. Together, a treatment approach that employs groove, auditory, bass-frequency, and adaptive (GABA) cues could help optimize rhythmic sensory cues for treating motor and timing deficits. C1 [Hove, Michael J.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. [Keller, Peter E.] Univ Western Sydney, MARCS Inst, Sydney, NSW, Australia. RP Hove, MJ (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, 149 13th St, Charlestown, MA 02129 USA. EM michaeljhove@gmail.com OI Keller, Peter/0000-0001-7579-6515 FU National Institute of Mental Health Grant [T32-MH16259] FX M.J.H. received support from a National Institute of Mental Health Grant (T32-MH16259). NR 71 TC 11 Z9 11 U1 3 U2 21 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 2015 VL 1337 BP 111 EP 117 DI 10.1111/nyas.12615 PG 7 WC Clinical Neurology; Psychology; Psychology, Experimental; Rehabilitation SC Neurosciences & Neurology; Psychology; Rehabilitation GA BC3ER UT WOS:000351580900016 PM 25773624 ER PT J AU Manchikanti, L Nampiaparampil, DE Candido, KD Bakshi, S Do, JSG Falco, FJE Sehgal, N Hirsch, JA AF Manchikanti, Laxmaiah Nampiaparampil, Devi E. Candido, Kenneth D. Bakshi, Sanjay Do, Jay S. Grider Falco, Frank J. E. Sehgal, Nalini Hirsch, Joshua A. TI Do Cervical Epidural Injections Provide Long-Term Relief in Neck and Upper Extremity Pain? A Systematic Review SO PAIN PHYSICIAN LA English DT Review DE Chronic neck pain; cervical disc herniation; cervical spinal stenosis; cervical post surgery syndrome; cervical discogenic pain; cervical epidural injections; interlaminar epidural injections; transforaminal epidural injections; steroids; local anesthetic ID ACTIVE-CONTROL TRIAL; 2-YEAR FOLLOW-UP; CHRONIC LOW-BACK; PHYSICIANS ASIPP GUIDELINES; LUMBAR DISC HERNIATION; STEROID INJECTION; DOUBLE-BLIND; INTERVENTIONAL TECHNIQUES; SPINAL STENOSIS; RADICULAR PAIN AB Background: The high prevalence of chronic persistent neck pain not only leads to disability but also has a significant economic, societal, and health impact. Among multiple modalities of treatments prescribed in the management of neck and upper extremity pain, surgical, interventional and conservative modalities have been described. Cervical epidural injections are also common modalities of treatments provided in managing neck and upper extremity pain. They are administered by either an interlaminar approach or transforaminal approach. Objectives: To determine the long-term efficacy of cervical interlaminar and transforaminal epidural injections in the treatment of cervical disc herniation, spinal stenosis, discogenic pain without facet joint pain, and post surgery syndrome. Methods: The literature search was performed from 1966 to October 2014 utilizing data from PubMed, Cochrane Library, US National Guideline Clearinghouse, previous systematic reviews, and cross-references. The evidence was assessed based on best evidence synthesis with Level I to Level V. Results: There were 7 manuscripts meeting inclusion criteria. Of these, 4 assessed the role of interlaminar epidural injections for managing disc herniation or radiculitis, and 3 assessed these injections for managing central spinal stenosis, discogenic pain without facet joint pain, and post surgery syndrome. There were 4 high quality manuscripts. A qualitative synthesis of evidence showed there is Level II evidence for each etiology category. The evidence is based on one relevant, high quality trial supporting the efficacy of cervical interlaminar epidural injections for each particular etiology. There were no randomized trials available assessing the efficacy of cervical transforaminal epidural injections. Limitations: Paucity of available literature, specifically conditions other than disc herniation. Conclusion: This systematic review with qualitative best evidence synthesis shows Level II evidence for the efficacy of cervical interlaminar epidural injections with local anesthetic with or without steroids, based on at least one high-quality relevant randomized control trial in each category for disc herniation, discogenic pain without facet joint pain, central spinal stenosis, and post surgery syndrome. C1 [Manchikanti, Laxmaiah] Pain Management Ctr Paducah, Paducah, KY 42003 USA. [Manchikanti, Laxmaiah] Univ Louisville, Louisville, KY 40292 USA. [Nampiaparampil, Devi E.] NYU, Sch Med, New York, NY USA. [Candido, Kenneth D.] Advocate Illinois Mason Med Ctr, Dept Anesthesiol, Chicago, IL USA. [Candido, Kenneth D.] Univ Illinois, Coll Med, Chicago, IL USA. [Bakshi, Sanjay] Manhattan Spine & Pain Med, New York, NY USA. [Do, Jay S. Grider] Univ Kentucky, UK Healthcare Pain Serv, Lexington, KY USA. [Falco, Frank J. E.] Mid Atlant Spine & Pain Phys, Newark, DE USA. [Falco, Frank J. E.] Temple Univ Hosp & Med Sch, Philadelphia, PA 19140 USA. [Sehgal, Nalini] Univ Wisconsin, Sch Med & Publ Hlth, Madison, WI USA. [Hirsch, Joshua A.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Hirsch, Joshua A.] Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Manchikanti, L (reprint author), MD 2831 Lone Oak Rd, Paducah, KY 42003 USA. EM drlm@thepainmd.com NR 123 TC 26 Z9 26 U1 0 U2 7 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 2015 VL 18 IS 1 BP 39 EP 60 PG 22 WC Anesthesiology; Clinical Neurology SC Anesthesiology; Neurosciences & Neurology GA CE0JF UT WOS:000351489600005 PM 25675059 ER PT J AU Koury, KM Tsui, B Gulur, P AF Koury, Katharine M. Tsui, Becky Gulur, Padma TI Incidence of Serotonin Syndrome in Patients Treated with Fentanyl on Serotonergic Agents SO PAIN PHYSICIAN LA English DT Article DE Fentanyl; serotonin syndrome; serotonergic drugs; opioids; SSRI; antidepressant ID PAROXETINE; TOXICITY AB Background: There has been a recent surge in the literature highlighting the association of fentanyl as precipitating serotonin syndrome in patients on a serotonergic agent. Objective: The purpose of our study was to understand the incidence of serotonin syndrome in patients who receive fentanyl while on serotonergic agents. Study Design: This retrospective analysis was conducted from 2012 to 2013 after approval from the Institutional Review Board. We searched for all patients that had received a serotonergic agent and were admitted to the hospital during the study period. Next, we split these patients into 2 groups by placing all patients who had received fentanyl and a serotonergic agent into one group. We then searched for any of the Hunter Serotonin Toxicity Criteria in the records of patients that had received both fentanyl and a serotonergic agent. Further, we searched for all patients with serotonin syndrome mentioned in their records. Setting: This study was conducted at a 900 bed tertiary care academic center. Results: Over the 2 year study period, 112,045 patients were on a serotonergic agent, and 4,538 of these patients were treated with both fentanyl and a serotonergic agent. A search for Hunter's Criteria through the records of the patients receiving both fentanyl and a serotonergic agent revealed 23 patients had been documented with some of these symptoms. On detailed chart review, only 4 [95% CI 1 - 10] of these patients truly met Hunter's Criteria for serotonin syndrome. We then searched all admissions for a diagnosis code of serotonin syndrome during the study period. Five additional cases of serotonin syndrome were found, but none of these patients were treated with fentanyl. Limitations: Some of the limitations of our study include that it represents a single institution, although it is a large academic center. An inherent limitation may be the under diagnosis of serotonin syndrome. Conclusion: The incidence of serotonin syndrome in patients who receive both fentanyl and a serotonergic agent is low. C1 [Koury, Katharine M.; Tsui, Becky; Gulur, Padma] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Gulur, P (reprint author), Massachusetts Gen Hosp, 15 Parkman St, Boston, MA 02114 USA. EM pgulur@yahoo.com NR 8 TC 4 Z9 4 U1 3 U2 3 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 2015 VL 18 IS 1 BP E27 EP E30 PG 4 WC Anesthesiology; Clinical Neurology SC Anesthesiology; Neurosciences & Neurology GA CE0JF UT WOS:000351489600014 PM 25675067 ER PT J AU Reish, A Bastas, G Popescu, A Friedberger, M AF Reish, Andrew Bastas, Gerasimos Popescu, Adrian Friedberger, Marylouis TI Newly Diagnosed Lumbar Nerve Root Intradural Mass in the Setting of Chronic Lumbar Radicular Pain Refractory to Conservative Management SO PAIN PHYSICIAN LA English DT Article ID DISK DISEASE; SHEATH; TUMORS C1 [Reish, Andrew] Univ Michigan, Dept Phys Med & Rehabil, Ann Arbor, MI 48108 USA. [Bastas, Gerasimos] Vanderbilt Univ, Med Ctr, Dept Phys Med & Rehabil, Nashville, TN USA. [Popescu, Adrian] Univ Penn, Dept Phys Med & Rehabil, Philadelphia, PA 19104 USA. [Friedberger, Marylouis] Vet Affairs Med Ctr, Pain Clin Philadelphia, Philadelphia, PA USA. RP Reish, A (reprint author), Univ Michigan, Dept Phys Med & Rehabil, 325 E Eisenhower Pkwy,Suite 100, Ann Arbor, MI 48108 USA. EM reisha@med.umich.edu NR 10 TC 0 Z9 0 U1 3 U2 4 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 2015 VL 18 IS 1 BP E79 EP E82 PG 4 WC Anesthesiology; Clinical Neurology SC Anesthesiology; Neurosciences & Neurology GA CE0JF UT WOS:000351489600022 PM 25675075 ER PT S AU Song, JW Bazou, D Munn, LL AF Song, Jonathan W. Bazou, Despina Munn, Lance L. BE Ribatti, D TI Microfluidic Model of Angiogenic Sprouting SO VASCULAR MORPHOGENESIS: METHODS AND PROTOCOLS SE Methods in Molecular Biology LA English DT Article; Book Chapter DE Angiogenesis on a chip; Sprouting; Microfluidics; Microfabrication; Shear stress; Gradients; bioMEMS ID CELL-CULTURE; SOFT LITHOGRAPHY; TISSUE ANALOG; DEVICES; ADHESION; DESIGN; FUTURE; FLOW AB Microfluidic systems have emerged as an important technology for modeling cellular microenvironments in vitro. These systems enable unprecedented levels of control of chemical gradients, fluid flow, and localized 3-D extracellular matrices (ECM), all of which can be integrated to provide a physiologically relevant context for studying complex cellular processes such as angiogenesis. Here, we describe the design and use of microfluidic systems for reproducing the dynamic events of vascular morphogenesis. C1 [Song, Jonathan W.; Bazou, Despina; Munn, Lance L.] Massachusetts Gen Hosp, Dept Radiat Oncol, Edwin L Steele Lab Tumor Biol, Charlestown, MA 02129 USA. [Song, Jonathan W.; Bazou, Despina; Munn, Lance L.] Harvard Univ, Sch Med, Charlestown, MA USA. RP Song, JW (reprint author), Massachusetts Gen Hosp, Dept Radiat Oncol, Edwin L Steele Lab Tumor Biol, Charlestown, MA 02129 USA. RI Munn, Lance/L-3950-2016; OI Munn, Lance/0000-0003-0698-7232; Song, Jonathan/0000-0002-6991-5298 FU NCI NIH HHS [R01CA149285, T32CA073479]; NHLBI NIH HHS [R01 HL106584] NR 27 TC 0 Z9 0 U1 0 U2 9 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DR, STE 208, TOTOWA, NJ 07512-1165 USA SN 1064-3745 BN 978-1-4939-1462-3; 978-1-4939-1461-6 J9 METHODS MOL BIOL JI Methods Mol. Biol. PY 2015 VL 1214 BP 243 EP 254 DI 10.1007/978-1-4939-1462-3_15 D2 10.1007/978-1-4939-1462-3 PG 12 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA BC1TI UT WOS:000350416800016 PM 25468609 ER PT J AU Cerulli, C Kothari, C Dichter, M Marcus, S Kim, TK Wiley, J Rhodes, KV AF Cerulli, Catherine Kothari, Catherine Dichter, Melissa Marcus, Steve Kim, Tae Kuen Wiley, Jim Rhodes, Karin V. TI Help-Seeking Patterns Among Women Experiencing Intimate Partner Violence: Do They Forgo the Criminal Justice System if Their Adjudication Wishes Are Not Met? SO VIOLENCE AND VICTIMS LA English DT Article DE domestic violence; prosecution; displacement; resources ID DOMESTIC VIOLENCE; PROCEDURAL JUSTICE; AFRICAN-AMERICAN; LEGAL; RISK; VICTIMS; CHRONICITY; PREVALENCE; DECISION; BARRIERS AB Following a criminal case disposition, an intimate partner violence (IPV) victim's willingness to seek future police and prosecutorial assistance may depend on her prior experiences within the system. This longitudinal study examines the relationship between IPV victims' future help-seeking based on past experiences. We hypothesized women would return to the criminal justice system if their adjudication wishes corresponded with prosecutors' actions. Contrary to the hypothesis, results suggest women return to the criminal system and other venues even if prosecutors' actions do not correspond to their earlier stated wishes. This has important policy implications given pro-prosecution protocols that encourage adjudication regardless of a woman's participation. C1 [Cerulli, Catherine] Univ Rochester, Sch Med & Dent, Rochester, NY USA. [Kothari, Catherine] Western Michigan Univ, Kalamazoo, MI 49008 USA. [Dichter, Melissa] Philadelphia VA Med Ctr, Ctr Hlth Equ Res & Promot, Philadelphia, PA USA. [Marcus, Steve; Rhodes, Karin V.] Univ Penn, Philadelphia, PA 19104 USA. [Kim, Tae Kuen] Adelphi Univ, New York, NY USA. [Wiley, Jim] Univ Calif San Francisco, Inst Hlth Policy Studies & Family & Community Med, San Francisco, CA 94143 USA. RP Cerulli, C (reprint author), Univ Rochester, Med Ctr, Rochester, NY 14642 USA. EM Catherine_Cerulli@urmc.rochester.edu NR 42 TC 0 Z9 0 U1 6 U2 20 PU SPRINGER PUBLISHING CO PI NEW YORK PA 11 WEST 42ND STREET, NEW YORK, NY 10036 USA SN 0886-6708 EI 1945-7073 J9 VIOLENCE VICTIMS JI Violence Vict. PY 2015 VL 30 IS 1 BP 16 EP 31 DI 10.1891/0886-6708.VV-D-13-00064 PG 16 WC Criminology & Penology SC Criminology & Penology GA CE1VR UT WOS:000351601300002 PM 25774412 ER PT S AU Hu, W MacDonald, ML Elswick, DE Sweet, RA AF Hu, Wei MacDonald, Matthew L. Elswick, Daniel E. Sweet, Robert A. BE Geschwind, DH TI The glutamate hypothesis of schizophrenia: evidence from human brain tissue studies SO YEAR IN NEUROLOGY AND PSYCHIATRY SE Annals of the New York Academy of Sciences LA English DT Article; Book Chapter DE brain tissue; EAAT; glutamate receptors; glutamatergic neurons; schizophrenia ID MESSENGER-RNA EXPRESSION; MEDIAL TEMPORAL-LOBE; AMINO-ACID OXIDASE; ANTERIOR CINGULATE CORTEX; DENDRITIC SPINE DENSITY; DORSOLATERAL PREFRONTAL CORTEX; CORTICAL PYRAMIDAL NEURONS; PRIMARY AUDITORY-CORTEX; D-ASPARTATE RECEPTOR; NEUROLEPTIC-FREE SCHIZOPHRENICS AB A number of studies have indicated that antagonists of the N-methyl-d-aspartate subtypes of glutamate receptors can cause schizophrenia-like symptoms in healthy individuals and exacerbate symptoms in individuals with schizophrenia. These findings have led to the glutamate hypothesis of schizophrenia. Here we review the evidence for this hypothesis in postmortem studies of brain tissue from individuals affected by schizophrenia, summarizing studies of glutamate neuron morphology, of expression of glutamate receptors and transporters, and of the synthesizing and metabolizing enzymes for glutamate and its co-agonists. We found consistent evidence of morphological alterations of dendrites of glutamatergic neurons in the cerebral cortex of subjects with schizophrenia and of reduced levels of the axon bouton marker synaptophysin. There were no consistent alterations of mRNA expression of glutamate receptors, although there has been limited study of the corresponding proteins. Studies of the glutamate metabolic pathway have been limited, although there is some evidence that excitatory amino acid transporter-2, glutamine synthetase, and glutaminase have altered expression in schizophrenia. Future studies would benefit from additional direct examination of glutamatergic proteins. Further advances, such as selective testing of synaptic microdomains, cortical layers, and neuronal subtypes, may also be required to elucidate the nature of glutamate signaling impairments in schizophrenia. C1 [Hu, Wei; Elswick, Daniel E.] W Virginia Univ, Hlth Sci Ctr, Dept Behav Med & Psychiat, Morgantown, WV 26506 USA. [MacDonald, Matthew L.; Sweet, Robert A.] Univ Pittsburgh, Dept Psychiat, Pittsburgh, PA USA. [Sweet, Robert A.] Univ Pittsburgh, Dept Neurol, Pittsburgh, PA 15260 USA. [Sweet, Robert A.] VA Pittsburgh Healthcare Syst, VISN Mental Illness Res Educ & Clin Ctr MIRECC 4, Pittsburgh, PA USA. RP Sweet, RA (reprint author), Biomed Sci Tower,Room W-1645,3811 OHara St, Pittsburgh, PA 15213 USA. EM sweetra@upmc.edu FU NIMH NIH HHS [R01 MH071533, MH 071533, MH 103204, MH 16804, P50 MH103204, R21 MH066231, T32 MH016804] NR 181 TC 18 Z9 18 U1 7 U2 27 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 2015 VL 1338 BP 38 EP 57 DI 10.1111/nyas.12547 PG 20 WC Clinical Neurology; Psychiatry SC Neurosciences & Neurology; Psychiatry GA BC3ES UT WOS:000351581400004 PM 25315318 ER PT J AU Axon, RN Gebregziabher, M Craig, J Zhang, JW Mauldin, P Moran, WP AF Axon, R. Neal Gebregziabher, Mulugeta Craig, Janet Zhang, Jingwen Mauldin, Patrick Moran, William P. TI Frequency and Costs of Hospital Transfers for Ambulatory Care-Sensitive Conditions SO AMERICAN JOURNAL OF MANAGED CARE LA English DT Article ID NURSING-HOME RESIDENTS; LONG-TERM-CARE; RANDOMIZED CONTROLLED-TRIAL; PREVENTABLE HOSPITALIZATIONS; EARLY READMISSION; INPATIENT CARE; HEALTH-CARE; QUALITY; MEDICAID; ASSOCIATION AB Objectives Nursing home (NH) patients are frequently transferred to emergency departments (EDs) and/or hospitalized in situations in which transfer might have been avoided. This study describes the frequency of NH transfers for ambulatory care-sensitive conditions (ACSCs) and estimates associated expenditures. Study Design Retrospective cohort study of 62,379 NH patients with Medicare coverage receiving care in South Carolina between 2007 and 2009. Methods Subjects were analyzed to determine the frequency of acute ED or hospital care for conditions. Comparison is made to similar patients transferred for acute treatment of non-ACSCs. Generalized linear models were used to estimate the costs attributable to treating ACSCs. Results Over 3 years, 20,867 NH subjects were transferred from NHs to acute care facilities, and 85.3% of subjects had at least 1 episode of care for an ACSC. An average of 13,317 subjects per year were transferred for an average of 17,060 episodes of ED or hospital care per year between 2007 and 2009. More ACSC patients transferred to EDs were subsequently admitted to the hospital (50.4% vs 25%; P < .0001). In adjusted analyses, mean ED costs per episode of care ($401 vs $294; P < .0001) were higher, but mean hospitalization costs per episode of care were lower ($8356 vs $10,226; P < .0001) for ACSC patients compared with non-ACSC patients. Conclusions A significant proportion of Medicare NH patients are treated acutely for ACSCs, which are associated with higher healthcare utilization and costs. Better access to onsite evaluation might enable significant cost savings and reduce morbidity in this population. C1 [Axon, R. Neal] Ralph H Johnson VA Med Ctr, Hlth Equ & Rural Outreach Innovat Ctr, Charleston, NC USA. [Axon, R. Neal; Zhang, Jingwen; Mauldin, Patrick; Moran, William P.] Med Univ S Carolina, Div Gen Internal Med & Geriatr, Charleston, SC 29425 USA. [Gebregziabher, Mulugeta] Med Univ S Carolina, Dept Publ Hlth Serv, Charleston, SC 29425 USA. [Craig, Janet] Clemson Univ, Sch Nursing, Clemson, SC USA. [Craig, Janet] Hlth Sci South Carolina, Columbia, SC USA. RP Axon, RN (reprint author), Ralph H Johnson VAMC, 109 Bee St, Charleston, SC 29401 USA. EM axon@musc.edu OI Gebregziabher, Mulugeta/0000-0002-4826-481X FU South Carolina Clinical & Translational Research Institute; NIH [UL1 RR029882, UL1 TR000062] FX This project was supported by the South Carolina Clinical & Translational Research Institute, with an academic home at the Medical University of South Carolina, through NIH grant numbers UL1 RR029882 and UL1 TR000062. NR 38 TC 1 Z9 1 U1 0 U2 2 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 2015 VL 21 IS 1 BP 51 EP 59 PG 9 WC Health Care Sciences & Services; Health Policy & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA CD3GC UT WOS:000350965300013 PM 25880150 ER PT J AU Rinne, ST Wong, ES Lemon, JM Perkins, M Bryson, CL Liu, CF AF Rinne, Seppo T. Wong, Edwin S. Lemon, Jaclyn M. Perkins, Mark Bryson, Christopher L. Liu, Chuan-Fen TI Survey Nonresponders Incurred Higher Medical Utilization and Lower Medication Adherence SO AMERICAN JOURNAL OF MANAGED CARE LA English DT Article ID HEALTH-CARE UTILIZATION; PATIENT SATISFACTION; DIABETES-MELLITUS; RISK-ADJUSTMENT; BIAS; POPULATION; VALIDATION; IMPACT; COHORT; ADULTS AB Objectives To compare healthcare costs, utilization, and medication adherence between diabetic responders and nonresponders to a patient satisfaction survey. Study Design We performed a retrospective cohort study of 40,766 patients with diabetes who had been randomly selected to receive the 2006 Veterans Affairs' Survey of Healthcare Experiences of Patients. Outcomes were measured during the following year. Methods We used multivariable models to compare healthcare costs (generalized linear models), utilization (negative binomial regression), and adherence to oral hypoglycemic medications (logistic regression) between survey responders and nonresponders. Results There were 26,051 patients (64%) who responded to the survey. Survey nonresponders incurred significantly higher healthcare costs (incremental effect, $792; 95% CI, $599-$986; P < .01). Nonresponders had a modest increase in primary care (incidence rate ratio [IRR], 1.06; 95% CI, 1.05-1.08; P < .01) and specialty care visits (IRR, 1.17; 95% CI, 1.12-1.22; P < .01), but more substantial increases in mental health visits (IRR, 1.74; 95% CI, 1.62-1.87; P < .01) and hospitalizations (IRR, 1.60; 95% CI, 1.46-1.75; P < .01). Medication adherence was significantly lower among survey nonresponders (odds ratio, 0.68; 95% CI, 0.65-0.74; P < .01). Conclusions Nonresponders to a patient satisfaction survey incurred higher healthcare costs and utilization, but had lower medication adherence. Understanding these characteristics helps to assess the impact of nonresponse bias on patient satisfaction surveys and identifies clinical practices to improve care delivery. C1 [Rinne, Seppo T.; Wong, Edwin S.; Lemon, Jaclyn M.; Perkins, Mark; Bryson, Christopher L.; Liu, Chuan-Fen] Dept Vet Affairs, VA Puget Sound Hlth Care Syst, Hlth Serv Res & Dev, Seattle, WA USA. [Rinne, Seppo T.] Univ Washington, Div Pulm, Seattle, WA 98195 USA. [Rinne, Seppo T.] Univ Washington, Div Crit Care, Seattle, WA 98195 USA. [Rinne, Seppo T.; Bryson, Christopher L.] Univ Washington, Dept Med, Seattle, WA USA. [Bryson, Christopher L.] Univ Washington, Div Gen Internal Med, Seattle, WA 98195 USA. [Liu, Chuan-Fen] Univ Washington, Dept Hlth Serv, Seattle, WA 98195 USA. RP Rinne, ST (reprint author), 1100 Ol Way,Ste 1400, Seattle, WA 98104 USA. EM srinne@uw.edu FU US Department of Veterans Affairs, Office of Research and Development, Health Services Research Development FX This research is based upon work supported by the US Department of Veterans Affairs, Office of Research and Development, Health Services Research & Development. The views expressed in this article are those of the authors and do not necessarily reflect the position or policy of the Department of Veterans Affairs or the United States government. NR 41 TC 0 Z9 0 U1 3 U2 4 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 2015 VL 21 IS 1 BP E1 EP E8 PG 8 WC Health Care Sciences & Services; Health Policy & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA CD3GC UT WOS:000350965300001 PM 25880264 ER PT S AU Mandal, AK Mount, DB AF Mandal, Asim K. Mount, David B. BE Julius, D TI The Molecular Physiology of Uric Acid Homeostasis SO ANNUAL REVIEW OF PHYSIOLOGY, VOL 77 SE Annual Review of Physiology LA English DT Review; Book Chapter DE uric acid; hyperuricemia; URAT1; SLC2A9; ABCG2 ID BRUSH-BORDER MEMBRANE; GENOME-WIDE ASSOCIATION; P-AMINOHIPPURATE TRANSPORT; ORGANIC ANION TRANSPORTER; XANTHINE OXIDOREDUCTASE GENE; HUMAN ARTICULAR CHONDROCYTES; NUTRITION EXAMINATION SURVEY; RENAL MICROVILLUS MEMBRANES; SERUM URATE CONCENTRATIONS; KIDNEY PROXIMAL TUBULES AB Uric acid, generated from the metabolism of purines, has proven and emerging roles in human disease. Serum uric acid is determined by production and the net balance of reabsorption or secretion by the kidney and intestine. A detailed understanding of epithelial absorption and secretion of uric acid has recently emerged, aided in particular by the results of genome-wide association studies of hyperuricemia. Novel genetic and regulatory networks with effects on uric acid homeostasis have also emerged. These developments promise to lead to a new understanding of the various diseases associated with hyperuricemia and to novel, targeted therapies for hyperuricemia. C1 [Mandal, Asim K.] Harvard Univ, Brigham & Womens Hosp, Div Renal, Sch Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, VA Boston Healthcare Syst, Boston, MA 02115 USA. RP Mandal, AK (reprint author), Harvard Univ, Brigham & Womens Hosp, Div Renal, Sch Med, Boston, MA 02115 USA. EM dmount@partners.org NR 179 TC 19 Z9 23 U1 5 U2 18 PU ANNUAL REVIEWS PI PALO ALTO PA 4139 EL CAMINO WAY, PO BOX 10139, PALO ALTO, CA 94303-0897 USA SN 0066-4278 BN 978-0-8243-0377-8 J9 ANNU REV PHYSIOL JI Annu. Rev. Physiol. PY 2015 VL 77 BP 323 EP 345 DI 10.1146/annurev-physiol-021113-170343 PG 23 WC Physiology SC Physiology GA BC2JD UT WOS:000350992800016 PM 25422986 ER PT J AU Grindle, GG Wang, HW Jeannis, H Teodorski, E Cooper, RA AF Grindle, Garrett G. Wang, Hongwu Jeannis, Hervens Teodorski, Emily Cooper, Rory A. TI Design and User Evaluation of a Wheelchair Mounted Robotic Assisted Transfer Device SO BIOMED RESEARCH INTERNATIONAL LA English DT Article ID SITTING PIVOT TRANSFERS; SPINAL-CORD-INJURY; MANIPULATION APPLIANCE; PERSONAL MOBILITY; CARE FACILITIES; LIFTING DEVICES; KINEMATICS; SHOULDER; OVERHEAD; SYSTEM AB Purpose. The aim of this study is to describe the robotic assisted transfer device (RATD) and an initial focus group evaluation by end users. The purpose of the device is to aid in the transfers of people with disabilities to and from their electric powered wheelchair (EPW) onto other surfaces. The device can be used for both stand-pivot transfers and fully dependent transfers, where the person being transferred is in a sling and weight is fully on the robot. The RATD is fixed to an EPW to allow for its use in community settings. Method. A functional prototype of the RATD was designed and fabricated. The prototype was presented to a group of 16 end users and feedback on the device was obtained via a survey and group discussion. Results. Thirteen out of sixteen (83%) participants agreed that it was important to develop this type of technology. They also indicated that user, caregiver, and robotic controls were important features to be included in the device. Conclusions. Participants in this study suggested that they would be accepting the use of robotic technology for transfers and a majority did not feel that they would be embarrassed to use this technology. C1 [Grindle, Garrett G.; Wang, Hongwu; Jeannis, Hervens; Teodorski, Emily; Cooper, Rory A.] VA Pittsburgh Healthcare Syst, Human Engn Res Labs, Pittsburgh, PA 15232 USA. [Grindle, Garrett G.; Wang, Hongwu; Jeannis, Hervens; Teodorski, Emily; Cooper, Rory A.] Univ Pittsburgh, Dept Rehabil Sci & Technol, Pittsburgh, PA 15232 USA. RP Cooper, RA (reprint author), VA Pittsburgh Healthcare Syst, Human Engn Res Labs, 6425 Penn Ave,Suite 400, Pittsburgh, PA 15232 USA. EM rcooper@pitt.edu RI Wang, Hongwu/J-6133-2013 OI Wang, Hongwu/0000-0002-6567-9144 FU National Science Foundation [EEC-540865, ERC-0540865]; Office of Research and Development; Rehabilitation Research & Development Service; Department of Veterans Affairs [B3142C]; Quality of Life Technology Engineering Research Center; VA Rehabilitation Research and Development Service [B6789C] FX This material is based upon work supported in part by the National Science Foundation Grant no. EEC-540865, Office of Research and Development, Rehabilitation Research & Development Service, Department of Veterans Affairs, Grant no. B3142C, Quality of Life Technology Engineering Research Center, National Science Foundation (ERC-0540865), and the VA Rehabilitation Research and Development Service (B6789C). The contents of this paper do not represent the views of the Department of Veterans Affairs or the United States Government. NR 26 TC 0 Z9 0 U1 1 U2 10 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 2015 AR 198476 DI 10.1155/2015/198476 PG 9 WC Biotechnology & Applied Microbiology; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Research & Experimental Medicine GA CD4ZX UT WOS:000351097200001 ER PT J AU Rehani, MM AF Rehani, M. M. TI Limitations of diagnostic reference level (DRL) and introduction of acceptable quality dose (AQD) SO BRITISH JOURNAL OF RADIOLOGY LA English DT Editorial Material C1 [Rehani, M. M.] Harvard Univ, Sch Med, Boston, MA 02138 USA. [Rehani, M. M.] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Rehani, MM (reprint author), Harvard Univ, Sch Med, Boston, MA 02138 USA. EM madan.rehani@gmail.com NR 6 TC 5 Z9 5 U1 0 U2 0 PU BRITISH INST RADIOLOGY PI LONDON PA 36 PORTLAND PLACE, LONDON W1N 4AT, ENGLAND SN 0007-1285 EI 1748-880X J9 BRIT J RADIOL JI Br. J. Radiol. PD JAN PY 2015 VL 88 IS 1045 AR 20140344 DI 10.1259/bjr.20140344 PG 3 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA CD2BX UT WOS:000350879900002 PM 25430807 ER PT J AU Gehlhausen, JR Park, SJ Hickox, AE Shew, M Staser, K Rhodes, SD Menon, K Lajiness, JD Mwanthi, M Yang, XL Yuan, J Territo, P Hutchins, G Nalepa, G Yang, FC Conway, SJ Heinz, MG Stemmer-Rachamimov, A Yates, CW Clapp, DW AF Gehlhausen, Jeffrey R. Park, Su-Jung Hickox, Ann E. Shew, Matthew Staser, Karl Rhodes, Steven D. Menon, Keshav Lajiness, Jacquelyn D. Mwanthi, Muithi Yang, Xianlin Yuan, Jin Territo, Paul Hutchins, Gary Nalepa, Grzegorz Yang, Feng-Chun Conway, Simon J. Heinz, Michael G. Stemmer-Rachamimov, Anat Yates, Charles W. Clapp, D. Wade TI A murine model of neurofibromatosis type 2 that accurately phenocopies human schwannoma formation SO HUMAN MOLECULAR GENETICS LA English DT Article ID NERVE SHEATH TUMORS; VESTIBULAR SCHWANNOMA; MOUSE MODELS; HEARING-LOSS; CELLS; MICE; ORIGIN; NF1 AB Neurofibromatosis type 2 (NF2) is an autosomal dominant genetic disorder resulting from germline mutations in the NF2 gene. Bilateral vestibular schwannomas, tumors on cranial nerve VIII, are pathognomonic for NF2 disease. Furthermore, schwannomas also commonly develop in other cranial nerves, dorsal root ganglia and peripheral nerves. These tumors are a major cause of morbidity and mortality, and medical therapies to treat them are limited. Animal models that accurately recapitulate the full anatomical spectrum of human NF2-related schwannomas, including the characteristic functional deficits in hearing and balance associated with cranial nerve VIII tumors, would allow systematic evaluation of experimental therapeutics prior to clinical use. Here, we present a genetically engineered NF2 mouse model generated through excision of the Nf2 gene driven by Cre expression under control of a tissue-restricted 3.9kbPeriostin promoter element. By 10 months of age, 100% of Postn-Cre; Nf2(flox/flox) mice develop spinal, peripheral and cranial nerve tumors histologically identical to human schwannomas. In addition, the development of cranial nerve VIII tumors correlates with functional impairments in hearing and balance, as measured by auditory brainstem response and vestibular testing. Overall, the Postn-Cre; Nf2(flox/flox) tumor model provides a novel tool for future mechanistic and therapeutic studies of NF2-associated schwannomas. C1 [Gehlhausen, Jeffrey R.; Park, Su-Jung; Shew, Matthew; Staser, Karl; Rhodes, Steven D.; Menon, Keshav; Lajiness, Jacquelyn D.; Mwanthi, Muithi; Yang, Xianlin; Yuan, Jin; Nalepa, Grzegorz; Yang, Feng-Chun; Conway, Simon J.; Clapp, D. Wade] Indiana Univ Sch Med, Herman B Wells Ctr Pediat Res, Dept Pediat, Indianapolis, IN 46202 USA. [Gehlhausen, Jeffrey R.; Park, Su-Jung; Staser, Karl; Lajiness, Jacquelyn D.; Nalepa, Grzegorz; Conway, Simon J.; Clapp, D. Wade] Indiana Univ Sch Med, Dept Biochem, Indianapolis, IN 46202 USA. [Rhodes, Steven D.; Yang, Feng-Chun; Conway, Simon J.] Indiana Univ Sch Med, Dept Anat & Cell Biol, Indianapolis, IN 46202 USA. [Mwanthi, Muithi; Clapp, D. Wade] Indiana Univ Sch Med, Dept Microbiol & Immunol, Indianapolis, IN 46202 USA. [Territo, Paul; Hutchins, Gary] Indiana Univ Sch Med, Dept Radiol, Indianapolis, IN 46202 USA. [Yates, Charles W.] Indiana Univ Sch Med, Dept Otolaryngol, Indianapolis, IN 46202 USA. [Hickox, Ann E.; Heinz, Michael G.] Purdue Univ, Dept Biomed Engn, W Lafayette, IN 47907 USA. [Hickox, Ann E.; Heinz, Michael G.] Purdue Univ, Dept Speech Language & Hearing Sci, W Lafayette, IN 47907 USA. [Stemmer-Rachamimov, Anat] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Stemmer-Rachamimov, Anat] Harvard Univ, Sch Med, Boston, MA USA. RP Yates, CW (reprint author), Dept Otolaryngol, 705 Riley Hosp Dr,RI0860, Indianapolis, IN 46202 USA. EM cwyates@iupui.edu; dclapp@iupui.edu OI Nalepa, Grzegorz/0000-0002-5779-9103; Lab, Nalepa/0000-0002-7560-1906; Hickox, Ann E./0000-0003-1033-9887 FU Department of Defense [NF110107]; National Institute of Health [P30 CA082709-14, P30 DC004665]; Children's Tumor Foundation [2012-01-013] FX This work was supported by the Department of Defense (NF110107 to D.W.C.); National Institute of Health (P30 CA082709-14 and P30 DC004665 to R.A.C.); and the Children's Tumor Foundation (2012-01-013 to J.R.G.). NR 30 TC 5 Z9 6 U1 2 U2 9 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0964-6906 EI 1460-2083 J9 HUM MOL GENET JI Hum. Mol. Genet. PD JAN 1 PY 2015 VL 24 IS 1 BP 1 EP 8 DI 10.1093/hmg/ddu414 PG 8 WC Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA CC1WH UT WOS:000350135400001 PM 25113746 ER PT J AU Bujakowska, KM Zhang, Q Siemiatkowska, AM Liu, Q Place, E Falk, MJ Consugar, M Lancelot, ME Antonio, A Lonjou, C Carpentier, W Mohand-Said, S den Hollander, AI Cremers, FPM Leroy, BP Gai, XW Sahel, JA van den Born, LI Collin, RWJ Zeitz, C Audo, I Pierce, EA AF Bujakowska, Kinga M. Zhang, Qi Siemiatkowska, Anna M. Liu, Qin Place, Emily Falk, Marni J. Consugar, Mark Lancelot, Marie-Elise Antonio, Aline Lonjou, Christine Carpentier, Wassila Mohand-Said, Saddek den Hollander, Anneke I. Cremers, Frans P. M. Leroy, Bart P. Gai, Xiaowu Sahel, Jose-Alain van den Born, L. Ingeborgh Collin, Rob W. J. Zeitz, Christina Audo, Isabelle Pierce, Eric A. TI Mutations in IFT172 cause isolated retinal degeneration and Bardet-Biedl syndrome SO HUMAN MOLECULAR GENETICS LA English DT Article ID LEBER CONGENITAL AMAUROSIS; NONSYNDROMIC RETINITIS-PIGMENTOSA; INTRAFLAGELLAR TRANSPORT PROTEIN; STATIONARY NIGHT BLINDNESS; CENTROSOMAL PROTEIN; JOUBERT-SYNDROME; GENE ABCR; IN-VIVO; DYSTROPHY; CILIARY AB Primary cilia are sensory organelles present on most mammalian cells. The assembly and maintenance of primary cilia are facilitated by intraflagellar transport (IFT), a bidirectional protein trafficking along the cilium. Mutations in genes coding for IFT components have been associated with a group of diseases called ciliopathies. These genetic disorders can affect a variety of organs including the retina. Using whole exome sequencing in three families, we identified mutations in Intraflagellar Transport 172 Homolog[IFT172(Chlamydomonas)] that underlie an isolated retinal degeneration and Bardet Biedl syndrome. Extensive functional analyses of the identified mutations in cell culture, rat retina and in zebrafish demonstrated their hypomorphic or null nature. It has recently been reported that mutations in IFT1 72 cause a severe ciliopathy syndrome involving skeletal, renal, hepatic and retinal abnormalities (Jeune and Mainzer-Saldino syndromes). Here, we report for the first time that mutations in this gene can also lead to an isolated form of retinal degeneration. The functional data for the mutations can partially explain milder phenotypes; however, the involvement of modifying alleles in the 1FT172-associated phenotypes cannot be excluded. These findings expand the spectrum of disease associated with mutations in IFT172and suggest that mutations in genes originally reported to be associated with syndromic ciliopathies should also be considered in subjects with non-syndromic retinal dystrophy. C1 [Bujakowska, Kinga M.; Zhang, Qi; Liu, Qin; Place, Emily; Consugar, Mark; Gai, Xiaowu; Pierce, Eric A.] Harvard Univ, Sch Med, Massachusetts Eye & Ear Infirm, Ocular Genom Inst, Boston, MA 02114 USA. [Bujakowska, Kinga M.; Lancelot, Marie-Elise; Antonio, Aline; Mohand-Said, Saddek; Sahel, Jose-Alain; Zeitz, Christina; Audo, Isabelle] Inst Natl Sante & Rech Med, U968, F-75012 Paris, France. [Bujakowska, Kinga M.; Lancelot, Marie-Elise; Antonio, Aline; Mohand-Said, Saddek; Sahel, Jose-Alain; Zeitz, Christina; Audo, Isabelle] Univ Paris 06, Sorbonne Univ, Inst Vis, UMR S 968, F-75012 Paris, France. [Bujakowska, Kinga M.; Lancelot, Marie-Elise; Antonio, Aline; Mohand-Said, Saddek; Sahel, Jose-Alain; Zeitz, Christina; Audo, Isabelle] CNRS, UMR 7210, F-75012 Paris, France. [Siemiatkowska, Anna M.; den Hollander, Anneke I.; Cremers, Frans P. M.; Collin, Rob W. J.] Radboud Univ Nijmegen Med Ctr, Dept Human Genet, NL-6500 HB Nijmegen, Netherlands. [den Hollander, Anneke I.; Cremers, Frans P. M.; Collin, Rob W. J.] Radboud Univ Nijmegen Med Ctr, Radboud Inst Mol Life Sci, NL-6500 HB Nijmegen, Netherlands. [den Hollander, Anneke I.] Radboud Univ Nijmegen Med Ctr, Dept Ophthalmol, NL-6500 HB Nijmegen, Netherlands. [Falk, Marni J.] Childrens Hosp Philadelphia, Div Human Genet, Dept Pediat, Philadelphia, PA 19104 USA. [Falk, Marni J.] Univ Penn, Perelman Sch Med, Philadelphia, PA 19104 USA. [Lonjou, Christine; Carpentier, Wassila] Hop La Pitie Salpetriere, Plateforme Postgenom P3S, F-75013 Paris, France. [Mohand-Said, Saddek; Sahel, Jose-Alain; Audo, Isabelle] Ctr Hosp Natl Ophtalmol Quinze Vingts, Inst Natl Sante & Rech Med, F-75012 Paris, France. [Mohand-Said, Saddek; Sahel, Jose-Alain; Audo, Isabelle] Ctr Hosp Natl Ophtalmol Quinze Vingts, Direct Hosp & Org Soins Ctr Invest Clin 1423, F-75012 Paris, France. [Leroy, Bart P.] Ghent Univ Hosp, Dept Ophthalmol, B-9000 Ghent, Belgium. [Leroy, Bart P.] Ghent Univ Hosp, Ctr Med Genet, B-9000 Ghent, Belgium. [Leroy, Bart P.] Univ Ghent, B-9000 Ghent, Belgium. [Leroy, Bart P.] Childrens Hosp Philadelphia, Div Ophthalmol, Ophthalm Genet & Visual Electrophysiol, Philadelphia, PA 19104 USA. [Sahel, Jose-Alain] Fdn Ophtalmol Adolphe Rothschild, F-75019 Paris, France. [Sahel, Jose-Alain] Inst France, Acad Sci, F-75006 Paris, France. [Sahel, Jose-Alain; Audo, Isabelle] UCL, Inst Ophthalmol, London EC1V 9EL, England. [van den Born, L. Ingeborgh] Rotterdam Eye Hosp, NL-3000 LM Rotterdam, Netherlands. RP Pierce, EA (reprint author), Massachusetts Eye & Ear, 243 Charles St, Boston, MA 02114 USA. EM eric_pierce@meei.harvard.edu RI Hollander, Anneke/N-4911-2014; Collin, Rob/N-3575-2014; Cremers, Frans/A-5625-2014; Tracewska, Anna/N-7087-2015; Zeitz, Christina/F-2757-2017; Sahel, Jose-Alain/F-3172-2017; OI Pierce, Eric/0000-0002-2354-4102 FU National Eye Institute [EY012910]; Foundation Fighting Blindness (FFB); Research to Prevent Blindness; Fleming Family Foundation; FFB [CD-CL-0808-0466-CHNO]; FFB center [C-CMM-0907-0428-INSERM04]; Foundation Voir et Entendre; Fondation Dalloz prix 'pour la recherche en ophtalmologie'; Ville de Paris and Region Ile de France; Labex LIFESENSES [ANR-10-LABX-65]; French state funds managed by the Agence Nationale de la Recherche within the Investissements d'Avenir program [ANR-11-IDEX-0004-0]; Netherlands Organisation for Scientific Research [91209047]; Stichting Wetenschappelijk Onderzoek Oogziekenhuis Prof Dr H.J. Flieringa Foundation FX This work was supported by grants from the National Eye Institute (EY012910, E.A.P), the Foundation Fighting Blindness (FFB) (E.A.P. and Q.L.), Research to Prevent Blindness (E.A.P.) and the Fleming Family Foundation (K.M.B); FFB grant CD-CL-0808-0466-CHNO (I.A.), FFB center grant C-CMM-0907-0428-INSERM04, Foundation Voir et Entendre (C.Z.), Fondation Dalloz prix 'pour la recherche en ophtalmologie' (C.Z.), Ville de Paris and Region Ile de France, and Labex LIFESENSES (ANR-10-LABX-65), supported by French state funds managed by the Agence Nationale de la Recherche within the Investissements d'Avenir program (ANR-11-IDEX-0004-0). The research studies of A.M.S. and R.W.J.C. were supported by the Netherlands Organisation for Scientific Research (TOP-grant 91209047, to F.P.M.C. and A.I.d.H.) and the Stichting Wetenschappelijk Onderzoek Oogziekenhuis Prof Dr H.J. Flieringa Foundation. NR 96 TC 26 Z9 27 U1 0 U2 13 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0964-6906 EI 1460-2083 J9 HUM MOL GENET JI Hum. Mol. Genet. PD JAN 1 PY 2015 VL 24 IS 1 BP 230 EP 242 DI 10.1093/hmg/ddu441 PG 13 WC Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA CC1WH UT WOS:000350135400018 PM 25168386 ER PT J AU Forbes, D Lockwood, E Elhai, JD Creamer, M Bryant, R McFarlane, A Silove, D Miller, MW Nickerson, A O'Donnell, M AF Forbes, David Lockwood, Emma Elhai, Jon D. Creamer, Mark Bryant, Richard McFarlane, Alexander Silove, Derrick Miller, Mark W. Nickerson, Angela O'Donnell, Meaghan TI An evaluation of the DSM-5 factor structure for posttraumatic stress disorder in survivors of traumatic injury SO JOURNAL OF ANXIETY DISORDERS LA English DT Article DE Posttraumatic stress disorder; PTSD; DSM-5; Factor analysis ID ADMINISTERED PTSD SCALE; NEUROPSYCHIATRIC INTERVIEW MINI; CONFIRMATORY FACTOR-ANALYSIS; SYMPTOM STRUCTURE; FIT INDEXES; MODEL; RELIABILITY; ANXIETY; COMORBIDITY; INSTRUMENT AB Confirmatory factor analytic studies of the latent structure of DSM-5 PTSD symptoms using self-report data (Elhai et al., 2012; Miller et al., 2013) have found that the four-factor model implied by the DSM-5 diagnostic criteria provided adequate fit to their data. However, the fit of this model is yet to be assessed using data derived from gold standard structured interview measures. This study evaluated the fit of the DSM-5 four-factor model and an alternative four-factor model in 570 injury survivors six years post-injury using the Clinician Administered PTSD Scale (Blake et al., 1990), updated to include items measuring new DSM-5 symptoms. While both four-factor models fitted the data well, very high correlations between the 'Intrusions' and 'Avoidance' factors in both models and between the 'Negative Alterations in Cognitions and Mood' and 'Arousal and Reactivity' factors in the DSM-5 model and the 'Dysphoria' and 'Hyperarousal' factors in the alternative model were evident, suggesting that a more parsimonious two-factor model combining these pairs of factors may adequately represent the latent structure. Such a two-factor model fitted the data less well according to chi(2) difference testing, but demonstrated broadly equivalent fit using other fit indices. Relationships between the factors of each of the four-factor models and the latent factors of Fear and Anxious-Misery/Distress underlying Internalizing disorders (Krueger, 1999) were also explored, with findings providing further support for the close relationship between the Intrusion and Avoidance factors. However, these findings also suggested that there may be some utility to distinguishing Negative Alterations in Cognition and Mood symptoms from Arousal and Reactivity symptoms, and/or Dysphoria symptoms from Hyperarousal symptoms. Further studies are required to assess the potential discriminant validity of the two four-factor models. (C) 2014 Elsevier Ltd. All rights reserved. C1 [Forbes, David; Lockwood, Emma; Creamer, Mark; O'Donnell, Meaghan] Australian Ctr Posttraumat Mental Hlth, Carlton, Vic 3053, Australia. [Forbes, David; Lockwood, Emma; Creamer, Mark; O'Donnell, Meaghan] Dept Psychiat, Melbourne, Vic 3053, Australia. [Elhai, Jon D.] Univ Toledo, Dept Psychol, Toledo, OH 43606 USA. [Elhai, Jon D.] Univ Toledo, Dept Psychiat, Toledo, OH 43606 USA. [Bryant, Richard; Nickerson, Angela] Univ New S Wales, Sch Psychol, Sydney, NSW 2052, Australia. [McFarlane, Alexander] Ctr Traumat Stress Studies, Adelaide, SA 5000, Australia. [Silove, Derrick] Liverpool Hosp, Psychiat Res & Teaching Unit, Mental Hlth Ctr, Liverpool, NSW 2170, Australia. [Miller, Mark W.] VA Boston Healthcare Syst, Natl Ctr PTSD 116B 2, Boston, MA 02130 USA. RP Forbes, D (reprint author), Australian Ctr Posttraumat Mental Hlth, Level 3,161 Barry St, Carlton, Vic 3053, Australia. EM dforbes@unimelb.edu.au RI Miller, Mark/G-7322-2011; OI Miller, Mark/0000-0001-6393-8563; Bryant, Richard/0000-0002-9607-819X FU National Health and Medical Research Council (NHMRC) [300304] FX This study was supported by a National Health and Medical Research Council (NHMRC) Program Grant (300304). NR 51 TC 9 Z9 9 U1 5 U2 10 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 2015 VL 29 BP 43 EP 51 DI 10.1016/j.janxdis.2014.11.004 PG 9 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA CC3RC UT WOS:000350265700007 PM 25465886 ER PT J AU Eddy, KT Lawson, EA Meade, C Meenaghan, E Horton, SE Misra, M Klibanski, A Miller, KK AF Eddy, Kamryn T. Lawson, Elizabeth A. Meade, Christina Meenaghan, Erinne Horton, Sarah E. Misra, Madhusmita Klibanski, Anne Miller, Karen K. TI Appetite Regulatory Hormones in Women With Anorexia Nervosa: Binge-Eating/Purging Versus Restricting Type SO JOURNAL OF CLINICAL PSYCHIATRY LA English DT Article ID BODY-MASS INDEX; BONE-MINERAL DENSITY; BULIMIA-NERVOSA; PEPTIDE YY; EATING-DISORDERS; LEPTIN LEVELS; WEIGHT REGULATION; FOOD-INTAKE; BDNF; GHRELIN AB Objective: Anorexia nervosa is a psychiatric illness characterized by low weight, disordered eating, and hallmark neuroendocrine dysfunction. Behavioral phenotypes are defined by predominant restriction or bingeing/purging; binge-eating/purging type anorexia nervosa is associated with poorer outcome. The pathophysiology underlying anorexia nervosa types is unknown, but altered hormones, known to be involved in eating behaviors, may play a role. Method: To examine the role of anorexigenic hormones in anorexia nervosa subtypes, we examined serum levels of peptide YY (PYY; total and active [3-36] forms), brain-derived neurotrophic factor (BDNF), and leptin as primary outcomes in women with DSM-5 restricting type anorexia nervosa (n = 50), binge-eating/purging type anorexia nervosa (n = 25), and healthy controls (n = 22). In addition, women completed validated secondary outcome measures of eating disorder psychopathology (Eating Disorder Examination-Questionnaire) and depression and anxiety symptoms (Hamilton Rating Scales for Depression [HDRS] and Anxiety [HARS]). The study samples were collected from May 22, 2004, to February 7, 2012. Results: Mean PYY 3-36 and leptin levels were lower and BDNF levels higher in binge-eating/purging type anorexia nervosa than in restricting type anorexia nervosa (all P values < .05). After controlling for body mass index, differences in PYY and PYY 3-36 between anorexia nervosa types were significant (P < .05) and differences in BDNF were at the trend level (P <.10). PYY 3-36 was positively (r = 0.27, P = .02) and leptin was negatively (r = -0.51, P < .0001) associated with dietary restraint; BDNF was positively associated with frequency of purging (r = 0.21, P = .04); and leptin was negatively associated with frequency of bingeing (r = -0.29, P = .007) and purging (r = -0.31, P = .004). Conclusions: Among women with anorexia nervosa, the anorexigenic hormones PYY, BDNF, and leptin are differentially regulated between the restricting and binge/purge types. Whether these hormone pathways play etiologic roles with regard to anorexia nervosa behavioral types or are compensatory merits further study. (C) Copyright 2014 Physicians Postgraduate Press, Inc. C1 [Eddy, Kamryn T.] Massachusetts Gen Hosp, Dept Psychiat, Eating Disorders Clin & Res Program, Boston, MA 02114 USA. [Lawson, Elizabeth A.; Meade, Christina; Meenaghan, Erinne; Misra, Madhusmita; Klibanski, Anne; Miller, Karen K.] Massachusetts Gen Hosp, Dept Med, Neuroendocrine Unit, Boston, MA 02114 USA. RP Eddy, KT (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Eating Disorders Clin & Res Program,Dept Psychiat, 2 Longfellow Pl,Ste 200, Boston, MA 02114 USA. EM keddy@mgh.harvard.edu FU National Institutes of Health [R01 MH083657, UL1 RR025758] FX Supported in part by National Institutes of Health grants R01 MH083657 and UL1 RR025758. NR 35 TC 7 Z9 7 U1 1 U2 20 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 PD JAN PY 2015 VL 76 IS 1 BP 19 EP 24 DI 10.4088/JCP.13m08753 PG 6 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA CD3JC UT WOS:000350973400015 PM 25098834 ER PT J AU Mischoulon, D Nierenberg, AA Schettler, PJ Kinkead, BL Fehling, K Martinson, MA Rapaport, MH AF Mischoulon, David Nierenberg, Andrew A. Schettler, Pamela J. Kinkead, Becky L. Fehling, Kiki Martinson, Max A. Rapaport, Mark Hyman TI A Double-Blind, Randomized Controlled Clinical Trial Comparing Eicosapentaenoic Acid Versus Docosahexaenoic Acid for Depression SO JOURNAL OF CLINICAL PSYCHIATRY LA English DT Article ID POLYUNSATURATED FATTY-ACIDS; PLACEBO-CONTROLLED TRIAL; POSTTRAUMATIC-STRESS-DISORDER; FISH-OIL SUPPLEMENTATION; STAR-ASTERISK-D; MAJOR DEPRESSION; OMEGA-3 SUPPLEMENTATION; PATIENT CHARACTERISTICS; ACCIDENTAL INJURY; RATING-SCALE AB Objective: To compare 2 omega-3 (n-3) preparations enriched with eicosapentaenoic acid (EPA) versus docosahexaenoic acid (DHA) as monotherapy for major depressive disorder (MDD) in a 2-site, placebo-controlled, randomized, double-blind clinical trial. Method: 196 adults (53% female; mean [SD] age = 44.7 [13.4] years) with DSM-IV MDD and a baseline 17-item Hamilton Depression Rating Scale (HDRS-17) score >= 15 were randomized equally from May 18, 2006, to June 30, 2011, to 8 weeks of double-blind treatment with oral EPA-enriched n-3 1000 mg/d, DHA-enriched n-3 1,000 mg/d, or placebo. Results: 154 subjects completed the study. Modified intent-to-treat (mITT) analysis (n = 177 subjects with >= 1 postbaseline visit; 59.3% female, mean [SD] age 45.8 [12.5] years) employed mixed-model repeated measures (MMRM). All 3 groups demonstrated statistically significant improvement in the HDRS-17 (primary outcome measure), 16-item Quick Inventory of Depressive Symptomatology-Self Report (QIDS-SR-16), and Clinical Global Improvement-Severity Scale (CGI-S) (P < .05), but neither n-3 preparation separated from placebo (P > .05). Response and remission rates were in the range of 40%-50% and 30%, respectively, for all treatments, with no significant differences between groups. One subject receiving EPA-enriched n-3 discontinued due to worsening depression, and 1 subject receiving placebo discontinued due to an unspecified "negative reaction" to pills. Conclusions: Neither EPA-enriched nor DHA-enriched n-3 was superior to placebo for the treatment of MDD. (C) Copyright 2014 Physicians Postgraduate Press, Inc. C1 [Mischoulon, David; Nierenberg, Andrew A.; Fehling, Kiki; Martinson, Max A.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Depress Clin & Res Program, Boston, MA USA. [Schettler, Pamela J.; Kinkead, Becky L.; Rapaport, Mark Hyman] Emory Univ, Dept Psychiat & Behav Sci, Atlanta, GA 30322 USA. RP Mischoulon, D (reprint author), 1 Bowdoin Sq,6th Floor, Boston, MA 02114 USA. EM dmisc.houlon@partners.org FU National Institutes of Health (NIH) [5R01MH74085] FX The study was funded by grant 5R01MH74085 from the National Institutes of Health (NIH) to Drs Mischoulon and Rapaport. EPA-enriched and DHA-enriched preparations and matching placebos were kindly provided by NordicNaturals. NR 51 TC 15 Z9 15 U1 8 U2 25 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 PD JAN PY 2015 VL 76 IS 1 BP 54 EP + DI 10.4088/JCP.14m08986 PG 11 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA CD3JC UT WOS:000350973400021 PM 25272149 ER PT J AU Walker, J AF Walker, Jennifer TI Practice improves performance on a coronary anastomosis simulator, attending surgeon supervision does not SO JOURNAL OF THORACIC AND CARDIOVASCULAR SURGERY LA English DT Editorial Material C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Walker, J (reprint author), Massachusetts Gen Hosp, 55 Fruit St,EDR 105, Boston, MA 02114 USA. EM jdwalker@partners.org NR 0 TC 0 Z9 0 U1 0 U2 0 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0022-5223 EI 1097-685X J9 J THORAC CARDIOV SUR JI J. Thorac. Cardiovasc. Surg. PD JAN PY 2015 VL 149 IS 1 BP 18 EP 18 DI 10.1016/j.jtcvs.2014.09.058 PG 1 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery SC Cardiovascular System & Cardiology; Respiratory System; Surgery GA CC7LW UT WOS:000350550100009 PM 25524669 ER PT J AU Lin, AY Kotova, S Yanagawa, J Elbuluk, O Wang, G Kar, N Elashoff, D Grogan, T Cameron, RB Singh, A Chmielowski, B Federman, N Nelson, SD Lee, P Eilber, FC Lee, JM AF Lin, Anthony Y. Kotova, Svetlana Yanagawa, Jane Elbuluk, Osama Wang, Gerald Kar, Nivedita Elashoff, David Grogan, Tristan Cameron, Robert B. Singh, Arun Chmielowski, Bartosz Federman, Noah Nelson, Scott D. Lee, Percy Eilber, Fritz C. Lee, Jay M. TI Risk stratification of patients undergoing pulmonary metastasectomy for soft tissue and bone sarcomas SO JOURNAL OF THORACIC AND CARDIOVASCULAR SURGERY LA English DT Article ID LONG-TERM SURVIVAL; HIGH-GRADE OSTEOSARCOMA; PROGNOSTIC-FACTORS; RESECTION; CHEMOTHERAPY; OUTCOMES; BENEFIT AB Objectives: Our objective was to identify risk factors associated with survival in patients who underwent pulmonary metastasectomy for soft tissue or bone sarcoma and to create a risk stratification model. Methods: A retrospective review of the prospectively maintained University of California Los Angeles Sarcoma Database was performed. Clinical, pathologic, and treatment variables were analyzed for overall survival and disease-free survival. Univariate and multivariate analyses were performed, and variables that were identified as significant were included to create a risk model. A total of 155 patients who underwent pulmonary metastasectomy for soft tissue sarcoma (n = 108 patients) or bone sarcoma (n = 47 patients) from 1994 to 2010 were identified. Results: Multivariate analysis identified 7 factors associated with poor overall survival: age more than 45 years, disease-free interval less than 1 year, thoracotomy, synchronous disease, location and type of sarcoma (soft tissue vs bone sarcoma), and performance of a lobectomy. The number of factors present was associated with poor overall survival, which varied widely from 64% in patients with 2 factors to 3% in those with 5 factors. Conclusions: We have identified prognostic variables associated with overall survival after lung metastasectomy. Our model may be used as a risk stratification model to guide treatment decisions on the basis of the number of risk factors present. Although prospective studies are warranted to determine the benefit of surgical intervention in all cohorts compared with other local therapies or medical therapy, given the attendant dismal prognosis in patients with 5 or more risk factors, the benefit of surgical resection in this group is questioned. C1 [Lin, Anthony Y.; Kotova, Svetlana; Yanagawa, Jane; Elbuluk, Osama; Cameron, Robert B.; Lee, Jay M.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Surg, Div Thorac Surg, Los Angeles, CA 90095 USA. [Wang, Gerald] Univ Calif Los Angeles, David Geffen Sch Med, Dept Med, Div Pulm & Crit Care Med, Los Angeles, CA 90095 USA. [Kar, Nivedita] Univ Calif Los Angeles, David Geffen Sch Med, Dept Biostat, Los Angeles, CA 90095 USA. [Kar, Nivedita] Univ Calif Los Angeles, David Geffen Sch Med, Dept Med, Los Angeles, CA 90095 USA. [Elashoff, David; Grogan, Tristan] Univ Calif Los Angeles, David Geffen Sch Med, Div Gen Internal Med & Hlth Serv Res, Los Angeles, CA 90095 USA. [Singh, Arun; Chmielowski, Bartosz] Univ Calif Los Angeles, David Geffen Sch Med, Dept Med, Div Hematol & Med Oncol, Los Angeles, CA 90095 USA. [Federman, Noah] Univ Calif Los Angeles, David Geffen Sch Med, Div Pediat Hematol & Med Oncol, Dept Pediat, Los Angeles, CA 90095 USA. [Nelson, Scott D.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Pathol & Lab Med, Los Angeles, CA 90095 USA. [Lee, Percy] Univ Calif Los Angeles, David Geffen Sch Med, Dept Radiat Oncol, Los Angeles, CA 90095 USA. [Eilber, Fritz C.] Univ Calif Los Angeles, David Geffen Sch Med, Div Surg Oncol, Dept Surg, Los Angeles, CA 90095 USA. [Kotova, Svetlana; Cameron, Robert B.] Vet Affairs Greater Los Angeles Healthcare Syst, Div Thorac Surg, Dept Surg, Los Angeles, CA USA. RP Lee, JM (reprint author), Univ Calif Los Angeles, Med Ctr, Div Thorac Surg, Box 957313,Room 64-128 CHS,10833 Le Conte Ave, Los Angeles, CA 90095 USA. EM jaymoonlee@mednet.ucla.edu OI Chmielowski, Bartosz/0000-0002-2374-3320 FU Jonsson Comprehensive Cancer Center Sarcoma Program FX Funded by the Jonsson Comprehensive Cancer Center Sarcoma Program. NR 20 TC 7 Z9 7 U1 0 U2 2 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0022-5223 EI 1097-685X J9 J THORAC CARDIOV SUR JI J. Thorac. Cardiovasc. Surg. PD JAN PY 2015 VL 149 IS 1 BP 85 EP 92 DI 10.1016/j.jtcvs.2014.09.039 PG 8 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery SC Cardiovascular System & Cardiology; Respiratory System; Surgery GA CC7LW UT WOS:000350550100030 PM 25312228 ER PT J AU You, ML Zhong, JJ Hong, Y Duan, ZF Lin, M Xu, F AF You, Minli Zhong, Junjie Hong, Yuan Duan, Zhenfeng Lin, Min Xu, Feng TI Inkjet printing of upconversion nanoparticles for anti-counterfeit applications SO NANOSCALE LA English DT Article ID CONTROLLED CONTACT-ANGLE; NAYF4 NANOCRYSTALS; REYNOLDS-NUMBERS; SOLID-SURFACE; LOW WEBER; LUMINESCENCE; PAPER; ELECTRONICS; GRAPHENE; INKS AB Patterning of upconversion luminescent materials has been widely used for anti-counterfeit and security applications, where the preferred method should be easy, fast, multicolor, high-throughput and designable. However, conventional patterning methods are complex and inflexible. Here, we report a digital and flexible inkjet printing based approach for producing high-resolution and high-luminescence anti-counterfeit patterns. We successfully printed different multicolor luminescent patterns by inkjet printing of upconversion nanoparticles with controlled and uniform luminescence intensity through optimizing the inks and substrates. Combined with another downconversion luminescent material, we achieved two different patterns in the same area, which show up separately under excitation by different wavelength laser sources. The developed technology is promising to use one single substrate for carrying abundant information by printing multilayer patterns composed of luminescent materials with different excitation light sources. C1 [You, Minli; Lin, Min; Xu, Feng] Xi An Jiao Tong Univ, Sch Life Sci & Technol, Minist Educ, Key Lab Biomed Informat Engn, Xian 710049, Peoples R China. [You, Minli; Zhong, Junjie; Hong, Yuan; Lin, Min; Xu, Feng] Xi An Jiao Tong Univ, BEBC, Xian 710049, Peoples R China. [Zhong, Junjie] Xi An Jiao Tong Univ, Sch Energy & Power Engn, Xian 710049, Peoples R China. [Hong, Yuan] Nanjing Agr Univ, Coll Life Sci, Nanjing 210095, Jiangsu, Peoples R China. [Duan, Zhenfeng; Lin, Min] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Sarcoma & Connect Tissue Oncol, Boston, MA 02114 USA. 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 minlin@mail.xjtu.edu.cn; fengxu@mail.xjtu.edu.cn RI Xu, Feng/C-7430-2011; Xu, Feng/H-4468-2011 OI Xu, Feng/0000-0003-4351-0222 FU Major International Joint Research Program of China [11120101002]; International Science & Technology Cooperation Program of China [2013DFG02930]; National Key Scientific Apparatus Development of Special Item [2013YQ190467]; Fundamental Research Funds for the Central Universities [2012jdhz46]; China Scholarship of Council; China Young 1000-Talent Program; Program for New Century Excellent Talents in University FX This work was financially supported by the Major International Joint Research Program of China (11120101002), the International Science & Technology Cooperation Program of China (2013DFG02930), National Key Scientific Apparatus Development of Special Item (2013YQ190467), and the Fundamental Research Funds for the Central Universities (2012jdhz46). Min Lin is supported by a scholarship from the China Scholarship of Council. Feng Xu was also partially supported by the China Young 1000-Talent Program and the Program for New Century Excellent Talents in University. The TEM work was done at International Center for Dielectric Research (ICDR), Xi'an Jiaotong University, Xi'an, China. The authors also thank Ms Lu Lu and Mr Ma Chuan Sheng for their help in using TEM. NR 55 TC 32 Z9 33 U1 622 U2 709 PU ROYAL SOC CHEMISTRY PI CAMBRIDGE PA THOMAS GRAHAM HOUSE, SCIENCE PARK, MILTON RD, CAMBRIDGE CB4 0WF, CAMBS, ENGLAND SN 2040-3364 EI 2040-3372 J9 NANOSCALE JI Nanoscale PY 2015 VL 7 IS 10 BP 4423 EP 4431 DI 10.1039/c4nr06944g PG 9 WC Chemistry, Multidisciplinary; Nanoscience & Nanotechnology; Materials Science, Multidisciplinary; Physics, Applied SC Chemistry; Science & Technology - Other Topics; Materials Science; Physics GA CC9ED UT WOS:000350669900017 PM 25613526 ER PT S AU Yang, XH Friedl, A AF Yang, Xinhai Friedl, Andreas BE Diakonova, M TI A Positive Feedback Loop Between Prolactin and STAT5 Promotes Angiogenesis SO RECENT ADVANCES IN PROLACTIN RESEARCH SE Advances in Experimental Medicine and Biology LA English DT Article; Book Chapter ID BREAST-CANCER-CELLS; CAPILLARY ENDOTHELIAL-CELLS; GROWTH-HORMONE FAMILY; N-TERMINAL FRAGMENTS; CYCLIN D1 PROMOTER; SIGNAL-TRANSDUCTION; MESSENGER-RNA; 16-KDA PROLACTIN; JAK/STAT PATHWAY; SERINE PHOSPHORYLATION AB The signal transduction events that orchestrate cellular activities required for angiogenesis remain incompletely understood. We and others recently described that proangiogenic mediators such as fibroblast growth factors can activate members of the signal transducers and activators of transcription (STAT) family. STAT5 activation is necessary and sufficient to induce migration, invasion and tube formation of endothelial cells. STAT5 effects on endothelial cells require the secretion of the prolactin (PRL) family member proliferin-1 (PLF1) in mice and PRL in humans. In human endothelial cells, PRL activates the PRL receptor (PRLR) resulting in MAPK and STAT5 activation, thus closing a positive feedback loop. In vivo, endothelial cell-derived PRL is expected to combine with PRL of tumor cell and pituitary origin to raise the concentration of this polypeptide hormone in the tumor microenvironment. Thus, PRL may stimulate tumor angiogenesis via autocrine, paracrine, and endocrine pathways. The disruption of tumor angiogenesis by interfering with PRL signaling may offer an attractive target for therapeutic intervention. C1 [Yang, Xinhai; Friedl, Andreas] Univ Wisconsin, Dept Pathol & Lab Med, Madison, WI 53705 USA. [Friedl, Andreas] William S Middleton Mem Vet Adm Med Ctr, Pathol & Lab Med Serv, Dept Vet Affairs, Med Ctr, Madison, WI 53705 USA. [Friedl, Andreas] Univ Wisconsin, Carbone Canc Ctr, Madison, WI USA. RP Friedl, A (reprint author), Univ Wisconsin, Dept Pathol & Lab Med, 6051 WIMR,MC-2275,1111 Highland Ave, Madison, WI 53705 USA. EM afriedl@wisc.edu FU NCI NIH HHS [P30 CA014520] NR 134 TC 4 Z9 4 U1 3 U2 10 PU SPRINGER-VERLAG BERLIN PI BERLIN PA HEIDELBERGER PLATZ 3, D-14197 BERLIN, GERMANY SN 0065-2598 BN 978-3-319-12114-7; 978-3-319-12113-0 J9 ADV EXP MED BIOL JI Adv.Exp.Med.Biol. PY 2015 VL 846 BP 265 EP 280 DI 10.1007/978-3-319-12114-7_12 D2 10.1007/978-3-319-12114-7 PG 16 WC Biology; Medicine, Research & Experimental; Physiology SC Life Sciences & Biomedicine - Other Topics; Research & Experimental Medicine; Physiology GA BC1TY UT WOS:000350422800013 PM 25472543 ER PT J AU Kalman, RS Pedrosa, MC AF Kalman, Richard S. Pedrosa, Marcos C. TI Evidence-based Review of Gastrointestinal Bleeding in the Chronic Kidney Disease Patient SO SEMINARS IN DIALYSIS LA English DT Article ID CHRONIC-RENAL-FAILURE; VASCULAR MALFORMATIONS; HEMODIALYSIS-PATIENTS; HORMONAL-THERAPY; ISCHEMIC COLITIS; STERCORAL ULCER; ANGIODYSPLASIA; PREVENTION; PREVALENCE; HEMORRHAGE AB Patients with end-stage renal disease are more likely to suffer from gastrointestinal (GI) problems, including bleeding from upper and lower sources. Peptic ulcer disease is the most common cause of upper GI bleeding, and although there is some debate in the literature regarding whether the frequency of ulcer disease is higher in patients with kidney disease, it is well established that outcomes are worse in patients with compromised renal function. Angioectasias can be found throughout the GI tract and are another common cause of bleeding; management can be divided into localized endoscopic therapy and systemic hormonal treatment, or surgery for refractory cases. The most frequent causes of lower GI bleeding in this population, in addition to angioectasias, are diverticulosis, hemorrhoids, and ischemic colitis. C1 [Kalman, Richard S.] Boston Univ, Med Ctr, Dept Med, Gastroenterol Sect, Boston, MA USA. [Pedrosa, Marcos C.] VA Boston Healthcare Syst, Dept Med, Gastroenterol Sect, Boston, MA USA. RP Kalman, RS (reprint author), Boston Med Ctr, 85 East Concord St,Suite 7720, Boston, MA 02118 USA. EM richard.kalman@bmc.org NR 42 TC 4 Z9 4 U1 1 U2 3 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0894-0959 EI 1525-139X J9 SEMIN DIALYSIS JI Semin. Dial. PD JAN-FEB PY 2015 VL 28 IS 1 BP 68 EP 74 DI 10.1111/sdi.12301 PG 7 WC Urology & Nephrology SC Urology & Nephrology GA CD4KA UT WOS:000351050000015 PM 25215610 ER PT J AU Dilwali, S Roberts, D Stankovic, KM AF Dilwali, Sonam Roberts, Daniel Stankovic, Konstantina M. TI Interplay between VEGF-A and cMET signaling in human vestibular schwannomas and schwann cells SO CANCER BIOLOGY & THERAPY LA English DT Article DE hepatocyte growth factor; Schwann cells; siRNA; cross-talk; vascular endothelial growth factor; vestibular schwannoma ID HEPATOCYTE GROWTH-FACTOR; NEUROFIBROMATOSIS TYPE-2; C-MET; BEVACIZUMAB; EXPRESSION; PATHWAYS; RECEPTOR AB Vestibular schwannoma (VS), the fourth most common intracranial tumor, arises from the Schwann cells of the vestibular nerve. Although several pathways have been independently implicated in VS pathobiology, interactions among these pathways have not been explored in depth. We have investigated the potential cross-talk between hepatocyte growth factor (HGF) and vascular endothelial growth factor-A (VEGF-A) in human VS, an interaction that has been described in other physiological and pathological cell types. We affirmed previous findings that VEGF-A signaling is aberrantly upregulated in VS, and established that expression of HGF and its receptor cMET is also significantly higher in sporadic VS than in healthy nerves. In primary human VS and Schwann cell cultures, we found that VEGF-A and HGF signaling pathways modulate each other. siRNAs targeting cMET decreased both cMET and VEGF-A protein levels, and siRNAs targeting VEGF-A reduced cMET expression. Additionally, siRNA-mediated knockdown of VEGF-A or cMET and pharmacologic inhibition of cMET decreased cellular proliferation in primary human VS cultures. Our data suggest cross-talk between these 2 prominent pathways in VS and highlight the HGF/cMET pathway as an additional important therapeutic target in VS. C1 [Dilwali, Sonam; Roberts, Daniel; Stankovic, Konstantina M.] Massachusetts Eye & Ear Infirm, Eaton Peabody Lab, Boston, MA 02114 USA. [Dilwali, Sonam; Roberts, Daniel; Stankovic, Konstantina M.] Massachusetts Eye & Ear Infirm, Dept Otolaryngol, Boston, MA 02114 USA. [Dilwali, Sonam; Stankovic, Konstantina M.] Harvard Massachusetts Inst Technol, Program Speech & Hearing Biosci & Technol, Boston, MA USA. [Roberts, Daniel; Stankovic, Konstantina M.] Harvard Univ, Sch Med, Dept Otol & Laryngol, Boston, MA USA. RP Stankovic, KM (reprint author), Massachusetts Eye & Ear Infirm, Eaton Peabody Lab, Boston, MA 02114 USA. EM konstantina_stankovic@meei.harvard.edu FU National Institute on Deafness and Other Communication Disorders [T32 DC00038, K08DC010419]; Bertarelli Foundation; US. Department of Defense [W81XWH-14-1-0091] FX This study was supported by the National Institute on Deafness and Other Communication Disorders Grants T32 DC00038 (SD, KMS) and K08DC010419 (KMS), the Bertarelli Foundation (KMS) and the US. Department of Defense Grant W81XWH-14-1-0091 (KMS). NR 15 TC 1 Z9 1 U1 1 U2 3 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 530 WALNUT STREET, STE 850, PHILADELPHIA, PA 19106 USA SN 1538-4047 EI 1555-8576 J9 CANCER BIOL THER JI Cancer Biol. Ther. PD JAN PY 2015 VL 16 IS 1 BP 170 EP 175 DI 10.4161/15384047.2014.972765 PG 6 WC Oncology SC Oncology GA CC0AJ UT WOS:000349996700021 PM 25692621 ER PT J AU Aguilar, C Beltran, B Quinones, P Carbajal, T Vilcapaza, J Yabar, A Segura, P Quintanilla-Martinez, L Miranda, RN Castillo, JJ AF Aguilar, Cristian Beltran, Brady Quinones, Pilar Carbajal, Tomas Vilcapaza, Jorge Yabar, Alejandro Segura, Pedro Quintanilla-Martinez, Leticia Miranda, Roberto N. Castillo, Jorge J. TI Large B-cell lymphoma arising in cardiac myxoma or intracardiac fibrinous mass: a localized lymphoma usually associated with Epstein-Barr virus? SO CARDIOVASCULAR PATHOLOGY LA English DT Article DE Cardiac myxoma; B-cell lymphoma; Epstein-Barr virus; EBER; Chronic inflammation ID LEFT ATRIAL-MYXOMA; INTERLEUKIN-6 AB Primary cardiac neoplasms are rare. However, among them, cardiac myxoma is the most common tumor. In contrast, primary cardiac lymphoma within a cardiac myxoma is extremely rare and might be difficult to diagnose because of non-specific clinical manifestations. We report the case of a previously healthy 52-year-old man who presented with acute onset of transient dysarthria and left hemiplegia. A transthoracic echocardiography showed a 6x2.5-cm solid mass in the left atrium, which was subsequently resected. Histological, immunohistochemical, and molecular analyses revealed an EBV-associated CD30-positive large B-cell lymphoma with anaplastic morphology within a cardiac myxoma and fibrinous material. Staging studies showed no evidence of lymphoma elsewhere. The patient achieved complete remission and is alive 42 months after diagnosis, and did not receive chemotherapy. We discuss the clinical and pathologic features of lymphoma arising in cardiac myxoma or in intra-atrial fibrinoid mass and the potential role of IL-6 in its pathogenesis. (C) 2014 Elsevier Inc. All rights reserved. C1 [Aguilar, Cristian; Quinones, Pilar; Carbajal, Tomas; Vilcapaza, Jorge; Yabar, Alejandro] Hosp Edgardo Rebagliati, Dept Patol, Lima, Peru. [Beltran, Brady] Edgardo Rebagliati Hosp, Dept Oncol & Radiotherapy, Lima, Peru. [Segura, Pedro] Edgardo Rebagliati Hosp, Dept Cardiol, Lima, Peru. [Quintanilla-Martinez, Leticia] Univ Tubingen, Inst Pathol, Tubingen, Germany. [Quintanilla-Martinez, Leticia] Univ Tubingen, Ctr Comprehens Canc, Tubingen, Germany. [Miranda, Roberto N.] Univ Texas MD Anderson Canc Ctr, Dept Hematopathol, Houston, TX 77030 USA. [Castillo, Jorge J.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Div Hematol Malignancies, Boston, MA 02115 USA. RP Aguilar, C (reprint author), Hosp Edgardo Rebagliati, Dept Patol, Ave Salaverry, Lima, Peru. EM dr.cris85@yahoo.com OI Miranda, Roberto/0000-0002-8467-5464; Segura-Saldana, Pedro/0000-0002-7859-8466; Beltran, Brady/0000-0003-4469-3817; Castillo, Jorge/0000-0001-9490-7532 NR 27 TC 6 Z9 6 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1054-8807 EI 1879-1336 J9 CARDIOVASC PATHOL JI Cardiovasc. Pathol. PD JAN-FEB PY 2015 VL 24 IS 1 BP 60 EP 64 DI 10.1016/j.carpath.2014.08.007 PG 5 WC Cardiac & Cardiovascular Systems; Pathology SC Cardiovascular System & Cardiology; Pathology GA CC3EU UT WOS:000350229400009 PM 25307939 ER PT J AU Boros, E Gale, EM Caravan, P AF Boros, Eszter Gale, Eric M. Caravan, Peter TI MR imaging probes: design and applications SO DALTON TRANSACTIONS LA English DT Article ID HUMAN SERUM-ALBUMIN; AORTOILIAC OCCLUSIVE DISEASE; ANGIOGRAPHY CONTRAST AGENT; SATURATION-TRANSFER CEST; WATER EXCHANGE-RATE; HIGH-RELAXIVITY; PROTEIN-BINDING; GADOLINIUM COMPLEX; GD3+ COMPLEXES; ENHANCED MRI AB This perspective outlines strategies towards the development of MR imaging probes that our lab has explored over the last 15 years. Namely, we discuss methods to enhance the signal generating capacity of MR probes and how to achieve tissue specificity through protein targeting or probe activation within the tissue microenvironment. C1 [Caravan, Peter] Massachusetts Gen Hosp, Dept Radiol, Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Charlestown, MA 02129 USA. RP Caravan, P (reprint author), Massachusetts Gen Hosp, Dept Radiol, Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA 02129 USA. EM caravan@nmr.mgh.harvard.edu FU National Cancer Institute [CA161221, CA009502]; National Institute for Biomedical Imaging and Bioengineering [EB009062]; Swiss National Science Foundation FX This work was supported by grants from the National Cancer Institute (CA161221 to PC and a T32 post-doctoral fellowship to EMG, CA009502) and the National Institute for Biomedical Imaging and Bioengineering (EB009062). E.B. thanks the Swiss National Science Foundation (advanced. postdoc mobility fellowship) for support. The contributions of our co-authors to the papers cited is warmly acknowledged. NR 154 TC 22 Z9 22 U1 7 U2 54 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 2015 VL 44 IS 11 BP 4804 EP 4818 DI 10.1039/c4dt02958e PG 15 WC Chemistry, Inorganic & Nuclear SC Chemistry GA CC6PO UT WOS:000350488300003 PM 25376893 ER PT J AU Locatelli, SM Turcios, S LaVela, SL AF Locatelli, Sara M. Turcios, Stephanie LaVela, Sherri L. TI Optimizing the Patient-Centered Environment: Results of Guided Tours With Health Care Providers and Employees SO HERD-HEALTH ENVIRONMENTS RESEARCH & DESIGN JOURNAL LA English DT Article DE patient-centered care; design; architecture; patient and/or family; health care ID PARTICIPATORY ACTION RESEARCH; DESIGN; COMPLEMENTARY; INTERVENTION; EXPERIENCE; VETERANS; MEDICINE; STORIES; QUALITY; EXPLORE AB Objective: To examine providers' perspectives on the care environment and patient-centered care (PCC) through the eyes of the veteran patient, using guided tours qualitative methodology. Background: Environmental factors, such as attractiveness and function, have the potential to improve patients' experiences. Participatory qualitative methods allow researchers to explore the environment and facilitate discussion. Methods: Guided tours were conducted with 25 health care providers/employees at two Veterans Affairs (VA) health care facilities. In guided tours, participants lead the researcher through an environment, commenting on their surroundings, thoughts, and feelings. The researcher walks along with the participant, asking open-ended questions as needed to foster discussion and gain an understanding of the participant's view. Participants were asked to walk through the facility as though they were a veteran. Tours were audio recorded, with participant permission, and transcribed verbatim by research assistants. Three qualitative researchers were responsible for code-book development and coding transcripts and used data-driven coding approaches. Results: Participants discussed physical appearance of the environment and how that influences perceptions about care. Overall, participants highlighted the need to shed the "institutional'' appearance. Differences between VA and non-VA health care facilities were discussed, including availability of private rooms and staff to assist with navigating the facility. They reviewed resources in the facility, such as the information desk to assist patients and families. Finally, they offered suggestions for future improvements, including improvements to waiting areas and quiet areas for patients to relax and "get away'' from their rooms. Conclusions: Participants highlighted many small changes to the care environment that could enhance the patient experience. Additionally, they examined the environment from the patient's perspective, to identify elements that enhance, or detract from, the patient's care experience. C1 [Locatelli, Sara M.; LaVela, Sherri L.] US Dept Vet Affairs, Vet Affairs Edward Hines Jr Hosp, Ctr Innovat Complex Chron Healthcare, Hines, IL 60141 USA. [Locatelli, Sara M.; Turcios, Stephanie; LaVela, Sherri L.] US Dept Vet Affairs, Vet Affairs Edward Hines Jr Hosp, Ctr Evaluat Practices & Experiences Patient Ctr C, Hines, IL 60141 USA. [LaVela, Sherri L.] Northwestern Univ, Feinberg Sch Med, Ctr Healthcare Studies, Chicago, IL 60611 USA. RP Locatelli, SM (reprint author), US Dept Vet Affairs, Vet Affairs Edward Hines Jr Hosp, Ctr Innovat Complex Chron Healthcare, Roosevelt Rd & 5th Ave, Hines, IL 60141 USA. EM sara.locatelli@va.gov FU Veterans Affairs (VA) Office of Patient-Centered Care & Cultural Transformation; VA Health Services Research & Development Quality Enhancement Research Initiative [PCE 13-002] FX The author(s) disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: This article is based on an evaluation funded by the Veterans Affairs (VA) Office of Patient-Centered Care & Cultural Transformation and the VA Health Services Research & Development Quality Enhancement Research Initiative (PCE 13-002, PI: LaVela). NR 42 TC 3 Z9 3 U1 1 U2 4 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 1937-5867 EI 2167-5112 J9 HERD-HEALTH ENV RES JI Herd-Health Env. Res. Des. J. PD JAN PY 2015 VL 8 IS 2 BP 18 EP 30 DI 10.1177/1937586714565610 PG 13 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA CC5QF UT WOS:000350414800004 PM 25816378 ER PT J AU Bloom, M Markovitz, S Silverman, S Yost, C AF Bloom, Mara Markovitz, Sarah Silverman, Susan Yost, Carl TI Ten Trends Transforming Cancer Care and Their Effects on Space Planning for Academic Medical Centers SO HERD-HEALTH ENVIRONMENTS RESEARCH & DESIGN JOURNAL LA English DT Article DE academic medical centers; cancer care; space planning; master planning; architecture; interior design AB Objective: This article aims to define the major trends currently affecting space needs for academic medical center (AMC) cancer centers. It will distinguish between the trends that promote the concentration of services with those that promote decentralization as well as identify opportunities for achieving greater effectiveness in cancer care space planning. Background: Changes in cancer care-higher survival rates, increased clinical trials, new technology, and changing practice models-increasingly fill hospitals' and clinicians' schedules and strain clinical space resources. Conflicts among these trends are concentrating some services and dispersing others. As a result, AMCs must expand and renovate intelligently to continue providing state-of-the-art, compassionate care. Conclusions: Although the typical AMC cancer center can expect to utilize more space than it would have 10 years ago, a deeper understanding of the cancer center enterprise can lead to opportunities for more effectively using available facility resources. Each AMC must determine for itself the appropriate balance of patient volume, clinical activity, and services between its main hospital campus and satellite branches. As well, space allocation should be flexible, as care trends, medical technology, and the provider's own priorities shift over time. The goal isn't necessarily more space-it's better space. C1 [Bloom, Mara] Massachusetts Gen Hosp, Ctr Canc, Boston, MA USA. [Markovitz, Sarah] NBBJ, Boston, MA USA. [Silverman, Susan; Yost, Carl] NBBJ, New York, NY 10006 USA. RP Silverman, S (reprint author), NBBJ, New York, NY 10006 USA. EM ssilverman@nbbj.com NR 25 TC 0 Z9 0 U1 2 U2 3 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 1937-5867 EI 2167-5112 J9 HERD-HEALTH ENV RES JI Herd-Health Env. Res. Des. J. PD JAN PY 2015 VL 8 IS 2 BP 85 EP 94 DI 10.1177/1937586714565598 PG 10 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA CC5QF UT WOS:000350414800010 PM 25816384 ER PT J AU Kawano, Y Moschetta, M Manier, S Glavey, S Gorgun, GT Roccaro, AM Anderson, KC Ghobrial, IM AF Kawano, Yawara Moschetta, Michele Manier, Salomon Glavey, Siobhan Goerguen, Guellue T. Roccaro, Aldo M. Anderson, Kenneth C. Ghobrial, Irene M. TI Targeting the bone marrow microenvironment in multiple myeloma SO IMMUNOLOGICAL REVIEWS LA English DT Review DE myeloma; bone marrow; immune cells; BMSCs; vessel formation ID REGULATORY T-CELLS; PLASMACYTOID DENDRITIC CELLS; NATURAL-KILLER-CELL; HYPOXIA-ACTIVATED PRODRUG; MESENCHYMAL STEM-CELLS; BREAST-CANCER PATIENTS; NF-KAPPA-B; SUPPRESSOR-CELLS; STROMAL CELLS; IN-VIVO AB Multiple myeloma (MM) is characterized by clonal expansion of malignant plasma cells in the bone marrow (BM). Despite the significant advances in treatment, MM is still a fatal malignancy. This is mainly due to the supportive role of the BM microenvironment in differentiation, migration, proliferation, survival, and drug resistance of the malignant plasma cells. The BM microenvironment is composed of a cellular compartment (stromal cells, osteoblasts, osteoclasts, endothelial cells, and immune cells) and a non-cellular compartment. In this review, we discuss the interaction between the malignant plasma cell and the BM microenvironment and the strategy to target them. C1 [Kawano, Yawara; Moschetta, Michele; Manier, Salomon; Glavey, Siobhan; Goerguen, Guellue T.; Roccaro, Aldo M.; Anderson, Kenneth C.; Ghobrial, Irene M.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. RP Ghobrial, IM (reprint author), Dana Farber Canc Inst, Dept Med Oncol, 450 Brookline Ave, Boston, MA 02115 USA. EM irene_ghobrial@dfci.harvard.edu OI Roccaro, Aldo/0000-0002-1872-5128 FU Leukemia & Lymphoma Society; [R01CA181683] FX This work was supported in part by the R01CA181683 and The Leukemia & Lymphoma Society. There are no conflicts of interest associated with this review. NR 166 TC 40 Z9 40 U1 5 U2 15 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0105-2896 EI 1600-065X J9 IMMUNOL REV JI Immunol. Rev. PD JAN PY 2015 VL 263 IS 1 SI SI BP 160 EP 172 DI 10.1111/imr.12233 PG 13 WC Immunology SC Immunology GA CC2HN UT WOS:000350166200011 PM 25510276 ER PT J AU Lamont, EB Schilsky, RL He, YL Muss, H Cohen, HJ Hurria, A Meilleur, A Kindler, HL Venook, A Lilenbaum, R Niell, H Goldberg, RM Joffe, S AF Lamont, Elizabeth B. Schilsky, Richard L. He, Yulei Muss, Hyman Cohen, Harvey Jay Hurria, Arti Meilleur, Ashley Kindler, Hedy L. Venook, Alan Lilenbaum, Rogerio Niell, Harvey Goldberg, Richard M. Joffe, Steven CA Alliance Clinical Trials Oncology TI Generalizability of Trial Results to Elderly Medicare Patients With Advanced Solid Tumors (Alliance 70802) SO JNCI-JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Article ID CELL LUNG-CANCER; LEUKEMIA GROUP-B; CLINICAL-TRIALS; OLDER WOMEN; CHEMOTHERAPY REGIMENS; SOCIOECONOMIC-STATUS; COLORECTAL-CANCER; BREAST-CANCER; DISPARITIES; PARTICIPATION AB In the United States, patients who enroll in chemotherapy trials seldom reflect the attributes of the general population with cancer, as they are often younger, more functional, and have less comorbidity. We compared survival following three chemotherapy regimens according to the setting in which care was delivered (ie, clinical trial vs usual care) to determine the generalizability of clinical trial results to unselected elderly Medicare patients. Using SEER-Medicare data, we estimated survival for elderly patients (ie, age 65 years or older, n = 14097) with advanced pancreatic or lung cancer following receipt of one of three guideline-recommended first-line chemotherapy regimens. We compared their survival to that of similarly treated clinical trial enrollees, without age restrictions, with the same diagnosis and stage (n = 937). All statistical tests were two-sided. Trial patients were 9.5 years younger than elderly Medicare patients. Medicare patients were more often white and tended to live in areas of greater educational attainment than trial enrollees. For each tumor type, Medicare patients who were 75 years or older had median survivals that were six to eight weeks shorter than those of trial patients (4.3 vs 5.8 months following treatment with single agent gemcitabine for advanced pancreatic cancer, P = .03; 7.3 vs 8.9 months following treatment with carboplatin and paclitaxel for stage IV non-small cell lung cancer, P = .91; 8.2 vs 10.2 months following treatment with CDDP/ VP16 for extensive stage small cell lung cancer, P a parts per thousand currency sign .01), whereas younger Medicare patients had survival times that were similar to those of trial patients. Results of clinical trials for advanced pancreatic cancer and lung cancers tended to correctly estimate survival for Medicare patients aged 65 to 74 years, but to overestimate survival for older Medicare patients by six to eight weeks. These estimates of Medicare patients' survival may aid subsequent patients and their oncologists in treatment decision-making. C1 [Lamont, Elizabeth B.] Massachusetts Gen Hosp, Ctr Canc, Boston, MA USA. [Lamont, Elizabeth B.; He, Yulei; Meilleur, Ashley] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. [Lamont, Elizabeth B.; He, Yulei; Meilleur, Ashley] Harvard Univ, Sch Med, Dept Hlth Care Policy, Boston, MA 02115 USA. [Schilsky, Richard L.] Amer Soc Clin Oncol, Alexandria, VA USA. [Muss, Hyman] Univ N Carolina, Dept Med, Chapel Hill, NC USA. [Cohen, Harvey Jay] Duke Univ, Dept Med, Durham, NC USA. [Hurria, Arti] City Hope Natl Med Ctr, Duarte, CA USA. [Kindler, Hedy L.] Univ Chicago, Dept Med, Chicago, IL 60637 USA. [Venook, Alan] Univ Calif San Francisco, Dept Med, San Francisco, CA USA. [Lilenbaum, Rogerio] Yale Canc Ctr, New Haven, CT USA. [Niell, Harvey] Univ Tennessee, Dept Med, Memphis, TN 38104 USA. [Goldberg, Richard M.] Ohio State Univ, Dept Med, Columbus, OH 43210 USA. [Joffe, Steven] Univ Penn, Perelman Sch Med, Dept Med Eth & Hlth Policy, Philadelphia, PA 19104 USA. RP Lamont, EB (reprint author), 180A Longwood Ave, Boston, MA 02115 USA. EM lamont@hcp.med.harvard.edu FU National Cancer Institute (NCI) [R01 CA132900, CA31946, CA33601] FX The research for 70802 (Alliance) was supported, in part, by grants from the National Cancer Institute (NCI) (R01 CA132900) to Harvard Medical School (Elizabeth B. Lamont, MD, Principal Investigator), (CA31946) to the Alliance for Clinical Trials in Oncology (Monica M. Bertagnolli, MD, Chair), and (CA33601) to the Alliance Statistics and Data Center (Daniel J. Sargent, PhD). The authors also acknowledge K07 CA9389204 (Lamont), without which this paper would not have been possible. NR 39 TC 1 Z9 1 U1 2 U2 3 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0027-8874 EI 1460-2105 J9 JNCI-J NATL CANCER I JI JNCI-J. Natl. Cancer Inst. PD JAN PY 2015 VL 107 IS 1 AR dju336 DI 10.1093/jnci/dju336 PG 7 WC Oncology SC Oncology GA CC3FW UT WOS:000350232800003 ER PT J AU Martinez-Quintanilla, J Shah, K AF Martinez-Quintanilla, Jordi Shah, Khalid TI RE: Reassurance Against Future Risk of Precancer and Cancer Conferred by a Negative Human Papillomavirus Test Response SO JNCI-JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Letter ID GLIOBLASTOMA STEM-CELLS; HERPES-SIMPLEX-VIRUS; GLIOMA; EFFICACY; THERAPY; MODEL C1 [Martinez-Quintanilla, Jordi; Shah, Khalid] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Mol Neurotherapy & Imaging Lab, Boston, MA USA. [Martinez-Quintanilla, Jordi; Shah, Khalid] Harvard Univ, Sch Med, Dept Radiol, Massachusetts Gen Hosp, Boston, MA 02115 USA. [Shah, Khalid] Harvard Univ, Sch Med, Dept Neurol, Massachusetts Gen Hosp, Boston, MA 02115 USA. [Shah, Khalid] Harvard Univ, Harvard Stem Cell Inst, Cambridge, MA 02138 USA. RP Shah, K (reprint author), 149,13th St, Charlestown, MA USA. EM kshah@mgh.harvard.edu NR 9 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0027-8874 EI 1460-2105 J9 JNCI-J NATL CANCER I JI JNCI-J. Natl. Cancer Inst. PD JAN PY 2015 VL 107 IS 1 AR dju370 DI 10.1093/jnci/dju370 PG 2 WC Oncology SC Oncology GA CC3FW UT WOS:000350232800021 ER PT J AU Ng, K Meyerhardt, JA Chan, AT Sato, K Chan, JA Niedzwiecki, D Saltz, LB Mayer, RJ Benson, A Schaefer, PL Whittom, R Hantel, A Goldberg, RM Venook, AP Ogino, S Giovannucci, EL Fuchs, CS AF Ng, Kimmie Meyerhardt, Jeffrey A. Chan, Andrew T. Sato, Kaori Chan, Jennifer A. Niedzwiecki, Donna Saltz, Leonard B. Mayer, Robert J. Benson, Al B., III Schaefer, Paul L. Whittom, Renaud Hantel, Alexander Goldberg, Richard M. Venook, Alan P. Ogino, Shuji Giovannucci, Edward L. Fuchs, Charles S. TI Aspirin and COX-2 Inhibitor Use in Patients With Stage III Colon Cancer SO JNCI-JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Article ID RANDOMIZED CONTROLLED-TRIAL; PREVENT COLORECTAL ADENOMAS; ANTIINFLAMMATORY DRUG-USE; IMPROVES SURVIVAL; PIK3CA MUTATION; CELL-GROWTH; DIAGNOSIS; MORTALITY; RISK; CELECOXIB AB We conducted a prospective, observational study of aspirin and COX-2 inhibitor use and survival in stage III colon cancer patients enrolled in an adjuvant chemotherapy trial. Among 799 eligible patients, aspirin use was associated with improved recurrence-free survival (RFS) (multivariable hazard ratio [HR] = 0.51, 95% confidence interval [CI] = 0.28 to 0.95), disease-free survival (DFS) (HR = 0.68, 95% CI = 0.42 to 1.11), and overall survival (OS) (HR = 0.63, 95% CI = 0.35 to 1.12). Adjusted HRs for DFS and OS censored at five years (in an attempt to minimize misclassification from noncancer death) were 0.61 (95% CI = 0.36 to 1.04) and 0.48 (95% CI = 0.23 to 0.99). Among 843 eligible patients, those who used COX-2 inhibitors had multivariable HRs for RFS, DFS, and OS of 0.53 (95% CI = 0.27 to 1.04), 0.60 (95% CI = 0.33 to 1.08), and 0.50 (95% CI = 0.23 to 1.07), and HRs of 0.47 (95% CI = 0.24 to 0.91) and 0.26 (95% CI = 0.08 to 0.81) for DFS and OS censored at five years. Aspirin and COX-2 inhibitor use may be associated with improved outcomes in stage III colon cancer patients. C1 [Ng, Kimmie; Meyerhardt, Jeffrey A.; Sato, Kaori; Chan, Jennifer A.; Mayer, Robert J.; Ogino, Shuji; Fuchs, Charles S.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02215 USA. [Chan, Andrew T.] Massachusetts Gen Hosp, Div Gastroenterol, Boston, MA 02114 USA. [Chan, Andrew T.; Giovannucci, Edward L.; Fuchs, Charles S.] Brigham & Womens Hosp, Dept Med, Channing Div Network Med, Boston, MA 02115 USA. [Niedzwiecki, Donna] Duke Univ, Med Ctr, Alliance Stat & Data Ctr, Durham, NC USA. [Saltz, Leonard B.] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. [Benson, Al B., III] Northwestern Univ, Robert H Lurie Comprehens Canc Ctr, Div Hematol Oncol, Chicago, IL 60611 USA. [Schaefer, Paul L.] Toledo Community Hosp Oncol Program, Toledo, OH USA. [Whittom, Renaud] Univ Montreal, Hop Sacre Coeur Montreal, Quebec City, PQ, Canada. [Hantel, Alexander] Edward Canc Ctr, Naperville, IL USA. [Goldberg, Richard M.] Ohio State Univ, Ctr Comprehens Canc, Div Med Oncol, Columbus, OH 43210 USA. [Venook, Alan P.] Univ Calif San Francisco, Div Med Oncol, San Francisco, CA 94143 USA. [Ogino, Shuji] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. [Ogino, Shuji] Harvard Univ, Sch Med, Boston, MA USA. [Ogino, Shuji; Giovannucci, Edward L.] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. [Giovannucci, Edward L.] Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA. RP Ng, K (reprint author), Dana Farber Canc Inst, 450 Brookline Ave, Boston, MA 02215 USA. EM kng4@partners.org OI Saltz, Leonard/0000-0001-8353-4670 FU National Cancer Institute, National Institutes of Health [P50 CA127003, K07 CA148894, CA31946, CA33601]; Conquer Cancer Foundation of the American Society of Clinical Oncology; Damon Runyan Cancer Research Foundation; Pfizer Oncology FX This work was supported by the National Cancer Institute, National Institutes of Health (P50 CA127003 and K07 CA148894 to KN), the Conquer Cancer Foundation of the American Society of Clinical Oncology (to KN), the Damon Runyan Cancer Research Foundation (to ATC), and the Pharmacia and Upjohn Company, now Pfizer Oncology. The research for CALGB 89803 was also supported, in part, by grants from the National Cancer Institute, National Institutes of Health (CA31946) to the Alliance for Clinical Trials in Oncology (Monica Bertagnolli, MD, Chairman) and to the Alliance Statistics and Data Center (Daniel J. Sargent, PhD, CA33601). NR 40 TC 1 Z9 1 U1 0 U2 7 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0027-8874 EI 1460-2105 J9 JNCI-J NATL CANCER I JI JNCI-J. Natl. Cancer Inst. PD JAN PY 2015 VL 107 IS 1 AR dju345 DI 10.1093/jnci/dju345 PG 5 WC Oncology SC Oncology GA CC3FW UT WOS:000350232800004 ER PT J AU Yeo, H Niland, J Milne, D ter Veer, A Bekaii-Saab, T Farma, JM Lai, L Skibber, JM Small, W Wilkinson, N Schrag, D Weiser, MR AF Yeo, Heather Niland, Joyce Milne, Dana ter Veer, Anna Bekaii-Saab, Tanios Farma, Jeffrey M. Lai, Lily Skibber, John M. Small, William, Jr. Wilkinson, Neal Schrag, Deborah Weiser, Martin R. TI Incidence of Minimally Invasive Colorectal Cancer Surgery at National Comprehensive Cancer Network Centers SO JNCI-JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Article ID SHORT-TERM OUTCOMES; LAPAROSCOPIC-ASSISTED COLECTOMY; TOTAL MESORECTAL EXCISION; MRC CLASICC TRIAL; RECTAL-CANCER; RANDOMIZED-TRIAL; COLON-CANCER; LEARNING-CURVE; UNITED-STATES; RESECTION AB Laparoscopic colectomy has been shown to have equivalent oncologic outcomes to open colectomy for the management of colon cancer, but its adoption nationally has been slow. This study investigates the prevalence and factors associated with laparoscopic colorectal resection at National Comprehensive Cancer Network (NCCN) centers. Data on patients undergoing surgery for colon and rectal cancer at NCCN centers from 2005 to 2010 were obtained from chart review of medical records for the NCCN Outcomes Project and included information on socioeconomic status, insurance coverage, comorbidity, and physician-reported Eastern Cooperative Oncology Group (ECOG) performance status. Associations between receipt of minimally invasive surgery and patient and clinical variables were analyzed with univariate and multivariable logistic regression. All statistical tests were two-sided. A total of 4032 patients, diagnosed between September 2005 and December 2010, underwent elective colon or rectal resection for cancer at NCCN centers. Median age of colon cancer patients was 62.6 years, and 49% were men. The percent of colon cancer patients treated with minimally invasive surgery (MIS) increased from 35% in 2006 to 51% in 2010 across all centers but varied statistically significantly between centers. On multivariable analysis, factors associated with minimally invasive surgery for colon cancer patients who had surgery at an NCCN institution were older age (P = .02), male sex (P = .006), fewer comorbidities (P a parts per thousand currency sign .001), lower final T-stage (P < .001), median household income greater than or equal to $80000 (P < .001), ECOG performance status = 0 (P = .02), and NCCN institution (P a parts per thousand currency sign .001). The use of MIS increased at NCCN centers. However, there was statistically significant variation in adoption of MIS technique among centers. C1 [Yeo, Heather; Weiser, Martin R.] Mem Sloan Kettering Canc Ctr, New York, NY 10065 USA. [Niland, Joyce; ter Veer, Anna; Lai, Lily; Schrag, Deborah] City Hope Comprehens Canc Ctr, Duarte, CA USA. [Milne, Dana; Lai, Lily] Dana Farber Brigham & Womens Canc Ctr, Boston, MA USA. [Bekaii-Saab, Tanios] Ohio State Univ, Ctr Comprehens Canc, James Canc Hosp, Columbus, OH 43210 USA. [Bekaii-Saab, Tanios] Solove Res Inst, Columbus, OH USA. [Farma, Jeffrey M.] Fox Chase Canc Ctr, Philadelphia, PA 19111 USA. [Skibber, John M.] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. [Small, William, Jr.] Northwestern Univ, Robert H Lurie Comprehens Canc Ctr, Chicago, IL 60611 USA. [Wilkinson, Neal] Roswell Pk Canc Inst, Buffalo, NY 14263 USA. RP Weiser, MR (reprint author), Mem Sloan Kettering Canc Ctr, Dept Surg, Colorectal Serv, 1275 York Ave,Room C-1075, New York, NY 10065 USA. EM weiser1@mskcc.org RI Bekaii-Saab, Tanios/E-2733-2011 FU cancer center core grant [P30 CA008748]; core grant FX This study was funded in part by the cancer center core grant P30 CA008748. The core grant provides funding to institutional cores, such as Biostatistics and Pathology, which were used in this study. NR 42 TC 1 Z9 1 U1 0 U2 3 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0027-8874 EI 1460-2105 J9 JNCI-J NATL CANCER I JI JNCI-J. Natl. Cancer Inst. PD JAN PY 2015 VL 107 IS 1 AR dju362 DI 10.1093/jnci/dju362 PG 8 WC Oncology SC Oncology GA CC3FW UT WOS:000350232800014 ER PT J AU Calderwood, SB Hooper, DC AF Calderwood, Stephen B. Hooper, David C. TI In Memoriam: Morton N. Swartz SO JOURNAL OF INFECTIOUS DISEASES LA English DT Biographical-Item C1 [Calderwood, Stephen B.; Hooper, David C.] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Calderwood, SB (reprint author), Massachusetts Gen Hosp, Div Infect Dis, 55 Fruit St, Boston, MA 02114 USA. EM scalderwood@partners.org NR 1 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0022-1899 EI 1537-6613 J9 J INFECT DIS JI J. Infect. Dis. PD JAN 1 PY 2015 VL 211 IS 1 BP 1 EP 3 DI 10.1093/infdis/jiu392 PG 3 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA CC3BY UT WOS:000350220600001 PM 25030059 ER PT J AU Powis, KM Shapiro, RL AF Powis, Kathleen M. Shapiro, Roger L. TI Protease Inhibitors and Adverse Birth Outcomes: Is Progesterone the Missing Piece to the Puzzle? SO JOURNAL OF INFECTIOUS DISEASES LA English DT Editorial Material DE HIV; protease inhibitors; progesterone; pregnancy outcomes ID ACTIVE ANTIRETROVIRAL THERAPY; HIV-INFECTED WOMEN; TO-CHILD TRANSMISSION; INDUCED BLOCKING FACTOR; PRETERM DELIVERY; INCREASED RISK; PREMATURE DELIVERY; DOSE NEVIRAPINE; PREGNANT-WOMEN; PREECLAMPSIA C1 [Powis, Kathleen M.] Massachusetts Gen Hosp, Dept Internal Med, Boston, MA 02114 USA. [Powis, Kathleen M.] Massachusetts Gen Hosp, Dept Pediat, Boston, MA 02114 USA. [Powis, Kathleen M.; Shapiro, Roger L.] Harvard Univ, Sch Publ Hlth, Dept Immunol & Infect Dis, Boston, MA 02115 USA. [Shapiro, Roger L.] Beth Israel Deaconess Med Ctr, Div Infect Dis, Boston, MA 02215 USA. RP Powis, KM (reprint author), Massachusetts Gen Hosp, 100 Cambridge St,15th Fl, Boston, MA 02114 USA. EM kpowis@mgh.harvard.edu FU NICHD NIH HHS [K23 HD070774, 1K23HD070774-01A1] NR 38 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 0022-1899 EI 1537-6613 J9 J INFECT DIS JI J. Infect. Dis. PD JAN 1 PY 2015 VL 211 IS 1 BP 4 EP 7 DI 10.1093/infdis/jiu397 PG 4 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA CC3BY UT WOS:000350220600002 PM 25030057 ER PT J AU Genther, DJ Betz, J Pratt, S Kritchevsky, SB Martin, KR Harris, TB Helzner, E Satterfield, S Xue, QL Yaffe, K Simonsick, EM Lin, FR AF Genther, Dane J. Betz, Joshua Pratt, Sheila Kritchevsky, Steven B. Martin, Kathryn R. Harris, Tamara B. Helzner, Elizabeth Satterfield, Suzanne Xue, Qian-Li Yaffe, Kristine Simonsick, Eleanor M. Lin, Frank R. CA Hlth ABC Study TI Association of Hearing Impairment and Mortality in Older Adults SO JOURNALS OF GERONTOLOGY SERIES A-BIOLOGICAL SCIENCES AND MEDICAL SCIENCES LA English DT Article DE Epidemiology; Longevity; Outcomes; Public health; Successful aging ID BLUE-MOUNTAINS HEARING; HEALTH INTERVIEW SURVEY; UNITED-STATES; LONGITUDINAL ANALYSIS; GAIT SPEED; SURVIVAL; RISK; PREDICTORS; DISEASE; DEPRESSION AB Background. Hearing impairment (HI) is highly prevalent in older adults and is associated with social isolation, depression, and risk of dementia. Whether HI is associated with broader downstream outcomes is unclear. We undertook this study to determine whether audiometric HI is associated with mortality in older adults. Methods. Prospective observational data from 1,958 adults >= 70 years of age from the Health, Aging, and Body Composition Study were analyzed using Cox proportional hazards regression. Participants were followed for 8 years after audiometric examination. Mortality was adjudicated by obtaining death certificates. Hearing was defined as the pure-tone average of hearing thresholds in decibels re: hearing level (dB HL) at frequencies from 0.5 to 4 kHz. HI was defined as pure-tone average >25 dB HL in the better ear. Results. Of the 1,146 participants with HI, 492 (42.9%) died compared with 255 (31.4%) of the 812 with normal hearing (odds ratio = 1.64, 95% CI: 1.36-1.98). After adjustment for demographics and cardiovascular risk factors, HI was associated with a 20% increased mortality risk compared with normal hearing (hazard ratio = 1.20, 95% CI: 1.03-1.41). Confirmatory analyses treating HI as a continuous predictor yielded similar results, demonstrating a nonlinear increase in mortality risk with increasing HI (hazard ratio = 1.14, 95% CI: 1.00-1.29 per 10 dB of threshold elevation up to 35 dB HL). Conclusions. HI in older adults is associated with increased mortality, independent of demographics and cardiovascular risk factors. Further research is necessary to understand the basis of this association and whether these pathways might be amenable to hearing rehabilitation. C1 [Genther, Dane J.; Lin, Frank R.] Johns Hopkins Univ, Sch Med, Dept Otolaryngol Head & Neck Surg, Baltimore, MD 21287 USA. [Genther, Dane J.; Betz, Joshua; Xue, Qian-Li; Lin, Frank R.] Johns Hopkins Ctr Aging & Hlth, Baltimore, MD USA. [Betz, Joshua] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Biostat, Baltimore, MD USA. [Pratt, Sheila] VA Pittsburgh Healthcare Syst, Geriatr Res Educ & Clin Ctr, Pittsburgh, PA 15261 USA. [Pratt, Sheila] Univ Pittsburgh, Dept Commun Sci & Disorders, Pittsburgh, PA 15260 USA. [Kritchevsky, Steven B.] Wake Forest Univ, Bowman Gray Sch Med, Dept Internal Med, Winston Salem, NC 27103 USA. [Kritchevsky, Steven B.] J Paul Sticht Ctr Aging, Winston Salem, NC USA. [Martin, Kathryn R.] Univ Aberdeen, Dept Epidemiol, Aberdeen AB9 1FX, Scotland. [Harris, Tamara B.] NIA, Lab Epidemiol & Populat Sci, Bethesda, MD 20892 USA. [Helzner, Elizabeth] Suny Downstate Med Ctr, Dept Epidemiol & Biostat, Brooklyn, NY 11203 USA. [Satterfield, Suzanne] Univ Tennessee, Ctr Hlth Sci, Dept Prevent Med, Memphis, TN 38163 USA. [Xue, Qian-Li; Simonsick, Eleanor M.; Lin, Frank R.] Johns Hopkins Univ, Sch Med, Div Geriatr Med & Gerontol, Dept Med, Baltimore, MD 21287 USA. [Yaffe, Kristine] Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA. [Yaffe, Kristine] Univ Calif San Francisco, Dept Psychiat, San Francisco, CA USA. [Yaffe, Kristine] Univ Calif San Francisco, Dept Neurol, San Francisco, CA USA. [Simonsick, Eleanor M.] NIA, Intramural Res Program, Bethesda, MD 20892 USA. [Lin, Frank R.] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD USA. [Lin, Frank R.] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Mental Hlth, Baltimore, MD USA. RP Genther, DJ (reprint author), Johns Hopkins Univ, Sch Med, Dept Otolaryngol Head & Neck Surg, 601 N Caroline St,JHOC 6210, Baltimore, MD 21287 USA. EM dgenthe2@jhmi.edu OI Genther, Dane/0000-0002-7925-012X; Betz, Joshua/0000-0003-4488-9799 FU National Institute on Aging (NIA) [N01-AG-6-2101, N01-AG-6-2103, N01-AG-6-2106, R01-AG028050, K24AG031155]; National Institute of Nursing Research (NINR) [R01-NR012459]; National Institutes of Health (NIH) [T32DC000027]; National Institute on Deafness and Other Communication Disorders (NIDCD) [K23DC011279]; Intramural Research Program of the National Institute on Aging; Triological Society; American College of Surgeons through the Clinician Scientist Award; Eleanor Schwartz Charitable Foundation FX This research was supported by National Institute on Aging (NIA) (N01-AG-6-2101, N01-AG-6-2103, N01-AG-6-2106); NIA grant (R01-AG028050); and National Institute of Nursing Research (NINR) grant (R01-NR012459). This study was further supported in part by National Institutes of Health (NIH) grant (T32DC000027), NIA grant (K24AG031155), National Institute on Deafness and Other Communication Disorders (NIDCD) grant (K23DC011279), Intramural Research Program of the National Institute on Aging, Triological Society and American College of Surgeons through the Clinician Scientist Award, and Eleanor Schwartz Charitable Foundation. S.P. was supported with resources and the use of facilities at the VA Pittsburgh Healthcare System, Pittsburgh, PA; however, the contents do not represent the views of the Department of Veterans Affairs or the United States Government. The sponsors had no role in the design and conduct of the study; in the collection, analysis, and interpretation of the data; or in the preparation of the manuscript. NR 41 TC 14 Z9 15 U1 1 U2 1 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1079-5006 EI 1758-535X J9 J GERONTOL A-BIOL JI J. Gerontol. Ser. A-Biol. Sci. Med. Sci. PD JAN PY 2015 VL 70 IS 1 BP 85 EP 90 DI 10.1093/gerona/glu094 PG 6 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA CC1RJ UT WOS:000350119900011 PM 25024235 ER PT J AU Zhang, YS Dai, TH Wang, M Vecchio, D Chiang, LY Hamblin, MR AF Zhang, Yunsong Dai, Tianhong Wang, Min Vecchio, Daniela Chiang, Long Y. Hamblin, Michael R. TI Potentiation of antimicrobial photodynamic inactivation mediated by a cationic fullerene by added iodide: in vitro and in vivo studies SO NANOMEDICINE LA English DT Article DE antimicrobial photodynamic therapy; bioluminescent bacteria; decacationic fullerene; decatertiary-amine chain; in vivo infection model; iodide potentiation ID ACINETOBACTER-BAUMANNII; YEAST PHASE; THERAPY; INFECTIONS; WATER; C-60; SYSTEM; MECHANISMS; TOXICITY; BACTERIA AB Background: Antimicrobial photodynamic inactivation with fullerenes bearing cationic charges may overcome resistant microbes. Methods & results: We synthesized C-60-fullerene (LC16) bearing decaquaternary chain and deca-tertiary-amino groups that facilitates electron-transfer reactions via the photoexcited fullerene. Addition of the harmless salt, potassium iodide (10 mM) potentiated the ultraviolet A (UVA) or white light-mediated killing of Gram-negative bacteria Acinetobacter baumannii, Gram-positive methicillin-resistant Staphylococcus aureus and fungal yeast Candida albicans by 1-2+ logs. Mouse model infected with bioluminescent Acinetobacter baumannii gave increased loss of bioluminescence when iodide (10 mM) was combined with LC16 and UVA/white light. Conclusion: The mechanism may involve photoinduced electron reduction of (1)(C-60>)* or (3)(C-60>)* by iodide producing I center dot or I-2 followed by subsequent intermolecular electron-transfer events of (C-60>)(-center dot) to produce reactive radicals. C1 [Zhang, Yunsong] Jinan Univ, Guangzhou Red Cross Hosp, Dept Burn & Plast Surg, Guangzhou, Guangdong, Peoples R China. [Zhang, Yunsong; Dai, Tianhong; Vecchio, Daniela; Hamblin, Michael R.] Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA. [Zhang, Yunsong; Dai, Tianhong; Vecchio, Daniela; Hamblin, Michael R.] Harvard Univ, Sch Med, Dept Dermatol, Boston, MA 02115 USA. [Wang, Min; Chiang, Long Y.] Univ Massachusetts, Dept Chem, Lowell, MA 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 FU US NIH [R01AI050875, R01CA137108]; Medical Science Foundation of Guangzhou City [20112121220025] FX This research was supported by US NIH grants R01AI050875 and R01CA137108. Yunsong Zhang was supported by the Medical Science Foundation of Guangzhou City (grant 20112121220025). 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 46 TC 11 Z9 11 U1 2 U2 20 PU FUTURE MEDICINE LTD PI LONDON PA UNITEC HOUSE, 3RD FLOOR, 2 ALBERT PLACE, FINCHLEY CENTRAL, LONDON, N3 1QB, ENGLAND SN 1743-5889 EI 1748-6963 J9 NANOMEDICINE-UK JI Nanomedicine PY 2015 VL 10 IS 4 BP 603 EP 614 DI 10.2217/nnm.14.131 PG 12 WC Biotechnology & Applied Microbiology; Nanoscience & Nanotechnology SC Biotechnology & Applied Microbiology; Science & Technology - Other Topics GA CC7YD UT WOS:000350583800007 PM 25723093 ER PT J AU Wen, PY AF Wen, Patrick Y. TI Message from the Editor-in-Chief SO NEURO-ONCOLOGY LA English DT Editorial Material C1 [Wen, Patrick Y.] Harvard Univ, Sch Med, Cambridge, MA 02138 USA. [Wen, Patrick Y.] Dana Farber Brigham & Womens Canc Ctr, Ctr Neurooncol, Boston, MA USA. RP Wen, PY (reprint author), Harvard Univ, Sch Med, Cambridge, MA 02138 USA. EM pwen@partners.org NR 2 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1522-8517 EI 1523-5866 J9 NEURO-ONCOLOGY JI Neuro-Oncology PD JAN PY 2015 VL 17 IS 1 BP 1 EP 1 DI 10.1093/neuonc/nou334 PG 1 WC Oncology; Clinical Neurology SC Oncology; Neurosciences & Neurology GA CC1XF UT WOS:000350138000001 PM 25538095 ER PT J AU Kaley, TJ Wen, P Schiff, D Ligon, K Haider, S Karimi, S Lassman, AB Nolan, CP DeAngelis, LM Gavrilovic, I Norden, A Drappatz, J Lee, EQ Purow, B Plotkin, SR Batchelor, T Abrey, LE Omura, A AF Kaley, Thomas J. Wen, Patrick Schiff, David Ligon, Keith Haider, Sam Karimi, Sasan Lassman, Andrew B. Nolan, Craig P. DeAngelis, Lisa M. Gavrilovic, Igor Norden, Andrew Drappatz, Jan Lee, Eudocia Quant Purow, Benjamin Plotkin, Scott R. Batchelor, Tracy Abrey, Lauren E. Omura, Antonio TI Phase II trial of sunitinib for recurrent and progressive atypical and anaplastic meningioma SO NEURO-ONCOLOGY LA English DT Article DE chemotherapy; malignant meningioma; sunitinib; tyrosine kinase ID GROWTH-FACTOR; THERAPY; PDGF; BEVACIZUMAB; EXPRESSION; RECEPTORS; ADULTS; TUMORS; BRAIN; CELLS AB Background. No proven effective medical therapy for surgery and radiation-refractory meningiomas exists. Sunitinib malate (SU011248) is a small-molecule tyrosine kinase inhibitor that targets vascular endothelial growth factor receptor (VEGFR) and platelet-derived growth factor receptor, abundant in meningiomas. Methods. This was a prospective, multicenter, investigator-initiated single-arm phase II trial. The primary cohort enrolled patients with surgery and radiation-refractory recurrent World Health Organization (WHO) grades II-III meningioma. An exploratory cohort enrolled patients with WHO grade I meningioma, hemangiopericytoma, or hemangioblastoma. Sunitinib was administered at 50 mg/d for days 1-28 of every 42-day cycle. The primary endpoint was the rate of 6-month progression-free survival (PFS6), with secondary endpoints of radiographic response rate, safety, PFS, and overall survival. Exploratory objectives include analysis of tumoral molecular markers and MR perfusion imaging. Results. Thirty-six patients with high-grade meningioma (30 atypical and 6 anaplastic) were enrolled. Patients were heavily pre-treated (median number of 5 recurrences, range 2-10). PFS6 rate was 42%, meeting the primary endpoint. Median PFS was 5.2 months (95% CI: 2.8-8.3 mo), and median overall survival was 24.6 months (95% CI: 16.5-38.4 mo). Thirteen patients enrolled in the exploratory cohort. Overall toxicity included 1 grade 5 intratumoral hemorrhage, 2 grade 3 and 1 grade 4 CNS/intratumoral hemorrhages, 1 grade 3 and 1 grade 4 thrombotic microangiopathy, and 1 grade 3 gastrointestinal perforation. Expression of VEGFR2 predicted PFS of a median of 1.4 months in VEGFR2-negative patients versus 6.4 months in VEGFR2-positive patients (P = .005). Conclusion. Sunitinib is active in recurrent atypical/malignant meningioma patients. A randomized trial should be performed. C1 [Kaley, Thomas J.; Karimi, Sasan; Lassman, Andrew B.; Nolan, Craig P.; DeAngelis, Lisa M.; Gavrilovic, Igor; Abrey, Lauren E.; Omura, Antonio] Mem Sloan Kettering Canc Ctr, Dept Neurol, New York, NY 10065 USA. [Wen, Patrick; Ligon, Keith; Haider, Sam; Norden, Andrew; Drappatz, Jan; Lee, Eudocia Quant] Brigham & Womens Ctr, Dana Farber Canc Inst, Ctr Neurooncol, Boston, MA USA. [Schiff, David; Purow, Benjamin] Univ Virginia, Dept Neurol, Charlottesville, VA USA. [Plotkin, Scott R.; Batchelor, Tracy] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. RP Kaley, TJ (reprint author), Mem Sloan Kettering Canc Ctr, Dept Neurol, 1275 York Ave, New York, NY 10065 USA. EM kaleyt@mskcc.org OI Nolan, Craig/0000-0003-3534-4615; Gavrilovic, Igor/0000-0001-9104-6132; Kaley, Thomas/0000-0002-2540-8518; Omuro, Antonio/0000-0003-4299-3664 FU Pfizer; Brain Science Foundation FX This work was supported by Pfizer and the Brain Science Foundation. NR 37 TC 33 Z9 33 U1 0 U2 7 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1522-8517 EI 1523-5866 J9 NEURO-ONCOLOGY JI Neuro-Oncology PD JAN PY 2015 VL 17 IS 1 BP 116 EP 121 DI 10.1093/neuonc/nou148 PG 6 WC Oncology; Clinical Neurology SC Oncology; Neurosciences & Neurology GA CC1XF UT WOS:000350138000013 PM 25100872 ER PT J AU Zhao, W Wang, J Varghese, M Ho, L Mazzola, P Haroutunian, V Katsel, PL Gibson, GE Levine, S Dubner, L Pasinetti, GM AF Zhao, Wei Wang, Jun Varghese, Merina Ho, Lap Mazzola, Paolo Haroutunian, Vahram Katsel, Pavel L. Gibson, Gary E. Levine, Samara Dubner, Lauren Pasinetti, Giulio Maria TI Impaired mitochondrial energy metabolism as a novel risk factor for selective onset and progression of dementia in oldest-old subjects SO NEUROPSYCHIATRIC DISEASE AND TREATMENT LA English DT Article DE Alzheimer disease; energy metabolism; neuropathology; mitochondria; dementia ID MILD COGNITIVE IMPAIRMENT; ALZHEIMERS-DISEASE; 6-PHOSPHOFRUCTO-1-KINASE ISOZYMES; OXIDATIVE STRESS; BRAIN; PATHOPHYSIOLOGY; NEUROPATHOLOGY; PREVALENCE; NITRATION; PROTEINS AB Recent evidence shows that Alzheimer disease (AD) dementia in the oldest-old subjects was associated with significantly less amyloid plaque and fibrillary tangle neuropathology than in the young-old population. In this study, using quantitative (q) PCR studies, we validated genome-wide microarray RNA studies previously conducted by our research group. We found selective downregulation of mitochondrial energy metabolism genes in the brains of oldest-old, but not young-old, AD dementia cases, despite a significant lack of classic AD neuropathology features. We report a significant decrease of genes associated with mitochondrial pyruvate metabolism, the tricarboxylic acid cycle (TCA), and glycolytic pathways. Moreover, significantly higher levels of nitrotyrosylated (3-NT)-proteins and 4-hydroxy-2-nonenal (HNE) adducts, which are indexes of cellular protein oxidation and lipid peroxidation, respectively, were detected in the brains of oldest-old subjects at high risk of developing AD, possibly suggesting compensatory mechanisms. These findings support the hypothesis that although oldest-old AD subjects, characterized by significantly lower AD neuropathology than young-old AD subjects, have brain mitochondrial metabolism impairment, which we hypothesize may selectively contribute to the development of dementia. Outcomes from this study provide novel insights into the molecular mechanisms underlying clinical dementia in young-old and oldest-old AD subjects and provide novel strategies for AD prevention and treatment in oldest-old dementia cases. C1 [Zhao, Wei; Wang, Jun; Varghese, Merina; Ho, Lap; Mazzola, Paolo; Levine, Samara; Dubner, Lauren; Pasinetti, Giulio Maria] Icahn Sch Med Mt Sinai, Dept Neurol, New York, NY 10029 USA. [Zhao, Wei; Wang, Jun; Ho, Lap; Haroutunian, Vahram; Katsel, Pavel L.; Pasinetti, Giulio Maria] James J Peter VA Med Ctr, Geriatr Res Educ Clin Ctr, Bronx, NY USA. [Mazzola, Paolo] Univ Milano Bicocca, Dept Hlth Sci, Monza, Italy. [Haroutunian, Vahram; Katsel, Pavel L.; Pasinetti, Giulio Maria] Icahn Sch Med Mt Sinai, Dept Psychiat, New York, NY 10029 USA. [Haroutunian, Vahram] Icahn Sch Med Mt Sinai, Dept Neurosci, New York, NY 10029 USA. [Gibson, Gary E.] Weill Cornell Med Coll, Burke Med Res Inst, Dept Neurol & Neurosci, New York, NY USA. [Pasinetti, Giulio Maria] Icahn Sch Med Mt Sinai, Dept Geriatr, New York, NY 10029 USA. RP Pasinetti, GM (reprint author), Icahn Sch Med Mt Sinai, Dept Neurol, 1 Gustave L Levy Pl,Box 1137, New York, NY 10029 USA. EM giulio.pasinetti@mssm.edu OI Mazzola, Paolo/0000-0002-0484-1136; Varghese, Merina/0000-0002-1517-3903 FU Career Scientist Award in the Research and Development unit FX This material is the result of work supported in part with resources and the use of facilities at the James J. Peters Veterans Affairs Medical Center, Bronx, NY. In addition, Dr. Pasinetti holds a Career Scientist Award in the Research and Development unit and is the Director of the Basic and Biomedical Research and Training Program, GRECC, James J. Peters Veterans Affairs Medical Center. We also acknowledge that the contents of this manuscript do not represent the views of the U.S. Department of Veterans Affairs or the United States Government. NR 40 TC 7 Z9 7 U1 1 U2 3 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 2015 VL 11 BP 565 EP 574 DI 10.2147/NDT.S74898 PG 10 WC Clinical Neurology; Psychiatry SC Neurosciences & Neurology; Psychiatry GA CC4SK UT WOS:000350343500001 PM 25784811 ER PT J AU Vassy, JL McLaughlin, HL MacRae, CA Seidman, CE Lautenbach, D Krier, JB Lane, WJ Kohane, IS Murray, MF McGuire, AL Rehm, HL Green, RC AF Vassy, Jason L. McLaughlin, Heather L. MacRae, Calum A. Seidman, Christine E. Lautenbach, Denise Krier, Joel B. Lane, William J. Kohane, Isaac S. Murray, Michael F. McGuire, Amy L. Rehm, Heidi L. Green, Robert C. CA MedSeq Project TI A One-Page Summary Report of Genome Sequencing for the Healthy Adult SO PUBLIC HEALTH GENOMICS LA English DT Article DE Whole-genome sequencing; Genomic screening; Laboratory reporting; Molecular testing ID MEDICINE; STANDARDS; DIAGNOSIS; KNOWLEDGE; CANCER AB As genome sequencing technologies increasingly enter medical practice, genetics laboratories must communicate sequencing results effectively to nongeneticist physicians. We describe the design and delivery of a clinical genome sequencing report, including a one-page summary suitable for interpretation by primary care physicians. To illustrate our preliminary experience with this report, we summarize the genomic findings from 10 healthy participants in a study of genome sequencing in primary care. (C) 2015 S. Karger AG, Basel C1 [Vassy, Jason L.] Brigham & Womens Hosp, Dept Med, Div Gen Internal Med & Primary Care, Boston, MA 02115 USA. [MacRae, Calum A.; Seidman, Christine E.; Lautenbach, Denise; Krier, Joel B.; Green, Robert C.] Brigham & Womens Hosp, Dept Med, Div Genet, Boston, MA 02115 USA. [MacRae, Calum A.; Seidman, Christine E.] Brigham & Womens Hosp, Dept Med, Div Cardiol, Boston, MA 02115 USA. [Vassy, Jason L.; MacRae, Calum A.; Seidman, Christine E.; Krier, Joel B.; Kohane, Isaac S.; Green, Robert C.] Harvard Univ, Sch Med, Boston, MA USA. [Vassy, Jason L.] Brigham & Womens Hosp, VA Boston Healthcare Syst, Boston, MA 02115 USA. [McLaughlin, Heather L.; Lane, William J.; Rehm, Heidi L.] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA USA. [McLaughlin, Heather L.; Rehm, Heidi L.; Green, Robert C.] Partners Personalized Med, Boston, MA USA. [Murray, Michael F.] Geisinger Hlth Syst, Genom Med Inst, Danville, PA USA. [McGuire, Amy L.] Baylor Coll Med, Ctr Med Eth & Hlth Policy, Houston, TX 77030 USA. RP Vassy, JL (reprint author), VA Boston Healthcare Syst, Gen Internal Med Sect, 150 South Huntington Ave,152-G, Boston, MA 02130 USA. EM jvassy@partners.org FU National Human Genome Research Institute of NIH [U01-HG006500, U41-HG006834, R01-HG005092]; National Institute of Child Health and Human Development of NIH [U19-HD077671] FX We thank the physician participants and patient participants of the MedSeq Project. We received funding through grants U01-HG006500, U41-HG006834 and R01-HG005092 from the National Human Genome Research Institute and grant U19-HD077671 from the National Institute of Child Health and Human Development, both of the NIH. The NIH had no role in the study design; collection, analysis, and interpretation of data; the writing of this report; or the decision to submit the paper for publication. NR 22 TC 4 Z9 4 U1 1 U2 3 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 1662-4246 EI 1662-8063 J9 PUBLIC HEALTH GENOM JI Pub. Health Genomics PY 2015 VL 18 IS 2 BP 123 EP 129 DI 10.1159/000370102 PG 7 WC Genetics & Heredity; Public, Environmental & Occupational Health SC Genetics & Heredity; Public, Environmental & Occupational Health GA CC8BV UT WOS:000350594000007 PM 25612602 ER PT J AU Ford, JM Palzes, VA Roach, BJ Potkin, SG van Erp, TGM Turner, JA Mueller, BA Calhoun, VD Voyvodic, J Belger, A Bustillo, J Vaidya, JG Preda, A McEwen, SC Mathalon, DH AF Ford, Judith M. Palzes, Vanessa A. Roach, Brian J. Potkin, Steven G. van Erp, Theo G. M. Turner, Jessica A. Mueller, Bryon A. Calhoun, Vincent D. Voyvodic, Jim Belger, Aysenil Bustillo, Juan Vaidya, Jatin G. Preda, Adrian McEwen, Sarah C. Mathalon, Daniel H. CA Functional Imaging Biomed TI Visual Hallucinations Are Associated With Hyperconnectivity Between the Amygdala and Visual Cortex in People With a Diagnosis of Schizophrenia SO SCHIZOPHRENIA BULLETIN LA English DT Article ID PARKINSONS-DISEASE PATIENTS; MULTI-FEATURE PARADIGM; AUDITORY HALLUCINATIONS; MISMATCH NEGATIVITY; CONSCIOUS PERCEPTION; BRAIN; FMRI; MEMORY; FRAMEWORK; SYSTEM AB While auditory verbal hallucinations (AH) are a cardinal symptom of schizophrenia, people with a diagnosis of schizophrenia (SZ) may also experience visual hallucinations (VH). In a retrospective analysis of a large sample of SZ and healthy controls (HC) studied as part of the functional magnetic resonance imaging (fMRI) Biomedical Informatics Research Network (FBIRN), we asked if SZ who endorsed experiencing VH during clinical interviews had greater connectivity between visual cortex and limbic structures than SZ who did not endorse experiencing VH. We analyzed resting state fMRI data from 162 SZ and 178 age- and gender-matched HC. SZ were sorted into groups according to clinical ratings on AH and VH: SZ with VH (VH-SZ; n = 45), SZ with AH but no VH (AH-SZ; n = 50), and SZ with neither AH nor VH (NoH-SZ; n = 67). Our primary analysis was seed based, extracting connectivity between visual cortex and the amygdala (because of its role in fear and negative emotion) and visual cortex and the hippocampus (because of its role in memory). Compared with the other groups, VH-SZ showed hyperconnectivity between the amygdala and visual cortex, specifically BA18, with no differences in connectivity among the other groups. In a voxel-wise, whole brain analysis comparing VH-SZ with AH-SZ, the amygdala was hyperconnected to left temporal pole and inferior frontal gyrus in VH-SZ, likely due to their more severe thought broadcasting. VH-SZ have hyperconnectivity between subcortical areas subserving emotion and cortical areas subserving higher order visual processing, providing biological support for distressing VH in schizophrenia. C1 [Ford, Judith M.; Palzes, Vanessa A.; Roach, Brian J.; Mathalon, Daniel H.] San Francisco VA Med Ctr, Psychiat Serv, San Francisco, CA 94121 USA. [Ford, Judith M.; Palzes, Vanessa A.; Roach, Brian J.; Mathalon, Daniel H.] Univ Calif San Francisco, Dept Psychiat, San Francisco, CA USA. [Potkin, Steven G.; van Erp, Theo G. M.; Preda, Adrian] Univ Calif Irvine, Dept Psychiat & Human Behav, Irvine, CA 92717 USA. [Turner, Jessica A.; Calhoun, Vincent D.] Mind Res Network, Albuquerque, NM USA. [Turner, Jessica A.] Georgia State Univ, Dept Psychol, Atlanta, GA 30303 USA. [Turner, Jessica A.] Georgia State Univ, Dept Neurosci, Atlanta, GA 30303 USA. [Mueller, Bryon A.] Univ Minnesota, Dept Psychiat, Minneapolis, MN 55455 USA. [Calhoun, Vincent D.] Univ New Mexico, Dept Elect & Comp Engn, Albuquerque, NM 87131 USA. [Voyvodic, Jim; Belger, Aysenil] Duke Univ, Univ N Carolina, Brain Imaging & Anal Ctr, Durham, NC USA. [Belger, Aysenil] Univ N Carolina, Dept Psychiat, Durham, NC USA. [Bustillo, Juan] Univ New Mexico, Dept Psychiat, Albuquerque, NM 87131 USA. [Vaidya, Jatin G.] Univ Iowa, Dept Psychiat, Iowa City, IA 52242 USA. [McEwen, Sarah C.] Univ Calif Los Angeles, Dept Psychiat & Biobehav Sci, Los Angeles, CA 90024 USA. [Functional Imaging Biomed] Funct Imaging Biomed Informat Res Network FBIRN, Sao Paulo, Brazil. RP Ford, JM (reprint author), San Francisco VA Med Ctr, Psychiat Serv 116D, 4150 Clement St, San Francisco, CA 94121 USA. EM Judith.Ford@ucsf.edu RI Preda, Adrian /K-8889-2013; OI Preda, Adrian /0000-0003-3373-2438; Roach, Brian/0000-0002-3264-1465; Potkin, Steven/0000-0003-1028-1013 FU Biomedical Informatics Research Network [U24RR021992] FX Biomedical Informatics Research Network (U24RR021992). NR 42 TC 20 Z9 20 U1 1 U2 23 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0586-7614 EI 1745-1701 J9 SCHIZOPHRENIA BULL JI Schizophr. Bull. PD JAN PY 2015 VL 41 IS 1 BP 223 EP 232 DI 10.1093/schbul/sbu031 PG 10 WC Psychiatry SC Psychiatry GA CC0WA UT WOS:000350057900031 PM 24619536 ER PT J AU Lener, MS Wong, E Tang, CY Byne, W Goldstein, KE Blair, NJ Haznedar, MM New, AS Chemerinski, E Chu, KW Rimsky, LS Siever, LJ Koenigsberg, HW Hazlett, EA AF Lener, Marc S. Wong, Edmund Tang, Cheuk Y. Byne, William Goldstein, Kim E. Blair, Nicholas J. Haznedar, M. Mehmet New, Antonia S. Chemerinski, Eran Chu, King-Wai Rimsky, Liza S. Siever, Larry J. Koenigsberg, Harold W. Hazlett, Erin A. TI White Matter Abnormalities in Schizophrenia and Schizotypal Personality Disorder SO SCHIZOPHRENIA BULLETIN LA English DT Article DE DTI; MRI; schizotypal personality disorder; schizophrenia; psychosis; white matter; genu; cingulum; inferior longitudinal fasciculus ID DIFFUSION TENSOR TRACTOGRAPHY; INTERNAL CAPSULE; CORPUS-CALLOSUM; 1ST-EPISODE SCHIZOPHRENIA; UNCINATE FASCICULUS; RHESUS-MONKEY; ANTERIOR LIMB; IMAGING DTI; BRAIN; INTEGRITY AB Prior diffusion tensor imaging (DTI) studies examining schizotypal personality disorder (SPD) and schizophrenia, separately have shown that compared with healthy controls (HCs), patients show frontotemporal white matter (WM) abnormalities. This is the first DTI study to directly compare WM tract coherence with tractography and fractional anisotropy (FA) across the schizophrenia spectrum in a large sample of demographically matched HCs (n = 55), medication-naive SPD patients (n = 49), and unmedicated/never-medicated schizophrenia patients (n = 22) to determine whether (a) frontal-striatal-temporal WM tract abnormalities in schizophrenia are similar to, or distinct from those observed in SPD; and (b) WM tract abnormalities are associated with clinical symptom severity indicating a common underlying pathology across the spectrum. Compared with both the HC and SPD groups, schizophrenia patients showed WM abnormalities, as indexed by lower FA in the temporal lobe (inferior longitudinal fasciculus) and cingulum regions. SPD patients showed lower FA in the corpus callosum genu compared with the HC group, but this regional abnormality was more widespread in schizophrenia patients. Across the schizophrenia spectrum, greater WM disruptions were associated with greater symptom severity. Overall, frontal-striatal-temporal WM dysconnectivity is attenuated in SPD compared with schizophrenia patients and may mitigate the emergence of psychosis. C1 [Lener, Marc S.; Byne, William; Goldstein, Kim E.; Haznedar, M. Mehmet; New, Antonia S.; Chemerinski, Eran; Rimsky, Liza S.; Siever, Larry J.; Koenigsberg, Harold W.; Hazlett, Erin A.] Icahn Sch Med Mt Sinai, Dept Psychiat, New York, NY 10029 USA. [Wong, Edmund; Tang, Cheuk Y.] Icahn Sch Med Mt Sinai, Translat & Mol Imaging Inst, Dept Radiol, New York, NY 10029 USA. [Byne, William; Blair, Nicholas J.; New, Antonia S.; Chu, King-Wai; Siever, Larry J.; Hazlett, Erin A.] James J Peters Vet Affairs Med Ctr, Mental Illness Res Educ & Clin Ctr MIRECC VISN 3, Bronx, NY USA. [Byne, William; Haznedar, M. Mehmet; Chemerinski, Eran; Siever, Larry J.; Koenigsberg, Harold W.] James J Peters Vet Affairs Med Ctr, Dept Outpatient Psychiat, Bronx, NY USA. [Blair, Nicholas J.; Chu, King-Wai; Hazlett, Erin A.] James J Peters Vet Affairs Med Ctr, Bronx, NY USA. RP Hazlett, EA (reprint author), James J Peters VA Med Ctr, Mental Illness Res Educ & Clin Ctr, 130 West Kingsbridge Rd,Room 6A-44, Bronx, NY 10468 USA. EM erin.hazlett@mssm.edu FU National Institutes of Health; Veterans Administration [NIMH-R01-MH073911, VA MERIT-I01CX00026] FX National Institutes of Health and the Veterans Administration (NIMH-R01-MH073911 and VA MERIT-I01CX00026 to E.A.H.). Partial support for the schizophrenia sample was also provided (NIMH-R01-MH069947 to H.W.K.). NR 71 TC 12 Z9 12 U1 8 U2 13 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0586-7614 EI 1745-1701 J9 SCHIZOPHRENIA BULL JI Schizophr. Bull. PD JAN PY 2015 VL 41 IS 1 BP 300 EP 310 DI 10.1093/schbul/sbu093 PG 11 WC Psychiatry SC Psychiatry GA CC0WA UT WOS:000350057900038 PM 24962608 ER PT J AU Patel, BR AF Patel, Bina R. TI Caregivers of Veterans with "Invisible" Injuries: What We Know and Implications for Social Work Practice SO SOCIAL WORK LA English DT Article DE caregivers; Iraq; Afghanistan caregivers; military caregivers; Operation Iraqi Freedom and Operation Enduring Freedom caregivers; veteran caregivers ID POSTTRAUMATIC-STRESS-DISORDER; TRAUMATIC BRAIN-INJURY; MENTAL-HEALTH; WAR VETERANS; MILITARY; FAMILIES; PARTNERS; SPOUSES; SUPPORT; BURDEN AB Today, as a result of the longest volunteer-fought conflict in U.S. history, there are many wounded coming home not only with posttraumatic stress disorder (PTSD), but also with traumatic brain injury (TBI), which together have been called the "signature" or "invisible" injuries of the Iraq and Afghanistan wars. Caregivers are an important part of their recovery, yet little is known about them, as previous research on caregivers mostly focused on geriatric populations. According to one estimate 275,000 to 1 million people are currently caring or have cared for loved ones who have returned from Iraq and Afghanistan. These caregivers are unique in that they are younger, some with children, and they are caring for a unique understudied population for longer periods of time. This article summarizes literature on caregivers of veterans who suffer from PTSD, TBI, or both; provides a theoretical framework; and discusses implications for social workers in assisting caregivers and their families. C1 US Dept Vet Affairs, Social Work, Gainesville, FL 32608 USA. RP Patel, BR (reprint author), US Dept Vet Affairs, Social Work, 1601 SW Archer Rd,Mail Code 116A-4, Gainesville, FL 32608 USA. EM beepat617@hotmail.com NR 52 TC 0 Z9 0 U1 3 U2 17 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0037-8046 EI 1545-6846 J9 SOC WORK JI Soc. Work PD JAN PY 2015 VL 60 IS 1 BP 9 EP 17 DI 10.1093/sw/swu043 PG 9 WC Social Work SC Social Work GA CC1PJ UT WOS:000350113200002 PM 25643571 ER PT J AU Lee, J Willis, L Newman, D Hazan, A Kurobe, A Giordano, L Kaafarani, H Laidlaw, C Shah, K AF Lee, Jarone Willis, Lucy Newman, David Hazan, Alberto Kurobe, Aileen Giordano, Lorraine Kaafarani, Haytham Laidlaw, Caitlin Shah, Kaushal TI Are Sexual Assault Victims Presenting to the Emergency Department in a Timely Manner? SO SOCIAL WORK LA English DT Article DE chi-square test; emergency department; multivariate regression; sexual assault; victims ID INJURY; WOMEN; RAPE; ACQUAINTANCE; PREDICTORS; STRANGER AB Social workers regularly assist sexual assault victims and would benefit from a greater understanding of causes for delayed presentation to seek medical care. Delays in presentation of sexual assault victims affect the legal value of collected evidence. The authors of this study sought to characterize the nature and frequency of delayed presentation among victims. To do so, they performed a chart review from 2001 to 2007 of the Sexual Assault Forensic Examiner program at their institution. Delayed presentation was defined as presentation more than 12 hours after the assault. Chi-square test was used to contrast frequencies, and multivariate regression was used to control for confounders. Among 482 victims, more than half presented delayed. Of the victims who documented whether they knew the perpetrator, 63 percent knew the perpetrator, with 58 percent of these presenting delayed. Knowing the perpetrator was significantly associated with delayed presentation. Age, ethnicity, and gender were not associated with delayed presentation. C1 [Lee, Jarone] Harvard Univ, Sch Med, Boston, MA 02114 USA. [Lee, Jarone] Massachusetts Gen Hosp, Div Trauma, Emergency Surg, Surg Crit Care, Boston, MA 02114 USA. [Willis, Lucy] New York Downtown Hosp, New York, NY USA. [Newman, David; Shah, Kaushal] Mt Sinai Sch Med, Emergency Med, New York, NY USA. [Hazan, Alberto] Valley Hlth Syst, Las Vegas, NV USA. [Kurobe, Aileen] Univ Calif Irvine, Irvine Sch Med, Irvine, CA USA. [Giordano, Lorraine] St Lukes Roosevelt Hosp, New York, NY USA. [Kaafarani, Haytham; Laidlaw, Caitlin] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Lee, J (reprint author), Harvard Univ, Sch Med, 165 Cambridge St,Suite 810, Boston, MA 02114 USA. EM lee.jarone@mgh.harvard.edu NR 11 TC 0 Z9 0 U1 0 U2 4 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0037-8046 EI 1545-6846 J9 SOC WORK JI Soc. Work PD JAN PY 2015 VL 60 IS 1 BP 29 EP 33 DI 10.1093/sw/swu051 PG 5 WC Social Work SC Social Work GA CC1PJ UT WOS:000350113200004 PM 25643573 ER PT J AU Patil, V Gupta, R Estepar, RS Lacson, R Cheung, A Wong, JM Popp, AJ Golby, A Ogilvy, C Vosburgh, KG AF Patil, Vaibhav Gupta, Rajiv Estepar, Raul San Jose Lacson, Ronilda Cheung, Arnold Wong, Judith M. Popp, A. John Golby, Alexandra Ogilvy, Christopher Vosburgh, Kirby G. TI Smart Stylet: The Development and Use of a Bedside External Ventricular Drain Image-Guidance System SO STEREOTACTIC AND FUNCTIONAL NEUROSURGERY LA English DT Article DE Ventriculostomy; Image-guided surgery; Electromagnetic concepts; Neuronavigation ID FRAMELESS STEREOTACTIC SYSTEMS; CATHETER PLACEMENT; PEDIATRIC-PATIENTS; RISK-FACTORS; ACCURACY; NAVIGATION; HYDROCEPHALUS; TRACKING; MONITOR AB Background: Placement accuracy of ventriculostomy catheters is reported in a wide and variable range. Development of an efficient image-guidance system may improve physician performance and patient safety. Objective: We evaluate the prototype of Smart Stylet, a new electromagnetic image-guidance system for use during bedside ventriculostomy. Methods: Accuracy of the Smart Stylet system was assessed. System operators were evaluated for their ability to successfully target the ipsilateral frontal horn in a phantom model. Results: Target registration error across 15 intracranial targets ranged from 1.3 to 4.6 mm (mean 3.1 mm). Using Smart Stylet guidance, a test operator successfully passed a ventriculostomy catheter to a shifted ipsilateral frontal horn 20/20 (100%) times from the frontal approach in a skull phantom. Without Smart Stylet guidance, the operator was successful 4/10 (40%) times from the right frontal approach and 6/10 (60%) times from the left frontal approach. In a separate experiment, resident operators were successful 2/4 (50%) times when targeting the shifted ipsilateral frontal horn with Smart Stylet guidance and 0/4 (0%) times without image guidance using a skull phantom. Conclusions: Smart Stylet may improve the ability to successfully target the ventricles during frontal ventriculostomy. (C) 2015 S. Karger AG, Basel C1 [Patil, Vaibhav; Estepar, Raul San Jose; Lacson, Ronilda; Golby, Alexandra; Vosburgh, Kirby G.] Brigham & Womens Hosp, Dept Radiol, Boston, MA 02115 USA. [Wong, Judith M.; Popp, A. John; Golby, Alexandra] Brigham & Womens Hosp, Dept Neurosurg, Boston, MA 02115 USA. [Gupta, Rajiv; Cheung, Arnold] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. [Ogilvy, Christopher] Beth Israel Deaconess Med Ctr, Dept Neurosurg, Boston, MA 02215 USA. RP Patil, V (reprint author), Harvard Univ, Brigham & Womens Hosp, Sch Med, 75 Francis St,ASBI L1-050, Boston, MA 02115 USA. EM patil@bwh.harvard.edu FU NIH [R42 CA115112-03, T15 M007092-19]; Center for Integration of Medicine and Innovative Technology (CIMIT), Boston, Mass., USA FX Funding: NIH, R42 CA115112-03, Kirby G. Vosburgh, PhD; NIH, T15 M007092-19, Alexa T. McCray, PhD; Center for Integration of Medicine and Innovative Technology (CIMIT), Boston, Mass., USA. NR 26 TC 0 Z9 0 U1 1 U2 4 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 1011-6125 EI 1423-0372 J9 STEREOT FUNCT NEUROS JI Stereotact. Funct. Neurosurg. PY 2015 VL 93 IS 1 BP 50 EP 58 DI 10.1159/000368906 PG 9 WC Neurosciences; Neuroimaging; Surgery SC Neurosciences & Neurology; Surgery GA CC3SC UT WOS:000350268700008 PM 25662506 ER PT J AU Saff, RR Banerji, A AF Saff, Rebecca R. Banerji, Aleena TI Management of patients with nonaspirin-exacerbated respiratory disease aspirin hypersensitivity reactions SO ALLERGY AND ASTHMA PROCEEDINGS LA English DT Article ID NONSTEROIDAL ANTIINFLAMMATORY DRUGS; STEVENS-JOHNSON-SYNDROME; TOXIC EPIDERMAL NECROLYSIS; CUTANEOUS REACTIONS; CONTACT-DERMATITIS; ASTHMATIC-PATIENTS; CHRONIC URTICARIA; NATURAL-HISTORY; DESENSITIZATION; SENSITIVITY AB Because of widespread use, nonsteroidal anti-inflammatory drugs (NSAIDs) are the second most common cause of all adverse drug reactions, with hypersensitivity reported in similar to 1% of the population. NSAID hypersensitivity can be categorized into five types by the underlying disease, symptoms of reaction, and timing of reaction. These include rhinitis and asthma induced by NSAIDs (also known as aspirin-exacerbated respiratory disease), NSAID-exacerbated cutaneous disease (NECD), urticaria or angioedema induced by multiple NSAIDs, single NSAID-induced reactions, and delayed NSAID reactions. NECD occurs in one-third of patients with chronic urticaria who develop an exacerbation of their urticaria, sometimes with angioedema, typically beginning 30-90 minutes after ingestion of NSAIDs that inhibit cyclooxygenase (COX)-1. In urticaria. or angioedema induced by multiple NSAIDs, patients without underlying disease develop urticaria or angioedema 30-90 minutes after ingestion of COX-1-inhibiting NSAIDs including aspirin. Single NSAID-induced reactions are immediate and specific to a single NSAID and are thought to occur because of an IgE-mediated reaction against a specific epitope of the NSAID. Delayed NSAID reactions occur days to weeks after initiating an NSAID. These are T-cell mediated and not amenable to desensitization or rechallenge. Classifying the type of NSAID hypersensitivity is important because many patients with a prior history of urticaria or angioedema induced by multiple NSAIDs will often tolerate aspirin test dose. This would allow the use of an aspirin for primary or secondary prevention in patients with coronary artery disease despite a presumed history of NSAID hypersensitivity. C1 [Saff, Rebecca R.; Banerji, Aleena] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Med,Div Rheumatol Allergy & Immunol, Boston, MA USA. RP Saff, RR (reprint author), Dept Med, Div Rheumatol Allergy & Immunol, 55 Fruit St,COX 201, Boston, MA 02114 USA. EM rsaff@partners.org NR 55 TC 4 Z9 4 U1 0 U2 2 PU OCEAN SIDE PUBLICATIONS INC PI PROVIDENCE PA 95 PITMAN ST, PROVIDENCE, RI 02906 USA SN 1088-5412 EI 1539-6304 J9 ALLERGY ASTHMA PROC JI Allergy Asthma Proc. PD JAN-FEB PY 2015 VL 36 IS 1 BP 34 EP 39 DI 10.2500/aap.2015.36.3800 PG 6 WC Allergy SC Allergy GA CC0EB UT WOS:000350007500008 PM 25562554 ER PT J AU Lorius, N Locascio, JJ Rentz, DM Johnson, KA Sperling, RA Viswanathan, A Marshall, GA AF Lorius, Natacha Locascio, Joseph J. Rentz, Dorene M. Johnson, Keith A. Sperling, Reisa A. Viswanathan, Anand Marshall, Gad A. CA Alzheimer's Dis Neuroimaging TI Vascular Disease and Risk Factors are Associated With Cognitive Decline in the Alzheimer Disease Spectrum SO ALZHEIMER DISEASE & ASSOCIATED DISORDERS LA English DT Article DE Alzheimer disease; processing speed; memory; mild cognitive impairment; vascular risk factors ID BODY-MASS INDEX; APOLIPOPROTEIN-E; DEMENTIA; PROGRESSION; HOMOCYSTEINE; IMPAIRMENT; PATHOLOGY; BURDEN; COHORT; BRAIN AB We investigated the relationship between vascular disease and risk factors versus cognitive decline cross-sectionally and longitudinally in normal older control, mild cognitive impairment, and mild Alzheimer disease (AD) dementia subjects. A total of 812 participants (229 normal older control, 395 mild cognitive impairment, 188 AD) underwent cognitive testing, brain magnetic resonance imaging, and clinical evaluations at baseline and over a period of 3 years. General linear, longitudinal mixed-effects, and Cox proportional hazards models were used. Greater homocysteine level and white matter hyperintensity volume were associated with processing speed impairment (homocysteine: P = 0.02; white matter hyperintensity: P < 0.0001); greater Vascular Index score was associated with memory impairment (P = 0.007); and greater number of apolipoprotein E epsilon 4 (APOE4) alleles was associated with global cognitive impairment (P = 0.007) at baseline. Apolipoprotein E epsilon 4 was associated with greater rate of increase in global cognitive impairment (P = 0.002) and processing speed impairment (P = 0.001) over time, whereas higher total cholesterol was associated with greater rate of increase in global cognitive impairment (P = 0.02) and memory impairment (P = 0.06) over time. These results suggest a significant association of increased vascular disease and risk factors with cognitive impairment at baseline and over time in the AD spectrum in a sample that was selected to have low vascular burden at baseline. C1 [Lorius, Natacha; Rentz, Dorene M.; Johnson, Keith A.; Sperling, Reisa A.; Marshall, Gad A.] Harvard Univ, Sch Med, Dept Neurol, Ctr Alzheimer Res & Treatment,Brigham & Womens Ho, Boston, MA 02115 USA. [Lorius, Natacha; Locascio, Joseph J.; Rentz, Dorene M.; Sperling, Reisa A.; Viswanathan, Anand; Marshall, Gad A.] Harvard Univ, Sch Med, Dept Neurol, Massachusetts Gen Hosp, Boston, MA 02115 USA. [Johnson, Keith A.] Harvard Univ, Sch Med, Dept Radiol, Massachusetts Gen Hosp, Boston, MA 02115 USA. RP Marshall, GA (reprint author), Harvard Univ, Sch Med, Dept Neurol, Ctr Alzheimer Res & Treatment,Brigham & Womens Ho, 221 Longwood Ave,BL-104H, Boston, MA 02115 USA. EM gamarshall@partners.org FU Gilbert Foundation/AFAR New Investigator Awards in Alzheimer's disease; Massachusetts Alzheimer's Disease Research Center [P50 AG005134]; Harvard Aging Brain Study [P01 AGO36694]; ADNI (NIH) [U01 AG024904]; Alzheimer's Disease Neuroimaging Initiative (ADNI) (National Institutes of Health) [U01 AG024904]; NIH [P30 AG010129, K01 AG030514]; Massachusetts General Hospital; Brigham and Women's Hospital; Harvard Medical School; NIA/NIH; [R01 AG027435]; [K23 AG033634]; [K24 AG035007]; [NIH/NIA2P50AG05134-26]; [1K23AG028726-01A2] FX Supported by R01 AG027435, K23 AG033634, K24 AG035007, Gilbert Foundation/AFAR New Investigator Awards in Alzheimer's disease, Massachusetts Alzheimer's Disease Research Center (P50 AG005134), Harvard Aging Brain Study (P01 AGO36694), and ADNI (NIH Grant U01 AG024904). Data collection and sharing for this project was funded by the Alzheimer's Disease Neuroimaging Initiative (ADNI) (National Institutes of Health Grant U01 AG024904). The grantee organization is the Northern California Institute for Research and Education, and the study is coordinated by the Alzheimer's Disease Cooperative Study at the University of California, San Diego. ADNI data are disseminated by the Laboratory for Neuroimaging at the University of California, Los Angeles. This research was also supported by NIH Grants P30 AG010129 and K01 AG030514.; A.V. has 2 conflicts of interest to report, the following grants/funds: NIH/NIA2P50AG05134-26 and 1K23AG028726-01A2. KAJ has the following conflicts of interest to report: Massachusetts General Hospital, Brigham and Women's Hospital, Harvard Medical School, NIA/NIH funds/grants, a consultant for GEHC, Piramal, Avid/Lilly, and Siemems. The remaining authors declare no conflicts of interest. NR 42 TC 11 Z9 11 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0893-0341 J9 ALZ DIS ASSOC DIS JI Alzheimer Dis. Assoc. Dis. PD JAN-MAR PY 2015 VL 29 IS 1 BP 18 EP 25 PG 8 WC Clinical Neurology; Pathology SC Neurosciences & Neurology; Pathology GA CC1RG UT WOS:000350119500004 PM 24787033 ER PT J AU Mendez, MF Sabodash, V AF Mendez, Mario F. Sabodash, Valeriy TI Clinical Amyloid Imaging in Logopenic Progressive Aphasia SO ALZHEIMER DISEASE & ASSOCIATED DISORDERS LA English DT Article DE primary progressive aphasia (PPA); logopenic; Alzheimer disease; amyloid imaging; florbetapir ID ALZHEIMERS-DISEASE AB The introduction of florbetapir (Amyvid) positron emission tomography biomarkers could dramatically change how we clinically evaluate young patients who present with nonamnestic cognitive complaints for possible Alzheimer disease (AD). Logopenic progressive aphasia (LPA) may be the most common example of this type of clinical problem. In most, but not all, cases, LPA is an early-onset AD variant presenting with language changes that can be difficult to distinguish from other progressive aphasias. We clinically evaluated 3 patients with LPA, in comparison with age-matched and severity-matched patients with typical amnestic AD, using florbetapir amyloid neuroimaging. The fluorodeoxyglucose-positron emission tomography scans of LPA patients revealed focal hypometabolism in the left temporoparietal areas, and the florbetapir scans were diffusely positive for the presence of amyloid deposition. The florbetapir scans did not differ in distribution between patients with LPA and those with typical amnestic AD. Clinical amyloid imaging, although lacking localizing value, is a major advance in the assessment of early-onset and nonamnestic patients for the presence of beta-amyloid Alzheimer pathology. C1 [Mendez, Mario F.; Sabodash, Valeriy] 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 & Biobehav Sci, Los Angeles, CA 90095 USA. [Mendez, Mario F.; Sabodash, Valeriy] VA Greater Los Angeles Healthcare Ctr, Neurobehav Unit, Los Angeles, CA 90073 USA. RP Mendez, MF (reprint author), VA Greater Los Angeles Healthcare Ctr, Neurobehav Unit 691 116AF, 11301 Wilshire Blvd, Los Angeles, CA 90073 USA. EM mmendez@UCLA.edu FU National Institute on Aging [R01 AG034499] FX M.F.M. supported by National Institute on Aging R01 AG034499. NR 10 TC 2 Z9 2 U1 1 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0893-0341 J9 ALZ DIS ASSOC DIS JI Alzheimer Dis. Assoc. Dis. PD JAN-MAR PY 2015 VL 29 IS 1 BP 94 EP 96 PG 3 WC Clinical Neurology; Pathology SC Neurosciences & Neurology; Pathology GA CC1RG UT WOS:000350119500016 PM 23995816 ER PT J AU Sadeghian, H Motiei-Langroudi, R AF Sadeghian, Homa Motiei-Langroudi, Rouzbeh TI Comparison of Levetiracetam and sodium Valproate in migraine prophylaxis: A randomized placebo-controlled study SO ANNALS OF INDIAN ACADEMY OF NEUROLOGY LA English DT Article DE Efficacy; levetiracetam; migraine; prophylaxis; valproate ID CORTICAL SPREADING DEPRESSION; HEALTH STROKE SCALE; PEDIATRIC MIGRAINE; OPEN-LABEL; MULTIPLE-SCLEROSIS; IRANIAN PATIENTS; UNITED-STATES; AGENTS; BRAIN; AURA AB Background: Migraine is a chronic and disabling disorder. Treatment of migraine often comprises of symptomatic (abortive) and preventive (prophylactic) treatment. The current drugs used in migraine prophylaxis include antidepressant drugs (Serotonin Reuptake Inhibitors, Tricyclic antidepressants), and anti-epileptic drugs (valproate, gabapentin, etc). Objective: The objective of our study was to assess the efficacy and tolerability of levetiracetam in adult migraine prophylaxis, compared to valproate and placebo. Materials and Methods: We conducted a prospective, randomized, placebo-controlled study. A total of 85 patients were randomized to receive levetiracetam 500 mg/d (n = 27), valproate 500 mg/d (n = 32) or placebo (n = 26). The patients were evaluated for treatment efficacy after 6 months. Efficacy was assessed as a more than 50% decrease in headache frequency. Results: In levetiracetam group, 17 (63.0%) patients experienced a more than 50% decrease in headache frequency, while this efficacy number was 21 (65.6%) for valproate group and 4 (15.4%) for placebo group. The difference was not statistically significant between levetiracetam and valproate, while it was significant when comparing either levetiracetam or valproate to placebo. Conclusion: Compared to placebo, levetiracetam offers improvement in headache frequency in patients with migraine. The efficacy of levetiracetam in migraine prophylaxis is comparable to currently used drugs such as valproate. C1 [Sadeghian, Homa] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Radiol,Neurovasc Res Lab, Charlestown, MA 02129 USA. [Motiei-Langroudi, Rouzbeh] Shefa Neurosci Res Ctr, Tehran, Iran. RP Sadeghian, H (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Radiol,Neurovasc Res Lab, Charlestown, MA 02129 USA. EM hsadeghian@mgh.harvard.edu NR 36 TC 3 Z9 3 U1 0 U2 4 PU MEDKNOW PUBLICATIONS & MEDIA PVT LTD PI MUMBAI PA B-9, KANARA BUSINESS CENTRE, OFF LINK RD, GHAKTOPAR-E, MUMBAI, 400075, INDIA SN 0972-2327 EI 1998-3549 J9 ANN INDIAN ACAD NEUR JI Ann. Indian Acad. Neurol. PD JAN-MAR PY 2015 VL 18 IS 1 BP 45 EP 48 DI 10.4103/0972-2327.144290 PG 4 WC Clinical Neurology SC Neurosciences & Neurology GA CB7XG UT WOS:000349841400010 PM 25745310 ER PT J AU Singh, JA Noorbaloochi, S MacDonald, R Maxwell, LJ AF Singh, Jasvinder A. Noorbaloochi, Shahrzad MacDonald, Roderick Maxwell, Lara J. TI Chondroitin for osteoarthritis SO COCHRANE DATABASE OF SYSTEMATIC REVIEWS LA English DT Review ID SYMPTOMATIC KNEE OSTEOARTHRITIS; PLACEBO-CONTROLLED TRIAL; CLINICALLY SIGNIFICANT DIFFERENCE; ANALOG SCALE PAIN; DOUBLE-BLIND; GLUCOSAMINE HYDROCHLORIDE; MANGANESE ASCORBATE; HIP OSTEOARTHRITIS; OSTEO-ARTHRITIS; 6 SULFATE AB Background Osteoarthritis, a common joint disorder, is one of the leading causes of disability. Chondroitin has emerged as a new treatment. Previous meta-analyses have shown contradictory results on the efficacy of chondroitin. This, in addition to the publication of more trials, necessitates a systematic review. Objectives To evaluate the benefit and harm of oral chondroitin for treating osteoarthritis compared with placebo or a comparator oral medication including, but not limited to, nonsteroidal anti-inflammatory drugs (NSAIDs), analgesics, opioids, and glucosamine or other "herbal" medications. Search methods We searched seven databases up to November 2013, including the Cochrane Central Register of Controlled Trials (CENTRAL), Ovid MEDLINE, CINAHL, EMBASE, Science Citation Index (Web of Science) and Current Controlled Trials. We searched the US Food andDrug Administration (FDA) and EuropeanMedicines Agency (EMEA) websites for adverse effects. Trial registers were not searched. Selection criteria All randomized or quasi-randomized clinical trials lasting longer than two weeks, studying adults with osteoarthritis in any joint, and comparing chondroitin with placebo, an active control such as NSAIDs, or other "herbal" supplements such as glucosamine. Data collection and analysis Two review authors independently performed all title assessments, data extractions, and risk of bias assessments. Main results Forty-three randomized controlled trials including 4,962 participants treated with chondroitin and 4,148 participants given placebo or another control were included. The majority of trials were in knee OA, with few in hip and hand OA. Trial duration varied from 1 month to 3 years. Participants treated with chondroitin achieved statistically significantly and clinically meaningful better pain scores (0-100) in studies less than 6 months than those given placebo with an absolute risk difference of 10% lower (95% confidence interval (CI), 15% to 6% lower; number needed to treat (NNT) = 5 (95% CI, 3 to 8; n = 8 trials) (level of evidence, low; risk of bias, high); but there was high heterogeneity between the trials (T-2 = 0.07; I-2 = 70%, which was not easily explained by differences in risk of bias or study sample size). In studies longer than 6 months, the absolute risk difference for pain was 9% lower (95% CI 18% lower to 0%); n = 6 trials; T-2 = 0.18; I-2 = 83%), again with low level of evidence. For the Western Ontario and McMaster Universities Osteoarthritis Index Minimal Clinically Important Improvement (WOMAC MCII Pain subscale) outcome, a reduction in knee pain by 20% was achieved by 53/100 in the chondroitin group versus 47/100 in the placebo group, an absolute risk difference of 6% (95% CI 1% to 11%), (RR 1.12, 95% CI 1.01 to 1.24; T-2 = 0.00; I-2 = 0%) (n = 2 trials, 1253 participants; level of evidence, high; risk of bias, low). Differences in Lequesne's index (composite of pain, function and disability) statistically significantly favoured chondroitin as compared with placebo in studies under six months, with an absolute risk difference of 8% lower (95% CI 12% to 5% lower; T-2 = 0.78; n = 7 trials) (level of evidence, moderate; risk of bias, unclear), also clinically meaningful. Loss of minimum joint space width in the chondroitin group was statistically significantly less than in the placebo group, with a relative risk difference of 4.7% less (95% CI 1.6% to 7.8% less; n = 2 trials) (level of evidence, high; risk of bias, low). Chondroitin was associated with statistically significantly lower odds of serious adverse events compared with placebo with Peto odds ratio of 0.40 (95% CI 0.19 to 0.82; n = 6 trials) (level of evidence, moderate). Chondroitin did not result in statistically significant numbers of adverse events or withdrawals due to adverse events compared with placebo or another drug. Adverse events were reported in a limited fashion, with some studies providing data and others not. Comparisons of chondroitin taken alone or in combination with glucosamine or another supplement showed a statistically significant reduction in pain (0-100) when compared with placebo or an active control, with an absolute risk difference of 10% lower (95% CI 14% to 5% lower); NNT = 4 (95% CI 3 to 6); T-2 = 0.33; I-2 = 91%; n = 17 trials) (level of evidence, low). For physical function, chondroitin in combination with glucosamine or another supplement showed no statistically significant difference from placebo or an active control, with an absolute risk difference of 1% lower (95% CI 6% lower to 3% higher with T-2 = 0.04; n = 5 trials) (level of evidence, moderate). Differences in Lequesne's index statistically significantly favoured chondroitin as compared with placebo, with an absolute risk difference of 8% lower (95% CI, 12% to 4% lower; T-2 = 0.12; n = 10 trials) (level of evidence, moderate). Chondroitin in combination with glucosamine did not result in statistically significant differences in the numbers of adverse events, withdrawals due to adverse events, or in the numbers of serious adverse events compared with placebo or with an active control. The beneficial effects of chondroitin in pain and Lequesne's index persisted when evidence was limited to studies with adequate blinding or studies that used appropriate intention to treat (ITT) analyses. These beneficial effects were uncertain when we limited data to studies with appropriate allocation concealment or a large study sample (>200) or to studies without pharmaceutical funding. Authors' conclusions A review of randomized trials of mostly low quality reveals that chondroitin (alone or in combination with glucosamine) was better than placebo in improving pain in participants with osteoarthritis in short-term studies. The benefit was small to moderate with an 8 point greater improvement in pain (range 0 to 100) and a 2 point greater improvement in Lequesne's index (range 0 to 24), both seeming clinically meaningful. These differences persisted in some sensitivity analyses and not others. Chondroitin had a lower risk of serious adverse events compared with control. More high-quality studies are needed to explore the role of chondroitin in the treatment of osteoarthritis. The combination of some efficacy and low risk associated with chondroitin may explain its popularity among patients as an over-the-counter supplement. C1 [Singh, Jasvinder A.] Birmingham VA Med Ctr, Dept Med, Birmingham, AL 35294 USA. [Noorbaloochi, Shahrzad] Minneapolis VA Med Ctr, Dept Med, Minneapolis, MN USA. [Noorbaloochi, Shahrzad] Univ Minnesota, Minneapolis, MN USA. [MacDonald, Roderick] VA Med Ctr, Minneapolis, MN USA. [Maxwell, Lara J.] Univ Ottawa, Inst Populat Hlth, Ctr Global Hlth, Ottawa, ON, Canada. RP Singh, JA (reprint author), Birmingham VA Med Ctr, Dept Med, Fac Off Tower 805B,510 20th St South, Birmingham, AL 35294 USA. EM jasvinder.md@gmail.com FU University of Alabama at Birmingham, Birmingham, Alabama, USA; Birmingham VA Medical Center, Birmingham, Alabama, USA; Center for Chronic Disease Outcomes Research and Center for Epidemiological and Clinical Research, Minneapolis VA Medical Center, Minneapolis, Minnesota, USA; Cochrane Complementary Medicine Field Bursary, USA; Cochrane Complementary Medicine Field Bursary FX Internal sources; University of Alabama at Birmingham and the Birmingham VA Medical Center, Birmingham, Alabama, USA.; Center for Chronic Disease Outcomes Research and Center for Epidemiological and Clinical Research, Minneapolis VA Medical Center, Minneapolis, Minnesota, USA.; External sources; Cochrane Complementary Medicine Field Bursary, USA.; We received a $5,000 Cochrane Complementary Medicine Field Bursary to complete this review. This money was used to pay research associates to perform data abstraction and data quality assurance/quality improvement. NR 153 TC 4 Z9 4 U1 3 U2 14 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 2015 IS 1 AR CD005614 DI 10.1002/14651858.CD005614.pub2 PG 304 WC Medicine, General & Internal SC General & Internal Medicine GA CB5ST UT WOS:000349688600008 ER PT J AU Ruggiero, KJ Davidson, TM McCauley, J Gros, KS Welsh, K Price, M Resnick, HS Danielson, CK Soltis, K Galea, S Kilpatrick, DG Saunders, BE Nissenboim, J Muzzy, W Fleeman, A Amstadter, AB AF Ruggiero, Kenneth J. Davidson, Tatiana M. McCauley, Jenna Gros, Kirstin Stauffacher Welsh, Kyleen Price, Matthew Resnick, Heidi S. Danielson, Carla Kmett Soltis, Kathryn Galea, Sandro Kilpatrick, Dean G. Saunders, Benjamin E. Nissenboim, Josh Muzzy, Wendy Fleeman, Anna Amstadter, Ananda B. TI Bounce Back Now! Protocol of a population-based randomized controlled trial to examine the efficacy of a Web-based intervention with disaster-affected families SO CONTEMPORARY CLINICAL TRIALS LA English DT Article DE Disaster mental health; Population-based research; Web intervention; Adolescents ID POSTTRAUMATIC-STRESS-DISORDER; COGNITIVE-BEHAVIORAL TREATMENT; NEW-YORK-CITY; MENTAL-HEALTH; SUBSTANCE USE; HURRICANE KATRINA; RARE VARIANTS; YOUNG-PEOPLE; CHILDREN; ADOLESCENTS AB Disasters have far-reaching and potentially long-lasting effects on youth and families. Research has consistently shown a clear increase in the prevalence of several mental health disorders after disasters, including depression and posttraumatic stress disorder. Widely accessible evidence-based interventions are needed to address this unmet need for youth and families, who are underrepresented in disaster research. Rapid growth in Internet and Smartphone access, as well as several Web based evaluation studies with various adult populations has shown that Web-based interventions are likely to be feasible in this context and can improve clinical outcomes. Such interventions also are generally cost-effective, can be targeted or personalized, and can easily be integrated in a stepped care approach to screening and intervention delivery. This is a protocol paper that describes an innovative study design in which we evaluate a self-help Web-based resource, Bounce Back Now, with a population-based sample of disaster affected adolescents and families. The paper includes description and justification for sampling selection and procedures, selection of assessment measures and methods, design of the intervention, and statistical evaluation of critical outcomes. Unique features of this study design include the use of address-based sampling to recruit a population-based sample of disaster-affected adolescents and parents, telephone and Web-based assessments, and development and evaluation of a highly individualized Web intervention for adolescents. Challenges related to large-scale evaluation of technology-delivered interventions with high-risk samples in time-sensitive research are discussed, as well as implications for future research and practice. Published by Elsevier Inc. C1 [Ruggiero, Kenneth J.; Davidson, Tatiana M.; Soltis, Kathryn; Muzzy, Wendy] Med Univ S Carolina, Coll Nursing, Technol Applicat Ctr Healthful Lifestyles, Charleston, SC 29425 USA. [Ruggiero, Kenneth J.; Gros, Kirstin Stauffacher; Welsh, Kyleen; Muzzy, Wendy] Ralph H Johnson Vet Affairs Med Ctr, Charleston, SC 29401 USA. [Davidson, Tatiana M.; Welsh, Kyleen; Resnick, Heidi S.; Danielson, Carla Kmett; Soltis, Kathryn; Kilpatrick, Dean G.; Saunders, Benjamin E.] MUSC, Dept Psychiat & Behav Sci, Natl Crime Victims Res & Treatment Ctr, Charleston, SC USA. [McCauley, Jenna] MUSC, Dept Psychiat & Behav Sci, Clin Neurosci Div, Charleston, SC USA. [Price, Matthew] Univ Vermont, Ctr Res Emot Stress & Technol, Burlington, VT USA. [Galea, Sandro] Columbia Univ, Mailman Sch Publ Hlth, Dept Epidemiol, New York, NY USA. [Nissenboim, Josh] Fuzzco Inc, Charleston, SC USA. [Fleeman, Anna] Abt SRBI, New York, NY USA. [Amstadter, Ananda B.] Virginia Commonwealth Univ, Virginia Inst Psychiat & Behav Genet, Dept Psychiat Psychol & Human & Mol Genet, Richmond, VA USA. RP Ruggiero, KJ (reprint author), Med Univ S Carolina, Coll Nursing, Technol Applicat Ctr Healthful Lifestyles, Charleston, SC 29425 USA. EM ruggierk@musc.edu RI Emchi, Karma/Q-1952-2016 FU National Institute of Mental Health (NIMH) [R01 MH081056]; NIMH [MH081056, T32 MH018869]; National Institute on Drug Abuse (NIDA) [R01 DA031285]; National Institute on Alcohol Abuse and Alcoholism (NIAAA) [P50 AA010761]; NIDA [K12 DA031794]; NIAAA [K02 AA023239]; [R21 MH086313] FX This research was supported by National Institute of Mental Health (NIMH) Grant R01 MH081056 (PI: KJ Ruggiero). This includes two supplements to NIMH Grant MH081056: an OppNet supplement awarded to Dr. Amstadter, and a Diversity supplement awarded to Dr. Davidson. Grant R21 MH086313 (PI: CK Danielson) also supported some elements of this work. The preparation of this manuscript was supported by National Institute on Drug Abuse (NIDA) Grant R01 DA031285 (PI: CK Danielson) and National Institute on Alcohol Abuse and Alcoholism (NIAAA) Grant P50 AA010761 (PI: Becker); NIDA Grant K12 DA031794 (PI: Brady; support to JM), NIMH Grant T32 MH018869 (PI: Kilpatrick; support to MP), and NIAAA K02 AA023239 (PI: Amstadter). All views and opinions expressed herein are those of the authors and do not necessarily reflect those of the funding agency or respective institutions. NR 85 TC 6 Z9 6 U1 0 U2 5 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1551-7144 EI 1559-2030 J9 CONTEMP CLIN TRIALS JI Contemp. Clin. Trials PD JAN PY 2015 VL 40 BP 138 EP 149 DI 10.1016/j.cct.2014.11.018 PG 12 WC Medicine, Research & Experimental; Pharmacology & Pharmacy SC Research & Experimental Medicine; Pharmacology & Pharmacy GA CB6IZ UT WOS:000349732000016 PM 25478956 ER PT J AU Oreskovic, NM Goodman, E Park, ER Robinson, AI Winickoff, JP AF Oreskovic, Nicolas M. Goodman, Elizabeth Park, Elyse R. Robinson, Alyssa I. Winickoff, Jonathan P. TI Design and implementation of a physical activity intervention to enhance children's use of the built environment (the CUBE study) SO CONTEMPORARY CLINICAL TRIALS LA English DT Article DE Physical activity; Built environment; Adolescents; Obesity; Intervention ID RANDOMIZED CONTROLLED-TRIAL; ADOLESCENT FEMALES; UNITED-STATES; ACCELEROMETER; OVERWEIGHT; CHILDHOOD; OBESITY; COMMUNITIES; PATTERNS AB Background: Adequate physical activity promotes physical and mental health and decreases obesity risk. However, most adolescents do not attain recommended physical activity levels and effective interventions are lacking. Physical activity trials rarely incorporate built environment use patterns. Purpose: This paper describes the design and rationale of the Children's Use of the Built Environment (CUBE) Study, an office-based intervention designed to teach youth how to use their surrounding built environment to increase physical activity. Methods: CUBE is a 6-month intervention trial among 60 overweight and obese 10-16 year old adolescents from a community health center in Massachusetts. The study began in the winter of 2013. Patients are sequentially assigned to either the intervention or control group. Baseline physical activity by accelerometry and location by GPS, along with measured height, weight, and blood pressure are collected. Control subjects receive standard of care lifestyle counseling. Intervention subjects receive tailored recommendations on how to increase their physical activity based on their accelerometer and GPS data. Data collections are repeated at end-of-treatment, and again 3 months later. Conclusion: The findings from this study should help guide future efforts to design interventions aimed at increasing adolescent physical activity as well as to inform design professionals and government officials charged with creating outdoor spaces where adolescents spend time. (C) 2014 Elsevier Inc. All rights reserved. C1 [Oreskovic, Nicolas M.; Goodman, Elizabeth; Robinson, Alyssa I.; Winickoff, Jonathan P.] MassGen Hosp Children, Div Gen Acad Pediat, Boston, MA USA. [Oreskovic, Nicolas M.; Goodman, Elizabeth; Winickoff, Jonathan P.] Massachusetts Gen Hosp, Dept Pediat, Boston, MA 02114 USA. [Oreskovic, Nicolas M.] Massachusetts Gen Hosp, Dept Internal Med, Boston, MA 02114 USA. [Oreskovic, Nicolas M.; Goodman, Elizabeth; Park, Elyse R.; Winickoff, Jonathan P.] Harvard Univ, Sch Med, Boston, MA USA. [Park, Elyse R.] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. RP Oreskovic, NM (reprint author), Massachusetts Gen Hosp, Div Gen Acad Pediat, 100 Cambridge St,15th Floor, Boston, MA 02114 USA. EM noreskovic@mgh.harvard.edu; egoodman3@mgh.hanrard.edu; epark@mgh.harvard.edu; arobinson13@mgh.harvard.edu; jwinickoff@mgh.harvard.edu OI Oreskovic, Nicolas/0000-0001-8702-8636; Goodman, Elizabeth/0000-0002-9640-9884 FU National Institutes of Health/National Heart, Lung, and Blood Institute [5K23HL103841] FX The authors wish to thank the CUBE study participants and the Massachusetts General Hospital Revere HealthCare Center staff for their participation and cooperation. This trial is sponsored by the National Institutes of Health/National Heart, Lung, and Blood Institute grant #5K23HL103841. NR 32 TC 3 Z9 3 U1 1 U2 10 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1551-7144 EI 1559-2030 J9 CONTEMP CLIN TRIALS JI Contemp. Clin. Trials PD JAN PY 2015 VL 40 BP 172 EP 179 DI 10.1016/j.cct.2014.12.009 PG 8 WC Medicine, Research & Experimental; Pharmacology & Pharmacy SC Research & Experimental Medicine; Pharmacology & Pharmacy GA CB6IZ UT WOS:000349732000020 PM 25533728 ER PT J AU Awad, MM Sullivan, RJ AF Awad, Mark M. Sullivan, Ryan J. TI Dabrafenib in combination with trametinib for the treatment of metastatic melanoma SO EXPERT REVIEW OF CLINICAL PHARMACOLOGY LA English DT Article DE BRAF; MEK; melanoma; resistance; targeted therapy ID DOSE-ESCALATION TRIAL; MEK INHIBITOR TRAMETINIB; ACQUIRED-RESISTANCE; IMPROVED SURVIVAL; BRAF INHIBITION; PHASE-III; CANCER; SAFETY; VEMURAFENIB; MUTATIONS AB Oncogenic BRAF mutations are present in approximately 40-50% of patients with metastatic melanoma. Targeting BRAF mutations with either small molecule inhibitors of BRAF or one of the downstream mediators of oncogenic BRAF - MEK - is associated with improved outcomes compared with chemotherapy and has led to the US FDA approval of two BRAF inhibitors - vemurafenib and dabrafenib - and the MEK inhibitor trametinib. Further, the combination of dabrafenib and trametinib is well tolerated and associated with higher responses and improved survival compared with single-agent BRAF inhibitors. C1 [Awad, Mark M.; Sullivan, Ryan J.] Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA. RP Sullivan, RJ (reprint author), Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA. EM rsullivan7@partners.org NR 40 TC 4 Z9 6 U1 0 U2 0 PU TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND SN 1751-2433 EI 1751-2441 J9 EXPERT REV CLIN PHAR JI Expert Rev. Clin. Pharmacol. PD JAN PY 2015 VL 8 IS 1 BP 25 EP 33 DI 10.1586/17512433.2015.974556 PG 9 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA CC0JV UT WOS:000350022500005 PM 25473943 ER PT J AU Linkov, F Edwards, RP Althouse, A Rauh-Hain, JA Del Carmen, MG Freese, KE Kelley, JL Olawaiye, AB AF Linkov, Faina Edwards, Robert P. Althouse, Andrew Rauh-Hain, Jose A. Del Carmen, Marcela G. Freese, Kyle E. Kelley, Joseph L. Olawaiye, Alexander B. TI Obesity, lymphadenectomy and survival outcomes in intermediate to high-risk, early-stage endometrial cancer patients SO FUTURE ONCOLOGY LA English DT Article DE endometrial cancer; gynecology; lymphadenectomy; obesity; oncology; survival ID BODY-MASS INDEX; GYNECOLOGIC-ONCOLOGY-GROUP; PARAAORTIC LYMPHADENECTOMY; THERAPEUTIC ROLE; TRIAL; CARCINOMA; PROGNOSIS; IMPACT; ASTEC AB Aim: Lymphadenectomy or lymph node dissection is a topic of controversy in endometrial cancer (EC) treatment. Materials & methods: Associations between lymph node dissections and clinical factors were retrospectively examined in obese, endometrioid endometrial cancer patients with early-stage disease between 1995 and 2005. Overall, EC-specific and recurrence-free survival were also evaluated. Results: Out of 192 patients, 61 (32%) did not have a lymph node examination, 55 (29%) had less than ten lymph nodes removed and 76 (39%) had 10 removed. Lymph node dissection count was not significantly associated with overall, EC-specific or recurrence-free survival. Conclusion: Analysis revealed no significant associations between 10 dissected lymph nodes and survival outcomes among obese, EC patients, which supports the need for additional investigation of the merit of lymphadenectomy among these patients. C1 [Linkov, Faina; Freese, Kyle E.] Univ Pittsburgh, Grad Sch Publ Hlth, Dept Epidemiol, Pittsburgh, PA 15260 USA. [Linkov, Faina; Edwards, Robert P.; Althouse, Andrew; Kelley, Joseph L.; Olawaiye, Alexander B.] Univ Pittsburgh, Sch Med, Dept Obstet Gynecol & Reprod Sci, Div Gynecol Oncol, Pittsburgh, PA 15261 USA. [Rauh-Hain, Jose A.; Del Carmen, Marcela G.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Gynecol Oncol Vincent Obstet & Gynecol, Boston, MA 02115 USA. RP Olawaiye, AB (reprint author), Univ Pittsburgh, Sch Med, Dept Obstet Gynecol & Reprod Sci, Div Gynecol Oncol, M240 Scaife Hall,3550 Terrace St, Pittsburgh, PA 15261 USA. EM olawaiyea@mail.magee.edu FU American Cancer Society [MRSG-10-079-01-CPPB] FX Funding for this study was partially provided by an American Cancer Society Mentored Research Award # MRSG-10-079-01-CPPB. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed. NR 35 TC 0 Z9 0 U1 0 U2 2 PU FUTURE MEDICINE LTD PI LONDON PA UNITEC HOUSE, 3RD FLOOR, 2 ALBERT PLACE, FINCHLEY CENTRAL, LONDON, N3 1QB, ENGLAND SN 1479-6694 EI 1744-8301 J9 FUTURE ONCOL JI Future Oncol. PY 2015 VL 11 IS 4 BP 607 EP 615 DI 10.2217/fon.14.247 PG 9 WC Oncology SC Oncology GA CC0UY UT WOS:000350054200009 PM 25686116 ER PT J AU Pascoe, VL Kimball, AB AF Pascoe, Vanessa L. Kimball, Alexandra B. TI Expanding Scope of Dermatologic Mid-Level Practitioners Includes Prescription of Complex Medication SO JAMA DERMATOLOGY LA English DT Letter C1 [Pascoe, Vanessa L.; Kimball, Alexandra B.] Massachusetts Gen Hosp, Dept Dermatol, Boston, MA 02114 USA. [Kimball, Alexandra B.] Harvard Univ, Sch Med, Boston, MA USA. RP Kimball, AB (reprint author), Massachusetts Gen Hosp, Dept Dermatol, Clin Unit Res Trials & Outcomes Skin, 50 Staniford St,Ste 240, Boston, MA 02114 USA. EM harvardskinstudies@partners.org NR 5 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 2015 VL 151 IS 1 BP 106 EP 107 DI 10.1001/jamadermatol.2014.3295 PG 3 WC Dermatology SC Dermatology GA CB6RI UT WOS:000349753900028 PM 25321608 ER PT J AU Karlin, BE Trockel, M Brown, GK Gordienko, M Yesavage, J Taylor, CB AF Karlin, Bradley E. Trockel, Mickey Brown, Gregory K. Gordienko, Maria Yesavage, Jerome Taylor, C. Barr TI Comparison of the Effectiveness of Cognitive Behavioral Therapy for Depression among Older Versus Younger Veterans: Results of a National Evaluation SO JOURNALS OF GERONTOLOGY SERIES B-PSYCHOLOGICAL SCIENCES AND SOCIAL SCIENCES LA English DT Article DE Cognitive behavioral therapy; Department of Veterans Affairs; Depression; Geriatrics; Older adultsVeterans ID LATE-LIFE DEPRESSION; WORKING ALLIANCE INVENTORY; COLLABORATIVE RESEARCH-PROGRAM; GERIATRIC MENTAL-HEALTH; QUALITY-OF-LIFE; PSYCHOMETRIC PROPERTIES; ELDERLY-PATIENTS; ADULTS; PSYCHOTHERAPY; CARE AB Objectives. The effectiveness of cognitive behavioral therapy for depression (CBT-D) among older adults in routine clinical settings has received limited attention. The current article examines and compares outcomes of older versus younger veterans receiving CBT-D nationally. Method. Patient outcomes were assessed using the Beck Depression Inventory-II and World Health Organization Quality of Life-BREF. Therapeutic alliance was assessed using the Working Alliance Inventory-Short Revised. Results. A total of 764 veterans aged 18-64 and 100 veterans aged 65+ received CBT-D; 68.0% of older and 68.3% of younger patients completed all sessions or finished early due to symptom relief, and mean depression scores declined from 27.0 (standard deviation [SD] = 10.7) to 16.2 (SD = 12.4) in the older group and from 29.1 (SD = 11.2) to 17.8 (SD = 13.5) in the younger group. Within-group effect sizes were d = 1.01 for both groups. Significant increases in quality of life and therapeutic alliance were observed for both groups. Discussion. CBT-D resulted in significant improvements in depression and quality of life among older patients. Outcomes and rate of attrition were equivalent to younger patients. Findings indicate that CBT-D is an effective and acceptable treatment for older veterans in real-world settings with often high levels of depression. C1 [Karlin, Bradley E.] US Dept Vet Affairs, Mental Hlth Serv, Cent Off, Washington, DC USA. [Karlin, Bradley E.] Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Dept Mental Hlth, Baltimore, MD USA. [Trockel, Mickey; Gordienko, Maria; Yesavage, Jerome; Taylor, C. Barr] Stanford Univ, Med Ctr, Dept Psychiat, Palo Alto, CA 94304 USA. [Trockel, Mickey; Gordienko, Maria; Yesavage, Jerome; Taylor, C. Barr] Vet Affairs Palo Alto Hlth Care Syst, VISN Mental Illness Res Educ & Clin Ctr 21, Palo Alto, CA 94304 USA. [Brown, Gregory K.] Philadelphia VA Med Ctr, VISN Mental Illness Res Educ & Clin Ctr 4, Philadelphia, PA USA. [Brown, Gregory K.] Univ Penn, Dept Psychiat, Perelman Sch Med, Philadelphia, PA 19104 USA. RP Karlin, BE (reprint author), VA Cent Off, Mental Hlth Serv 10P4M, 810 Vermont Ave NW, Washington, DC 20420 USA. EM Bradley.Karlin2@va.gov FU Mental Health Services, U. S. Department of Veterans Affairs (VA) Central Office FX This project was supported by Mental Health Services, U. S. Department of Veterans Affairs (VA) Central Office. NR 71 TC 2 Z9 2 U1 2 U2 18 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1079-5014 EI 1758-5368 J9 J GERONTOL B-PSYCHOL JI J. Gerontol. Ser. B-Psychol. Sci. Soc. Sci. PD JAN PY 2015 VL 70 IS 1 BP 3 EP 12 DI 10.1093/geronb/gbt096 PG 10 WC Geriatrics & Gerontology; Gerontology; Psychology; Psychology, Multidisciplinary SC Geriatrics & Gerontology; Psychology GA CC0QA UT WOS:000350039400002 PM 24218096 ER PT J AU Phipps, C Gopal, AK Storer, BE Cassaday, RD Press, OW Till, BG Pagel, JM Palanca-Wessels, MC Philip, M Bensinger, WI Holmberg, LA Shustov, AR Green, DJ Chauncey, T Maloney, DG Libby, EN AF Phipps, Colin Gopal, Ajay K. Storer, Barry E. Cassaday, Ryan D. Press, Oliver W. Till, Brian G. Pagel, John M. Palanca-Wessels, Maria C. Philip, Mary Bensinger, William I. Holmberg, Leona A. Shustov, Andrei R. Green, Damian J. Chauncey, Thomas Maloney, David G. Libby, Edward N., III TI Autologous transplant for relapsed follicular lymphoma: impact of pre-transplant rituximab sensitivity SO LEUKEMIA & LYMPHOMA LA English DT Article DE Follicular lymphoma; autologous transplant; rituximab-refractory ID STEM-CELL TRANSPLANTATION; INTERNATIONAL PROGNOSTIC INDEX; NON-HODGKIN-LYMPHOMA; EVENT-FREE SURVIVAL; MARROW-TRANSPLANTATION; THERAPY; EXPRESSION; RESISTANCE; BENDAMUSTINE; CHEMOTHERAPY AB Patients with rituximab-refractory follicular lymphoma (FL) have limited options. Before the rituximab era, autologous stem cell transplant (ASCT) was shown to improve outcomes in chemotherapy-sensitive, relapsed FL, but the impact of rituximab-sensitivity on these results is unknown. We analyzed 194 consecutive relapsed patients with FL who underwent ASCT at out center and categorized them as rituximab-sensitive (RS, n = 35), rituximab-refractory (RR, n = 65) or no rituximab (NoR, n = 94) if transplanted before rituximab was used. Progression-free survival at 3 years was 85% in RS and 35% in RR patients (p = 0.0004). Only rituximab-sensitivity was significant on multivariate analysis with improved overall survival (OS) (hazard ratio [HR] 0.24, p = 0.01) and progression-free survival (PFS) (HR 0.35, p = 0.006) in RS patients and increased relapse in RR patients (HR 2.11, p = 0.01). Pre-transplant rituximab-sensitivity is a strong independent predictor of post-transplant outcomes in relapsed FL, although one-third of RR patients achieved a PFS of over 3 years with ASCT. C1 [Phipps, Colin; Gopal, Ajay K.; Storer, Barry E.; Cassaday, Ryan D.; Press, Oliver W.; Till, Brian G.; Pagel, John M.; Palanca-Wessels, Maria C.; Philip, Mary; Bensinger, William I.; Holmberg, Leona A.; Shustov, Andrei R.; Green, Damian J.; Chauncey, Thomas; Maloney, David G.; Libby, Edward N., III] Fred Hutchinson Canc Res Ctr, Div Basic Sci, Seattle, WA 98104 USA. [Phipps, Colin] Singapore Gen Hosp, Dept Haematol, Singapore, Singapore. [Gopal, Ajay K.; Press, Oliver W.; Till, Brian G.; Pagel, John M.; Palanca-Wessels, Maria C.; Philip, Mary; Bensinger, William I.; Holmberg, Leona A.; Shustov, Andrei R.; Green, Damian J.; Chauncey, Thomas; Maloney, David G.; Libby, Edward N., III] Univ Washington, Sch Med, Seattle, WA USA. [Storer, Barry E.] Univ Washington, Sch Publ Hlth & Biostat, Seattle, WA USA. [Chauncey, Thomas] Vet Affairs Puget Sound Hlth Care Syst, Seattle, WA USA. RP Phipps, C (reprint author), Seattle Canc Care Alliance, 825 Eastlake Ave East, Seattle, WA 98109 USA. EM phipps_8@msn.com FU NIH [PO1CA44991]; Mary A. Wright Memorial Research Fund FX This study received funding from NIH PO1CA44991, the Mary A. Wright Memorial Research Fund and a donation from Frank and Betty Vandermeer. A.K.G. is a Scholar in Clinical Research of the Leukemia and Lymphoma Society. The authors also thank members of the research and clinical staff at the Seattle Cancer Care Alliance, and referring physicians for their contribution to the care of our patients. NR 23 TC 0 Z9 0 U1 0 U2 0 PU INFORMA HEALTHCARE PI LONDON PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND SN 1042-8194 EI 1029-2403 J9 LEUKEMIA LYMPHOMA JI Leuk. Lymphoma PD JAN PY 2015 VL 56 IS 1 BP 92 EP 96 DI 10.3109/10428194.2014.911866 PG 5 WC Oncology; Hematology SC Oncology; Hematology GA CB5IR UT WOS:000349661200016 PM 24707941 ER PT J AU Hui, T Sorensen, ES Rittling, SR AF Hui, Tommy Sorensen, Esben S. Rittling, Susan R. TI Osteopontin binding to the alpha 4 integrin requires highest affinity integrin conformation, but is independent of post-translational modifications of osteopontin SO MATRIX BIOLOGY LA English DT Article DE Osteopontin; Adhesion; Integrin Alpha4; VLA-4; Phosphorylation; VCAM ID REAL-TIME ANALYSIS; CELL-ADHESION; ALPHA(4)BETA(1) INTEGRIN; ALPHA-4-BETA-1; LIGAND; INFLAMMATION; ACTIVATION; RECEPTOR; SITES AB Osteopontin (OPN) is a ligand for the alpha 4 beta 1 integrin, but the physiological importance of this binding is not well understood. Here, we have assessed the effect of post-translational modifications on OPN binding to the alpha 4 integrin on cultured human leukocyte cell lines and compared OPN interaction with alpha 4 integrin to that of VCAM and fibronectin. Jurkat cells, whose alpha 4 integrins are inherently activated, adhered to different preparations of OPN in the presence of Mn2+: the EC50 of adhesion was not affected by phosphorylation or glycosylation status. Thrombin cleavage of OPN at the C-terminus of the alpha 4 integrin-binding site also did not affect binding affinity. THP-1 cells express a low-affinity conformation of the integrin and adhered to OPN only in the presence of Mn2+ plus PMA or an activating antibody. This was in contrast to VCAM and fibronectin: THP-1 cells adhered to these ligands without integrin activation. Studies with ligand-induced binding site antibodies demonstrated that the SVVYGLR peptide of OPN bound to the alpha 4 integrin with a similar affinity as the LDV peptide of fibronectin, suggesting that a high off-rate is responsible for the reduced binding of OPN to the low-affinity forms of this integrin. Together, the results suggest OPN has very low affinity for the alpha 4 integrin on human leukocytes under physiological conditions. (C) 2014 The Authors. Published by Elsevier B.V. C1 [Hui, Tommy; Rittling, Susan R.] Forsyth Inst, Dept Immunol & Infect Dis, Cambridge, MA 02115 USA. [Sorensen, Esben S.] Aarhus Univ, Dept Mol Biol & Genet, Aarhus, Denmark. [Rittling, Susan R.] Harvard Univ, Sch Dent Med, Dept Dev Biol, Boston, MA 02115 USA. RP Rittling, SR (reprint author), Forsyth Inst, Dept Immunol & Infect Dis, Cambridge, MA 02115 USA. EM srittling@forsyth.org FU NIDCR of the NIH [RO1DE022380] FX The authors thank Dr. Toshimitsu Uede for the kind gift of the RAA OPN construct, Dr. Aritsune Matsui for help with the FACS analysis, Dr. Toshi Kawai for the gift of Jurkat cells, and Dr. Markus Hardt for mass spectrometry. Research reported in this publication was supported by the NIDCR of the NIH under award no. RO1DE022380. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. NR 30 TC 3 Z9 3 U1 0 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0945-053X EI 1569-1802 J9 MATRIX BIOL JI Matrix Biol. PD JAN PY 2015 VL 41 BP 19 EP 25 DI 10.1016/j.matbio.2014.11.005 PG 7 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA CB8LZ UT WOS:000349882400004 PM 25446551 ER PT B AU Walker, RH AF Walker, Ruth H. BE LeDoux, MS TI Genetics of Huntington Disease (HD), HD-Like Disorders, and Other Choreiform Disorders SO MOVEMENT DISORDERS: GENETICS AND MODELS, 2ND EDITION LA English DT Article; Book Chapter ID BENIGN HEREDITARY CHOREA; AGE-OF-ONSET; CAG REPEAT LENGTH; PAROXYSMAL KINESIGENIC DYSKINESIA; MCLEOD-SYNDROME; TRINUCLEOTIDE REPEAT; INFANTILE CONVULSIONS; CLINICAL PROGRESSION; HEMIPLEGIC MIGRAINE; JAPANESE FAMILY C1 [Walker, Ruth H.] James J Peters Vet Affairs Med Ctr, Bronx, NY 10468 USA. [Walker, Ruth H.] Mt Sinai Sch Med, New York, NY USA. RP Walker, RH (reprint author), James J Peters Vet Affairs Med Ctr, Bronx, NY 10468 USA. NR 132 TC 0 Z9 0 U1 0 U2 1 PU ACADEMIC PRESS LTD-ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL ROAD, LONDON NW1 7DX, ENGLAND BN 978-0-12-405516-2; 978-0-12-405195-9 PY 2015 BP 519 EP 532 DI 10.1016/B978-0-12-405195-9.00030-5 PG 14 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA BB9KO UT WOS:000348389700032 ER PT B AU Handforth, A AF Handforth, Adrian BE LeDoux, MS TI Use of the Harmaline and alpha 1 Knockout Models to Identify Molecular Targets for Essential Tremor SO MOVEMENT DISORDERS: GENETICS AND MODELS, 2ND EDITION LA English DT Article; Book Chapter ID INFERIOR OLIVARY NEURONS; DRUG-INDUCED TREMOR; OPEN-LABEL TRIAL; CEREBELLAR CLIMBING FIBERS; GABA(A) RECEPTOR SUBTYPES; CALCIUM-CHANNEL BLOCKERS; PLACEBO-CONTROLLED TRIAL; COMPLEX SPIKE ACTIVITY; RAT SENSORY NEURONS; OLIVOCEREBELLAR SYSTEM C1 Vet Affairs Greater Los Angeles Healthcare Syst, Neurol Serv, Los Angeles, CA 90073 USA. RP Handforth, A (reprint author), Vet Affairs Greater Los Angeles Healthcare Syst, Neurol Serv, Los Angeles, CA 90073 USA. NR 150 TC 1 Z9 1 U1 0 U2 1 PU ACADEMIC PRESS LTD-ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL ROAD, LONDON NW1 7DX, ENGLAND BN 978-0-12-405516-2; 978-0-12-405195-9 PY 2015 BP 615 EP 629 DI 10.1016/B978-0-12-405195-9.00037-8 PG 15 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA BB9KO UT WOS:000348389700039 ER PT B AU Daneshvar, DH McKee, AC AF Daneshvar, Daniel H. McKee, Ann C. BE Zigmond, MJ Rowland, LP Coyle, JT TI Traumatic Brain Injury SO NEUROBIOLOGY OF BRAIN DISORDERS: BIOLOGICAL BASIS OF NEUROLOGICAL AND PSYCHIATRIC DISORDERS LA English DT Article; Book Chapter ID HEAD-INJURY; ALZHEIMERS-DISEASE; TAU; ENCEPHALOPATHY; DEMENTIA; BETA; CONCUSSION; PATHOLOGY; FOOTBALL; PET C1 [Daneshvar, Daniel H.; McKee, Ann C.] Boston Univ, Sch Med, Ctr Study Traumat Encephalopathy, Boston, MA 02118 USA. [Daneshvar, Daniel H.; McKee, Ann C.] Boston Univ, Sch Med, Alzheimers Dis Ctr, Boston, MA 02118 USA. [Daneshvar, Daniel H.; McKee, Ann C.] Boston Univ, Sch Med, Dept Neurol, Boston, MA 02118 USA. [McKee, Ann C.] Boston Univ, Sch Med, Dept Pathol, Boston, MA 02118 USA. [McKee, Ann C.] VA Boston HealthCare Syst, Boston, MA USA. RP Daneshvar, DH (reprint author), Boston Univ, Sch Med, Ctr Study Traumat Encephalopathy, Boston, MA 02118 USA. NR 54 TC 0 Z9 0 U1 1 U2 6 PU ACADEMIC PRESS LTD-ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL ROAD, LONDON NW1 7DX, ENGLAND BN 978-0-12-398280-3; 978-0-12-398270-4 PY 2015 BP 219 EP 235 DI 10.1016/B978-0-12-398270-4.00016-1 PG 17 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA BB9KQ UT WOS:000348393900017 ER PT J AU Jain, D Sheth, H Green, JA Bender, FH Weisbord, SD AF Jain, Deepika Sheth, Heena Green, Jamie A. Bender, Filitsa H. Weisbord, Steven D. TI Health Literacy in Patients on Maintenance Peritoneal Dialysis: Prevalence and Outcomes SO PERITONEAL DIALYSIS INTERNATIONAL LA English DT Article ID ASSOCIATIONS; HEMODIALYSIS; ADHERENCE; DISEASE C1 [Jain, Deepika; Sheth, Heena; Bender, Filitsa H.; Weisbord, Steven D.] Univ Pittsburgh, Sch Med, Renal Electrolyte Div, Pittsburgh, PA 15260 USA. [Green, Jamie A.] Geisinger Med Ctr, Dept Nephrol, Danville, PA 17822 USA. [Weisbord, Steven D.] VA Pittsburgh Healthcare Syst, Renal Sect, Pittsburgh, PA USA. [Weisbord, Steven D.] VA Pittsburgh Healthcare Syst, Ctr Hlth Equ Res & Promot, Pittsburgh, PA USA. RP Jain, D (reprint author), Univ Pittsburgh, Sch Med, Renal Electrolyte Div, Pittsburgh, PA 15260 USA. EM 26.deepika@gmail.com NR 14 TC 3 Z9 3 U1 0 U2 6 PU MULTIMED INC PI TORONTO PA 66 MARTIN ST, TORONTO, ON L9T 2R2, CANADA SN 0896-8608 J9 PERITON DIALYSIS INT JI Perit. Dial. Int. PD JAN-FEB PY 2015 VL 35 IS 1 DI 10.3747/pdi.2013.00211 PG 3 WC Urology & Nephrology SC Urology & Nephrology GA CB9XM UT WOS:000349987600017 PM 25700462 ER PT J AU Shadel, WG Elliott, MN Haas, AC Haviland, AM Orr, N Farmer, MM Ma, S Weech-Maldonado, R Farley, DO Cleary, PD AF Shadel, William G. Elliott, Marc N. Haas, Ann C. Haviland, Amelia M. Orr, Nate Farmer, Melissa M. Ma, Sai Weech-Maldonado, Robert Farley, Donna O. Cleary, Paul D. TI Clinician advice to quit smoking among seniors SO PREVENTIVE MEDICINE LA English DT Article DE Physician/patient communication; Medicare; Patient education; Smoking cessation ID ALZHEIMER-DISEASE; TOBACCO MEASURES; HEALTH-CARE; CESSATION; SMOKERS; OLDER; RISK; INTERVENTIONS; US; DISPARITIES AB Objective. Little smoking research in the past 20 years includes persons 50 and older; herein we describe patterns of clinician cessation advice to US seniors, including variation by Medicare beneficiary characteristics. Method. In 2012-4, we analyzed 2010 Consumer Assessment of Healthcare Providers and Systems (CAHPS) survey data from Medicare beneficiaries over age 64 (n=346,674). We estimated smoking rates and the proportion of smokers whose clinicians encouraged cessation. Results. 12% of male and 8% of female respondents aged 65 and older smoke. The rate decreases with age (14% of 65-69,3% of 85+) and education (12-15% with no high school degree, 5-6% with BA +). Rates are highest among American Indian/Alaskan Native (16%), multiracial (14%), and African-American (13%) seniors, and in the Southeast (14%). Only 51% of smokers say they receive cessation advice "always" or "usually" at doctor visits, with advice more often given to the young, those in low-smoking regions, Asians, and women. For all results cited p < 0.05. Conclusions. Smoking cessation advice to seniors is variable. Providers may focus on groups or areas in which smoking is less common or when they are most comfortable giving advice. More consistent interventions are needed, including cessation advice from clinicians. (C) 2014 Elsevier Inc. All rights reserved. C1 [Shadel, William G.; Haas, Ann C.; Haviland, Amelia M.; Farley, Donna O.] RAND Corp, Pittsburgh, PA 15213 USA. [Elliott, Marc N.; Orr, Nate] RAND Corp, Santa Monica, CA 90407 USA. [Haviland, Amelia M.] Carnegie Mellon Univ, H John Heinz Coll 3, Pittsburgh, PA 15213 USA. [Orr, Nate] Ctr Medicare & Medicaid Serv, Baltimore, MD 21244 USA. [Weech-Maldonado, Robert] Univ Alabama Birmingham, Dept Hlth Serv Adm, Birmingham, AL 35294 USA. [Farmer, Melissa M.] VA Greater Los Angeles Healthcare Syst, Vet Adm HSR&D Ctr Study Healthcare Innovat Implem, Sepulveda, CA 91343 USA. [Cleary, Paul D.] Yale Univ, Sch Publ Hlth, New Haven, CT 06520 USA. RP Elliott, MN (reprint author), RAND Corp, 1776 Main St, Santa Monica, CA 90401 USA. EM shadel@rand.org; elliott@rand.org; ahaas@rand.org; haviland@cmu.edu; orr@rand.org; Melissa.Farmer@va.gov; sai.ma@cms.hhs.gov; rweech@uab.edu; farley@rand.org; paul.cleary@yale.edu FU CMS [HHSM-500-2005-00028I] FX This study was funded by CMS contract HHSM-500-2005-00028I to RAND. NR 48 TC 5 Z9 5 U1 1 U2 5 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0091-7435 EI 1096-0260 J9 PREV MED JI Prev. Med. PD JAN PY 2015 VL 70 BP 83 EP 89 DI 10.1016/j.ypmed.2014.11.020 PG 7 WC Public, Environmental & Occupational Health; Medicine, General & Internal SC Public, Environmental & Occupational Health; General & Internal Medicine GA CB9GB UT WOS:000349938900016 PM 25482423 ER PT J AU Lauriol, J Jaffre, F Kontaridis, MI AF Lauriol, Jessica Jaffre, Fabrice Kontaridis, Maria I. TI The role of the protein tyrosine phosphatase SHP2 in cardiac development and disease SO SEMINARS IN CELL & DEVELOPMENTAL BIOLOGY LA English DT Review DE PTPN11; SHP2; Phosphatase; Cardiac development; Congenital heart disease; Myocardium ID CONGENITAL HEART-DISEASES; LEFT-RIGHT ASYMMETRY; NOONAN-SYNDROME; LEOPARD-SYNDROME; VALVE DEVELOPMENT; SIGNALING PATHWAY; EMBRYONIC HEART; CELL-MIGRATION; NUCLEAR-FACTOR; NEURAL CREST AB Congenital heart disease is the most common human developmental disorder, affecting similar to 1:100 newborns, and is the primary cause of birth-defect related deaths worldwide. As a major regulator of receptor tyrosine kinase (RTK), cytokine and G-protein coupled receptor signaling, the non-receptor protein tyrosine phosphatase SHP2 plays a critical role in normal cardiac development and function. Indeed, SHP2 participates in a wide variety of cellular functions, including proliferation, survival, differentiation, migration, and cell-cell communication. Moreover, human activating and inactivating mutations of SHP2 are responsible for two related developmental disorders called Noonan and LEOPARD Syndromes, respectively, which are both characterized, in part, by congenital heart defects. Structural, enzymologic, biochemical, and SHP2 mouse model studies have together greatly enriched our knowledge of SHP2 and, as such, have also uncovered the diverse roles for SHP2 in cardiac development, including its contribution to progenitor cell specification, cardiac morphogenesis, and maturation of cardiac valves and myocardial chambers. By delineating the precise mechanisms by which SHP2 is involved in regulating these processes, we can begin to better understand the pathogenesis of cardiac disease and find more strategic and effective therapies for treatment of patients with congenital heart disorders. (C) 2014 Elsevier Ltd. All rights reserved. C1 [Lauriol, Jessica; Jaffre, Fabrice; Kontaridis, Maria I.] Beth Israel Deaconess Med Ctr, Dept Med, Boston, MA 02215 USA. [Kontaridis, Maria I.] Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA. RP Kontaridis, MI (reprint author), BIDMC, Div Cardiol, Dept Med, Ctr Life Sci, Room 908,3 Blackfan Circle, Boston, MA 02115 USA. EM mkontari@bidmc.harvard.edu OI Kontaridis, Maria/0000-0002-6121-0533 FU National Institutes of Health [R01-HL102368, R01-HL114775]; Children's Cardiomyopathy Foundation Grant; Harvard Stem Cell Institute Seed Grant; American Heart Association Postdoctoral Fellowship; Beth Israel Deaconess Medical Center Division of Cardiology FX This work was supported by National Institutes of Health Grants R01-HL102368 and R01-HL114775 to M.I.K., Children's Cardiomyopathy Foundation Grant to M.I.K., the Harvard Stem Cell Institute Seed Grant to M.I.K., and by an American Heart Association Postdoctoral Fellowship to J.L. This work was also supported in part by the Beth Israel Deaconess Medical Center Division of Cardiology. NR 85 TC 3 Z9 3 U1 0 U2 2 PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 1084-9521 J9 SEMIN CELL DEV BIOL JI Semin. Cell Dev. Biol. PD JAN PY 2015 VL 37 BP 73 EP 81 DI 10.1016/j.semcdb.2014.09.013 PG 9 WC Cell Biology; Developmental Biology SC Cell Biology; Developmental Biology GA CC2ES UT WOS:000350158600011 PM 25256404 ER PT J AU Kveraga, K Boshyan, J Adams, RB Mote, J Betz, N Ward, N Hadjikhani, N Bar, M Barrett, LF AF Kveraga, Kestutis Boshyan, Jasmine Adams, Reginald B., Jr. Mote, Jasmine Betz, Nicole Ward, Noreen Hadjikhani, Nouchine Bar, Moshe Barrett, Lisa F. TI If it bleeds, it leads: separating threat from mere negativity SO SOCIAL COGNITIVE AND AFFECTIVE NEUROSCIENCE LA English DT Article DE affect; emotion; scenes; fMRI; valence; arousal ID MIDBRAIN PERIAQUEDUCTAL GRAY; AMINO-ACID MICROINJECTION; PARAHIPPOCAMPAL CORTEX; CONTEXTUAL ASSOCIATIONS; PREFRONTAL CORTEX; MACAQUE MONKEYS; HUMAN AMYGDALA; RHESUS-MONKEY; EMOTION; BRAIN AB Most theories of emotion hold that negative stimuli are threatening and aversive. Yet in everyday experiences some negative sights (e.g. car wrecks) attract curiosity, whereas others repel (e.g. a weapon pointed in our face). To examine the diversity in negative stimuli, we employed four classes of visual images (Direct Threat, Indirect Threat, Merely Negative and Neutral) in a set of behavioral and functional magnetic resonance imaging studies. Participants reliably discriminated between the images, evaluating Direct Threat stimuli most quickly, and Merely Negative images most slowly. Threat images evoked greater and earlier blood oxygen level-dependent (BOLD) activations in the amygdala and periaqueductal gray, structures implicated in representing and responding to the motivational salience of stimuli. Conversely, the Merely Negative images evoked larger BOLD signal in the para-hippocampal, retrosplenial, and medial prefrontal cortices, regions which have been implicated in contextual association processing. Ventrolateral as well as medial and lateral orbitofrontal cortices were activated by both threatening and Merely Negative images. In conclusion, negative visual stimuli can repel or attract scrutiny depending on their current threat potential, which is assessed by dynamic shifts in large-scale brain network activity. C1 [Kveraga, Kestutis; Boshyan, Jasmine; Ward, Noreen; Hadjikhani, Nouchine; Bar, Moshe; Barrett, Lisa F.] Massachusetts Gen Hosp, Dept Radiol, Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA 02129 USA. [Kveraga, Kestutis; Hadjikhani, Nouchine; Bar, Moshe] Harvard Univ, Sch Med, Dept Radiol, Boston, MA 02215 USA. [Boshyan, Jasmine] Brandeis Univ, Dept Psychol, Waltham, MA 02453 USA. [Adams, Reginald B., Jr.] Penn State Univ, Dept Psychol, University Pk, PA 16802 USA. [Mote, Jasmine] Univ Calif Berkeley, Dept Psychol, Berkeley, CA 94720 USA. [Betz, Nicole; Barrett, Lisa F.] Northeastern Univ, Dept Psychol, Boston, MA 02115 USA. [Bar, Moshe; Barrett, Lisa F.] Massachusetts Gen Hosp, Dept Psychiat, Charlestown, MA 02129 USA. [Bar, Moshe] Bar Ilan Univ, Gonda Multidisciplinary Brain Res Ctr, IL-5290002 Ramat Gan, Israel. RP Kveraga, K (reprint author), Massachusetts Gen Hosp, Martinos Ctr Biomed Imaging, Dept Radiol, Room 2301, Charlestown, MA 02129 USA. EM kestas@nmr.mgh.harvard.edu OI Hadjikhani, Nouchine/0000-0003-4075-3106 FU NIMH NIH HHS [K01 MH084011] NR 66 TC 3 Z9 3 U1 1 U2 7 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1749-5016 EI 1749-5024 J9 SOC COGN AFFECT NEUR JI Soc. Cogn. Affect. Neurosci. PD JAN PY 2015 VL 10 IS 1 BP 28 EP 35 DI 10.1093/scan/nsu007 PG 8 WC Neurosciences; Psychology; Psychology, Experimental SC Neurosciences & Neurology; Psychology GA CC1NT UT WOS:000350108600005 PM 24493851 ER PT J AU Jash, S Adhya, S AF Jash, Sukanta Adhya, Samit TI Effects of Transient Hypoxia versus Prolonged Hypoxia on Satellite Cell Proliferation and Differentiation In Vivo SO STEM CELLS INTERNATIONAL LA English DT Article ID MUSCLE REGENERATION; ADULT MYOGENESIS; OXYGEN; NOTCH; MICE; ANGIOGENESIS; TISSUE AB The microenvironment of the injury site can have profound effects on wound healing. Muscle injury results in ischemia leading to short-term local hypoxia, but there are conflicting reports on the role of hypoxia on the myogenic program in vivo and in vitro. In our rat model of mitochondrial restoration (MR), temporary upregulation of mitochondrial activity by a cocktail of organelle-encoded RNAs results in satellite cell proliferation and initiation of myogenesis. We now report that MR leads to a transient hypoxic response in situ. Inhibition of hypoxia by lowering mitochondrial O-2 consumption, either by respiratory electron transport inhibitors, or by NO-mediated inhibition of O-2 binding to cytochrome c oxidase, resulted in exacerbation of inflammation. Lentivirus-mediated knockdown of hypoxia-inducible factor 1 alpha(HIF1 alpha) or of Notch signaling components had a similar effect, and pharmacologic inhibition of HIF orNotch reduced the number of proliferating Pax(7+) cells. In contrast, a prolonged hypoxic response induced either by uncoupling of respiration from oxidative phosphorylation or through HIF stabilization by dimethyloxalylglycine (DMOG) had an immediate anti-inflammatory effect. Although significant satellite cell proliferation occurred in presence of DMOG, expression of differentiation markers was affected. These results emphasize the importance of transient hypoxia as opposed to prolonged hypoxia for myogenesis. C1 [Jash, Sukanta; Adhya, Samit] CSIR, Indian Inst Chem Biol, Mol & Human Genet Div, Kolkata 700032, India. [Jash, Sukanta] Massachusetts Gen Hosp, Ctr Regenerat Med, Boston, MA 02114 USA. RP Adhya, S (reprint author), CSIR, Indian Inst Chem Biol, Mol & Human Genet Div, 4 Raja SC Mullick Rd, Kolkata 700032, India. EM nilugrandson@gmail.com FU CSIR; Council of Scientific and Industrial Research FX This work is supported by the CSIR Suprainstitutional Project BeND. Sukanta Jash received a Senior Research Fellowship from the Council of Scientific and Industrial Research. NR 24 TC 1 Z9 1 U1 0 U2 6 PU HINDAWI PUBLISHING CORPORATION PI NEW YORK PA 410 PARK AVENUE, 15TH FLOOR, #287 PMB, NEW YORK, NY 10022 USA SN 1687-966X EI 1687-9678 J9 STEM CELLS INT JI Stem Cells Int. PY 2015 AR 961307 DI 10.1155/2015/961307 PG 9 WC Cell & Tissue Engineering SC Cell Biology GA CC9CV UT WOS:000350666200001 ER PT J AU Shamran, HA Kadhim, HS Hussain, AR Kareem, A Taub, DD Price, RL Nagarkatti, M Nagarkatti, PS Singh, UP AF Shamran, Haidar A. Kadhim, Haider S. Hussain, Aws R. Kareem, Abdulameer Taub, Dennis D. Price, Robert L. Nagarkatti, Mitzi Nagarkatti, Prakash S. Singh, Udai P. TI Detection of Human Cytomegalovirus in Different Histopathological Types of Glioma in Iraqi Patients SO BIOMED RESEARCH INTERNATIONAL LA English DT Article ID GROWTH-FACTOR RECEPTOR; HUMAN BRAIN-TUMORS; CELL-TO-CELL; GLYCOPROTEIN-B; GLIOBLASTOMA; EXPRESSION; INFECTION; FUSION; ASSOCIATION; THERAPY AB Human Cytomegalovirus (HCMV) is an endemic herpes virus that reemerges in cancer patients enhancing oncogenic potential. HCMV infection is associated with certain types of cancer morbidity such as glioblastomas. HCMV, like all other herpes viruses, has the ability to remain latent within the body of the host and can contribute in chronic inflammation. To determine the role of HCMV in glioma pathogenesis, paraffin-embedded blocks from glioma patients (n = 50) and from benign meningioma patients (n = 30) were obtained and evaluated by immunohistochemistry and polymerase chain reaction for the evidence of HCMV antigen expression and the presence of viral DNA. We detected HCMV antigen and DNA for IEI-72, pp65, and late antigen in 33/36, 28/36, and 26/36 in glioblastoma multiforme patients whereas 12/14, 10/14, and 9/14 in anaplastic astrocytoma patients, respectively. Furthermore, 84% of glioma patients were positive for immunoglobulin G (IgG) compared to 72.5% among control samples (P = 0.04). These data indicate the presence of the HCMV virus in a high percentage of glioma samples demonstrating distinct histopathological grades and support previous reports showing the presence of HCMV infection in glioma tissue. These studies demonstrate that detection of low-levels of latent viral infections may play an active role in glioma development and pathogenesis. C1 [Shamran, Haidar A.] Univ Al Nahrain, Sch Med, Med Res Unit, Baghdad 10066, Iraq. [Kadhim, Haider S.] Univ Al Nahrain, Sch Med, Dept Microbiol, Baghdad 10066, Iraq. [Hussain, Aws R.] Univ Al Qadisiya, Sch Med, Dept Pathol, Dewaniya 58011, Iraq. [Kareem, Abdulameer] Univ Al Qadisiya, Sch Nursing, Dept Med Sci, Dewaniya 58011, Iraq. [Taub, Dennis D.] US Dept Vet Affairs, Ctr Translat Studies, VA Med Ctr, Med Serv, Washington, DC 20422 USA. [Price, Robert L.] Univ S Carolina, Sch Med, Dept Cell Biol & Anat, Columbia, SC 29208 USA. [Nagarkatti, Mitzi; Nagarkatti, Prakash S.; Singh, Udai P.] Univ S Carolina, Sch Med, Dept Pathol Microbiol & Immunol, Columbia, SC 29208 USA. RP Singh, UP (reprint author), Univ S Carolina, Sch Med, Dept Pathol Microbiol & Immunol, Columbia, SC 29208 USA. EM udai.singh@uscmed.sc.edu OI Kadhim, Haider/0000-0003-4561-5669; Nagarkatti, Mitzi/0000-0002-5977-5615 NR 37 TC 0 Z9 0 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 2314-6133 EI 2314-6141 J9 BIOMED RES INT JI Biomed Res. Int. PY 2015 AR 642652 DI 10.1155/2015/642652 PG 7 WC Biotechnology & Applied Microbiology; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Research & Experimental Medicine GA CB5WN UT WOS:000349698700001 ER PT J AU Fishman, JA AF Fishman, Jay A. TI Immune Reconstitution Syndrome: How Do We "Tolerate" Our Microbiome? SO CLINICAL INFECTIOUS DISEASES LA English DT Editorial Material DE immune reconstitution; regulatory T lymphocytes; immunopathogenesis; Cryptococcus neoformans; meningitis ID REGULATORY T-CELLS; NERVOUS-SYSTEM CRYPTOCOCCOSIS; ACTIVE ANTIRETROVIRAL THERAPY; ORGAN TRANSPLANT RECIPIENTS; INFLAMMATORY SYNDROME; DISEASE; NEOFORMANS; HIV; CALCINEURIN; INFECTION C1 [Fishman, Jay A.] Massachusetts Gen Hosp, Div Infect Dis, Transplant Infect Dis & Immunocompromised Host Pr, Boston, MA 02114 USA. [Fishman, Jay A.] Massachusetts Gen Hosp, Transplant Ctr, Boston, MA 02114 USA. [Fishman, Jay A.] Harvard Univ, Sch Med, Boston, MA USA. RP Fishman, JA (reprint author), Massachusetts Gen Hosp, Div Infect Dis, 55 Fruit St,WH510A, Boston, MA 02114 USA. EM jfishman@mgh.harvard.edu NR 40 TC 1 Z9 1 U1 0 U2 4 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1058-4838 EI 1537-6591 J9 CLIN INFECT DIS JI Clin. Infect. Dis. PD JAN 1 PY 2015 VL 60 IS 1 BP 45 EP 47 DI 10.1093/cid/ciu717 PG 3 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA CB5LJ UT WOS:000349668300009 PM 25210022 ER PT J AU Kadri, SS Hohmann, SF Orav, EJ Bonne, SL Moffa, MA Timpone, JG Strich, JR Palmore, T Christopher, KB Varughese, C Hooper, DC Danner, RL AF Kadri, Sameer S. Hohmann, Samuel F. Orav, E. John Bonne, Stephanie L. Moffa, Matthew A. Timpone, Joseph G. Strich, Jeffrey R. Palmore, Tara Christopher, Kenneth B. Varughese, Christy Hooper, David C. Danner, Robert L. TI Tracking Colistin-Treated Patients to Monitor the Incidence and Outcome of Carbapenem-Resistant Gram-Negative Infections SO CLINICAL INFECTIOUS DISEASES LA English DT Article DE colistin; carbapenem resistance; gram-negative infection; extensively drug resistant; surveillance ID BLOOD-STREAM INFECTIONS; CRITICALLY-ILL PATIENTS; PSEUDOMONAS-AERUGINOSA COLONIZATION; CYSTIC-FIBROSIS; ANTIMICROBIAL THERAPY; BACTERIAL-INFECTIONS; SEVERE SEPSIS; EPIDEMIOLOGY; MORTALITY; ENTEROBACTERIACEAE AB Background. Existing surveillance mechanisms may underestimate the incidence of carbapenem-resistant gram-negative infections (CRGNIs). Although carbapenem resistance increases the risk of death, the trend in mortality over time is unknown. Methods. A retrospective cohort study was conducted at 40 academic medical centers using a discharge database to identify adult hospital admissions without cystic fibrosis in 2006-2012 and received intravenous colistin for >3 consecutive days or died during therapy (termed colistin cases). The primary outcomes were the number of colistin cases per 100 000 admissions per year and change in the hospital mortality rate over time compared with the rate of discharges to home. Secondary outcomes included median overall and intensive care unit lengths of stay. Results. From 2006 to 2012, a total of 5011 unique patients were identified as colistin cases. The number per 100 000 admissions per year increased from 35.56 to 92.98 during the 7-year study (P < .001). The odds of in-hospital death among colistin cases (compared with discharge to home) decreased by a mean of 5.2%/y (P = .04), whereas discharge to an institution (P = .24) or hospice (P = .89) remained steady over time. The median overall and intensive care unit lengths of stay decreased by 7.5 and 6 days, respectively (P < .001). In a 4-hospital chart review, 81.6% of colistin cases were found to have culture-positive CRGNIs. Conversely, 53% of extensively drug-resistant bloodstream CRGNIs at 2 of these hospitals met colistin case criteria. Conclusions. Colistin cases represent a severely ill population with a high probability of having culture-confirmed CRGNIs. Colistin tracking is a novel strategy for monitoring the incidence and mortality of CRGNIs, particularly those caused by extensively drug-resistant bacteria. Although the incidence of colistin cases nearly tripled within 7 years, more of these patients are surviving hospitalization and going home. C1 [Kadri, Sameer S.; Danner, Robert L.] NIH, Dept Crit Care Med, Ctr Clin, Bethesda, MD 20892 USA. [Palmore, Tara] NIH, Hosp Epidemiol Serv, Ctr Clin, Bethesda, MD 20892 USA. [Kadri, Sameer S.; Hooper, David C.] Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA. [Varughese, Christy] Massachusetts Gen Hosp, Dept Pharm, Boston, MA 02114 USA. [Orav, E. John] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. [Christopher, Kenneth B.] Brigham & Womens Hosp, Div Renal, Boston, MA 02115 USA. [Hohmann, Samuel F.] Rush Univ, Univ HealthSyst Consortium, Chicago, IL 60612 USA. [Hohmann, Samuel F.] Rush Univ, Dept Hlth Syst Management, Chicago, IL 60612 USA. [Bonne, Stephanie L.] Barnes Jewish Hosp, Dept Gen Surg, St Louis, MO 63110 USA. [Moffa, Matthew A.; Timpone, Joseph G.] Georgetown Univ Hosp, Div Infect Dis & Travel Med, Washington, DC 20007 USA. [Strich, Jeffrey R.] Georgetown Univ Hosp, Dept Med, Washington, DC 20007 USA. RP Kadri, SS (reprint author), NIH, Dept Crit Care Med, Ctr Clin, 10 Ctr Dr,Room 2C145, Bethesda, MD 20892 USA. EM sameer.kadri@nih.gov FU intramural National Institutes of Health funds FX This work was supported by intramural National Institutes of Health funds. NR 38 TC 6 Z9 7 U1 2 U2 9 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1058-4838 EI 1537-6591 J9 CLIN INFECT DIS JI Clin. Infect. Dis. PD JAN 1 PY 2015 VL 60 IS 1 BP 79 EP 87 DI 10.1093/cid/ciu741 PG 9 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA CB5LJ UT WOS:000349668300014 PM 25246597 ER PT J AU Lyons, JL Erkkinen, MG Vodopivec, I AF Lyons, Jennifer L. Erkkinen, Michael G. Vodopivec, Ivana TI Cerebrospinal Fluid (1,3)-beta-D-Glucan in Isolated Candida Meningitis SO CLINICAL INFECTIOUS DISEASES LA English DT Letter ID FUNGAL MENINGITIS; (1-3)-BETA-D-GLUCAN; INFECTIONS; DIAGNOSIS C1 [Lyons, Jennifer L.; Erkkinen, Michael G.; Vodopivec, Ivana] Brigham & Womens Hosp, Dept Neurol, Boston, MA 02115 USA. [Lyons, Jennifer L.; Erkkinen, Michael G.; Vodopivec, Ivana] Harvard Univ, Sch Med, Boston, MA USA. [Erkkinen, Michael G.; Vodopivec, Ivana] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Lyons, JL (reprint author), Brigham & Womens Hosp, Div Neurol Infect, Dept Neurol, 45 Francis St, Boston, MA 02115 USA. EM jlyons5@partners.org NR 4 TC 2 Z9 2 U1 0 U2 0 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1058-4838 EI 1537-6591 J9 CLIN INFECT DIS JI Clin. Infect. Dis. PD JAN 1 PY 2015 VL 60 IS 1 BP 161 EP U3333 DI 10.1093/cid/ciu737 PG 2 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA CB5LJ UT WOS:000349668300028 PM 25228700 ER PT J AU Limbago, BM Pierce, VM Lonsway, DR Ferraro, MJ AF Limbago, Brandi M. Pierce, Virginia M. Lonsway, David R. Ferraro, Mary Jane TI Elevated Staphylococcus Ceftriaxone MICs are an Etest Artifact SO CLINICAL INFECTIOUS DISEASES LA English DT Letter C1 [Limbago, Brandi M.; Lonsway, David R.] Ctr Dis Control & Prevent, Div Healthcare Qual Promot, Atlanta, GA 30329 USA. [Pierce, Virginia M.; Ferraro, Mary Jane] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Pierce, Virginia M.; Ferraro, Mary Jane] Harvard Univ, Sch Med, Boston, MA USA. RP Limbago, BM (reprint author), Ctr Dis Control & Prevent, 1600 Clifton Rd,MS C-16, Atlanta, GA 30329 USA. EM BBL7@cdc.gov NR 5 TC 0 Z9 0 U1 1 U2 2 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1058-4838 EI 1537-6591 J9 CLIN INFECT DIS JI Clin. Infect. Dis. PD JAN 1 PY 2015 VL 60 IS 1 BP 162 EP U4444 DI 10.1093/cid/ciu743 PG 2 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA CB5LJ UT WOS:000349668300029 PM 25266286 ER PT J AU Deutsch, MB Mendez, MF Teng, E AF Deutsch, Mariel B. Mendez, Mario F. Teng, Edmond TI Interactions between Traumatic Brain Injury and Frontotemporal Degeneration SO DEMENTIA AND GERIATRIC COGNITIVE DISORDERS LA English DT Article DE Brain injuries; Frontotemporal degeneration; Frontotemporal dementia; Frontotemporal lobar degeneration; Primary progressive aphasia; Neuropsychological features in subjects with dementia ID ENVIRONMENTAL RISK-FACTORS; MILD COGNITIVE IMPAIRMENT; DATA SET UDS; HEAD-INJURY; FUNCTIONAL-ACTIVITIES; CLINICAL PHENOTYPE; LOBAR DEGENERATION; ALZHEIMERS-DISEASE; SEMANTIC DEMENTIA; ENCEPHALOPATHY AB Background/Aims: Prior work in smaller cohorts suggests that traumatic brain injury (TBI) may be a risk factor for frontotemporal degeneration (FTD). We sought to confirm and extend these results using the National Alzheimer's Coordinating Center Uniform Data Set. Methods: We compared the TBI prevalence between FTD subjects and matched normal controls. Indices of cognitive, behavioral, functional, and global dementia severity were compared between FTD subjects with and without prior TBI. Results: Remote TBI with extended loss of consciousness (TBI-ext) was more common in individuals with FTD than in controls (OR: 1.67; 95% CI: 1.004-2.778). With TBI-ext, less functional and global impairment was seen in the behavioral variant of FTD, but more behavioral pathology was seen in the semantic variant. Conclusion: TBI may increase the FTD risk and influence clinical symptomatology and severity in FTD sub-types. (C) 2014 S. Karger AG, Basel C1 [Deutsch, Mariel B.; Mendez, Mario F.; Teng, Edmond] Univ Calif Los Angeles, David Geffen Sch Med, Dept Neurol Sci, Los Angeles, CA 90095 USA. [Mendez, Mario F.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Psychiat & Biobehav Sci, Los Angeles, CA 90095 USA. [Deutsch, Mariel B.; Mendez, Mario F.; Teng, Edmond] Vet Affairs Greater Los Angeles Healthcare Syst, Los Angeles, CA 90073 USA. RP Deutsch, MB (reprint author), Vet Affairs Greater Los Angeles Healthcare Syst, Neurobehav Serv 116AF, 11301 Wilshire Blvd, Los Angeles, CA 90073 USA. EM mdeutsch@mednet.ucla.edu OI Deutsch, Mariel/0000-0003-1228-8868 FU NIA [P50 AG16570, K08 AG34628, R01AG034499-05, U01 AG016976]; NIA (American Federation for Aging Research); NIA (John A. Hartford Foundation); NIA (Atlantic Philanthropies); NIA (Starr Foundation); Alzheimer's Disease Research Centers of California; Sidell-Kagan Foundation FX This study was supported by the NIA (P50 AG16570 and K08 AG34628 to E.T.; jointly sponsored by the NIA, the American Federation for Aging Research, the John A. Hartford Foundation, the Atlantic Philanthropies, the Starr Foundation, and an anonymous donor) and R01AG034499-05 (M. F. M., principle investigator), the Alzheimer's Disease Research Centers of California, and the Sidell-Kagan Foundation. The NACC database is funded by the NIA (U01 AG016976). NR 47 TC 3 Z9 3 U1 1 U2 7 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 2015 VL 39 IS 3-4 BP 143 EP 153 DI 10.1159/000369787 PG 11 WC Geriatrics & Gerontology; Clinical Neurology; Psychiatry SC Geriatrics & Gerontology; Neurosciences & Neurology; Psychiatry GA CB5UJ UT WOS:000349692800003 PM 25531628 ER PT J AU Teng, E Chow, N Hwang, KS Thompson, PM Gylys, KH Cole, GM Jack, CR Shaw, LM Trojanowski, JQ Soares, HD Weiner, MW Apostolova, LG AF Teng, Edmond Chow, Nicole Hwang, Kristy S. Thompson, Paul M. Gylys, Karen H. Cole, Gregory M. Jack, Clifford R., Jr. Shaw, Leslie M. Trojanowski, John Q. Soares, Holly D. Weiner, Michael W. Apostolova, Liana G. CA Alzheimer's Dis Neuroimaging Initi TI Low Plasma ApoE Levels Are Associated with Smaller Hippocampal Size in the Alzheimer's Disease Neuroimaging Initiative Cohort SO DEMENTIA AND GERIATRIC COGNITIVE DISORDERS LA English DT Article DE Alzheimer's disease; Mild cognitive impairment; Magnetic resonance imaging; Hippocampus; Biomarkers; ADNI; Apolipoprotein E ID MILD COGNITIVE IMPAIRMENT; APOLIPOPROTEIN-E; BRAIN; GENOTYPE; MRI; POLYMORPHISM; SEGMENTATION; BIOMARKERS; DEPOSITION; CLEARANCE AB Apolipoprotein E (APOE) genotype is the strongest known genetic risk factor for sporadic Alzheimer's disease (AD), but the utility of plasma ApoE levels for assessing the severity of underlying neurodegenerative changes remains uncertain. Here, we examined cross-sectional associations between plasma ApoE levels and volumetric magnetic resonance imaging indices of the hippocampus from 541 participants [57 with normal cognition (NC), 375 with mild cognitive impairment (MCI), and 109 with mild AD] who were enrolled in the Alzheimer's Disease Neuroimaging Initiative. Across the NC and MCI groups, lower plasma ApoE levels were significantly correlated with smaller hippocampal size, as measured by either hippocampal volume or hippocampal radial distance. These associations were driven primarily by findings from carriers of an APOE epsilon 4 allele and are consistent with prior reports that lower plasma ApoE levels correlate with greater global cortical Pittsburgh Compound B retention. In this high-risk group, plasma ApoE levels may represent a peripheral marker of underlying AD neuropathology in nondemented elderly individuals. (C) 2014 S. Karger AG, Basel C1 [Teng, Edmond; Chow, Nicole; Hwang, Kristy S.; Thompson, Paul M.; Cole, Gregory M.; Apostolova, Liana G.] Univ Calif Los Angeles, Dept Neurol, Los Angeles, CA 90024 USA. [Chow, Nicole; Hwang, Kristy S.; Thompson, Paul M.; Apostolova, Liana G.] Univ Calif Los Angeles, Lab Neuro Imaging, Imaging Genet Ctr, Los Angeles, CA USA. [Thompson, Paul M.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Psychiat & Biobehav Sci, Semel Inst, Los Angeles, CA 90095 USA. [Gylys, Karen H.] Univ Calif Los Angeles, Sch Nursing, Los Angeles, CA 90024 USA. [Teng, Edmond; Cole, Gregory M.] Vet Affairs Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. [Jack, Clifford R., Jr.] Mayo Clin, Dept Diagnost Radiol, Rochester, MN USA. [Shaw, Leslie M.; Trojanowski, John Q.] Univ Penn, Sch Med, Dept Pathol & Lab Med, Philadelphia, PA 19104 USA. [Soares, Holly D.] Bristol Myers Squibb Co, Wallingford, CT 06492 USA. [Weiner, Michael W.] Univ Calif San Francisco, Dept Med, San Francisco, CA USA. [Weiner, Michael W.] Univ Calif San Francisco, Dept Radiol, San Francisco, CA USA. [Weiner, Michael W.] Univ Calif San Francisco, Dept Psychiat, San Francisco, CA USA. [Weiner, Michael W.] Vet Affairs Med Ctr, San Francisco, CA 94121 USA. RP Teng, E (reprint author), West Los Angeles Vet Affairs Healthcare Ctr, Neurobehav Serv 116AF, 11301 Wilshire Blvd, Los Angeles, CA 90073 USA. EM eteng@ucla.edu RI Jack, Clifford/F-2508-2010 OI Jack, Clifford/0000-0001-7916-622X FU ADNI; National Institute on Aging [U01 AG024904]; National Institute of Biomedical Imaging and Bioengineering; NIH [K01 AG030514, K08 AG34628, R01 MH097268, R01 AG040060, R01 AG040770, P50 AG16570]; Easton Consortium for Alzheimer's Drug Discovery and Biomarker Development FX Data collection and sharing for this project was funded by ADNI, which is supported by the National Institute on Aging (U01 AG024904), the National Institute of Biomedical Imaging and Bioengineering, and contributions from: Abbott; Alzheimer's Association; Alzheimer's Drug Discovery Foundation; Amorfix Life Sciences Ltd.; AstraZeneca; Bayer HealthCare; BioClinica, Inc.; Biogen Idec Inc.; Bristol-Myers Squibb Company; Eisai Inc.; Elan Pharmaceuticals Inc.; Eli Lilly and Company; F. Hoffmann-La Roche Ltd./Genentech, Inc.; GE Healthcare; Innogenetics, N.V.; IXICO Ltd.; Janssen Alzheimer Immunotherapy Research and Development, LLC.; Johnson & Johnson Pharmaceutical Research and Development LLC.; Medpace, Inc.; Merck & Co., Inc.; Meso Scale Diagnostics, LLC.; Novartis Pharmaceuticals Corporation; Pfizer Inc.; Servier; Synarc Inc., and Takeda Pharmaceutical Company. Private sector contributions are facilitated by the Foundation for the National Institutes of Health (www.fnih.org). The grantee organization is the Northern California Institute for Research and Education, and the study is coordinated by the Alzheimer's Disease Cooperative Study at the University of California San Diego. ADNI data are disseminated by the Laboratory for Neuro Imaging at the University of Southern California. This research was also supported by NIH grants (K01 AG030514, K08 AG34628, R01 MH097268, R01 AG040060, R01 AG040770, P50 AG16570, and P30 AG010129) and the Easton Consortium for Alzheimer's Drug Discovery and Biomarker Development. NR 51 TC 7 Z9 8 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 2015 VL 39 IS 3-4 BP 154 EP 166 DI 10.1159/000368982 PG 13 WC Geriatrics & Gerontology; Clinical Neurology; Psychiatry SC Geriatrics & Gerontology; Neurosciences & Neurology; Psychiatry GA CB5UJ UT WOS:000349692800004 PM 25547651 ER PT J AU Prokosch-Willing, V Hoerste, MMZ Mertsch, S Stupp, T Thanos, S AF Prokosch-Willing, Verena Hoerste, Melissa Meyer zu Mertsch, Sonja Stupp, Tobias Thanos, Solon TI Postnatal Visual Deprivation in Rats Regulates Several Retinal Genes and Proteins, Including Differentiation-Associated Fibroblast Growth Factor-2 SO DEVELOPMENTAL NEUROSCIENCE LA English DT Article DE Visual deprivation; Amblyopia; Rat; Retina; Transcripts ID OPTICAL COHERENCE TOMOGRAPHY; EARLY MONOCULAR DEPRIVATION; GANGLION-CELL LAYER; MESSENGER-RNA; MULLER CELLS; ADULT-RATS; ENVIRONMENTAL ENRICHMENT; SUPRACHIASMATIC NUCLEUS; UNILATERAL AMBLYOPIA; EXPRESSION AB Little is known about the retinal cellular basis of amblyopia, which is a developmental disease characterized by impaired visual acuity. This study examined the retinal transcripts associated with experimentally induced unilateral amblyopia in rats. Surgical tarsorrhaphy of the eyelids on one side was performed in pups prior to eye opening at postnatal day 14, thereby preventing any visual experience. This condition was maintained for over 2 months, after which electroretino-grams (ERGs) were recorded, the retinal ganglion cell (RGC) arrangement and number were determined using neuroanatomical tracing, the retinal transcripts were studied using microarray analysis, regulated mRNAs were confirmed with quantitative reverse-transcriptase PCR, and proteins were stained using Western blotting and immunohistochemistry. An attenuated ERG was found in eyes that were deprived of visual experience. Retrograde neuroanatomical staining disclosed a larger number of RGCs within the retina on the visually deprived side compared to the non-deprived, control side, and a multilayered distribution of RGCs. At the retinomic level, several transcripts associated with retinal differentiation, such as fibroblast growth factor 2 (FGF-2), were either up-or downregulated. Most of the transcripts could be verified at the mRNA level. To unravel the role of a differentiation-associated protein, we tested FGF-2 in dissociated postnatal retinal cell cultures and found that FGF-2 is a potent factor triggering ganglion cell differentiation. The data suggest that visual experience shapes the postnatal retinal differentiation, whereas visual deprivation induces changes at the functional, cellular and molecular levels within the retina. (C) 2014 S. Karger AG, Basel C1 [Prokosch-Willing, Verena; Mertsch, Sonja; Stupp, Tobias; Thanos, Solon] Univ Munster, Sch Med, Inst Expt Ophthalmol, DE-48149 Munster, Germany. [Hoerste, Melissa Meyer zu] Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Boston, MA USA. RP Thanos, S (reprint author), Univ Munster, Sch Med, Inst Expt Ophthalmol, Albert Schweitzer Campus 1,D15, DE-48149 Munster, Germany. EM solon@uni-muenster.de OI Mertsch, Sonja/0000-0001-8803-9150 NR 92 TC 2 Z9 2 U1 0 U2 3 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 2015 VL 37 IS 1 BP 14 EP 28 DI 10.1159/000367651 PG 15 WC Developmental Biology; Neurosciences SC Developmental Biology; Neurosciences & Neurology GA CB5IK UT WOS:000349660500002 PM 25402196 ER PT J AU Haley, KP Gaddy, JA AF Haley, Kathryn P. Gaddy, Jennifer A. TI Helicobacter pylori: Genomic Insight into the Host-Pathogen Interaction SO INTERNATIONAL JOURNAL OF GENOMICS LA English DT Review ID GASTRIC EPITHELIAL-CELLS; IV SECRETION SYSTEM; VACUOLATING TOXIN; IRON-DEFICIENCY; INFECTION; VACA; CANCER; EAST; CARCINOGENESIS; EXPRESSION AB The advent of genomic analyses has revolutionized the study of human health. Infectious disease research in particular has experienced an explosion of bacterial genomic, transcriptomic, and proteomic data complementing the phenotypic methods employed in traditional bacteriology. Together, these techniques have revealed novel virulence determinants in numerous pathogens and have provided information for potential chemotherapeutics. The bacterial pathogen, Helicobacter pylori, has been recognized as a class 1 carcinogen and contributes to chronic inflammation within the gastric niche. Genomic analyses have uncovered remarkable coevolution between the human host and H. pylori. Perturbation of this coevolution results in dysregulation of the host-pathogen interaction, leading to oncogenic effects. This review discusses the relationship of H. pylori with the human host and environment and the contribution of each of these factors to disease progression, with an emphasis on features that have been illuminated by genomic tools. C1 [Haley, Kathryn P.; Gaddy, Jennifer A.] Vanderbilt Univ, Dept Med, Sch Med, Nashville, TN 37232 USA. [Gaddy, Jennifer A.] US Dept Vet Affairs, Tennessee Valley Healthcare Syst, Nashville, TN 37212 USA. RP Gaddy, JA (reprint author), Vanderbilt Univ, Dept Med, Sch Med, Nashville, TN 37232 USA. EM jennifer.a.gaddy@vanderbilt.edu FU Office of Medical Research, Department of Veterans Affairs [IK2BX001701]; NIH [P30DK058404]; National Center for Research Resources [UL1 RR024975-01]; National Center for Advancing Translational Sciences [2 UL1 TR000445-06] FX This work has been funded primarily by a Career Development Award IK2BX001701 (to Jennifer A. Gaddy) from the Office of Medical Research, Department of Veterans Affairs. Core Services including use of the Cell Imaging Shared Resource were performed through both Vanderbilt University Medical Center's Digestive Disease Research Center supported by NIH Grant P30DK058404 Core Scholarship and Vanderbilt Institute for Clinical and Translational Research Program supported by the National Center for Research Resources, Grant UL1 RR024975-01, and the National Center for Advancing Translational Sciences, Grant 2 UL1 TR000445-06. The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH. NR 73 TC 7 Z9 7 U1 1 U2 13 PU HINDAWI PUBLISHING CORP PI NEW YORK PA 410 PARK AVENUE, 15TH FLOOR, #287 PMB, NEW YORK, NY 10022 USA SN 2314-436X EI 2314-4378 J9 INT J GENOMICS JI Int. J. Genomics PY 2015 AR 386905 DI 10.1155/2015/386905 PG 8 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity GA CB6ZS UT WOS:000349776200001 ER PT J AU Claxton, A Baker, LD Hanson, A Trittschuh, EH Cholerton, B Morgan, A Callaghan, M Arbuckle, M Behl, C Craft, S AF Claxton, Amy Baker, Laura D. Hanson, Angela Trittschuh, Emily H. Cholerton, Brenna Morgan, Amy Callaghan, Maureen Arbuckle, Matthew Behl, Colin Craft, Suzanne TI Long-Acting Intranasal Insulin Detemir Improves Cognition for Adults with Mild Cognitive Impairment or Early-Stage Alzheimer's Disease Dementia SO JOURNAL OF ALZHEIMERS DISEASE LA English DT Article DE Alzheimer's disease; clinical trials; randomized; insulin; intranasal drug administration; mild cognitive impairment ID APOLIPOPROTEIN-E GENOTYPE; AMYLOID PRECURSOR PROTEIN; NPH INSULIN; BETA; BRAIN; MEMORY; RESISTANCE; GLUCOSE; THERAPY; ALBUMIN AB Previous trials have shown promising effects of intranasally administered insulin for adults with Alzheimer's disease dementia (AD) or amnestic mild cognitive impairment (MCI). These trials used regular insulin, which has a shorter half-life compared to long-lasting insulin analogues such as insulin detemir. The current trial examined whether intranasal insulin detemir improves cognition or daily functioning for adults with MCI or AD. Sixty adults diagnosed with MCI or mild to moderate AD received placebo (n = 20), 20 IU of insulin detemir (n = 21), or 40 IU of insulin detemir (n = 19) for 21 days, administered with a nasal drug delivery device. Results revealed a treatment effect for the memory composite for the 40 IU group compared with placebo (p < 0.05). This effect was moderated by APOE status (p < 0.05), reflecting improvement for APOE-epsilon 4 carriers (p < 0.02), and worsening for non-carriers (p < 0.02). Higher insulin resistance at baseline predicted greater improvement with the 40 IU dose (r = 0.54, p < 0.02). Significant treatment effects were also apparent for verbal working memory (p < 0.03) and visuospatial working memory (p < 0.04), reflecting improvement for subjects who received the high dose of intranasal insulin detemir. No significant differences were found for daily functioning or executive functioning. In conclusion, daily treatment with 40 IU insulin detemir modulated cognition for adults with AD or MCI, with APOE-related differences in treatment response for the primary memory composite. Future research is needed to examine the mechanistic basis of APOE-related treatment differences, and to further assess the efficacy and safety of intranasal insulin detemir. C1 [Claxton, Amy; Hanson, Angela; Trittschuh, Emily H.; Morgan, Amy; Callaghan, Maureen; Behl, Colin] Vet Affairs Puget Sound Hlth Care Syst, Geriatr Res Educ & Clin Ctr, Seattle, WA USA. [Claxton, Amy; Hanson, Angela; Trittschuh, Emily H.; Cholerton, Brenna; Morgan, Amy; Callaghan, Maureen; Behl, Colin] Univ Washington, Sch Med, Dept Psychiat & Behav Sci, Seattle, WA 98195 USA. [Baker, Laura D.; Craft, Suzanne] Wake Forest Sch Med, Dept Internal Med, Winston Salem, NC 27157 USA. [Arbuckle, Matthew] Oregon Hlth & Sci Univ, Dept Psychiat, Portland, OR 97201 USA. RP Craft, S (reprint author), Wake Forest Sch Med, Med Ctr Blvd, Winston Salem, NC 27157 USA. EM suzcraft@wakehealth.edu FU National Institute of Aging [P50 AG05136, T32 AG000258]; Department of Veterans Affairs FX Suzanne Craft and Amy Claxton had full access to all of the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis. This research was supported by National Institute of Aging grants P50 AG05136 (to Dr. Craft) and T32 AG000258 (to Dr. Claxton), and the Department of Veterans Affairs. NR 48 TC 47 Z9 48 U1 4 U2 24 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 2015 VL 44 IS 3 BP 897 EP 906 DI 10.3233/JAD-141791 PG 10 WC Neurosciences SC Neurosciences & Neurology GA CB4RQ UT WOS:000349616000018 PM 25374101 ER PT J AU West, RK Ravona-Springer, R Heymann, A Schmeidler, J Leroith, D Koifman, K Guerrero-Berroa, E Preiss, R Hoffman, H Silverman, JM Beeri, MS AF West, Rebecca K. Ravona-Springer, Ramit Heymann, Anthony Schmeidler, James Leroith, Derek Koifman, Keren Guerrero-Berroa, Elizabeth Preiss, Rachel Hoffman, Hadas Silverman, Jeremy M. Beeri, Michal Schnaider TI Shorter Adult Height is Associated with Poorer Cognitive Performance in Elderly Men with Type II Diabetes SO JOURNAL OF ALZHEIMERS DISEASE LA English DT Article DE Cognitive performance; height; risk factors; type 2 diabetes mellitus; vascular dementia ID CORONARY-HEART-DISEASE; ALZHEIMERS-DISEASE; BODY HEIGHT; RISK-FACTORS; LATE-LIFE; LEG LENGTH; DEMENTIA; CIRCUMFERENCE; EDUCATION; GROWTH AB We studied the relationship of adult body height with five cognitive outcomes (executive functioning, semantic categorization, attention/working memory, episodic memory, and an overall cognition measure) in 897 cognitively normal elderly with type 2 diabetes. Regression analyses controlling for sociodemographic, cardiovascular, and diabetes-related risk factors and depression demonstrated that in males, shorter stature was associated with poorer executive functioning (p = 0.001), attention/working memory (p = 0.007), and overall cognition (p = 0.016), but not with episodic memory (p = 0.715) or semantic categorization (p = 0.948). No relationship between height and cognition was found for females. In cognitively normal type 2 diabetes male subjects, shorter stature, a surrogate for early-life stress and poor nutrition, was associated with cognitive functions. C1 [West, Rebecca K.; Schmeidler, James; Guerrero-Berroa, Elizabeth; Silverman, Jeremy M.; Beeri, Michal Schnaider] Icahn Sch Med Mt Sinai, Dept Psychiat, New York, NY 10029 USA. [Ravona-Springer, Ramit; Koifman, Keren; Preiss, Rachel; Hoffman, Hadas; Beeri, Michal Schnaider] Sheba Med Ctr, Joseph Sagol Neurosci Ctr, Ramat Gan, Israel. [Silverman, Jeremy M.] James J Peters Vet Affairs Med Ctr, Bronx, NY USA. [Heymann, Anthony] Maccabi Healthcare Serv, Tel Aviv, Israel. [Leroith, Derek] Icahn Sch Med Mt Sinai, Dept Med, Div Med Endocrinol Diabet & Bone Dis, New York, NY 10029 USA. RP West, RK (reprint author), Mt Sinai Sch Med, Dept Psychiat, Box 1230,One Gustave L Levy Pl,Box 1230, New York, NY 10029 USA. EM rebecca.west@mssm.edu FU NIA [R01 AG034087, P50 AG05138]; Helen Bader Foundation; Leroy Schecter Foundation; Irma T. Hirschl Scholar award; American Federation for Aging Research (AFAR) Young Investigator award; Alzheimer's Association [NIRG-11-205083] FX This study was supported by NIA grants R01 AG034087 to Dr. Beeri and P50 AG05138 to Dr. Sano, the Helen Bader Foundation, the Leroy Schecter Foundation, and the Irma T. Hirschl Scholar award to Dr. Beeri, the American Federation for Aging Research (AFAR) Young Investigator award, and the Alzheimer's Association grant NIRG-11-205083 to Dr. Ravona-Springer. NR 40 TC 2 Z9 2 U1 1 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 2015 VL 44 IS 3 BP 927 EP 935 DI 10.3233/JAD-142049 PG 9 WC Neurosciences SC Neurosciences & Neurology GA CB4RQ UT WOS:000349616000021 PM 25374105 ER PT J AU Saidi, LJ Polydoro, M Kay, KR Sanchez, L Mandelkow, EM Hyman, BT Spires-Jones, TL AF Saidi, Laiq-Jan Polydoro, Manuela Kay, Kevin R. Sanchez, Laura Mandelkow, Eva-Maria Hyman, Bradley T. Spires-Jones, Tara L. TI Carboxy Terminus Heat Shock Protein 70 Interacting Protein Reduces Tau-Associated Degenerative Changes SO JOURNAL OF ALZHEIMERS DISEASE LA English DT Article DE Alzheimer's disease; caspase; CHIP; mitochondrial transport; tau protein ID UBIQUITIN-PROTEASOME SYSTEM; ALZHEIMERS-DISEASE; PHOSPHORYLATED TAU; AXONAL-TRANSPORT; 4-REPEAT TAU; MOUSE MODEL; IN-VIVO; ACCUMULATION; AGGREGATION; DEGRADATION AB One of the hallmarks of Alzheimer's disease is the formation of neurofibrillary tangles, intracellular aggregates of hyperphosphorylated, mislocalized tau protein, which are associated with neuronal loss. Changes in tau are known to impair cellular transport (including that of mitochondria) and are associated with cell death in cell culture and mouse models of tauopathy. Thus clearing pathological forms of tau from cells is a key therapeutic strategy. One critical modulator in the degradation and clearance of misfolded proteins is the co-chaperone CHIP (Carboxy terminus Hsp70 interacting Protein), which is known to play a role in refolding and clearance of hyperphosphorylated tau. Here, we tested the hypothesis that CHIP could ameliorate pathological changes associated with tau. We find that co-expressing CHIP with full-length tau, tau truncated at D421 mimicking caspase cleavage, or the short tau(RD)Delta K280 tau construct containing only the tau repeat domain with a tauopathy mutation, decreases tau protein levels in human H4 neuroglioma cells in a manner dependent on the Hsp70-binding TPR domain of CHIP. The observed reduction in tau levels by CHIP is associated with a decrease of tau phosphorylation and reduced levels of cleaved Caspase 3 indicating that CHIP plays an important role in preventing tau-induced pathological changes. Furthermore, tau-associated mitochondrial transport deficits are rescued by CHIP co-expression in H4 cells. Together, these data suggest that the co-chaperone CHIP can rescue the pathological effects of tau, and indicate that other diseases of protein misfolding and accumulation may also benefit from CHIP upregulation. C1 [Saidi, Laiq-Jan; Polydoro, Manuela; Kay, Kevin R.; Sanchez, Laura; Hyman, Bradley T.; Spires-Jones, Tara L.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Charlestown, MA USA. [Saidi, Laiq-Jan; Mandelkow, Eva-Maria] German Ctr Neurodegenerat Dis, DZNE, Bonn, Germany. [Mandelkow, Eva-Maria] Caesar Res Ctr, Bonn, Germany. [Mandelkow, Eva-Maria] Max Planck Inst Metab Res, Cologne, Germany. [Spires-Jones, Tara L.] Univ Edinburgh, Ctr Cognit & Neural Syst, Edinburgh EH9 3EL, Midlothian, Scotland. [Spires-Jones, Tara L.] Univ Edinburgh, Euan MacDonald Ctr, Edinburgh EH9 3EL, Midlothian, Scotland. RP Spires-Jones, TL (reprint author), Univ Edinburgh, Coll Med & Vet Med, Sch Biomed Sci, Ctr Cognit & Neural Syst, 1 George Sq, Edinburgh EH9 3EL, Midlothian, Scotland. EM Tara.spires-jones@ed.ac.uk FU Alzheimer's Association Zenith Award; Alzheimer's Research UK/Chief Scientist Office Scotland; German National Academic Foundation; Foundation Family Klee Young Scientist Award; DZNE; Tau Consortium (USA) FX This work was funded by The Alzheimer's Association Zenith Award, Alzheimer's Research UK/Chief Scientist Office Scotland, German National Academic Foundation, Foundation Family Klee Young Scientist Award, DZNE, Tau Consortium (USA). NR 34 TC 5 Z9 5 U1 0 U2 2 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 2015 VL 44 IS 3 BP 937 EP 947 DI 10.3233/JAD-142094 PG 11 WC Neurosciences SC Neurosciences & Neurology GA CB4RQ UT WOS:000349616000022 PM 25374103 ER PT J AU Vaduganathan, M Gheorghiade, M AF Vaduganathan, Muthiah Gheorghiade, Mihai TI A roadmap to inpatient heart failure management SO JOURNAL OF CARDIOLOGY LA English DT Review DE Diuretics; Heart failure; Outcomes ID OBSTRUCTIVE PULMONARY-DISEASE; REDUCED EJECTION FRACTION; CLINICAL CHARACTERISTICS; EVEREST TRIAL; POSTDISCHARGE OUTCOMES; NONINVASIVE VENTILATION; MEDICARE BENEFICIARIES; RENAL-FUNCTION; OPTIMIZE-HF; OF-LIFE AB Heart failure (HF) accounts for over 1 million primary hospitalizations in the USA each year and carries a tremendous burden on costs and patient outcomes. The clinical syndrome of HF is not a single disease, but represents the complex interplay between various cardiac and non-cardiac processes, each of which need to be individually addressed. This review provides an updated, contemporary roadmap for inpatient worsening chronic HF management with a focus on identifying and addressing initiating mechanisms, amplifying factors, and cardiac structural abnormalities. Inpatient risk stratification should guide patient education, team structuring, disposition, and post-discharge monitoring. (C) 2014 Japanese College of Cardiology. Published by Elsevier Ltd. All rights reserved. C1 [Vaduganathan, Muthiah] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Med, Boston, MA USA. [Gheorghiade, Mihai] Northwestern Univ, Ctr Cardiovasc Innovat, Feinberg Sch Med, Chicago, IL 60601 USA. RP Gheorghiade, M (reprint author), Northwestern Univ, Ctr Cardiovasc Innovat, Feinberg Sch Med, 201 East Huron,Galter 3-150, Chicago, IL 60601 USA. EM m-gheorghiade@northwestern.edu NR 45 TC 0 Z9 0 U1 4 U2 6 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0914-5087 EI 1876-4738 J9 J CARDIOL JI J. Cardiol. PD JAN-FEB PY 2015 VL 65 IS 1-2 BP 26 EP 31 DI 10.1016/j.jjcc.2014.08.011 PG 6 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA CB4FI UT WOS:000349583200005 PM 25238886 ER PT S AU Mendez-Ferrer, S Scadden, DT Sanchez-Aguilera, A AF Mendez-Ferrer, Simon Scadden, David T. Sanchez-Aguilera, Abel BE Zaidi, M TI Bone marrow stem cells: current and emerging concepts SO MARROW SE Annals of the New York Academy of Sciences LA English DT Review; Book Chapter DE mesenchymal stem/stromal cells; hematopoietic stem cells; bone marrow stem cell niche; hierarchical crosstalk ID HEMATOPOIETIC STEM; IN-VIVO; PROGENITOR CELLS; STROMAL CELLS; CD34 EXPRESSION; SELF-RENEWAL; NICHE; QUIESCENCE; MICE; DIFFERENTIATION AB The interactions of stromal cells with hematopoietic cells in the bone marrow have long been a subject of research, but only recently have technologies allowed us to dissect them at the stem cell level. On the other hand, limitations of these technical tools might explain numerous discrepancies in this field. It is becoming increasingly clear that mesenchymal stem cells (MSCs) represent an important component of the hematopoietic stem cell (HSC) niche in the bone marrow. However, there is heterogeneity among HSCs, and many putatively different mesenchymal progenitors identified in the bone marrow using Cre recombinase-driven mouse lines seem to exhibit HSC niche properties. Development of better reporter lines has demonstrated that some of these Cre lines do not always specifically mark the expected cells. Also, characterization of different cell populations has often been partial, and issues of redundancy and compensation might explain apparently contradictory results. Recognizing and overcoming these limitations, while also clearly defining the distinctions between subgroups of mesenchymal cells, will be essential to advance the field. C1 [Mendez-Ferrer, Simon; Sanchez-Aguilera, Abel] CNIC, Stem Cell Niche Pathophysiol Grp, Madrid, Spain. [Scadden, David T.] Harvard Univ, Stem Cell & Regenerat Biol Dept, Cambridge, MA 02138 USA. [Scadden, David T.] Massachusetts Gen Hosp, Ctr Regenerat Med, Boston, MA 02114 USA. [Scadden, David T.] Harvard Stem Cell Inst, Cambridge, MA USA. RP Mendez-Ferrer, S (reprint author), Natl Cardiovasc Res Ctr CNIC, Calle Melchor Fernandez Almagro 3,Planta 3 Sur, Madrid 28029, Spain. EM smendez@cnic.es; abel.sanchez-aguilera@cnic.es OI Mendez-Ferrer, Simon/0000-0002-9805-9988 FU Howard Hughes Medical Institute NR 83 TC 17 Z9 17 U1 9 U2 23 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 2015 VL 1335 BP 32 EP 44 DI 10.1111/nyas.12641 PG 13 WC Cell Biology SC Cell Biology GA BC0DA UT WOS:000348920600004 PM 25573321 ER PT J AU Chu, Q Moellering, RE Hilinski, GJ Kim, YW Grossmann, TN Yeh, JTH Verdine, GL AF Chu, Qian Moellering, Raymond E. Hilinski, Gerard J. Kim, Young-Woo Grossmann, Tom N. Yeh, Johannes T. -H. Verdine, Gregory L. TI Towards understanding cell penetration by stapled peptides SO MEDCHEMCOMM LA English DT Article ID SUPERCHARGED PROTEINS; MECHANISMS; TAT; INTERNALIZATION; STABILIZATION; THERAPEUTICS; TRANSDUCTION; ENDOCYTOSIS; INHIBITION; DELIVERY AB Hydrocarbon-stapled a-helical peptides are a new class of targeting molecules capable of penetrating cells and engaging intracellular targets formerly considered intractable. This technology has been applied to the development of cell-permeable ligands targeting key intracellular protein-protein interactions. However, the properties governing cell penetration of hydrocarbon-stapled peptides have not yet been rigorously investigated. Herein we report our studies to systematically probe cellular uptake of stapled peptides. We developed a high-throughput epifluorescence microscopy assay to quantitatively measure stapled peptide intracellular accumulation and demonstrated that this assay yielded highly reproducible results. Using this assay, we analyzed more than 200 peptides with various sequences, staple positions and types, and found that cell penetration ability is strongly related to staple type and formal charge, whereas other physicochemical parameters do not appear to have a significant effect. We next investigated the mechanism(s) involved in stapled peptide internalization and have demonstrated that stapled peptides penetrate cells through a clathrin-and caveolin-independent endocytosis pathway that involves, in part, sulfated cell surface proteoglycans, but that also seems to exploit a novel, uncharacterized pathway. Taken together, staple type and charge are the key physical properties in determining the cell penetration ability of stapled peptides, and anionic cell surface proteoglycans might serve as receptors to mediate stapled peptide internalization. These findings improve our understanding of stapled peptides as chemical probes and potential targeted therapeutics, and provide useful guidelines for the design of next-generation stapled peptides with enhanced cell permeability. C1 [Chu, Qian; Moellering, Raymond E.; Hilinski, Gerard J.; Kim, Young-Woo; Grossmann, Tom N.; Yeh, Johannes T. -H.; Verdine, Gregory L.] Harvard Univ, Dept Stem Cell & Regenerat Biol, Cambridge, MA 02138 USA. [Chu, Qian; Moellering, Raymond E.; Hilinski, Gerard J.; Kim, Young-Woo; Grossmann, Tom N.; Yeh, Johannes T. -H.; Verdine, Gregory L.] Harvard Univ, Cambridge, MA 02138 USA. [Verdine, Gregory L.] Dana Farber Canc Inst, Program Canc Chem Biol, Boston, MA 02115 USA. RP Verdine, GL (reprint author), Harvard Univ, Dept Stem Cell & Regenerat Biol, 12 Oxford St, Cambridge, MA 02138 USA. EM gregory_verdine@harvard.edu RI Grossmann, Tom/A-4175-2015 OI Grossmann, Tom/0000-0003-0179-4116 FU Deutsche Akademie der Naturforscher Leopoldina [LPDS 2009-2]; Susan G. Komen for the Cure fellowship; AACR Centennial Pre-doctoral Research Fellowship in Cancer Research; Damon Runyon Cancer Research Foundation FX This research was supported by GlaxoSmithKline. We thank J. McGee, R.-J. Sung and S. Berkovitch for useful discussions and comments on the manuscript. We also thank N. Tolliday and T. Hasaka at the Broad Institute for the access to instrumentation. We are grateful for Professor David R. Liu at Harvard University for kindly providing the wild- type CHO cells (CHO-K1) and proteoglycan-deficient CHO cells (pgsA-745). T.N.G. is grateful for a fellowship from Deutsche Akademie der Naturforscher Leopoldina (LPDS 2009-2). J.T.-H.Y. is the recipient of a Susan G. Komen for the Cure fellowship. R.E.M was supported by an AACR Centennial Pre-doctoral Research Fellowship in Cancer Research and an HHMI Fellowship from the Damon Runyon Cancer Research Foundation. NR 41 TC 33 Z9 34 U1 6 U2 61 PU ROYAL SOC CHEMISTRY PI CAMBRIDGE PA THOMAS GRAHAM HOUSE, SCIENCE PARK, MILTON RD, CAMBRIDGE CB4 0WF, CAMBS, ENGLAND SN 2040-2503 EI 2040-2511 J9 MEDCHEMCOMM JI MedChemComm PY 2015 VL 6 IS 1 BP 111 EP 119 DI 10.1039/c4md00131a PG 9 WC Biochemistry & Molecular Biology; Chemistry, Medicinal SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy GA CB5XD UT WOS:000349700400011 ER PT J AU Bove, R Healy, BC Secor, E Vaughan, T Katic, B Chitnis, T Wicks, P De Jager, PL AF Bove, R. Healy, B. C. Secor, E. Vaughan, T. Katic, B. Chitnis, T. Wicks, P. De Jager, P. L. TI Patients report worse MS symptoms after menopause: Findings from an online cohort SO MULTIPLE SCLEROSIS AND RELATED DISORDERS LA English DT Article DE Estrogen; Multiple sclerosis; Hot flashes; Menopause; Patient-powered research networks; Online communities ID MULTIPLE-SCLEROSIS; WOMEN; AMENORRHEA; ESTROGEN; THERAPY; DISEASE AB Background: Many women with multiple sclerosis (MS) are postmenopausal, yet the impact of menopause on MS symptoms is unknown. Objective: To investigate patient-reported impact of menopause in a large online research platform, PatientsLikeMe (PLM). Methods: A detailed reproductive history survey was deployed to PLM members, and responses were linked to PLM's prospectively collected patient-reported severity score (MS Rating Scale, MSRS). The MSRS has previously shown good correlation with physician-derived EDSS scores. Results: Of the 513 respondents, 55% were postmenopausal; 54% of these reported induced menopause. Median age at natural menopause was 51. Surgical menopause occurred at an earlier age (p<0.001) and was associated with more hormone replacement therapy use (p=0.02) than natural menopause. Postmenopausal status, surgical menopause, and earlier age at menopause were all associated with worse MSRS scores (p <= 0.01) in regressions adjusting for age, disease type and duration. Conclusion: Postmenopausal patients in this study reported worse MS disease severity. Further, this study highlights a utility for online research platforms, which allow for rapid generation of hypotheses that then require validation in clinical settings. (C) 2014 Elsevier B.V. All rights reserved. C1 [Bove, R.; Healy, B. C.; Chitnis, T.; De Jager, P. L.] Brigham & Womens Hosp, Partners Multiple Sclerosis Ctr, Dept Neurol, Brookline, MA 02445 USA. [Bove, R.; Healy, B. C.; Chitnis, T.; De Jager, P. L.] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Bove, R.; Healy, B. C.; Secor, E.; Chitnis, T.; De Jager, P. L.] Harvard Univ, Sch Med, Ctr Neurol Dis, Boston, MA 02115 USA. [Healy, B. C.] Massachusetts Gen Hosp, Ctr Biostat, Boston, MA 02114 USA. [Vaughan, T.; Katic, B.; Wicks, P.] PatientsLikeMe Inc, Cambridge, MA USA. RP Bove, R (reprint author), Brigham & Womens Hosp, Partners Multiple Sclerosis Ctr, 1 Brookline Pl,2nd Floor, Brookline, MA 02445 USA. EM rbove@partners.org; bchealy@partners.org; secor.elizabeth@gmail.com; tvaughan@patientslikeme.com; bkatic@patientslikeme.com; tchitnis@rics.bwh.harvard.edu; pwicks@patientslikeme.com; pdejager@rics.bwh.harvard.edu FU National Multiple Sclerosis Society/American Brain Foundation Clinician Scientist Award [FAN 1761-A-1]; National MS Society Harry Weaver Neuroscience Scholar Award FX This research was supported by the National Multiple Sclerosis Society/American Brain Foundation Clinician Scientist Award FAN 1761-A-1 (RB). PLD is a National MS Society Harry Weaver Neuroscience Scholar Award Recipient. NR 22 TC 4 Z9 4 U1 0 U2 0 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 2211-0348 EI 2211-0356 J9 MULT SCLER RELAT DIS JI Mult. Scler. Relat. Disord. PD JAN PY 2015 VL 4 IS 1 BP 18 EP 24 DI 10.1016/j.msard.2014.11.009 PG 7 WC Clinical Neurology SC Neurosciences & Neurology GA CB5KR UT WOS:000349666400004 PM 25787049 ER PT J AU Chen, HH Yuan, HS Cho, H Sosnovik, DE Josephson, L AF Chen, Howard H. Yuan, Hushan Cho, Hoonsung Sosnovik, David E. Josephson, Lee TI Cytoprotective nanoparticles by conjugation of a polyhis tagged annexin V to a nanoparticle drug SO NANOSCALE LA English DT Article ID MAGNETIC-RESONANCE; ISCHEMIA-REPERFUSION; APOPTOTIC CELLS; PURIFICATION; PHOSPHATIDYLSERINE; EXPRESSION; DIANNEXIN; INJURY AB We synthesized a cytoprotective magnetic nanoparticle by reacting a maleimide functionalized Feraheme (FH) with a disulfide linked dimer of a polyhis tagged annexin V. Following reductive cleavage of disulfide, the resulting annexin-nanoparticle (diameter = 28.0 +/- 2.0 nm by laser light scattering, 7.6 annexin's/nanoparticle) was cytoprotective to cells subjected to plasma membrane disrupting chemotherapeutic or mechanical stresses, and significantly more protective than the starting annexin V. Annexin-nanoparticles provide an approach to the design of nanomaterials which antagonize the plasma membrane permeability characteristic of necrosis and which may have applications as cytoprotective agents. C1 [Yuan, Hushan; Josephson, Lee] Massachusetts Gen Hosp, Ctr Adv Med Imaging Sci, Boston, MA 02129 USA. [Chen, Howard H.; Sosnovik, David E.; Josephson, Lee] Massachusetts Gen Hosp, Martinos Ctr Biomed Imaging, Boston, MA 02129 USA. [Cho, Hoonsung] Chonnam Natl Univ, Sch Mat Sci & Engn, Kwangju 500757, South Korea. RP Josephson, L (reprint author), Massachusetts Gen Hosp, Ctr Adv Med Imaging Sci, Boston, MA 02129 USA. EM ljosephson@mgh.harvard.edu FU NIH [EB011996, EB009691, HL093038, HL112831, K99 HL121152] FX This work was supported by NIH R01's EB011996 (LJ), EB009691 (LJ), HL093038 (DES), HL112831 (DES), and K99 HL121152 (HHC). NR 31 TC 1 Z9 1 U1 3 U2 4 PU ROYAL SOC CHEMISTRY PI CAMBRIDGE PA THOMAS GRAHAM HOUSE, SCIENCE PARK, MILTON RD, CAMBRIDGE CB4 0WF, CAMBS, ENGLAND SN 2040-3364 EI 2040-3372 J9 NANOSCALE JI Nanoscale PY 2015 VL 7 IS 6 BP 2255 EP 2259 DI 10.1039/c4nr06861k PG 5 WC Chemistry, Multidisciplinary; Nanoscience & Nanotechnology; Materials Science, Multidisciplinary; Physics, Applied SC Chemistry; Science & Technology - Other Topics; Materials Science; Physics GA CB2QH UT WOS:000349472300011 PM 25572921 ER PT J AU Rosas, HD AF Rosas, H. Diana TI Paradigm for Neuroprotection in Presymptomatic Huntington Disease SO NEUROTHERAPEUTICS LA English DT Meeting Abstract C1 [Rosas, H. Diana] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1933-7213 EI 1878-7479 J9 NEUROTHERAPEUTICS JI Neurotherapeutics PD JAN PY 2015 VL 12 IS 1 BP 264 EP 265 PG 2 WC Clinical Neurology; Neurosciences; Pharmacology & Pharmacy SC Neurosciences & Neurology; Pharmacology & Pharmacy GA CB3PX UT WOS:000349541800028 ER PT J AU Zhang, QX Ren, H Baker, GL AF Zhang, Quanxuan Ren, Hong Baker, Gregory L. TI Synthesis and click chemistry of a new class of biodegradable polylactide towards tunable thermo-responsive biomaterials SO POLYMER CHEMISTRY LA English DT Article ID DRUG-DELIVERY SYSTEMS; RING-OPENING POLYMERIZATION; TRANSITION TEMPERATURES; BIOMEDICAL APPLICATIONS; TRIBLOCK COPOLYMERS; AQUEOUS-SOLUTIONS; BLOCK-COPOLYMERS; GRAFT-COPOLYMERS; C-13 NMR; POLYMERS AB A new class of clickable and biodegradable polylactide was designed and prepared via bulk polymerization of 3,6-dipropargyloxymethyl-1,4-dioxane-2,5-dione (1) which was synthesized from easily accessible propargyloxylactic acid (5). A homopolymer of 1 and random copolymer of 1 with L-lactide were obtained as amorphous materials and exhibit low T-g of 8.5 and 34 degrees C, respectively, indicating their promising potentials for biomedical applications. The statistical nature of random copolymers was investigated by DSC analysis and C-13 NMR spectroscopy, which implies the random distribution of terminal alkyne groups along the back bone of copolymers. The efficient click post-modification of this new class of polylactide with alkyl and mPEG azides affords novel hydrophilic biomaterials, which exhibit reversible thermo-responsive properties as evidenced by their tunable LCST ranging from 22 to 69 degrees C depending on the balance of the incorporated hydrophilic/hydrophobic side chains. These results indicate the generality of this new class of clickable polylactide in preparing novel smart biomaterials in a simple and efficient manner via click chemistry. C1 [Zhang, Quanxuan; Baker, Gregory L.] Michigan State Univ, Dept Chem, E Lansing, MI 48824 USA. [Ren, Hong] Harvard Univ, Dept Chem & Chem Biol, Cambridge, MA 02138 USA. [Ren, Hong] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Athinoula A Martinos Ctr Biomed Imaging,Dept Radi, Charlestown, MA 02129 USA. RP Zhang, QX (reprint author), Michigan State Univ, Dept Chem, E Lansing, MI 48824 USA. EM zhangqua@msu.edu RI Ren, Hong/J-5191-2015 OI Ren, Hong/0000-0003-0375-0360 FU NIH [5RC2ES018756-02] FX This manuscript is in memory of my advisor, Prof. Gregory L. Baker, who passed away unexpectedly while this paper was under preparation. The authors are grateful to Prof. William D. Wulff at Michigan State University for his invaluable guidance, discussions and assistance during preparation of this manuscript. This work was funded by NIH 5RC2ES018756-02. NR 62 TC 3 Z9 3 U1 6 U2 41 PU ROYAL SOC CHEMISTRY PI CAMBRIDGE PA THOMAS GRAHAM HOUSE, SCIENCE PARK, MILTON RD, CAMBRIDGE CB4 0WF, CAMBS, ENGLAND SN 1759-9954 EI 1759-9962 J9 POLYM CHEM-UK JI Polym. Chem. PY 2015 VL 6 IS 8 BP 1275 EP 1285 DI 10.1039/c4py01425a PG 11 WC Polymer Science SC Polymer Science GA CB5KT UT WOS:000349666600008 PM 25685199 ER PT B AU Gray, PJ Aizer, AA Efstathiou, JA AF Gray, Phillip J. Aizer, Ayal A. Efstathiou, Jason A. BE Dicker, AP Kelly, WK Zaorsky, NG Trabulsi, EJ TI Treatment of Low-Risk, Localized Prostate Cancer: Use of Proton Therapy SO PROSTATE CANCER: A MULTIDISCIPLINARY APPROACH TO DIAGNOSIS AND MANAGEMENT SE Current Multidisciplinary Oncology LA English DT Article; Book Chapter ID INTENSITY-MODULATED RADIOTHERAPY; CONFORMAL RADIATION-THERAPY; RADICAL PROSTATECTOMY; ADENOCARCINOMA; CONTROVERSIES; SURGERY; CARE C1 [Gray, Phillip J.] Massachusetts Gen Hosp, Dept Radiat Oncol, Harvard Radiat Oncol Program, Boston, MA 02114 USA. [Aizer, Ayal A.; Efstathiou, Jason A.] Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. RP Gray, PJ (reprint author), Massachusetts Gen Hosp, Dept Radiat Oncol, Harvard Radiat Oncol Program, Boston, MA 02114 USA. NR 27 TC 0 Z9 0 U1 0 U2 0 PU DEMOS MEDICAL PUBLICATIONS PI NEW YORK PA 11 WEST 42ND STREET, 15TH FLOOR, NEW YORK, NY 10036 USA BN 978-1-936287-59-8 J9 CURR MULTIDISC ONCOL PY 2015 BP 196 EP 200 PG 5 WC Oncology SC Oncology GA BB8YU UT WOS:000347857300028 ER PT B AU Orio, P Bittner, N AF Orio, Peter Bittner, Nathan BE Dicker, AP Kelly, WK Zaorsky, NG Trabulsi, EJ TI Prognosis After Biochemical Failure and Surrogate Endpoints for Prostate Cancer-Specific Mortality SO PROSTATE CANCER: A MULTIDISCIPLINARY APPROACH TO DIAGNOSIS AND MANAGEMENT SE Current Multidisciplinary Oncology LA English DT Article; Book Chapter ID ANDROGEN SUPPRESSION THERAPY; CAPRA-S SCORE; RADICAL PROSTATECTOMY; RADIATION-THERAPY; CLINICAL-TRIALS; DEPRIVATION THERAPY; NATURAL-HISTORY; PSA RECURRENCE; FREE SURVIVAL; RADIOTHERAPY C1 [Orio, Peter] Brigham & Womens Hosp, Dana Farber Canc Inst, Boston, MA 02115 USA. [Orio, Peter] Harvard Univ, Sch Med, Dept Radiat Oncol, Boston, MA USA. [Bittner, Nathan] Tacoma Valley Radiat Oncol Ctr, Tacoma, WA USA. RP Orio, P (reprint author), Brigham & Womens Hosp, Dana Farber Canc Inst, 75 Francis St, Boston, MA 02115 USA. NR 35 TC 0 Z9 0 U1 1 U2 1 PU DEMOS MEDICAL PUBLICATIONS PI NEW YORK PA 11 WEST 42ND STREET, 15TH FLOOR, NEW YORK, NY 10036 USA BN 978-1-936287-59-8 J9 CURR MULTIDISC ONCOL PY 2015 BP 269 EP 273 PG 5 WC Oncology SC Oncology GA BB8YU UT WOS:000347857300041 ER PT J AU Admon, R Nickerson, LD Dillon, DG Holmes, AJ Bogdan, R Kumar, P Dougherty, DD Iosifescu, DV Mischoulon, D Fava, M Pizzagalli, DA AF Admon, R. Nickerson, L. D. Dillon, D. G. Holmes, A. J. Bogdan, R. Kumar, P. Dougherty, D. D. Iosifescu, D. V. Mischoulon, D. Fava, M. Pizzagalli, D. A. TI Dissociable cortico-striatal connectivity abnormalities in major depression in response to monetary gains and penalties SO PSYCHOLOGICAL MEDICINE LA English DT Article DE Caudate; cingulate; depression; PPI; reward; treatment prediction ID PSYCHOPHYSIOLOGICAL INTERACTIONS; FUNCTIONAL CONNECTIVITY; UNIPOLAR DEPRESSION; NEURAL RESPONSES; DECISION-MAKING; POSITIVE AFFECT; DISORDER; REWARD; PERFORMANCE; ACTIVATION AB Background. Individuals with major depressive disorder (MDD) are characterized by maladaptive responses to both positive and negative outcomes, which have been linked to localized abnormal activations in cortical and striatal brain regions. However, the exact neural circuitry implicated in such abnormalities remains largely unexplored. Method. In this study 26 unmedicated adults with MDD and 29 matched healthy controls (HCs) completed a monetary incentive delay task during functional magnetic resonance imaging (fMRI). Psychophysiological interaction (PPI) analyses probed group differences in connectivity separately in response to positive and negative outcomes (i.e. monetary gains and penalties). Results. Relative to HCs, MDD subjects displayed decreased connectivity between the caudate and dorsal anterior cingulate cortex (dACC) in response to monetary gains, yet increased connectivity between the caudate and a different, more rostral, dACC subregion in response to monetary penalties. Moreover, exploratory analyses of 14 MDD patients who completed a 12-week, double-blind, placebo-controlled clinical trial after the baseline fMRI scans indicated that a more normative pattern of cortico-striatal connectivity pre-treatment was associated with greater improvement in symptoms 12 weeks later. Conclusions. These results identify the caudate as a region with dissociable incentive-dependent dACC connectivity abnormalities in MDD, and provide initial evidence that cortico-striatal circuitry may play a role in MDD treatment response. Given the role of cortico-striatal circuitry in encoding action-outcome contingencies, such dysregulated connectivity may relate to the prominent disruptions in goal-directed behavior that characterize MDD. C1 [Admon, R.; Dillon, D. G.; Kumar, P.; Pizzagalli, D. A.] Harvard Univ, McLean Hosp, Sch Med, Ctr Depress Anxiety & Stress Res, Belmont, MA USA. [Nickerson, L. D.; Pizzagalli, D. A.] Harvard Univ, McLean Hosp, Sch Med, McLean Imaging Ctr, Belmont, MA USA. [Holmes, A. J.] Harvard Univ, Dept Psychol, Cambridge, MA 02138 USA. [Holmes, A. J.; Dougherty, D. D.; Mischoulon, D.; Fava, M.] Harvard Univ, Sch Med, Dept Psychiat, Massachusetts Gen Hosp, Boston, MA 02115 USA. [Bogdan, R.] Washington Univ, Dept Psychol, St Louis, MO 63130 USA. [Iosifescu, D. V.] Mt Sinai Sch Med, Mood & Anxiety Disorders Program, New York, NY USA. RP Pizzagalli, DA (reprint author), McLean Hosp, Ctr Depress Anxiety & Stress Res, Room 233C,115 Mill St, Belmont, MA 02478 USA. EM dap@mclean.harvard.edu OI Dillon, Daniel/0000-0002-1977-700X; Bogdan, Ryan/0000-0002-1430-1045 FU National Institute of Mental Health (NIMH) [R01 MH068376]; National Center for Complementary and Alternative Medicine (NCCAM) [R21 AT002974]; NCCAM [R01 AT001638]; [K01 MH099232]; [K99 MH094438] FX We are grateful to E. L. Goetz, J. Birk, S. J. Dutra and N. B. Hall for their skilled assistance with this study. This study was supported by National Institute of Mental Health (NIMH) grant R01 MH068376 and National Center for Complementary and Alternative Medicine (NCCAM) grant R21 AT002974 (both awarded to D.A.P.) and NCCAM grant R01 AT001638 (awarded to M.F). A.J.H. and D.G.D. were supported by grants K01 MH099232 and K99 MH094438 respectively. NR 60 TC 12 Z9 13 U1 4 U2 15 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 32 AVENUE OF THE AMERICAS, NEW YORK, NY 10013-2473 USA SN 0033-2917 EI 1469-8978 J9 PSYCHOL MED JI Psychol. Med. PD JAN PY 2015 VL 45 IS 1 BP 121 EP 131 DI 10.1017/S0033291714001123 PG 11 WC Psychology, Clinical; Psychiatry; Psychology SC Psychology; Psychiatry GA CB4RY UT WOS:000349616800010 PM 25055809 ER PT J AU Tsai, J El-Gabalawy, R Sledge, WH Southwick, SM Pietrzak, RH AF Tsai, J. El-Gabalawy, R. Sledge, W. H. Southwick, S. M. Pietrzak, R. H. TI Post-traumatic growth among veterans in the USA: results from the National Health and Resilience in Veterans Study SO PSYCHOLOGICAL MEDICINE LA English DT Article DE Coping behavior; post-traumatic stress disorder; spirituality; veterans ID SOCIAL SUPPORT; STRESS SYMPTOMS; 5-FACTOR MODEL; PHYSICAL HEALTH; MENTAL-HEALTH; TRAUMA; DISORDER; PTSD; WAR; VALIDATION AB Background. There is increasing recognition that, in addition to negative psychological consequences of trauma such as post-traumatic stress disorder (PTSD), some individuals may develop post-traumatic growth (PTG) following such experiences. To date, however, data regarding the prevalence, correlates and functional significance of PTG in population-based samples are lacking. Method. Data were analysed from the National Health and Resilience in Veterans Study, a contemporary, nationally representative survey of 3157 US veterans. Veterans completed a survey containing measures of sociodemographic, military, health and psychosocial characteristics, and the Posttraumatic Growth Inventory-Short Form. Results. We found that 50.1% of all veterans and 72.0% of veterans who screened positive for PTSD reported at least 'moderate' PTG in relation to their worst traumatic event. An inverted U-shaped relationship was found to best explain the relationship between PTSD symptoms and PTG. Among veterans with PTSD, those with PTSD reported better mental functioning and general health than those without PTG. Experiencing a life-threatening illness or injury and re-experiencing symptoms were most strongly associated with PTG. In multivariable analysis, greater social connectedness, intrinsic religiosity and purpose in life were independently associated with greater PTG. Conclusions. PTG is prevalent among US veterans, particularly among those who screen positive for PTSD. These results suggest that there may be a 'positive legacy' of trauma that has functional significance for veterans. They further suggest that interventions geared toward helping trauma-exposed US veterans process their re-experiencing symptoms, and to develop greater social connections, sense of purpose and intrinsic religiosity may help promote PTG in this population. C1 [Tsai, J.] US Dept Vet Affairs, New England Mental Illness Res Educ & Clin Ctr, West Haven, CT USA. [Tsai, J.; Sledge, W. H.; Southwick, S. M.; Pietrzak, R. H.] Yale Univ, Sch Med, Dept Psychiat, New Haven, CT USA. [El-Gabalawy, R.] Univ Manitoba, Dept Psychol, Winnipeg, MB R3T 2N2, Canada. [Southwick, S. M.; Pietrzak, R. H.] US Dept Vet Affairs, Natl Ctr Posttraumat Stress Disorder, Clin Neurosci Div, West Haven, CT USA. RP Tsai, J (reprint author), 950 Campbell Ave,151D, West Haven, CT 06516 USA. EM Jack.Tsai@yale.edu FU United States Department of Veterans Affairs National Center for Posttraumatic Stress Disorder; United States Department of Veterans Affairs, Office of Research and Development FX This work was supported in part by the United States Department of Veterans Affairs National Center for Posttraumatic Stress Disorder, the United States Department of Veterans Affairs, Office of Research and Development, and a private donation. The views presented here are those of the authors alone and do not represent the position of any federal agency or of the United States Government. None of the authors reports any conflicts of interest with this work. NR 58 TC 15 Z9 15 U1 8 U2 31 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 32 AVENUE OF THE AMERICAS, NEW YORK, NY 10013-2473 USA SN 0033-2917 EI 1469-8978 J9 PSYCHOL MED JI Psychol. Med. PD JAN PY 2015 VL 45 IS 1 BP 165 EP 179 DI 10.1017/S0033291714001202 PG 15 WC Psychology, Clinical; Psychiatry; Psychology SC Psychology; Psychiatry GA CB4RY UT WOS:000349616800014 PM 25065450 ER PT J AU Shin, SS Grandhi, R Henchir, J Yan, HQ Badylak, SF Dixon, CE AF Shin, Samuel S. Grandhi, Ramesh Henchir, Jeremy Yan, Hong Q. Badylak, Stephen F. Dixon, C. Edward TI Neuroprotective effects of collagen matrix in rats after traumatic brain injury SO RESTORATIVE NEUROLOGY AND NEUROSCIENCE LA English DT Article DE Collagen; matrix; traumatic brain injury; bioscaffold; neuroregeneration; neurorepair ID CONTROLLED CORTICAL IMPACT; NEURAL STEM-CELLS; SYSTEM EXTRACELLULAR-MATRIX; SPINAL-CORD; CEREBRAL-ISCHEMIA; PROGENITOR CELLS; DURAL GRAFT; SCAFFOLDS; GROWTH; TRANSPLANTATION AB Purpose: In previous studies, collagen based matrices have been implanted into the site of lesion in different models of brain injury. We hypothesized that semisynthetic collagen matrix can have neuroprotective function in the setting of traumatic brain injury. Methods: Rats were subjected to sham injury or controlled cortical impact. They either received extracellular matrix graft (DuraGen) over the injury site or did not receive any graft and underwent beam balance/beam walking test at post injury days 1-5 and Morris water maze at post injury days 14-18. Animals were sacrificed at day 18 for tissue analysis. Results: Collagen matrix implantation in injured rats did not affect motor function (beam balance test: p = 0.627, beam walking test: p = 0.921). However, injured group with collagen matrix had significantly better spatial memory acquisition (p < 0.05). There was a significant reduction in lesion volume, as well as neuronal loss in CA1 (p < 0.001) and CA3 (p < 0.05) regions of the hippocampus in injured group with collagen matrix (p < 0.05). Conclusions: Collagen matrix reduces contusional lesion volume, neuronal loss, and cognitive deficit after traumatic brain injury. Further studies are needed to demonstrate the mechanisms of neuroprotection by collagen matrix. C1 [Shin, Samuel S.; Henchir, Jeremy; Yan, Hong Q.; Dixon, C. Edward] Univ Pittsburgh, Brain Trauma Res Ctr, Pittsburgh, PA 15260 USA. [Shin, Samuel S.; Grandhi, Ramesh; Henchir, Jeremy; Yan, Hong Q.; Dixon, C. Edward] Univ Pittsburgh, Dept Neurol Surg, Pittsburgh, PA 15260 USA. [Shin, Samuel S.; Yan, Hong Q.; Dixon, C. Edward] Univ Pittsburgh, Safar Ctr Resuscitat Res, Pittsburgh, PA 15260 USA. [Badylak, Stephen F.] Univ Pittsburgh, McGowan Inst Regenerat Med, Pittsburgh, PA 15260 USA. [Dixon, C. Edward] Vet Affairs Pittsburgh Healthcare Syst, Pittsburgh, PA USA. RP Dixon, CE (reprint author), Univ Pittsburgh, Dept Neurol Surg, 201 Hill Bldg,3434 Fifth Ave, Pittsburgh, PA 15260 USA. EM dixonec@upmc.edu OI Badylak, Stephen/0000-0003-3555-0689 FU NIH/NINDS; Pittsburgh Foundation Walter L. Copeland Fund FX This work was supported by NIH/NINDS and by the Pittsburgh Foundation Walter L. Copeland Fund. NR 34 TC 1 Z9 1 U1 0 U2 5 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 2015 VL 33 IS 2 BP 95 EP 104 DI 10.3233/RNN-140430 PG 10 WC Neurosciences SC Neurosciences & Neurology GA CB7UX UT WOS:000349835000001 PM 25624423 ER PT J AU Giampietro, PF Armstrong, L Stoddard, A Blank, RD Livingston, J Raggio, CL Rasmussen, K Pickart, M Lorier, R Turner, A Sund, S Sobrera, N Neptune, E Sweetser, D Santiago-Cornier, A Broeckel, U AF Giampietro, Philip F. Armstrong, Linlea Stoddard, Alex Blank, Robert D. Livingston, Janet Raggio, Cathy L. Rasmussen, Kristen Pickart, Michael Lorier, Rachel Turner, Amy Sund, Sarah Sobrera, Nara Neptune, Enid Sweetser, David Santiago-Cornier, Alberto Broeckel, Ulrich TI Whole Exome Sequencing Identifies a POLRID Mutation Segregating in a Father and Two Daughters with Findings of Klippel-Feil and Treacher Collins Syndromes SO AMERICAN JOURNAL OF MEDICAL GENETICS PART A LA English DT Article DE Klippel-Feil; autosomal dominant; Treacher Collins syndrome ID CAUSES SPONDYLOCOSTAL DYSOSTOSIS; OSTEOGENESIS IMPERFECTA; VERTEBRAL MALFORMATIONS; CLEFT-PALATE; ANOMALIES; PROTEIN; GENE; SEGMENTATION; DEFICIENCY; SCOLIOSIS AB We report on a father and his two daughters diagnosed with Klippel-Feil syndrome (KFS) but with craniofacial differences (zygomatic and mandibular hypoplasia and cleft palate) and external ear abnormalities suggestive of Treacher Collins syndrome (TCS). The diagnosis of KFS was favored, given that the neck anomalies were the predominant manifestations, and that the diagnosis predated later recognition of the association between spinal segmentation abnormalities and TCS. Genetic heterogeneity and the rarity of large families with KFS have limited the ability to identify mutations by traditional methods. Whole exome sequencing identified a nonsynonymous mutation in POLR1D (subunit of RNA polymerase I and II): exon2:c. T332C:p.L111P. Mutations in POLR1D are present in about 5% of individuals diagnosed with TCS. We propose that this mutation is causal in this family, suggesting a pathogenetic link between KFS and TCS. (C) 2014 Wiley Periodicals, Inc. C1 [Giampietro, Philip F.; Sund, Sarah] Univ Wisconsin, Madison, WI 53705 USA. [Armstrong, Linlea; Livingston, Janet] Univ British Columbia, Vancouver, BC V5Z 1M9, Canada. [Stoddard, Alex; Blank, Robert D.; Lorier, Rachel; Turner, Amy; Broeckel, Ulrich] Med Coll Wisconsin, Milwaukee, WI 53226 USA. [Raggio, Cathy L.] Hosp Special Surg, New York, NY 10021 USA. [Rasmussen, Kristen] Marshfield Clin Fdn Med Res & Educ, Marshfield, WI USA. [Pickart, Michael] Concordia Univ, Mequon, WI USA. [Sobrera, Nara; Neptune, Enid] Johns Hopkins Univ, Baltimore, MD USA. [Sweetser, David] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Santiago-Cornier, Alberto] Ponce Sch Med, San Juan, PR USA. RP Giampietro, PF (reprint author), Univ Wisconsin, Dept Pediat, Waisman Ctr Room 351,1500 Highland Ave, Madison, WI 53705 USA. EM pfgiampietro@pediatrics.wisc.edu OI Blank, Robert Daniel/0000-0003-2950-1944 FU University of Wisconsin-Madison Pediatrics Research and Development fund FX Grant sponsor: University of Wisconsin-Madison Pediatrics Research and Development fund. NR 40 TC 0 Z9 1 U1 0 U2 3 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1552-4825 EI 1552-4833 J9 AM J MED GENET A JI Am. J. Med. Genet. A PD JAN PY 2015 VL 167 IS 1 BP 95 EP 102 DI 10.1002/ajmg.a.36799 PG 8 WC Genetics & Heredity SC Genetics & Heredity GA CA3ZD UT WOS:000348843000013 PM 25348728 ER PT J AU Wiederhold, NP Najvar, LK Fothergill, AW McCarthy, DI Bocanegra, R Olivo, M Kirkpatrick, WR Everson, MP Duncanson, FP Patterson, TF AF Wiederhold, Nathan P. Najvar, Laura K. Fothergill, Annette W. McCarthy, Dora I. Bocanegra, Rosie Olivo, Marcos Kirkpatrick, William R. Everson, Michael P. Duncanson, Frederick P. Patterson, Thomas F. TI The Investigational Agent E1210 Is Effective in Treatment of Experimental Invasive Candidiasis Caused by Resistant Candida albicans SO ANTIMICROBIAL AGENTS AND CHEMOTHERAPY LA English DT Article ID BROAD-SPECTRUM ANTIFUNGAL; IN-VITRO ACTIVITY; BROTH MICRODILUTION METHODS; SUSCEPTIBILITY; CLSI; MODELS; FAMILY; SPP. AB The in vitro and in vivo activity of the inositol acyltransferase inhibitor E1210 was evaluated against echinocandin-resistant Candida albicans. E1210 demonstrated potent in vitro activity, and in mice with invasive candidiasis caused by echinocandin-resistant C. albicans, oral doses of 10 and 40 mg E1210/kg of body weight twice daily significantly improved survival and reduced fungal burden compared to those of controls and mice treated with caspofungin (10 mg/kg/day). These results demonstrate the potential use of E1210 against resistant C. albicans infections. C1 [Wiederhold, Nathan P.; Najvar, Laura K.; Fothergill, Annette W.; McCarthy, Dora I.; Bocanegra, Rosie; Olivo, Marcos; Kirkpatrick, William R.; Patterson, Thomas F.] Univ Texas Hlth Sci Ctr San Antonio, San Antonio, TX 78229 USA. [Najvar, Laura K.; Bocanegra, Rosie; Olivo, Marcos; Kirkpatrick, William R.; Patterson, Thomas F.] South Texas Vet Hlth Care Syst, San Antonio, TX USA. [Everson, Michael P.; Duncanson, Frederick P.] Eisai Inc, Woodcliff Lake, NJ USA. RP Wiederhold, NP (reprint author), Univ Texas Hlth Sci Ctr San Antonio, San Antonio, TX 78229 USA. EM wiederholdn@uthscsa.edu OI Wiederhold, Nathan/0000-0002-2225-5122 FU National Institute of Allergy and Infectious Diseases, National Institutes of Health, Department of Health and Human Services [HHS272201000018I, HHSN272201000038I, A03, A13]; Astellas; Dow; F2G; Merck; Merz; Viamet FX This project utilized preclinical services funded by the National Institute of Allergy and Infectious Diseases, National Institutes of Health, Department of Health and Human Services, under contract no. HHS272201000018I and HHSN272201000038I, task orders A03 and A13, respectively.; N.P.W. has received research support from Astellas, Dow, F2G, Merck, Merz, and Viamet and has served on advisory boards for Merck, Astellas, Toyama, and Viamet. T.F.P. has received research grants to UT Health Science Center San Antonio from Astellas and Merck and has served as a consultant for Astellas, Merck, Toyama, Viamet, and Scynexis. M.P.E. and F.P.D. are salaried employees of Eisai Inc. All other authors have no conflicts. NR 18 TC 4 Z9 6 U1 2 U2 2 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0066-4804 EI 1098-6596 J9 ANTIMICROB AGENTS CH JI Antimicrob. Agents Chemother. PD JAN PY 2015 VL 59 IS 1 BP 690 EP 692 DI 10.1128/AAC.03944-14 PG 3 WC Microbiology; Pharmacology & Pharmacy SC Microbiology; Pharmacology & Pharmacy GA CA0LO UT WOS:000348609500089 PM 25331706 ER PT B AU Katz, DH Rasmussen-Torvik, LJ AF Katz, Daniel H. Rasmussen-Torvik, Laura J. BE Shah, SJ Arnett, DK TI Genome-Wide Association Studies SO CARDIOVASCULAR GENETICS AND GENOMICS IN CLINICAL PRACTICE LA English DT Article; Book Chapter ID CORONARY-ARTERY-DISEASE; COMPLEX HUMAN-DISEASES; LINKAGE DISEQUILIBRIUM; CARDIOVASCULAR-DISEASE; SUSCEPTIBILITY LOCI; COMMON DISEASES; QUALITY-CONTROL; VARIANTS; RISK; GENE C1 [Katz, Daniel H.] Harvard Univ, Sch Med, Dept Med, Massachusetts Gen Hosp, Boston, MA 02138 USA. [Rasmussen-Torvik, Laura J.] Northwestern Univ, Dept Prevent Med, Feinberg Sch Med, Chicago, IL 60611 USA. RP Katz, DH (reprint author), Harvard Univ, Sch Med, Dept Med, Massachusetts Gen Hosp, Boston, MA 02138 USA. NR 68 TC 0 Z9 0 U1 1 U2 1 PU DEMOS MEDICAL PUBLICATIONS PI NEW YORK PA 11 WEST 42ND STREET, 15TH FLOOR, NEW YORK, NY 10036 USA BN 978-1-62070-014-3 PY 2015 BP 23 EP 33 PG 11 WC Cardiac & Cardiovascular Systems; Genetics & Heredity SC Cardiovascular System & Cardiology; Genetics & Heredity GA BB8EI UT WOS:000346457500004 ER PT B AU Shaikh, AY Lubitz, SA Lin, HH Benjamin, EJ McManus, DD AF Shaikh, Amir Y. Lubitz, Steven A. Lin, Honghuang Benjamin, Emelia J. McManus, David D. BE Shah, SJ Arnett, DK TI Atrial Fibrillation Genetics and Genomics SO CARDIOVASCULAR GENETICS AND GENOMICS IN CLINICAL PRACTICE LA English DT Article; Book Chapter ID FAMILIAL AGGREGATION; WIDE ASSOCIATION; CHROMOSOME 4Q25; CARDIOVASCULAR-DISEASE; CIRCULATING MICRORNAS; CARDIAC CONDUCTION; AFRICAN-AMERICANS; RANDOMIZED-TRIAL; DOWN-REGULATION; HEART-FAILURE C1 [Shaikh, Amir Y.] Univ Massachusetts, Sch Med, Dept Med, Worcester, MA 01605 USA. [Lubitz, Steven A.] Massachusetts Gen Hosp, Cardiovasc Res Ctr, Boston, MA 02114 USA. [Lubitz, Steven A.] Massachusetts Gen Hosp, Cardiac Arrhythmia Serv, Boston, MA 02114 USA. [Lubitz, Steven A.] Harvard Univ, Sch Med, Boston, MA USA. [Lin, Honghuang] Boston Univ, Sch Med, Dept Med, Boston, MA 02118 USA. [Benjamin, Emelia J.] Boston Univ, Sch Med, Boston, MA 02118 USA. [Benjamin, Emelia J.] Boston Univ, Sch Publ Hlth, Boston, MA USA. [McManus, David D.] Univ Massachusetts, Sch Med, Div Cardiol, Worcester, MA USA. RP Shaikh, AY (reprint author), Univ Massachusetts, Sch Med, Dept Med, Worcester, MA 01605 USA. NR 102 TC 0 Z9 0 U1 0 U2 0 PU DEMOS MEDICAL PUBLICATIONS PI NEW YORK PA 11 WEST 42ND STREET, 15TH FLOOR, NEW YORK, NY 10036 USA BN 978-1-62070-014-3 PY 2015 BP 140 EP 152 PG 13 WC Cardiac & Cardiovascular Systems; Genetics & Heredity SC Cardiovascular System & Cardiology; Genetics & Heredity GA BB8EI UT WOS:000346457500014 ER PT B AU Mauer, AC Owens, DS O'Donnell, CJ Post, WS Thanassoulis, G AF Mauer, Andreas C. Owens, David S. O'Donnell, Christopher J. Post, Wendy S. Thanassoulis, George BE Shah, SJ Arnett, DK TI Genetics of Valvular Heart Disease SO CARDIOVASCULAR GENETICS AND GENOMICS IN CLINICAL PRACTICE LA English DT Article; Book Chapter ID MITRAL-VALVE-PROLAPSE; BICUSPID AORTIC-VALVE; LATE SYSTOLIC-MURMUR; CORONARY-ARTERY-DISEASE; POSITRON-EMISSION-TOMOGRAPHY; OUTFLOW TRACT OBSTRUCTION; WILLIAMS-BEUREN-SYNDROME; GENOME-WIDE ASSOCIATION; ALL-CAUSE MORTALITY; ANNULAR CALCIFICATION C1 [Mauer, Andreas C.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Cardiol, Boston, MA 02138 USA. [Owens, David S.] Univ Washington, Div Cardiol, Seattle, WA 98195 USA. [O'Donnell, Christopher J.] NHLBI, Cardiovasc Epidemiol & Human Genom Branch, Div Intramural Res, Bethesda, MD 20892 USA. [O'Donnell, Christopher J.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, NHLBIs Framingham Heart Study,Cardiol Div, Boston, MA USA. [Post, Wendy S.] Johns Hopkins Sch Med, Baltimore, MD USA. [Thanassoulis, George] McGill Univ, Ctr Hlth, Montreal, PQ, Canada. [Thanassoulis, George] McGill Univ, Dept Med, Montreal, PQ, Canada. RP Mauer, AC (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Cardiol, Boston, MA 02138 USA. NR 183 TC 0 Z9 0 U1 0 U2 1 PU DEMOS MEDICAL PUBLICATIONS PI NEW YORK PA 11 WEST 42ND STREET, 15TH FLOOR, NEW YORK, NY 10036 USA BN 978-1-62070-014-3 PY 2015 BP 265 EP 286 PG 22 WC Cardiac & Cardiovascular Systems; Genetics & Heredity SC Cardiovascular System & Cardiology; Genetics & Heredity GA BB8EI UT WOS:000346457500022 ER PT J AU Bhatt, AB Rajabali, A He, W Benavidez, OJ AF Bhatt, Ami B. Rajabali, Alefiyah He, Wei Benavidez, Oscar J. TI High Resource Use among Adult Congenital Heart Surgery Admissions in Adult Hospitals: Risk Factors and Association with Death and Comorbidities SO CONGENITAL HEART DISEASE LA English DT Article DE Adult Congenital Heart Disease; Outcomes; Resource Use ID PEDIATRIC HOSPITALS; DISEASE PATIENTS; CARE; DYSFUNCTION; ADJUSTMENT; TETRALOGY; MORBIDITY; MORTALITY; FALLOT; REPAIR AB ObjectiveAdult hospitals are a common location of adult congenital heart disease (ACHD) admissions, including cardiac surgical admissions. Understanding the patterns and predictors of resource use could aid these institutions by identifying and targeting potentially modifiable determinants of high resource use (HRU). Our objectives were to examine resource use during adult congenital heart surgical admissions in adult hospitals, determine the association of HRU with mortality, and identify risk factors for HRU. DesignPopulation-based retrospective study We obtained data from the Nationwide Inpatient Sample 2005-2009 and examined ACHD surgical admissions ages 18-49 years (n = 16 231). Outcome MeasuresWe defined HRU as admissions with >90th percentile for total hospital charges. ResultsDespite representing 10% of admissions, HRU admissions accounted for 32% of total charges. HRU admissions had a higher mortality rate (9.7% vs. 1.8%, P < .001). Multivariable analysis demonstrated that HRU is associated with government insurance adjusted odds ratio (AOR) 2.0 (95% confidence interval [CI] 1.6,2.4), emergency admissions AOR 3.9 (95% CI 3.1,4.8), complications AOR 4.2 (95% CI 3.3,5.2), renal failure AOR 1.8 (95% CI 1.4,2.2), congestive heart failure AOR 1.2 (95% CI 1,1.4), surgical complexity risk category-2 AOR 2.0 (95% CI 1.0,3.6), and category-3+ AOR 2.3 (95% CI 1.4,3.8). ConclusionsHRU admissions for adult congenital heart surgery consumed a disproportionate amount of resources and were associated with higher mortality. HRU risk factors included nonelective admissions, government insurance, heart failure, surgical complexity, renal failure, and complications. Complications, if preventable, may be a target for improvement strategies to decrease resource use. Other risk factors may require a broader patient care approach. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Pediat Congenital Cardiol,Heart Ctr, Boston, MA USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Adult Congenital Heart Dis Program,Heart Ctr, Boston, MA USA. RP Benavidez, OJ (reprint author), Massachusetts Gen Hosp, Div Pediat Congenital Cardiol, 175 Cambridge St, Boston, MA 02114 USA. EM ojbenavidez@partners.org FU Robert Wood Johnson foundation Amos Medical Faculty Development Program FX Dr. Benavidez is supported by the Robert Wood Johnson foundation Amos Medical Faculty Development Program. NR 21 TC 3 Z9 3 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1747-079X EI 1747-0803 J9 CONGENIT HEART DIS JI Congenit. Heart Dis. PD JAN-FEB PY 2015 VL 10 IS 1 BP 13 EP 20 DI 10.1111/chd.12169 PG 8 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA CB2MU UT WOS:000349462600009 PM 24521268 ER PT J AU Juillerat, P Sokol, H Froehlich, F Yajnik, V Beaugerie, L Lucci, M Burnand, B Macpherson, AJ Cosnes, J Korzenik, JR AF Juillerat, Pascal Sokol, Harry Froehlich, Florian Yajnik, Vijay Beaugerie, Laurent Lucci, Matthew Burnand, Bernard Macpherson, Andrew J. Cosnes, Jacques Korzenik, Joshua R. TI Factors Associated with Durable Response to Infliximab in Crohn's Disease 5 Years and Beyond: A Multicenter International Cohort SO INFLAMMATORY BOWEL DISEASES LA English DT Article DE Crohn's disease; inflammatory bowel disease; infliximab; long-term; clinical; response ID INFLAMMATORY-BOWEL-DISEASE; PATIENTS LOSING RESPONSE; LONG-TERM DURABILITY; MAINTENANCE INFLIXIMAB; BIOLOGICAL THERAPIES; EFFICACY; ANTIBODIES; METAANALYSIS; SWITZERLAND; PREVALENCE AB Background: Infliximab (IFX) has been used for over a decade worldwide. Less is known about the natural history of IFX use beyond a few years and which patients are more likely to sustain benefits. Methods: Patients with Crohn's disease (CD) exposed to IFX from Massachusetts General Hospital, Boston, Saint-Antoine Hospital, Paris, and the Swiss IBD Cohort Study were identified through retrospective and prospective data collection, complemented by chart abstraction of electronic medical records. We compared long-term users of IFX (>5 yr of treatment, long-term users of infliximab [LTUI]), with non-LTUI patients to identify prognostic factors. Results: We pooled data on 1014 patients with CD from 3 different databases, of whom 250 were defined as LTUI. The comparison group comprised 290 patients with CD who discontinued IFX: 48 primary nonresponses, 95 loss of responses, and 147 adverse events. Factors associated with LTUI were colonic involvements and an earlier age at the start of IFX. The prevalence of active smokers and obese patients differed markedly, but inversely, between American and European centers but did not impact outcome. The discontinuation rate was stable around 3% to 6%, each year from years 3 to 10. Conclusions: Young age at start of IFX and colonic CD are factors associated with a beneficial long-term use of IFX. After 5 years of IFX, there is still a 3% to 5% discontinuation rate annually. Several factors associated with a good initial response such as nonsmoker and shorter disease duration at IFX initiation do not seem associated with a longer term response. C1 [Juillerat, Pascal; Yajnik, Vijay; Lucci, Matthew; Korzenik, Joshua R.] Massachusetts Gen Hosp, Dept Gastroenterol & Hepatol, MGH Crohns & Colitis Ctr, Boston, MA 02114 USA. [Juillerat, Pascal; Macpherson, Andrew J.] Univ Hosp Bern, Inselspital, Clin Visceral Surg & Med, Dept Gastroenterol, CH-3010 Bern, Switzerland. [Sokol, Harry; Beaugerie, Laurent; Cosnes, Jacques] Univ Paris 06, St Antoine Hosp, Dept Gastroenterol & Nutr, Paris, France. [Froehlich, Florian; Burnand, Bernard] Univ Lausanne Hosp, Inst Social & Prevent Med, Healthcare Evaluat Unit, Lausanne, Switzerland. [Froehlich, Florian] Univ Hosp Bern, Div Gastroenterol & Hepatol, CH-3010 Bern, Switzerland. [Lucci, Matthew; Korzenik, Joshua R.] Brigham & Womens Hosp, Dept Gastroenterol, Boston, MA 02115 USA. RP Juillerat, P (reprint author), Univ Hosp Bern, Inselspital, Clin Visceral Surg & Med, CH-3010 Bern, Switzerland. EM pascal.juillerat@insel.ch OI sokol, harry/0000-0002-2914-1822 FU AbbVie; UCB; Merck Sharp Dohme; Vifor; Enterome; Danone; Astellas; Ferring; Tilliots; Takeda; Procter and Gamble; Warner Chilcott FX Supported by the Swiss National Science Foundation (SNF): grant PBLAP3-124341.; P. Juillerat has received consulting and lecture fees from AbbVie, UCB, Merck Sharp & Dohme and Vifor. H. Sokol has received consulting fees from Enterome, Danone, and Astellas. L. Beaugerie has received consulting fees from Ferring and has been involved in advisory committees or review panels for AbbVie and Merck Sharp & Dohme. J. Cosnes has received consulting fees from Tilliots and has been involved in advisory committees or review panels for AbbVie and Merck Sharp & Dohme. V. Yajnik has received consulting fees from Takeda. J. R. Korzenik has been a consultant and a member of advisory boards for Shire Pharmaceuticals, Prometheus, Roche, AbbVie, Merck Sharp & Dohme, Pfizer, and Warner-Chilcott and receives research support from Procter and Gamble and Warner Chilcott. The remaining authors have no conflicts of interest to disclose. NR 41 TC 4 Z9 5 U1 1 U2 5 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 1078-0998 EI 1536-4844 J9 INFLAMM BOWEL DIS JI Inflamm. Bowel Dis. PD JAN PY 2015 VL 21 IS 1 BP 60 EP 70 DI 10.1097/MIB.0000000000000225 PG 11 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA CA4WD UT WOS:000348906500012 PM 25517594 ER PT J AU Liu, S Ren, JN Li, JS AF Liu, Song Ren, Jianan Li, Jieshou TI IL-17RA in Intestinal Inflammation: Structure, Signaling, Function, and Clinical Application SO INFLAMMATORY BOWEL DISEASES LA English DT Article DE IL-17RA; IL-17; IL-25; IBD; signaling; trial ID PLACEBO-CONTROLLED TRIAL; NF-KAPPA-B; CHRONIC PLAQUE PSORIASIS; PROOF-OF-CONCEPT; INTERLEUKIN-12/23 MONOCLONAL-ANTIBODY; ACTIVE RHEUMATOID-ARTHRITIS; TO-SEVERE PSORIASIS; EXPERIMENTAL AUTOIMMUNE ENCEPHALOMYELITIS; MODIFYING ANTIRHEUMATIC DRUGS; ALLERGIC AIRWAY INFLAMMATION AB Interleukin-17 receptor A (IL-17RA) is responsible for both IL-17A and IL-25 (IL-17E) signaling pathways. Current evidences suggest distinct but interactive responses between IL-17A and IL-25 signaling, both of which are critical for intestinal immune homeostasis. IL-17RA is assumed to regulate this counterbalance and therefore becomes a crucial molecule in mucosal immunology. In this review, we will describe the structure of IL-17RA, compare IL-17A and IL-25 signaling pathways, and emphasize on the function of IL-17RA in intestinal inflammation and discuss current evidences of accomplished and ongoing clinical trials with monoclonal antibodies targeting Th17 pathway, especially IL-17RA. C1 [Liu, Song; Ren, Jianan; Li, Jieshou] Nanjing Univ, Jinling Hosp, Dept Surg, Sch Med, Nanjing 210008, Jiangsu, Peoples R China. [Liu, Song] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Med,Gastrointestinal Unit, Boston, MA USA. [Liu, Song] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Study Inflammatory Bowel Dis, Boston, MA USA. RP Ren, JN (reprint author), 305 East Zhongshan Rd, Nanjing 210002, Jiangsu, Peoples R China. EM jiananr@gmail.com FU China Scholarship Council; Program B for Outstanding PhD candidate of Nanjing University; National Natural Science Foundation of China [81270478] FX Supported by China Scholarship Council (SL), Program B for Outstanding PhD candidate of Nanjing University (SL), and National Natural Science Foundation of China (No. 81270478) (JR). NR 155 TC 3 Z9 3 U1 1 U2 10 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 1078-0998 EI 1536-4844 J9 INFLAMM BOWEL DIS JI Inflamm. Bowel Dis. PD JAN PY 2015 VL 21 IS 1 BP 154 EP 166 DI 10.1097/MIB.0000000000000217 PG 13 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA CA4WD UT WOS:000348906500021 PM 25272188 ER PT J AU Goracci, A Casamassima, F Iovieno, N di Volo, S Benbow, J Bolognesi, S Fagiolini, A AF Goracci, Arianna Casamassima, Francesco Iovieno, Nadia di Volo, Silvia Benbow, Jim Bolognesi, Simone Fagiolini, Andrea TI Binge Eating Disorder: From Clinical Research to Clinical Practice SO JOURNAL OF ADDICTION MEDICINE LA English DT Editorial Material DE anticonvulsants; antidepressants; binge eating disorder; substance abuse treatment agents ID PLACEBO-CONTROLLED TRIAL; BULIMIA-NERVOSA; FOOD ADDICTION; OBESITY; NALTREXONE; ANTIDEPRESSANT; ZONISAMIDE AB This case report describes the clinical course of a young woman suffering from binge eating disorder (BED) associated with obesity. It illustrates the efficacy of different medications in the treatment of BED and related conditions and is followed by the comments and clinical observations of 2 practicing psychiatrists. The issues described in this paper have important clinical implications and are topical, given that BED is now recognized as a specific disorder in the new Diagnostic and Statistical Manual of Mental Disorders, fifth edition classification system, but neither the US Food and Drug Administration nor any other regulatory agency has yet approved a drug for treatment of this disease, despite its very prevalent and disabling nature. Growing evidence from the fields of psychopathology and neurobiology, including preclinical and clinical studies, converges to support the idea that "overeating" has much in common with other behavioral addictions, and substance abuse treatment agents may show promise for the treatment of BED. C1 [Goracci, Arianna; di Volo, Silvia; Bolognesi, Simone; Fagiolini, Andrea] Univ Siena, Sch Med, Dept Mol Med, Div Psychiat, I-53100 Siena, Italy. [Casamassima, Francesco] Univ Pisa, Dept Psychiat Neurobiol Pharmacol & Biotechnol, Pisa, Italy. [Iovieno, Nadia] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. [Benbow, Jim] Univ Washington, Sch Social Work, Seattle, WA 98195 USA. RP Goracci, A (reprint author), Univ Siena, Sch Med, Dept Neurosci, Div Psychiat, Viale Bracci 1, I-53100 Siena, Italy. EM agoracci@gmail.com OI FAGIOLINI, ANDREA/0000-0001-5827-0853 NR 23 TC 0 Z9 0 U1 1 U2 8 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 1932-0620 EI 1935-3227 J9 J ADDICT MED JI J. Addict. Med. PD JAN-FEB PY 2015 VL 9 IS 1 BP 20 EP 24 DI 10.1097/ADM.0000000000000085 PG 5 WC Substance Abuse SC Substance Abuse GA CB0TP UT WOS:000349340500002 PM 25629882 ER PT J AU Restrepo, P Jameson, DL Carroll, DL AF Restrepo, Paula Jameson, Deborah L. Carroll, Diane L. TI Improving Deep Vein Thrombosis Prophylaxis With Mechanical Modalities in Surgical Intensive Care Unit SO JOURNAL OF NURSING CARE QUALITY LA English DT Article DE deep vein thrombosis prophylaxis; graduated compression stockings; guidelines; intermittent pneumatic compression device; quality improvement; surgery ID GRADUATED COMPRESSION STOCKINGS; CLINICAL-PRACTICE GUIDELINES; RANDOMIZED CONTROLLED-TRIAL; ED AMERICAN-COLLEGE; ANTITHROMBOTIC THERAPY; PNEUMATIC COMPRESSION; PREVENTION; PHYSICIANS; MULTICENTER; RISK AB Deep vein thrombosis remains a source of adverse outcomes in surgical patients. Deep vein thrombosis is preventable with prophylactic intervention. The success of noninvasive mechanical modalities for prophylaxis relies on compliance with correct application. The goals of this project were to create a guideline that reflected current evidence and expert thinking about mechanical modalities use, assess compliance with mechanical modalities, and develop strategies to disseminate an evidence-based guideline for deep vein thrombosis prophylaxis. C1 [Restrepo, Paula] Massachusetts Gen Hosp, Patient Care Serv, Boston, MA 02114 USA. [Jameson, Deborah L.] Massachusetts Gen Hosp, Treadwell Lib, Boston, MA 02114 USA. [Carroll, Diane L.] Massachusetts Gen Hosp, Yvonne L Munn Ctr Nursing Res, Inst Patient Care, Boston, MA 02114 USA. RP Carroll, DL (reprint author), Massachusetts Gen Hosp, Yvonne L Munn Ctr Nursing Res, POB 430, Boston, MA 02114 USA. EM dcarroll3@mgh.harvard.edu FU NCRR NIH HHS [UL1 RR025758, UL1RR025758] NR 17 TC 0 Z9 0 U1 0 U2 5 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 1057-3631 EI 1550-5065 J9 J NURS CARE QUAL JI J. Nurs. Care Qual. PD JAN-MAR PY 2015 VL 30 IS 1 BP 31 EP 37 DI 10.1097/NCQ.0000000000000075 PG 7 WC Nursing SC Nursing GA CB3SR UT WOS:000349549300007 PM 24991980 ER PT J AU Bober, SL Recklitis, CJ Bakan, J Garber, JE Patenaude, AF AF Bober, Sharon L. Recklitis, Christopher J. Bakan, Jennifer Garber, Judy E. Patenaude, Andrea F. TI Addressing Sexual Dysfunction After Risk-Reducing Salpingo-Oophorectomy: Effects of a Brief, Psychosexual Intervention SO JOURNAL OF SEXUAL MEDICINE LA English DT Article DE Risk-Reducing Salpingo-Oophorectomy and Sexual Dysfunction; Sexual Health and Cancer; Quality of Life and Cancer ID QUALITY-OF-LIFE; FUNCTION INDEX FSFI; CANCER SURVIVORS; OVARIAN-CANCER; GYNECOLOGICAL CANCER; BRCA MUTATION; BODY-IMAGE; WOMEN; CARRIERS; THERAPY AB IntroductionWomen at high risk for ovarian cancer due to BRCA1 orBRCA2 mutation or family history are recommended to undergo risk-reducing salpingo-oophorectomy (RRSO) after age 35 or completion of childbearing. This potentially life-saving surgery leads to premature menopause, frequently resulting in distressing and unaddressed sexual dysfunction. AimTo pilot a novel sexual health intervention for women with BRCA1/2 mutations who previously underwent RRSO a using a single-arm trial. Feasibility and primary outcomes including sexual dysfunction and psychological distress were assessed. MethodsThis single-arm trial included a one-time, half-day educational session comprised of targeted sexual health education, body awareness and relaxation training, and mindfulness-based cognitive therapy strategies, followed by two sessions of tailored telephone counseling. Assessments were completed at baseline and 2 months postintervention. Main Outcome MeasureStudy end points include feasibility and effectiveness as reported by the participant. ResultsThirty-seven women completed baseline and postintervention assessments. At baseline, participants had a mean age of 44.4 (standard deviation [SD]=3.9) years and mean duration of 3.8 (SD=2.7) years since RRSO. Overall sexual functioning (P=0.018), as well as desire (P=0.003), arousal (P=0.003), satisfaction (P=0.028), and pain (P=0.018), improved significantly. There were significant reductions in somatization (P=0.029) and anxiety scores (P<0.001), and, overall, for the Global Severity Index (P<0.001) of the Brief Symptom Inventory. Sexual self-efficacy and sexual knowledge also improved significantly from baseline to postintervention (both P<0.001). Women were highly satisfied with the intervention content and reported utilizing new skills to manage sexual dysfunction. ConclusionsThis intervention integrates elements of cognitive behavioral therapy with sexual health education to address a much-neglected problem after RRSO. Results from this promising single-arm study provide preliminary data to move toward conducting a randomized, controlled trial. Bober SL, Recklitis CJ, Bakan J, Garber JE, and Patenaude AF. Addressing sexual dysfunction after risk-reducing salpingo-oophorectomy: Effects of a brief, psychosexual intervention. J Sex Med 2015;12:189-197. C1 [Bober, Sharon L.; Recklitis, Christopher J.; Bakan, Jennifer; Garber, Judy E.; Patenaude, Andrea F.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Bober, Sharon L.; Recklitis, Christopher J.; Garber, Judy E.; Patenaude, Andrea F.] Harvard Univ, Sch Med, Boston, MA 02115 USA. FU NCI NIH HHS [R03 CA153815, 1 R03 CA153815-01A1] NR 39 TC 8 Z9 8 U1 1 U2 6 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1743-6095 EI 1743-6109 J9 J SEX MED JI J. Sex. Med. PD JAN PY 2015 VL 12 IS 1 BP 189 EP 197 DI 10.1111/jsm.12713 PG 9 WC Urology & Nephrology SC Urology & Nephrology GA CA4CO UT WOS:000348852100021 PM 25311333 ER PT J AU Arora, P Reingold, J Baggish, A Guanaga, DP Wu, C Ghorbani, A Song, YN Chen-Tournaux, A Khan, AM Tainsh, LT Buys, ES Williams, JS Heublein, DM Burnett, JC Semigran, MJ Bloch, KD Scherrer-Crosbie, M Newton-Cheh, C Kaplan, LM Wang, TJ AF Arora, Pankaj Reingold, Jason Baggish, Aaron Guanaga, Derek P. Wu, Connie Ghorbani, Anahita Song, Yanna Chen-Tournaux, Annabel Khan, Abigail May Tainsh, Laurel T. Buys, Emmanuel S. Williams, Jonathan S. Heublein, Denise M. Burnett, John C. Semigran, Marc J. Bloch, Kenneth D. Scherrer-Crosbie, Marielle Newton-Cheh, Christopher Kaplan, Lee M. Wang, Thomas J. TI Weight Loss, Saline Loading, and the Natriuretic Peptide System SO JOURNAL OF THE AMERICAN HEART ASSOCIATION LA English DT Article DE natriuretic peptide; obesity; salt intake ID BODY-MASS INDEX; PLASMA-LEVELS; BLOOD-PRESSURE; OBESE SUBJECTS; EXPRESSION; ATRIAL; DISEASE; RISK; ECHOCARDIOGRAPHY; HYPERTENSION AB Background-In epidemiologic studies, obesity has been associated with reduced natriuretic peptide (NP) concentrations. Reduced NP production could impair the ability of obese individuals to respond to salt loads, increasing the risk of hypertension and other disorders. We hypothesized that weight loss enhances NP production before and after salt loading. Methods and Results-We enrolled 15 obese individuals (mean BMI 45 +/- 5.4 kg/m(2)) undergoing gastric bypass surgery. Before and 6 months after surgery, subjects were admitted to the clinical research center and administered a large-volume intravenous saline challenge. Echocardiography and serial blood sampling were performed. From the pre-operative visit to 6 months after surgery, subjects had a mean BMI decrease of 27%. At the 6-month visit, N-terminal pro-atrial NP (Nt-proANP) levels were 40% higher before, during, and after the saline infusion, compared with levels measured at the same time points during the pre-operative visit (P<0.001). The rise in Nt-pro-ANP induced by the saline infusion (approximate to 50%) was similar both before and after surgery (saline, P<0.001; interaction, P=0.2). Similar results were obtained for BNP and Nt-proBNP; resting concentrations increased by 50% and 31%, respectively, after gastric bypass surgery. The increase in NP concentrations after surgery was accompanied by significant decreases in mean arterial pressure (P=0.004) and heart rate (P<0.001), and an increase in mitral annular diastolic velocity (P=0.02). Conclusion-In obese individuals, weight loss is associated with a substantial increase in the "setpoint" of circulating NP concentrations. Higher NP concentrations could contribute to an enhanced ability to handle salt loads after weight loss. C1 [Arora, Pankaj] Univ Alabama Birmingham, Dept Med, Div Cardiol, Birmingham, AL USA. [Reingold, Jason] St Josephs Res Inst, Atlanta Cardiol & Primary Care, Atlanta, GA USA. [Baggish, Aaron; Guanaga, Derek P.; Ghorbani, Anahita; Semigran, Marc J.; Bloch, Kenneth D.; Scherrer-Crosbie, Marielle; Newton-Cheh, Christopher] Massachusetts Gen Hosp, Dept Med, Div Cardiol, Boston, MA 02114 USA. [Wu, Connie; Tainsh, Laurel T.; Buys, Emmanuel S.; Bloch, Kenneth D.] Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, Div Cardiol, Boston, MA 02114 USA. [Kaplan, Lee M.] Massachusetts Gen Hosp, Gastrointestinal Unit, Div Cardiol, Boston, MA 02114 USA. [Song, Yanna] Vanderbilt Univ, Dept Biostat, Nashville, TN 37235 USA. [Chen-Tournaux, Annabel] McGill Univ, Jewish Gen Hosp, Div Cardiol, Montreal, PQ H3T 1E2, Canada. [Khan, Abigail May] Univ Penn, Perelman Sch Med, Div Cardiovasc Med, Philadelphia, PA 19104 USA. [Williams, Jonathan S.] Brigham & Womens Hosp, Dept Med, Div Endocrinol Diabet & Hypertens, Boston, MA 02115 USA. [Heublein, Denise M.; Burnett, John C.] Mayo Clin, Div Cardiol, Rochester, MN USA. [Wang, Thomas J.] Vanderbilt Univ, Div Cardiovasc Med, Nashville, TN 37235 USA. RP Wang, TJ (reprint author), Vanderbilt Univ, Med Ctr, Div Cardiovasc Med, 2220 Pierce Ave,383 PRB, Nashville, TN 37232 USA. EM thomas.j.wang@vanderbilt.edu OI Arora, Pankaj/0000-0003-2420-3550 FU National Institutes of Health [R01 HL102780, R21 DK092909, 1 UL1 RR025758-01]; National Center for Research Resources; Foundation LeDucq FX This study has been supported by the following grants: R01 HL102780, R21 DK092909, and 1 UL1 RR025758-01 from the National Institutes of Health and the National Center for Research Resources. The research was also supported by a grant from the Foundation LeDucq. NR 26 TC 7 Z9 7 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 2047-9980 J9 J AM HEART ASSOC JI J. Am. Heart Assoc. PD JAN PY 2015 VL 4 IS 1 AR e001265 DI 10.1161/JAHA.114.001265 PG 6 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA CA0HI UT WOS:000348597500011 PM 25595796 ER PT J AU Landenhed, M Engstrom, G Gottsater, A Caulfield, MP Hedblad, B Newton-Cheh, C Melander, O Smith, JG AF Landenhed, Maya Engstrom, Gunnar Gottsater, Anders Caulfield, Michael P. Hedblad, Bo Newton-Cheh, Christopher Melander, Olle Smith, J. Gustav TI Risk Profiles for Aortic Dissection and Ruptured or Surgically Treated Aneurysms: A Prospective Cohort Study SO JOURNAL OF THE AMERICAN HEART ASSOCIATION LA English DT Article DE aneurysm; aorta; dissection; epidemiology; risk factor ID INTERNATIONAL REGISTRY; PRACTICE GUIDELINES; EUROPEAN-SOCIETY; TASK-FORCE; DISEASE; MANAGEMENT; HEALTH; IRAD; VALIDATION; SURGERY AB Background-Community screening to guide preventive interventions for acute aortic disease has been recommended in high-risk individuals. We sought to prospectively assess risk factors in the general population for aortic dissection (AD) and severe aneurysmal disease in the thoracic and abdominal aorta. Methods and Results-We studied the incidence of AD and ruptured or surgically treated aneurysms in the abdominal (AAA) or thoracic aorta (TAA) in 30 412 individuals without diagnosis of aortic disease at baseline from a contemporary, prospective cohort of middle-aged individuals, the Malmo Diet and Cancer study. During up to 20 years of follow-up (median 16 years), the incidence rate per 100 000 patient-years at risk was 15 (95% CI 11.7 to 18.9) for AD, 27 (95% CI 22.5 to 32.1) for AAA, and 9 (95% CI 6.8 to 12.6) for TAA. The acute and in-hospital mortality was 39% for AD, 34% for ruptured AAA, and 41% for ruptured TAA. Hypertension was present in 86% of individuals who subsequently developed AD, was strongly associated with incident AD (hazard ratio [HR] 2.64, 95% CI 1.33 to 5.25), and conferred a population-attributable risk of 54%. Hypertension was also a risk factor for AAA with a smaller effect. Smoking (HR 5.07, 95% CI 3.52 to 7.29) and high apolipoprotein B/A1 ratio (HR 2.48, 95% CI 1.73 to 3.54) were strongly associated with AAA and conferred a population-attributable risk of 47% and 25%, respectively. Smoking was also a risk factor for AD and TAA with smaller effects. Conclusions-This large prospective study identified distinct risk factor profiles for different aortic diseases in the general population. Hypertension accounted for more than half of the population risk for AD, and smoking for half of the population risk of AAA. C1 [Landenhed, Maya] Lund Univ, Dept Cardiothorac Surg, S-22185 Lund, Sweden. [Smith, J. Gustav] Lund Univ, Dept Cardiol, S-22185 Lund, Sweden. Skane Univ Hosp, Lund, Sweden. [Engstrom, Gunnar; Hedblad, Bo; Smith, J. Gustav] Lund Univ, Dept Clin Sci, Malmo, Sweden. [Gottsater, Anders] Skane Univ Hosp, Vasc Ctr, Malmo, Sweden. [Caulfield, Michael P.] Quest Diagnost Nichols Inst, Dept Endocrinol, San Juan Capistrano, CA USA. [Caulfield, Michael P.] Quest Diagnost Nichols Inst, CVD, San Juan Capistrano, CA USA. [Newton-Cheh, Christopher; Smith, J. Gustav] Harvard Univ, Sch Med, Cardiovasc Res Ctr, Boston, MA USA. [Newton-Cheh, Christopher; Smith, J. Gustav] Harvard Univ, Sch Med, Ctr Human Genet Res, Boston, MA USA. [Newton-Cheh, Christopher; Smith, J. Gustav] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Newton-Cheh, Christopher; Smith, J. Gustav] Broad Inst Harvard & MIT, Cambridge, MA USA. [Melander, Olle] Lund Univ, Dept Internal Med, Malmo, Sweden. [Melander, Olle] Skane Univ Hosp, Malmo, Sweden. RP Landenhed, M (reprint author), Lund Univ, Dept Cardiothorac Surg, S-22185 Lund, Sweden. EM maya.landenhed@med.lu.se OI Engstrom, Gunnar/0000-0002-8618-9152 FU Swedish Cancer Society; Swedish Medical Research Council; Swedish Dairy Association; Albert Pahlsson and Gunnar Nilsson Foundations; Malmo City Council; Hulda Almroths Research Foundation; Skane University Hospital in Malmo; Ernhold Lundstroms Research Foundation; US National Institutes of Health [HL080025, HL098283]; Burroughs Wellcome Fund; Medical Faculty of Lund University; Albert Pahlsson Research Foundation; Crafoord Foundation; Swedish National Health Service; Hulda and Conrad Mossfelt Foundation; King Gustaf V and Queen Victoria Fund; Lennart Hanssons Memorial Fund; Marianne and Marcus Wallenberg Foundation; Knut and Alice Wallenberg Foundation; Swedish Heart-Lung Foundation; Swedish Research Council; Skane University Hospital in Lund; Quest Diagnostics FX The MDCS was made possible by grants from the Swedish Cancer Society, the Swedish Medical Research Council, the Swedish Dairy Association, the Albert Pahlsson and Gunnar Nilsson Foundations, and the Malmo City Council. Dr Gottsater was supported by the Hulda Almroths Research Foundation. Drs Gottsater and Melander were supported by Skane University Hospital in Malmo and the Ernhold Lundstroms Research Foundation. Drs Hedblad and Melander were supported by the Swedish Medical Research Council. Dr Newton-Cheh was supported by grants from the US National Institutes of Health (HL080025, HL098283) and the Burroughs Wellcome Fund. Dr Melander was supported by grants from the Medical Faculty of Lund University, the Albert Pahlsson Research Foundation, the Crafoord Foundation, the Swedish National Health Service, the Hulda and Conrad Mossfelt Foundation, the King Gustaf V and Queen Victoria Fund, the Lennart Hanssons Memorial Fund, the Marianne and Marcus Wallenberg Foundation, and the Knut and Alice Wallenberg Foundation. Dr Smith was supported by the Swedish Heart-Lung Foundation, the Swedish Research Council, the Crafoord Foundation, the Swedish National Health Service, and Skane University Hospital in Lund. Measurement of apolipoproteins was performed and supported by Quest Diagnostics. The funding sources had no role in the study design; in the collection, analysis, and interpretation of data; in the writing of the report; or in the decision to submit the manuscript for publication. NR 41 TC 20 Z9 21 U1 1 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 2047-9980 J9 J AM HEART ASSOC JI J. Am. Heart Assoc. PD JAN PY 2015 VL 4 IS 1 AR e001513 DI 10.1161/JAHA.114.001513 PG 10 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA CA0HI UT WOS:000348597500017 PM 25609416 ER PT J AU Shaefi, S O'Gara, B Kociol, RD Joynt, K Mueller, A Nizamuddin, J Mahmood, E Talmor, D Shahul, S AF Shaefi, Shahzad O'Gara, Brian Kociol, Robb D. Joynt, Karen Mueller, Ariel Nizamuddin, Junaid Mahmood, Eitezaz Talmor, Daniel Shahul, Sajid TI Effect of Cardiogenic Shock Hospital Volume on Mortality in Patients With Cardiogenic Shock SO JOURNAL OF THE AMERICAN HEART ASSOCIATION LA English DT Article DE acute coronary syndromes; cardiogenic shock; hospital volume ID ACUTE MYOCARDIAL-INFARCTION; PERCUTANEOUS CORONARY INTERVENTION; TO-BALLOON TIME; MECHANICAL VENTILATION; ADMINISTRATIVE DATA; HEART-FAILURE; CARE UNITS; OUTCOMES; SUPPORT; ANGIOPLASTY AB Background-Cardiogenic shock (CS) is associated with significant morbidity, and mortality rates approach 40% to 60%. Treatment for CS requires an aggressive, sophisticated, complex, goal-oriented, therapeutic regimen focused on early revascularization and adjunctive supportive therapies, suggesting that hospitals with greater CS volume may provide better care. The association between CS hospital volume and inpatient mortality for CS is unclear. Methods and Results-We used the Nationwide Inpatient Sample to examine 533 179 weighted patient discharges from 2675 hospitals with CS from 2004 to 2011 and divided them into quartiles of mean annual hospital CS case volume. The primary outcome was in-hospital mortality. Multivariate adjustments were performed to account for severity of illness, relevant comorbidities, hospital characteristics, and differences in treatment. Compared with the highest volume quartile, the adjusted odds ratio for inpatient mortality for persons admitted to hospitals in the lowest-volume quartile (<= 27 weighted cases per year) was 1.27 (95% CI 1.15 to 1.40), whereas for admission to hospitals in the low-volume and medium-volume quartiles, the odds ratios were 1.20 (95% CI 1.08 to 1.32) and 1.12 (95% CI 1.01 to 1.24), respectively. Similarly, improved survival was observed across quartiles, with an adjusted inpatient mortality incidence of 41.97% (95% CI 40.87 to 43.08) for hospitals with the lowest volume of CS cases and a drop to 37.01% (95% CI 35.11 to 38.96) for hospitals with the highest volume of CS cases. Analysis of treatments offered between hospital quartiles revealed that the centers with volumes in the highest quartile demonstrated significantly higher numbers of patients undergoing coronary artery bypass grafting, percutaneous coronary intervention, or intra-aortic balloon pump counterpulsation. A similar relationship was demonstrated with the use of mechanical circulatory support (ventricular assist devices and extracorporeal membrane oxygenation), for which there was significantly higher use in the higher volume quartiles. Conclusions-We demonstrated an association between lower CS case volume and higher mortality. There is more frequent use of both standard supportive and revascularization techniques at the higher volume centers. Future directions may include examining whether early stabilization and transfer improve outcomes of patients with CS who are admitted to lower volume centers. C1 [Shaefi, Shahzad; O'Gara, Brian; Mueller, Ariel; Nizamuddin, Junaid; Mahmood, Eitezaz; Talmor, Daniel; Shahul, Sajid] Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Dept Anesthesia Crit Care & Pain Med, Boston, MA 02215 USA. [Kociol, Robb D.] Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Cardiovasc Inst,Dept Med, Boston, MA 02215 USA. [Joynt, Karen] Harvard Univ, Brigham & Womens Hosp, Sch Med, Div Cardiovasc Med,Dept Med, Boston, MA 02115 USA. RP Shahul, S (reprint author), Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Dept Anesthesia Crit Care & Pain Med, Boston, MA 02215 USA. EM sshahul@bidmc.harvard.edu FU Foundation for Anesthesia Research (FAER); Beth Israel Deaconess Department of Anesthesia; Critical Care and Pain Medicine; Center for Anesthesia Research Excellence (CARE) FX This study was supported by Foundation for Anesthesia Research (FAER), Beth Israel Deaconess Department of Anesthesia, Critical Care and Pain Medicine, Center for Anesthesia Research Excellence (CARE). NR 34 TC 4 Z9 4 U1 1 U2 3 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 2047-9980 J9 J AM HEART ASSOC JI J. Am. Heart Assoc. PD JAN PY 2015 VL 4 IS 1 AR e001462 DI 10.1161/JAHA.114.001462 PG 9 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA CA0HI UT WOS:000348597500023 PM 25559014 ER PT J AU Waks, JW Soliman, EZ Henrikson, CA Sotoodehnia, N Han, L Agarwal, SK Arking, DE Siscovick, DS Solomon, SD Post, WS Josephson, ME Coresh, J Tereshchenko, LG AF Waks, Jonathan W. Soliman, Elsayed Z. Henrikson, Charles A. Sotoodehnia, Nona Han, Lichy Agarwal, Sunil K. Arking, Dan E. Siscovick, David S. Solomon, Scott D. Post, Wendy S. Josephson, Mark E. Coresh, Josef Tereshchenko, Larisa G. TI Beat-to-Beat Spatiotemporal Variability in the T Vector Is Associated With Sudden Cardiac Death in Participants Without Left Ventricular Hypertrophy: The Atherosclerosis Risk in Communities (ARIC) Study SO JOURNAL OF THE AMERICAN HEART ASSOCIATION LA English DT Article DE atherosclerosis; electrocardiography; electrophysiology; epidemiology; sudden cardiac death; TT' angle ID CORONARY-HEART-DISEASE; VECTORCARDIOGRAPHIC LOOP ALIGNMENT; REPOLARIZATION VARIABILITY; QT VARIABILITY; ECG; ELECTROCARDIOGRAM; ANGLE; STRATIFICATION; MECHANISMS; PREDICTION AB Background-Despite advances in prevention and treatment of cardiovascular disease, sudden cardiac death (SCD) remains a clinical challenge. Risk stratification in the general population is needed. Methods and Results-Beat-to-beat spatiotemporal variability in the T vector was measured as the mean angle between consecutive T-wave vectors (mean TT' angle) on standard 12-lead ECGs in 14 024 participants in the Atherosclerosis Risk in Communities (ARIC) study. Subjects with left ventricular hypertrophy, atrial arrhythmias, frequent ectopy, ventricular pacing, or QRS duration >= 120 ms were excluded. The mean spatial TT' angle was 5.21 +/- 3.55 degrees. During a median of 14 years of follow-up, 235 SCDs occurred (1.24 per 1000 person-years). After adjustment for demographics, coronary heart disease risk factors, and known ECG markers for SCD, mean TT' angle was independently associated with SCD (hazard ratio 1.089; 95% CI 1.044 to 1.137; P<0.0001). A mean TT' angle >90th percentile (>9.57 degrees) was associated with a 2-fold increase in the hazard for SCD (hazard ratio 2.01; 95% CI 1.28 to 3.16; P=0.002). In a subgroup of patients with T-vector amplitude >= 0.2 mV, the association with SCD was almost twice as strong (hazard ratio 3.92; 95% CI 1.91 to 8.05; P<0.0001). A significant interaction between mean TT' angle and age was found: TT' angle was associated with SCD in participants aged <55 years (hazard ratio 1.096; 95% CI 0.043 to 1.152; P<0.0001) but not in participants aged >= 55 years (P-interaction=0.009). Conclusions-In a large, prospective, community-based cohort of left ventricular hypertrophy-free participants, increased beat-to-beat spatiotemporal variability in the T vector, as assessed by increasing TT' angle, was associated with SCD. C1 [Waks, Jonathan W.; Josephson, Mark E.] Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Div Cardiovasc Med, Boston, MA USA. [Soliman, Elsayed Z.] Epidemiol Cardiol Res Ctr EPICARE, Div Publ Hlth Sci, Winston Salem, NC USA. [Soliman, Elsayed Z.] Wake Forest Sch Med, Dept Med, Cardiol Sect, Winston Salem, NC USA. [Henrikson, Charles A.; Tereshchenko, Larisa G.] Oregon Hlth & Sci Univ, Knight Cardiovascular Inst, Portland, OR 97201 USA. [Sotoodehnia, Nona; Siscovick, David S.] Univ Washington, Seattle, WA 98195 USA. [Han, Lichy] Johns Hopkins Univ, Whitening Sch Engn, Baltimore, MD USA. [Agarwal, Sunil K.; Coresh, Josef] Johns Hopkins Sch Publ Hlth, Dept Epidemiol, Baltimore, MD USA. [Agarwal, Sunil K.; Coresh, Josef] Johns Hopkins Sch Publ Hlth, Welch Ctr Prevent Epidemiol & Clin Res, Baltimore, MD USA. [Arking, Dan E.] Johns Hopkins Univ, Sch Med, McKusick Nathans Inst Genet Med, Baltimore, MD USA. [Post, Wendy S.; Tereshchenko, Larisa G.] Johns Hopkins Univ, Sch Med, Dept Med, Div Cardiol, Baltimore, MD 21205 USA. [Solomon, Scott D.] Harvard Univ, Sch Med, Brigham & Womens Hosp, Boston, MA USA. [Siscovick, David S.] New York Acad Med, New York, NY USA. RP Tereshchenko, LG (reprint author), 3181 SW Sam Jackson Pk Rd,UHN62, Portland, OR 97239 USA. EM tereshch@ohsu.edu OI Tereshchenko, Larisa/0000-0002-6976-1313 FU National Institutes of Health (NIH) [HHSN268201100005C, HHSN268201100006C, HHSN268201100007C, HHSN2682 01100008C, HHSN268201100009C, HHSN268201100010C, HHSN268201100011C, HHSN268201100012C, 1R01HL118277]; Johns Hopkins Institute for Clinical and Translational Research grant FX The Atherosclerosis Risk in Communities study is carried out as a collaborative study supported by the National Institutes of Health (NIH) contracts (HHSN268201100005C, HHSN268201100006C, HHSN268201100007C, HHSN268201100008C, HHSN268201100009C, HHSN268201100010C, HHSN268201100011C, and HHSN268201100012C). This work was supported by the NIH (1R01HL118277) and the Johns Hopkins Institute for Clinical and Translational Research grant (Tereshchenko). NR 45 TC 6 Z9 6 U1 0 U2 2 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 2047-9980 J9 J AM HEART ASSOC JI J. Am. Heart Assoc. PD JAN PY 2015 VL 4 IS 1 AR e001357 DI 10.1161/JAHA.114.001357 PG 11 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA CA0HI UT WOS:000348597500005 PM 25600143 ER PT J AU Perl, L Zemer-Wassercug, N Rechavia, E Vaduganathan, M Orvin, K Weissler-Snir, A Lerman-Shivek, H Kornowski, R Lev, EI AF Perl, Leor Zemer-Wassercug, Noa Rechavia, Eldad Vaduganathan, Muthiah Orvin, Katia Weissler-Snir, Adaya Lerman-Shivek, Hila Kornowski, Ran Lev, Eli I. TI Comparison of platelet inhibition by prasugrel versus ticagrelor over time in patients with acute myocardial infarction SO JOURNAL OF THROMBOSIS AND THROMBOLYSIS LA English DT Article DE Prasugrel; Ticagrelor; Platelet reactivity; Acute myocardial infarction ID PERCUTANEOUS CORONARY INTERVENTION; ASPIRIN-TREATED PATIENTS; ARTERY-DISEASE; ADENOSINE-DIPHOSPHATE; RETICULATED PLATELETS; CARDIOVASCULAR EVENTS; CLOPIDOGREL; REACTIVITY; CYP2C19; IMPACT AB High on-treatment platelet reactivity (HTPR) despite use of P2Y12 antagonists is associated with adverse cardiac events. The long-term variability in response to prasugrel and ticagrelor is unclear. Our aim was to assess residual platelet reactivity (PR) and rates of HTPR during treatment with prasugrel versus ticagrelor in patients with myocardial infarction (MI). 114 patients with MI treated with percutaneous coronary intervention (PCI) were included. Sixty-two patients were treated with prasugrel (mean age 58 +/- 8 years, 21 % women, 29 % diabetes), and 52 patients with ticagrelor (mean age 63 +/- 9, 19 % women, 37 % diabetes). Patients were tested for PR at 2-4 days and 30 days post-PCI, using the VerifyNow P2Y12 assay and the multiple-electrode aggregometry. Our results show a higher residual PR in patients treated with prasugrel than those treated with ticagrelor (VerifyNow: 65.4 +/- 60.6 vs. 26.0 +/- 24.2 P2Y12 reaction units, p < 0.001 at 2-4 days, and 67.3 +/- 62.5 vs. 21.1 +/- 26.1, p < 0.001 at follow-up). HTPR rates were higher in the prasugrel group (8.1-11.3 % vs. none with ticagrelor in the early test, and 8.7-10.9 % vs. none with ticagrelor at follow-up). In conclusion, in patients with MI undergoing PCI, treatment with ticagrelor resulted in greater platelet inhibition and lower HTPR rates compared with prasugrel, up to 30 days after the event. C1 [Perl, Leor; Zemer-Wassercug, Noa; Rechavia, Eldad; Orvin, Katia; Weissler-Snir, Adaya; Kornowski, Ran; Lev, Eli I.] Rabin Med Ctr, Dept Cardiol, IL-49100 Petah Tiqwa, Israel. [Perl, Leor; Zemer-Wassercug, Noa; Rechavia, Eldad; Orvin, Katia; Weissler-Snir, Adaya; Kornowski, Ran; Lev, Eli I.] Tel Aviv Univ, Sackler Fac Med, IL-69978 Tel Aviv, Israel. [Vaduganathan, Muthiah] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Med, Boston, MA USA. [Lerman-Shivek, Hila] Hebrew Univ Jerusalem, Sch Pharm, Dept Clin Pharm, IL-91120 Jerusalem, Israel. RP Lev, EI (reprint author), Rabin Med Ctr, Dept Cardiol, Jabotinski St 39, IL-49100 Petah Tiqwa, Israel. EM elil@clalit.org.il NR 31 TC 9 Z9 9 U1 0 U2 4 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0929-5305 EI 1573-742X J9 J THROMB THROMBOLYS JI J. Thromb. Thrombolysis PD JAN PY 2015 VL 39 IS 1 BP 1 EP 7 DI 10.1007/s11239-014-1119-9 PG 7 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA CA1GH UT WOS:000348660300001 PM 25085573 ER PT J AU Halaby, R Popma, CJ Cohen, A Chi, G Zacarkim, MR Romero, G Goldhaber, SZ Hull, R Hernandez, A Mentz, R Harrington, R Lip, G Peacock, F Welker, J Martin-Loeches, I Daaboul, Y Korjian, S Gibson, CM AF Halaby, Rim Popma, Christopher J. Cohen, Ander Chi, Gerald Zacarkim, Marcelo Rodrigues Romero, Gonzalo Goldhaber, Samuel Z. Hull, Russell Hernandez, Adrian Mentz, Robert Harrington, Robert Lip, Gregory Peacock, Frank Welker, James Martin-Loeches, Ignacio Daaboul, Yazan Korjian, Serge Gibson, C. Michael TI D-Dimer elevation and adverse outcomes SO JOURNAL OF THROMBOSIS AND THROMBOLYSIS LA English DT Review DE D-Dimer; Deep vein thrombosis; Mortality; Prognosis; Pulmonary embolism ID POSTOPERATIVE VENOUS THROMBOEMBOLISM; COMMUNITY-ACQUIRED PNEUMONIA; ACUTE AORTIC DISSECTION; CRITICALLY-ILL PATIENTS; DEEP-VEIN THROMBOSIS; LUNG-CANCER PATIENTS; PLASMA D-DIMER; PULMONARY-EMBOLISM; RISK-FACTORS; ANTICOAGULANT-THERAPY AB D-Dimer is a biomarker of fibrin formation and degradation. While a D-dimer within normal limits is used to rule out the diagnosis of deep venous thrombosis and pulmonary embolism among patients with a low clinical probability of venous thromboembolism (VTE), the prognostic association of an elevated D-dimer with adverse outcomes has received far less emphasis. An elevated D-dimer is independently associated with an increased risk for incident VTE, recurrent VTE, and mortality. An elevated D-dimer is an independent correlate of increased mortality and subsequent VTE across a broad variety of disease states. Therefore, medically ill subjects in whom the D-dimer is elevated constitute a high risk subgroup in which the prospective evaluation of the efficacy and safety of antithrombotic therapy is warranted. C1 [Halaby, Rim; Popma, Christopher J.; Chi, Gerald; Zacarkim, Marcelo Rodrigues; Romero, Gonzalo; Daaboul, Yazan; Korjian, Serge; Gibson, C. Michael] Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Div Cardiovasc,Dept Med, Boston, MA 02215 USA. [Cohen, Ander] Kings Coll Hosp London, London, England. [Goldhaber, Samuel Z.] Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Med,Div Cardiovasc, Boston, MA 02215 USA. [Hull, Russell] Foothills Prov Gen Hosp, Dept Med Calgary, Calgary, AB T2N 2T9, Canada. [Hernandez, Adrian; Mentz, Robert] Duke Univ, Med Ctr, Dept Med, Div Cardiol, Durham, NC 27710 USA. [Harrington, Robert] Stanford Univ, Dept Med, Stanford, CA 94305 USA. [Lip, Gregory] Univ Birmingham, City Hosp, Ctr Cardiovasc Sci, Birmingham, W Midlands, England. [Peacock, Frank] Baylor Coll Med, Emergency Dept, Houston, TX 77030 USA. [Welker, James] Univ Maryland, Sch Med, Anne Arundel Hlth Syst Res Inst, Anne Arundel Med Ctr, Baltimore, MD 21201 USA. [Martin-Loeches, Ignacio] Corp Sanitaria I Univ Parc, Tauli Hosp Sabadell Parc Tauli, Crit Care Ctr, Barcelona, Spain. RP Gibson, CM (reprint author), Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Div Cardiovasc,Dept Med, East Campus,RW 459, Boston, MA 02215 USA. EM charlesmichaelgibson@gmail.com RI Hernandez, Adrian F./A-7818-2016; OI Hernandez, Adrian F./0000-0003-3387-9616; Chi, Gerald/0000-0002-8371-1689 NR 51 TC 3 Z9 6 U1 2 U2 7 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0929-5305 EI 1573-742X J9 J THROMB THROMBOLYS JI J. Thromb. Thrombolysis PD JAN PY 2015 VL 39 IS 1 BP 55 EP 59 DI 10.1007/s11239-014-1101-6 PG 5 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA CA1GH UT WOS:000348660300008 PM 25006010 ER PT J AU Quesada, CJG Giugliano, RP AF Quesada, Carlos J. Gonzalez Giugliano, Robert P. TI Selecting an oral anticoagulant for patients with nonvalvular atrial fibrillation SO JOURNAL OF THROMBOSIS AND THROMBOLYSIS LA English DT Article DE Atrial fibrillation; Dabigatran; Apixaban; Rivaroxaban; Edoxaban; Warfarin ID WARFARIN; METAANALYSIS AB While the use of warfarin has been the cornerstone of thromboembolism prevention in patients with atrial fibrillation (AF), its limitations have led to the introduction of a new generation of direct-acting oral anticoagulants. Evidence from large phase III clinical trials, observational studies and pharmacokinetic analyses can guide clinicians to select the most effective and safest form of anticoagulation for patients with nonvalvular AF. This manuscript describes the main pharmacologic, clinical and epidemiological characteristics of each new oral anticoagulant and their use in selected clinical scenarios, including patients with: advanced age; at low or high risk of stroke; potential drug-drug interactions; on concomitant antiplatelet therapy; at high risk for acute coronary syndrome; with recent gastrointestinal bleeding; with renal impairment; and with hepatic dysfunction. C1 [Quesada, Carlos J. Gonzalez] Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. [Giugliano, Robert P.] Brigham & Womens Hosp, TIMI Study Grp, Div Cardiovasc Med, Boston, MA 02115 USA. RP Giugliano, RP (reprint author), Brigham & Womens Hosp, TIMI Study Grp, Div Cardiovasc Med, 350 Longwood Ave 1st Floor Off, Boston, MA 02115 USA. EM carlosjgquesada@mail.harvard.edu; rgiugliano@partners.org FU Daiichi Sankyo; Janssen Pharmaceuticals; Merck; Portola; Bristol-Myers Squibb; Sanofi; Johnson Johnson; AstraZeneca FX Dr. Gonzalez Quesada reports no conflict of interests. Dr. Giugliano reports receiving consulting fees from Daiichi Sankyo, Janssen Pharmaceuticals, Merck, and Portola; lecture fees from Bristol-Myers Squibb, Daiichi Sankyo, Merck, and Sanofi; and Grant support through his institution from Daiichi Sankyo, Merck, Johnson & Johnson, Sanofi, and AstraZeneca. NR 10 TC 2 Z9 2 U1 0 U2 2 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0929-5305 EI 1573-742X J9 J THROMB THROMBOLYS JI J. Thromb. Thrombolysis PD JAN PY 2015 VL 39 IS 1 BP 129 EP 138 DI 10.1007/s11239-014-1148-4 PG 10 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA CA1GH UT WOS:000348660300018 ER PT J AU Goral, VN Au, SH Faris, RA Yuen, PK AF Goral, Vasiliy N. Au, Sam H. Faris, Ronald A. Yuen, Po Ki TI Methods for advanced hepatocyte cell culture in microwells utilizing air bubbles SO LAB ON A CHIP LA English DT Article ID MULTICELLULAR SPHEROIDS; PERFUSION-CULTURE; GROWTH; SYSTEM; ARRAY AB Flat, two-dimensional (2D) cell culture substrates are simple to use but offer little control over cell morphologies and behavior. In this article, we present a number of novel and unique methods for advanced cell culture in microwells utilizing air bubbles as a way to seed cells in order to provide substantial control over cellular microenvironments and organization to achieve specific cell-based applications. These cell culture methods enable controlled formation of stable air bubbles in the microwells that spontaneously formed when polar solvents such as cell culture media are loaded. The presence of air bubbles (air bubble masking) enables highly controllable cell patterning and organization of seeded cells as well as cell co-culture in microwells. In addition, these cell culture methods are simple to use and implement, yet versatile, and have the potential to provide a wide range of microenvironments to improve in vivo-like behavior for a number of cell types and applications. The air bubble masking technique can also be used to produce a micron thick layer of collagen film suspended on top of the microwells. These collagen film enclosed microwells could provide an easy way for high throughput drug screening and cytotoxicity assays as different drug compounds could be pre-loaded and dried in selected microwells and then released during cell culture. C1 [Goral, Vasiliy N.; Faris, Ronald A.; Yuen, Po Ki] Corning Inc, Sci & Technol, Corning, NY 14831 USA. [Au, Sam H.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Charlestown, MA 02129 USA. RP Goral, VN (reprint author), Corning Inc, Sci & Technol, Corning, NY 14831 USA. EM goralvn@corning.com; yuenp@corning.com NR 18 TC 2 Z9 2 U1 3 U2 16 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 2015 VL 15 IS 4 BP 1032 EP 1037 DI 10.1039/c4lc01178c PG 6 WC Biochemical Research Methods; Chemistry, Multidisciplinary; Nanoscience & Nanotechnology SC Biochemistry & Molecular Biology; Chemistry; Science & Technology - Other Topics GA CB1QY UT WOS:000349404200011 PM 25474691 ER PT J AU Ng, EX Miller, MA Jing, TY Lauffenburger, DA Chen, CH AF Ng, Ee Xien Miller, Miles A. Jing, Tengyang Lauffenburger, Doug A. Chen, Chia-Hung TI Low-volume multiplexed proteolytic activity assay and inhibitor analysis through a pico-injector array SO LAB ON A CHIP LA English DT Article ID BREAST-CANCER CELLS; EPIDERMAL-GROWTH-FACTOR; MICROFLUIDIC PLATFORM; DROPLETS; GENERATION; ADAM10; METALLOPROTEINASE-9; EXPRESSION; ADAM-10; MODEL AB Secreted active proteases, from families of enzymes such as matrix metalloproteinases (MMPs) and ADAMs (a disintegrin and metalloproteinases), participate in diverse pathological processes. To simultaneously measure multiple specific protease activities, a series of parallel enzyme reactions combined with a series of inhibitor analyses for proteolytic activity matrix analysis (PrAMA) are essential but limited due to the sample quantity requirements and the complexity of performing multiple reactions. To address these issues, we developed a pico-injector array to generate 72 different reactions in picoliter-volume droplets by controlling the sequence of combinational injections, which allowed simultaneous recording of a wide range of multiple enzyme reactions and measurement of inhibitor effects using small sample volumes (similar to 10 mu L). Multiple MMP activities were simultaneously determined by 9 different substrates and 2 inhibitors using injections from a pico-injector array. Due to the advantages of inhibitor analysis, the MMP/ADAM activities of MDA-MB-231, a breast cancer cell line, were characterized with high MMP-2, MMP-3 and ADAM-10 activity. This platform could be customized for a wide range of applications that also require multiple reactions with inhibitor analysis to enhance the sensitivity by encapsulating different chemical sensors. C1 [Ng, Ee Xien; Jing, Tengyang; Chen, Chia-Hung] Natl Univ Singapore, Dept Biomed Engn, Singapore 117575, Singapore. [Miller, Miles A.] Massachusetts Gen Hosp, Ctr Syst Biol, Boston, MA 02114 USA. [Miller, Miles A.; Lauffenburger, Doug A.] MIT, Dept Biol Engn, Cambridge, MA 02139 USA. [Jing, Tengyang] Singapore MIT Alliance Res & Technol SMART Ctr, Singapore 1385602, Singapore. [Chen, Chia-Hung] Singapore Inst Neurotechnol SINAPSE, Singapore 117456, Singapore. RP Chen, CH (reprint author), Natl Univ Singapore, Dept Biomed Engn, 9 Engn Dr 1, Singapore 117575, Singapore. EM biecch@nus.edu.sg FU NUS start-up grant [R-397-000-137-133]; NUS Engineering-Medicine Seed grant [R-397-000-152-112]; MOE Tier-1 [R-397-000-153-112]; Singapore MIT Alliance for Research and Technology (SMART) research [R-397-000-146-592] FX We gratefully acknowledge the funding provided by the NUS start-up grant R-397-000-137-133, NUS Engineering-Medicine Seed grant R-397-000-152-112, MOE Tier-1 R-397-000-153-112 the Singapore MIT Alliance for Research and Technology (SMART) research grant R-397-000-146-592, and the facilities provided by Singapore Institute for Neurotechnology (SINAPSE). NR 34 TC 7 Z9 7 U1 3 U2 15 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 2015 VL 15 IS 4 BP 1153 EP 1159 DI 10.1039/c4lc01162g PG 7 WC Biochemical Research Methods; Chemistry, Multidisciplinary; Nanoscience & Nanotechnology SC Biochemistry & Molecular Biology; Chemistry; Science & Technology - Other Topics GA CB1QY UT WOS:000349404200026 PM 25553996 ER PT S AU Haake, DA Levett, PN AF Haake, David A. Levett, Paul N. BE Adler, B TI Leptospirosis in Humans SO LEPTOSPIRA AND LEPTOSPIROSIS SE Current Topics in Microbiology and Immunology LA English DT Review; Book Chapter ID ACUTE-RENAL-FAILURE; LINKED-IMMUNOSORBENT-ASSAY; INTERROGANS SEROVAR ICTEROHAEMORRHAGIAE; LATEX AGGLUTINATION ASSAY; POLYMERASE-CHAIN-REACTION; QUANTITATIVE PCR ASSAY; TANDEM-REPEAT ANALYSIS; ACUTE FEBRILE ILLNESS; ACUTE KIDNEY INJURY; REAL-TIME PCR AB Leptospirosis is a widespread and potentially fatal zoonosis that is endemic in many tropical regions and causes large epidemics after heavy rainfall and flooding. Infection results from direct or indirect exposure to infected reservoir host animals that carry the pathogen in their renal tubules and shed pathogenic leptospires in their urine. Although many wild and domestic animals can serve as reservoir hosts, the brown rat (Rattus norvegicus) is the most important source of human infections. Individuals living in urban slum environments characterized by inadequate sanitation and poor housing are at high risk of rat exposure and leptospirosis. The global burden of leptospirosis is expected to rise with demographic shifts that favor increases in the number of urban poor in tropical regions subject to worsening storms and urban flooding due to climate change. Data emerging from prospective surveillance studies suggest that most human leptospiral infections in endemic areas are mild or asymptomatic. Development of more severe outcomes likely depends on three factors: epidemiological conditions, host susceptibility, and pathogen virulence (Fig. 1). Mortality increases with age, particularly in patients older than 60 years of age. High levels of bacteremia are associated with poor clinical outcomes and, based on animal model and in vitro studies, are related in part to poor recognition of leptospiral LPS by human TLR4. Patients with severe leptospirosis experience a cytokine storm characterized by high levels of IL-6, TNF-alpha, and IL-10. Patients with the HLA DQ6 allele are at higher risk of disease, suggesting a role for lymphocyte stimulation by a leptospiral superantigen. Leptospirosis typically presents as a nonspecific, acute febrile illness characterized by fever, myalgia, and headache and may be confused with other entities such as influenza and dengue fever. Newer diagnostic methods facilitate early diagnosis and antibiotic treatment. Patients progressing to multisystem organ failure have widespread hematogenous dissemination of pathogens. Nonoliguric (high output) renal dysfunction should be supported with fluids and electrolytes. When oliguric renal failure occurs, prompt initiation of dialysis can be life saving. Elevated bilirubin levels are due to hepatocellular damage and disruption of intercellular junctions between hepatocytes, resulting in leaking of bilirubin out of bile caniliculi. Hemorrhagic complications are common and are associated with coagulation abnormalities. Severe pulmonary hemorrhage syndrome due to extensive alveolar hemorrhage has a fatality rate of >50 %. Readers are referred to earlier, excellent summaries related to this subject (Adler and de la Pena-Moctezuma 2010; Bharti et al. 2003; Hartskeerl et al. 2011; Ko et al. 2009; Levett 2001; McBride et al. 2005). C1 [Haake, David A.] VA Greater Los Angeles Healthcare Syst, Div Infect Dis, Los Angeles, CA 90073 USA. [Haake, David A.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Med, Los Angeles, CA 90095 USA. [Haake, David A.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Urol, Los Angeles, CA 90095 USA. [Haake, David A.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Microbiol Immunol & Mol Genet, Los Angeles, CA 90095 USA. [Levett, Paul N.] Saskatchewan Dis Control Lab, Regina, SK, Canada. RP Haake, DA (reprint author), VA Greater Los Angeles Healthcare Syst, Div Infect Dis, Los Angeles, CA 90073 USA. EM dhaake@ucla.edu; plevett@health.gov.sk.ca FU BLRD VA [I01 BX002003]; NIAID NIH HHS [R01 AI034431] NR 186 TC 25 Z9 27 U1 3 U2 32 PU SPRINGER-VERLAG BERLIN PI BERLIN PA HEIDELBERGER PLATZ 3, D-14197 BERLIN, GERMANY SN 0070-217X BN 978-3-662-45059-8; 978-3-662-45058-1 J9 CURR TOP MICROBIOL JI Curr.Top.Microbiol.Immunol. PY 2015 VL 387 BP 65 EP 97 DI 10.1007/978-3-662-45059-8_5 D2 10.1007/978-3-662-45059-8 PG 33 WC Immunology; Microbiology SC Immunology; Microbiology GA BC0EH UT WOS:000348986500006 PM 25388133 ER PT S AU Haake, DA Zuckert, WR AF Haake, David A. Zueckert, Wolfram R. BE Adler, B TI The Leptospiral Outer Membrane SO LEPTOSPIRA AND LEPTOSPIROSIS SE Current Topics in Microbiology and Immunology LA English DT Review; Book Chapter ID INTERROGANS SEROVAR COPENHAGENI; SURFACE-EXPOSED LIPOPROTEIN; IMMUNOGLOBULIN-LIKE PROTEINS; PROXIMAL TUBULE CELLS; PATHOGENIC LEPTOSPIRA; ESCHERICHIA-COLI; BORRELIA-BURGDORFERI; EXTRACELLULAR-MATRIX; PROTECTIVE IMMUNITY; MOLECULAR-CLONING AB The outer membrane (OM) is the front line of leptospiral interactions with their environment and the mammalian host. Unlike most invasive spirochetes, pathogenic leptospires must be able to survive in both free-living and host-adapted states. As organisms move from one set of environmental conditions to another, the OM must cope with a series of conflicting challenges. For example, the OM must be porous enough to allow nutrient uptake, yet robust enough to defend the cell against noxious substances. In the host, the OM presents a surface decorated with adhesins and receptors for attaching to, and acquiring, desirable host molecules such as the complement regulator, Factor H. On the other hand, the OM must enable leptospires to evade detection by the host's immune system on their way from sites of invasion through the bloodstream to the protected niche of the proximal tubule. The picture that is emerging of the leptospiral OM is that, while it shares many of the characteristics of the OMs of spirochetes and Gram-negative bacteria, it is also unique and different in ways that make it of general interest to microbiologists. For example, unlike most other pathogenic spirochetes, the leptospiral OM is rich in lipopolysaccharide (LPS). Leptospiral LPS is similar to that of Gram-negative bacteria but has a number of unique structural features that may explain why it is not recognized by the LPS-specific Toll-like receptor 4 of humans. As in other spirochetes, lipoproteins are major components of the leptospiral OM, though their roles are poorly understood. The functions of transmembrane outer membrane proteins (OMPs) in many cases are better understood, thanks to homologies with their Gram-negative counterparts and the emergence of improved genetic techniques. This chapter will review recent discoveries involving the leptospiral OM and its role in leptospiral physiology and pathogenesis. C1 [Haake, David A.] VA Greater Los Angeles Healthcare Syst, Div Infect Dis, Los Angeles, CA 90073 USA. [Haake, David A.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Med, Los Angeles, CA 90095 USA. [Haake, David A.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Urol, Los Angeles, CA 90095 USA. [Haake, David A.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Microbiol Immunol & Mol Genet, Los Angeles, CA 90095 USA. [Zueckert, Wolfram R.] Univ Kansas, Sch Med, Dept Microbiol Mol Genet & Immunol, Kansas City, KS 66160 USA. RP Haake, DA (reprint author), VA Greater Los Angeles Healthcare Syst, Div Infect Dis, Los Angeles, CA 90073 USA. EM dhaake@ucla.edu; wzueckert@kumc.edu FU BLRD VA [I01 BX002003]; NIAID NIH HHS [R01 AI034431]; NIGMS NIH HHS [P30 GM103326] NR 117 TC 3 Z9 3 U1 2 U2 9 PU SPRINGER-VERLAG BERLIN PI BERLIN PA HEIDELBERGER PLATZ 3, D-14197 BERLIN, GERMANY SN 0070-217X BN 978-3-662-45059-8; 978-3-662-45058-1 J9 CURR TOP MICROBIOL JI Curr.Top.Microbiol.Immunol. PY 2015 VL 387 BP 187 EP 221 DI 10.1007/978-3-662-45059-8_8 D2 10.1007/978-3-662-45059-8 PG 35 WC Immunology; Microbiology SC Immunology; Microbiology GA BC0EH UT WOS:000348986500009 PM 25388136 ER PT B AU Klein, E AF Klein, Eran BE VanRysewyk, SP Pontier, M TI Models of the Patient-Machine-Clinician Relationship in Closed-Loop Machine Neuromodulation SO MACHINE MEDICAL ETHICS SE Intelligent Systems Control and Automation Science and Engineering LA English DT Article; Book Chapter ID DEEP BRAIN-STIMULATION; SUBTHALAMIC NUCLEUS; PARKINSONS-DISEASE; PROFESSION AB Closed-loop neuromodulation represents an emerging area in clinical medicine. Neural devices capable of measuring brain function and using measurements to iteratively guide output, such as deep brain stimulation, will be a significant advance in neuromodulatory technology. The introduction of closed-loop devices, particularly "smart" machines, will require changes in clinical ethical practice. A model of the clinical relationship could be a useful tool for addressing ethical challenges arising in this new area. Traditional models of the clinical relationship, like Emanuel and Emanuel's "four models," are suited to current unidirectional forms of neuromodulation. An adequate model of the patient-machine-clinician relationship may need to move beyond traditional models. Thus, I explore three new models: the design model, the customer service model, and the quality monitoring model. The exploration of these models of the patient-machine-clinician relationship will benefit from keeping an Aristotelian ideal of friendship in mind. C1 [Klein, Eran] Oregon Hlth & Sci Univ, Dept Neurol, Portland, OR 97201 USA. [Klein, Eran] Portland VA Med Ctr, Portland, OR USA. [Klein, Eran] Univ Washington, Dept Philosophy, Seattle, WA 98195 USA. [Klein, Eran] Univ Washington, Ctr Sensorimotor Neural Engn, Seattle, WA 98195 USA. RP Klein, E (reprint author), Oregon Hlth & Sci Univ, Dept Neurol, Portland, OR 97201 USA. EM kleine@ohsu.edu NR 36 TC 2 Z9 2 U1 0 U2 2 PU SPRINGER PI DORDRECHT PA PO BOX 17, 3300 AA DORDRECHT, NETHERLANDS BN 978-3-319-08108-3; 978-3-319-08107-6 J9 INTEL SYST CONTR AUT PY 2015 VL 74 BP 273 EP 290 DI 10.1007/978-3-319-08108-3_17 D2 10.1007/978-3-319-08108-3 PG 18 WC Ethics; Robotics SC Social Sciences - Other Topics; Robotics GA BB8KL UT WOS:000346771800018 ER PT J AU Hiremath, SV Intille, SS Kelleher, A Cooper, RA Ding, D AF Hiremath, Shivayogi V. Intille, Stephen S. Kelleher, Annmarie Cooper, Rory A. Ding, Dan TI Detection of physical activities using a physical activity monitor system for wheelchair users SO MEDICAL ENGINEERING & PHYSICS LA English DT Article DE Spinal cord injury; Physical activity; Wheelchair users; Activity monitor system; Smartphones; Machine learning; Classification ID SPINAL-CORD-INJURY; ENERGY-EXPENDITURE; VALIDATION AB Availability of physical activity monitors for wheelchair users can potentially assist these individuals to track regular physical activity (PA), which in turn could lead to a healthier and more active lifestyle. Therefore, the aim of this study was to develop and validate algorithms for a physical activity monitoring system (PAMS) to detect wheelchair based activities. The PAMS consists of a gyroscope based wheel rotation monitor (G-WRM) and an accelerometer device (wocket) worn on the upper arm or on the wrist. A total of 45 persons with spinal cord injury took part in the study, which was performed in a structured university-based laboratory environment, a semi-structured environment at the National Veterans Wheelchair Games, and in the participants' home environments. Participants performed at least ten PAs, other than resting, taken from a list of PAs. The classification performance for the best classifiers on the testing dataset for PAMS-Arm (G-WRM and wocket on upper arm) and PAMS-Wrist (G-WRM and wocket on wrist) was 89.26% and 88.47%, respectively. The outcomes of this study indicate that multi-modal information from the PAMS can help detect various types of wheelchair-based activities in structured laboratory, semi-structured organizational, and unstructured home environments. (C) 2014 IPEM. Published by Elsevier Ltd. All rights reserved. C1 [Hiremath, Shivayogi V.; Kelleher, Annmarie; Cooper, Rory A.; Ding, Dan] VA Pittsburgh Healthcare Syst, Human Engn Res Labs, Dept Vet Affairs, Pittsburgh, PA USA. [Kelleher, Annmarie; Cooper, Rory A.; Ding, Dan] Univ Pittsburgh, Dept Rehabil Sci & Technol, Pittsburgh, PA 15206 USA. [Hiremath, Shivayogi V.] Univ Pittsburgh, Dept Phys Med & Rehabil, Pittsburgh, PA 15206 USA. [Intille, Stephen S.] Northeastern Univ, Coll Comp & Informat Sci, Boston, MA 02115 USA. [Intille, Stephen S.] Northeastern Univ, Dept Hlth Sci, Boston, MA 02115 USA. [Cooper, Rory A.; Ding, Dan] Univ Pittsburgh, Dept Bioengn, Pittsburgh, PA 15206 USA. RP Ding, D (reprint author), Univ Pittsburgh, Dept Rehabil Sci & Technol, Human Engn Res Labs, VA Pittsburgh Healthcare Syst, 6425 Penn Ave,Suite 400, Pittsburgh, PA 15206 USA. EM dad5@pitt.edu FU Department of Defense [W81XWH-10-1-0816]; National Institute on Disability and Rehabilitation Research, Department of Education [H133F110032]; Human Engineering Research Laboratories, VA Pittsburgh Healthcare System FX The work is supported by the Department of Defense (W81XWH-10-1-0816). SVH's work on this article was funded through the Switzer Research Fellowship (H133F110032) awarded by the National Institute on Disability and Rehabilitation Research, Department of Education. The work is 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. The authors thank their colleagues at the Human Engineering Research Laboratories, especially Alejandra Manoela Ojeda, Monsak Socharoentum, Natthasit Wongsirikul, and Matthew Hannan for their input and effort during development and data collection. NR 17 TC 5 Z9 5 U1 0 U2 7 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 1350-4533 EI 1873-4030 J9 MED ENG PHYS JI Med. Eng. Phys. PD JAN PY 2015 VL 37 IS 1 BP 68 EP 76 DI 10.1016/j.medengphy.2014.10.009 PG 9 WC Engineering, Biomedical SC Engineering GA CB4GB UT WOS:000349585100009 PM 25465284 ER PT J AU Nilsagard, Y Gunn, H Freeman, J Hoang, P Lord, S Mazumder, R Cameron, M AF Nilsagard, Y. Gunn, H. Freeman, J. Hoang, P. Lord, S. Mazumder, Rajarshi Cameron, Michelle TI Falls in people with MS-an individual data meta-analysis from studies from Australia, Sweden, United Kingdom and the United States SO MULTIPLE SCLEROSIS JOURNAL LA English DT Article DE Accidental falls; multiple sclerosis; risk factors; cohort studies; meta-analysis ID DISABILITY STATUS SCALE; PREDICTING ACCIDENTAL FALLS; MULTIPLE-SCLEROSIS; RISK-FACTORS; OLDER-ADULTS; BALANCE; PREVENTION; IMBALANCE; STRENGTH; COHORT AB Background: Falls are common in people with multiple sclerosis (PwMS). Previous studies have generally included small samples and had varied methods. Objectives: The objectives of this paper are to compile fall rates across a broad range of ages and disease severity and to definitively assess the extent to which MS-associated and demographic factors influence fall rates. Methods: Individual data from studies in four countries that prospectively measured falls for three months were analyzed. We determined fall rates, prevalence of fallers (1 falls) and frequent fallers (2 falls), location and timing of falls, and fall-related demographic factors. Results: A total of 537 participants reported 1721 falls: 56% were fallers and 37% frequent fallers. Most falls occurred indoors (65%) between 6 a.m. and 6 p.m. (75%). Primary progressive MS was associated with significantly increased odds of being a faller (odds ratio (OR) 2.02; CI 1.08-3.78). Fall risk peaked at EDSS levels of 4.0 and 6.0 with significant ORs between 5.30 (2.23-12.64) and 5.10 (2.08-12.47). The fall rate was lower in women than men (relative risk (RR) 0.80; CI 0.67-0.94) and decreased with increasing age (RR 0.97 for each year, CI 0.95-0.98). Conclusion: PwMS are at high risk of falls and there are important associations between falls and MS-associated disability, gender and age. C1 [Nilsagard, Y.] Orebro Cty Council, Ctr Hlth Care Sci, Orebro, Sweden. [Nilsagard, Y.] Orebro Univ, Sch Hlth & Med Sci, SE-70113 Orebro, Sweden. [Gunn, H.; Freeman, J.] Univ Plymouth, Sch Hlth Profess, Plymouth PL4 8AA, Devon, England. [Hoang, P.; Lord, S.] Univ NSW, Neurosci Res Australia NeuRA, Sydney, NSW, Australia. [Mazumder, Rajarshi; Cameron, Michelle] Oregon Hlth & Sci Univ, Portland, OR 97201 USA. [Cameron, Michelle] Oregon Hlth & Sci Univ, Portland VA Med Ctr, Portland, OR 97201 USA. RP Nilsagard, Y (reprint author), Orebro Univ, Sch Hlth & Med Sci, Orebro Cty Council, Ctr Hlth Care Sci, POB 1324, SE-70113 Orebro, Sweden. EM ylva.nilsagard@orebroll.se RI Lord, Stephen/C-9612-2011 FU Research Committee in Orebro County Council; Biogen Idec; Norrbacka- Eugenia Foundation; VA, Rehabilitation Research & Development Service; Agency for Healthcare Research and Quality (AHRQ) [T32 HS017582]; Foundation of the Consortium of Multiple Sclerosis Centers; NHMRC; Multiple Sclerosis Research Australia; Physiotherapy Research Foundation, Chartered Society of Physiotherapy, UK FX SE: Ylva Nilsagard was supported by the Research Committee in Orebro County Council, Biogen Idec and the Norrbacka- Eugenia Foundation.; US: Michelle Cameron was supported by a Career Development Award from the VA, Rehabilitation Research & Development Service.; Rajarshi Mazumder was supported by the Oregon Multidisciplinary Training Program in Health Services Research, grant number T32 HS017582 from the Agency for Healthcare Research and Quality (AHRQ) and the 2012 Foundation of the Consortium of Multiple Sclerosis Centers.; AUS: Phu Hoang and Stephen Lord were supported by NHMRC Fellowships and a grant from Multiple Sclerosis Research Australia.; UK: Hillary Gunn and Jennifer Freeman were supported by a grant from the Physiotherapy Research Foundation, Chartered Society of Physiotherapy, UK. NR 35 TC 11 Z9 11 U1 2 U2 8 PU SAGE PUBLICATIONS LTD PI LONDON PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND SN 1352-4585 EI 1477-0970 J9 MULT SCLER J JI Mult. Scler. J. PD JAN PY 2015 VL 21 IS 1 BP 92 EP 100 DI 10.1177/1352458514538884 PG 9 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA CB0AW UT WOS:000349288100014 PM 24948687 ER PT J AU Bag, S Tseng, JC Rochford, J AF Bag, S. Tseng, J. -C. Rochford, J. TI A BODIPY-luminol chemiluminescent resonance energy-transfer (CRET) cassette for imaging of cellular superoxide SO ORGANIC & BIOMOLECULAR CHEMISTRY LA English DT Article ID IN-VIVO; INFLAMMATION; MYELOPEROXIDASE; DISEASE; OXIDANTS AB Spectroscopic and in cellulo studies are here reported on the very first BODIPY-luminol chemiluminescent resonance energy-transfer (CRET) cassette where the luminol CL agent is covalently linked to the BODIPY energy-transfer acceptor in a molecular dyad. The efficiency of intramolecular CRET investigated for the BODIPY-luminol dyad was found to be 64% resulting in a dual emissive response. Successful in cellulo biochemiluminescence via CRET was achieved in PMA activated splenocytes. C1 [Bag, S.; Rochford, J.] Univ Massachusetts, Dept Chem, Boston, MA 02125 USA. [Tseng, J. -C.] Dana Farber Canc Inst, Lurie Family Imaging Ctr, Boston, MA 02215 USA. RP Tseng, JC (reprint author), Dana Farber Canc Inst, Lurie Family Imaging Ctr, Boston, MA 02215 USA. EM Jen-Chieh.Tseng@perkinelmer.com; jonathan.rochford@umb.edu NR 25 TC 4 Z9 4 U1 2 U2 26 PU ROYAL SOC CHEMISTRY PI CAMBRIDGE PA THOMAS GRAHAM HOUSE, SCIENCE PARK, MILTON RD, CAMBRIDGE CB4 0WF, CAMBS, ENGLAND SN 1477-0520 EI 1477-0539 J9 ORG BIOMOL CHEM JI Org. Biomol. Chem. PY 2015 VL 13 IS 6 BP 1763 EP 1767 DI 10.1039/c4ob02413c PG 5 WC Chemistry, Organic SC Chemistry GA CA6NV UT WOS:000349032400021 PM 25500943 ER PT J AU Yildiz, A Nikodem, M Vieta, E Correll, CU Baldessarini, RJ AF Yildiz, A. Nikodem, M. Vieta, E. Correll, C. U. Baldessarini, R. J. TI A network meta-analysis on comparative efficacy and all-cause discontinuation of antimanic treatments in acute bipolar mania SO PSYCHOLOGICAL MEDICINE LA English DT Article DE All-cause discontinuations; antimanic; bipolar; mania; multiple treatments meta-analysis ID MULTIPLE-TREATMENTS METAANALYSIS; DOUBLE-BLIND; I DISORDER; CONTROLLED-TRIALS; MOOD DISORDERS; LITHIUM; VALPROATE; CARBAMAZEPINE; SCHIZOPHRENIA; HALOPERIDOL AB Background. Evidence synthesis methods enabling direct and indirect comparisons over the entire set of relevant clinical data produce quantitative point estimates for the treatments contrasts between competing interventions, and provide a hierarchical rank ordering between them. We aimed to provide evidence-based guidance on the efficacy and all-cause discontinuation of antimanic treatments. Method. We conducted a network meta-analysis within a Bayesian framework. We searched all standard literature databases without language restrictions up to 15 January 2014 to identify reports of short-term, randomized, blinded trials of putative antimanic drugs as monotherapy for adults with bipolar-I mania. Results. Altogether, 14256 manic patients randomized to one of 18 active treatments or placebo provided 95 direct comparisons on 128 data points. For the primary outcome, standardized mean difference as Hedges' g (standardized mean difference; SMD), the hierarchies indicated by surface under the cumulative ranking (SUCRA) probabilities were in agreement with the point estimates for all antimanic drugs identified as effective. For the 12 effective antimanic drugs on clinical use, SMDs against placebo ranged from 0.32 to 0.66 without superiority of one over another, except for risperidone v. aripiprazole and valproate. Aripiprazole, olanzapine, quetiapine, risperidone, and valproate had less all-cause discontinuation rates than placebo. Sensitivity analysis by drug class indicated similar efficacy profiles for haloperidol, second-generation antipsychotics, and mood stabilizers. Conclusions. Hierarchical rank ordering by comparative efficacy and risk of all-cause discontinuations should help to guide antimanic treatment choices by clinicians, healthcare policy makers, and guideline developers. C1 [Yildiz, A.] Dokuz Eylul Univ, Dept Psychiat, Izmir, Turkey. [Yildiz, A.; Vieta, E.; Baldessarini, R. J.] Massachusetts Gen Hosp, Int Consortium Bipolar Disorder Res, Boston, MA 02114 USA. [Yildiz, A.; Vieta, E.; Baldessarini, R. J.] Massachusetts Gen Hosp, Psychopharmacol Program, McLean Div, Boston, MA 02114 USA. [Nikodem, M.] AGH Univ Sci & Technol, Fac Appl Math, PL-30059 Krakow, Poland. [Vieta, E.] Univ Barcelona, CIBERSAM, Barcelona,IDIBAPS, Bipolar Disorders Program,Inst Clin Neurosci,Hosp, Barcelona, Catalonia, Spain. [Correll, C. U.] Zucker Hillside Hosp, Dept Psychiat, Div Psychiat Res, New York, NY USA. [Baldessarini, R. J.] Harvard Univ, Med Sch Boston, Dept Psychiat, Cambridge, MA 02138 USA. RP Yildiz, A (reprint author), Depress & Bipolar Disorders Fdn Duygudurum Vakfi, Yenikale Mah Sutculer Sok 7-3 Narlidere, Izmir, Turkey. EM agul_yildiz@hotmail.com OI Vieta, Eduard/0000-0002-0548-0053 FU Abdi Ibrahim Corporation; Actavis Corporation; Ali Raif Corporation; AstraZeneca Corporation; Bristol-Myers-Squibb Corporation; Janssen-Cilag Corporation; Pfizer Corporation; Sanofi-Aventis Corporation; Servier Corporation; Janssen/Johnson Johnson; Otsuka; Adamed; Alexza; Almirall; Cephalon; Eli Lilly; Ferrer; Forest Research Institute; Gedeon Richter; Glaxo-Smith-Kline; Janssen; Jazz; Johnson Johnson; Lundbeck; Merck Sharpe Dohme; Novartis; Roche; Sanofi; Senovel; Servier; Shering-Plough; Shire; Sunovion; Takeda; Teva; United Biosource Corporation FX A. Yildiz has received research grants from and/or served as a consultant or speaker for Abdi Ibrahim, Actavis, Ali Raif, AstraZeneca, Bristol-Myers-Squibb, Janssen-Cilag, Pfizer, Sanofi-Aventis, and Servier Corporations. C. U. Correll has been a consultant or advisor to or has received honoraria from: Actelion, Alexza, AstraZeneca, Bristol-Myers-Squibb, Cephalon, Eli Lilly, Gerson Lehrman Group, Genentech, IntraCellular Therapies, Lundbeck, Medavante, Medscape, Merck, Novartis, Ortho-McNeill/Janssen/Johnson & Johnson, Otsuka, Pfizer, ProPhase, Roche, Sunovion, Takeda, Teva and Vanda. He has received grant support from Bristol-Myers-Squibb, Janssen/Johnson & Johnson, and Otsuka. E. Vieta has received grants and honoraria related to consultancy or advisory boards from several pharmaceutical companies, including Adamed, Alexza, Almirall, AstraZeneca, Bristol-Myers-Squibb, Cephalon, Eli Lilly, Ferrer, Forest Research Institute, Gedeon Richter, Glaxo-Smith-Kline, Janssen, Jazz, Johnson & Johnson, Lundbeck, Merck Sharpe & Dohme, Novartis, Otsuka, Pfizer, Roche, Sanofi, Senovel, Servier, Shering-Plough, Shire, Sunovion, Takeda, Teva, and United Biosource Corporation. M. Nikodem, R. J. Baldessarini, and the immediate family members of all authors have no current financial relationships with commercial entities that might represent potential conflicts of interest in this work. NR 73 TC 11 Z9 12 U1 2 U2 4 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 32 AVENUE OF THE AMERICAS, NEW YORK, NY 10013-2473 USA SN 0033-2917 EI 1469-8978 J9 PSYCHOL MED JI Psychol. Med. PD JAN PY 2015 VL 45 IS 2 BP 299 EP 317 DI 10.1017/S0033291714001305 PG 19 WC Psychology, Clinical; Psychiatry; Psychology SC Psychology; Psychiatry GA CB4SB UT WOS:000349617100007 PM 25036226 ER PT J AU Harris, AHS Bowe, T Del Re, AC Finlay, AK Oliva, E Myrick, HL Rubinsky, AD AF Harris, Alex H. S. Bowe, Thomas Del Re, Aaron C. Finlay, Andrea K. Oliva, Elizabeth Myrick, Hugh L. Rubinsky, Anna D. TI Extended Release Naltrexone for Alcohol Use Disorders: Quasi-Experimental Effects on Mortality and Subsequent Detoxification Episodes SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Article DE Alcohol Use Disorders; Alcohol Dependence; Naltrexone; Medication-Assisted Treatment; Veterans Health Administration; Veterans ID DEPENDENCE; PHARMACOTHERAPY; BARRIERS; METAANALYSIS; REGRESSION; TRIAL; DEPOT AB BackgroundUtilization of extended release naltrexone (XRN) for alcohol use disorders (AUDs) in the U.S. Veterans Health Administration (VHA) has been limited, perhaps due to high cost, lack of established superiority over less expensive alternatives including oral naltrexone, and related formulary restrictions. Despite these barriers, pockets of higher utilization exist in VHA, allowing for the quasi-experimental examination of the effects of XRN on 1-year mortality and number of subsequent detoxification episodes among patients with high rates of psychiatric comorbidities and previous psychosocial and pharmacological addiction treatment. MethodsUsing propensity score-weighted mixed-effects logistic regression, 1-year mortality was compared between patients with AUDs who received XRN in fiscal year 2010 (n=387) and a random sample of patients with AUDs who did not receive XRN (n=3,759). Among the subgroup of patients who had at least 1 detoxification episode in the previous year, 1-year mortality and number of subsequent detoxification episodes were compared between those who did and did not receive XRN. ResultsOverall, 1-year mortality for the patients receiving XRN was significantly lower than for the comparison group who did not receive XRN (odds ratio [OR]=0.30; p<0.001). Among patients with a detoxification episode in the previous year, those receiving XRN had, on average, 0.80 fewer subsequent detoxification episodes (p<0.001) and significantly lower mortality (OR=0.78, p<0.001) in the postindex year. ConclusionsAmong patients with AUDs, those receiving XRN had lower 1-year mortality and fewer detoxifications compared to similar patients not receiving XRN. These results, although observational, support the use of XRN, especially among patients with high rates of psychiatric comorbidities and previous addiction treatment who are still struggling with AUDs and/or facing a period of vulnerability to relapse. C1 [Harris, Alex H. S.; Bowe, Thomas; Del Re, Aaron C.; Finlay, Andrea K.; Oliva, Elizabeth; Rubinsky, Anna D.] VA Palo Alto Hlth Care Syst, Ctr Innovat Implementat, VA Subst Use Disorder Qual Enhancement Res Initia, Menlo Pk, CA 94025 USA. [Myrick, Hugh L.] Med Univ S Carolina, Ralph H Johnson Vet Affairs Med Ctr, Charleston, SC 29425 USA. RP Harris, AHS (reprint author), VA Palo Alto Hlth Care Syst, Ctr Innovat Implementat MPD 152, 795 Willow Rd, Menlo Pk, CA 94025 USA. EM alexander.harris2@va.gov OI Del Re, Aaron/0000-0002-9571-7623 FU VA Substance Use Disorder Quality Enhancement Research Initiative Locally Initiated Project [LIP QLP 59-028] FX This work was supported by a VA Substance Use Disorder Quality Enhancement Research Initiative Locally Initiated Project (LIP QLP 59-028). The views expressed do not represent those of the U.S. Department of Veterans Affairs. NR 17 TC 1 Z9 1 U1 0 U2 4 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0145-6008 EI 1530-0277 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD JAN PY 2015 VL 39 IS 1 BP 79 EP 83 DI 10.1111/acer.12597 PG 5 WC Substance Abuse SC Substance Abuse GA CA2DM UT WOS:000348719100010 PM 25623408 ER PT J AU Worley, MJ Witkiewitz, K Brown, SA Kivlahan, DR Longabaugh, R AF Worley, Matthew J. Witkiewitz, Katie Brown, Sandra A. Kivlahan, Daniel R. Longabaugh, Richard TI Social Network Moderators of Naltrexone and Behavioral Treatment Effects on Heavy Drinking in the COMBINE Study SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Article DE Alcohol Dependence; Naltrexone; Pharmacotherapy; Social Network; Moderators ID ALCOHOL-USE DISORDERS; COMBINED PHARMACOTHERAPIES; CONTROLLED-TRIAL; MISSING DATA; DEPENDENCE; OUTCOMES; SUPPORT; PHARMACOGENETICS; INTERVENTIONS; MEDICATIONS AB BackgroundOral naltrexone is an efficacious medication for treatment of alcohol dependence, but small effect sizes and variability in outcomes suggest the presence of person-level moderators of naltrexone response. Identification of contextual or psychosocial moderators may assist in guiding clinical recommendations. Given the established importance of social networks in drinking outcomes, as well as the potential effects of naltrexone in reducing cue reactivity which may be especially important among those with more heavy drinkers and more alcohol cues in their networks, we examined pretreatment social network variables as potential moderators of naltrexone treatment effects in the COMBINE study. MethodsThe sample included all COMBINE study participants in medication conditions with full data on the Important People Inventory (IPI) and covariates at intake (N=1,197). The intake IPI assessed whether participants had any frequent drinkers in their network and the average frequency of contact with these drinkers. The effects of treatment condition, pretreatment network variables, and their interactions on percent heavy drinking days were tested in hierarchical linear models, controlling for demographics and baseline clinical covariates. ResultsIn treatment conditions involving medical management and combined behavioral intervention (CBI), the effects of active naltrexone on heavy drinking were significantly greater for individuals with frequent drinkers in their network (z=-2.66, p<0.01) and greater frequency of contact with those drinkers (z=-3.19, p<0.01). These network variables did not moderate the effects of active naltrexone without CBI. ConclusionsWhen delivered in conjunction with behavioral interventions, naltrexone can be more potent for alcohol-dependent adults who have greater contact with frequent drinkers prior to treatment, which may indicate patterns of environmental exposure to alcohol. Contextual, social risk factors are a potential avenue to guide personalized treatment of alcohol dependence. C1 [Worley, Matthew J.] Univ Calif Los Angeles, Dept Family Med, Los Angeles, CA 90024 USA. [Witkiewitz, Katie] Univ New Mexico, Dept Psychol, Albuquerque, NM 87131 USA. [Brown, Sandra A.] Univ Calif San Diego, Off Res Affairs, La Jolla, CA 92093 USA. [Kivlahan, Daniel R.] VA Puget Sound Healthcare Syst, Ctr Excellence Subst Abuse Treatment & Educ, Seattle, WA USA. Univ Washington, Seattle, WA 98195 USA. [Longabaugh, Richard] Brown Univ, Ctr Alcohol & Addict Studies, Providence, RI 02912 USA. RP Worley, MJ (reprint author), Univ Calif Los Angeles, 10880 Wilshire Blvd,Suite 1800, Los Angeles, CA 90024 USA. EM mworley@mednet.ucla.edu FU NIAAA NIH HHS [R01 AA022328]; NIDA NIH HHS [F31 DA030861] NR 50 TC 2 Z9 2 U1 3 U2 11 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0145-6008 EI 1530-0277 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD JAN PY 2015 VL 39 IS 1 BP 93 EP 100 DI 10.1111/acer.12605 PG 8 WC Substance Abuse SC Substance Abuse GA CA2DM UT WOS:000348719100012 PM 25623409 ER PT J AU Khawaja, RDA Singh, S Vettiyil, B Lim, R Gee, M Westra, S Kalra, MK AF Khawaja, Ranish Deedar Ali Singh, Sarabjeet Vettiyil, Beth Lim, Ruth Gee, Michael Westra, Sjirk Kalra, Mannudeep K. TI Simplifying Size-Specific Radiation Dose Estimates in Pediatric CT SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Article DE body diameter; body weight; pediatric CT; size-specific dose estimate ID COMPUTED-TOMOGRAPHY; PROTOCOLS; INDEX AB OBJECTIVE. Size-specific dose estimates (SSDEs) require manual measurement of torso diameters for individual patients-anteroposterior (hereafter, D-AP), lateral (hereafter, D-LAT), and effective (hereafter, D-E)-which can be tedious in clinical settings. We aimed to determine whether body weight can be used as a surrogate for measuring diameter in children. MATERIALS AND METHODS. D-AP and D-LAT were measured in 522 consecutive CT examinations (chest, 187 and abdomen-pelvis, 335) performed in 483 (+/- SD) children (13 +/- 7 years). Effective diameter (D-E1) was calculated as the square root of the product of D-AP and D-LAT. A second measurement of effective diameter (D-E2) was obtained using automated software. Correlation coefficients between patient body weight, age, and diameter were measured in addition to 95% prediction interval analysis for diameters corresponding to body weight. RESULTS. Median body weight was 51 kg, and mean D-AP, D-LAT, D-E1, and D-E2 were 207.1 +/- 50.8 mm, 289.8 +/- 72.6 mm, 243.3 +/- 62.0 mm, and 233.6 +/- 55.4 mm, respectively. Overall body weight had a strong correlation with diameter (0.88, 0.85, 0.86, and 0.93 respectively; all p < 0.0001). SSDE measured using body weight was statistically not different than SSDE measured using effective diameters (p = 0.9). Children weighing less than 27 kg and between 46 and 100 kg had statistically significant correlations with torso diameters, whereas only anteroposterior and effective diameters were correlated with children weighing between 27 and 45 kg. Children less than 4 years old had strong correlation with all diameters. Adolescents (15-18 years) did not have statistically significant correlation with any of the diameters. CONCLUSION. Body weight, instead of body diameter, can be used as a surrogate to estimate size-specific dose in children, making dose estimation clinically simpler and more rapid. C1 [Khawaja, Ranish Deedar Ali; Singh, Sarabjeet; Vettiyil, Beth; Gee, Michael; Kalra, Mannudeep K.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiol, Boston, MA 02114 USA. [Lim, Ruth; Westra, Sjirk] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiol,Div Pediat Imaging, Boston, MA 02114 USA. RP Khawaja, RDA (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiol, 25 New Chardon St,4th Fl, Boston, MA 02114 USA. EM rkhawaja@mgh.harvard.edu NR 10 TC 3 Z9 3 U1 1 U2 2 PU AMER ROENTGEN RAY SOC PI RESTON PA 1891 PRESTON WHITE DR, SUBSCRIPTION FULFILLMENT, RESTON, VA 22091 USA SN 0361-803X EI 1546-3141 J9 AM J ROENTGENOL JI Am. J. Roentgenol. PD JAN PY 2015 VL 204 IS 1 BP 167 EP 176 DI 10.2214/AJR.13.12191 PG 10 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA AZ9UO UT WOS:000348562300048 PM 25539253 ER PT J AU Kambadakone, A Yoon, SS Kim, TM Karl, DL Duda, DG DeLaney, TF Sahani, DV AF Kambadakone, Avinash Yoon, Sam S. Kim, Tae-Min Karl, Daniel L. Duda, Dan G. DeLaney, Thomas F. Sahani, Dushyant V. TI CT Perfusion as an Imaging Biomarker in Monitoring Response to Neoadjuvant Bevacizumab and Radiation in Soft-Tissue Sarcomas: Comparison With Tumor Morphology, Circulating and Tumor Biomarkers, and Gene Expression SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Article DE bevacizumab; CT perfusion; radiation therapy; soft-tissue sarcoma ID ADVANCED HEPATOCELLULAR-CARCINOMA; COMPUTED-TOMOGRAPHY PERFUSION; ELECTRON-BEAM RADIOTHERAPY; GUIDELINE VERSION 1.1; RECTAL-CANCER; SOLID TUMORS; EVALUATION CRITERIA; PANCREATIC-CANCER; TARGETED THERAPY; RANDOMIZED-TRIAL AB OBJECTIVE. The purpose of this study was to evaluate the role of CT perfusion in monitoring response to neoadjuvant antiangiogenic and radiation therapy in resectable soft-tissue-sarcomas and correlate the findings with tumor size, circulating and tumor biomarkers, and gene expression. SUBJECTS AND METHODS. This phase II clinical trial included 20 patients (13 men and 7 women; mean age, 55 years) with soft-tissue sarcomas who were undergoing treatment with the antiangiogenic drug bevacizumab followed by bevacizumab, radiation, and surgical resection. The patients underwent CT perfusion and diagnostic contrast-enhanced CT at baseline, at 2 weeks after bevacizumab therapy, and after completion of bevacizumab and radiation therapy. Multiple CT perfusion parameters (blood flow, blood volume, mean transit time, and permeability) were correlated with tumor size, circulating and tumor biomarkers, and gene expression. RESULTS. Two weeks after bevacizumab therapy, there was substantial fall in blood volume (31.9% reduction, p = 0.01) with more pronounced reduction in blood flow, blood volume, and permeability after treatment completion (53-64% reduction in blood flow, blood volume, and permeability; p = 0.001), whereas tumor size showed no significant change (p = 0.34). Tumors with higher baseline blood volume and lower baseline tumor size showed superior response to bevacizumab and radiation (p = 0.05). There was also an increase in median plasma vascular endothelial growth factor and placental-derived growth factor concentration after bevacizumab therapy paralleled by a decrease in tumor perfusion depicted by CT perfusion, although this was not statistically significant (p = 0.4). The baseline tumor microvessel density (MVD) correlated with blood flow (p = 0.04). At least 20 different genes were differentially expressed in tumors with higher and lower baseline perfusion. CONCLUSION. CT perfusion is more sensitive than tumor size for monitoring early and late response to bevacizumab and radiation therapy. CT perfusion parameters correlate with MVD, and the gene expression levels of baseline tumors could potentially predict treatment response. C1 [Kambadakone, Avinash; Sahani, Dushyant V.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiol,Div Abdominal Imaging & Intervent, Boston, MA 02114 USA. [Yoon, Sam S.; Karl, Daniel L.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Surg, Boston, MA 02114 USA. [Yoon, Sam S.] Mem Sloan Kettering Canc Ctr, Dept Surg, New York, NY 10021 USA. [Kim, Tae-Min] Harvard Univ, Sch Med, Ctr Biomed Informat, Boston, MA 02114 USA. [Kim, Tae-Min] Ctr Personalized Genet Med, New York, NY USA. [Duda, Dan G.; DeLaney, Thomas F.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiat Oncol, Boston, MA 02114 USA. RP Kambadakone, A (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiol,Div Abdominal Imaging & Intervent, White 270,55 Fruit St, Boston, MA 02114 USA. EM akambadakone@mgh.harvard.edu FU National Institutes of Health/National Cancer Institute [1R21 CA117128-01, 1R01 CA158301-01]; Society for Surgical Oncology Clinical Investigator Award FX The phase II clinical trial was supported by National Institutes of Health/National Cancer Institute grants 1R21 CA117128-01 and 1R01 CA158301-01 (S. S. Yoon), Society for Surgical Oncology Clinical Investigator Award (S. S. Yoon), and Ira J. Spiro Translational Research Award (D. G. Duda). NR 47 TC 8 Z9 8 U1 0 U2 8 PU AMER ROENTGEN RAY SOC PI RESTON PA 1891 PRESTON WHITE DR, SUBSCRIPTION FULFILLMENT, RESTON, VA 22091 USA SN 0361-803X EI 1546-3141 J9 AM J ROENTGENOL JI Am. J. Roentgenol. PD JAN PY 2015 VL 204 IS 1 BP W11 EP W18 DI 10.2214/AJR.13.12412 PG 8 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA AZ9UO UT WOS:000348562300003 PM 25539263 ER PT J AU Lira, D Padole, A Kalra, MK Singh, S AF Lira, Diego Padole, Atul Kalra, Mannudeep K. Singh, Sarabjeet TI Tube Potential and CT Radiation Dose Optimization SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Review DE image quality; radiation dose; tube potential ID IMAGE-QUALITY; PEDIATRIC CT; ABDOMINAL CT; REDUCTION; ANGIOGRAPHY; VOLTAGE; PROTOCOLS; CHEST; SIZE AB OBJECTIVE. This article describes tube potential and its effect on image quality and radiation dose for CT in different body regions and clinical indications. CONCLUSION. Tube potential is an important scanning parameter for radiation dose optimization. Reduction of tube potential results in increased image contrast of iodine-enhanced CT as well as increased image noise. C1 [Lira, Diego; Padole, Atul; Kalra, Mannudeep K.; Singh, Sarabjeet] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiol, Boston, MA 02114 USA. RP Singh, S (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiol, 55 Fruit St,Founders 202, Boston, MA 02114 USA. EM ssingh6@mgh.harvard.edu NR 15 TC 7 Z9 7 U1 0 U2 4 PU AMER ROENTGEN RAY SOC PI RESTON PA 1891 PRESTON WHITE DR, SUBSCRIPTION FULFILLMENT, RESTON, VA 22091 USA SN 0361-803X EI 1546-3141 J9 AM J ROENTGENOL JI Am. J. Roentgenol. PD JAN PY 2015 VL 204 IS 1 BP W4 EP W10 DI 10.2214/AJR.14.13281 PG 7 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA AZ9UO UT WOS:000348562300002 PM 25539272 ER PT J AU Nishino, M Araki, T Sholl, LM AF Nishino, Mizuki Araki, Tetsuro Sholl, Lynette M. TI Reply to "Usefulness of CT in Differentiating Lymphoid Thymic Hyperplasia From True Thymic Hyperplasia: Added Value of Thymic Measurements and CT Attenuation" SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Letter ID AGE C1 [Nishino, Mizuki] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. [Araki, Tetsuro; Sholl, Lynette M.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Boston, MA 02115 USA. RP Nishino, M (reprint author), Harvard Univ, Brigham & Womens Hosp, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. NR 8 TC 0 Z9 0 U1 0 U2 0 PU AMER ROENTGEN RAY SOC PI RESTON PA 1891 PRESTON WHITE DR, SUBSCRIPTION FULFILLMENT, RESTON, VA 22091 USA SN 0361-803X EI 1546-3141 J9 AM J ROENTGENOL JI Am. J. Roentgenol. PD JAN PY 2015 VL 204 IS 1 BP W115 EP W115 DI 10.2214/AJR.14.13368 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA AZ9UO UT WOS:000348562300021 PM 25539268 ER PT J AU Vassileva, J Rehani, M AF Vassileva, Jenia Rehani, Madan TI Diagnostic Reference Levels SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Editorial Material DE diagnostic reference levels; dose optimization; patient doses C1 [Vassileva, Jenia] Natl Ctr Radiobiol & Radiat Protect, Sofia, Bulgaria. [Rehani, Madan] IAEA, Vienna Int Ctr, A-1400 Vienna, Austria. [Rehani, Madan] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. RP Rehani, M (reprint author), IAEA, Vienna Int Ctr, A-1400 Vienna, Austria. EM madan.rehani@gmail.com NR 10 TC 3 Z9 3 U1 1 U2 1 PU AMER ROENTGEN RAY SOC PI RESTON PA 1891 PRESTON WHITE DR, SUBSCRIPTION FULFILLMENT, RESTON, VA 22091 USA SN 0361-803X EI 1546-3141 J9 AM J ROENTGENOL JI Am. J. Roentgenol. PD JAN PY 2015 VL 204 IS 1 BP W1 EP W3 DI 10.2214/AJR.14.12794 PG 3 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA AZ9UO UT WOS:000348562300001 PM 25539261 ER PT S AU Halperin, DM Kulke, MH Yao, JC AF Halperin, Daniel M. Kulke, Matthew H. Yao, James C. BE Caskey, CT TI A Tale of Two Tumors: Treating Pancreatic and Extrapancreatic Neuroendocrine Tumors SO ANNUAL REVIEW OF MEDICINE, VOL 66 SE Annual Review of Medicine LA English DT Review; Book Chapter DE gastroenteropancreatic neuroendocrine tumors; carcinoid; therapy ID ISLET-CELL-CARCINOMA; ZOLLINGER-ELLISON-SYNDROME; SOMATOSTATIN ANALOG SMS-201-995; LIVER-TRANSPLANTATION; ENDOCRINE TUMORS; LOW-GRADE; HEPATIC METASTASES; PROGNOSTIC-FACTORS; WATERY-DIARRHEA; CHROMOGRANIN-A AB Despite their perceived rarity, gastroenteropancreatic neuroendocrine tumors (GEP-NETs) are rising in incidence and prevalence. The biology, natural history, and therapeutic options for GEP-NETs are heterogeneous: NETs arising in the pancreas can be distinguished from those arising elsewhere in the gastrointestinal tract, and therapy is dichotomized between these two groups. Somatostatin analogues are the mainstay of oncologic management of bowel NETs; everolimus, streptozocin, and sunitinib are approved to treat pancreatic NETs. There are significant differences in molecular genetics between pancreatic and extrapancreatic NETs, and studies are evaluating whether additional NET patients may benefit from targeted agents. We discuss the distinguishing features of these two groups of tumors, as well as the therapeutic implications of the distinction. We also examine the evolving therapeutic landscape and discuss the likelihood that treatment will be developed independently for pancreatic and extrapancreatic gastrointestinal NETs, with novel therapeutics effective for newly identified pathologically or molecularly defined subgroups. C1 [Halperin, Daniel M.; Yao, James C.] Univ Texas MD Anderson Canc Ctr, Dept Gastrointestinal Med Oncol, Houston, TX 77030 USA. [Kulke, Matthew H.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02215 USA. RP Halperin, DM (reprint author), Univ Texas MD Anderson Canc Ctr, Dept Gastrointestinal Med Oncol, Houston, TX 77030 USA. EM dmhalperin@mdanderson.org; Matthew_Kulke@dfci.harvard.edu; jyao@mdanderson.org OI Halperin, Daniel M/0000-0002-3113-930X FU NCI NIH HHS [P30 CA016672] NR 96 TC 5 Z9 5 U1 0 U2 7 PU ANNUAL REVIEWS PI PALO ALTO PA 4139 EL CAMINO WAY, PO BOX 10139, PALO ALTO, CA 94303-0897 USA SN 0066-4219 BN 978-0-8243-0566-6 J9 ANNU REV MED JI Annu. Rev. Med. PY 2015 VL 66 BP 1 EP 16 DI 10.1146/annurev-med-061813-012908 PG 16 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA BB9PT UT WOS:000348560300001 PM 25341008 ER PT S AU Lipshultz, SE Franco, VI Miller, TL Colan, SD Sallan, SE AF Lipshultz, Steven E. Franco, Vivian I. Miller, Tracie L. Colan, Steven D. Sallan, Stephen E. BE Caskey, CT TI Cardiovascular Disease in Adult Survivors of Childhood Cancer SO ANNUAL REVIEW OF MEDICINE, VOL 66 SE Annual Review of Medicine LA English DT Review; Book Chapter DE etiology; screening; prevention; treatment ID ACUTE LYMPHOBLASTIC-LEUKEMIA; CHILDRENS ONCOLOGY GROUP; ANTHRACYCLINE-INDUCED CARDIOTOXICITY; LONG-TERM SURVIVORS; DEXRAZOXANE-ASSOCIATED RISK; PEDIATRIC HODGKINS-DISEASE; CONGESTIVE-HEART-FAILURE; DOXORUBICIN-TREATED SURVIVORS; CHRONIC MYELOID-LEUKEMIA; REFRACTORY SOLID TUMORS AB Treatment advances have increased survival in children with cancer, but subclinical, progressive, irreversible, and sometimes fatal treatment-related cardiovascular effects may appear years later. Cardio-oncologists have identified promising preventive and treatment strategies. Dexrazoxane provides long-term cardioprotection from doxorubicin-associated cardiotoxicity without compromising the efficacy of anticancer treatment. Continuous infusion of doxorubicin is as effective as bolus administration in leukemia treatment, but no evidence has indicated that it provides long-term cardioprotection; continuous infusions should be eliminated from pediatric cancer treatment. Angiotensin-converting enzyme inhibitors can delay the progression of subclinical and clinical cardiotoxicity. All survivors, regardless of whether they were treated with anthracyclines or radiation, should be monitored for systemic inflammation and the risk of premature cardiovascular disease. Echocardiographic screening must be supplemented with screening for biomarkers of cardiotoxicity and perhaps by identification of genetic susceptibilities to cardiovascular diseases; optimal strategies need to be identified. The health burden related to cancer treatment will increase as this population expands and ages. C1 [Lipshultz, Steven E.; Franco, Vivian I.] Wayne State Univ, Sch Med, Dept Pediat, Detroit, MI 48201 USA. [Lipshultz, Steven E.] Childrens Hosp Michigan, Detroit, MI 48201 USA. [Miller, Tracie L.] Univ Miami, Miller Sch Med, Dept Pediat, Miami, FL 33101 USA. [Colan, Steven D.] Boston Childrens Hosp, Dept Cardiol, Boston, MA 02115 USA. [Colan, Steven D.; Sallan, Stephen E.] Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. [Sallan, Stephen E.] Dana Farber Canc Inst, Div Pediat Oncol, Boston, MA 02115 USA. [Sallan, Stephen E.] Boston Childrens Hosp, Boston, MA 02115 USA. RP Lipshultz, SE (reprint author), Wayne State Univ, Sch Med, Dept Pediat, Detroit, MI 48201 USA. EM slipshultz@med.wayne.edu; vfranco@med.wayne.edu; tmiller2@med.miami.edu; steven.colan@cardio.chboston.org; stephen_sallan@dfci.harvard.edu FU NCI NIH HHS [CA068484, CA127642, P01 CA068484, R01 CA127642]; NHLBI NIH HHS [F31 HL094100, HL004537, HL007188, HL053392, HL072705, HL078522, HL079233, HL087000, HL087708, HL094100, HL095127, K30 HL004537, R01 HL053392, R01 HL072705, R01 HL078522, R01 HL087000, R01 HL095127, R13 HL087708, T32 HL007188]; NIAID NIH HHS [AI50274, U01 AI050274]; NICHD NIH HHS [U01 HD052104, HD052102, HD052104, HD80002, U01 HD052102] NR 103 TC 15 Z9 15 U1 0 U2 9 PU ANNUAL REVIEWS PI PALO ALTO PA 4139 EL CAMINO WAY, PO BOX 10139, PALO ALTO, CA 94303-0897 USA SN 0066-4219 BN 978-0-8243-0566-6 J9 ANNU REV MED JI Annu. Rev. Med. PY 2015 VL 66 BP 161 EP 176 DI 10.1146/annurev-med-070213-054849 PG 16 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA BB9PT UT WOS:000348560300011 PM 25587648 ER PT S AU Lin, MV King, LY Chung, RT AF Lin, Ming V. King, Lindsay Y. Chung, Raymond T. BE Abbas, AK Galli, SJ Howley, PM TI Hepatitis C Virus-Associated Cancer SO ANNUAL REVIEW OF PATHOLOGY: MECHANISMS OF DISEASE, VOL 10 SE Annual Review of Pathology-Mechanisms of Disease LA English DT Review; Book Chapter DE liver; cirrhosis; hepatocellular carcinoma; cancer ID EPIDERMAL-GROWTH-FACTOR; HUMAN HEPATOCELLULAR-CARCINOMA; GENOTYPE 1 INFECTION; SUSTAINED VIROLOGICAL RESPONSE; NONSTRUCTURAL 5A PROTEIN; TREATMENT-NAIVE PATIENTS; RNA-POLYMERASE ACTIVITY; INTERFERON-ALPHA 2A; THAN-G POLYMORPHISM; BETA-CATENIN GENE AB Hepatitis C virus (HCV) is one of the major etiologic agents of liver cancer. HCV is an RNA virus that, unlike hepatitis B virus, is unable to integrate into the host genome. Through complex interactions between viral and host proteins that induce host responses and promote inflammation, fibrosis, and ultimately cirrhosis, HCV infection can result in the development of hepatocellular carcinoma (HCC). The HCV oncogenic process involves genetic and epigenetic alterations and oncogenic effects mediated by viral proteins in the activation of cellular oncogenes, inactivation of tumor-suppressor genes, and dysregulation of multiple signal-transduction pathways. Advances in genetics and gene expression profiling have enhanced our current understanding of the pathways involved in HCV-associated liver cancer development. In this review, we summarize the current understanding of mechanisms of hepatocarcinogenesis induced by HCV infection. C1 [Lin, Ming V.] Massachusetts Gen Hosp, Dept Med, Gastrointestinal Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Lin, MV (reprint author), Massachusetts Gen Hosp, Dept Med, Gastrointestinal Unit, Boston, MA 02114 USA. EM mvlin@mgh.harvard.edu; lyking@partners.org; rtchung@partners.org NR 193 TC 15 Z9 15 U1 2 U2 14 PU ANNUAL REVIEWS PI PALO ALTO PA 4139 EL CAMINO WAY, PO BOX 10139, PALO ALTO, CA 94303-0897 USA SN 1553-4006 BN 978-0-8243-4310-1 J9 ANNU REV PATHOL-MECH JI Annu. Rev. Pathol.-Mech Dis. PY 2015 VL 10 BP 345 EP 370 DI 10.1146/annurev-pathol-012414-040323 PG 26 WC Pathology SC Pathology GA BB9PX UT WOS:000348560600012 PM 25387053 ER PT S AU Parker-Lue, S Santoro, M Koski, G AF Parker-Lue, Sara Santoro, Michael Koski, Greg BE Insel, PA TI The Ethics and Economics of Pharmaceutical Pricing SO ANNUAL REVIEW OF PHARMACOLOGY AND TOXICOLOGY, VOL 55 SE Annual Review of Pharmacology and Toxicology LA English DT Review; Book Chapter DE drug access; patents; innovation; differential pricing; price controls; rationing; prescribing ID PATIENT-ASSISTANCE PROGRAMS; MEDICARE PART D; INTELLECTUAL PROPERTY-RIGHTS; RESEARCH-AND-DEVELOPMENT; UNITED-STATES; ORPHAN DRUGS; HEALTH-CARE; GENERIC SUBSTITUTION; PATENT CHALLENGES; PARALLEL IMPORTS AB The cost of drugs is a major and rapidly rising component of health-care expenditures. We survey recent literature on the ethics and economics of skyrocketing pharmaceutical prices and find that advances in economic research have increased the sharpness and focus of the ethically based calls to increase access by modifying patent protection and reducing prices. In some cases, research supports ethical arguments for broader access. Other research suggests that efforts to broaden access result in unintended consequences for innovation and the medical needs of patients. Both ethicists and economists need to be more cognizant of the real clinical settings in which physicians practice medicine with real patients. Greater cross-disciplinary interaction among economists, ethicists, and physicians can help reduce the disjunction between innovation and access and improve access and patient care. This dialogue will impact private industry and may spur new multistakeholder paradigms for drug discovery, development, and pricing. C1 [Parker-Lue, Sara; Santoro, Michael] Rutgers Business Sch Newark & New Brunswick, Dept Management & Global Business, Newark, NJ 07102 USA. [Koski, Greg] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Anesthesia & Crit Care,James Mongan Inst Hlt, Boston, MA 02114 USA. RP Parker-Lue, S (reprint author), Rutgers Business Sch Newark & New Brunswick, Dept Management & Global Business, Newark, NJ 07102 USA. EM sparker@business.rutgers.edu; msantoro@business.rutgers.edu; gkoski@mgh.harvard.edu NR 127 TC 6 Z9 6 U1 13 U2 40 PU ANNUAL REVIEWS PI PALO ALTO PA 4139 EL CAMINO WAY, PO BOX 10139, PALO ALTO, CA 94303-0897 USA SN 0362-1642 BN 978-0-8243-0455-3 J9 ANNU REV PHARMACOL JI Annu. Rev. Pharmacol. Toxicol. PY 2015 VL 55 BP 191 EP + DI 10.1146/annurev-pharmtox-010814-124649 PG 7 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA BB9PW UT WOS:000348560500012 PM 25149920 ER PT S AU Gyorgy, B Hung, ME Breakefield, XO Leonard, JN AF Gyoergy, Bence Hung, Michelle E. Breakefield, Xandra O. Leonard, Joshua N. BE Insel, PA TI Therapeutic Applications of Extracellular Vesicles: Clinical Promise and Open Questions SO ANNUAL REVIEW OF PHARMACOLOGY AND TOXICOLOGY, VOL 55 SE Annual Review of Pharmacology and Toxicology LA English DT Review; Book Chapter DE exosomes; extracellular RNA; microvesicles; drug delivery; liposomes; gene medicine; gene therapy; mesenchymal stem cells; nanoparticles ID CELL-DERIVED EXOSOMES; OUTER-MEMBRANE VESICLES; MESENCHYMAL STROMAL CELLS; MARROW DENDRITIC CELLS; ENDOTHELIAL-CELLS; IMMUNE-RESPONSES; CANCER-CELLS; STEM-CELLS; T-CELLS; INTERCELLULAR TRANSFER AB This review provides an updated perspective on rapidly proliferating efforts to harness extracellular vesicles (EVs) for therapeutic applications. We summarize current knowledge, emerging strategies, and open questions pertaining to clinical potential and translation. Potentially useful EVs comprise diverse products of various cell types and species. EV components may also be combined with liposomes and nanoparticles to facilitate manufacturing as well as product safety and evaluation. Potential therapeutic cargoes include RNA, proteins, and drugs. Strategic issues considered herein include choice of therapeutic agent, means of loading cargoes into EVs, promotion of EV stability, tissue targeting, and functional delivery of cargo to recipient cells. Some applications may harness natural EV properties, such as immune modulation, regeneration promotion, and pathogen suppression. These properties can be enhanced or customized to enable a wide range of therapeutic applications, including vaccination, improvement of pregnancy outcome, and treatment of autoimmune disease, cancer, and tissue injury. C1 [Gyoergy, Bence; Breakefield, Xandra O.] Massachusetts Gen Hosp, Dept Neurol, Mol Neurogenet Unit, Boston, MA 02114 USA. [Gyoergy, Bence; Breakefield, Xandra O.] Massachusetts Gen Hosp, Dept Radiol, Ctr Mol Imaging Res, Boston, MA 02114 USA. [Gyoergy, Bence; Breakefield, Xandra O.] Harvard Univ, Sch Med, Program Neurosci, Boston, MA 02114 USA. [Gyoergy, Bence] Harvard Univ, Sch Med, Howard Hughes Med Inst, Boston, MA 02115 USA. [Hung, Michelle E.] Northwestern Univ, Interdept Biol Sci Grad Program, Evanston, IL 60208 USA. [Leonard, Joshua N.] Northwestern Univ, Robert H Lurie Comprehens Canc Ctr, Chem Life Proc Inst, Dept Chem & Biol Engn, Evanston, IL 60208 USA. RP Gyorgy, B (reprint author), Massachusetts Gen Hosp, Dept Neurol, Mol Neurogenet Unit, Boston, MA 02114 USA. EM breakefield@hms.harvard.edu; j-leonard@northwestern.edu RI Leonard, Joshua/B-7649-2009; Hung, Michelle/J-3336-2014 OI Hung, Michelle/0000-0002-1909-8162 FU Howard Hughes Medical Institute; NCI NIH HHS [P50 CA090386, CA069246, P01 CA069246, U19 CA179563] NR 147 TC 67 Z9 67 U1 11 U2 65 PU ANNUAL REVIEWS PI PALO ALTO PA 4139 EL CAMINO WAY, PO BOX 10139, PALO ALTO, CA 94303-0897 USA SN 0362-1642 BN 978-0-8243-0455-3 J9 ANNU REV PHARMACOL JI Annu. Rev. Pharmacol. Toxicol. PY 2015 VL 55 BP 439 EP 464 DI 10.1146/annurev-pharmtox-010814-124630 PG 26 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA BB9PW UT WOS:000348560500024 PM 25292428 ER PT J AU Freire, M Choi, JH Nguyen, A Chee, YD Kook, JK You, HK Zadeh, HH AF Freire, Marcelo Choi, Jeong-Ho Nguyen, Anthony Chee, Young Deok Kook, Joong-Ki You, Hyung-Keun Zadeh, Homayoun H. TI Application of AMOR in Craniofacial Rabbit Bone Bioengineering SO BIOMED RESEARCH INTERNATIONAL LA English DT Review ID MEDIATED OSSEOUS REGENERATION; LUMBAR INTERBODY FUSION; GROWTH-FACTOR DELIVERY; MORPHOGENETIC PROTEIN-2; MONOCLONAL-ANTIBODIES; CLINICAL-EVALUATION; DEVELOPMENT TRENDS; IN-VITRO; TISSUE; RECOMBINANT AB Endogenous molecular and cellular mediators modulate tissue repair and regeneration. We have recently described antibody mediated osseous regeneration (AMOR) as a novel strategy for bioengineering bone in rat calvarial defect. This entails application of anti-BMP-2 antibodies capable of in vivo capturing of endogenous osteogenic BMPs (BMP-2, BMP-4, and BMP-7). The present study sought to investigate the feasibility of AMOR in other animal models. To that end, we examined the efficacy of a panel of anti-BMP-2 monoclonal antibodies (mAbs) and a polyclonal Ab immobilized on absorbable collagen sponge (ACS) to mediate bone regeneration within rabbit calvarial critical size defects. After 6 weeks, de novo bone formation was demonstrated by micro-CT imaging, histology, and histomorphometric analysis. Only certain anti-BMP-2 mAb clones mediated significant in vivo bone regeneration, suggesting that the epitopes with which anti-BMP-2 mAbs react are critical to AMOR. Increased localization of BMP-2 protein and expression of osteocalcin were observed within defects, suggesting accumulation of endogenous BMP-2 and/or increased de novo expression of BMP-2 protein within sites undergoing bone repair by AMOR. Considering the ultimate objective of translation of this therapeutic strategy in humans, preclinical studies will be necessary to demonstrate the feasibility of AMOR in progressively larger animal models. C1 [Freire, Marcelo] Forsyth Inst, Dept Appl Oral Sci, Cambridge, MA USA. [Freire, Marcelo] Harvard Univ, Sch Dent Med, Dept Infect & Immun, Boston, MA 02115 USA. [Choi, Jeong-Ho] Seoul Natl Univ, Sch Dent, Dept Orthodont, Seoul 110749, South Korea. [Nguyen, Anthony; Zadeh, Homayoun H.] Univ So Calif, Ostrow Sch Dent, Los Angeles, CA 90033 USA. [Chee, Young Deok; You, Hyung-Keun] Wonkwang Univ, Coll Dent, Dept Periodontol, Iksan, South Korea. [Kook, Joong-Ki] Chosun Univ, Sch Dent, Dept Oral Biochem, Kwangju, South Korea. [Zadeh, Homayoun H.] Univ So Calif, Herman Ostrow Sch Dent, Lab Immunoregulat & Tissue Engn, Los Angeles, CA 90089 USA. RP Zadeh, HH (reprint author), Univ So Calif, Ostrow Sch Dent, Los Angeles, CA 90033 USA. EM zadeh@usc.edu OI Choi, Jeong-Ho/0000-0003-4529-7218; You, Hyung-Keun/0000-0002-4585-0477; Freire, Marcelo/0000-0003-4906-7698 NR 48 TC 0 Z9 0 U1 1 U2 5 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 2015 AR 628769 DI 10.1155/2015/628769 PG 7 WC Biotechnology & Applied Microbiology; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Research & Experimental Medicine GA CA9PQ UT WOS:000349257600001 ER PT J AU Nakao, S Kimura, A Hagiwara, Y Hasegawa, K AF Nakao, Shunichiro Kimura, Akio Hagiwara, Yusuke Hasegawa, Kohei CA Japanese Emergency Med Network TI Trauma airway management in emergency departments: a multicentre, prospective, observational study in Japan SO BMJ OPEN LA English DT Article ID INTUBATION; MEDICINE; INJURY AB Objectives: Although successful airway management is essential for emergency trauma care, comprehensive studies are limited. We sought to characterise current trauma care practice of airway management in the emergency departments (EDs) in Japan. Design: Analysis of data from a prospective, observational, multicentre registry-the Japanese Emergency Airway Network (JEAN) registry. Setting: 13 academic and community EDs from different geographic regions across Japan. Participants: 723 trauma patients who underwent emergency intubation from March 2010 through August 2012. Outcome measures: ED characteristics, patient and operator demographics, methods of airway management, intubation success or failure at each attempt and adverse events. Results: A total of 723 trauma patients who underwent emergency intubation were eligible for the analysis. Traumatic cardiac arrest comprised 32.6% (95% CI 29.3% to 36.1%) of patients. Rapid sequence intubation (RSI) was the initial method chosen in 23.9% (95% CI 21.0% to 27.2%) of all trauma patients and in 35.5% (95% CI 31.4% to 39.9%) of patients without cardiac arrest. Overall, intubation was successful in <= 3 attempts in 96% of patients (95% CI 94.3% to 97.2%). There was a wide variation in the initial methods of intubation; RSI as the initial method was performed in 0-50.9% of all trauma patients among 12 EDs. Similarly, there was a wide variation in success rates and adverse event rates across the EDs. Success rates varied between 35.5% and 90.5% at the first attempt, and 85.1% and 100% within three attempts across the 12 EDs. Conclusions: In this multicentre prospective study in Japan, we observed a high overall success rate in airway management during trauma care. However, the methods of intubation and success rates were highly variable among hospitals. C1 [Nakao, Shunichiro; Kimura, Akio] Natl Ctr Global Hlth & Med, Dept Emergency Med & Crit Care, Shinjuku Ku, Tokyo, Japan. [Hagiwara, Yusuke] Tokyo Metropolitan Childrens Med Ctr, Dept Emergency Med, Fuchu, Tokyo, Japan. [Hasegawa, Kohei] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Emergency Med, Boston, MA USA. RP Nakao, S (reprint author), Natl Ctr Global Hlth & Med, Dept Emergency Med & Crit Care, Shinjuku Ku, Tokyo, Japan. EM shunichiro-nakao@umin.ac.jp FU St Luke's Life Science Institute; Massachusetts General Hospital; Brigham and Women's Hospital FX This study was supported by a grant from St Luke's Life Science Institute and a grant from Massachusetts General Hospital and Brigham and Women's Hospital. NR 20 TC 1 Z9 1 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 2015 VL 5 IS 2 AR e006623 DI 10.1136/bmjopen-2014-006623 PG 6 WC Medicine, General & Internal SC General & Internal Medicine GA CA2ZK UT WOS:000348774900008 PM 25652800 ER PT J AU Blashill, AJ Safren, SA AF Blashill, Aaron J. Safren, Steven A. TI Body dissatisfaction and condom use self-efficacy: A meta-analysis SO BODY IMAGE LA English DT Review DE Body image; Body dissatisfaction; Condom use self-efficacy; Meta-analysis; Sexual risk behaviors ID PSYCHOSOCIAL HEALTH-PROBLEMS; SEXUAL-BEHAVIOR; RISK BEHAVIORS; HIV RISK; IMAGE; MEN; WOMEN; INTERVENTIONS; ADOLESCENTS; ADULTS AB The consistent use of condoms is the most effective behavior for reducing the acquisition of sexually transmitted infections (STIs), and condom use self-efficacy has been shown to be a key construct related to condom use. However, the examination of modifiable psychosocial and behavioral correlates of condom use self-efficacy is lacking. Recent investigations have highlighted the association of body dissatisfaction with condom use self-efficacy, and the current study conducted a meta-analysis on all available data addressing this relationship. Eleven individual effect-size parameters from nine studies yielded a total sample of 2495 men and women participants. A random-effects model revealed an average effect-size of r=-.25, Cohen's d= -0.52, which is moderate in strength. As body dissatisfaction increases, ones' self-efficacy regarding the use of condoms diminishes. Integrating interventions to decrease body dissatisfaction and sexual risk behaviors may prove to be an effective strategy to decrease STIs. (C) 2014 Elsevier Ltd. All rights reserved. C1 [Blashill, Aaron J.; Safren, Steven A.] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. [Blashill, Aaron J.; Safren, Steven A.] Harvard Univ, Sch Med, Dept Psychiat, Boston, MA USA. RP Blashill, AJ (reprint author), Massachusetts Gen Hosp, Dept Psychiat, 1 Bowdoin Sq,7th Floor, Boston, MA 02114 USA. EM ablashill@mgh.harvard.edu FU National Institute of Mental Health of the National Institutes of Health [K23MH096647, K24MH094214] FX Research reported in this publication was supported by the National Institute of Mental Health of the National Institutes of Health under award numbers K23MH096647, to Aaron Blashill, and K24MH094214, to Steven Safren. NR 38 TC 5 Z9 5 U1 3 U2 9 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1740-1445 EI 1873-6807 J9 BODY IMAGE JI Body Image PD JAN PY 2015 VL 12 BP 73 EP 77 DI 10.1016/j.bodyim.2014.10.002 PG 5 WC Psychology, Clinical; Psychiatry; Psychology, Multidisciplinary SC Psychology; Psychiatry GA CA5NG UT WOS:000348954500010 PM 25462884 ER PT J AU Hall, KT Tolkin, BR Chinn, GM Kirsch, I Kelley, JM Lembo, AJ Kaptchuk, TJ Kokkotou, E Davis, RB Conboy, LA AF Hall, Kathryn T. Tolkin, Benjamin R. Chinn, Garrett M. Kirsch, Irving Kelley, John M. Lembo, Anthony J. Kaptchuk, Ted J. Kokkotou, Efi Davis, Roger B. Conboy, Lisa A. TI Conscientiousness is modified by genetic variation in catechol-O-methyltransferase to reduce symptom complaints in IBS patients SO BRAIN AND BEHAVIOR LA English DT Article DE Catechol-O-methyltransferase; complaints; COMT; conscientiousness; personality ID IRRITABLE-BOWEL-SYNDROME; PERSONALITY-TRAITS; PLACEBO GROUPS; POLYMORPHISMS; ANXIETY; NOCEBO; SEVERITY; GENOTYPE AB Background Attention to and perception of physical sensations and somatic states can significantly influence reporting of complaints and symptoms in the context of clinical care and randomized trials. Although anxiety and high neuroticism are known to increase the frequency and severity of complaints, it is not known if other personality dimensions or genes associated with cognitive function or sympathetic tone can influence complaints. Genetic variation in catechol-O-methyltransferase (COMT) is associated with anxiety, personality, pain, and response to placebo treatment. We hypothesized that the association of complaint reporting with personality might be modified by variation in the COMT val158met genotype. Methods We administered a standard 25-item complaint survey weekly over 3-weeks to a convenience sample of 187 irritable bowel syndrome patients enrolled in a placebo intervention trial and conducted a repeated measures analysis. Results We found that complaint severity rating, our primary outcome, was negatively associated with the personality measures of conscientiousness (=-0.31 SE 0.11, P=0.003) and agreeableness (=-0.38 SE 0.12, P=0.002) and was positively associated with neuroticism (=0.24 SE 0.09, P=0.005) and anxiety (=0.48 SE 0.09, P<0.0001). We also found a significant interaction effect of COMT met alleles (=-32.5 SE 14.1, P=0.021). in patients genotyped for COMT val158met (N =87) specifically COMTxconscientiousness (=0.73 SE 0.26, P=0.0042) and COMTxanxiety (=-0.42 SE 0.16, P=0.0078) interaction effects. Conclusion These findings potentially broaden our understanding of the factors underlying clinical complaints to include the personality dimension of conscientiousness and its modification by COMT. C1 [Hall, Kathryn T.; Tolkin, Benjamin R.; Kirsch, Irving; Kelley, John M.; Lembo, Anthony J.; Kaptchuk, Ted J.; Kokkotou, Efi; Davis, Roger B.; Conboy, Lisa A.] Beth Israel Deaconess Med Ctr, Program Placebo Studies, Boston, MA 02215 USA. [Hall, Kathryn T.; Tolkin, Benjamin R.; Chinn, Garrett M.; Kirsch, Irving; Kelley, John M.; Lembo, Anthony J.; Kaptchuk, Ted J.; Kokkotou, Efi; Davis, Roger B.; Conboy, Lisa A.] Harvard Univ, Sch Med, Boston, MA USA. [Hall, Kathryn T.; Tolkin, Benjamin R.; Kaptchuk, Ted J.; Davis, Roger B.; Conboy, Lisa A.] Beth Israel Deaconess Med Ctr, Div Gen Med & Primary Care, Boston, MA 02215 USA. [Chinn, Garrett M.] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. [Kirsch, Irving] Univ Plymouth, Sch Psychol, Plymouth PL4 8AA, Devon, England. [Kelley, John M.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Psychiat, Boston, MA USA. [Kelley, John M.] Endicott Coll, Beverly, MA USA. [Lembo, Anthony J.; Kokkotou, Efi] Beth Israel Deaconess Med Ctr, Dept Gastroenterol, Boston, MA 02215 USA. RP Hall, KT (reprint author), Beth Israel Deaconess Med Ctr, Program Placebo Studies, Boston, MA 02215 USA. EM kthall@bidmc.harvard.edu FU National Center for Complementary and Alternative Medicine (NCCAM), National Institute Health (NIH) [R01 AT004662, K24 AT004095, 3R01AT004662-02S1, T32 AT000051, R21 AT002860] FX This work was supported by National Center for Complementary and Alternative Medicine (NCCAM), National Institute Health (NIH), grants # R01 AT004662, K24 AT004095, 3R01AT004662-02S1, T32 AT000051, and R21 AT002860. NR 32 TC 6 Z9 6 U1 1 U2 8 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 2162-3279 J9 BRAIN BEHAV JI Brain Behav. PD JAN PY 2015 VL 5 IS 1 AR e00294 DI 10.1002/brb3.294 PG 6 WC Behavioral Sciences; Neurosciences SC Behavioral Sciences; Neurosciences & Neurology GA CA6OO UT WOS:000349034700005 PM 25722948 ER PT J AU Jahshan, C Wynn, JK Mathis, KI Green, MF AF Jahshan, Carol Wynn, Jonathan K. Mathis, Kristopher I. Green, Michael F. TI The neurophysiology of biological motion perception in schizophrenia SO BRAIN AND BEHAVIOR LA English DT Article DE Biological motion; electroencephalography; event-related potential; schizophrenia; visual perception ID EVENT-RELATED POTENTIALS; RECOGNITION; ATTENTION; COGNITION; SPECTRUM; FORM AB Introduction: The ability to recognize human biological motion is a fundamental aspect of social cognition that is impaired in people with schizophrenia. However, little is known about the neural substrates of impaired biological motion perception in schizophrenia. In the current study, we assessed event-related potentials (ERPs) to human and nonhuman movement in schizophrenia. Methods: Twenty-four subjects with schizophrenia and 18 healthy controls completed a biological motion task while their electroencephalography (EEG) was simultaneously recorded. Subjects watched clips of point-light animations containing 100%, 85%, or 70% biological motion, and were asked to decide whether the clip resembled human or nonhuman movement. Three ERPs were examined: P1, N1, and the late positive potential (LPP). Results: Behaviorally, schizophrenia subjects identified significantly fewer stimuli as human movement compared to healthy controls in the 100% and 85% conditions. At the neural level, P1 was reduced in the schizophrenia group but did not differ among conditions in either group. There were no group differences in N1 but both groups had the largest N1 in the 70% condition. There was a conditionxgroup interaction for the LPP: Healthy controls had a larger LPP to 100% versus 85% and 70% biological motion; there was no difference among conditions in schizophrenia subjects. Conclusions: Consistent with previous findings, schizophrenia subjects were impaired in their ability to recognize biological motion. The EEG results showed that biological motion did not influence the earliest stage of visual processing (P1). Although schizophrenia subjects showed the same pattern of N1 results relative to healthy controls, they were impaired at a later stage (LPP), reflecting a dysfunction in the identification of human form in biological versus nonbiological motion stimuli. C1 [Jahshan, Carol; Wynn, Jonathan K.; Mathis, Kristopher I.; Green, Michael F.] VA Greater Los Angeles Healthcare Syst, Mental Illness Res Educ & Clin Ctr, Los Angeles, CA 90073 USA. [Jahshan, Carol; Wynn, Jonathan K.; Mathis, Kristopher I.; Green, Michael F.] Univ Calif Los Angeles, Semel Inst Neurosci & Human Behav, Los Angeles, CA 90024 USA. RP Jahshan, C (reprint author), VA Greater Los Angeles Healthcare Syst, Mental Illness Res Educ & Clin Ctr, Bldg 210,Room 117,11301 Wilshire Blvd, Los Angeles, CA 90073 USA. EM carol.jahshan@ucla.edu RI Wynn, Jonathan/H-3749-2014 OI Wynn, Jonathan/0000-0002-1763-8540 FU Department of Veterans Affairs Desert Pacific Mental Illness Research, Education and Clinical Center (MIRECC); National Institute of Mental Health [MH065707] FX Funding for this study was provided by grants from the Department of Veterans Affairs Desert Pacific Mental Illness Research, Education and Clinical Center (MIRECC), and the National Institute of Mental Health (MH065707 to MFG). The MIRECC and National Institutes of Health had no role in study design; in the collection, analysis, and interpretation of data; in the writing of the report; and in the decision to submit the paper for publication. The authors thank C. Gibson, C. Tripp, K. Weiner, M. McGee, and A. Bender for their assistance with recruitment and testing. The authors also thank Jejoong Kim, Ph.D. for providing the biological motion task. NR 31 TC 0 Z9 0 U1 0 U2 3 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 2162-3279 J9 BRAIN BEHAV JI Brain Behav. PD JAN PY 2015 VL 5 IS 1 AR e00303 DI 10.1002/brb3.303 PG 10 WC Behavioral Sciences; Neurosciences SC Behavioral Sciences; Neurosciences & Neurology GA CA6OO UT WOS:000349034700008 ER PT J AU Pinheiro, AP Vasconcelos, M Dias, M Arrais, N Goncalves, OF AF Pinheiro, Ana P. Vasconcelos, Margarida Dias, Marcelo Arrais, Nuno Goncalves, Oscar F. TI The music of language: An ERP investigation of the effects of musical training on emotional prosody processing SO BRAIN AND LANGUAGE LA English DT Article DE Event-related potentials; Emotional prosody; Language; Musical training ID EVENT-RELATED POTENTIALS; SPEECH PROSODY; AUDITORY-CORTEX; VOCAL EMOTION; FOREIGN-LANGUAGE; NEURAL RESPONSES; HESCHLS GYRUS; EVOKED FIELDS; BRAIN; PERCEPTION AB Recent studies have demonstrated the positive effects of musical training on the perception of vocally expressed emotion. This study investigated the effects of musical training on event-related potential (ERP) correlates of emotional prosody processing. Fourteen musicians and fourteen control subjects listened to 228 sentences with neutral semantic content, differing in prosody (one third with neutral, one third with happy and one third with angry intonation), with intelligible semantic content (semantic content condition - SCC) and unintelligible semantic content (pure prosody condition - PPC). Reduced P50 amplitude was found in musicians. A difference between SCC and PPC conditions was found in P50 and N100 amplitude in non-musicians only, and in P200 amplitude in musicians only. Furthermore, musicians were more accurate in recognizing angry prosody in PPC sentences. These findings suggest that auditory expertise characterizing extensive musical training may impact different stages of vocal emotional processing. (C) 2014 Elsevier Inc. All rights reserved. C1 [Pinheiro, Ana P.; Vasconcelos, Margarida; Dias, Marcelo; Goncalves, Oscar F.] Univ Minho, Sch Psychol, CIPsi, Neuropsychophysiol Lab, P-4710057 Braga, Portugal. [Pinheiro, Ana P.] Harvard Univ, Sch Med, Dept Psychiat, Cognit Neurosci Lab, Boston, MA 02115 USA. [Arrais, Nuno] Univ Minho, Inst Arts & Human Sci, Music Dept, P-4710057 Braga, Portugal. [Goncalves, Oscar F.] Harvard Univ, Spaulding Rehabil Hosp, Spaulding Ctr Neuromodulat, Dept Phys Med & Rehabil, Boston, MA 02115 USA. [Goncalves, Oscar F.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA 02115 USA. RP Pinheiro, AP (reprint author), Univ Minho, Sch Psychol, CIPsi, Neuropsychophysiol Lab, Campus Gualtar, P-4710057 Braga, Portugal. EM ana.pinheiro@psi.uminho.pt RI Goncalves, Oscar/G-5278-2010; OI Goncalves, Oscar/0000-0003-2735-9155; Pinheiro, Ana/0000-0002-7981-3682 FU Fundacao para a Ciencia e a Tecnologia (FCT, Portugal) [IF/00334/2012, PTDC/PSI-PCL/116626/2010, PTDC/MHN-PCN/3606/2012]; FEDER (Fundo Europeu de Desenvolvimento Regional) through the European programs QREN (Quadro de Referenda Estrategico Nacional); COMPETE (Programa Operacional Factores de Competitividade) FX This work was supported by Grants IF/00334/2012, PTDC/PSI-PCL/116626/2010 and PTDC/MHN-PCN/3606/2012 funded by Fundacao para a Ciencia e a Tecnologia (FCT, Portugal) and FEDER (Fundo Europeu de Desenvolvimento Regional) through the European programs QREN (Quadro de Referenda Estrategico Nacional), and COMPETE (Programa Operacional Factores de Competitividade), awarded to A.P.P. NR 107 TC 1 Z9 3 U1 9 U2 26 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0093-934X EI 1090-2155 J9 BRAIN LANG JI Brain Lang. PD JAN PY 2015 VL 140 BP 24 EP 34 DI 10.1016/j.bandl.2014.10.009 PG 11 WC Audiology & Speech-Language Pathology; Linguistics; Neurosciences; Psychology, Experimental SC Audiology & Speech-Language Pathology; Linguistics; Neurosciences & Neurology; Psychology GA CA0UF UT WOS:000348631100004 PM 25461917 ER PT J AU Chan, ST Evans, KC Rosen, BR Song, TY Kwong, KK AF Chan, Suk-tak Evans, Karleyton C. Rosen, Bruce R. Song, Tian-yue Kwong, Kenneth K. TI A case study of magnetic resonance imaging of cerebrovascular reactivity: A powerful imaging marker for mild traumatic brain injury SO BRAIN INJURY LA English DT Article DE Cerebrovascular reactivity; functional magnetic resonance imaging; mild brain injury ID LEVEL-DEPENDENT MRI; RECURRENT CONCUSSION; FOOTBALL PLAYERS; WHITE-MATTER; IMPAIRMENT; PERFUSION; CO2; SOFTWARE; FMRI AB Primary objective: To use breath-hold functional magnetic resonance imaging (fMRI) to localize the brain regions with impaired cerebrovascular reactivity (CVR) in a female patient diagnosed with mild traumatic brain injury (mTBI). The extent of impaired CVR was evaluated 2 months after concussion. Follow-up scan was performed 1 year post-mTBI using the same breath-hold fMRI technique. Research design: Case report. Methods and procedures: fMRI blood oxygenation dependent level (BOLD) signals were measured under breath-hold challenge in a female mTBI patient 2 months after concussion followed by a second fMRI with breath-hold challenge 1 year later. CVR was expressed as the percentage change of BOLD signals per unit time of breath-hold. Main outcomes: In comparison with CVR measurement of normal control subjects, statistical maps of CVR revealed substantial neurovascular deficits and hemispheric asymmetry within grey and white matter in the initial breath-hold fMRI scan. Follow-up breath-hold fMRI performed 1 year post-mTBI demonstrated normalization of CVR accompanied with symptomatic recovery. Conclusions: CVR may serve as an imaging biomarker to detect subtle deficits in both grey and white matter for individual diagnosis of mTBI. The findings encourage further investigation of hypercapnic fMRI as a diagnostic tool for mTBI. C1 [Chan, Suk-tak; Rosen, Bruce R.; Song, Tian-yue; Kwong, Kenneth K.] Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Dept Radiol, Boston, MA 02114 USA. [Evans, Karleyton C.; Song, Tian-yue] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. RP Chan, ST (reprint author), Athinoula A Martinos Ctr Biomed Imaging, Bldg 149,Thirteenth St,Mail Code 149-2301, Charlestown, MA 02129 USA. EM phoebe@nmr.mgh.harvard.edu RI Chan, Suk-tak/G-5846-2015 FU National Institute of Biomedical Imaging and Bioengineering (NIBIB), National Institutes of Health [P41EB015896]; [NIH-K23MH086619] FX This research was carried out in whole at the Athinoula A. Martinos Center for Biomedical Imaging at the Massachusetts General Hospital, using resources provided by the Center for Functional Neuroimaging Technologies, P41EB015896, a P41 Biotechnology Resource Grant supported by the National Institute of Biomedical Imaging and Bioengineering (NIBIB), National Institutes of Health. This work was also supported, in part, by NIH-K23MH086619. The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper. NR 26 TC 5 Z9 6 U1 1 U2 5 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 530 WALNUT STREET, STE 850, PHILADELPHIA, PA 19106 USA SN 0269-9052 EI 1362-301X J9 BRAIN INJURY JI Brain Inj. PY 2015 VL 29 IS 3 BP 403 EP 407 DI 10.3109/02699052.2014.974209 PG 5 WC Neurosciences; Rehabilitation SC Neurosciences & Neurology; Rehabilitation GA CB0HQ UT WOS:000349307000015 PM 25384127 ER PT J AU Braunstein, LZ Brock, JE Chen, YH Truong, L Russo, AL Arvold, ND Harris, JR AF Braunstein, Lior Z. Brock, Jane E. Chen, Yu-Hui Linh Truong Russo, Andrea L. Arvold, Nils D. Harris, Jay R. TI Invasive lobular carcinoma of the breast: local recurrence after breast-conserving therapy by subtype approximation and surgical margin SO BREAST CANCER RESEARCH AND TREATMENT LA English DT Article DE Breast cancer; Invasive lobular carcinoma; Local recurrence; Breast-conserving surgery; Lumpectomy; Biologic subtype ID CLINICAL-PATHOLOGICAL FEATURES; ONCOLOGY CONSENSUS GUIDELINE; DUCTAL CARCINOMA; TUMOR CHARACTERISTICS; CONSERVATION SURGERY; AMERICAN SOCIETY; HORMONAL-THERAPY; STAGES I; CANCER; OUTCOMES AB Invasive lobular carcinoma (ILC) typically presents at a later stage than invasive ductal carcinoma (IDC) and poses unique radiographic and surgical challenges. However, current principles of breast-conserving therapy (BCT) do not distinguish between histologic subtypes, raising uncertainty about the optimal approach for patients with ILC. We studied 998 BCT patients from 1998-2007, comprised 74 % IDC, 8 % ILC, and 18 % with mixed ILC/IDC. In light of recent guidelines addressing surgical margins, specimens were assessed for margin width and biologic subtype. The Kaplan-Meier method and Cox proportional hazards models were used to analyze effects of patient and disease characteristics on local recurrence (LR). At a median of 119 months, 45 patients had an isolated LR. 10-year LR was 5.5 % for patients with IDC, 4.4 % for ILC, and 1.2 % for mixed histology (p = 0.08). The majority of ILC cases had luminal A biologic subtype (91.1 %), and analysis among all luminal A cases revealed 10-year LR of 2.6 % for IDC, 3.4 % for ILC, and 0 % for mixed tumors (p = 0.12). Patients with ILC were more likely to have initially positive surgical margins (45.0 vs 17.5 %; p < 0.001) resulting in more frequent re-excision (57.1 % vs 40.4 %; p = 0.02), though final margins were similar between ILC and IDC (p = 0.88). No LR was observed among ILC or mixed histology patients with margins < 2 mm (n = 28). On multivariate analysis, histologic subtype was not associated with LR (p = 0.52). Modern approaches confer similarly favorable LR rates for ILC, IDC, and mixed histology breast cancers despite inherent histologic differences. Patients with ILC did not require more extensive surgical margins than those with IDC. C1 [Braunstein, Lior Z.] Harvard Radiat Oncol Program, Boston, MA USA. [Brock, Jane E.] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02215 USA. [Brock, Jane E.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Chen, Yu-Hui] Dana Farber Canc Inst, Dept Biostat, Boston, MA 02115 USA. [Linh Truong; Arvold, Nils D.; Harris, Jay R.] Brigham & Womens Hosp, Dept Radiat Oncol, Boston, MA 02215 USA. [Linh Truong; Arvold, Nils D.; Harris, Jay R.] Dana Farber Canc Inst, Dept Radiat Oncol, Boston, MA 02215 USA. [Russo, Andrea L.] Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. RP Harris, JR (reprint author), Brigham & Womens Hosp, Dept Radiat Oncol, Dana 1622,450 Brookline Ave, Boston, MA 02215 USA. EM jharris@lroc.harvard.edu NR 38 TC 2 Z9 2 U1 0 U2 2 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0167-6806 EI 1573-7217 J9 BREAST CANCER RES TR JI Breast Cancer Res. Treat. PD JAN PY 2015 VL 149 IS 2 BP 555 EP 564 DI 10.1007/s10549-015-3273-y PG 10 WC Oncology SC Oncology GA CA5VT UT WOS:000348976600024 PM 25604797 ER PT J AU Pusztaszeri, M Wang, H Cibas, ES Powers, CN Bongiovanni, M Ali, S Khurana, KK Michaels, PJ Faquin, WC AF Pusztaszeri, Marc Wang, He Cibas, Edmund S. Powers, Celeste N. Bongiovanni, Massimo Ali, Syed Khurana, Kamal K. Michaels, Paul J. Faquin, William C. TI Fine-Needle Aspiration Biopsy of Secondary Neoplasms of the Thyroid Gland: A Multi-Institutional Study of 62 Cases SO CANCER CYTOPATHOLOGY LA English DT Article DE thyroid; secondary neoplasm; metastasis; renal cell carcinoma; squamous cell carcinoma; adenocarcinoma; lymphoma; adenoid cystic carcinoma; fine-needle aspiration; cytology ID ADENOID CYSTIC CARCINOMA; RENAL-CELL CARCINOMA; TO-TUMOR METASTASIS; FOLLICULAR ADENOMA; PAPILLARY CARCINOMA; DIAGNOSIS; CYTOLOGY; MALIGNANCY; EXPERIENCE; MANAGEMENT AB BACKGROUNDSecondary neoplasms of the thyroid gland (SNTGs) are uncommon, and it is important to recognize them in thyroid fine-needle aspiration biopsy (FNAB). METHODSThe authors report a cohort of 62 SNTGs from 7 institutions in the United States and Europe. Patients were identified retrospectively by searching through medical records of the respective institutions. All initial diagnoses were rendered by FNAB. RESULTSSNTGs represented 0.16% of all thyroid FNABs and were more frequent among women (ratio of women to men, 1.2:1.0). The mean patient age was of 59 years (range, 7-84 years), the mean tumor size was 3 cm (range, 0.9-7 cm), and the mean interval from diagnosis of the primary tumor was 45 months (range, 0-156 months). Eighty-seven percent of SNTGs were diagnosed as malignant by FNAB, and there was a specific SNTG diagnosis in 93% of patients. Immunocytochemistry and flow cytometry, which were used in 30% of patients, were useful ancillary studies. Adenocarcinomas (n=23; 37%) and squamous cell carcinomas (SCCs) (n=22; 35.5%) represented the majority of SNTGs, followed by lymphoma (n=5; 8%), melanoma (n=5; 8%), adenoid cystic carcinoma (n=3; 5%), and various sarcomas (n=3; 5%). Adenocarcinomas originated from the kidney (n=9; 39%), lung (n=6; 26%), breast (n=5; 22%), and colon (n=3; 13%). SCCs originated mostly from the head and neck (n=13; 59%), followed by lung (n=3; 13%), esophagus (n=3; 14%), and unknown primary sites (n=3; 14%). CONCLUSIONSAdenocarcinomas from the kidney, lung, breast, and colon along with SCCs represent the majority of SNTGs. The current results indicate that FNAB is a sensitive and accurate method for diagnosing SNTG; however, diagnostic difficulties can occur. Knowledge of clinical history and the judicious application of ancillary studies can increase the sensitivity and accuracy of FNAB for detecting SNTGs. Cancer (Cancer Cytopathol) 2015;123:19-29. (c) 2014 American Cancer Society. Adenocarcinomas from the kidney, lung, breast, and colon along with squamous cell carcinomas represent the majority of secondary neoplasms of the thyroid gland (SNTGs). Fine-needle aspiration biopsy is a sensitive and accurate method for diagnosing SNTGs; however, diagnostic difficulties can occur, and knowledge of clinical history and judicious application of ancillary studies can increase the sensitivity and accuracy of fine-needle aspiration biopsy for detecting SNTGs. C1 [Pusztaszeri, Marc] Hop Univ Geneve, Dept Pathol, CH-1211 Geneva 14, Switzerland. [Wang, He] Univ Penn, Sch Med, Dept Pathol & Lab Med, Philadelphia, PA 19104 USA. [Cibas, Edmund S.] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. [Cibas, Edmund S.; Faquin, William C.] Harvard Univ, Sch Med, Boston, MA USA. [Powers, Celeste N.] Virginia Commonwealth Univ Hlth Syst, Dept Pathol, Richmond, VA USA. [Bongiovanni, Massimo] Inst Pathol, Locarno, Switzerland. [Ali, Syed] Johns Hopkins Univ Hosp, Dept Pathol, Baltimore, MD 21287 USA. [Khurana, Kamal K.] SUNY Upstate Med Univ, Dept Pathol, Syracuse, NY 13210 USA. [Michaels, Paul J.; Faquin, William C.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. RP Pusztaszeri, M (reprint author), Hop Univ Geneve, Serv Pathol Clin, 1 Rue Michel Servet, CH-1211 Geneva 14, Switzerland. EM marc.pusztaszeri@hcuge.ch RI Bongiovanni, Massimo/C-3144-2017 OI Bongiovanni, Massimo/0000-0001-9846-6682 NR 70 TC 10 Z9 10 U1 0 U2 3 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1934-662X EI 1934-6638 J9 CANCER CYTOPATHOL JI Cancer Cytopathol. PD JAN PY 2015 VL 123 IS 1 BP 19 EP 29 DI 10.1002/cncy.21494 PG 11 WC Oncology; Pathology SC Oncology; Pathology GA CA7AP UT WOS:000349069700006 PM 25369542 ER PT J AU Nakshatri, H Appaiah, HN Anjanappa, M Gilley, D Tanaka, H Badve, S Crooks, PA Mathews, W Sweeney, C Bhat-Nakshatri, P AF Nakshatri, H. Appaiah, H. N. Anjanappa, M. Gilley, D. Tanaka, H. Badve, S. Crooks, P. A. Mathews, W. Sweeney, C. Bhat-Nakshatri, P. TI NF-kappa B-dependent and -independent epigenetic modulation using the novel anti-cancer agent DMAPT SO CELL DEATH & DISEASE LA English DT Article ID BREAST-CANCER CELLS; GENE-EXPRESSION SIGNATURE; HISTONE H3; LYSINE 36; PROTEIN; PARTHENOLIDE; METHYLATION; APOPTOSIS; METHYLTRANSFERASE; TRIMETHYLATION AB The transcription factor nuclear factor-kappaB (NF-kappa B) is constitutively active in several cancers and is a target of therapeutic development. We recently developed dimethylaminoparthenolide (DMAPT), a clinical grade water-soluble analog of parthenolide, as a potent inhibitor of NF-kappa B and demonstrated in vitro and in vivo anti-tumor activities in multiple cancers. In this study, we show DMAPT is an epigenetic modulator functioning in an NF-kappa B-dependent and -independent manner. DMAPT-mediated NF-kappa B inhibition resulted in elevated histone H3K36 trimethylation (H3K36me3), which could be recapitulated through genetic ablation of the p65 subunit of NF-kappa B or inhibitor-of-kappaB alpha super-repressor overexpression. DMAPT treatment and p65 ablation increased the levels of H3K36 trimethylases NSD1 (KMT3B) and SETD2 (KMT3A), suggesting that NF-kappa B directly represses their expression and that lower H3K36me3 is an epigenetic marker of constitutive NF-kappa B activity. Overexpression of a constitutively active p65 subunit of NF-kappa B reduced NSD1 and H3K36me3 levels. NSD1 is essential for DMAPT-induced expression of pro-apoptotic BIM, indicating a functional link between epigenetic modification and gene expression. Interestingly, we observed enhanced H4K20 trimethylation and induction of H4K20 trimethylase KMT5C in DMAPT-treated cells independent of NF-kappa B inhibition. These results add KMT5C to the list NF-kappa B-independent epigenetic targets of parthenolide, which include previously described histone deacetylase 1 (HDAC-1) and DNA methyltransferase 1. As NSD1 and SETD2 are known tumor suppressors and loss of H4K20 trimethylation is an early event in cancer progression, which contributes to genomic instability, we propose DMAPT as a potent pharmacologic agent that can reverse NF-kappa B-dependent and -independent cancer-specific epigenetic abnormalities. C1 [Nakshatri, H.; Appaiah, H. N.; Anjanappa, M.; Bhat-Nakshatri, P.] Indiana Univ Sch Med, Dept Surg, Indianapolis, IN 46202 USA. [Nakshatri, H.] Indiana Univ Sch Med, Dept Biochem & Mol Biol, Indianapolis, IN 46202 USA. [Gilley, D.; Tanaka, H.] Indiana Univ Sch Med, Dept Med & Mol Genet, Indianapolis, IN 46202 USA. [Badve, S.] Indiana Univ Sch Med, Dept Pathol & Lab Med, Indianapolis, IN 46202 USA. [Crooks, P. A.] Univ Arkansas, Dept Pharmaceut Sci, Little Rock, AR 72204 USA. [Mathews, W.] Leuchemix Inc, Woodside, CA USA. [Sweeney, C.] Dana Farber Canc Inst, Lank Ctr Genitourinary Oncol, Boston, MA 02115 USA. RP Nakshatri, H (reprint author), Indiana Univ Sch Med, Dept Surg, 980 Walther Hall,West Walnut St C218C, Indianapolis, IN 46202 USA. EM hnakshat@iupui.edu FU NIH [CA143994-01A1]; IUPUI Breast Cancer Signature Center initiative FX We thank Dr. Alex Hoffman for MEFs and Nikail R Collins for technical assistance. This work is supported by a grant from NIH CA143994-01A1 to HN. IUPUI Breast Cancer Signature Center initiative provided funding for establishing prognostic database. NR 55 TC 5 Z9 5 U1 1 U2 5 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 2041-4889 J9 CELL DEATH DIS JI Cell Death Dis. PD JAN PY 2015 VL 6 AR e1608 DI 10.1038/cddis.2014.569 PG 11 WC Cell Biology SC Cell Biology GA CA6JZ UT WOS:000349020500027 PM 25611383 ER PT J AU Marechal, A Zou, L AF Marechal, Alexandre Zou, Lee TI RPA-coated single-stranded DNA as a platform for post-translational modifications in the DNA damage response SO CELL RESEARCH LA English DT Review DE RPA; post-translational modification; phosphorylation; ubiquitination; SUMOylation ID REPLICATION-PROTEIN-A; NUCLEOTIDE EXCISION-REPAIR; UBIQUITIN E3 LIGASE; S-PHASE CHECKPOINT; N-TERMINAL DOMAIN; HOMOLOGOUS RECOMBINATION; IN-VITRO; BINDING-PROTEIN; CELL-CYCLE; PHYSICAL INTERACTION AB The Replication Protein A (RPA) complex is an essential regulator of eukaryotic DNA metabolism. RPA avidly binds to single-stranded DNA (ssDNA) through multiple oligonucleotide/oligosaccharide-binding folds and coordinates the recruitment and exchange of genome maintenance factors to regulate DNA replication, recombination and repair. The RPA-ssDNA platform also constitutes a key physiological signal which activates the master ATR kinase to protect and repair stalled or collapsed replication forks during replication stress. In recent years, the RPA complex has emerged as a key target and an important regulator of post-translational modifications in response to DNA damage, which is critical for its genome guardian functions. Phosphorylation and SUMOylation of the RPA complex, and more recently RPA-regulated ubiquitination, have all been shown to control specific aspects of DNA damage signaling and repair by modulating the interactions between RPA and its partners. Here, we review our current understanding of the critical functions of the RPA-ssDNA platform in the maintenance of genome stability and its regulation through an elaborate network of covalent modifications. C1 [Marechal, Alexandre; Zou, Lee] Harvard Univ, Massachusetts Gen Hosp, Ctr Canc, Sch Med, Charlestown, MA 02129 USA. [Zou, Lee] Harvard Univ, Massachusetts Gen Hosp, Ctr Canc, Sch Med,Dept Pathol, Boston, MA 02114 USA. RP Marechal, A (reprint author), Harvard Univ, Massachusetts Gen Hosp, Ctr Canc, Sch Med, Charlestown, MA 02129 USA. EM amarechal@mgh.harvard.edu; zou.lee@mgh.harvard.edu FU NIH [GM076388]; federal share of proton program FX We apologize to all of our colleagues whose work we could not cite due to space restrictions. We want to thank Remi Buisson, Jian Ouyang, Hai Dang Nguyen and Stephanie A Yazinski for critical reading of the manuscript and all members of the Zou Lab for fruitful discussions. This work is supported by the NIH grant GM076388 and the federal share of proton program to LZ. NR 183 TC 29 Z9 30 U1 1 U2 19 PU INST BIOCHEMISTRY & CELL BIOLOGY PI SHANGHAI PA SIBS, CAS, 319 YUEYANG ROAD, SHANGHAI, 200031, PEOPLES R CHINA SN 1001-0602 EI 1748-7838 J9 CELL RES JI Cell Res. PD JAN PY 2015 VL 25 IS 1 BP 9 EP 23 DI 10.1038/cr.2014.147 PG 15 WC Cell Biology SC Cell Biology GA CB0QE UT WOS:000349330800005 PM 25403473 ER PT J AU Sahara, M Hansson, EM Wernet, O Lui, KO Spater, D Chien, KR AF Sahara, Makoto Hansson, Emil M. Wernet, Oliver Lui, Kathy O. Spaeter, Daniela Chien, Kenneth R. TI Manipulation of a VEGF-Notch signaling circuit drives formation of functional vascular endothelial progenitors from human pluripotent stem cells (vol 24, pg 820, 2014) SO CELL RESEARCH LA English DT Correction C1 [Sahara, Makoto; Hansson, Emil M.; Lui, Kathy O.; Spaeter, Daniela; Chien, Kenneth R.] Harvard Univ, Dept Stem Cell & Regenerat Biol, Cambridge, MA 02138 USA. [Sahara, Makoto; Hansson, Emil M.; Lui, Kathy O.; Spaeter, Daniela; Chien, Kenneth R.] Harvard Univ, Harvard Stem Cell Inst, Cambridge, MA 02138 USA. [Sahara, Makoto; Lui, Kathy O.; Spaeter, Daniela] Massachusetts Gen Hosp, Ctr Regenerat Med, Boston, MA 02114 USA. [Sahara, Makoto; Chien, Kenneth R.] Karolinska Inst, Dept Med Cardiol Cell & Mol Biol, SE-17177 Stockholm, Sweden. [Wernet, Oliver] Charite, Dept Anesthesiol & Intens Care Med, D-10117 Berlin, Germany. RP Sahara, M (reprint author), Harvard Univ, Dept Stem Cell & Regenerat Biol, 7 Divin Ave, Cambridge, MA 02138 USA. RI Lui, Kathy O./E-4883-2015 OI Lui, Kathy O./0000-0002-1616-3643 NR 1 TC 2 Z9 2 U1 1 U2 6 PU INST BIOCHEMISTRY & CELL BIOLOGY PI SHANGHAI PA SIBS, CAS, 319 YUEYANG ROAD, SHANGHAI, 200031, PEOPLES R CHINA SN 1001-0602 EI 1748-7838 J9 CELL RES JI Cell Res. PD JAN PY 2015 VL 25 IS 1 BP 148 EP 148 DI 10.1038/cr.2015.2 PG 1 WC Cell Biology SC Cell Biology GA CB0QE UT WOS:000349330800017 PM 25553820 ER PT J AU Qian, F Goel, G Meng, HL Wang, XM You, FP Devine, L Raddassi, K Garcia, MN Murray, KO Bolen, CR Gaujoux, R Shen-Orr, SS Hafler, D Fikrig, E Xavier, R Kleinstein, SH Montgomery, RR AF Qian, Feng Goel, Gautam Meng, Hailong Wang, Xiaomei You, Fuping Devine, Lesley Raddassi, Khadir Garcia, Melissa N. Murray, Kristy O. Bolen, Christopher R. Gaujoux, Renaud Shen-Orr, Shai S. Hafler, David Fikrig, Erol Xavier, Ramnik Kleinstein, Steven H. Montgomery, Ruth R. TI Systems Immunology Reveals Markers of Susceptibility to West Nile Virus Infection SO CLINICAL AND VACCINE IMMUNOLOGY LA English DT Article ID GENE-EXPRESSION; INFLUENZA; ENCEPHALITIS; RESPONSES; CELLS; PATHOGENESIS; INTERFERON; MICROARRAY; RESISTANCE; PROTEINS AB West Nile virus (WNV) infection is usually asymptomatic but can cause severe neurological disease and death, particularly in older patients, and how individual variations in immunity contribute to disease severity is not yet defined. Animal studies identified a role for several immunity-related genes that determine the severity of infection. We have integrated systems-level transcriptional and functional data sets from stratified cohorts of subjects with a history of WNV infection to define whether these markers can distinguish susceptibility in a human population. Transcriptional profiles combined with immunophenotyping of primary cells identified a predictive signature of susceptibility that was detectable years after acute infection (67% accuracy), with the most prominent alteration being decreased IL1B induction following ex vivo infection of macrophages with WNV. Deconvolution analysis also determined a significant role for CXCL10 expression in myeloid dendritic cells. This systems analysis identified markers of pathogenic mechanisms and offers insights into potential therapeutic strategies. C1 [Qian, Feng; Wang, Xiaomei; Montgomery, Ruth R.] Yale Univ, Sch Med, Rheumatol Sect, New Haven, CT 06520 USA. [Meng, Hailong; Bolen, Christopher R.; Kleinstein, Steven H.] Yale Univ, Sch Med, Interdept Program Computat Biol & Bioinformat, New Haven, CT USA. [You, Fuping] Yale Univ, Sch Med, Infect Dis Sect, New Haven, CT USA. [Devine, Lesley] Yale Univ, Sch Med, Dept Lab Med, New Haven, CT 06510 USA. [Raddassi, Khadir; Hafler, David] Yale Univ, Sch Med, Dept Neurol, New Haven, CT 06510 USA. [Kleinstein, Steven H.] Yale Univ, Sch Med, Dept Pathol, New Haven, CT 06510 USA. [Fikrig, Erol] Yale Univ, Sch Med, Howard Hughes Med Inst, New Haven, CT 06510 USA. [Garcia, Melissa N.; Murray, Kristy O.] Baylor Coll Med, Houston, TX 77030 USA. [Goel, Gautam; Xavier, Ramnik] Massachusetts Gen Hosp, Ctr Computat & Integrat Biol, Boston, MA 02114 USA. [Gaujoux, Renaud; Shen-Orr, Shai S.] Technion Israel Inst Technol, Fac Med, Rappaport Inst Med Res, Dept Immunol, Haifa, Israel. [Gaujoux, Renaud; Shen-Orr, Shai S.] Technion Israel Inst Technol, Fac Biol, Haifa, Israel. RP Montgomery, RR (reprint author), Yale Univ, Sch Med, Rheumatol Sect, New Haven, CT 06520 USA. EM ruth.montgomery@yale.edu RI Qian, Feng/F-8186-2010; OI Montgomery, Ruth/0000-0002-8661-4454 FU National Institutes of Health (HHS grants) [N272201100019C, U19AI089992, AI091816, AI057229]; Gillson Longenbaugh Foundation FX This work was supported in part by the National Institutes of Health (HHS grants N272201100019C, U19AI089992, AI091816, and AI057229) and the Gillson Longenbaugh Foundation. NR 49 TC 11 Z9 11 U1 3 U2 14 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 1556-6811 EI 1556-679X J9 CLIN VACCINE IMMUNOL JI Clin. Vaccine Immunol. PD JAN PY 2015 VL 22 IS 1 BP 6 EP 16 DI 10.1128/CVI.00508-14 PG 11 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA CA2YK UT WOS:000348771800002 PM 25355795 ER PT J AU Yachimski, P Wani, S Givens, T Howard, E Higginbotham, T Price, A Berman, K Hosford, L Katcher, PM Ozanne, E Perzan, K Hur, C AF Yachimski, Patrick Wani, Sachin Givens, Tonya Howard, Eric Higginbotham, Tina Price, Angie Berman, Kenneth Hosford, Lindsay Katcher, Paul Menard Ozanne, Elissa Perzan, Katherine Hur, Chin TI Preference of Endoscopic Ablation Over Medical Prevention of Esophageal Adenocarcinoma by Patients With Barrett's Esophagus SO CLINICAL GASTROENTEROLOGY AND HEPATOLOGY LA English DT Article DE COX Inhibitor; Surgery; Patient Choice; Esophageal Cancer ID HIGH-GRADE DYSPLASIA; RADIOFREQUENCY ABLATION; DECISION AIDS; CANCER-RISK; SURVEILLANCE; METAANALYSIS; CRITERIA; THERAPY AB BACKGROUND & AIMS: Endoscopic intervention or pharmacologic inhibition of cyclooxygenase might be used to prevent progression of Barrett's esophagus (BE) to esophageal adenocarcinoma (EAC). We investigated whether patients with BE prefer endoscopic therapy or chemoprevention of EAC. METHODS: Eighty-one subjects with nondysplastic BE were given a survey that described 2 scenarios. The survey explained that treatment A (ablation), endoscopy, reduced lifetime risk of EAC by 50%, with 5% risk for esophageal stricture, whereas treatment B (aspirin) reduced lifetime risk of EAC by 50% and the risk of heart attack by 30%, yet increased the risk for ulcer by 75%. Subjects indicated their willingness to undergo either treatment A and/or treatment B if endoscopic surveillance were required every 3-5 years, every 10 years, or were not required. Visual aids were included to represent risk and benefit percentages. RESULTS: When surveillance was required every 3-5 years, more subjects were willing to undergo treatment A than treatment B (78%, 63 of 81 vs 53%, 43 of 81; P < .01). There were no differences in age, sex, education level, or history of cancer, heart disease, or ulcer between patients willing to undergo treatment A and those willing to undergo treatment B. Altering the frequency of surveillance did not affect patients' willingness to undergo either treatment. CONCLUSIONS: In a simulated scenario, patients with BE preferred endoscopic intervention over chemoprevention for EAC. Further investigation of the shared decision-making process regarding preventive strategies for patients with BE may be warranted. C1 [Yachimski, Patrick; Givens, Tonya; Howard, Eric; Higginbotham, Tina] Vanderbilt Univ, Div Gastroenterol Hepatol & Nutr, Med Ctr, Nashville, TN 37232 USA. [Wani, Sachin; Hosford, Lindsay; Katcher, Paul Menard] Univ Colorado, Div Gastroenterol & Hepatol, Aurora, CO USA. [Price, Angie; Berman, Kenneth] Vet Adm Eastern Colorado Hlth Care Syst, Denver, CO USA. [Ozanne, Elissa] Dartmouth Coll, Geisel Sch Med, Hanover, NH 03755 USA. [Perzan, Katherine; Hur, Chin] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Inst Technol Assessment, Boston, MA USA. RP Yachimski, P (reprint author), Vanderbilt Univ, Div Gastroenterol Hepatol & Nutr, Med Ctr, 1660 Vanderbilt Clin, Nashville, TN 37232 USA. EM patrick.yachimski@vanderbilt.edu OI Hur, Chin/0000-0002-2819-7576 FU National Institutes of Health [R01CA140574]; AGA Takeda Research Scholar Award in GERD and Barrett's esophagus; Barrett's esophagus; NCATS/NIH [UL1 TR000445] FX Supported by the National Institutes of Health grant R01CA140574 to Dr Hur. Dr Wani is supported by the AGA Takeda Research Scholar Award in GERD and Barrett's esophagus. Research Electronic Data Capture (REDCap) is supported by grant UL1 TR000445 from NCATS/NIH. NR 26 TC 4 Z9 4 U1 3 U2 5 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1542-3565 EI 1542-7714 J9 CLIN GASTROENTEROL H JI Clin. Gastroenterol. Hepatol. PD JAN PY 2015 VL 13 IS 1 BP 84 EP 90 DI 10.1016/j.cgh.2014.03.017 PG 7 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA AZ2BW UT WOS:000348040500016 PM 24681073 ER PT J AU Beste, LA Ioannou, GN Yang, Y Chang, MF Ross, D Dominitz, JA AF Beste, Lauren A. Ioannou, George N. Yang, Yin Chang, Michael F. Ross, David Dominitz, Jason A. TI Improved Surveillance for Hepatocellular Carcinoma With a Primary Care-Oriented Clinical Reminder SO CLINICAL GASTROENTEROLOGY AND HEPATOLOGY LA English DT Article DE Liver Cancer; Screening; Veterans; Cirrhosis ID UNITED-STATES; HEPATITIS-C; LIVER-TRANSPLANTATION; PATIENT SURVIVAL; CIRRHOSIS; CANCER; RATES; STAGE; VETERANS; FUTURE AB BACKGROUND & AIMS: Surveillance of patients with cirrhosis for hepatocellular carcinoma (HCC) with liver ultrasound every 6 months has been linked to longer survival and greater use of definitive treatment. However, less than 20% of patients typically undergo routine surveillance. METHODS: We conducted a quasi-experimental study to assess whether a primary care-oriented, point-of-care clinical reminder improves HCC surveillance. Our study included patients with cirrhosis who made 1 or more primary care visits to 8 Veterans Affairs (VA) facilities over 18 months. Clinicians at 1 facility were sent a reminder to perform liver ultrasound assessments for patients with cirrhosis who had not received surveillance in the preceding 6 months. Outcomes included the proportion of patients receiving adequate HCC surveillance (defined as >2 instances of liver imaging >6 months apart) and HCC diagnosis and stage. Because it was a quality improvement project, this study did not require approval by an institutional review board under Federal law and VA policy. RESULTS: Baseline rates of adequate HCC surveillance were similar at all facilities (18.2% at the intervention site vs 16.1% elsewhere; P = .23). After the reminder was implemented, adequate surveillance at the intervention site (for 790 patients) increased by 51%, but was unchanged at the other facilities (for 2094 patients) (27.6% vs 17.5%; P < .001). Adequate surveillance occurred more often at the intervention site (adjusted odds ratio, 1.29; 95% confidence interval, 1.03-1.61; P = .02). A higher crude percentage of patients was diagnosed with HCC at the intervention site than elsewhere (3.2% vs 1.9%; P = .03). We detected no difference in tumor stage at diagnosis. CONCLUSIONS: In a VA population, a clinical reminder system increased HCC surveillance in patients with cirrhosis. C1 [Beste, Lauren A.] Vet Affairs Puget Sound Hlth Care Syst, Gen Internal Med, Seattle, WA USA. [Beste, Lauren A.; Yang, Yin; Dominitz, Jason A.] Vet Affairs Puget Sound Hlth Care Syst, Hlth Serv Res & Dev, Seattle, WA USA. [Ioannou, George N.; Dominitz, Jason A.] Vet Affairs Puget Sound Hlth Care Syst, Gastroenterol Sect, Seattle, WA USA. [Beste, Lauren A.] Univ Washington, Div Gen Internal Med, Seattle, WA 98195 USA. [Ioannou, George N.; Dominitz, Jason A.] Univ Washington, Div Gastroenterol, Seattle, WA 98195 USA. [Chang, Michael F.] Portland VA Med Ctr, Dept Gastroenterol & Hepatol, Portland, OR USA. [Chang, Michael F.] Oregon Hlth & Sci Univ, Div Gastroenterol & Hepatol, Portland, OR 97201 USA. [Ross, David] Dept Vet Affairs, Off Clin Publ Hlth, HIV Hepatitis & Publ Hlth Pathogens Program C, Washington, DC USA. [Ross, David] George Washington Univ, Div Infect Dis, Washington, DC USA. RP Beste, LA (reprint author), VA Puget Sound Hlth Care Syst, Seattle Div, 1660 S Columbian Way, Seattle, WA 98018 USA. EM lauren.beste@va.gov OI Dominitz, Jason/0000-0002-8070-7086 FU Veterans Affairs Puget Sound Health Care System; Veterans Affairs National Hepatitis C Resource Centers program, through the Office of HIV, Hepatitis C, and Public Health Pathogens FX This material is the result of work supported by resources from the Veterans Affairs Puget Sound Health Care System and the Portland Veterans Affairs Medical Center. Funding also was provided by the Veterans Affairs National Hepatitis C Resource Centers program, through the Office of HIV, Hepatitis C, and Public Health Pathogens. The views expressed in this article are those of the authors and do not necessarily reflect the position or policy of the Department of Veterans Affairs. NR 32 TC 15 Z9 15 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1542-3565 EI 1542-7714 J9 CLIN GASTROENTEROL H JI Clin. Gastroenterol. Hepatol. PD JAN PY 2015 VL 13 IS 1 BP 172 EP 179 DI 10.1016/j.cgh.2014.04.033 PG 8 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA AZ2BW UT WOS:000348040500030 PM 24813175 ER PT J AU Ghany, MG Perrillo, R Li, RS Belle, SH Janssen, HLA Terrault, NA Shuhart, MC Lau, DTY Kim, WR Fried, MW Sterling, RK Di Bisceglie, AM Han, SHB Ganova-Raeva, LM Chang, KM Lok, ASF AF Ghany, Marc G. Perrillo, Robert Li, Ruosha Belle, Steven H. Janssen, Harry L. A. Terrault, Norah A. Shuhart, Margaret C. Lau, Daryl T-Y. Kim, W. Ray Fried, Michael W. Sterling, Richard K. Di Bisceglie, Adrian M. Han, Steven-Huy B. Ganova-Raeva, Lilia Milkova Chang, Kyong-Mi Lok, Anna Suk-Fong CA Hepatitis B Res Network TI Characteristics of Adults in the Hepatitis B Research Network in North America Reflect Their Country of Origin and Hepatitis B Virus Genotype SO CLINICAL GASTROENTEROLOGY AND HEPATOLOGY LA English DT Article DE HBeAg; Chronic Hepatitis B Virus Infection; USA; ALT ID UNITED-STATES; HBV INFECTION; EPIDEMIOLOGY; PREVALENCE; WORLDWIDE; DISEASE; BURDEN; HEALTH AB BACKGROUND & AIMS: Chronic hepatitis B virus (HBV) infection is an important cause of cirrhosis and hepatocellular carcinoma worldwide; populations that migrate to the United States and Canada might be affected disproportionately. The Hepatitis B Research Network (HBRN) is a cooperative network of investigators from the United States and Canada, created to facilitate clinical, therapeutic, and translational research in adults and children with hepatitis B. We describe the structure of the network and baseline characteristics of adults with hepatitis B enrolled in the network. METHODS: The HBRN collected data on the clinical characteristics of 1625 adults with chronic HBV infection who are not receiving antiviral therapy from 21 clinical centers in North America. RESULTS: Half of the subjects in the HBRN are men, and the median age is 42 years; 72% are Asian, 15% are black, and 11% are white; with 82% born outside of North America. The most common HBV genotype was B (39%); 74% of subjects were negative for the hepatitis B e antigen. The median serum level of HBV DNA when the study began was 3.6 log(10) IU/mL; 68% of male subjects and 67% of female subjects had alanine aminotransferase levels higher than the normal range. CONCLUSIONS: The HBRN cohort is used to address important clinical and therapeutic questions for North Americans infected with chronic HBV and to guide health policies on HBV prevention and management in North America. C1 [Ghany, Marc G.] NIDDK, Liver Dis Branch, NIH, Bethesda, MD 20892 USA. [Perrillo, Robert] Baylor Univ, Med Ctr, Hepatol Div, Dallas, TX USA. [Li, Ruosha; Belle, Steven H.] Univ Pittsburgh, Dept Epidemiol, Pittsburgh, PA 15261 USA. [Janssen, Harry L. A.] Toronto Western Hosp, Div Gastroenterol, Univ Hlth Network, Toronto, ON M5T 2S8, Canada. [Janssen, Harry L. A.] Toronto Gen Hosp, Div Gastroenterol, Univ Hlth Network, Toronto, ON, Canada. [Terrault, Norah A.] Univ Calif San Francisco, Div Gastroenterol, San Francisco, CA 94143 USA. [Shuhart, Margaret C.] Univ Washington, Harborview Med Ctr, Viral Hepatitis & Liver Clin, Seattle, WA 98104 USA. [Lau, Daryl T-Y.] Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Div Gastroenterol, Boston, MA 02215 USA. [Kim, W. Ray] Stanford Univ, Sch Med, Div Gastroenterol, Palo Alto, CA 94304 USA. [Fried, Michael W.] Univ N Carolina, Ctr Liver, Sect Hepatol, Chapel Hill, NC USA. [Sterling, Richard K.] Virginia Commonwealth Univ Hlth Syst, Sect Hepatol, Richmond, VA USA. [Di Bisceglie, Adrian M.] St Louis Univ, Sch Med, Dept Internal Med, St Louis, MO USA. [Han, Steven-Huy B.] Univ Calif Los Angeles, David Geffen Sch Med, Pfleger Liver Inst Clin, Los Angeles, CA 90095 USA. [Ganova-Raeva, Lilia Milkova] Ctr Dis Control & Prevent, Div Viral Hepatitis, Mol Epidemiol & Bioinformat Sequencing Lab, Atlanta, GA USA. [Chang, Kyong-Mi] Univ Penn, Sch Med, Philadelphia Vet Affairs Med Ctr, Penn Ctr Viral Hepatitis, Philadelphia, PA 19104 USA. [Lok, Anna Suk-Fong] Univ Michigan, Div Gastroenterol & Hepatol, Ann Arbor, MI 48109 USA. RP Ghany, MG (reprint author), NIDDK, Liver Dis Branch, NIH, Bdg 10,Room 9B-16,10 Ctr Dr,MSC 1800, Bethesda, MD 20892 USA. EM marcg@intra.niddk.nih.gov OI Barritt, Alfred/0000-0002-4200-3256; Cloonan, Yona/0000-0003-3893-3693; Wahed, Abdus/0000-0001-6911-7221 FU National Institute of Diabetes and Digestive and Kidney Diseases [U01 DK082872, DK082864, DK082874, U01 DK082944, DK082943, DK082919, DK 082843, DK082867, DK082923, DK082871, DK082927, DK082866, DK082863, A-DK-3002-001]; National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health; Immunology Center (National Institutes of Health/National Institute of Diabetes and Digestive and Kidney Diseases, Center of Molecular Studies in Digestive and Liver Diseases) [P30DK50306]; Immunology Center (National Institutes of Health Public Health Service Research) [M01RR00040]; National Center for Advancing Translational Sciences, National Institutes of Health [UL1TR000058]; Clinical and Translational Science Awards [UL1TR000004, UL1TR001111, UL1RR024986]; Gilead Sciences, Inc; Roche Molecular Systems through National Institute of Diabetes and Digestive and Kidney Diseases FX The Hepatitis B Research Network was funded by grants from the National Institute of Diabetes and Digestive and Kidney Diseases to the following investigators: U01 DK082872 (W.L.), DK082864 (S.B.), DK082874 (H.J.), U01 DK082944 (N.T.), DK082943 (R.C.), DK082919 (D.T.-Y.L.), DK 082843 (L.R.R.), DK082867 (M.W.F.), DK082923 (R.K.S.), DK082871 (A.D.B.), DK082927 (S.-H.B.H.), DK082866 (K.-M.C.), and DK082863 (A.S.-F.L.); an interagency agreement with the National Institute of Diabetes and Digestive and Kidney Diseases: A-DK-3002-001 (L.M.G.-R.); and support from the intramural program, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health (M.G.G.). Additional funding for this study was provided by the Immunology Center (National Institutes of Health/National Institute of Diabetes and Digestive and Kidney Diseases, Center of Molecular Studies in Digestive and Liver Diseases: P30DK50306; and a National Institutes of Health Public Health Service Research grant: M01RR00040 to K.-M.C.), by the National Center for Advancing Translational Sciences, National Institutes of Health (UL1TR000058 to R.K.S.); and Clinical and Translational Science Awards grants: UL1TR000004 (N.A.T.), UL1TR001111 (M.W.F.), and UL1RR024986 (A.S.-F.L.). Additional support was provided by Gilead Sciences, Inc, and Roche Molecular Systems via a Cooperative Research And Development Agreement through the National Institute of Diabetes and Digestive and Kidney Diseases. NR 15 TC 11 Z9 11 U1 2 U2 6 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1542-3565 EI 1542-7714 J9 CLIN GASTROENTEROL H JI Clin. Gastroenterol. Hepatol. PD JAN PY 2015 VL 13 IS 1 BP 183 EP 192 DI 10.1016/j.cgh.2014.06.028 PG 10 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA AZ2BW UT WOS:000348040500032 PM 25010003 ER PT J AU Toiviainen, A Jalasvuori, H Lahti, E Gursoy, U Salminen, S Fontana, M Flannagan, S Eckert, G Kokaras, A Paster, B Soderling, E AF Toiviainen, Aino Jalasvuori, Heli Lahti, Emilia Gursoy, Ulvi Salminen, Seppo Fontana, Margherita Flannagan, Susan Eckert, George Kokaras, Alexis Paster, Bruce Soderling, Eva TI Impact of orally administered lozenges with Lactobacillus rhamnosus GG and Bifidobacterium animalis subsp lactis BB-12 on the number of salivary mutans streptococci, amount of plaque, gingival inflammation and the oral microbiome in healthy adults SO CLINICAL ORAL INVESTIGATIONS LA English DT Article DE Lactobacillus rhamnosus GG; Bifidobacterium lactis BB-12; Probiotic; HOMIM; Mutans streptococci; Lactobacilli; Plaque index; Gingival index ID LONG-TERM CONSUMPTION; PROBIOTIC LACTOBACILLI; EARLY-CHILDHOOD; DENTAL-CARIES; DOUBLE-BLIND; ATCC 55730; INFECTIONS; CHILDREN; REUTERI; MILK AB The aim was to evaluate the effects of orally administered Lactobacillus rhamnosus GG (LGG) and Bifidobacterium animalis subsp. lactis BB-12 (BB-12) on the number of salivary mutans streptococci (MS), amount of plaque, gingival inflammation and the oral microbiota in healthy young adults. The study was a randomised, controlled, double-blind trial. Healthy volunteers used lozenges containing a combination of LGG and BB-12 (test group, n = 29) or lozenges without added probiotics (control group, n = 31) for 4 weeks. At baseline and at the end of the test period, the plaque index (PI) and gingival index (GI) were determined, and stimulated saliva was collected. The microbial composition of saliva was assessed using human oral microbe identification microarray (n = 30). MS and lactobacilli (LB) were plate cultured. The probiotic lozenge decreased both PI and GI (p < 0.05) while no changes were observed in the control group. However, no probiotic-induced changes were found in the microbial compositions of saliva in either group. The probiotic lozenge improved the periodontal status without affecting the oral microbiota. Short-term consumption of LGG and BB-12 decreased the amount of plaque which was associated with a clinical impact: a decrease in gingival inflammation. C1 [Toiviainen, Aino; Jalasvuori, Heli; Lahti, Emilia; Gursoy, Ulvi; Soderling, Eva] Univ Turku, Inst Dent, FIN-20520 Turku, Finland. [Salminen, Seppo] Univ Turku, Funct Foods Forum, FIN-20520 Turku, Finland. [Fontana, Margherita; Flannagan, Susan; Eckert, George] Univ Michigan, Sch Dent, Dept Cariol Restorat Sci & Endodont, Ann Arbor, MI 48109 USA. [Kokaras, Alexis; Paster, Bruce] Forsyth Inst, Dept Microbiol, Cambridge, MA 02142 USA. [Paster, Bruce] Harvard Univ, Dept Oral Med Infect & Immun, Sch Dent Med, Boston, MA 02115 USA. RP Soderling, E (reprint author), Univ Turku, Inst Dent, Lemminkaisenkatu 2, FIN-20520 Turku, Finland. EM eva.soderling@utu.fi OI Fontana, Margherita/0000-0003-2357-7534; Gursoy, Ulvi Kahraman/0000-0002-1225-5751 FU TEKES, Finland; Finnish Dental Society Apollonia; Turku University Foundation FX The excellent technical assistance of biomedical research technician Oona Hallfors is gratefully acknowledged. The STABPRO project (funded by TEKES, Finland), Finnish Dental Society Apollonia and Turku University Foundation are acknowledged for providing funding for the study. NR 44 TC 12 Z9 12 U1 6 U2 15 PU SPRINGER HEIDELBERG PI HEIDELBERG PA TIERGARTENSTRASSE 17, D-69121 HEIDELBERG, GERMANY SN 1432-6981 EI 1436-3771 J9 CLIN ORAL INVEST JI Clin. Oral Investig. PD JAN PY 2015 VL 19 IS 1 BP 77 EP 83 DI 10.1007/s00784-014-1221-6 PG 7 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA CA5XG UT WOS:000348981100010 PM 24638207 ER PT J AU Thames, AD Panos, SE Arentoft, A Byrd, DA Hinkin, CH Arbid, N AF Thames, April D. Panos, Stella E. Arentoft, Alyssa Byrd, Desiree A. Hinkin, Charles H. Arbid, Natalie TI Mild Test Anxiety Influences Neurocognitive Performance Among African Americans and European Americans: Identifying Interfering and Facilitating Sources SO CULTURAL DIVERSITY & ETHNIC MINORITY PSYCHOLOGY LA English DT Article DE anxiety; assessment; cognition; ethnicity; performance ID OBSESSIVE-COMPULSIVE DISORDER; STEREOTYPE THREAT; NEUROPSYCHOLOGICAL PERFORMANCE; WORKING-MEMORY; ACADEMIC-PERFORMANCE; SELF-REPORT; RACE; CORTISOL; ABILITY; CORTICOSTEROIDS AB The current study examined ethnic/racial differences in test-related anxiety and its relationship to neurocognitive performance in a community sample of African American (n = 40) and European American (n = 36) adults. The authors hypothesized the following: (a) Test-anxiety related to negative performance evaluation would be associated with lower neurocognitive performance, whereas anxiety unrelated to negative evaluation would be associated with higher neurocognitive performance. (b) African American participants would report higher levels of anxiety about negative performance evaluation than European Americans. (c) European Americans would report higher levels of anxiety unrelated to negative performance evaluation. The first two hypotheses were supported: Ethnic/racial differences in test-taking anxiety emerged such that African Americans reported significantly higher levels of negative performance evaluation, which was associated with lower cognitive performance. The third hypothesis was not supported: African Americans and European Americans reported similar levels of test-anxiety unrelated to negative evaluation. C1 [Thames, April D.; Panos, Stella E.; Arentoft, Alyssa; Hinkin, Charles H.] Univ Calif Los Angeles, Dept Psychiat & Biobehav Sci, Los Angeles, CA 90095 USA. [Panos, Stella E.; Arentoft, Alyssa; Hinkin, Charles H.; Arbid, Natalie] Greater Los Angeles VA Healthcare Syst, Los Angeles, CA USA. [Byrd, Desiree A.] Mt Sinai Sch Med, Dept Neurol & Psychiat, New York, NY USA. RP Thames, AD (reprint author), Univ Calif Los Angeles, Dept Psychiat & Biobehav Sci, 760 Westwood Plaza C8-226, Los Angeles, CA 90095 USA. EM athames@mednet.ucla.edu OI Arentoft, Alyssa/0000-0002-4235-4638 FU National Academy of Neuropsychology, Clinical Research Grants; National Institutes of Health/National Institute of Mental Health Career Development Award [K23 MH095661] FX This work was supported by the National Academy of Neuropsychology, Clinical Research Grants (Principal Investigator: April D. Thames) and National Institutes of Health/National Institute of Mental Health Career Development Award K23 MH095661 (Principal Investigator: April D. Thames). NR 61 TC 3 Z9 3 U1 8 U2 15 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 2015 VL 21 IS 1 BP 105 EP 113 DI 10.1037/a0037530 PG 9 WC Ethnic Studies; Psychology, Social SC Ethnic Studies; Psychology GA AZ6YH UT WOS:000348364300011 PM 25111554 ER PT J AU Leonard, MM Cureton, PA Fasano, A AF Leonard, M. M. Cureton, P. A. Fasano, A. TI Managing coeliac disease in patients with diabetes SO DIABETES OBESITY & METABOLISM LA English DT Review DE coeliac disease; gluten-free diet; type 1 diabetes ID GLUTEN-FREE DIET; METABOLIC-CONTROL; BONE MINERALIZATION; AUTOIMMUNE-DISEASES; GLYCEMIC INDEX; MELLITUS; CHILDREN; PREVALENCE; DIAGNOSIS; GROWTH AB The association between coeliac disease and type 1 diabetes has long been established. The combination of genetic susceptibility along with a potential role for gluten in the pathogenesis of autoimmunity makes defining gluten's role in type 1 diabetes extremely important. Evidence supporting the role of a gluten-free diet to improve complications associated with type 1 diabetes is not robust. However there is evidence to support improved growth, bone density and potentially the prevention of additional autoimmune diseases in patients with coeliac disease and type 1 diabetes. The gluten free diet is expensive and challenging to adhere to in people already on a modified diet. Early identification of those who have coeliac disease and would benefit from a gluten-free diet is of utmost importance to prevent complications associated with type 1 diabetes and coeliac disease. C1 [Leonard, M. M.; Cureton, P. A.; Fasano, A.] Massachusetts Gen Hosp, Ctr Celiac Res, Boston, MA 02114 USA. [Leonard, M. M.; Cureton, P. A.; Fasano, A.] Massachusetts Gen Hosp Children, Div Pediat Gastroenterol & Nutr, Boston, MA 02111 USA. [Cureton, P. A.] Univ Maryland, Sch Med, Baltimore, MD 21201 USA. RP Leonard, MM (reprint author), Massachusetts Gen Hosp Children, Dept Pediat Gastroenterol & Nutr, 165 Cambridge St, Boston, MA 02111 USA. EM Mleonard7@mgh.harvard.edu NR 54 TC 2 Z9 2 U1 2 U2 9 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1462-8902 EI 1463-1326 J9 DIABETES OBES METAB JI Diabetes Obes. Metab. PD JAN PY 2015 VL 17 IS 1 BP 3 EP 8 DI 10.1111/dom.12310 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA CA4BD UT WOS:000348848300002 PM 24814173 ER PT J AU Zhu, YJ Fotinos, A Mao, LLJ Atassi, N Zhou, EW Ahmad, S Guan, YJ Berry, JD Cudkowicz, ME Wang, X AF Zhu, Yongjin Fotinos, Anastasios Mao, Lilly L. J. Atassi, Nazem Zhou, Edward W. Ahmad, Sarfraz Guan, Yingjun Berry, James D. Cudkowicz, Merit E. Wang, Xin TI Neuroprotective agents target molecular mechanisms of disease in ALS SO DRUG DISCOVERY TODAY LA English DT Review ID AMYOTROPHIC-LATERAL-SCLEROSIS; TRANSGENIC MOUSE MODEL; HEAT-SHOCK PROTEINS; BODY-MASS INDEX; CANNABINOID CB2 RECEPTOR; PROLONGS SURVIVAL; EXTENDS SURVIVAL; SYMPTOM ONSET; CELL-DEATH; REACTIVE ASTROGLIOSIS AB Amyotrophic lateral sclerosis (ALS) is a debilitating disease characterized by progressive loss of voluntary motor neurons leading to muscle atrophy, weight loss and respiratory failure. Evidence suggests that inflammation, oxidative stress, mitochondrial dysfunction, apoptosis, glutamate excitotoxicity and proteasomal dysfunction are all responsible for ALS pathogenesis. We review neuroprotective agents with the ability to reduce ALS-related bodyweight loss, summarize the various therapies tested on animal models targeting the proposed molecular mechanisms, compare their effects on bodyweight loss, muscle damage, disease onset, duration and survival, and analyze their structure-activity relationships, with the overall goal of creating a screening strategy for further clinical application. C1 [Zhu, Yongjin; Fotinos, Anastasios; Zhou, Edward W.; Wang, Xin] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Neurosurg, Boston, MA 02115 USA. [Mao, Lilly L. J.; Ahmad, Sarfraz] Aimcan Pharma Res & Technol, Guelph, ON N1G 3X7, Canada. [Atassi, Nazem; Berry, James D.; Cudkowicz, Merit E.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Neurol Clin Res Inst, Boston, MA USA. [Guan, Yingjun] Weifang Med Univ, Dept Histol & Embryol, Weifang, Shandong, Peoples R China. RP Wang, X (reprint author), Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Neurosurg, Boston, MA 02115 USA. EM xwang@rics.bwh.harvard.edu RI Zhu, Yongjin/N-9617-2014 FU Muscular Dystrophy Association [254530]; ALS Therapy Alliance; Bill & Melinda Gates Foundation; National Natural Science Foundation of China [81271413] FX The authors thank Drs Rachna S. Pandya and Wei Li for review discussion. This work is supported by grants from the Muscular Dystrophy Association (254530 to X.W.), the ALS Therapy Alliance (to X.W.), the Bill & Melinda Gates Foundation (to X.W.) and the National Natural Science Foundation of China (81271413 to Y.G.). NR 99 TC 14 Z9 14 U1 2 U2 10 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 1359-6446 EI 1878-5832 J9 DRUG DISCOV TODAY JI Drug Discov. Today PD JAN PY 2015 VL 20 IS 1 BP 65 EP 75 DI 10.1016/j.drudis.2014.08.016 PG 11 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA CA8TL UT WOS:000349193700008 PM 25205348 ER PT J AU Abramovitch, A Pizzagalli, DA Geller, DA Reuman, L Wilhelm, S AF Abramovitch, Amitai Pizzagalli, Diego A. Geller, Daniel A. Reuman, Lillian Wilhelm, Sabine TI Cigarette smoking in obsessive-compulsive disorder and unaffected parents of OCD patients SO EUROPEAN PSYCHIATRY LA English DT Article DE Obsessive-compulsive disorder OCD; Cigarette smoking; Nicotine; Familial; Unaffected relatives ID NATIONAL EPIDEMIOLOGIC SURVEY; NICOTINE DEPENDENCE; SELF-MEDICATION; TOBACCO SMOKING; UNITED-STATES; PSYCHIATRIC-DISORDERS; PERSONALITY-TRAITS; ANXIETY DISORDERS; CHECKING BEHAVIOR; MENTAL-ILLNESS AB Background: Cigarette smoking is more prevalent among individuals with psychiatric disorders than the general population. Obsessive-compulsive disorder (OCD) may be an intriguing exception, although no recent study has investigated this hypothesis in OCD patients. Moreover, it is unknown whether reduced smoking rates are present in unaffected first-degree relatives of OCD patients. Methods: We assessed smoking prevalence in adults with OCD and unaffected parents of youth with OCD (PYOCD). To this end, 113 adults with OCD completed online questionnaires assessing symptom severity and smoking status. Smoking status was obtained from an independent sample of 210 PYOCD assessed for psychiatric diagnoses. Results: Smoking prevalence rates in adults with OCD (13.3%; n = 15) and PYOCD (9.5%; n = 20) samples were significantly lower than those found in representative samples of the general population (19-24%, all P < .001) and Axis I disorders (36-64%; all P < .001). There were no smokers in the adult OCD subset without clinically significant depressive symptoms (n = 54). Conclusion: Low prevalence of smoking in OCD may be familial and unique among psychiatric disorders, and might represent a possible state-independent OCD marker. Hypotheses concerning the uncharacteristically low prevalence rates are discussed with relation to OCD phenomenology and pathophysiology. (C) 2014 Elsevier Masson SAS. All rights reserved. C1 [Abramovitch, Amitai; Pizzagalli, Diego A.; Geller, Daniel A.; Wilhelm, Sabine] Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA. [Abramovitch, Amitai; Geller, Daniel A.; Reuman, Lillian; Wilhelm, Sabine] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. [Pizzagalli, Diego A.] McLean Hosp, Ctr Depress Anxiety & Stress Res, Belmont, MA 02178 USA. RP Abramovitch, A (reprint author), Massachusetts Gen Hosp, Dept Psychiat, OCD & Related Disorders Program, 185 Cambridge St,Suite 2000, Boston, MA 02114 USA. EM aabramovitch@mgh.harvard.edu OI Abramovitch, Amitai/0000-0001-9640-0970 FU National Institute of Mental Health [K08 MH01481]; Boehringer Ingelheim FX The present work was funded in part by a grant from the National Institute of Mental Health K08 MH01481 (Dr Geller). Dr Pizzagalli served as a consultant for AstraZeneca, Shire, Ono Pharma USA and Servier, and received royalties from Advanced Neuro Technology. Dr Geller received research support from Boehringer Ingelheim and received honoraria for speaking engagements from Eli Lily and has sat on the Eli Lily Bureau and Medical Advisory Board. The other authors have not transmitted any conflicts of interest pertaining to the present work. NR 81 TC 5 Z9 5 U1 2 U2 10 PU ELSEVIER FRANCE-EDITIONS SCIENTIFIQUES MEDICALES ELSEVIER PI PARIS PA 23 RUE LINOIS, 75724 PARIS, FRANCE SN 0924-9338 EI 1778-3585 J9 EUR PSYCHIAT JI Eur. Psychiat. PD JAN PY 2015 VL 30 IS 1 DI 10.1016/j.eurpsy.2013.12.003 PG 8 WC Psychiatry SC Psychiatry GA AZ1YX UT WOS:000348032300022 PM 24637253 ER PT J AU Jung, M AF Jung, Minsoo TI National Cancer Screening Programs and Evidence-Based Healthcare Policy in South Korea SO HEALTH POLICY LA English DT Review DE Cancer screening; National Program; Bias; Effectiveness; South Korea ID SERVICES TASK-FORCE; BREAST AB Background: South Korea has managed its National Cancer Screening Program (NCSP) since 1999 with free cancer screenings for the five major types of cancer (stomach, liver, colorectal, breast, and cervical cancer). Despite the tremendous amount of government funding, the necessity of this policy and scientific evidence pertaining to it have been questioned. Objective: This study reviewed the NCSP's effectiveness and its evidence. Findings: First, the lead-time bias of diagnosis and the length-time bias regarding the average survival time may increase the misunderstanding that the early detection of cancer will contribute to lower mortality rates and higher survival rates. Second, the positive predictive values (PPVs) of the five major types of cancer checked by the NCSP have remained at 0.6-5.7%. The sensitivity of the screening programs also stood at less than 50% on average. Conclusion: This study showed that the NCSP program has been less effective, as shown by its low PPVs and sensitivity values, and that its anticipated contribution to lowering the number of cancer-related deaths may have been a product of biased reasoning. To develop the NCSP, adequate explanations of the benefits and potential risks of cancer examinations as well as the accuracy of examinations need to be provided to patients. (c) 2014 Elsevier Ireland Ltd. All rights reserved. C1 [Jung, Minsoo] Dana Farber Canc Inst, Ctr Community Based Res, Boston, MA 02215 USA. [Jung, Minsoo] Dongduk Womens Univ, Dept Hlth Sci, Seoul, South Korea. RP Jung, M (reprint author), Dana Farber Canc Inst, Ctr Community Based Res, 450 Brookline Ave,LW 601, Boston, MA 02215 USA. EM mins.jung@gmail.com OI Jung, Minsoo/0000-0003-3317-6507 NR 30 TC 5 Z9 5 U1 0 U2 1 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0168-8510 EI 1872-6054 J9 HEALTH POLICY JI Health Policy PD JAN PY 2015 VL 119 IS 1 BP 26 EP 32 DI 10.1016/j.healthpol.2014.08.012 PG 7 WC Health Care Sciences & Services; Health Policy & Services SC Health Care Sciences & Services GA CA4RI UT WOS:000348891800004 PM 25220569 ER PT J AU Damodarasamy, M Vernon, RB Chan, CK Plymate, SR Wight, TN Reed, MJ AF Damodarasamy, Mamatha Vernon, Robert B. Chan, Christina K. Plymate, Stephen R. Wight, Thomas N. Reed, May J. TI Hyaluronan in aged collagen matrix increases prostate epithelial cell proliferation SO IN VITRO CELLULAR & DEVELOPMENTAL BIOLOGY-ANIMAL LA English DT Article DE Aging; Benign prostatic hypertrophy; Collagen gel; 3-Dimensional; Extracellular matrix; In vitro ID TUMOR PROGRESSION; I COLLAGEN; CANCER; EXPRESSION; GROWTH; MICROENVIRONMENT; ANGIOGENESIS; MIGRATION; DENSITY; GLYCOSAMINOGLYCANS AB The extracellular matrix (ECM) of the prostate, which is comprised primarily of collagen, becomes increasingly disorganized with age, a property that may influence the development of hyperplasia and cancer. Collageous ECM extracted from the tails of aged mice exhibits many characteristics of collagen in aged tissues, including the prostate. When polymerized into a 3-dimensional (3D) gel, these collagen extracts can serve as models for the study of specific cell-ECM interactions. In the present study, we examined the behaviors of human prostatic epithelial cell lines representing normal prostate epithelial cells (PEC), benign prostatic hyperplasia (BPH-1), and adenocarcinoma (LNCaP) cultured in contact with 3D gels made from collagen extracts of young and aged mice. We found that proliferation of PEC, BPH-1, and LNCaP cells were all increased by culture on aged collagen gels relative to young collagen gels. In examining age-associated differences in the composition of the collagen extracts, we found that aged and young collagen had a similar amount of several collagen-associated ECM components, but aged collagen had a much greater content of the glycosaminoglycan hyaluronan (HA) than young collagen. The addition of HA (of similar size and concentration to that found in aged collagen extracts) to cells placed in young collagen elicited significantly increased proliferation in BPH-1 cells, but not in PEC or LNCaP cells, relative to controls not exposed to HA. Of note, histochemical analyses of human prostatic tissues showed significantly higher expression of HA in BPH and prostate cancer stroma relative to stroma of normal prostate. Collectively, these results suggest that changes in ECM involving increased levels of HA contribute to the growth of prostatic epithelium with aging. C1 [Damodarasamy, Mamatha; Plymate, Stephen R.; Reed, May J.] Univ Washington, Harborview Med Ctr, Dept Med, Seattle, WA 98104 USA. [Vernon, Robert B.; Chan, Christina K.; Wight, Thomas N.] Benaroya Res Inst Virginia Mason, Matrix Biol Program, Seattle, WA 98101 USA. [Plymate, Stephen R.] Vet Affairs Puget Sound Hlth Care Syst, Seattle, WA USA. RP Reed, MJ (reprint author), Univ Washington, Harborview Med Ctr, Dept Med, 325 9th Ave,Box 359625, Seattle, WA 98104 USA. EM mjr@uw.edu FU NIA/NIH [R21 AG033391]; NIBIB/NIH [R01 EB012558] FX R21 AG033391 NIA/NIH (M.J.R.); R01 EB012558, NIBIB/NIH (R.B.V./T.N.W) NR 51 TC 3 Z9 3 U1 0 U2 4 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1071-2690 EI 1543-706X J9 IN VITRO CELL DEV-AN JI In Vitro Cell. Dev. Biol.-Anim. PD JAN PY 2015 VL 51 IS 1 BP 50 EP 58 DI 10.1007/s11626-014-9800-z PG 9 WC Cell Biology; Developmental Biology SC Cell Biology; Developmental Biology GA CA6AF UT WOS:000348989700008 PM 25124870 ER PT J AU Michel, SG Madariaga, MLL Villani, V Shanmugarajah, K AF Michel, Sebastian G. Madariaga, Maria Lucia L. Villani, Vincenzo Shanmugarajah, Kumaran TI Current progress in xenotransplantation and organ bioengineering SO INTERNATIONAL JOURNAL OF SURGERY LA English DT Review DE Organ shortage; Xenotransplantation; Bioengineering ID PORCINE ENDOGENOUS RETROVIRUS; DECAY-ACCELERATING FACTOR; ACUTE LIVER-FAILURE; CARDIAC XENOTRANSPLANTATION; BIOARTIFICIAL LIVER; PHASE-I; HEPATOCYTE TRANSPLANTATION; ORTHOTOPIC TRANSPLANTATION; REGENERATIVE MEDICINE; PULMONARY XENOGRAFTS AB Organ transplantation represents a unique method of treatment to cure people with end-stage organ failure. Since the first successful organ transplant in 1954, the field of transplantation has made great strides forward. However, despite the ability to transform and save lives, transplant surgery is still faced with a fundamental problem the number of people requiring organ transplants is simply higher than the number of organs available. To put this in stark perspective, because of this critical organ shortage 18 people every day in the United States alone die on a transplant waiting list (U. S. Department of Health & Human Services, http://organdonor. gov/about/data. html). To address this problem, attempts have been made to increase the organ supply through xenotransplantation and more recently, bioengineering. Here we trace the development of both fields, discuss their current status and highlight limitations going forward. Ultimately, lessons learned in each field may prove widely applicable and lead to the successful development of xenografts, bioengineered constructs, and bioengineered xeno-organs, thereby increasing the supply of organs for transplantation. (C) 2014 Surgical Associates Ltd. Published by Elsevier Ltd. All rights reserved. C1 [Michel, Sebastian G.; Madariaga, Maria Lucia L.; Villani, Vincenzo; Shanmugarajah, Kumaran] Massachusetts Gen Hosp, Transplantat Biol Res Ctr, Boston, MA 02114 USA. [Michel, Sebastian G.] Univ Munich, Dept Cardiac Surg, D-81377 Munich, Germany. [Madariaga, Maria Lucia L.] Massachusetts Gen Hosp, Dept Surg, Boston, MA 02129 USA. [Shanmugarajah, Kumaran] Univ London Imperial Coll Sci Technol & Med, Div Surg, London SW7 2AZ, England. RP Michel, SG (reprint author), Massachusetts Gen Hosp, Transplantat Biol Res Ctr, Bldg 149,13th St, Boston, MA 02114 USA. EM sebastian.michel@med.uni-muenchen.de; kumaran.shanmugarajah@tbrc.mgh.harvard.edu NR 83 TC 7 Z9 7 U1 3 U2 20 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1743-9191 EI 1743-9159 J9 INT J SURG JI Int. J. Surg. PD JAN PY 2015 VL 13 BP 239 EP 244 DI 10.1016/j.ijsu.2014.12.011 PG 6 WC Surgery SC Surgery GA CA1IL UT WOS:000348666000044 PM 25496853 ER PT J AU Goyal, A Moore, JB Gimbel, D Carter, JB Kroshinsky, D Ferry, JA Harris, NL Duncan, LM AF Goyal, Amrita Moore, Johanna B. Gimbel, Devon Carter, Joi B. Kroshinsky, Daniela Ferry, Judith A. Harris, Nancy L. Duncan, Lyn M. TI PD-1, S-100 and CD1a expression in pseudolymphomatous folliculitis, primary cutaneous marginal zone B-cell lymphoma (MALT lymphoma) and cutaneous lymphoid hyperplasia SO JOURNAL OF CUTANEOUS PATHOLOGY LA English DT Article DE CD1a; lymphoid hyperplasia; MALT lymphoma; PD-1; pseudolymphomatous folliculitis ID PROGRAMMED DEATH-1; CLASSIFICATION; ENTITIES; FEATURES; MARKERS; TISSUE; SKIN AB BackgroundPseudolymphomatous folliculitis is a lymphoid proliferation that clinically and histopathologically mimics primary cutaneous extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue (MALT lymphoma). In this study, we assessed the diagnostic value of three immunohistochemical markers, programmed death-1 (PD-1), CD1a and S100. MethodsWe evaluated 25 cases of cutaneous lymphoid proliferations with established diagnoses, including 9 patients with pseudolymphomatous folliculitis, 11 with MALT lymphoma, and 5 with cutaneous lymphoid hyperplasia (CLH). The clinical, histopathologic and immunohistochemical characteristics were reviewed and three major characteristics assessed: (a) proportion of T cells expressing PD-1, (b) pattern of expression of CD1a by dendritic cells and (c) pattern of expression of S100 by dendritic cells. ResultsWe found pseudolymphomatous folliculitis to have a significant increase in PD-1+ T cells compared with MALT lymphoma (p < 0.0001). The pattern of CD1a staining is also informative: MALT lymphoma is significantly more likely to demonstrate a peripheral concentration of CD1a+ dendritic cells around lymphoid nodules than pseudolymphomatous folliculitis (p < 0.0003) or CLH (p < 0.05). Pseudolymphomatous folliculitis demonstrates an interstitial distribution of CD1a+ cells more often than MALT lymphoma (p < 0.04). S100 staining was not a helpful discriminator. ConclusionsHistopathologic factors including PD-1 and CD1a staining patterns may allow for more certainty in distinguishing lymphoid hyperplasia, including pseudolymphomatous folliculitis, from MALT lymphoma. C1 [Goyal, Amrita; Moore, Johanna B.; Gimbel, Devon; Carter, Joi B.; Kroshinsky, Daniela; Ferry, Judith A.; Harris, Nancy L.; Duncan, Lyn M.] Massachusetts Gen Hosp, Dermatopathol Unit, Boston, MA 02114 USA. RP Duncan, LM (reprint author), Massachusetts Gen Hosp, Dermatopathol Unit, WRN 825, 55 Fruit St, Boston, MA 02114 USA. EM duncan@helix.mgh.harvard.edu NR 39 TC 2 Z9 2 U1 0 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0303-6987 EI 1600-0560 J9 J CUTAN PATHOL JI J. Cutan. Pathol. PD JAN PY 2015 VL 42 IS 1 BP 6 EP 15 DI 10.1111/cup.12440 PG 10 WC Dermatology; Pathology SC Dermatology; Pathology GA CA5BD UT WOS:000348921300002 PM 25384543 ER PT J AU Kahraman, S Aydin, C Elpek, GO Dirice, E Sanlioglu, AD AF Kahraman, S. Aydin, C. Elpek, G. O. Dirice, E. Sanlioglu, A. D. TI Diabetes-Resistant NOR Mice Are More Severely Affected by Streptozotocin Compared to the Diabetes-Prone NOD Mice: Correlations with Liver and Kidney GLUT2 Expressions SO JOURNAL OF DIABETES RESEARCH LA English DT Review ID PANCREATIC BETA-CELLS; GLUCOSE-TRANSPORTER; UP-REGULATION; GENE; ALLOXAN; ISLETS; CYCLOPHOSPHAMIDE; CYTOTOXICITY; HEPATOCYTES; PREVENTION AB Nonobese Diabetic (NOD) mice are susceptible strains for Type 1 diabetes development, and Nonobese Diabetes-Resistant (NOR) mice are defined as suitable controls for NOD mice in non-MHC-related research. Diabetes is often accelerated in NOD mice via Streptozotocin (STZ). STZ is taken inside cells via GLUT2 transmembrane carrier proteins, the major glucose transporter isoforms in pancreatic beta cells, liver, kidneys, and the small intestine. We observed severe adverse effects in NOR mice treated with STZ compared to NOD mice that were made diabetic with a similar dose. We suggested that the underlying mechanism could be differential GLUT2 expressions in pancreatic beta cells, yet immunofluorescent and immunohistochemical studies revealed similar GLUT2 expression levels. We also detected GLUT2 expression profiles in NOD and NOR hepatic and renal tissues by western blot analysis and observed considerably higher GLUT2 expression levels in liver and kidney tissues of NOR mice. Although beta cell GLUT2 expression levels are frequently evaluated as a marker predicting STZ sensitivity in animal models, we report here very different diabetic responses to STZ in two different animal strains, in spite of similar initial GLUT2 expressions in beta cells. Furthermore, use of NOR mice in STZ-mediated experimental diabetes settings should be considered accordingly. C1 [Kahraman, S.; Sanlioglu, A. D.] Akdeniz Univ, Ctr Gene & Cell Therapy, TR-07058 Antalya, Turkey. [Aydin, C.] Akdeniz Univ, Ctr Genet Diag, TR-07058 Antalya, Turkey. [Elpek, G. O.] Akdeniz Univ, Fac Med, Dept Pathol, TR-07058 Antalya, Turkey. [Dirice, E.] Harvard Univ, Sch Med, Joslin Diabet Ctr, Sect Islet Cell & Regenerat Med, Boston, MA 02215 USA. RP Sanlioglu, AD (reprint author), Akdeniz Univ, Ctr Gene & Cell Therapy, TR-07058 Antalya, Turkey. EM ahter@akdeniz.edu.tr RI Sanlioglu, Ahter/C-6504-2016; Dirice, Ercument/B-2825-2017; OI Sanlioglu, Ahter/0000-0003-4504-0375; Kahraman, Sevim/0000-0002-2880-6589 FU Akdeniz University Research Fund [2011.01.0103.001]; Scientific and Technological Research Council of Turkey (TUBITAK) [SBAG 112S450] FX This work was supported by Akdeniz University Research Fund no. 2011.01.0103.001 and the Scientific and Technological Research Council of Turkey (TUBITAK), by the Project no. SBAG 112S450. NR 30 TC 0 Z9 0 U1 1 U2 5 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 2015 AR 450128 DI 10.1155/2015/450128 PG 8 WC Endocrinology & Metabolism; Medicine, Research & Experimental SC Endocrinology & Metabolism; Research & Experimental Medicine GA CB0AI UT WOS:000349286700001 ER PT J AU Norden, AD Schiff, D Ahluwalia, MS Lesser, GJ Nayak, L Lee, EQ Rinne, ML Muzikansky, A Dietrich, J Purow, B Doherty, LM LaFrankie, DC Pulverenti, JR Rifenburg, JA Ruland, SF Smith, KH Gaffey, SC McCluskey, C Ligon, KL Reardon, DA Wen, PY AF Norden, Andrew D. Schiff, David Ahluwalia, Manmeet S. Lesser, Glenn J. Nayak, Lakshmi Lee, Eudocia Q. Rinne, Mikael L. Muzikansky, Alona Dietrich, Jorg Purow, Benjamin Doherty, Lisa M. LaFrankie, Debra C. Pulverenti, Julee R. Rifenburg, Jennifer A. Ruland, Sandra F. Smith, Katrina H. Gaffey, Sarah C. McCluskey, Christine Ligon, Keith L. Reardon, David A. Wen, Patrick Y. TI Phase II trial of triple tyrosine kinase receptor inhibitor nintedanib in recurrent high-grade gliomas SO JOURNAL OF NEURO-ONCOLOGY LA English DT Article DE High-grade glioma; Nintedanib; Anti-angiogenic therapy ID ADVANCED SOLID TUMORS; MALIGNANT GLIOMA; BIBF 1120; GLIOBLASTOMA; ANGIOGENESIS; BEVACIZUMAB; COMBINATION; MECHANISMS; SORAFENIB; EFFICACY AB Bevacizumab is FDA-approved for patients with recurrent GBM. However, the median duration of response is only 4 months. Potential mechanisms of resistance include upregulated FGF signaling and increased PDGF-mediated pericyte coverage. Nintedanib is an oral, small-molecule tyrosine kinase inhibitor of PDGFR a/b, FGFR 1-3, and VEGFR 1-3 that may overcome resistance to anti-VEGF therapy. This was a two-stage phase II trial in adults with first or second recurrence of GBM, stratified by prior bevacizumab therapy (ClinicalTrials.gov number NCT01380782;1199.94). The primary endpoint was PFS6 in the bevacizumab-naive arm (Arm A) and PFS3 in the post-bevacizumab arm (Arm B). Up to 10 anaplastic glioma (AG) patients were accrued to each arm in exploratory cohorts. Twenty-two patients enrolled in Arm A and 14 in Arm B. Arm A included 12 GBMs (55%), 13 patients with one prior regimen (59%), and median age 54 years (range 28-75). Arm B included 10 GBMs (71%), one patient with one prior regimen (7%), and median age 52 years (range 32-70). Median KPS overall was 90 (range 60-100). There were no responses. In Arm A (GBM only), PFS6 was 0%, median PFS 28 days (95% CI 27-83), and median OS 6.9 months (3.7-8.1). In Arm B (GBM only), PFS3 was 0%, median PFS 28 days (22-28), and median OS 2.6 months (1.0-6.9). Among AG patients in each arm, PFS6 was 0%. Treatment was well tolerated. In conclusion, nintedanib is not active against recurrent high-grade glioma, regardless of prior bevacizumab therapy. C1 [Norden, Andrew D.; Nayak, Lakshmi; Lee, Eudocia Q.; Rinne, Mikael L.; Wen, Patrick Y.] Brigham & Womens Hosp, Dept Neurol, Div Neurooncol, Boston, MA 02115 USA. [Norden, Andrew D.; Nayak, Lakshmi; Lee, Eudocia Q.; Rinne, Mikael L.; Doherty, Lisa M.; LaFrankie, Debra C.; Pulverenti, Julee R.; Rifenburg, Jennifer A.; Ruland, Sandra F.; Smith, Katrina H.; Gaffey, Sarah C.; McCluskey, Christine; Reardon, David A.; Wen, Patrick Y.] Dana Farber Canc Inst, Ctr Neurooncol, Boston, MA 02215 USA. [Norden, Andrew D.; Nayak, Lakshmi; Lee, Eudocia Q.; Rinne, Mikael L.; Ligon, Keith L.; Reardon, David A.; Wen, Patrick Y.] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Schiff, David; Purow, Benjamin] Univ Virginia, Sch Med, Charlottesville, VA 22908 USA. [Ahluwalia, Manmeet S.] Cleveland Clin, Cleveland, OH 44195 USA. [Lesser, Glenn J.] Wake Forest Univ, Ctr Comprehens Canc, Winston Salem, NC 27157 USA. [Muzikansky, Alona] Massachusetts Gen Hosp, Biostat Ctr, Boston, MA 02114 USA. [Dietrich, Jorg] Massachusetts Gen Hosp, Ctr Canc, Pappas Ctr Neurooncol, Boston, MA 02114 USA. [Ligon, Keith L.] Dana Farber Canc Inst, Ctr Mol Oncol Pathol, Dept Med Oncol, Boston, MA 02215 USA. [Ligon, Keith L.] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. RP Norden, AD (reprint author), Dana Farber Canc Inst, Ctr Neurooncol, 450 Brookline Ave, Boston, MA 02215 USA. EM anorden@partners.org NR 25 TC 5 Z9 5 U1 0 U2 2 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0167-594X EI 1573-7373 J9 J NEURO-ONCOL JI J. Neuro-Oncol. PD JAN PY 2015 VL 121 IS 2 BP 297 EP 302 DI 10.1007/s11060-014-1631-y PG 6 WC Oncology; Clinical Neurology SC Oncology; Neurosciences & Neurology GA CA6GZ UT WOS:000349010200008 PM 25338318 ER PT J AU Harper, DC Selleck, CS Eagerton, G Froelich, K AF Harper, Doreen C. Selleck, Cynthia S. Eagerton, Gregory Froelich, Kimberly TI PARTNERSHIP TO IMPROVE QUALITY CARE FOR VETERANS: THE VA NURSING ACADEMY SO JOURNAL OF PROFESSIONAL NURSING LA English DT Article DE Veterans; Partnerships; Nursing education; VA Nursing Academy AB More than 22 million living veterans reside in the United States. In fact, understanding military culture and the experiences of these veterans is important to their ongoing health care and the unique challenges faced by many. The Veterans Affairs (VA) Nursing Academy began in 2007 to fund pilot partnerships between schools of nursing and local VA health care facilities to better serve our veteran population. Fifteen academic/service partnerships were selected for funding between 2007 and 2009 with the goals of expanding faculty and professional development, increasing nursing student enrollment, providing opportunities for educational and practice innovations, and increasing the recruitment and retention of VA nurses. This article details critical components of the partnership developed between the Birmingham VA Medical Center and the University of Alabama at Birmingham School of Nursing, a VA Nursing Academy partnership funded in the 2009 cohort. Site-specific goals of the partnership are described along with a discussion of the framework used to develop the Birmingham VA Nursing Academy, which includes relationship building, engagement, governance, evaluation of outcomes, and sustainability. The logic model developed for the partnership is included, and the interim outputs and outcomes of this practice academic partnership are detailed, a number of which can be replicated by VAs and schools of nursing across the country. (C) 2015 Elsevier Inc. All rights reserved. C1 [Harper, Doreen C.; Selleck, Cynthia S.] Univ Alabama Birmingham, Sch Nursing, Birmingham, AL 35294 USA. [Eagerton, Gregory] Durham VA Med Ctr, Durham, NC 27705 USA. [Eagerton, Gregory] Birmingharn VA Med Ctr, Birmingham, AL 35233 USA. [Froelich, Kimberly] Birmingham VA Med Ctr, Patient Care Serv Outpatient & Staff Dev, Birmingham, AL 35294 USA. RP Selleck, CS (reprint author), Univ Alabama Birmingham, Sch Nursing, 1720 2nd Ave South, Birmingham, AL 35294 USA. EM cselleck@uab.edu NR 4 TC 3 Z9 3 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 8755-7223 EI 1532-8481 J9 J PROF NURS JI J. Prof. Nurs. PD JAN-FEB PY 2015 VL 31 IS 1 BP 57 EP 63 DI 10.1016/j.profnurs.2014.06.004 PG 7 WC Nursing SC Nursing GA CA1RR UT WOS:000348689800009 PM 25601246 ER PT J AU Schumacher, S Herwig, U Baur, V Mueller-Pfeiffer, C Martin-Soelch, C Rufer, M Bruhl, AB AF Schumacher, Sonja Herwig, Uwe Baur, Volker Mueller-Pfeiffer, Christoph Martin-Soelch, Chantal Rufer, Michael Bruehl, Annette B. TI Psychophysiological Responses During the Anticipation of Emotional Pictures SO JOURNAL OF PSYCHOPHYSIOLOGY LA English DT Article DE emotion; anticipation; facial electromyogram; skin conductance; heart rate ID STARTLE MODULATION; NEURAL RESPONSES; FACIAL REACTIONS; UNCERTAINTY; EXPERIENCE; STIMULI; VALENCE; EXPECTANCY; ATTENTION; AVERSION AB The present study sought to investigate peripheral physiological responses to the anticipation of explicitly and ambiguously cued emotional pictures. Emotionally positive and negative as well as neutral pictures were presented to 32 healthy subjects. At the beginning of an anticipation period they were cued about the valence of the upcoming picture (neutral, positive, negative, or ambiguous). Skin conductance, heart rate, and zygomaticus and corrugator electromyogram responses were measured during anticipation and perception. Responses specific to the emotional conditions were observed during anticipation as well as during perception. During the anticipation of ambiguously cued pictures, responses were similar to responses elicited by anticipating negative pictures. In line with results from brain imaging studies, peripheral physiological responses could be interpreted to reflect a negative bias for ambiguous events. C1 [Schumacher, Sonja; Baur, Volker; Mueller-Pfeiffer, Christoph; Martin-Soelch, Chantal; Rufer, Michael] Univ Zurich Hosp, Dept Psychiat & Psychotherapy, CH-8091 Zurich, Switzerland. [Herwig, Uwe; Bruehl, Annette B.] Univ Zurich, Dept Psychiat Psychotherapy & Psychosomat, CH-8006 Zurich, Switzerland. [Herwig, Uwe] Univ Ulm, Dept Psychiat & Psychotherapy 3, D-89069 Ulm, Germany. [Mueller-Pfeiffer, Christoph] Ctr Educ & Res COEUR, Psychiat Serv Cty St Gallen North, Wil, Switzerland. [Mueller-Pfeiffer, Christoph] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. [Mueller-Pfeiffer, Christoph] Harvard Univ, Sch Med, Boston, MA USA. [Martin-Soelch, Chantal] Univ Fribourg, Dept Psychol, Div Clin & Hlth Psychol, CH-1700 Fribourg, Switzerland. [Bruehl, Annette B.] Univ Cambridge, Dept Psychiat, Cambridge CB2 1TN, England. [Bruehl, Annette B.] Univ Cambridge, Behav & Clin Neurosci Inst, Cambridge CB2 1TN, England. RP Schumacher, S (reprint author), Univ Zurich Hosp, Dept Psychiat & Psychotherapy, Haldenbachstr 18, CH-8091 Zurich, Switzerland. EM sonja.schumacher@usz.ch NR 34 TC 0 Z9 0 U1 5 U2 12 PU HOGREFE & HUBER PUBLISHERS PI GOTTINGEN PA ROHNSWEG 25, D-37085 GOTTINGEN, GERMANY SN 0269-8803 EI 2151-2124 J9 J PSYCHOPHYSIOL JI J. Psychophysiol. PY 2015 VL 29 IS 1 BP 13 EP 19 DI 10.1027/0269-8803/a000129 PG 7 WC Psychology, Biological; Neurosciences SC Psychology; Neurosciences & Neurology GA CA9BX UT WOS:000349216500002 ER PT J AU Nargiso, JE Ballard, EL Skeer, MR AF Nargiso, Jessica E. Ballard, Erica L. Skeer, Margie R. TI A Systematic Review of Risk and Protective Factors Associated With Nonmedical Use of Prescription Drugs Among Youth in the United States: A Social Ecological Perspective SO JOURNAL OF STUDIES ON ALCOHOL AND DRUGS LA English DT Review ID NATIONALLY REPRESENTATIVE SAMPLE; OF-THE-LITERATURE; COLLEGE-STUDENTS; OPIOID MISUSE; SUBSTANCE USE; YOUNG-ADULTS; ADOLESCENTS; STIMULANTS; PREVALENCE; ABUSE AB Objective: The purpose of this study was to identify the strongest and most consistent risk and protective factors associated with nonmedical use of prescription drugs (NMUPD) in multiple contexts, specifically in community-, school-, interpersonal-, and individual-level domains. Method: A literature search was conducted to review studies published from 2006 to 2012 that examined NMUPD among adolescents. Included were original research studies that focused specifically on risk and protective factors or review articles that included a section on factors associated with NMUPD. Risk and protective factors were included only if a minimum of two methodologically sound research studies reviewed the variable. Results: A variety of risk and protective factors were associated with adolescent NMUPD. At the community level, evidence suggested that ease of access increased the risk of NMUPD. Parental and peer prescription drug use and approval of NMUPD were associated with misuse of prescription drugs within the interpersonal domain. At the school level, academic failure/low educational attainment was associated with high school student NMUPD. However, results for college students' academic failure and NMUPD were inconclusive. At the individual level, previous use of substances was found to be a significant risk factor for NMUPD, as was adolescent aggressive/delinquent behavior and greater perceived risk or harm of use. Conclusions: NMUPD is a serious concern among adolescents and emerging adults. Several areas exist for prevention efforts within the context of the community, school, interpersonal, and individual domains. Thus, to curb NMUPD, multifaceted approaches are needed that target factors across multiple domains. C1 [Nargiso, Jessica E.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. [Ballard, Erica L.; Skeer, Margie R.] Tufts Univ, Sch Med, Dept Publ Hlth & Community Med, Boston, MA 02111 USA. [Skeer, Margie R.] Harvard Univ, Sch Med, Dept Social & Behav Sci, Boston, MA 02114 USA. RP Nargiso, JE (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, 151 Merrimac St,6th Floor, Boston, MA 02114 USA. EM jnargiso@partners.org NR 60 TC 10 Z9 10 U1 6 U2 22 PU ALCOHOL RES DOCUMENTATION INC CENT ALCOHOL STUD RUTGERS UNIV PI PISCATAWAY PA C/O DEIRDRE ENGLISH, 607 ALLISON RD, PISCATAWAY, NJ 08854-8001 USA SN 1937-1888 EI 1938-4114 J9 J STUD ALCOHOL DRUGS JI J. Stud. Alcohol Drugs PD JAN PY 2015 VL 76 IS 1 BP 5 EP 20 PG 16 WC Substance Abuse; Psychology SC Substance Abuse; Psychology GA CA0RX UT WOS:000348625300001 PM 25486389 ER PT J AU Gabayan, GZ Sarkisian, CA Liang, LJ Sun, BC AF Gabayan, Gelareh Z. Sarkisian, Catherine A. Liang, Li-Jung Sun, Benjamin C. TI Predictors of Admission After Emergency Department Discharge in Older Adults SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Article DE emergency department; Medicare; outcomes ID PUBLIC HOSPITAL EMERGENCY; ADVERSE HEALTH OUTCOMES; DEATH AFTER-DISCHARGE; ELDERLY-PATIENTS; UNSCHEDULED RETURNS; MEDICAL ADVICE; RISK-FACTORS; CARE; ACCIDENT; VISITS AB ObjectivesTo identify predictors of hospital inpatient admission of older Medicare beneficiaries after discharge from the emergency department (ED). DesignRetrospective cohort study. SettingNonfederal California hospitals (n=284). ParticipantsVisits of Medicare beneficiaries aged 65 and older discharged from California EDs in 2007 (n=505,315). MeasurementsUsing the California Office of Statewide Health Planning and Development files, predictors ofhospital inpatient admission within 7days of ED discharge in older adults (65) with Medicare were evaluated. ResultsHospital inpatient admissions within 7days of ED discharge occurred in 23,340 (4.6%) visits and were associated with older age (70-74: adjusted odds ratio (AOR)=1.12, 95% confidence interval (CI)=1.07-1.17; 75-79: AOR=1.18, 95% CI=1.13-1.23; 80: AOR= 1.4, 95% CI=1.35-1.46), skilled nursing facility use (AOR=1.82, 95% CI=1.72-1.94), leaving the ED against medical advice (AOR=1.82, 95% CI=1.67-1.98), and the following diagnoses with the highest odds of admission: end-stage renal disease (AOR=3.83, 95% CI=2.42-6.08), chronic renal disease (AOR=3.19, 95% CI=2.26-4.49), and congestive heart failure (AOR= 3.01, 95% CI=2.59-3.50). ConclusionFive percent of older Medicare beneficiaries have a hospital inpatient admission after discharge from the ED. Chronic conditions such as renal disease and heart failure were associated with the greatest odds of admission. C1 [Gabayan, Gelareh Z.; Sarkisian, Catherine A.; Liang, Li-Jung] Univ Calif Los Angeles, Dept Med, Los Angeles, CA 90024 USA. [Gabayan, Gelareh Z.; Sarkisian, Catherine A.] Greater Los Angeles Vet Affairs Healthcare Syst, Dept Med, Portland, OR USA. [Sun, Benjamin C.] Oregon Hlth & Sci Univ, Dept Emergency Med, Portland, OR 97201 USA. RP Gabayan, GZ (reprint author), Dept Med, 11301 Wilshire Blvd,Bldg 500,111-G, Los Angeles, CA 90073 USA. EM Gelareh@gabayan.com FU Emergency Medicine Foundation; Agency for Healthcare Research and Quality [R03 HS18098]; University of California at Los Angeles Older American Independence Center National Institutes of Health (NIH); National Institute on Aging (NIA) pilot grant; NIH, National Center for Research Resources; National Center for Advancing Translational Sciences; University of California at Los Angeles Clinical and Translational Science Institute [KL2TR000122] FX This research was supported by the Emergency Medicine Foundation (Sun), the Agency for Healthcare Research and Quality (Sun R03 HS18098), and the University of California at Los Angeles Older American Independence Center National Institutes of Health (NIH), National Institute on Aging (NIA) pilot grant. Dr. Gabayan receives support from the NIH, National Center for Research Resources, National Center for Advancing Translational Sciences, University of California at Los Angeles Clinical and Translational Science Institute (Grant KL2TR000122). The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH or the NIA. NR 32 TC 2 Z9 2 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0002-8614 EI 1532-5415 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD JAN PY 2015 VL 63 IS 1 BP 39 EP 45 DI 10.1111/jgs.13185 PG 7 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA AZ7BW UT WOS:000348374200005 PM 25537073 ER PT J AU Ganz, DA Kim, SB Zingmond, DS Ramirez, KD Roth, CP Jennings, LA Mori, T Keeler, EB Wenger, NS Reuben, DB AF Ganz, David A. Kim, Sung-Bou Zingmond, David S. Ramirez, Karina D. Roth, Carol P. Jennings, Lee A. Mori, Takahiro Keeler, Emmett B. Wenger, Neil S. Reuben, David B. TI Effect of a Falls Quality Improvement Program on Serious Fall-Related Injuries SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Article DE quality improvement; practice redesign; ACOVE; falls; fall-related injuries ID OLDER-ADULTS; CONTROLLED-TRIAL; PREVENTION; RISK; FRACTURES; CARE; DISSEMINATION; INTERVENTION; PEOPLE AB ObjectivesTo determine whether a program that improves the quality of care for falls reduces the number of episodes of care for serious fall-related injuries. DesignNonrandomized controlled trial. SettingFour community-based primary care practices. ParticipantsIndividuals aged 75 and older who screened positive for fall risk. InterventionA multicomponent quality improvement program (Assessing Care of Vulnerable Elders Practice Redesign for Improved Medical Care for Elders) involving face-to-face clinician education about falls and decision support to prompt primary care providers to implement appropriate care, including referral to appropriate community resources, in response to individuals screening positive for fall risk. MeasurementsEpisodes of care for selected fall-related injuries, based on healthcare claims. ResultsOf 1,791 individuals with data available for analysis, 1,187 were in the intervention group, and 604 were in the control group. Mean age was 83, and more than two-thirds of the sample were women. After adjusting for potential confounders, there were no statistically significant differences between intervention and control groups in episodes of care for fall-related injuries during the 12-month (incidence rate ratio (IRR) 1.27, 95% confidence interval (CI)=0.93-1.73) or 24-month (IRR 1.18, 95% CI=0.93-1.49) period after initiation of the intervention. ConclusionDespite improving the care of falls, this quality improvement initiative did not result in a change in the number of episodes of care for serious fall-related injuries. Future work in community-based settings should test higher-intensity interventions to reduce fall-related injuries. C1 [Ganz, David A.; Ramirez, Karina D.; Jennings, Lee A.; Mori, Takahiro; Reuben, David B.] Univ Calif Los Angeles, David Geffen Sch Med, Multicampus Program Geriatr Med & Gerontol, Los Angeles, CA 90095 USA. [Ganz, David A.; Mori, Takahiro] Vet Affairs Los Greater Angeles Healthcare Syst, Geriatr Res Educ & Clin Ctr, Los Angeles, CA USA. [Ganz, David A.; Roth, Carol P.; Keeler, Emmett B.; Wenger, Neil S.] RAND Hlth, Santa Monica, CA USA. [Kim, Sung-Bou] Pardee RAND Grad Sch, Santa Monica, CA USA. [Zingmond, David S.; Wenger, Neil S.] Univ Calif Los Angeles, David Geffen Sch Med, Div Gen Internal Med & Hlth Serv Res, Los Angeles, CA 90095 USA. RP Ganz, DA (reprint author), VA Greater Los Angeles Healthcare Syst 11G, 11301 Wilshire Blvd,Bldg 220,Room 313, Los Angeles, CA 90073 USA. EM dganz@mednet.ucla.edu FU National Institute on Aging (NIA) [R01AG036776]; UCLA Claude Pepper Older Americans Independence Center - NIA [5P30AG028748]; National Institutes of Health; National Center for Advancing Translational Science UCLA Clinical and Translational Science Institute Grant [UL1TR000124] FX This project was supported by Grant R01AG036776 from the National Institute on Aging (NIA). Dr. Jennings was supported by the UCLA Claude Pepper Older Americans Independence Center funded by the NIA (5P30AG028748) and National Institutes of Health. National Center for Advancing Translational Science UCLA Clinical and Translational Science Institute Grant UL1TR000124. NR 24 TC 3 Z9 3 U1 1 U2 6 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0002-8614 EI 1532-5415 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD JAN PY 2015 VL 63 IS 1 BP 63 EP 70 DI 10.1111/jgs.13154 PG 8 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA AZ7BW UT WOS:000348374200008 PM 25597558 ER PT J AU Aspinall, SL Zhao, XH Semla, TP Cunningham, FE Paquin, AM Pugh, MJ Schmader, KE Stone, RA Hanlon, JT AF Aspinall, Sherrie L. Zhao, Xinhua Semla, Todd P. Cunningham, Francesca E. Paquin, Allison M. Pugh, Mary Jo Schmader, Kenneth E. Stone, Roslyn A. Hanlon, Joseph T. CA Vet Affairs Community Living Ctr TI Epidemiology of Drug-Disease Interactions in Older Veteran Nursing Home Residents SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Article DE drug-disease interactions; Beers criteria; nursing homes ID INAPPROPRIATE MEDICATION USE; PHARMACOLOGICAL MANAGEMENT; BEERS CRITERIA; RISK; CARE; PEOPLE; ADULTS; FALLS; DEMENTIA; HOSPITALIZATIONS AB ObjectivesTo describe the prevalence of and factors associated with drug-disease interactions (DDIs) in older nursing home residents according to the American Geriatrics Society 2012 Beers Criteria. DesignCross-sectional. SettingFifteen Veterans Affairs Community Living Centers. ParticipantsIndividuals aged 65 and older with a diagnosis of dementia or cognitive impairment, a history of falls or hip fracture, heart failure (HF), a history of peptic ulcer disease (PUD), or Stage IV or V chronic kidney disease (CKD). MeasurementsMedications that could exacerbate the above conditions (DDIs). ResultsThree hundred sixty-one of 696 (51.9%) eligible residents had one or more DDIs. None involved residents with a history of PUD, one involved a resident with CKD, and four occurred in residents with HF. Of 540 residents with dementia or cognitive impairment, 50.7% took a drug that could exacerbate these conditions; the most commonly involved medications were antipsychotics (35.4%) and benzodiazepines (14.4%). Of 267 with a history of falls or hip fracture, 67.8% received an interacting medication, with selective serotonin reuptake inhibitors (33.1%), antipsychotics (30.7%), and anticonvulsants (25.1%) being most commonly involved. Using separate multivariable logistic regression models, factors associated with DDIs in dementia or cognitive impairment and falls or fractures included age 85 and older (adjusted odds ratio (aOR)=0.38, 95% confidence interval (CI)=0.24-0.60 and aOR=0.48, 95% CI=0.24-0.96, respectively), taking five to eight medications (aOR=2.06, 95% CI=1.02-4.16 and aOR=4.76, 95% CI=1.68-13.5, respectively), taking nine or more medications (aOR=1.99, 95% CI=1.03-3.85 and aOR=3.68, 95% CI=1.41-9.61, respectively), and being a long-stay resident (aOR=1.80, 95% CI=1.04-3.12 and aOR=2.35, 95% CI=1.12-4.91, respectively). ConclusionDDIs were common in older nursing home residents with dementia or cognitive impairment or a history of falls or fractures. C1 [Aspinall, Sherrie L.; Semla, Todd P.; Cunningham, Francesca E.] Vet Affairs Pharm Benefits Management Serv, Hines, IL USA. [Aspinall, Sherrie L.; Zhao, Xinhua; Stone, Roslyn A.; Hanlon, Joseph T.] Vet Affairs Pittsburgh Healthcare Syst, Ctr Hlth Equity Res & Promot, Pittsburgh, PA USA. [Aspinall, Sherrie L.; Hanlon, Joseph T.] Univ Pittsburgh, Sch Pharm, Pittsburgh, PA USA. [Semla, Todd P.] Northwestern Univ, Dept Med, Chicago, IL 60611 USA. [Semla, Todd P.] Northwestern Univ, Dept Psychiat & Behav Sci, Chicago, IL 60611 USA. [Paquin, Allison M.] Vet Affairs Boston Healthcare Syst, Dept Pharm, Boston, MA USA. [Pugh, Mary Jo] South Texas Vet Hlth Care Syst, Res, San Antonio, TX USA. [Pugh, Mary Jo] Univ Texas Hlth Sci Ctr San Antonio, Dept Epidemiol & Biostat, San Antonio, TX 78229 USA. [Schmader, Kenneth E.] Durham Vet Affairs Med Ctr, Geriatr Res Educ & Clin Ctr, Durham, NC USA. [Schmader, Kenneth E.] Duke Univ, Med Ctr, Div Geriatr, Durham, NC USA. [Stone, Roslyn A.] Univ Pittsburgh, Grad Sch Publ Hlth, Pittsburgh, PA USA. [Hanlon, Joseph T.] Vet Affairs Pittsburgh Healthcare Syst, Geriatr Res Educ & Clin Ctr, Pittsburgh, PA USA. [Hanlon, Joseph T.] Univ Pittsburgh, Sch Med, Dept Med, Div Geriatr, Pittsburgh, PA 15213 USA. RP Aspinall, SL (reprint author), VA Pittsburgh Healthcare Syst, VA Ctr Hlth Equity Res & Promot, Univ Dr 151C,Bldg 30, Pittsburgh, PA 15240 USA. EM sherrie.aspinall@va.gov FU National Institute on Aging [R01-AG 027017, P30-AG024827, K07-AG033174, R01 AG037451]; Agency for Healthcare Research and Quality Grant [R01 HS018721]; ASHP Grant FX Dr. Hanlon was supported by National Institute on Aging Grants R01-AG 027017, P30-AG024827, K07-AG033174, and R01 AG037451 and Agency for Healthcare Research and Quality Grant R01 HS018721.; Dr. Semla has author or editor royalties from LexiComp, Inc. and honoraria from Omnicare, Inc. for serving on its Pharmacy and Therapeutics Committee. His spouse is an employee of AbbVie and owns stock in Hospira, Abbott, and Abbvie through her employment benefits. Dr. Paquin has an ASHP Grant for Award in Excellence in Medication-Use Safety to support dissemination of a postdischarge telephone program focused on helping older adults with cognitive difficulties transition from hospital to home. NR 38 TC 2 Z9 2 U1 1 U2 6 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0002-8614 EI 1532-5415 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD JAN PY 2015 VL 63 IS 1 BP 77 EP 84 DI 10.1111/jgs.13197 PG 8 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA AZ7BW UT WOS:000348374200010 PM 25537124 ER PT J AU Lo-Ciganic, WH Perera, S Gray, SL Boudreau, RM Zgibor, JC Strotmeyer, ES Donohue, JM Bunker, CH Newman, AB Simonsick, EM Bauer, DC Satterfield, S Caserotti, P Harris, T Shorr, RI Hanlon, JT AF Lo-Ciganic, Wei-Hsuan Perera, Subashan Gray, Shelly L. Boudreau, Robert M. Zgibor, Janice C. Strotmeyer, Elsa S. Donohue, Julie M. Bunker, Clareann H. Newman, Anne B. Simonsick, Eleanor M. Bauer, Douglas C. Satterfield, Suzanne Caserotti, Paolo Harris, Tamara Shorr, Ronald I. Hanlon, Joseph T. CA Hlth Aging Body Composition Study TI Statin Use and Decline in Gait Speed in Community-Dwelling Older Adults SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Article DE hydroxymethylglutaryl-CoA reductase inhibitors; statins; gait speed; physical function; aged ID PERIPHERAL ARTERIAL-DISEASE; COA REDUCTASE INHIBITORS; PHYSICAL PERFORMANCE; HEALTH; ATORVASTATIN; CHOLESTEROL; PREDICTOR; SYMPTOMS; THERAPY; PEOPLE AB ObjectivesTo examine the association between statin use and objectively assessed decline in gait speed in community-dwelling older adults. DesignLongitudinal cohort study. SettingHealth, Aging and Body Composition (Health ABC) Study. ParticipantsTwo thousand five participants aged 70-79 at baseline with medication and gait speed data at 1998-99, 1999-2000, 2001-02, and 2002-03. MeasurementsThe independent variables were any statin use and their standardized daily doses (low, moderate, high) and lipophilicity. The primary outcome measure was decline in gait speed of 0.1m/s or more in the following year of statin use. Multivariable generalized estimating equations were used, adjusting for demographic characteristics, health-related behaviors, health status, and access to health care. ResultsStatin use increased from 16.2% in 1998-99 to 25.6% in 2002-03. The overall proportions of those with decline in gait speed of 0.1m/s or more increased from 22.2% in 1998 to 23.9% in 2003. Statin use was not associated with decline in gait speed of 0.1m/s or more (adjusted odds ratio (AOR)=0.90, 95% confidence interval (CI)=0.77-1.06). Similar nonsignificant trends were also seen with the use of hydrophilic or lipophilic statins. Users of low-dose statins were found to have a 22% lower risk of decline in gait speed than nonusers (AOR=0.78, 95% CI=0.61-0.99), which was mainly driven by the results from 1999-2000 follow-up. ConclusionThese results suggest that statin use did not increase decline in gait speed in community-dwelling older adults. C1 [Lo-Ciganic, Wei-Hsuan; Hanlon, Joseph T.] Univ Pittsburgh, Ctr Pharmaceut Policy & Prescribing, Hlth Policy Inst, Pittsburgh, PA 15261 USA. [Perera, Subashan; Newman, Anne B.; Hanlon, Joseph T.] Univ Pittsburgh, Div Geriatr, Dept Med, Sch Med, Pittsburgh, PA 15261 USA. [Gray, Shelly L.] Univ Washington, Sch Pharm, Seattle, WA 98195 USA. [Boudreau, Robert M.; Zgibor, Janice C.; Strotmeyer, Elsa S.; Bunker, Clareann H.; Newman, Anne B.; Hanlon, Joseph T.] Univ Pittsburgh, Dept Epidemiol, Grad Sch Publ Hlth, Pittsburgh, PA 15261 USA. [Donohue, Julie M.] Univ Pittsburgh, Dept Hlth Policy & Management, Grad Sch Publ Hlth, Pittsburgh, PA 15261 USA. [Simonsick, Eleanor M.; Harris, Tamara] NIA, Intramural Res Program, Baltimore, MD 21224 USA. [Bauer, Douglas C.] Univ Calif San Francisco, Sch Med, Div Gen Med, San Francisco, CA USA. [Satterfield, Suzanne] Univ Tennessee, Ctr Hlth Sci, Dept Prevent Med, Memphis, TN 38163 USA. [Caserotti, Paolo] Univ Southern Denmark, Inst Sports Sci & Clin Biomech, Odense, Denmark. [Shorr, Ronald I.] North Florida South Georgia Vet Hlth Syst, Geriatr Res Educ & Clin Ctr, Gainesville, FL USA. [Hanlon, Joseph T.] Vet Affairs Pittsburgh Healthcare Syst, Ctr Hlth Equity Res, Pittsburgh, PA USA. [Hanlon, Joseph T.] Vet Affairs Pittsburgh Healthcare Syst, Geriatr Res Educ & Clin Ctr, Pittsburgh, PA USA. RP Lo-Ciganic, WH (reprint author), Univ Pittsburgh, Ctr Pharmaceut Policy & Prescribing, 130 DeSoto St,A636, Pittsburgh, PA 15261 USA. EM wel32@pitt.edu RI Newman, Anne/C-6408-2013; OI Newman, Anne/0000-0002-0106-1150; Strotmeyer, Elsa/0000-0002-4093-6036; Boudreau, Robert/0000-0003-0162-5187; Donohue, Julie/0000-0003-2418-6017 FU National Institute on Aging [R01-AG 027017, P30-AG024827, T32-AG021885, K07-AG033174, R01-AG034056, R01-AG028050, N01-AG-6-2101, N01-AG-6-2103, N01-AG-6-2106]; National Institute of Nursing Research grants [R01-NR010135, R01-NR012459]; Agency for Healthcare Research and Quality grants [R01-HS017695, R01-HS018721]; Intramural Research Program of the National Institutes of Health, National Institute on Aging FX This work was supported by National Institute on Aging grants and contracts (R01-AG 027017, P30-AG024827, T32-AG021885, K07-AG033174, R01-AG034056, R01-AG028050, N01-AG-6-2101, N01-AG-6-2103, N01-AG-6-2106), National Institute of Nursing Research grants (R01-NR010135, R01-NR012459), Agency for Healthcare Research and Quality grants (R01-HS017695, R01-HS018721), and the Intramural Research Program of the National Institutes of Health, National Institute on Aging. NR 30 TC 3 Z9 3 U1 0 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0002-8614 EI 1532-5415 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD JAN PY 2015 VL 63 IS 1 BP 124 EP 129 DI 10.1111/jgs.13134 PG 6 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA AZ7BW UT WOS:000348374200017 PM 25537649 ER PT J AU Inouye, SK Robinson, T Blaum, C Busby-Whitehead, J Boustani, M Chalian, A Deiner, S Fick, D Hutchison, L Johanning, J Katlic, M Kempton, J Kennedy, M Kimchi, E Ko, C Leung, J Mattison, M Mohanty, S Nana, A Needham, D Neufeld, K Richter, H Radcliff, S Weston, C Patil, S Rocco, G Yue, JR Aiello, SE Drootin, M Ickowicz, E Samuel, MJ AF Inouye, Sharon K. Robinson, Tom Blaum, Caroline Busby-Whitehead, Jan Boustani, Malaz Chalian, Ara Deiner, Stacie Fick, Donna Hutchison, Lisa Johanning, Jason Katlic, Mark Kempton, James Kennedy, Maura Kimchi, Eyal Ko, Cliff Leung, Jacqueline Mattison, Melissa Mohanty, Sanjay Nana, Arvind Needham, Dale Neufeld, Karin Richter, Holly Radcliff, Sue Weston, Christine Patil, Sneeha Rocco, Gina Yue, Jirong Aiello, Susan E. Drootin, Marianna Ickowicz, Elvy Samuel, Mary Jordan CA Amer Geriatrics Soc Expert Panel TI American Geriatrics Society Abstracted Clinical Practice Guideline for Postoperative Delirium in Older Adults SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Article DE delirium; clinical practice guidelines; post-operative delirium; delirium prevention ID ELDER LIFE PROGRAM; PREVENT DELIRIUM; HIP-FRACTURE; MULTICOMPONENT INTERVENTION; TARGETED INTERVENTION; QUALITY IMPROVEMENT; REDUCING DELIRIUM; CARE; TRIAL; WARDS AB The abstracted set of recommendations presented here provides essential guidance both on the prevention of postoperative delirium in older patients at risk of delirium and on the treatment of older surgical patients with delirium, and is based on the 2014 American Geriatrics Society (AGS) Guideline. The full version of the guideline, American Geriatrics Society Clinical Practice Guideline for Postoperative Delirium in Older Adults is available at the website of the AGS. The overall aims of the study were twofold: first, to present nonpharmacologic and pharmacologic interventions that should be implemented perioperatively for the prevention of postoperative delirium in older adults; and second, to present nonpharmacologic and pharmacologic interventions that should be implemented perioperatively for the treatment of postoperative delirium in older adults. Prevention recommendations focused on primary prevention (i.e., preventing delirium before it occurs) in patients who are at risk for postoperative delirium (e.g., those identified as moderate-to-high risk based on previous risk stratification models such as the National Institute for Health and Care Excellence (NICE) guidelines, Delirium: Diagnosis, Prevention and Management. Clinical Guideline 103; London (UK): 2010 July 29). For management of delirium, the goals of this guideline are to decrease delirium severity and duration, ensure patient safety and improve outcomes. C1 [Amer Geriatrics Soc Expert Panel] Amer Geriatr Soc, New York, NY 10024 USA. [Inouye, Sharon K.] Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Boston, MA USA. [Inouye, Sharon K.] Aging Brain Ctr, Inst Aging Res, Boston, MA USA. [Robinson, Tom] Univ Colorado, Sch Med, Aurora, CO USA. [Blaum, Caroline] NYU, Sch Med, New York, NY USA. [Busby-Whitehead, Jan] Univ N Carolina, Sch Med, Ctr Aging & Hlth, Chapel Hill, NC USA. [Boustani, Malaz] Indiana Univ Sch Med, Indianapolis, IN 46202 USA. [Chalian, Ara] Hosp Univ Penn, Philadelphia, PA 19104 USA. [Deiner, Stacie] Mt Sinai Hosp, New York, NY 10029 USA. [Fick, Donna] Penn State Univ, Coll Nursing & Med, University Pk, PA 16802 USA. [Hutchison, Lisa] Univ Arkansas Med Sci, Little Rock, AR 72205 USA. [Johanning, Jason] Univ Nebraska Med Ctr, Omaha, NE USA. [Katlic, Mark] Sinai Hosp, Baltimore, MD 21215 USA. [Kempton, James] Yale Univ, New Haven, CT 06520 USA. [Kennedy, Maura] Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. [Kimchi, Eyal] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Ko, Cliff] Univ Calif Los Angeles, Los Angeles, CA USA. [Leung, Jacqueline] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Mattison, Melissa] Harvard Univ, Boston, MA 02115 USA. [Mattison, Melissa] Beth Israel Deaconess Med Sch, Boston, MA USA. [Mohanty, Sanjay] Amer Coll Surg, Chicago, IL USA. [Nana, Arvind] JPS Hlth, Ft Worth, TX USA. [Needham, Dale] Johns Hopkins Univ, Baltimore, MD USA. [Neufeld, Karin] Johns Hopkins Univ Hosp, Baltimore, MD 21287 USA. [Richter, Holly] Univ Alabama Birmingham, Birmingham, AL USA. RP Samuel, MJ (reprint author), Amer Geriatr Soc, 40 Fulton St,18th Floor, New York, NY 10024 USA. EM mjsamuel@americangeriatrics.org FU American Geriatrics Society Geriatrics-for-Specialists Initiative (AGS-GSI) through John A. Hartford Foundation; NIH; ADRC; AGS Foundation for Anesthesia Education and Research; Brookdale; SLACK Inc.; National Institute of Nursing Research; MedEd Portal/Josiah Macy Foundation IPE Award; Practical Reviews in Hospital Medicine; ORNIM medical manufacturing; Pelvalon; Medtronics, Inc.; Karl Storz Endoscopy America; Covidien FX Sue Radcliff, Independent Researcher, Denver, CO, and Christine Weston, Independent Researcher, Baltimore, MD, led the literature review efforts of the panel. Additional research assistance was provided by Sneeha Patil, Gina Rocco, and Jirong Yue. Susan E. Aiello, DVM, ELS, provided editorial services. Marianna Drootin, MPA, Elvy Ickowicz, MPH, and Mary Jordan Samuel provided additional research and administrative support. The development of this paper was supported in part by the American Geriatrics Society Geriatrics-for-Specialists Initiative (AGS-GSI) through an unrestricted grant from the John A. Hartford Foundation.; Conflict of Interest: Drs. Blaum, Boustani, Chalian, Inouye, Katlic, Kempton, Kennedy, Kimchi, Ko, Mattison, Mohanty, and Nana indicated no conflicts of interest. Dr. Busby-Whitehead indicated her spouse is a paid consultant for Ironwood Pharma, Ono Pharma: Fecal Incontinence and Irritable Bowel Syndrome, and her spouse has received a grant from Salix Pharma, Ono Pharma: Fecal Incontinence and Irritable Bowel Syndrome. Dr. Deiner has received grants from the NIH, ADRC, and AGS Foundation for Anesthesia Education and Research, and Dr. Deiner's spouse has received grants from NIH, ADRC, AGS Foundation for Anesthesia Education and Research, and Brookdale. Dr. Deiner's spouse is also on the speaker's panel for Baxter. Both Dr. Deiner and spouse receive product support from Covidien and Aspect. Dr. Fick is a paid consultant for SLACK Inc. as Editor of the Journal of Gerontological Nursing. Dr. Fick has current R01 funding from the NIH and from the National Institute of Nursing Research. Ms. Giovannetti is employed by the National Committee for Quality Assurance (NCQA) which conducts healthcare quality research, develops healthcare quality measures, publishes healthcare quality data, and distributes healthcare quality products (e.g., Accreditation, Certification). Dr. Hutchison received grants from MedEd Portal/Josiah Macy Foundation IPE Award, and Dr. Hutchison and spouse hold shares in Cardinal Health and Care Fusion. Dr. Johanning received a royalty on Isolation Station from Harloff Corporation. Dr. Mattison is a paid consultant for Practical Reviews in Hospital Medicine and is an UpToDate contributor. Dr. Leung and her husband receive funding from the NIH. Dr. Leung's husband is the cofounder of Mynosys Inc. Dr. Needham is Chair of the Early Mobility Committee for the upcoming Society of Critical Care Medicine Clinical Practice Guideline for pain, agitation, delirium, early mobility, and sleep. Dr. Neufeld is participating on a grant from ORNIM medical manufacturing that is funding a portion of her salary. Dr. Richter is a paid consultant for and has received a research grant from Pelvalon. She has also received royalties from UpToDate. Dr. Robinson has received research grants from Medtronics, Inc., Karl Storz Endoscopy America, and Covidien. Gina Rocco and Jirong Yue have no conflicts of interest to disclose. Sneha Patil has commercial interest in Oracle. NR 35 TC 21 Z9 23 U1 1 U2 13 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0002-8614 EI 1532-5415 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD JAN PY 2015 VL 63 IS 1 BP 142 EP 150 DI 10.1111/jgs.13281 PG 9 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA AZ7BW UT WOS:000348374200020 ER PT J AU Ventura, MM Brittain, K Pruskowski, J Hogan, D Walker, T AF Ventura, MaryAnne M. Brittain, Kevin Pruskowski, Jennifer Hogan, Diana Walker, Tiffany TI DEVELOPMENT OF AN AGE-DEPENDENT ANTIBIOGRAM IN A VETERANS AFFAIRS COMMUNITY SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Letter C1 [Ventura, MaryAnne M.; Brittain, Kevin; Pruskowski, Jennifer; Hogan, Diana; Walker, Tiffany] William Jennings Bryan Dorn Vet Affairs Med Ctr, Columbia, SC 29209 USA. [Pruskowski, Jennifer] James J Peters Vet Affairs Med Ctr, Bronx, NY USA. RP Ventura, MM (reprint author), William Jennings Bryan Dorn Vet Affairs Med Ctr, Columbia, SC 29209 USA. NR 4 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0002-8614 EI 1532-5415 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD JAN PY 2015 VL 63 IS 1 BP 186 EP 188 DI 10.1111/jgs.13224 PG 3 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA AZ7BW UT WOS:000348374200034 PM 25597575 ER PT J AU Xu, N Yao, M Farinelli, W Hajjarian, Z Wang, Y Redmond, RW Kochevar, IE AF Xu, Nan Yao, Min Farinelli, William Hajjarian, Zeinab Wang, Ying Redmond, Robert W. Kochevar, Irene E. TI Light-Activated Sealing of Skin Wounds SO LASERS IN SURGERY AND MEDICINE LA English DT Article DE wound closure; incision closure; Rose Bengal; photochemical tissue bonding; photo tissue bonding; protein crosslinking; Yucatan swine skin; Yorkshire swine skin; sealing incisions; pigmented skin; melanin; epidermal melanin ID PHOTOCHEMICAL KERATODESMOS; CORNEAL INCISIONS; PORCINE SKIN; IN-VIVO; REPAIR; LASER; CLOSURE AB Background and ObjectivesWe have developed a light-activated technology for rapidly sealing skin surgical wounds called photochemical tissue bonding (PTB). The goals of this study were to evaluate parameters influencing PTB in order to optimize its clinical efficacy and to determine whether PTB can be used to seal wounds in moderately to highly pigmented skin. Study Design/Materials and MethodsApplication of Rose Bengal (RB) followed by exposure to 532nm was used to seal linear incisions (1.5mm deep, 2cm long) in lightly pigmented (Yorkshire) and darkly pigmented (Yucatan) swine skin. The force required to open the seal (the bonding strength) was measured by in situ tensiometry. Reflectance spectra, epidermal transmission spectra, and histology were used to characterize the skin. The relationships of RB concentration and fluence to bonding strength were established in Yorkshire skin. Surface temperature was measured during irradiations and cooling was used while sealing incisions in Yucatan skin. Monte Carlo simulations were carried out to estimate the effect of epidermal melanin on the power absorbed in the dermis at the incision interface. ResultsThe lowest fluence, 25J/cm(2), delivered at an irradiance of 0.5W/cm(2) substantially increased the bonding strength (approximate to 10-fold) compared to controls in Yorkshire swine skin. Increasing the fluence to 100J/cm(2) enhanced bonding strength by a further 1.5-fold. Application of 0.1% RB for 2minutes produced the greatest bonding strength using 100J/cm(2) and limited the penetration of RB to an approximate to 50m band on the dermal incision wall. Reflectance spectra indicated that Yorkshire skin had minimal melanin and that Yucatan skin was a good model for highly pigmented human skin. In Yucatan skin, the bonding strength increased 1.7-fold using 0.1% RB and 200J/cm(2) at 1.5W/cm(2) with cooling and epinephrine. Monte Carlo simulation indicated that absorption of 532nm light by epidermal melanin in dark skin decreased the power absorbed along the incision in the dermis by a factor of 2.7. ConclusionsThese results suggest that in lightly pigmented skin the PTB treatment time can be shortened without compromising the bonding strength. Sealing incisions using PTB in moderately and highly pigmented skin will require a careful balance of irradiance and cooling. Lasers Surg. Med. 47:17-29, 2015. (c) 2014 Wiley Periodicals, Inc. C1 [Xu, Nan; Yao, Min; Farinelli, William; Hajjarian, Zeinab; Wang, Ying; Redmond, Robert W.; Kochevar, Irene E.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Wellman Ctr Photomed, Boston, MA USA. [Xu, Nan] Tongji Univ, Shanghai East Hosp, Dept Dermatol, Shanghai 200092, Peoples R China. [Yao, Min] Shanghai Jiao Tong Univ, Sch Med, Inst Traumat Med, Shanghai 200030, Peoples R China. [Yao, Min] 3 Peoples Hosp, Dept Burns & Plast Surg, Shanghai, Peoples R China. RP Kochevar, IE (reprint author), Massachusetts Gen Hosp, Wellman Ctr Photomed, Thier 224,50 Fruit St, Boston, MA 02114 USA. EM kochevar@helix.mgh.harvard.edu FU US Department of Defense [FA9550-11-1-033]; Aura Medsystems; Chinese National Natural Science Foundation [81201234]; Shanghai Health Bureau [2012143] FX Contract grant sponsor: US Department of Defense Contract; Contract grant number: FA9550-11-1-033; Contract grant sponsor: Aura Medsystems; Contract grant sponsor: Chinese National Natural Science Foundation, 2013; Contract grant number: 81201234; Contract grant sponsor: Shanghai Health Bureau; Contract grant number: 2012143. NR 27 TC 6 Z9 7 U1 1 U2 7 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0196-8092 EI 1096-9101 J9 LASER SURG MED JI Lasers Surg. Med. PD JAN PY 2015 VL 47 IS 1 BP 17 EP 29 DI 10.1002/lsm.22308 PG 13 WC Dermatology; Surgery SC Dermatology; Surgery GA CA4BP UT WOS:000348849600003 PM 25418831 ER PT J AU Phillips, E Pojednic, R Polak, R Bush, J Trilk, J AF Phillips, Edward Pojednic, Rachele Polak, Rani Bush, Jennifer Trilk, Jennifer TI Including lifestyle medicine in undergraduate medical curricula SO MEDICAL EDUCATION ONLINE LA English DT Article DE behavior change; lifestyle medicine; physician education; undergraduate medical education; curriculum ID PHYSICIANS; EDUCATION; STUDENTS; EXERCISE; CARE AB Purpose: Currently, there is no model to integrate the discipline of lifestyle medicine (LM) into undergraduate medical education. Furthermore, there are no guidelines, validated assessment tools, or evaluation or implementation plans in place. Background: The World Health Organization predicts that by 2020, two-thirds of disease worldwide will be the result of poor lifestyle choices. Fewer than 50% of US primary care physicians routinely provide specific guidance on nutrition, physical activity, or weight control. Methods: We are establishing a plan to integrate LM into medical school education in collaboration with the investing stakeholders, including medical school deans and students, medical curriculum developers and researchers, medical societies, governing bodies, and policy institutes. Three planning and strategy meetings are being held to address key areas of focus - with a particular interest in nutrition, physical activity, student self-care, and behavior change - to develop specific implementation guidelines and landmarks. Results: After the first two meetings, the proposed areas of focus were determined to be: 1) supporting of deans and key personnel, 2) creation of federal and state policy commitments, 3) use of assessment as a driver of LM, 4) provision of high-quality evidence-based curricular material on an easily navigated site, and 5) engaging student interest. Implementation strategies for each focus area will be addressed in an upcoming planning meeting in early 2015. Conclusion: This initiative is expected to have important public health implications by efficiently promoting the prevention and treatment of non-communicable chronic disease with a scalable and sustainable model to educate physicians in training and practice. C1 [Phillips, Edward; Pojednic, Rachele; Polak, Rani] Harvard Univ, Sch Med, Joslin Diabet Ctr, Inst Lifestyle Med, Boston, MA 02115 USA. [Bush, Jennifer] LevelSmart Consulting, Atlanta, GA USA. [Trilk, Jennifer] Univ S Carolina, Sch Med Greenville, Dept Biomed Sci, Greenville, SC 29605 USA. RP Trilk, J (reprint author), Univ S Carolina, Sch Med Greenville, Dept Biomed Sci, Hlth Sci Adm Bldg,701 Grove Rd, Greenville, SC 29605 USA. EM TRILK@greenvillemed.sc.edu NR 15 TC 3 Z9 3 U1 1 U2 5 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 2015 VL 20 AR 26150 DI 10.3402/meo.v20.26150 PG 4 WC Education & Educational Research SC Education & Educational Research GA CB0VG UT WOS:000349345100001 PM 28229659 ER PT J AU Verzi, MP Shin, H Roman, AKS Liu, XS Shivdasani, RA AF Verzi, Michael P. Shin, Hyunjin Roman, Adrianna K. San Liu, X. Shirley Shivdasani, Ramesh A. TI Intestinal Master Transcription Factor CDX2 Controls Chromatin Access for Partner Transcription Factor Binding (vol 33, pg 281, 2013) SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Correction C1 [Verzi, Michael P.; Liu, X. Shirley; Shivdasani, Ramesh A.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Shin, Hyunjin; Liu, X. Shirley] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA. [Verzi, Michael P.; Shivdasani, Ramesh A.] Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. [Verzi, Michael P.; Roman, Adrianna K. San; Shivdasani, Ramesh A.] Harvard Univ, Sch Med, Boston, MA USA. [Verzi, Michael P.] Rutgers State Univ, Dept Genet, New Brunswick, NJ 08903 USA. [Shivdasani, Ramesh A.] Harvard Univ, Sch Med, Grad Program Biol & Biomed Sci, Boston, MA USA. RP Verzi, MP (reprint author), Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. NR 1 TC 0 Z9 0 U1 0 U2 6 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0270-7306 EI 1098-5549 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD JAN PY 2015 VL 35 IS 2 BP 496 EP 496 DI 10.1128/MCB.01396-14 PG 1 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA CB0CW UT WOS:000349293700012 ER PT J AU Betz, RC Petukhova, L Ripke, S Huang, HL Menelaou, A Redler, S Becker, T Heilmann, S Yamany, T Duvic, M Hordinsky, M Norris, D Price, VH Mackay-Wiggan, J de Jong, A DeStefano, GM Moebus, S Bohm, M Blume-Peytavi, U Wolff, H Lutz, G Kruse, R Bian, L Amos, CI Lee, A Gregersen, PK Blaumeiser, B Altshuler, D Clynes, R de Bakker, PIW Nothen, MM Daly, MJ Christiano, AM AF Betz, Regina C. Petukhova, Lynn Ripke, Stephan Huang, Hailiang Menelaou, Androniki Redler, Silke Becker, Tim Heilmann, Stefanie Yamany, Tarek Duvic, Madeliene Hordinsky, Maria Norris, David Price, Vera H. Mackay-Wiggan, Julian de Jong, Annemieke DeStefano, Gina M. Moebus, Susanne Boehm, Markus Blume-Peytavi, Ulrike Wolff, Hans Lutz, Gerhard Kruse, Roland Bian, Li Amos, Christopher I. Lee, Annette Gregersen, Peter K. Blaumeiser, Bettina Altshuler, David Clynes, Raphael de Bakker, Paul I. W. Noethen, Markus M. Daly, Mark J. Christiano, Angela M. TI Genome-wide meta-analysis in alopecia areata resolves HLA associations and reveals two new susceptibility loci SO NATURE COMMUNICATIONS LA English DT Article ID BH3-ONLY PROTEIN BIM; LATENT TGF-BETA; RHEUMATOID-ARTHRITIS; RISK LOCUS; T-CELLS; GARP; APOPTOSIS; CANCER; AUTOPHAGOSOMES; EXPRESSION AB Alopecia areata (AA) is a prevalent autoimmune disease with 10 known susceptibility loci. Here we perform the first meta-analysis of research on AA by combining data from two genome-wide association studies (GWAS), and replication with supplemented ImmunoChip data for a total of 3,253 cases and 7,543 controls. The strongest region of association is the major histocompatibility complex, where we fine-map four independent effects, all implicating human leukocyte antigen-DR as a key aetiologic driver. Outside the major histocompatibility complex, we identify two novel loci that exceed the threshold of statistical significance, containing ACOXL/BCL2L11(BIM) (2q13); GARP (LRRC32) (11q13.5), as well as a third nominally significant region SH2B3(LNK)/ATXN2 (12q24.12). Candidate susceptibility gene expression analysis in these regions demonstrates expression in relevant immune cells and the hair follicle. We integrate our results with data from seven other autoimmune diseases and provide insight into the alignment of AA within these disorders. Our findings uncover new molecular pathways disrupted in AA, including autophagy/apoptosis, transforming growth factor beta/Tregs and JAK kinase signalling, and support the causal role of aberrant immune processes in AA. C1 [Betz, Regina C.; Redler, Silke; Heilmann, Stefanie; Noethen, Markus M.] Univ Bonn, Inst Human Genet, D-53127 Bonn, Germany. [Petukhova, Lynn; Yamany, Tarek; Mackay-Wiggan, Julian; de Jong, Annemieke; Bian, Li; Clynes, Raphael; Christiano, Angela M.] Columbia Univ, Dept Dermatol, New York, NY 10032 USA. [Petukhova, Lynn] Columbia Univ, Dept Epidemiol, New York, NY 10032 USA. [Ripke, Stephan; Huang, Hailiang; Altshuler, David; Daly, Mark J.] Massachusetts Gen Hosp, Analyt & Translat Genet Unit, Boston, MA 02114 USA. [Ripke, Stephan; Huang, Hailiang; Altshuler, David; Daly, Mark J.] Harvard Univ, Sch Med, Boston, MA 02114 USA. [Ripke, Stephan; Huang, Hailiang; Altshuler, David; Daly, Mark J.] Broad Inst MIT & Harvard, Stanley Ctr Psychiat Res, Cambridge, MA 02114 USA. [Menelaou, Androniki; de Bakker, Paul I. W.] Univ Med Ctr Utrecht, Dept Med Genet, NL-3584 CG Utrecht, Netherlands. [Becker, Tim] German Ctr Neurodegenerat Dis, D-53175 Bonn, Germany. [Becker, Tim] Univ Bonn, Inst Med Biometry Informat & Epidemiol, D-53127 Bonn, Germany. [Heilmann, Stefanie; Noethen, Markus M.] Univ Bonn, Life & Brain Ctr, Dept Genom, D-53127 Bonn, Germany. [Duvic, Madeliene] Univ Texas MD Anderson Canc Ctr, Dept Dermatol, Houston, TX 77030 USA. [Hordinsky, Maria] Univ Minnesota, Dept Dermatol, Minneapolis, MN 55455 USA. [Norris, David] Univ Colorado, Dept Dermatol, Denver, CO 80204 USA. [Price, Vera H.] Univ Calif San Francisco, Dept Dermatol, San Francisco, CA 94110 USA. [DeStefano, Gina M.; Christiano, Angela M.] Columbia Univ, Dept Genet & Dev, New York, NY 10032 USA. [Moebus, Susanne] Univ Duisburg Essen, Inst Med Informat Biometry & Epidemiol, D-45122 Essen, Germany. [Boehm, Markus] Univ Munster, Dept Dermatol, D-48149 Munster, Germany. [Blume-Peytavi, Ulrike] Charite, Clin Res Ctr Hair & Skin Sci, Dept Dermatol & Allergy, D-10117 Berlin, Germany. [Wolff, Hans] Univ Munich, Dept Dermatol, D-80337 Munich, Germany. [Amos, Christopher I.] Dartmouth Coll, Hanover, NH 03755 USA. [Lee, Annette; Gregersen, Peter K.] Feinstein Inst Med Res, Manhasset, NY 11030 USA. [Blaumeiser, Bettina] Univ Antwerp, Dept Med Genet, BE-2650 Antwerp, Belgium. [Clynes, Raphael] Columbia Univ, Dept Med, New York, NY 10032 USA. [de Bakker, Paul I. W.] Univ Med Ctr Utrecht, Dept Epidemiol, NL-3584 CG Utrecht, Netherlands. RP Christiano, AM (reprint author), Columbia Univ, Dept Dermatol, New York, NY 10032 USA. EM amc65@columbia.edu RI de Bakker, Paul/B-8730-2009; OI de Bakker, Paul/0000-0001-7735-7858; de Jong, Annemieke/0000-0001-6707-6585; Heilmann-Heimbach, Stefanie/0000-0003-1057-465X; Nothen, Markus/0000-0002-8770-2464 FU National Alopecia Areata Foundation; Heinz Nixdorf Foundation; DFG-funded Excellence Cluster ImmunoSensation; German Research Foundation (DFG); DFG [BE 2346/5-1]; BONFOR; Netherlands Organization for Scientific Research [016.126.354]; USPHS NIH/NIAMS [R01AR52579, R01AR56016] FX We are deeply indebted to the many patients and their family members who participated in this study. We are thankful to Drs Lawrence Shapiro and Tatyana Gindin for guidance on the structural effects of HLA associations. We thank Spandon V. Shah, Holly Jiang, Matthew Ding and Steven Chiu for their assistance and contributions in isolating the immune cells by FACS and Jane E. Cerise for her bioinformatic expertise. We are most grateful for the support of the National Alopecia Areata Foundation for funding the initial studies, and Ms Vicki Kalabokes and her staff at NAAF for their efforts on our behalf. The US patient cohort was collected and maintained by the National Alopecia Areata Registry (N01-AR62279) (to M.D.). Some controls were drawn from the Heinz Nixdorf Recall Study cohort, which was established with the support of the Heinz Nixdorf Foundation. R.C.B. and M.M.N. are members, T.B. is an associate member, of the DFG-funded Excellence Cluster ImmunoSensation. R.C.B. is a recipient of a Heisenberg Professorship of the German Research Foundation (DFG). This work was supported in part by the DFG grant BE 2346/5-1, as well as by local funding (BONFOR) to R.C.B., Vernieuwingsimpuls VIDI Award from the Netherlands Organization for Scientific Research for project 016.126.354 to P.I.W.d.B., and USPHS NIH/NIAMS grants R01AR52579 and R01AR56016 (to A.M.C.). NR 41 TC 21 Z9 20 U1 6 U2 22 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 2015 VL 6 AR 5966 DI 10.1038/ncomms6966 PG 8 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA CA3MO UT WOS:000348811100010 PM 25608926 ER PT J AU Wessel, J Chu, AY Willems, SM Wang, S Yaghootkar, H Brody, JA Dauriz, M Hivert, MF Raghavan, S Lipovich, L Hidalgo, B Fox, K Huffman, JE An, P Lu, YC Rasmussen-Torvik, LJ Grarup, N Ehm, MG Li, L Baldridge, AS Stancakova, A Abrol, R Besse, CL Boland, A Bork-Jensen, J Fornage, M Freitag, DF Garcia, ME Guo, XQ Hara, K Isaacs, A Jakobsdottir, J Lange, LA Layton, JC Li, M Zhao, JH Meidtner, K Morrison, AC Nalls, MA Peters, MJ Sabater-Lleal, M Schurmann, C Silveira, A Smith, AV Southam, L Stoiber, MH Strawbridge, RJ Taylor, KD Varga, TV Allin, KH Amin, N Aponte, JL Aung, T Barbieri, C Bihlmeyer, NA Boehnke, M Bombieri, C Bowden, DW Burns, SM Chen, YN Chen, YD Cheng, CY Correa, A Czajkowski, J Dehghan, A Ehret, GB Eiriksdottir, G Escher, SA Farmaki, AE Franberg, M Gambaro, G Giulianini, F Goddard, WA Goel, A Gottesman, O Grove, ML Gustafsson, S Hai, Y Hallmans, G Heo, J Hoffmann, P Ikram, MK Jensen, RA Jorgensen, ME Jorgensen, T Karaleftheri, M Khor, CC Kirkpatrick, A Kraja, AT Kuusisto, J Lange, EM Lee, IT Lee, WJ Leong, A Liao, JM Liu, CY Liu, YM Lindgren, CM Linneberg, A Malerba, G Mamakou, V Marouli, E Maruthur, NM Matchan, A McKean-Cowdin, R McLeod, O Metcalf, GA Mohlke, KL Muzny, DM Ntalla, I Palmer, ND Pasko, D Peter, A Rayner, NW Renstrom, F Rice, K Sala, CF Sennblad, B Serafetinidis, I Smith, JA Soranzo, N Speliotes, EK Stahl, EA Stirrups, K Tentolouris, N Thanopoulou, A Torres, M Traglia, M Tsafantakis, E Javad, S Yanek, LR Zengini, E Becker, DM Bis, JC Brown, JB Cupples, LA Hansen, T Ingelsson, E Karter, AJ Lorenzo, C Mathias, RA Norris, JM Peloso, GM Sheu, WHH Toniolo, D Vaidya, D Varma, R Wagenknecht, LE Boeing, H Bottinger, EP Dedoussis, G Deloukas, P Ferrannini, E Franco, OH Franks, PW Gibbs, RA Gudnason, V Hamsten, A Harris, TB Hattersley, AT Hayward, C Hofman, A Jansson, JH Langenberg, C Launer, LJ Levy, D Oostra, BA O'Donnell, CJ O'Rahilly, S Padmanabhan, S Pankow, JS Polasek, O Province, MA Rich, SS Ridker, PM Rudan, I Schulze, MB Smith, BH Uitterlinden, AG Walker, M Watkins, H Wong, TY Zeggini, E Laakso, M Borecki, IB Chasman, DI Pedersen, O Psaty, BM Tai, ES van Duijn, CM Wareham, NJ Waterworth, DM Boerwinkle, E Kao, WHL Florez, JC Loos, RJF Wilson, JG Frayling, TM Siscovick, DS Dupuis, J Rotter, JI Meigs, JB Scott, RA Goodarzi, MO Sharp, SJ Forouhi, NG Kerrison, ND Lucarelli, DM Sims, M Barroso, I McCarthy, MI Arriola, L Balkau, B Barricarte, A Gonzalez, C Grioni, S Kaaks, R Key, TJ Navarro, C Nilsson, PM Overvad, K Palli, D Panico, S Quiros, JR Rolandsson, O Sacerdote, C Sanchez, MJ Slimani, N Tjonneland, A Tumino, R van der A, DL van der Schouw, YT Riboli, E AF Wessel, Jennifer Chu, Audrey Y. Willems, Sara M. Wang, Shuai Yaghootkar, Hanieh Brody, Jennifer A. Dauriz, Marco Hivert, Marie-France Raghavan, Sridharan Lipovich, Leonard Hidalgo, Bertha Fox, Keolu Huffman, Jennifer E. An, Ping Lu, Yingchang Rasmussen-Torvik, Laura J. Grarup, Niels Ehm, Margaret G. Li, Li Baldridge, Abigail S. Stancakova, Alena Abrol, Ravinder Besse, Celine Boland, Anne Bork-Jensen, Jette Fornage, Myriam Freitag, Daniel F. Garcia, Melissa E. Guo, Xiuqing Hara, Kazuo Isaacs, Aaron Jakobsdottir, Johanna Lange, Leslie A. Layton, Jill C. Li, Man Zhao, Jing Hua Meidtner, Karina Morrison, Alanna C. Nalls, Mike A. Peters, Marjolein J. Sabater-Lleal, Maria Schurmann, Claudia Silveira, Angela Smith, Albert V. Southam, Lorraine Stoiber, Marcus H. Strawbridge, Rona J. Taylor, Kent D. Varga, Tibor V. Allin, Kristine H. Amin, Najaf Aponte, Jennifer L. Aung, Tin Barbieri, Caterina Bihlmeyer, Nathan A. Boehnke, Michael Bombieri, Cristina Bowden, Donald W. Burns, Sean M. Chen, Yuning Chen, Yii-Deri Cheng, Ching-Yu Correa, Adolfo Czajkowski, Jacek Dehghan, Abbas Ehret, Georg B. Eiriksdottir, Gudny Escher, Stefan A. Farmaki, Aliki-Eleni Franberg, Mattias Gambaro, Giovanni Giulianini, Franco Goddard, William A., III Goel, Anuj Gottesman, Omri Grove, Megan L. Gustafsson, Stefan Hai, Yang Hallmans, Goeran Heo, Jiyoung Hoffmann, Per Ikram, Mohammad K. Jensen, Richard A. Jorgensen, Marit E. Jorgensen, Torben Karaleftheri, Maria Khor, Chiea C. Kirkpatrick, Andrea Kraja, Aldi T. Kuusisto, Johanna Lange, Ethan M. Lee, I. T. Lee, Wen-Jane Leong, Aaron Liao, Jiemin Liu, Chunyu Liu, Yongmei Lindgren, Cecilia M. Linneberg, Allan Malerba, Giovanni Mamakou, Vasiliki Marouli, Eirini Maruthur, Nisa M. Matchan, Angela McKean-Cowdin, Roberta McLeod, Olga Metcalf, Ginger A. Mohlke, Karen L. Muzny, Donna M. Ntalla, Ioanna Palmer, Nicholette D. Pasko, Dorota Peter, Andreas Rayner, Nigel W. Renstroem, Frida Rice, Ken Sala, Cinzia F. Sennblad, Bengt Serafetinidis, Ioannis Smith, Jennifer A. Soranzo, Nicole Speliotes, Elizabeth K. Stahl, Eli A. Stirrups, Kathleen Tentolouris, Nikos Thanopoulou, Anastasia Torres, Mina Traglia, Michela Tsafantakis, Emmanouil Javad, Sundas Yanek, Lisa R. Zengini, Eleni Becker, Diane M. Bis, Joshua C. Brown, James B. Cupples, L. Adrienne Hansen, Torben Ingelsson, Erik Karter, Andrew J. Lorenzo, Carlos Mathias, Rasika A. Norris, Jill M. Peloso, Gina M. Sheu, Wayne H. -H. Toniolo, Daniela Vaidya, Dhananjay Varma, Rohit Wagenknecht, Lynne E. Boeing, Heiner Bottinger, Erwin P. Dedoussis, George Deloukas, Panos Ferrannini, Ele Franco, Oscar H. Franks, Paul W. Gibbs, Richard A. Gudnason, Vilmundur Hamsten, Anders Harris, Tamara B. Hattersley, Andrew T. Hayward, Caroline Hofman, Albert Jansson, Jan-Hakan Langenberg, Claudia Launer, Lenore J. Levy, Daniel Oostra, Ben A. O'Donnell, Christopher J. O'Rahilly, Stephen Padmanabhan, Sandosh Pankow, James S. Polasek, Ozren Province, Michael A. Rich, Stephen S. Ridker, Paul M. Rudan, Igor Schulze, Matthias B. Smith, Blair H. Uitterlinden, Andre G. Walker, Mark Watkins, Hugh Wong, Tien Y. Zeggini, Eleftheria Laakso, Markku Borecki, Ingrid B. Chasman, Daniel I. Pedersen, Oluf Psaty, Bruce M. Tai, E. Shyong van Duijn, Cornelia M. Wareham, Nicholas J. Waterworth, Dawn M. Boerwinkle, Eric Kao, W. H. Linda Florez, Jose C. Loos, Ruth J. F. Wilson, James G. Frayling, Timothy M. Siscovick, David S. Dupuis, Josee Rotter, Jerome I. Meigs, James B. Scott, Robert A. Goodarzi, Mark O. Sharp, Stephen J. Forouhi, Nita G. Kerrison, Nicola D. Lucarelli, Debora M. E. Sims, Matt Barroso, Ines McCarthy, Mark I. Arriola, Larraitz Balkau, Beverley Barricarte, Aurelio Gonzalez, Carlos Grioni, Sara Kaaks, Rudolf Key, Timothy J. Navarro, Carmen Nilsson, Peter M. Overvad, Kim Palli, Domenico Panico, Salvatore Quiros, J. Ramon Rolandsson, Olov Sacerdote, Carlotta Sanchez, Maria-Jose Slimani, Nadia Tjonneland, Anne Tumino, Rosario van der A, Daphne L. van der Schouw, Yvonne T. Riboli, Elio CA The EPIC-InterAct Consortium TI Low-frequency and rare exome chip variants associate with fasting glucose and type 2 diabetes susceptibility SO NATURE COMMUNICATIONS LA English DT Article ID GLUCAGON-LIKE PEPTIDE-1; GENOME-WIDE ASSOCIATION; RECEPTOR GENE; TRIGLYCERIDE LEVELS; GERMLINE MUTATIONS; INSULIN-RESISTANCE; CODING VARIATION; GLYCEMIC TRAITS; SEQUENCING DATA; PLASMA-GLUCOSE AB Fasting glucose and insulin are intermediate traits for type 2 diabetes. Here we explore the role of coding variation on these traits by analysis of variants on the HumanExome BeadChip in 60,564 non-diabetic individuals and in 16,491 T2D cases and 81,877 controls. We identify a novel association of a low-frequency nonsynonymous SNV in GLP1R (A316T; rs10305492; MAF = 1.4%) with lower FG (beta = -0.09 +/- 0.01 mmol l(-1), P = 3.4 x 10(-12)), T2D risk (OR[95% CI] = 0.86[0.76-0.96], P = 0.010), early insulin secretion (beta = -0.07 +/- 0.035 pmol(insulin) mmol(glucose)(-1), P = 0.048), but higher 2-h glucose (beta = 0.16 +/- 0.05 mmol l(-1), P = 4.3 x 10(-4)). We identify a gene-based association with FG at G6PC2 (p(SKAT) = 6.8 x 10(-6)) driven by four rare protein-coding SNVs (H177Y, Y207S, R283X and S324P). We identify rs651007 (MAF = 20%) in the first intron of ABO at the putative promoter of an antisense lncRNA, associating with higher FG (beta = 0.02 +/- 0.004 mmol l(-1), P = 1.3 x 10(-8)). Our approach identifies novel coding variant associations and extends the allelic spectrum of variation underlying diabetes-related quantitative traits and T2D susceptibility. 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EM robert.scott@mrc-epid.cam.ac.uk; mark.goodarzi@cshs.org RI Grioni, Sara/K-5320-2016; SANCHEZ-PEREZ, MARIA JOSE/D-1087-2011; Grarup, Niels/K-2807-2015; Gudnason, Vilmundur/K-6885-2015; Polasek, Ozren/B-6002-2011; Smith, Albert/K-5150-2015; Schurmann, Claudia/L-1204-2016; Deloukas, Panos/B-2922-2013; Padmanabhan, Sandosh/S-3963-2016; Dauriz, Marco/S-5843-2016; OI Hattersley, Andrew/0000-0001-5620-473X; Dehghan, Abbas/0000-0001-6403-016X; Linneberg, Allan/0000-0002-0994-0184; Sabater Lleal, Maria/0000-0002-0128-379X; Schulze, Matthias B./0000-0002-0830-5277; Sacerdote, Carlotta/0000-0002-8008-5096; Forouhi, Nita/0000-0002-5041-248X; Jorgensen, Torben/0000-0001-9453-2830; Watkins, Hugh/0000-0002-5287-9016; Khor, Chiea Chuen/0000-0002-1128-4729; Varga, Tibor/0000-0002-2383-699X; Smith, Blair/0000-0002-5362-9430; Vaidya, Dhananjay/0000-0002-7164-1601; Smith, Jennifer/0000-0002-3575-5468; Tai, E Shyong/0000-0003-2929-8966; Pankow, James/0000-0001-7076-483X; Strawbridge, Rona/0000-0001-8506-3585; Malerba, Giovanni/0000-0001-8705-8560; THANOPOULOU, ANASTASIA/0000-0002-2902-8053; Peters, Marjolein/0000-0003-3167-9063; Padmanabhan, Sandosh/0000-0003-3869-5808; Zeggini, Eleftheria/0000-0003-4238-659X; Wessel, Jennifer/0000-0002-7031-0085; Grioni, Sara/0000-0002-5891-8426; SANCHEZ-PEREZ, MARIA JOSE/0000-0003-4817-0757; Grarup, Niels/0000-0001-5526-1070; Franks, Paul/0000-0002-0520-7604; Soranzo, Nicole/0000-0003-1095-3852; Gudnason, Vilmundur/0000-0001-5696-0084; Polasek, Ozren/0000-0002-5765-1862; Smith, Albert/0000-0003-1942-5845; Schurmann, Claudia/0000-0003-4158-9192; Deloukas, Panos/0000-0001-9251-070X; Dauriz, Marco/0000-0002-5542-5941; Meidtner, Karina/0000-0001-5810-4062 FU NIH through the American Recovery and Reinvestment Act [5RC2HL102419]; Eric Boerwinkle on behalf of the Atherosclerosis Risk in Communities (ARIC) Study; NHLBI [HHSN268201200036C, HHSN268200800007C, N01HC55222, N01HC85079, N01HC85080, N01HC85081, N01HC85082, N01HC85083, N01HC85086, HL080295, HL087652, HL103612, HL068986, N02-HL-6-4278]; CHARGE infrastructure grant [HL105756]; LDRD [14-200, 4R00HG006698-03]; NIA [N01-AG-12100, N01AG62101, N01AG62103, N01AG62106, 1R01AG032098-01A1]; NEI; NIDCD; NIA Intramural Research Program; Hjartavernd (the Icelandic Heart Association); Althingi (the Icelandic Parliament); National Heart, Lung, and Blood Institute (NHLBI) [HHSN268201100005C, HHSN268201100006C, HHSN268201100007C, HHSN268201100008C, HHSN268201100009C, HHSN268201100010C, HHSN268201100011C, HHSN268201100012C, R01HL087641, R01HL59367, R01HL086694, N01-HC-95159, N01-HC-95169, RR-024156]; National Human Genome Research Institute [U01HG004402]; National Institutes of Health [HHSN268200625226C, U01-HG004729, R01-HL093029, R01-HL084099]; NIH Roadmap for Medical Research; National Heart, Lung, and Blood Institute; University of Alabama at Birmingham [HHSN268201300025C, HHSN268201300026C]; Northwestern University [HHSN268201300027C]; University of Minnesota [HHSN268201300028C]; Kaiser Foundation Research Institute [HHSN268201300029C]; Johns Hopkins University School of Medicine [HHSN268200900041C]; Intramural Research Program of the National Institute on Aging; Chinese-American Eye Study (CHES) [EY017337]; Research to Prevent Blindness; Genetics of Latinos Diabetic Retinopathy (GOLDR) [EY14684]; National Institute of Neurological Disorders and Stroke (NINDS); National Institute on Aging (NIA) [AG023629]; National Center for Advancing Translational Sciences; CTSI [UL1TR000124]; National Institute of Diabetes and Digestive and Kidney Disease Diabetes Research Center (DRC) [DK063491]; GlaxoSmithKline; Faculty of Biology and Medicine of Lausanne, Switzerland; Swiss National Science Foundation [3200B0-105993, 33CSCO-122661]; GlaxoSmithKline (Drug Discovery-Verona, RD); Medical Research Council UK; Ministry of Science, Education and Sport in the Republic of Croatia [108-1080315-0302]; South West NHS Research and Development; Exeter NHS Research and Development; Darlington Trust; Peninsula NIHR Clinical Research Facility at the University of Exeter; European Research Council [SZ-245 50371-GLUCOSEGENES-FP7-IDEAS-ERC, ERC-2011-StG 280559-SEPI]; German Federal Ministry of Education and Research (BMBF); Federal Ministry of Science, Germany [01 EA 9401]; European Union [SOC 95201408 05 F02]; German Cancer Aid [70-2488-Ha I]; European Community [SOC 98200769 05 F02]; Netherlands Organization for Scientific Research (NWO); NWO; Russian Foundation for Basic research [047.016.009, 047.017.043]; Erasmus MC; Centre for Medical Systems Biology (CMSB; National Genomics Initiative); ZonMw [91111025]; NIH from NHLBI [R01-HL-087700, R01-HL-088215]; NIH from NIDDK [R01-DK-8925601, R01-DK-075681]; Medical Research Council [MC_U106179471, G0700931]; Wellcome Trust [098051, WT098051, WT091310, 084723/Z/08/Z]; National Heart, Lung and Blood Institute Division of Intramural Research; National Institute for Diabetes and Digestive and Kidney Diseases (NIDDK) [R01 DK078616, R01DK079888, P30DK063491]; NIDDK [K24 DK080140]; American Diabetes Association Mentor-Based Postdoctoral Fellowship [7-09-MN-32]; Canadian Diabetes Association Research Fellowship Award; University of Verona, Italy; NIDDK Research Career Award [K23 DK65978]; Massachusetts General Hospital Physician Scientist Development Award; Doris Duke Charitable Foundation Clinical Scientist Development Award; Swedish Heart-Lung Foundation; Umea Medical Research Foundation; Vasterbotten County Council; NIH grants through the National Heart, Lung, and Blood Institute [HL58625-01A1, HL59684, HL071025-01A1, U01HL72518, HL112064, HL087698]; National Institute of Nursing Research [NR0224103]; U.S. Federal Government from the National Heart, Lung, and Blood Institute [HHSN268201100037C]; Novo Nordisk; Swedish Research Council; Pahlssons Foundation; Heart Foundation of Northern Sweden; Swedish Heart Lung Foundation; Skane Regional Health Authority; Swedish Diabetes Association; Chief Scientist Office of the Scottish Government Health Directorates [CZD/16/6]; Scottish Funding Council; Faculty of Biology and Medicine of Lausanne; Intramural Research Program of the NIH, National Institute on Aging [Z01 AG000949-02, Z01 AG007390-07]; Timber Merchant Vilhelm Bang's Foundation; Danish Heart Foundation [07-10-R61-A1754-B838-22392F]; Health Insurance Foundation (Helsefonden) [2012B233]; EU FP7 [257082, HEALTH-F5-2011-282510]; Danish Research Council; Danish Centre for Health Technology Assessment; Novo Nordisk Inc.; Research Foundation of Copenhagen County; Ministry of Internal Affairs and Health; Danish Heart Foundation; Danish Pharmaceutical Association; Augustinus Foundation; Ib Henriksen Foundation; Becket Foundation; Danish Diabetes Association; Lundbeck Foundation; Novo Nordisk Foundation; EU FP6 programme [LSHM_CT_2006_037197]; Andrea and Charles Bronfman Philanthropies; Department of Scientific Computing at the Icahn School of Medicine at Mount Sinai; National Institute of Diabetes and Digestive and Kidney Diseases [HL060944, HL061019, HL060919, HL047887, HL047889, HL047890, HL47902]; National Heart, Lung and Blood Institute [HHSN268201300046C, HHSN268201300047C, HHSN268201300048C, HHSN268201300049C, HHSN268201300050C]; National Institute on Minority Health and Health Disparities; NHLBI of the National Institutes of Health [R01HL107816]; National Institute for Health Research Comprehensive Biomedical Research Centre Imperial College Healthcare NHS Trust; British Heart Foundation [SP/04/002]; National Institute for Health Research [RP-PG-0407-10371]; United States Environmental Protection Agency (EPA) [RD83169701]; National Center for Advancing Translational Sciences [UL1-TR000124]; Cedars-Sinai Winnick Clinical Scholars Award; Academy of Finland [77299, 124243]; NIH [DK062370, DK093757, DK072193]; Diabetes UK; Magnus Bergvall Foundation; Foundation for Old Servants; Tore Nilsson foundation; Fredrik and Ingrid Thuring foundation; Ake-wiberg Foundation; Karolinska Institutet Foundation; Swedish e-science Research Center (SeRC); EU [QLG1-CT-2001-01252]; AstraZeneca (Sweden); European Union grant [QLG1-CT-2001-01252]; AstraZeneca; Boehringer-Ingelheim; LillyCo; Research Institute for Diseases in the Elderly [014-93-015; RIDE2]; Netherlands Genomics Initiative (NGI)/Netherlands Organization for Scientific Research (NWO) [050-060-810]; CHANCES [242244]; Erasmus Medical Center; Erasmus University Rotterdam; Netherlands Organization for the Health Research and Development (ZonMw); Research Institute for Diseases in the Elderly (RIDE); Ministry of Education, Culture and Science; Ministry for Health, Welfare and Sports; European Commission (DG XII); Municipality of Rotterdam; NWO grant veni (veni) [916.12.154]; EUR Fellowship; Foundation for Strategic Research; Swedish Research Council [8691, 12660, 20653]; European Commission [LSHM-CT-2007-037273]; Knut and Alice Wallenberg Foundation; Torsten and Ragnar Soderberg Foundation; Strategic Cardiovascular and Diabetes Programmes of Karolinska Institutet; Stockholm County Council [560183]; National Medical Research Council (NMRC), Singapore [0796/2003, IRG07nov013, IRG09nov014, NMRC 1176/2008, STaR/0003/2008, CG/SERI/2010]; Biomedical Research Council (BMRC), Singapore [08/1/35/19/550, 09/1/35/19/616]; European Union (European Social Fund-ESF); National Strategic Reference Framework (NSRF); Uppsala University; Knut och Alice Wallenberg Foundation; European Research Council; Swedish Diabetes Foundation [2013-024]; Swedish Heart-Lung Foundation [20120197]; Wellcome Trust Research Career Development Fellowship [086596/Z/08/Z]; Fondazione Compagnia di San Paolo-Torino; Fondazione Cariplo-Milano; Italian Ministry of Health Progetto Finalizzato; Italian Ministry of Health Progetto [CCM 2010, PRIN 2009]; National Heart, Lung, and Blood Institute [HL043851, HL080467]; National Cancer Institute [CA047988]; Donald W. Reynolds Foundation; Fondation Leducq; [HL120393]; [UL1RR025005]; [M01-RR000052]; [DK081350]; [HG007112]; [R01HL071051]; [R01HL071205]; [R01HL071250]; [R01HL071251]; [R01HL071252]; [R01HL071258]; [R01HL071259] FX CHARGE: Funding support for 'Building on GWAS for NHLBI-diseases: the U.S. CHARGE consortium' was provided by the NIH through the American Recovery and Reinvestment Act of 2009 (ARRA) (5RC2HL102419). Sequence data for 'Building on GWAS for NHLBI-diseases: the U.S. CHARGE consortium' was provided by Eric Boerwinkle on behalf of the Atherosclerosis Risk in Communities (ARIC) Study, L. Adrienne Cupples, principal investigator for the Framingham Heart Study, and Bruce Psaty, principal investigator for the Cardiovascular Health Study. Sequencing was carried out at the Baylor Genome Center (U54 HG003273). Further support came from HL120393, 'Rare variants and NHLBI traits in deeply phenotyped cohorts' (Bruce Psaty, principal investigator). Supporting funding was also provided by NHLBI with the CHARGE infrastructure grant HL105756. In addition, M.J.P. was supported through the 2014 CHARGE Visiting Fellow grant-HL105756, Dr Bruce Psaty, PI.; ENCODE: ENCODE collaborators Ben Brown and Marcus Stoiber were supported by the LDRD# 14-200 (B.B. and M.S.) and 4R00HG006698-03 (B.B.) grants.; AGES: This study has been funded by NIA contract N01-AG-12100 with contributions from NEI, NIDCD and NHLBI, the NIA Intramural Research Program, Hjartavernd (the Icelandic Heart Association) and the Althingi (the Icelandic Parliament).; ARIC: The Atherosclerosis Risk in Communities (ARIC) Study is carried out as a collaborative study supported by National Heart, Lung, and Blood Institute (NHLBI) contracts (HHSN268201100005C, HHSN268201100006C, HHSN268201100007C, HHSN268201100008C, HHSN268201100009C, HHSN268201100010C, HHSN268201100011C and HHSN268201100012C), R01HL087641, R01HL59367 and R01HL086694; National Human Genome Research Institute contract U01HG004402; and National Institutes of Health contract HHSN268200625226C. We thank the staff and participants of the ARIC study for their important contributions. Infrastructure was partly supported by Grant Number UL1RR025005, a component of the National Institutes of Health and NIH Roadmap for Medical Research.; CARDIA: The CARDIA Study is conducted and supported by the National Heart, Lung, and Blood Institute in collaboration with the University of Alabama at Birmingham (HHSN268201300025C & HHSN268201300026C), Northwestern University (HHSN268201300027C), University of Minnesota (HHSN268201300028C), Kaiser Foundation Research Institute (HHSN268201300029C), and Johns Hopkins University School of Medicine (HHSN268200900041C). CARDIA is also partially supported by the Intramural Research Program of the National Institute on Aging. Exome chip genotyping and data analyses were funded in part by grants U01-HG004729, R01-HL093029 and R01-HL084099 from the National Institutes of Health to Dr Myriam Fornage. This manuscript has been reviewed by CARDIA for scientific content.; CHES: This work was supported in part by The Chinese-American Eye Study (CHES) grant EY017337, an unrestricted departmental grant from Research to Prevent Blindness, and the Genetics of Latinos Diabetic Retinopathy (GOLDR) Study grant EY14684.; CHS: This CHS research was supported by NHLBI contracts HHSN268201200036C, HHSN268200800007C, N01HC55222, N01HC85079, N01HC85080, N01HC85081, N01HC85082, N01HC85083, N01HC85086; and NHLBI grants HL080295, HL087652, HL103612, HL068986 with additional contribution from the National Institute of Neurological Disorders and Stroke (NINDS). Additional support was provided through AG023629 from the National Institute on Aging (NIA). A full list of CHS investigators and institutions can be found at http://www.chs-nhlbi.org/pi.htm. The provision of genotyping data was supported in part by the National Center for Advancing Translational Sciences, CTSI grant UL1TR000124, and the National Institute of Diabetes and Digestive and Kidney Disease Diabetes Research Center (DRC) grant DK063491 to the Southern California Diabetes Endocrinology Research Center. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.; The CoLaus Study: We thank the co-primary investigators of the CoLaus study, Gerard Waeber and Peter Vollenweider, and the PI of the PsyColaus Study Martin Preisig. We gratefully acknowledge Yolande Barreau, Anne-Lise Bastian, Binasa Ramic, Martine Moranville, Martine Baumer, Marcy Sagette, Jeanne Ecoffey and Sylvie Mermoud for their role in the CoLaus data collection. The CoLaus study was supported by research grants from GlaxoSmithKline and from the Faculty of Biology and Medicine of Lausanne, Switzerland. The PsyCoLaus study was supported by grants from the Swiss National Science Foundation (#3200B0-105993) and from GlaxoSmithKline (Drug Discovery-Verona, R&D).; CROATIA-Korcula: The CROATIA-Korcula study would like to acknowledge the invaluable contributions of the recruitment team in Korcula, the administrative teams in Croatia and Edinburgh and the people of Korcula. Exome array genotyping was performed at the Wellcome Trust Clinical Research Facility Genetics Core at Western General Hospital, Edinburgh, UK. The CROATIA-Korcula study on the Croatian island of Korucla was supported through grants from the Medical Research Council UK and the Ministry of Science, Education and Sport in the Republic of Croatia (number 108-1080315-0302).; EFSOCH: We are extremely grateful to the EFSOCH study participants and the EFSOCH study team. The opinions given in this paper do not necessarily represent those of NIHR, the NHS or the Department of Health. The EFSOCH study was supported by South West NHS Research and Development, Exeter NHS Research and Development, the Darlington Trust, and the Peninsula NIHR Clinical Research Facility at the University of Exeter. Timothy Frayling, PI, is supported by the European Research Council grant: SZ-245 50371-GLUCOSEGENES-FP7-IDEAS-ERC.; EPIC-Potsdam: We thank all EPIC-Potsdam participants for their invaluable contribution to the study. The study was supported in part by a grant from the German Federal Ministry of Education and Research (BMBF) to the German Center for Diabetes Research (DZD e.V.). The recruitment phase of the EPIC-Potsdam study was supported by the Federal Ministry of Science, Germany (01 EA 9401) and the European Union (SOC 95201408 05 F02). The follow-up of the EPIC-Potsdam study was supported by German Cancer Aid (70-2488-Ha I) and the European Community (SOC 98200769 05 F02). Furthermore, we thank Ellen Kohlsdorf for data management as well as the follow-up team headed by Dr Manuala Bergmann for case ascertainment.; ERF: The ERF study was supported by grants from the Netherlands Organization for Scientific Research (NWO) and a joint grant from NWO and the Russian Foundation for Basic research (Pionier, 047.016.009, 047.017.043), Erasmus MC, and the Centre for Medical Systems Biology (CMSB; National Genomics Initiative). Exome sequencing analysis in ERF was supported by the ZonMw grant (91111025).; For the ERF Study, we are grateful to all participants and their relatives, to general practitioners and neurologists for their contributions, to P. Veraart for her help in genealogy and to P. Snijders for his help in data collection.; FamHS: The Family Heart Study (FamHS) was supported by NIH grants R01-HL-087700 and R01-HL-088215 (Michael A. Province, PI) from NHLBI; and R01-DK-8925601 and R01-DK-075681 (Ingrid B. Borecki, PI) from NIDDK.; FENLAND: The Fenland Study is funded by the Medical Research Council (MC_U106179471) and Wellcome Trust. We are grateful to all the volunteers for their time and help, and to the General Practitioners and practice staff for assistance with recruitment. We thank the Fenland Study Investigators, Fenland Study Co-ordination team and the Epidemiology Field, Data and Laboratory teams. The Fenland Study is funded by the Medical Research Council (MC_U106179471) and Wellcome Trust.; FHS: Genotyping, quality control and calling of the Illumina HumanExome BeadChip in the Framingham Heart Study was supported by funding from the National Heart, Lung and Blood Institute Division of Intramural Research (Daniel Levy and Christopher J. O'Donnell, Principle Investigators). A portion of this research was conducted using the Linux Clusters for Genetic Analysis (LinGA) computing resources at Boston University Medical Campus. Also supported by National Institute for Diabetes and Digestive and Kidney Diseases (NIDDK) R01 DK078616, NIDDK K24 DK080140 and American Diabetes Association Mentor-Based Postdoctoral Fellowship Award #7-09-MN-32, all to Dr Meigs, a Canadian Diabetes Association Research Fellowship Award to Dr Leong, a research grant from the University of Verona, Italy to Dr Dauriz, and NIDDK Research Career Award K23 DK65978, a Massachusetts General Hospital Physician Scientist Development Award and a Doris Duke Charitable Foundation Clinical Scientist Development Award to Dr Florez.; FIA3: We are indebted to the study participants who dedicated their time and samples to these studies. We thank Asa Agren (Umea Medical Biobank) for data organization and Kerstin Enquist and Thore Johansson (Vasterbottens County Council) for technical assistance with DNA extraction. This particular project was supported by project grants from the Swedish Heart-Lung Foundation, Umea Medical Research Foundation and Vasterbotten County Council.; The Genetics Epidemiology of Metabolic Syndrome (GEMS) Study: We thank Metabolic Syndrome GEMs investigators: Scott Grundy, Jonathan Cohen, Ruth McPherson, Antero Kesaniemi, Robert Mahley, Tom Bersot, Philip Barter and Gerard Waeber. We gratefully acknowledge the contributions of the study personnel at each of the collaborating sites: John Farrell, Nicholas Nikolopoulos and Maureen Sutton (Boston); Judy Walshe, Monica Prentice, Anne Whitehouse, Julie Butters and Tori Nicholls (Australia); Heather Doelle, Lynn Lewis and Anna Toma (Canada); Kari Kervinen, Seppo Poykko, Liisa Mannermaa and Sari Paavola (Finland); Claire Hurrel, Diane Morin, Alice Mermod, Myriam Genoud and Roger Darioli (Switzerland); Guy Pepin, Sibel Tanir, Erhan Palaoglu, Kerem Ozer, Linda Mahley and Aysen Agacdiken (Turkey); and Deborah A. Widmer, Rhonda Harris and Selena Dixon (United States). Funding for the GEMS study was provided by GlaxoSmithKline.; GeneSTAR: The Johns Hopkins Genetic Study of Atherosclerosis Risk (GeneSTAR) Study was supported by NIH grants through the National Heart, Lung, and Blood Institute (HL58625-01A1, HL59684, HL071025-01A1, U01HL72518, HL112064, and HL087698) and the National Institute of Nursing Research (NR0224103) and by M01-RR000052 to the Johns Hopkins General Clinical Research Center. Genotyping services were provided through the RS&G Service by the Northwest Genomics Center at the University of Washington, Department of Genome Sciences, under U.S. Federal Government contract number HHSN268201100037C from the National Heart, Lung, and Blood Institute.; GLACIER: We are indebted to the study participants who dedicated their time, data and samples to the GLACIER Study as part of the Vasterbottens halsoundersokningar (Vasterbottens Health Survey). We thank John Hutiainen and Asa Agren (Northern Sweden Biobank) for data organization and Kerstin Enquist and Thore Johansson (Vasterbottens County Council) for extracting DNA. We also thank M. Sterner, M. Juhas and P. Storm (Lund University Diabetes Center) for their expert technical assistance with genotyping and genotype data preparation. The GLACIER Study was supported by grants from Novo Nordisk, the Swedish Research Council, Pahlssons Foundation, The Heart Foundation of Northern Sweden, the Swedish Heart Lung Foundation, the Skane Regional Health Authority, Umea Medical Research Foundation and the Wellcome Trust. This particular project was supported by project grants from the Swedish Heart-Lung Foundation, the Swedish Research Council, the Swedish Diabetes Association, Pahlssons Foundation and Novo nordisk (all grants to P. W. Franks).; GOMAP (Genetic Overlap between Metabolic and Psychiatric Disease): This work was funded by the Wellcome Trust (098051). We thank all participants for their important contribution. We are grateful to Georgia Markou, Laiko General Hospital Diabetes Centre, Maria Emetsidou and Panagiota Fotinopoulou, Hippokratio General Hospital Diabetes Centre, Athina Karabela, Dafni Psychiatric Hospital, Eirini Glezou and Marios Matzioros, Dromokaiteio Psychiatric Hospital, Angela Rentari, Harokopio University of Athens, and Danielle Walker, Wellcome Trust Sanger Institute.; Generation Scotland: Scottish Family Health Study (GS:SFHS): GS:SFHS is funded by the Chief Scientist Office of the Scottish Government Health Directorates, grant number CZD/16/6 and the Scottish Funding Council. Exome array genotyping for GS:SFHS was funded by the Medical Research Council UK and performed at the Wellcome Trust Clinical Research Facility Genetics Core at Western General Hospital, Edinburgh, UK. We also acknowledge the invaluable contributions of the families who took part in the Generation Scotland: Scottish Family Health Study, the general practitioners and Scottish School of Primary Care for their help in recruiting them, and the whole Generation Scotland team, which includes academic researchers, IT staff, laboratory technicians, statisticians and research managers. The chief investigators of Generation Scotland are David J. Porteous (University of Edinburgh), Lynne Hocking (University of Aberdeen), Blair Smith (University of Dundee), and Sandosh Padmanabhan (University of Glasgow).; GSK (CoLaus, GEMS, Lolipop): We thank the GEMS Study Investigators: Philip Barter, PhD; Y. Antero Kesaniemi, PhD; Robert W. Mahley, PhD; Ruth McPherson, FRCP; and Scott M. Grundy, PhD. Dr Waeber MD, the CoLaus PI's Peter Vollenweider MD and Gerard Waeber MD, the LOLIPOP PI's, Jaspal Kooner MD and John Chambers MD, as well as the participants in all the studies. The GEMS study was sponsored in part by GlaxoSmithKline. The CoLaus study was supported by grants from GlaxoSmithKline, the Swiss National Science Foundation (Grant 33CSCO-122661) and the Faculty of Biology and Medicine of Lausanne.; Health ABC: The Health, Aging and Body Composition (HABC) Study is supported by NIA contracts N01AG62101, N01AG62103 and N01AG62106. The exome-wide association study was funded by NIA grant 1R01AG032098-01A1 to Wake Forest University Health Sciences and was supported in part by the Intramural Research Program of the NIH, National Institute on Aging (Z01 AG000949-02 and Z01 AG007390-07, Human subjects protocol UCSF IRB is H5254-12688-11). Portions of this study utilized the high-performance computational capabilities of the Biowulf Linux cluster at the National Institutes of Health, Bethesda, MD. (http:/biowulf.nih.gov).; Health2008: The Health2008 cohort was supported by the Timber Merchant Vilhelm Bang's Foundation, the Danish Heart Foundation (Grant number 07-10-R61-A1754-B838-22392F), and the Health Insurance Foundation (Helsefonden) (Grant number 2012B233).; HELIC: This work was funded by the Wellcome Trust (098051) and the European Research Council (ERC-2011-StG 280559-SEPI). The MANOLIS cohort is named in honour of Manolis Giannakakis, 1978-2010. We thank the residents of Anogia and surrounding Mylopotamos villages, and of the Pomak villages, for taking part. The HELIC study has been supported by many individuals who have contributed to sample collection (including Antonis Athanasiadis, Olina Balafouti, Christina Batzaki, Georgios Daskalakis, Eleni Emmanouil, Chrisoula Giannakaki, Margarita Giannakopoulou,; Anastasia Kaparou, Vasiliki Kariakli, Stella Koinaki, Dimitra Kokori, Maria Konidari, Hara Koundouraki, Dimitris Koutoukidis, Vasiliki Mamakou, Eirini Mamalaki, Eirini Mpamiaki, Maria Tsoukana, Dimitra Tzakou, Katerina Vosdogianni, Niovi Xenaki, Eleni Zengini), data entry (Thanos Antonos, Dimitra Papagrigoriou, Betty Spiliopoulou), sample logistics (Sarah Edkins, Emma Gray), genotyping (Robert Andrews, Hannah Blackburn, Doug Simpkin, Siobhan Whitehead), research administration (Anja Kolb-Kokocinski, Carol Smee, Danielle Walker) and informatics (Martin Pollard, Josh Randall).; INCIPE: NIcole Soranzo's research is supported by the Wellcome Trust (Grant Codes WT098051 and WT091310), the EU FP7 (EPIGENESYS Grant Code 257082 and BLUEPRINT Grant Code HEALTH-F5-2011-282510).; Inter99: The Inter99 was initiated by Torben Jorgensen (PI), Knut Borch-Johnsen (co-PI), Hans Ibsen and Troels F. Thomsen. The steering committee comprises the former two and Charlotta Pisinger. The study was financially supported by research grants from the Danish Research Council, the Danish Centre for Health Technology Assessment, Novo Nordisk Inc., Research Foundation of Copenhagen County, Ministry of Internal Affairs and Health, the Danish Heart Foundation, the Danish Pharmaceutical Association, the Augustinus Foundation, the Ib Henriksen Foundation, the Becket Foundation and the Danish Diabetes Association. Genetic studies of both Inter99 and Health 2008 cohorts were funded by the Lundbeck Foundation and produced by The Lundbeck Foundation Centre for Applied Medical Genomics in Personalised Disease Prediction, Prevention and Care (LuCamp, www.lucamp.org). The Novo Nordisk Foundation Center for Basic Metabolic Research is an independent Research Center at the University of Copenhagen partially funded by an unrestricted donation from the Novo Nordisk Foundation (www.metabol.ku.dk).; InterAct Consortium: Funding for the InterAct project was provided by the EU FP6 programme (grant number LSHM_CT_2006_037197). We thank all EPIC participants and staff for their contribution to the study. We thank the lab team at the MRC Epidemiology Unit for sample management and Nicola Kerrison for data management.; IPM BioMe Biobank: The Mount Sinai IPM BioMe Program is supported by The Andrea and Charles Bronfman Philanthropies. Analyses of BioMe data was supported in part through the computational resources and staff expertise provided by the Department of Scientific Computing at the Icahn School of Medicine at Mount Sinai.; The Insulin Resistance Atherosclerosis Family Study (IRASFS): The IRASFS was conducted and supported by the National Institute of Diabetes and Digestive and Kidney Diseases (HL060944, HL061019, and HL060919). Exome chip genotyping and data analyses were funded in part by grants DK081350 and HG007112. A subset of the IRASFS exome chips were contributed with funds from the Department of Internal Medicine at the University of Michigan. Computing resources were provided, in part, by the Wake Forest School of Medicine Center for Public Health Genomics.; The Insulin Resistance Atherosclerosis Study (IRAS): The IRAS was conducted and supported by the National Institute of Diabetes and Digestive and Kidney Diseases (HL047887, HL047889, HL047890 and HL47902). Exome chip genotyping and data analyses were funded in part by grants DK081350 and HG007112). Computing resources were provided, in part, by the Wake Forest School of Medicine Center for Public Health Genomics.; JHS: The JHS is supported by contracts HHSN268201300046C, HHSN268201300047C, HHSN268201300048C, HHSN268201300049C, HHSN268201300050C from the National Heart, Lung and Blood Institute and the National Institute on Minority Health and Health Disparities. ExomeChip genotyping was supported by the NHLBI of the National Institutes of Health under award number R01HL107816 to S. Kathiresan. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.; The London Life Sciences Prospective Population (LOLIPOP) Study: We thank the co-primary investigators of the LOLIPOP study: Jaspal Kooner, John Chambers and Paul Elliott. The LOLIPOP study is supported by the National Institute for Health Research Comprehensive Biomedical Research Centre Imperial College Healthcare NHS Trust, the British Heart Foundation (SP/04/002), the Medical Research Council (G0700931), the Wellcome Trust (084723/Z/08/Z) and the National Institute for Health Research (RP-PG-0407-10371).; MESA: The Multi-Ethnic Study of Atherosclerosis (MESA) and MESA SHARe project are conducted and supported by contracts N01-HC-95159 through N01-HC-95169 and RR-024156 from the National Heart, Lung, and Blood Institute (NHLBI). Funding for MESA SHARe genotyping was provided by NHLBI Contract N02-HL-6-4278. MESA Family is conducted and supported in collaboration with MESA investigators; support is provided by grants and contracts R01HL071051, R01HL071205, R01HL071250, R01HL071251, R01HL071252, R01HL071258, R01HL071259. MESA Air is conducted and supported by the United States Environmental Protection Agency (EPA) in collaboration with MESA Air investigators; support is provided by grant RD83169701. We thank the participants of the MESA study, the Coordinating Center, MESA investigators, and study staff for their valuable contributions. A full list of participating MESA investigators and institutions can be found at http://www.mesa-nhlbi.org. Additional support was provided by the National Institute for Diabetes and Digestive and Kidney Diseases (NIDDK) grants R01DK079888 and P30DK063491 and the National Center for Advancing Translational Sciences grant UL1-TR000124. Further support came from the Cedars-Sinai Winnick Clinical Scholars Award (to M.O. Goodarzi).; METSIM: The METSIM study was funded by the Academy of Finland (grants no. 77299 and 124243). M.L. acknowledges funding from the Academy of Finland. M.B. and K.M. acknowledge grant funding from NIH grants DK062370, DK093757, DK072193.; MRC Ely: The Ely Study was funded by the Medical Research Council (MC_U106179471) and Diabetes UK. We are grateful to all the volunteers, and to the staff of St Mary's Street Surgery, Ely and the study team.; PROCARDIS: We thank all participants in this study. The European Community Sixth Framework Program (LSHM-CT-2007-037273), AstraZeneca, the British Heart Foundation, the Oxford British Heart Foundation Centre of Research Excellence, the Wellcome Trust (075491/Z/04), the Swedish Research Council, the Knut and Alice Wallenberg Foundation, the Swedish Heart-Lung Foundation, the Torsten and Ragnar Soderberg Foundation, the Strategic Cardiovascular and Diabetes Programs of Karolinska Institutet and Stockholm County Council, the Foundation for Strategic Research and the Stockholm County Council (560283). Bengt Sennblad acknowledges funding from the Magnus Bergvall Foundation and the Foundation for Old Servants. Rona J. Strawbridge is supported by the Swedish Heart-Lung Foundation, the Tore Nilsson foundation, the Fredrik and Ingrid Thuring foundation and the Foundation for Old Servants. Maria Sabater-Lleal acknowledges funding from Ake-wiberg, Tore Nilsson and Karolinska Institutet Foundations. Mattias Frnberg acknowledges funding from the Swedish e-science Research Center (SeRC).; RISC: We are extremely grateful to the RISC study participants and the RISC study team. The RISC Study is partly supported by EU grant QLG1-CT-2001-01252. Additional support for the RISC Study has been provided by AstraZeneca (Sweden). The RISC Study was supported by European Union grant QLG1-CT-2001-01252 and AstraZeneca. Ele Ferrannini acknowledges grant funding from Boehringer-Ingelheim and Lilly&Co and works as a consultant for Boehringer-Ingelheim, Lilly&Co., MSD, Sanofi, GSK, Janssen, Menarini, Novo Nordisk, AstraZeneca.; Rotterdam Study: The Rotterdam Study is funded by the Research Institute for Diseases in the Elderly (014-93-015; RIDE2), the Netherlands Genomics Initiative (NGI)/Netherlands Organization for Scientific Research (NWO) project nr. 050-060-810, CHANCES (nr 242244), Erasmus Medical Center and Erasmus University Rotterdam, Netherlands Organization for the Health Research and Development (ZonMw), the Research Institute for Diseases in the Elderly (RIDE), the Ministry of Education, Culture and Science, the Ministry for Health, Welfare and Sports, the European Commission (DG XII) and the Municipality of Rotterdam. Abbas Dehghan is supported by NWO grant veni (veni, 916.12.154) and the EUR Fellowship. We are grateful to the study participants, the staff from the Rotterdam Study and the participating general practitioners and pharmacists.; SCARF: We thank all participants in this study. The study was funded by the Foundation for Strategic Research, the Swedish Heart-Lung Foundation, the Swedish Research Council (8691, 12660, 20653), the European Commission (LSHM-CT-2007-037273), the Knut and Alice Wallenberg Foundation, the Torsten and Ragnar Soderberg Foundation, the Strategic Cardiovascular and Diabetes Programmes of Karolinska Institutet and the Stockholm County Council, and the Stockholm County Council (560183). Bengt Sennblad acknowledges funding from the Magnus Bergvall Foundation and the Foundation for Old Servants. Mattias Franberg acknowledges funding from the Swedish e-Science Research Center (SeRC).; SCES: The Singapore Chinese Eye Study (SCES) was supported by the National Medical Research Council (NMRC), Singapore (grants 0796/2003, IRG07nov013, IRG09nov014, NMRC 1176/2008, STaR/0003/2008, CG/SERI/2010) and Biomedical Research Council (BMRC), Singapore (08/1/35/19/550 and 09/1/35/19/616).; TEENAGE (TEENs of Attica: Genes and Environment): This research has been co-financed by the European Union (European Social Fund-ESF) and Greek national funds through the Operational Program 'Education and Lifelong Learning' of the National Strategic Reference Framework (NSRF)-Research Funding Program: Heracleitus II. Investing in knowledge society through the European Social Fund. This work was funded by the Wellcome Trust (098051).; Uppsala Longitudinal Study of Adult Men (ULSAM): The exome chip genotyping and data analyses were supported by Uppsala University, Knut och Alice Wallenberg Foundation, European Research Council, Swedish Diabetes Foundation (grant no. 2013-024), Swedish Research Council (grant no. 2012-1397), and Swedish Heart-Lung Foundation (20120197). C.M.L. is supported by a Wellcome Trust Research Career Development Fellowship (086596/Z/08/Z).; INGI-VB: The Val Borbera study (INGI-VB) thanks the inhabitants of the Val Borbera for participating in the study, the local administrations and the ASL-Novi Ligure for support and Fiammetta Vigano for technical help. We also thank Professor Clara Camaschella, Professor Federico Caligaris-Cappio and the MDs of the Medicine Dept. of the San Raffaele Hospital for help with clinical data collection. The study was supported by funds from Fondazione Compagnia di San Paolo-Torino, Fondazione Cariplo-Milano, Italian Ministry of Health Progetto Finalizzato 2007 and 2012, Italian Ministry of Health Progetto CCM 2010, and PRIN 2009.; WGHS: The WGHS is supported by HL043851 and HL080467 from the National Heart, Lung, and Blood Institute and CA047988 from the National Cancer Institute, the Donald W. Reynolds Foundation and the Fondation Leducq, with collaborative scientific support and funding for genotyping provided by Amgen. NR 70 TC 43 Z9 43 U1 5 U2 37 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 2015 VL 6 AR 5897 DI 10.1038/ncomms6897 PG 16 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA CA2ME UT WOS:000348741700001 PM 25631608 ER PT J AU Dickey, MW Warren, T AF Dickey, Michael Walsh Warren, Tessa TI The influence of event-related knowledge on verb-argument processing in aphasia SO NEUROPSYCHOLOGIA LA English DT Article DE Language comprehension; Conceptual semantics; Aphasia; Sentence processing ID MINI-MENTAL STATE; LANGUAGE COMPREHENSION; EYE-MOVEMENTS; SENTENCE COMPREHENSION; SELECTIONAL RESTRICTION; SEMANTIC IMPAIRMENT; WORLD KNOWLEDGE; CORTEX; PLAUSIBILITY; INTEGRATION AB Event-related conceptual knowledge outside the language system rapidly affects verb-argument processing in unimpaired adults (McRae and Matsuki, 2009). Some have argued that verb-argument processing is in fact reducible to the activation of such event-related knowledge. However, data favoring this conclusion have come primarily from college-aged healthy adults, for whom both linguistic and conceptual semantic processing is fast and automatic. This study examined the influence of event-related knowledge on verb-argument processing among adults with aphasia (n=8) and older unimpaired controls (n=60), in two self-paced reading studies. Participants read sentences containing a plausible verb-argument combination (Mary used a knife to chop the large carrots before dinner), a combination that violated event-related world knowledge (Mary used some bleach to clean the large carrots before dinner), or a combination that violated the verb's selectional restrictions (Mary used a pump to inflate the large carrots before dinner). The participants with aphasia naturally split into two groups: Group 1 (n=4) had conceptual-semantic impairments (evidenced by poor performance on tasks like Pyramids & Palm Trees) but reasonably intact language processing (higher Western Aphasia Battery Aphasia Quotients), while Group 2 (n=4) had intact conceptual semantics but poorer language processing. Older unimpaired controls and aphasic Group 1 showed rapid on-line disruption for sentences with selectional-restriction violations (SRVs) and event-related knowledge violations, and also showed SRV-specific penalties in sentence-final acceptability judgments (Experiment 1) and comprehension questions (Experiment 2). In contrast, Group 2 showed very few reliable differences across conditions in either on-line or off-line measures. This difference between aphasic groups suggests that verb-related information and event-related knowledge may be dissociated in aphasia. Furthermore, it suggests that intact language processing is more critical for successful verb-argument integration than intact access to event-related world knowledge. This pattern is unexpected if verb-argument processing is reducible to activation of event-related conceptual knowledge. Published by Elsevier Ltd. C1 [Dickey, Michael Walsh] VA Pittsburgh Healthcare Syst, Pittsburgh, PA 15240 USA. [Dickey, Michael Walsh; Warren, Tessa] Univ Pittsburgh, Learning Res & Dev Ctr, Pittsburgh, PA 15213 USA. RP Dickey, MW (reprint author), Dept Commun Sci & Disorders, 4032 Forbes Tower, Pittsburgh, PA 15260 USA. EM mdickey@pitt.edu OI Dickey, Michael Walsh/0000-0002-9068-3313 FU National Institutes of Health [R01DC011520]; University of Pittsburgh [UL1TR000005] FX This research was supported by the National Institutes of Health through Grant number R01DC011520 to the authors and by Grant number UL1TR000005 to the Clinical and Translational Science Institute of the University of Pittsburgh. It is the result of work supported with resources and the use of facilities at the VA Pittsburgh Healthcare System. Thanks are due to Minas Abovyan, Amanda Fryd, Emily Kosenske, Molly Lane, Evelyn Milburn, Hannah Rosenberg, Hyunsoo Yoo, and Lidia Zacharczuk for help running participants, to Alice Proverbio and Federica Riva for sharing their picture stimuli from Proverbio and Riva (2009), and to audiences at the 2012 and 2013 CUNY Sentence Processing Conference and the 2013 Academy of Aphasia meeting for comments and suggestions. Special thanks are due to the adults with aphasia who participated in these studies. A preliminary version of this work was published as Warren and Dickey (2013). NR 62 TC 3 Z9 3 U1 1 U2 11 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0028-3932 EI 1873-3514 J9 NEUROPSYCHOLOGIA JI Neuropsychologia PD JAN PY 2015 VL 67 BP 63 EP 81 DI 10.1016/j.neuropsychologia.2014.12.003 PG 19 WC Behavioral Sciences; Neurosciences; Psychology, Experimental SC Behavioral Sciences; Neurosciences & Neurology; Psychology GA CA4NH UT WOS:000348880800007 PM 25484306 ER PT J AU Williams, BA Ibinson, JW Mangione, MP Scanlan, RL Cohen, PZ AF Williams, Brian A. Ibinson, James W. Mangione, Michael P. Scanlan, Rick L. Cohen, Peter Z. TI Clinical Benchmarks Regarding Multimodal Peripheral Nerve Blocks for Postoperative Analgesia: Observations Regarding Combined Perineural Midazolam-Clonidine-Buprenorphine-Dexamethasone SO PAIN MEDICINE LA English DT Editorial Material ID OUTPATIENT KNEE SURGERY; CARE-UNIT BYPASS; SAME-DAY DISCHARGE; LOCAL-ANESTHETICS; ARTHROPLASTY; FALLS; ADJUVANTS; PAIN; TIME C1 [Williams, Brian A.; Ibinson, James W.; Mangione, Michael P.] Univ Pittsburgh, Sch Med, Dept Anesthesiol, Pittsburgh, PA 15261 USA. [Cohen, Peter Z.] Univ Pittsburgh, Sch Med, Dept Orthopaed Surg, Pittsburgh, PA 15261 USA. [Williams, Brian A.; Ibinson, James W.] Vet Affairs Pittsburgh Healthcare Syst, Dept Anesthesiol, Pittsburgh, PA USA. [Williams, Brian A.; Ibinson, James W.; Mangione, Michael P.; Scanlan, Rick L.; Cohen, Peter Z.] Vet Affairs Pittsburgh Healthcare Syst, Surg Serv Line, Pittsburgh, PA USA. [Williams, Brian A.; Ibinson, James W.; Mangione, Michael P.; Scanlan, Rick L.; Cohen, Peter Z.] Vet Affairs Pittsburgh Healthcare Syst, Pittsburgh, PA USA. RP Williams, BA (reprint author), Univ Pittsburgh, Sch Med, Dept Anesthesiol, Pittsburgh, PA 15261 USA. OI Ibinson, James/0000-0002-5525-5225 NR 20 TC 4 Z9 4 U1 0 U2 2 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1526-2375 EI 1526-4637 J9 PAIN MED JI Pain Med. PD JAN PY 2015 VL 16 IS 1 BP 1 EP 6 DI 10.1111/pme.12599 PG 6 WC Medicine, General & Internal SC General & Internal Medicine GA CA2IN UT WOS:000348732200001 PM 25351887 ER PT J AU Williams, BA Ibinson, JW Mangione, MP Modrak, RT Tonarelli, EJ Rakesh, H Kmatz, AM Cohen, PZ AF Williams, Brian A. Ibinson, James W. Mangione, Michael P. Modrak, Robert T. Tonarelli, Elizabeth J. Rakesh, Hulimangala Kmatz, Alissa M. Cohen, Peter Z. TI Research Priorities Regarding Multimodal Peripheral Nerve Blocks for Postoperative Analgesia and Anesthesia Based on Hospital Quality Data Extracted from Over 1,300 Cases (2011-2014) SO PAIN MEDICINE LA English DT Editorial Material ID LOCAL-ANESTHETICS; PAIN; PREDICTORS C1 [Williams, Brian A.; Ibinson, James W.; Mangione, Michael P.; Cohen, Peter Z.] Univ Pittsburgh, Pittsburgh, PA 15260 USA. [Williams, Brian A.; Ibinson, James W.; Mangione, Michael P.; Rakesh, Hulimangala] Vet Affairs Pittsburgh Healthcare Syst, Anesthesia Serv, Pittsburgh, PA USA. [Modrak, Robert T.; Cohen, Peter Z.] Vet Affairs Pittsburgh Healthcare Syst, Orthopaed Surg Serv, Pittsburgh, PA USA. [Tonarelli, Elizabeth J.; Kmatz, Alissa M.] Vet Affairs Pittsburgh Healthcare Syst, Pittsburgh, PA USA. RP Williams, BA (reprint author), Univ Pittsburgh, Pittsburgh, PA 15260 USA. OI Ibinson, James/0000-0002-5525-5225 NR 13 TC 7 Z9 7 U1 0 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1526-2375 EI 1526-4637 J9 PAIN MED JI Pain Med. PD JAN PY 2015 VL 16 IS 1 BP 7 EP 12 DI 10.1111/pme.12609 PG 6 WC Medicine, General & Internal SC General & Internal Medicine GA CA2IN UT WOS:000348732200002 PM 25377071 ER PT J AU Oliva, EM Midboe, AM Lewis, ET Henderson, PT Dalton, AL Im, JJ Seal, K Paik, MC Trafton, JA AF Oliva, Elizabeth M. Midboe, Amanda M. Lewis, Eleanor T. Henderson, Patricia T. Dalton, Aaron L. Im, Jinwoo J. Seal, Karen Paik, Meenah C. Trafton, Jodie A. TI Sex Differences in Chronic Pain Management Practices for Patients Receiving Opioids from the Veterans Health Administration SO PAIN MEDICINE LA English DT Article DE Pain Management; Opioids; Sex; Veterans ID PRIMARY-CARE; MUSCULOSKELETAL PAIN; IRAQI FREEDOM; GENDER; WOMEN; PREVALENCE; ORGANIZATION; COMORBIDITY; POPULATION; PATTERNS AB BackgroundWomen experience chronic pain and use pain-related health care at higher rates than men. It is not known whether the pain-related health care female veterans receive is consistent with clinical practice guideline recommendations or whether receipt of this care differs between men and women. ObjectiveThe aim of this study was to identify whether sex differences in chronic pain management care exist for patients served by the Veterans Health Administration (VHA). DesignData on patient demographics, diagnostic criteria, and health care utilization were extracted from VHA administrative databases for fiscal year 2010 (FY10). PatientsPatients in this study included all VHA patients (excluding metastatic cancer patients) who received more than 90 days of a short-acting opioid medication or a long-acting opioid medication prescription in FY10 study. MeasuresMultilevel logistic regressions were conducted to identify sex differences in receipt of guideline-recommended chronic pain management. ResultsA total of 480,809 patients met inclusion criteria. Female patients were more likely to receive most measures of guideline-recommended care for chronic pain including mental health assessments, psychotherapy, rehabilitation therapy, and pharmacy reconciliation. However, women were more likely to receive concurrent sedative prescriptions, which is inconsistent with guideline recommendations. Most of the observed sex differences persisted after controlling for key demographic and diagnostic differences. ConclusionsFindings suggest that female VHA patients are more likely to receive an array of pain management practices than male patients, including both contraindicated and recommended polypharmacy. Quality improvement efforts to address underutilization of mental health and rehabilitative services for pain by male patients and polypharmacy in female patients should be considered. C1 [Oliva, Elizabeth M.; Midboe, Amanda M.; Lewis, Eleanor T.; Henderson, Patricia T.; Dalton, Aaron L.; Paik, Meenah C.; Trafton, Jodie A.] Ctr Innovat Implementat, Dept Vet Affairs, Menlo Pk, CA USA. [Seal, Karen] San Francisco VA Med Ctr, Integrated Care Clin, San Francisco, CA USA. [Seal, Karen] San Francisco VA Med Ctr, Med Practice Pain Clin, San Francisco, CA USA. [Trafton, Jodie A.] Univ Calif San Francisco, Dept Med, San Francisco, CA USA. [Trafton, Jodie A.] Univ Calif San Francisco, Dept Psychiat, San Francisco, CA USA. [Im, Jinwoo J.] Stanford Univ, Dept Psychiat & Behav Sci, Sch Med, Stanford, CA 94305 USA. [Seal, Karen] Samsung Econ Res Inst, Ind & Strategy Dept, Seoul, South Korea. RP Oliva, EM (reprint author), VA Ctr Innovat Implementat, 795Willow Rd 152, Menlo Pk, CA 94025 USA. EM Elizabeth.Oliva@va.gov FU Department of Veterans' Affairs (VA) Health Services Research and Development program (HSRD); Quality Enhancement Research Initiative (QUERI) [RRP 10-106, RRP 12-445]; VA Office of Mental Health FX This project was funded by grants awarded by the Department of Veterans' Affairs (VA) Health Services Research and Development program (HSR&D) and Quality Enhancement Research Initiative (QUERI) to Dr. Trafton-RRP 10-106 entitled "Assessment of Gaps in Chronic Opioid Therapy Guideline Adherence"-and Dr. Lewis-RRP 12-445 entitled "Adherence to Practice Recommendations for Veterans with SUDs Receiving Opioids." Additional funding was provided by the VA Office of Mental Health Operations to the Program Evaluation and Resource Center (PERC). The authors gratefully acknowledge Dr. Robert Kerns, Dr. William Becker, Dr. Francine Goodman, Dr. Jack Rosenberg, and Dr. Rollin (Mac) Gallagher for their role in creating the CPG adherence metrics. We gratefully acknowledge the sacrifices of the men and women who have served in the United States military. NR 20 TC 3 Z9 3 U1 1 U2 2 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1526-2375 EI 1526-4637 J9 PAIN MED JI Pain Med. PD JAN PY 2015 VL 16 IS 1 BP 112 EP 118 DI 10.1111/pme.12501 PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA CA2IN UT WOS:000348732200018 PM 25039721 ER PT J AU Williams, BA Butt, MT Zeller, JR Coffee, S Pippi, MA AF Williams, Brian A. Butt, Mark T. Zeller, Jillynne R. Coffee, Samantha Pippi, Michael A. TI Multimodal Perineural Analgesia with Combined Bupivacaine-Clonidine-Buprenorphine-Dexamethasone: Safe In Vivo and Chemically Compatible in Solution SO PAIN MEDICINE LA English DT Article DE Bupivacaine; Clonidine; Buprenorphine; Dexamethasone; Midazolam; Nerve Block ID BRACHIAL-PLEXUS BLOCKADE; PERIPHERAL-NERVE BLOCKS; LOCAL-ANESTHETICS; NEUROTOXICITY; ROPIVACAINE; ADJUVANTS; PROLONGS; MEPIVACAINE; LIDOCAINE; TRIALS AB ObjectivesThe use of adjuvants in regional anesthesia has increased. However, there are knowledge gaps pertaining to 1) in vivo local tissue effects of these adjuvants; and 2) chemical compatibility and solubility of these drugs in solution with each other and with local anesthetics. This study addresses these gaps in knowledge. DesignIn vivo rat safety/toxicopathology study and analytical chemistry study. SettingCollaborating Good Laboratory Practice laboratories under the direction of the university-based principal investigator. MethodsSingle-injection formulations of clonidine, buprenorphine, and dexamethasone were combined with either bupivacaine or midazolam, and were administered to groups of rats. Post-injection behavior was monitored to assess changes related to the block. A continuous infusion of bupivacaine, clonidine, and dexamethasone was administered to another group of rats, and behavioral effects were recorded. After 15 days, rats were sacrificed and their nerves/dorsal root ganglia were examined by the pathologist. Samples of combined drug solutions were processed at an analytical chemistry laboratory for compatibility, solubility, and stability. ResultsEach of the single-injection formulations produced reversible sensory and/or motor block. None of the study drugs caused damage to any of the nerve segments or related tissue. The text describes the concentrations at which compatibility and solubility of the combined drug solutions were achieved. ConclusionsFour-drug single-injection formulations are described that 1) had compatible and stable concentrations in solution; and 2) produced reversible nerve block without causing long-term motor or sensory deficits or damage to sciatic nerves/dorsal root ganglia. C1 [Williams, Brian A.] Vet Affairs Pittsburgh Healthcare Syst, Dept Anesthesiol, Pittsburgh, PA USA. [Williams, Brian A.; Pippi, Michael A.] Univ Pittsburgh, Dept Anesthesiol, Pittsburgh, PA 15261 USA. [Butt, Mark T.] TPS, Frederick, MD USA. [Zeller, Jillynne R.] NBR, Spring Lake, MI USA. [Coffee, Samantha] WIL Res Labs, Ashland, OH USA. RP Williams, BA (reprint author), Univ Pittsburgh, Sch Med, Dept Anesthesiol, 200 Lothrop St,A-1305 Scaife Hall, Pittsburgh, PA 15261 USA. EM williamsba@anes.upmc.edu FU VA Pittsburgh Health System FX The methodology was designed in detailed consultation with the participating GLP facilities (animal surgery and behavioral experiments, along with animal sacrifice and tissue harvest/preservation at Northern Biomedical Research [NBR], Inc., Spring Lake, Michigan, United States; Randall Reed, BA, SRS, laboratory director; and Tox Path Specialists [TPS], LLC, Frederick, Maryland, United States; co-author Mark T. Butt, DVM, DAVCP, study pathologist and company president). The contents of this manuscript do not reflect the views of the Department of Veterans Affairs or the United States Government. VA Pittsburgh Health System is acknowledged for support of lead author BAW. This manuscript/study was underwritten by the Department of Defense (OR090012 to author BAW) Peer Reviewed Orthopaedic Research Program (PRORP), Translational Research Partnership Award (TRPA), of the Office of the Congressionally Directed Medical Research Programs (CDMRP). NR 20 TC 8 Z9 8 U1 2 U2 4 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1526-2375 EI 1526-4637 J9 PAIN MED JI Pain Med. PD JAN PY 2015 VL 16 IS 1 BP 186 EP 198 DI 10.1111/pme.12592 PG 13 WC Medicine, General & Internal SC General & Internal Medicine GA CA2IN UT WOS:000348732200026 PM 25339320 ER PT J AU Mahajan, A Sim, X Ng, HJ Manning, A Rivas, MA Highland, HM Locke, AE Grarup, N Im, HK Cingolani, P Flannick, J Fontanillas, P Fuchsberger, C Gaulton, KJ Teslovich, TM Rayner, NW Robertson, NR Beer, NL Rundle, JK Bork-Jensen, J Ladenvall, C Blancher, C Buck, D Buck, G Burtt, NP Gabriel, S Gjesing, AP Groves, CJ Hollensted, M Huyghe, JR Jackson, AU Jun, G Justesen, JM Mangino, M Murphy, J Neville, M Onofrio, R Small, KS Stringham, HM Syvanen, AC Trakalo, J Abecasis, G Bell, GI Blangero, J Cox, NJ Duggirala, R Hanis, CL Seielstad, M Wilson, JG Christensen, C Brandslund, I Rauramaa, R Surdulescu, GL Doney, ASF Lannfelt, L Linneberg, A Isomaa, B Tuomi, T Jorgensen, ME Jorgensen, T Kuusisto, J Uusitupa, M Salomaa, V Spector, TD Morris, AD Palmer, CNA Collins, FS Mohlke, KL Bergman, RN Ingelsson, E Lind, L Tuomilehto, J Hansen, T Watanabe, RM Prokopenko, I Dupuis, J Karpe, F Groop, L Laakso, M Pedersen, O Florez, JC Morris, AP Altshuler, D Meigs, JB Boehnke, M McCarthy, MI Lindgren, CM Gloyn, AL AF Mahajan, Anubha Sim, Xueling Ng, Hui Jin Manning, Alisa Rivas, Manuel A. Highland, Heather M. Locke, Adam E. Grarup, Niels Im, Hae Kyung Cingolani, Pablo Flannick, Jason Fontanillas, Pierre Fuchsberger, Christian Gaulton, Kyle J. Teslovich, Tanya M. Rayner, N. William Robertson, Neil R. Beer, Nicola L. Rundle, Jana K. Bork-Jensen, Jette Ladenvall, Claes Blancher, Christine Buck, David Buck, Gemma Burtt, Noel P. Gabriel, Stacey Gjesing, Anette P. Groves, Christopher J. Hollensted, Mette Huyghe, Jeroen R. Jackson, Anne U. Jun, Goo Justesen, Johanne Marie Mangino, Massimo Murphy, Jacquelyn Neville, Matt Onofrio, Robert Small, Kerrin S. Stringham, Heather M. Syvanen, Ann-Christine Trakalo, Joseph Abecasis, Goncalo Bell, Graeme I. Blangero, John Cox, Nancy J. Duggirala, Ravindranath Hanis, Craig L. Seielstad, Mark Wilson, James G. Christensen, Cramer Brandslund, Ivan Rauramaa, Rainer Surdulescu, Gabriela L. Doney, Alex S. F. Lannfelt, Lars Linneberg, Allan Isomaa, Bo Tuomi, Tiinamaija Jorgensen, Marit E. Jorgensen, Torben Kuusisto, Johanna Uusitupa, Matti Salomaa, Veikko Spector, Timothy D. Morris, Andrew D. Palmer, Colin N. A. Collins, Francis S. Mohlke, Karen L. Bergman, Richard N. Ingelsson, Erik Lind, Lars Tuomilehto, Jaakko Hansen, Torben Watanabe, Richard M. Prokopenko, Inga Dupuis, Josee Karpe, Fredrik Groop, Leif Laakso, Markku Pedersen, Oluf Florez, Jose C. Morris, Andrew P. Altshuler, David Meigs, James B. Boehnke, Michael McCarthy, Mark I. Lindgren, Cecilia M. Gloyn, Anna L. CA T2D-GENES Consortium Go T2D Consortium TI Identification and Functional Characterization of G6PC2 Coding Variants Influencing Glycemic Traits Define an Effector Transcript at the G6PC2-ABCB11 Locus SO PLOS GENETICS LA English DT Article ID TYPE-2 DIABETES RISK; FASTING PLASMA-GLUCOSE; GENETIC ARCHITECTURE; TRIGLYCERIDE LEVELS; QUANTITATIVE TRAIT; P446L VARIANT; ASSOCIATION; GENOME; PROTEIN; POLYMORPHISMS AB Genome wide association studies (GWAS) for fasting glucose (FG) and insulin (FI) have identified common variant signals which explain 4.8% and 1.2% of trait variance, respectively. It is hypothesized that low-frequency and rare variants could contribute substantially to unexplained genetic variance. To test this, we analyzed exome-array data from up to 33,231 non-diabetic individuals of European ancestry. We found exome-wide significant (P<5x10-7) evidence for two loci not previously highlighted by common variant GWAS: GLP1R (p.Ala316Thr, minor allele frequency (MAF)=1.5%) influencing FG levels, and URB2 (p.Glu594Val, MAF = 0.1%) influencing FI levels. Coding variant associations can highlight potential effector genes at (non-coding) GWAS signals. At the G6PC2/ABCB11 locus, we identified multiple coding variants in G6PC2 (p.Val219Leu, p.His177Tyr, and p Tyr207Ser) influencing FG levels, conditionally independent of each other and the non-coding GWAS signal. In vitro assays demonstrate that these associated coding alleles result in reduced protein abundance via proteasomal degradation, establishing G6PC2 as an effector gene at this locus. Reconciliation of single-variant associations and functional effects was only possible when haplotype phase was considered. In contrast to earlier reports suggesting that, paradoxically, glucose-raising alleles at this locus are protective against type 2 diabetes (T2D), the p.Val219Leu G6PC2 variant displayed a modest but directionally consistent association with T2D risk. Coding variant associations for glycemic traits in GWAS signals highlight PCSK1, RREB1, and ZHX3 as likely effector transcripts. These coding variant association signals do not have a major impact on the trait variance explained, but they do provide valuable biological insights. C1 [Mahajan, Anubha; Rivas, Manuel A.; Gaulton, Kyle J.; Rayner, N. William; Robertson, Neil R.; Morris, Andrew D.; Ingelsson, Erik; Prokopenko, Inga; Morris, Andrew P.; McCarthy, Mark I.; Lindgren, Cecilia M.] Univ Oxford, Wellcome Trust Ctr Human Genet, Nuffield Dept Med, Oxford, England. [Sim, Xueling; Locke, Adam E.; Fuchsberger, Christian; Teslovich, Tanya M.; Huyghe, Jeroen R.; Jackson, Anne U.; Jun, Goo; Stringham, Heather M.; Abecasis, Goncalo; Boehnke, Michael] Univ Michigan, Dept Biostat, Ann Arbor, MI 48109 USA. [Sim, Xueling; Locke, Adam E.; Fuchsberger, Christian; Teslovich, Tanya M.; Huyghe, Jeroen R.; Jackson, Anne U.; Jun, Goo; Stringham, Heather M.; Abecasis, Goncalo; Boehnke, Michael] Univ Michigan, Ctr Stat Genet, Ann Arbor, MI 48109 USA. [Ng, Hui Jin; Rayner, N. William; Robertson, Neil R.; Beer, Nicola L.; Rundle, Jana K.; Groves, Christopher J.; Neville, Matt; Prokopenko, Inga; Karpe, Fredrik; McCarthy, Mark I.; Gloyn, Anna L.] Univ Oxford, Radcliffe Dept Med, Oxford Ctr Diabet Endocrinol & Metab, Oxford, England. [Manning, Alisa; Flannick, Jason; Fontanillas, Pierre; Burtt, Noel P.; Gabriel, Stacey; Murphy, Jacquelyn; Onofrio, Robert; Florez, Jose C.; Altshuler, David; Lindgren, Cecilia M.] Broad Inst, Program Med & Populat Genet, Cambridge, MA USA. [Highland, Heather M.] Univ Texas Hlth Sci Ctr Houston, Univ Texas Grad Sch Biomed Sci Houston, Ctr Human Genet, Houston, TX 77030 USA. [Grarup, Niels; Bork-Jensen, Jette; Gjesing, Anette P.; Hollensted, Mette; Justesen, Johanne Marie; Hansen, Torben; Pedersen, Oluf] Univ Copenhagen, Fac Hlth & Med Sci, Novo Nordisk Fdn Ctr Basic Metab Res, Copenhagen, Denmark. [Im, Hae Kyung] Univ Chicago, Dept Hlth Studies, Biostat Lab, Chicago, IL 60637 USA. [Cingolani, Pablo] McGill Univ, Sch Comp Sci, Montreal, PQ, Canada. [Cingolani, Pablo] McGill Univ, Montreal, PQ, Canada. [Cingolani, Pablo] Genome Quebec Innovat Ctr, Montreal, PQ, Canada. [Flannick, Jason; Altshuler, David] Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. [Rayner, N. William] Wellcome Trust Sanger Inst, Dept Human Genet, Hinxton, Cambs, England. [Ladenvall, Claes; Groop, Leif] Lund Univ, Ctr Diabet, Dept Clin Sci Diabet & Endocrinol, Malmo, Sweden. [Blancher, Christine; Buck, David; Buck, Gemma; Trakalo, Joseph] Univ Oxford, Nuffield Dept Med, Wellcome Trust Ctr Human Genet, High Throughput Genom Oxford Genom Ctr, Oxford, England. [Mangino, Massimo; Small, Kerrin S.; Surdulescu, Gabriela L.; Spector, Timothy D.] Kings Coll London, Dept Twin Res & Genet Epidemiol, London, England. [Syvanen, Ann-Christine] Uppsala Univ, Dept Med Sci, Mol Med & Sci Life Lab, Uppsala, Sweden. [Bell, Graeme I.] Univ Chicago, Dept Med, Chicago, IL 60637 USA. [Bell, Graeme I.] Univ Chicago, Dept Human Genet, Chicago, IL 60637 USA. [Blangero, John; Duggirala, Ravindranath] Texas Biomed Res Inst, Dept Genet, San Antonio, TX USA. [Cox, Nancy J.] Univ Chicago, Dept Med, Med Genet Sect, Chicago, IL 60637 USA. [Hanis, Craig L.] Univ Texas Hlth Sci Ctr Houston, Sch Publ Hlth, Ctr Human Genet, Houston, TX 77030 USA. [Seielstad, Mark] Blood Syst Res Inst, San Francisco, CA USA. [Seielstad, Mark] Univ Calif San Francisco, Dept Lab Med, San Francisco, CA 94143 USA. [Seielstad, Mark] Univ Calif San Francisco, Inst Human Genet, San Francisco, CA 94143 USA. [Wilson, James G.] Univ Mississippi, Med Ctr, Dept Physiol & Biophys, Jackson, MS 39216 USA. [Christensen, Cramer] Vejle Hosp, Dept Internal Med & Endocrinol, Vejle, Denmark. [Brandslund, Ivan] Vejle Hosp, Dept Clin Biochem, Vejle, Denmark. [Brandslund, Ivan] Univ Southern Denmark, Inst Reg Hlth Res, Odense, Denmark. [Rauramaa, Rainer] Kuopio Res Inst Exercise Med, Fdn Res Hlth Exercise & Nutr, Kuopio, Finland. [Doney, Alex S. F.] Univ Dundee, Ninewells Hosp & Med Sch, Med Res Inst, Div Cardiovasc & Diabet Med, Dundee DD1 9SY, Scotland. [Lannfelt, Lars] Uppsala Univ, Dept Publ Hlth & Caring Sci, Uppsala, Sweden. [Linneberg, Allan] Glostrup Univ Hosp, Dept Clin Expt Res, Glostrup, Denmark. [Linneberg, Allan] Univ Copenhagen, Dept Clin Med, Fac Hlth & Med Sci, Copenhagen, Denmark. [Linneberg, Allan; Jorgensen, Torben] Glostrup Univ Hosp, Res Ctr Prevent & Hlth, Glostrup, Denmark. [Isomaa, Bo] Dept Social Serv & Hlth Care, Pietarsaari, Finland. [Isomaa, Bo; Tuomi, Tiinamaija] Folkhalsan Res Ctr, Helsinki, Finland. [Tuomi, Tiinamaija] Univ Helsinki, Cent Hosp, Dept Endocrinol, Helsinki, Finland. [Jorgensen, Marit E.] Steno Diabet Ctr, DK-2820 Gentofte, Denmark. [Jorgensen, Torben] Aalborg Univ, Fac Med, Aalborg, Denmark. [Kuusisto, Johanna; Laakso, Markku] Univ Eastern Finland, Inst Clin Med Internal Med, Fac Hlth Sci, Kuopio, Finland. [Kuusisto, Johanna; Laakso, Markku] Kuopio Univ Hosp, SF-70210 Kuopio, Finland. [Uusitupa, Matti] Univ Eastern Finland, Inst Publ Hlth & Clin Nutr, Kuopio, Finland. [Salomaa, Veikko] Natl Inst Hlth & Welf, Helsinki, Finland. [Morris, Andrew D.] Univ Dundee, Ninewells Hosp & Med Sch, Clin Res Ctr, Ctr Mol Med, Dundee DD1 9SY, Scotland. [Palmer, Colin N. A.] Univ Dundee, Ninewells Hosp & Med Sch, Med Res Inst, Pat Macpherson Ctr Pharmacogenet & Pharmacogenom, Dundee DD1 9SY, Scotland. [Collins, Francis S.] NHGRI, Med Genom & Metab Genet Branch, NIH, Bethesda, MD 20892 USA. [Mohlke, Karen L.] Univ N Carolina, Dept Genet, Chapel Hill, NC USA. [Bergman, Richard N.] Cedars Sinai Diabet & Obes Res Inst, Los Angeles, CA USA. [Ingelsson, Erik] Uppsala Univ, Dept Med Sci, Mol Epidemiol & Sci Life Lab, Uppsala, Sweden. [Lind, Lars] Uppsala Univ, Dept Med Sci, Uppsala, Sweden. [Tuomilehto, Jaakko] King Abdulaziz Univ, Diabet Res Grp, Jeddah 21413, Saudi Arabia. [Tuomilehto, Jaakko] Autonomous Univ Madrid, Univ Hosp LaPaz, Inst Invest Sanitaria Hosp Univ LaPaz IdiPAZ, E-28049 Madrid, Spain. [Tuomilehto, Jaakko] Danube Univ Krems, Ctr Vasc Prevent, Krems, Austria. [Tuomilehto, Jaakko] Natl Inst Hlth & Welf, Diabet Prevent Unit, Helsinki, Finland. [Hansen, Torben] Univ Southern Denmark, Fac Hlth Sci, Odense, Denmark. [Watanabe, Richard M.] Univ So Calif, Keck Sch Med, Dept Physiol & Biophys, Los Angeles, CA 90033 USA. [Watanabe, Richard M.] Univ So Calif, Keck Sch Med, Dept Prevent Med, Los Angeles, CA 90033 USA. [Watanabe, Richard M.] Univ So Calif, Keck Sch Med, Diabet & Obes Res Inst, Los Angeles, CA 90033 USA. [Prokopenko, Inga] Univ London Imperial Coll Sci Technol & Med, Sch Publ Hlth, Dept Genom Common Dis, London, England. [Dupuis, Josee] Natl Heart Lung & Blood Inst Framingham Heart Stu, Framingham, MA USA. [Dupuis, Josee] Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA USA. [Karpe, Fredrik; McCarthy, Mark I.; Gloyn, Anna L.] Oxford Univ Hosp Trust, Oxford NIHR Biomed Res Ctr, Oxford, England. [Florez, Jose C.; Altshuler, David] Massachusetts Gen Hosp, Dept Med, Diabet Res Ctr, Diabet Unit, Boston, MA 02114 USA. [Florez, Jose C.; Altshuler, David] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. [Florez, Jose C.] Massachusetts Gen Hosp, Dept Med, Ctr Human Genet Res, Boston, MA 02114 USA. [Morris, Andrew P.] Univ Liverpool, Dept Biostat, Liverpool L69 3BX, Merseyside, England. [Morris, Andrew P.] Univ Tartu, Estonian Genome Ctr, EE-50090 Tartu, Estonia. [Altshuler, David] MIT, Dept Biol, Cambridge, MA USA. [Altshuler, David] Harvard Univ, Sch Med, Dept Genet, Boston, MA USA. [Meigs, James B.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Gen Med, Boston, MA USA. [Meigs, James B.] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. RP Mahajan, A (reprint author), Univ Oxford, Wellcome Trust Ctr Human Genet, Nuffield Dept Med, Oxford, England. EM celi@well.ox.ac.uk; anna.gloyn@drl.ox.ac.uk RI Palmer, Colin/C-7053-2008; Grarup, Niels/K-2807-2015; Prokopenko, Inga/H-3241-2014; Justesen, Johanne Marie/L-6023-2015; kinnunen, leena/B-7059-2012; Study, GoDARTS/K-9448-2016; mangino, massimo/F-5134-2011; Hrabe de Angelis, Martin/F-5531-2012; Jun, Goo/F-1941-2017; OI Gieger, Christian/0000-0001-6986-9554; Meisinger, Christa/0000-0002-9026-6544; Tuomi, Tiinamaija/0000-0002-8306-6202; Jorgensen, Torben/0000-0001-9453-2830; Small, Kerrin/0000-0003-4566-0005; Khor, Chiea Chuen/0000-0002-1128-4729; Tai, E Shyong/0000-0003-2929-8966; Linneberg, Allan/0000-0002-0994-0184; Palmer, Colin/0000-0002-6415-6560; Grarup, Niels/0000-0001-5526-1070; Prokopenko, Inga/0000-0003-1624-7457; Justesen, Johanne Marie/0000-0002-0484-8522; kinnunen, leena/0000-0001-8739-4812; mangino, massimo/0000-0002-2167-7470; Hrabe de Angelis, Martin/0000-0002-7898-2353; Jun, Goo/0000-0003-0891-0204; Fuchsberger, Christian/0000-0002-5918-8947; Kim, Yongkang/0000-0002-8837-2620; Locke, Adam/0000-0001-6227-198X FU Agency for Science, Technology and Research in Singapore; Austrian Science Fund (FWF) [J-3401]; MGH Research Scholars Award; NIDDK [R01 DK078616, K24 DK080140, DK098032]; NIH [U01 DK085526, U01 DK085501, U01 DK085524, U01 DK085545, U01 DK085584, U01 DK088389]; Wellcome Trust [090367, 098381, 090532, 083948, 085475, WT098017, WT064890, WT090532]; MRC [G0601261]; EU (Framework 7) [HEALTH-F4-2007-201413]; Oxford Biomedical Research Centre; National NIHR Bioresource; Uppsala University; Uppsala University Hospital; Swedish Research Council; Swedish Heart-Lung Foundation; Wellcome Trust Study Cohort Wellcome Trust Functional Genomics Grant [072960/2/03/2]; Wellcome Trust Scottish Health Informatics Programme (SHIP) [086113/Z/08/Z]; Wellcome Trust; European Community's Seventh Framework Programme (FP7); National Institute for Health Research (NIHR) BioResource Clinical Research Facility and Biomedical Research Centre based at Guy's and St Thomas' NHS Foundation Trust; King's College London; ERC Advanced Principal Investigator award; Lundbeck Foundation (Lundbeck Foundation Centre for Applied Medical Genomics in Personalised Disease Prediction, Prevention and Care (LuCamp)); Danish Council for Independent Research; Novo Nordisk Foundation; Academy of Finland [124243, 139635, 129293, 117844, 40758, 211497, 118590, 102318, 123885]; Finnish Heart Foundation; Finnish Diabetes Foundation; Tekes [1510/31/06, 70103/06, 40058/07]; Commission of the European Community [HEALTH-F2-2007-201681]; US National Institutes of Health [DK093757, DK072193, DK062370, 1Z01 HG000024]; Finnish Foundation for Cardiovascular Research; hospital district of Pirkanmaa; hospital district of South Ostrobothnia; hospital district of Central Finland; National Institute for Health and Welfare; Finnish Diabetes Association; Ministry of Social Affairs and Health in Finland; Commission of the European Communities; Directorate C-Public Health [2004310]; Finland's Slottery Machine Association; Ministry of Health and Social Affairs [5254]; Finnish Funding Agency for Technology and Innovation [40058/07]; Nordic Centre of Excellence on 'Systems biology in controlled dietary interventions and cohort studies, SYSDIET [070014]; Finnish Diabetes Research Foundation; Yrjo Jahnsson Foundation [56358]; Sigrid Juselius Foundation; Ministry of Education and Culture of Finland [627]; Kuopio University Hospital; Finnish Heart Association; Paivikki and Sakari Sohlberg Foundation; European Commission FP6 Integrated Project (EXGENESIS); City of Kuopio and Social Insurance Institution of Finland [LSHM-CT-2004-005272] FX HJN was supported by the Agency for Science, Technology and Research in Singapore. CF was supported by the Austrian Science Fund (FWF) grant J-3401. JCF was supported by MGH Research Scholars Award. APM is a Wellcome Trust Senior Research Fellow in Basic and Biomedical Science. JBM was supported by NIDDK R01 DK078616 and K24 DK080140. MIM is a Wellcome Trust Senior Investigator (WT098381); and a National Institute of Health Research Senior Investigator. CML is a Wellcome Trust Research Career Development Fellow (086596/Z/08/Z). ALG is a Wellcome Trust Senior Research Fellow in Basic and Biomedical Science (095010/Z/10/Z). Funding for the GoT2D and T2D-GENES studies was provided by grants NIH U01s DK085526, DK085501, DK085524, DK085545, and DK085584 (Multiethnic Study of Type 2 Diabetes Genes) and DK088389 (Low-Pass Sequencing and High-Density SNP Genotyping for Type 2 Diabetes). Analysis and genotyping of the British UK cohorts was supported by Wellcome Trust funding 090367, 098381, 090532, 083948, 085475, MRC (G0601261), EU (Framework 7) HEALTH-F4-2007-201413, and NIDDK DK098032. The Oxford Biobank is supported by the Oxford Biomedical Research Centre and part of the National NIHR Bioresource. The PIVUS/ULSAM cohort was supported by Wellcome Trust Grants WT098017, WT064890, WT090532, Uppsala University, Uppsala University Hospital, the Swedish Research Council and the Swedish Heart-Lung Foundation. GoDARTS study was funded by The Wellcome Trust Study Cohort Wellcome Trust Functional Genomics Grant (2004-2008) (Grant No: 072960/2/03/2) and The Wellcome Trust Scottish Health Informatics Programme (SHIP) (2009-2012) (Grant No: 086113/Z/08/Z). TwinsUK study was funded by the Wellcome Trust; European Community's Seventh Framework Programme (FP7/2007-2013). The study also receives support from the National Institute for Health Research (NIHR) BioResource Clinical Research Facility and Biomedical Research Centre based at Guy's and St Thomas' NHS Foundation Trust and King's College London. TDS is holder of an ERC Advanced Principal Investigator award. The Danish studies were supported by the Lundbeck Foundation (Lundbeck Foundation Centre for Applied Medical Genomics in Personalised Disease Prediction, Prevention and Care (LuCamp); http://www.lucamp.org/) and the Danish Council for Independent Research. The Novo Nordisk Foundation Center for Basic Metabolic Research is an independent Research Center at the University of Copenhagen, partially funded by an unrestricted donation from the Novo Nordisk Foundation (http://www.metabol.ku.dk/). The METSIM study was supported by the Academy of Finland (contract 124243), the Finnish Heart Foundation, the Finnish Diabetes Foundation, Tekes (contract 1510/31/06), and the Commission of the European Community (HEALTH-F2-2007-201681), and the US National Institutes of Health grants DK093757, DK072193, DK062370, and 1Z01 HG000024. The FUSION study was supported by DK093757, DK072193, DK062370, and 1Z01 HG000024. Genotyping of the METSIM and DPS studies was conducted at the Genetic Resources Core Facility (GRCF) at the Johns Hopkins Institute of Genetic Medicine. VS is funded by the Finnish Foundation for Cardiovascular Research and the Academy of Finland (grant # 139635).; The FIN-D2D 2007 study has been financially supported by the hospital districts of Pirkanmaa, South Ostrobothnia, and Central Finland, the Finnish National Public Health Institute (current National Institute for Health and Welfare), the Finnish Diabetes Association, the Ministry of Social Affairs and Health in Finland, the Academy of Finland (grant number 129293), Commission of the European Communities, Directorate C-Public Health (grant agreement no. 2004310) and Finland's Slottery Machine Association. The DPS has been financially supported by grants from the Academy of Finland (117844 and 40758, 211497, and 118590 (MU); The EVO funding of the Kuopio University Hospital from Ministry of Health and Social Affairs (5254), Finnish Funding Agency for Technology and Innovation (40058/07), Nordic Centre of Excellence on 'Systems biology in controlled dietary interventions and cohort studies, SYSDIET (070014), The Finnish Diabetes Research Foundation, Yrjo Jahnsson Foundation (56358), Sigrid Juselius Foundation and TEKES grants 70103/06 and 40058/07. The DR's EXTRA Study was supported by grants to RR by the Ministry of Education and Culture of Finland (627; 2004-2011), Academy of Finland (102318; 123885), Kuopio University Hospital, Finnish Diabetes Association, Finnish Heart Association, Paivikki and Sakari Sohlberg Foundation and by grants from European Commission FP6 Integrated Project (EXGENESIS); LSHM-CT-2004-005272, City of Kuopio and Social Insurance Institution of Finland (4/26/2010). The Broad Genomics Platform for genotyping of the FIN-D2D 2007, FINRISK 2007, DR'sEXTRA, FUSION, and PPP studies. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 41 TC 21 Z9 21 U1 2 U2 15 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1553-7404 J9 PLOS GENET JI PLoS Genet. PD JAN PY 2015 VL 11 IS 1 AR e1004876 DI 10.1371/journal.pgen.1004876 PG 25 WC Genetics & Heredity SC Genetics & Heredity GA CB0KL UT WOS:000349314600012 PM 25625282 ER PT J AU Murdoch, JD Gupta, AR Sanders, SJ Walker, MF Keaney, J Fernandez, TV Murtha, MT Anyanwu, S Ober, GT Raubeson, MJ DiLullo, NM Villa, N Waqar, Z Sullivan, C Gonzalez, L Willsey, AJ Choe, SY Neale, BM Daly, MJ State, MW AF Murdoch, John D. Gupta, Abha R. Sanders, Stephan J. Walker, Michael F. Keaney, John Fernandez, Thomas V. Murtha, Michael T. Anyanwu, Samuel Ober, Gordon T. Raubeson, Melanie J. DiLullo, Nicholas M. Villa, Natalie Waqar, Zainabdul Sullivan, Catherine Gonzalez, Luis Willsey, A. Jeremy Choe, So-Yeon Neale, Benjamin M. Daly, Mark J. State, Matthew W. TI No Evidence for Association of Autism with Rare Heterozygous Point Mutations in Contactin-Associated Protein-Like 2 (CNTNAP2), or in Other Contactin-Associated Proteins or Contactins SO PLOS GENETICS LA English DT Article ID SPECTRUM DISORDERS; RISK; GENE; LINKAGE; SPEECH; IDENTIFICATION; VARIANTS; CONTACTIN-ASSOCIATED-PROTEIN-LIKE-2; DISRUPTION; EPILEPSY AB Contactins and Contactin-Associated Proteins, and Contactin-Associated Protein-Like 2 (CNTNAP2) in particular, have been widely cited as autism risk genes based on findings from homozygosity mapping, molecular cytogenetics, copy number variation analyses, and both common and rare single nucleotide association studies. However, data specifically with regard to the contribution of heterozygous single nucleotide variants (SNVs) have been inconsistent. In an effort to clarify the role of rare point mutations in CNTNAP2 and related gene families, we have conducted targeted next-generation sequencing and evaluated existing sequence data in cohorts totaling 2704 cases and 2747 controls. We find no evidence for statistically significant association of rare heterozygous mutations in any of the CNTN or CNTNAP genes, including CNTNAP2, placing marked limits on the scale of their plausible contribution to risk. C1 [Murdoch, John D.; Sanders, Stephan J.; Willsey, A. Jeremy; State, Matthew W.] Yale Univ, Dept Genet, New Haven, CT USA. [Gupta, Abha R.; Fernandez, Thomas V.; Murtha, Michael T.; Anyanwu, Samuel; Ober, Gordon T.; Raubeson, Melanie J.; DiLullo, Nicholas M.; Waqar, Zainabdul; Sullivan, Catherine; Gonzalez, Luis; State, Matthew W.] Yale Univ, Ctr Child Study, New Haven, CT 06520 USA. [Gupta, Abha R.] Yale Univ, Dept Pediat, New Haven, CT 06520 USA. [Sanders, Stephan J.; Walker, Michael F.; Willsey, A. Jeremy; State, Matthew W.] Univ Calif San Francisco, Dept Psychiat, San Francisco, CA USA. [Keaney, John] Yale Coll, New Haven, CT USA. [Villa, Natalie] Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90095 USA. [Choe, So-Yeon] Univ Calif Los Angeles, Sch Law, Los Angeles, CA 90024 USA. [Neale, Benjamin M.; Daly, Mark J.] Broad Inst Harvard, Cambridge, MA USA. [Neale, Benjamin M.; Daly, Mark J.] MIT, Cambridge, MA 02139 USA. [Neale, Benjamin M.; Daly, Mark J.] Massachusetts Gen Hosp, Dept Med, Analyt & Translat Genet Unit, Boston, MA 02114 USA. [Neale, Benjamin M.; Daly, Mark J.] Harvard Univ, Sch Med, Boston, MA USA. RP Murdoch, JD (reprint author), European Neurosci Inst, Gottingen, Germany. EM matthew.state@ucsf.edu RI Fernandez, Thomas/D-4295-2009; OI Fernandez, Thomas/0000-0003-0830-022X; Sanders, Stephan/0000-0001-9112-5148 FU [R01 MH081754]; [RC2 MH089956]; [K08MH087639] FX This work was supported by grants R01 MH081754 and RC2 MH089956 to MWS, and by K08MH087639 to ARG. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 42 TC 15 Z9 15 U1 1 U2 6 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 2015 VL 11 IS 1 AR e1004852 DI 10.1371/journal.pgen.1004852 PG 15 WC Genetics & Heredity SC Genetics & Heredity GA CB0KL UT WOS:000349314600008 PM 25621974 ER PT J AU Wood, NE Rosasco, ML Suris, AM Spring, JD Marin, MF Lasko, NB Goetz, JM Fischer, AM Orr, SP Pitman, RK AF Wood, Nellie E. Rosasco, Maria L. Suris, Alina M. Spring, Justin D. Marin, Marie-France Lasko, Natasha B. Goetz, Jared M. Fischer, Avital M. Orr, Scott P. Pitman, Roger K. TI Pharmacological blockade of memory reconsolidation in posttraumatic stress disorder: Three negative psychophysiological studies SO PSYCHIATRY RESEARCH LA English DT Article DE Stress disorders; Post-traumatic; Propranolol; Mifepristone; Cycloserine; Imagery; Psychophysiology (all MeSH terms) ID ADMINISTERED PTSD SCALE; FEAR MEMORY; GLUCOCORTICOID-RECEPTORS; RETRIEVAL; AMYGDALA; CONSOLIDATION; REACTIVATION; PROPRANOLOL; IMAGERY AB Posttraumatic stress disorder (PTSD) may involve over-consolidated emotional memories of the traumatic event. Reactivation (RP) can return a memory to an unstable state, from which it must be restabilized (reconsolidated) if it is to persist. Pharmacological agents administered while the memory is unstable have been shown to impair reconsolidation. The N-methyl-D-aspartate (NMDA) partial agonist D-cycloserine (DCS) may promote memory destabilization. In the three studies reported here, we investigated whether the beta-adrenergic blocker propranolol or the glucocorticoid (GR) antagonist mifepristone, given at the time of traumatic memory reactivation, could reduce PTSD symptoms and physiological responding during subsequent traumatic imagery. Individuals with PTSD were randomized as follows: Study One: propranolol with memory reactivation (n=10) or without reactivation (n=8); Study Two: reactivation mifepristone (n=13), non-reactivation (NRP) mifepristone (n=15), or double placebo (PL) (0=15); Study Three: reactivation mifepristone plus D-cycloserine (n=16), or two placebos (n=15). Subjects underwent memory retrieval by describing their traumatic event. A week later they engaged in script-driven traumatic mental imagery, while heart rate (HR), skin conductance (SC), and facial electromyogram (EMG) responses were measured. There were no significant group differences in physiological responsivity or change in PTSD symptoms in any of the studies. These results do not support successful blockade of reconsolidation of traumatic memories in PTSD. (C) 2014 Elsevier Ireland Ltd. All rights reserved. C1 [Wood, Nellie E.] Tufts Univ, Sch Med, Boston, MA 02111 USA. [Rosasco, Maria L.] Univ Pittsburgh, Sch Med, Pittsburgh, PA USA. [Suris, Alina M.] Univ Texas SW Med Ctr Dallas, VA North Texas Hlth Care Syst, Dallas, TX 75390 USA. [Suris, Alina M.] Univ Texas SW Med Ctr Dallas, Dept Psychiat, Dallas, TX 75390 USA. [Spring, Justin D.] Columbia Univ Coll Phys & Surg, New York, NY USA. [Marin, Marie-France; Lasko, Natasha B.; Goetz, Jared M.; Orr, Scott P.; Pitman, Roger K.] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02129 USA. [Marin, Marie-France; Lasko, Natasha B.; Goetz, Jared M.; Orr, Scott P.; Pitman, Roger K.] Harvard Univ, Sch Med, Boston, MA 02129 USA. [Fischer, Avital M.] Boston Univ, Sch Med, Boston, MA 02118 USA. RP Pitman, RK (reprint author), Massachusetts Gen Hosp, Dept Psychiat, 120 Second Ave, Boston, MA 02129 USA. EM roger_pitman@hms.harvard.edu FU U.S. Army [W81XWH-08-2-0126] FX This study was funded by U.S. Army grant # W81XWH-08-2-0126. NR 34 TC 30 Z9 30 U1 14 U2 40 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0165-1781 J9 PSYCHIAT RES JI Psychiatry Res. PD JAN PY 2015 VL 225 IS 1-2 BP 31 EP 39 DI 10.1016/j.psychres.2014.09.005 PG 9 WC Psychiatry SC Psychiatry GA CA5LJ UT WOS:000348949600003 PM 25441015 ER PT J AU Bhuvaneswar, C Colon, J Matthews, J Burke, B Stern, TA AF Bhuvaneswar, Chaya Colon, Jesus Matthews, John Burke, Bethany Stern, Theodore A. TI Psychiatric Care of Deaf Patients in the General Hospital: An Overview SO PSYCHOSOMATICS LA English DT Review ID HEARING INPATIENTS; HEALTH; LANGUAGE; ADULTS; PREVALENCE; ISSUES; BRAIN; ABUSE AB Background: While the number of Deaf and hard-alhearing patients worldwide is estimated at six hundred million, few specialized psychiatric services or training resources exist to support the provision of mental health care to this population. This presents a particularly acute problem in the general hospital, where the consultant psychiatrist is likely to be confronted with the challenges of providing comprehensive psychiatric evaluation, diagnosis and treatment to patients with whom he or she may have limited experience or confidence. Method: We review critical considerations in the work-up differential diagnosis, and management of commonly-presenting psychiatric disorders among Deaf patients in the general hospital setting. C1 [Bhuvaneswar, Chaya] Univ Massachusetts, Sch Med, Dept Psychiat, Worcester, MA 01655 USA. Univ Massachusetts, Worcester Recovery Ctr, Worcester, MA 01655 USA. [Matthews, John; Stern, Theodore A.] Harvard Univ, Sch Med, Dept Psychiat, Massachusetts Gen Hosp, Boston, MA 02115 USA. RP Bhuvaneswar, C (reprint author), Univ Massachusetts, Sch Med, Dept Psychiat, 55 Lake Ave, Worcester, MA 01655 USA. EM chayab77@gmail.com NR 47 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 0033-3182 J9 PSYCHOSOMATICS JI Psychosomatics PD JAN-FEB PY 2015 VL 56 IS 1 BP 1 EP 11 PG 11 WC Psychiatry; Psychology SC Psychiatry; Psychology GA AZ9CY UT WOS:000348510300001 PM 25619669 ER PT J AU Brown, TM AF Brown, Thomas M. TI Neuropsychiatric Scurvy SO PSYCHOSOMATICS LA English DT Review ID ACETYL-L-CARNITINE; VITAMIN-C-DEFICIENCY; ASCORBIC ACID DEFICIENCY; PARKINSONS-DISEASE; CATALYTIC METALS; BRAIN; STRIATUM; OXYGEN; PREVALENCE; DOPAMINE AB Background: Scurvy is a disease with well-known peripheral symptoms, such as bleeding and pain. Method: The clinical and historical evidence for a distinct form of scurvy affecting the central nervous system, called neuropsychiatric scurvy, is reviewed. Pathophysiologic factors are described, as well as its diagnosis and management. C1 Audie L Murphy Mem Vet Adm Med Ctr, San Antonio, TX 78229 USA. RP Brown, TM (reprint author), Audie L Murphy Mem Vet Adm Med Ctr, 7400 Merton Minton Blvd, San Antonio, TX 78229 USA. EM thomas.brown5@va.gov NR 61 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 0033-3182 J9 PSYCHOSOMATICS JI Psychosomatics PD JAN-FEB PY 2015 VL 56 IS 1 BP 12 EP 20 PG 9 WC Psychiatry; Psychology SC Psychiatry; Psychology GA AZ9CY UT WOS:000348510300002 PM 25619670 ER PT J AU Rustad, JK Stern, TA Prabhakar, M Musselman, D AF Rustad, James K. Stern, Theodore A. Prabhakar, Maithri Musselman, Dominique TI Risk Factors for Alcohol Relapse Following Orthotopic Liver Transplantation: A Systematic Review SO PSYCHOSOMATICS LA English DT Review ID SCORING SYSTEM; UNITED-STATES; DISEASE; PREDICTORS; ABSTINENCE; HEPATITIS; DRINKING; RECIDIVISM; DEPENDENCE; CIRRHOSIS AB Background: Each year, 5000-6000 individuals undergo orthotopic liver transplantation (OLT) in the United States, and of these, nearly 18N have alcoholic liver disease. Relapse to alcohol occurs in more than 40% of patients with OLT for alcoholic liver disease. Objectives: We sought to identify factors that predict relapse to alcohol or medication nonadherence following OLT in patients with alcoholic liver disease and to review what randomized clinical interventions have addressed these factors following OLT Our hypothesis was that there would be factors before and after OLT that predict relapse to alcohol following OLT, and that these, if targeted, might improve sobriety and associated outcomes of adherence with medications and appointments. Methods: We performed a review (focusing on articles published since 2004) with Pub Med and MEDLINE searches using the following search terms: liver transplantation, recidivism, alcohol relapse, and predictors of alcohol relapse. We supplemented the online searches with manual reviews' of article reference lists and selected relevant articles far farther review by author consensus. Results: In largely white populations, prospective studies document that shorter length of pretransplantation sobriety is a significant predictor of time to first drink and time to binge use. Presence of psychiatric comorbidity, high score on standardized High-risk Alcoholism Relapse Scale, and diagnosis of Diagnostic and Statistical Manual of Mental Disorders (Fourth Edition) alcohol dependence are predictive of posttran,splantation alcohol relapse, Pretransplantation alcohol use history variables (e.g., family history of alcoholism) reliably discriminate between complete abstainers' and those who drink, while medical and psychosocial characteristics at early post liver transplantation period (e.g., More bodily pain) maximally discriminate patterns of alcohol use Alcoholic individuals with early-onset, rapidly accelerating moderate use and early-onset, continuously increasing heavy use have more than double the prevalence of steatohepatitis or rejection on biopsy and graft failure and more,frequent mortality resulting from recurrent alcoholic liver disease than late-onset (i.e., peak of heaviest drinking at 6 y posttransplantation) alcohol users do. Fortunately, pretransplantation screening combined with a structured pretransplantation management program and a 12-step program attendance reduced recidivism. No randomized clinical trials have been performed that target pretransplantation risk factors in individuals with alcoholic liver disease before or after OLT to improve post-OLT outcomes. Conclusions: Recent research findings suggest that screening can reveal individuals who are vulnerable to alcohol relapse and targeted intervention can prevent their relapse to alcohol. Based on existing addiction treatments (e.g., relapse prevention plan construction), randomized clinical trials tailored to post-OLT patients should be conducted to improve their survival and quality of life. C1 [Rustad, James K.] Univ S Florida, Morsani Coll Med, Dept Psychiat & Behav Neurosci, Tampa, FL USA. [Stern, Theodore A.] Harvard Univ, Sch Med, Dept Psychiat, Massachusetts Gen Hosp, Boston, MA 02115 USA. [Prabhakar, Maithri] Florida Int Univ, Robert Stempel Coll Publ Hlth & Social Work, Dept Epidemiol, Miami, FL 33199 USA. [Musselman, Dominique] Univ Miami, Leonard H Miller Sch Med, Dept Psychiat & Behav Sci, Miami, FL USA. RP Rustad, JK (reprint author), 3515 E Fletcher Ave, Tampa, FL 33613 USA. EM jkrustad@health.usf.edu NR 70 TC 5 Z9 5 U1 0 U2 7 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0033-3182 J9 PSYCHOSOMATICS JI Psychosomatics PD JAN-FEB PY 2015 VL 56 IS 1 BP 21 EP 35 PG 15 WC Psychiatry; Psychology SC Psychiatry; Psychology GA AZ9CY UT WOS:000348510300003 PM 25619671 ER PT J AU Penzkofer, T Tuncali, K Fedorov, A Song, SE Tokuda, J Fennessy, FM Vangel, MG Kibel, AS Mulkern, RV Wells, WM Hata, N Tempany, CMC AF Penzkofer, Tobias Tuncali, Kemal Fedorov, Andriy Song, Sang-Eun Tokuda, Junichi Fennessy, Fiona M. Vangel, Mark G. Kibel, Adam S. Mulkern, Robert V. Wells, William M. Hata, Nobuhiko Tempany, Clare M. C. TI Transperineal In-Bore 3-T MR Imaging-guided Prostate Biopsy: A Prospective Clinical Observational Study SO RADIOLOGY LA English DT Article ID TRANSRECTAL ULTRASOUND BIOPSY; CANCER-DETECTION; RADICAL PROSTATECTOMY; FUSION; REGISTRATION; FEASIBILITY; VALIDATION; SOFTWARE; SYSTEM; FUTURE AB Purpose: To determine the detection rate, clinical relevance, Gleason grade, and location of prostate cancer (PCa) diagnosed with and the safety of an in-bore transperineal 3-T magnetic resonance (MR) imaging-guided prostate biopsy in a clinically heterogeneous patient population. Materials and Methods: This prospective retrospectively analyzed study was HIPAA compliant and institutional review board approved, and informed consent was obtained. Eighty-seven men (mean age, 66.2 years +/- 6.9) underwent multiparametric endorectal prostate MR imaging at 3 T and transperineal MR imaging-guided biopsy. Three subgroups of patients with at least one lesion suspicious for cancer were included: men with no prior PCa diagnosis, men with PCa who were undergoing active surveillance, and men with treated PCa and suspected recurrence. Exclusion criteria were prior prostatectomy and/or contraindication to 3-T MR imaging. The transperineal MR imaging-guided biopsy was performed in a 70-cm wide-bore 3-T device. Overall patient biopsy outcomes, cancer detection rates, Gleason grade, and location for each subgroup were evaluated and statistically compared by using x(2) and one-way analysis of variance followed by Tukey honestly significant difference post hoc comparisons. Results: Ninety biopsy procedures were performed with no serious adverse events, with a mean of 3.7 targets sampled per gland. Cancer was detected in 51 (56.7%) men: 48.1% (25 of 52) with no prior PCa, 61.5% (eight of 13) under active surveillance, and 72.0% (18 of 25) in whom recurrence was suspected. Gleason pattern 4 or higher was diagnosed in 78.1% (25 of 32) in the no prior PCa and active surveillance groups. Gleason scores were not assigned in the suspected recurrence group. MR targets located in the anterior prostate had the highest cancer yield (40 of 64, 62.5%) compared with those for the other parts of the prostate (P < .001). Conclusion: In-bore 3-T transperineal MR imaging-guided biopsy, with a mean of 3.7 targets per gland, allowed detection of many clinically relevant cancers, many of which were located anteriorly. (C) RSNA, 2014 C1 [Penzkofer, Tobias; Tuncali, Kemal; Fedorov, Andriy; Song, Sang-Eun; Tokuda, Junichi; Fennessy, Fiona M.; Mulkern, Robert V.; Wells, William M.; Hata, Nobuhiko; Tempany, Clare M. C.] Brigham & Womens Hosp, Dept Radiol, Div MRI, Boston, MA 02115 USA. [Kibel, Adam S.] Brigham & Womens Hosp, Div Urol, Boston, MA 02115 USA. [Penzkofer, Tobias] RWTH Aachen Univ Hosp, Dept Diagnost & Intervent Radiol, Aachen, Germany. [Vangel, Mark G.] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. [Fennessy, Fiona M.] Dana Farber Canc Inst, Dept Radiol, Boston, MA 02115 USA. [Mulkern, Robert V.] Childrens Hosp, Dept Radiol, Boston, MA 02115 USA. RP Tempany, CMC (reprint author), Brigham & Womens Hosp, Dept Radiol, Div MRI, 75 Francis St, Boston, MA 02115 USA. EM ctempanyafdhal@partners.org OI Fedorov, Andrey/0000-0003-4806-9413 FU National Institutes of Health [R01CA111288, P41RR019703, P41EB015898, P01CA067165, U01CA151261, U54EB005149] FX This research was supported by the National Institutes of Health (grants R01CA111288, P41RR019703, P41EB015898, P01CA067165, U01CA151261, and U54EB005149). NR 49 TC 18 Z9 18 U1 0 U2 5 PU RADIOLOGICAL SOC NORTH AMERICA PI OAK BROOK PA 820 JORIE BLVD, OAK BROOK, IL 60523 USA SN 0033-8419 J9 RADIOLOGY JI Radiology PD JAN PY 2015 VL 274 IS 1 BP 170 EP 180 DI 10.1148/radiol.14140221 PG 11 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA CA1WK UT WOS:000348699400021 PM 25222067 ER PT J AU Ginat, DT Moonis, G AF Ginat, Daniel Thomas Moonis, Gul TI CASE 217 SO RADIOLOGY LA English DT Article AB History A 15-year-old boy presented to the emergency department with intractable epistaxis. He had a prior history of epistaxis typically lasting 5-10 minutes and consisting of up to four episodes per year for several years. Otherwise, the patient had no relevant medical history, and he denied having prior trauma, surgery, bleeding diathesis, fever, chills, or vision changes. Likewise, the patient had no relevant family history. The patient's coagulation panel was unremarkable and included a prothrombin time of 15.4 seconds, an international normalized ratio of 1.2, and a partial thromboplastin time of 29.3 seconds. A thin-section unenhanced sinus computed tomography (CT) examination was performed (Fig 1). In addition, magnetic resonance (MR) imaging of the sinuses without and with intravenous contrast material was performed (Fig 2). The epistaxis was treated with nasal packing, which prevented further bleeding. Biopsy of the lesion was subsequently performed. C1 [Ginat, Daniel Thomas] Univ Chicago, Dept Radiol, Chicago, IL 60637 USA. [Moonis, Gul] Beth Israel Deaconess Med Ctr, Dept Radiol, Boston, MA 02215 USA. [Moonis, Gul] Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. RP Ginat, DT (reprint author), Univ Chicago, Dept Radiol, 5841 S Maryland Ave, Chicago, IL 60637 USA. EM ginatd01@gmail.com NR 0 TC 0 Z9 0 U1 0 U2 0 PU RADIOLOGICAL SOC NORTH AMERICA PI OAK BROOK PA 820 JORIE BLVD, OAK BROOK, IL 60523 USA SN 0033-8419 J9 RADIOLOGY JI Radiology PD JAN PY 2015 VL 274 IS 1 BP 296 EP 297 DI 10.1148/radiol.14131965 PG 2 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA CA1WK UT WOS:000348699400034 PM 25531482 ER PT J AU Ng, MC Gaspard, N Cole, AJ Hoch, DB Cash, SS Bianchi, M O'Rourke, DA Rosenthal, ES Chu, CJ Westover, MB AF Ng, Marcus C. Gaspard, Nicolas Cole, Andrew J. Hoch, Daniel B. Cash, Sydney S. Bianchi, Matt O'Rourke, Deirdre A. Rosenthal, Eric S. Chu, Catherine J. Westover, M. Brandon TI The standardization debate: A conflation trap in critical care electroencephalography SO SEIZURE-EUROPEAN JOURNAL OF EPILEPSY LA English DT Review DE Electroencephalography Critical care; Intensive care; Long-term monitoring; Standardization; Nomenclature ID NONCONVULSIVE STATUS EPILEPTICUS; TRIPHASIC WAVES; EEG PATTERNS; THERAPEUTIC HYPOTHERMIA; SEIZURES DAMAGE; CARDIAC-ARREST; ILL; TERMINOLOGY; BRAIN; ENCEPHALOPATHY AB Purpose: Persistent uncertainty over the clinical significance of various pathological continuous electroencephalography (cEEG) findings in the intensive care unit (ICU) has prompted efforts to standardize ICU cEEG terminology and an ensuing debate. We set out to understand the reasons for, and a satisfactory resolution to, this debate. Method: We review the positions for and against standardization, and examine their deeper philosophical basis. Results: We find that the positions for and against standardization are not fundamentally irreconcilable. Rather, both positions stem from conflating the three cardinal steps in the classic approach to EEG, which we term "description", "interpretation", and "prescription". Using real-world examples we show how this conflation yields muddled clinical reasoning and unproductive debate among electroencephalographers that is translated into confusion among treating clinicians. We propose a middle way that judiciously uses both standardized terminology and clinical reasoning to disentangle these critical steps and apply them in proper sequence. Conclusion: The systematic approach to ICU cEEG findings presented herein not only resolves the standardization debate but also clarifies clinical reasoning by helping electroencephalographers assign appropriate weights to cEEG findings in the face of uncertainty. (C) 2014 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved. C1 [Ng, Marcus C.] Univ Manitoba, Dept Internal Med, Hlth Sci Ctr, Neurol Sect, Winnipeg, MB, Canada. [Gaspard, Nicolas] Yale Univ, Sch Med, Dept Neurol, Comprehens Epilepsy Ctr, New Haven, CT 06510 USA. [Cole, Andrew J.; Hoch, Daniel B.; Cash, Sydney S.; Bianchi, Matt; O'Rourke, Deirdre A.; Rosenthal, Eric S.; Chu, Catherine J.; Westover, M. Brandon] Harvard Univ, Sch Med, Dept Neurol, Epilepsy Serv,Massachusetts Gen Hosp, Boston, MA 02115 USA. RP Westover, MB (reprint author), Massachusetts Gen Hosp, 55 Fruit St, Boston, MA 02114 USA. EM mng2@hsc.mb.ca; nicolas.gaspard@yale.edu; ajcole1@mgh.harvard.edu; dhoch@mgh.harvard.edu; scash@mgh.harvard.edu; mtbianchi@mgh.harvard.edu; daorourke@mgh.harvard.edu; erosenthal@mgh.harvard.edu; cjchu@mgh.harvard.edu; mwestover@mgh.harvard.edu OI Rosenthal, Eric/0000-0003-3900-356X FU NINDS NIH HHS [K12 NS066225] NR 33 TC 1 Z9 1 U1 1 U2 3 PU W B SAUNDERS CO LTD PI LONDON PA 32 JAMESTOWN RD, LONDON NW1 7BY, ENGLAND SN 1059-1311 EI 1532-2688 J9 SEIZURE-EUR J EPILEP JI Seizure PD JAN PY 2015 VL 24 BP 52 EP 58 DI 10.1016/j.seizure.2014.09.017 PG 7 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA CA5OK UT WOS:000348957500010 PM 25457454 ER PT J AU Tsai, AC Pierce, CM Papachristos, AV AF Tsai, Alexander C. Pierce, Chester M. Papachristos, Andrew V. TI From social networks to health: Durkheim after the turn of the millennium Introduction SO SOCIAL SCIENCE & MEDICINE LA English DT Editorial Material ID INTEGRATION; MORTALITY; SPREAD; TIES; INTERVENTIONS; EPIDEMIOLOGY; ADOLESCENTS; CONTAGION; BEHAVIOR; SUPPORT C1 [Tsai, Alexander C.] Massachusetts Gen Hosp, Ctr Global Hlth, Boston, MA 02114 USA. [Pierce, Chester M.] Massachusetts Gen Hosp, Div Global Psychiat, Boston, MA 02114 USA. [Pierce, Chester M.] Harvard Univ, Sch Med, Boston, MA USA. [Pierce, Chester M.] Mbarara Univ Sci & Technol, Mbarara, Uganda. [Papachristos, Andrew V.] Yale Univ, Dept Sociol, New Haven, CT USA. RP Tsai, AC (reprint author), Massachusetts Gen Hosp, Ctr Global Hlth, 100 Cambridge St,15th Floor, Boston, MA 02114 USA. EM actsai@partners.org OI Tsai, Alexander/0000-0001-6397-7917 FU NIMH NIH HHS [K23 MH096620] NR 70 TC 4 Z9 4 U1 9 U2 28 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0277-9536 J9 SOC SCI MED JI Soc. Sci. Med. PD JAN PY 2015 VL 125 SI SI BP 1 EP 7 DI 10.1016/j.socscimed.2014.10.045 PG 7 WC Public, Environmental & Occupational Health; Social Sciences, Biomedical SC Public, Environmental & Occupational Health; Biomedical Social Sciences GA CA5LI UT WOS:000348949500001 PM 25695107 ER PT J AU Pachucki, MC Ozer, EJ Barrat, A Cattuto, C AF Pachucki, Mark C. Ozer, Emily J. Barrat, Alain Cattuto, Ciro TI Mental health and social networks in early adolescence: A dynamic study of objectively-measured social interaction behaviors SO SOCIAL SCIENCE & MEDICINE LA English DT Article DE Social networks; Self-esteem; Depression; Early adolescence; Stochastic actor-based modeling ID DEPRESSIVE SYMPTOMS; FRIENDSHIP NETWORKS; SELF-ESTEEM; PEER CONTAGION; AMERICAN ADOLESCENTS; PHYSICAL-ACTIVITY; SCHOOL; MECHANISMS; SOCIALIZATION; EXPERIENCE AB How are social interaction dynamics associated with mental health during early stages of adolescence? The goal of this study is to objectively measure social interactions and evaluate the roles that multiple aspects of the social environment such as physical activity and food choice may jointly play in shaping the structure of children's relationships and their mental health. The data in this study are drawn from a longitudinal network-behavior study conducted in 2012 at a private K-8 school in an urban setting in California. We recruited a highly complete network sample of sixth-graders (n = 40, 91% of grade, mean age = 12.3), and examined how two measures of distressed mental health (self-esteem and depressive symptoms) are positionally distributed in an early adolescent interaction network. We ascertained how distressed mental health shapes the structure of relationships over a three-month period, adjusting for relevant dimensions of the social environment. Cross-sectional analyses of interaction networks revealed that self-esteem and depressive symptoms are differentially stratified by gender. Specifically, girls with more depressive symptoms have interactions consistent with social inhibition, while boys' interactions suggest robustness to depressive symptoms. Girls higher in self-esteem tended towards greater sociability. Longitudinal network behavior models indicate that gender similarity and perceived popularity are influential in the formation of social ties. Greater school connectedness predicts the development of self-esteem, though social ties contribute to more self-esteem improvement among students who identify as European-American. Cross-sectional evidence shows associations between distressed mental health and students' network peers. However, there is no evidence that connected students' mental health status becomes more similar in their over time because of their network interactions. These findings suggest that mental health during early adolescence may be less subject to mechanisms of social influence than network research in even slightly older adolescents currently indicates. (C) 2014 Published by Elsevier Ltd. C1 [Pachucki, Mark C.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Gen Acad Pediat Massachusetts Gen Hosp Children,M, Boston, MA 02114 USA. [Ozer, Emily J.] Univ Calif Berkeley, Sch Publ Hlth, Dept Community Hlth & Human Dev, Berkeley, CA 94720 USA. [Barrat, Alain] Aix Marseille Univ, Univ Toulon, CNRS, CPT,UMR 7332, F-13288 Marseille, France. [Barrat, Alain; Cattuto, Ciro] ISI Fdn, Data Sci Lab, Turin, Italy. RP Pachucki, MC (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Gen Acad Pediat Massachusetts Gen Hosp Children,M, 50 Staniford St,9th Floor, Boston, MA 02114 USA. EM mpachucki@mgh.harvard.org RI Cattuto, Ciro/K-6133-2016 OI Cattuto, Ciro/0000-0001-9526-4364 FU Robert Wood Johnson Foundation (RWJF) Health & Society Scholars program; RWJF pilot grant FX This work was conducted while MCP was in the Robert Wood Johnson Foundation (RWJF) Health & Society Scholars program, and the project benefited from an RWJF pilot grant. There are no reported conflicts of interest. The Committee on Human Subjects at UC Berkeley approved the original study protocol. NR 73 TC 7 Z9 7 U1 4 U2 32 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0277-9536 J9 SOC SCI MED JI Soc. Sci. Med. PD JAN PY 2015 VL 125 SI SI BP 40 EP 50 DI 10.1016/j.socscimed.2014.04.015 PG 11 WC Public, Environmental & Occupational Health; Social Sciences, Biomedical SC Public, Environmental & Occupational Health; Biomedical Social Sciences GA CA5LI UT WOS:000348949500005 PM 24797692 ER PT J AU Dzik, S Murphy, MF AF Dzik, Sunny Murphy, Michael F. TI Clinical Guidelines in Transfusion Medicine SO TRANSFUSION MEDICINE REVIEWS LA English DT Editorial Material C1 [Dzik, Sunny] J 224 Massachusetts Gen Hosp 55, Blood Transfus Serv, Boston, MA 02114 USA. RP Dzik, S (reprint author), J 224 Massachusetts Gen Hosp 55, Blood Transfus Serv, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0887-7963 EI 1532-9496 J9 TRANSFUS MED REV JI Transf. Med. Rev. PD JAN PY 2015 VL 29 IS 1 BP 1 EP 2 DI 10.1016/j.tmrv.2014.11.005 PG 2 WC Hematology SC Hematology GA CA5TV UT WOS:000348971600001 PM 25542643 ER PT J AU Israeli, M Pollack, MS Shaut, CAE Halpin, A DiPaola, NR Youngs, D Saidman, SL AF Israeli, Moshe Pollack, Marilyn S. Shaut, Carley A. E. Halpin, Anne DiPaola, Nicholas R. Youngs, Danny Saidman, Susan L. CA ASHI Proficiency Testing Program TI Concordance and discordance in anti-HLA antibody testing SO TRANSPLANT IMMUNOLOGY LA English DT Article DE Antibodies; ASHI; Consensus; HLA; Proficiency testing; Luminex ID HUMAN-LEUKOCYTE ANTIGEN; DONOR-SPECIFIC ANTIBODIES; KIDNEY-TRANSPLANTATION; CLINICAL-RELEVANCE; HEART-TRANSPLANTATION; MEDIATED REJECTION; GRAFT LOSS; ASSAY; LUMINEX(R) AB Background: Correct identification of the specificity of antibodies directed against HLA using single antigen Luminex beads (SALB) is essential in current HLA laboratory practice for transplantation. The aim of this study was to investigate the magnitude of concordance and discordance among laboratories in testing for anti-HLA antibodies using SALB. Method: 35 sera were distributed by the ASHI Proficiency Testing Program to HLA laboratories worldwide. We analyzed 4335 test results submitted between April 2010 and April 2013 by participating laboratories. Results: SALB was used by approximately 94% of the participating laboratories, yet concordant assignment of antibody specificity was imperfect. For each serum, the assignment of an average of 10 antibody specificities was discordant. Disagreement was observed for antibodies directed against common as well as uncommon antigens. The assignment of an average of 15 antibody specificities in each "positive" serum appeared to be influenced by vendor-dependent causes. Inter-vendor concordance was lower than intra-vendor concordance, indicating that vendor dependent factors may be a central cause for disagreement. Conclusions: Our study illustrates the prevalence of concordance and discordance, also affected by unpremeditated causes, in reporting SALB antibody results. Insufficient concordance and standardization in antibody testing may have practical implications for organ allocation and organ sharing programs. (C) 2014 Elsevier B.V. All rights reserved. C1 [Israeli, Moshe] Rabin Med Ctr, Tissue Typing Lab, IL-49100 Petah Tiqwa, Israel. [Israeli, Moshe] Leiden Univ, Med Ctr, Dept lmmunohematol & Blood Transfus, Leiden, Netherlands. [Pollack, Marilyn S.] Univ Texas Hlth Sci Ctr San Antonio, Dept Pathol, San Antonio, TX 78229 USA. [Shaut, Carley A. E.] Oregon Hlth & Sci Univ, Sch Med, Portland, OR 97239 USA. [Halpin, Anne] Univ Alberta Hosp, Histocompatibil Lab, Edmonton, AB T6G 2B7, Canada. [DiPaola, Nicholas R.] Ohio State Univ, Wexner Med Ctr, Clin Histocompatibil Lab, Columbus, OH 43210 USA. [Youngs, Danny] Puget Sound Blood Ctr, Seattle, WA 98104 USA. [Saidman, Susan L.] Massachusetts Gen Hosp, Histocompatibil Lab, Boston, MA 02114 USA. RP Israeli, M (reprint author), Leiden Univ, Med Ctr, Dept lmmunohematol & Blood Transfus, Leiden, Netherlands. EM israelimoshe@yahoo.com OI Israeli, Moshe/0000-0002-3776-8692 NR 34 TC 1 Z9 1 U1 0 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0966-3274 EI 2210-3384 J9 TRANSPL IMMUNOL JI Transpl. Immunol. PD JAN PY 2015 VL 32 IS 1 BP 1 EP 8 DI 10.1016/j.trim.2014.10.003 PG 8 WC Immunology; Transplantation SC Immunology; Transplantation GA CA4RT UT WOS:000348892900001 PM 25460810 ER PT J AU Chait, SR Thompson, JK Jacobsen, PB AF Chait, Sari R. Thompson, J. Kevin Jacobsen, Paul B. TI Preliminary development and evaluation of an appearance-based dissonance induction intervention for reducing UV exposure SO BODY IMAGE LA English DT Article DE Appearance-based tanning interventions; Cognitive dissonance; Tanning; UV exposure; Skin cancer ID EATING-DISORDER PREVENTION; RANDOMIZED EFFICACY TRIAL; SUN PROTECTION; YOUNG-WOMEN; MOTIVATION; PROGRAMS; VALIDITY AB The current study examined the feasibility of an appearance-based dissonance induction approach for the modification of tanning and sunscreen use behaviors. Undergraduate female students were randomized to: a healthy lifestyle condition, an appearance-based dissonance condition, or an appearance-based psychoeducation condition. Reports of tanning and sunscreen use were collected immediately before and 1 month following intervention (N=225). Relative to the healthy lifestyle condition, participants in the dissonance condition reported a significant reduction in daily hours spent tanning. Additionally, sunscreen use on the body decreased significantly for the healthy lifestyle group, but did not change for the dissonance group. The psychoeducation condition did not differ from the healthy lifestyle condition on any measure. These findings should encourage additional research into the use of dissonance induction as an appearance-based strategy for promoting reductions in UV exposure. (C) 2014 Elsevier Ltd. All rights reserved. C1 [Chait, Sari R.] VA Boston Healthcare Syst, Boston, MA USA. [Chait, Sari R.] Boston Univ, Sch Med, Boston, MA 02118 USA. [Thompson, J. Kevin] Univ S Florida, Dept Psychol, Tampa, FL 33620 USA. [Jacobsen, Paul B.] Univ S Florida, Moffitt Canc Ctr, Tampa, FL USA. [Jacobsen, Paul B.] Univ S Florida, Dept Psychol, Tampa, FL 33620 USA. RP Thompson, JK (reprint author), Univ S Florida, Dept Psychol, Tampa, FL 33620 USA. EM JKThompson@usf.edu NR 26 TC 1 Z9 1 U1 1 U2 6 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1740-1445 EI 1873-6807 J9 BODY IMAGE JI Body Image PD JAN PY 2015 VL 12 BP 68 EP 72 DI 10.1016/j.bodyim.2014.09.004 PG 5 WC Psychology, Clinical; Psychiatry; Psychology, Multidisciplinary SC Psychology; Psychiatry GA CA5NG UT WOS:000348954500009 PM 25462883 ER PT J AU Zheng, BH Zhu, SY Wu, X AF Zheng, Baohui Zhu, Shunying Wu, Xu TI Clickable Analogue of Cerulenin as Chemical Probe to Explore Protein Palmitoylation SO ACS CHEMICAL BIOLOGY LA English DT Article ID MAMMALIAN-CELLS; ACYLTRANSFERASES; 2-BROMOPALMITATE; IDENTIFICATION; TRAFFICKING; STABILITY; CANCER; YEAST AB Dynamic palmitoylation is an important post-translational modification regulating protein localization, trafficking, and signaling activities. The Asp-His-His-Cys (DHHC) domain containing enzymes are evolutionarily conserved palmitoyl acyltransferases (PATs) mediating diverse protein S-palmitoylation. Cerulenin is a natural product inhibitor of fatty acid biosynthesis and protein palmitoylation, through irreversible alkylation of the cysteine residues in the enzymes. Here, we report the synthesis and characterization of a clickable and long alkyl chain analogue of cerulenin as a chemical probe to investigate its cellular targets and to label and profile PATs in vitro and in live cells. Our results showed that the probe could stably label the DHHC-family PATs and enable mass spectrometry studies of PATs and other target proteins in the cellular proteome. Such probe provides a new chemical tool to dissect the functions of palmitoylating enzymes in cell signaling and diseases and reveals new cellular targets of the natural product cerulenin. C1 [Zheng, Baohui; Zhu, Shunying; Wu, Xu] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Cutaneous Biol Res Ctr, Charlestown, MA 02129 USA. RP Wu, X (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Cutaneous Biol Res Ctr, Bldg 149,13th St, Charlestown, MA 02129 USA. EM xwu@cbrc2.mgh.harvard.edu RI zheng, baohui/O-6828-2014 OI zheng, baohui/0000-0002-3272-843X FU Stewart Rahr-MRA (Melanoma Research Alliance) Young Investigator Award; Department of Defense (DoD) Career Development Award [W81XWH-13-1-0203]; MGH Institutional fund FX This work is supported by Stewart Rahr-MRA (Melanoma Research Alliance) Young Investigator Award, Department of Defense (DoD) Career Development Award (W81XWH-13-1-0203) and MGH Institutional fund (to X. W.). We thank Drs. M. DeRan, Q. Wu, and M. Fukata for reagents and discussions, and the Taplin Mass Spec Facility at Harvard Medical School for proteomic studies. NR 36 TC 6 Z9 7 U1 1 U2 10 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 1554-8929 EI 1554-8937 J9 ACS CHEM BIOL JI ACS Chem. Biol. PD JAN PY 2015 VL 10 IS 1 BP 115 EP 121 DI 10.1021/cb500758s PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA AZ6LU UT WOS:000348332100011 PM 25322207 ER PT J AU Huang, ZF Tan, L Wang, HY Liu, Y Blais, S Deng, JJ Neubert, TA Gray, NS Li, XK Mohammadi, M AF Huang, Zhifeng Tan, Li Wang, Huiyan Liu, Yang Blais, Steven Deng, Jingjing Neubert, Thomas A. Gray, Nathanael S. Li, Xiaokun Mohammadi, Moosa TI DFG-out Mode of Inhibition by an Irreversible Type-1 Inhibitor Capable of Overcoming Gate-Keeper Mutations in FGF Receptors SO ACS CHEMICAL BIOLOGY LA English DT Article ID GROWTH-FACTOR-RECEPTOR; TYROSINE KINASE DOMAIN; ACTIVATING MUTATIONS; PONATINIB AP24534; MULTIPLE-MYELOMA; BREAST-CANCER; PD173074; DESIGN; IDENTIFICATION; CONFORMATIONS AB Drug-resistance acquisition through kinase gate-keeper mutations is a major hurdle in the clinic. Here, we determined the first crystal structures of the human FGFR4 kinase domain (FGFR4K) alone and complexed with ponatinib, a promiscuous type-2 (DFG-out) kinase inhibitor, and an oncogenic FGFR4K harboring the V550L gate-keeper mutation bound to FIIN-2, a new type-1 irreversible inhibitor. Remarkably, like ponatinib, FIIN-2 also binds in the DFG-out mode despite lacking a functional group necessary to occupy the pocket vacated upon the DFG-out flip. Structural analysis reveals that the covalent bond between FIIN-2 and a cysteine, uniquely present in the glycine-rich loop of FGFR kinases, facilitates the DFG-out conformation, which together with the internal flexibility of FIIN-2 enables FIIN-2 to avoid the steric clash with the gate-keeper mutation that causes the ponatinib resistance. The structural data provide a blueprint for the development of next generation anticancer inhibitors through combining the salient inhibitory mechanisms of ponatinib and FIIN-2. C1 [Huang, Zhifeng; Wang, Huiyan; Li, Xiaokun] Wenzhou Med Univ, Sch Pharm, Wenzhou 325035, Zhejiang, Peoples R China. [Huang, Zhifeng; Wang, Huiyan; Liu, Yang; Neubert, Thomas A.; Mohammadi, Moosa] NYU, Sch Med, Skirball Inst, Dept Biochem & Mol Pharmacol, New York, NY 10016 USA. [Blais, Steven; Deng, Jingjing; Neubert, Thomas A.] NYU, Sch Med, Skirball Inst, Kimmel Ctr Biol & Med, New York, NY 10016 USA. [Tan, Li; Gray, Nathanael S.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA. RP Li, XK (reprint author), Wenzhou Med Univ, Sch Pharm, Wenzhou 325035, Zhejiang, Peoples R China. EM xiaokunli@163.net; moosa.mohammadi@nyumc.org OI Mohammadi, Moosa/0000-0003-2434-9437 FU U.S. National Institutes of Health NIDCR [DE13686, CA130876-05]; DF/HCC Lung Spore Developmental Project [CA016087]; National Institutes of Health [S10RR027990]; Natural Science Foundation of China [31270789, 81102486, 81273421] FX The authors are thankful to R. Goetz and A. Belov for critically reading the manuscript and making thoughtful suggestions. This work was supported by the U.S. National Institutes of Health NIDCR Grant DE13686 (to M.M.), CA130876-05 and DF/HCC Lung Spore Developmental Project (to N.S.G), CA016087 and National Institutes of Health Shared Instrumentation Grant S10RR027990 (to T.A.N.) and grants from Natural Science Foundation of China 31270789, 81102486, and 81273421 (to H.C, Z.H. and H.W.). NR 55 TC 9 Z9 10 U1 0 U2 20 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 1554-8929 EI 1554-8937 J9 ACS CHEM BIOL JI ACS Chem. Biol. PD JAN PY 2015 VL 10 IS 1 BP 299 EP 309 DI 10.1021/cb500674s PG 11 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA AZ6LU UT WOS:000348332100030 PM 25317566 ER PT S AU Khaleghi, M Furlong, C Guignard, J Dobrev, I Cheng, JT Rosowski, JJ AF Khaleghi, Morteza Furlong, Cosme Guignard, Jeremie Dobrev, Ivo Cheng, Jeffrey Tao Rosowski, John J. BE Jin, H Sciammarella, C Yoshida, S Lamberti, L TI Multiplexed Holography for Single-Shot Three-Dimensional Shape and Displacement Measurements SO ADVANCEMENT OF OPTICAL METHODS IN EXPERIMENTAL MECHANICS, VOL 3 SE Conference Proceedings of the Society for Experimental Mechanics Series LA English DT Proceedings Paper CT SEM Annual Conference and Exposition on Experimental and Applied Mechanics CY JUN 02-05, 2014 CL Greenville, SC SP Soc Expt Mech DE 3D Displacement measurements; Digital holography; Image registration; Multiplexed hologram; Tympanic membrane AB Holographic interferometric methods for measuring 3D displacement fields require at least three individual sensitivity vectors. Methods based on multiple directions of illumination have limited application when studying transient phenomena, including, but not limited to, measurements of biological tissues that have temporally-varying responses, such as the eardrum or Tympanic Membrane (TM). Therefore, to measure 3D displacements in such applications, all the measurements have to be done concomitantly. In this paper, we propose a new multiple illumination direction approach to measure 3D displacements from a single-shot hologram that contains displacement information from three sensitivity vectors. In our approach, the hologram of an object of interest is recorded with three simultaneous incoherently-superimposed pairs of reference and object beams, such that the modulation image corresponding to each illumination direction is reconstructed at a particular position on the image. Incoherent superposition of the beams is implemented by using three different laser diodes. Because of the differences in the position of each reference beam and wavelength of each pair of beams, the reconstruction distance and magnification of each sensitivity vector are different. We, therefore, developed and implemented a registration algorithm to accurately translate individual views into a single global coordinate system. Representative results will include measurements of shape and sound-induced 3D displacements of the TM. C1 [Khaleghi, Morteza; Furlong, Cosme; Dobrev, Ivo] Worcester Polytech Inst, Ctr Holograph Studies & Laser MicromechaTron CHS, Dept Mech Engn, Worcester, MA 01609 USA. [Furlong, Cosme; Guignard, Jeremie; Cheng, Jeffrey Tao; Rosowski, John J.] Massachusetts Eye & Ear Infirm, Eaton Peabody Lab, Boston, MA 02114 USA. [Furlong, Cosme; Guignard, Jeremie; Cheng, Jeffrey Tao; Rosowski, John J.] Harvard Med Sch, Dept Otol & Laryngol, Boston, MA 02114 USA. RP Khaleghi, M (reprint author), Worcester Polytech Inst, Ctr Holograph Studies & Laser MicromechaTron CHS, Dept Mech Engn, Worcester, MA 01609 USA. EM mkm@wpi.edu NR 8 TC 0 Z9 0 U1 0 U2 6 PU SPRINGER-VERLAG BERLIN PI BERLIN PA HEIDELBERGER PLATZ 3, D-14197 BERLIN, GERMANY SN 2191-5644 BN 978-3-319-06985-2 J9 C PROC SOC EXP MECH PY 2015 BP 103 EP 108 DI 10.1007/978-3-319-06986-9_10 PG 6 WC Optics; Physics, Applied SC Optics; Physics GA BB8XF UT WOS:000347773500010 ER PT S AU Dobrev, I Furlong, C Rosowski, JJ Cheng, JT AF Dobrev, I. Furlong, C. Rosowski, J. J. Cheng, J. T. BE Jin, H Sciammarella, C Yoshida, S Lamberti, L TI High-Speed Digital Holography for Transient Response of the Human Tympanic Membrane SO ADVANCEMENT OF OPTICAL METHODS IN EXPERIMENTAL MECHANICS, VOL 3 SE Conference Proceedings of the Society for Experimental Mechanics Series LA English DT Proceedings Paper CT SEM Annual Conference and Exposition on Experimental and Applied Mechanics CY JUN 02-05, 2014 CL Greenville, SC SP Soc Expt Mech DE Acoustic-solid interaction; Digital holography; High-speed cameras; Local phase correlation; Otology ID MIDDLE-EAR; EMISSIONS; SURFACE; MOTION AB The tympanic membrane (TM; eardrum) transforms sound energy from the ear canal into mechanical vibrations of the ossicles (middle-ear bones), whence energy enters the inner ear and stimulates auditory hair cells for hearing. Our past efforts toward understanding of the energy transformation within the middle-ear has been focused on the TM's response to single tones. In this paper, we report results of the development of high-speed holographic capabilities to measure the transient characteristics of the TM. We have developed a high-speed holographic system (HHS) that incorporates a transient (i.e., >40 kHz) acquisition method to quantify the displacements on the TM surface excited by sharp (i.e., <50 mu s) acoustic clicks. The performance of the HHS is compared with Laser-Doppler Vibrometery (LDV) measurements on both artificial membrane and human cadaveric TM. The instantaneous response of > 100 k data points on the TM surface measured by the HHS can be used to quantify spatially-dependent motion parameters such as modal frequencies, mode shapes, time constants, and acoustic delays. In addition, the local material properties across the surface of the TM can be inferred. C1 [Dobrev, I.; Furlong, C.] Ctr Holog Studies & Laser MicromechaTron CHSLT, 100 Inst Rd, Worcester, MA 01609 USA. [Dobrev, I.; Furlong, C.] Wrocester Polytech Inst, Dept Mech Engn, Worcester, MA 01609 USA. [Furlong, C.; Rosowski, J. J.; Cheng, J. T.] Massachusetts Eye & Ear Infirm, Eaton Peabody Lab, Boston, MA 02114 USA. [Furlong, C.; Rosowski, J. J.; Cheng, J. T.] Harvard Med Sch, Dept Otol & Laryngol, Boston, MA 02114 USA. RP Dobrev, I (reprint author), Ctr Holog Studies & Laser MicromechaTron CHSLT, 100 Inst Rd, Worcester, MA 01609 USA. EM ivo_d@wpi.edu FU National Institute on Deafness and Other Communication Disorders ( NIDCD); National Institute of Health ( NIH); Massachusetts Eye and Ear Infirmary ( MEEI); Mittal Fund FX This work has been funded by the National Institute on Deafness and Other Communication Disorders ( NIDCD), the National Institute of Health ( NIH), the Massachusetts Eye and Ear Infirmary ( MEEI), and the Mittal Fund. The authors should like to acknowledge the help of Michael Ravicz at the Eaton- Peabody Laboratory ( EPL) of the Massachusetts Eye and Ear Infirmary ( MEEI), Ellery Harrington and Morteza Khaleghi at the Center for Holographic Studies and Laser micro- mechaTronics ( CHSLT) at Worcester Polytechnic Institute. NR 13 TC 1 Z9 1 U1 0 U2 3 PU SPRINGER-VERLAG BERLIN PI BERLIN PA HEIDELBERGER PLATZ 3, D-14197 BERLIN, GERMANY SN 2191-5644 BN 978-3-319-06985-2 J9 C PROC SOC EXP MECH PY 2015 BP 337 EP 342 DI 10.1007/978-3-319-06986-9_39 PG 6 WC Optics; Physics, Applied SC Optics; Physics GA BB8XF UT WOS:000347773500039 ER PT J AU Klunk, WE Koeppe, RA Price, JC Benzinger, TL Devous, MD Jagust, WJ Johnson, KA Mathis, CA Minhas, D Pontecorvo, MJ Rowe, CC Skovronsky, DM Mintun, MA AF Klunk, William E. Koeppe, Robert A. Price, Julie C. Benzinger, Tammie L. Devous, Michael D., Sr. Jagust, William J. Johnson, Keith A. Mathis, Chester A. Minhas, Davneet Pontecorvo, Michael J. Rowe, Christopher C. Skovronsky, Daniel M. Mintun, Mark A. TI The Centiloid Project: Standardizing quantitative amyloid plaque estimation by PET SO ALZHEIMERS & DEMENTIA LA English DT Article DE Amyloid imaging; Positron emission tomography; Pittsburgh compound B; Centiloid scale; Standardize ID PITTSBURGH COMPOUND-B; ALZHEIMERS-DISEASE; COGNITIVE IMPAIRMENT; TAU PATHOLOGY; BETA; DEPOSITION; DEMENTIA; BRAIN; SEGMENTATION; MULTICENTER AB Although amyloid imaging with PiB-PET ([C-11]Pittsburgh Compound-B positron emission tomography), and now with F-18-labeled tracers, has produced remarkably consistent qualitative findings across a large number of centers, there has been considerable variability in the exact numbers reported as quantitative outcome measures of tracer retention. In some cases this is as trivial as the choice of units, in some cases it is scanner dependent, and of course, different tracers yield different numbers. Our working group was formed to standardize quantitative amyloid imaging measures by scaling the outcome of each particular analysis method or tracer to a 0 to 100 scale, anchored by young controls (<= 45 years) and typical Alzheimer's disease patients. The units of this scale have been named "Centiloids." Basically, we describe a "standard" method of analyzing PiB PET data and then a method for scaling any "nonstandard" method of PIE PET analysis (or any other tracer) to the Centiloid scale. (C) 2015 The Alzheimer's Association. Published by Elsevier Inc. All rights reserved. C1 [Klunk, William E.] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. [Klunk, William E.] Univ Pittsburgh, Dept Neurol, Pittsburgh, PA 15260 USA. [Koeppe, Robert A.] Univ Michigan, Dept Radiol, Ann Arbor, MI 48109 USA. [Price, Julie C.; Minhas, Davneet] Univ Pittsburgh, Dept Radiol, Pittsburgh, PA 15260 USA. [Benzinger, Tammie L.; Johnson, Keith A.] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. [Benzinger, Tammie L.] Washington Univ, Dept Neurosurg, St Louis, MO USA. [Devous, Michael D., Sr.] UT Southwestern Med Ctr Dallas, Dept Neurol, Dallas, TX USA. [Devous, Michael D., Sr.] UT Southwestern Med Ctr Dallas, Dept Radiol, Dallas, TX USA. [Jagust, William J.] Univ Calif Berkeley, Helen Wills Neurosci Inst, Berkeley, CA 94720 USA. [Johnson, Keith A.] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. [Mathis, Chester A.] Univ Pittsburgh, Dept Radiol, Dept Pharmacol & Biol Chem, Pittsburgh, PA 15260 USA. [Mathis, Chester A.] Univ Pittsburgh, Dept Pharmaceut Sci, Pittsburgh, PA 15260 USA. [Pontecorvo, Michael J.; Skovronsky, Daniel M.; Mintun, Mark A.] Avid Radiopharmaceut, Philadelphia, PA USA. [Rowe, Christopher C.] Austin Hlth, Dept Nucl Med, Melbourne, Vic, Australia. [Rowe, Christopher C.] Austin Hlth, Ctr PET, Melbourne, Vic, Australia. RP Klunk, WE (reprint author), Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. EM klunkwe@upmc.edu FU National Institute on Aging [R37 AG025516, P01 AG025204, P50 AG005133, R01 AG034570, P01 A0026276, U19 AG032438] FX This work was supported in-part by grants from the National Institute on Aging: R37 AG025516 (WEK), P01 AG025204 (WEK), P50 AG005133 (WEK), R01 AG034570 (WJ), P01 A0026276 (TB), and U19 AG032438 (TB). We would like to thank Marybeth Howlett for her organizational and administrative support. NR 38 TC 37 Z9 38 U1 4 U2 11 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1552-5260 EI 1552-5279 J9 ALZHEIMERS DEMENT JI Alzheimers. Dement. PD JAN PY 2015 VL 11 IS 1 BP 1 EP 15 DI 10.1016/j.jalz.2014.07.003 PG 15 WC Clinical Neurology SC Neurosciences & Neurology GA CA0UX UT WOS:000348632800001 PM 25443857 ER PT J AU Albers, MW Gilmore, GC Kaye, J Murphy, C Wingfield, A Bennett, DA Boxer, AL Buchman, AS Cruickshanks, KJ Devanand, DP Duffy, CJ Gall, CM Gates, GA Granholm, AC Hensch, T Holtzer, R Hyman, BT Lin, FR Mc Kee, AC Morris, JC Petersen, RC Silbert, LC Stuble, RG Trojanowski, JQ Verghese, J Wilson, DA Xu, S Zhang, LI AF Albers, Mark W. Gilmore, Grover C. Kaye, Jeffrey Murphy, Claire Wingfield, Arthur Bennett, David A. Boxer, Adam L. Buchman, Aron S. Cruickshanks, Karen J. Devanand, Davangere P. Duffy, Charles J. Gall, Christine M. Gates, George A. Granholm, Ann-Charlotte Hensch, Takao Holtzer, Roee Hyman, Bradley T. Lin, Frank R. Mc Kee, Ann C. Morris, John C. Petersen, Ronald C. Silbert, Lisa C. Stuble, Robert G. Trojanowski, John Q. Verghese, Joe Wilson, Donald A. Xu, Shunbin Zhang, Li I. TI At the interface of sensory and motor dysfunctions and Alzheimer's disease SO ALZHEIMERS & DEMENTIA LA English DT Article DE Sensory; Motor; Olfaction; Vision; Auditory function; Alzheimer's disease; Aging ID MILD COGNITIVE IMPAIRMENT; AMYLOID PRECURSOR PROTEIN; CENTRAL AUDITORY DYSFUNCTION; AGE-RELATED-CHANGES; OPTICAL COHERENCE TOMOGRAPHY; EVENT-RELATED POTENTIALS; NERVE-FIBER LAYER; FRONTOTEMPORAL LOBAR DEGENERATION; TRANSCRANIAL MAGNETIC STIMULATION; POSTERIOR CORTICAL ATROPHY AB Recent evidence indicates that sensory and motor changes may precede the cognitive symptoms of Alzheimer's disease (AD) by several years and may signify increased risk of developing AD. Traditionally, sensory and motor dysfunctions in aging and AD have been studied separately. To ascertain the evidence supporting the relationship between age-related changes in sensory and motor systems and the development of AD and to facilitate communication between several disciplines, the National Institute on Aging held an exploratory workshop titled "Sensory and Motor Dysfunctions in Aging and AD." The scientific sessions of the workshop focused on age-related and neuropathologic changes in the olfactory, visual, auditory, and motor systems, followed by extensive discussion and hypothesis generation related to the possible links. among sensory, cognitive, and motor domains in aging and AD. Based on the data presented and discussed at this workshop, it is clear that sensory and motor regions of the central nervous system are affected by AD pathology and that interventions targeting. amelioration of sensory-motor deficits in AD may enhance patient function as AD progresses. (C) 2015 The Alzheimer's Association. Published by Elsevier Inc. All rights reserved. C1 [Albers, Mark W.; Hyman, Bradley T.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Neurol, Charlestown, MA 02129 USA. [Gilmore, Grover C.] Case Western Reserve Univ, Jack Joseph & Morton Mandel Sch Appl Social Sci, Cleveland, OH 44106 USA. [Kaye, Jeffrey; Silbert, Lisa C.] Oregon Hlth & Sci Univ, Dept Neurol, Portland, OR 97201 USA. [Murphy, Claire] San Diego State Univ, SDSU UCSD Joint Doctoral Program Clin Psychol, San Diego, CA 92182 USA. [Wingfield, Arthur] Brandeis Univ, Volen Natl Ctr Complex Syst, Waltham, MA USA. [Wingfield, Arthur] Brandeis Univ, Dept Psychol, Waltham, MA USA. [Bennett, David A.; Buchman, Aron S.; Xu, Shunbin] Rush Univ, Ctr Med, Rush Alzheimers Dis Ctr, Chicago, IL 60612 USA. [Boxer, Adam L.] Univ Calif San Francisco, Dept Neurol, San Francisco, CA 94143 USA. [Cruickshanks, Karen J.] Univ Wisconsin, Sch Med & Publ Hlth, Dept Ophthalmol & Visual Sci, Madison, WI USA. [Cruickshanks, Karen J.] Univ Wisconsin, Sch Med & Publ Hlth, Dept Populat Hlth Sci, Madison, WI USA. [Devanand, Davangere P.] Columbia Univ, Coll Phys & Surg, Dept Psychiat, New York, NY USA. [Duffy, Charles J.] Univ Rochester, Sch Med & Dent, Dept Neurol, Rochester, NY 14642 USA. [Gall, Christine M.] Univ Calif Irvine, Dept Anat & Neurobiol, Irvine, CA 92717 USA. [Gates, George A.] Univ Washington, Bloedel Hearing Res Ctr, Seattle, WA 98195 USA. [Granholm, Ann-Charlotte] Med Univ S Carolina, Dept Neurosci, Charleston, SC 29425 USA. [Granholm, Ann-Charlotte] Med Univ S Carolina, Ctr Aging, Charleston, SC 29425 USA. [Hensch, Takao] Harvard Univ, Dept Mol & Cellular Biol, Cambridge, MA 02138 USA. [Holtzer, Roee; Verghese, Joe] Yeshiva Univ, Albert Einstein Coll Med, Dept Neurol, Bronx, NY USA. [Lin, Frank R.] Johns Hopkins Sch Med, Div Otol Neurotol & Skull Base Surg, Baltimore, MD USA. [Mc Kee, Ann C.] Boston Univ, Sch Med, Dept Neurol, Bedford, MA USA. [Mc Kee, Ann C.] Boston Univ, Sch Med, Dept Pathol, Bedford, MA USA. [Morris, John C.] Washington Univ, Sch Med, Dept Neurol, St Louis, MO 63110 USA. [Petersen, Ronald C.] Mayo Clin, Coll Med, Mayo Alzheimers Dis Res Ctr, Rochester, MN USA. [Stuble, Robert G.] So Illinois Univ, Sch Med, Ctr Alzheimer Dis & Related Disorders, Springfield, IL USA. [Trojanowski, John Q.] Univ Penn, Perelman Sch Med, Ctr Neurodegenerat Dis Res, Philadelphia, PA 19104 USA. [Trojanowski, John Q.] Univ Penn, Perelman Sch Med, Inst Aging, Philadelphia, PA 19104 USA. [Wilson, Donald A.] Nathan S Kline Inst Psychiat Res, Emot Brain Inst, Orangeburg, NY USA. [Zhang, Li I.] Univ So Calif, Keck Sch Med, Zilkha Neurogenat Inst, Los Angeles, CA 90033 USA. RP Albers, MW (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Neurol, Charlestown, MA 02129 USA. EM albers.mark@mgh.harvard.edu OI Kaye, Jeffrey/0000-0002-9971-3478 FU NIA NIH HHS [P30 AG010124, P50 AG005134, R01 AG017917, R01 AG019714, R01 AG031278, R01 AG037693, R01 AG038791, R01 AG041795, R01 AG044920, RF1 AG015819]; NIDCD NIH HHS [K23 DC011279, R01 DC008983]; NIH HHS [DP2 OD006662]; NINDS NIH HHS [R21 NS085711] NR 354 TC 33 Z9 35 U1 6 U2 22 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1552-5260 EI 1552-5279 J9 ALZHEIMERS DEMENT JI Alzheimers. Dement. PD JAN PY 2015 VL 11 IS 1 BP 70 EP 98 DI 10.1016/j.jalz.2014.04.514 PG 29 WC Clinical Neurology SC Neurosciences & Neurology GA CA0UX UT WOS:000348632800008 PM 25022540 ER PT J AU Scripko, P Oaklander, AL Koeppen, AH Frosch, MP Schmahmann, JD AF Scripko, Patricia Oaklander, Anne Louise Koeppen, Arnulf H. Frosch, Matthew P. Schmahmann, Jeremy D. TI A 40-Year-Old Woman with Difficulty Going Down Stairs in High-Heeled Shoes SO ANNALS OF NEUROLOGY LA English DT Editorial Material ID DOMINANT CEREBELLAR-ATAXIA; ALPHA-SYNUCLEIN TOXICITY; RETINAL DEGENERATION; REPEAT EXPANSION; MUTANT ATAXIN-7; CAG REPEATS; 7 SCA7; SPINOCEREBELLAR; ATROPHY; PHENOTYPE C1 [Scripko, Patricia; Schmahmann, Jeremy D.] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. [Oaklander, Anne Louise] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. [Oaklander, Anne Louise] Massachusetts Gen Hosp, Dept Pathol Neuropathol, Boston, MA 02114 USA. [Koeppen, Arnulf H.] Albany Med Coll, Albany, NY 12208 USA. [Koeppen, Arnulf H.] VA Med Ctr, Res Serv, Albany, NY USA. [Koeppen, Arnulf H.] VA Med Ctr, Neurol Serv, Albany, NY USA. [Frosch, Matthew P.] Massachusetts Gen Hosp, CS Kubik Lab Neuropathol, Boston, MA 02114 USA. [Frosch, Matthew P.] MassGen Inst Neurodegenerat Dis, Charlestown, MA USA. [Schmahmann, Jeremy D.] Harvard Univ, Sch Med, Boston, MA USA. RP Scripko, P (reprint author), Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. FU NIA NIH HHS [P50AG005134]; NINDS NIH HHS [K24NS059892, R01NS069454] NR 34 TC 0 Z9 0 U1 1 U2 2 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 2015 VL 77 IS 1 BP 1 EP 7 DI 10.1002/ana.24301 PG 7 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA AZ7UN UT WOS:000348423200001 PM 25380064 ER PT J AU Butovsky, O Jedrychowski, MP Cialic, R Krasemann, S Murugaiyan, G Fanek, Z Greco, DJ Wu, PM Doykan, CE Kiner, O Lawson, RJ Frosch, MP Pochet, N El Fatimy, R Krichevsky, AM Gygi, SP Lassmann, H Berry, J Cudkowicz, ME Weiner, HL AF Butovsky, Oleg Jedrychowski, Mark P. Cialic, Ron Krasemann, Susanne Murugaiyan, Gopal Fanek, Zain Greco, David J. Wu, Pauline M. Doykan, Camille E. Kiner, Olga Lawson, Robert J. Frosch, Matthew P. Pochet, Nathalie El Fatimy, Rachid Krichevsky, Anna M. Gygi, Steven P. Lassmann, Hans Berry, James Cudkowicz, Merit E. Weiner, Howard L. TI Targeting miR-155 Restores Abnormal Microglia and Attenuates Disease in SOD1 Mice SO ANNALS OF NEUROLOGY LA English DT Article ID AMYOTROPHIC-LATERAL-SCLEROSIS; MOUSE MODEL; EXTRACELLULAR NUCLEOTIDES; DENDRITIC CELLS; INHERITED ALS; MICRORNA-155; MACROPHAGES; EXPRESSION; BRAIN; PROGRESSION AB ObjectiveTo investigate miR-155 in the SOD1 mouse model and human sporadic and familial amyotrophic lateral sclerosis (ALS). MethodsNanoString microRNA, microglia and immune gene profiles, protein mass spectrometry, and RNA-seq analyses were measured in spinal cord microglia, splenic monocytes, and spinal cord tissue from SOD1 mice and in spinal cord tissue of familial and sporadic ALS. miR-155 was targeted by genetic ablation or by peripheral or centrally administered anti-miR-155 inhibitor in SOD1 mice. ResultsIn SOD1 mice, we found loss of the molecular signature that characterizes homeostatic microglia and increased expression of miR-155. There was loss of the microglial molecules P2ry12, Tmem119, Olfml3, transcription factors Egr1, Atf3, Jun, Fos, and Mafb, and the upstream regulators Csf1r, Tgfb1, and Tgfbr1, which are essential for microglial survival. Microglia biological functions were suppressed including phagocytosis. Genetic ablation of miR-155 increased survival in SOD1 mice by 51 days in females and 27 days in males and restored the abnormal microglia and monocyte molecular signatures. Disease severity in SOD1 males was associated with early upregulation of inflammatory genes, including Apoe in microglia. Treatment of adult microglia with apolipoprotein E suppressed the M0-homeostatic unique microglia signature and induced an M1-like phenotype. miR-155 expression was increased in the spinal cord of both familial and sporadic ALS. Dysregulated proteins that we identified in human ALS spinal cord were restored in SOD1(G93A)/miR-155(-/-) mice. Intraventricular anti-miR-155 treatment derepressed microglial miR-155 targeted genes, and peripheral anti-miR-155 treatment prolonged survival. InterpretationWe found overexpression of miR-155 in the SOD1 mouse and in both sporadic and familial human ALS. Targeting miR-155 in SOD1 mice restores dysfunctional microglia and ameliorates disease. These findings identify miR-155 as a therapeutic target for the treatment of ALS. ANN NEUROL 2015;77:75-99 C1 [Butovsky, Oleg; Cialic, Ron; Murugaiyan, Gopal; Fanek, Zain; Greco, David J.; Wu, Pauline M.; Doykan, Camille E.; Kiner, Olga; El Fatimy, Rachid; Krichevsky, Anna M.; Weiner, Howard L.] Harvard Univ, Brigham & Womens Hosp, Ann Romney Ctr Neurol Dis, Dept Neurol,Med Sch, Boston, MA 02115 USA. [Jedrychowski, Mark P.; Gygi, Steven P.] Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA USA. [Krasemann, Susanne] Univ Med Ctr Hamburg Eppendorf, Inst Neuropathol, Hamburg, Germany. [Lawson, Robert J.; Berry, James; Cudkowicz, Merit E.] Harvard Univ, Sch Med, Dept Neurol, Massachusetts Gen Hosp,Neurol Clin Res Inst, Boston, MA 02115 USA. [Frosch, Matthew P.] Harvard Univ, Massachusetts Gen Hosp, Alzheimers Dis Res Ctr, Boston, MA 02115 USA. [Pochet, Nathalie] Harvard Med Sch Broad Inst Massachusetts Inst Tec, Brigham & Womens Hosp, Program Translat NeuroPsychiat Genom, Cambridge, MA USA. [Lassmann, Hans] Med Univ Vienna, Ctr Brain Res, Vienna, Austria. [Butovsky, Oleg; Weiner, Howard L.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Evergrande Ctr Immunol Dis, Boston, MA 02112 USA. RP Butovsky, O (reprint author), Brigham & Womens Hosp, Ann Romney Ctr Neurol Dis, 77 Ave Louis Pasteur HIM 614, Boston, MA 02115 USA. EM obutovsky@rics.bwh.harvard.edu OI Cialic, Ron/0000-0002-1589-2262 FU Amyotrophic Lateral Sclerosis Association [1V78RI, ALSA2087]; Department of Defense ALS Research Program [AL120029]; Nancy Davis Foundation; Edward N. and Della L. Thome Memorial Foundation; National Multiple Sclerosis Society [5092A1]; NIH-NINDS [1R01NS088137] FX This work was supported by the Amyotrophic Lateral Sclerosis Association (1V78RI (H.L.W.), ALSA2087 (O.B.)), Department of Defense ALS Research Program (AL120029 (H.L.W.)), Nancy Davis Foundation Junior Faculty Award (O.B.), Edward N. and Della L. Thome Memorial Foundation (H.L.W.), National Multiple Sclerosis Society (5092A1) (O.B.), NIH-NINDS (1R01NS088137) (O.B.). We thank Prize4Life, a non-profit organization dedicated to the discovery of treatments and a cure for ALS, for providing SOD1 mice. NR 61 TC 39 Z9 39 U1 4 U2 12 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 2015 VL 77 IS 1 BP 75 EP 99 DI 10.1002/ana.24304 PG 25 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA AZ7UN UT WOS:000348423200009 PM 25381879 ER PT J AU Evans, KC Song, TY Zimmerman, JP Gustin, MJ McLaren, DG AF Evans, Karleyton C. Song, Tian-Yue Zimmerman, Jared P. Gustin, Michael J. McLaren, Donald G. TI Air hunger evokes greater anxiety and insular cortical activity in panic disorder than in healthy individuals: An arterial spin labeled fMRI study SO BIOLOGICAL PSYCHOLOGY LA English DT Meeting Abstract CT 20th Annual Meeting of the International-Society-for-the-Advancement-of-Respiratory-Psychophysiolog y (ISARP) CY SEP 27-29, 2013 CL Leuven, BELGIUM SP Int Soc Advancement Respiratory Psychophysiol C1 [Evans, Karleyton C.; Song, Tian-Yue; Zimmerman, Jared P.; Gustin, Michael J.] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. [Evans, Karleyton C.; McLaren, Donald G.] Harvard Univ, Sch Med, Boston, MA USA. [McLaren, Donald G.] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0301-0511 EI 1873-6246 J9 BIOL PSYCHOL JI Biol. Psychol. PD JAN PY 2015 VL 104 BP 150 EP 151 PG 2 WC Psychology, Biological; Behavioral Sciences; Psychology; Psychology, Experimental SC Psychology; Behavioral Sciences GA AZ1ZS UT WOS:000348034700029 ER PT J AU Badejo, OA Chang, CC So-Armah, KA Tracy, RP Baker, JV Rimland, D Butt, AA Gordon, AJ Rinaldo, CR Kraemer, K Samet, JH Tindle, HA Goetz, MB Rodriguez-Barradas, MC Bedimo, R Gibert, CL Leaf, DA Kuller, LH Deeks, SG Justice, AC Freiberg, MS AF Badejo, Oluwatosin A. Chang, Chung-Chou So-Armah, Kaku A. Tracy, Russell P. Baker, Jason V. Rimland, David Butt, Adeel A. Gordon, Adam J. Rinaldo, Charles R., Jr. Kraemer, Kevin Samet, Jeffrey H. Tindle, Hilary A. Goetz, Matthew B. Rodriguez-Barradas, Maria C. Bedimo, Roger Gibert, Cynthia L. Leaf, David A. Kuller, Lewis H. Deeks, Steven G. Justice, Amy C. Freiberg, Matthew S. TI CD8(+) T-Cells Count in Acute Myocardial Infarction in HIV Disease in a Predominantly Male Cohort SO Biomed Research International LA English DT Article ID INFECTED WOMEN; RISK; ACTIVATION; SYSTEM; RATES AB Human Immunodeficiency Virus-(HIV-) infected persons have a higher risk for acute myocardial infarction (AMI) than HIVuninfected persons. Earlier studies suggest that HIV viral load, CD4 + T-cell count, and antiretroviral therapy are associated with cardiovascular disease (CVD) risk. Whether CD8 + T-cell count is associated with CVD risk is not clear. We investigated the association between CD8 + T-cell count and incident AMI in a cohort of 73,398 people (of which 97.3% were men) enrolled in the U. S. Veterans Aging Cohort Study-Virtual Cohort (VACS-VC). Compared to uninfected people, HIV-infected people with high baselineCD8 + T-cell counts (> 1065 cells/ mm 3) had increasedAMI risk (adjustedHR = 1.82,.. < 0.001, 95% CI: 1.46 to 2.28). There was evidence that the effect of CD8 + T-cell tertiles on AMI risk differed by CD4 + T-cell level: compared to uninfected people, HIVinfected people with CD4 + T-cell counts = 200 cells/ mm 3 had increased AMI risk with high CD8 + T-cell count, while those with CD4 + T-cell counts < 200 cells/ mm 3 had increased AMI risk with low CD8 + T-cell count. CD8 + T-cell counts may add additional AMI risk stratification information beyond that provided by CD4 + T-cell counts alone. C1 [Badejo, Oluwatosin A.; Chang, Chung-Chou; Gordon, Adam J.; Kraemer, Kevin] Univ Pittsburgh, UPMC, Div Gen Internal Med, Montefiore Hosp, Pittsburgh, PA 15213 USA. [Chang, Chung-Chou] Univ Pittsburgh, Grad Sch Publ Hlth, Dept Biostat, Pittsburgh, PA 15261 USA. [So-Armah, Kaku A.] Yale Univ, Sch Med, New Haven, CT 06510 USA. [Tracy, Russell P.] Univ Vermont, Burlington, VT 05446 USA. [Baker, Jason V.] Univ Minnesota, Hennepin Cty Med Ctr, Dept Med, Minneapolis, MN 55415 USA. [Rimland, David] Emory Univ, Sch Med, VA Med Ctr, Atlanta, GA 30033 USA. [Butt, Adeel A.] Univ Pittsburgh, Sch Med, Div Infect Dis, Pittsburgh, PA 15213 USA. [Butt, Adeel A.; Gordon, Adam J.] VA Pittsburgh Healthcare Syst, Pittsburgh, PA 15240 USA. [Butt, Adeel A.] Hamad Med Corp, Doha, Qatar. [Rinaldo, Charles R., Jr.] Univ Pittsburgh, Sch Med, Dept Pathol, Pittsburgh, PA 15213 USA. [Rinaldo, Charles R., Jr.] Univ Pittsburgh, Grad Sch Publ Hlth, Dept Infect Dis & Microbiol, Pittsburgh, PA 15261 USA. [Samet, Jeffrey H.] Boston Univ, Sch Med, Clin Addict Res & Educ Unit, Boston, MA 02118 USA. [Samet, Jeffrey H.] Boston Univ, Sch Publ Hlth, Boston, MA 02118 USA. [Tindle, Hilary A.] Vanderbilt Univ, Med Ctr, Dept Gen Internal Med & Publ Hlth, Nashville, TN 37203 USA. [Goetz, Matthew B.; Leaf, David A.] VA Greater Los Angeles Healthcare Syst, Dept Med, Los Angeles, CA 90073 USA. [Goetz, Matthew B.; Leaf, David A.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Med, Los Angeles, CA 90095 USA. [Rodriguez-Barradas, Maria C.] Baylor Coll Med, Infect Dis Sect, Michael E DeBakey VA Med Ctr, Houston, TX 77030 USA. [Bedimo, Roger] VA North Texas Healthcare Syst, Dallas, TX 75216 USA. [Bedimo, Roger] Univ Texas SW Med Ctr Dallas, Div Infect Dis, Dallas, TX 75390 USA. [Gibert, Cynthia L.] Washington DC VA Med Ctr, Washington, DC 20422 USA. [Gibert, Cynthia L.] George Washington Univ, Med Ctr, Washington, DC 20037 USA. [Kuller, Lewis H.] Univ Pittsburgh, Grad Sch Publ Hlth, Dept Epidemiol, Pittsburgh, PA 15261 USA. [Deeks, Steven G.] Univ Calif San Francisco, Dept Med, San Francisco, CA 94143 USA. [Justice, Amy C.] Yale Univ, Sch Med, West Haven Vet Adm Med Ctr, Vet Affairs Connecticut Hlth Care Syst, New Haven, CT 06516 USA. [Freiberg, Matthew S.] Vanderbilt Univ, Med Ctr, Div Cardiovasc Med, Nashville, TN 37203 USA. RP Freiberg, MS (reprint author), Vanderbilt Univ, Med Ctr, Div Cardiovasc Med, 2525 West End,Suite 300-A, Nashville, TN 37203 USA. EM matthew.s.freiberg@vanderbilt.edu OI Butt, Adeel/0000-0002-1118-1826; Goetz, Matthew/0000-0003-4542-992X; Justice, Amy/0000-0003-0139-5502 NR 12 TC 0 Z9 0 U1 1 U2 4 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 2015 AR 246870 DI 10.1155/2015/246870 PG 5 WC Biotechnology & Applied Microbiology; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Research & Experimental Medicine GA CA7DU UT WOS:000349078600001 ER PT J AU Nislow, C Lee, AY Allen, PL Giaever, G Smith, A Gebbia, M Stodieck, LS Hammond, JS Birdsall, HH Hammond, TG AF Nislow, Corey Lee, Anna Y. Allen, Patricia L. Giaever, Guri Smith, Andrew Gebbia, Marinella Stodieck, Louis S. Hammond, Jeffrey S. Birdsall, Holly H. Hammond, Timothy G. TI Genes Required for Survival in Microgravity Revealed by Genome-Wide Yeast Deletion Collections Cultured during Spaceflight SO Biomed Research International LA English DT Article ID SACCHAROMYCES-CEREVISIAE; DNA-DAMAGE; SMALL MOLECULES; APOPTOSIS; ORGANISM; CELLS; MITOXANTRONE; PATHWAY AB Spaceflight is a unique environment with profound effects on biological systems including tissue redistribution and musculoskeletal stresses. However, the more subtle biological effects of spaceflight on cells and organisms are difficult to measure in a systematic, unbiased manner. Here we test the utility of the molecularly barcoded yeast deletion collection to provide a quantitative assessment of the effects of microgravity on a model organism. We developed robust hardware to screen, in parallel, the complete collection of similar to 4800 homozygous and similar to 5900 heterozygous (including similar to 1100 single-copy deletions of essential genes) yeast deletion strains, each carrying unique DNA that acts as strain identifiers. We compared strain fitness for the homozygous and heterozygous yeast deletion collections grown in spaceflight and ground, as well as plus and minus hyperosmolar sodium chloride, providing a second additive stressor. The genome-wide sensitivity profiles obtained from these treatments were then queried for their similarity to a compendium of drugs whose effects on the yeast collection have been previously reported. We found that the effects of spaceflight have high concordance with the effects of DNA-damaging agents and changes in redox state, suggesting mechanisms by which spaceflight may negatively affect cell fitness. C1 [Nislow, Corey; Giaever, Guri] Univ British Columbia, Fac Pharmaceut Sci, Vancouver, BC V6T 1Z3, Canada. [Lee, Anna Y.; Smith, Andrew; Gebbia, Marinella] Univ Toronto, Donnelly CCBR, Toronto, ON M5S 3E1, Canada. [Allen, Patricia L.; Hammond, Timothy G.] Durham VA Med Ctr, Res & Dev Serv, Durham, NC 27705 USA. [Stodieck, Louis S.] Univ Colorado, Bioserve Space Technol, Boulder, CO 80309 USA. [Hammond, Jeffrey S.] Inst Med Res, Durham, NC 27705 USA. [Birdsall, Holly H.; Hammond, Timothy G.] US Dept Vet Affairs, Off Res & Dev, Washington, DC 20420 USA. [Birdsall, Holly H.] Baylor Coll Med, Dept Otorhinolaryngol, Houston, TX 77030 USA. [Birdsall, Holly H.] Baylor Coll Med, Dept Immunol, Houston, TX 77030 USA. [Birdsall, Holly H.] Baylor Coll Med, Dept Psychiat, Houston, TX 77030 USA. [Hammond, Timothy G.] Duke Univ, Sch Med, Dept Internal Med, Div Nephrol, Durham, NC 27705 USA. [Hammond, Timothy G.] George Washington Univ, Sch Med, Dept Internal Med, Nephrol Sect, Washington, DC 20052 USA. RP Hammond, TG (reprint author), Durham VA Med Ctr, Res & Dev Serv, Durham, NC 27705 USA. EM grumpy70115@yahoo.com OI Nislow, Corey/0000-0002-4016-8874 FU NASA [NNX10AP01G] FX These studies were supported by NASA Grant no. NNX10AP01G. The authors thank NASA for spaceflight access under the auspices of the International Space Station National Lab Pathfinder program. This material is the result of work supported with resources and the use of facilities at the Durhan Veterans Affairs Medical Center and the Office of Research and Development, Department of Veterans Affairs, Veterans Health Administration. Sequencing was performed, in part at UBCSeq, Vancouver. Contents do not represent the views of the Department of Veterans Affairs or the United States of America. NR 33 TC 0 Z9 0 U1 0 U2 5 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 2015 AR 976458 DI 10.1155/2015/976458 PG 10 WC Biotechnology & Applied Microbiology; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Research & Experimental Medicine GA CA3DL UT WOS:000348786200001 ER PT J AU Tan, EK Srivastava, AK Arnold, WD Singh, MP Zhang, YY AF Tan, E. K. Srivastava, Amit K. Arnold, W. David Singh, Mahendra P. Zhang, Yiying TI Neurodegeneration: Etiologies and New Therapies SO Biomed Research International LA English DT Editorial Material C1 [Tan, E. K.] Singapore Gen Hosp, Natl Inst Neurosci, Dept Neurol, Singapore 169857, Singapore. [Tan, E. K.] Duke NUS Grad Med Sch, Singapore 169857, Singapore. [Srivastava, Amit K.] Johns Hopkins Univ, Sch Med, Russell H Morgan Dept Radiol & Radiol Sci, Baltimore, MD 21205 USA. [Srivastava, Amit K.] Johns Hopkins Univ, Sch Med, Inst Cell Engn, Baltimore, MD 21205 USA. [Arnold, W. David] Ohio State Univ, Dept Neurol, Div Neuromuscular Med, Columbus, OH 43210 USA. [Arnold, W. David] Ohio State Univ, Dept Phys Med & Rehabil, Columbus, OH 43210 USA. [Singh, Mahendra P.] Indian Inst Toxicol Res, CSIR, Toxicogen & Predict Toxicol Div, Lucknow 226001, Uttar Pradesh, India. [Zhang, Yiying] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, Charlestown, MA 02129 USA. RP Tan, EK (reprint author), Singapore Gen Hosp, Natl Inst Neurosci, Dept Neurol, Singapore 169857, Singapore. EM tan.eng.king@sgh.com.sg NR 2 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 2015 AR 272630 DI 10.1155/2015/272630 PG 2 WC Biotechnology & Applied Microbiology; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Research & Experimental Medicine GA CA7EA UT WOS:000349079200001 ER PT J AU Mansour, MR Reed, C Eisenberg, AR Tseng, JC Twizere, JC Daakour, S Yoda, A Rodig, SJ Tal, N Shochat, C Berezovskaya, A DeAngelo, DJ Sallan, SE Weinstock, DM Izraeli, S Kung, AL Kentsis, A Look, AT AF Mansour, Marc R. Reed, Casie Eisenberg, Amy R. Tseng, Jen-Chieh Twizere, Jean-Claude Daakour, Sarah Yoda, Akinori Rodig, Scott J. Tal, Noa Shochat, Chen Berezovskaya, Alla DeAngelo, Daniel J. Sallan, Stephen E. Weinstock, David M. Izraeli, Shai Kung, Andrew L. Kentsis, Alex Look, A. Thomas TI Targeting oncogenic interleukin-7 receptor signalling with N-acetylcysteine in T cell acute lymphoblastic leukaemia SO BRITISH JOURNAL OF HAEMATOLOGY LA English DT Article DE acute leukaemia; T-cell lymphoma; therapy ID OF-FUNCTION MUTATIONS; PHOSPHATIDYLINOSITOL-3 KINASE; ACETAMINOPHEN OVERDOSE; PHARMACOKINETICS; ACTIVATION; IL7R; PROLIFERATION; VIABILITY; EFFICACY; PATHWAY AB Activating mutations of the interleukin-7 receptor (IL7R) occur in approximately 10% of patients with T cell acute lymphoblastic leukaemia (T-ALL). Most mutations generate a cysteine at the transmembrane domain leading to receptor homodimerization through disulfide bond formation and ligand-independent activation of STAT5. We hypothesized that the reducing agent N-acetylcysteine (NAC), a well-tolerated drug used widely in clinical practice to treat acetaminophen overdose, would reduce disulfide bond formation, and inhibit mutant IL7R-mediated oncogenic signalling. We found that treatment with NAC disrupted IL7R homodimerization in IL7R-mutant DND-41 cells as assessed by non-reducing Western blot, as well as in a luciferase complementation assay. NAC led to STAT5 dephosphorylation and cell apoptosis at clinically achievable concentrations in DND-41 cells, and Ba/F3 cells transformed by an IL7R-mutant construct containing a cysteine insertion. The apoptotic effects of NAC could be rescued in part by a constitutively active allele of STAT5. Despite using doses lower than those tolerated in humans, NAC treatment significantly inhibited the progression of human DND-41 cells engrafted in immunodeficient mice. Thus, targeting leukaemogenic IL7R homodimerization with NAC offers a potentially effective and feasible therapeutic strategy that warrants testing in patients with T-ALL. C1 [Mansour, Marc R.; Reed, Casie; Eisenberg, Amy R.; Berezovskaya, Alla; DeAngelo, Daniel J.; Sallan, Stephen E.; Kentsis, Alex; Look, A. Thomas] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. [Mansour, Marc R.] UCL, UCL Canc Inst, Dept Haematol, London, England. [Eisenberg, Amy R.; Kentsis, Alex] Mem Sloan Kettering Canc Ctr, Dept Pediat, Sloan Kettering Inst, Mol Pharmacol & Chem Program, New York, NY 10065 USA. [Tseng, Jen-Chieh] Harvard Univ, Sch Med, Dana Farber Canc Inst, Lurie Family Imaging Ctr, Boston, MA 02115 USA. [Twizere, Jean-Claude; Daakour, Sarah] Univ Liege, Interdisciplinary Cluster Appl Genoprote GIGA R, Lab Prot Signalling & Interact, B-4000 Sart Tilman Par Liege, Belgium. [Yoda, Akinori; Weinstock, David M.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Rodig, Scott J.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Pathol, Boston, MA 02115 USA. [Tal, Noa; Shochat, Chen; Izraeli, Shai] Chaim Sheba Med Ctr, Canc Res Ctr, IL-52621 Tel Hashomer, Israel. [Tal, Noa; Shochat, Chen; Izraeli, Shai] Tel Aviv Univ, Sch Med, IL-69978 Tel Aviv, Israel. [Shochat, Chen] Migal Galilee Bio Technol Ctr, Tel Hai, Israel. [Shochat, Chen] Tel Hai Acad Coll, Tel Hai, Israel. [Kung, Andrew L.] Columbia Univ, Dept Pediat, New York, NY 10027 USA. [Look, A. Thomas] Childrens Hosp, Div Hematol Oncol, Boston, MA 02115 USA. RP Look, AT (reprint author), Dana Farber Canc Inst, Dept Pediat Oncol, 450 Brookline Ave,Mayer 630, Boston, MA 02115 USA. EM kentsisresearchgroup@gmail.com; thomas_look@dfci.harvard.edu OI Kung, Andrew/0000-0002-9091-488X FU Kay Kendall Leukaemia Fund of the UK; Claudia Adams Barr Innovative Basic Science Research Program; National Cancer Institute [5P01CA109901, 5P01CA68484, 5K08CA160660]; Intramural Research Program of the NIH, National Cancer Institute, Center for Cancer Research; ISF, ICRF and WLBH foundation FX This research was supported by the Kay Kendall Leukaemia Fund of the UK (M.R.M), the Claudia Adams Barr Innovative Basic Science Research Program (M.R.M), grants from the National Cancer Institute (5P01CA109901, 5P01CA68484 and 5K08CA160660) by the Intramural Research Program of the NIH, National Cancer Institute, Center for Cancer Research and by the ISF, ICRF and WLBH foundation (to SI). We would like to thank John Gilbert for editorial advice. NR 46 TC 4 Z9 4 U1 1 U2 6 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0007-1048 EI 1365-2141 J9 BRIT J HAEMATOL JI Br. J. Haematol. PD JAN PY 2015 VL 168 IS 2 BP 230 EP 238 DI 10.1111/bjh.13115 PG 9 WC Hematology SC Hematology GA AZ9WF UT WOS:000348564000008 PM 25256574 ER PT J AU Demner-Fushman, D Antani, S Kalpathy-Cramer, J Muller, H AF Demner-Fushman, Dina Antani, Sameer Kalpathy-Cramer, Jayashree Mueller, Henning TI A decade of community-wide efforts in advancing medical image understanding and retrieval SO COMPUTERIZED MEDICAL IMAGING AND GRAPHICS LA English DT Editorial Material C1 [Demner-Fushman, Dina; Antani, Sameer] Natl Lib Med, NIH, Bethesda, MD USA. [Kalpathy-Cramer, Jayashree] Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Boston, MA 02114 USA. [Kalpathy-Cramer, Jayashree] Harvard Univ, Sch Med, Boston, MA USA. [Mueller, Henning] Univ Appl Sci Western Switzerland HES SO, Sierre, Switzerland. RP Muller, H (reprint author), Univ Appl Sci Western Switzerland HES SO, Sierre, Switzerland. EM henning.mueller@hevs.ch OI Muller, Henning/0000-0001-6800-9878; Kalpathy-Cramer, Jayashree/0000-0001-8906-9618 NR 11 TC 0 Z9 0 U1 3 U2 8 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0895-6111 EI 1879-0771 J9 COMPUT MED IMAG GRAP JI Comput. Med. Imaging Graph. PD JAN PY 2015 VL 39 SI SI BP 1 EP 2 DI 10.1016/j.compmedimag.2014.12.002 PG 2 WC Engineering, Biomedical; Radiology, Nuclear Medicine & Medical Imaging SC Engineering; Radiology, Nuclear Medicine & Medical Imaging GA AZ6NZ UT WOS:000348337500001 PM 25572585 ER PT J AU Kalpathy-Cramer, J de Herrera, AGS Demner-Fushman, D Antani, S Bedrick, S Muller, H AF Kalpathy-Cramer, Jayashree de Herrera, Alba Garcia Seco Demner-Fushman, Dina Antani, Sameer Bedrick, Steven Mueller, Henning TI Evaluating performance of biomedical image retrieval systems An overview of the medical image retrieval task at ImageCLEF 2004-2013 SO COMPUTERIZED MEDICAL IMAGING AND GRAPHICS LA English DT Article DE Multimodal medical retrieval; Image retrieval; Biomedical literature; Content-based retrieval; Text-based image retrieval ID INFORMATION; FUSION; TRACK; TEXT AB Medical image retrieval and classification have been extremely active research topics over the past 15 years. Within the ImageCLEF benchmark in medical image retrieval and classification, a standard test bed was created that allows researchers to compare their approaches and ideas on increasingly large and varied data sets including generated ground truth. This article describes the lessons learned in ten evaluation campaigns. A detailed analysis of the data also highlights the value of the resources created. (C) 2014 Elsevier Ltd. All rights reserved. C1 [Kalpathy-Cramer, Jayashree] Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Boston, MA 02114 USA. [Kalpathy-Cramer, Jayashree] Harvard Univ, Sch Med, Boston, MA USA. [de Herrera, Alba Garcia Seco; Mueller, Henning] Univ Appl Sci Western Switzerland HES SO, Sierre, Switzerland. [Demner-Fushman, Dina; Antani, Sameer] Natl Lib Med, NIH, Bethesda, MD USA. [Bedrick, Steven] Oregon Hlth & Sci Univ, Portland, OR 97201 USA. RP Kalpathy-Cramer, J (reprint author), Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Boston, MA 02114 USA. EM kalpathy@nmr.mgh.harvard.edu OI Bedrick, Steven/0000-0002-0163-9397; Muller, Henning/0000-0001-6800-9878; Kalpathy-Cramer, Jayashree/0000-0001-8906-9618; Antani, Sameer/0000-0002-0040-1387 FU NIH [U01CA154602, R00LM009889] FX JKC is funded in part by the NIH grants U01CA154602 and R00LM009889. NR 46 TC 11 Z9 11 U1 2 U2 9 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0895-6111 EI 1879-0771 J9 COMPUT MED IMAG GRAP JI Comput. Med. Imaging Graph. PD JAN PY 2015 VL 39 SI SI BP 55 EP 61 DI 10.1016/j.compmedimag.2014.03.004 PG 7 WC Engineering, Biomedical; Radiology, Nuclear Medicine & Medical Imaging SC Engineering; Radiology, Nuclear Medicine & Medical Imaging GA AZ6NZ UT WOS:000348337500007 PM 24746250 ER PT J AU Oldenburg, CE Jain, S Mayer, KH Mimiaga, MJ AF Oldenburg, Catherine E. Jain, Sachin Mayer, Kenneth H. Mimiaga, Matthew J. TI Post-exposure prophylaxis use and recurrent exposure to HIV among men who have sex with men who use crystal methamphetamine SO DRUG AND ALCOHOL DEPENDENCE LA English DT Article DE Post-exposure prophylaxis; HIV prevention; Crystal methamphetamine; Men who have sex with men ID SUBSTANCE-ABUSE TREATMENT; CONTINGENCY MANAGEMENT; BISEXUAL MEN; PREVENTION; GAY; INFECTION AB Background: Men who have sex with men (MSM) who use aystal methamphetamine (CM) are at increased risk for HIV infection. Post-exposure prophylaxis (PEP) is a useful HIV prevention strategy if individuals are able to identify high-risk exposures and seek timely care, however to date there has been limited data on the use of PEP by CM users. Methods: A: Retrospective cohort study of all PEP prescriptions (N = 1130 prescriptions among 788 MSM) at Fenway Community Health in Boston, MA was undertaken. Multivariable models were used to assess the association between CM use during exposure (7.4% used CM during exposure) and chronically (7.4% of MSM were chronic CM users) and individual-level and event-level outcomes among MSM who used PEP at least once. Results: Compared to those who had not used CM, MSM PEP users who used CM more frequently returned for repeat PEP (aOR 5.13, 95% CI 2.82 to 9.34) and were significantly more likely to seroconvert over the follow-up period (aHR 3.61, 95% CI 1.51 to 8.60). MSM who used CM had increased odds of unprotected anal intercourse as the source of exposure (aOR 2.12,95% CI 1.16 to 3.87) and knowing that their partner was HIV infected (aOR 2.27,95% CI 1.42 to 3.64). Conclusions: While MSM who use CM may have challenges accessing ART in general, these data highlight the fact that those who were able to access PEP subsequently remained at increased risk of HIV seroconversion. Counseling and/or substance use interventions during the PEP course should be considered for CM-using MSM. (C) 2014 Elsevier Ireland Ltd. All rights reserved. C1 [Oldenburg, Catherine E.; Mimiaga, Matthew J.] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. [Oldenburg, Catherine E.; Jain, Sachin; Mayer, Kenneth H.] Fenway Community Hlth, Fenway Inst, Boston, MA USA. [Jain, Sachin; Mayer, Kenneth H.; Mimiaga, Matthew J.] Beth Israel Deaconess Med Ctr, Div Infect Dis, Boston, MA 02215 USA. [Mayer, Kenneth H.] Harvard Univ, Sch Publ Hlth, Dept Global Hlth & Populat, Boston, MA 02115 USA. [Mimiaga, Matthew J.] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. RP Oldenburg, CE (reprint author), Harvard Univ, Sch Publ Hlth, Dept Epidemiol, 677 Huntington Ave,9th Floor, Boston, MA 02115 USA. EM ceo242@mail.harvard.edu FU NIAID NIH HHS [T32 AI007535]; NIDA NIH HHS [T32 DA013911] NR 25 TC 3 Z9 3 U1 2 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 2015 VL 146 BP 75 EP 80 DI 10.1016/j.drugalcdep.2014.11.010 PG 6 WC Substance Abuse; Psychiatry SC Substance Abuse; Psychiatry GA AZ5LD UT WOS:000348261600011 PM 25482500 ER PT J AU Dunn, EC Richmond, TK Milliren, CE Subramanian, SV AF Dunn, Erin C. Richmond, Tracy K. Milliren, Carly E. Subramanian, S. V. TI Using cross-classified multilevel models to disentangle school and neighborhood effects: An example focusing on smoking behaviors among adolescents in the United States SO HEALTH & PLACE LA English DT Article DE Cross-classified; Multilevel modeling; Adolescents; School environments; Neighborhoods ID HEALTH; OUTCOMES; DISADVANTAGE; GLOSSARY AB Background: Despite much interest in understanding the influence of contexts on health, most research has focused on one context at a time, ignoring the reality that individuals have simultaneous memberships in multiple settings. Method: Using the example of smoking behavior among adolescents in the National Longitudinal Study of Adolescent Health, we applied cross classified multilevel modeling (CCMM) to examine fixed and random effects for schools and neighborhoods. We compared the CCMM results with those obtained from a traditional multilevel model (MEM) focused on either the school and neighborhood separately. Results: In the MEMs, 52% of the variation in smoking was due to differences between neighborhoods (when schools were ignored) and 6.3% of the variation in smoking was due to differences between schools (when neighborhoods were ignored). However in the CCMM examining neighborhood and school variation simultaneously, the neighborhood level variation was reduced to 0.4%. Conclusion: Results suggest that using MEM, instead of CCMM, could lead to overestimating the importance of certain contexts and could ultimately lead to targeting interventions or policies to the wrong settings. (C) 2014 Elsevier Ltd. All rights reserved. C1 [Dunn, Erin C.] Massachusetts Gen Hosp, Ctr Human Genet Res, Psychiat & Neurodev Genet Unit, Boston, MA 02114 USA. [Dunn, Erin C.] Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA. [Dunn, Erin C.] Broad Inst, Stanley Ctr Psychiat Res, Cambridge, MA 02142 USA. [Richmond, Tracy K.] Boston Childrens Hosp, Div Adolescent Med, Boston, MA 02115 USA. [Milliren, Carly E.] Boston Childrens Hosp, Dept Med, Clin Res Ctr, Boston, MA 02115 USA. [Subramanian, S. V.] Harvard Univ, Sch Publ Hlth, Dept Social & Behav Sci, Boston, MA 02115 USA. RP Subramanian, SV (reprint author), Harvard Univ, Sch Publ Hlth, Dept Social & Behav Sci, 677 Huntington Ave, Boston, MA 02115 USA. EM edunn2@mgh.harvard.edu; tracy.k.richmond@childrens.harvard.edu; carly.milliren@childrens.harvard.edu; svsubram@hsph.harvard.edu FU Eunice Kennedy Shriver National Institute of Child Health and Human Development [P01-HD31921]; Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) [K01HD058042]; RWJ Investigator Award in Health Policy Research FX This research uses data from Add Health, a program project directed by Kathleen Mullan Harris and designed by J. Richard Udry, Peter S. Bearman, and Kathleen Mullan Harris at the University of North Carolina at Chapel Hill, and funded by grant P01-HD31921 from the Eunice Kennedy Shriver National Institute of Child Health and Human Development, with cooperative funding from 23 other federal agencies and foundations. Special acknowledgment is due Ronald R. Rindfuss and Barbara Entwisle for assistance in the original design. Information on how to obtain the Add Health data files is available on the Add Health website (http://www.cpc.unc.edu/addhealth). No direct support was received from grant P01-HD31921 for this analysis.; Research reported in this publication was supported by the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) under Award Number K01HD058042. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. SVS was supported in part by the RWJ Investigator Award in Health Policy Research. NR 30 TC 9 Z9 9 U1 1 U2 8 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 1353-8292 EI 1873-2054 J9 HEALTH PLACE JI Health Place PD JAN PY 2015 VL 31 BP 224 EP 232 DI 10.1016/j.healthplace.2014.12.001 PG 9 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA AZ4ON UT WOS:000348202100028 PM 25579227 ER PT J AU McCarthy, AJ Lauwers, GY Sheahan, K AF McCarthy, Aoife J. Lauwers, Gregory Y. Sheahan, Kieran TI Iatrogenic pathology of the intestines SO HISTOPATHOLOGY LA English DT Review DE colon; damage; drug-induced; gastrointestinal tract; iatrogenic; injury; large intestine; medication-induced; side effects; small intestine ID SODIUM POLYSTYRENE SULFONATE; NONSTEROIDAL ANTIINFLAMMATORY DRUGS; OF-THE-LITERATURE; MOFETIL-RELATED COLITIS; VERSUS-HOST-DISEASE; SOLID-ORGAN TRANSPLANTATION; T-LYMPHOCYTE ANTIGEN-4; CHRONIC HEPATITIS-C; MYCOPHENOLATE-MOFETIL; ISCHEMIC COLITIS AB Many drugs and chemical agents can cause enteritis and colitis, producing clinical gastrointestinal side effects, the most common of which are diarrhoea, constipation, nausea and vomiting. Significant histological overlap exists between some patterns of medication or chemical injury and various disease entities. A particular medication may cause multiple patterns of injury and may mimic common entities such as coeliac disease, Crohn's disease, infectious enteritis and colitis. Thus, given the common absence of specific histopathological features, the diagnosis often relies upon thorough clinicopathological correlation. This review concentrates on selected examples of medication-induced injury of the intestinal tract in which the pathology can be recognized, particularly on biopsies, with a focus on newly described medication-induced gastrointestinal effects. C1 [McCarthy, Aoife J.; Sheahan, Kieran] St Vincents Univ Hosp, Dept Histopathol, Dublin 4, Ireland. [Lauwers, Gregory Y.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. RP Sheahan, K (reprint author), St Vincents Univ Hosp, Dept Histopathol, Elm Pk, Dublin 4, Ireland. EM k.sheahan@st-vincents.ie NR 116 TC 5 Z9 5 U1 2 U2 7 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0309-0167 EI 1365-2559 J9 HISTOPATHOLOGY JI Histopathology PD JAN PY 2015 VL 66 IS 1 BP 15 EP 28 DI 10.1111/his.12598 PG 14 WC Cell Biology; Pathology SC Cell Biology; Pathology GA AZ8CX UT WOS:000348443500003 PM 25639479 ER PT J AU Jaff, MR AF Jaff, Michael R. TI The THUNDER Trial Results Clearing the Way or Ushering the Storm?* SO JACC-CARDIOVASCULAR INTERVENTIONS LA English DT Editorial Material DE drug coated balloons; peripheral artery disease; restenosis ID PERIPHERAL ARTERY-DISEASE; ANGIOPLASTY; PACLITAXEL; LESIONS C1 [Jaff, Michael R.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA 02115 USA. RP Jaff, MR (reprint author), Massachusetts Gen Hosp, 55 Fruit St,Warren 905, Boston, MA 02114 USA. EM mjaff@partners.org NR 15 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 1936-8798 EI 1876-7605 J9 JACC-CARDIOVASC INTE JI JACC-Cardiovasc. Interv. PD JAN PY 2015 VL 8 IS 1 BP 109 EP 110 DI 10.1016/j.jcin.2014.09.008 PN A PG 2 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA AZ4MP UT WOS:000348195900022 PM 25616823 ER PT J AU Ravona-Springer, R Haratz, S Tanne, D Schmeidler, J Efrati, S Rosendorff, C Beeri, MS Silverman, JM AF Ravona-Springer, Ramit Haratz, Salo Tanne, David Schmeidler, James Efrati, Shai Rosendorff, Clive Beeri, Michal Schnaider Silverman, Jeremy M. TI Arterial Wall Function is Associated with Cognitive Performance Primarily in Elderly with Type 2 Diabetes SO JOURNAL OF ALZHEIMERS DISEASE LA English DT Article DE Arterial wall function; cognitive function; large artery elasticity index; total vascular impedance; type 2 diabetes ID PULSE-WAVE VELOCITY; MINI-MENTAL-STATE; ALZHEIMER-DISEASE; CEREBROVASCULAR REACTIVITY; CAROTID ATHEROSCLEROSIS; ENDOTHELIAL FUNCTION; FASTING GLUCOSE; OLDEST-OLD; STIFFNESS; DEMENTIA AB Regression analyses compared 41 type 2 diabetes (T2D) and 131 non-T2D cognitively normal elderly males on the associations of arterial wall function measures [large artery elasticity index (LAEI), small artery elasticity index (SAEI), systemic vascular resistance (SVR), and total vascular impedance (TVI)] with cognitive performance (memory, language, and executive functions), controlling for socio-demographic and cardiovascular factors. Higher LAEI and lower TVI were significantly associated with better executive functions performance in T2D but not in non-T2D subjects. Lower TVI was more associated with better language performance in T2D. Results suggest that arterial wall function is associated with cognition in T2D. C1 [Ravona-Springer, Ramit] Sheba Med Ctr, Memory Clin, IL-52621 Ramat Gan, Israel. [Ravona-Springer, Ramit; Haratz, Salo; Tanne, David; Efrati, Shai] Tel Aviv Univ, Sackler Fac Med, IL-69978 Tel Aviv, Israel. [Haratz, Salo; Tanne, David] Sheba Med Ctr, Dept Neurol, Stroke Unit, IL-52621 Ramat Gan, Israel. [Schmeidler, James; Beeri, Michal Schnaider; Silverman, Jeremy M.] Icahn Sch Med Mt Sinai, Dept Psychiat, New York, NY 10029 USA. [Efrati, Shai] Assaf Harofeh Med Ctr, Inst Hyperbar Med, IL-70300 Zerifin, Israel. [Efrati, Shai] Assaf Harofeh Med Ctr, Res & Dev Unit, IL-70300 Zerifin, Israel. [Efrati, Shai] Tel Aviv Univ, Sagol Sch Neurosci, IL-69978 Tel Aviv, Israel. [Rosendorff, Clive; Silverman, Jeremy M.] James J Peters Vet Affairs Med Ctr, Bronx, NY USA. [Rosendorff, Clive] Mt Sinai Sch Med, Dept Med Cardiol, New York, NY USA. [Beeri, Michal Schnaider] Sheba Med Ctr, Josef Sagol Neurosci Ctr, IL-52621 Ramat Gan, Israel. RP Ravona-Springer, R (reprint author), Sheba Med Ctr, IL-52621 Ramat Gan, Israel. EM ramit.ravona@sheba.health.gov.il RI Tanne, David/F-2560-2010 OI Tanne, David/0000-0002-6699-2220 FU American Federation for Aging Research (AFAR) [NIRG-11-205083]; NIA [R01 AG034087, NIA-AG02219]; Helen Bader Foundation; Leroy Schecter Foundation; National Institute of Aging [P01-AG02219]; United States Department of Veterans Affairs FX This study was supported by the American Federation for Aging Research (AFAR), Young investigator award 2011 and NIRG-11-205083 Alzheimer's Association, 2012 to Dr. Ravona-Springer, NIA grant R01 AG034087 to Dr. Beeri, NIA-AG02219 (VH), the Helen Bader Foundation and the Irma T. Hirschl Scholar Award as well as the Leroy Schecter Foundation Award to Dr. Beeri, National Institute of Aging grant P01-AG02219 (to Mary Sano), a Merit Award to Dr. Silverman from the United States Department of Veterans Affairs. NR 46 TC 0 Z9 0 U1 1 U2 2 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 2015 VL 44 IS 2 BP 687 EP 693 DI 10.3233/JAD-141197 PG 7 WC Neurosciences SC Neurosciences & Neurology GA AZ6WC UT WOS:000348357600029 PM 25352451 ER PT J AU Lo, WK Burakoff, R Goldberg, HJ Feldman, N Chan, WW AF Lo, Wai-Kit Burakoff, Robert Goldberg, Hilary J. Feldman, Natan Chan, Walter W. TI Pre-transplant impedance measures of reflux are associated with early allograft injury after lung transplantation SO JOURNAL OF HEART AND LUNG TRANSPLANTATION LA English DT Article DE gastroesophageal reflux disease; lung transplantation; esophageal multichannel intraluminal impedance; pre-transplant evaluation; early allograft injury; acute rejection; lymphocytic bronchiolitis ID BRONCHIOLITIS OBLITERANS SYNDROME; GASTROESOPHAGEAL-REFLUX; LYMPHOCYTIC BRONCHIOLITIS; ACUTE REJECTION; INTERNATIONAL-SOCIETY; ESOPHAGEAL MOTILITY; NORMAL VALUES; PH-IMPEDANCE; RISK-FACTORS; DISEASE AB BACKGROUND: Acid reflux has been associated with poorer outcomes after lung transplantation. Standard pre-transplant reflux assessment has not been universally adopted. Non-acid reflux may also induce a pulmonary inflammatory cascade, leading to acute and chronic rejection. Esophageal multichannel intraluminal impedance and pH testing (MII-pH) may be valuable in standard pre-transplant evaluation. We assessed the association between pre-transplant MIT-pH measures and early allograft injury in lung transplant patients. METHODS: This was a retrospective cohort study of lung transplant recipients who underwent pre-transplant MII-pH at a tertiary center from 2007 to 2012. Results from pre-transplant MII-pH, cardiopulmonary function testing, and results of biopsy specimen analysis of the transplanted lung were recorded. Time-to-event analyses were performed using Cox proportional hazards and Kaplan-Maier methods to assess the associations between MII-pH measures and development of acute rejection or lymphocytic bronchiolitis. RESULTS: Thirty patients (46.7% men; age, 54.2 years) met the inclusion criteria. Pre-transplant cardiopulmonary function and pulmonary diagnoses were similar between outcome groups. Prolonged bolus clearance (hazard ratio [HR], 4.11; 95% confidence interval [CI], 1.34-12.57; p = 0.01), increased total distal reflux episodes (HR, 4.80; 95% CI, 1.33-17.25; p = 0.02), and increased total proximal reflux episodes (HR, 4.43; 95% CI, 1.14-17.31; p = 0.03) were significantly associated with decreased time to early allograft injury. Kaplan-Meier curves also demonstrated differences in time to rejection by prolonged bolus clearance.(p = 0.01) and increased total distal reflux episodes (p = 0.01). Sub-group analysis including only patients with MII-pH performed off proton pump inhibitors (n = 24) showed similar results. CONCLUSIONS: Prolonged bolus clearance, increased total distal reflux episodes, and increased total proximal reflux episodes on pre-transplant MII-pH were associated with decreased time to early allograft injury after lung transplantation. Routine pre-transplant MII-pH may provide clinically relevant data regarding transplant outcomes and pen-transplant care. (C) 2015 International Society for Heart and Lung Transplantation. All rights reserved. C1 [Lo, Wai-Kit; Burakoff, Robert; Feldman, Natan; Chan, Walter W.] Brigham & Womens Hosp, Div Gastroenterol Hepatol & Endoscopy, Boston, MA 02115 USA. [Lo, Wai-Kit] Boston VA Healthcare Syst, Dept Gastroenterol, Boston, MA USA. [Lo, Wai-Kit; Burakoff, Robert; Goldberg, Hilary J.; Chan, Walter W.] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Goldberg, Hilary J.] Brigham & Womens Hosp, Div Pulm & Crit Care Med, Boston, MA 02115 USA. RP Chan, WW (reprint author), Brigham & Womens Hosp, Div Gastroenterol, 75 Francis St, Boston, MA 02115 USA. EM wwchan@partners.org OI Lo, Wai-Kit/0000-0002-1526-352X NR 40 TC 6 Z9 6 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1053-2498 EI 1557-3117 J9 J HEART LUNG TRANSPL JI J. Heart Lung Transplant. PD JAN PY 2015 VL 34 IS 1 BP 26 EP 35 DI 10.1016/j.healun.2014.09.005 PG 10 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery; Transplantation SC Cardiovascular System & Cardiology; Respiratory System; Surgery; Transplantation GA AZ5PW UT WOS:000348273400003 PM 25444368 ER PT J AU Speicher, PJ Ganapathi, AM Englum, BR Gulack, BC Osho, AA Hirji, SA Castleberry, AW Snyder, LD Davis, RD Hartwig, MG AF Speicher, Paul. J. Ganapathi, Asvin M. Englum, Brian R. Gulack, Brian C. Osho, Asishana A. Hirji, Sameer A. Castleberry, Anthony W. Snyder, Laurie D. Davis, R. Duane Hartwig, Matthew G. TI Single-lung transplantation in the United States: What happens to the other lung? SO JOURNAL OF HEART AND LUNG TRANSPLANTATION LA English DT Article DE single-lung transplantation; resource utilization; donor allocation ID OBSTRUCTIVE PULMONARY-DISEASE; DONOR SELECTION; MANAGEMENT; SURVIVAL; REGISTRY AB BACKGROUND: This study assessed treatment patterns and examined organ utilization in the setting of single-lung transplantation (SLT). METHODS: The United Network for Organ Sharing database was queried for all SLTs performed from 1987 to 2011. Trends in utilization of the second donor lung were assessed, both from recipient and donor perspectives. Donors were stratified into 2 groups: those donating both lungs and those donating only 1 lung. Independent predictors of using only 1 donor lung were identified using multivariable logistic regression. RESULTS: We identified 10,361 SLTs originating from 7,232 unique donors. Of these donors, both lungs were used in only 3,129 (43.3%), resulting in more than 200 second donor lungs going unused annually since 2005, with no significant increase in use over time (p = 0.95). After adjustment, donor characteristics predicting the second donor lung going unused included B/AB blood groups (adjusted odds ratio [AOR]: 1.69 and 2.62, respectively; p < 0.001), smaller body surface area (AOR, 1.30; p = 0.02), lower donor partial pressure of arterial oxygen (AOR, 0.90 per 50 mm Hg increase; p < 0.001), pulmonary infection (AOR, 1.15; p = 0.04), extended criteria donor Status (AOR, 1.66; p < 0.001), and death caused by head trauma (AOR, 1.57; p < 0.001) or anoxia (AOR, 1.53; p = 0.001). CONCLUSIONS: Among donors for SLT, less than half of all cases led to use of the second donor lung. Although anatomic, infectious, or other pathophysiologic issues prohibit 100% utilization, more aggressive donor matching efforts may be a simple method of increasing the utilization of this scarce resource, particularly for less common blood types. (C) 2015 International Society for Heart and Lung Transplantation. All rights reserved. C1 [Speicher, Paul. J.; Ganapathi, Asvin M.; Englum, Brian R.; Gulack, Brian C.; Castleberry, Anthony W.; Davis, R. Duane; Hartwig, Matthew G.] Duke Univ, Med Ctr, Dept Surg, Durham, NC 27710 USA. [Osho, Asishana A.] Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. [Hirji, Sameer A.] Duke Univ, Sch Med, Durham, NC 27710 USA. [Snyder, Laurie D.] Duke Univ, Med Ctr, Dept Med, Durham, NC 27710 USA. RP Speicher, PJ (reprint author), Duke Univ, Med Ctr, Campus Box 3443, Durham, NC 27710 USA. EM paul.speicher@duke.edu FU National Institutes of Health-funded Cardiothoracic Surgery Trials Network [5U01-HL-088953-05] FX This work was supported by the National Institutes of Health-funded Cardiothoracic Surgery Trials Network (5U01-HL-088953-05; M.G.H.). NR 15 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 1053-2498 EI 1557-3117 J9 J HEART LUNG TRANSPL JI J. Heart Lung Transplant. PD JAN PY 2015 VL 34 IS 1 BP 36 EP 42 DI 10.1016/j.healun.2014.08.018 PG 7 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery; Transplantation SC Cardiovascular System & Cardiology; Respiratory System; Surgery; Transplantation GA AZ5PW UT WOS:000348273400004 PM 25305097 ER PT J AU Choi, HR Kwon, YM AF Choi, Ho-Rim Kwon, Young-Min TI Calf swelling associated with a long-standing total knee arthroplasty SO JOURNAL OF ORTHOPAEDIC SCIENCE LA English DT Article ID DISSECTING POPLITEAL CYST; PATELLAR COMPONENT; WEAR DEBRIS; MIMICKING; FAILURE; MASS C1 [Choi, Ho-Rim; Kwon, Young-Min] Massachusetts Gen Hosp, Dept Orthopaed Surg, Harris Orthopaed Lab, Boston, MA 02114 USA. RP Choi, HR (reprint author), Massachusetts Gen Hosp, Dept Orthopaed Surg, Harris Orthopaed Lab, 55 Fruit St,GRJ-1126, Boston, MA 02114 USA. EM choinagoya@yahoo.co.kr FU MAKO FX No benefits in any form have been received from a commercial party related directly or indirectly to the subject of this article. The institution of one or more of the authors (HRC, YMK) has received funding from the MAKO for participation in review activities such as data monitoring boards, statistical analysis, end point committees, and the like. NR 11 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER JAPAN KK PI TOKYO PA CHIYODA FIRST BLDG EAST, 3-8-1 NISHI-KANDA, CHIYODA-KU, TOKYO, 101-0065, JAPAN SN 0949-2658 EI 1436-2023 J9 J ORTHOP SCI JI J. Orthop. Sci. PD JAN PY 2015 VL 20 IS 1 BP 209 EP 212 DI 10.1007/s00776-013-0425-y PG 4 WC Orthopedics SC Orthopedics GA AZ6CY UT WOS:000348307300028 PM 23779270 ER PT J AU Wang, C Du, XL Yang, R Liu, J Xu, D Shi, JD Chen, LF Shao, R Fan, GW Gao, XM Tian, G Zhu, Y Zhang, J AF Wang, Chao Du, Xiaoling Yang, Rui Liu, Jie Xu, Da Shi, Jiandang Chen, Linfeng Shao, Rui Fan, Guanwei Gao, Xiumei Tian, Guo Zhu, Yan Zhang, Ju TI The prevention and treatment effects of tanshinone IIA on oestrogen/androgen-induced benign prostatic hyperplasia in rats SO JOURNAL OF STEROID BIOCHEMISTRY AND MOLECULAR BIOLOGY LA English DT Article DE Benign prostatic hyperplasia; Tanshinone IIA; Androgen receptor; Oestrogen receptor alpha; Cyclins ID SALVIA-MILTIORRHIZA BUNGE; ESTROGEN-RECEPTOR-ALPHA; SMOOTH-MUSCLE-CELLS; CANCER-CELLS; ANDROGEN RECEPTOR; STROMAL CELLS; ANTICANCER ACTIVITY; GROWTH-INHIBITION; BREAST-CANCER; CYCLIN D1 AB Benign prostatic hyperplasia (BPH) is one of the major diseases of the urinary system in elderly men. Tanshinone IIA (Tan IIA) is the active ingredient extracted from the traditional Chinese medicine Salvia, and it has effects of anti-oxidation, anti-inflammation, vascular smooth muscle relaxation and tumour growth inhibition. The present study aimed to investigate the therapeutic potential of Tan IIA in the prevention and treatment of BPH. In a rat model of oestradiol/testosterone-induced BPH, Tan IIA inhibited the increase in the thickness of the pen-glandular smooth muscle layer, suppressed the expression of proliferating cell nuclear antigen (PCNA) in both prostate epithelial cells and stromal cells, downregulated the expression of androgen receptor (AR), oestrogen receptor alpha (ER alpha), cyclin B1 (CCNB1) and cyclin D1 (CCND1), and effectively prevented the development of the disorder. In vitro, Tan IIA inhibited the proliferation of human prostate stromal cell line WPMY-1 and epithelial cell line RWPE-1 in a dose- and time-dependent manner. In WPMY-1 cells, Tan IIA treatment arrested the cell cycle at the G2/ M phase and downregulated the expression of CCNB1. However, in RWPE-1 cells, Tan IIA treatment arrested cell cycle at the G0/G1 phase and reduced the expression of CCND1. Tan IIA also reduced the expression of ER alpha and AR in WPMY-1 and RWPE-1 cells. These results suggest that Tan IIA can inhibit the growth of prostate stromal and epithelial cells both in vivo and in vitro by a mechanism that may involve arresting the cell cycle and downregulating ER alpha and AR expression. (C) 2014 Elsevier Ltd. All rights reserved. C1 [Wang, Chao; Du, Xiaoling; Yang, Rui; Xu, Da; Shi, Jiandang; Shao, Rui; Tian, Guo; Zhang, Ju] Nankai Univ, Coll Life Sci, Dept Biochem & Mol Biol, Bioact Mat Key Lab,Minist Educ, Tianjin 300071, Peoples R China. [Liu, Jie; Fan, Guanwei; Gao, Xiumei; Zhu, Yan] Tianjin Univ Tradit Chinese Med, Tianjin State Key Lab Modern Chinese Med, Tianjin 300193, Peoples R China. [Chen, Linfeng] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02445 USA. RP Shi, JD (reprint author), Nankai Univ, Coll Life Sci, Dept Biochem & Mol Biol, Bioact Mat Key Lab,Minist Educ, Tianjin 300071, Peoples R China. EM shijd@nankai.edu.cn; zhangju@nankai.edu.cn FU National Natural Science Foundation of China [81370859]; National Basic Research Programs (973 Programs) [2010CB945003, 2012CB723500]; Tianjin Municipal Science and Technology Commission [12ZCDZSY17000]; 111 Project [B08011] FX This research was funded by the National Natural Science Foundation of China, grant no. 81370859; the National Basic Research Programs (973 Programs), grants no. 2010CB945003 and 2012CB723500; the Tianjin Municipal Science and Technology Commission, grant no. 12ZCDZSY17000; and The 111 Project, grant no. B08011. NR 55 TC 7 Z9 8 U1 1 U2 9 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0960-0760 J9 J STEROID BIOCHEM JI J. Steroid Biochem. Mol. Biol. PD JAN PY 2015 VL 145 BP 28 EP 37 DI 10.1016/j.jsbmb.2014.09.026 PG 10 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA AY7YJ UT WOS:000347771400004 PM 25290459 ER PT J AU Cheng, TM Freund, KM Winter, M Orlander, JD AF Cheng, Teresa M. Freund, Karen M. Winter, Michael Orlander, Jay D. TI Limited Adoption of Current Guidelines for Clinical Breast Examination by Primary Care Physician Educators SO JOURNAL OF WOMENS HEALTH LA English DT Article ID CANCER; MAMMOGRAPHY; PERFORMANCE; EXAM AB Background: In 2004, the CDC and the American Cancer Society (ACS) published performance guidelines recommending a validated method of clinical breast exams (CBE) using the vertical strips method (VSM) along with other key exam components. We examined the use of the VSM by academic medicine physicians and identified predictor variables for its adoption. Methods: Clinician educators in the Society of General Internal Medicine (SGIM) and physicians in the Society of Teachers of Family Medicine (STFM) were administered web-based surveys on CBE practices in 2009. Results: A total of 1,772 (42%) physicians responded. Only 40% of respondents reported using the VSM, compared with 53% using the circular search method. Variables and their odds ratios (ORs) associated with an increase adoption of the VSM were having a primary teaching hospital affiliation (OR 1.4 [1.1, 1.9]), having taken a course on breast health or breast cancer in the past 5 years (OR 1.5 [1.1, 2.0]), and having completed residency in the past 5 years (OR 2.3 [1.6, 3.4]) and/or 10-15 years (OR 1.6 [1.2, 2.2]) compared to more than 15 years. The extent of teaching responsibilities was not associated with adoption of the VSM. Conclusions: A majority of physician responders highly involved in education of students and residents continue to practice methods of CBE that do not reflect the current guidelines. Faculty development and training on updated CBE practices may accelerate adoption of guideline-recommended care. C1 [Cheng, Teresa M.; Freund, Karen M.] Boston Univ, Sch Med, Div Gen Internal Med, Boston, MA 01118 USA. [Freund, Karen M.] Tufts Univ, Sch Med, Inst Clin Res & Hlth Policy Studies, Boston, MA 02111 USA. [Winter, Michael] Boston Univ, Sch Publ Hlth, Data Coordinating Ctr, Boston, MA 01118 USA. [Orlander, Jay D.] Boston Univ, Sch Med, Dept Med, Boston, MA 01118 USA. [Orlander, Jay D.] VA Boston HealthCare Syst, West Roxbury, MA USA. RP Freund, KM (reprint author), Boston Univ, Sch Med, Div Gen Internal Med, 801 Massachusetts Ave,2nd Floor, Boston, MA 01118 USA. EM tmcheng@bu.edu NR 24 TC 1 Z9 1 U1 1 U2 2 PU MARY ANN LIEBERT, INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1540-9996 EI 1931-843X J9 J WOMENS HEALTH JI J. Womens Health PD JAN 1 PY 2015 VL 24 IS 1 BP 11 EP 17 DI 10.1089/jwh.2014.4772 PG 7 WC Public, Environmental & Occupational Health; Medicine, General & Internal; Obstetrics & Gynecology; Women's Studies SC Public, Environmental & Occupational Health; General & Internal Medicine; Obstetrics & Gynecology; Women's Studies GA AZ6JC UT WOS:000348325100003 PM 25405388 ER PT J AU Bakhoum, SF Kabeche, L Wood, MD Laucius, CD Qu, D Laughney, AM Reynolds, GE Louie, RJ Phillips, J Chan, DA Zaki, BI Murnane, JP Petritsch, C Compton, DA AF Bakhoum, Samuel F. Kabeche, Lilian Wood, Matthew D. Laucius, Christopher D. Qu, Dian Laughney, Ashley M. Reynolds, Gloria E. Louie, Raymond J. Phillips, Joanna Chan, Denise A. Zaki, Bassem I. Murnane, John P. Petritsch, Claudia Compton, Duane A. TI Numerical chromosomal instability mediates susceptibility to radiation treatment SO NATURE COMMUNICATIONS LA English DT Article ID INDUCED CELL-DEATH; EXTRA CENTROSOMES; MIS-SEGREGATION; DNA; MITOSIS; CANCER; FRACTIONATION; ANEUPLOIDY; MECHANISM; SENSITIZERS AB The exquisite sensitivity of mitotic cancer cells to ionizing radiation (IR) underlies an important rationale for the widely used fractionated radiation therapy. However, the mechanism for this cell cycle-dependent vulnerability is unknown. Here we show that treatment with IR leads to mitotic chromosome segregation errors in vivo and long-lasting aneuploidy in tumour-derived cell lines. These mitotic errors generate an abundance of micronuclei that predispose chromosomes to subsequent catastrophic pulverization thereby independently amplifying radiation-induced genome damage. Experimentally suppressing whole-chromosome missegregation reduces downstream chromosomal defects and significantly increases the viability of irradiated mitotic cells. Further, orthotopically transplanted human glioblastoma tumours in which chromosome missegregation rates have been reduced are rendered markedly more resistant to IR, exhibiting diminished markers of cell death in response to treatment. This work identifies a novel mitotic pathway for radiation-induced genome damage, which occurs outside of the primary nucleus and augments chromosomal breaks. This relationship between radiation treatment and whole-chromosome missegregation can be exploited to modulate therapeutic response in a clinically relevant manner. C1 [Bakhoum, Samuel F.] Mem Sloan Kettering Canc Ctr, Dept Radiat Oncol, New York, NY 10065 USA. [Kabeche, Lilian; Laucius, Christopher D.; Compton, Duane A.] Geisel Sch Med Dartmouth, Dept Biochem, Hanover, NH 03755 USA. [Kabeche, Lilian; Laucius, Christopher D.; Compton, Duane A.] Geisel Sch Med Dartmouth, Norris Cotton Canc Ctr, Lebanon, NH 03756 USA. [Wood, Matthew D.] Univ Calif San Francisco, Dept Pathol, San Francisco, CA 94143 USA. [Qu, Dian; Phillips, Joanna; Petritsch, Claudia] Univ Calif San Francisco, Dept Neurol Surg, San Francisco, CA 94143 USA. [Qu, Dian; Phillips, Joanna; Petritsch, Claudia] Univ Calif San Francisco, Brain Tumor Res Ctr, San Francisco, CA 94143 USA. [Qu, Dian; Phillips, Joanna; Petritsch, Claudia] Univ Calif San Francisco, Helen Diller Comprehens Canc Ctr, San Francisco, CA 94143 USA. [Laughney, Ashley M.] Harvard Univ, Sch Med, Dept Radiol, Ctr Syst Biol,Massachusetts Gen Hosp, Boston, MA 02114 USA. [Reynolds, Gloria E.; Louie, Raymond J.; Chan, Denise A.; Murnane, John P.] Univ Calif San Francisco, Dept Radiat Oncol, San Francisco, CA 94143 USA. [Zaki, Bassem I.] Geisel Sch Med, Sect Radiat Oncol, Dept Med, Lebanon, NH 03756 USA. RP Bakhoum, SF (reprint author), Mem Sloan Kettering Canc Ctr, Dept Radiat Oncol, 1275 York Ave, New York, NY 10065 USA. EM samuel.bakhoum@gmail.com OI Bakhoum, Samuel/0000-0002-4779-8422 FU National Institutes of Health [R37GM051542, R01GM008704, R01CA120205, R01CA164746, R01NS080619]; John H. Copenhaver Jr and William H. Thomas, MD Junior Fellowship; Hitchcock-Foundation [250-4041]; RSNA [1304] FX We thank Bernardo Orr, Alan C. Hartford, Ethan Dmitrosvky and Hal Swartz (Dartmouth College), Mathieu Bakhoum (University of Texas Medical Branch), Giulio Genovese (Broad Institute of Harvard and MIT), Jeffrey Guenette (Harvard Medical School), Daphne Haas-Kogan (University of California San Francisco), Barry Rosenstein (Mount Sinai School of Medicine) and members of the Murnane (UCSF) and Compton (Dartmouth) Laboratories for critical feedback. This study was supported by the following grants: R37GM051542 (D. A. Compton), R01GM008704 (L.K.), R01CA120205 (J.P.M., G.E.R.) R01CA164746 and R01NS080619 (C.P., D.Q.) from the National Institutes of Health, and the John H. Copenhaver Jr and William H. Thomas, MD 1952 Junior Fellowship (L.K.), Hitchcock-Foundation 250-4041 and RSNA 1304 (S.B.). NR 44 TC 7 Z9 7 U1 2 U2 7 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 2015 VL 6 AR 5990 DI 10.1038/ncomms6990 PG 10 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA CA3MY UT WOS:000348812100008 PM 25606712 ER PT J AU The, I Ruijtenberg, S Bouchet, BP Cristobal, A Prinsen, MBW van Mourik, T Koreth, J Xu, HH Heck, AJR Akhmanova, A Cuppen, E Boxem, M Munoz, J van den Heuvel, S AF The, Inge Ruijtenberg, Suzan Bouchet, Benjamin P. Cristobal, Alba Prinsen, Martine B. W. van Mourik, Tim Koreth, John Xu, Huihong Heck, Albert J. R. Akhmanova, Anna Cuppen, Edwin Boxem, Mike Munoz, Javier van den Heuvel, Sander TI Rb and FZR1/Cdh1 determine CDK4/6-cyclin D requirement in C. elegans and human cancer cells SO NATURE COMMUNICATIONS LA English DT Article ID ANAPHASE-PROMOTING COMPLEX; CYCLIN-DEPENDENT KINASES; HUMAN BREAST-CANCER; CAENORHABDITIS-ELEGANS; S-PHASE; UBIQUITIN LIGASE; MITOTIC CYCLINS; DISTINCT ROLES; PERSISTS UNTIL; PROTEOLYSIS AB Cyclin-dependent kinases 4 and 6 (CDK4/6) in complex with D-type cyclins promote cell cycle entry. Most human cancers contain overactive CDK4/6-cyclin D, and CDK4/6-specific inhibitors are promising anti-cancer therapeutics. Here, we investigate the critical functions of CDK4/6-cyclin D kinases, starting from an unbiased screen in the nematode Caenorhabditis elegans. We found that simultaneous mutation of lin-35, a retinoblastoma (Rb)-related gene, and fzr-1, an orthologue to the APC/C co-activator Cdh1, completely eliminates the essential requirement of CDK4/6-cyclin D (CDK-4/CYD-1) in C. elegans. CDK-4/CYD-1 phosphorylates specific residues in the LIN-35 Rb spacer domain and FZR-1 amino terminus, resembling inactivating phosphorylations of the human proteins. In human breast cancer cells, simultaneous knockdown of Rb and FZR1 synergistically bypasses cell division arrest induced by the CDK4/6-specific inhibitor PD-0332991. Our data identify FZR1 as a candidate CDK4/6-cyclin D substrate and point to an APC/C-FZR1 activity as an important determinant in response to CDK4/6-inhibitors. C1 [The, Inge; Ruijtenberg, Suzan; Bouchet, Benjamin P.; Prinsen, Martine B. W.; van Mourik, Tim; Akhmanova, Anna; Boxem, Mike; van den Heuvel, Sander] Univ Utrecht, Fac Sci, Dept Biol, NL-3584 CH Utrecht, Netherlands. [Cristobal, Alba; Heck, Albert J. R.; Munoz, Javier] Univ Utrecht, Bijvoet Ctr Biomol Res, Biomol Mass Spectrometry & Prote Grp, NL-3584 CH Utrecht, Netherlands. [Cristobal, Alba; Heck, Albert J. R.; Munoz, Javier] Univ Utrecht, Utrecht Inst Pharmaceut Sci, NL-3584 CH Utrecht, Netherlands. [Koreth, John] Dana Farber Canc Inst, Boston, MA 02215 USA. [Xu, Huihong] Boston Univ, Sch Med, Dept Pathol & Lab Med, Boston, MA 02118 USA. [Xu, Huihong] Boston Med Ctr, Boston, MA 02118 USA. [Cuppen, Edwin] Hubrecht Inst, NL-3584 CT Utrecht, Netherlands. RP van den Heuvel, S (reprint author), Univ Utrecht, Fac Sci, Dept Biol, Padualaan 8, NL-3584 CH Utrecht, Netherlands. EM s.j.l.vandenHeuvel@uu.nl RI Munoz, Javier/I-4891-2012; Cuppen, Edwin/H-2389-2016; van den Heuvel, Sander/B-8892-2011; Boxem, Mike/B-8857-2011 OI Munoz, Javier/0000-0003-3288-3496; Cuppen, Edwin/0000-0002-0400-9542; Boxem, Mike/0000-0003-3966-4173 FU NIH Office of Research Infrastructure Programs [P40 OD010440]; Netherlands Organisation for Scientific Research (NWO) [819.02.016]; Marie Curie Intra-European Fellowships for Career Development [273872]; NWO ALW; NWO [H01.205] FX We thank E. Kipreos, A. Hyman and A. Pozniakovsky for reagents; A. Thomas for critically reading the manuscript; and members of the van den Heuvel and Boxem groups for help and critical comments. Several strains were provided by the CGC, which is funded by NIH Office of Research Infrastructure Programs (P40 OD010440). This work is part of research programme 819.02.016, financed by the Netherlands Organisation for Scientific Research (NWO). B.P.B. was supported by a Marie Curie Intra-European Fellowships for Career Development 273872, NWO ALW provided support for TvM (CGDB graduate programme grant from NWO H01.205), M.B. (Innovational Research Incentives Scheme VIDI grant 864.09.008) and A. A. (ALW VICI 865.08.002). We acknowledge the PRIDE team for proteomics data dissemination. NR 58 TC 7 Z9 7 U1 1 U2 12 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 2015 VL 6 AR 5906 DI 10.1038/ncomms6906 PG 11 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA CA2MG UT WOS:000348741900004 PM 25562820 ER PT J AU Wang, LZ Liu, RH Ye, PY Wong, CS Chen, GY Zhou, PH Sakabe, K Zheng, X Wu, W Zhang, P Jiang, TJ Bassetti, MF Jube, S Sun, Y Zhang, YP Zheng, P Liu, Y AF Wang, Lizhong Liu, Runhua Ye, Peiying Wong, Chunshu Chen, Guo-Yun Zhou, Penghui Sakabe, Kaoru Zheng, Xincheng Wu, Wei Zhang, Peng Jiang, Taijiao Bassetti, Michael F. Jube, Sandro Sun, Yi Zhang, Yanping Zheng, Pan Liu, Yang TI Intracellular CD24 disrupts the ARF-NPM interaction and enables mutational and viral oncogene-mediated p53 inactivation SO NATURE COMMUNICATIONS LA English DT Article ID INDEPENDENT PROGNOSTIC MARKER; TUMOR-SUPPRESSOR; PROSTATE-CANCER; CARCINOMA-CELLS; RETINOBLASTOMA-PROTEIN; MULTIPLE-SCLEROSIS; CERVICAL-CARCINOMA; P-SELECTIN; IN-VIVO; MOUSE AB CD24 is overexpressed in nearly 70% human cancers, whereas TP53 is the most frequently mutated tumour-suppressor gene that functions in a context-dependent manner. Here we show that both targeted mutation and short hairpin RNA (shRNA) silencing of CD24 retard the growth, progression and metastasis of prostate cancer. CD24 competitively inhibits ARF binding to NPM, resulting in decreased ARF, increase MDM2 and decrease levels of p53 and the p53 target p21/CDKN1A. CD24 silencing prevents functional inactivation of p53 by both somatic mutation and viral oncogenes, including the SV40 large T antigen and human papilloma virus 16 E6-antigen. In support of the functional interaction between CD24 and p53, in silico analyses reveal that TP53 mutates at a higher rate among glioma and prostate cancer samples with higher CD24 mRNA levels. These data provide a general mechanism for functional inactivation of ARF and reveal an important cellular context for genetic and viral inactivation of TP53. C1 [Wang, Lizhong; Liu, Runhua] Univ Alabama Birmingham, Dept Genet, Birmingham, AL 35294 USA. [Ye, Peiying; Wong, Chunshu; Chen, Guo-Yun; Sakabe, Kaoru; Jube, Sandro; Zheng, Pan; Liu, Yang] Childrens Natl Med Ctr, Childrens Res Inst, Ctr Canc & Immunol Res, Washington, DC 20010 USA. [Ye, Peiying; Wong, Chunshu; Chen, Guo-Yun; Sakabe, Kaoru; Jube, Sandro; Zheng, Pan; Liu, Yang] Childrens Natl Med Ctr, Childrens Res Inst, Div Pathol, Washington, DC 20010 USA. [Ye, Peiying] Univ Michigan, Sch Med, Program Immunol, Integrated Biomed Grad Program, Ann Arbor, MI 48103 USA. [Zhou, Penghui] Harvard Univ, Sch Med, Dept Pathol, Dana Farber Canc Inst, Boston, MA 02115 USA. [Zheng, Xincheng; Wu, Wei] OncoImmune Inc, Rockville, MD 20852 USA. [Zhang, Peng; Jiang, Taijiao] Chinese Acad Sci, Inst Biophys, Beijing 100101, Peoples R China. [Bassetti, Michael F.; Sun, Yi] Univ Michigan, Sch Med, Dept Radiat Oncol, Ann Arbor, MI 48105 USA. [Zhang, Yanping] Univ N Carolina, Dept Radiat Oncol, Chapel Hill, NC 27599 USA. [Zhang, Yanping] Univ N Carolina, Lineberger Comprehens Canc Ctr, Chapel Hill, NC 27599 USA. RP Zheng, P (reprint author), Univ Alabama Birmingham, Dept Genet, Birmingham, AL 35294 USA. EM lwang12@uab.edu; pzheng@cnmc.org; yaliu@cnmc.org OI Zhang, Peng/0000-0002-6218-1885; Zheng, Pan/0000-0003-2598-3544 FU National Institutes of Health [AI64350, CA171972, CA58033, AG036690, R21CA164688, U54 CA118948]; Department of Defense [DOD-W81XWH-10-PCRP-SIDA]; NIH [P50 CA093990] FX This study was supported by grants from the National Institutes of Health (AI64350, CA171972 and CA58033 and to Y.L., AG036690 to P.Z., R21CA164688 and a pilot grant from U54 CA118948 to L.W.) and the Department of Defense (DOD-W81XWH-10-PCRP-SIDA to Y.L.). We thank the Department of Radiology at the University of Michigan for the use of the Center for Molecular Imaging, which is supported in part by NIH grant P50 CA093990. NR 70 TC 11 Z9 12 U1 1 U2 6 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 2015 VL 6 DI 10.1038/ncomms6909 PG 15 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA CA2MG UT WOS:000348741900007 PM 25600590 ER PT J AU Yoda, A Adelmant, G Tamburini, J Chapuy, B Shindoh, N Yoda, Y Weigert, O Kopp, N Wu, SC Kim, SS Liu, H Tivey, T Christie, AL Elpek, KG Card, J Gritsman, K Gotlib, J Deininger, MW Makishima, H Turley, SJ Javidi-Sharifi, N Maciejewski, JP Jaiswal, S Ebert, BL Rodig, SJ Tyner, JW Marto, JA Weinstock, DM Lane, AA AF Yoda, Akinori Adelmant, Guillaume Tamburini, Jerome Chapuy, Bjoern Shindoh, Nobuaki Yoda, Yuka Weigert, Oliver Kopp, Nadja Wu, Shuo-Chieh Kim, Sunhee S. Liu, Huiyun Tivey, Trevor Christie, Amanda L. Elpek, Kutlu G. Card, Joseph Gritsman, Kira Gotlib, Jason Deininger, Michael W. Makishima, Hideki Turley, Shannon J. Javidi-Sharifi, Nathalie Maciejewski, Jaroslaw P. Jaiswal, Siddhartha Ebert, Benjamin L. Rodig, Scott J. Tyner, Jeffrey W. Marto, Jarrod A. Weinstock, David M. Lane, Andrew A. TI Mutations in G protein beta subunits promote transformation and kinase inhibitor resistance SO NATURE MEDICINE LA English DT Article ID ACUTE LYMPHOBLASTIC-LEUKEMIA; DENDRITIC CELL NEOPLASM; GAMMA-SUBUNITS; MYELODYSPLASTIC SYNDROMES; COUPLED RECEPTORS; GENOME; CANCER; ACTIVATION; LANDSCAPE; MELANOMA AB Activating mutations in genes encoding G protein alpha (G alpha) subunits occur in 4-5% of all human cancers(1), but oncogenic alterations in G beta subunits have not been defined. Here we demonstrate that recurrent mutations in the G beta proteins GNB1 and GNB2 confer cytokine-independent growth and activate canonical G protein signaling. Multiple mutations in GNB1 affect the protein interface that binds G alpha subunits as well as downstream effectors and disrupt G alpha interactions with the dimer G beta gamma Different mutations in G beta proteins clustered partly on the basis of lineage; for example, all 11 GNB1 K57 mutations were in myeloid neoplasms, and seven of eight GNB1 180 mutations were in B cell neoplasms. Expression of patient-derived GNB1 variants in Cdkn2a-deficient mouse bone marrow followed by transplantation resulted in either myeloid or B cell malignancies. In vivo treatment with the dual PI3K-mTOR inhibitor BEZ235 suppressed GNB1-induced signaling and markedly increased survival. In several human tumors, mutations in the gene encoding GNB1 co-occurred with oncogenic kinase alterations, including the BCR-ABL fusion protein, the V617F substitution in JAK2 and the V600K substitution in BRAF. Coexpression of patient-derived GNB1 variants with these mutant kinases resulted in inhibitor resistance in each context. Thus, GNB1 and GNB2 alterations confer transformed and resistance phenotypes across a range of human tumors and may be targetable with inhibitors of G protein signaling. C1 [Yoda, Akinori; Tamburini, Jerome; Chapuy, Bjoern; Shindoh, Nobuaki; Yoda, Yuka; Kopp, Nadja; Wu, Shuo-Chieh; Kim, Sunhee S.; Liu, Huiyun; Tivey, Trevor; Christie, Amanda L.; Gritsman, Kira; Weinstock, David M.; Lane, Andrew A.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Adelmant, Guillaume; Card, Joseph; Marto, Jarrod A.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA. [Adelmant, Guillaume; Marto, Jarrod A.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Blais Prote Ctr, Boston, MA 02115 USA. [Shindoh, Nobuaki] Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA. [Weigert, Oliver] Astellas Pharma Inc, Drug Discovery Res, Tsukuba, Ibaraki, Japan. [Weigert, Oliver] Univ Munich, Dept Med 3, Munich, Germany. [Elpek, Kutlu G.; Turley, Shannon J.] Helmholtz Ctr, Munich, Germany. [Elpek, Kutlu G.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA. [Gotlib, Jason] Jounce Therapeut Inc, Cambridge, MA USA. [Deininger, Michael W.] Stanford Univ, Sch Med, Stanford Canc Inst, Dept Hematol, Stanford, CA USA. [Makishima, Hideki] Univ Utah, Huntsman Canc Inst, Div Hematol & Hematol Malignancies, Salt Lake City, UT USA. [Javidi-Sharifi, Nathalie; Tyner, Jeffrey W.] Cleveland Clin, Taussig Canc Inst, Dept Translat Hematol & Oncol Res, Cleveland, OH 44106 USA. [Jaiswal, Siddhartha; Rodig, Scott J.] Oregon Hlth & Sci Univ, Knight Canc Inst, Dept Cell Dev & Canc Biol, Portland, OR 97201 USA. [Jaiswal, Siddhartha; Ebert, Benjamin L.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Ebert, Benjamin L.; Weinstock, David M.] Brigham & Womens Hosp, Div Hematol, Boston, MA 02115 USA. Broad Inst, Cambridge, MA USA. RP Weinstock, DM (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, 44 Binney St, Boston, MA 02115 USA. EM dweinstock@partners.org; andrew_lane@dfci.harvard.edu FU Aplastic Anemia and MDS International Foundation; Edwards P. Evans Foundation; Max-Eder Program of the Deutsche Krebshilfe [110659]; Leukemia and Lymphoma Society; US National Institutes of Health NCI [1R01CA183947, 5R00CA151457]; V Foundation for Cancer Research; Gabrielle's Angel Foundation; Claudia Adams Barr Fund; American Cancer Society Research Scholar Grant; Stand Up To Cancer Innovative Research Grant; American Society of Hematology Scholar Award FX We thank T. Radimersld, T. Haferlach, L. Garraway, M. Walter and N. Wagle for contributing to the manuscript. We thank A. Hawkins and the Brigham and Women's Hospital Cytogenomics Core Facility for karyotyping. This research was supported by the Aplastic Anemia and MDS International Foundation (AT.), the Edwards P. Evans Foundation (A.Y.), the Max-Eder Program of the Deutsche Krebshilfe (#110659 to O.W), the Leukemia and Lymphoma Society (J.W.T.), US National Institutes of Health NCI (1R01CA183947 and 5R00CA151457 to J.W.T.), the V Foundation for Cancer Research (J.W.T.), Gabrielle's Angel Foundation for Cancer Research (J.W.T.), the Claudia Adams Barr Fund (A.Y. and D.M.W.), an American Cancer Society Research Scholar Grant (D.M.W.), a Stand Up To Cancer Innovative Research Grant (D.M.W.), and an American Society of Hematology Scholar Award (A.A.L.). NR 30 TC 10 Z9 10 U1 3 U2 8 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1078-8956 EI 1546-170X J9 NAT MED JI Nat. Med. PD JAN PY 2015 VL 21 IS 1 BP 71 EP 75 DI 10.1038/nm.3751 PG 5 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA AZ7OM UT WOS:000348408000015 PM 25485910 ER PT J AU Sabuncu, MR Konukoglu, E AF Sabuncu, Mert R. Konukoglu, Ender CA Alzheimer's Dis Neuroimaging TI Clinical Prediction from Structural Brain MRI Scans: A Large-Scale Empirical Study SO NEUROINFORMATICS LA English DT Article DE Image-based prediction; Computer aided diagnosis; Machine learning; MRI ID SUPPORT VECTOR MACHINE; MILD COGNITIVE IMPAIRMENT; VOXEL-BASED MORPHOMETRY; SURFACE-BASED ANALYSIS; ALZHEIMERS-DISEASE; FEATURE-SELECTION; PATTERN-CLASSIFICATION; CORTICAL SURFACE; HEALTHY CONTROLS; SCHIZOPHRENIA-PATIENTS AB Multivariate pattern analysis (MVPA) methods have become an important tool in neuroimaging, revealing complex associations and yielding powerful prediction models. Despite methodological developments and novel application domains, there has been little effort to compile benchmark results that researchers can reference and compare against. This study takes a significant step in this direction. We employed three classes of state-of-the-art MVPA algorithms and common types of structural measurements from brain Magnetic Resonance Imaging (MRI) scans to predict an array of clinically relevant variables (diagnosis of Alzheimer's, schizophrenia, autism, and attention deficit and hyperactivity disorder; age, cerebrospinal fluid derived amyloid-beta levels and mini-mental state exam score). We analyzed data from over 2,800 subjects, compiled from six publicly available datasets. The employed data and computational tools are freely distributed , making this the largest, most comprehensive, reproducible benchmark image-based prediction experiment to date in structural neuroimaging. Finally, we make several observations regarding the factors that influence prediction performance and point to future research directions. Unsurprisingly, our results suggest that the biological footprint (effect size) has a dramatic influence on prediction performance. Though the choice of image measurement and MVPA algorithm can impact the result, there was no universally optimal selection. Intriguingly, the choice of algorithm seemed to be less critical than the choice of measurement type. Finally, our results showed that cross-validation estimates of performance, while generally optimistic, correlate well with generalization accuracy on a new dataset. C1 [Sabuncu, Mert R.; Konukoglu, Ender] Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA 02129 USA. [Sabuncu, Mert R.] MIT, Comp Sci & Artificial Intelligence Lab, Cambridge, MA 02139 USA. RP Sabuncu, MR (reprint author), Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Bldg 149,13th St,Room 2301, Charlestown, MA 02129 USA. EM msabuncu@nmr.mgh.harvard.edu FU National Institute of Biomedical Imaging and Bioengineering (NIBIB), National Institutes of Health [P41EB015896]; AHAF (BrightFocus) Alzheimer's Disease pilot grant [AHAF A2012333]; NIH K25 grant [NIBIB 1K25EB013649-01]; National Center for Research Resources [U24 RR021382]; National Institute for Biomedical Imaging and Bioengineering [R01EB006758]; National Institute for Neurological Disorders and Stroke [R01 NS052585-01, 1R21NS072652-01, 1R01NS070963, R01NS083534]; Shared Instrumentation Grants [1S10RR023401, 1S10RR019307, 1S10RR023043]; NIH Blueprint for Neuroscience Research part of the multi-institutional Human Connectome Project [5U01-MH093765] FX This research was carried out in whole or in part at the Athinoula A. Martinos Center for Biomedical Imaging at the Massachusetts General Hospital, using resources provided by the Center for Functional Neuroimaging Technologies, P41EB015896, a P41 Biotechnology Resource Grant supported by the National Institute of Biomedical Imaging and Bioengineering (NIBIB), National Institutes of Health. Dr. Sabuncu received support from an AHAF (BrightFocus) Alzheimer's Disease pilot grant (AHAF A2012333), and an NIH K25 grant (NIBIB 1K25EB013649-01). Further support for this research was provided in part by the National Center for Research Resources (U24 RR021382), the National Institute for Biomedical Imaging and Bioengineering (R01EB006758), National Institute for Neurological Disorders and Stroke (R01 NS052585-01, 1R21NS072652-01, 1R01NS070963, R01NS083534), and was made possible by the resources provided by Shared Instrumentation Grants 1S10RR023401, 1S10RR019307, and 1S10RR023043. Additional support was provided by the NIH Blueprint for Neuroscience Research (5U01-MH093765), part of the multi-institutional Human Connectome Project. NR 85 TC 11 Z9 11 U1 2 U2 14 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DRIVE SUITE 208, TOTOWA, NJ 07512 USA SN 1539-2791 EI 1559-0089 J9 NEUROINFORMATICS JI Neuroinformatics PD JAN PY 2015 VL 13 IS 1 BP 31 EP 46 DI 10.1007/s12021-014-9238-1 PG 16 WC Computer Science, Interdisciplinary Applications; Neurosciences SC Computer Science; Neurosciences & Neurology GA AZ7UD UT WOS:000348422200004 PM 25048627 ER PT J AU Wells, TS Seelig, AD Ryan, MAK Jones, JM Hooper, TI Jacobson, IG Boyko, EJ AF Wells, Timothy S. Seelig, Amber D. Ryan, Margaret A. K. Jones, Jason M. Hooper, Tomoko I. Jacobson, Isabel G. Boyko, Edward J. TI Hearing loss associated with US military combat deployment SO NOISE & HEALTH LA English DT Article DE Combat disorders; hearing loss; military personnel ID TRAUMATIC BRAIN-INJURY; MILLENNIUM COHORT; SERVICE MEMBERS; NATIONAL-HEALTH; IMPULSE NOISE; ADULTS; PERSONNEL; RISK; POPULATION; IMPAIRMENT AB The objective of this study was to define the risk of hearing loss among US military members in relation to their deployment experiences. Data were drawn from the Millennium Cohort Study. Self-reported data and objective military service data were used to assess exposures and outcomes. Among all 48,540 participants, 7.5% self-reported new-onset hearing loss. Self-reported hearing loss showed moderate to substantial agreement (k = 0.57-0.69) with objective audiometric measures. New-onset hearing loss was associated with combat deployment (adjusted odds ratio [AOR] = 1.63, 95% confidence interval [CI] = 1.49-1.77), as well as male sex and older age. Among deployers, new-onset hearing loss was also associated with proximity to improvised explosive devices (AOR = 2.10, 95% CI = 1.62-2.73) and with experiencing a combat-related head injury (AOR = 6.88, 95% CI = 3.77-12.54). These findings have implications for health care and disability planning, as well as for prevention programs. C1 [Wells, Timothy S.] Adv Analyt Optum, Ann Arbor, MI USA. [Wells, Timothy S.] Adv Analyt Optum, San Diego, CA USA. [Seelig, Amber D.; Jacobson, Isabel G.] Naval Hlth Res Ctr, San Diego, CA USA. [Ryan, Margaret A. K.; Jones, Jason M.] Naval Hosp Camp Pendleton, San Diego, CA USA. [Hooper, Tomoko I.] Uniformed Serv Univ Hlth Sci, Dept Prevent Med & Biometr, Bethesda, MD 20814 USA. [Seelig, Amber D.; Boyko, Edward J.] VA Puget Sound Hlth Care Syst, Epidemiol Res & Informat Ctr, Seattle, WA USA. [Boyko, Edward J.] Univ Washington, Dept Med, Seattle, WA USA. RP Wells, TS (reprint author), 1839 Waverly Rd, Holt, MI USA. EM tmlbwells@wowway.com NR 48 TC 2 Z9 2 U1 3 U2 7 PU MEDKNOW PUBLICATIONS & MEDIA PVT LTD PI MUMBAI PA B-9, KANARA BUSINESS CENTRE, OFF LINK RD, GHAKTOPAR-E, MUMBAI, 400075, INDIA SN 1463-1741 EI 1998-4030 J9 NOISE HEALTH JI Noise Health PD JAN-FEB PY 2015 VL 17 IS 74 BP 34 EP 42 PG 9 WC Audiology & Speech-Language Pathology; Public, Environmental & Occupational Health SC Audiology & Speech-Language Pathology; Public, Environmental & Occupational Health GA AZ7EH UT WOS:000348381200005 PM 25599756 ER PT J AU Chabner, BA AF Chabner, Bruce A. TI Two Decades of The Oncologist SO ONCOLOGIST LA English DT Editorial Material C1 [Chabner, Bruce A.] Massachusetts Gen Hosp, Ctr Canc, Boston, MA USA. RP Chabner, BA (reprint author), 10 North Grove St,LRH 214, Boston, MA 02114 USA. EM bchabner@partners.org NR 1 TC 0 Z9 0 U1 0 U2 0 PU ALPHAMED PRESS PI DURHAM PA 318 BLACKWELL ST, STE 260, DURHAM, NC 27701-2884 USA SN 1083-7159 EI 1549-490X J9 ONCOLOGIST JI Oncologist PD JAN PY 2015 VL 20 IS 1 BP 1 EP 2 DI 10.1634/theoncologist.2014-0490 PG 2 WC Oncology SC Oncology GA AZ8IO UT WOS:000348459100001 PM 25589499 ER PT J AU Dizon, DS AF Dizon, Don S. TI Toward Eubiosia: Bridging Oncology and Palliative Care SO ONCOLOGIST LA English DT Editorial Material C1 [Dizon, Don S.] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Dizon, DS (reprint author), 55 Fruit St,Yawkey 9E, Boston, MA 02114 USA. EM ddizon@partners.org NR 0 TC 0 Z9 0 U1 0 U2 0 PU ALPHAMED PRESS PI DURHAM PA 318 BLACKWELL ST, STE 260, DURHAM, NC 27701-2884 USA SN 1083-7159 EI 1549-490X J9 ONCOLOGIST JI Oncologist PD JAN PY 2015 VL 20 IS 1 BP 5 EP 6 DI 10.1634/theoncologist.2014-0462 PG 2 WC Oncology SC Oncology GA AZ8IO UT WOS:000348459100003 PM 25492921 ER PT J AU Sikalidis, AK AF Sikalidis, Angelos K. TI Amino Acids and Immune Response: A Role for Cysteine, Glutamine, Phenylalanine, Tryptophan and Arginine in T-cell Function and Cancer? SO PATHOLOGY & ONCOLOGY RESEARCH LA English DT Review DE T-cell; Amino acids; Cysteine; Glutamine; Phenylalanine; Tryptophan; Arginine; Immune response; Signaling; Immunomodulation; Avidity ID INDOLEAMINE 2,3-DIOXYGENASE EXPRESSION; GENE-EXPRESSION; SUPPRESSOR-CELLS; OXIDATIVE-STRESS; DENDRITIC CELLS; PROTEIN-KINASE; IN-VIVO; METABOLISM; ACTIVATION; RECEPTOR AB While proteins are critical for immunity, T-cells constitute a critical component of adaptive immunity by clearing cancerous cells among other abnormal cells. However, cancer cells exhibit a potential to escape T-cell control by employing mechanisms not completely delineated. Interesting work has investigated how certain amino acids affect the proliferation rate of T-cells as well as their effectiveness in clearing tumors. The role of amino acids cysteine, glutamine, phenylalanine, tryptophan and arginine in immunomodulation and particularly regarding T-cell proliferation and activation is discussed. The redox balance is reported to affect T-cell proliferation via modulation of cysteine availability. In addition antigen presenting cells (APCs), similar to myeloid cells determine the availability of amino acids in the extracellular microenvironment affecting T-cell proliferation and activation. A better mechanistic understanding of T-cell function modulation via amino acid signaling or metabolic properties may be helpful towards optimization of adaptive immunity with implications for cancer prognosis and treatment. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Harvard Inst Med,Immunobiol Lab, Boston, MA 02115 USA. RP Sikalidis, AK (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Harvard Inst Med,Immunobiol Lab, 77 Ave Louis Pasteur, Boston, MA 02115 USA. EM angelos_sikalidis@dfci.harvard.edu NR 76 TC 13 Z9 14 U1 7 U2 27 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 1219-4956 EI 1532-2807 J9 PATHOL ONCOL RES JI Pathol. Oncol. Res. PD JAN PY 2015 VL 21 IS 1 BP 9 EP 17 DI 10.1007/s12253-014-9860-0 PG 9 WC Oncology; Pathology SC Oncology; Pathology GA AY8AL UT WOS:000347776700002 PM 25351939 ER PT J AU Baumer, FM Kamihara, J Gorman, MP AF Baumer, Fiona M. Kamihara, Junne Gorman, Mark P. TI Neuromyelitis Optica in an Adolescent After Bone Marrow Transplantation SO PEDIATRIC NEUROLOGY LA English DT Article DE myelitis; optic neuritis; neuromyelitis optica; bone marrow transplantation; stem cell transplant; acute myeloid leukemia ID STEM-CELL TRANSPLANTATION; IMMUNE-MEDIATED MYELOPATHY; VERSUS-HOST-DISEASE; AQUAPORIN-4; MYELITIS; ANTIBODY AB BACKGROUND: Central nervous system complications of bone marrow transplant are a common occurrence and the differential diagnosis is quite broad, including opportunistic infections, medications toxicities, graft versus host disease, and other autoimmune processes. PATIENT DESCRIPTION: We summarize previously reported cases of autoimmune myelitis in post-transplant patients and discuss a 17-year-old boy who presented with seronegative neuromyelitis optica after a bone marrow transplant for acute myeloid leukemia. Our patient had a marked improvement in symptoms after plasmapheresis. CONCLUSION: Including our patient, there have been at least eight cases of post-transplant autoimmune myelitis presented in the literature, and at least three of these are suspicious for neuromyelitis optica. Several of these patients had poor outcomes with persistent symptoms after the myelitis. Autoimmune processes such as neuromyelitis optica should be carefully considered in patients after transplant as aggressive treatment like early plasmapheresis may improve outcomes. C1 [Baumer, Fiona M.; Gorman, Mark P.] Harvard Univ, Sch Med, Dept Neurol, Boston Childrens Hosp, Boston, MA 02115 USA. [Kamihara, Junne] Harvard Univ, Sch Med, Dept Pediat Oncol, Div Hematol Oncol,Dana Farber Canc Inst, Boston, MA USA. RP Baumer, FM (reprint author), Boston Childrens Hosp, 300 Longwood Ave,Fegan 11, Boston, MA 02115 USA. EM Fiona.baumer@childrens.harvard.edu NR 11 TC 1 Z9 1 U1 1 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0887-8994 EI 1873-5150 J9 PEDIATR NEUROL JI Pediatr. Neurol. PD JAN PY 2015 VL 52 IS 1 BP 119 EP 124 DI 10.1016/j.pediatrneurol.2014.07.007 PG 6 WC Clinical Neurology; Pediatrics SC Neurosciences & Neurology; Pediatrics GA AZ7QA UT WOS:000348411800019 PM 25444090 ER PT J AU Rybin, D Doros, G Rosenheck, R Lew, R AF Rybin, Denis Doros, Gheorghe Rosenheck, Robert Lew, Robert TI The impact of missing data on the results of a schizophrenia study SO PHARMACEUTICAL STATISTICS LA English DT Article DE missing data; sensitivity analysis; Bayesian analysis; pattern mixture ID PATTERN-MIXTURE MODELS; RISPERIDONE; HALOPERIDOL; OLANZAPINE; TRIAL AB Missing data pose a serious challenge to the integrity of randomized clinical trials, especially of treatments for prolonged illnesses such as schizophrenia, in which long-term impact assessment is of great importance, but the follow-up rates are often no more than 50%. Sensitivity analysis using Bayesian modeling for missing data offers a systematic approach to assessing the sensitivity of the inferences made on the basis of observed data. This paper uses data from an 18-month study of veterans with schizophrenia to demonstrate this approach. Data were obtained from a randomized clinical trial involving 369 patients diagnosed with schizophrenia that compared long-acting injectable risperidone with a psychiatrist's choice of oral treatment. Bayesian analysis utilizing a pattern-mixture modeling approach was used to validate the reported results by detecting bias due to non-random patterns of missing data. The analysis was applied to several outcomes including standard measures of schizophrenia symptoms, quality of life, alcohol use, and global mental status. The original study results for several measures were confirmed against a wide range of patterns of non-random missingness. Robustness of the conclusions was assessed using sensitivity parameters. The missing data in the trial did not likely threaten the validity of previously reported results. Copyright (c) 2014 John Wiley & Sons, Ltd. C1 [Rybin, Denis; Doros, Gheorghe; Lew, Robert] Boston Univ, Boston, MA 02215 USA. [Rybin, Denis] VA Boston Healthcare Syst, Boston VA Res Inst, Boston, MA USA. [Doros, Gheorghe; Lew, Robert] VA Boston Healthcare Syst, Massachusetts Vet Epidemiol Res & Informat Ctr, Boston, MA USA. [Rosenheck, Robert] VA New England, Mental Illness Res Educ & Clin Ctr, West Haven, CT USA. [Rosenheck, Robert] Yale Univ, Sch Med, New Haven, CT USA. RP Rybin, D (reprint author), Boston Univ, Boston, MA 02215 USA. EM drybine@bu.edu OI Rybin, Denis/0000-0002-3657-4829 NR 16 TC 1 Z9 1 U1 1 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1539-1604 EI 1539-1612 J9 PHARM STAT JI Pharm. Stat. PD JAN-FEB PY 2015 VL 14 IS 1 BP 4 EP 10 DI 10.1002/pst.1651 PG 7 WC Pharmacology & Pharmacy; Statistics & Probability SC Pharmacology & Pharmacy; Mathematics GA AZ9FZ UT WOS:000348520200002 PM 25327503 ER PT J AU Katiyar, SK AF Katiyar, Santosh K. TI Proanthocyanidins from Grape Seeds Inhibit UV-Radiation-Induced Immune Suppression in Mice: Detection and Analysis of Molecular and Cellular Targets SO PHOTOCHEMISTRY AND PHOTOBIOLOGY LA English DT Review ID ULTRAVIOLET-INDUCED CARCINOGENESIS; CD8(+) T-CELLS; SKIN-CANCER; CONTACT HYPERSENSITIVITY; DENDRITIC CELLS; INDUCED IMMUNOSUPPRESSION; TRANSPLANT RECIPIENTS; PYRIMIDINE DIMERS; IRRADIATED MICE; RISK-FACTOR AB Ultraviolet (UV)-radiation-induced immunosuppression has been linked with the risk of skin carcinogenesis. Approximately, 2million new cases of skin cancers, including melanoma and nonmelanoma, diagnosed each year in the USA and therefore have a tremendous bad impact on public health. Dietary phytochemicals are promising options for the development of effective strategy for the prevention of photodamaging effects of UV radiation including the risk of skin cancer. Grape seed proanthocyanidins (GSPs) are such phytochemicals. Dietary administration of GSPs with AIN76A control diet significantly inhibits UV-induced skin tumor development as well as suppression of immune system. UV-induced suppression of immune system is commonly determined using contact hypersensitivity (CHS) model which is a prototype of T-cell-mediated immune response. We present evidence that inhibition of UV-induced suppression of immune system by GSPs is mediated through: (i) the alterations in immunoregulatory cytokines, interleukin (IL)-10 and IL-12, (ii) DNA repair, (iii) stimulation of effector T cells and (iv) DNA repair-dependent functional activation of dendritic cells in mouse model. These information have important implications for the use of GSPs as a dietary supplement in chemoprevention of UV-induced immunosuppression as well as photocarcinogenesis. C1 [Katiyar, Santosh K.] Univ Alabama Birmingham, Dept Dermatol, Birmingham, AL 35294 USA. [Katiyar, Santosh K.] Univ Alabama Birmingham, Ctr Comprehens Canc, Birmingham, AL 35294 USA. [Katiyar, Santosh K.] Univ Alabama Birmingham, Nutr Obes Res Ctr, Birmingham, AL USA. [Katiyar, Santosh K.] Birmingham Vet Affairs Med Ctr, Birmingham, AL USA. RP Katiyar, SK (reprint author), Univ Alabama Birmingham, Dept Dermatol, Birmingham, AL 35294 USA. EM skatiyar@uab.edu FU National Cancer Institute/NCCAM/NIH [CA140197, CA140832]; Veterans Administration Merit Review Award FX The work reported from Dr. Katiyar's laboratory was supported by the funds from National Cancer Institute/NCCAM/NIH (CA140197, CA140832) and Veterans Administration Merit Review Award (S.K.K.). The content of this article does not necessarily reflect the views or policies of the funding agencies. NR 55 TC 1 Z9 1 U1 4 U2 20 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0031-8655 EI 1751-1097 J9 PHOTOCHEM PHOTOBIOL JI Photochem. Photobiol. PD JAN-FEB PY 2015 VL 91 IS 1 BP 156 EP 162 DI 10.1111/php.12330 PG 7 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA AZ8CN UT WOS:000348442600019 PM 25112437 ER PT J AU Nasti, TH Timares, L AF Nasti, Tahseen H. Timares, Laura TI MC1R, Eumelanin and Pheomelanin: Their Role in Determining the Susceptibility to Skin Cancer SO PHOTOCHEMISTRY AND PHOTOBIOLOGY LA English DT Review ID MELANOCYTE-STIMULATING HORMONE; MOUSE EPIDERMAL MELANOCYTES; T-CELL-ACTIVATION; NF-KAPPA-B; HUMAN MELANOCORTIN-1 RECEPTOR; FIBROBLAST-GROWTH-FACTOR; ALPHA-MSH; RED HAIR; TRANSCRIPTION FACTOR; 1,25-DIHYDROXYVITAMIN D-3 AB Skin pigmentation is due to the accumulation of two types of melanin granules in the keratinocytes. Besides being the most potent blocker of ultraviolet radiation, the role of melanin in photoprotection is complex. This is because one type of melanin called eumelanin is UV absorbent, whereas the other, pheomelanin, is photounstable and may even promote carcinogenesis. Skin hyperpigmentation may be caused by stress or exposure to sunlight, which stimulates the release of -melanocyte stimulating hormone (-MSH) from damaged keratinocytes. Melanocortin 1 receptor (MC1R) is a key signaling molecule on melanocytes that responds to -MSH by inducing expression of enzymes responsible for eumelanin synthesis. Persons with red hair have mutations in the MC1R causing its inactivation; this leads to a paucity of eumelanin production and makes red-heads more susceptible to skin cancer. Apart from its effects on melanin production, the -MSH/MC1R signaling is also a potent anti-inflammatory pathway and has been shown to promote antimelanoma immunity. This review will focus on the role of MC1R in terms of its regulation of melanogenesis and influence on the immune system with respect to skin cancer susceptibility. C1 [Nasti, Tahseen H.; Timares, Laura] Univ Alabama Birmingham, Dept Dermatol, Sch Med, Birmingham, AL 35294 USA. [Timares, Laura] Univ Alabama Birmingham, Skin Dis Res Ctr, Sch Med, Birmingham, AL USA. [Timares, Laura] Birmingham VA Med Ctr, Birmingham, AL USA. RP Timares, L (reprint author), Univ Alabama Birmingham, Dept Dermatol, Sch Med, Birmingham, AL 35294 USA. EM timares@uab.edu FU VA Merit Award from NIAMS; UAB Skin Diseases Research Center award from NIAMS FX The authors extend their thanks to Dr. Craig Elmets for his constant support and intellectual guidance for our research-most recently on the regulation of melanoma initiation and progression by immune factors. It was he who pointed out that the increased susceptibility to melanoma development in C3H mouse strains mimics one of the most important risk factors for humans, specifically blond and red hair color-which was the inspiration for this review article. This work was supported by funding from a VA Merit Award and The UAB Skin Diseases Research Center award from NIAMS. NR 133 TC 7 Z9 8 U1 3 U2 26 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0031-8655 EI 1751-1097 J9 PHOTOCHEM PHOTOBIOL JI Photochem. Photobiol. PD JAN-FEB PY 2015 VL 91 IS 1 BP 188 EP 200 DI 10.1111/php.12335 PG 13 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA AZ8CN UT WOS:000348442600022 PM 25155575 ER PT J AU Li, H Prasad, R Katiyar, SK Yusuf, N Elmets, CA Xu, H AF Li, Hui Prasad, Ram Katiyar, Santosh K. Yusuf, Nabiha Elmets, Craig A. Xu, Hui TI Interleukin-17 Mediated Inflammatory Responses Are Required for Ultraviolet Radiation-Induced Immune Suppression SO PHOTOCHEMISTRY AND PHOTOBIOLOGY LA English DT Article ID CONTACT HYPERSENSITIVITY RESPONSES; POLYMORPHIC LIGHT ERUPTION; CD8(+) T-CELLS; INDUCED IMMUNOSUPPRESSION; LANGERHANS CELLS; UV-RADIATION; SKIN-CANCER; IN-VIVO; SYSTEMIC IMMUNOSUPPRESSION; TUMOR-DEVELOPMENT AB Ultraviolet radiation (UVR) induces immunosuppression and is a major factor for development of skin cancer. Numerous efforts have been made to determine mechanisms for UVR-induced immunosuppression and to develop strategies for prevention and treatment of UVR-induced cancers. In the current study, we use IL-17 receptor (IL-17R) deficient mice to examine whether IL-17 mediated responses have a role in UVB (290-320)-induced immunosuppression of contact hypersensitivity responses. Results demonstrate that IL-17 mediated responses are required for UVB-induced immunosuppression of contact hypersensitivity responses. The systemic immune suppression and development of regulatory T cells are inhibited in UVB-treated IL-17R deficient mice compared to wild-type animals. The deficiency in IL-17R inhibits the infiltration and development of a tolerogenic myeloid cell population in UVB-treated skin, which expresses CD11b and Gr-1 and produces reactive oxygen species. We speculate that the development of the tolerogenic myeloid cells is dependent on IL-17-induced chemokines and inflammatory mediators in UVB-treated skin. The inhibition of the tolerogenic myeloid cells may be attributed to the suppression of regulatory T cells in UVR-treated IL-17R(-/-) mice. The findings may be exploited to new strategies for prevention and treatment of UVR-induced skin diseases and cancers. C1 [Li, Hui; Prasad, Ram; Katiyar, Santosh K.; Yusuf, Nabiha; Elmets, Craig A.; Xu, Hui] Univ Alabama Birmingham, Dept Dermatol, Birmingham, AL 35294 USA. [Katiyar, Santosh K.; Yusuf, Nabiha; Elmets, Craig A.; Xu, Hui] Univ Alabama Birmingham, Skin Dis Res Ctr, Birmingham, AL USA. [Katiyar, Santosh K.; Yusuf, Nabiha; Elmets, Craig A.; Xu, Hui] Birmingham VA Med Ctr, Birmingham, AL USA. RP Xu, H (reprint author), Univ Alabama Birmingham, Dept Dermatol, Birmingham, AL 35294 USA. EM xuhui@uabmc.edu FU VA Merit Review [18-103-02]; [R01CA140197]; [P30 AR050948]; [P30 CA013148] FX This study was supported by R01CA140197, P30 AR050948, P30 CA013148, and by VA Merit Review18-103-02. NR 68 TC 3 Z9 3 U1 0 U2 6 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0031-8655 EI 1751-1097 J9 PHOTOCHEM PHOTOBIOL JI Photochem. Photobiol. PD JAN-FEB PY 2015 VL 91 IS 1 BP 235 EP 241 DI 10.1111/php.12351 PG 7 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA AZ8CN UT WOS:000348442600027 PM 25250896 ER PT J AU Lovejoy, T Heckman, T Sikkema, K Hansen, N Kochman, A AF Lovejoy, Travis I. Heckman, Timothy G. Sikkema, Kathleen J. Hansen, Nathan B. Kochman, Arlene TI Changes in Sexual Behavior of HIV-Infected Older Adults Enrolled in a Clinical Trial of Standalone Group Psychotherapies Targeting Depression SO AIDS AND BEHAVIOR LA English DT Article DE HIV/AIDS; Aging; Depression; Clinical trial; Unprotected sex ID RANDOMIZED CONTROLLED-TRIAL; IMPROVEMENT GROUP INTERVENTION; SECONDARY PREVENTION; RISK BEHAVIORS; MEN; HIV/AIDS; AGE AB By 2015, one-half of all HIV-positive persons in the U.S. will be 50-plus years of age, and as many as 30 % of older adults living with HIV/AIDS continue to engage in unprotected sexual intercourse. Contemporary positive prevention models often include mental health treatment as a key component of HIV prevention interventions. This secondary data analysis characterized longitudinal patterns of sexual behavior in HIV-positive older adults enrolled in a randomized controlled trial of group mental health interventions and assessed the efficacy of psychosocial treatments that targeted depression to reduce sexual risk behavior. Participants were 295 HIV-positive adults a parts per thousand yen50 years of age experiencing mild to severe depressive symptoms, randomized to one of three study conditions: a 12-session coping improvement group intervention, a 12-session interpersonal support group intervention, or individual therapy upon request. Approximately one-fifth of participants reported one or more occasions of unprotected anal or vaginal intercourse with HIV-negative sexual partners or persons of unknown HIV serostatus over the study period. Changes in sexual behavior did not vary by intervention condition, indicating that standalone treatments that target and reduce depression may be insufficient to reduce sexual risk behavior in depressed HIV-positive older adults. C1 [Lovejoy, Travis I.] Oregon Hlth & Sci Univ, Dept Psychiat, Portland, OR 97201 USA. [Lovejoy, Travis I.] Portland VA Med Ctr, Mental Hlth & Clin Neurosci Div, Portland, OR 97239 USA. [Heckman, Timothy G.; Hansen, Nathan B.] Univ Georgia, Coll Publ Hlth, Athens, GA 30602 USA. [Sikkema, Kathleen J.] Duke Univ, Dept Psychol & Neurosci, Durham, NC USA. RP Lovejoy, T (reprint author), Portland VA Med Ctr, Mental Hlth & Clin Neurosci Div, 3710 SW US Vet Hosp Rd, Portland, OR 97239 USA. EM travis.lovejoy@va.gov RI Hansen, Nathan/F-2074-2016 FU NIMH NIH HHS [R01 MH067566, R01-MH067568, R01 MH067568] NR 29 TC 3 Z9 3 U1 1 U2 9 PU SPRINGER/PLENUM PUBLISHERS PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1090-7165 EI 1573-3254 J9 AIDS BEHAV JI AIDS Behav. PD JAN PY 2015 VL 19 IS 1 BP 1 EP 8 DI 10.1007/s10461-014-0746-7 PG 8 WC Public, Environmental & Occupational Health; Social Sciences, Biomedical SC Public, Environmental & Occupational Health; Biomedical Social Sciences GA AZ6OT UT WOS:000348339500001 PM 24668254 ER PT J AU Chan, B Weiser, S Boum, Y Haberer, J Kembabazi, A Hunt, P Martin, J Mocello, A Bangsberg, D Tsai, A AF Chan, Brian T. Weiser, Sheri D. Boum, Yap Haberer, Jessica E. Kembabazi, Annet Hunt, Peter W. Martin, Jeffrey N. Mocello, A. Rain Bangsberg, David R. Tsai, Alexander C. TI Declining Prevalence of Probable Depression Among Patients Presenting for Antiretroviral Therapy in Rural Uganda: The Role of Early Treatment Initiation SO AIDS AND BEHAVIOR LA English DT Article DE Depression; Trends; Physical health; Antiretroviral therapy; HIV; Uganda ID QUALITY-OF-LIFE; ANTIDEPRESSANT MEDICATION TREATMENT; RANDOMIZED CONTROLLED-TRIAL; HIV-POSITIVE WOMEN; CD4 CELL COUNT; SOUTH-AFRICA; SYMPTOMS; DISEASE; MORTALITY; ADULTS AB Little is known about trends in depression at antiretroviral therapy (ART) initiation among people living with HIV (PLHIV) in low- and middle-income countries. We used data from an ongoing cohort of treatment-na < ve PLHIV in rural Uganda to estimate secular trends in depression among PLHIV at ART initiation. We fitted linear regression models with depression symptom severity as the outcome variable and year of cohort entry (2005-2012) as the explanatory variable, adjusting for socio-demographic variables and assessing physical health score, body mass index (BMI), and CD4 count as potential mediators of a secular trend in depression symptom severity. There was a statistically significant negative association between year of entry and depression symptom severity, suggesting a 3.1 % relative decline in the mean depression symptom severity score at ART initiation in each year of study recruitment after the first year. This trend remained statistically significant after inclusion of baseline socio-demographic characteristics to the model and appeared to be driven by improved physical health scores, but not CD4 count or BMI. C1 [Chan, Brian T.] Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA. [Chan, Brian T.] Brigham & Womens Hosp, Div Infect Dis, Boston, MA 02115 USA. [Chan, Brian T.; Haberer, Jessica E.; Bangsberg, David R.; Tsai, Alexander C.] Harvard Univ, Sch Med, Boston, MA USA. [Weiser, Sheri D.; Hunt, Peter W.] Univ Calif San Francisco, San Francisco Gen Hosp, Div HIV AIDS, San Francisco, CA USA. [Weiser, Sheri D.] Univ Calif San Francisco, Ctr AIDS Prevent Studies, San Francisco, CA 94143 USA. [Boum, Yap] Epictr, Mbarara, Uganda. [Haberer, Jessica E.; Bangsberg, David R.; Tsai, Alexander C.] Massachusetts Gen Hosp, Ctr Global Hlth, Boston, MA 02114 USA. [Kembabazi, Annet; Bangsberg, David R.; Tsai, Alexander C.] Mbarara Univ Sci & Technol, Mbarara, Uganda. [Martin, Jeffrey N.; Mocello, A. Rain] Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA. [Tsai, Alexander C.] Massachusetts Gen Hosp, Dept Psychiat, MD Div Global Psychiat, Boston, MA 02114 USA. RP Chan, B (reprint author), Massachusetts Gen Hosp, Div Infect Dis, 55 Fruit St GRJ 504, Boston, MA 02114 USA. EM bchan@partners.org OI Tsai, Alexander/0000-0001-6397-7917 FU NCI NIH HHS [U01CA066529, U01 CA066529]; NIAID NIH HHS [P30 AI027763, P30AI27763, T32 AI007433, T32AI007433]; NIMH NIH HHS [K23 MH079713, K23 MH087228, K23 MH096620, K23MH079713, K23MH087228, K23MH096620, K24 MH087227, K24MH087227, R01 MH054907, R01MH054907] NR 43 TC 0 Z9 0 U1 1 U2 3 PU SPRINGER/PLENUM PUBLISHERS PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1090-7165 EI 1573-3254 J9 AIDS BEHAV JI AIDS Behav. PD JAN PY 2015 VL 19 IS 1 BP 19 EP 26 DI 10.1007/s10461-014-0785-0 PG 8 WC Public, Environmental & Occupational Health; Social Sciences, Biomedical SC Public, Environmental & Occupational Health; Biomedical Social Sciences GA AZ6OT UT WOS:000348339500003 PM 24788780 ER PT J AU Psaros, C Haberer, JE Boum, Y Tsai, AC Martin, JN Hunt, PW Bangsberg, DR Safren, SA AF Psaros, Christina Haberer, Jessica E. Boum, Yap, II Tsai, Alexander C. Martin, Jeffrey N. Hunt, Peter W. Bangsberg, David R. Safren, Steven A. TI The Factor Structure and Presentation of Depression Among HIV-Positive Adults in Uganda SO AIDS AND BEHAVIOR LA English DT Article DE HIV/AIDS; Depression; Assessment; Validity ID QUALITY-OF-LIFE; ANTIDEPRESSANT MEDICATION TREATMENT; HOPKINS SYMPTOM CHECKLIST-25; SURVEY MOS-HIV; RURAL UGANDA; ANTIRETROVIRAL THERAPY; SOUTH-AFRICA; INITIATING HAART; SOMATIC SYMPTOMS; FOOD INSECURITY AB Depression is one of the most prevalent psychiatric comorbidities of HIV and one of the greatest barriers to HIV self-care and adherence. Despite this, little consensus exists on how to best measure depression among people living with HIV/AIDS (PLWHA) in African settings. Measurement of depression among PLWHA may be confounded by somatic symptoms. Some research recommends excluding these items to enhance measurement validity; sensitivity may be lost with this approach. We sought to characterize depression among a cohort (N = 453) of PLWHA initiating antiretroviral therapy in Uganda via factor analysis of a widely used measure of depression, the Hopkins Symptom Checklist (HSCLD). Common factor analysis was performed, associations between HSCLD and the Mental Health subscale of the Medical Outcomes Study HIV (MOS-HIV) estimated, and a Cronbach's alpha calculated to examine validity. Factor analysis yielded two factors: (1) somatic-cognitive symptoms and (2) behavioral disengagement. Persons with more versus less advanced disease (CD4 cell count of a parts per thousand currency sign200 cells/mm(3)) showed no statistically significant differences in depression scores (1.7 vs. 1.7, P a parts per thousand yen 0.5). Both factors were significantly associated with the MOS-HIV (P < .01). Factor one was highly reliable (alpha = .81); factor two had only modest reliability (alpha = .65). Somatic-cognitive symptoms of depression and disengagement from life's activities appear to be distinct components of depression in this sample. Consideration of somatic items may be valuable in identifying depression in this setting. C1 [Psaros, Christina; Safren, Steven A.] Massachusetts Gen Hosp, Behav Med Serv, Dept Psychiat, Boston, MA 02114 USA. [Psaros, Christina; Haberer, Jessica E.; Tsai, Alexander C.; Bangsberg, David R.; Safren, Steven A.] Harvard Univ, Sch Med, Boston, MA USA. [Haberer, Jessica E.; Tsai, Alexander C.; Bangsberg, David R.] Massachusetts Gen Hosp, Ctr Global Hlth, Boston, MA 02114 USA. [Boum, Yap, II; Bangsberg, David R.] Mbarara Univ Sci & Technol, Mbarara, Uganda. [Boum, Yap, II] Uganda Res Ctr, Epictr, Mbarara, Uganda. [Martin, Jeffrey N.] Univ San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94117 USA. [Hunt, Peter W.] Univ Calif San Francisco, San Francisco Gen Hosp, Div HIV AIDS, San Francisco, CA USA. RP Psaros, C (reprint author), Massachusetts Gen Hosp, Behav Med Serv, Dept Psychiat, One Bowdoin Sq,7th Floor, Boston, MA 02114 USA. EM cpsaros@partners.org OI Tsai, Alexander/0000-0001-6397-7917 FU NIAID NIH HHS [P30 AI027763, P30AI27763]; NIMH NIH HHS [K23MH096620, K23 MH087228, K23 MH096620, K23 MH096651, K23MH087228, K23MH096651, K24 MH087227, K24 MH094214, K24MH087227, K24MH094214, R01 MH054907, R01MH054907] NR 47 TC 1 Z9 1 U1 12 U2 15 PU SPRINGER/PLENUM PUBLISHERS PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1090-7165 EI 1573-3254 J9 AIDS BEHAV JI AIDS Behav. PD JAN PY 2015 VL 19 IS 1 BP 27 EP 33 DI 10.1007/s10461-014-0796-x PG 7 WC Public, Environmental & Occupational Health; Social Sciences, Biomedical SC Public, Environmental & Occupational Health; Biomedical Social Sciences GA AZ6OT UT WOS:000348339500004 PM 24854877 ER PT J AU Magidson, JF Blashill, AJ Safren, SA Wagner, GJ AF Magidson, Jessica F. Blashill, Aaron J. Safren, Steven A. Wagner, Glenn J. TI Depressive Symptoms, Lifestyle Structure, and ART Adherence Among HIV-Infected Individuals: A Longitudinal Mediation Analysis SO AIDS AND BEHAVIOR LA English DT Article DE Depression; Antiretroviral therapy; Adherence; Lifestyle structure; Mediation ID RANDOMIZED CONTROLLED-TRIAL; COGNITIVE-BEHAVIORAL THERAPY; SELF-REPORTED ADHERENCE; ANTIRETROVIRAL THERAPY; MEDICATION ADHERENCE; INHIBITOR THERAPY; DRUG-USERS; VIRAL LOAD; CBT-AD; ACTIVATION AB Despite the well-documented relationship between depression and antiretroviral therapy (ART) nonadherence, few studies have identified explanatory pathways through which depression affects adherence. The current study tested lifestyle structure-the degree of organization and routinization of daily activities-as a mediator of this relationship, given previous evidence of lifestyle structure being associated with both depression and ART nonadherence. HIV-infected individuals starting or re-starting ART in the California Collaborative Treatment Group 578 study (n = 199) were assessed over 48 weeks. Adherence was measured using electronic monitoring caps to determine dose timing and doses taken, and viral load was assessed. The mediating role of lifestyle structure was tested using generalized linear mixed-effects modeling and bootstrapping. Lifestyle significantly mediated the relationship between depression and both measures of ART adherence behavior. Interventions that minimize disruptions to lifestyle structure and link adherence to daily activities may be useful for individuals with depression and ART nonadherence. C1 [Magidson, Jessica F.; Blashill, Aaron J.; Safren, Steven A.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. [Wagner, Glenn J.] RAND Corp, Santa Monica, CA USA. RP Magidson, JF (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Psychiat, One Bowdoin Sq,7th Floor, Boston, MA 02114 USA. EM jmagidson@partners.org FU NIDA NIH HHS [R36 DA034513, R36DA034513]; NIMH NIH HHS [K23 MH096647, K23MH096647, K24 MH094214, K24MH094214, R01 MH061695, R01MH61695, T32 MH093310, T32MH093310] NR 44 TC 3 Z9 3 U1 4 U2 5 PU SPRINGER/PLENUM PUBLISHERS PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1090-7165 EI 1573-3254 J9 AIDS BEHAV JI AIDS Behav. PD JAN PY 2015 VL 19 IS 1 BP 34 EP 40 DI 10.1007/s10461-014-0802-3 PG 7 WC Public, Environmental & Occupational Health; Social Sciences, Biomedical SC Public, Environmental & Occupational Health; Biomedical Social Sciences GA AZ6OT UT WOS:000348339500005 PM 24874725 ER PT J AU O'Cleirigh, C Valentine, SE Pinkston, M Herman, D Bedoya, CA Gordon, JR Safren, SA AF O'Cleirigh, Conall Valentine, Sarah E. Pinkston, Megan Herman, Debra Bedoya, C. Andres Gordon, Janna R. Safren, Steven A. TI The Unique Challenges Facing HIV-Positive Patients Who Smoke Cigarettes: HIV Viremia, Art Adherence, Engagement in HIV care, and Concurrent Substance Use SO AIDS AND BEHAVIOR LA English DT Article DE HIV/AIDS; Smoking; Adherence; Substance use; Engagement in care ID QUALITY-OF-LIFE; ACTIVE ANTIRETROVIRAL THERAPY; ADDICTION SEVERITY INDEX; CLINICAL-TRIAL; CESSATION STRATEGIES; MEDICATION ADHERENCE; INCREASED RISK; HEALTH-RISKS; TOBACCO USE; HAART ERA AB Evidence suggests that smoking may have negative associations with HIV health outcomes. The smoking rate in our sample of people living with HIV (N = 333) was triple that of the general population (57 v. 19 %). Regression analyses revealed that (smokers v. non-smokers) reported lower medication adherence (unstandardized beta = 9.01) and were more likely to have a detectable viral load (OR = 2.85, 95 % CI [1.53-5.30]). Smokers attended fewer routine medical visits (beta = -0.16) and were more likely to report recent hospitalization (OR = 1.89, 95 % CI [0.99, 3.57]). Smokers ranked "health" as less important to their quality of life (beta = -0.13) and were more likely to report problematic alcohol (OR = 2.40, 95 % CI [1.35, 4.30]), cocaine (OR = 2.87, 95 % CI [1.48-5.58]), heroin (OR = 4.75, 95 % CI [1.01, 22.30]), or marijuana use (OR = 3.08, 95 % CI [1.76-5.38]). Findings underscore the need for integrated behavioral smoking cessation interventions and routine tobacco screenings in HIV primary care. C1 [O'Cleirigh, Conall; Valentine, Sarah E.; Bedoya, C. Andres; Gordon, Janna R.; Safren, Steven A.] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. [O'Cleirigh, Conall; Valentine, Sarah E.; Bedoya, C. Andres; Gordon, Janna R.; Safren, Steven A.] Harvard Univ, Sch Med, Boston, MA USA. [O'Cleirigh, Conall; Safren, Steven A.] Fenway Inst, Boston, MA USA. [Pinkston, Megan] Miriam Hosp, Providence, RI 02906 USA. [Herman, Debra] Butler Hosp, Providence, RI 02906 USA. RP O'Cleirigh, C (reprint author), Massachusetts Gen Hosp, Dept Psychiat, One Bowdoin Sq,7th Floor, Boston, MA 02114 USA. EM cocleirigh@mgh.harvard.edu FU NIMH NIH HHS [R01 MH084757, K24 MH094214, 5R01MH084757] NR 46 TC 7 Z9 7 U1 2 U2 5 PU SPRINGER/PLENUM PUBLISHERS PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1090-7165 EI 1573-3254 J9 AIDS BEHAV JI AIDS Behav. PD JAN PY 2015 VL 19 IS 1 BP 178 EP 185 DI 10.1007/s10461-014-0762-7 PG 8 WC Public, Environmental & Occupational Health; Social Sciences, Biomedical SC Public, Environmental & Occupational Health; Biomedical Social Sciences GA AZ6OT UT WOS:000348339500020 PM 24770984 ER PT J AU Timpone, VM Lev, MH Kamalian, S Morais, LT Franceschi, AM Souza, L Schaefer, PW AF Timpone, V. M. Lev, M. H. Kamalian, S. Morais, L. T. Franceschi, A. M. Souza, L. Schaefer, P. W. TI Percentage Insula Ribbon Infarction of > 50% Identifies Patients Likely to Have Poor Clinical Outcome Despite Small DWI Infarct Volume SO AMERICAN JOURNAL OF NEURORADIOLOGY LA English DT Article ID CEREBRAL-ARTERY INFARCTION; ACUTE STROKE; ISCHEMIC-STROKE; LESION VOLUMES; CT; PREDICTOR; SCALE AB BACKGROUND AND PURPOSE: Large admission DWI infarct volume (>70 mL) is an established marker for poor clinical outcome in acute stroke. Outcome is more variable in patients with small infarcts (<70 mL). Percentage insula ribbon infarct correlates with infarct growth. We hypothesized that percentage insula ribbon infarct can help identify patients with stroke likely to have poor clinical outcome, despite small admission DWI lesion volumes. MATERIALS AND METHODS: We analyzed the admission NCCT, CTP, and DWI scans of 55 patients with proximal anterior circulation occlusions on CTA. Percentage insula ribbon infarct (>50%, <= 50%) on DWI, NCCT, CT-CBF, and CT-MIT were recorded. DWI infarct volume, percentage DWI motor strip infarct, NCCT-ASPECTS, and CTA collateral score were also recorded. Statistical analyses were performed to determine accuracy in predicting poor outcome (mRS >2 at 90 days). RESULTS: Admission DWI of >70 mL and DWI percentage insula ribbon infarct of >50% were among significant univariate imaging markers of poor outcome (P < .001). In the multivariate analysis, DWI percentage insula ribbon infarct of >50% (P = .045) and NIHSS score (P < .001) were the only independent predictors of poor outcome. In the subgroup with admission DWI infarct of <70 mL (n = 40), 90-day mRS was significantly worse in those with DWI percentage insula ribbon infarct of <= 50% (n = 9, median mRS = 5, interquartile range = 2-5) compared with those with DWI percentage insula ribbon infarct of <= 50% (n = 31, median mRS = 2, interquartile range = 0.25-4, P = .036). In patients with admission DWI infarct of >70 mL, DWI percentage insula ribbon infarct did not have added predictive value for poor outcome (P = .931). CONCLUSIONS: DWI percentage insula ribbon infarct of >50% independently predicts poor clinical outcome and can help identify patients with stroke likely to have poor outcome despite small admission DWI lesion volumes. C1 Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Schaefer, PW (reprint author), Massachusetts Gen Hosp, Div Neuroradiol, Dept Radiol, Gray B241H,55 Fruit St, Boston, MA 02114 USA. EM pschaefer@partners.org RI Kamalian, Shervin/D-7667-2013; OI Kamalian, Shervin/0000-0001-8962-4773; Franceschi, Ana/0000-0003-2577-9738 FU National Institute of Neurological Disorders and Stroke FX Michael H. Lev-RELATED: Grant: for Specialized Programs of Translational Research in Acute Stroke, National Institute of Neurological Disorders and Stroke,star for Screening Technology and Outcomes Project in Stroke, National Institute of Neurological Disorders and Strokestar: UNRELATED: Consultancy: GE Healthcare, Grants/Grants Pending: GE Healthcare. Sheryin Kamalian-UNRELATED: Grants/Grants Pending: GE Healthcare. starMoney paid to the institution. NR 18 TC 3 Z9 3 U1 0 U2 4 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 2015 VL 36 IS 1 BP 40 EP 45 DI 10.3174/ajnr.A4091 PG 6 WC Clinical Neurology; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA AZ1ON UT WOS:000348008200009 PM 25190204 ER PT J AU Wellen, J Chatterjee, P Venkataramani, A Vijayan, A Martin, E AF Wellen, Jason Chatterjee, Paula Venkataramani, Atheendar Vijayan, Anitha Martin, Erika TI The Impact of State Policies on Organ Donation and Transplantation in the United States SO AMERICAN JOURNAL OF TRANSPLANTATION LA English DT Meeting Abstract CT 15th Annual State of the Art Winter Symposium of the American-Society-of-Transplant-Surgeons (ASTS) CY JAN 15-18, 2015 CL Miami, FL SP Amer Soc Transplant Surg C1 [Wellen, Jason; Vijayan, Anitha] Washington Univ, Sch Med, St Louis, MO USA. [Chatterjee, Paula] Brigham & Womens Hosp, Boston, MA 02115 USA. [Venkataramani, Atheendar] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Martin, Erika] SUNY Albany, Albany, NY 12222 USA. NR 0 TC 0 Z9 0 U1 1 U2 2 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1600-6135 EI 1600-6143 J9 AM J TRANSPLANT JI Am. J. Transplant. PD JAN PY 2015 VL 15 SU 1 SI SI MA O-7 BP 50 EP 50 PG 1 WC Surgery; Transplantation SC Surgery; Transplantation GA AZ1YF UT WOS:000348030600025 ER PT J AU Adler, J Yeh, HD Markmann, J Nguyen, L Axelrod, D AF Adler, Joel Yeh, Heidi Markmann, James Nguyen, Louis Axelrod, David TI Does DSA Market Competition Influence OPO Performance? SO AMERICAN JOURNAL OF TRANSPLANTATION LA English DT Meeting Abstract CT 15th Annual State of the Art Winter Symposium of the American-Society-of-Transplant-Surgeons (ASTS) CY JAN 15-18, 2015 CL Miami, FL SP Amer Soc Transplant Surg C1 [Adler, Joel; Yeh, Heidi; Markmann, James] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Nguyen, Louis] Brigham & Womens Hosp, Boston, MA 02115 USA. [Axelrod, David] Dartmouth Hitchcock Med Ctr, Lebanon, NH 03766 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1600-6135 EI 1600-6143 J9 AM J TRANSPLANT JI Am. J. Transplant. PD JAN PY 2015 VL 15 SU 1 SI SI MA P-1 BP 53 EP 53 PG 1 WC Surgery; Transplantation SC Surgery; Transplantation GA AZ1YF UT WOS:000348030600031 ER PT J AU Patel, M Kohn, R Kratz, J Shah, J Markmann, J Vagefi, P AF Patel, Madhukar Kohn, Rachel Kratz, Johannes Shah, Jigesh Markmann, James Vagefi, Parsia TI The Race To Liver Transplant: A Comparison Between HCC and Non-HCC Candidates SO AMERICAN JOURNAL OF TRANSPLANTATION LA English DT Meeting Abstract CT 15th Annual State of the Art Winter Symposium of the American-Society-of-Transplant-Surgeons (ASTS) CY JAN 15-18, 2015 CL Miami, FL SP Amer Soc Transplant Surg C1 [Patel, Madhukar; Shah, Jigesh; Markmann, James; Vagefi, Parsia] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Kohn, Rachel] Hosp Univ Penn, Philadelphia, PA 19104 USA. [Kratz, Johannes] Univ Calif San Francisco, San Francisco, CA 94143 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1600-6135 EI 1600-6143 J9 AM J TRANSPLANT JI Am. J. Transplant. PD JAN PY 2015 VL 15 SU 1 SI SI MA P-100 BP 92 EP 92 PG 1 WC Surgery; Transplantation SC Surgery; Transplantation GA AZ1YF UT WOS:000348030600127 ER PT J AU LaQuaglia, M Grijalva, J Mueller, K Sadri-Vakili, G Vakili, K AF LaQuaglia, Michael Grijalva, James Mueller, Kaly Sadri-Vakili, Ghazaleh Vakili, Khashayar TI siRNA Knockdown of YAP Inhibits Liver Regeneration in Rat Model SO AMERICAN JOURNAL OF TRANSPLANTATION LA English DT Meeting Abstract CT 15th Annual State of the Art Winter Symposium of the American-Society-of-Transplant-Surgeons (ASTS) CY JAN 15-18, 2015 CL Miami, FL SP Amer Soc Transplant Surg C1 [LaQuaglia, Michael; Grijalva, James; Vakili, Khashayar] Boston Childrens Hosp, Boston, MA USA. [Mueller, Kaly; Sadri-Vakili, Ghazaleh] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1600-6135 EI 1600-6143 J9 AM J TRANSPLANT JI Am. J. Transplant. PD JAN PY 2015 VL 15 SU 1 SI SI MA P-107 BP 94 EP 94 PG 1 WC Surgery; Transplantation SC Surgery; Transplantation GA AZ1YF UT WOS:000348030600133 ER PT J AU Adler, J Hyder, J Markmann, J Yeh, HD AF Adler, Joel Hyder, Joseph Markmann, James Yeh, Heidi TI "Traveling" Livers: Measuring the Flow Between Donors and Recipients SO AMERICAN JOURNAL OF TRANSPLANTATION LA English DT Meeting Abstract CT 15th Annual State of the Art Winter Symposium of the American-Society-of-Transplant-Surgeons (ASTS) CY JAN 15-18, 2015 CL Miami, FL SP Amer Soc Transplant Surg C1 [Adler, Joel; Markmann, James; Yeh, Heidi] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Hyder, Joseph] Mayo Clin, Rochester, MN USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1600-6135 EI 1600-6143 J9 AM J TRANSPLANT JI Am. J. Transplant. PD JAN PY 2015 VL 15 SU 1 SI SI MA P-110 BP 95 EP 95 PG 1 WC Surgery; Transplantation SC Surgery; Transplantation GA AZ1YF UT WOS:000348030600136 ER PT J AU Avruch, J Bruinsma, B Weeder, P Yeh, HD Uygun, K Markmann, J AF Avruch, James Bruinsma, Bote Weeder, Pepijn Yeh, Heidi Uygun, Korkut Markmann, James TI Simulated Transplantation By Ex Vivo Diluted Whole Blood Reperfusion Following Liver Preservation SO AMERICAN JOURNAL OF TRANSPLANTATION LA English DT Meeting Abstract CT 15th Annual State of the Art Winter Symposium of the American-Society-of-Transplant-Surgeons (ASTS) CY JAN 15-18, 2015 CL Miami, FL SP Amer Soc Transplant Surg C1 [Avruch, James; Bruinsma, Bote; Weeder, Pepijn; Yeh, Heidi; Uygun, Korkut; Markmann, James] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1600-6135 EI 1600-6143 J9 AM J TRANSPLANT JI Am. J. Transplant. PD JAN PY 2015 VL 15 SU 1 SI SI MA P-130 BP 101 EP 101 PG 1 WC Surgery; Transplantation SC Surgery; Transplantation GA AZ1YF UT WOS:000348030600154 ER PT J AU Weeder, P op den Dries, S Yeh, HD Markmann, J Uygun, K Porte, R Martins, P AF Weeder, Pepijn op den Dries, Sanna Yeh, Heidi Markmann, Jim Uygun, Korkut Porte, Robert Martins, Paulo TI Bile Duct Histopathology and Donor Demographics as Predictors of Ischemic Cholangiopathy After Liver Transplant: A Prospective Study SO AMERICAN JOURNAL OF TRANSPLANTATION LA English DT Meeting Abstract CT 15th Annual State of the Art Winter Symposium of the American-Society-of-Transplant-Surgeons (ASTS) CY JAN 15-18, 2015 CL Miami, FL SP Amer Soc Transplant Surg C1 [Weeder, Pepijn; Yeh, Heidi; Markmann, Jim] Massachusetts Gen Hosp, Boston, MA 02114 USA. [op den Dries, Sanna; Porte, Robert] Univ Med Ctr Groningen, NL-9713 AV Groningen, Netherlands. [Uygun, Korkut] Harvard Univ, Sch Med, Boston, MA USA. [Martins, Paulo] UMass Mem Med Ctr, Worcester, MA USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1600-6135 EI 1600-6143 J9 AM J TRANSPLANT JI Am. J. Transplant. PD JAN PY 2015 VL 15 SU 1 SI SI MA P-139 BP 104 EP 104 PG 1 WC Surgery; Transplantation SC Surgery; Transplantation GA AZ1YF UT WOS:000348030600161 ER PT J AU Sarantopoulos, S Blazar, BR Cutler, C Ritz, J AF Sarantopoulos, Stefanie Blazar, Bruce R. Cutler, Corey Ritz, Jerome TI B Cells in Chronic Graft-versus-Host Disease SO BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION LA English DT Article DE Stem cell transplantation; Chronic graft-versus-host; disease; B cell ID MINOR HISTOCOMPATIBILITY ANTIGEN; SYSTEMIC-LUPUS-ERYTHEMATOSUS; CD4(+) T-CELLS; CHRONIC GVHD; BRONCHIOLITIS OBLITERANS; TYROSINE KINASE; MARROW TRANSPLANT; ANTIBODY-RESPONSE; ACTIVATING FACTOR; DENDRITIC CELLS AB Chronic graft-versus-host disease (cGVHD) continues to be a common complication of allogeneic hematopoietic stem cell transplantation. Unlike acute graft-versus-host disease, which is mediated almost entirely by donor T cells, the immune pathology of cGVHD is more complex and donor B cells have also been found to play an important role. Recent studies from several laboratories have enhanced our understanding of how donor B cells contribute to this clinical syndrome and this has led to new therapeutic opportunities. Here, Dr Sarantopoulos reviews some of the important mechanisms responsible for persistent B cell activation and loss of B cell tolerance in patients with cGVHD. Dr Blazar describes recent studies in preclinical models that have identified novel B cell directed agents that may be effective for prevention or treatment of cGVHD. Some B cell directed therapies have already been tested in patients with cGVHD and Dr Cutler reviews the results of these studies documenting the potential efficacy of this approach. Supported by mechanistic studies in patients and preclinical models, new B cell directed therapies for cGVHD will now be evaluated in clinical trials. (C) 2015 American Society for Blood and Marrow Transplantation. C1 [Sarantopoulos, Stefanie] Duke Univ, Duke Canc Inst, Dept Med, Div Cell Therapy & Hematol Malignancies, Durham, NC USA. [Blazar, Bruce R.] Univ Minnesota, Mason Canc Ctr, Dept Pediat, Div Blood & Marrow Transplantat, Minneapolis, MN USA. [Cutler, Corey; Ritz, Jerome] Harvard Univ, Sch Med, Dana Farber Canc Inst, Div Hematol Malignancies, Boston, MA 02215 USA. RP Ritz, J (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Div Hematol Malignancies, 450 Brookline Ave, Boston, MA 02215 USA. EM jerome_ritz@dfci.harvard.edu OI Ritz, Jerome/0000-0001-5526-4669 FU NIH [CA142106, K08HL107756, AI056299]; DOD [CA100254]; Kadmon Pharmaceuticals Inc; Leukemia and Lymphoma Society of America [6458-15] FX The authors thank jing Du, Katelyn Goodman, and Drs Ryan Flynn, Jay Bradner, Jun Qi, An Melnick, Raphael Clynes, Alexandra Zanin-Zhorov, Jason Dubovsky, John Byrd, and Lawrence Elias for performing experiments, providing reagents and/or helpful discussions. We thank Rigel Pharmaceuticals for providing fostamatinib, Kadmon Pharmaceuticals for KD025, and Pharmacyclics for providing ibrutinib for laboratory studies. Studies described in this review were supported by NIH grants CA142106, K08HL107756, and AI056299, DOD grant CA100254, Kadmon Pharmaceuticals Inc and a translational grant from the Leukemia and Lymphoma Society of America (LLS Grant 6458-15). NR 87 TC 16 Z9 17 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1083-8791 EI 1523-6536 J9 BIOL BLOOD MARROW TR JI Biol. Blood Marrow Transplant. PD JAN PY 2015 VL 21 IS 1 BP 16 EP 23 DI 10.1016/j.bbmt.2014.10.029 PG 8 WC Hematology; Immunology; Transplantation SC Hematology; Immunology; Transplantation GA AY6JB UT WOS:000347671600005 PM 25452031 ER PT J AU Eapen, M Logan, BR Appelbaum, FR Antin, JH Anasetti, C Couriel, DR Chen, JF Maziarz, RT McCarthy, PL Nakamura, R Ratanatharathorn, V Vij, R Champlin, RE AF Eapen, Mary Logan, Brent R. Appelbaum, Fredrick R. Antin, Joseph H. Anasetti, Claudio Couriel, Daniel R. Chen, Junfang Maziarz, Richard T. McCarthy, Philip L. Nakamura, Ryotaro Ratanatharathorn, Voravit Vij, Ravi Champlin, Richard E. TI Long-Term Survival after Transplantation of Unrelated Donor Peripheral Blood or Bone Marrow Hematopoietic Cells for Hematologic Malignancy SO BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION LA English DT Article DE Chronic graft-versus-host; disease; Mortality; Leukemia ID VERSUS-HOST-DISEASE; RANDOMIZED-TRIAL; CHRONIC GRAFT; MOBILIZED BLOOD; STEM-CELLS; FOLLOW-UP; PROPHYLAXIS; GLOBULIN AB We sought to determine whether differences in chronic graft-versus-host disease (GVHD) rates would lead to survival differences by comparing 2463 peripheral blood (PB) and 1713 bone marrow (BM) hematopoietic cell transplant recipients. Patients had acute leukemia, chronic myeloid leukemia (CML), or myelodysplastic syndrome, and they received myeloablative conditioning regimens and calcineurin-inhibitor GVHD prophylaxis. There were no significant differences in long-term survival after transplantation of PB and BM, except for patients in first chronic phase CML. For these patients, the 5-year rate of survival was lower after transplantation of PB compared with transplantation of BM (35% versus 56%, P = .001). Although mortality risks were higher in patients with chronic GVHD after both PB (hazard ratio [HR], 1.58; P < .001) and BM (HR 1.73; P < .001) transplantations, its effect on mortality did not differ by graft type (P = 42). BM is the preferred graft for first chronic phase CML, whereas as either graft is suitable for other leukemias. (C) 2015 American Society for Blood and Marrow Transplantation. C1 [Eapen, Mary; Logan, Brent R.; Chen, Junfang] Med Coll Wisconsin, Dept Med, Ctr Int Blood & Marrow Transplant Res, Milwaukee, WI 53226 USA. [Logan, Brent R.] Med Coll Wisconsin, Inst Hlth & Soc, Div Biostat, Milwaukee, WI 53226 USA. [Appelbaum, Fredrick R.] Fred Hutchinson Canc Res Ctr, Div Clin Res, Seattle, WA 98104 USA. [Antin, Joseph H.] Dana Farber Canc Inst, Ctr Hematol Oncol, Boston, MA 02115 USA. [Anasetti, Claudio] H Lee Moffitt Canc Ctr & Res Inst, Tampa, FL USA. [Couriel, Daniel R.] Univ Michigan, Dept Med, Ann Arbor, MI 48109 USA. [Maziarz, Richard T.] Oregon Hlth & Sci Univ, Knight Canc Inst, Portland, OR 97201 USA. [McCarthy, Philip L.] Roswell Pk Canc Inst, Dept Med, Blood & Marrow Transplant Program, Buffalo, NY 14263 USA. [Nakamura, Ryotaro] City Hope Natl Med Ctr, Dept Hematol & Hematopoiet Cell Transplantat, Duarte, CA USA. [Ratanatharathorn, Voravit] Wayne State Univ, Karmanos Canc Inst, Dept Clin Arrangements, Detroit, MI USA. [Ratanatharathorn, Voravit] JP McCarthy Cord Stem Cell Bank, Detroit, MI USA. [Vij, Ravi] Washington Univ, Sch Med, Div Hematol & Oncol, St Louis, MO USA. [Champlin, Richard E.] Univ Texas MD Anderson Canc Ctr, Div Canc Med, Dept Stem Cell Transplantat & Cellular Therapy, Houston, TX 77030 USA. RP Eapen, M (reprint author), Med Coll Wisconsin, Dept Med, Ctr Int Blood & Marrow Transplant Res, 9200 W Wisconsin Ave, Milwaukee, WI 53226 USA. EM meapen@mcw.edu FU Public Health Service from the National Cancer Institute [U24-CA76518]; National Heart Lung and Blood Institute; National Institute of Allergy and Infectious Diseases; Health Resources and Services Administration [HHSH234200637015C]; Public Health Service FX Supported by a Public Health Service grant (U24-CA76518) from the National Cancer Institute, the National Heart Lung and Blood Institute and the National Institute of Allergy and Infectious Diseases, and Health Resources and Services Administration (HHSH234200637015C) for the CW Bill Young Stem Cell Transplantation program's contract for the Stem Cell Therapeutic Outcomes Database. M.E. is a Clinical Scholar of the Leukemia and Lymphoma Society. NR 12 TC 8 Z9 8 U1 1 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1083-8791 EI 1523-6536 J9 BIOL BLOOD MARROW TR JI Biol. Blood Marrow Transplant. PD JAN PY 2015 VL 21 IS 1 BP 55 EP 59 DI 10.1016/j.bbmt.2014.09.006 PG 5 WC Hematology; Immunology; Transplantation SC Hematology; Immunology; Transplantation GA AY6JB UT WOS:000347671600010 PM 25255165 ER PT J AU Duncan, CN Majhail, NS Brazauskas, R Wang, Z Cahn, JY Frangoul, HA Hayashi, RJ Hsu, JW Kamble, RT Kasow, KA Khera, N Lazarus, HM Loren, AW Marks, DI Maziarz, RT Mehta, P Myers, KC Norkin, M Pidala, JA Porter, DL Reddy, V Saber, W Savani, BN Schouten, HC Steinberg, A Wall, DA Warwick, AB Wood, WA Yu, LC Jacobsohn, DA Sorror, ML AF Duncan, Christine N. Majhail, Navneet S. Brazauskas, Ruta Wang, Zhiwei Cahn, Jean-Yves Frangoul, Haydar A. Hayashi, Robert J. Hsu, Jack W. Kamble, Rammurti T. Kasow, Kimberly A. Khera, Nandita Lazarus, Hillard M. Loren, Alison W. Marks, David I. Maziarz, Richard T. Mehta, Paulette Myers, Kasiani C. Norkin, Maxim Pidala, Joseph A. Porter, David L. Reddy, Vijay Saber, Wael Savani, Bipin N. Schouten, Harry C. Steinberg, Amir Wall, Donna A. Warwick, Anne B. Wood, William A. Yu, Lolie C. Jacobsohn, David A. Sorror, Mohamed L. TI Long-Term Survival and Late Effects among One-Year Survivors of Second Allogeneic Hematopoietic Cell Transplantation for Relapsed Acute Leukemia and Myelodysplastic Syndromes SO BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION LA English DT Article DE Hematopoietic cell transplantation; Allogeneic transplantation; Second transplantation; Long-term survival; Late effects ID BONE-MARROW-TRANSPLANTATION; ACUTE LYMPHOBLASTIC-LEUKEMIA; ACUTE MYELOID-LEUKEMIA; PREVENTIVE PRACTICES; OUTCOMES; MALIGNANCIES; CHILDREN; BURDEN; ADULTS AB We analyzed the outcomes of patients who survived disease-free for 1 year or more after a second allogeneic hematopoietic cell transplantation (HCT) for relapsed acute leukemia or myelodysplastic syndromes between 1980 and 2009. A total of 1285 patients received a second allogeneic transplant after disease relapse; among these, 325 were relapse free at 1 year after the second HCT. The median time from first to second HO' was 17 and 24 months for children and adults, respectively. A myeloablative preparative regimen was used in the second transplantation in 62% of children and 45% of adult patients. The overall 10-year conditional survival rates after second transplantation in this cohort of patients who had survived disease-free for at least 1 year was 55% in children and 39% in adults. Relapse was the leading cause of mortality (77% and 54% of deaths in children and adults, respectively). In multivariate analyses, only disease status before second HCT was significantly associated with higher risk for overall mortality (hazard ratio, 1.71 for patients with disease not in complete remission before second HCT; P < .01). Chronic graft-versus-host disease (GVHD) developed in 43% and 75% of children and adults after second transplantation. Chronic GVHD was the leading cause of nonrelapse mortality, followed by organ failure and infection. The cumulative incidence of developing at least 1 of the studied late effects within 10 years after second HCT was 63% in children and 55% in adults. The most frequent late effects in children were growth disturbance (10-year cumulative incidence, 22%) and cataracts (20%); in adults they were cataracts (20%) and avascular necrosis (13%). Among patients with acute leukemia and myelodysplastic syndromes who receive a second allogeneic HCT for relapse and survive disease free for at least 1 year, many can be expected to survive long term. However, they continue to be at risk for relapse and nonrelapse morbidity and mortality. Novel approaches are needed to minimize relapse risk and long-term transplantation morbidity in this population. (C) 2015 American Society for Blood and Marrow Transplantation. C1 [Duncan, Christine N.] Dana Farber Canc Inst, Dept Pediat Stem Cell Transplant, Boston, MA 02115 USA. [Majhail, Navneet S.] Cleveland Clin, Taussig Canc Inst, Dept Hematol & Oncol, Cleveland, OH 44106 USA. [Brazauskas, Ruta; Wang, Zhiwei; Saber, Wael] Med Coll Wisconsin, Ctr Int Blood & Marrow Transplant Res, Milwaukee, WI 53226 USA. [Brazauskas, Ruta] Med Coll Wisconsin, Inst Hlth & Soc, Div Biostat, Milwaukee, WI 53226 USA. [Cahn, Jean-Yves] Univ Hosp, Dept Hematol, Grenoble, France. [Frangoul, Haydar A.] Vanderbilt Univ, Sch Med, Dept Pediat, Div Hematol Oncol, Nashville, TN 37235 USA. [Hayashi, Robert J.] Washington Univ, Sch Med, Dept Pediat, Div Pediat Hematol Oncol, St Louis, MO 63110 USA. [Hsu, Jack W.; Norkin, Maxim] Shands HealthCare, Dept Med, Div Hematol & Oncol, Gainesville, FL USA. [Hsu, Jack W.; Norkin, Maxim] Univ Florida, Gainesville, FL USA. [Kamble, Rammurti T.] Baylor Coll Med, Ctr Cell & Gene Therapy, Div Hematol & Oncol, Houston, TX 77030 USA. [Kasow, Kimberly A.] Univ N Carolina, Dept Pediat, Div Hematol Oncol, Chapel Hill, NC USA. [Khera, Nandita] Mayo Clin, Dept Hematol Oncol, Phoenix, AZ USA. [Lazarus, Hillard M.] Univ Hosp, Case Med Ctr, Seidman Canc Ctr, Div Hematol & Oncol, Cleveland, OH USA. [Loren, Alison W.; Porter, David L.] Univ Penn, Perelman Sch Med, Dept Med, Div Hematol Oncol, Philadelphia, PA 19104 USA. [Marks, David I.] Univ Hosp Bristol NHS Trust, Dept Pediat Bone Marrow Transplant, Bristol, Avon, England. [Maziarz, Richard T.] Oregon Hlth & Sci Univ, Ctr Hematol Malignancies, Portland, OR 97201 USA. [Mehta, Paulette] Cent Arkansas Vet Healthcare Syst, Little Rock, AR USA. [Mehta, Paulette] Univ Arkansas Med Sci, Little Rock, AR 72205 USA. [Myers, Kasiani C.] Cincinnati Childrens Hosp Med Ctr, Dept Pediat, Div Bone Marrow Transplant & Immune Deficiency, Cincinnati, OH 45229 USA. [Pidala, Joseph A.] H Lee Moffitt Canc Ctr & Res Inst, Dept Blood & Marrow Transplant, Tampa, FL USA. [Reddy, Vijay] Univ Cent Florida, Coll Med, Dept Internal Med, Orlando, FL 32816 USA. [Savani, Bipin N.] Vanderbilt Univ, Med Ctr, Dept Med, Div Hematol Oncol, Nashville, TN 37235 USA. [Schouten, Harry C.] Acad Ziekenhuis, Dept Hematol, Maastricht, Netherlands. [Steinberg, Amir] Mt Sinai Hosp, Dept Hematol Oncol, New York, NY 10029 USA. [Wall, Donna A.] CancerCare Manitoba, Cellular Therapy Lab, Winnipeg, MB, Canada. [Wall, Donna A.] Univ Manitoba, Dept Pediat & Child Hlth & Immunol, Winnipeg, MB, Canada. [Warwick, Anne B.] Uniformed Serv Univ Hlth Sci, Dept Pediat, Bethesda, MD 20814 USA. [Wood, William A.] Univ N Carolina, Div Hematol Oncol, Chapel Hill, NC USA. [Yu, Lolie C.] Louisiana State Univ, Med Ctr, Ctr Canc & Blood Disorders, Div Hematol Oncol,Childrens Hosp, New Orleans, LA USA. [Jacobsohn, David A.] Childrens Natl Hlth Syst, Ctr Canc & Blood Disorders, Div Blood & Marrow Transplantat, Washington, DC USA. [Sorror, Mohamed L.] Fred Hutchinson Canc Res Ctr, Div Clin Res, Seattle, WA 98104 USA. [Sorror, Mohamed L.] Univ Washington, Sch Med, Dept Med, Div Med Oncol, Seattle, WA 98195 USA. RP Majhail, NS (reprint author), Cleveland Clin, Taussig Canc Inst, Blood & Marrow Transplant Program, 9500 Euclid Ave,Desk R35, Cleveland, OH 44195 USA. EM majhain@cccf.org FU National Cancer Institute (NCI) [U24-CA76518]; National Heart, Lung, and Blood Institute (NHLBI); National Institute of Allergy and Infectious Diseases (NIAID); NHLBI [5U01HL069294]; Health Resources and Services Administration (HRSA/DHHS); Office of Naval Research [N00014-06-1-0704, N00014-08-1-0058]; Allos, Inc.; Amgen, Inc.; Angioblast; [HHSH234200637015C] FX CIBMTR funding support: CIBMTR is supported by Public Health Service grant/cooperative agreement U24-CA76518 from the National Cancer Institute (NCI), the National Heart, Lung, and Blood Institute (NHLBI) and the National Institute of Allergy and Infectious Diseases (NIAID); a grant/cooperative agreement 5U01HL069294 from NHLBI and NCI; a contract HHSH234200637015C with Health Resources and Services Administration (HRSA/DHHS); 2 grants N00014-06-1-0704 and N00014-08-1-0058 from the Office of Naval Research; and grants from Allos, Inc.; Amgen, Inc.; Angioblast; anonymous donation to the Medical College of Wisconsin; Ariad; Be The Match Foundation; Blue Cross and Blue Shield Association; Buchanan Family Foundation; CaridianBCT; Celgene Corporation; CellGenix, GmbH; Children's Leukemia Research Association; Fresenius-Biotech North America, Inc.; Gamida Cell Teva Joint Venture Ltd.; Genentech, Inc.; Genzyme Corporation; GlaxoSmithKline; HistoGenetics, Inc.; Kiadis Pharma; The Leukemia & Lymphoma Society; The Medical College of Wisconsin; Merck & Co., Inc.; Millennium: The Takeda Oncology Co.; Milliman USA, Inc.; Miltenyi Biotec, Inc.; National Marrow Donor Program; Optum Healthcare Solutions, Inc.; Osiris Therapeutics, Inc.; Otsuka America Pharmaceutical, Inc.; RemedyMD; Sanofi; Seattle Genetics; Sigma-Tau Pharmaceuticals; Soligenix, Inc.; StemCyte, A Global Cord Blood Therapeutics Co.; Stemsoft Software, Inc.; Swedish Orphan Biovitrum; Tarix Pharmaceuticals; Teva Neuroscience, Inc.; THERAKOS, Inc.; and WellPoint, Inc.. The views expressed in this article do not reflect the official policy or position of the National Institute of Health, the Department of the Navy, the Department of Defense, or any other agency of the US Government. NR 34 TC 10 Z9 11 U1 2 U2 6 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1083-8791 EI 1523-6536 J9 BIOL BLOOD MARROW TR JI Biol. Blood Marrow Transplant. PD JAN PY 2015 VL 21 IS 1 BP 151 EP 158 DI 10.1016/j.bbmt.2014.10.006 PG 8 WC Hematology; Immunology; Transplantation SC Hematology; Immunology; Transplantation GA AY6JB UT WOS:000347671600023 PM 25316109 ER PT J AU Allegretti, AS Flythe, JE Benda, V Robinson, ES Charytan, D AF Allegretti, Andrew S. Flythe, Jennifer E. Benda, Vinod Robinson, Emily S. Charytan, DavidM. TI The Effect of Bicarbonate Administration via Continuous Venovenous Hemofiltration on Acid-Base Parameters in Ventilated Patients SO BIOMED RESEARCH INTERNATIONAL LA English DT Article ID CRITICALLY-ILL PATIENTS; RENAL-REPLACEMENT THERAPY; INTENSIVE-CARE-UNIT; SODIUM-BICARBONATE; METABOLIC-ACIDOSIS; LACTIC-ACIDOSIS; INTRACELLULAR PH; MIXED ACIDEMIA; CARDIAC-ARREST; FAILURE AB Background. Acute kidney injury (AKI) and metabolic acidosis are common in the intensive care unit. The effect of bicarbonate administration on acid-base parameters is unclear in those receiving continuous venovenous hemofiltration (CVVH) and mechanical ventilatory support. Methods. Metabolic and ventilatory parameters were prospectively examined in 19 ventilated subjects for up to 96 hours following CVV Hinitiation for AKI at an academic tertiary care center. Mixed linear regression modeling was performed to measure changes in pH, partial pressure of carbon dioxide (pCO(2)), serum bicarbonate, and base excess over time. Results. During the 96-hour study period, pCO(2) levels remained stable overall (initial pCO(2) 42.0 +/- 14.6 versus end-study pCO(2) 43.8 +/- 16.1 mmHg; P = 0.13 for interaction with time), for those with initial pCO(2) <= 40 mmHg (31.3 +/- 5.7 versus 35.0 +/- 4.8; P = 0.06) and for those with initial pCO(2) >40 mmHg (52.7 +/- 12.8 versus 53.4 +/- 19.2; P = 0.57). pCO(2) decreased during the immediate hours following CVVH initiation (42.0 +/- 14.6 versus 37.3 +/- 12.6 mmHg), though this change was nonsignificant (P = 0.052). Conclusions. We did not detect a significant increase in pCO(2) in response to the administration of bicarbonate via CVVH in a ventilated population. Additional studies of larger populations are needed to confirm this finding. C1 [Allegretti, Andrew S.] Massachusetts Gen Hosp, Dept Med, Div Nephrol, Boston, MA 02114 USA. [Flythe, Jennifer E.] Univ N Carolina, Sch Med, Kidney Ctr, Dept Med & Genet,Div Nephrol & Hypertens, Chapel Hill, NC 27599 USA. [Benda, Vinod; Robinson, Emily S.; Charytan, DavidM.] Brigham & Womens Hosp, Dept Med, Div Renal, Boston, MA 02115 USA. RP Allegretti, AS (reprint author), Massachusetts Gen Hosp, Dept Med, Div Nephrol, 7 Whittier Pl,Suite 106, Boston, MA 02114 USA. EM aallegretti@partners.org FU NIH [DK096189, HL11831402, DK100772, 5T32DK007540-29] FX David M. Charytan is supported by NIH Grants DK096189, HL11831402, and DK100772. Andrew S. Allegretti is supported by NIH Grant 5T32DK007540-29. David M. Charytan has consulted to Tengion, Keryx, and Medtronic Inc. and has provided expert witness services to Fresenius Inc. in matters related to maintenance hemodialysis and the dialysis prescription. Jennifer E. Flythe has received speaking honorarium from Dialysis Clinic, incorporated on matters related to maintenance hemodialysis. NR 32 TC 0 Z9 0 U1 0 U2 3 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 2015 AR 901590 DI 10.1155/2015/901590 PG 8 WC Biotechnology & Applied Microbiology; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Research & Experimental Medicine GA AZ5ZR UT WOS:000348297800001 ER PT J AU Rinker, JR Salter, AR Walker, H Amara, A Meador, W Cutter, GR AF Rinker, John R., II Salter, Amber R. Walker, Harrison Amara, Amy Meador, William Cutter, Gary R. TI Prevalence and characteristics of tremor in the NARCOMS multiple sclerosis registry: a cross-sectional survey SO BMJ OPEN LA English DT Article ID ADULT MOVEMENT-DISORDER; POPULATION; DISABILITY; VALIDATION; COMMON AB Objectives: (1) To describe the prevalence and severity of tremor in patients with multiple sclerosis (MS) registered within a large North American MS registry; (2) to provide detailed descriptions on the characteristics and severity of tremor in a subset of registrants and (3) to compare several measures of tremor severity for strength of agreement. Setting: The North American Research Committee on MS (NARCOMS) registry. Participants: Registrants of NARCOMS reporting mild or greater tremor severity. Outcome measures: We determined the cross-sectional prevalence of tremor in the NARCOMS registry over three semiannual updates between fall 2010 and fall 2011. A subset of registrants (n=552) completed a supplemental survey providing detailed descriptions of their tremor. Outcomes included descriptive characteristics of their tremors and correlations between outcome measures to determine the strength of agreement in assessing tremor severity. Results: The estimated prevalence of tremor in NARCOMS ranged from 45% to 46.8%, with severe tremor affecting 5.5-5.9% of respondents. In the subset completing the supplemental survey, mild tremor severity was associated with younger age of MS diagnosis and tremor onset than those with moderate or severe tremor. However, tremor severity did not differ by duration of disease or tremor. Respondents provided descriptions of tremor symptoms on the Clinical Ataxia Rating Scale, which had a moderate to good (rho=0.595) correlation with the Tremor Related Activities of Daily Living (TRADL) scale. Objectively scored Archimedes' spirals had a weaker (rho=0.358) correlation with the TRADL. Rates of unemployment, disability and symptomatic medication use increased with tremor severity, but were high even among those with mild tremor. Conclusions: Tremor is common among NARCOMS registrants and severely disabling for some. Both ADL-based and symptom-descriptive measures of tremor severity can be used to stratify patients. C1 [Rinker, John R., II; Walker, Harrison; Amara, Amy; Meador, William] Univ Alabama Birmingham, Dept Neurol, Birmingham, AL 35294 USA. [Rinker, John R., II] Birmingham VA Med Ctr, Birmingham, AL USA. [Salter, Amber R.; Cutter, Gary R.] Univ Alabama Birmingham, Dept Biostat, Birmingham, AL 35294 USA. RP Rinker, JR (reprint author), Univ Alabama Birmingham, Dept Neurol, UAB Stn, Birmingham, AL 35294 USA. EM rinkerj@uab.edu OI Amara, Amy/0000-0003-0762-9656 FU Biogen Idec [US-TYS-11-10238]; National Institutes of Health/National Institutes of Neurological Disorders and Stroke; [K23NS067053]; [K23NS080912] FX This study was funded by an Investigator Initiated Grant/Trial Award from Biogen Idec (US-TYS-11-10238). HW and AA receive grant support from the National Institutes of Health/National Institutes of Neurological Disorders and Stroke. HW is supported by K23NS067053 and AA is supported by K23NS080912. NR 18 TC 3 Z9 3 U1 1 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 2015 VL 5 IS 1 AR e006714 DI 10.1136/bmjopen-2014-006714 PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA AZ4DH UT WOS:000348171800041 PM 25573524 ER PT J AU Reijmer, YD Fotiadis, P Martinez-Ramirez, S Salat, DH Schultz, A Shoamanesh, A Ayres, AM Vashkevich, A Rosas, D Schwab, K Leemans, A Biessels, GJ Rosand, J Johnson, KA Viswanathan, A Gurol, ME Greenberg, SM AF Reijmer, Yael D. Fotiadis, Panagiotis Martinez-Ramirez, Sergi Salat, David H. Schultz, Aaron Shoamanesh, Ashkan Ayres, Alison M. Vashkevich, Anastasia Rosas, Diana Schwab, Kristin Leemans, Alexander Biessels, Geert-Jan Rosand, Jonathan Johnson, Keith A. Viswanathan, Anand Gurol, M. Edip Greenberg, Steven M. TI Structural network alterations and neurological dysfunction in cerebral amyloid angiopathy SO BRAIN LA English DT Article DE small vessel disease; mild cognitive impairment; stroke: imaging; amyloid imaging; executive function; tractography ID SMALL-VESSEL DISEASE; INFORMATION-PROCESSING SPEED; DIFFUSION TENSOR; COGNITIVE IMPAIRMENT; ALZHEIMER-DISEASE; TOPOLOGICAL ORGANIZATION; HUMAN CONNECTOME; BRAIN; DISRUPTION; LESIONS AB Cerebral amyloid angiopathy is an important risk factor for cognitive impairment. Reijmer et al. use multimodal MRI and amyloid PET imaging to report changes in the brain network structure, which may represent a key step between small vessel brain disease and cognitive and gait impairment.Cerebral amyloid angiopathy is a common form of small-vessel disease and an important risk factor for cognitive impairment. The mechanisms linking small-vessel disease to cognitive impairment are not well understood. We hypothesized that in patients with cerebral amyloid angiopathy, multiple small spatially distributed lesions affect cognition through disruption of brain connectivity. We therefore compared the structural brain network in patients with cerebral amyloid angiopathy to healthy control subjects and examined the relationship between markers of cerebral amyloid angiopathy-related brain injury, network efficiency, and potential clinical consequences. Structural brain networks were reconstructed from diffusion-weighted magnetic resonance imaging in 38 non-demented patients with probable cerebral amyloid angiopathy (69 +/- 10 years) and 29 similar aged control participants. The efficiency of the brain network was characterized using graph theory and brain amyloid deposition was quantified by Pittsburgh compound B retention on positron emission tomography imaging. Global efficiency of the brain network was reduced in patients compared to controls (0.187 +/- 0.018 and 0.201 +/- 0.015, respectively, P < 0.001). Network disturbances were most pronounced in the occipital, parietal, and posterior temporal lobes. Among patients, lower global network efficiency was related to higher cortical amyloid load (r = -0.52; P = 0.004), and to magnetic resonance imaging markers of small-vessel disease including increased white matter hyperintensity volume (P < 0.001), lower total brain volume (P = 0.02), and number of microbleeds (trend P = 0.06). Lower global network efficiency was also related to worse performance on tests of processing speed (r = 0.58, P < 0.001), executive functioning (r = 0.54, P = 0.001), gait velocity (r = 0.41, P = 0.02), but not memory. Correlations with cognition were independent of age, sex, education level, and other magnetic resonance imaging markers of small-vessel disease. These findings suggest that reduced structural brain network efficiency might mediate the relationship between advanced cerebral amyloid angiopathy and neurologic dysfunction and that such large-scale brain network measures may represent useful outcome markers for tracking disease progression. C1 [Reijmer, Yael D.; Fotiadis, Panagiotis; Martinez-Ramirez, Sergi; Shoamanesh, Ashkan; Ayres, Alison M.; Vashkevich, Anastasia; Schwab, Kristin; Rosand, Jonathan; Viswanathan, Anand; Gurol, M. Edip; Greenberg, Steven M.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Stroke Res, Boston, MA USA. [Salat, David H.; Schultz, Aaron] Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Boston, MA 02114 USA. [Rosas, Diana; Johnson, Keith A.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Neurol, Boston, MA USA. [Leemans, Alexander] Univ Med Ctr Utrecht, Image Sci Inst, Utrecht, Netherlands. [Biessels, Geert-Jan] Univ Med Ctr Utrecht, Brain Ctr Rudolf Magnus, Dept Neurol, Utrecht, Netherlands. [Johnson, Keith A.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiol, Boston, MA USA. RP Greenberg, SM (reprint author), JP Kistler Stroke Res Ctr, 175 Cambridge St,Suite 300, Boston, MA 02114 USA. EM sgreenberg@mgh.harvard.edu RI Leemans, Alexander/A-1784-2011; Gurol, Edip/J-2279-2014 OI Gurol, Edip/0000-0002-2169-4457 FU National Institutes of Health [R01 AG26484, R01 NS070834, K23 NS083711, R01NR010827]; American Heart Association [14POST20010031]; Netherlands Organization for Scientific Research (NWO) [VIDI] [639.072.411] FX This work is supported by grants from the National Institutes of Health [R01 AG26484 and R01 NS070834, K23 NS083711 and R01NR010827], from the American Heart Association [14POST20010031], and from the Netherlands Organization for Scientific Research (NWO) [VIDI grant 639.072.411]. NR 59 TC 29 Z9 29 U1 5 U2 10 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0006-8950 EI 1460-2156 J9 BRAIN JI Brain PD JAN 1 PY 2015 VL 138 BP 179 EP 188 DI 10.1093/brain/awu316 PN 1 PG 10 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA AZ4KM UT WOS:000348189800025 PM 25367025 ER PT J AU Iverson, GL Schatz, P AF Iverson, Grant L. Schatz, Philip TI Advanced topics in neuropsychological assessment following sport-related concussion SO BRAIN INJURY LA English DT Article DE Cognitive functioning; concussion; mild traumatic brain injury; neuropsychological assessment; psychometrics; reliable change ID TEST-RETEST RELIABILITY; HEALTHY OLDER-ADULTS; SCHOOL FOOTBALL PLAYERS; TRAUMATIC BRAIN-INJURY; IMPACT TEST BATTERY; TEST-PERFORMANCE; PROFESSIONAL FOOTBALL; CLINICAL-SIGNIFICANCE; BASE RATES; INTERNATIONAL-CONFERENCE AB Objective: This study examined seven topics relating to neuropsychological assessment following sport-related concussion: (i) traditional vs. computerized tests; (ii) the value of baseline, pre-season testing; (iii) invalid baseline scores and poor effort; (iv) when to assess following injury; (v) the reliability of neuropsychological tests; (vi) reliable change methodology; and (vii) new methods for identifying cognitive impairment. Main results: Baseline testing can be helpful for quantifying cognitive deficits following injury and for assessing recovery. At present, however, there is insufficient evidence to conclude that having baseline test results is clearly superior to not having baseline test results. Although invalid baseline test performance can be detected in some athletes, validity indicators cannot determine the extent to which the results were due to deliberately poor performance, confusion or misunderstanding regarding some aspect of the test, distractions in group testing environments or some combination of factors. When interpreting baseline and post-injury data, sophisticated psychometric methods (e.g. reliable change, multivariate base rates) are available to assist with more accurate identification of cognitive impairment and the serial monitoring of recovery. Conclusions: The value of neuropsychological assessment in the management of sport-related concussion has a strong empirical foundation. Additional research is needed, however, to refine its use. C1 [Iverson, Grant L.] Harvard Univ, Sch Med, Dept Phys Med & Rehabil, Charlestown, MA 02129 USA. [Iverson, Grant L.] Spaulding Rehabil Hosp, Charlestown, MA USA. [Iverson, Grant L.] MassGeneral Hosp Children Sport Concuss Program, 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. [Iverson, Grant L.; Schatz, Philip] St Josephs Univ, Dept Psychol, Philadelphia, PA 19131 USA. RP Iverson, GL (reprint author), Harvard Univ, Sch Med, Dept Phys Med & Rehabil, Neuropsychol Outcome Assessment Lab, 79-96 Thirteenth St, Charlestown, MA 02129 USA. EM giverson@mgh.harvard.edu FU ImPACT Applications, Inc.; CNS Vital Signs; Psychological Assessment Resources (PAR, Inc.) FX Grant Iverson, PhD, has been reimbursed by the government, professional scientific bodies and commercial organizations for discussing or presenting research relating to mild TBI and sport-related concussion at meetings, scientific conferences and symposiums. He has a clinical and consulting practice in forensic neuropsychology involving individuals who have sustained mild TBIs (including professional athletes). He has received research funding from several test publishing companies, including ImPACT Applications, Inc., CNS Vital Signs and Psychological Assessment Resources (PAR, Inc.). He has not received research support from ImPACT Applications, Inc. in the past 3 years. He receives royalties from two books relating to neuropsychology and one test (WCST-64). Philip Schatz, PhD, has served as a consultant to the International Brain Research Foundation, the Sports Concussion Center of New Jersey and ImPACT Applications, Inc., to study the effects of concussion in high school and collegiate athletes. However, these entities had no role in the conceptualization or content of the current manuscript or the decision to submit for publication. NR 101 TC 7 Z9 7 U1 2 U2 15 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 2015 VL 29 IS 2 BP 263 EP 275 DI 10.3109/02699052.2014.965214 PG 13 WC Neurosciences; Rehabilitation SC Neurosciences & Neurology; Rehabilitation GA AZ4OI UT WOS:000348201500015 PM 25313596 ER PT J AU Tolaney, S Burris, H Gartner, E Mayer, IA Saura, C Maurer, M Ciruelos, E Garcia, AA Campana, F Wu, B Xu, Y Jiang, J Winer, E Krop, I AF Tolaney, Sara Burris, Howard Gartner, Elaina Mayer, Ingrid A. Saura, Cristina Maurer, Matthew Ciruelos, Eva Garcia, Agustin A. Campana, Frank Wu, Bin Xu, Yi Jiang, Jason Winer, Eric Krop, Ian TI Phase I/II study of pilaralisib (SAR245408) in combination with trastuzumab or trastuzumab plus paclitaxel in trastuzumab-refractory HER2-positive metastatic breast cancer SO BREAST CANCER RESEARCH AND TREATMENT LA English DT Article DE HER2-positive; PI3K; Pilaralisib; Trastuzumab; Metastatic breast cancer ID ADVANCED SOLID TUMORS; I PI3K INHIBITOR; PIK3CA MUTATIONS; DOUBLE-BLIND; CHEMOTHERAPY; DOCETAXEL; PATHWAY; SAFETY; PERTUZUMAB; RESISTANCE AB This phase I/II dose-escalation study investigated the maximum tolerated dose (MTD), safety, pharmacokinetics, and efficacy of the pan-class I phosphoinositide 3-kinase inhibitor pilaralisib in combination with trastuzumab (Arm 1) or trastuzumab plus paclitaxel (Arm 2) in patients with HER2-positive metastatic breast cancer. Patients had progressed on prior trastuzumab (Arms 1 and 2) and received prior taxane (Arm 2). The MTD of pilaralisib was determined using a 3 + 3 dose-escalation design (starting dose 200 mg once daily). Forty-two patients were enrolled (21 in each arm). Five patients had a dose-limiting toxicity (DLT; three in Arm 1 and two in Arm 2). Dose-limiting toxicities were rash (three patients) and neutropenia (two patients). The MTD of pilaralisib was determined at 400 mg once daily in both arms. The most frequently reported treatment-related adverse events (AEs) were diarrhea (23.8 % in Arm 1 vs. 66.7 % in Arm 2), fatigue (14.3 vs. 42.9 %), and rash (33.3 vs. 38.1 %). The most frequently reported treatment-related grade a parts per thousand yen3 AEs were erythematous rash (9.5 %) in Arm 1 and diarrhea, peripheral neuropathy, and neutropenia (14.3 % each) in Arm 2. Steady-state pilaralisib exposure was similar to previous studies with pilaralisib monotherapy. No responses occurred in Arm 1; four of 20 evaluable patients (20 %) in Arm 2 had a partial response. Observed PIK3CA mutations in cell-free circulating DNA did not correlate with response. Pilaralisib in combination with trastuzumab with or without paclitaxel had an acceptable safety profile in metastatic HER2-positive breast cancer, with clinical activity in the paclitaxel arm. C1 [Tolaney, Sara; Winer, Eric; Krop, Ian] Dana Farber Canc Inst, Boston, MA 02215 USA. [Burris, Howard] Sarah Cannon Res Inst, Nashville, TN USA. [Gartner, Elaina] Wayne State Univ, Karmanos Canc Inst, Detroit, MI USA. [Mayer, Ingrid A.] Vanderbilt Ingram Canc Ctr, Nashville, TN USA. [Saura, Cristina] Vall dHebron Univ Hosp, VHIO, Barcelona, Spain. [Maurer, Matthew] Columbia Univ, Med Ctr, New York, NY USA. [Ciruelos, Eva] Hosp 12 Octubre, E-28041 Madrid, Spain. [Garcia, Agustin A.] Univ So Calif, Los Angeles, CA USA. [Campana, Frank; Wu, Bin; Xu, Yi] Sanofi, Cambridge, MA USA. [Jiang, Jason] Sanofi, Bridgewater, NJ USA. RP Tolaney, S (reprint author), Dana Farber Canc Inst, 450 Brookline Ave, Boston, MA 02215 USA. EM stolaney@partners.org OI Ciruelos, Eva /0000-0002-2796-1042; Saura, Cristina/0000-0001-8296-5065 FU Sanofi FX This study was funded by Sanofi. The authors received editorial support from Simone Blagg of MediTech Media, funded by Sanofi. The authors would like to thank the patients included in the trial and Patricia M. LoRusso, DO at the Yale Cancer Center for her contributions to the study. NR 30 TC 12 Z9 12 U1 0 U2 2 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0167-6806 EI 1573-7217 J9 BREAST CANCER RES TR JI Breast Cancer Res. Treat. PD JAN PY 2015 VL 149 IS 1 BP 151 EP 161 DI 10.1007/s10549-014-3248-4 PG 11 WC Oncology SC Oncology GA AZ4IB UT WOS:000348183700016 PM 25537644 ER PT J AU Strasser-Weippl, K Ramchandani, R Fan, L Li, JJ Hurlbert, M Finkelstein, D Shao, ZM Goss, PE AF Strasser-Weippl, Kathrin Ramchandani, Ritesh Fan, Lei Li, Junjie Hurlbert, Marc Finkelstein, Dianne Shao, Zhi-Ming Goss, Paul E. TI Pregnancy-associated breast cancer in women from Shanghai: risk and prognosis SO BREAST CANCER RESEARCH AND TREATMENT LA English DT Article DE Breast cancer; Pregnancy; Risk; Prognosis; Asian ID PROGESTERONE-RECEPTOR STATUS; JOINT ESTROGEN-RECEPTOR; FULL-TERM PREGNANCY; REPRODUCTIVE FACTORS; TRANSIENT INCREASE; YOUNG-WOMEN; 1ST BIRTH; AGE; DIAGNOSIS; LACTATION AB Breast cancer (BC) has been associated with pregnancy if diagnosed within 5-10 years after delivery (pregnancy-associated BC, PABC). PABC carries a poor prognosis compared to sporadic BC in Western populations. Data are limited regarding PABC in Asian populations, where longer periods of breastfeeding, higher birth rates and a lower median age of BC at diagnosis have been noted, all of which are known to influence prognosis. We used two datasets of women treated for early BC in Shanghai 1990-2012 (n = 10,161 and n = 7,411). For the analysis of BC risk after pregnancy we compared the distribution of pregnancy in our dataset to that in Shanghai using age-specific fertility rates. For disease-free survival (DFS) evaluation, we restricted our data to women a parts per thousand currency sign45 years. Women < 30 years had a significantly elevated BC risk within 5 years of completing a pregnancy compared to women who had not been pregnant in the previous 5 years. In women aged 20-24 the relative risk (RR) was 3.33 (P = 0.012), and for women aged 25-29 the RR was 1.76 (P = 0.0074). For women > 30, the RR was decreased. Patients with PABC had a higher risk of recurrence or death (hazard ratio (HR) for DFS 1.72, P = 0.019) compared to women with non-PABC by univariable analysis. Age was eliminated from the multivariable model by backward selection, resulting in tumor stage (3 versus 1, HR 3.08, P < .001) and recent pregnancy (HR 1.62, P < 0.05) as significant independent prognosticators. Having had a full-term pregnancy in the previous 5 years was associated with a 62 % increased risk of recurrence. We show that recent full-term pregnancy significantly elevates BC risk in women < 30 in Shanghai, and that women diagnosed with PABC have a particularly adverse prognosis. Health care providers and women in Asian populations should be made aware of these results. C1 [Strasser-Weippl, Kathrin] Wilhelminen Hosp, Vienna, Austria. [Ramchandani, Ritesh; Finkelstein, Dianne] Massachusetts Gen Hosp, Ctr Biostat, Boston, MA 02114 USA. [Fan, Lei; Li, Junjie; Shao, Zhi-Ming] Fudan Univ, Breast Canc Inst, Shanghai 200032, Peoples R China. [Hurlbert, Marc; Goss, Paul E.] Avon Fdn Women, New York, NY USA. [Hurlbert, Marc; Goss, Paul E.] Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA. RP Shao, ZM (reprint author), Fudan Univ, Breast Canc Inst, 399 Ling Ling Rd, Shanghai 200032, Peoples R China. EM pabc.research@yahoo.com OI Hurlbert, Marc/0000-0003-3301-3572 FU Avon Foundation, NY FX This work was supported be the Avon Foundation, NY. NR 42 TC 2 Z9 2 U1 0 U2 2 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0167-6806 EI 1573-7217 J9 BREAST CANCER RES TR JI Breast Cancer Res. Treat. PD JAN PY 2015 VL 149 IS 1 BP 255 EP 261 DI 10.1007/s10549-014-3219-9 PG 7 WC Oncology SC Oncology GA AZ4IB UT WOS:000348183700027 PM 25504083 ER PT J AU Robinson, ES Feng, R Okawa, J Werth, VP AF Robinson, E. S. Feng, R. Okawa, J. Werth, V. P. TI Improvement in the cutaneous disease activity of patients with dermatomyositis is associated with a better quality of life SO BRITISH JOURNAL OF DERMATOLOGY LA English DT Article ID RHEUMATOID-ARTHRITIS; LUPUS-ERYTHEMATOSUS; SEVERITY INDEX; SKIN-DISEASE; VALIDITY; SMOKING; RESPONSIVENESS; RELIABILITY; INSTRUMENT; IMPACT AB BackgroundCutaneous dermatomyositis (DM) disease activity is associated with decreased quality of life. ObjectivesTo assess if an improvement in quality of life, as measured by the Skindex-29 and patient-reported itch and pain on a 10-point visual analogue scale (VAS), correlated with an improvement in cutaneous DM disease activity. MethodsPatients with a completed cutaneous DM disease area and severity index [Cutaneous Dermatomyositis Disease Area and Severity Index (CDASI)] at two visits separated by at least 2months were classified into responder (n=15) and nonresponder (n=30) groups according to the point change in the CDASI activity scores between visits. Responders had at least a four-point improvement in CDASI activity, indicating clinically relevant improvement. ResultsThe change from baseline to the follow-up visit of the Skindex-29 subscale scores for the responders vs. the nonresponders were significantly different for emotions (P<001), functioning (P<001) and symptoms (P<001). The change in VAS score between responders and nonresponders was also significant for itch (P=001) and pain (P=004). There was no significant difference between the groups in terms of disease subtype, sex, race, age, treatment for DM, smoking history or a history of malignancy within 5years of a diagnosis of DM. ConclusionsThis is the first study to demonstrate that the quality of life of patients with DM improved as their cutaneous disease activity decreased. C1 [Robinson, E. S.; Okawa, J.; Werth, V. P.] Vet Affairs Med Ctr, Philadelphia, PA 19104 USA. [Robinson, E. S.; Okawa, J.; Werth, V. P.] Univ Penn, Dept Dermatol, Philadelphia, PA 19104 USA. [Feng, R.] Univ Penn, Dept Biostat & Epidemiol, Philadelphia, PA 19104 USA. RP Werth, VP (reprint author), Vet Affairs Med Ctr, Philadelphia, PA 19104 USA. EM werth@mail.med.upenn.edu FU NIAMS NIH HHS [K24 AR002207, K24-AR 02207, R21 AR066286] NR 16 TC 4 Z9 5 U1 1 U2 2 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0007-0963 EI 1365-2133 J9 BRIT J DERMATOL JI Br. J. Dermatol. PD JAN PY 2015 VL 172 IS 1 BP 169 EP 174 DI 10.1111/bjd.13167 PG 6 WC Dermatology SC Dermatology GA AY7FK UT WOS:000347726500026 PM 24909747 ER PT J AU Haak, CS Togsverd-Bo, K Thaysen-Petersen, D Wulf, HC Paasch, U Anderson, RR Haedersdal, M AF Haak, C. S. Togsverd-Bo, K. Thaysen-Petersen, D. Wulf, H. C. Paasch, U. Anderson, R. R. Haedersdal, M. TI Fractional laser-mediated photodynamic therapy of high-risk basal cell carcinomas - a randomized clinical trial SO BRITISH JOURNAL OF DERMATOLOGY LA English DT Article ID TOPICAL METHYL AMINOLEVULINATE; NONMELANOMA SKIN-CANCER; 5-YEAR FOLLOW-UP; 5-AMINOLEVULINIC ACID; PROTOPORPHYRIN-IX; ACTINIC KERATOSES; GUIDELINES; SURGERY; DELIVERY; PHOTOTHERMOLYSIS AB BackgroundPhotodynamic therapy (PDT) is approved for selected nodular basal cell carcinomas (nBCC) but efficacy is reduced for large and thick tumours. Ablative fractional lasers (AFXL) facilitate uptake of methyl aminolaevulinate (MAL) and may thus improve PDT outcome. ObjectivesTo evaluate efficacy and safety of AFXL-mediated PDT (AFXL-PDT) compared with conventional PDT of high-risk nBCC. MethodsPatients with histologically verified facial nBCC (n=32) defined as high-risk tumours were included; diameter >15mm, tumours located in high-risk zones, or on severely sun-damaged skin. Tumours were debulked and patients randomized to either AFXL-PDT (n=16) or PDT (n=16). Fractional CO2 laser treatment was applied at 5% density and 1000m (80mJ) ablation depth. MAL was applied under occlusion for 3h and illuminated with a 633-nm light-emitting diode source, 37Jcm(-2). Clinical assessments were performed at 3, 6, 9 and 12months and biopsies were taken at 12months. ResultsClinical cure rates at 3months were 100% (16 of 16 AFXL-PDT) and 88% (14 of 16 PDT, P=0484). Recurrences tended to occur later and in lower numbers after AFXL-PDT at 6, 9 and 12months (6%, 19%, 19%) than PDT (25%, 38%, 44%) (P=0114). Histology at 12months documented equal tumour clearance after AFXL-PDT (63%, 10 of 16) and PDT (56%, 9 of 16). Cosmetic outcomes were highly satisfactory after both treatments (P>0090). ConclusionsLong-term efficacy was similar after PDT and AFXL-PDT with a trend for a favourable short-term cure rate after AFXL-PDT. AFXL-PDT needs further refinement for nBCC and at present is not recommended over PDT. C1 [Haak, C. S.; Togsverd-Bo, K.; Thaysen-Petersen, D.; Wulf, H. C.; Haedersdal, M.] Univ Copenhagen, Bispebjerg Hosp, Dept Dermatol, DK-2400 Copenhagen NV, Denmark. [Haak, C. S.; Anderson, R. R.; Haedersdal, M.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Wellman Ctr Photomed, Boston, MA USA. [Paasch, U.] Univ Leipzig, Dept Dermatol, D-04109 Leipzig, Germany. [Paasch, U.] Univ Leipzig, Dept Venereol, D-04109 Leipzig, Germany. [Paasch, U.] Univ Leipzig, Dept Allergol, D-04109 Leipzig, Germany. RP Haak, CS (reprint author), Univ Copenhagen, Bispebjerg Hosp, Dept Dermatol, D-92,Bispebjerg Bakke 23, DK-2400 Copenhagen NV, Denmark. EM christinahaak@dadlnet.dk NR 43 TC 11 Z9 11 U1 1 U2 7 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0007-0963 EI 1365-2133 J9 BRIT J DERMATOL JI Br. J. Dermatol. PD JAN PY 2015 VL 172 IS 1 BP 215 EP 222 DI 10.1111/bjd.13166 PG 8 WC Dermatology SC Dermatology GA AY7FK UT WOS:000347726500032 PM 24903544 ER PT J AU Ananthakrishnan, AN Du, MM Berndt, SI Brenner, H Caan, BJ Casey, G Chang-Claude, J Duggan, D Fuchs, CS Gallinger, S Giovannucci, EL Harrison, TA Hayes, RB Hoffmeister, M Hopper, JL Hou, LF Hsu, L Jenkins, MA Kraft, P Ma, J Nan, HM Newcomb, PA Ogino, S Potter, JD Seminara, D Slattery, ML Thornquist, M White, E Wu, KN Peters, U Chan, AT AF Ananthakrishnan, Ashwin N. Du, Mengmeng Berndt, Sonja I. Brenner, Hermann Caan, Bette J. Casey, Graham Chang-Claude, Jenny Duggan, David Fuchs, Charles S. Gallinger, Steven Giovannucci, Edward L. Harrison, Tabitha A. Hayes, Richard B. Hoffmeister, Michael Hopper, John L. Hou, Lifang Hsu, Li Jenkins, Mark A. Kraft, Peter Ma, Jing Nan, Hongmei Newcomb, Polly A. Ogino, Shuji Potter, John D. Seminara, Daniela Slattery, Martha L. Thornquist, Mark White, Emily Wu, Kana Peters, Ulrike Chan, Andrew T. TI Red Meat Intake, NAT2, and Risk of Colorectal Cancer: A Pooled Analysis of 11 Studies SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID GENOME-WIDE ASSOCIATION; GENETIC SUSCEPTIBILITY; COLON-CANCER; HETEROCYCLIC AMINES; EXCISION-REPAIR; POULTRY INTAKE; POLYMORPHISMS; CONSUMPTION; SMOKING; COHORT AB Background: Red meat intake has been associated with risk of colorectal cancer, potentially mediated through heterocyclic amines. The metabolic efficiency of N-acetyltransferase 2 (NAT2) required for the metabolic activation of such amines is influenced by genetic variation. The interaction between red meat intake, NAT2 genotype, and colorectal cancer has been inconsistently reported. Methods: We used pooled individual-level data from the Colon Cancer Family Registry and the Genetics and Epidemiology of Colorectal Cancer Consortium. Red meat intake was collected by each study. We inferred NAT2 phenotype based on polymorphism at rs1495741, highly predictive of enzyme activity. Interaction was assessed using multiplicative interaction terms in multivariate-adjusted models. Results: From 11 studies, 8,290 colorectal cancer cases and 9,115 controls were included. The highest quartile of red meat intake was associated with increased risk of colorectal cancer compared with the lowest quartile [ OR, 1.41; 95% confidence interval (CI), 1.29-1.55]. However, a significant association was observed only for studies with retrospective diet data, not for studies with diet prospectively assessed before cancer diagnosis. Combining all studies, high red meat intake was similarly associated with colorectal cancer in those with a rapid/intermediate NAT2 genotype (OR, 1.38; 95% CI, 1.20-1.59) as with a slow genotype (OR, 1.43; 95% CI, 1.28-1.61; P interaction = 0.9). Conclusion: We found that high red meat intake was associated with increased risk of colorectal cancer only from retrospective case-control studies and not modified by NAT2 enzyme activity. Impact: Our results suggest no interaction between NAT2 genotype and red meat intake in mediating risk of colorectal cancer. (C)2014 AACR. C1 [Ananthakrishnan, Ashwin N.; Chan, Andrew T.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Ananthakrishnan, Ashwin N.; Ogino, Shuji; Chan, Andrew T.] Harvard Univ, Sch Med, Boston, MA USA. [Du, Mengmeng; Harrison, Tabitha A.; Hsu, Li; Newcomb, Polly A.; Potter, John D.; Seminara, Daniela; Slattery, Martha L.; White, Emily; Peters, Ulrike] Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA. [Berndt, Sonja I.] NCI, NIH, Bethesda, MD 20892 USA. [Brenner, Hermann] German Canc Res Ctr, Div Clin Epidemiol & Aging Res, Heidelberg, Germany. [Caan, Bette J.] German Canc Consortium, Heidelberg, Germany. [Caan, Bette J.] Kaiser Permanente Med Care, Oakland, CA USA. [Casey, Graham] Univ So Calif, Los Angeles, CA USA. [Chang-Claude, Jenny] German Canc Res Ctr DFKZ, Div Canc Epidemiol, Heidelberg, Germany. [Duggan, David] Translat Genom Res Inst, Phoenix, AZ USA. [Fuchs, Charles S.; Ma, Jing] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Fuchs, Charles S.; Giovannucci, Edward L.; Ma, Jing; Ogino, Shuji; Wu, Kana] Channing Div Network Med, Boston, MA USA. [Gallinger, Steven] Mt Sinai Hosp, Toronto, ON M5G 1X5, Canada. [Giovannucci, Edward L.] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. [Hayes, Richard B.] NYU, Sch Med, New York, NY USA. [Hopper, John L.; Jenkins, Mark A.] Univ Melbourne, Melbourne Sch Populat Hlth, Melbourne, Vic, Australia. [Hou, Lifang] Northwestern Univ, Dept Prevent Med, Evanston, IL USA. [Hou, Lifang] Northwestern Univ, Robert H Lurie Comprehens Canc Ctr, Feinberg Sch Med, Evanston, IL USA. [Nan, Hongmei] Indiana Univ, Simon Canc Ctr, Richard M Fairbanks Sch Publ Hlth, Dept Epidemiol, Indianapolis, IN 46204 USA. [Ogino, Shuji] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. [Potter, John D.; Peters, Ulrike] Univ Washington, Sch Publ Hlth, Seattle, WA 98195 USA. [Potter, John D.] Massey Univ, Ctr Publ Hlth Res, Wellington, New Zealand. [Slattery, Martha L.] Univ Utah Hlth Sci, Salt Lake City, UT USA. RP Chan, AT (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, 55 Fruit St, Boston, MA 02114 USA. EM upeters@fhcrc.org; achan@mgh.harvard.edu RI Hoffmeister, Michael/B-5745-2012; Jenkins, Mark/P-7803-2015; Gallinger, Steven/E-4575-2013; Brenner, Hermann/B-4627-2017; OI Hoffmeister, Michael/0000-0002-8307-3197; Jenkins, Mark/0000-0002-8964-6160; Brenner, Hermann/0000-0002-6129-1572; Potter, John/0000-0001-5439-1500; Hayes, Richard/0000-0002-0918-661X FU NIH [K23 DK097142, UM1 CA167551, U01 CA122839, R01 CA143237, R01 CA48998, P01 CA 055075, UM1 CA167552, R01 CA137178, R01 CA151993, P01 CA 087969, P50 CA 127003, R01 CA042182, U01 HG004446, K05 CA154337]; GECCO; NCI; U.S. Department of Health and Human Services [U01 CA137088, R01 CA059045, R25 CA094880]; Australasian Colorectal Cancer Family Registry [U01/U24 CA097735]; Ontario Registry for Studies of Familial Colorectal Cancer [U01/U24 CA074783]; Seattle Colorectal Cancer Family Registry [U01/U24 CA074794]; German Research Council (Deutsche Forschungsgemeinschaft) [BR 1704/6-1, BR 1704/6-3, BR 1704/6-4, CH 117/1-1]; German Federal Ministry of Education and Research [01KH0404, 01ER0814]; NIH through Ontario Registry for Studies of Familial Colorectal Cancer [U01 CA074783]; Ontario Research Fund [GL2]; Canadian Institutes of Health Research; Cancer Risk Evaluation (CaRE) Program grant from the Canadian Cancer Society Research Institute; Intramural Research Program of the Division of Cancer Epidemiology and Genetics and; Division of Cancer Prevention, NCI, NIH, DHHS; NIH, Genes, Environment and Health Initiative (GEI) [Z01 CP 010200]; NIH GEI [U01 HG 004438]; National Heart, Lung, and Blood Institute, National Institutes of Health, U.S. Department of Health and Human Services [HHSN268201100046C, HHSN268201100001C, HHSN268201100002C, HHSN268201100003C, HHSN268201100004C, HHSN271201100004C] FX A. Ananthakrishnan is supported by a grant from the NIH (K23 DK097142). M. Du, T. A Harrison, L. Hsu, M. Thornquist, and U. Peters are affiliated with GECCO, which is supported by the following grants from the NCI, NIH and U.S. Department of Health and Human Services (U01 CA137088, R01 CA059045, R25 CA094880; to M. Du).; G. Casey, J.L. Hopper, M.A. Jenkins, and P.A. Newcomb are affiliated with CCFR, which is supported by the NIH (UM1 CA167551) and through cooperative agreements with members of the Colon Cancer Family Registry and Principal Investigators. This genome-wide scan was supported by the NCI, NIH by U01 CA122839 and R01 CA143237 (to G. Casey). The following Colon CFR centers contributed data to this article and were supported by the NIH:; Australasian Colorectal Cancer Family Registry (U01/U24 CA097735), Ontario Registry for Studies of Familial Colorectal Cancer (U01/U24 CA074783). Seattle Colorectal Cancer Family Registry (U01/U24 CA074794).; H. Brenner, J. Chang-Claude, and M. Hoffmeister are affiliated with DACHS, which was supported by grants from the German Research Council (Deutsche Forschungsgemeinschaft, BR 1704/6-1, BR 1704/6-3, BR 1704/6-4, and CH 117/1-1), and the German Federal Ministry of Education and Research (01KH0404 and 01ER0814).; J.D. Potter and M.L. Slattery are affiliated with DALS, which was supported by the NIH (R01 CA48998; to M.L. Slattery).; A.T. Chan, C.S. Fuchs, K. Wu, E.L. Giovannucci, J. Ma, and S. Ogino are affiliated with HPFS, NHS, and PHS, which are supported by the NIH. HPFS is supported by the NIH (P01 CA 055075, UM1 CA167552, R01 CA137178, R01 CA151993, and P50 CA 127003), NHS by the NIH (R01 CA137178, R01 CA151993, P01 CA 087969, and P50 CA 127003) and PHS by the NIH (R01 CA042182).; S. Gallinger is affiliated with theOFCCR, which is supported by funding from the NIH through funding allocated to the Ontario Registry for Studies of Familial Colorectal Cancer (U01 CA074783); see CCFR section above. As subset of ARCTIC, OFCCR is supported by a GL2 grant from the Ontario Research Fund, the Canadian Institutes of Health Research, and the Cancer Risk Evaluation (CaRE) Program grant from the Canadian Cancer Society Research Institute.; S.I. Berndt and R.B. Hayes are affiliated with the PLCO, which is supported by the Intramural Research Program of the Division of Cancer Epidemiology and Genetics and supported by contracts from the Division of Cancer Prevention, NCI, NIH, DHHS. In addition, a subset of control samples were genotyped as part of the Cancer Genetic Markers of Susceptibility (CGEMS) Prostate Cancer GWAS (Yeager and colleagues Nat Genet 2007; 39: 645-9), Colon CGEMS pancreatic cancer scan (PanScan; Amundadottir and colleagues Nat Genet 2009; 41: 986-90 and Petersen and colleagues Nat Genet 2010; 42: 224-8), and the Lung Cancer and Smoking study. The prostate and PanScan study datasets were accessed with appropriate approval through the dbGaP online resource (http://cgems.cancer.gov/data/) accession numbers phs000207.v1.p1 and phs000206. v3. p2, respectively, and the lung datasets were accessed from the dbGaP website (http://www. ncbi. nlm. nih. gov/gap) through accession number phs000093.v2.p2. Funding for the Lung Cancer and Smoking study was provided by NIH, Genes, Environment and Health Initiative (GEI) Z01 CP 010200, NIH U01 HG004446, and NIH GEI U01 HG 004438. For the lung study, the GENEVA Coordinating Center provided assistance with genotype cleaning and general study coordination, and the Johns Hopkins University Center for Inherited Disease Research conducted genotyping.; P. A. Newcomb is affiliated with PMH, which is supported by the NIH (R01 CA076366; to P. A. Newcomb).; E. White is affiliated with VITAL, which is supported by the NIH (K05 CA154337).; D. Duggan is affiliated with TGEN and funded through a subaward with GECCO (R01 CA059045).; The WHI program is funded by the National Heart, Lung, and Blood Institute, National Institutes of Health, U.S. Department of Health and Human Services through contracts HHSN268201100046C, HHSN268201100001C, HHSN268201100002C, HHSN268201100003C, HHSN268201100004C, and HHSN271201100004C. NR 51 TC 6 Z9 6 U1 1 U2 19 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 2015 VL 24 IS 1 BP 198 EP 205 DI 10.1158/1055-9965.EPI-14-0897 PG 8 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA AZ1YG UT WOS:000348030700023 PM 25342387 ER PT J AU Penney, KL Sinnott, JA Tyekucheva, S Gerke, T Shui, IM Kraft, P Sesso, HD Freedman, ML Loda, M Mucci, LA Stampfer, MJ AF Penney, Kathryn L. Sinnott, Jennifer A. Tyekucheva, Svitlana Gerke, Travis Shui, Irene M. Kraft, Peter Sesso, Howard D. Freedman, Matthew L. Loda, Massimo Mucci, Lorelei A. Stampfer, Meir J. TI Association of Prostate Cancer Risk Variants with Gene Expression in Normal and Tumor Tissue SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID GENOME-WIDE ASSOCIATION; PROBE LEVEL DATA; SUSCEPTIBILITY LOCI; COMMON VARIANT; MULTIPLE LOCI; HNF1B GENE; 8Q24; IDENTIFICATION; SUMMARIES; ARRAY AB Background: Numerous germline genetic variants are associated with prostate cancer risk, but their biologic role is not well understood. One possibility is that these variants influence gene expression in prostate tissue. We therefore examined the association of prostate cancer risk variants with the expression of genes nearby and genome-wide. Methods: We generated mRNA expression data for 20,254 genes with the Affymetrix GeneChip Human Gene 1.0 ST microarray from normal prostate (N = 160) and prostate tumor (N = 264) tissue from participants of the Physicians' Health Study and Health Professionals Follow-up Study. With linear models, we tested the association of 39 risk variants with nearby genes and all genes, and the association of each variant with canonical pathways using a global test. Results: In addition to confirming previously reported associations, we detected several new significant (P < 0.05) associations of variants with the expression of nearby genes including C2orf43, ITGA6, MLPH, CHMP2B, BMPR1B, and MTL5. Genome-wide, five genes (MSMB, NUDT11, RBPMS2, NEFM, and KLHL33) were significantly associated after accounting for multiple comparisons for each SNP (P < 2.5 x 10(-6)). Many more genes had an FDR <10%, including SRD5A1 and PSCA, and we observed significant associations with pathways in tumor tissue. Conclusions: The risk variants were associated with several genes, including promising prostate cancer candidates and lipid metabolism pathways, suggesting mechanisms for their impact on disease. These genes should be further explored in biologic and epidemiologic studies. Impact: Determining the biologic role of these variants can lead to improved understanding of prostate cancer etiology and identify new targets for chemoprevention. (C) 2014 AACR. C1 [Penney, Kathryn L.; Sinnott, Jennifer A.; Gerke, Travis; Shui, Irene M.; Kraft, Peter; Sesso, Howard D.; Mucci, Lorelei A.; Stampfer, Meir J.] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. [Penney, Kathryn L.; Sinnott, Jennifer A.; Mucci, Lorelei A.; Stampfer, Meir J.] Brigham & Womens Hosp, Channing Div Network Med, Dept Med, Boston, MA 02115 USA. [Penney, Kathryn L.; Sinnott, Jennifer A.; Sesso, Howard D.; Loda, Massimo; Mucci, Lorelei A.; Stampfer, Meir J.] Harvard Univ, Sch Med, Boston, MA USA. [Sinnott, Jennifer A.; Tyekucheva, Svitlana; Kraft, Peter] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. [Tyekucheva, Svitlana] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA. [Sesso, Howard D.] Brigham & Womens Hosp, Dept Med, Div Prevent Med, Boston, MA 02115 USA. [Freedman, Matthew L.; Loda, Massimo] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Freedman, Matthew L.; Loda, Massimo] Broad Inst, Cambridge, MA USA. [Loda, Massimo] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. [Stampfer, Meir J.] Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA. RP Penney, KL (reprint author), Brigham & Womens Hosp, Channing Div Network Med, 181 Longwood Ave, Boston, MA 02115 USA. EM kpenney@hsph.harvard.edu FU Prostate Cancer Foundation Young Investigator Awards; Department of Defense Prostate Cancer Research Fellowship; A. David Mazzone Research Awards Program; [CA34944]; [CA40360]; [CA097193]; [HL26490]; [HL34595]; [CA133891]; [CA141298]; [P01CA055075]; [5U01CA098233]; [CA136578]; [CA131945]; [P50CA090381]; [T32CA09001] FX The PHS was supported by grants CA34944, CA40360, CA097193, HL26490, and HL34595. The HPFS was supported by grants CA133891, CA141298, and P01CA055075. This study and the following authors were supported by 5U01CA098233 (P. Kraft), CA136578 (L.A. Mucci), CA141298 (M.J. Stampfer), CA131945 (M. Loda), and P50CA090381 (L.A. Mucci and S. Tyekucheva). J.A. Sinnott received support from T32CA09001. K.L. Penney and L.A. Mucci were supported by Prostate Cancer Foundation Young Investigator Awards. I.M. Shui was supported by a Department of Defense Prostate Cancer Research Fellowship. K.L. Penney was supported by the A. David Mazzone Research Awards Program. NR 34 TC 13 Z9 13 U1 2 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 2015 VL 24 IS 1 BP 255 EP 260 DI 10.1158/1055-9965.EPI-14-0694-T PG 6 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA AZ1YG UT WOS:000348030700030 PM 25371445 ER PT J AU Peterlongo, P Chang-Claude, J Moysich, KB Rudolph, A Schmutzler, RK Simard, J Soucy, P Eeles, RA Easton, DF Hamann, U Wilkening, S Chen, BW Rookus, MA Schmidt, M van der Baan, FH Spurdle, AB Walker, LC Lose, F Maia, AT Montagna, M Matricardi, L Lubinski, J Jakubowska, A Garcia, EBG Olopade, OI Nussbaum, RL Nathanson, KL Domchek, SM Rebbeck, TR Arun, BK Karlan, BY Orsulic, S Lester, J Chung, WK Miron, A Southey, MC Goldgar, DE Buys, SS Janavicius, R Dorfling, CM van Rensburg, EJ Ding, YC Neuhausen, SL Hansen, TVO Gerdes, AM Ejlertsen, B Jonson, L Osorio, A Martinez-Bouzas, C Benitez, J Conway, EE Blazer, KR Weitzel, JN Manoukian, S Peissel, B Zaffaroni, D Scuvera, G Barile, M Ficarazzi, F Mariette, F Fortuzzi, S Viel, A Giannini, G Papi, L Martayan, A Tibiletti, MG Radice, P Vratimos, A Fostira, F Garber, JE Donaldson, A Brewer, C Foo, C Evans, DGR Frost, D Eccles, D Brady, A Cook, J Tischkowitz, M Adlard, J Barwell, J Walker, L Izatt, L Side, LE Kennedy, MJ Rogers, MT Porteous, ME Morrison, PJ Platte, R Davidson, R Hodgson, SV Ellis, S Cole, T Godwin, AK Claes, K Van Maerken, T Meindl, A Gehrig, A Sutter, C Engel, C Niederacher, D Steinemann, D Plendl, H Kast, K Rhiem, K Ditsch, N Arnold, N Varon-Mateeva, R Wappenschmidt, B Wang-Gohrke, S Bressac-de Paillerets, B Buecher, B Delnatte, C Houdayer, C Stoppa-Lyonnet, D Damiola, F Coupier, I Barjhoux, L Venat-Bouvet, L Golmard, L Boutry-Kryza, N Sinilnikova, OM Caron, O Pujol, P Mazoyer, S Belotti, M Piedmonte, M Friedlander, ML Rodriguez, GC Copeland, LJ de la Hoya, M Segura, PP Nevanlinna, H Aittomaki, K van Os, TAM Meijers-Heijboer, HEJ van der Hout, AH Vreeswijk, MPG Hoogerbrugge, N Ausems, MGEM van Doorn, HC Collee, JM Olah, E Diez, O Blanco, I Lazaro, C Brunet, J Feliubadalo, L Cybulski, C Gronwald, J Durda, K Jaworska-Bieniek, K Sukiennicki, G Arason, A Chiquette, J Teixeira, MR Olswold, C Couch, FJ Lindor, NM Wang, XS Szabo, CI Offit, K Corines, M Jacobs, L Robson, ME Zhang, LY Joseph, V Berger, A Singer, CF Rappaport, C Kaulich, DG Pfeiler, G Tea, MKM Phelan, CM Greene, MH Mai, PL Rennert, G Mulligan, AM Glendon, G Tchatchou, S Andrulis, IL Toland, AE Bojesen, A Pedersen, IS Thomassen, M Jensen, UB Laitman, Y Rantala, J von Wachenfeldt, A Ehrencrona, H Askmalm, MS Borg, A Kuchenbaecker, KB McGuffog, L Barrowdale, D Healey, S Lee, A Pharoah, PDP Chenevix-Trench, G Antoniou, AC Friedman, E AF Peterlongo, Paolo Chang-Claude, Jenny Moysich, Kirsten B. Rudolph, Anja Schmutzler, Rita K. Simard, Jacques Soucy, Penny Eeles, Rosalind A. Easton, Douglas F. Hamann, Ute Wilkening, Stefan Chen, Bowang Rookus, Matti A. Schmidt, MarjankaK. van der Baan, Frederieke H. Spurdle, Amanda B. Walker, Logan C. Lose, Felicity Maia, Ana-Teresa Montagna, Marco Matricardi, Laura Lubinski, Jan Jakubowska, Anna Garcia, Encarna B. Gomez Olopade, Olufunmilayo I. Nussbaum, Robert L. Nathanson, Katherine L. Domchek, Susan M. Rebbeck, Timothy R. Arun, Banu K. Karlan, Beth Y. Orsulic, Sandra Lester, Jenny Chung, Wendy K. Miron, Alex Southey, Melissa C. Goldgar, David E. Buys, Saundra S. Janavicius, Ramunas Dorfling, Cecilia M. van Rensburg, Elizabeth J. Ding, Yuan Chun Neuhausen, Susan L. Hansen, Thomas V. O. Gerdes, Anne-Marie Ejlertsen, Bent Jonson, Lars Osorio, Ana Martinez-Bouzas, Cristina Benitez, Javier Conway, Edye E. Blazer, Kathleen R. Weitzel, Jeffrey N. Manoukian, Siranoush Peissel, Bernard Zaffaroni, Daniela Scuvera, Giulietta Barile, Monica Ficarazzi, Filomena Mariette, Frederique Fortuzzi, Stefano Viel, Alessandra Giannini, Giuseppe Papi, Laura Martayan, Aline Tibiletti, Maria Grazia Radice, Paolo Vratimos, Athanassios Fostira, Florentia Garber, Judy E. Donaldson, Alan Brewer, Carole Foo, Claire Evans, D. Gareth R. Frost, Debra Eccles, Diana Brady, Angela Cook, Jackie Tischkowitz, Marc Adlard, Julian Barwell, Julian Walker, Lisa Izatt, Louise Side, Lucy E. Kennedy, M. John Rogers, Mark T. Porteous, Mary E. Morrison, Patrick J. Platte, Radka Davidson, Rosemarie Hodgson, Shirley V. Ellis, Steve Cole, Trevor Godwin, Andrew K. Claes, Kathleen Van Maerken, Tom Meindl, Alfons Gehrig, Andrea Sutter, Christian Engel, Christoph Niederacher, Dieter Steinemann, Doris Plendl, Hansjoerg Kast, Karin Rhiem, Kerstin Ditsch, Nina Arnold, Norbert Varon-Mateeva, Raymonda Wappenschmidt, Barbara Wang-Gohrke, Shan Bressac-de Paillerets, Brigitte Buecher, Bruno Delnatte, Capucine Houdayer, Claude Stoppa-Lyonnet, Dominique Damiola, Francesca Coupier, Isabelle Barjhoux, Laure Venat-Bouvet, Laurence Golmard, Lisa Boutry-Kryza, Nadia Sinilnikova, Olga M. Caron, Olivier Pujol, Pascal Mazoyer, Sylvie Belotti, Muriel Piedmonte, Marion Friedlander, Michael L. Rodriguez, Gustavo C. Copeland, Larry J. de la Hoya, Miguel Perez Segura, Pedro Nevanlinna, Heli Aittomaeki, Kristiina van Os, Theo A. M. Meijers-Heijboer, Hanne E. J. van der Hout, Annemarie H. Vreeswijk, Maaike P. G. Hoogerbrugge, Nicoline Ausems, Margreet G. E. M. van Doorn, Helena C. Collee, J. Margriet Olah, Edith Diez, Orland Blanco, Ignacio Lazaro, Conxi Brunet, Joan Feliubadalo, Lidia Cybulski, Cezary Gronwald, Jacek Durda, Katarzyna Jaworska-Bieniek, Katarzyna Sukiennicki, Grzegorz Arason, Adalgeir Chiquette, Jocelyne Teixeira, Manuel R. Olswold, Curtis Couch, Fergus J. Lindor, Noralane M. Wang, Xianshu Szabo, Csilla I. Offit, Kenneth Corines, Marina Jacobs, Lauren Robson, Mark E. Zhang, Liying Joseph, Vijai Berger, Andreas Singer, Christian F. Rappaport, Christine Kaulich, Daphne Geschwantler Pfeiler, Georg Tea, Muy-Kheng M. Phelan, Catherine M. Greene, Mark H. Mai, Phuong L. Rennert, Gad Mulligan, Anna Marie Glendon, Gord Tchatchou, Sandrine Andrulis, Irene L. Toland, Amanda Ewart Bojesen, Anders Pedersen, Inge Sokilde Thomassen, Mads Jensen, Uffe Birk Laitman, Yael Rantala, Johanna von Wachenfeldt, Anna Ehrencrona, Hans Askmalm, Marie Stenmark Borg, Ake Kuchenbaecker, Karoline B. McGuffog, Lesley Barrowdale, Daniel Healey, Sue Lee, Andrew Pharoah, Paul D. P. Chenevix-Trench, Georgia Antoniou, Antonis C. Friedman, Eitan CA EMBRACE GEMO Study Collaborators HEBON KConFab Investigators TI Candidate Genetic Modifiers for Breast and Ovarian Cancer Risk in BRCA1 and BRCA2 Mutation Carriers SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID ASSOCIATION AB Background: BRCA1 and BRCA2 mutation carriers are at substantially increased risk for developing breast and ovarian cancer. The incomplete penetrance coupled with the variable age at diagnosis in carriers of the same mutation suggests the existence of genetic and nongenetic modifying factors. In this study, we evaluated the putative role of variants in many candidate modifier genes. Methods: Genotyping data from 15,252 BRCA1 and 8,211 BRCA2 mutation carriers, for known variants (n = 3,248) located within or around 445 candidate genes, were available through the iCOGS custom-designed array. Breast and ovarian cancer association analysis was performed within a retrospective cohort approach. Results: The observed P values of association ranged between 0.005 and 1.000. None of the variants was significantly associated with breast or ovarian cancer risk in either BRCA1 or BRCA2 mutation carriers, after multiple testing adjustments. Conclusion: There is little evidence that any of the evaluated candidate variants act as modifiers of breast and/or ovarian cancer risk in BRCA1 or BRCA2 mutation carriers. Impact: Genome-wide association studies have been more successful at identifying genetic modifiers of BRCA1/2 penetrance than candidate gene studies. (C)2014 AACR. C1 [Peterlongo, Paolo; Ficarazzi, Filomena; Mariette, Frederique; Fortuzzi, Stefano] Fdn Ist FIRC Oncol Molecolare, IFOM, I-20139 Milan, Italy. [Peterlongo, Paolo; Radice, Paolo] Fdn IRCCS Ist Nazl Tumori INT, Dept Prevent & Predict Med, Unit Mol Bases Genet Risk & Genet Testing, Milan, Italy. [Chang-Claude, Jenny; Rudolph, Anja] German Canc Res Ctr, Div Cancer Epidemiol, Heidelberg, Germany. [Moysich, Kirsten B.] Roswell Pk Canc Inst, Dept Canc Prevent & Control, Buffalo, NY 14263 USA. [Schmutzler, Rita K.; Rhiem, Kerstin; Wappenschmidt, Barbara] Univ Hosp Cologne, Fac Med, Ctr Hereditary Breast & Ovarian Canc, Cologne, Germany. [Schmutzler, Rita K.; Rhiem, Kerstin; Wappenschmidt, Barbara] Univ Hosp Cologne, Fac Med, Ctr Integrated Oncol, Cologne, Germany. [Schmutzler, Rita K.] Univ Cologne, Ctr Mol Med Cologne, Cologne, Germany. [Simard, Jacques; Soucy, Penny] Ctr Hosp Univ Quebec Res Ctr, Quebec City, PQ, Canada. [Simard, Jacques; Soucy, Penny] Univ Laval, Quebec City, PQ, Canada. [Eeles, Rosalind A.] Inst Canc Res, Oncogenet Team, Surrey, England. [Eeles, Rosalind A.] Royal Marsden NHS Fdn Trust, Surrey, England. [Easton, Douglas F.; Frost, Debra; Platte, Radka; Ellis, Steve; Kuchenbaecker, Karoline B.; McGuffog, Lesley; Barrowdale, Daniel; Lee, Andrew; Antoniou, Antonis C.; EMBRACE] Univ Cambridge, Dept Publ Hlth & Primary Care, Ctr Canc Genet Epidemiol, Cambridge, England. [Hamann, Ute; Wilkening, Stefan; Chen, Bowang] German Canc Res Ctr, Heidelberg, Germany. [Rookus, Matti A.; van der Baan, Frederieke H.; HEBON] Netherlands Canc Inst, Dept Epidemiol, Amsterdam, Netherlands. [Schmidt, MarjankaK.] Netherlands Canc Inst, Div Psychosocial Res & Epidemiol, Amsterdam, Netherlands. [Spurdle, Amanda B.; Lose, Felicity; Healey, Sue; Chenevix-Trench, Georgia] QIMR Berghofer, Dept Genet & Computat Biol, Brisbane, Qld, Australia. [Walker, Logan C.] Univ Otago, Dept Pathol, Christchurch, New Zealand. [Maia, Ana-Teresa] Univ Algarve, Dept Biomed Sci & Med, Algarve, Portugal. [Montagna, Marco; Matricardi, Laura] IRCCS, Ist Oncol Veneto, Immunol & Mol Oncol Unit, Padua, Italy. [Lubinski, Jan; Jakubowska, Anna; Cybulski, Cezary; Gronwald, Jacek; Durda, Katarzyna; Jaworska-Bieniek, Katarzyna; Sukiennicki, Grzegorz] Pomeranian Med Univ, Dept Genet & Pathol, Szczecin, Poland. [Garcia, Encarna B. Gomez] MUMC, Dept Clin Genet, Maastricht, Netherlands. [Olopade, Olufunmilayo I.] Univ Chicago, Med Ctr, Dept Med & Human Genet, Ctr Clin Canc Genet, Chicago, IL 60637 USA. [Nussbaum, Robert L.] Univ Calif San Francisco, Dept Med, San Francisco, CA USA. [Nussbaum, Robert L.] Univ Calif San Francisco, Inst Human Genet, San Francisco, CA 94143 USA. [Nathanson, Katherine L.; Domchek, Susan M.] Univ Penn, Perelman Sch Med, Abramson Canc Ctr, Dept Med, Philadelphia, PA 19104 USA. [Rebbeck, Timothy R.] Univ Penn, Dept Epidemiol & Biostat, Abramson Canc Ctr, Perelman Sch Med, Philadelphia, PA 19104 USA. [Arun, Banu K.] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. [Karlan, Beth Y.; Orsulic, Sandra; Lester, Jenny] Cedars Sinai Med Ctr, Samuel Oschin Comprehens Canc Inst, Womens Canc Program, Los Angeles, CA 90048 USA. [Chung, Wendy K.] Columbia Univ, Dept Pediat, New York, NY 10027 USA. [Chung, Wendy K.] Columbia Univ, Dept Med, New York, NY USA. [Miron, Alex] Case Western Reserve Med Sch, Dept Genet & Genom, Cleveland, OH USA. [Southey, Melissa C.] Univ Melbourne, Dept Pathol, Genet Epidemiol Lab, Parkville, Vic 3052, Australia. [Goldgar, David E.] Univ Utah, Sch Med, Dept Dermatol, Salt Lake City, UT USA. [Buys, Saundra S.] Univ Utah, Sch Med, Huntsman Canc Inst, Dept Oncol Sci, Salt Lake City, UT USA. [Janavicius, Ramunas] Vilnius Univ Hosp Santariskiu Clin, Hematol Oncol & Transfus Med Ctr, Dept Mol & Regenerat Med, Vilnius, Lithuania. [Janavicius, Ramunas] State Res Inst Ctr Innovat Med, Vilnius, Lithuania. [Dorfling, Cecilia M.; van Rensburg, Elizabeth J.] Univ Pretoria, Dept Genet, ZA-0002 Pretoria, South Africa. 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[Vratimos, Athanassios; Fostira, Florentia] Natl Ctr Sci Res Demokritos, INRASTES, Mol Diagnost Lab, Athens, Greece. [Garber, Judy E.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Donaldson, Alan] St Michaels Hosp, Dept Clin Genet, Bristol, Avon, England. [Brewer, Carole] Royal Devon & Exeter Hosp, Dept Clin Genet, Exeter EX2 5DW, Devon, England. [Foo, Claire] Liverpool Womens NHS Fdn Trust, Cheshire & Merseyside Clin Genet Serv, Liverpool, Merseyside, England. [Evans, D. Gareth R.] Cent Manchester Univ Hosp NHS Fdn Trust, Manchester Acad Hlth Sci Ctr, Manchester, Lancs, England. [Eccles, Diana] Univ Southampton, Fac Med, Southampton Univ Hosp NHS Trust, Southampton SO9 5NH, Hants, England. [Brady, Angela] Kennedy Galton Ctr, North West Thames Reg Genet Serv, Harrow, Middx, England. [Cook, Jackie] Sheffield Childrens Hosp, Sheffield Clin Genet Serv, Sheffield, S Yorkshire, England. [Tischkowitz, Marc] Addenbrookes Hosp, East Anglian Reg Genet Serv, Dept Clin Genet, Cambridge, England. [Adlard, Julian] Yorkshire Reg Genet Serv, Leeds, W Yorkshire, England. [Barwell, Julian] Univ Hosp Leicester NHS Trust, Leicestershire Clin Genet Serv, Leicester, Leics, England. [Walker, Lisa] Churchill Hosp, Oxford Reg Genet Serv, Oxford OX3 7LJ, England. [Izatt, Louise] Guys & St Thomas NHS Fdn Trust, London, England. [Side, Lucy E.] Great Ormond St Hosp Sick Children, North East Thames Reg Genet Serv, London WC1N 3JH, England. [Kennedy, M. John] Univ Dublin Trinity Coll, Acad Unit Clin & Mol Oncol, Dublin 2, Ireland. [Kennedy, M. John] St James Hosp, Dublin 8, Ireland. [Rogers, Mark T.] Univ Wales Hosp, All Wales Med Genet Serv, Cardiff CF4 4XW, S Glam, Wales. [Porteous, Mary E.] Western Gen Hosp, South East Scotland Reg Genet Serv, Edinburgh EH4 2XU, Midlothian, Scotland. [Morrison, Patrick J.] Queens Univ Belfast, Dept Med Genet, Belfast HSC Trust, Ctr Canc Res & Cell Biol, Belfast, Antrim, North Ireland. [Davidson, Rosemarie] So Gen Hosp, West Scotland Reg Genet Serv, Glasgow G51 4TF, Lanark, Scotland. [Hodgson, Shirley V.] St Georges Univ London, Med Genet Unit, London, England. [Cole, Trevor] Birmingham Womens Hosp Healthcare NHS Trust, West Midlands Reg Genet Serv, Birmingham, W Midlands, England. [Godwin, Andrew K.] Univ Kansas, Med Ctr, Dept Pathol & Lab Med, Kansas City, MO USA. [Claes, Kathleen; Van Maerken, Tom] Univ Ghent, Ctr Genet Med, B-9000 Ghent, Belgium. [Meindl, Alfons] Tech Univ Munich, Klinikum Rechts Isar, Div Tumor Genet, Dept Gynecol & Obstet, D-80290 Munich, Germany. [Gehrig, Andrea] Univ Wurzburg, Inst Human Genet, Wurzburg, Germany. [Sutter, Christian] Heidelberg Univ, Heidelberg, Germany. [Engel, Christoph] Univ Leipzig, Inst Med Informat Stat & Epidemiol, D-04109 Leipzig, Germany. [Niederacher, Dieter] Univ Dusseldorf, Dusseldorf, Germany. [Steinemann, Doris] Hannover Med Sch, Hannover, NH, Germany. [Plendl, Hansjoerg] Univ Kiel, Inst Human Genet, Univ Hosp Schleswig Holstein, Kiel, Germany. [Kast, Karin] Tech Univ Dresden, Univ Hosp Carl Gustav Carus, Dept Gynecol & Obstet, Dresden, Germany. [Rhiem, Kerstin; Wappenschmidt, Barbara] Univ Cologne, Ctr Mol Med Cologne, Cologne, Germany. [Ditsch, Nina] Univ Munich, Dept Gynecol & Obstet, Munich, Germany. [Arnold, Norbert] Univ Kiel, Dept Gynecol & Obstet, Univ Hosp Schleswig Holstein, Kiel, Germany. [Varon-Mateeva, Raymonda] Charite, Inst Human Genet, Berlin, Germany. [Wang-Gohrke, Shan] Univ Hosp Ulm, Dept Gynecol & Obstet, Ulm, Germany. [Bressac-de Paillerets, Brigitte] Fdn Jean Dausset, INSERM U946, Paris, France. [Bressac-de Paillerets, Brigitte] Inst Cancerol Gustave Roussy, Serv Genet, Villejuif, France. [Buecher, Bruno; Houdayer, Claude; Stoppa-Lyonnet, Dominique; Golmard, Lisa; Belotti, Muriel] Inst Curie, Dept Tumour Biol, Paris, France. [Delnatte, Capucine] Ctr Rene Gauducheau, F-44035 Nantes, France. [Houdayer, Claude; Stoppa-Lyonnet, Dominique] Univ Paris 05, Sorbonne Paris Cite, Paris, France. [Stoppa-Lyonnet, Dominique] INSERM U830, Inst Curie, Paris, France. [Damiola, Francesca; Sinilnikova, Olga M.; Mazoyer, Sylvie] Univ Lyon 1, Ctr Rech Cancerol Lyon, INSERM U1052, CNRS UMR5286, F-69365 Lyon, France. [Coupier, Isabelle; Pujol, Pascal] CHU Arnaud Villeneuve, Unit Oncogenet, Montpellier, France. [Coupier, Isabelle; Barjhoux, Laure] CRLCC Val Aurelle, Unit Oncogenet, Montpellier, France. [Venat-Bouvet, Laurence] Ctr Hosp Univ Dupuytren, Dept Med Oncol, Limoges, France. [Boutry-Kryza, Nadia; Sinilnikova, Olga M.] Hosp Civils Lyon, Ctr Leon Berard, Unite Mixte Genet Constitutionnelle Canc Frequent, Lyon, France. [Caron, Olivier] Inst Cancerol Gustave Roussy, Dept Med, Villejuif, France. [Pujol, Pascal] INSERM 896, CRCM Val Aurelle, Montpellier, France. [GEMO Study Collaborators] GEMO Study Natl Canc Genet Network, UNICANCER Genet Grp, Paris, France. [Piedmonte, Marion] Roswell Pk Canc Inst, Stat & Data Ctr, Gynecol Oncol Grp, Buffalo, NY 14263 USA. [Friedlander, Michael L.] Australia New Zealand Gynaecol Oncol Grp, Coordinating Ctr, Camperdown, NSW, Australia. [Rodriguez, Gustavo C.] NorthShore Univ HealthSyst, Div Gynecol Oncol, Evanston, IL USA. [Copeland, Larry J.] Ohio State Univ, Dept Obstet & Gynecol, Hilliard, OH USA. [de la Hoya, Miguel] Hosp Clin San Carlos, IdISSC, Mol Oncol Lab, Madrid, Spain. [Perez Segura, Pedro] Hosp Clin San Carlos, IdISSC, Dept Oncol, Madrid, Spain. [Nevanlinna, Heli] Univ Helsinki, Cent Hosp, Dept Obstet & Gynecol, FIN-00290 Helsinki, Finland. [Nevanlinna, Heli] Univ Helsinki, Helsinki, Finland. [Aittomaeki, Kristiina] Univ Helsinki, Cent Hosp, Dept Clin Genet, Helsinki, Finland. [van Os, Theo A. M.] Univ Amsterdam, Acad Med Ctr, Dept Clin Genet, NL-1105 AZ Amsterdam, Netherlands. [Meijers-Heijboer, Hanne E. J.] Vrije Univ Amsterdam Med Ctr, Dept Clin Genet, Amsterdam, Netherlands. [van der Hout, Annemarie H.] Univ Groningen, Univ Med Ctr Groningen, Dept Genet, Groningen, Netherlands. [Vreeswijk, Maaike P. G.] Leiden Univ, Med Ctr LUMC, Dept Human Genet, Leiden, Netherlands. [Hoogerbrugge, Nicoline] Radboud Univ Nijmegen, Med Ctr, Dept Human Genet, Nijmegen, Netherlands. [Ausems, Margreet G. E. M.] Univ Med Ctr Utrecht, Dept Med Genet, Utrecht, Netherlands. [van Doorn, Helena C.] Erasmus Univ, Dept Obstet & Ginecol, Div Gynecol Oncol, MC Canc Inst, Rotterdam, Netherlands. [Collee, J. Margriet] Erasmus Univ, Med Ctr, Dept Clin Genet, Family Canc Clin, Rotterdam, Netherlands. [Olah, Edith] Natl Inst Oncol, Dept Mol Genet, Budapest, Hungary. [Diez, Orland] Univ Hosp Vall Hebron, Oncol Grp, Barcelona, Spain. [Diez, Orland] Univ Autonoma Barcelona, E-08193 Barcelona, Spain. [Diez, Orland] Vall Hebron Inst Oncol, Barcelona, Spain. [Diez, Orland] Vall Hebron Res Inst, Barcelona, Spain. [Blanco, Ignacio] IDIBELL Catalan Inst Oncol, Hereditary Canc Program, Genet Counseling Unit, Barcelona, Spain. [Lazaro, Conxi] IDIBELL Catalan Inst Oncol, Hereditary Canc Program, Mol Diagnost Unit, Barcelona, Spain. [Brunet, Joan] IDIBGI Catalan Inst Oncol, Hereditary Canc Program, Genet Counseling Unit, Girona, Spain. [Feliubadalo, Lidia; Arason, Adalgeir] Univ Iceland, Fac Med, BMC, Reykjavik, Iceland. [Arason, Adalgeir] Landspitali Univ Hosp, Dept Pathol, Reykjavik, Iceland. [Chiquette, Jocelyne] Univ Quebec, Ctr Rech FRSQ Ctr Hosp Affilie, Ctr Malad Sein Deschenes Fabia, Unite Rech Sante Populat, Quebec City, PQ, Canada. [Teixeira, Manuel R.] Univ Porto, Biomed Sci Inst ICBAS, P-4100 Oporto, Portugal. [Teixeira, Manuel R.] Portuguese Oncol Inst, Dept Genet, Oporto, Portugal. [Olswold, Curtis] Mayo Clin, Dept Hlth Sci Res, Rochester, NY USA. [Couch, Fergus J.] Mayo Clin, Dept Lab Med & Pathol & Hlth Sci Res, Rochester, NY USA. [Lindor, Noralane M.] Mayo Clin, Scottsdale, AZ USA. [Wang, Xianshu] Mayo Clin, Dept Lab Med & Pathol, Rochester, NY USA. [Szabo, Csilla I.] NIH, NHGRI, Bethesda, MD 20892 USA. [Offit, Kenneth; Robson, Mark E.; Joseph, Vijai] Mem Sloan Kettering Canc Ctr, Clin Genet Res Lab, New York, NY 10021 USA. [Corines, Marina; Jacobs, Lauren] Mem Sloan Kettering Canc Ctr, Dept Med, Clin Genet Serv, New York, NY 10021 USA. [Zhang, Liying] Mem Sloan Kettering Canc Ctr, Dept Pathol, Diagnost Mol Genet Lab, New York, NY 10021 USA. [Berger, Andreas; Singer, Christian F.; Rappaport, Christine; Kaulich, Daphne Geschwantler; Pfeiler, Georg; Tea, Muy-Kheng M.] Med Univ Vienna, Dept OB GYN, Vienna, Austria. [Berger, Andreas; Singer, Christian F.; Rappaport, Christine; Kaulich, Daphne Geschwantler; Pfeiler, Georg; Tea, Muy-Kheng M.] Med Univ Vienna, Ctr Comprehens Canc, Vienna, Austria. [Phelan, Catherine M.] H Lee Moffitt Canc Ctr & Res Inst, Dept Canc Epidemiol, Tampa, FL USA. [Greene, Mark H.; Mai, Phuong L.] NIH, Natl Canc Inst, Div Canc Epidemiol & Genet, Clin Genet Branch, Rockville, MD USA. [Rennert, Gad] Clalit Natl Canc Control Ctr, Haifa, Israel. [Mulligan, Anna Marie] Univ Toronto, Dept Lab Med & Pathol, Toronto, ON, Canada. [Mulligan, Anna Marie] Univ Hlth Network, Lab Med Program, Toronto, ON, Canada. [Glendon, Gord] Mt Sinai Hosp, Lunenfeld Tanenbaum Res Inst, Ontario Canc Genet Network, Toronto, ON M5G 1X5, Canada. [Tchatchou, Sandrine; Andrulis, Irene L.] Mt Sinai Hosp, Lunenfeld Tanenbaum Res Inst, Toronto, ON M5G 1X5, Canada. [Andrulis, Irene L.] Ohio State Univ, Ctr Comprehens Canc, Dept Med Genet, Columbus, OH 43210 USA. [Toland, Amanda Ewart] Ohio State Univ, Ctr Comprehens Canc, Dept Immunol, Columbus, OH 43210 USA. [Toland, Amanda Ewart] Ohio State Univ, Ctr Comprehens Canc, Dept Internal Med & Mol Virol, Div Human Canc Genet, Columbus, OH 43210 USA. [Bojesen, Anders] Vejle Hosp, Dept Clin Genet, Vejle, Denmark. [Pedersen, Inge Sokilde] Aalborg Univ Hosp, Dept Biochem, Sect Mol Diagnost, Aalborg, Denmark. [Thomassen, Mads] Odense Univ Hosp, Dept Clin Genet, DK-5000 Odense, Denmark. [Jensen, Uffe Birk] Aarhus Univ Hosp, Dept Clin Genet, DK-8000 Aarhus, Denmark. [Laitman, Yael] Sheba Med Ctr, Tel Aviv, Israel. [Rantala, Johanna] Karolinska Univ Hosp, Dept Clin Genet, Stockholm, Sweden. [von Wachenfeldt, Anna] Karolinska Univ Hosp, Dept Oncol, Stockholm, Sweden. [Ehrencrona, Hans] Univ Lund Hosp, Dept Clin Genet, S-22185 Lund, Sweden. [Ehrencrona, Hans] Uppsala Univ, Dept Immunol Genet & Pathol, Uppsala, Sweden. [Askmalm, Marie Stenmark] Linkoping Univ, Dept Clin & Expt Med, Div Clin Genet, Linkoping, Sweden. [Borg, Ake] Lund Univ, Dept Oncol, Lund, Sweden. [Pharoah, Paul D. P.] Univ Cambridge, Dept Oncol, Cambridge, England. [KConFab Investigators] kConFab Kathleen Cuningham Consortium Res Familia, Peter Mac Callum Canc Ctr, Melbourne, Vic, Australia. RP Peterlongo, P (reprint author), Fdn Ist FIRC Oncol Molecolare, IFOM, Via Adamello 16, I-20139 Milan, Italy. EM paolo.peterlongo@ifom.eu; eitan.friedman@sheba.health.gov.il RI Spurdle, Amanda/A-4978-2011; Feliubadalo, Lidia/G-4577-2016; Andrulis, Irene/E-7267-2013; Jansen van Rensburg, Elizabeth (Lizette)/B-9104-2011; Giannini, Giuseppe/B-5672-2013; montagna, marco/E-2225-2012; Hoogerbrugge, Nicoline/O-1016-2013; Osorio, Ana/I-4324-2014; Maia, Ana-Teresa/F-4404-2012; Teixeira, Manuel/E-4885-2011; Gronwald, Jacek/A-4576-2017; manoukian, siranoush/E-7132-2017; Peissel, Bernard/E-8187-2017; OI Brunet, Joan/0000-0003-1945-3512; Joseph, Vijai/0000-0002-7933-151X; VENAT-BOUVET, Laurence/0000-0002-0716-2550; Evans, Gareth/0000-0002-8482-5784; Papi, Laura/0000-0003-4552-9517; Robson, Mark/0000-0002-3109-1692; Barrowdale, Daniel/0000-0003-1661-3939; Lose, Felicity/0000-0001-8337-3547; Nevanlinna, Heli/0000-0002-0916-2976; Eeles, Rosalind/0000-0002-3698-6241; Blanco, Ignacio/0000-0002-7414-7481; Spurdle, Amanda/0000-0003-1337-7897; Feliubadalo, Lidia/0000-0002-1736-0112; Ehrencrona, Hans/0000-0002-5589-3622; Rappaport-Fuerhauser, Christine/0000-0002-6820-0020; Giannini, Giuseppe/0000-0003-0299-4056; montagna, marco/0000-0002-4929-2150; Osorio, Ana/0000-0001-8124-3984; Maia, Ana-Teresa/0000-0002-0454-9207; Teixeira, Manuel/0000-0002-4896-5982; Gronwald, Jacek/0000-0002-3643-2871; manoukian, siranoush/0000-0002-6034-7562; Peissel, Bernard/0000-0001-9233-3571; Fortuzzi, Stefano/0000-0002-5662-3800 FU European Community (COGS) [223175, HEALTH-F2-2009-223175]; Cancer Research UK [C1287/A10118, C1287/A 10710, C12292/A11174, C1281/A12014, C5047/A8384, C5047/ A15007, C5047/A10692, C1287/A16563, C1287/A17523, C5047/A8385]; NIH [CA128978, R01-CA102776, R01CA083855]; Post-Cancer GWAS initiative [1U19CA148537, 1U19 CA148065, 1U19 CA148112]; Department of Defence [W81XWH-10-1-0341]; Canadian Institutes of Health Research (CIHR) for the CIHR Team in Familial Risks of Breast Cancer; Komen Foundation; Breast Cancer Research Foundation; Ovarian Cancer Research Fund; National Cancer Institute [UM1 CA164920, RC4CA153828]; Research Council of Lithuania [LIG-07/2012]; Cancer Association of South Africa (CANSA); Spanish Association against Cancer [AECC08, RTICC 06/0020/1060, FISPI12/00070]; Mutua Madrilena Foundation (FMMA); City of Hope Clinical Cancer Genetics Community Research Network and the Hereditary Cancer Research Registry (COH-CCGCRN); Fondazione IRCCS Istituto Nazionale dei Tumori; DKFZ; NIHR grant to the Biomedical Research Centre, Manchester; NIHR grant to the Biomedical Research Centre at The Institute of Cancer Research; Royal Marsden NHS Foundation Trust; German Cancer Aid [109078]; Center for Molecular Medicine Cologne (CMMC); Ligue National Contre le Cancer; Association "Le cancer du sein, parlons-en!" Award; Canadian Institutes of Health Research for the "CIHR Team in Familial Risks of Breast Cancer" program; Helsinki University Central Hospital Research Fund, Academy of Finland [266528]; Finnish Cancer Society and the Sigrid Juselius Foundation; Dutch Cancer Society [NKI1998-1854, NKI2004-3088, NKI2007-3756]; Netherlands Organization of Scientific Research [NWO 91109024]; Pink Ribbon [110005]; BBMRI [NWO 184.021.007/CP46]; Hungarian Research Grants [KTIA OTKA CK-80745, OTKA K-112228]; Asociacion Espanola Contra el Cancer; Spanish Health Research Fund; Carlos III Health Institute; Catalan Health Institute and Autonomous Government of Catalonia [ISCIIIRETIC RD06/0020/1051, RD12/0036/008, PI10/01422, PI10/00748, PI13/00285, 2009SGR290]; Icelandic Association "Walking for Breast Cancer Research"; Landspitali University Hospital Research Fund; Ministero della Salute; Istituto Oncologico Veneto; National Breast Cancer Foundation; National Health and Medical Research Council (NHMRC); Queensland Cancer Fund; Cancer Councils of New South Wales, Victoria, Tasmania and South Australia; Cancer Foundation of Western Australia; NCI Specialized Program of Research Excellence (SPORE) in Breast Cancer [CA116201]; U.S. Department of Defence Ovarian Cancer Idea award [W81XWH-10-1-0341]; David and Margaret T. Grohne Family Foundation; Ting Tsung and Wei Fong Chao Foundation; Robert and Kate Niehaus Clinical Cancer Genetics Initiative; Ohio State University Comprehensive Cancer Center; Swedish Cancer Society; Women's Cancer Program (WCP) at the Samuel Oschin Comprehensive Cancer Institute - American Cancer Society Early Detection Professorship [SIOP-06-258-01-COUN]; NEYE Foundation; European Union (European Social Fund - ESF); Greek national funds through the Operational Program "Education and Lifelong Learning" of the National Strategic Reference Framework (NSRF) - Research Funding Program of the General Secretariat for Research Technology:; University of Kansas Cancer Center [P30 CA168524]; Kansas Bioscience Authority Eminent Scholar Program; National Cancer Institute grants to the Gynecologic Oncology Group (GOG) Administrative Office and Tissue Bank [CA 27469]; GOG Statistical and Data Center [CA 37517]; NCI's Community Clinical Oncology Program (CCOP) grant [CA 101165]; Canadian Breast Cancer Research Alliance-grant [019511]; Ministry of Economic Development, Innovation and Export Trade - grant [PSR-SIIRI-701]; Israel Cancer Association; Israeli Inherited Breast Cancer Consortium; Susan G. Komen Foundation; Basser Research Center; ISCIII [RD12/00369/0006]; European Regional Development funds, Spain; Morris and Horowitz Families Endowed Professorship; Chancellors Distinguished Chair in Biomedical Sciences Professorship; Intramural Research Program of the US National Cancer Institute; NIH; Westat, Inc; [PBZ_KBN_122/P05/2004]; [1R01 CA149429-01]; [5U01CA113916]; [R01CA140323]; [NO2-CP-11019- 50]; [N02-CP-65504]; Associazione Italiana per la Ricerca sul Cancro FX Funding for the iCOGS infrastructure came from: the European Community's Seventh Framework Programme under grant agreement no 223175 (HEALTH-F2-2009-223175; COGS), Cancer Research UK (C1287/A10118, C1287/A 10710, C12292/A11174, C1281/A12014, C5047/A8384, C5047/ A15007, C5047/A10692), the NIH (CA128978) and Post-Cancer GWAS initiative (1U19CA148537, 1U19 CA148065 and 1U19 CA148112 - the GAMEON initiative), the Department of Defence (W81XWH-10-1-0341), the Canadian Institutes of Health Research (CIHR) for the CIHR Team in Familial Risks of Breast Cancer, Komen Foundation for the Cure, the Breast Cancer Research Foundation, and the Ovarian Cancer Research Fund. BCFR was supported by grant UM1 CA164920 from the National Cancer Institute. BFBOCC was partly supported by: Research Council of Lithuania grant LIG-07/2012; BRCA-gene mutations and breast cancer in South African women (BMBSA) was supported by grants from the Cancer Association of South Africa (CANSA) to Elizabeth J. van Rensburg; the CNIO study was supported by Spanish Association against Cancer (AECC08), RTICC 06/0020/1060 and FISPI12/00070 and Mutua Madrilena Foundation (FMMA); City of Hope Clinical Cancer Genetics Community Research Network and the Hereditary Cancer Research Registry (COH-CCGCRN) was supported in part by Award Number RC4CA153828 (PI: J. Weitzel) from the National Cancer Institute and the Office of the Director, NIH. CONSIT TEAM was partially supported by funds from Italian citizens who allocated the 5 x 1000 share of their tax payment in support of the Fondazione IRCCS Istituto Nazionale dei Tumori, according to Italian laws (INT-Institutional strategic projects '5 x 1000'); the DKFZ study was supported by the DKFZ; EMBRACE was supported by Cancer Research UK Grants C1287/A10118, C1287/A16563 and C1287/A17523. D. Gareth Evans and Fiona Lalloo are supported by an NIHR grant to the Biomedical Research Centre, Manchester. The Investigators at The Institute of Cancer Research and The Royal Marsden NHS Foundation Trust were supported by an NIHR grant to the Biomedical Research Centre at The Institute of Cancer Research and The Royal Marsden NHS Foundation Trust. Ros Eeles and Elizabeth Bancroft were supported by Cancer Research UK Grant C5047/A8385; the German Consortium of Hereditary Breast and Ovarian Cancer (GC-HBOC) is kindly supported by the German Cancer Aid to Rita K. Schmutzler (grant no. 109078) and by the Center for Molecular Medicine Cologne (CMMC); the GEMO study was supported by the Ligue National Contre le Cancer; the Association "Le cancer du sein, parlons-en!" Award; and the Canadian Institutes of Health Research for the "CIHR Team in Familial Risks of Breast Cancer" program; the HEBCS was financially supported by the Helsinki University Central Hospital Research Fund, Academy of Finland (266528), the Finnish Cancer Society and the Sigrid Juselius Foundation; The HEBON study was supported by the Dutch Cancer Society grants NKI1998-1854, NKI2004-3088, NKI2007-3756, the Netherlands Organization of Scientific Research grant NWO 91109024, the Pink Ribbon grant 110005 and the BBMRI grant NWO 184.021.; 007/CP46; Hungarian Breast and Ovarian Cancer Study (HUNBOCS) was supported by Hungarian Research Grants KTIA OTKA CK-80745 and OTKA K-112228; ICO was sponsored by Asociacion Espanola Contra el Cancer, Spanish Health Research Fund; Carlos III Health Institute; Catalan Health Institute and Autonomous Government of Catalonia, contract grant numbers: ISCIIIRETIC RD06/0020/1051, RD12/0036/008, PI10/01422, PI10/00748, PI13/00285, and 2009SGR290; The IHCC was supported by Grant PBZ_KBN_122/P05/2004; The ILUH group was supported by the Icelandic Association "Walking for Breast Cancer Research" and by the Landspitali University Hospital Research Fund; IOVHBOCS was supported by Ministero della Salute and "5 x 1000" Istituto Oncologico Veneto grant; kConFab was supported by grants from the National Breast Cancer Foundation, the National Health and Medical Research Council (NHMRC) and by the Queensland Cancer Fund, the Cancer Councils of New South Wales, Victoria, Tasmania and South Australia, and the Cancer Foundation of Western Australia; MAYO was supported by NIH grant CA128978, an NCI Specialized Program of Research Excellence (SPORE) in Breast Cancer (CA116201), a U.S. Department of Defence Ovarian Cancer Idea award (W81XWH-10-1-0341) and a grant from the Breast Cancer Research Foundation, the David and Margaret T. Grohne Family Foundation, and the Ting Tsung and Wei Fong Chao Foundation; MSKCC was supported by grants from the Breast Cancer Research Foundation and Robert and Kate Niehaus Clinical Cancer Genetics Initiative; OSUCCG was supported by the Ohio State University Comprehensive Cancer Center; SWE-BRCA collaborators are supported by the Swedish Cancer Society; the Women's Cancer Program (WCP) at the Samuel Oschin Comprehensive Cancer Institute was funded by the American Cancer Society Early Detection Professorship (SIOP-06-258-01-COUN).; This work was supported by the NEYE Foundation; by the European Union (European Social Fund - ESF) and Greek national funds through the Operational Program "Education and Lifelong Learning" of the National Strategic Reference Framework (NSRF) - Research Funding Program of the General Secretariat for Research& Technology: ARISTEIA, Investing in knowledge society through the European Social Fund; by the University of Kansas Cancer Center (P30 CA168524) and the Kansas Bioscience Authority Eminent Scholar Program; by National Cancer Institute grants to the Gynecologic Oncology Group (GOG) Administrative Office and Tissue Bank (CA 27469), the GOG Statistical and Data Center (CA 37517), and by NCI's Community Clinical Oncology Program (CCOP) grant (CA 101165); by the Canadian Institutes of Health Research for the "CIHR Team in Familial Risks of Breast Cancer" program, the Canadian Breast Cancer Research Alliance-grant #019511 and the Ministry of Economic Development, Innovation and Export Trade - grant #PSR-SIIRI-701; through a grant by the Israel Cancer Association and the funding for the Israeli Inherited Breast Cancer Consortium; by NIH (R01-CA102776 and R01CA083855; by Breast Cancer Research Foundation; by Susan G. Komen Foundation; by Basser Research Center; by RD12/00369/0006 from ISCIII and the European Regional Development funds, Spain and by 1R01 CA149429-01 grant.; Susan L. Neuhausen was partially supported by the Morris and Horowitz Families Endowed Professorship; Andrew K. Godwin was funded by 5U01CA113916, R01CA140323, and by the Chancellors Distinguished Chair in Biomedical Sciences Professorship; the research of Mark H Greene and Phuong L Mai was supported by the Intramural Research Program of the US National Cancer Institute, NIH, and by support services contracts NO2-CP-11019- 50 and N02-CP-65504 with Westat, Inc, Rockville, MD. NR 8 TC 3 Z9 3 U1 3 U2 29 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 2015 VL 24 IS 1 BP 308 EP 316 DI 10.1158/1055-9965.EPI-14-0532 PG 9 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA AZ1YG UT WOS:000348030700038 PM 25336561 ER PT J AU Takx, RAP Blomberg, BA El Aidi, H Habets, J de Jong, PA Nagel, E Hoffmann, U Leiner, T AF Takx, Richard A. P. Blomberg, Bjorn A. El Aidi, Hamza Habets, Jesse de Jong, Pim A. Nagel, Eike Hoffmann, Udo Leiner, Tim TI Diagnostic Accuracy of Stress Myocardial Perfusion Imaging Compared to Invasive Coronary Angiography With Fractional Flow Reserve Meta-Analysis SO CIRCULATION-CARDIOVASCULAR IMAGING LA English DT Article DE fractional flow reserve, myocardial; meta-analysis; myocardial perfusion imaging ID CARDIAC MAGNETIC-RESONANCE; ARTERY-DISEASE; CLINICAL-OUTCOMES; STATEMENT; SEVERITY; REVASCULARIZATION; CATHETERIZATION; QUANTIFICATION; INTERVENTION; ASSOCIATION AB Background-Hemodynamically significant coronary artery disease is an important indication for revascularization. Stress myocardial perfusion imaging is a noninvasive alternative to invasive fractional flow reserve for evaluating hemodynamically significant coronary artery disease. The aim was to determine the diagnostic accuracy of myocardial perfusion imaging by single-photon emission computed tomography, echocardiography, MRI, positron emission tomography, and computed tomography compared with invasive coronary angiography with fractional flow reserve for the diagnosis of hemodynamically significant coronary artery disease. Methods and Results-The meta-analysis adhered to the Preferred Reporting Items for Systematic Reviews and Meta-analyses statement. PubMed, EMBASE, and Web of Science were searched until May 2014. Thirty-seven studies, reporting on 4721 vessels and 2048 patients, were included. Meta-analysis yielded pooled sensitivity, pooled specificity, pooled likelihood ratios (LR), pooled diagnostic odds ratio, and summary area under the receiver operating characteristic curve. The negative LR (NLR) was chosen as the primary outcome. At the vessel level, MRI (pooled NLR, 0.16; 95% confidence interval [CI], 0.13-0.21) was performed similar to computed tomography (pooled NLR, 0.22; 95% CI, 0.12-0.39) and positron emission tomography (pooled NLR, 0.15; 95% CI, 0.05-0.44), and better than single-photon emission computed tomography (pooled NLR, 0.47; 95% CI, 0.37-0.59). At the patient level, MRI (pooled NLR, 0.14; 95% CI, 0.10-0.18) performed similar to computed tomography (pooled NLR, 0.12; 95% CI, 0.04-0.33) and positron emission tomography (pooled NLR, 0.14; 95% CI, 0.02-0.87), and better than single-photon emission computed tomography (pooled NLR, 0.39; 95% CI, 0.27-0.55) and echocardiography (pooled NLR, 0.42; 95% CI, 0.30-0.59). Conclusions-Stress myocardial perfusion imaging with MRI, computed tomography, or positron emission tomography can accurately rule out hemodynamically significant coronary artery disease and can act as a gatekeeper for invasive revascularization. Single-photon emission computed tomography and echocardiography are less suited for this purpose. C1 [Takx, Richard A. P.; Blomberg, Bjorn A.; El Aidi, Hamza; Habets, Jesse; de Jong, Pim A.; Leiner, Tim] UMC Utrecht, Dept Radiol, NL-3584 CX Utrecht, Netherlands. [El Aidi, Hamza] UMC Utrecht, Dept Cardiol, NL-3584 CX Utrecht, Netherlands. [Takx, Richard A. P.; Hoffmann, Udo] Harvard Univ, Sch Med, Dept Radiol, Cardiac MR PET CT Program,Massachusetts Gen Hosp, Boston, MA 02115 USA. [Takx, Richard A. P.; Hoffmann, Udo] St Thomas Hosp, Div Imaging Sci & Biomed Engn, London, England. RP Takx, RAP (reprint author), UMC Utrecht, Dept Radiol, Heidelberglaan 100,POB 85500, NL-3584 CX Utrecht, Netherlands. EM rtakx@umcutrecht.nl RI de Jong, Pim/G-7220-2014 OI de Jong, Pim/0000-0003-4840-6854 FU Bayer Healthcare; Philips Healthcare FX Dr Nagel has received significant grant support from Bayer Healthcare and Philips Healthcare. The other authors report no conflicts. NR 26 TC 25 Z9 25 U1 1 U2 9 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 1941-9651 EI 1942-0080 J9 CIRC-CARDIOVASC IMAG JI Circ.-Cardiovasc. Imaging PD JAN PY 2015 VL 8 IS 1 AR e002666 DI 10.1161/CIRCIMAGING.114.002666 PG 7 WC Cardiac & Cardiovascular Systems; Radiology, Nuclear Medicine & Medical Imaging SC Cardiovascular System & Cardiology; Radiology, Nuclear Medicine & Medical Imaging GA AZ3SL UT WOS:000348146900007 ER PT J AU Kumar, A Matheny, ME Ho, KKL Yeh, RW Piemonte, TC Waldman, H Shah, PB Cope, R Normand, SLT Donnelly, S Robbins, S Resnic, FS AF Kumar, Amit Matheny, Michael E. Ho, Kalon K. L. Yeh, Robert W. Piemonte, Thomas C. Waldman, Howard Shah, Pinak B. Cope, Richard Normand, Sharon-Lise T. Donnelly, Sharon Robbins, Susan Resnic, Frederic S. TI The Data Extraction and Longitudinal Trend Analysis Network Study of Distributed Automated Postmarket Cardiovascular Device Safety Surveillance SO CIRCULATION-CARDIOVASCULAR QUALITY AND OUTCOMES LA English DT Article DE safety ID MEDICAL DEVICES; VASCULAR COMPLICATIONS; CLOSURE DEVICES; CARDIOLOGY; COMMITTEE; RISK AB Background-Current approaches for postmarket medical device safety surveillance are limited in their ability to produce timely and accurate assessments of adverse event rates. Methods and Results-The Data Extraction and Longitudinal Trend Analysis (DELTA) network study was a multicenter prospective observational study designed to evaluate the safety of devices used during percutaneous coronary interventions. All adult patients undergoing percutaneous coronary intervention from January 2008 to December 2012 at 5 participating Massachusetts sites were included. A safety alert was triggered if the cumulative observed adverse event rates for the study device exceeded the upper 95% confidence interval of the event rates of propensity-matched control cohort. Prespecified sensitivity analyses were developed to validate any identified safety signal. A total of 23 805 consecutive percutaneous coronary intervention procedures were evaluated. Two of 24 safety analyses triggered safety alerts. Patients receiving Perclose vascular closure device experienced an increased risk of minor vascular complications (relative risk, 4.14; P < 0.01) and any vascular complication (relative risk, 2.06; P = 0.01) when compared with propensitymatched patients receiving alternative vascular closure device, a result primarily driven by relatively high event rates at 1 participating center. Sensitivity analyses based on alternative risk adjustment methods confirmed a pattern of increased rate of complications at 1 of the 5 participating sites in their use of Perclose vascular closure device. Conclusions-The DELTA network study demonstrates that distributed automated prospective safety surveillance has the potential of providing near real-time assessment of safety risks of newly approved medical devices. C1 [Kumar, Amit; Piemonte, Thomas C.; Robbins, Susan; Resnic, Frederic S.] Lahey Hosp & Med Ctr, Burlington, MA USA. [Kumar, Amit; Piemonte, Thomas C.; Resnic, Frederic S.] Tufts Sch Med, Boston, MA USA. [Matheny, Michael E.] VA Tennessee Valley Healthcare Syst, Nashville, TN USA. [Matheny, Michael E.] Vanderbilt Univ, Nashville, TN 37235 USA. [Ho, Kalon K. L.] Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. [Ho, Kalon K. L.; Yeh, Robert W.; Waldman, Howard; Shah, Pinak B.; Normand, Sharon-Lise T.] Harvard Univ, Sch Med, Boston, MA USA. [Yeh, Robert W.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Waldman, Howard] North Shore Med Ctr, Salem, MA USA. [Shah, Pinak B.; Donnelly, Sharon] Brigham & Womens Hosp, Boston, MA 02115 USA. [Cope, Richard] Boston Adv Analyt, Newton, MA USA. [Normand, Sharon-Lise T.] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. RP Resnic, FS (reprint author), Lahey Clin Fdn, Dept Cardiovasc Med, 41 Mall Rd, Burlington, MA 01805 USA. EM frederic.resnic@lahey.org FU National Library of Medicine [R01 LM008142]; US Food and Drug Administration (HHSF) [223200830058C]; MDEpiNet Methodology Center from US Food and Drug Administration [HHSF223201110172C]; MDEpiNet from US Food and Drug Administration [1U01 FD004493-01] FX This research was supported through research grants from the National Library of Medicine (R01 LM008142) and the US Food and Drug Administration (HHSF contract 223200830058C). In addition, efforts of Drs Resnic and Dr Normand were funded, in part, by contract HHSF223201110172C (MDEpiNet Methodology Center) and grant 1U01 FD004493-01 (MDEpiNet Medical Counter Measures Study), both from the US Food and Drug Administration. NR 28 TC 2 Z9 2 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 1941-7705 EI 1941-7713 J9 CIRC-CARDIOVASC QUAL JI Circ.-Cardiovasc. Qual. Outcomes PD JAN PY 2015 VL 8 IS 1 BP 38 EP 46 DI 10.1161/CIRCOUTCOMES.114.001123 PG 9 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA AZ3RT UT WOS:000348145100008 PM 25491915 ER PT J AU Yeh, RW Czarny, MJ Normand, SLT Kereiakes, DJ Holmes, DR Brindis, RG Weaver, WD Rumsfeld, JS Roe, MT Kim, S Driscoll-Shempp, P Mauri, L AF Yeh, Robert W. Czarny, Matthew J. Normand, Sharon-Lise T. Kereiakes, Dean J. Holmes, David R., Jr. Brindis, Ralph G. Weaver, W. Douglas Rumsfeld, John S. Roe, Matthew T. Kim, Sunghee Driscoll-Shempp, Priscilla Mauri, Laura TI Evaluating the Generalizability of a Large Streamlined Cardiovascular Trial Comparing Hospitals and Patients in the Dual Antiplatelet Therapy Study Versus the National Cardiovascular Data Registry SO CIRCULATION-CARDIOVASCULAR QUALITY AND OUTCOMES LA English DT Article DE clinical trial; coronary disease; methods; stents ID PERCUTANEOUS CORONARY INTERVENTION; ACUTE MYOCARDIAL-INFARCTION; CLINICAL-TRIALS; EXTERNAL VALIDITY; ACCESS SITE; SAFE-PCI; WOMEN; DESIGN; REPRESENTATION; PARTICIPANTS AB Background-The Dual Antiplatelet Therapy Study is large streamlined clinical trial designed to evaluate antiplatelet treatment strategies in a broadly inclusive population of subjects treated with coronary stents. Whether large streamlined trials can successfully include a representative group of study sites and patients has not been formally assessed. Methods and Results-Within the National Cardiovascular Data Registry CathPCI Registry, we compared characteristics and outcomes of hospitals participating versus not participating in the Dual Antiplatelet Therapy Study. We also compared clinical and procedural characteristics of trial subjects undergoing percutaneous coronary intervention (PCI) with drug-eluting stents to contemporaneous patients within the National Cardiovascular Data Registry CathPCI Registry. Standardized differences between groups were estimated. Between September 2009 and July 2011, 1.1 million PCIs were performed among 1276 hospitals, of which 309 (24.2%) participated in the Dual Antiplatelet Therapy Study. Participating hospitals were larger (468 versus 311 beds), more frequently located in urban settings (61.2% versus 42.6%), and had higher annual PCI volumes (858 versus 378) compared with nonparticipating hospitals, although hospital case mix and procedural outcomes were similar. Compared with CathPCI patients, trial patients undergoing PCI with drug-eluting stents were similar with respect to race, sex, and rates of diabetes mellitus, hypertension, and smoking, although they had lower rates of prior cardiovascular disease. Conclusions-Within the Dual Antiplatelet Therapy Study, clinical trial sites had similar patient case mix and clinical outcomes as nonparticipating sites. Although trial participants were representative of PCI patients with respect to race, sex and most comorbidities, they had a lower prevalence of chronic cardiovascular disease compared with registry patients. Although a streamlined cardiovascular clinical trial may successfully involve a large number of hospitals and rapidly enroll a diverse population of patients, differences between eligible patients and those actually enrolled remained. Clinical Trial Registration-URL: http://www.clinicaltrials.gov. Unique identifier: NCT00977938. C1 [Yeh, Robert W.] Massachusetts Gen Hosp, Div Cardiol, Dept Med, Boston, MA 02114 USA. [Normand, Sharon-Lise T.] Brigham & Womens Hosp, Dept Hlth Care Policy Biostat, Boston, MA 02115 USA. [Mauri, Laura] Brigham & Womens Hosp, Dept Med, Div Cardiovasc Med, Boston, MA 02115 USA. [Yeh, Robert W.; Normand, Sharon-Lise T.; Mauri, Laura] Harvard Univ, Sch Med, Boston, MA USA. [Yeh, Robert W.; Driscoll-Shempp, Priscilla; Mauri, Laura] Harvard Clin Res Inst, Boston, MA USA. [Czarny, Matthew J.] Johns Hopkins Univ, Sch Med, Dept Med, Cardiol Div,Johns Hopkins Hosp, Baltimore, MD 21205 USA. [Normand, Sharon-Lise T.] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. [Kereiakes, Dean J.] Christ Hosp, Heart & Vasc Ctr, Lindner Res Ctr, Cincinnati, OH 45219 USA. [Holmes, David R., Jr.] Mayo Clin, Div Cardiol, Rochester, MN USA. [Brindis, Ralph G.] Univ Calif San Francisco, Dept Med, Philip R Lee Inst Hlth Policy Studies, San Francisco, CA USA. [Weaver, W. Douglas] Henry Ford Hlth Syst, Inst Heart & Vasc, Detroit, MI USA. [Rumsfeld, John S.] Vet Hlth Adm, Denver VA Med Ctr, Div Cardiol, Denver, CO USA. [Roe, Matthew T.; Kim, Sunghee] Duke Clin Res Inst, Durham, NC USA. RP Yeh, RW (reprint author), Massachusetts Gen Hosp, Div Cardiol, GRB 800, Boston, MA 02114 USA. EM ryeh@partners.org FU Abbott Vascular; Boston Scientific; Cordis; Medtronic Cardiovascular; Health and Human Services [1R01FD003870-01]; American College of Cardiology Foundation; National Heart, Lung, and Blood Institute [1K23HL118138] FX Funding for the Dual Antiplatelet Therapy (DAPT) Study is provided by four US manufacturers of drug-eluting stents (Abbott Vascular, Boston Scientific, Cordis, and Medtronic Cardiovascular) and the current manufacturers of thienopyridine medications (Eli Lilly/Daiichii Sankyo and Bristol Myers Squibb/Sanofi-Aventis) with supplementary funding from the Health and Human Services 1R01FD003870-01 (PI Dr Mauri). The National Cardiovascular Data Registry CathPCI Registry is funded by the American College of Cardiology Foundation. Dr Yeh is supported by a Career Development Award (1K23HL118138) from the National Heart, Lung, and Blood Institute. NR 26 TC 4 Z9 4 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 1941-7705 EI 1941-7713 J9 CIRC-CARDIOVASC QUAL JI Circ.-Cardiovasc. Qual. Outcomes PD JAN PY 2015 VL 8 IS 1 BP 96 EP 102 DI 10.1161/CIRCOUTCOMES.114.001239 PG 7 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA AZ3RT UT WOS:000348145100014 PM 25399847 ER PT J AU Drye, BD Drye, EE AF Drye, Barbara D. Drye, Elizabeth E. TI Older Patients With Cardiac Devices The Need for Better Patient-Doctor Conversations SO CIRCULATION-CARDIOVASCULAR QUALITY AND OUTCOMES LA English DT Editorial Material DE communication; defibrilators, implantable; informed consent; patient care planning; patient preference C1 San Francisco VA Med Ctr, Dept Med, San Francisco, CA USA. Yale Univ, Sch Med, Dept Pediat, New Haven, CT 06510 USA. Yale New Haven Med Ctr, Ctr Outcomes Res & Evaluat, New Haven, CT 06504 USA. RP Drye, EE (reprint author), Yale Univ, Sch Med, 1 Church St,Suite 200, New Haven, CT 06510 USA. EM Elizabeth.Drye@Yale.edu NR 3 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 1941-7705 EI 1941-7713 J9 CIRC-CARDIOVASC QUAL JI Circ.-Cardiovasc. Qual. Outcomes PD JAN PY 2015 VL 8 IS 1 BP 112 EP 113 DI 10.1161/CIRCOUTCOMES.114.000916 PG 2 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA AZ3RT UT WOS:000348145100017 PM 25604558 ER PT J AU Jones, LG Sin, MK Hage, FG Kheirbek, RE Morgan, CJ Zile, MR Wu, WC Deedwania, P Fonarow, GC Aronow, WS Prabhu, SD Fletcher, RD Ahmed, A Allman, RM AF Jones, Linda G. Sin, Mo-Kyung Hage, Fadi G. Kheirbek, Raya E. Morgan, Charity J. Zile, Michael R. Wu, Wen-Chih Deedwania, Prakash Fonarow, Gregg C. Aronow, Wilbert S. Prabhu, Sumanth D. Fletcher, Ross D. Ahmed, Ali Allman, Richard M. TI Characteristics and Outcomes of Patients With Advanced Chronic Systolic Heart Failure Receiving Care at the Veterans Affairs Versus Other Hospitals Insights From the Beta-blocker Evaluation of Survival Trial (BEST) SO CIRCULATION-HEART FAILURE LA English DT Article DE hospitals; outcomes; systolic heart failure; veterans ID VENTRICULAR EJECTION FRACTION; VASODILATOR THERAPY; ATRIAL-FIBRILLATION; INCREASED MORTALITY; NATURAL-HISTORY; HEALTH; RACE; ASSOCIATION; AMIODARONE; BUCINDOLOL AB Background-Characteristics and outcomes of patients with heart failure and reduced ejection fraction receiving care at Veterans Affairs (VA) versus non-VA hospitals have not been previously reported. Methods and Results-In the randomized controlled Beta-blocker Evaluation of Survival Trial (BEST; 1995-1999), of the 2707 (bucindolol=1353; placebo=1354) patients with heart failure and left ventricular ejection fraction <= 35%, 918 received care at VA hospitals, of which 98% (n=898) were male. Of the 1789 receiving care at non-VA hospitals, 68% (n=1216) were male. Our analyses were restricted to these 2114 male patients. VA patients were older with higher symptom and comorbidity burdens. There was no significant between-group difference in unadjusted primary end point of 2-year all-cause mortality (35% VA versus 32% non-VA; hazard ratio associated with VA hospitals, 1.09; 95% confidence interval, 0.94-1.26), which remained unchanged after adjustment for age and race (hazard ratio, 1.00; 95% confidence interval, 0.86-1.16) or multivariable adjustment, including cardiovascular morbidities (hazard ratio, 0.94; 95% confidence interval, 0.80-1.10). There was no between-group difference in cause-specific mortalities or hospitalizations. Chronic kidney disease, pulmonary edema, left ventricular ejection fraction <20%, and peripheral arterial disease were significant predictors of mortality for both groups. African America race, New York Heart Association class IV symptoms, atrial fibrillation, and right ventricular ejection fraction <20% were associated with higher mortality among non-VA hospital patients only; however, these differences from VA patients were not significant. Conclusions-Patients with heart failure and reduced ejection fraction receiving care at VA hospitals were older and sicker; yet their risk of mortality and hospitalization was similar to younger and healthier patients receiving care at non-VA hospitals. C1 [Jones, Linda G.; Hage, Fadi G.; Prabhu, Sumanth D.] Vet Affairs Med Ctr, Dept Med, Birmingham, AL USA. [Jones, Linda G.; Hage, Fadi G.; Prabhu, Sumanth D.] Univ Alabama Birmingham, Dept Med, Birmingham, AL USA. [Morgan, Charity J.] Univ Alabama Birmingham, Dept Biostat, Birmingham, AL USA. [Sin, Mo-Kyung] Seattle Univ, Coll Nursing, Dept Adult Hlth, Seattle, WA 98122 USA. [Kheirbek, Raya E.; Fletcher, Ross D.; Ahmed, Ali] Vet Affairs Med Ctr, Off Chief Staff, Washington, DC USA. [Zile, Michael R.] Ralph H Johnson Vet Affairs Med Ctr, Dept Med, Charleston, SC USA. [Zile, Michael R.] Med Univ S Carolina, Dept Med, Charleston, SC USA. [Wu, Wen-Chih] Vet Affairs Med Ctr, Dept Med, Providence, RI USA. [Wu, Wen-Chih] Brown Univ, Dept Med, Providence, RI 02912 USA. [Deedwania, Prakash] Univ Calif San Francisco, Dept Med, Fresno, CA USA. [Fonarow, Gregg C.] Univ Calif Los Angeles, Dept Med, Los Angeles, CA 90024 USA. [Aronow, Wilbert S.] New York Med Coll, Dept Med, Valhalla, NY 10595 USA. [Allman, Richard M.] Dept Vet Affairs, Geriatr Serv, Washington, DC USA. [Allman, Richard M.] Dept Vet Affairs, Extended Care Serv, Washington, DC USA. RP Ahmed, A (reprint author), Washington DC VA Med Ctr, 50 Irving St NW, Washington, DC 20422 USA. EM aliahmedmdmph@gmail.com OI Hage, Fadi/0000-0002-1397-4942 FU National Heart, Lung, and Blood Institute (NHLBI), Bethesda, Maryland [R01-HL085561, R01-HL097047]; University of Alabama at Birmingham Comprehensive Cardiovascular Center, Birmingham, Alabama FX Dr Ahmed was in part supported by grants (R01-HL085561 and R01-HL097047) from the National Heart, Lung, and Blood Institute (NHLBI), Bethesda, Maryland, and an intramural support from the University of Alabama at Birmingham Comprehensive Cardiovascular Center, Birmingham, Alabama. NR 35 TC 3 Z9 3 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 1941-3289 EI 1941-3297 J9 CIRC-HEART FAIL JI Circ.-Heart Fail. PD JAN PY 2015 VL 8 IS 1 BP 17 EP 24 DI 10.1161/CIRCHEARTFAILURE.114.001300 PG 8 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA AZ3RX UT WOS:000348145400004 PM 25480782 ER PT J AU Jotwani, V Scherzer, R Abraham, A Estrella, MM Bennett, M Cohen, MH Nowicki, M Sharma, A Young, M Tien, PC Ix, JH Sarnak, MJ Parikh, CR Shlipak, MG AF Jotwani, Vasantha Scherzer, Rebecca Abraham, Alison Estrella, Michelle M. Bennett, Michael Cohen, Mardge H. Nowicki, Marek Sharma, Anjali Young, Mary Tien, Phyllis C. Ix, Joachim H. Sarnak, Mark J. Parikh, Chirag R. Shlipak, Michael G. TI Association of Urine alpha 1-Microglobulin with Kidney Function Decline and Mortality in HIV-Infected Women SO CLINICAL JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Article DE HIV nephropathy; CKD; proximal tubule ID SERUM CYSTATIN-C; IMMUNODEFICIENCY-VIRUS-INFECTION; ACUTE TUBULAR-NECROSIS; STAGE RENAL-DISEASE; ANTIRETROVIRAL THERAPY; INTERAGENCY HIV; PROXIMAL TUBULE; ESTIMATING GFR; TENOFOVIR; INJURY AB Background and objectivesDespite advances in therapy, HIV-infected individuals remain at higher risk for kidney dysfunction than uninfected individuals. It was hypothesized that urine levels of 1-microglobulin, a biomarker of proximal tubular dysfunction, would predict kidney function decline and mortality risk in HIV-infected and uninfected women.Design, setting, participants, & measurementsIn the Women's Interagency HIV Study, urine 1-microglobulin and creatinine concentrations were measured in 903 HIV-infected and 287 uninfected women using stored urine from 1999 to 2000, when prevalence of tenofovir use was <1%. Participants were categorized into three categories by level of 1-microglobulin-to-creatinine ratio, and associations with kidney decline and all-cause mortality over 8 years were evaluated.ResultsUrine 1-microglobulin was detectable in 60% of HIV-infected and 40% of uninfected women (P<0.001). Among HIV-infected women, there were 177 (22%), 61 (7%), and 128 (14%) patients with incident CKD, with 10% annual eGFR decline, and who died, respectively. Compared with HIV-infected women in the lowest 1-microglobulin category, HIV-infected women in the highest 1-microglobulin category had a 2.1-fold risk of incident CKD (95% confidence interval, 1.3 to 3.4), 2.7-fold risk of 10% annual eGFR decline (95% confidence interval, 1.2 to 5.9), and 1.6-fold mortality risk (95% confidence interval, 1.0 to 2.6) in models adjusting for kidney risk factors, baseline eGFR, and albuminuria. Among uninfected women, the highest 1-microglobulin category was associated with 3% (relative risk, 2.2; 95% confidence interval, 1.4 to 3.5) and 5% (relative risk, 2.2; 95% confidence interval, 1.1 to 4.3) annual eGFR decline relative to the lowest 1-microglobulin category.ConclusionsProximal tubular dysfunction, indicated by urine 1-microglobulin, was independently associated with kidney function decline in HIV-infected and uninfected women and mortality risk among HIV-infected women. C1 San Francisco VA Med Ctr, Dept Med, San Francisco, CA 94121 USA. RP Shlipak, MG (reprint author), San Francisco VA Med Ctr, Dept Med, 4150 Clement Street, San Francisco, CA 94121 USA. EM Michael.Shlipak@ucsf.edu FU National Institute of Allergy and Infectious Diseases; Eunice Kennedy Shriver National Institute of Child Health and Human Development; National Cancer Institute; National Institute on Drug Abuse; National Institute on Mental Health; National Institute of Dental and Craniofacial Research; National Institute on Alcohol Abuse and Alcoholism; National Institute on Deafness and Other Communication Disorders; National Institutes of Health (NIH) Office of Research on Women's Health; [1 R01 AG034853-01A2]; [1K23-DK-081317]; [U01-AI-103401]; [U01-AI-103408]; [U01-AI-035004]; [U01-AI-031834]; [U01-AI-034993]; [U01-AI-034994]; [U01-AI-103397]; [U01-AI-103390]; [U01-AI-034989]; [U01-AI-042590]; [U01-HD-032632]; [UL1-TR000004]; [UL1-TR000454] FX The WIHS Kidney Aging Study is funded by Grant 1 R01 AG034853-01A2 (Principal Investigator: M.G.S.), which was administered by the Northern California Institute for Research and Education with resources of the Veterans Affairs Medical Center (San Francisco, California). M.M.E. is supported by Grant 1K23-DK-081317. Data in this manuscript were collected by the Women's Interagency HIV Study (WIHS). WIHS (Principal Investigators): UAB-MS WIHS (Michael Saag, Mirjam-Colette Kempf, and Deborah Konkle-Parker), Grant U01-AI-103401; Atlanta WIHS (Ighovwerha Ofotokun and Gina Wingood), Grant U01-AI-103408; Bronx WIHS (Kathryn Anastos), Grant U01-AI-035004; Brooklyn WIHS (Howard Minkoff and Deborah Gustafson), Grant U01-AI-031834; Chicago WIHS (M.H.C.), Grant U01-AI-034993; Metropolitan Washington WIHS (M.Y.), Grant U01-AI-034994; Miami WIHS (Margaret Fischl and Lisa Metsch), Grant U01-AI-103397; UNC WIHS (Adaora Adimora), Grant U01-AI-103390; Connie Wofsy Women's HIV Study, northern California (Ruth Greenblatt, Bradley Aouizerat, and Phyllis Tien), Grant U01-AI-034989; WIHS Data Management and Analysis Center (Stephen Gange and Elizabeth Golub), Grant U01-AI-042590; and Southern California WIHS (Alexandra Levine and M.N.), Grant U01-HD-032632 (WIHS I to WIHS IV). The WIHS is funded primarily by the National Institute of Allergy and Infectious Diseases, with additional cofunding from the Eunice Kennedy Shriver National Institute of Child Health and Human Development, the National Cancer Institute, the National Institute on Drug Abuse, and the National Institute on Mental Health. Targeted supplemental funding for specific projects is also provided by the National Institute of Dental and Craniofacial Research, the National Institute on Alcohol Abuse and Alcoholism, the National Institute on Deafness and Other Communication Disorders, and the National Institutes of Health (NIH) Office of Research on Women's Health. WIHS data collection is also supported by Grants UL1-TR000004 (to UCSF CTSA) and UL1-TR000454 (to Atlanta CTSA). NR 41 TC 7 Z9 7 U1 0 U2 4 PU AMER SOC NEPHROLOGY PI WASHINGTON PA 1725 I ST, NW STE 510, WASHINGTON, DC 20006 USA SN 1555-9041 EI 1555-905X J9 CLIN J AM SOC NEPHRO JI Clin. J. Am. Soc. Nephrol. PD JAN PY 2015 VL 10 IS 1 BP 63 EP 73 DI 10.2215/CJN.03220314 PG 11 WC Urology & Nephrology SC Urology & Nephrology GA AY7BS UT WOS:000347716900011 PM 25370597 ER PT J AU Alge, JL Arthur, JM AF Alge, Joseph L. Arthur, John M. TI Biomarkers of AKI: A Review of Mechanistic Relevance and Potential Therapeutic Implications SO CLINICAL JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Review DE acute renal failure; pathophysiology of renal disease and progression; renin-angiotensin system ID ACUTE KIDNEY INJURY; ACID-BINDING PROTEIN; ACUTE-RENAL-FAILURE; GELATINASE-ASSOCIATED LIPOCALIN; ISCHEMIA-REPERFUSION INJURY; EARLY URINARY BIOMARKER; ADULT CARDIAC-SURGERY; INTENSIVE-CARE-UNIT; CHAIN FATTY-ACID; GROWTH-FACTOR-I AB AKI is a common clinical condition associated with a number of adverse outcomes. More timely diagnosis would allow for earlier intervention and could improve patient outcomes. The goal of early identification of AKI has been the primary impetus for AKI biomarker research, and has led to the discovery of numerous novel biomarkers. However, in addition to facilitating more timely intervention, AKI biomarkers can provide valuable insight into the molecular mechanisms of this complex and heterogeneous disease. Furthermore, AKI biomarkers could also function as molecular phenotyping tools that could be used to direct clinical intervention. This review highlights the major studies that have characterized the diagnostic and prognostic predictive power of these biomarkers. The mechanistic relevance of neutrophil gelatinase-associated lipocalin, kidney injury molecule 1, IL-18, liver-type fatty acid-binding protein, angiotensinogen, tissue inhibitor of metalloproteinase-2, and IGF-binding protein 7 to the pathogenesis and pathobiology of AKI is discussed, putting these biomarkers in the context of the progressive phases of AKI. A biomarker-integrated model of AKI is proposed, which summarizes the current state of knowledge regarding the roles of these biomarkers and the molecular and cellular biology of AKI. C1 [Alge, Joseph L.; Arthur, John M.] Med Univ S Carolina, Div Nephrol, Charleston, SC 29425 USA. [Arthur, John M.] Ralph H Johnson Vet Affairs Med Ctr, Med Serv, Charleston, SC USA. RP Arthur, JM (reprint author), Med Univ S Carolina, Dept Med, Div Nephrol, 96 Jonathan Lucas Street,MSC 629, Charleston, SC 29425 USA. EM arthurj@musc.edu OI Alge, Joseph/0000-0002-2491-1066 FU Department of Veterans Affairs; National Institutes of Health [R01-DK080234] FX This manuscript was supported by the Department of Veterans Affairs and National Institutes of Health Grant R01-DK080234. NR 86 TC 37 Z9 39 U1 1 U2 16 PU AMER SOC NEPHROLOGY PI WASHINGTON PA 1725 I ST, NW STE 510, WASHINGTON, DC 20006 USA SN 1555-9041 EI 1555-905X J9 CLIN J AM SOC NEPHRO JI Clin. J. Am. Soc. Nephrol. PD JAN PY 2015 VL 10 IS 1 BP 147 EP 155 DI 10.2215/CJN.12191213 PG 9 WC Urology & Nephrology SC Urology & Nephrology GA AY7BS UT WOS:000347716900020 PM 25092601 ER PT J AU Goldenberg, D Goyal, N AF Goldenberg, David Goyal, Neerav TI Impact factor: What is it and is it still relevant? SO ENT-EAR NOSE & THROAT JOURNAL LA English DT Editorial Material ID JOURNALS; CITATION; INDEX C1 [Goldenberg, David] Penn State Univ, Coll Med, Hershey, PA 17033 USA. [Goldenberg, David] Penn State Hershey Canc Inst, Hershey, PA USA. [Goyal, Neerav] Harvard Univ, Sch Med, Dept Otolaryngol, Massachusetts Eye & Ear Infirm, Boston, MA 02115 USA. RP Goldenberg, D (reprint author), Penn State Univ, Coll Med, Hershey, PA 17033 USA. OI Goyal, Neerav/0000-0001-7783-1097 NR 15 TC 0 Z9 0 U1 1 U2 4 PU VENDOME GROUP LLC PI NEW YORK PA 6 EAST 32 ST, 8 FLOOR, NEW YORK, NY 10016 USA SN 0145-5613 EI 1942-7522 J9 ENT-EAR NOSE THROAT JI ENT-Ear Nose Throat J. PD JAN PY 2015 VL 94 IS 1 BP 14 EP + PG 4 WC Otorhinolaryngology SC Otorhinolaryngology GA AZ4GX UT WOS:000348180800001 PM 25606828 ER PT J AU Metra, M Mentz, RJ Chiswell, K Bloomfield, DM Cleland, JGF Cotter, G Davison, BA Dittrich, HC Fiuzat, M Givertz, MM Lazzarini, V Mansoor, GA Massie, BM Ponikowski, P Teerlink, JR Voors, AA O'Connor, CM AF Metra, Marco Mentz, Robert J. Chiswell, Karen Bloomfield, Daniel M. Cleland, John G. F. Cotter, Gad Davison, Beth A. Dittrich, Howard C. Fiuzat, Mona Givertz, Michael M. Lazzarini, Valentina Mansoor, George A. Massie, Barry M. Ponikowski, Piotr Teerlink, John R. Voors, Adriaan A. O'Connor, Christopher M. TI Acute heart failure in elderly patients: worse outcomes and differential utility of standard prognostic variables. Insights from the PROTECT trial SO EUROPEAN JOURNAL OF HEART FAILURE LA English DT Article DE Age; Elderly; Acute heart failure; Blood pressure ID CLINICAL CHARACTERISTICS; EJECTION FRACTION; PULSE PRESSURE; TASK-FORCE; RISK; ASSOCIATION; AGE; ROLOFYLLINE; PREVALENCE; ANTAGONIST AB AimsPrevious heart failure (HF) trials suggested that age influences patient characteristics and outcome; however, under-representation of elderly patients has limited characterization of this cohort. Whether standard prognostic variables have differential utility in various age groups is unclear. Methods and resultsThe PROTECT trial investigated 2033 patients (median age 72 years) with acute HF randomized to rolofylline or placebo. Patients were divided into five groups based on the quintiles of age: 59, 60-68, 69-74, 75-79, and 80years. Baseline characteristics, medications, and outcomes (30-day death or cardiovascular/renal hospitalization, and death at 30 and 180 days) were explored. The prognostic utility of baseline characteristics for outcomes was investigated in the different groups and in those aged <80years vs. 80years. With increasing age, patients were more likely to be women with hypertension, AF, and higher EF. Increased age was associated with increased risk of 30- and 180-day outcomes, which persisted after multivariable adjustment (hazard ratio for 180-day death=1.17; 95% confidence interval 1.11-1.24 for each 5-year increase). The prognostic utility of baseline characteristics such as previous HF hospitalization and serum sodium, systolic blood pressure, and NYHA class was attenuated in the elderly for the endpoint of 180-day mortality. An increase in albumin was associated with a greater reduction in risk in patients aged 80years vs. <80years. ConclusionsIn a large trial of acute HF, there were differences in baseline characteristics and outcomes amongst patients of different ages. Standard prognostic variables exhibit different utility in elderly patients. C1 [Metra, Marco; Lazzarini, Valentina] Univ Brescia, Dept Med & Surg Specialties, Brescia, Italy. [Mentz, Robert J.; Fiuzat, Mona; O'Connor, Christopher M.] Duke Univ, Med Ctr, Duke Clin Res Inst, Div Cardiovasc Med, Durham, NC USA. [Chiswell, Karen] Duke Univ, Med Ctr, Duke Clin Res Inst, Durham, NC USA. [Bloomfield, Daniel M.; Mansoor, George A.] Merck Res Labs, Rahway, NJ USA. [Cleland, John G. F.] Univ London Imperial Coll Sci Technol & Med, Natl Heart & Lung Inst, Royal Brompton Hosp, Kingston Upon Hull, Yorks, England. [Cleland, John G. F.] Univ London Imperial Coll Sci Technol & Med, Natl Heart & Lung Inst, Harefield Hosp, Kingston Upon Hull, Yorks, England. [Cleland, John G. F.] Univ Hull, Dept Cardiol, Castle Hill Hosp, Kingston Upon Hull, Yorks, England. [Cotter, Gad; Davison, Beth A.] Momentum Res Inc, Durham, NC USA. [Dittrich, Howard C.] Univ Iowa, Carver Coll Med Cardiovasc Res Ctr, Iowa City, IA USA. [Givertz, Michael M.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Cardiovasc Div,Dept Med, Boston, MA 02115 USA. [Massie, Barry M.; Teerlink, John R.] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Massie, Barry M.; Teerlink, John R.] San Francisco VA Med Ctr, San Francisco, CA USA. [Ponikowski, Piotr] Med Univ, Mil Hosp, Wroclaw, Poland. [Voors, Adriaan A.] Univ Groningen, Univ Med Ctr Groningen, Dept Cardiol, Groningen, Netherlands. RP Metra, M (reprint author), Spedali Civil Brescia, Piazza Spedali Civili 1, I-25123 Brescia, Italy. EM metramarco@libero.it RI Ponikowski, Piotr/O-6454-2015; OI Ponikowski, Piotr/0000-0002-3391-7064; Cleland, John/0000-0002-1471-7016; Metra, Marco/0000-0001-6691-8568 FU National Institute of General Medical Sciences [5-T32GM086330] FX R.J.M. is supported by grant no. 5-T32GM086330 from the National Institute of General Medical Sciences. NR 23 TC 15 Z9 15 U1 1 U2 5 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1388-9842 EI 1879-0844 J9 EUR J HEART FAIL JI Eur. J. Heart Fail. PD JAN PY 2015 VL 17 IS 1 BP 109 EP 118 DI 10.1002/ejhf.207 PG 10 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA AZ2IU UT WOS:000348058300014 PM 25431336 ER PT J AU Littman, AJ Damschroder, LJ Verchinina, L Lai, ZS Kim, HM Hoerster, KD Klingaman, EA Goldberg, RW Owen, RR Goodrich, DE AF Littman, Alyson J. Damschroder, Laura J. Verchinina, Lilia Lai, Zongshan Kim, Hyungjin Myra Hoerster, Katherine D. Klingaman, Elizabeth A. Goldberg, Richard W. Owen, Richard R. Goodrich, David E. TI National evaluation of obesity screening and treatment among veterans with and without mental health disorders SO GENERAL HOSPITAL PSYCHIATRY LA English DT Article DE Obesity; Weight management; Veterans; Serious mental illness; Depressive disorder ID WEIGHT-MANAGEMENT PROGRAM; LIFE-STYLE INTERVENTION; UNITED-STATES; CARDIOVASCULAR RISK; METABOLIC SYNDROME; ANXIETY DISORDERS; CONTROLLED-TRIAL; PRIMARY-CARE; ILLNESS; ADULTS AB Objective: The objective was to determine whether obesity screening and weight management program participation and outcomes are equitable for individuals with serious mental illness (SMI) and depressive disorder (DD) compared to those without SMI/DD in Veterans Health Administration (VHA), the largest integrated US health system, which requires obesity screening and offers weight management to all in need. Methods: We used chart-reviewed, clinical and administrative VHA data from fiscal years 2010-2012 to estimate obesity screening and participation in the VHA's weight management program (MOVE!) across groups. Six-and 12-month weight changes in MOVE! participants were estimated using linear mixed models adjusted for confounders. Results: Compared to individuals without SMI/DD, individuals with SMI or DD were less frequently screened for obesity (94%-94.7% vs. 95.7%) but had greater participation in MOVE! (10.1%-10.4% vs. 7.4%). MOVE! participants with SMI or DD lost approximately 1 lb less at 6 months. At 12 months, average weight loss for individuals with SMI or neither SMI/DD was comparable (-3.5 and -3.3 lb, respectively), but individuals with DD lost less weight (mean=-2.7 lb). Conclusions: Disparities in obesity screening and treatment outcomes across mental health diagnosis groups were modest. However, participation in MOVE! was low for every group, which limits population impact. Published by Elsevier Inc. C1 [Littman, Alyson J.] VA Puget Sound Healthcare Syst, Seattle Div Epidemiol Res & Informat Ctr ERIC, Seattle, WA 98108 USA. [Littman, Alyson J.] Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA. [Damschroder, Laura J.; Verchinina, Lilia; Lai, Zongshan; Kim, Hyungjin Myra; Goodrich, David E.] VA Ann Arbor Healthcare Syst, CCMR, Ann Arbor, MI 48105 USA. [Lai, Zongshan; Goodrich, David E.] Univ Michigan, Sch Med, Dept Psychiat, Ann Arbor, MI 48109 USA. [Kim, Hyungjin Myra] Univ Michigan, Ctr Stat Consultat & Res, Ann Arbor, MI 48109 USA. [Hoerster, Katherine D.] VA Puget Sound Healthcare Syst, Seattle Div Mental Hlth Serv, Seattle, WA 98108 USA. [Hoerster, Katherine D.] Univ Washington, Dept Psychiat & Behav Sci, Seattle, WA 98195 USA. [Klingaman, Elizabeth A.; Goldberg, Richard W.] VA Capitol Hlth Care Network, Mental Illness Res Educ & Clin Ctr, Baltimore, MD USA. [Owen, Richard R.] Cent Arkansas Vet Healthcare Syst, Ctr Mental Healthcare & Outcomes Res, Little Rock, AR USA. [Owen, Richard R.] Univ Arkansas Med Sci, Coll Med, Dept Psychiat, Little Rock, AR 72205 USA. [Klingaman, Elizabeth A.] Univ Maryland, Sch Med, Dept Psychiat, Baltimore, MD 21201 USA. RP Littman, AJ (reprint author), VA Puget Sound Healthcare Syst, Seattle Epidemiol Res & Informat Ctr ERIC, 1660 South Columbia Way,S-152-E, Seattle, WA 98108 USA. EM Alyson.littman@va.gov; Laura.damschroder@va.gov; Lilia.verchinina@va.gov; Zongshan.Lai@va.gov; Myrakim@umich.edu; Katherine.hoerster@va.gov; Elizabeth.klingaman@va.gov; Richard.goldberg@va.gov; Richard.Owen2@va.gov; David.goodrich2@va.gov OI Damschroder, Laura/0000-0002-3657-8459; Goodrich, David/0000-0003-3232-2189 FU VHA Center for Health Promotion & Disease Prevention (NCP); VA Health Services Research and Development Quality Enhancement Research Initiative (QUERI) [QLP 55-017]; Rehabilitation R&D Career Development Award [6982] FX This study was funded by was initiated at the request of the VHA Center for Health Promotion & Disease Prevention (NCP). Funding was provided by VA Health Services Research and Development Quality Enhancement Research Initiative (QUERI) programs for Diabetes and Mental Health research as a locally initiated project (QLP 55-017). Dr. Littman's time was supported by a Rehabilitation R&D Career Development Award (#6982). The authors would like to acknowledge the support of Dr. Amy M. Kilbourne, Dr. Kenneth J. Jones, Dr. Caroline R. Richardson and Ms. Trang Lance in this work. The views expressed in this article are those of the authors and do not necessarily represent the views of the Veterans Administration. NR 59 TC 10 Z9 10 U1 3 U2 7 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0163-8343 EI 1873-7714 J9 GEN HOSP PSYCHIAT JI Gen. Hosp. Psych. PD JAN-FEB PY 2015 VL 37 IS 1 BP 7 EP 13 DI 10.1016/j.genhosppsych.2014.11.005 PG 7 WC Psychiatry SC Psychiatry GA AZ2CQ UT WOS:000348042700005 PM 25500194 ER PT J AU Iyer, SP Young, AS AF Iyer, Sharat P. Young, Alexander S. TI Health screening, counseling, and hypertension control for people with serious mental illness at primary care visits SO GENERAL HOSPITAL PSYCHIATRY LA English DT Article DE Primary care; Serious mental illness; Health screening; Health counseling; Hypertension ID MEDICAL-CARE; SCHIZOPHRENIA; MORTALITY; COHORT; OUTPATIENTS; DISORDERS; BARRIERS; RECEIPT; STATE AB Objective: This study sought to determine if primary care visits for people with serious mental illness (SMI) demonstrate different rates of basic physical health services compared to others, and to determine factors associated with differing rates of these measures in people with SMI. Method: The study used 2005-2010 visit-level primary care data from the National Ambulatory Medical Care Survey and the National Hospital Ambulatory Medical Care Survey. The provision of health counseling, receipt of any diagnostic or screening test, measurement of blood pressure or weight and evidence of hypertension control were assessed, adjusting for identified patient, provider and visit-level factors. Results: After adjustment for covariates, we found no significant differences between visits for people with SMI and those without for any outcome. Probability of blood pressure measurement and diagnostic or screening testing significantly increased over time. Conclusion: The lack of significant differences found here might be due to adjustment for covariates, a focus only on primary care visits, the use of visit-level data or evolution over time. Mortality differences for people with SMI may be attributable to those not receiving primary care, self-management of disease or subsets of the population requiring targeted interventions. Published by Elsevier Inc. C1 [Iyer, Sharat P.] James J Peters VA Med Ctr, Mental Illness Res Educ & Clin Ctr VISN3, Bronx, NY 10468 USA. [Iyer, Sharat P.] Icahn Sch Med Mt Sinai, Dept Psychiat, New York, NY 10029 USA. [Young, Alexander S.] West Los Angeles VA Med Ctr, Desert Pacific Mental Illness Res Educ & Clin Ctr, Los Angeles, CA 90073 USA. [Young, Alexander S.] Univ Calif Los Angeles, Dept Psychiat & Biobehav Sci, Los Angeles, CA 90024 USA. RP Iyer, SP (reprint author), VA Med Ctr MIRECC OOMH, 130 W Kingsbridge Rd,Room 6A-44, Bronx, NY 10468 USA. EM sharu.p@mssm.edu; ayoung@ucla.edu RI Young, Alexander/A-1523-2009 OI Young, Alexander/0000-0002-9367-9213 FU Robert Wood Johnson Foundation Clinical Scholars program; US Department of Veterans Affairs FX This material is the result of work supported with resources and the use of facilities at the James J. Peters VA Medical Center, Bronx, NY, and the West Los Angeles VA Medical Center, Los Angeles, CA. Additional support was provided by the Mount Sinai Conduits Institutes for Translational Sciences. Assistance for this article was provided by Kenneth Wells, M.D., M.P.H., and Lisa Dixon, M.D., M.P.H., who reviewed the manuscript and contributed to the discussion, and Alan Weinberg, M.S., who contributed to the analytic plan. Funding for Dr. Parameswaran was provided by the Robert Wood Johnson Foundation Clinical Scholars program and the US Department of Veterans Affairs. The views expressed in this article are those of the authors and do not necessarily reflect the position or policy of the Department of Veterans Affairs or the United States government. NR 24 TC 0 Z9 0 U1 2 U2 6 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0163-8343 EI 1873-7714 J9 GEN HOSP PSYCHIAT JI Gen. Hosp. Psych. PD JAN-FEB PY 2015 VL 37 IS 1 BP 60 EP 66 DI 10.1016/j.genhosppsych.2014.10.003 PG 7 WC Psychiatry SC Psychiatry GA AZ2CQ UT WOS:000348042700014 PM 25480463 ER PT J AU Smith, SL Grelotti, DJ Fils-Aime, R Uwimana, E Ndikubwimana, JS Therosme, T Severe, J Dushimiyimana, D Uwamariya, C Bienvenu, R Alcindor, Y Eustache, E Raviola, GJ Fricchione, GL AF Smith, Stephanie L. Grelotti, David J. Fils-Aime, Reginald Uwimana, Eugenie Ndikubwimana, Jean-Sauveur Therosme, Tatiana Severe, Jennifer Dushimiyimana, Dominique Uwamariya, Clemence Bienvenu, Robert Alcindor, Yoldie Eustache, Eddy Raviola, Giuseppe J. Fricchione, Gregory L. TI Catatonia in resource-limited settings: A case series and treatment protocol SO GENERAL HOSPITAL PSYCHIATRY LA English DT Article DE Catatonia; Africa; Caribbean region; Psychosomatic medicine; Neuropsychiatry ID GLOBAL MENTAL-HEALTH; LORAZEPAM AB Objective: The catatonic syndrome ("catatonia") is characterized by motor and motivation dysregulation and is associated with a number of neuropsychiatric and medical disorders. It is recognizable in a variety of clinical settings. We present observations from the treatment of four individuals with catatonia in Haiti and Rwanda and introduce a treatment protocol for use in resource-limited settings. Methods: Four patients from rural Haiti and Rwanda with clinical signs of catatonia and a positive screen using the Bush-Francis Catatonia Rating Scale were treated collaboratively by general physicians and mental health clinicians with either lorazepam or diazepam. Success in treatment was clinically assessed by complete remittance of catatonia symptoms. Results: The four patients in this report exhibited a range of characteristic and recognizable signs of catatonia, including immobility/stupor, stereotypic movements, echophenomena, posturing, odd mannerisms, mutism and refusal to eat or drink. All four cases presented initially to rural outpatient general health services in resource-limited settings. In some cases, diagnostic uncertainty initially led to treatment with typical antipsychotics. In each case, proper identification and treatment of catatonia with benzodiazepines led to significant clinical improvement. Conclusion: Catatonia can be effectively and inexpensively treated in resource-limited settings. Identification and management of catatonia are critical for the health and safety of patients with this syndrome. Familiarity with the clinical features of catatonia is essential for health professionals working in any setting. To facilitate early recognition of this treatable disorder, catatonia should feature more prominently in global mental health discourse. (C) 2015 Elsevier Inc. All rights reserved. C1 [Smith, Stephanie L.; Raviola, Giuseppe J.] Harvard Univ, Sch Med, Dept Global Hlth & Social Med, Boston, MA 02115 USA. [Smith, Stephanie L.; Grelotti, David J.; Raviola, Giuseppe J.] Partners Hlth, Boston, MA 02215 USA. [Smith, Stephanie L.] Brigham & Womens Hosp, Div Med Psychiat, Boston, MA 02115 USA. [Grelotti, David J.] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. [Fils-Aime, Reginald; Therosme, Tatiana; Severe, Jennifer; Alcindor, Yoldie; Eustache, Eddy] Dept Mental Hlth & Psychosocial Serv, Zanmi Lasante, Haiti. [Uwimana, Eugenie; Ndikubwimana, Jean-Sauveur; Dushimiyimana, Dominique; Uwamariya, Clemence; Bienvenu, Robert] Minist Hlth, Butaro Hosp, Burera Dist, Rwanda. [Fricchione, Gregory L.] Massachusetts Gen Hosp, Pierce Div Global Psychiat, Div Psychiat & Med, Boston, MA 02114 USA. RP Smith, SL (reprint author), Harvard Univ, Sch Med, Dept Global Hlth & Social Med, 641 Huntington Ave, Boston, MA 02115 USA. EM Stephanie_Smith@hms.harvard.edu OI FILS-AIME, Joseph/0000-0002-1840-8755 FU NIMH NIH HHS [T32 MH017119] NR 24 TC 1 Z9 1 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0163-8343 EI 1873-7714 J9 GEN HOSP PSYCHIAT JI Gen. Hosp. Psych. PD JAN-FEB PY 2015 VL 37 IS 1 BP 89 EP 93 DI 10.1016/j.genhosppsych.2014.10.009 PG 5 WC Psychiatry SC Psychiatry GA AZ2CQ UT WOS:000348042700018 PM 25467078 ER PT J AU Scheuner, MT Peredo, J Benkendorf, J Bowdish, B Feldman, G Fleisher, L Mulvihill, JJ Watson, M Herman, GE Evans, J AF Scheuner, Maren T. Peredo, Jane Benkendorf, Judith Bowdish, Bruce Feldman, Gerald Fleisher, Lynn Mulvihill, John J. Watson, Michael Herman, Gail E. Evans, James TI Reporting genomic secondary findings: ACMG members weigh in SO GENETICS IN MEDICINE LA English DT Article DE incidental findings; informed consent; next-generation sequencing; return of results; secondary findings ID INCIDENTAL FINDINGS; GENETICS PROFESSIONALS; CLINICAL GENOME; RETURN; EXOME; PERSPECTIVES; VIEWS AB Purpose: The aim of this study was to survey American College of Medical Genetics and Genomics members about secondary findings from clinical genome-scale sequencing. Methods: A Web-based survey was mailed to 1,687 members of the American College of Medical Genetics and Genomics. Exploratory factor analysis identified underlying factors assessed by survey items. Linear regression assessed associations between factor scores and respondent characteristics. Results: The response rate was 29%. Four factors explained 51% of the survey variance: best practices, patient preferences, guidance, and informed consent. Most agreed with "best practice" items describing seeking and reporting of secondary findings as consistent with medical standards, having sufficient evidence, and, for adults, the benefits generally outweighing potential harms. There was lack of agreement regarding benefits versus harms for children and impact on health-care resources. The majority agreed that patient preferences should be considered, including ability to opt out, and that informed consent was feasible and critical. Characteristics significantly associated with factor scores included country of residence, sequencing experience, and years in practice. Conclusion: The American College of Medical Genetics and Genomics should update a list of genes to be assessed when clinical genome-scale sequencing is performed. Informed consent is necessary, and reporting of secondary findings should be optional. Research on implementation of secondary findings reporting is needed. C1 [Scheuner, Maren T.; Peredo, Jane] VA Greater Los Angeles Healthcare Syst, Dept Med, Div Med Genet, Los Angeles, CA 90073 USA. [Scheuner, Maren T.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Med, Los Angeles, CA 90095 USA. [Benkendorf, Judith; Bowdish, Bruce; Watson, Michael] Amer Coll Med Genet & Genom, Bethesda, MD USA. [Feldman, Gerald] Wayne State Univ, Sch Med, Ctr Mol Med & Genet, Detroit, MI USA. [Feldman, Gerald] Wayne State Univ, Sch Med, Dept Pediat, Detroit, MI 48201 USA. [Feldman, Gerald] Wayne State Univ, Sch Med, Dept Pathol, Detroit, MI 48201 USA. [Fleisher, Lynn] Sidley & Austin, Chicago, IL USA. [Mulvihill, John J.] Univ Oklahoma, Dept Pediat, Oklahoma City, OK USA. [Herman, Gail E.] Ohio State Univ, Nationwide Childrens Res Inst, Columbus, OH 43210 USA. [Herman, Gail E.] Ohio State Univ, Dept Pediat, Columbus, OH 43210 USA. [Evans, James] Univ N Carolina, Dept Genet, Chapel Hill, NC USA. [Evans, James] Univ N Carolina, Dept Med, Chapel Hill, NC USA. RP Scheuner, MT (reprint author), VA Greater Los Angeles Healthcare Syst, Dept Med, Div Med Genet, Los Angeles, CA 90073 USA. EM maren.scheuner@va.gov NR 19 TC 9 Z9 9 U1 1 U2 4 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1098-3600 EI 1530-0366 J9 GENET MED JI Genet. Med. PD JAN PY 2015 VL 17 IS 1 BP 27 EP 35 DI 10.1038/gim.2014.165 PG 9 WC Genetics & Heredity SC Genetics & Heredity GA AY7MT UT WOS:000347744900005 PM 25394173 ER PT J AU Dunn, EC Brown, RC Dai, Y Rosand, J Nugent, NR Amstadter, AB Smoller, JW AF Dunn, Erin C. Brown, Ruth C. Dai, Yael Rosand, Jonathan Nugent, Nicole R. Amstadter, Ananda B. Smoller, Jordan W. TI Genetic Determinants of Depression: Recent Findings and Future Directions SO HARVARD REVIEW OF PSYCHIATRY LA English DT Review DE copy-number variant; depression; genetics; gene-environment interaction; genome-wide association study; genome-wide environment interaction study; rare variants ID GENOME-WIDE ASSOCIATION; NATIONAL COMORBIDITY SURVEY; SEROTONIN TRANSPORTER GENE; RESEARCH DOMAIN CRITERIA; STRESSFUL LIFE EVENTS; REPLICATION NCS-R; DSM-IV-DISORDERS; DE-NOVO CNVS; MAJOR DEPRESSION; ENVIRONMENT INTERACTIONS AB Depression is one of the most prevalent, disabling, and costly mental health conditions in the Unite States and also worldwide. One promising avenue for preventing depression and informing its clinical treatment lies in uncovering the genetic and environmental determinants of the disorder as well as their interaction (GxE). The overarching goal of this review article is to translate recent findings from studies of genetic association and GxE related to depression, particularly for readers without in-depth knowledge of genetics or genetic methods. The review is organized into three major sections. In the first, we summarize what is currently known about the genetic determinants of depression, focusing on findings from genome-wide association studies (GWAS). In the second section, we review findings from studies of GxE, which seek to simultaneously examine the role of genes and exposure to specific environments or experiences in the etiology of depression. In the third section, we describe the challenges to genetic discovery in depression and promising strategies for future progress. C1 [Dunn, Erin C.; Smoller, Jordan W.] Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA. [Dunn, Erin C.; Dai, Yael; Rosand, Jonathan; Smoller, Jordan W.] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA. [Dunn, Erin C.; Smoller, Jordan W.] Stanley Ctr Psychiat Res, Cambridge, MA USA. [Rosand, Jonathan] Program Med & Populat Genet, Cambridge, MA USA. [Brown, Ruth C.; Amstadter, Ananda B.] Broad Inst Harvard, Cambridge, MA USA. [Brown, Ruth C.; Amstadter, Ananda B.] MIT, Cambridge, MA 02139 USA. [Brown, Ruth C.; Amstadter, Ananda B.] Virginia Commonwealth Univ, Virginia Inst Psychiat & Behav Genet, Boston, MA USA. [Rosand, Jonathan] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. [Nugent, Nicole R.] Alpert Brown Med Sch, Dept Psychiat & Human Behav, Providence, RI USA. [Smoller, Jordan W.] Harvard Univ, Ctr Dev Child, Cambridge, MA 02138 USA. RP Dunn, EC (reprint author), Massachusetts Gen Hosp, Ctr Human Genet Res, Psychiat & Neurodev Genet Unit, Simches Res Bldg,6th Floor,185 Cambridge St, Boston, MA 02114 USA. EM edunn2@mgh.harvard.edu FU Harvard University Center on the Developing Child; National Institute of Mental Health [K01MH087240, K24MH094614] FX Supported, in part, by the Harvard University Center on the Developing Child (Dr. Dunn) and by National Institute of Mental Health grant nos. K01MH087240 (Dr. Nugent) and K24MH094614 (Dr. Smoller). NR 162 TC 20 Z9 21 U1 8 U2 47 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 1067-3229 EI 1465-7309 J9 HARVARD REV PSYCHIAT JI Harv. Rev. Psychiatr. PD JAN-FEB PY 2015 VL 23 IS 1 BP 1 EP 18 DI 10.1097/HRP.0000000000000054 PG 18 WC Psychiatry SC Psychiatry GA AZ3XM UT WOS:000348157100001 PM 25563565 ER PT J AU Saini, S Pratt, DS AF Saini, Sanjay Pratt, Daniel S. TI Time to update radiological criteria for non-invasive diagnosis of hepatocellular carcinoma SO HEPATOLOGY INTERNATIONAL LA English DT Editorial Material ID LIVER-TRANSPLANTATION; GUIDELINES; MANAGEMENT; PATHOLOGY C1 [Saini, Sanjay] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. [Saini, Sanjay; Pratt, Daniel S.] Harvard Univ, Sch Med, Boston, MA 02114 USA. [Pratt, Daniel S.] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. RP Saini, S (reprint author), Massachusetts Gen Hosp, Dept Radiol, 32 Fruit St, Boston, MA 02114 USA. EM ssaini@partners.org NR 16 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1936-0533 EI 1936-0541 J9 HEPATOL INT JI Hepatol. Int. PD JAN PY 2015 VL 9 IS 1 BP 1 EP 2 DI 10.1007/s12072-014-9584-y PG 2 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA AZ4XH UT WOS:000348223800001 PM 25788371 ER PT J AU Sayegh, AI Washington, MC Johnson, RE Johnson-Rouse, T Freeman, C Harrison, A Lucas, J Shelby, M Fisher, B Willis, W Reeve, JJ AF Sayegh, Ayman I. Washington, Martha C. Johnson, Ruth E. Johnson-Rouse, Tanisha Freeman, Corren Harrison, Anna Lucas, Jennifer Shelby, Mandy Fisher, Brittley Willis, William Reeve, Joseph J., Jr. TI Celiac and the cranial mesenteric arteries supply gastrointestinal sites that regulate meal size and intermeal interval length via cholecystokinin-58 in male rats SO HORMONES AND BEHAVIOR LA English DT Article DE Cholecystokinin-58; Meal size; Intermeal interval; Celiac artery; Cranial mesenteric artery ID DORSAL VAGAL COMPLEX; REDUCE FOOD-INTAKE; MYENTERIC PLEXUS; INTESTINAL-MUCOSA; CCK1 RECEPTOR; CCK-58; SATIETY; SECRETION; TRACT; IMMUNOREACTIVITY AB The site(s) of action that control meal size and intermeal interval (IMI) length by cholecystokinin-58 (CCK-58), the only detectable endocrine form of CCK in the rat, are not known. To test the hypothesis that the gastrointestinal tract may contain such sites, we infused low doses of CCK-58 (0.01, 0.05, 0.15 and 0.25 nmol/kg) into the celiac artery (CA, supplying stomach and upper duodenum), the cranial mesenteric artery (CMA, supplying small and most of the large intestines), the femoral artery (FA, control) and the portal vein (PV, draining the gastrointestinal tract) prior to the onset of the dark cycle in freely fed male rats. We measured the first meal size (chow), second meal size, IMI and satiety ratio (SR, IMI/meal size). We found that (1) all doses of CCK-58 given in the CA and the highest dose given in the CMA reduced the first meal size, (2) all doses of CCK-58 given in the CA reduced the second meal size, (3) a CCK-58 dose of 0.15 nmol/kg given in the CA and 0.15 and 0.25 nmol/kg given in the CMA prolonged the IMI, (4) CCK-58.(0.05, 0.15, 0.25 nmol/kg) given in the CA and 0.25 nmol/kg given in the CMA increased the SR, and (5) CCK-58 given in the FA and PV had no effect on the meal size or intermeal interval. These results support our hypothesis that the gastrointestinal tract contains sites of action that regulate meal size and IMI length via CCK-58. The stomach and upper duodenum may contain sites regulating meal size, whereas the small intestine and part of the large intestine may contain sites regulating the IMI. Published by Elsevier Inc. C1 [Sayegh, Ayman I.; Washington, Martha C.; Johnson, Ruth E.; Johnson-Rouse, Tanisha; Freeman, Corren; Harrison, Anna; Lucas, Jennifer; Shelby, Mandy; Fisher, Brittley; Willis, William; Reeve, Joseph J., Jr.] Tuskegee Univ, Coll Vet Med, Dept Biomed Sci, Gastroenterol Lab, Tuskegee, AL 36088 USA. [Reeve, Joseph J., Jr.] Vet Adm Greater Los Angeles Healthcare Syst, CURE Digest Dis Res Ctr, Los Angeles, CA USA. [Reeve, Joseph J., Jr.] Univ Calif Los Angeles, Sch Med, Div Digest Dis, Los Angeles, CA USA. RP Sayegh, AI (reprint author), Tuskegee Univ, Coll Vet Med, Dept Biomed Sci, Gastroenterol Lab, Tuskegee, AL 36088 USA. EM sayeghai@mytu.tuskegee.edu FU NIH [5R01DK083449]; [1SC1DK094972-01A1] FX The research was supported by grant 1SC1DK094972-01A1 (AS) and NIH grant 5R01DK083449 (J.R.R, Jr.) NR 40 TC 8 Z9 8 U1 0 U2 3 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0018-506X EI 1095-6867 J9 HORM BEHAV JI Horm. Behav. PD JAN PY 2015 VL 67 BP 48 EP 53 DI 10.1016/j.yhbeh.2014.11.011 PG 6 WC Behavioral Sciences; Endocrinology & Metabolism SC Behavioral Sciences; Endocrinology & Metabolism GA AZ5GX UT WOS:000348249300006 PM 25479193 ER PT J AU Pauk, M Grgurevic, L Brkljacic, J Kufner, V Bordukalo-Niksic, T Grabusic, K Razdorov, G Rogic, D Zuvic, M Oppermann, H Babitt, JL Lin, HY Volarevic, S Vukicevic, S AF Pauk, Martina Grgurevic, Lovorka Brkljacic, Jelena Kufner, Vera Bordukalo-Niksic, Tatjana Grabusic, Kristina Razdorov, Genadij Rogic, Dunja Zuvic, Marijan Oppermann, Hermann Babitt, Jodie L. Lin, Herbert Y. Volarevic, Sinisa Vukicevic, Slobodan TI Exogenous BMP7 corrects plasma iron overload and bone loss in Bmp6-/- mice SO INTERNATIONAL ORTHOPAEDICS LA English DT Article DE Iron; Haemochromatosis; Hepcidin; Bone morphogenetic protein ID HEPCIDIN EXPRESSION; PROTEIN 6; IN-VIVO; MORPHOGENETIC PROTEINS; PEPTIDE HEPCIDIN; MOUSE-LIVER; GENE; CELLS; HFE; HEMOCHROMATOSIS AB Purpose Iron overload accelerates bone loss in mice lacking the bone morphogenetic protein 6 (Bmp6) gene, which is the key endogenous regulator of hepcidin, iron homeostasis gene. We investigated involvement of other BMPs in preventing haemochromatosis and subsequent osteopenia in Bmp6-/- mice. Methods Iron-treated wild-type (WT) and Bmp6-/- mice were analysed for hepcidin messenger RNA (mRNA) and tissue and blood BMP levels by quantitative reverse-transcriptase polymerase chain reaction (qRT-PCR), immunohistochemistry, Western blot, enzyme-linked immunosorbent assay (ELISA) and proximity extension assay. BMPs labeled with technetium-99m were used in pharmacokinetic studies. Results In WT mice, 4 h following iron challenge, liver Bmp6 and hepcidin expression were increased, while expression of other Bmps was not affected. In parallel, we provided the first evidence that BMP6 circulates in WT mice and that iron increased the BMP6 serum level and the specific liver uptake of Tc-99m-BMP6. In Bmp6-/- mice, iron challenge led to blunted activation of liver Smad signaling and hepcidin expression with a delay of 24 h, associated with increased Bmp5 and Bmp7 expression and increased Bmp2, 4, 5 and 9 expression in the duodenum. Liver Bmp7 expression and increased circulating BMP9 eventually contributed to the late hepcidin response. This was further supported by exogenous BMP7 therapy resulting in an effective hepcidin expression followed by a rapid normalisation of plasma iron values and restored osteopenia in Bmp6-/- mice. Conclusion In Bmp6-/- mice, iron activated endogenous compensatory mechanisms of other BMPs that were not sufficient for preventing hemochromatosis and bone loss. Administration of exogenous BMP7 was effective in correcting the plasma iron level and bone loss, indicating that BMP6 is an essential but not exclusive in vivo regulator of iron homeostasis. C1 [Pauk, Martina; Grgurevic, Lovorka; Brkljacic, Jelena; Kufner, Vera; Bordukalo-Niksic, Tatjana; Razdorov, Genadij; Vukicevic, Slobodan] Univ Zagreb, Ctr Translat & Clin Res, Sch Med, Zagreb 10000, Croatia. [Grabusic, Kristina; Volarevic, Sinisa] Univ Rijeka, Sch Med, Dept Mol Med & Biotechnol, Rijeka, Croatia. [Rogic, Dunja] Univ Hosp Ctr Zagreb, Dept Lab Diag, Zagreb, Croatia. [Zuvic, Marijan] Univ Hosp Ctr Zagreb, Dept Nucl Med & Radiat Protect, Div Haematol, Zagreb, Croatia. [Oppermann, Hermann] Genera Res, Rakov Potok, Croatia. [Babitt, Jodie L.; Lin, Herbert Y.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Syst Biol,Div Nephrol,Program Membrane Biol, Boston, MA USA. RP Vukicevic, S (reprint author), Univ Zagreb, Ctr Translat & Clin Res, Sch Med, Salata 11, Zagreb 10000, Croatia. EM martina.pauk@mef.hr; lovorka.grgurevic@mef.hr; jelena.brkljacic@mef.hr; vera.kufner@gmail.com; tbordukalo@gmail.com; grabusic@medri.hr; genadijrazdorov@yahoo.com; dunjarogic@hotmail.com; mzuvic@kbc-zagreb.hr; hermann.oppermann@gmail.com; Babitt.Jodie@mgh.harvard.edu; Lin.Herbert@mgh.harvard.edu; vsinisa@medri.hr; vukicev@mef.hr FU Ministry of Science and Technology of the Republic of Croatia; NIH [RO1 DK087727] FX This study was supported by grants from the Ministry of Science and Technology of the Republic of Croatia. No conflict of interest for any authors. JLB was supported in part by NIH grant RO1 DK087727. NR 37 TC 4 Z9 4 U1 0 U2 4 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0341-2695 EI 1432-5195 J9 INT ORTHOP JI Int. Orthop. PD JAN PY 2015 VL 39 IS 1 BP 161 EP 172 DI 10.1007/s00264-014-2550-4 PG 12 WC Orthopedics SC Orthopedics GA AY7GX UT WOS:000347730200022 PM 25300398 ER PT J AU Phipps, JE Vela, D Hoyt, T Halaney, DL Mancuso, JJ Buja, LM Asmis, R Milner, TE Feldman, MD AF Phipps, Jennifer E. Vela, Deborah Hoyt, Taylor Halaney, David L. Mancuso, J. Jacob Buja, L. Maximilian Asmis, Reto Milner, Thomas E. Feldman, Marc D. TI Macrophages and Intravascular OCT Bright Spots A Quantitative Study SO JACC-CARDIOVASCULAR IMAGING LA English DT Article DE intravascular optical; coherence tomography; macrophages; quantitative analysis bright spots ID OPTICAL COHERENCE TOMOGRAPHY; CORONARY PLAQUE CHARACTERISTICS; VULNERABLE PLAQUE; ATHEROSCLEROSIS; INFLAMMATION AB OBJECTIVES This study hypothesized that bright spots in intravascular optical coherence tomography (IVOCT) images may originate by colocalization of plaque materials of differing indexes of refraction. To quantitatively identify bright spots, we developed an algorithm that accounts for factors including tissue depth, distance from light source, and signal-to-noise ratio. We used this algorithm to perform a bright spot analysis of IVOCT images and compared these results with histological examination of matching tissue sections. BACKGROUND Bright spots are thought to represent macrophages in IVOCT images, and studies of alternative etiologies have not been reported. METHODS Fresh human coronary arteries (n = 14 from 10 hearts) were imaged with IVOCT in a mock catheterization Laboratory and then processed for histological analysis. The quantitative bright spot algorithm was applied to all images. RESULTS Results are reported for 1,599 IVOCT images co-registered with histology. Macrophages alone were responsible for only 23% of the bright spot-positive regions, although they were present in 57% of bright spot-positive regions (as determined by histology). Additional etiologies for bright spots included cellular fibrous tissue (8%), interfaces between calcium and fibrous tissue (10%), calcium and Lipids (5%), and fibrous cap and Lipid pool (3%). Additionally, we showed that Large pools of macrophages in CD68(+) histology sections corresponded to dark regions in comparative IVOCT images; this is due to the fact that a pool of lipid-rich macrophages will have the same index of refraction as a pool of Lipid and thus will not cause bright spots. CONCLUSIONS Bright spots in IVOCT images were correlated with a variety of plaque components that cause sharp changes in the index of refraction. Algorithms that incorporate these correlations may be developed to improve the identification of some types of vulnerable plaque and allow standardization of IVOCT image interpretation. (C) 2015 by the American College of Cardiology Foundation. C1 [Phipps, Jennifer E.; Hoyt, Taylor; Halaney, David L.; Mancuso, J. Jacob; Asmis, Reto; Feldman, Marc D.] Univ Texas Hlth Sci Ctr San Antonio, San Antonio, TX 78229 USA. [Vela, Deborah; Buja, L. Maximilian] Texas Heart Inst, Houston, TX 77025 USA. [Halaney, David L.; Feldman, Marc D.] South Texas Vet Hlth Care Syst, Dept Vet Affairs, San Antonio, TX USA. [Milner, Thomas E.] Univ Texas Austin, Austin, TX 78712 USA. RP Feldman, MD (reprint author), Univ Texas Hlth Sci Ctr San Antonio, 7703 Floyd Curl Dr,MSC 7872, San Antonio, TX 78229 USA. EM feldmanm@uthscsa.edu OI Buja, Louis Maximilian/0000-0001-8386-7029; Halaney, David/0000-0003-4437-0516 FU Veterans Health Administration merit grant [I01 BX000397]; Clayton Foundation; Janey and Dolph Briscoe Division of Cardiology at the University of Texas Health Science Center [NIH T32 HL007446]; American Heart Association [13POST17080074]; Biomedical Engineering Advancement fund at the University of Texas at Austin FX This study was funded by the Veterans Health Administration merit grant I01 BX000397, Clayton Foundation, Janey and Dolph Briscoe Division of Cardiology at the University of Texas Health Science Center (NIH T32 HL007446), American Heart Association (13POST17080074), and the Biomedical Engineering Advancement fund at the University of Texas at Austin. The intravascular optical coherence tomography system used in this study was provided by Volcano Corporation. All authors have reported that they have no relationships relevant to the contents of this paper to disdose. NR 27 TC 22 Z9 22 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1936-878X EI 1876-7591 J9 JACC-CARDIOVASC IMAG JI JACC-Cardiovasc. Imag. PD JAN PY 2015 VL 8 IS 1 BP 63 EP 72 DI 10.1016/j.jcmg.2014.07.027 PG 10 WC Cardiac & Cardiovascular Systems; Radiology, Nuclear Medicine & Medical Imaging SC Cardiovascular System & Cardiology; Radiology, Nuclear Medicine & Medical Imaging GA AZ4GZ UT WOS:000348181000011 PM 25499133 ER PT J AU Tearney, GJ AF Tearney, Guillermo J. TI OCT Imaging of Macrophages A Bright Spot in the Study of Inflammation in Human Atherosclerosis SO JACC-CARDIOVASCULAR IMAGING LA English DT Editorial Material DE intravascular imaging; macrophage; optical coherence tomography; vulnerable plaque ID OPTICAL COHERENCE TOMOGRAPHY; STENTS C1 [Tearney, Guillermo J.] Harvard Univ, Sch Med, Wellman Ctr Photomed, Boston, MA USA. [Tearney, Guillermo J.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. RP Tearney, GJ (reprint author), Massachusetts Gen Hosp, Dept Pathol, BHX604A, Boston, MA 02114 USA. EM gtearney@partners.org NR 11 TC 4 Z9 4 U1 2 U2 4 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1936-878X EI 1876-7591 J9 JACC-CARDIOVASC IMAG JI JACC-Cardiovasc. Imag. PD JAN PY 2015 VL 8 IS 1 BP 73 EP 75 DI 10.1016/j.jcmg.2014.09.019 PG 3 WC Cardiac & Cardiovascular Systems; Radiology, Nuclear Medicine & Medical Imaging SC Cardiovascular System & Cardiology; Radiology, Nuclear Medicine & Medical Imaging GA AZ4GZ UT WOS:000348181000012 PM 25592697 ER PT J AU Chang, DC Evans, C Parker, J AF Chang, David C. Evans, Christopher Parker, Joseph TI Conceptualizing Administrative Databases as Screening Tools for Health System Quality Rethinking the Issue of Data Accuracy SO JAMA SURGERY LA English DT Editorial Material ID COMPLICATIONS C1 [Chang, David C.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Surg, Boston, MA 02114 USA. [Chang, David C.] Univ Calif San Diego, Dept Surg, San Diego, CA 92103 USA. [Evans, Christopher] Univ Calif San Diego, Sch Med, San Diego, CA 92103 USA. [Parker, Joseph] Off Statewide Hlth Planning & Dev, Sacramento, CA USA. RP Chang, DC (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Surg, 165 Cambridge St,Ste 403, Boston, MA 02114 USA. EM dchang8@mgh.harvard.edu NR 7 TC 6 Z9 6 U1 1 U2 3 PU AMER MEDICAL ASSOC PI CHICAGO PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA SN 2168-6254 EI 2168-6262 J9 JAMA SURG JI JAMA Surg. PD JAN PY 2015 VL 150 IS 1 BP 5 EP 6 DI 10.1001/jamasurg.2014.1352 PG 2 WC Surgery SC Surgery GA AZ5AO UT WOS:000348232900001 PM 25409092 ER PT J AU Ju, MH Ko, CY Hall, BL Bosk, CL Bilimoria, KY Wick, EC AF Ju, Mila H. Ko, Clifford Y. Hall, Bruce L. Bosk, Charles L. Bilimoria, Karl Y. Wick, Elizabeth C. TI A Comparison of 2 Surgical Site Infection Monitoring Systems SO JAMA SURGERY LA English DT Article ID CARE-ASSOCIATED INFECTIONS; ADMINISTRATIVE DATA; RISK ADJUSTMENT; NATIONAL-HEALTH; SAFETY NETWORK; SURVEILLANCE; HOSPITALS; COSTS; STATE AB IMPORTANCE Surgical site infection (SSI) has emerged as the leading publicly reported surgical outcome and is tied to payment determinations. Many hospitals monitor SSIs using the American College of Surgeons National Surgical Quality Improvement Program (ACS NSQIP), in addition to mandatory participation (for most states) in the Centers for Disease Control and Prevention's National Healthcare Safety Network (NHSN), which has resulted in duplication of effort and incongruent data. OBJECTIVE To identify discrepancies in the implementation of the NHSN and the ACS NSQIP at hospitals that may be affecting the respective SSI rates. DESIGN, SETTING, AND PARTICIPANTS A pilot sample of hospitals that participate in both the NHSN and the ACS NSQIP. INTERVENTIONS For each hospital, observed rates and risk-adjusted observed to expected ratios for year 2012 colon SSIs were collected from both programs. The implementation methods of both programs were identified, including telephone interviews with infection preventionists who collect data for the NHSN at each hospital. MAIN OUTCOMES AND MEASURES Collection methods and colon SSI rates for the NHSN at each hospital were compared with those of the ACS NSQIP. RESULTS Of 16 hospitals, 11 were teaching hospitals with at least 500 beds. The mean observed colon SSI rates were dissimilar between the 2 programs, 5.7%(range, 2.0%-14.5%) for the NHSN vs 13.5%(range, 4.6%-26.7%) for the ACS NSQIP. The mean difference between the NHSN and the ACS NSQIP was 8.3%(range, 1.6%-18.8%), with the ACS NSQIP rate always higher. The correlation between the observed to expected ratios for the 2 programs was nonsignificant (Pearson product moment correlation, rho = 0.4465; P =.08). The NHSN collection methods were dissimilar among interviewed hospitals. An SSI managed as an outpatient case would usually be missed under the current NHSN practices. CONCLUSIONS AND RELEVANCE Colon SSI rates from the NHSN and the ACS NSQIP cannot be used interchangeably to evaluate hospital performance and determine reimbursement. Hospitals should not use the ACS NSQIP colon SSI rates for the NHSN reports because that would likely result in the hospital being an outlier for performance. It is imperative to reconcile SSI monitoring, develop consistent definitions, and establish one reliable method. The current state hinders hospital improvement efforts by adding unnecessary confusion to the already complex arena of perioperative improvement. C1 [Ju, Mila H.; Ko, Clifford Y.; Hall, Bruce L.; Bilimoria, Karl Y.] Amer Coll Surg, Div Res & Optimal Patient Care, Chicago, IL USA. [Ju, Mila H.; Bilimoria, Karl Y.] Northwestern Univ, NW Mem Hosp, Feinberg Sch Med, Surg Outcomes & Qual Improvement Ctr,Dept Surg, Chicago, IL 60611 USA. [Ko, Clifford Y.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Surg, Los Angeles, CA 90095 USA. [Ko, Clifford Y.] Vet Affairs Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. [Hall, Bruce L.] Washington Univ, Dept Surg, St Louis, MO USA. [Hall, Bruce L.] Washington Univ, Olin Business Sch, St Louis, MO USA. [Hall, Bruce L.] Washington Univ, Ctr Hlth Policy, St Louis, MO USA. [Hall, Bruce L.] St Louis Vet Affairs Med Ctr, St Louis, MO USA. [Hall, Bruce L.] BJC HealthCare, St Louis, MO USA. [Bosk, Charles L.] Univ Penn, Leonard Davis Inst Hlth Econ, Dept Sociol, Philadelphia, PA 19104 USA. [Bosk, Charles L.] Univ Penn, Dept Anesthesiol & Crit Care, Philadelphia, PA 19104 USA. [Wick, Elizabeth C.] Johns Hopkins Univ, Dept Surg, Baltimore, MD 21287 USA. RP Wick, EC (reprint author), Johns Hopkins Univ, Dept Surg, 600 N Wolfe St,Blalock Room 658, Baltimore, MD 21287 USA. EM ewick1@jhmi.edu FU National Institutes of Health [5T32HL094293]; American College of Surgeons Clinical Scholars in Residence program FX Dr Ju reported receiving a stipend that is partially supported by grant 5T32HL094293 from the National Institutes of Health and the American College of Surgeons Clinical Scholars in Residence program. Dr Hall reported being a paid consultant for the American College of Surgeons. No other disclosures were reported. NR 23 TC 16 Z9 16 U1 1 U2 3 PU AMER MEDICAL ASSOC PI CHICAGO PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA SN 2168-6254 EI 2168-6262 J9 JAMA SURG JI JAMA Surg. PD JAN PY 2015 VL 150 IS 1 BP 51 EP 57 DI 10.1001/jamasurg.2014.2891 PG 7 WC Surgery SC Surgery GA AZ5AO UT WOS:000348232900011 PM 25426765 ER PT J AU Golberg, A Broelsch, GF Vecchio, D Khan, S Hamblin, MR Austen, WG Sheridan, RL Yarmush, ML AF Golberg, Alexander Broelsch, G. Felix Vecchio, Daniela Khan, Saiqa Hamblin, Michael R. Austen, William G., Jr. Sheridan, Robert L. Yarmush, Martin L. TI Pulsed Electric Fields for Burn Wound Disinfection in a Murine Model SO JOURNAL OF BURN CARE & RESEARCH LA English DT Article ID IRREVERSIBLE ELECTROPORATION; ACINETOBACTER-BAUMANNII; PHOTODYNAMIC THERAPY; IN-VIVO; INFECTIONS; MANAGEMENT; RESISTANCE; CELLS; ABLATION; EFFICACY AB Emerging bacterial resistance renders many antibiotics ineffective, making alternative strategies of wound disinfection important. Here the authors report on a new, physical burn wound disinfection method: pulsed electric fields (PEFs). High voltage, short PEFs create nonthermal, permanent damage to cell membranes, possibly by irreversible electroporation. In medicine, PEF technology has recently been used for nonthermal ablation of solid tumors. The authors have expanded the spectrum of PEF applications in medicine to burn wound disinfection. A third-degree burn was induced on the dorsal skin of C57BL/6 mice. Immediately after the injury, the burn wound was infected with Acinetobacter baumannii expressing the luxCDABE operon. Thirty minutes after infection, the infected areas were treated with 80 pulses delivered at 500 V/mm, 70 mu s, 1 Hz. The authors used bioluminescence to quantify bacteria on skin. Three animals were used for each experimental condition. PEFs were effective in the disinfection of infected burned murine skin. The bacterial load reduction correlated with the number of delivered pulses. Forty pulses of 500 V/mm led to a 2.04 +/- 0.29 Log10 reduction in bacterial load; 80 pulses led to the immediate 5.53 +/- 0.30 Log10 reduction. Three hours after PEF, the bacterial reduction of the skin treated with 500 V/mm, 80 pulses was 4.91 +/- 0.71 Log10. The authors introduce a new method of wound disinfection using high voltage, short PEFs. They believe that PEF technology may represent an important alternative to antibiotics in addressing bacterial contamination of wounds, particularly those contaminated with multidrug-resistant bacteria. C1 [Golberg, Alexander; Yarmush, Martin L.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Engn Med,Dept Surg, Boston, MA 02114 USA. [Golberg, Alexander; Yarmush, Martin L.] Shriners Burns Hosp, Boston, MA 02114 USA. [Broelsch, G. Felix; Khan, Saiqa; Austen, William G., Jr.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Plast & Reconstruct Surg, Boston, MA 02114 USA. [Vecchio, Daniela; Hamblin, Michael R.] Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA. [Hamblin, Michael R.] Harvard Univ, Sch Med, Dept Dermatol, Boston, MA 02114 USA. [Hamblin, Michael R.] MIT, Harvard Mit Div Hlth Sci & Technol, Cambridge, MA 02139 USA. [Sheridan, Robert L.] Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. [Sheridan, Robert L.] Shriners Hosp Children, Boston, MA USA. [Yarmush, Martin L.] Rutgers State Univ, Dept Biomed Engn, Piscataway, 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 FU Shriners Grant [85120-BOS]; MGH ECOR postdoctoral award; U.S. grant [NIH R01AI050875] FX The research of A.G. and M.L.Y. was supported by Shriners Grant #85120-BOS and MGH ECOR postdoctoral award. Research in the Hamblin laboratory was supported by U.S. grant NIH R01AI050875 NR 48 TC 8 Z9 8 U1 2 U2 14 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 1559-047X EI 1559-0488 J9 J BURN CARE RES JI J. Burn Care Res. PD JAN-FEB PY 2015 VL 36 IS 1 BP 7 EP 13 DI 10.1097/BCR.0000000000000157 PG 7 WC Emergency Medicine; Dermatology; Surgery SC Emergency Medicine; Dermatology; Surgery GA AY3AG UT WOS:000347456400005 PM 25167374 ER PT J AU Ryan, CM Lee, A Kazis, LE Schneider, JC Shapiro, GD Sheridan, RL Meyer, WJ Palmieri, T Pidcock, FS Reilly, D Tompkins, RG AF Ryan, Colleen M. Lee, Austin Kazis, Lewis E. Schneider, Jeffrey C. Shapiro, Gabriel D. Sheridan, Robert L. Meyer, Walter J. Palmieri, Tina Pidcock, Frank S. Reilly, Debra Tompkins, Ronald G. CA Multictr Burn Outcome Grp TI Recovery Trajectories After Burn Injury in Young Adults: Does Burn Size Matter? SO JOURNAL OF BURN CARE & RESEARCH LA English DT Article ID QUALITY-OF-LIFE; ASSOCIATION/SHRINERS-HOSPITALS; FAMILY ENVIRONMENT; POSTBURN PRURITUS; CHILDREN; SURVIVORS; OUTCOMES; QUESTIONNAIRE; VALIDATION; EXERCISE AB The impact of burn size on mortality is well known, but the association of burn size with the trajectories of long-term functional outcomes remains poorly studied. This prospective multi-center study included burned adults ages 19 to 30 years who completed the Young Adult Burn Outcome Questionnaire at initial baseline contact, 2 weeks, and at 6 and 12 months after initial questionnaire administration. Non-burned adults of comparable ages also completed the questionnaire as a reference group. The association between functional recovery and TBSA burned was analyzed longitudinally using generalized linear models with the generalized estimation equation technique. Functional status was characterized in 15 domains: physical function, fine motor function, pain, itch, social function limited by physical function, perceived appearance, social function limited by appearance, sexual function, emotion, family function, family concern, satisfaction with symptom relief, satisfaction with role, work reintegration, and religion. Scores were standardized to a mean of 50 and a SD of 10 based on non-burned controls. There were 153 burned and 112 non-burned subjects with a total of 620 questionnaires. TBSA burned was 11 +/- 14% (mean +/- SD); 31% had face involvement and 57% had hand involvement. The lag time from burn injury to questionnaire administration was on average 7 +/- 7.7 months, with a maximum of 36 months. Lower recovery levels were associated with increasing burn size for physical function, pain, itch, work reintegration, emotion, satisfaction with symptom relief, satisfaction with role, family function, and family concern (P value ranged from .04-<.0001). No significant differences in recovery levels were found with increasing burn size for fine motor function, social function limited by physical function, sexual function, and religion; these areas tracked toward the age-matched non-burned group regardless of burn size. Perceived appearance and social function limited by appearance remained below the non-burn levels throughout the 3-year period regardless of burn size. Three-year recovery trajectories of survivors with larger burn size showed improvements in most areas, but these improvements lagged behind those with smaller burns. Poor perceived appearance was persistent and prevalent regardless of burn size and was found to limit social function in these young adult burn survivors. Expectations for multidimensional recovery from burns in young adults can be benchmarked based on burn size with important implications for patient monitoring and intervening in clinical care. C1 [Ryan, Colleen M.; Lee, Austin; Schneider, Jeffrey C.; Sheridan, Robert L.; Tompkins, Ronald G.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Ryan, Colleen M.; Schneider, Jeffrey C.; Sheridan, Robert L.; Tompkins, Ronald G.] Harvard Univ, Sch Med, Boston, MA USA. [Ryan, Colleen M.; Schneider, Jeffrey C.; Sheridan, Robert L.] Shriners Hosp Children, Boston, MA USA. [Kazis, Lewis E.] Boston Univ, Sch Publ Hlth, Dept Hlth Policy & Management, CAPP, Boston, MA USA. [Schneider, Jeffrey C.] Spaulding Rehabil Hosp, Boston, MA USA. [Shapiro, Gabriel D.] St Justine Univ, Ctr Hlth, Montreal, PQ, Canada. [Shapiro, Gabriel D.] Univ Montreal, Montreal, PQ H3C 3J7, Canada. [Meyer, Walter J.] Shriners Hosp Children, Galveston, TX 77550 USA. [Meyer, Walter J.] Univ Texas Med Branch, Galveston, TX 77555 USA. [Palmieri, Tina] Shriners Hosp Children, Sacramento, CA USA. [Palmieri, Tina] Univ Calif Davis, Los Angeles, CA USA. [Pidcock, Frank S.] Kennedy Krieger Inst, Baltimore, MD USA. [Reilly, Debra] Univ Nebraska, Omaha, NE 68182 USA. [Lee, Austin] Xian Univ Finance & Econ, Res Ctr Med Stat & Actuarial Sci, Xian, Peoples R China. [Lee, Austin] Bentley Univ, Dept Math Sci, Waltham, MA USA. RP Ryan, CM (reprint author), Massachusetts Gen Hosp, Bigelow 1302,55 Fruit St, Boston, MA 02114 USA. EM cryan@mgh.harvard.edu FU Fraser Fund at the Massachusetts General Hospital; American Burn Association; Shriners Hospitals for Children; National Institute of Disability and Rehabilitation Research [H133A120034, H133A130023] FX This work is supported in part by the authors' institutions, the Fraser Fund at the Massachusetts General Hospital, the American Burn Association, the Shriners Hospitals for Children and the National Institute of Disability and Rehabilitation Research #H133A120034 and #H133A130023. NR 53 TC 7 Z9 8 U1 3 U2 7 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 1559-047X EI 1559-0488 J9 J BURN CARE RES JI J. Burn Care Res. PD JAN-FEB PY 2015 VL 36 IS 1 BP 118 EP 129 DI 10.1097/BCR.0000000000000214 PG 12 WC Emergency Medicine; Dermatology; Surgery SC Emergency Medicine; Dermatology; Surgery GA AY3AG UT WOS:000347456400019 PM 25501787 ER PT J AU Schneider, JC Nadler, DL Herndon, DN Kowalske, K Matthews, K Wiechman, SA Carrougher, GJ Gibran, NS Meyer, WJ Sheridan, RL Ryan, CM AF Schneider, Jeffrey C. Nadler, Deborah L. Herndon, David N. Kowalske, Karen Matthews, Katie Wiechman, Shelley A. Carrougher, Gretchen J. Gibran, Nicole S. Meyer, Walter J. Sheridan, Robert L. Ryan, Colleen M. TI Pruritus in Pediatric Burn Survivors: Defining the Clinical Course SO JOURNAL OF BURN CARE & RESEARCH LA English DT Article ID VISUAL ANALOG SCALE; QUALITY-OF-LIFE; ASSOCIATION/SHRINERS-HOSPITALS; OUTCOMES QUESTIONNAIRE; POSTBURN PRURITUS; FOR-CHILDREN; PAIN; ITCH; RELIABILITY; GABAPENTIN AB Pruritus is a frequent and severe symptom and a significant cause of distress for adult burn patients. Its effects in children are largely unstudied. The aim of this study is to characterize postburn itch in the pediatric population. This is a retrospective review from 2006 to 2013 for pediatric burn survivors who were enrolled in a longitudinal multicenter outcomes study. Demographic data, injury characteristics, associated symptoms (skin-related problems, pain, and sleep), and incidence and intensity (Numerical Rating Scale) of itch were examined. Measures were completed at hospital discharge and at 6, 12, and 24 months after injury. Spearman's correlations were used to examine the correlation between itch intensity and associated symptoms. Multivariate regression analyses examined the impact of associated symptoms on itch intensity. There were 430 pediatric burn survivors with a mean age of 7.8 years and a mean TBSA of 40.8%. Pruritus is present in most children (93%) and is of moderate intensity (5.7 +/- 3.1) at discharge. The frequency and intensity of pruritus decreases over time; a majority of children continue to report symptoms at 2 years (63%). Itch was significantly correlated with associated symptoms. Regression analyses showed a correlation between itch intensity and pain at each time point. There was no association between itch intensity and burn etiology, age, gender, or burn size. Pruritus is a frequent complication that lasts for at least 2 years after injury in a majority of pediatric burn survivors. This information will enable better tracking of outcomes and will serve as a baseline for assessing interventions. C1 [Schneider, Jeffrey C.; Nadler, Deborah L.; Matthews, Katie; Ryan, Colleen M.] Spaulding Rehabil Hosp, Dept Phys Med & Rehabil, Boston, MA 02129 USA. [Schneider, Jeffrey C.; Sheridan, Robert L.; Ryan, Colleen M.] Harvard Univ, Massachusetts Gen Hosp, Sch Med,Sumner Redstone Burn Ctr, Surg Serv,Shriners Hosp Children, Boston, MA USA. [Herndon, David N.; Meyer, Walter J.] Univ Texas Med Branch, Shriners Hosp Children, Galveston, TX 77555 USA. [Kowalske, Karen] Univ Texas SW Med Ctr Dallas, Dept Phys Med & Rehabil, Dallas, TX 75390 USA. [Wiechman, Shelley A.; Carrougher, Gretchen J.; Gibran, Nicole S.] Univ Washington, UW Med Reg Burn Ctr, Seattle, WA 98195 USA. RP Schneider, JC (reprint author), Spaulding Rehabil Hosp, Dept Phys Med & Rehabil, 300 First Ave, Boston, MA 02129 USA. FU Department of Education, NIDRR [H133A120034] FX The contents of this article were developed under a grant from the Department of Education, NIDRR grant number H133A120034. However, those contents do not necessarily represent the policy of the Department of Education, and you should not assume endorsement by the Federal Government. NR 38 TC 5 Z9 6 U1 1 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 1559-047X EI 1559-0488 J9 J BURN CARE RES JI J. Burn Care Res. PD JAN-FEB PY 2015 VL 36 IS 1 BP 151 EP 158 DI 10.1097/BCR.0000000000000145 PG 8 WC Emergency Medicine; Dermatology; Surgery SC Emergency Medicine; Dermatology; Surgery GA AY3AG UT WOS:000347456400023 PM 25162949 ER PT J AU Gamelli, L Mykychack, I Kushnir, A Driscoll, DN Fuzaylov, G AF Gamelli, Liza Mykychack, Iryna Kushnir, Antin Driscoll, Daniel N. Fuzaylov, Gennadiy TI Targeting Burn Prevention in Ukraine: Evaluation of Base Knowledge in Burn Prevention and First Aid Treatment SO JOURNAL OF BURN CARE & RESEARCH LA English DT Article ID CHILDREN; ZAMBIA; TRENDS; CARE AB Burn prevention has been identified by the World Health Organization (WHO) as a topic in need of further investigation and education throughout the world, with an increased need in low-income countries. It has been noted that implementing educational programs for prevention in high income countries has aided in lowering the rate of burn injuries. The purpose of this study is to evaluate the current education level of knowledge of prevention and first aid treatment of scald burns. A prevention campaign will target these educational needs as a part of an outreach program to improve burn care in Ukraine. The research team evaluated the current health structure in Ukraine and how it could benefit from the increased knowledge of burn prevention and first aid. A test was designed to assess the baseline level of knowledge with regard to first aid and scald prevention in parents, pregnant woman, and healthcare and daycare providers. A total of 14,456 tests were sent to pediatric clinics, obstetrician clinics, and daycare facilities to test respondents. A total of 6,120 completed tests were returned. Doctors presented with the highest level of knowledge averaging 77.0% on prevention and 67.5% on first aid while daycare workers presented the largest gap in knowledge at 65.0% in prevention and 54.3% in first aid. Interest in further educational materials was reported by 92% of respondents. The results of this study clearly show a lack of knowledge in first aid and prevention of scald burn injury in all the populations tested. C1 [Gamelli, Liza] Shriners Hosp Children, Boston, MA 02114 USA. [Mykychack, Iryna] State Adm, Dept Hlth, Lvov, Ukraine. [Mykychack, Iryna] Western Ukrainian Specialized Children Med Ctr, Lvov, Ukraine. [Driscoll, Daniel N.; Fuzaylov, Gennadiy] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Gamelli, L (reprint author), Shriners Hosp Children, Boston, MA 02114 USA. NR 21 TC 2 Z9 2 U1 1 U2 5 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 1559-047X EI 1559-0488 J9 J BURN CARE RES JI J. Burn Care Res. PD JAN-FEB PY 2015 VL 36 IS 1 BP 225 EP 231 DI 10.1097/BCR.0000000000000103 PG 7 WC Emergency Medicine; Dermatology; Surgery SC Emergency Medicine; Dermatology; Surgery GA AY3AG UT WOS:000347456400033 PM 25055008 ER PT J AU Wibbenmeyer, L Gittelman, MA Kluesner, K Liao, JL Xing, YF Faraklas, I Anyan, W Gamero, C Moulton, S Nederveld, C Banks, A Ryan, CM Conway, JA Reilly, DA Fish, J Kelly, C Peltier, G Schwantke, E Conrad, PF Caruso, DM Richey, KJ McCrory, K Elfar, MSA Pittinger, T Sadie, C Greenhalgh, D Palmieri, T Grossman, PH Richards, KM Joyce, T Pozez, AL Savetamal, A Harrington, DT Duncan, K Pomerantz, WJ Dillard, BD AF Wibbenmeyer, Lucy Gittelman, Michael A. Kluesner, Karen Liao, Junlin Xing, Yunfan Faraklas, Iris Anyan, Walter Gamero, Chelsea Moulton, Steven Nederveld, Cindy Banks, Ashley Ryan, Colleen M. Conway, Jennifer A. Reilly, Debra A. Fish, Joel Kelly, Charis Peltier, George Schwantke, Emily Conrad, Peggie F. Caruso, Daniel M. Richey, Karen J. McCrory, Kristine Elfar, Mohamed S. A. Pittinger, Timothy Sadie, Christine Greenhalgh, David Palmieri, Tina Grossman, Peter H. Richards, Kurt M. Joyce, Teresa Pozez, Andrea L. Savetamal, Alisa Harrington, David T. Duncan, Kimberley Pomerantz, Wendy J. Dillard, B. Daniel TI A Multicenter Study of Preventable Contact Burns From Glass Fronted Gas Fireplaces SO JOURNAL OF BURN CARE & RESEARCH LA English DT Article ID PEDIATRIC BURNS; FACIAL BURNS; HAND BURNS; MANAGEMENT; EXPERIENCE; TODDLERS; CHILDREN; PALM AB Glass fronted gas fireplaces (GFGFs) have exterior surfaces that can reach extremely high temperatures. Burn injuries from contact with the glass front can be severe with long-term sequelae. The Consumer Product Safety Commission reported that these injuries are uncommon, whereas single-center studies indicate a much higher frequency. The purpose of this multi-institutional study was to determine the magnitude and severity of GFGF injuries in North America. Seventeen burn centers elected to participate in this retrospective chart review. Chart review identified 402 children <= 10 years of age who sustained contact burns from contact with GFGF, who were seen or admitted to the study hospitals from January 2006 to December 2010. Demographic, burn, treatment, and financial data were collected. The mean age of the study group was 16.8 +/- 13.3 months. The majority suffered burns to their hands (396, 98.5%), with burns to the face being the second, much less common site (14, 3.5%). Two hundred and sixty-nine required rehabilitation therapy (66.9%). The number of GFGF injuries reported was 20 times greater than the approximately 30 injuries estimated by the Consumer Product Safety Commission's 10-year review. For the affected children, these injuries are painful, often costly and occasionally can lead to long-term sequelae. Given that less than a quarter of burn centers contributed data, the injury numbers reported herein support a need for broader safety guidelines for gas fireplaces in order to have a significant impact on future injuries. C1 [Wibbenmeyer, Lucy; Kluesner, Karen; Liao, Junlin; Xing, Yunfan] Univ Iowa, Carver Coll Med, Dept Surg, Iowa City, IA 52246 USA. [Gittelman, Michael A.; Pomerantz, Wendy J.] Cincinnati Childrens Hosp Med Ctr, Comprehens Childrens Injury Ctr, Div Emergency Med, Cincinnati, OH 45229 USA. [Faraklas, Iris; Anyan, Walter; Gamero, Chelsea] Univ Utah, Dept Surg, Salt Lake City, UT USA. [Moulton, Steven; Nederveld, Cindy; Banks, Ashley] Childrens Hosp, Dept Surg, Denver, CO 80218 USA. [Ryan, Colleen M.; Conway, Jennifer A.] Shriners Hosp Children, Dept Surg, Boston, MA USA. [Ryan, Colleen M.; Conway, Jennifer A.] Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. [Ryan, Colleen M.; Conway, Jennifer A.] Harvard Univ, Sch Med, Boston, MA USA. [Reilly, Debra A.] Univ Nebraska, Dept Surg, Omaha, NE 68182 USA. [Fish, Joel; Kelly, Charis] Hosp Sick Children, Dept Surg, Toronto, ON M5G 1X8, Canada. [Peltier, George; Schwantke, Emily] Hennepin Cty Hosp, Dept Surg, St Paul, MN USA. [Conrad, Peggie F.] Loyola Univ, Dept Surg, Chicago, IL 60611 USA. [Caruso, Daniel M.; Richey, Karen J.; McCrory, Kristine] Maricopa Cty Gen Hosp, Arizona Burn Ctr, Dept Surg, Phoenix, AZ USA. [Elfar, Mohamed S. A.] SUNY Upstate Med Univ, Dept Surg, Clark Burn Ctr, Syracuse, NY 13210 USA. [Pittinger, Timothy; Sadie, Christine] Akron Childrens Hosp, Dept Surg, Akron, OH USA. [Greenhalgh, David; Palmieri, Tina] Shriners Hosp Children Northern Calif Sacramento, Dept Surg, Sacramento, CA USA. [Grossman, Peter H.; Richards, Kurt M.] West Hills Hosp West Hills, Dept Burn Med, West Hills, CA USA. [Joyce, Teresa] Shriners Hosp Children, Dept Surg, Cincinnati, OH USA. [Pozez, Andrea L.] Virginia Commonwealth Univ, Richmond, VA USA. [Savetamal, Alisa] Bridgeport Hosp, Dept Surg, Bridgeport, CT USA. [Harrington, David T.; Duncan, Kimberley] Rhode Isl Hosp, Dept Surg, Providence, RI USA. [Dillard, B. Daniel] Burn Prevent Network, Allentown, PA USA. RP Wibbenmeyer, L (reprint author), Univ Iowa, Carver Coll Med, 200 Hawkins Dr,8321 JCP, Iowa City, IA 52246 USA. EM lucy-wibbenmeyer@uiowa.edu FU University of Iowa Injury Prevention Center FX This study was supported by a grant from the University of Iowa Injury Prevention Center. The study sponsor did not have any role in study design; collection, analysis, or interpretation of data. The study sponsor had no role in writing the report and the decision as to where to submit the report for publication. NR 27 TC 0 Z9 0 U1 2 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 1559-047X EI 1559-0488 J9 J BURN CARE RES JI J. Burn Care Res. PD JAN-FEB PY 2015 VL 36 IS 1 BP 240 EP 245 DI 10.1097/BCR.0000000000000215 PG 6 WC Emergency Medicine; Dermatology; Surgery SC Emergency Medicine; Dermatology; Surgery GA AY3AG UT WOS:000347456400036 PM 25559733 ER EF