FN Thomson Reuters Web of Science™ VR 1.0 PT S AU Li, L Subramaniam, B Aguirre, AD Andrawes, MN Tearney, GJ AF Li, Li Subramaniam, Balachundhar Aguirre, Aaron D. Andrawes, Michael N. Tearney, Guillermo J. BE Choi, B Kollias, N Zeng, H Kang, HW Wong, BJF Ilgner, JF Tearney, GJ Gregory, KW Marcu, L Skala, MC Campagnola, PJ Mandelis, A TI In-vivo continuous monitoring of mixed venous oxygen saturation by photoacoustic transesophageal echocardiography SO PHOTONIC THERAPEUTICS AND DIAGNOSTICS XII SE Proceedings of SPIE LA English DT Proceedings Paper CT Conference on Photonic Therapeutics and Diagnostics XII CY FEB 13-14, 2016 CL San Francisco, CA SP SPIE C1 [Li, Li] Harvard Univ, Sch Med, Cambridge, MA 02138 USA. [Subramaniam, Balachundhar] Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. [Aguirre, Aaron D.; Andrawes, Michael N.; Tearney, Guillermo J.] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Li, L (reprint author), Harvard Univ, Sch Med, Cambridge, MA 02138 USA. NR 0 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 978-1-62841-924-5 J9 PROC SPIE PY 2016 VL 9689 AR 96892U DI 10.1117/12.2211112 PG 1 WC Microscopy; Optics SC Microscopy; Optics GA BE9FK UT WOS:000377396200078 ER PT S AU Osseiran, S Wang, HQ Suita, Y Roider, E Fisher, DE Evans, CL AF Osseiran, Sam Wang, Hequn Suita, Yusuke Roider, Elisabeth Fisher, David E. Evans, Conor L. BE Choi, B Kollias, N Zeng, H Kang, HW Wong, BJF Ilgner, JF Tearney, GJ Gregory, KW Marcu, L Skala, MC Campagnola, PJ Mandelis, A TI Towards label-free evaluation of oxidative stress in human skin exposed to sun filters (Conference Presentation) SO PHOTONIC THERAPEUTICS AND DIAGNOSTICS XII SE Proceedings of SPIE LA English DT Proceedings Paper CT Conference on Photonic Therapeutics and Diagnostics XII CY FEB 13-14, 2016 CL San Francisco, CA SP SPIE C1 [Osseiran, Sam] Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA. [Wang, Hequn; Suita, Yusuke; Roider, Elisabeth; Fisher, David E.; Evans, Conor L.] Massachusetts Gen Hosp, Cutaneous Biol Res Ctr, Boston, MA 02114 USA. RP Osseiran, S (reprint author), Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA. NR 0 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 978-1-62841-924-5 J9 PROC SPIE PY 2016 VL 9689 AR 968906 DI 10.1117/12.2213406 PG 1 WC Microscopy; Optics SC Microscopy; Optics GA BE9FK UT WOS:000377396200004 ER PT S AU Singh, K Yamada, D Tearney, GJ AF Singh, Kanwarpal Yamada, Daisuke Tearney, Guillermo J. BE Choi, B Kollias, N Zeng, H Kang, HW Wong, BJF Ilgner, JF Tearney, GJ Gregory, KW Marcu, L Skala, MC Campagnola, PJ Mandelis, A TI Common path ball lens probe for optical coherence tomography (Conference Presentation) SO PHOTONIC THERAPEUTICS AND DIAGNOSTICS XII SE Proceedings of SPIE LA English DT Proceedings Paper CT Conference on Photonic Therapeutics and Diagnostics XII CY FEB 13-14, 2016 CL San Francisco, CA SP SPIE C1 [Singh, Kanwarpal; Yamada, Daisuke; Tearney, Guillermo J.] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Singh, K (reprint author), Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 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 978-1-62841-924-5 J9 PROC SPIE PY 2016 VL 9689 AR 96893C DI 10.1117/12.2214236 PG 1 WC Microscopy; Optics SC Microscopy; Optics GA BE9FK UT WOS:000377396200090 ER PT S AU Tripathi, MM Tshikudi, DM Kashany, ZH Van Cott, EM Nadkarni, SK AF Tripathi, Markandey M. Tshikudi, Diane M. Kashany, Zeinab Hajjarian Van Cott, Elizabeth M. Nadkarni, Seemantini K. BE Choi, B Kollias, N Zeng, H Kang, HW Wong, BJF Ilgner, JF Tearney, GJ Gregory, KW Marcu, L Skala, MC Campagnola, PJ Mandelis, A TI Blood coagulation profiling in patients using optical thromboelastography (OTEG) SO PHOTONIC THERAPEUTICS AND DIAGNOSTICS XII SE Proceedings of SPIE LA English DT Proceedings Paper CT Conference on Photonic Therapeutics and Diagnostics XII CY FEB 13-14, 2016 CL San Francisco, CA SP SPIE C1 [Tripathi, Markandey M.; Tshikudi, Diane M.; Kashany, Zeinab Hajjarian; Nadkarni, Seemantini K.] Wellman Ctr Photomed, Boston, MA 02114 USA. [Van Cott, Elizabeth M.] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Tripathi, MM (reprint author), Wellman Ctr Photomed, Boston, MA 02114 USA. NR 0 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 978-1-62841-924-5 J9 PROC SPIE PY 2016 VL 9689 AR 96892R DI 10.1117/12.2213014 PG 1 WC Microscopy; Optics SC Microscopy; Optics GA BE9FK UT WOS:000377396200075 ER PT S AU Tshikudi, DM Tripathi, MM Kashany, ZH Nadkarni, SK AF Tshikudi, Diane M. Tripathi, Markandey M. Kashany, Zeinab Hajjarian Nadkarni, Seemantini K. BE Choi, B Kollias, N Zeng, H Kang, HW Wong, BJF Ilgner, JF Tearney, GJ Gregory, KW Marcu, L Skala, MC Campagnola, PJ Mandelis, A TI Optical profiling of anticoagulation status SO PHOTONIC THERAPEUTICS AND DIAGNOSTICS XII SE Proceedings of SPIE LA English DT Proceedings Paper CT Conference on Photonic Therapeutics and Diagnostics XII CY FEB 13-14, 2016 CL San Francisco, CA SP SPIE C1 [Tshikudi, Diane M.; Kashany, Zeinab Hajjarian; Nadkarni, Seemantini K.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Tripathi, Markandey M.] Wellman Ctr Photomed, Boston, MA USA. RP Tshikudi, DM (reprint author), Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 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 978-1-62841-924-5 J9 PROC SPIE PY 2016 VL 9689 AR 96892S DI 10.1117/12.2213043 PG 1 WC Microscopy; Optics SC Microscopy; Optics GA BE9FK UT WOS:000377396200076 ER PT S AU Wang, HQ Osseiran, S Roider, E Fisher, DE Evans, CL AF Wang, Hequn Osseiran, Sam Roider, Elisabeth Fisher, David E. Evans, Conor L. BE Choi, B Kollias, N Zeng, H Kang, HW Wong, BJF Ilgner, JF Tearney, GJ Gregory, KW Marcu, L Skala, MC Campagnola, PJ Mandelis, A TI New imaging-based biomarkers for melanoma diagnosis using coherent Raman Scattering microscopy (Conference Presentation) SO PHOTONIC THERAPEUTICS AND DIAGNOSTICS XII SE Proceedings of SPIE LA English DT Proceedings Paper CT Conference on Photonic Therapeutics and Diagnostics XII CY FEB 13-14, 2016 CL San Francisco, CA SP SPIE C1 [Wang, Hequn; Osseiran, Sam] Wellman Ctr Photomed, Boston, MA 02114 USA. [Roider, Elisabeth; Fisher, David E.] Massachusetts Gen Hosp, Cutaneous Biol Res Ctr, Boston, MA 02114 USA. [Evans, Conor L.] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Wang, HQ (reprint author), Wellman Ctr Photomed, Boston, MA 02114 USA. NR 0 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 978-1-62841-924-5 J9 PROC SPIE PY 2016 VL 9689 AR 968904 DI 10.1117/12.2213360 PG 1 WC Microscopy; Optics SC Microscopy; Optics GA BE9FK UT WOS:000377396200002 ER PT S AU Wang, Y Ortega-Martinez, A Farinelli, B Anderson, RR Franco, W AF Wang, Ying Ortega-Martinez, Antonio Farinelli, Bill Anderson, R. Rox Franco, Walfre BE Choi, B Kollias, N Zeng, H Kang, HW Wong, BJF Ilgner, JF Tearney, GJ Gregory, KW Marcu, L Skala, MC Campagnola, PJ Mandelis, A TI Fluorescence imaging of tryptophan and collagen cross-links to evaluate wound closure ex vivo SO PHOTONIC THERAPEUTICS AND DIAGNOSTICS XII SE Proceedings of SPIE LA English DT Proceedings Paper CT Conference on Photonic Therapeutics and Diagnostics XII CY FEB 13-14, 2016 CL San Francisco, CA SP SPIE DE autofluorescence; imaging; skin; wound healing; epithelialization AB Wound size is a key parameter in monitoring healing. Current methods to measure wound size are often subjective, time-consuming and marginally invasive. Recently, we developed a non-invasive, non-contact, fast and simple but robust fluorescence imaging (u-FEI) method to monitor the healing of skin wounds. This method exploits the fluorescence of native molecules to tissue as functional and structural markers. The objective of the present study is to demonstrate the feasibility of using variations in the fluorescence intensity of tryptophan and cross-links of collagen to evaluate proliferation of keratinocyte cells and quantitate size of wound during healing, respectively. Circular dermal wounds were created in ex vivo human skin and cultured in different media. Two serial fluorescence images of tryptophan and collagen cross-links were acquired every two days. Histology and immunohistology were used to validate correlation between fluorescence and epithelialization. Images of collagen cross-links show fluorescence of the exposed dermis and, hence, are a measure of wound area. Images of tryptophan show higher fluorescence intensity of proliferating keratinocytes forming new epithelium, as compared to surrounding keratinocytes not involved in epithelialization. These images are complementary since collagen cross-links report on structure while tryptophan reports on function. H&E and immunohistology show that tryptophan fluorescence correlates with newly formed epidermis. We have established a fluorescence imaging method for studying epithelialization processes during wound healing in a skin organ culture model, our approach has the potential to provide a non-invasive, non-contact, quick, objective and direct method for quantitative measurements in wound healing in vivo. C1 [Wang, Ying; Ortega-Martinez, Antonio; Farinelli, Bill; Anderson, R. Rox; Franco, Walfre] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Wellman Ctr Photomed,Dept Dermatol, 55 Fruit St, Boston, MA 02114 USA. RP Wang, Y (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Wellman Ctr Photomed,Dept Dermatol, 55 Fruit St, Boston, MA 02114 USA. EM ywang29@mgh.harvard.edu NR 7 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 978-1-62841-924-5 J9 PROC SPIE PY 2016 VL 9689 AR 96890G DI 10.1117/12.2211045 PG 4 WC Microscopy; Optics SC Microscopy; Optics GA BE9FK UT WOS:000377396200014 ER PT B AU Bighamian, R Reisner, AT Hahn, JO AF Bighamian, Ramin Reisner, Andrew T. Hahn, Jin-Oh GP ASME TI A CONTROL-ORIENTED MODEL OF BLOOD VOLUME RESPONSE TO HEMORRHAGE AND FLUID RESUSCITATION SO PROCEEDINGS OF THE ASME 8TH ANNUAL DYNAMIC SYSTEMS AND CONTROL CONFERENCE, 2015, VOL 1 LA English DT Proceedings Paper CT 8th ASME Annual Dynamic Systems and Control Conference (DSCC 2015) CY OCT 28-30, 2015 CL Columbus, OH SP ASME, Dynam Syst & Control Div ID COMPUTER-SIMULATION; MATHEMATICAL-MODEL; ABDOMINAL-SURGERY; DECISION-SUPPORT; MANAGEMENT; THERAPY; RESTITUTION; VALIDATION; KINETICS; BALANCE AB This paper presents a control-oriented model of blood volume response to hemorrhage and fluid resuscitation that can be potentially utilized in closed-loop control of fluid resuscitation. A unique characteristic of the proposed model is that it is built to ensure structural parsimony while retaining physiological transparency. To accomplish this characteristic, blood volume regulation in the body to external perturbations of hemorrhage and fluid resuscitation was modeled as a low order control system in which the fluid transfer between blood and interstitial fluid is governed by a proportional-integral controller. This in essence resulted in a minimal model with four parameters to be adapted to each individual. The validity of the proposed model was tested using data available in the literature. The results indicated that the proposed model was able to reproduce the blood volume response to hemorrhage and fluid resuscitation with high fidelity: on the average, the prediction error was only 1.53 +/- 11.5 %, thus strongly supporting our claim that it can be used as viable basis for the design of closed-loop fluid resuscitation controllers. C1 [Bighamian, Ramin; Hahn, Jin-Oh] Univ Maryland, Mech Engn, College Pk, MD 20742 USA. [Reisner, Andrew T.] Massachusetts Gen Hosp, Emergency Med, Boston, MA 02142 USA. RP Bighamian, R (reprint author), Univ Maryland, Mech Engn, College Pk, MD 20742 USA. EM rbighami@umd.edu; areisner@partners.org; jhahn12@umd.edu NR 36 TC 0 Z9 0 U1 2 U2 2 PU AMER SOC MECHANICAL ENGINEERS PI NEW YORK PA THREE PARK AVENUE, NEW YORK, NY 10016-5990 USA BN 978-0-7918-5724-3 PY 2016 AR V001T16A004 PG 6 WC Automation & Control Systems; Engineering, Mechanical SC Automation & Control Systems; Engineering GA BE9IX UT WOS:000377639000082 ER PT J AU Miller, MB Borsari, B Fernandez, AC Yurasek, AM Hustad, JTP AF Miller, Mary Beth Borsari, Brian Fernandez, Anne C. Yurasek, Ali M. Hustad, John T. P. TI Drinking Location and Pregaming as Predictors of Alcohol Intoxication Among Mandated College Students SO SUBSTANCE USE & MISUSE LA English DT Article DE Alcohol; college students; drinking; location; pregaming ID DESCRIPTIVE NORMS; INJUNCTIVE NORMS; BINGE DRINKING; CONSUMPTION; PREVENTION; OUTCOMES; MISPERCEPTIONS; INTERVENTIONS; VALIDATION; BEHAVIOR AB Background: Both drinking location and pregaming have been associated with heavy alcohol use among college students, yet the manner by which they uniquely contribute to alcohol intoxication remains unclear. Objective: The current study examined the unique utility of drinking location and pregaming in predicting alcohol intoxication among college students who violated campus alcohol policy. Method: Eietween 2011 and 2012, mandated college students who reported drinking prior to heir referral events (N = 212, 41% female, 80% White, A4 =19.4 y) completed a computerized assessment of drinking location arid related behaviors as part of larger research trial Chi-squared statistics, tests, one-way analyses of covariance, and regression were used to examine study aims. Results: Parcipants were most likely (44%) to report drinking in off-campus housing prior to the referral event, and approximately half (47%) reported pregaming. Alcohol intoxication on the night of the referral event differed significantly as a function of both drinking location and pregaming, but pregaming did not moderate the association between drinking location arid alcohol intoxication among marl dated students. Female birth sex, pregaming, arid drinking at either fraternities or off-campus housng predicted greater levels of alcohol intoxication on the night of the referral incident, while drinking n a residence hall/dorm predicted lovver intoxication. Fonclusions/fmportance: Drinking location and pregaming are distinct predictors of alcohol intoxication among mandated college students. Future n e veritions may benefitfrom targeting both where arid how college students consume alcohol C1 [Miller, Mary Beth; Borsari, Brian; Fernandez, Anne C.; Yurasek, Ali M.] Brown Univ, Ctr Alcohol & Addict Studies, Providence, RI 02912 USA. [Borsari, Brian] San Francisco VA Med Ctr, Mental Hlth & Behav Sci Serv, San Francisco, CA USA. [Hustad, John T. P.] Penn State Univ, Coll Med, Dept Med & Publ Hlth Sci, Hershey, PA USA. RP Miller, MB (reprint author), Brown Univ, Ctr Alcohol & Addict Studies, Dept Behav & Social Sci, Box G-S121-5, Providence, RI 02912 USA. EM mary_miller@brown.edu FU National Institute on Alcohol Abuse and Alcoholism (NIAAA) [R01-AA015518, 01-AA017874]; VISN1 Career Development Award [V1CDA2012-18]; National Institute on Drug Abuse (NIDA) [T32 DA016184]; National Center for Advancing Translational Sciences (NCATS); National Institutes of Health (NIH) [UL1 TR000127, KL2 TR000126] FX Brian Borsari's contribution to this manuscript was supported by National Institute on Alcohol Abuse and Alcoholism (NIAAA) Grants R01-AA015518 and 01-AA017874 and VISN1 Career Development Award V1CDA2012-18. Anne Fernandez's and Ali Yurasek's contributions to this manuscript were supported by the National Institute on Drug Abuse (NIDA) grant T32 DA016184. John Hustad's contribution was supported by the National Center for Advancing Translational Sciences (NCATS) and the National Institutes of Health (NIH) through Grants UL1 TR000127 and KL2 TR000126 to Lawrence Sinoway. The contents of this article do not represent the views of the National Institutes of Health, the Department of Veterans Affairs, or the United States Government. NR 39 TC 2 Z9 2 U1 0 U2 0 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 530 WALNUT STREET, STE 850, PHILADELPHIA, PA 19106 USA SN 1082-6084 EI 1532-2491 J9 SUBST USE MISUSE JI Subst. Use Misuse PY 2016 VL 51 IS 8 BP 983 EP 992 DI 10.3109/10826084.2016.1152496 PG 10 WC Substance Abuse; Psychiatry; Psychology SC Substance Abuse; Psychiatry; Psychology GA DN8AR UT WOS:000377301800004 PM 27070480 ER PT J AU Yurasek, A Miller, MB Mastroleo, N Lazar, V Borsari, B AF Yurasek, Ali Miller, Mary Beth Mastroleo, Nadine Lazar, Vanessa Borsari, Brian TI Pregaming, Drinking Duration, and Movement as Unique Predictors of Alcohol Use and Cognitions Among Mandated College Students SO SUBSTANCE USE & MISUSE LA English DT Article DE Pregaming; duration of drinking; movement; event-related cognitions; mandated college students; alcohol ID EVENT-LEVEL ASSOCIATIONS; RISK-FACTORS; CONSUMPTION; ADOLESCENTS; AGGRESSION; MOTIVATION; HEALTH; TRENDS; PARTY AB Background: Pregaming is a common phenomenon among college students and is associated with increased risks such as heavy drinking, alcohol-related consequences, and violating campus alcohol policies. However, the mechanism by which pregaming increases student risk is unclear. Objectives: The current study aimed to delineate, the role of personal endorsement of pregaming; duration of an entire drinking episode on the night of an alcohol violation, and movement from one ()cation to another in predicting alcohol use and violation-related cognitions. Methods: Participants (N = 113) were college students who had received an alcohol violation. Hierarchical multiple regressions were conducted to investigate the predictive value of pregaming endorsement, duration of drinking, and movement on drinking behaviors (number of drinks consumed and estimated blood alcohol content (eBAC)] on the night of the alcohol violation as well as violation-related cognitions (responsibility, aversiveness). Results: Pregaming and duration of drinking were significant predictors of alcohol consumption and eBAC on the night of the violation, whereas movement was not, Duration of the drinking episode was significantly related to increased perceived responsibility for the alcohol violation. Conclusions/importance: Self-reported pregaming and the duration of the drinking episode appear to be better targets than movement for prevention and intervention efforts addressing pregaming on college campuses. Interventions should continue focusing on reducing pregaming and its associated consequences, especially for those who report a longer duration of drinking following a pregaming episode C1 [Yurasek, Ali; Miller, Mary Beth; Lazar, Vanessa] Brown Univ, Sch Publ Hlth, Ctr Alcohol & Addict Studies, Providence, RI 02912 USA. [Mastroleo, Nadine] Binghamton Univ, Community & Publ Affairs Dept, Binghamton, NY USA. [Borsari, Brian] San Francisco VA Med Ctr, Mental Hlth & Behav Sci Serv, San Francisco, CA USA. [Borsari, Brian] Univ Calif San Francisco, Dept Psychiat, San Francisco, CA USA. RP Yurasek, A (reprint author), Brown Univ, Dept Publ Hlth, Ctr Alcohol & Addict Studies, 121 South Main St, Providence, RI 02906 USA. EM ali_yurasek@brown.edu FU National Institute on Alcohol Abuse and Alcoholism [R01 AA015518] FX This work was supported by the National Institute on Alcohol Abuse and Alcoholism [Grant number R01 AA015518]. NR 37 TC 2 Z9 2 U1 4 U2 4 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 530 WALNUT STREET, STE 850, PHILADELPHIA, PA 19106 USA SN 1082-6084 EI 1532-2491 J9 SUBST USE MISUSE JI Subst. Use Misuse PY 2016 VL 51 IS 8 BP 993 EP 1001 DI 10.3109/10826084.2016.1152491 PG 9 WC Substance Abuse; Psychiatry; Psychology SC Substance Abuse; Psychiatry; Psychology GA DN8AR UT WOS:000377301800005 PM 27070369 ER PT S AU Lee, JK Choi, YL Kwon, M Park, PJ AF Lee, June-Koo Choi, Yoon-La Kwon, Mijung Park, Peter J. BE Abbas, AK Aster, JC Galli, SJ TI Mechanisms and Consequences of Cancer Genome Instability: Lessons from Genome Sequencing Studies SO ANNUAL REVIEW OF PATHOLOGY: MECHANISMS OF DISEASE, VOL 11 SE Annual Review of Pathology-Mechanisms of Disease LA English DT Review; Book Chapter DE chromosomal instability; aneuploidy; chromosomal rearrangement; microsatellite instability; hypermutation; cancer evolution ID CELL LUNG-CANCER; ONCOGENE-INDUCED SENESCENCE; BREAK-INDUCED REPLICATION; COPY-NUMBER ALTERATION; OXIDATIVE DNA-DAMAGE; MICROSATELLITE-INSTABILITY; CHROMOSOMAL INSTABILITY; COLORECTAL-CANCER; COLON-CANCER; XERODERMA-PIGMENTOSUM AB During tumor evolution, cancer cells can accumulate numerous genetic alterations, ranging from single nucleotide mutations to whole-chromosomal changes. Although a great deal of progress has been made in the past decades in characterizing genomic alterations, recent cancer genome sequencing studies have provided a wealth of information on the detailed molecular profiles of such alterations in various types of cancers. Here, we review our current understanding of the mechanisms and consequences of cancer genome instability, focusing on the findings uncovered through analysis of exome and whole-genome sequencing data. These analyses have shown that most cancers have evidence of genome instability, and the degree of instability is variable within and between cancer types. Importantly, we describe some recent evidence supporting the idea that chromosomal instability could be a major driving force in tumorigenesis and cancer evolution, actively shaping the genomes of cancer cells to maximize their survival advantage. C1 [Lee, June-Koo] Korea Adv Inst Sci & Technol, Grad Sch Med Sci & Engn, Daejeon 34141, South Korea. [Choi, Yoon-La] Sungkyunkwan Univ, Dept Pathol & Translat Genom, Samsung Med Ctr, Sch Med, Seoul 06351, South Korea. [Choi, Yoon-La] Sungkyunkwan Univ, Sch Med, Dept Hlth Sci & Technol, SAIHST, Seoul 06351, South Korea. [Kwon, Mijung] Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA 02115 USA. [Kwon, Mijung] Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. [Park, Peter J.] Harvard Univ, Sch Med, Dept Biomed Informat, Boston, MA 02115 USA. RP Lee, JK (reprint author), Korea Adv Inst Sci & Technol, Grad Sch Med Sci & Engn, Daejeon 34141, South Korea. EM junekoo_lee@kaist.ac.kr; yla.choi@samsung.com; mijung_kwon@dfci.harvard.edu; peter_park@hms.harvard.edu NR 213 TC 3 Z9 3 U1 3 U2 7 PU ANNUAL REVIEWS PI PALO ALTO PA 4139 EL CAMINO WAY, PO BOX 10139, PALO ALTO, CA 94303-0897 USA SN 1553-4006 BN 978-0-8243-4311-8 J9 ANNU REV PATHOL-MECH JI Annu. Rev. Pathol.-Mech Dis. PY 2016 VL 11 BP 283 EP 312 DI 10.1146/annurev-pathol-012615-044446 PG 30 WC Pathology SC Pathology GA BE8UN UT WOS:000377037200012 PM 26907526 ER PT S AU Filbin, MG Suva, ML AF Filbin, Mariella G. Suva, Mario L. BE Abbas, AK Aster, JC Galli, SJ TI Gliomas Genomics and Epigenomics: Arriving at the Start and Knowing It for the First Time SO ANNUAL REVIEW OF PATHOLOGY: MECHANISMS OF DISEASE, VOL 11 SE Annual Review of Pathology-Mechanisms of Disease LA English DT Review; Book Chapter DE glioblastoma; astrocytoma; diffuse intrinsic pontine glioma; oligodendroglioma; histone mutations; IDH1 ID HIGH-GRADE GLIOMAS; INTRINSIC PONTINE GLIOMA; TUMOR-INITIATING CELLS; CANCER STEM-CELLS; JUVENILE PILOCYTIC ASTROCYTOMAS; NEWLY-DIAGNOSED GLIOBLASTOMA; ACTIVATING ACVR1 MUTATIONS; HISTONE H3.3 MUTATIONS; CENTRAL-NERVOUS-SYSTEM; BRAF V600E MUTATION AB Gliomas are the most common primary human brain tumors and occur in both adults and children. Over the past few years, systematic large-scale genomic and epigenomic profiling has provided unprecedented insight into their pathogenesis, uncovering alterations in an unanticipated number of genes and regulatory elements. In this review, we discuss recent discoveries about the genomics and epigenomics of adult and pediatric gliomas and highlight how some of the founding genetic mutations reshape the cancer epigenome. These studies provide an in-depth view of the molecular routes leading to glioma development, offer insight into the cancer stem cell model, help refine classifications, and should lay the foundation for improved clinical care. C1 [Filbin, Mariella G.; Suva, Mario L.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Pathol, Boston, MA 02114 USA. [Filbin, Mariella G.; Suva, Mario L.] Massachusetts Gen Hosp, Ctr Canc Res, Boston, MA 02114 USA. [Filbin, Mariella G.; Suva, Mario L.] Broad Inst Harvard & MIT, Cambridge, MA 02142 USA. [Filbin, Mariella G.] Dana Farber Canc Inst, Canc & Blood Disorders Ctr, Boston, MA 02215 USA. [Filbin, Mariella G.] Boston Childrens Hosp, Boston, MA 02215 USA. RP Filbin, MG (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Pathol, Boston, MA 02114 USA.; Filbin, MG (reprint author), Massachusetts Gen Hosp, Ctr Canc Res, Boston, MA 02114 USA.; Filbin, MG (reprint author), Broad Inst Harvard & MIT, Cambridge, MA 02142 USA.; Filbin, MG (reprint author), Dana Farber Canc Inst, Canc & Blood Disorders Ctr, Boston, MA 02215 USA.; Filbin, MG (reprint author), Boston Childrens Hosp, Boston, MA 02215 USA. EM Mariella_GruberFilbin@dfci.harvard.edu; Suva.Mario@mgh.harvard.edu NR 142 TC 5 Z9 5 U1 3 U2 3 PU ANNUAL REVIEWS PI PALO ALTO PA 4139 EL CAMINO WAY, PO BOX 10139, PALO ALTO, CA 94303-0897 USA SN 1553-4006 BN 978-0-8243-4311-8 J9 ANNU REV PATHOL-MECH JI Annu. Rev. Pathol.-Mech Dis. PY 2016 VL 11 BP 497 EP 521 DI 10.1146/annurev-pathol-012615-044208 PG 25 WC Pathology SC Pathology GA BE8UN UT WOS:000377037200019 PM 26980161 ER PT S AU Hoggatt, J Kfoury, Y Scadden, DT AF Hoggatt, Jonathan Kfoury, Youmna Scadden, David T. BE Abbas, AK Aster, JC Galli, SJ TI Hematopoietic Stem Cell Niche in Health and Disease SO ANNUAL REVIEW OF PATHOLOGY: MECHANISMS OF DISEASE, VOL 11 SE Annual Review of Pathology-Mechanisms of Disease LA English DT Review; Book Chapter DE bone marrow; leukemia; hematopoiesis; mesenchymal cell; hypoxia; malignancy ID COLONY-STIMULATING FACTOR; BONE-MARROW NICHE; HUMAN CD34(+) CELLS; HUMAN CORD BLOOD; PROGENITOR CELLS; SELF-RENEWAL; ENDOTHELIAL-CELLS; GROWTH-FACTOR; IN-VITRO; VASCULAR NICHE AB Regulation of stem cells in adult tissues is a key determinant of how well an organism can respond to the stresses of physiological challenge and disease. This is particularly true of the hematopoietic system, where demands on host defenses can call for an acute increase in cell production. Hematopoietic stem cells receive the regulatory signals for cell production in adult mammals in the bone marrow, a tissue with higher-order architectural and functional organization than previously appreciated. Here, we review the data defining particular structural components and heterologous cells in the bone marrow that participate in hematopoietic stem cell function. Further, we explore the case for stromal-hematopoietic cell interactions contributing to neoplastic myeloid disease. As the hematopoietic regulatory networks in the bone marrow are revealed, it is anticipated that strategies will emerge for how to enhance or inhibit production of specific blood cells. In that way, the control of hematopoiesis will enter the domain of therapies to modulate broad aspects of hematopoiesis, both normal and malignant. C1 [Hoggatt, Jonathan; Kfoury, Youmna; Scadden, David T.] Harvard Stem Cell Inst, Cambridge, MA 02138 USA. [Hoggatt, Jonathan; Kfoury, Youmna; Scadden, David T.] Harvard Univ, Dept Stem Cell & Regenerat Biol, Cambridge, MA 02138 USA. [Hoggatt, Jonathan; Kfoury, Youmna; Scadden, David T.] Massachusetts Gen Hosp, Ctr Regenerat Med, Boston, MA 02114 USA. RP Scadden, DT (reprint author), Harvard Stem Cell Inst, Cambridge, MA 02138 USA.; Scadden, DT (reprint author), Harvard Univ, Dept Stem Cell & Regenerat Biol, Cambridge, MA 02138 USA.; Scadden, DT (reprint author), Massachusetts Gen Hosp, Ctr Regenerat Med, Boston, MA 02114 USA. EM dscadden@mgh.harvard.edu NR 175 TC 7 Z9 7 U1 6 U2 10 PU ANNUAL REVIEWS PI PALO ALTO PA 4139 EL CAMINO WAY, PO BOX 10139, PALO ALTO, CA 94303-0897 USA SN 1553-4006 BN 978-0-8243-4311-8 J9 ANNU REV PATHOL-MECH JI Annu. Rev. Pathol.-Mech Dis. PY 2016 VL 11 BP 555 EP 581 DI 10.1146/annurev-pathol-012615-044414 PG 27 WC Pathology SC Pathology GA BE8UN UT WOS:000377037200021 PM 27193455 ER PT J AU Damar, U Gersner, R Johnstone, JT Schachter, S Rotenberg, A AF Damar, U. Gersner, R. Johnstone, J. T. Schachter, S. Rotenberg, A. TI Huperzine A as a neuroprotective and antiepileptic drug: a review of preclinical research SO EXPERT REVIEW OF NEUROTHERAPEUTICS LA English DT Review DE Huperzine A; acetylcholinesterase; nicotinic receptors; GABAergic transmission; excitotoxicity; neuroprotection ID NICOTINIC ACETYLCHOLINE-RECEPTORS; ATTENUATES MITOCHONDRIAL DYSFUNCTION; CHOLINERGIC ANTIINFLAMMATORY PATHWAY; POSTTRAUMATIC EPILEPSY DEVELOPMENT; CENTRAL-NERVOUS-SYSTEM; RAT CEREBRAL-CORTEX; MOLECULAR-FORMS; ALZHEIMERS-DISEASE; IN-VITRO; PARKINSONS-DISEASE AB Huperzine A (HupA) is an acetylcholinesterase (AChE) inhibitor extracted from Huperzia Serrata, a firmoss, which has been used for various diseases in traditional Chinese medicine for fever and inflammation. More recently, it has been used in Alzheimer's disease and other forms of dementia with a presumed mechanism of action via central nicotinic and muscarinic receptors. HupA is marketed as a dietary supplement in the U.S. This article reviews newly proposed neuroprotective and anticonvulsant HupA properties based on animal studies. HupA exerts its effects mainly via alpha 7nAChRs and alpha 4 beta 2nAChRs, thereby producing a potent anti-inflammatory response by decreasing IL-1 beta, TNF-alpha protein expression, and suppressing transcriptional activation of NF-kappa B signaling. Thus, it provides protection from excitotoxicity and neuronal death as well as increase in GABAergic transmission associated with anticonvulsant activity. C1 [Damar, U.; Gersner, R.; Rotenberg, A.] Harvard Univ, Sch Med, Boston Childrens Hosp, FM Kirby Neurobiol Ctr,Dept Neurol, Boston, MA USA. [Johnstone, J. T.] Biscayne Pharmaceut Inc, Res & Dev Neurol, Miami, FL USA. [Schachter, S.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Beth Israel Deaconess Med Ctr,Dept Neurol, Boston, MA USA. RP Rotenberg, A (reprint author), Boston Childrens Hosp, Dept Neurol, 300 Longwood Ave, Boston, MA 02115 USA. EM Alexander.Rotenberg@childrens.harvard.edu FU DoD [09082006]; CIMIT; Harvard Medical School; NIH NINDS [R01NS066019]; NIH NIMH [R21MH104318]; Boston Children's Hospital Translational Research Program; Smith Family Foundation; King Saud University; Sage therapeutics Inc.; Wuhan Yirude Medical Equipment New Technology Co., Ltd.; Neuropace Inc.; Nexstim Inc.; Neuronetics Inc; Brainsway Inc.; Eisai Pharmaceuticals FX This work was supported by DoD 09082006 (A Rotenberg, S Schachter), CIMIT (A Rotenberg, S Schachter), and research support from the Harvard Medical School(S Schachter). A. Rotenberg's research is also supported by grants from NIH NINDS (R01NS066019), NIH NIMH (R21MH104318), Boston Children's Hospital Translational Research Program, the Smith Family Foundation, and King Saud University. A. Rotenberg is co-founder of and consultant to Neuro'motion Inc., consultant to NeuroRex Inc., and receives or has received in recent past research support from Sage therapeutics Inc., Wuhan Yirude Medical Equipment New Technology Co., Ltd., Neuropace Inc., Nexstim Inc., Neuronetics Inc, Brainsway Inc. and Eisai Pharmaceuticals. None of the aforementioned relationships conflict with work described in this manuscript. S. Schachter is inventor on a patent for the use of Huperzine for treatment of epilepsy, which is licensed by Harvard Medical School, to Biscayne Pharmaceuticals, Inc., in which he holds less than 5% equity and for which he serves on the scientific advisory board. J. Johnstone is an employee of Biscayne Pharmaceuticals, Inc., which has licensed technology from Harvard Medical School involving the use of Huperzine for epilepsy disorders. He holds less than 5% equity in Biscayne Pharmaceuticals. 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 133 TC 2 Z9 2 U1 8 U2 14 PU TAYLOR & FRANCIS LTD PI ABINGDON PA 2-4 PARK SQUARE, MILTON PARK, ABINGDON OR14 4RN, OXON, ENGLAND SN 1473-7175 EI 1744-8360 J9 EXPERT REV NEUROTHER JI Expert Rev. Neurother. PY 2016 VL 16 IS 6 BP 671 EP 680 DI 10.1080/14737175.2016.1175303 PG 10 WC Clinical Neurology; Pharmacology & Pharmacy SC Neurosciences & Neurology; Pharmacology & Pharmacy GA DN7JX UT WOS:000377252700011 PM 27086593 ER PT J AU Silbert, LC Dodge, HH Lahna, D Promjunyakul, NO Austin, D Mattek, N Erten-Lyons, D Kaye, JA AF Silbert, Lisa C. Dodge, Hiroko H. Lahna, David Promjunyakul, Nutta-on Austin, Daniel Mattek, Nora Erten-Lyons, Deniz Kaye, Jeffrey A. TI Less Daily Computer Use is Related to Smaller Hippocampal Volumes in Cognitively Intact Elderly SO JOURNAL OF ALZHEIMERS DISEASE LA English DT Article DE Alzheimer's disease; assessment of cognitive disorders/dementia; cognitive aging; MRI; volumetric MRI ID ALZHEIMERS-DISEASE; IMPAIRMENT AB Background: Computer use is becoming a common activity in the daily life of older individuals and declines over time in those with mild cognitive impairment (MCI). The relationship between daily computer use (DCU) and imaging markers of neurodegeneration is unknown. Objective: The objective of this study was to examine the relationship between average DCU and volumetric markers of neurodegeneration on brain MRI. Methods: Cognitively intact volunteers enrolled in the Intelligent Systems for Assessing Aging Change study underwent MRI. Total in-home computer use per day was calculated using mouse movement detection and averaged over a one-month period surrounding the MRI. Spearman's rank order correlation (univariate analysis) and linear regression models (multivariate analysis) examined hippocampal, gray matter (GM), white matter hyperintensity (WMH), and ventricular cerebral spinal fluid (vCSF) volumes in relation to DCU. A voxel-based morphometry analysis identified relationships between regional GM density and DCU. Results: Twenty-seven cognitively intact participants used their computer for 51.3 minutes per day on average. Less DCU was associated with smaller hippocampal volumes (r= 0.48, p = 0.01), but not total GM, WMH, or vCSF volumes. After adjusting for age, education, and gender, less DCU remained associated with smaller hippocampal volume (p = 0.01). Voxel-wise analysis demonstrated that less daily computer use was associated with decreased GM density in the bilateral hippocampi and temporal lobes. Conclusions: Less daily computer use is associated with smaller brain volume in regions that are integral to memory function and known to be involved early with Alzheimer's pathology and conversion to dementia. Continuous monitoring of daily computer use may detect signs of preclinical neurodegeneration in older individuals at risk for dementia. C1 [Silbert, Lisa C.; Dodge, Hiroko H.; Lahna, David; Promjunyakul, Nutta-on; Austin, Daniel; Mattek, Nora; Erten-Lyons, Deniz; Kaye, Jeffrey A.] Oregon Hlth & Sci Univ, NIA Layton Aging & Alzheimers Dis Ctr, Dept Neurol, 3181 SW Sam Jackson Pk Rd, Portland, OR 97239 USA. [Dodge, Hiroko H.; Austin, Daniel; Mattek, Nora; Kaye, Jeffrey A.] Oregon Hlth & Sci Univ, NIA Oregon Ctr Aging & Technol ORCATECH, Portland, OR 97239 USA. [Dodge, Hiroko H.] Univ Michigan, Dept Neurol, Michigan Alzheimers Dis Ctr, Ann Arbor, MI USA. [Silbert, Lisa C.; Erten-Lyons, Deniz; Kaye, Jeffrey A.] Portland VA Med Ctr, Portland, OR USA. RP Silbert, LC (reprint author), Oregon Hlth & Sci Univ, NIA Layton Aging & Alzheimers Dis Ctr, Dept Neurol, 3181 SW Sam Jackson Pk Rd, Portland, OR 97239 USA. EM silbertl@ohsu.edu FU NIH [1RO1AG036772, P30 AG008017, P30 AG024978, RO1 AG024059, R01 AG042191] FX This study was sponsored by the NIH (1RO1AG036772, P30 AG008017, P30 AG024978; RO1 AG024059; R01 AG042191). NR 16 TC 2 Z9 2 U1 1 U2 1 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 2016 VL 52 IS 2 BP 713 EP 717 DI 10.3233/JAD-160079 PG 5 WC Neurosciences SC Neurosciences & Neurology GA DN1PU UT WOS:000376838700027 PM 26967228 ER PT J AU Pasi, M Charidimou, A Boulouis, G Auriel, E Haley, K Ayres, A Schwab, K Rosand, J Viswanathan, A Pantoni, L Greenberg, S Gurol, E AF Pasi, M. Charidimou, A. Boulouis, G. Auriel, E. Haley, K. Ayres, A. Schwab, K. Rosand, J. Viswanathan, A. Pantoni, L. Greenberg, S. Gurol, E. TI Patients with mixed location (deep and lobar) cerebral macrobleeds and microbleeds: baseline characteristics and follow up data SO JOURNAL OF ALZHEIMERS DISEASE LA English DT Meeting Abstract C1 [Pasi, M.; Pantoni, L.] Univ Florence, Neurosci Sect, NEUROFARBA, I-50121 Florence, Italy. [Charidimou, A.; Boulouis, G.; Haley, K.; Ayres, A.; Schwab, K.; Viswanathan, A.; Greenberg, S.; Gurol, E.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Stroke Res, Boston, MA USA. [Auriel, E.] Tel Aviv Med Ctr & Sch Med, Dept Neurol, Tel Aviv, IL, Israel. [Rosand, J.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Neurocrit Care & Emergency Neurol, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 2016 VL 52 SU 1 BP S80 EP S81 PG 2 WC Neurosciences SC Neurosciences & Neurology GA DN5VB UT WOS:000377138200117 ER PT J AU Pasi, M Boulouis, G Charidimou, A Auriel, E Haley, K Ayres, A Schwab, K Rosand, J Viswanathan, A Pantoni, L Greenberg, S Gurol, E AF Pasi, M. Boulouis, G. Charidimou, A. Auriel, E. Haley, K. Ayres, A. Schwab, K. Rosand, J. Viswanathan, A. Pantoni, L. Greenberg, S. Gurol, E. TI Topographic distribution of lacunes in cerebral amyloid angiopathy and hypertensive deep intracerebral hemorrhage SO JOURNAL OF ALZHEIMERS DISEASE LA English DT Meeting Abstract C1 [Pasi, M.; Pantoni, L.] Univ Florence, NEUROFARBA Dept, Neurosci Sect, I-50121 Florence, Italy. [Boulouis, G.; Charidimou, A.; Haley, K.; Ayres, A.; Schwab, K.; Rosand, J.; Viswanathan, A.; Greenberg, S.; Gurol, E.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Stroke Res, Boston, MA USA. [Auriel, E.] Tel Aviv Med Ctr & Sch Med, Dept Neurol, Tel Aviv, IL, Israel. NR 0 TC 0 Z9 0 U1 0 U2 0 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 2016 VL 52 SU 1 BP S81 EP S81 PG 1 WC Neurosciences SC Neurosciences & Neurology GA DN5VB UT WOS:000377138200118 ER PT J AU Lin, T Liu, JL Huang, F van Engelen, TSR Thundivalappil, SR Riley, FE Super, M Watters, AL Smith, A Brinkman, N Ingber, DE Warren, HS AF Lin, Tian Liu, Jialin Huang, Feng van Engelen, Tjitske S. R. Thundivalappil, Sujatha R. Riley, Frank E. Super, Michael Watters, Alexander L. Smith, Ann Brinkman, Nathan Ingber, Donald E. Warren, H. Shaw TI Purified and Recombinant Hemopexin: Protease Activity and Effect on Neutrophil Chemotaxis SO MOLECULAR MEDICINE LA English DT Article ID IN-HOSPITAL MORTALITY; RED-BLOOD-CELLS; PLASMA HEMOPEXIN; FREE HEMOGLOBIN; CRITICALLY-ILL; HEME; TRANSFUSION; SEPSIS; LIPOPOLYSACCHARIDE; INFLAMMATION AB Infusion of the heme-binding protein hemopexin has been proposed as a novel approach to decrease heme-induced inflammation in settings of red blood cell breakdown, but questions have been raised as to possible side effects related to protease activity and inhibition of chemotaxis. We evaluated protease activity and effects on chemotaxis of purified plasma hemopexin obtained from multiple sources as well as a novel recombinant fusion protein Fc-hemopexin. Amidolytic assay was performed to measure the protease activity of several plasma-derived hemopexin and recombinant Fc-hemopexin. Hemopexin was added to the human monocyte culture in the presence of lipopolysaccharides (LPS), and also injected into mice intravenously (i.v.) 30 min before inducing neutrophil migration via intraperitoneal (i.p.) injection of thioglycolate. Control groups received the same amount of albumin. Protease activity varied widely between hemopexins. Recombinant Fc-hemopexin bound heme, inhibited the synergy of heme with LPS on tumor necrosis factor (TNF) production from monocytes, and had minor but detectable protease activity. There was no effect of any hemopexin preparation on chemotaxis, and purified hemopexin did not alter the migration of neutrophils into the peritoneal cavity of mice. Heme and LPS synergistically induced the release of LTB4 from human monocytes, and hemopexin blocked this release, as well as chemotaxis of neutrophils in response to activated monocyte supernatants. These results suggest that hemopexin does not directly affect chemotaxis through protease activity, but may decrease heme-driven chemotaxis and secondary inflammation by attenuating the induction of chemoattractants from monocytes. This property could be beneficial in some settings to control potentially damaging inflammation induced by heme. C1 [Lin, Tian] Massachusetts Gen Hosp, Dept Pediat, Infect Dis Unit, Boston, MA 02114 USA. [Lin, Tian; Warren, H. Shaw] Harvard Univ, Sch Med, Boston, MA USA. [Liu, Jialin; Huang, Feng; van Engelen, Tjitske S. R.; Thundivalappil, Sujatha R.; Riley, Frank E.] Massachusetts Gen Hosp, Infect Dis Unit, Dept Pediat, Boston, MA 02114 USA. [Super, Michael; Watters, Alexander L.; Ingber, Donald E.] Harvard Univ, Wyss Inst, Ctr Life Sci, Boston, MA 02115 USA. [Smith, Ann] Univ Missouri, Div Mol Biol & Biochem, Sch Biol Sci, Kansas City, MO 64110 USA. [Brinkman, Nathan] CSL Behring LLC, Res & Dev, Kankakee, IL USA. [Warren, H. Shaw] Massachusetts Gen Hosp, Infect Dis Unit, Dept Pediat & Med, Boston, MA 02114 USA. RP Lin, T (reprint author), Massachusetts Gen Hosp, Dept Pediat, Infect Dis Unit, Boston, MA 02114 USA.; Lin, T (reprint author), Harvard Univ, Sch Med, Boston, MA USA.; Lin, T (reprint author), Massachusetts Gen Hosp, Dept Pediat, Infect Dis Unit, Rm 5-234,149 13th St, Charlestown, MA 02129 USA. EM tlin7@mgh.harvard.edu FU National Institutes of Health [AI059010]; Shriners Hospital for Crippled Children [87200, 84298]; DARPA [W911NF-13-1-0070, W911NF-10-1-0271, N66001-11-1-4180]; Wang Kuancheng Fund from Ruijin Hospital, Shanghai Jiaotong University School of Medicine in China FX This work was funded by the National Institutes of Health (AI059010), the Shriners Hospital for Crippled Children (87200, 84298), DARPA (W911NF-13-1-0070, W911NF-10-1-0271, N66001-11-1-4180), and Wang Kuancheng Fund from Ruijin Hospital, Shanghai Jiaotong University School of Medicine in China. NR 40 TC 0 Z9 0 U1 1 U2 1 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 2016 VL 22 BP 22 EP 31 DI 10.2119/molmed.2016.00006 PG 10 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA DN7LN UT WOS:000377257400003 ER PT J AU Gremmel, T Michelson, AD Frelinger, AL AF Gremmel, Thomas Michelson, Alan D. Frelinger, Andrew L., III TI In Vivo and protease-activated receptor-1-mediated platelet activation in patients presenting for cardiac catheterization SO PLATELETS LA English DT Article DE Cardiac catheterization; Platelet activation; protease-activated receptor-1 ID ACUTE CORONARY SYNDROMES; ACUTE MYOCARDIAL-INFARCTION/; ARTERY-DISEASE; ADENOSINE-DIPHOSPHATE; P-SELECTIN; TISSUE FACTOR; THROMBIN; REACTIVITY; ASPIRIN; CLOPIDOGREL AB Pathways of platelet activation that are not targeted by current antithrombotic therapy may be crucial for the development of ischemic events in patients undergoing coronary angiography. We therefore investigated whether in vivo and thrombin receptor activating peptide (TRAP)stimulated platelet activation and monocyte-platelet aggregate (MPA) levels can serve as independent risk markers for adverse outcomes in aspirin-treated patients presenting for cardiac catheterization. In vivo and TRAP-stimulated platelet surface P-selectin, activated glycoprotein IIb/IIIa (GPIIb/IIIa) and MPA levels were determined in 682 consecutive patients undergoing cardiac catheterization and in 47 healthy controls. Two-year follow-up data were obtained from 562 patients. In vivo platelet surface P-selectin, activated GPIIb/IIIa and MPA levels were significantly higher in patients with angiographically-proven coronary artery disease than in healthy controls (all p=0.02). Patients with an acute coronary syndrome (ACS; n=125) had significantly higher levels of in vivo MPA than patients without ACS (n=437; p=0.01). In the overall study population (n=562) the surface expression of P-selectin and activated GPIIb/IIIa, and the levels of MPA in vivo and in response to TRAP were similar in patients without and with subsequent ischemic events (all p>0.05). Similar results were obtained when only patients with angiographically-proven coronary artery disease (n=459), stent implantation (n=205) or ACS (n=125) were analyzed. Receiver-operating characteristic curve analyses did not reveal cut-off values for P-selectin, activated GPIIb/IIIa, and MPA levels for the prediction of ischemic events. In conclusion, in vivo and TRAP-stimulated platelet activation and MPA levels did not predict adverse ischemic outcomes in aspirin-treated patients presenting for cardiac catheterization. C1 [Gremmel, Thomas; Michelson, Alan D.; Frelinger, Andrew L., III] Harvard Univ, Sch Med, Dana Farber Canc Inst, Div Hematol Oncol,Ctr Platelet Res Studies,Boston, 44 Binney St, Boston, MA 02115 USA. [Gremmel, Thomas] Med Univ Vienna, Dept Internal Med 2, Vienna, Austria. RP Gremmel, T (reprint author), Boston Children s Hosp, Ctr Platelet Res Studies, Div Hematol Oncol, 300 Longwood Ave, Boston, MA 02115 USA. EM thomas.gremmel@meduniwien.ac.at OI Gremmel, Thomas/0000-0001-9554-7292 FU Bristol-Myers Squibb; GLSynthesis; Lilly/Daiichi Sankyo; Pfizer FX Alan D. Michelson has received grant support from Bristol-Myers Squibb, GLSynthesis, Lilly/Daiichi Sankyo and Pfizer, and served on data monitoring committees of Lilly/Daiichi Sankyo clinical trials. Andrew L. Frelinger has received grant support from Bristol-Myers Squibb, GLSynthesis, Lilly/Daiichi Sankyo and Pfizer. NR 40 TC 0 Z9 0 U1 0 U2 0 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 530 WALNUT STREET, STE 850, PHILADELPHIA, PA 19106 USA SN 0953-7104 EI 1369-1635 J9 PLATELETS JI Platelets PY 2016 VL 27 IS 4 BP 308 EP 316 DI 10.3109/09537104.2015.1095876 PG 9 WC Cell Biology; Hematology SC Cell Biology; Hematology GA DN5JX UT WOS:000377104000006 PM 26556638 ER PT J AU Sousa, C AF Sousa, Cristina TI Bridging Darwin's Origin of Species & Wegener's Origin of Continents and Oceans: Using Biogeography, Phylogeny, Geology & Interactive Learning SO AMERICAN BIOLOGY TEACHER LA English DT Article DE Evolution; tree of life; common ancestor; ratites; interactive activities; databases ID PLACENTAL MAMMAL ANCESTOR; K-PG RADIATION; MODERN BIRDS; EVOLUTION; TREE; PALEOBIOGEOGRAPHY; SUPPORT; RATITES; LOSSES; CLOCKS AB The common ancestor and evolution by natural selection, concepts introduced by Charles Darwin, constitute the central core of biology research and education. However, students generally struggle to understand these concepts and commonly form misconceptions about them. To help teachers select the most revelant portions of Darwin's work, I suggest some sentences from On the Origin of Species and briefly discuss their implications. I also suggest a teaching strategy that uses history of science and curriculum crosscutting concepts (cause and effect) that constitute the framework to explain the evolutionary history of ratites (flightless birds) as described by Darwin, starting in the Jurassic, with the breakup of Gondwanaland, as first described by Alfred Wegener in The Origin of Continents and Oceans. C1 [Sousa, Cristina] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Sousa, Cristina] Harvard Univ, Sch Med, Cambridge, MA 02138 USA. RP Sousa, C (reprint author), Univ Porto, Fac Ciencias, Rua Campo Alegre 823, P-4100 Oporto, Portugal. EM up199502480@fc.up.pt FU Faculdade de Ciencias, Universidade do Porto, Portugal FX I thank the anonymous reviewers for useful comments and suggestions. I thank Faculdade de Ciencias, Universidade do Porto, Portugal, for financial support. Special thanks to my students for participating in the activities and to all who have inspired and encouraged me. NR 53 TC 0 Z9 0 U1 5 U2 9 PU NATL ASSOC BIOLOGY TEACHERS INC PI RESTON PA 12030 SUNRISE VALLEY DR, #110, RESTON, VA 20191 USA SN 0002-7685 EI 1938-4211 J9 AM BIOL TEACH JI Am. Biol. Teach. PD JAN PY 2016 VL 78 IS 1 BP 24 EP 32 DI 10.1525/abt.2016.78.1.24 PG 9 WC Biology; Education, Scientific Disciplines SC Life Sciences & Biomedicine - Other Topics; Education & Educational Research GA DN0PE UT WOS:000376765000004 ER PT J AU Proano, A Bravard, MA Tracey, BH Lopez, JW Comina, G Zimic, M Coronel, J Lee, GO Caviedes, L Cabrera, JL Salas, A Ticona, E Kirwan, DE Friedland, JS Evans, CA Moore, DA Gilman, RH AF Proano, Alvaro Bravard, Marjory A. Tracey, Brian H. Lopez, Jose W. Comina, German Zimic, Mirko Coronel, Jorge Lee, Gwenyth O'Neill Caviedes, Luz Luis Cabrera, Jose Salas, Antonio Ticona, Eduardo Kirwan, Daniela E. Friedland, Jon S. Evans, Carlton A. Moore, David A. Gilman, Robert H. CA TB Working Grp Peru TI Protocol for studying cough frequency in people with pulmonary tuberculosis SO BMJ OPEN LA English DT Article ID DRUG-SUSCEPTIBILITY ASSAY; MICROSCOPIC-OBSERVATION; TREATMENT RESPONSE; CONTROLLED-TRIAL; INFECTIOUSNESS; DISEASE; SYSTEM; SPUTUM; DISSEMINATION; CHEMOTHERAPY AB Introduction: Cough is a key symptom of tuberculosis (TB) as well as the main cause of transmission. However, a recent literature review found that cough frequency (number of coughs per hour) in patients with TB has only been studied once, in 1969. The main aim of this study is to describe cough frequency patterns before and after the start of TB treatment and to determine baseline factors that affect cough frequency in these patients. Secondarily, we will evaluate the correlation between cough frequency and TB microbiological resolution. Methods: This study will select participants with culture confirmed TB from 2 tertiary hospitals in Lima, Peru. We estimated that a sample size of 107 patients was sufficient to detect clinically significant changes in cough frequency. Participants will initially be evaluated through questionnaires, radiology, microscopic observation drug susceptibility broth TB-culture, auramine smear microscopy and cough recordings. This cohort will be followed for the initial 60 days of anti-TB treatment, and throughout the study several microbiological samples as well as 24 h recordings will be collected. We will describe the variability of cough episodes and determine its association with baseline laboratory parameters of pulmonary TB. In addition, we will analyse the reduction of cough frequency in predicting TB cure, adjusted for potential confounders. Ethics and dissemination: Ethical approval has been obtained from the ethics committees at each participating hospital in Lima, Peru, Asociacion Benefica PRISMA in Lima, Peru, the Universidad Peruana Cayetano Heredia in Lima, Peru and Johns Hopkins University in Baltimore, USA. We aim to publish and disseminate our findings in peer-reviewed journals. We also expect to create and maintain an online repository for TB cough sounds as well as the statistical analysis employed. C1 [Proano, Alvaro] Univ Peruana Cayetano Heredia, Fac Med Alberto Hurtado, Lima, Peru. [Bravard, Marjory A.; Moore, David A.; Gilman, Robert H.] Asociac Benef PRISMA, Lima, Peru. [Bravard, Marjory A.] Massachusetts Gen Hosp, Dept Gen Internal Med, Boston, MA 02114 USA. [Bravard, Marjory A.; Evans, Carlton A.] Univ Peruana Cayetano Heredia, Res & Dev Lab, Innovat Hlth & Dev IFHAD, Lima, Peru. [Tracey, Brian H.] Tufts Univ, Dept Elect & Comp Engn, Medford, MA 02155 USA. [Lopez, Jose W.] Inst Nacl Salud Nino San Borja, Lima, Peru. [Lopez, Jose W.] Univ Peruana Cayetano Heredia, Fac Ciencias & Filosofia, Lab Bioinformat & Biol Mol, Lima, Peru. [Comina, German; Lee, Gwenyth O'Neill] Tulane Univ, Dept Global Community Hlth & Behav Sci, New Orleans, LA 70118 USA. [Comina, German] Univ Nacl Ingn, Fac Ciencias, Escuela Profes Ingn Fis, Lima, Peru. [Zimic, Mirko; Coronel, Jorge; Caviedes, Luz; Moore, David A.; Gilman, Robert H.] Univ Peruana Cayetano Heredia, Fac Ciencias & Filosofia, Lab Invest & Desarrollo, Lab Invest Enfermedades Infecciosas, Lima, Peru. [Luis Cabrera, Jose] Hosp Nacl Alcides Carrion, Serv Neumol, Lima, Peru. [Salas, Antonio] Hosp Nacl Dos de Mayo, Serv Neumol, Lima, Peru. [Ticona, Eduardo] Univ Nacl Mayor San Marcos, Fac Med, Lima 14, Peru. [Ticona, Eduardo] Hosp Nacl Dos de Mayo, Serv Enfermedades Infecciosas & Trop, Lima, Peru. [Kirwan, Daniela E.; Friedland, Jon S.; Evans, Carlton A.] Univ London Imperial Coll Sci Technol & Med, Infect Dis & Immun, London, England. [Friedland, Jon S.; Evans, Carlton A.] Wellcome Trust Imperial Coll Ctr Global Hlth Res, London, England. [Moore, David A.] London Sch Hyg & Trop Med, TB Ctr, London WC1, England. [Gilman, Robert H.] Johns Hopkins Univ, Dept Int Hlth, Bloomberg Sch Publ Hlth, Program Global Dis Epidemiol & Control, Baltimore, MD USA. RP Gilman, RH (reprint author), Asociac Benef PRISMA, Lima, Peru.; Gilman, RH (reprint author), Univ Peruana Cayetano Heredia, Fac Ciencias & Filosofia, Lab Invest & Desarrollo, Lab Invest Enfermedades Infecciosas, Lima, Peru.; Gilman, RH (reprint author), Johns Hopkins Univ, Dept Int Hlth, Bloomberg Sch Publ Hlth, Program Global Dis Epidemiol & Control, Baltimore, MD USA. EM rgilman@jhsph.edu OI Proano, Alvaro/0000-0002-4057-7686; Lopez, Jose/0000-0003-0614-7284; Comina, German/0000-0003-2114-0486 FU National Institutes of Health [5D43TW006581, 5D43TW009349-03, 0539-01-10, 5R21AI094143-02]; Imperial College Biomedical Research Centre; Joint Global Health Trials consortium of the Wellcome Trust; UK-MRC; DFID [MR/K007467/1]; Wellcome Trust [078340/Z/05/Z, 105788/Z/14/Z, 201251/Z/16/Z]; Bill and Melinda Gates Foundation [OPP1118545]; IFHAD: Innovation For Health And Development FX This work was funded in part by the National Institutes of Health award 5D43TW006581 'Infectious Diseases Training Program in Peru', award 5D43TW009349-03 'Inter-American Training for Innovations in Emerging Infectious Diseases', Grand Challenges Canada Contract No. 0539-01-10 'Smartphone app for cough monitoring of tuberculosis patients', and award 5R21AI094143-02 'Cough-a rapid indicator of response to therapy in pulmonary TB'. CAE and JSF thank the Imperial College Biomedical Research Centre for financial support. The contributions of CAE to this research were funded by: the Joint Global Health Trials consortium of the Wellcome Trust, UK-MRC and DFID (award MR/K007467/1); The Wellcome Trust (awards 078340/Z/05/Z, 105788/Z/14/Z and 201251/Z/16/Z); The Bill and Melinda Gates Foundation award OPP1118545; and IFHAD: Innovation For Health And Development. NR 60 TC 3 Z9 3 U1 0 U2 0 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 2016 VL 6 IS 4 AR e010365 DI 10.1136/bmjopen-2015-010365 PG 9 WC Medicine, General & Internal SC General & Internal Medicine GA DM5LV UT WOS:000376391400063 PM 27105713 ER PT J AU Muresanu, DF Sharma, A Patnaik, R Nozari, A Tian, ZR Ozkizilcik, A Moessler, H Sharma, HS AF Muresanu, Dafin F. Sharma, Aruna Patnaik, Ranjana Nozari, Ala Tian, Z. Ryan Ozkizilcik, Asya Moessler, Herbert Sharma, Hari Shanker TI Nanodelivery of cerebrolysin induces profound neuroprotection in heat stroke following chronic hypertension in combination with carbon nanoparticles induced exacerbation of brain damage SO BRAIN INJURY LA English DT Meeting Abstract C1 [Muresanu, Dafin F.] Univ Med & Pharm, Dept Neurosci, Cluj Napoca, Romania. [Sharma, Aruna; Sharma, Hari Shanker] Univ Uppsala Hosp, Dept Surg Sci Anesthesiol & Intens Care Med, Uppsala, Sweden. [Patnaik, Ranjana] Banaras Hindu Univ, Indian Inst Technol, Varanasi 221005, Uttar Pradesh, India. [Nozari, Ala] Harvard Univ, Massachusetts Gen Hosp, Anesthesiol, Boston, MA 02115 USA. [Tian, Z. Ryan; Ozkizilcik, Asya] Univ Arkansas, Chem & Biochem, Fayetteville, AR 72701 USA. [Moessler, Herbert] Ever NeuroPharma, Oberburgau, Austria. RI Tian, Z. Ryan /R-6671-2016 OI Tian, Z. Ryan /0000-0002-5644-8483 NR 0 TC 0 Z9 0 U1 1 U2 1 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 2016 VL 30 IS 5-6 MA 0075 BP 506 EP 507 PG 2 WC Neurosciences; Rehabilitation SC Neurosciences & Neurology; Rehabilitation GA DM5KP UT WOS:000376388200064 ER PT J AU Losoi, H Silverberg, N Waljas, M Turunen, S Rosti-Otajarvi, E Helminen, M Luoto, T Julkunen, J Ohman, J Iverson, G AF Losoi, Heidi Silverberg, Noah Waljas, Minna Turunen, Senni Rosti-Otajarvi, Eija Helminen, Mika Luoto, Teemu Julkunen, Juhani Ohman, Juha Iverson, Grant TI Recovery from mild traumatic brain injury in previously healthy adults SO BRAIN INJURY LA English DT Meeting Abstract C1 [Losoi, Heidi; Waljas, Minna; Turunen, Senni; Rosti-Otajarvi, Eija; Luoto, Teemu; Ohman, Juha] Tampere Univ Hosp, Dept Neurosci & Rehabil, Tampere, Finland. [Silverberg, Noah] Univ British Columbia, Div Phys Med & Rehabil, Vancouver, BC V5Z 1M9, Canada. [Silverberg, Noah] GF Strong Rehab Ctr, Vancouver, BC, Canada. [Helminen, Mika] Univ Tampere, Sch Hlth Sci, FIN-33101 Tampere, Finland. [Helminen, Mika] Pirkanmaa Hosp Dist, Ctr Sci, Tampere, Finland. [Julkunen, Juhani] Univ Helsinki, Inst Behav Sci, Helsinki, Finland. [Iverson, Grant] Harvard Univ, Sch Med, Dept Phys Med & Rehabil, Spaulding Rehabil Hosp, Boston, MA 02115 USA. [Iverson, Grant] Red Sox Fdn, Boston, MA USA. [Iverson, Grant] Massachusetts Gen Hosp, Home Base Program, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 2016 VL 30 IS 5-6 MA 0094 BP 511 EP 511 PG 1 WC Neurosciences; Rehabilitation SC Neurosciences & Neurology; Rehabilitation GA DM5KP UT WOS:000376388200074 ER PT J AU Gauvin-Lepage, J Friedman, D Grilli, L Kocilowicz, H Sufrategui, M DeMatteo, C Iverson, GL Gagnon, I AF Gauvin-Lepage, Jerome Friedman, Debbie Grilli, Lisa Kocilowicz, Helen Sufrategui, Maria DeMatteo, Carol Iverson, Grant L. Gagnon, Isabelle TI Active rehabilitation for youth who are slow to recover from concussion SO BRAIN INJURY LA English DT Meeting Abstract C1 [Gauvin-Lepage, Jerome; Gagnon, Isabelle] McGill Univ, Montreal, PQ, Canada. [Gauvin-Lepage, Jerome; Gagnon, Isabelle] McGill Univ, Res Inst, Ctr Hlth, Montreal, PQ, Canada. [Friedman, Debbie; Grilli, Lisa; Kocilowicz, Helen; Sufrategui, Maria] McGill Univ, Montreal Childrens Hosp, Ctr Hlth, Montreal, PQ H3H 1P3, Canada. [DeMatteo, Carol] McMaster Univ, Hamilton, ON, Canada. [DeMatteo, Carol] CanChild Ctr Childhood Disabil Res, Hamilton, ON, Canada. [Iverson, Grant L.] Harvard Univ, Sch Med, Boston, MA USA. [Iverson, Grant L.] Spaulding Rehabil Hosp, Boston, MA USA. [Iverson, Grant L.] MassGen Hosp, Children Sports Concuss Program, Boston, MA USA. [Gagnon, Isabelle] Red Sox Fdn, Boston, MA USA. [Iverson, Grant L.] Massachusetts Gen Hosp, Home Base Program, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 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 2016 VL 30 IS 5-6 MA 0197 BP 551 EP 551 PG 1 WC Neurosciences; Rehabilitation SC Neurosciences & Neurology; Rehabilitation GA DM5KP UT WOS:000376388200165 ER PT J AU McAllister, T Zafonte, R Jain, S Flashman, L George, M Grant, G He, F Lohr, J Andaluz, N Summerall, L Paulus, M Raman, R Stein, M AF McAllister, Thomas Zafonte, Ross Jain, Sonia Flashman, Laura George, Mark Grant, Gerald He, Feng Lohr, James Andaluz, Norberto Summerall, Lanier Paulus, Martin Raman, Rema Stein, Murray TI Randomized placebo-controlled trial of methylphenidate or galantamine for persistent emotional and cognitive symptoms associated with TBI and PTSD SO BRAIN INJURY LA English DT Meeting Abstract C1 [McAllister, Thomas] Indiana Univ Sch Med, Indianapolis, IN 46202 USA. [Zafonte, Ross] Spaulding Rehabil Hosp, Boston, MA USA. [Jain, Sonia; He, Feng; Lohr, James; Raman, Rema; Stein, Murray] Univ Calif San Diego, San Diego, CA 92103 USA. [Flashman, Laura] Geisel Sch Med Dartmouth, Lebanon, NH USA. [George, Mark; Summerall, Lanier] Ralph H Johnson VAMC, Charleston, SC USA. [Grant, Gerald] Stanford Univ, Sch Med, Palo Alto, CA 94304 USA. [Andaluz, Norberto] Univ Cincinnati, Coll Med, Cincinnati, OH USA. [Paulus, Martin] Laureate Inst Brain Res, Tulsa, OK USA. NR 0 TC 0 Z9 0 U1 1 U2 1 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 2016 VL 30 IS 5-6 MA 0306 BP 594 EP 595 PG 2 WC Neurosciences; Rehabilitation SC Neurosciences & Neurology; Rehabilitation GA DM5KP UT WOS:000376388200260 ER PT J AU Pape, T Rosenow, J Herrold, A Harton, B Patil, V Guernon, A AF Pape, Therea Rosenow, Joshua Herrold, Amy Harton, Brett Patil, Vijaya Guernon, Ann TI Neurobiological model for use of rTMS plus amantadine as a treatment to modulate and shape neural repair for persons in states of disordered consciousness SO BRAIN INJURY LA English DT Meeting Abstract C1 [Pape, Therea; Herrold, Amy; Harton, Brett] US Dept Vet Affairs, Hines, VA USA. [Pape, Therea; Rosenow, Joshua; Herrold, Amy; Harton, Brett] Northwestern Univ, Feinberg Sch Med, Chicago, IL 60611 USA. [Patil, Vijaya] Hines VA & Loyola Stritch Sch Med, Hines, IL USA. [Guernon, Ann] Hines VA & Marianjoy Rehabil Hosp, Hines, IL USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 2016 VL 30 IS 5-6 MA 0357 BP 615 EP 616 PG 2 WC Neurosciences; Rehabilitation SC Neurosciences & Neurology; Rehabilitation GA DM5KP UT WOS:000376388200308 ER PT J AU Pape, T Harton, B Bhaumik, D Guernon, A Mallinson, T AF Pape, Theresa Harton, Brett Bhaumik, Dulal Guernon, Ann Mallinson, Trudy TI Functional connectivity of networks supporting arousal and awareness: VS versus MCS and clinically meaningful gain from VS and MCS SO BRAIN INJURY LA English DT Meeting Abstract C1 [Pape, Theresa] US Dept Vet Affairs, Hines, VA USA. [Pape, Theresa] Northwestern Univ, Feinberg Sch Med, Hines, IL USA. [Harton, Brett; Bhaumik, Dulal; Guernon, Ann] Hines VA, Hines, IL USA. [Bhaumik, Dulal] Univ Illinois, Sch Publ Hlth, Chicago, IL USA. [Guernon, Ann] Marianjoy Rehabil Hosp, Hines, IL USA. [Mallinson, Trudy] George Washington Univ, Washington, DC USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 2016 VL 30 IS 5-6 MA 0380 BP 625 EP 626 PG 2 WC Neurosciences; Rehabilitation SC Neurosciences & Neurology; Rehabilitation GA DM5KP UT WOS:000376388200331 ER PT J AU Wershba, R Silverberg, N Schatz, P Maxwell, B Zafonte, R Berkner, P Iverson, G AF Wershba, Rebecca Silverberg, Noah Schatz, Philip Maxwell, Bruce Zafonte, Ross Berkner, Paul Iverson, Grant TI Normative data for the post-concussion scale in high school girls SO BRAIN INJURY LA English DT Meeting Abstract C1 [Wershba, Rebecca; Zafonte, Ross; Iverson, Grant] Harvard Univ, Sch Med, Boston, MA USA. [Wershba, Rebecca; Zafonte, Ross; Iverson, Grant] Spaulding Rehabil Hosp, Boston, MA USA. [Silverberg, Noah; Iverson, Grant] Univ British Columbia, Vancouver, BC V5Z 1M9, Canada. [Silverberg, Noah] GF Strong Rehab Ctr, Vancouver, BC, Canada. [Schatz, Philip] St Josephs Univ, Philadelphia, PA 19131 USA. [Maxwell, Bruce; Berkner, Paul] Colby Coll, Waterville, ME 04901 USA. [Iverson, Grant] Red Sox Fdn, Boston, MA USA. [Iverson, Grant] Massachusetts Gen Hosp, Home Base Program, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 2016 VL 30 IS 5-6 MA 0385 BP 627 EP 627 PG 1 WC Neurosciences; Rehabilitation SC Neurosciences & Neurology; Rehabilitation GA DM5KP UT WOS:000376388200334 ER PT J AU Waljas, M Losoi, H Silverberg, ND Luoto, T Ohman, J Iverson, GL AF Waljas, Minna Losoi, Heidi Silverberg, Noah D. Luoto, Teemu Ohman, Juha Iverson, Grant L. TI Method matters: Approach to collecting post-concussion symptoms influences the outcome SO BRAIN INJURY LA English DT Meeting Abstract C1 [Waljas, Minna; Losoi, Heidi; Luoto, Teemu] Tampere Univ Hosp, Dept Neurosurg, Tampere, Finland. [Silverberg, Noah D.; Iverson, Grant L.] Red Sox Fdn, Boston, MA USA. [Silverberg, Noah D.; Iverson, Grant L.] Massachusetts Gen Hosp, Home Base Program, Boston, MA 02114 USA. [Ohman, Juha] Tampere Univ Hosp, Div 3, Tampere, Finland. [Iverson, Grant L.] Harvard Univ, Sch Med, Dept Phys Med & Rehabil, Boston, MA USA. [Iverson, Grant L.] Spaulding Rehabil Hosp, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 2016 VL 30 IS 5-6 MA 0400 BP 632 EP 633 PG 2 WC Neurosciences; Rehabilitation SC Neurosciences & Neurology; Rehabilitation GA DM5KP UT WOS:000376388200347 ER PT J AU Hanninen, T Tuominen, M Vartiainen, M Parkkari, J Ohman, J Iverson, GL Luoto, T AF Hanninen, Timo Tuominen, Markku Vartiainen, Matti Parkkari, Jari Ohman, Juha Iverson, Grant L. Luoto, Teemu TI Sport concussion assessment tool 3-Day of injury scores of professional ice hockey players SO BRAIN INJURY LA English DT Meeting Abstract C1 [Hanninen, Timo; Parkkari, Jari] UKK Inst Hlth Promot Res, Tampere Res Ctr Sports Med, Tampere, Finland. [Tuominen, Markku] Medisport Inc, Tampere, Finland. [Vartiainen, Matti] Univ Helsinki, Inst Behav Sci, Helsinki, Finland. [Ohman, Juha; Luoto, Teemu] Univ Tampere, Tampere Univ Hosp, Dept Neurosurg, FIN-33101 Tampere, Finland. [Ohman, Juha; Luoto, Teemu] Univ Tampere, Sch Med, FIN-33101 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. NR 0 TC 0 Z9 0 U1 1 U2 1 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 2016 VL 30 IS 5-6 MA 0438 BP 649 EP 649 PG 1 WC Neurosciences; Rehabilitation SC Neurosciences & Neurology; Rehabilitation GA DM5KP UT WOS:000376388200382 ER PT J AU Mazwi, NL Izzy, S Martinez, S Spencer, C Glenn, MB Wu, O Giacino, JT Zafonte, RD Edlow, B AF Mazwi, Nicole L. Izzy, Saef Martinez, Sergi Spencer, Camille Glenn, Mel B. Wu, Ona Giacino, Joseph T. Zafonte, Ross D. Edlow, Brian TI Location, location, location: Distribution of traumatic microbleeds predicts duration of post-traumatic amnesia SO BRAIN INJURY LA English DT Meeting Abstract C1 [Mazwi, Nicole L.; Glenn, Mel B.; Giacino, Joseph T.; Zafonte, Ross D.] Spaulding Rehabil Hosp, Boston, MA USA. [Izzy, Saef; Martinez, Sergi; Spencer, Camille; Wu, Ona; Edlow, Brian] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 2016 VL 30 IS 5-6 MA 0584 BP 708 EP 708 PG 1 WC Neurosciences; Rehabilitation SC Neurosciences & Neurology; Rehabilitation GA DM5KP UT WOS:000376388200506 ER PT J AU McAllister, T Temkin, N Dikmen, S Flashman, L Pagulayan, K Cissell, S Duncan, C Thomas, E Grant, G Summerall, L Stein, M AF McAllister, Thomas Temkin, Nancy Dikmen, Sureyya Flashman, Laura Pagulayan, Kathleen Cissell, Shadha Duncan, Connie Thomas, Elissa Grant, Gerald Summerall, Lanier Stein, Murray TI The structured assessment for evaluation of TBI (SAFE-TBI): A new instrument for assessing previous exposure to TBI SO BRAIN INJURY LA English DT Meeting Abstract C1 [McAllister, Thomas] Indiana Univ Sch Med, Indianapolis, IN 46202 USA. [Temkin, Nancy; Dikmen, Sureyya; Pagulayan, Kathleen] Univ Washington, Sch Med, Seattle, WA USA. [Flashman, Laura] Geisel Sch Med Dartmouth, Dartmouth, NS, Lebanon. [Cissell, Shadha; Stein, Murray] Univ Calif San Diego, San Diego, CA 92103 USA. [Duncan, Connie] Uniform Serv Univ Hlth Sci, Bethesda, MD USA. [Thomas, Elissa] Madigan Army Med Ctr, Tacoma, WA 98431 USA. [Grant, Gerald] Stanford Univ, Sch Med, Palo Alto, CA 94304 USA. [Summerall, Lanier] Ralph Johnson VAMC, Charleston, SC USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 2016 VL 30 IS 5-6 MA 0603 BP 714 EP 715 PG 2 WC Neurosciences; Rehabilitation SC Neurosciences & Neurology; Rehabilitation GA DM5KP UT WOS:000376388200519 ER PT J AU Byoj, L Duff, M Turkstra, L AF Byoj, Lindsey Duff, Melissa Turkstra, Lyn TI Emotion recognition of older and younger adults with traumatic brain injury SO BRAIN INJURY LA English DT Meeting Abstract C1 [Byoj, Lindsey] William S Middleton Mem Vet Adm Med Ctr, Madison, WI USA. [Duff, Melissa] Univ Iowa, Iowa City, IA USA. [Turkstra, Lyn] Univ Wisconsin, Madison, WI USA. NR 0 TC 0 Z9 0 U1 2 U2 2 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 2016 VL 30 IS 5-6 MA 0624 BP 722 EP 723 PG 2 WC Neurosciences; Rehabilitation SC Neurosciences & Neurology; Rehabilitation GA DM5KP UT WOS:000376388200537 ER PT J AU Strigo, I Simmons, A AF Strigo, Irina Simmons, Alan TI Avoiding pain: Compromised pain processing after combat trauma SO BRAIN INJURY LA English DT Meeting Abstract C1 [Strigo, Irina] San Francisco VA Med Ctr, San Francisco, CA USA. [Strigo, Irina] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Simmons, Alan] San Diego Vet Healthcare Syst, San Diego, CA USA. [Simmons, Alan] Univ Calif San Diego, San Diego, CA 92103 USA. RI strigo, irina/L-9882-2016 OI strigo, irina/0000-0002-8799-716X NR 0 TC 0 Z9 0 U1 0 U2 0 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 2016 VL 30 IS 5-6 MA 0625 BP 723 EP 723 PG 1 WC Neurosciences; Rehabilitation SC Neurosciences & Neurology; Rehabilitation GA DM5KP UT WOS:000376388200538 ER PT J AU Bhaumik, D Bhaumik, R Pape, T AF Bhaumik, Dulal Bhaumik, Runa Pape, Theresa TI Statistical methods for analysing advanced imaging data for traumatic brain injury SO BRAIN INJURY LA English DT Meeting Abstract C1 [Bhaumik, Dulal; Bhaumik, Runa] Univ Illinois, Sch Publ Hlth, Chicago, IL USA. [Bhaumik, Dulal; Bhaumik, Runa] Univ Illinois, Dept Psychiat, Chicago, IL 60612 USA. [Pape, Theresa] US Dept Vet Affairs, Hines, VA USA. [Pape, Theresa] Northwestern Univ, Feinberg Sch Med, Hines, IL USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 2016 VL 30 IS 5-6 MA 0634 BP 726 EP 727 PG 2 WC Neurosciences; Rehabilitation SC Neurosciences & Neurology; Rehabilitation GA DM5KP UT WOS:000376388200546 ER PT J AU Mallinson, T Pape, T Guernon, A AF Mallinson, Trudy Pape, Theresa Guernon, Ann TI Identifying patterns of clinically meaningful recovery of NBF in persons in states of disordered consciousness due to TBI SO BRAIN INJURY LA English DT Meeting Abstract C1 [Mallinson, Trudy] George Washington Univ, Washington, DC USA. [Pape, Theresa] US Dept Vet Affairs, Hines, VA USA. [Pape, Theresa] Northwestern Univ, Feinberg Sch Med, Hines, IL USA. [Guernon, Ann] Hines VA & Marianjoy Rehabil Hosp, Hines, IL USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 2016 VL 30 IS 5-6 MA 0633 BP 726 EP 726 PG 1 WC Neurosciences; Rehabilitation SC Neurosciences & Neurology; Rehabilitation GA DM5KP UT WOS:000376388200545 ER PT J AU Ingelfinger, JR Kalantar-Zadeh, K Schaefer, F AF Ingelfinger, J. R. Kalantar-Zadeh, K. Schaefer, F. CA World Kidney Day Steering Comm TI Averting the legacy of kidney disease - focus on childhood SO BRAZILIAN JOURNAL OF MEDICAL AND BIOLOGICAL RESEARCH LA English DT Review ID NEPHROLOGY ASSOCIATION IPNA; RENAL REPLACEMENT THERAPY; LOW-BIRTH-WEIGHT; NONCOMMUNICABLE DISEASES; INTERNATIONAL SOCIETY; CONSENSUS STATEMENT; PROSPECTIVE COHORT; BLOOD-PRESSURE; GLOBAL HEALTH; CHILDREN AB World Kidney Day 2016 focuses on kidney disease in childhood and the antecedents of adult kidney disease that can begin in earliest childhood. Chronic kidney disease (CKD) in childhood differs from that in adults, in that the largest diagnostic group among children includes congenital anomalies and inherited disorders, with glomerulopathies and kidney disease as a consequence of diabetes being relatively uncommon. In addition, many children with acute kidney injury will ultimately develop sequelae that may lead to hypertension and CKD in later childhood or in adult life. Children born early or who are small-for-date newborns have relatively increased risk for the development of CKD later in life. Persons with a high-risk birth and early childhood history should be watched closely in order to help detect early signs of kidney disease in time to provide effective prevention or treatment. Successful therapy is feasible for advanced CKD in childhood; there is evidence that children fare better than adults, if they receive kidney replacement therapy including dialysis and transplantation, although only a minority of children may require this ultimate intervention. Because there are disparities in access to care, effort is needed so that children with kidney disease, wherever they live, may be treated effectively, irrespective of their geographic or economic circumstances. Our hope is that the World Kidney Day will inform the general public, policy makers and caregivers about the needs and possibilities surrounding kidney disease in childhood. C1 [Ingelfinger, J. R.] Massachusetts Gen Hosp, MassGen Hosp Children, Pediat Nephrol Unit, Boston, MA 02114 USA. [Ingelfinger, J. R.] Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. [Kalantar-Zadeh, K.] Univ Calif Irvine, Irvine Sch Med, Div Nephrol & Hypertens, Irvine, CA USA. [Kalantar-Zadeh, K.] VA Long Beach Healthcare Syst, Long Beach, CA USA. [Kalantar-Zadeh, K.] UCLA Fielding Sch Publ Hlth, Dept Epidemiol, Los Angeles, CA USA. [Schaefer, F.] Heidelberg Univ, Ctr Pediat & Adolescent Med, Div Pediat Nephrol, Heidelberg, Germany. RP Ingelfinger, JR (reprint author), Massachusetts Gen Hosp, MassGen Hosp Children, Pediat Nephrol Unit, Boston, MA 02114 USA.; Ingelfinger, JR (reprint author), Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. OI Kalantar-Zadeh, Kamyar/0000-0002-8666-0725 NR 34 TC 1 Z9 1 U1 3 U2 3 PU ASSOC BRAS DIVULG CIENTIFICA PI SAO PAULO PA FACULDADE MEDICINA, SALA 21, 14049 RIBEIRAO PRETO, SAO PAULO, 00, BRAZIL SN 0100-879X EI 1678-4510 J9 BRAZ J MED BIOL RES JI Brazilian J. Med. Biol. Res. PY 2016 VL 49 IS 5 AR e5314 DI 10.1590/1414-431X20165314 PG 6 WC Biology; Medicine, Research & Experimental SC Life Sciences & Biomedicine - Other Topics; Research & Experimental Medicine GA DM9KF UT WOS:000376684000009 PM 27096201 ER PT S AU Miyabe, Y Kim, ND Miyabe, C Luster, AD AF Miyabe, Yoshishige Kim, Nancy D. Miyabe, Chie Luster, Andrew D. BE Handel, TM TI Studying Chemokine Control of Neutrophil Migration In Vivo in a Murine Model of Inflammatory Arthritis SO CHEMOKINES SE Methods in Enzymology LA English DT Review; Book Chapter ID AUTOANTIBODY-MEDIATED ARTHRITIS; RHEUMATOID-ARTHRITIS; AMMATORY ARTHRITIS; MYELOPEROXIDASE; RECRUITMENT; MACROPHAGES; SUPPRESSION; RECEPTORS; DISEASE; SITES AB Chemokines regulate the migration of cells in vivo and dysregulated expression of chemokines and their receptors are implicated in autoimmune and inflammatory diseases. Inflammatory arthritides, such as rheumatoid arthritis (RA), are characterized by the recruitment of inflammatory cells into joints. The K/BxN serum transfer mouse model of inflammatory arthritis shares many similar features with RA. In this autoantibody-induced model of arthritis, neutrophils are the critical immune cells necessary for the development of joint inflammation and damage. In this review, we describe the use of several methods to study the role of chemoattractant receptors, including chemokine receptors, on the recruitment of neutrophils into the joint in the K/BxN model of inflammatory arthritis. This includes both traditional methods, such as flow cytometry, immunohistochemistry, and enzyme assays, as well as multiphoton in vivo microscopy that we have adapted to study the role of immune cell trafficking in and around the joint in live mice. C1 [Miyabe, Yoshishige; Kim, Nancy D.; Miyabe, Chie; Luster, Andrew D.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Immunol & Inflammatory Dis,Div Rheumatol Alle, Boston, MA USA. RP Luster, AD (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Immunol & Inflammatory Dis,Div Rheumatol Alle, Boston, MA USA. EM aluster@mgh.harvard.edu NR 28 TC 0 Z9 0 U1 2 U2 2 PU ELSEVIER ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA SN 0076-6879 BN 978-0-12-802195-8; 978-0-12-802171-2 J9 METHOD ENZYMOL JI Methods Enzymol. PY 2016 VL 570 BP 207 EP 231 DI 10.1016/bs.mie.2015.11.002 PG 25 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA BE7PB UT WOS:000375648700011 PM 26921948 ER PT J AU Loehrer, AP Ferrone, CR AF Loehrer, Andrew P. Ferrone, Cristina R. TI Treatment of Locally Advanced Pancreatic Ductal Adenocarcinoma SO DIGESTIVE SURGERY LA English DT Review DE Pancreas cancer; Chemotherapy; Radiotherapy; Chemoradiation; Combined modality therapy ID INTRAOPERATIVE RADIATION-THERAPY; RANDOMIZED CONTROLLED-TRIAL; LONG-TERM OUTCOMES; NEOADJUVANT CHEMORADIATION; VASCULAR RESECTION; IRREVERSIBLE ELECTROPORATION; MULTIMODALITY THERAPY; SURGICAL RESECTION; PLUS RADIOTHERAPY; SURVIVAL DURATION AB Pancreatic ductal adenocarcinoma (PDAC) is increasingly common and a leading cause of cancer-related mortality. Surgery remains the only possibility for cure. Upwards of 40% of patients present with locally advanced PDAC (LA-PDAC), where management strategies continue to evolve. In this review, we highlight current trends in neoadjuvant chemotherapy, surgical resection, and other multimodality approaches for patients with LA-PDAC. Despite promising early results, additional work is needed to more accurately and appropriately tailor treatment for patients with LA-PDAC. (C) 2016 S. Karger AG, Basel C1 [Loehrer, Andrew P.; Ferrone, Cristina R.] Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. RP Loehrer, AP (reprint author), Massachusetts Gen Hosp, Codman Ctr Clin Effectiveness Surg, 165 Cambridge St,Suite 403, Boston, MA 02114 USA. EM aloehrer@partners.org NR 72 TC 2 Z9 2 U1 2 U2 2 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0253-4886 EI 1421-9883 J9 DIGEST SURG JI Dig. Surg. PY 2016 VL 33 IS 4 BP 343 EP 350 DI 10.1159/000445020 PG 8 WC Gastroenterology & Hepatology; Surgery SC Gastroenterology & Hepatology; Surgery GA DM7WK UT WOS:000376570500013 PM 27216011 ER PT J AU Spring, L Bardia, A Modi, S AF Spring, Laura Bardia, Aditya Modi, Shanu TI Targeting the Cyclin D-Cyclin-dependent Kinase (CDK) 4/6-Retinoblastoma Pathway with Selective CDK 4/6 Inhibitors in Hormone Receptor-positive Breast Cancer: Rationale, Current Status, and Future Directions SO DISCOVERY MEDICINE LA English DT Article ID PD 0332991; ESTROGEN; PALBOCICLIB; EXPRESSION; THERAPY; COMBINATION; MECHANISMS AB Dysregulation of the cyclin D-cyclin-dependent kinase (CDK) 4/6-INK4-retinoblastoma (Rb) pathway is an important contributor to endocrine therapy resistance. Recent clinical development of selective inhibitors of CDK4 and CDK6 kinases has led to renewed interest in cell cycle regulators, following experience with relatively nonselective pan-CDK inhibitors that often resulted in limited activity and poor safety profiles in the clinic. The highly selective oral CDK 4/6 inhibitors palbociclib (PD0332991), ribociclib (LEE011), and abemaciclib (LY2835219) are able to inhibit the proliferation of Rb-positive tumor cells and have demonstrated dose-dependent growth inhibition in estrogen receptor-positive (ER+) breast cancer models. In metastatic breast cancer, all three agents are being explored in combination with endocrine therapy in Phase III studies. Results so far indicated promising efficacy and manageable safety profiles, and led to the FDA approval of palbociclib. Phase II-III studies of these agents, in combination with endocrine therapy, are also underway in early breast cancer in the neoadjuvant and adjuvant settings. Selective CDK 4/6 inhibitors are also being investigated with other targeted agents or chemotherapy in the advanced setting. This article reviews the ration-ale for targeting cyclin D-CDK 4/6 in hormone receptor-positive (HR+) breast cancer, provides an overview of the available preclinical and clinical data with CDK 4/6 inhibitors in breast cancer to date, and summarizes the main features of ongoing clinical trials of these new agents in breast cancer. Future trials evaluating further combination strategies with a CDK 4/6 inhibitor backbone and translational studies refining predictive biomarkers are needed to help personalize the optimal treatment regimen for individual patients with HR+ breast cancer. C1 [Spring, Laura; Bardia, Aditya] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Targeted Therapies, Boston, MA 02114 USA. [Modi, Shanu] Mem Sloan Kettering Canc Ctr, New York, NY 10065 USA. [Modi, Shanu] Weill Cornell Med Coll, New York, NY 10065 USA. RP Bardia, A (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Targeted Therapies, Boston, MA 02114 USA. EM Bardia.Aditya@mgh.harvard.edu FU Novartis Pharmaceuticals Corporation FX Financial support for medical editorial assistance was provided by Novartis Pharmaceuticals Corporation. Novartis did not have input on content or approval of the manuscript. Eisha Comar, Ph.D., has no conflicts of interest to disclose. NR 50 TC 4 Z9 4 U1 1 U2 3 PU DISCOVERY MEDICINE PI TIMONIUM PA 10 GERARD AVE, STE 201, TIMONIUM, MD 21093 USA SN 1539-6509 EI 1944-7930 J9 DISCOV MED JI Discov. Med. PD JAN PY 2016 VL 21 IS 113 BP 65 EP 74 PG 10 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA DM5PR UT WOS:000376402800008 PM 26896604 ER PT J AU Sauser, K Alkhawam, L Pierchala, L Pang, PS AF Sauser, Kori Alkhawam, Lora Pierchala, Linda Pang, Peter S. TI Lactate levels as a marker of tissue hypoperfusion in acute heart failure patients seen in the emergency department: a pilot study SO EMERGENCY CARE JOURNAL LA English DT Article DE Acute heart failure; Lactate; Emergency department; Hypoperfusion ID SHOCK AB Acute heart failure (AHF) may lead to subclinical tissue ischemia due to hypoperfusion from inadequate forward flow or congestion. The aim of the present study is to test whether lactate levels are elevated in emergency department (ED) patients with AHF. A prospective pilot study of ED AHF patients was conducted. Venous lactate level was measured at baseline and 6-12 hours after initial draw. Of the 50 patients enrolled, mean age was 65.3 years, 68% were male. Only 7 (14%) had an elevated lactate on either draw, with no differences in baseline characteristics between patients with and without elevated lactate. Patients with an elevated lactate had a higher mean heart rate (99 vs 81, P=0.03) and trended toward an increased rate of abnormal initial temperature (57 vs 23%, P=0.06). In this pilot study, only a minority of acute HF patients had an elevated lactate on presentation. C1 [Sauser, Kori] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Emergency Med, Boston, MA USA. [Alkhawam, Lora] Northwestern Univ, Feinberg Sch Med, Dept Emergency Med, Chicago, IL 60611 USA. [Pierchala, Linda] Loyola Univ, Med Ctr, Chicago, IL 60611 USA. [Pang, Peter S.] Indiana Univ Sch Med, Dept Emergency Med, 720 Eskenazi Ave,FOB 3rd Floor, Indianapolis, IN 46202 USA. RP Pang, PS (reprint author), Indiana Univ Sch Med, Dept Emergency Med, 720 Eskenazi Ave,FOB 3rd Floor, Indianapolis, IN 46202 USA. EM ppang@iu.edu OI Sauser-Zachrison, Kori/0000-0001-8160-3257 NR 7 TC 0 Z9 0 U1 0 U2 0 PU PAGEPRESS PUBL PI PAVIA PA MEDITGROUP, VIA G BELLI, 4, PAVIA, 27100, ITALY SN 1826-9826 EI 2282-2054 J9 EMER CARE J JI Emer. Care J. PY 2016 VL 12 IS 1 BP 6 EP 10 DI 10.4081/ecj.2016.5458 PG 5 WC Emergency Medicine SC Emergency Medicine GA DM7KS UT WOS:000376539700002 ER PT B AU Blicher, B Pryles, RL Lin, J AF Blicher, Brooke Pryles, Rebekah Lucier Lin, Jarshen BA Blicher, B Pryles, RL Lin, J BF Blicher, B Pryles, RL Lin, J TI Evidence-Based Dentistry SO ENDODONTICS REVIEW: A STUDY GUIDE LA English DT Article; Book Chapter ID ENDODONTIC TREATMENT C1 [Blicher, Brooke; Pryles, Rebekah Lucier] Private Practice Ltd Endodont, White River Jct, VT USA. [Blicher, Brooke] Harvard Univ, Sch Dent Med, Dept Restorat Dent & Biomat Sci, 188 Longwood Ave, Boston, MA 02115 USA. [Blicher, Brooke; Pryles, Rebekah Lucier] Tufts Univ, Sch Dent Med, Dept Endodont, Boston, MA 02111 USA. [Blicher, Brooke] Dartmouth Med Sch, Surg, Hanover, NH USA. [Lin, Jarshen] Harvard Univ, Sch Dent Med, Predoctoral Endodont, Dept Restorat Dent & Biomat Sci, Cambridge, MA 02138 USA. [Lin, Jarshen] Massachusetts Gen Hosp, Dept Oral & Maxillofacial Surg, Boston, MA 02114 USA. RP Blicher, B (reprint author), Private Practice Ltd Endodont, White River Jct, VT USA.; Blicher, B (reprint author), Harvard Univ, Sch Dent Med, Dept Restorat Dent & Biomat Sci, 188 Longwood Ave, Boston, MA 02115 USA.; Blicher, B (reprint author), Tufts Univ, Sch Dent Med, Dept Endodont, Boston, MA 02111 USA.; Blicher, B (reprint author), Dartmouth Med Sch, Surg, Hanover, NH USA. NR 8 TC 0 Z9 0 U1 0 U2 0 PU QUINTESSENCE PUBLISHING CO INC PI HANOVER PARK PA 4350 CHANDLER DRIVE, HANOVER PARK, IL 60133 USA BN 978-0-86715-696-6 PY 2016 BP 1 EP 6 PG 6 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA BE6UQ UT WOS:000374799300001 ER PT B AU Blicher, B Pryles, RL Lin, J AF Blicher, Brooke Pryles, Rebekah Lucier Lin, Jarshen BA Blicher, B Pryles, RL Lin, J BF Blicher, B Pryles, RL Lin, J TI Microbiology SO ENDODONTICS REVIEW: A STUDY GUIDE LA English DT Article; Book Chapter ID POLYMERASE-CHAIN-REACTION; PRIMARY ENDODONTIC INFECTIONS; INDIGENOUS ORAL BACTERIA; DNA-DNA HYBRIDIZATION; EPSTEIN-BARR-VIRUS; ENTEROCOCCUS-FAECALIS; APICAL PERIODONTITIS; ROOT CANALS; PERIAPICAL PATHOSIS; TEETH C1 [Blicher, Brooke; Pryles, Rebekah Lucier] Private Practice Ltd Endodont, White River Jct, VT USA. [Blicher, Brooke] Harvard Univ, Sch Dent Med, Dept Restorat Dent & Biomat Sci, 188 Longwood Ave, Boston, MA 02115 USA. [Blicher, Brooke; Pryles, Rebekah Lucier] Tufts Univ, Sch Dent Med, Dept Endodont, Boston, MA 02111 USA. [Blicher, Brooke] Dartmouth Med Sch, Surg, Hanover, NH USA. [Lin, Jarshen] Harvard Univ, Sch Dent Med, Predoctoral Endodont, Dept Restorat Dent & Biomat Sci, Cambridge, MA 02138 USA. [Lin, Jarshen] Massachusetts Gen Hosp, Dept Oral & Maxillofacial Surg, Boston, MA 02114 USA. RP Blicher, B (reprint author), Private Practice Ltd Endodont, White River Jct, VT USA.; Blicher, B (reprint author), Harvard Univ, Sch Dent Med, Dept Restorat Dent & Biomat Sci, 188 Longwood Ave, Boston, MA 02115 USA.; Blicher, B (reprint author), Tufts Univ, Sch Dent Med, Dept Endodont, Boston, MA 02111 USA.; Blicher, B (reprint author), Dartmouth Med Sch, Surg, Hanover, NH USA. NR 62 TC 0 Z9 0 U1 1 U2 1 PU QUINTESSENCE PUBLISHING CO INC PI HANOVER PARK PA 4350 CHANDLER DRIVE, HANOVER PARK, IL 60133 USA BN 978-0-86715-696-6 PY 2016 BP 7 EP 23 PG 17 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA BE6UQ UT WOS:000374799300002 ER PT B AU Blicher, B Pryles, RL Lin, J AF Blicher, Brooke Pryles, Rebekah Lucier Lin, Jarshen BA Blicher, B Pryles, RL Lin, J BF Blicher, B Pryles, RL Lin, J TI Pulpal and Periapical Anatomy and Physiology SO ENDODONTICS REVIEW: A STUDY GUIDE LA English DT Article; Book Chapter ID HUMAN DENTAL-PULP; SCANNING ELECTRON-MICROSCOPE; BEAM COMPUTED-TOMOGRAPHY; ROOT-CANAL MORPHOLOGY; MAXILLARY 1ST MOLAR; C-SHAPED CANALS; DENS-INVAGINATUS; MENTAL FORAMEN; EXTRACELLULAR-MATRIX; MANDIBULAR INCISORS C1 [Blicher, Brooke; Pryles, Rebekah Lucier] Private Practice Ltd Endodont, White River Jct, VT USA. [Blicher, Brooke] Harvard Univ, Sch Dent Med, Dept Restorat Dent & Biomat Sci, 188 Longwood Ave, Boston, MA 02115 USA. [Blicher, Brooke; Pryles, Rebekah Lucier] Tufts Univ, Sch Dent Med, Dept Endodont, Boston, MA 02111 USA. [Blicher, Brooke] Dartmouth Med Sch, Surg, Hanover, NH USA. [Lin, Jarshen] Harvard Univ, Sch Dent Med, Predoctoral Endodont, Dept Restorat Dent & Biomat Sci, Cambridge, MA 02138 USA. [Lin, Jarshen] Massachusetts Gen Hosp, Dept Oral & Maxillofacial Surg, Boston, MA 02114 USA. RP Blicher, B (reprint author), Private Practice Ltd Endodont, White River Jct, VT USA.; Blicher, B (reprint author), Harvard Univ, Sch Dent Med, Dept Restorat Dent & Biomat Sci, 188 Longwood Ave, Boston, MA 02115 USA.; Blicher, B (reprint author), Tufts Univ, Sch Dent Med, Dept Endodont, Boston, MA 02111 USA.; Blicher, B (reprint author), Dartmouth Med Sch, Surg, Hanover, NH USA. NR 99 TC 0 Z9 0 U1 0 U2 0 PU QUINTESSENCE PUBLISHING CO INC PI HANOVER PARK PA 4350 CHANDLER DRIVE, HANOVER PARK, IL 60133 USA BN 978-0-86715-696-6 PY 2016 BP 24 EP 44 PG 21 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA BE6UQ UT WOS:000374799300003 ER PT B AU Blicher, B Pryles, RL Lin, J AF Blicher, Brooke Pryles, Rebekah Lucier Lin, Jarshen BA Blicher, B Pryles, RL Lin, J BF Blicher, B Pryles, RL Lin, J TI Pulpal and Periapical Pathology SO ENDODONTICS REVIEW: A STUDY GUIDE LA English DT Article; Book Chapter ID HUMAN DENTAL-PULP; APICAL PERIODONTITIS LESIONS; CRACKED TOOTH SYNDROME; INFECTED ROOT CANALS; EPSTEIN-BARR-VIRUS; PERIRADICULAR LESIONS; IRREVERSIBLE PULPITIS; HISTOLOGICAL-EVALUATION; INFLAMMATORY LESIONS; OCCLUSAL REDUCTION C1 [Blicher, Brooke; Pryles, Rebekah Lucier] Private Practice Ltd Endodont, White River Jct, VT USA. [Blicher, Brooke] Harvard Univ, Sch Dent Med, Dept Restorat Dent & Biomat Sci, 188 Longwood Ave, Boston, MA 02115 USA. [Blicher, Brooke; Pryles, Rebekah Lucier] Tufts Univ, Sch Dent Med, Dept Endodont, Boston, MA 02111 USA. [Blicher, Brooke] Dartmouth Med Sch, Surg, Hanover, NH USA. [Lin, Jarshen] Harvard Univ, Sch Dent Med, Predoctoral Endodont, Dept Restorat Dent & Biomat Sci, Cambridge, MA 02138 USA. [Lin, Jarshen] Massachusetts Gen Hosp, Dept Oral & Maxillofacial Surg, Boston, MA 02114 USA. RP Blicher, B (reprint author), Private Practice Ltd Endodont, White River Jct, VT USA.; Blicher, B (reprint author), Harvard Univ, Sch Dent Med, Dept Restorat Dent & Biomat Sci, 188 Longwood Ave, Boston, MA 02115 USA.; Blicher, B (reprint author), Tufts Univ, Sch Dent Med, Dept Endodont, Boston, MA 02111 USA.; Blicher, B (reprint author), Dartmouth Med Sch, Surg, Hanover, NH USA. NR 155 TC 0 Z9 0 U1 0 U2 0 PU QUINTESSENCE PUBLISHING CO INC PI HANOVER PARK PA 4350 CHANDLER DRIVE, HANOVER PARK, IL 60133 USA BN 978-0-86715-696-6 PY 2016 BP 45 EP 66 PG 22 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA BE6UQ UT WOS:000374799300004 ER PT B AU Blicher, B Pryles, RL Lin, J AF Blicher, Brooke Pryles, Rebekah Lucier Lin, Jarshen BA Blicher, B Pryles, RL Lin, J BF Blicher, B Pryles, RL Lin, J TI Medicine and Pharmacology SO ENDODONTICS REVIEW: A STUDY GUIDE LA English DT Article; Book Chapter ID ALVEOLAR NERVE BLOCK; ROOT-CANAL TREATMENT; BISPHOSPHONATE-ASSOCIATED OSTEONECROSIS; CORONARY-ARTERY-DISEASE; IRREVERSIBLE PULPITIS; APICAL PERIODONTITIS; ENDODONTIC TREATMENT; POSTOPERATIVE PAIN; DIABETES-MELLITUS; DENTAL-PULP C1 [Blicher, Brooke; Pryles, Rebekah Lucier] Private Practice Ltd Endodont, White River Jct, VT USA. [Blicher, Brooke] Harvard Univ, Sch Dent Med, Dept Restorat Dent & Biomat Sci, 188 Longwood Ave, Boston, MA 02115 USA. [Blicher, Brooke; Pryles, Rebekah Lucier] Tufts Univ, Sch Dent Med, Dept Endodont, Boston, MA 02111 USA. [Blicher, Brooke] Dartmouth Med Sch, Surg, Hanover, NH USA. [Lin, Jarshen] Harvard Univ, Sch Dent Med, Predoctoral Endodont, Dept Restorat Dent & Biomat Sci, Cambridge, MA 02138 USA. [Lin, Jarshen] Massachusetts Gen Hosp, Dept Oral & Maxillofacial Surg, Boston, MA 02114 USA. RP Blicher, B (reprint author), Private Practice Ltd Endodont, White River Jct, VT USA.; Blicher, B (reprint author), Harvard Univ, Sch Dent Med, Dept Restorat Dent & Biomat Sci, 188 Longwood Ave, Boston, MA 02115 USA.; Blicher, B (reprint author), Tufts Univ, Sch Dent Med, Dept Endodont, Boston, MA 02111 USA.; Blicher, B (reprint author), Dartmouth Med Sch, Surg, Hanover, NH USA. NR 78 TC 0 Z9 0 U1 1 U2 1 PU QUINTESSENCE PUBLISHING CO INC PI HANOVER PARK PA 4350 CHANDLER DRIVE, HANOVER PARK, IL 60133 USA BN 978-0-86715-696-6 PY 2016 BP 67 EP 81 PG 15 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA BE6UQ UT WOS:000374799300005 ER PT B AU Blicher, B Pryles, RL Lin, J AF Blicher, Brooke Pryles, Rebekah Lucier Lin, Jarshen BA Blicher, B Pryles, RL Lin, J BF Blicher, B Pryles, RL Lin, J TI Diagnosis SO ENDODONTICS REVIEW: A STUDY GUIDE LA English DT Article; Book Chapter ID BEAM COMPUTED-TOMOGRAPHY; VERTICAL ROOT FRACTURES; ENDODONTIC WORKING LENGTH; CONE-BEAM; PERIAPICAL RADIOGRAPHY; INTRAORAL RADIOGRAPHY; VOLUMETRIC TOMOGRAPHY; IRREVERSIBLE PULPITIS; MAXILLARY SINUS; VITALITY TESTS C1 [Blicher, Brooke; Pryles, Rebekah Lucier] Private Practice Ltd Endodont, White River Jct, VT USA. [Blicher, Brooke] Harvard Univ, Sch Dent Med, Dept Restorat Dent & Biomat Sci, 188 Longwood Ave, Boston, MA 02115 USA. [Blicher, Brooke; Pryles, Rebekah Lucier] Tufts Univ, Sch Dent Med, Dept Endodont, Boston, MA 02111 USA. [Blicher, Brooke] Dartmouth Med Sch, Surg, Hanover, NH USA. [Lin, Jarshen] Harvard Univ, Sch Dent Med, Predoctoral Endodont, Dept Restorat Dent & Biomat Sci, Cambridge, MA 02138 USA. [Lin, Jarshen] Massachusetts Gen Hosp, Dept Oral & Maxillofacial Surg, Boston, MA 02114 USA. RP Blicher, B (reprint author), Private Practice Ltd Endodont, White River Jct, VT USA.; Blicher, B (reprint author), Harvard Univ, Sch Dent Med, Dept Restorat Dent & Biomat Sci, 188 Longwood Ave, Boston, MA 02115 USA.; Blicher, B (reprint author), Tufts Univ, Sch Dent Med, Dept Endodont, Boston, MA 02111 USA.; Blicher, B (reprint author), Dartmouth Med Sch, Surg, Hanover, NH USA. NR 82 TC 0 Z9 0 U1 1 U2 1 PU QUINTESSENCE PUBLISHING CO INC PI HANOVER PARK PA 4350 CHANDLER DRIVE, HANOVER PARK, IL 60133 USA BN 978-0-86715-696-6 PY 2016 BP 82 EP 104 PG 23 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA BE6UQ UT WOS:000374799300006 ER PT B AU Blicher, B Pryles, RL Lin, J AF Blicher, Brooke Pryles, Rebekah Lucier Lin, Jarshen BA Blicher, B Pryles, RL Lin, J BF Blicher, B Pryles, RL Lin, J TI Diagnosis of Non-Endodontic Disease Entities SO ENDODONTICS REVIEW: A STUDY GUIDE LA English DT Article; Book Chapter ID TRIGEMINAL NEURALGIA; CRANIOFACIAL PAIN; CEMENTAL TEAR; MYOFASCIAL PAIN; PULP; CALCIFICATION; CLASSIFICATION; TOOTHACHE; THERAPY; LESIONS C1 [Blicher, Brooke; Pryles, Rebekah Lucier] Private Practice Ltd Endodont, White River Jct, VT USA. [Blicher, Brooke] Harvard Univ, Sch Dent Med, Dept Restorat Dent & Biomat Sci, 188 Longwood Ave, Boston, MA 02115 USA. [Blicher, Brooke; Pryles, Rebekah Lucier] Tufts Univ, Sch Dent Med, Dept Endodont, Boston, MA 02111 USA. [Blicher, Brooke] Dartmouth Med Sch, Surg, Hanover, NH USA. [Lin, Jarshen] Harvard Univ, Sch Dent Med, Predoctoral Endodont, Dept Restorat Dent & Biomat Sci, Cambridge, MA 02138 USA. [Lin, Jarshen] Massachusetts Gen Hosp, Dept Oral & Maxillofacial Surg, Boston, MA 02114 USA. RP Blicher, B (reprint author), Private Practice Ltd Endodont, White River Jct, VT USA.; Blicher, B (reprint author), Harvard Univ, Sch Dent Med, Dept Restorat Dent & Biomat Sci, 188 Longwood Ave, Boston, MA 02115 USA.; Blicher, B (reprint author), Tufts Univ, Sch Dent Med, Dept Endodont, Boston, MA 02111 USA.; Blicher, B (reprint author), Dartmouth Med Sch, Surg, Hanover, NH USA. NR 49 TC 0 Z9 0 U1 0 U2 0 PU QUINTESSENCE PUBLISHING CO INC PI HANOVER PARK PA 4350 CHANDLER DRIVE, HANOVER PARK, IL 60133 USA BN 978-0-86715-696-6 PY 2016 BP 105 EP 119 PG 15 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA BE6UQ UT WOS:000374799300007 ER PT B AU Blicher, B Pryles, RL Lin, J AF Blicher, Brooke Pryles, Rebekah Lucier Lin, Jarshen BA Blicher, B Pryles, RL Lin, J BF Blicher, B Pryles, RL Lin, J TI Treatment of Endodontic Disease SO ENDODONTICS REVIEW: A STUDY GUIDE LA English DT Article; Book Chapter ID MINERAL TRIOXIDE AGGREGATE; RANDOMIZED CONTROLLED-TRIAL; ELECTRONIC APEX LOCATOR; ALVEOLAR NERVE BLOCK; ROOT-END PREPARATION; BEAM COMPUTED-TOMOGRAPHY; TERM-FOLLOW-UP; 2-PERCENT CHLORHEXIDINE GEL; PLATELET-RICH PLASMA; GUTTA-PERCHA REMOVAL C1 [Blicher, Brooke; Pryles, Rebekah Lucier] Private Practice Ltd Endodont, White River Jct, VT USA. [Blicher, Brooke] Harvard Univ, Sch Dent Med, Dept Restorat Dent & Biomat Sci, 188 Longwood Ave, Boston, MA 02115 USA. [Blicher, Brooke; Pryles, Rebekah Lucier] Tufts Univ, Sch Dent Med, Dept Endodont, Boston, MA 02111 USA. [Blicher, Brooke] Dartmouth Med Sch, Surg, Hanover, NH USA. [Lin, Jarshen] Harvard Univ, Sch Dent Med, Predoctoral Endodont, Dept Restorat Dent & Biomat Sci, Cambridge, MA 02138 USA. [Lin, Jarshen] Massachusetts Gen Hosp, Dept Oral & Maxillofacial Surg, Boston, MA 02114 USA. RP Blicher, B (reprint author), Private Practice Ltd Endodont, White River Jct, VT USA.; Blicher, B (reprint author), Harvard Univ, Sch Dent Med, Dept Restorat Dent & Biomat Sci, 188 Longwood Ave, Boston, MA 02115 USA.; Blicher, B (reprint author), Tufts Univ, Sch Dent Med, Dept Endodont, Boston, MA 02111 USA.; Blicher, B (reprint author), Dartmouth Med Sch, Surg, Hanover, NH USA. NR 422 TC 0 Z9 0 U1 0 U2 0 PU QUINTESSENCE PUBLISHING CO INC PI HANOVER PARK PA 4350 CHANDLER DRIVE, HANOVER PARK, IL 60133 USA BN 978-0-86715-696-6 PY 2016 BP 120 EP 176 PG 57 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA BE6UQ UT WOS:000374799300008 ER PT B AU Blicher, B Pryles, RL Lin, J AF Blicher, Brooke Pryles, Rebekah Lucier Lin, Jarshen BA Blicher, B Pryles, RL Lin, J BF Blicher, B Pryles, RL Lin, J TI Traumatic Dental Injuries SO ENDODONTICS REVIEW: A STUDY GUIDE LA English DT Article; Book Chapter ID REPLANTED DOG TEETH; INTRAALVEOLAR ROOT FRACTURES; BEAM COMPUTED-TOMOGRAPHY; PERMANENT INCISORS; INTERNATIONAL ASSOCIATION; PULP; RESORPTION; DIAGNOSIS; GUIDELINES; MANAGEMENT C1 [Blicher, Brooke; Pryles, Rebekah Lucier] Private Practice Ltd Endodont, White River Jct, VT USA. [Blicher, Brooke] Harvard Univ, Sch Dent Med, Dept Restorat Dent & Biomat Sci, 188 Longwood Ave, Boston, MA 02115 USA. [Blicher, Brooke; Pryles, Rebekah Lucier] Tufts Univ, Sch Dent Med, Dept Endodont, Boston, MA 02111 USA. [Blicher, Brooke] Dartmouth Med Sch, Surg, Hanover, NH USA. [Lin, Jarshen] Harvard Univ, Sch Dent Med, Predoctoral Endodont, Dept Restorat Dent & Biomat Sci, Cambridge, MA 02138 USA. [Lin, Jarshen] Massachusetts Gen Hosp, Dept Oral & Maxillofacial Surg, Boston, MA 02114 USA. RP Blicher, B (reprint author), Private Practice Ltd Endodont, White River Jct, VT USA.; Blicher, B (reprint author), Harvard Univ, Sch Dent Med, Dept Restorat Dent & Biomat Sci, 188 Longwood Ave, Boston, MA 02115 USA.; Blicher, B (reprint author), Tufts Univ, Sch Dent Med, Dept Endodont, Boston, MA 02111 USA.; Blicher, B (reprint author), Dartmouth Med Sch, Surg, Hanover, NH USA. NR 53 TC 0 Z9 0 U1 0 U2 0 PU QUINTESSENCE PUBLISHING CO INC PI HANOVER PARK PA 4350 CHANDLER DRIVE, HANOVER PARK, IL 60133 USA BN 978-0-86715-696-6 PY 2016 BP 177 EP 198 PG 22 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA BE6UQ UT WOS:000374799300009 ER PT B AU Blicher, B Pryles, RL Lin, J AF Blicher, Brooke Pryles, Rebekah Lucier Lin, Jarshen BA Blicher, B Pryles, RL Lin, J BF Blicher, B Pryles, RL Lin, J TI Resorption SO ENDODONTICS REVIEW: A STUDY GUIDE LA English DT Article; Book Chapter ID INVASIVE CERVICAL RESORPTION; EXTERNAL ROOT RESORPTION; TEETH; PERFORATIONS; PREVALENCE; REMOVAL C1 [Blicher, Brooke; Pryles, Rebekah Lucier] Private Practice Ltd Endodont, White River Jct, VT USA. [Blicher, Brooke] Harvard Univ, Sch Dent Med, Dept Restorat Dent & Biomat Sci, 188 Longwood Ave, Boston, MA 02115 USA. [Blicher, Brooke; Pryles, Rebekah Lucier] Tufts Univ, Sch Dent Med, Dept Endodont, Boston, MA 02111 USA. [Blicher, Brooke] Dartmouth Med Sch, Surg, Hanover, NH USA. [Lin, Jarshen] Harvard Univ, Sch Dent Med, Predoctoral Endodont, Dept Restorat Dent & Biomat Sci, Cambridge, MA 02138 USA. [Lin, Jarshen] Massachusetts Gen Hosp, Dept Oral & Maxillofacial Surg, Boston, MA 02114 USA. RP Blicher, B (reprint author), Private Practice Ltd Endodont, White River Jct, VT USA.; Blicher, B (reprint author), Harvard Univ, Sch Dent Med, Dept Restorat Dent & Biomat Sci, 188 Longwood Ave, Boston, MA 02115 USA.; Blicher, B (reprint author), Tufts Univ, Sch Dent Med, Dept Endodont, Boston, MA 02111 USA.; Blicher, B (reprint author), Dartmouth Med Sch, Surg, Hanover, NH USA. NR 26 TC 0 Z9 0 U1 0 U2 0 PU QUINTESSENCE PUBLISHING CO INC PI HANOVER PARK PA 4350 CHANDLER DRIVE, HANOVER PARK, IL 60133 USA BN 978-0-86715-696-6 PY 2016 BP 199 EP 207 PG 9 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA BE6UQ UT WOS:000374799300010 ER PT B AU Blicher, B Pryles, RL Lin, J AF Blicher, Brooke Pryles, Rebekah Lucier Lin, Jarshen BA Blicher, B Pryles, RL Lin, J BF Blicher, B Pryles, RL Lin, J TI Prognosis SO ENDODONTICS REVIEW: A STUDY GUIDE LA English DT Article; Book Chapter ID MINERAL TRIOXIDE AGGREGATE; ENDODONTICALLY TREATED TEETH; ROOT-CANAL TREATMENT; RANDOMIZED CONTROLLED-TRIAL; APICAL PERIODONTITIS; CORONAL RESTORATION; FILLING MATERIALS; NECROTIC TEETH; FOLLOW-UP; ONE-VISIT C1 [Blicher, Brooke; Pryles, Rebekah Lucier] Private Practice Ltd Endodont, White River Jct, VT USA. [Blicher, Brooke] Harvard Univ, Sch Dent Med, Dept Restorat Dent & Biomat Sci, 188 Longwood Ave, Boston, MA 02115 USA. [Blicher, Brooke; Pryles, Rebekah Lucier] Tufts Univ, Sch Dent Med, Dept Endodont, Boston, MA 02111 USA. [Blicher, Brooke] Dartmouth Med Sch, Surg, Hanover, NH USA. [Lin, Jarshen] Harvard Univ, Sch Dent Med, Predoctoral Endodont, Dept Restorat Dent & Biomat Sci, Cambridge, MA 02138 USA. [Lin, Jarshen] Massachusetts Gen Hosp, Dept Oral & Maxillofacial Surg, Boston, MA 02114 USA. RP Blicher, B (reprint author), Private Practice Ltd Endodont, White River Jct, VT USA.; Blicher, B (reprint author), Harvard Univ, Sch Dent Med, Dept Restorat Dent & Biomat Sci, 188 Longwood Ave, Boston, MA 02115 USA.; Blicher, B (reprint author), Tufts Univ, Sch Dent Med, Dept Endodont, Boston, MA 02111 USA.; Blicher, B (reprint author), Dartmouth Med Sch, Surg, Hanover, NH USA. NR 56 TC 0 Z9 0 U1 0 U2 0 PU QUINTESSENCE PUBLISHING CO INC PI HANOVER PARK PA 4350 CHANDLER DRIVE, HANOVER PARK, IL 60133 USA BN 978-0-86715-696-6 PY 2016 BP 208 EP 220 PG 13 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA BE6UQ UT WOS:000374799300011 ER PT B AU Blicher, B Pryles, RL Lin, J AF Blicher, Brooke Pryles, Rebekah Lucier Lin, Jarshen BA Blicher, B Pryles, RL Lin, J BF Blicher, B Pryles, RL Lin, J TI Complications SO ENDODONTICS REVIEW: A STUDY GUIDE LA English DT Article; Book Chapter ID INFERIOR ALVEOLAR NERVE; ROOT-CANAL THERAPY; MINERAL TRIOXIDE AGGREGATE; CALCIUM HYDROXIDE PASTE; ENDODONTIC FLARE-UPS; GUTTA-PERCHA; SODIUM-HYPOCHLORITE; MAXILLARY SINUS; TISSUE REACTION; SURFACE TEMPERATURES C1 [Blicher, Brooke; Pryles, Rebekah Lucier] Private Practice Ltd Endodont, White River Jct, VT USA. [Blicher, Brooke] Harvard Univ, Sch Dent Med, Dept Restorat Dent & Biomat Sci, 188 Longwood Ave, Boston, MA 02115 USA. [Blicher, Brooke; Pryles, Rebekah Lucier] Tufts Univ, Sch Dent Med, Dept Endodont, Boston, MA 02111 USA. [Blicher, Brooke] Dartmouth Med Sch, Surg, Hanover, NH USA. [Lin, Jarshen] Harvard Univ, Sch Dent Med, Predoctoral Endodont, Dept Restorat Dent & Biomat Sci, Cambridge, MA 02138 USA. [Lin, Jarshen] Massachusetts Gen Hosp, Dept Oral & Maxillofacial Surg, Boston, MA 02114 USA. RP Blicher, B (reprint author), Private Practice Ltd Endodont, White River Jct, VT USA.; Blicher, B (reprint author), Harvard Univ, Sch Dent Med, Dept Restorat Dent & Biomat Sci, 188 Longwood Ave, Boston, MA 02115 USA.; Blicher, B (reprint author), Tufts Univ, Sch Dent Med, Dept Endodont, Boston, MA 02111 USA.; Blicher, B (reprint author), Dartmouth Med Sch, Surg, Hanover, NH USA. NR 95 TC 0 Z9 0 U1 0 U2 0 PU QUINTESSENCE PUBLISHING CO INC PI HANOVER PARK PA 4350 CHANDLER DRIVE, HANOVER PARK, IL 60133 USA BN 978-0-86715-696-6 PY 2016 BP 221 EP 244 PG 24 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA BE6UQ UT WOS:000374799300012 ER PT J AU Kekre, N Antin, JH AF Kekre, Natasha Antin, Joseph H. TI Emerging drugs for graft-versus-host disease SO EXPERT OPINION ON EMERGING DRUGS LA English DT Review DE Graft-versus-host disease; transplantation; alpha-1 antitrypsin; ruxolitinib and interleukin-2 ID STEM-CELL TRANSPLANTATION; BONE-MARROW-TRANSPLANTATION; RELAPSING MULTIPLE-SCLEROSIS; PLACEBO-CONTROLLED TRIAL; REGULATORY T-CELLS; PHASE 1/2 TRIAL; ACUTE GVHD; EXTRACORPOREAL PHOTOPHERESIS; APOPTOTIC CELLS; INITIAL THERAPY AB Introduction: Graft-versus-host disease (GVHD) leads to significant morbidity and mortality after allogeneic stem cell transplantation. While corticosteroids alone are adequate in some cases, they are often insufficient, leading to poor quality of life associated with the symptoms of disease, or mortality from infection and GVHD. Moreover, corticosteroids have significant side effects and often do not lead to durable responses. New therapies are needed to improve the development and progression of acute and chronic GVHD. Areas covered: We discuss the spectrum of emerging drugs for GVHD prevention and therapy. Cellular therapies will be briefly discussed. The available pre-clinical and clinical data regarding monoclonal antibodies, interleukin-2, alpha-1 antitrypsin, histone deacetylase inhibitors, tyrosine kinase inhibitors, and proteasome inhibitors will be reviewed. Expert opinion: Although therapies emerging for GVHD remain promising, most of these drugs are still in early phase clinical trials and require randomized comparisons before formal conclusions can be drawn. It is likely that in the near future some of these agents will show improvements in response when compared with corticosteroids alone. Although it is difficult to predict which of these agents will be most promising, alpha-1 antitrypsin, ruxolitinib and interleukin-2 have demonstrated encouraging results. C1 [Kekre, Natasha] Ottawa Hosp, Ottawa Hlth Res Inst, Div Hematol, Ottawa, ON, Canada. [Kekre, Natasha] Univ Ottawa, Ottawa, ON, Canada. [Antin, Joseph H.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Blood & Marrow Transplantat Program,Div Hematol M, 44 Binney St, Boston, MA 02115 USA. RP Kekre, N (reprint author), Ottawa Hosp, Ottawa Hlth Res Inst, Div Hematol, Ottawa, ON, Canada.; Kekre, N (reprint author), Univ Ottawa, Ottawa, ON, Canada. EM nkekre@toh.on.ca NR 72 TC 0 Z9 0 U1 2 U2 3 PU TAYLOR & FRANCIS LTD PI ABINGDON PA 2-4 PARK SQUARE, MILTON PARK, ABINGDON OR14 4RN, OXON, ENGLAND SN 1472-8214 EI 1744-7623 J9 EXPERT OPIN EMERG DR JI Expert Opin Emerg. Drugs PY 2016 VL 21 IS 2 BP 209 EP 218 DI 10.1517/14728214.2016.1170117 PG 10 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA DM7DL UT WOS:000376514900008 PM 27007595 ER PT S AU Song, Y AF Song, Yan BE White, J Smythe, G TI Function of Membrane-Associated Proteoglycans in the Regulation of Satellite Cell Growth SO GROWTH FACTORS AND CYTOKINES IN SKELETAL MUSCLE DEVELOPMENT, GROWTH, REGENERATION AND DISEASE SE Advances in Experimental Medicine and Biology LA English DT Article; Book Chapter DE Cytokine; Growth factor; Proteoglycan; Satellite cell; Skeletal muscle ID HEPARAN-SULFATE PROTEOGLYCANS; LEUKEMIA INHIBITORY FACTOR; PROTEIN-KINASE-C; SKELETAL-MUSCLE DIFFERENTIATION; NECROSIS-FACTOR-ALPHA; SYNDECAN-4 CYTOPLASMIC DOMAIN; GRANULE-MEDIATED APOPTOSIS; FACTOR-DEPENDENT MECHANISM; MAMMARY EPITHELIAL-CELLS; FOCAL ADHESION FORMATION AB Muscle growth can be divided into embryonic and postnatal periods. During the embryonic period, mesenchymal stem cells proliferate and differentiate to form muscle fibers. Postnatal muscle growth (hypertrophy) is characterized by the enlargement of existing muscle fiber size. Satellite cells (also known as adult myoblasts) are responsible for hypertrophy. The activity of satellite cells can be regulated by their extracellular matrix (ECM). The ECM is composed of collagens, proteoglycans, non-collagenous glycoproteins, cytokines and growth factors. Proteoglycans contain a central core protein with covalently attached glycosaminoglycans (GAGs: chondroitin sulfate, keratan sulfate, dermatan sulfate, and heparan sulfate) and N- or O-linked glycosylation chains. Membrane-associated proteoglycans attach to the cell membrane either through a glycosylphosphatidylinositol anchor or transmembrane domain. The GAGs can bind proteins including cytokines and growth factors. Both cytokines and growth factors play important roles in regulating satellite cell growth and development. Cytokines are generally associated with immune cells. However, cytokines can also affect muscle cell development. For instance, interleukin-6, tumor necrosis factor-a, and leukemia inhibitory factor have been reported to affect the proliferation and differentiation of satellite cells and myoblasts. Growth factors are potent stimulators or inhibitors of satellite cell proliferation and differentiation. The proper function of some cytokines and growth factors requires an interaction with the cell membrane-associated proteoglycans to enhance the affinity to bind to their primary receptors to initiate downstream signal transduction. This chapter is focused on the interaction of membrane-associated proteoglycans with cytokines and growth factors, and their role in satellite cell growth and development. C1 [Song, Yan] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02215 USA. RP Song, Y (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02215 USA. EM yan_song@dfci.harvard.edu NR 281 TC 0 Z9 0 U1 1 U2 1 PU SPRINGER-VERLAG BERLIN PI BERLIN PA HEIDELBERGER PLATZ 3, D-14197 BERLIN, GERMANY SN 0065-2598 BN 978-3-319-27511-6; 978-3-319-27509-3 J9 ADV EXP MED BIOL JI Adv.Exp.Med.Biol. PY 2016 VL 900 BP 61 EP 95 DI 10.1007/978-3-319-27511-6_4 D2 10.1007/978-3-319-27511-6 PG 35 WC Biology; Physiology SC Life Sciences & Biomedicine - Other Topics; Physiology GA BE8MX UT WOS:000376609000005 PM 27003397 ER PT S AU Tritos, NA Klibanski, A AF Tritos, Nicholas A. Klibanski, Anne BE Casanueva, FF TI Effects of Growth Hormone on Bone SO GROWTH HORMONE IN HEALTH AND DISEASE SE Progress in Molecular Biology and Translational Science LA English DT Review; Book Chapter ID ONSET GH DEFICIENCY; CHRONIC KIDNEY-DISEASE; RADIOLOGICAL SPINAL DEFORMITIES; JUVENILE IDIOPATHIC ARTHRITIS; CLINICAL-PRACTICE GUIDELINE; PLACEBO-CONTROLLED TRIAL; KIMS DATABASE ANALYSIS; OSTEOBLAST-LIKE CELLS; RECOMBINANT HUMAN GH; FOR-GESTATIONAL-AGE AB Purpose Describe the effects of growth hormone (GH) and insulin-like growth factor 1 (IGF-1) on the skeleton. Findings The GH and IGF-1 axis has pleiotropic effects on the skeleton throughout the lifespan by influencing bone formation and resorption. GH deficiency leads to decreased bone turnover, delayed statural growth in children, low bone mass, and increased fracture risk in adults. GH replacement improves adult stature in GH deficient children, increases bone mineral density (BMD) in adults, and helps to optimize peak bone acquisition in patients, during the transition from adolescence to adulthood, who have persistent GH deficiency. Observational studies suggest that GH replacement may mitigate the excessive fracture risk associated with GH deficiency. Acromegaly, a state of GH and IGF-1 excess, is associated with increased bone turnover and decreased BMD in the lumbar spine observed in some studies, particularly in patients with hypogonadism. In addition, patients with acromegaly appear to be at an increased risk of morphometric-vertebral fractures, especially in the presence of active disease or concurrent hypogonadism. GH therapy also has beneficial effects on statural growth in several conditions characterized by GH insensitivity, including chronic renal failure, Turner syndrome, Prader-Willi syndrome, postnatal growth delay in patients with intrauterine growth retardation who do not demonstrate catchup growth, idiopathic short stature, short stature homeobox-containing (SHOX) gene mutations, and Noonan syndrome. Summary GH and IGF-1 have important roles in skeletal physiology, and GH has an important therapeutic role in both GH deficiency and insensitivity states. C1 [Tritos, Nicholas A.; Klibanski, Anne] Massachusetts Gen Hosp, Neuroendocrine Unit, Boston, MA 02114 USA. [Tritos, Nicholas A.; Klibanski, Anne] Harvard Univ, Sch Med, Boston, MA USA. RP Tritos, NA (reprint author), Massachusetts Gen Hosp, Neuroendocrine Unit, Boston, MA 02114 USA.; Tritos, NA (reprint author), Harvard Univ, Sch Med, Boston, MA USA. EM ntritos@mgh.harvard.edu NR 108 TC 1 Z9 1 U1 6 U2 9 PU ELSEVIER ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA SN 1877-1173 BN 978-0-12-805243-3; 978-0-12-804827-6 J9 PROG MOL BIOL TRANSL JI Prog. Molec. Biol. Transl. Sci. PY 2016 VL 138 BP 193 EP 211 DI 10.1016/bs.pmbts.2015.10.008 PG 19 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA BE7PH UT WOS:000375654600010 PM 26940392 ER PT J AU Gupta, N Duda, DG AF Gupta, Nisha Duda, Dan G. TI Role of stromal cell-derived factor 1 alpha pathway in bone metastatic prostate cancer SO JOURNAL OF BIOMEDICAL RESEARCH LA English DT Review DE SDF1 alpha; CXCR4; bone metastasis; prostate cancer ID MESENCHYMAL STEM-CELLS; BREAST-CANCER; IN-VIVO; PROMOTES METASTASIS; CXCR4 INHIBITION; INITIATING CELLS; TUMOR-GROWTH; EXPRESSION; AXIS; HYPOXIA AB Metastatic prostate cancer is one of the leading causes of cancer-related death in men. The primary site of metastasis from prostate cancers is the bone. During the last decade, multiple studies have pointed to the role of the stromal cell-derived factor 1 alpha (SDF1 alpha)/CXCR4 axis in the metastatic spread of the disease, but the mechanisms that underlie this effect are still incompletely understood. In this review, we summarize the current understanding of the role of the SDF1 alpha/CXCR4 pathway in bone metastatic prostate cancer. We also discuss the therapeutic potential of disrupting the interaction between prostate tumor cells and bone environment with focus on the SDF1 alpha pathway. C1 [Gupta, Nisha; Duda, Dan G.] Harvard Univ, Sch Med, Massachusetts Gen Hosp,Res Inst, Steele Labs Tumor Biol,Dept Radiat Oncol, 100 Blossom St, Boston, MA 02114 USA. RP Duda, DG (reprint author), Massachusetts Gen Hosp, Res Inst, Dept Radiat Oncol, Steele Labs Tumor Biol, 100 Blossom St, Boston, MA 02114 USA. EM gduda@partners.org FU NCI NIH HHS [P01 CA080124, R01 CA159258] NR 39 TC 0 Z9 0 U1 1 U2 1 PU NANJING MEDICAL UNIV PI NANJING PA 140, HANZHONG LU, NANJING, 210029, PEOPLES R CHINA SN 1674-8301 EI 1876-4819 J9 J BIOMED RES JI J. Biomed. Res. PY 2016 VL 30 IS 3 BP 181 EP 185 DI 10.7555/JBR.30.20150114 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA DM9HG UT WOS:000376675500003 PM 27533927 ER PT J AU Maher, DP Lee, J Woo, P Zhang, X White, PF Yumul, R Conte, AH AF Maher, Dermot P. Lee, Jacqueline Woo, Pauline Zhang, Xiao White, Paul F. Yumul, Roya Conte, Antonio Hernandez TI Ritonavir Use in Human Immunodeficiency Virus-Positive Surgical Patients Is Not Associated with an Increase in Postoperative Critical Respiratory Events SO JOURNAL OF PAIN & PALLIATIVE CARE PHARMACOTHERAPY LA English DT Article DE Critical events; drug interaction; HIV; opioid; respiratory; ritonavir ID PHARMACOKINETIC DRUG-INTERACTIONS; PROTEASE INHIBITORS; ANTIRETROVIRAL THERAPY; CYTOCHROME P4503A; METHADONE; HIV; LOPINAVIR/RITONAVIR; BUPRENORPHINE; PHARMACOLOGY; MANAGEMENT AB This study evaluated whether highly active antiretroviral therapy for human immunodeficiency virus (HIV) including ritonavir is independently associated with increased critical respiratory events after general anesthesia with opioid analgesia. The impact of ritonavir on hepatic microsomal enzymes was considered due to the effect of these enzymes on opioid metabolism. Medical records of over 1900 patients were reviewed, and those of 941 patients met inclusion criteria and were analyzed. Chronic treatment with ritonavir was not associated with critical respiratory events in HIV-positive patients. C1 [Maher, Dermot P.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Pain Med, Cambridge, MA 02138 USA. [Lee, Jacqueline; Woo, Pauline; Conte, Antonio Hernandez] Cedars Sinai Med Ctr, Dept Anesthesia, Los Angeles, CA 90048 USA. [White, Paul F.] Cedars Sinai Med Ctr, Dept Anesthesiol, Res & Educ, Los Angeles, CA 90048 USA. [White, Paul F.] Univ Bologna, Inst Ortoped Rizzoli, I-40126 Bologna, Italy. [Zhang, Xiao] Cedars Sinai Med Ctr, Samuel Oschin Comprehens Canc Inst, Los Angeles, CA 90048 USA. [Yumul, Roya] Cedars Sinai Med Ctr, Anesthesiol, Los Angeles, CA 90048 USA. [Yumul, Roya] Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90095 USA. [Yumul, Roya] Cedars Sinai Med Ctr, Residency Program, Los Angeles, CA 90048 USA. [Yumul, Roya] Cedars Sinai Med Ctr, Dept Anesthesiol, Educ Programs, Los Angeles, CA 90048 USA. RP Maher, DP (reprint author), 8700 Beverly Blvd,Room 4209, Los Angeles, CA 90048 USA. EM dermot.maher@cshs.org FU White Mountain Institute, The Sea Ranch, California FX Dr. Paul F. White receives support from the White Mountain Institute, The Sea Ranch, California. NR 26 TC 0 Z9 0 U1 0 U2 0 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 530 WALNUT STREET, STE 850, PHILADELPHIA, PA 19106 USA SN 1536-0288 EI 1536-0539 J9 J PAIN PALLIAT CARE JI J. Pain Palliat. Care Pharmacother. PY 2016 VL 30 IS 1 BP 25 EP 30 DI 10.3109/15360288.2015.1135846 PG 6 WC Anesthesiology; Pharmacology & Pharmacy SC Anesthesiology; Pharmacology & Pharmacy GA DM7UK UT WOS:000376565300005 PM 26861563 ER PT S AU Meng, C Culhane, A AF Meng, Chen Culhane, Aedin BE Mathe, E Davis, S TI Integrative Exploratory Analysis of Two or More Genomic Datasets SO STATISTICAL GENOMICS: METHODS AND PROTOCOLS SE Methods in Molecular Biology LA English DT Article; Book Chapter DE Multivariate; Dimension reduction; Multi-omics; Multiassay; Data integration ID GENE-EXPRESSION DATA; CO-INERTIA ANALYSIS AB Exploratory analysis is an essential step in the analysis of high throughput data. Multivariate approaches such as correspondence analysis (CA), principal component analysis, and multidimensional scaling are widely used in the exploratory analysis of single dataset. Modern biological studies often assay multiple types of biological molecules (e.g., mRNA, protein, phosphoproteins) on a same set of biological samples, thereby creating multiple different types of omics data or multiassay data. Integrative exploratory analysis of these multiple omics data is required to leverage the potential of multiple omics studies. In this chapter, we describe the application of co-inertia analysis (CIA; for analyzing two datasets) and multiple co-inertia analysis (MCIA; for three or more datasets) to address this problem. These methods are powerful yet simple multivariate approaches that represent samples using a lower number of variables, allowing a more easily identification of the correlated structure in and between multiple high dimensional datasets. Graphical representations can be employed to this purpose. In addition, the methods simultaneously project samples and variables (genes, proteins) onto the same lower dimensional space, so the most variant variables from each dataset can be selected and associated with samples, which can be further used to facilitate biological interpretation and pathway analysis. We applied CIA to explore the concordance between mRNA and protein expression in a panel of 60 tumor cell lines from the National Cancer Institute. In the same 60 cell lines, we used MCIA to perform a cross-platform comparison of mRNA gene expression profiles obtained on four different microarray platforms. Last, as an example of integrative analysis of multiassay or multiomics data we analyzed transcriptomic, proteomic, and phosphoproteomic data from pluripotent (iPS) and embryonic stem (ES) cell lines. C1 [Meng, Chen] Tech Univ Mnchen, Chair Prote & Bioanalyt, Freising Weihenstephan, Germany. [Culhane, Aedin] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA. [Culhane, Aedin] Harvard Univ, TH Chan Sch Publ Hlth, Boston, MA 02115 USA. RP Meng, C (reprint author), Tech Univ Mnchen, Chair Prote & Bioanalyt, Freising Weihenstephan, Germany. NR 9 TC 0 Z9 0 U1 0 U2 1 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DR, STE 208, TOTOWA, NJ 07512-1165 USA SN 1064-3745 BN 978-1-4939-3578-9; 978-1-4939-3576-5 J9 METHODS MOL BIOL JI Methods Mol. Biol. PY 2016 VL 1418 BP 19 EP 38 DI 10.1007/978-1-4939-3578-9_2 D2 10.1007/978-1-4939-3578-9 PG 20 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA BE8KT UT WOS:000376532300003 PM 27008008 ER PT J AU Coleman, RR Starr, PA Katz, M Glass, GA Volz, M Khandhar, SM Ostrem, JL AF Coleman, Robert R. Starr, Philip A. Katz, Maya Glass, Graham A. Volz, Monica Khandhar, Suketu M. Ostrem, Jill L. TI Bilateral Ventral Intermediate Nucleus Thalamic Deep Brain Stimulation in Orthostatic Tremor SO STEREOTACTIC AND FUNCTIONAL NEUROSURGERY LA English DT Article DE Orthostatic tremor; Deep brain stimulation; Tremor; Ventral intermediate nucleus; Outcome; Surgical treatment; Thalamic stimulation AB Background: Orthostatic tremor (OT) is characterized by high-frequency leg tremor when standing still, resulting in a sense of imbalance, with limited treatment options. Ventral intermediate (Vim) nucleus thalamic deep brain stimulation (DBS) has been reported as beneficial in a few cases. Objective: To report clinical outcomes, lead locations, and stimulation parameters in 2 patients with severe medication-refractory OT treated with Vim DBS. Methods: The patients underwent surface electromyography (EMG) to confirm the OT diagnosis. Outcomes were measured as change in tolerated standing time at the last follow-up. Lead locations were quantified using postoperative MRI. Results: Vim DBS was well tolerated and resulted in improvement in standing time (patient 1: 50 s at baseline to 15 min 16 months after surgery; patient 2: 34 s at baseline to 4.2 min 7 months after surgery). Postoperative surface EMG for patient 1 demonstrated a delayed onset of tremor, lower-amplitude tremor, and periods of quiescence, but an unchanged tremor frequency. Conclusion: These cases provide further support for Vim DBS to improve standing time in severe medication-refractory OT. The location of the effective thalamic target for OT does not differ from the effective target for essential tremor. (C) 2016 S. Karger AG, Basel C1 [Coleman, Robert R.; Katz, Maya; Glass, Graham A.; Volz, Monica; Ostrem, Jill L.] Univ Calif San Francisco, Neurol, San Francisco, CA 94143 USA. [Starr, Philip A.] Univ Calif San Francisco, Neurosurg, San Francisco, CA 94143 USA. [Coleman, Robert R.; Starr, Philip A.; Katz, Maya; Glass, Graham A.; Ostrem, Jill L.] San Francisco VA Med Ctr, Parkinsons Dis Res Educ & Clin Ctr, San Francisco, CA USA. [Khandhar, Suketu M.] Kaiser Fdn Hosp, Neurol, Sacramento, CA USA. RP Coleman, RR (reprint author), Univ Calif San Francisco, 1635 Divisadero St,Suite 520-530, San Francisco, CA 94115 USA. EM robert.coleman@ucsf.edu NR 12 TC 2 Z9 2 U1 1 U2 2 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 2016 VL 94 IS 2 BP 69 EP 74 DI 10.1159/000444127 PG 6 WC Neurosciences; Neuroimaging; Surgery SC Neurosciences & Neurology; Surgery GA DM7WQ UT WOS:000376571100001 PM 27002536 ER PT J AU Nguyen, VHV Wong, BM Shen, DD Woo, DT Vu, AV Lie, JD AF Nguyen, Viet-Huong V. Wong, Bonnie M. Shen, Diana D. Woo, Denny T. Vu, Amanda V. Lie, Janette D. TI Early Management of Acute Ischemic Stroke: Focus on IV tPA and Timely Reperfusion SO US PHARMACIST LA English DT Article AB Alteplase (Activase), an intravenous (IV) tissue plasminogen activator (tPA), is the only FDA-approved thrombolytic agent for acute ischemic stroke (AIS). Recently updated American Heart Association/American Stroke Association (AHA/ASA) Guidelines for the Early Management of Patients with Acute Ischemic Stroke and revisions to Activase labeling have expanded the time window eligibility for tPA treatment and have loosened contraindications surrounding tPA treatment. These changes should promote increased utilization of tPA in AIS, resulting in more instances of timely reperfusion and reduction of neurologic sequelae. C1 [Nguyen, Viet-Huong V.] Chapman Univ, Sch Pharm, Dept Pharm Practice, Pharm Practice, Irvine, CA USA. [Wong, Bonnie M.; Shen, Diana D.; Woo, Denny T.; Vu, Amanda V.] Univ So Calif, Sch Pharm, Los Angeles, CA USA. [Wong, Bonnie M.; Shen, Diana D.; Woo, Denny T.; Vu, Amanda V.] Vet Affairs Greater Los Angeles Healthcare Syst, Pharm VA Learning Opportun Residency VALOR, Los Angeles, CA USA. [Lie, Janette D.] Vet Affairs Greater Los Angeles Healthcare Syst, Pharm Educ & Training, Los Angeles, CA USA. RP Nguyen, VHV (reprint author), Chapman Univ, Sch Pharm, Dept Pharm Practice, Pharm Practice, Irvine, CA USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU JOBSON PUBLISHING LLC PI NEW YORK PA 100 AVE OF THE AMERICAS, NEW YORK, NY 10013-1678 USA SN 0148-4818 EI 2331-3501 J9 US PHARM JI US Pharm. PD JAN PY 2016 VL 41 IS 1 BP HS9 EP HS12 PG 4 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA DN0KC UT WOS:000376751800004 ER PT S AU Fedorenko, E Varley, R AF Fedorenko, Evelina Varley, Rosemary BE Kingstone, A Miller, MB TI Language and thought are not the same thing: evidence from neuroimaging and neurological patients SO YEAR IN COGNITIVE NEUROSCIENCE SE Annals of the New York Academy of Sciences LA English DT Article; Book Chapter DE language; syntax; semantics; functional specificity; numerical cognition; cognitive control; executive functions; theory of mind; music; navigation; fMRI; neuropsychology; aphasia ID TEMPORO-PARIETAL JUNCTION; EVENT-RELATED POTENTIALS; COMPARATIVE CYTOARCHITECTONIC ANALYSIS; CORTICOCORTICAL CONNECTION PATTERNS; ELECTRICAL BRAIN ACTIVITY; WORKING-MEMORY RESOURCES; MISMATCH NEGATIVITY MMN; INFERIOR FRONTAL-CORTEX; RIGHT-HEMISPHERE DAMAGE; OF-MIND DEVELOPMENT AB Is thought possible without language? Individuals with global aphasia, who have almost no ability to understand or produce language, provide a powerful opportunity to find out. Surprisingly, despite their near-total loss of language, these individuals are nonetheless able to add and subtract, solve logic problems, think about another person's thoughts, appreciate music, and successfully navigate their environments. Further, neuroimaging studies show that healthy adults strongly engage the brain's language areas when they understand a sentence, but not when they perform other nonlinguistic tasks such as arithmetic, storing information in working memory, inhibiting prepotent responses, or listening to music. Together, these two complementary lines of evidence provide a clear answer: many aspects of thought engage distinct brain regions from, and do not depend on, language. C1 [Fedorenko, Evelina] Massachusetts Gen Hosp, Dept Psychiat, Bldg 149,East 13th St, Charlestown, MA 02129 USA. [Fedorenko, Evelina] Harvard Univ, Sch Med, Boston, MA USA. [Fedorenko, Evelina] Univ Calif San Diego, CARTA, La Jolla, CA 92093 USA. [Varley, Rosemary] UCL, London, England. RP Fedorenko, E (reprint author), Massachusetts Gen Hosp, Dept Psychiat, Bldg 149,East 13th St, Charlestown, MA 02129 USA. EM evelina.fedorenko@mgh.harvard.edu FU NICHD NIH HHS [R00 HD057522] NR 280 TC 2 Z9 2 U1 15 U2 20 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 2016 VL 1369 BP 132 EP 153 DI 10.1111/nyas.13046 PG 22 WC Psychology, Biological; Neurosciences; Psychology; Psychology, Experimental SC Psychology; Neurosciences & Neurology GA BE8MD UT WOS:000376588900008 PM 27096882 ER PT J AU Paul, S Evans, R Maurer, T Muhe, LM Freeman, EE AF Paul, Suchismita Evans, Rachel Maurer, Toby Muhe, Lulu M. Freeman, Esther E. TI Treatment of Dermatological Conditions Associated with HIV/AIDS: The Scarcity of Guidance on a Global Scale SO AIDS RESEARCH AND TREATMENT LA English DT Review ID HIV-INFECTION; MUCOCUTANEOUS MANIFESTATIONS; SKIN DISEASES; CARE; RECOMMENDATIONS; GUIDELINES; QUALITY AB Background. Skin diseases associated with Human Immunodeficiency Virus (HIV) infection are associated with significant morbidity and mortality. In resource-limited settings, nondermatologists and lay health care providers on the front line of HIV care provide much of the treatment for these conditions. Objective. To evaluate guidelines for treatment of HIV-related skin conditions and assess their accessibility, comprehensiveness, and quality of evidence employed. Methods. A review was undertaken of all national and society guidelines which included treatment information on the ten highest burden HIV-related skin conditions. The search strategy included gray and peer-reviewed literature. Results. Of 430 potential guidelines, 86 met inclusion criteria, and only 2 were written specifically to address HIV-related skin diseases as a whole. Treatment information for HIV-related skin conditions was embedded within guidelines written for other purposes, primarily HIV/AIDs treatment guidelines (49%). Development of guidelines relied either partially or completely on expert opinion (62%). Only 16% of guidelines used gradation of evidence quality and these were primarily from high-income countries (p = 0.001). Limitations. Due to the nature of gray literature, not all guidelines may have been identified. Conclusion. This review highlights the need for evidence-based summary guidelines that address treatment for HIV-related skin conditions in an accessible format. C1 [Paul, Suchismita] Harvard Univ, Sch Med, Boston, MA 02114 USA. [Evans, Rachel] WHO, HIV Dept, CH-1211 Geneva, Switzerland. [Maurer, Toby] Univ Calif San Francisco, Sch Med, Dept Dermatol, San Francisco, CA USA. [Muhe, Lulu M.] WHO, Dept Maternal Child & Adolescent Hlth, CH-1211 Geneva, Switzerland. [Freeman, Esther E.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Dermatol, Bartlett Hall 6R,55 Fruit St, Boston, MA 02114 USA. RP Freeman, EE (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Dermatol, Bartlett Hall 6R,55 Fruit St, Boston, MA 02114 USA. EM esther.freeman@gmail.com NR 24 TC 0 Z9 0 U1 3 U2 3 PU HINDAWI PUBLISHING CORP PI NEW YORK PA 410 PARK AVENUE, 15TH FLOOR, #287 PMB, NEW YORK, NY 10022 USA SN 2090-1240 EI 2090-1259 J9 AIDS RES TREAT JI AIDS Res. Treat. PY 2016 AR 3272483 DI 10.1155/2016/3272483 PG 21 WC Psychiatry SC Psychiatry GA DM1DN UT WOS:000376085500001 ER PT S AU Peloquin, JM Goel, G Villablanca, EJ Xavier, RJ AF Peloquin, Joanna M. Goel, Gautam Villablanca, Eduardo J. Xavier, Ramnik J. BE Littman, DR Yokoyama, WM TI Mechanisms of Pediatric Inflammatory Bowel Disease SO ANNUAL REVIEW OF IMMUNOLOGY, VOL 34 SE Annual Review of Immunology LA English DT Review; Book Chapter DE Crohn disease; ulcerative colitis; intestinal homeostasis; genetics; microbiome; therapeutics ID INNATE LYMPHOID-CELLS; ARYL-HYDROCARBON RECEPTOR; ONSET CROHNS-DISEASE; CHRONIC GRANULOMATOUS-DISEASE; MEVALONATE KINASE-DEFICIENCY; EXCLUSIVE ENTERAL NUTRITION; POPULATION-BASED COHORT; OF-FUNCTION MUTATIONS; DENDRITIC CELLS; INTESTINAL INFLAMMATION AB Inflammatory bowel disease (IBD), including Crohn disease and ulcerative colitis, is characterized by chronic intestinal inflammation due to a complex interaction of genetic determinants, disruption of mucosal barriers, aberrant inflammatory signals, loss of tolerance, and environmental triggers. Importantly, the incidence of pediatric IBD is rising, particularly in children younger than 10 years. In this review, we discuss the clinical presentation of these patients and highlight environmental exposures that may affect disease risk, particularly among people with a background genetic risk. With regard to both children and adults, we review advancements in understanding the intestinal epithelium, the mucosal immune system, and the resident microbiota, describing how dysfunction at any level can lead to diseases like IBD. We conclude with future directions for applying advances in IBD genetics to better understand pathogenesis and develop therapeutics targeting key pathogenic nodes. C1 [Peloquin, Joanna M.; Villablanca, Eduardo J.; Xavier, Ramnik J.] Massachusetts Gen Hosp, Gastrointestinal Unit, Boston, MA 02114 USA. [Peloquin, Joanna M.; Villablanca, Eduardo J.; Xavier, Ramnik J.] Massachusetts Gen Hosp, Ctr Study Inflammatory Bowel Dis, Boston, MA 02114 USA. [Peloquin, Joanna M.; Goel, Gautam; Villablanca, Eduardo J.; Xavier, Ramnik J.] Massachusetts Gen Hosp, Ctr Computat & Integrat Biol, Boston, MA 02114 USA. [Peloquin, Joanna M.; Goel, Gautam; Villablanca, Eduardo J.; Xavier, Ramnik J.] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Xavier, Ramnik J.] Broad Inst Massachusetts Inst Technol & Harvard U, Cambridge, MA 02142 USA. [Xavier, Ramnik J.] MIT, Ctr Microbiome Informat & Therapeut, 77 Massachusetts Ave, Cambridge, MA 02139 USA. RP Peloquin, JM; Villablanca, EJ; Xavier, RJ (reprint author), Massachusetts Gen Hosp, Gastrointestinal Unit, Boston, MA 02114 USA.; Peloquin, JM; Villablanca, EJ; Xavier, RJ (reprint author), Massachusetts Gen Hosp, Ctr Study Inflammatory Bowel Dis, Boston, MA 02114 USA.; Peloquin, JM; Goel, G; Villablanca, EJ; Xavier, RJ (reprint author), Massachusetts Gen Hosp, Ctr Computat & Integrat Biol, Boston, MA 02114 USA.; Peloquin, JM; Goel, G; Villablanca, EJ; Xavier, RJ (reprint author), Harvard Univ, Sch Med, Boston, MA 02115 USA.; Xavier, RJ (reprint author), Broad Inst Massachusetts Inst Technol & Harvard U, Cambridge, MA 02142 USA.; Xavier, RJ (reprint author), MIT, Ctr Microbiome Informat & Therapeut, 77 Massachusetts Ave, Cambridge, MA 02139 USA. EM joanna.peloquin@jhmi.edu; ggoel@ccib.mgh.harvard.edu; eduardo.villablanca@ki.se; xavier@molbio.mgh.harvard.edu OI Villablanca, Eduardo/0000-0001-9522-9729 FU NIDDK NIH HHS [P30 DK043351] NR 232 TC 2 Z9 2 U1 4 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 978-0-8243-3034-7 J9 ANNU REV IMMUNOL JI Annu. Rev. Immunol. PY 2016 VL 34 BP 31 EP 64 DI 10.1146/annurev-immunol-032414-112151 PG 34 WC Immunology SC Immunology GA BE7XH UT WOS:000376011300002 PM 27168239 ER PT S AU Baumeister, SH Freeman, GJ Dranoff, G Sharpe, AH AF Baumeister, Susanne H. Freeman, Gordon J. Dranoff, Glenn Sharpe, Arlene H. BE Littman, DR Yokoyama, WM TI Coinhibitory Pathways in Immunotherapy for Cancer SO ANNUAL REVIEW OF IMMUNOLOGY, VOL 34 SE Annual Review of Immunology LA English DT Review; Book Chapter DE tumor immunity; cancer immunotherapy; CTLA-4; PD-1; PD-L1 ID REGULATORY T-CELLS; PHASE-I TRIAL; LYMPHOCYTE-ASSOCIATED ANTIGEN-4; RESISTANT PROSTATE-CANCER; COLONY-STIMULATING FACTOR; CHRONIC VIRAL-INFECTION; MHC CLASS-II; MEDIATED CYTOTOXIC IMMUNOTHERAPY; RANDOMIZED CLINICAL-TRIAL; DOSE-ESCALATION TRIAL AB The immune system is capable of recognizing tumors and eliminates many early malignant cells. However, tumors evolve to evade immune attack, and the tumor microenvironment is immunosuppressive. Immune responses are regulated by a number of immunological checkpoints that promote protective immunity and maintain tolerance. T cell coinhibitory pathways restrict the strength and duration of immune responses, thereby limiting immune-mediated tissue damage, controlling resolution of inflammation, and maintaining tolerance to prevent autoimmunity. Tumors exploit these coinhibitory pathways to evade immune eradication. Blockade of the PD-1 and CTLA-4 checkpoints is proving to be an effective and durable cancer immunotherapy in a subset of patients with a variety of tumor types, and additional combinations are further improving response rates. In this review we discuss the immunoregulatory functions of coinhibitory pathways and their translation to effective immunotherapies for cancer. C1 [Baumeister, Susanne H.; Freeman, Gordon J.; Dranoff, Glenn] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02215 USA. [Baumeister, Susanne H.] Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02215 USA. [Baumeister, Susanne H.] Boston Childrens Hosp, Div Pediat Hematol Oncol, Boston, MA 02115 USA. [Baumeister, Susanne H.; Freeman, Gordon J.] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Dranoff, Glenn] Novartis Inst BioMed Res, Exploratory Immunooncol, Cambridge, MA 02139 USA. [Sharpe, Arlene H.] Harvard Univ, Sch Med, Dept Microbiol & Immunobiol, Boston, MA 02115 USA. [Sharpe, Arlene H.] Harvard Univ, Sch Med, Evergrande Ctr Immunol Dis, Boston, MA 02115 USA. RP Sharpe, AH (reprint author), Harvard Univ, Sch Med, Dept Microbiol & Immunobiol, Boston, MA 02115 USA.; Sharpe, AH (reprint author), Harvard Univ, Sch Med, Evergrande Ctr Immunol Dis, Boston, MA 02115 USA. EM arlene_sharpe@hms.harvard.edu NR 240 TC 15 Z9 15 U1 8 U2 21 PU ANNUAL REVIEWS PI PALO ALTO PA 4139 EL CAMINO WAY, PO BOX 10139, PALO ALTO, CA 94303-0897 USA SN 0732-0582 BN 978-0-8243-3034-7 J9 ANNU REV IMMUNOL JI Annu. Rev. Immunol. PY 2016 VL 34 BP 539 EP 573 DI 10.1146/annurev-immunol-032414-112049 PG 35 WC Immunology SC Immunology GA BE7XH UT WOS:000376011300020 PM 26927206 ER PT S AU Burton, DR Hangartner, L AF Burton, Dennis R. Hangartner, Lars BE Littman, DR Yokoyama, WM TI Broadly Neutralizing Antibodies to HIV and Their Role in Vaccine Design SO ANNUAL REVIEW OF IMMUNOLOGY, VOL 34 SE Annual Review of Immunology LA English DT Review; Book Chapter DE vaccination; rational vaccine design; passive immunotherapy; conserved epitopes; immunization strategies ID IMMUNODEFICIENCY-VIRUS TYPE-1; HUMAN MONOCLONAL-ANTIBODY; PROXIMAL EXTERNAL REGION; MUCOSAL SHIV CHALLENGE; CD4 BINDING-SITE; ENVELOPE GLYCOPROTEIN TRIMERS; HIV-1/SIV CHIMERIC VIRUS; INFECTION IN-VIVO; CRYO-EM STRUCTURE; PBL-SCID MICE AB HIV employs multiple means to evade the humoral immune response, particularly the elicitation of and recognition by broadly neutralizing antibodies (bnAbs). Such antibodies can act antivirally against a wide spectrum of viruses by targeting relatively conserved regions on the surface HIV envelope trimer spike. Elicitation of and recognition by bnAbs are hindered by the arrangement of spikes on virions and the relatively difficult access to bnAb epitopes on spikes, including the proximity of variable regions and a high density of glycans. Yet, in a small proportion of HIV-infected individuals, potent bnAb responses do develop, and isolation of the corresponding monoclonal antibodies has been facilitated by identification of favorable donors with potent bnAb sera and by development of improved methods for human antibody generation. Molecular studies of recombinant Env trimers, alone and in interaction with bnAbs, are providing new insights that are fueling the development and testing of promising immunogens aimed at the elicitation of bnAbs. C1 [Burton, Dennis R.; Hangartner, Lars] Scripps Res Inst, Dept Immunol & Microbial Sci, La Jolla, CA 92037 USA. [Burton, Dennis R.] Scripps Res Inst, Neutralizing Antibody Ctr, Int AIDS Vaccine Initiat, La Jolla, CA 92037 USA. [Burton, Dennis R.; Hangartner, Lars] Scripps Res Inst, Ctr HIV AIDS Vaccine Immunol & Immunogen Discover, La Jolla, CA 92037 USA. [Burton, Dennis R.] Ragon Inst Massachusetts Gen Hosp Massachusetts I, Boston, MA 02142 USA. RP Burton, DR; Hangartner, L (reprint author), Scripps Res Inst, Dept Immunol & Microbial Sci, La Jolla, CA 92037 USA.; Burton, DR (reprint author), Scripps Res Inst, Neutralizing Antibody Ctr, Int AIDS Vaccine Initiat, La Jolla, CA 92037 USA.; Burton, DR; Hangartner, L (reprint author), Scripps Res Inst, Ctr HIV AIDS Vaccine Immunol & Immunogen Discover, La Jolla, CA 92037 USA.; Burton, DR (reprint author), Ragon Inst Massachusetts Gen Hosp Massachusetts I, Boston, MA 02142 USA. EM burton@scripps.edu; lhangart@scripps.edu NR 161 TC 31 Z9 31 U1 10 U2 21 PU ANNUAL REVIEWS PI PALO ALTO PA 4139 EL CAMINO WAY, PO BOX 10139, PALO ALTO, CA 94303-0897 USA SN 0732-0582 BN 978-0-8243-3034-7 J9 ANNU REV IMMUNOL JI Annu. Rev. Immunol. PY 2016 VL 34 BP 635 EP 659 DI 10.1146/annurev-immunol-041015-055515 PG 25 WC Immunology SC Immunology GA BE7XH UT WOS:000376011300023 PM 27168247 ER PT J AU Mihos, CG Pineda, AM Capoulade, R Larrauri-Reyes, MC Melnitchouk, S Hung, J Santana, O AF Mihos, Christos G. Pineda, Andres M. Capoulade, Romain Larrauri-Reyes, Maiteder C. Melnitchouk, Serguei Hung, Judy Santana, Orlando TI Early Echocardiographic Outcomes of Mitral Valve Annuloplasty versus Annuloplasty Combined with a Papillary Muscle Sling for Moderate to Severe Functional Mitral Regurgitation SO CARDIOLOGY LA English DT Meeting Abstract C1 [Mihos, Christos G.; Capoulade, Romain; Melnitchouk, Serguei; Hung, Judy] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Pineda, Andres M.; Larrauri-Reyes, Maiteder C.; Santana, Orlando] Columbia Univ, Div Cardiol, Mt Sinai Heart Inst, Miami Beach, FL USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0008-6312 EI 1421-9751 J9 CARDIOLOGY JI Cardiology PY 2016 VL 134 IS 2 BP 151 EP 151 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA DL6UB UT WOS:000375773900041 ER PT J AU Mihos, CG Pineda, AM Santana, O AF Mihos, Christos G. Pineda, Andres M. Santana, Orlando TI Early versus Delayed Surgery for Patients with Valvular Infective Endocarditis Complicated by Embolic Ischemic Cerebrovascular Events: A Meta-Analysis of 14 Studies SO CARDIOLOGY LA English DT Meeting Abstract C1 [Mihos, Christos G.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Pineda, Andres M.; Santana, Orlando] Columbia Univ, Div Cardiol, Mt Sinai Heart Inst, Miami Beach, FL USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0008-6312 EI 1421-9751 J9 CARDIOLOGY JI Cardiology PY 2016 VL 134 IS 2 BP 157 EP 157 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA DL6UB UT WOS:000375773900049 ER PT J AU Dahou, A Clavel, MA Capoulade, R Bartko, PE Magne, J Mundigler, G Bergler-Klein, J Burwash, I Mascherbauer, J Ribeiro, HB O'Connor, K Baumgartner, H Senechal, M Dumesnil, JG Rosenhek, R Rodes-Cabau, J Pibarot, P AF Dahou, Abdellaziz Clavel, Marie-Annick Capoulade, Romain Bartko, Philipp E. Magne, Julien Mundigler, Gerald Bergler-Klein, Jutta Burwash, Ian Mascherbauer, Julia Ribeiro, Henrique B. O'Connor, Kim Baumgartner, Helmut Senechal, Mario Dumesnil, Jean G. Rosenhek, Raphael Rodes-Cabau, Josep Pibarot, Philippe TI Right Ventricular Function By Speckle Tracking and Outcomes in Low-Flow, Low Gradient Aortic Stenosis with Low LVEF SO CARDIOLOGY LA English DT Meeting Abstract C1 [Dahou, Abdellaziz; Clavel, Marie-Annick; Ribeiro, Henrique B.; O'Connor, Kim; Senechal, Mario; Rodes-Cabau, Josep; Pibarot, Philippe] Quebec Heart Lung Inst, Quebec City, PQ, Canada. [Capoulade, Romain; Bartko, Philipp E.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Magne, Julien] Ctr Hosp Univ Limoges, Limoges, France. [Mundigler, Gerald; Bergler-Klein, Jutta; Mascherbauer, Julia; Rosenhek, Raphael] Med Univ Vienna, Div Cardiol, Vienna, Austria. [Burwash, Ian] Univ Ottawa, Inst Heart, Ottawa, ON, Canada. [Baumgartner, Helmut] Univ Hosp Muenster, Dept Cardiovasc Med, Munster, Germany. [Dumesnil, Jean G.] Univ Laval, Quebec City, PQ, Canada. NR 0 TC 0 Z9 0 U1 1 U2 1 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0008-6312 EI 1421-9751 J9 CARDIOLOGY JI Cardiology PY 2016 VL 134 IS 2 BP 160 EP 160 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA DL6UB UT WOS:000375773900054 ER PT J AU Dina, C Tucker, N Delling, F Slaugenhaupt, S Levine, RA Hagege, AA Schott, JJ Jeunemaitre, X Milan, D Norris, R Bouatia-Naji, N AF Dina, Christian Tucker, Nathan Delling, Francescaca Slaugenhaupt, Susan Levine, Robert A. Hagege, Albert A. Schott, Jean-Jacques Jeunemaitre, Xavier Milan, David Norris, Russell Bouatia-Naji, Nabila TI Genetic Association and Functional Studies Identifies GLIS1 As a Risk Locus for Mitral Valve Prolapse SO CARDIOLOGY LA English DT Meeting Abstract C1 [Dina, Christian; Schott, Jean-Jacques] CHU Nantes, INSERM, UMR1087, CNRS,UMR 6291,Inst Thorax, F-44035 Nantes 01, France. [Tucker, Nathan; Milan, David] Massachusetts Gen Hosp, Cardiovasc Res Ctr, Charlestown, MA USA. [Delling, Francescaca] Framingham Heart Dis Epidemiol Study, Framingham, MA USA. [Slaugenhaupt, Susan] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA. [Slaugenhaupt, Susan; Levine, Robert A.] Harvard Univ, Sch Med, Boston, MA USA. [Levine, Robert A.] Massachusetts Gen Hosp, Cardiac Ultrasound Lab, Boston, MA 02114 USA. [Hagege, Albert A.] Hop Europeen Georges Pompidou, AP HP, Dept Cardiol, INSERM,UMR9701,Europeen Georges Pompidou,UMR970, Paris, France. [Jeunemaitre, Xavier] Hop Europeen Georges Pompidou, AP HP, Dept Genet, INSERM,U970,Paris Cardiovasc Res Ctr, Paris, France. [Norris, Russell] Med Univ S Carolina, Cardiovasc Dev Biol Ctr, Childrens Res Inst, Med Univ South Carolinach Inst, Charleston, SC 29425 USA. [Bouatia-Naji, Nabila] Paris Cardiovasc Res Ctr, INSERM, UMR970, Paris, France. RI BOUATIA-NAJI, NABILA/D-5863-2013 NR 0 TC 0 Z9 0 U1 0 U2 0 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0008-6312 EI 1421-9751 J9 CARDIOLOGY JI Cardiology PY 2016 VL 134 IS 2 BP 169 EP 170 PG 2 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA DL6UB UT WOS:000375773900069 ER PT J AU Heydarpour, M Monteiro-Vieira, V Habchi, K Sliwa, J Sigurdsson, M Muehlschlegel, J Shekar, P Isselbacher, E Sundt, T Body, S AF Heydarpour, Mahyar Monteiro-Vieira, Vanessa Habchi, Karam Sliwa, Jan Sigurdsson, Martin Muehlschlegel, Jochen Shekar, Prem Isselbacher, Eric Sundt, Thoralf Body, Simon TI GWAS of Aortic Stenosis (AS) in Patients with Bicuspid Aortic Valve (BAV) Disease SO CARDIOLOGY LA English DT Meeting Abstract C1 [Heydarpour, Mahyar; Monteiro-Vieira, Vanessa; Habchi, Karam; Sigurdsson, Martin; Muehlschlegel, Jochen; Body, Simon] Brigham & Womens Hosp, Perioperat Genom Ctr, 75 Francis St, Boston, MA 02115 USA. [Sliwa, Jan] Brigham & Womens Hosp, Cardiothorac Anaesthesia, 75 Francis St, Boston, MA 02115 USA. [Shekar, Prem] Brigham & Womens Hosp, Heart & Vasc Ctr, 75 Francis St, Boston, MA 02115 USA. [Isselbacher, Eric; Sundt, Thoralf] Massachusetts Gen Hosp, Corrigan Minehan Heart Ctr, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0008-6312 EI 1421-9751 J9 CARDIOLOGY JI Cardiology PY 2016 VL 134 IS 2 BP 169 EP 169 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA DL6UB UT WOS:000375773900068 ER PT J AU Pantoja, JL Morgan, AE Ge, L Grossi, EA Weinsaft, JW Jensen, MO Levine, RA Ratcliffe, MB AF Pantoja, Joe L. Morgan, Ashley E. Ge, Liang Grossi, Eugene A. Weinsaft, Jonathan W. Jensen, Morton O. Levine, Robert A. Ratcliffe, Mark B. TI Undersized Ring Annuloplasty Increases Strain in the Left Ventricle: Finite Element Analysis SO CARDIOLOGY LA English DT Meeting Abstract C1 [Pantoja, Joe L.] UCSF Sch Med, San Francisco, CA USA. [Morgan, Ashley E.; Ge, Liang; Ratcliffe, Mark B.] San Francisco VA Med Ctr, San Francisco, CA USA. [Grossi, Eugene A.] NYU, New York, NY USA. [Weinsaft, Jonathan W.] Cornell Univ, New York, NY 10021 USA. [Jensen, Morton O.] Univ Arkansas, Fayetteville, AR 72701 USA. [Levine, Robert A.] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0008-6312 EI 1421-9751 J9 CARDIOLOGY JI Cardiology PY 2016 VL 134 IS 2 BP 181 EP 181 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA DL6UB UT WOS:000375773900088 ER PT J AU Elmariah, S Farrell, LA Daher, M Shi, X Morningstar, JE Keyes, MJ Vlahakes, GJ Inglessis, I Passeri, JJ Palacios, IF Fox, CS Rhee, EP Gerszten, RE AF Elmariah, Sammy Farrell, Laurie A. Daher, Maureen Shi, Xu Morningstar, Jordan E. Keyes, Michelle J. Vlahakes, Gus J. Inglessis, Ignacio Passeri, Jonathan J. Palacios, Igor F. Fox, Caroline S. Rhee, Eugene P. Gerszten, Robert E. TI Ketoisocaproic Acid Predicts Acute Kidney Injury and Mortality after Transcatheter Aortic Valve Replacement: A Metabolomic Profiling Study SO CARDIOLOGY LA English DT Meeting Abstract C1 [Elmariah, Sammy; Farrell, Laurie A.; Daher, Maureen; Shi, Xu; Morningstar, Jordan E.; Keyes, Michelle J.; Vlahakes, Gus J.; Inglessis, Ignacio; Passeri, Jonathan J.; Palacios, Igor F.; Rhee, Eugene P.; Gerszten, Robert E.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. [Fox, Caroline S.] NHLBI, Framingham Heart Study, Framingham, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0008-6312 EI 1421-9751 J9 CARDIOLOGY JI Cardiology PY 2016 VL 134 IS 2 BP 194 EP 194 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA DL6UB UT WOS:000375773900111 ER PT J AU Milan, D Toomer, K Fraher, D Talkowski, M Durst, R Delling, F Levine, R Slaugenhaupt, S Norris, R AF Milan, David Toomer, Katelin Fraher, Dan Talkowski, Michael Durst, Ronen Delling, Francesca Levine, Robert Slaugenhaupt, Susan Norris, Russell TI Mutations in DZIP Cause Mitral Valve Prolapse SO CARDIOLOGY LA English DT Meeting Abstract C1 [Milan, David; Fraher, Dan; Talkowski, Michael; Levine, Robert; Slaugenhaupt, Susan] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Toomer, Katelin; Norris, Russell] Med Univ S Carolina, Charleston, SC 29425 USA. [Durst, Ronen] Hadassah Hebrew Univ, Med Ctr, Jerusalem, Israel. [Delling, Francesca] Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0008-6312 EI 1421-9751 J9 CARDIOLOGY JI Cardiology PY 2016 VL 134 IS 2 BP 207 EP 207 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA DL6UB UT WOS:000375773900137 ER PT J AU Rafael, A Bartko, P Starobinska, EI Choi, AJ Zilinski, JL John, KJ Roka, A Lubitz, SA Milan, DJ AF Rafael, Allon Bartko, Philipp Starobinska, Ella I. Choi, Anthony J. Zilinski, Jodi L. John, Keaney J. Roka, Attila Lubitz, Steven A. Milan, David J. TI Sudden Cardiac Death and Mitral Valve Prolapse: A Single Center Experience SO CARDIOLOGY LA English DT Meeting Abstract C1 [Rafael, Allon; Bartko, Philipp; Choi, Anthony J.; Zilinski, Jodi L.; John, Keaney J.; Roka, Attila; Lubitz, Steven A.; Milan, David J.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Starobinska, Ella I.] Univ Arizona, Coll Med, Phoenix, AZ USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0008-6312 EI 1421-9751 J9 CARDIOLOGY JI Cardiology PY 2016 VL 134 IS 2 BP 229 EP 229 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA DL6UB UT WOS:000375773900177 ER PT J AU Safi, L Meyersohn, N Ghoshhajra, B Dal-Bianco, J Elmariah, S Inglessis, I Palacios, I Melnitchouk, S Vlahakes, G Passeri, J AF Safi, Lucy Meyersohn, Nandini Ghoshhajra, Brian Dal-Bianco, Jacob Elmariah, Sammy Inglessis, Ignacio Palacios, Igor Melnitchouk, Serguei Vlahakes, Gus Passeri, Jonathan TI Transcatheter Aortic Valve Replacement Planning Imaging in Patients with Chronic Kidney Disease SO CARDIOLOGY LA English DT Meeting Abstract C1 [Safi, Lucy; Meyersohn, Nandini; Ghoshhajra, Brian; Dal-Bianco, Jacob; Elmariah, Sammy; Inglessis, Ignacio; Palacios, Igor; Melnitchouk, Serguei; Vlahakes, Gus; Passeri, Jonathan] Massachusetts Gen Hosptial, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0008-6312 EI 1421-9751 J9 CARDIOLOGY JI Cardiology PY 2016 VL 134 IS 2 BP 248 EP 248 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA DL6UB UT WOS:000375773900220 ER PT J AU Mihos, CG Pineda, AM Larrauri-Reyes, MC Beohar, N Santana, O AF Mihos, Christos G. Pineda, Andres M. Larrauri-Reyes, Maiteder C. Beohar, Nirat Santana, Orlando TI Staged Percutaneous Coronary Intervention Followed by Minimally Invasive Mitral Valve Surgery versus Combined Coronary Artery Bypass Graft and Mitral Valve Surgery for Multi-Vessel Coronary Artery Disease and Severe Ischemic Mitral Regurgitation SO CARDIOLOGY LA English DT Meeting Abstract C1 [Mihos, Christos G.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Pineda, Andres M.; Larrauri-Reyes, Maiteder C.; Beohar, Nirat; Santana, Orlando] Columbia Univ, Div Cardiol, Mt Sinai Heart Inst, Miami Beach, FL USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0008-6312 EI 1421-9751 J9 CARDIOLOGY JI Cardiology PY 2016 VL 134 IS 2 BP 261 EP 261 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA DL6UB UT WOS:000375773900247 ER PT S AU Adams, DC Hariri, LP Holz, JA Szabari, MV Harris, RS Cho, JL Hamilos, DL Luster, AD Medoff, BD Suter, MJ AF Adams, David C. Hariri, Lida P. Holz, Jasmin A. Szabari, Margit V. Harris, R. Scott Cho, Jocelyn L. Hamilos, Daniel L. Luster, Andrew D. Medoff, Benjamin D. Suter, Melissa J. BE Tearney, GJ Wang, TD Suter, MJ Lam, S Brenner, M TI Exploiting the relationship between birefringence and force to measure airway smooth muscle contraction with PS-OCT SO ENDOSCOPIC MICROSCOPY XI; AND OPTICAL TECHNIQUES IN PULMONARY MEDICINE III SE Proceedings of SPIE LA English DT Proceedings Paper CT Conference on Endoscopic Microscopy XI and Optical Techniques in Pulmonary Medicine III CY FEB 14-15, 2016 CL San Francisco, CA SP SPIE C1 [Adams, David C.; Hariri, Lida P.; Holz, Jasmin A.; Szabari, Margit V.; Harris, R. Scott; Cho, Jocelyn L.; Hamilos, Daniel L.; Luster, Andrew D.; Medoff, Benjamin D.; Suter, Melissa J.] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Adams, DC (reprint author), Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 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 978-1-62841-925-2 J9 PROC SPIE PY 2016 VL 9691 AR 96911E DI 10.1117/12.2214738 PG 1 WC Optics; Radiology, Nuclear Medicine & Medical Imaging SC Optics; Radiology, Nuclear Medicine & Medical Imaging GA BE8CD UT WOS:000376268400028 ER PT S AU Adams, DC Holz, JA Szabari, MV Hariri, LP Harris, RS Cho, JL Hamilos, DL Luster, AD Medoff, BD Suter, MJ AF Adams, David C. Holz, Jasmin A. Szabari, Margit V. Hariri, Lida P. Harris, R. Scott Cho, Jocelyn L. Hamilos, Daniel L. Luster, Andrew D. Medoff, Benjamin D. Suter, Melissa J. BE Tearney, GJ Wang, TD Suter, MJ Lam, S Brenner, M TI A study of airway smooth muscle in asthmatic and non-asthmatic airways using PS-OCT SO ENDOSCOPIC MICROSCOPY XI; AND OPTICAL TECHNIQUES IN PULMONARY MEDICINE III SE Proceedings of SPIE LA English DT Proceedings Paper CT Conference on Endoscopic Microscopy XI and Optical Techniques in Pulmonary Medicine III CY FEB 14-15, 2016 CL San Francisco, CA SP SPIE C1 [Adams, David C.; Holz, Jasmin A.; Szabari, Margit V.; Hariri, Lida P.; Harris, R. Scott; Cho, Jocelyn L.; Hamilos, Daniel L.; Luster, Andrew D.; Medoff, Benjamin D.; Suter, Melissa J.] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Adams, DC (reprint author), Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 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 978-1-62841-925-2 J9 PROC SPIE PY 2016 VL 9691 AR 969111 DI 10.1117/12.2214735 PG 1 WC Optics; Radiology, Nuclear Medicine & Medical Imaging SC Optics; Radiology, Nuclear Medicine & Medical Imaging GA BE8CD UT WOS:000376268400021 ER PT S AU Adams, DC Miller, AJ Holz, JA Szabari, MV Hariri, LP Harris, RS Cho, JL Hamilos, DL Luster, AD Medoff, BD Suter, MJ AF Adams, David C. Miller, Alyssa J. Holz, Jasmin A. Szabari, Margit V. Hariri, Lida P. Harris, R. Scott Cho, Jocelyn L. Hamilos, Daniel L. Luster, Andrew D. Medoff, Benjamin D. Suter, Melissa J. BE Tearney, GJ Wang, TD Suter, MJ Lam, S Brenner, M TI Assessing mucus and airway morphology in response to a segmental allergen challenge using OCT SO ENDOSCOPIC MICROSCOPY XI; AND OPTICAL TECHNIQUES IN PULMONARY MEDICINE III SE Proceedings of SPIE LA English DT Proceedings Paper CT Conference on Endoscopic Microscopy XI and Optical Techniques in Pulmonary Medicine III CY FEB 14-15, 2016 CL San Francisco, CA SP SPIE C1 [Adams, David C.; Miller, Alyssa J.; Holz, Jasmin A.; Szabari, Margit V.; Hariri, Lida P.; Harris, R. Scott; Cho, Jocelyn L.; Hamilos, Daniel L.; Luster, Andrew D.; Medoff, Benjamin D.; Suter, Melissa J.] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Adams, DC (reprint author), Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 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 978-1-62841-925-2 J9 PROC SPIE PY 2016 VL 9691 AR 96910Z DI 10.1117/12.2214756 PG 1 WC Optics; Radiology, Nuclear Medicine & Medical Imaging SC Optics; Radiology, Nuclear Medicine & Medical Imaging GA BE8CD UT WOS:000376268400020 ER PT S AU Cui, D Chu, KK Unglert, CI Ford, TN Carruth, RW Hyun, D Singh, K Birket, SE Solomon, GM Rowe, SM Tearney, GJ AF Cui, Dongyao Chu, Kengyeh K. Unglert, Carolin I. Ford, Timothy N. Carruth, Robert W. Hyun, Daryl Singh, Kanwarpal Birket, Susan E. Solomon, George M. Rowe, Steven M. Tearney, Guillermo J. BE Tearney, GJ Wang, TD Suter, MJ Lam, S Brenner, M TI Flexible micro-OCT endobronchial probe for imaging of mucociliary transport SO ENDOSCOPIC MICROSCOPY XI; AND OPTICAL TECHNIQUES IN PULMONARY MEDICINE III SE Proceedings of SPIE LA English DT Proceedings Paper CT Conference on Endoscopic Microscopy XI and Optical Techniques in Pulmonary Medicine III CY FEB 14-15, 2016 CL San Francisco, CA SP SPIE C1 [Cui, Dongyao; Unglert, Carolin I.; Tearney, Guillermo J.] Wellman Ctr Photomed, Boston, MA USA. [Chu, Kengyeh K.; Ford, Timothy N.; Carruth, Robert W.; Hyun, Daryl; Singh, Kanwarpal] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Birket, Susan E.; Solomon, George M.; Rowe, Steven M.] Gregory Fleming James Cyst Fibrosis Res Ctr, Birmingham, AL USA. RP Cui, D (reprint author), Wellman Ctr Photomed, Boston, MA USA. NR 0 TC 0 Z9 0 U1 2 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 978-1-62841-925-2 J9 PROC SPIE PY 2016 VL 9691 AR 969107 DI 10.1117/12.2213057 PG 1 WC Optics; Radiology, Nuclear Medicine & Medical Imaging SC Optics; Radiology, Nuclear Medicine & Medical Imaging GA BE8CD UT WOS:000376268400002 ER PT S AU Do, D Kang, D Ikuta, M Tearney, GJ AF Do, Dukho Kang, Dongkyun Ikuta, Mitsuhiro Tearney, Guillermo J. BE Tearney, GJ Wang, TD Suter, MJ Lam, S Brenner, M TI Simple, monolithic optical element for forward-viewing spectrally encoded endoscopy SO ENDOSCOPIC MICROSCOPY XI; AND OPTICAL TECHNIQUES IN PULMONARY MEDICINE III SE Proceedings of SPIE LA English DT Proceedings Paper CT Conference on Endoscopic Microscopy XI and Optical Techniques in Pulmonary Medicine III CY FEB 14-15, 2016 CL San Francisco, CA SP SPIE C1 [Do, Dukho; Tearney, Guillermo J.] Wellman Ctr Photomed, Boston, MA 02114 USA. [Kang, Dongkyun] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Ikuta, Mitsuhiro] Canon USA Inc, Irvine, CA USA. RP Do, D (reprint author), Wellman Ctr Photomed, Boston, MA 02114 USA. NR 0 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 978-1-62841-925-2 J9 PROC SPIE PY 2016 VL 9691 AR 96910O DI 10.1117/12.2213394 PG 1 WC Optics; Radiology, Nuclear Medicine & Medical Imaging SC Optics; Radiology, Nuclear Medicine & Medical Imaging GA BE8CD UT WOS:000376268400014 ER PT S AU Do, D Alali, S Kang, D Tabatabaie, N Lu, WN Grant, CN Soomro, AR Nishioka, NS Rosenberg, M Hesterberg, PE Yuan, Q Garber, JJ Katz, AJ Shreffler, WG Tearney, GJ AF Do, Dukho Alali, Sanaz Kang, DongKyun Tabatabaie, Nima Lu, Weina Grant, Catriona N. Soomro, Amna R. Nishioka, Norman S. Rosenberg, Mireille Hesterberg, Paul E. Yuan, Qian Garber, John J. Katz, Aubrey J. Shreffler, Wayne G. Tearney, Guillermo J. BE Tearney, GJ Wang, TD Suter, MJ Lam, S Brenner, M TI Clinical experience using the tethered capsule-based spectrally encoded confocal microendoscopy for diagnosis of eosinophilic esophagitis SO ENDOSCOPIC MICROSCOPY XI; AND OPTICAL TECHNIQUES IN PULMONARY MEDICINE III SE Proceedings of SPIE LA English DT Proceedings Paper CT Conference on Endoscopic Microscopy XI and Optical Techniques in Pulmonary Medicine III CY FEB 14-15, 2016 CL San Francisco, CA SP SPIE C1 [Do, Dukho; Kang, DongKyun; Lu, Weina; Soomro, Amna R.; Rosenberg, Mireille; Tearney, Guillermo J.] Wellman Ctr Photomed, Boston, MA 02114 USA. [Alali, Sanaz; Grant, Catriona N.; Nishioka, Norman S.; Hesterberg, Paul E.; Yuan, Qian; Garber, John J.; Katz, Aubrey J.; Shreffler, Wayne G.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Tabatabaie, Nima] York Univ, N York, ON M3J 1P3, Canada. RP Do, D (reprint author), Wellman Ctr Photomed, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 3 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 978-1-62841-925-2 J9 PROC SPIE PY 2016 VL 9691 AR 96910L DI 10.1117/12.2218559 PG 1 WC Optics; Radiology, Nuclear Medicine & Medical Imaging SC Optics; Radiology, Nuclear Medicine & Medical Imaging GA BE8CD UT WOS:000376268400011 ER PT S AU Dong, J Gora, MJ Reddy, R Trasischker, W Poupart, O Lu, WN Carruth, RW Grant, CN Soomro, AR Tiernan, AR Rosenberg, M Nishioka, NS Tearney, GJ AF Dong, Jing Gora, Michalina J. Reddy, Rohith Trasischker, Wolfgang Poupart, Oriane Lu, Weina Carruth, Robert W. Grant, Catriona N. Soomro, Amna R. Tiernan, Aubrey R. Rosenberg, Mireille Nishioka, Norman S. Tearney, Guillermo J. BE Tearney, GJ Wang, TD Suter, MJ Lam, S Brenner, M TI Tethered capsule OCT endomicroscopy for upper gastrointestinal tract imaging by using ball lens probe SO ENDOSCOPIC MICROSCOPY XI; AND OPTICAL TECHNIQUES IN PULMONARY MEDICINE III SE Proceedings of SPIE LA English DT Proceedings Paper CT Conference on Endoscopic Microscopy XI and Optical Techniques in Pulmonary Medicine III CY FEB 14-15, 2016 CL San Francisco, CA SP SPIE C1 [Dong, Jing; Reddy, Rohith; Trasischker, Wolfgang; Poupart, Oriane; Carruth, Robert W.; Soomro, Amna R.; Rosenberg, Mireille] Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA. [Gora, Michalina J.] CNRS, F-75700 Paris, France. [Lu, Weina; Grant, Catriona N.; Tearney, Guillermo J.] Wellman Ctr Photomed, Boston, MA USA. [Tiernan, Aubrey R.] Harvard Univ, Sch Med, Cambridge, MA 02138 USA. [Nishioka, Norman S.] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Dong, J (reprint author), Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA. NR 0 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 978-1-62841-925-2 J9 PROC SPIE PY 2016 VL 9691 AR 96910R DI 10.1117/12.2213931 PG 1 WC Optics; Radiology, Nuclear Medicine & Medical Imaging SC Optics; Radiology, Nuclear Medicine & Medical Imaging GA BE8CD UT WOS:000376268400015 ER PT S AU Gora, MJ Simmons, LH Tiernan, AR Grant, CN Soomro, AR Corkery, ESW Rosenberg, M Metlay, JP Tearney, GJ AF Gora, Michalina J. Simmons, Leigh H. Tiernan, Aubrey R. Grant, Catriona N. Soomro, Amna R. Corkery, Elizabeth S. Walker Rosenberg, Mireille Metlay, Joshua P. Tearney, Guillermo J. BE Tearney, GJ Wang, TD Suter, MJ Lam, S Brenner, M TI Tethered capsule OCT endomicroscopy: from bench to bedside at the primary care office SO ENDOSCOPIC MICROSCOPY XI; AND OPTICAL TECHNIQUES IN PULMONARY MEDICINE III SE Proceedings of SPIE LA English DT Proceedings Paper CT Conference on Endoscopic Microscopy XI and Optical Techniques in Pulmonary Medicine III CY FEB 14-15, 2016 CL San Francisco, CA SP SPIE C1 [Gora, Michalina J.] CNRS, F-75700 Paris, France. [Simmons, Leigh H.; Corkery, Elizabeth S. Walker; Metlay, Joshua P.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Tiernan, Aubrey R.; Grant, Catriona N.; Soomro, Amna R.; Rosenberg, Mireille; Tearney, Guillermo J.] Wellman Ctr Photomed, Boston, MA USA. RP Gora, MJ (reprint author), CNRS, F-75700 Paris, France. NR 0 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 978-1-62841-925-2 J9 PROC SPIE PY 2016 VL 9691 AR 969106 DI 10.1117/12.2211393 PG 1 WC Optics; Radiology, Nuclear Medicine & Medical Imaging SC Optics; Radiology, Nuclear Medicine & Medical Imaging GA BE8CD UT WOS:000376268400001 ER PT S AU Hariri, LP Adams, DC Miller, AJ Mino-Kenudson, M Suter, MJ AF Hariri, Lida P. Adams, David C. Miller, Alyssa J. Mino-Kenudson, Mari Suter, Melissa J. BE Tearney, GJ Wang, TD Suter, MJ Lam, S Brenner, M TI Using polarization-sensitive optical coherence tomography to identify tumor stromal fibrosis and increase tumor biopsy yield SO ENDOSCOPIC MICROSCOPY XI; AND OPTICAL TECHNIQUES IN PULMONARY MEDICINE III SE Proceedings of SPIE LA English DT Proceedings Paper CT Conference on Endoscopic Microscopy XI and Optical Techniques in Pulmonary Medicine III CY FEB 14-15, 2016 CL San Francisco, CA SP SPIE C1 [Hariri, Lida P.; Adams, David C.; Miller, Alyssa J.; Mino-Kenudson, Mari; Suter, Melissa J.] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Hariri, LP (reprint author), Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 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 978-1-62841-925-2 J9 PROC SPIE PY 2016 VL 9691 AR 96911D DI 10.1117/12.2214662 PG 1 WC Optics; Radiology, Nuclear Medicine & Medical Imaging SC Optics; Radiology, Nuclear Medicine & Medical Imaging GA BE8CD UT WOS:000376268400027 ER PT S AU Hariri, LP Adams, DC Colby, TV Tager, AM Suter, MJ AF Hariri, Lida P. Adams, David C. Colby, Thomas V. Tager, Andrew M. Suter, Melissa J. BE Tearney, GJ Wang, TD Suter, MJ Lam, S Brenner, M TI Assessing idiopathic pulmonary fibrosis (IPF) with bronchoscopic OCT SO ENDOSCOPIC MICROSCOPY XI; AND OPTICAL TECHNIQUES IN PULMONARY MEDICINE III SE Proceedings of SPIE LA English DT Proceedings Paper CT Conference on Endoscopic Microscopy XI and Optical Techniques in Pulmonary Medicine III CY FEB 14-15, 2016 CL San Francisco, CA SP SPIE C1 [Hariri, Lida P.; Adams, David C.; Tager, Andrew M.; Suter, Melissa J.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Colby, Thomas V.] Mayo Clin Arizona, Phoenix, AZ USA. RP Hariri, LP (reprint author), Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 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 978-1-62841-925-2 J9 PROC SPIE PY 2016 VL 9691 AR 96911B DI 10.1117/12.2214663 PG 1 WC Optics; Radiology, Nuclear Medicine & Medical Imaging SC Optics; Radiology, Nuclear Medicine & Medical Imaging GA BE8CD UT WOS:000376268400026 ER PT S AU Hariri, LP Niederst, MJ Mulvey, H Adams, DC Hu, HC Chico-Calero, I Szabari, MV Vakoc, BJ Hasan, T Bouma, BE Engelman, JA Suter, MJ AF Hariri, Lida P. Niederst, Matthew J. Mulvey, Hillary Adams, David C. Hu, Haichuan Chico-Calero, Isabel Szabari, Margit V. Vakoc, Benjamin J. Hasan, Tayyaba Bouma, Brett E. Engelman, Jeffrey A. Suter, Melissa J. BE Tearney, GJ Wang, TD Suter, MJ Lam, S Brenner, M TI Multimodal imaging of lung cancer and its microenvironment SO ENDOSCOPIC MICROSCOPY XI; AND OPTICAL TECHNIQUES IN PULMONARY MEDICINE III SE Proceedings of SPIE LA English DT Proceedings Paper CT Conference on Endoscopic Microscopy XI and Optical Techniques in Pulmonary Medicine III CY FEB 14-15, 2016 CL San Francisco, CA SP SPIE C1 [Hariri, Lida P.; Niederst, Matthew J.; Mulvey, Hillary; Adams, David C.; Hu, Haichuan; Chico-Calero, Isabel; Szabari, Margit V.; Vakoc, Benjamin J.; Hasan, Tayyaba; Bouma, Brett E.; Engelman, Jeffrey A.; Suter, Melissa J.] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Hariri, LP (reprint author), Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 1 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 978-1-62841-925-2 J9 PROC SPIE PY 2016 VL 9691 AR 96911F DI 10.1117/12.2214658 PG 1 WC Optics; Radiology, Nuclear Medicine & Medical Imaging SC Optics; Radiology, Nuclear Medicine & Medical Imaging GA BE8CD UT WOS:000376268400029 ER PT S AU Kang, D Kim, M Carruth, RW Lu, WN Wu, T Alali, S Do, D Soomro, AR Grant, CN Tiernan, AR Rosenberg, M Nishioka, NS Tearney, GJ AF Kang, DongKyun Kim, Minkyu Carruth, Robert W. Lu, Weina Wu, Tao Alali, Sanaz Do, Dukho Soomro, Amna R. Grant, Catriona N. Tiernan, Aubrey R. Rosenberg, Mireille Nishioka, Norman S. Tearney, Guillermo J. BE Tearney, GJ Wang, TD Suter, MJ Lam, S Brenner, M TI SECM half-inch tethered endoscopic capsule (HITEC) for esophageal imaging SO ENDOSCOPIC MICROSCOPY XI; AND OPTICAL TECHNIQUES IN PULMONARY MEDICINE III SE Proceedings of SPIE LA English DT Proceedings Paper CT Conference on Endoscopic Microscopy XI and Optical Techniques in Pulmonary Medicine III CY FEB 14-15, 2016 CL San Francisco, CA SP SPIE C1 [Kang, DongKyun; Kim, Minkyu; Carruth, Robert W.; Lu, Weina; Wu, Tao; Alali, Sanaz; Do, Dukho; Soomro, Amna R.; Grant, Catriona N.; Tiernan, Aubrey R.; Rosenberg, Mireille; Nishioka, Norman S.; Tearney, Guillermo J.] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Kang, D (reprint author), Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 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 978-1-62841-925-2 J9 PROC SPIE PY 2016 VL 9691 AR 96910M DI 10.1117/12.2208942 PG 1 WC Optics; Radiology, Nuclear Medicine & Medical Imaging SC Optics; Radiology, Nuclear Medicine & Medical Imaging GA BE8CD UT WOS:000376268400012 ER PT S AU Szabari, MV Miller, AJ Hariri, LP Hamblin, MR Musch, G Stroh, H Suter, MJ AF Szabari, Margit V. Miller, Alyssa J. Hariri, Lida P. Hamblin, Michael R. Musch, Guido Stroh, Helene Suter, Melissa J. BE Tearney, GJ Wang, TD Suter, MJ Lam, S Brenner, M TI The effect of low level laser therapy on ventilator-induced lung injury in mice SO ENDOSCOPIC MICROSCOPY XI; AND OPTICAL TECHNIQUES IN PULMONARY MEDICINE III SE Proceedings of SPIE LA English DT Proceedings Paper CT Conference on Endoscopic Microscopy XI and Optical Techniques in Pulmonary Medicine III CY FEB 14-15, 2016 CL San Francisco, CA SP SPIE C1 [Szabari, Margit V.; Miller, Alyssa J.; Hariri, Lida P.; Hamblin, Michael R.; Musch, Guido; Stroh, Helene; Suter, Melissa J.] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Szabari, MV (reprint author), Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 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 978-1-62841-925-2 J9 PROC SPIE PY 2016 VL 9691 AR 969115 DI 10.1117/12.2214731 PG 1 WC Optics; Radiology, Nuclear Medicine & Medical Imaging SC Optics; Radiology, Nuclear Medicine & Medical Imaging GA BE8CD UT WOS:000376268400023 ER PT S AU Szabari, MV Kelly, VJ Applegate, MB Chee, C Tan, KM Hariri, LP Harris, RS Winkler, T Suter, MJ AF Szabari, Margit V. Kelly, Vanessa J. Applegate, Matthew B. Chee, Chunmin Tan, Khay M. Hariri, Lida P. Harris, R. Scott Winkler, Tilo Suter, Melissa J. BE Tearney, GJ Wang, TD Suter, MJ Lam, S Brenner, M TI Using optical coherence tomography (OCT) imaging in the evaluation of airway dynamics SO ENDOSCOPIC MICROSCOPY XI; AND OPTICAL TECHNIQUES IN PULMONARY MEDICINE III SE Proceedings of SPIE LA English DT Proceedings Paper CT Conference on Endoscopic Microscopy XI and Optical Techniques in Pulmonary Medicine III CY FEB 14-15, 2016 CL San Francisco, CA SP SPIE C1 [Szabari, Margit V.; Kelly, Vanessa J.; Applegate, Matthew B.; Chee, Chunmin; Tan, Khay M.; Hariri, Lida P.; Harris, R. Scott; Winkler, Tilo; Suter, Melissa J.] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Szabari, MV (reprint author), Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 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 978-1-62841-925-2 J9 PROC SPIE PY 2016 VL 9691 AR 969112 DI 10.1117/12.2216306 PG 1 WC Optics; Radiology, Nuclear Medicine & Medical Imaging SC Optics; Radiology, Nuclear Medicine & Medical Imaging GA BE8CD UT WOS:000376268400022 ER PT J AU Tu, CY Santo, L Mishima, Y Raje, N Smilansky, Z Zoldan, J AF Tu, Chengyi Santo, Loredana Mishima, Yuko Raje, Noopur Smilansky, Zeev Zoldan, Janet TI Monitoring protein synthesis in single live cancer cells SO INTEGRATIVE BIOLOGY LA English DT Article ID LABELED TRANSFER-RNA; PROTEASOME INHIBITION; INTRACELLULAR DELIVERY; MYELOMA CELLS; PHOSPHORYLATION; APOPTOSIS; EIF2-ALPHA; PLATFORM; STRESS; SUNSET AB Protein synthesis is generally under sophisticated and dynamic regulation to meet the ever-changing demands of a cell. Global up or down-regulation of protein synthesis and the shift of protein synthesis location (as shown, for example, during cellular stress or viral infection) are recognized as cellular responses to environmental changes such as nutrient/oxygen deprivation or to alterations such as pathological mutations in cancer cells. Monitoring protein synthesis in single live cells can be a powerful tool for cancer research. Here we employed a microfluidic platform to perform high throughput delivery of fluorescent labeled tRNAs into multiple myeloma cells with high transfection efficiency (similar to 45%) and high viability (>80%). We show that the delivered tRNAs were actively recruited to the ER for protein synthesis and that treatment with puromycin effectively disrupted this process. Interestingly, we observed the scattered distribution of tRNAs in cells undergoing mitosis, which has not been previously reported. Fluorescence lifetime analysis detected extensive FRET signals generated from tRNAs labeled as FRET pairs, further confirming that the delivered tRNAs were used by active ribosomes for protein translation. Our work demonstrates that the microfluidic delivery of FRET labeled tRNAs into living cancer cells can provide new insights into basic cancer metabolism and has the potential to serve as a platform for drug screening, diagnostics, or personalized medication. C1 [Tu, Chengyi; Zoldan, Janet] Univ Texas Austin, Dept Biomed Engn, Austin, TX 78712 USA. [Santo, Loredana; Mishima, Yuko; Raje, Noopur] Harvard Univ, Sch Med, Boston, MA USA. [Santo, Loredana; Mishima, Yuko; Raje, Noopur] Massachusetts Gen Hosp, Ctr Multiple Myeloma, Boston, MA 02114 USA. [Smilansky, Zeev] Anima Cell Metrol, Bernardsville, NJ USA. RP Zoldan, J (reprint author), Univ Texas Austin, Dept Biomed Engn, Austin, TX 78712 USA. EM zjanet@utexas.edu FU Anima Cell Metrology, Ltd. FX Z. S. has a financial interest in Anima Cell Metrology, Ltd. NR 25 TC 0 Z9 0 U1 7 U2 11 PU ROYAL SOC CHEMISTRY PI CAMBRIDGE PA THOMAS GRAHAM HOUSE, SCIENCE PARK, MILTON RD, CAMBRIDGE CB4 0WF, CAMBS, ENGLAND SN 1757-9694 EI 1757-9708 J9 INTEGR BIOL-UK JI Integr. Biol. PY 2016 VL 8 IS 5 BP 645 EP 653 DI 10.1039/c5ib00279f PG 9 WC Cell Biology SC Cell Biology GA DM1CW UT WOS:000376083700007 PM 26956582 ER PT J AU Bagnall, JS Byun, S Miyamoto, DT Kang, JH Maheswaran, S Stott, SL Toner, M Manalis, SR AF Bagnall, Josephine Shaw Byun, Sangwon Miyamoto, David T. Kang, Joon Ho Maheswaran, Shyamala Stott, Shannon L. Toner, Mehmet Manalis, Scott R. TI Deformability-based cell selection with downstream immunofluorescence analysis SO INTEGRATIVE BIOLOGY LA English DT Article ID CIRCULATING TUMOR-CELLS; ATOMIC-FORCE MICROSCOPE; LIVING CELLS; TRACKING MICRORHEOLOGY; PROSTATE-CANCER; FLOW-CYTOMETRY; SINGLE CELLS; LUNG-CANCER; BLOOD-CELLS; SIZE AB Mechanical properties of single cells have been shown to relate to cell phenotype and malignancy. However, until recently, it has been difficult to directly correlate each cell's biophysical characteristics to its molecular traits. Here, we present a cell sorting technique for use with a suspended microchannel resonator (SMR), which can measure biophysical characteristics of a single cell based on the sensor's record of its buoyant mass as well as its precise position while it traverses through a constricted microfluidic channel. The measurement provides information regarding the amount of time a cell takes to pass through a constriction (passage time), as related to the cell's deformability and surface friction, as well as the particular manner in which it passes through. In the method presented here, cells of interest are determined based on passage time, and are collected off-chip for downstream immunofluorescence imaging. The biophysical single-cell SMR measurement can then be correlated to the molecular expression of the collected cell. This proof-of-principle is demonstrated by sorting and collecting tumor cells from cell line-spiked blood samples as well as a metastatic prostate cancer patient blood sample, identifying them by their surface protein expression and relating them to distinct SMR signal trajectories. C1 [Bagnall, Josephine Shaw; Byun, Sangwon; Manalis, Scott R.] MIT, Dept Biol Engn, 77 Massachusetts Ave, Cambridge, MA 02139 USA. [Miyamoto, David T.; Maheswaran, Shyamala; Stott, Shannon L.] Harvard Univ, Massachusetts Gen Hosp, Ctr Canc, Sch Med, Boston, MA 02114 USA. [Miyamoto, David T.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiat Oncol, Boston, MA USA. [Kang, Joon Ho] MIT, Dept Phys, Cambridge, MA 02139 USA. [Maheswaran, Shyamala; Toner, Mehmet] Harvard Univ, Sch Med, Dept Surg, Massachusetts Gen Hosp, Boston, MA 02115 USA. [Stott, Shannon L.] Harvard Univ, Sch Med, Dept Med, Massachusetts Gen Hosp, Boston, MA USA. [Stott, Shannon L.; Toner, Mehmet] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Engn & Med, Boston, MA USA. [Manalis, Scott R.] MIT, Dept Mech Engn, Cambridge, MA 02139 USA. [Manalis, Scott R.] MIT, Koch Inst Integrat Canc Res, 77 Massachusetts Ave, Cambridge, MA 02139 USA. [Byun, Sangwon] Elect & Telecommun Res Inst, Biomed IT Convergence Res Dept, Daejeon, South Korea. RP Manalis, SR (reprint author), MIT, Dept Biol Engn, 77 Massachusetts Ave, Cambridge, MA 02139 USA.; Manalis, SR (reprint author), MIT, Dept Mech Engn, Cambridge, MA 02139 USA.; Manalis, SR (reprint author), MIT, Koch Inst Integrat Canc Res, 77 Massachusetts Ave, Cambridge, MA 02139 USA. EM srm@mit.edu FU Janssen Pharmaceuticals, Inc.; Physical Sciences Oncology Center [U54CA143874]; CCNE-T [26697290-47281-A]; Stand Up to Cancer; National Institute of Health P41 Biotechnology Resource Center and Quantum Grant [EB008047]; Koch Institute Support Grant from the National Cancer Institute [P30-CA14051] FX We thank Nathan Cermak for providing the basis and groundwork for the LABVIEW code used in the presented method. We also thank Katherine Broderick and Wooseok Kim for preparing and processing the tumor cell line-spiked blood samples, the metastatic prostate cancer patient blood sample, as well as some healthy donor blood samples in the CTC-iChip. We are grateful to Philipp Spuhler for processing healthy donor blood samples in the CTC-iChip. We appreciate the patient and healthy blood donors who participated in this work. We are also thankful to the Koch Institute Swanson Biotechnology Center, including Eliza Vasile at the Microscopy Core Facility. This work was supported by Janssen Pharmaceuticals, Inc., Physical Sciences Oncology Center U54CA143874, CCNE-T grant 26697290-47281-A, Stand Up to Cancer, National Institute of Health P41 Biotechnology Resource Center and Quantum Grant (EB008047), and Koch Institute Support Grant P30-CA14051 from the National Cancer Institute. NR 52 TC 1 Z9 1 U1 4 U2 8 PU ROYAL SOC CHEMISTRY PI CAMBRIDGE PA THOMAS GRAHAM HOUSE, SCIENCE PARK, MILTON RD, CAMBRIDGE CB4 0WF, CAMBS, ENGLAND SN 1757-9694 EI 1757-9708 J9 INTEGR BIOL-UK JI Integr. Biol. PY 2016 VL 8 IS 5 BP 654 EP 664 DI 10.1039/c5ib00284b PG 11 WC Cell Biology SC Cell Biology GA DM1CW UT WOS:000376083700008 ER PT S AU Beca, F Polyak, K AF Beca, Francisco Polyak, Kornelia BE Stearns, V TI Intratumor Heterogeneity in Breast Cancer SO NOVEL BIOMARKERS IN THE CONTINUUM OF BREAST CANCER SE Advances in Experimental Medicine and Biology LA English DT Article; Book Chapter DE Heterogeneity; Breast cancer; Evolution; Selection; Clonality; Phenotype; Therapy; Resistance; Progression ID IN-SITU HYBRIDIZATION; DNA METHYLATION PROFILES; MESSENGER-RNA MOLECULES; TUMOR HETEROGENEITY; GENE-EXPRESSION; CLINICAL ONCOLOGY/COLLEGE; AMERICAN SOCIETY; CLONAL EVOLUTION; CELL; AMPLIFICATION AB Intratumor heterogeneity is the main obstacle to effective cancer treatment and personalized medicine. Both genetic and epigenetic sources of intratumor heterogeneity are well recognized and several technologies have been developed for their characterization. With the technological advances in recent years, investigators are now elucidating intratumor heterogeneity at the single cell level and in situ. However, translating the accumulated knowledge about intratumor heterogeneity to clinical practice has been slow. We are certain that better understanding of the composition and evolution of tumors during disease progression and treatment will improve cancer diagnosis and the design of therapies. Here we review some of the most important considerations related to intratumor heterogeneity. We discuss both genetic and epigenetic sources of intratumor heterogeneity and review experimental approaches that are commonly used to quantify it. We also discuss the impact of intratumor heterogeneity on cancer diagnosis and treatment and share our perspectives on the future of this field. C1 [Beca, Francisco; Polyak, Kornelia] Dana Farber Canc Inst, Dept Med Oncol, 450 Brookline Ave D740, Boston, MA 02215 USA. [Beca, Francisco] Univ Porto, IPATIMUP Inst Mol Pathol & Immunol, Rua Campo Alegre 823, P-4100 Oporto, Portugal. [Polyak, Kornelia] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. [Polyak, Kornelia] Brigham & Womens Hosp, Dept Med, 75 Francis St, Boston, MA 02115 USA. RP Beca, F (reprint author), Dana Farber Canc Inst, Dept Med Oncol, 450 Brookline Ave D740, Boston, MA 02215 USA. EM francisco.beca@hms.harvard.edu; kornelia_polyak@dfci.harvard.edu OI Beca, Francisco/0000-0002-4409-012X NR 93 TC 7 Z9 7 U1 2 U2 5 PU SPRINGER INT PUBLISHING AG PI CHAM PA GEWERBESTRASSE 11, CHAM, CH-6330, SWITZERLAND SN 0065-2598 BN 978-3-319-22909-6; 978-3-319-22908-9 J9 ADV EXP MED BIOL JI Adv.Exp.Med.Biol. PY 2016 VL 882 BP 169 EP 189 DI 10.1007/978-3-319-22909-6_7 D2 10.1007/978-3-319-22909-6 PG 21 WC Oncology; Medicine, Research & Experimental SC Oncology; Research & Experimental Medicine GA BE7YE UT WOS:000376034700008 PM 26987535 ER PT J AU Gao, BS Rong, CS Porcheray, F Moore, C Girouard, TC Saidman, SL Wong, WC Fu, YW Zorn, E AF Gao, Baoshan Rong, Chunshu Porcheray, Fabrice Moore, Carolina Girouard, Timothy C. Saidman, Susan L. Wong, Waichi Fu, Yaowen Zorn, Emmanuel TI Evidence to Support a Contribution of Polyreactive Antibodies to HLA Serum Reactivity SO TRANSPLANTATION LA English DT Article ID APOPTOTIC CELLS; KIDNEY GRAFTS; B-CELLS; DONOR; TRANSPLANTATION; REJECTION; EPITOPES AB Background Assessing the serum reactivity to HLA is essential for the evaluation of transplant candidates and the follow-up of allograft recipients. In this study, we look for evidence at the clonal level that polyreactive antibodies cross-reactive to apoptotic cells and multiple autoantigens can also react to HLA and contribute to the overall serum reactivity. Methods We immortalized B cell clones from the blood of 2 kidney transplant recipients and characterized their reactivity to self-antigens, apoptotic cells as well as native, denatured, and cryptic HLA determinants using enzyme-linked immunosorbent assay (ELISA), immunofluorescence, flow cytometry and Luminex assays. We also assessed the reactivity of 300 pretransplant serum specimens to HLA and apoptotic cells. Results We report here 4 distinct B cell clones cross-reactive to self and HLA class I. All 4 clones reacted to numerous HLA class I alleles but did not appear to target canonical shared epitopes. In parallel experiments, we observed a strong correlation between IgG reactivity to HLA and apoptotic cells in pretransplant serum samples collected from 300 kidney transplant recipients. Further analysis revealed that samples with higher reactivity to apoptotic cells displayed significantly higher class I percent panel-reactive antibodies compared to samples with low reactivity to apoptotic cells. Conclusions We provide here (1) proof of principle at the clonal level that human polyreactive antibodies can cross-react to HLA, multiple self-antigens and apoptotic cells and (2) supportive evidence that polyreactive antibodies contribute to overall HLA reactivity in the serum of patients awaiting kidney transplant. C1 [Gao, Baoshan; Rong, Chunshu; Porcheray, Fabrice; Moore, Carolina; Zorn, Emmanuel] Harvard Univ, Sch Med, Dept Surg, Transplant Ctr,Massachusetts Gen Hosp, Boston, MA 02115 USA. [Gao, Baoshan; Fu, Yaowen] Jilin Univ, Hosp 1, Transplant Ctr, Changchun 130023, Peoples R China. [Rong, Chunshu] Changchun Univ Chinese Med, Affiliated Hosp, Changchun, Peoples R China. [Girouard, Timothy C.; Wong, Waichi] Columbia Univ, New York Presbyterian Hosp, Med Ctr, Div Nephrol, New York, NY USA. [Saidman, Susan L.] Harvard Univ, Sch Med, Dept Pathol, Massachusetts Gen Hosp, Boston, MA 02115 USA. RP Zorn, E (reprint author), Columbia Univ, Med Ctr, Columbia Ctr Translat Immunol, 630 West 168th St,Black Bldg,Mailbox 127, New York, NY 10032 USA. EM ez2184@cumc.columbia.edu FU Roche Organ Transplantation Research Foundation (ROTRF); National Institute of Health, National Institute of Diabetes, Digestive and Kidney Diseases [DK083352] FX This work was supported by the Roche Organ Transplantation Research Foundation (ROTRF) and the National Institute of Health, National Institute of Diabetes, Digestive and Kidney Diseases Grant DK083352. NR 23 TC 4 Z9 4 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0041-1337 EI 1534-6080 J9 TRANSPLANTATION JI Transplantation PD JAN PY 2016 VL 100 IS 1 BP 217 EP 226 DI 10.1097/TP.0000000000000840 PG 10 WC Immunology; Surgery; Transplantation SC Immunology; Surgery; Transplantation GA DA7NA UT WOS:000367989800005 PM 26285015 ER PT J AU Chen, H Ding, P Geng, Z Zhou, XH AF Chen, Hua Ding, Peng Geng, Zhi Zhou, Xiao-Hua TI Semiparametric Inference of the Complier Average Causal Effect with Nonignorable Missing Outcomes SO ACM TRANSACTIONS ON INTELLIGENT SYSTEMS AND TECHNOLOGY LA English DT Article DE Experimentation; Measurement; Theory; Causal inference; instrumental variable; missing not at random; noncompliance; outcome-dependent missing; principal stratification ID RANDOMIZED EXPERIMENTS; PRINCIPAL STRATIFICATION; TREATMENT-NONCOMPLIANCE; ENCOURAGEMENT DESIGN; CLINICAL-TRIALS; IDENTIFIABILITY; LIKELIHOOD AB Noncompliance and missing data often occur in randomized trials, which complicate the inference of causal effects. When both noncompliance and missing data are present, previous papers proposed moment and maximum likelihood estimators for binary and normally distributed continuous outcomes under the latent ignorable missing data mechanism. However, the latent ignorable missing data mechanism may be violated in practice, because the missing data mechanism may depend directly on the missing outcome itself. Under noncompliance and an outcome-dependent nonignorable missing data mechanism, previous studies showed the identifiability of complier average causal effect for discrete outcomes. In this article, we study the semiparametric identifiability and estimation of complier average causal effect in randomized clinical trials with both all-or-none noncompliance and outcome-dependent nonignorable missing continuous outcomes, and propose a two-step maximum likelihood estimator in order to eliminate the infinite dimensional nuisance parameter. Our method does not need to specify a parametric form for the missing data mechanism. We also evaluate the finite sample property of our method via extensive simulation studies and sensitivity analysis, with an application to a double-blinded psychiatric clinical trial. C1 [Chen, Hua] Inst Appl Phys & Computat Math, POB 8009, Beijing 100088, Peoples R China. [Ding, Peng] Univ Calif Berkeley, Dept Stat, Berkeley, CA 94720 USA. [Geng, Zhi] Peking Univ, Sch Math Sci, Beijing 100871, Peoples R China. [Zhou, Xiao-Hua] Univ Washington, Dept Biostat, Seattle, WA 98101 USA. [Zhou, Xiao-Hua] VA Puget Sound Hlth Care Syst, HSR&D Ctr Excellence, Biostat Unit, Seattle, WA 98101 USA. RP Chen, H (reprint author), Inst Appl Phys & Computat Math, POB 8009, Beijing 100088, Peoples R China.; Ding, P (reprint author), Univ Calif Berkeley, Dept Stat, Berkeley, CA 94720 USA.; Geng, Z (reprint author), Peking Univ, Sch Math Sci, Beijing 100871, Peoples R China.; Zhou, XH (reprint author), Univ Washington, Dept Biostat, Seattle, WA 98101 USA.; Zhou, XH (reprint author), VA Puget Sound Hlth Care Syst, HSR&D Ctr Excellence, Biostat Unit, Seattle, WA 98101 USA. EM chen_hua@iapcm.ac.cn; pengdingpku@gmail.com; zhigeng@pku.edu.cn; azhou@uw.edu FU NSFC [11101045, 11021463, 10931002, 11171365]; CAEP [2012A0201011, 2013A0101004]; Department of Veterans Affairs HSRD RCS Award [05-196] FX Chen's research was supported in part by NSFC 11101045, CAEP 2012A0201011 and CAEP 2013A0101004. Geng's research was supported by NSFC 11021463, 10931002, and 11171365. Zhou's research was supported in part by the Department of Veterans Affairs HSR&D RCS Award 05-196. It does not necessarily represent the views of the VA HSR&D Service. NR 21 TC 0 Z9 0 U1 1 U2 1 PU ASSOC COMPUTING MACHINERY PI NEW YORK PA 2 PENN PLAZA, STE 701, NEW YORK, NY 10121-0701 USA SN 2157-6904 EI 2157-6912 J9 ACM T INTEL SYST TEC JI ACM Trans. Intell. Syst. Technol. PD JAN PY 2016 VL 7 IS 2 SI SI AR 19 DI 10.1145/2668135 PG 15 WC Computer Science, Artificial Intelligence; Computer Science, Information Systems SC Computer Science GA DJ8FB UT WOS:000374446800007 ER PT J AU Esaki, S Rabkin, SD Martuza, RL Wakimoto, H AF Esaki, Shinichi Rabkin, Samuel D. Martuza, Robert L. Wakimoto, Hiroaki TI Transient fasting enhances replication of oncolytic herpes simplex virus in glioblastoma SO AMERICAN JOURNAL OF CANCER RESEARCH LA English DT Article DE Oncolytic HSV; fasting; glioblastoma; JNK; eIF2 alpha; mTOR ID N-TERMINAL KINASE; MALIGNANT GLIOMA; CANCER-TREATMENT; BRAIN-TUMORS; ACTIVATION; THERAPY; CELLS; RESISTANCE; APOPTOSIS; PROTEIN AB Short-term nutritional restriction (fasting) has been shown to enhance the efficacy of chemotherapy by sensitizing cancer cells and protecting normal cells in a variety of cancer models, including glioblastoma (GBM). Cancer cells, unlike normal cells, respond to fasting by promoting oncogenic signaling and protein synthesis. We hypothesized that fasting would increase the replication of oncolytic herpes simplex virus (oHSV) in GBM. Patient-derived GBM cell lines were fasted by growth in glucose and fetal calf serum restricted culture medium. "Transient fasting", 24-hour fasting followed by 24-hour recovery in complete medium, increased late virus gene expression and G47 Delta yields about 2-fold in GBM cells, but not in human astrocytes, and enhanced G47 Delta killing of GBM cells. Mechanistically, "transient fasting" suppressed phosphorylation of the subunit of eukaryotic initiation factor 2 alpha (eIF2 alpha) and c-Jun N-terminal kinases (JNK) in GBM cells, but not in astrocytes. Pharmacological inhibition of JNK also increased G47 Delta yield. In vivo, transient fasting (48-hour food restriction and 24-hour recovery) doubled luciferase activity after intratumoral G47 Delta-US11fluc injection into orthotopic GBM xenografts. Thus, "transient fasting" increases G47 Delta replication and oncolytic activity in human GBM cells. These results suggest that "transient fasting" may be effectively combined to enhance oncolytic HSV therapy of GBM. C1 [Esaki, Shinichi; Rabkin, Samuel D.; Martuza, Robert L.; Wakimoto, Hiroaki] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Neurosurg, Boston, MA 02114 USA. [Esaki, Shinichi] Nagoya City Univ, Grad Sch Med Sci, Dept Otolaryngol Head & Neck Surg, Nagoya, Aichi, Japan. [Esaki, Shinichi] Sch Med, Nagoya, Aichi, Japan. RP Wakimoto, H (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Neurosurg, Boston, MA 02114 USA. EM hwakimo-to@mgh.harvard.edu FU National Institutes of Health [R01CA160-762, R01NS032677]; Japan Herpesvirus Infections Forum Scholarship FX These studies were supported in part by National Institutes of Health Grants R01CA160-762 (S.D.R.), R01NS032677 (R.L.M.), and Japan Herpesvirus Infections Forum Scholarship (S.E.). The authors thank John Chen and Greg Wojtkiewicz (Center for Systems Biology, MGH) for bioluminescence imaging. NR 34 TC 1 Z9 1 U1 1 U2 1 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 2016 VL 6 IS 2 BP 300 EP 311 PG 12 WC Oncology SC Oncology GA DJ4ZO UT WOS:000374216800014 PM 27186404 ER PT J AU Fong, ZV Patel, MS Yeh, H Markmann, JF Vagefi, PA AF Fong, Zhi Ven Patel, Madhukar S. Yeh, Heidi Markmann, James F. Vagefi, Parsia A. TI Liver transplantation utilizing a severely fractured graft: every organ counts SO ANNALS OF HEPATOLOGY LA English DT Article DE Liver trauma; Liver transplantation; Organ pool expansion ID TRAUMA; DONOR AB In our current era where shortage of liver grafts is commonplace, utilization of traumatic liver grafts may represent an opportunity to expand the organ donor pool without compromising graft survival. However, data on liver transplantation using a fractured liver allograt is scarce, with only small case series and reports found in the literature. In this report, we describe our experience with utilizing a liver graft with grade IV hepatic fracture for transplantation. At 12 months follow up, the recipient has excellent graft function and has regained an excellent quality of life. We demonstrate that the ability to safely use a fractured liver graft represents an additional avenue for expansion of the deceased donor population; especially in regions with prolonged waitlist times. C1 [Fong, Zhi Ven; Patel, Madhukar S.; Yeh, Heidi; Markmann, James F.; Vagefi, Parsia A.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Transplant Surg,Dept Surg, Boston, MA USA. RP Vagefi, PA (reprint author), Massachusetts Gen Hosp, Liver Transplantat, 55 Fruit St, Boston, MA 02114 USA. EM pvagefi@mgh.harvard.edu NR 4 TC 0 Z9 0 U1 0 U2 0 PU MEXICAN ASSOC HEPATOLOGY PI MEXICO PA PUNTE DE PIEDRA 150, COLONIA TORIELLO GUERRA, MEXICO, DF CP 14040, MEXICO SN 1665-2681 J9 ANN HEPATOL JI Ann. Hepatol. PD JAN-FEB PY 2016 VL 15 IS 1 BP 131 EP 134 DI 10.5604/16652681.1184290 PG 4 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA DL8KD UT WOS:000375890000017 PM 26626650 ER PT J AU Whalen, K Bavuso, K Bouyer-Ferullo, S Goldsmith, D Fairbanks, A Gesner, E Lagor, C Collins, S AF Whalen, Kimberly Bavuso, Karen Bouyer-Ferullo, Sharon Goldsmith, Denise Fairbanks, Amanda Gesner, Emily Lagor, Charles Collins, Sarah TI Analysis of Nursing Clinical Decision Support Requests and Strategic Plan in a Large Academic Health System SO APPLIED CLINICAL INFORMATICS LA English DT Article DE Electronic health records; evidence-based nursing; hospital information systems; clinical decision support; nursing informatics ID INFORMATICS; WISDOM AB Objectives: To understand requests for nursing Clinical Decision Support (CDS) interventions at a large integrated health system undergoing vendor-based EHR implementation. In addition, to establish a process to guide both short-term implementation and long-term strategic goals to meet nursing CDS needs. Materials and Methods: We conducted an environmental scan to understand current state of nursing CDS over three months. The environmental scan consisted of a literature review and an analysis of CDS requests received from across our health system. We identified existing high priority CDS and paper-based tools used in nursing practice at our health system that guide decision-making. Results: A total of 46 nursing CDS requests were received. Fifty-six percent (n=26) were specific to a clinical specialty; 22 percent (n= 10) were focused on facilitating clinical consults in the inpatient setting. "Risk Assessments/Risk Reduction/Promotion of Healthy Habits" (n=23) was the most requested High Priority Category received for nursing CDS. A continuum of types of nursing CDS needs emerged using the Data-Information-Knowledge-Wisdom Conceptual Framework: 1) facilitating data capture, 2) meeting information needs, 3) guiding knowledge-based decision making, and 4) exposing analytics for wisdom-based clinical interpretation by the nurse. Conclusion: Identifying and prioritizing paper-based tools that can be modified into electronic CDS is a challenge. CDS strategy is an evolving process that relies on close collaboration and engagement with clinical sites for short-term implementation and should be incorporated into a long-term strategic plan that can be optimized and achieved overtime. The Data-Information-Knowledge-Wisdom Conceptual Framework in conjunction with the High Priority Categories established may be a useful tool to guide a strategic approach for meeting short-term nursing CDS needs and aligning with the organizational strategic plan. C1 [Whalen, Kimberly] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Bavuso, Karen; Bouyer-Ferullo, Sharon; Fairbanks, Amanda; Gesner, Emily; Lagor, Charles; Collins, Sarah] Partners Healthcare Syst, Wellesley, MA USA. [Goldsmith, Denise; Collins, Sarah] Brigham & Womens Hosp, 75 Francis St, Boston, MA 02115 USA. [Collins, Sarah] Harvard Univ, Sch Med, Boston, MA USA. [Whalen, Kimberly] Univ Colorado, Denver, CO 80202 USA. RP Whalen, K (reprint author), Massachusetts Gen Hosp, Boston, MA 02114 USA. EM Kwhalen3@partners.org NR 16 TC 0 Z9 0 U1 3 U2 4 PU SCHATTAUER GMBH-VERLAG MEDIZIN NATURWISSENSCHAFTEN PI STUTTGART PA HOLDERLINSTRASSE 3, D-70174 STUTTGART, GERMANY SN 1869-0327 J9 APPL CLIN INFORM JI Appl. Clin. Inform. PY 2016 VL 7 IS 2 BP 227 EP 237 DI 10.4338/ACI-2015-10-RA-0128 PG 11 WC Medical Informatics SC Medical Informatics GA DL5KT UT WOS:000375676600002 PM 27437036 ER PT J AU Burgess, BJ O'Malley, JT Kamakura, T Kristiansen, K Robertson, NG Morton, CC Nadol, JB AF Burgess, Barbara J. O'Malley, Jennifer T. Kamakura, Takefumi Kristiansen, Kris Robertson, Nahid G. Morton, Cynthia C. Nadol, Joseph B., Jr. TI Histopathology of the Human Inner Ear in the p.L114P COCH Mutation (DFNA9) SO AUDIOLOGY AND NEURO-OTOLOGY LA English DT Article DE Histopathology; Human inner ear; p.L114P COCH mutation; DFNA9; Immunostaining; Cochlear implant ID SENSORINEURAL HEARING-LOSS; TEMPORAL BONE FINDINGS; VESTIBULAR DISORDER; DEAFNESS; DYSFUNCTION; LOCALIZATION; SECRETION; DEPOSITS AB The histopathology of the inner ear in a patient with hearing loss caused by the p.L114P COCH mutation and its correlation with the clinical phenotype are presented. To date, 23 COCH mutations causative of DFNA9 autosomal dominant sensorineural hearing loss and vestibular disorder have been reported, and the histopathology of the human inner ear has been described in 4 of these. The p.L114P COCH mutation was first described in a Korean family. We have identified the same mutation in a family of non-Asian ancestry in the USA, and the temporal bone histopathology and clinical findings are presented herein. The histopathology found in the inner ear was similar to that shown in the 4 other COCH mutations and included degeneration of the spiral ligament with deposition of an eosinophilic acellular material, which was also found in the distal osseous spiral lamina, at the base of the spiral limbus, and in mesenchymal tissue at the base of the vestibular neuroepithelium. This is the first description of human otopathology of the COCH p.L114P mutation. In addition, it is the only case with otopathology characterization in an individual with any COCH mutation and residual hearing, thus allowing assessment of primary histopathological events in DFNA9, before progression to more profound hearing loss. A quantitative cytologic analysis of atrophy in this specimen and immunostaining using anti-neurofilament and anti-myelin protein zero antibodies confirmed that the principal histopathologic correlate of hearing loss was degeneration of the dendritic fibers of spiral ganglion cells in the osseous spiral lamina. The implications for cochlear implantation in this disorder are discussed. (C) 2016 S. Karger AG, Basel C1 [Burgess, Barbara J.; O'Malley, Jennifer T.; Kamakura, Takefumi; Kristiansen, Kris; Nadol, Joseph B., Jr.] Massachusetts Eye & Ear Infirm, Dept Otolaryngol, Human Otopathol Lab, 243 Charles St, Boston, MA 02114 USA. [Robertson, Nahid G.; Morton, Cynthia C.] Brigham & Womens Hosp, Dept Obstet Gynecol & Reprod Biol, 75 Francis St, Boston, MA 02115 USA. [Robertson, Nahid G.; Morton, Cynthia C.] Brigham & Womens Hosp, Dept Pathol, 75 Francis St, Boston, MA 02115 USA. [Kamakura, Takefumi; Morton, Cynthia C.; Nadol, Joseph B., Jr.] Harvard Univ, Sch Med, Boston, MA USA. [Morton, Cynthia C.] Broad Inst MIT & Harvard, Cambridge, MA USA. [Morton, Cynthia C.] Univ Manchester, Sch Psychol Sci, Manchester, Lancs, England. RP Nadol, JB (reprint author), Massachusetts Eye & Ear Infirm, 243 Charles St, Boston, MA 02114 USA. EM joseph_nadol@meei.harvard.edu FU National Institute on Deafness and Other Communication Disorders (NIH) [5R01DC152, 5R01DC03402] FX This study was supported by grants 5R01DC152 (J.B. Nadol Jr.) and 5R01DC03402 (C.C. Morton) from the National Institute on Deafness and Other Communication Disorders (NIH). NR 21 TC 1 Z9 1 U1 2 U2 4 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 2016 VL 21 IS 2 BP 88 EP 97 DI 10.1159/000443822 PG 10 WC Audiology & Speech-Language Pathology; Neurosciences; Otorhinolaryngology SC Audiology & Speech-Language Pathology; Neurosciences & Neurology; Otorhinolaryngology GA DL6WD UT WOS:000375779700004 PM 27023102 ER PT J AU Ingelfinger, JR Kalantar-Zadeh, K Schaefer, F AF Ingelfinger, Julie R. Kalantar-Zadeh, Kamyar Schaefer, Franz CA World Kidney Day Steering Comm TI Averting the Legacy of Kidney Disease - Focus on Childhood SO BLOOD PURIFICATION LA English DT Editorial Material ID NEPHROLOGY ASSOCIATION IPNA; RENAL REPLACEMENT THERAPY; LOW-BIRTH-WEIGHT; NONCOMMUNICABLE DISEASES; INTERNATIONAL SOCIETY; CONSENSUS STATEMENT; PROSPECTIVE COHORT; GLOBAL HEALTH; CHILDREN; EPIDEMIOLOGY AB World Kidney Day 2016 focuses on kidney disease in childhood and the antecedents of adult kidney disease that can begin in earliest childhood. Chronic kidney disease (CKD) in childhood differs from that in adults, as the largest diagnostic group among children includes congenital anomalies and inherited disorders, with glomerulopathies and kidney disease in the setting of diabetes being relatively uncommon. In addition, many children with acute kidney injury will ultimately develop sequelae that may lead to hypertension and CKD in later childhood or in adult life. Children born early or who are small-for date newborns have relatively increased risk for the development of CKD later in life. Persons with a high-risk birth and early childhood history should be watched closely in order to help detect early signs of kidney disease in time to provide effective prevention or treatment. Successful therapy is feasible for advanced CKD in childhood; there is evidence that children fare better than adults, if they receive kidney replacement therapy including dialysis and transplantation, while only a minority of children may require this ultimate intervention. Because there are disparities in access to care, effort is needed so that those children with kidney disease, wherever they live, may be treated effectively, irrespective of their geographic or economic circumstances. Our hope is that World Kidney Day will inform the general public, policy makers and caregivers about the needs and possibilities surrounding kidney disease in childhood. (C) 2016 S. Karger AG, Basel C1 [Ingelfinger, Julie R.] Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. [Ingelfinger, Julie R.] Massachusetts Gen Hosp, Mass Gen Hosp Children, Pediat Nephrol, Boston, MA 02114 USA. [Ingelfinger, Julie R.] Massachusetts Gen Hosp, Mass Gen Hosp Children, Pediactr, Boston, MA 02114 USA. [Kalantar-Zadeh, Kamyar] Univ Calif Irvine, Sch Med, Dept Med, Div Nephrol & Hypertens, Irvine, CA 92717 USA. [Kalantar-Zadeh, Kamyar] Univ Calif Irvine, Sch Med, Div Pediat & Publ Hlth, Irvine, CA 92717 USA. [Kalantar-Zadeh, Kamyar] Vet Affairs Long Beach Healthcare Syst, Long Beach, CA USA. [Kalantar-Zadeh, Kamyar] Univ Calif Los Angeles, Fielding Sch Publ Hlth, Dept Epidemiol, Los Angeles, CA USA. [Schaefer, Franz] Heidelberg Univ, Dept Pediat, Heidelberg, Germany. [Schaefer, Franz] Univ Heidelberg Hosp, Ctr Pediat & Adolescent Med, Div Pediat Nephrol, Heidelberg, Germany. RP Ingelfinger, JR (reprint author), Care of Fahssis M, World Kidney Day, Rues Fabriques 1B, BE-1000 Brussels, Belgium. OI Kalantar-Zadeh, Kamyar/0000-0002-8666-0725 NR 33 TC 1 Z9 1 U1 0 U2 0 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0253-5068 EI 1421-9735 J9 BLOOD PURIFICAT JI Blood Purif. PY 2016 VL 41 IS 4 BP 332 EP 338 DI 10.1159/000444510 PG 7 WC Hematology; Urology & Nephrology SC Hematology; Urology & Nephrology GA DL6RH UT WOS:000375765800014 PM 26930219 ER PT J AU Lim, PA McLean, AM Kilpatrick, C DeForge, D Iverson, GL Silverberg, ND AF Lim, Patricia A. McLean, Alison M. Kilpatrick, Christiane DeForge, Daniel Iverson, Grant L. Silverberg, Noah D. TI Temporal stability and responsiveness of the Montreal Cognitive Assessment following acquired brain injury SO BRAIN INJURY LA English DT Article DE Brain injuries; cognition disorders; neuropsychological tests; psychometrics; stroke ID MEDICAL REHABILITATION REPORT; MENTAL-STATE-EXAMINATION; BRIEF SCREENING TOOL; UNIFORM DATA SYSTEM; ASSESSMENT MOCA; IMPAIRMENT; VALIDITY; STROKE; VERSION; RELIABILITY AB Objectives: To evaluate the temporal stability and responsiveness of the Montreal Cognitive Assessment (MoCA) in acquired brain injury (ABI). Research design and methods: English-speaking adults with stroke or moderate-to-severe traumatic brain injury were administered alternate forms of the MoCA (version 1, then 2), 6 weeks apart. Chronic group participants (n = 40) were community-dwelling, at least 1 year post-ABI (mean = 12.1 years, SD = 9.0), and presumed clinically stable. Sub-acute group participants (n = 36) were 30.8 days post-ABI (SD = 12.4) and were undergoing intensive rehabilitation. Individuals with an unstable medical or psychiatric condition or severe receptive aphasia were not eligible. Results: The chronic group scored 21.6 (SD = 4.5) initially and 22.7 (SD = 3.8) on the second administration, demonstrating a small but significant practise effect (p = 0.009). The Pearson test-re-test correlation coefficient was 0.83. Using reliable change methodology in the chronic group, the 80% confidence interval (CI) for change across the two administrations was -2 to +4, adjusting for practise. Applied to the sub-acute group, 39% improved and 0% declined. Conclusions: The MoCA is a brief standardized tool that appears useful for monitoring cognitive change after ABI. The findings enable clinicians to detect statistically reliable change across serial MoCA administrations in individuals with an ABI. C1 [Lim, Patricia A.; DeForge, Daniel; Silverberg, Noah D.] Univ British Columbia, Div Phys Med & Rehabil, Vancouver, BC V5Z 1M9, Canada. [McLean, Alison M.] Univ British Columbia, Dept Occupat Sci & Occupat Therapy, Vancouver, BC V5Z 1M9, Canada. [McLean, Alison M.; Kilpatrick, Christiane; DeForge, Daniel; Silverberg, Noah D.] GF Strong Rehabil Ctr, Vancouver, BC, Canada. [Iverson, Grant L.] Harvard Univ, Sch Med, Dept Phys Med & Rehabil, Boston, MA USA. [Iverson, Grant L.] Spaulding Rehabil Hosp, Boston, MA USA. [Iverson, Grant L.] Red Sox Fdn, Boston, MA USA. [Iverson, Grant L.] Massachusetts Gen Hosp, Home Base Program, Boston, MA 02114 USA. RP Silverberg, ND (reprint author), Rehabil Res Ctr, GF Strong Rehabil Ctr, 4255 Laurel St, Vancouver, BC V5Z 2G9, Canada. EM noah.silverberg@vch.ca FU B.C. Rehab Foundation through Research and Innovation Fund [20R67148]; ImPACT(R) Applications Systems FX Financial support was gratefully received from the B.C. Rehab Foundation through its Research and Innovation Fund (Project Grant #20R67148). GLI has been reimbursed by the government, professional scientific bodies and commercial organizations for discussing or presenting research relating to traumatic brain injury (TBI) and sport-related concussion at meetings, scientific conferences and symposiums. He has a clinical practice in forensic neuropsychology involving individuals who have sustained mild TBIs (including athletes). He has received honorariums for serving on research panels that provide scientific peer review of programmes. He is a co-investigator, collaborator or consultant on grants relating to mild TBI funded by several organizations. He has received research support from test publishing companies in the past, including ImPACT (R) Applications Systems (not in the past 5 years). The other authors have no conflicts of interest to report. NR 40 TC 1 Z9 1 U1 0 U2 0 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 2016 VL 30 IS 1 BP 29 EP 35 DI 10.3109/02699052.2015.1079732 PG 7 WC Neurosciences; Rehabilitation SC Neurosciences & Neurology; Rehabilitation GA DJ8YT UT WOS:000374501200005 PM 26556208 ER PT J AU Winter, L Moriarty, HJ Robinson, K Piersol, CV Vause-Earland, T Newhart, B Iacovone, DB Hodgson, N Gitlin, LN AF Winter, Laraine Moriarty, Helene J. Robinson, Keith Piersol, Catherine V. Vause-Earland, Tracey Newhart, Brian Iacovone, Delores Blazer Hodgson, Nancy Gitlin, Laura N. TI Efficacy and acceptability of a home-based, family-inclusive intervention for veterans with TBI: A randomized controlled trial SO BRAIN INJURY LA English DT Article DE Community reintegration; family; in-home service; rehabilitation; traumatic brain injury; veterans ID TRAUMATIC BRAIN-INJURY; COGNITIVE REHABILITATION; COMMUNITY REINTEGRATION; SERVICE MEMBERS; NEUROREHABILITATION PROGRAM; OLDER-ADULTS; CAREGIVER; MILITARY; OUTCOMES; INTEGRATION AB Objective: Traumatic brain injury (TBI) often undermines community re-integration, impairs functioning and produces other symptoms. This study tested an innovative programme for veterans with TBI, the Veterans' In-home Programme (VIP), delivered in veterans' homes, involving a family member and targeting the environment (social and physical) to promote community re-integration, mitigate difficulty with the most troubling TBI symptoms and facilitate daily functioning. Setting: Interviews and intervention sessions were conducted in homes or by telephone. Participants: Eighty-one veterans with TBI at a VA polytrauma programme and a key family member. Design: This was a 2-group randomized controlled trial. Control-group participants received usual-care enhanced by two attention-control telephone calls. Follow-up interviews occurred up to 4 months after baseline interview. Main measures: VIP's efficacy was evaluated using measures of community re-integration, target outcomes reflecting veterans' self-identified problems and self-rated functional competence. Results: At follow-up, VIP participants had significantly higher community re-integration scores and less difficulty managing targeted outcomes, compared to controls. Self-rated functional competence did not differ between groups. In addition, VIP's acceptability was high. Conclusion: A home-based, family-inclusive service for veterans with TBI shows promise for improving meaningful outcomes and warrants further research and clinical application. C1 [Winter, Laraine] Philadelphia Res & Educ Fdn, Philadelphia, PA 19104 USA. [Winter, Laraine; Moriarty, Helene J.] Dept Vet Affairs Med Ctr, Nursing Serv, Philadelphia, PA 19104 USA. [Moriarty, Helene J.] Villanova Univ, Coll Nursing, Villanova, PA 19085 USA. [Robinson, Keith; Newhart, Brian; Iacovone, Delores Blazer] Dept Vet Affairs Med Ctr, Med Rehabil Serv, Philadelphia, PA 19104 USA. [Robinson, Keith] Univ Penn, Perelman Sch Med, Philadelphia, PA 19104 USA. [Piersol, Catherine V.; Vause-Earland, Tracey] Thomas Jefferson Univ, Sch Hlth Profess, Philadelphia, PA 19107 USA. [Hodgson, Nancy; Gitlin, Laura N.] Johns Hopkins Univ, Sch Nursing, Ctr Innovat Care Aging, Baltimore, MD USA. RP Winter, L (reprint author), Philadelphia Res & Educ Fdn, Philadelphia VA Med Ctr, Univ & Woodland Ave, Philadelphia, PA 19104 USA. EM laraine.winter@gmail.com NR 69 TC 2 Z9 2 U1 6 U2 6 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 2016 VL 30 IS 4 BP 373 EP 387 DI 10.3109/02699052.2016.1144080 PG 15 WC Neurosciences; Rehabilitation SC Neurosciences & Neurology; Rehabilitation GA DK1BF UT WOS:000374646200002 PM 26983578 ER PT J AU Brahmer, J Rasco, D Chen, MJ Masteller, E Qazi, I Rogers, S Sankar, N Sikorski, R Hambleton, J Hodi, FS AF Brahmer, Julie Rasco, Drew Chen, Minjia Masteller, Emma Qazi, Ibrahim Rogers, Seema Sankar, Neil Sikorski, Robert Hambleton, Julie Hodi, F. Stephen TI A phase 1a/1b study of FPA008 in combination with nivolumab in patients with selected advanced cancers SO CANCER IMMUNOLOGY RESEARCH LA English DT Meeting Abstract C1 [Brahmer, Julie] Johns Hopkins, Sidney Kimmel Comprehens Canc Ctr, Baltimore, MD USA. [Rasco, Drew] South Texas Accelerated Res Therapeut, San Antonio, TX USA. [Chen, Minjia; Masteller, Emma; Qazi, Ibrahim; Rogers, Seema; Sankar, Neil; Sikorski, Robert; Hambleton, Julie] Five Prime Therapeut, San Francisco, CA USA. [Hodi, F. Stephen] 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 2326-6066 EI 2326-6074 J9 CANCER IMMUNOL RES JI Cancer Immunol. Res. PD JAN PY 2016 VL 4 IS 1 SU S MA B143 PG 2 WC Oncology; Immunology SC Oncology; Immunology GA DL2SB UT WOS:000375484400215 ER PT J AU Li, B Liu, J Liu, XS AF Li, Bo Liu, Jun Liu, X. Shirley TI Comprehensive analyses of tumor immunity with implications to cancer immunotherapies SO CANCER IMMUNOLOGY RESEARCH LA English DT Meeting Abstract C1 [Li, Bo; Liu, X. Shirley] Dana Farber Canc Inst, Boston, MA 02115 USA. [Liu, Jun] Harvard Univ, Dept Stat, 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 2326-6066 EI 2326-6074 J9 CANCER IMMUNOL RES JI Cancer Immunol. Res. PD JAN PY 2016 VL 4 IS 1 SU S MA B162 DI 10.1158/2326-6074.CRICIMTEATIAACR15-B162 PG 1 WC Oncology; Immunology SC Oncology; Immunology GA DL2SB UT WOS:000375484400282 ER PT J AU Li, H McSharry, M Clambey, E Nguyen, T McNamee, E Weiser-Evans, M Nemenoff, R AF Li, Howard McSharry, Maria Clambey, Eric Nguyen, Teresa McNamee, Eoin Weiser-Evans, Mary Nemenoff, Raphael TI Non-small cell lung cancer cells induce PD-L1 expression in the tumor microenvironment in an orthotopic mouse model of lung cancer SO CANCER IMMUNOLOGY RESEARCH LA English DT Meeting Abstract C1 [Li, Howard] Denver VA Med Ctr, Denver, CO USA. [McSharry, Maria; Clambey, Eric; Nguyen, Teresa; McNamee, Eoin; Weiser-Evans, Mary; Nemenoff, Raphael] Univ Colorado, Anschutz Med Campus, Aurora, CO USA. NR 0 TC 1 Z9 1 U1 0 U2 1 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 2326-6066 EI 2326-6074 J9 CANCER IMMUNOL RES JI Cancer Immunol. Res. PD JAN PY 2016 VL 4 IS 1 SU S MA A122 DI 10.1158/2326-6074.CRICIMTEATIAACR15-A122 PG 2 WC Oncology; Immunology SC Oncology; Immunology GA DL2SB UT WOS:000375484400265 ER PT J AU Miller, MA Pittet, M Weissleder, R AF Miller, Miles A. Pittet, Mikael Weissleder, Ralph TI In vivo imaging of innate immune cells to measure drug response SO CANCER IMMUNOLOGY RESEARCH LA English DT Meeting Abstract C1 [Miller, Miles A.; Pittet, Mikael; Weissleder, Ralph] Massachusetts Gen Hosp, Boston, MA 02114 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 2326-6066 EI 2326-6074 J9 CANCER IMMUNOL RES JI Cancer Immunol. Res. PD JAN PY 2016 VL 4 IS 1 SU S MA B133 DI 10.1158/2326-6074.CRICIMTEATIAACR15-B133 PG 2 WC Oncology; Immunology SC Oncology; Immunology GA DL2SB UT WOS:000375484400190 ER PT J AU Reardon, DA Dietrich, J Kaley, T Gan, H Dunn, GP Cloughesy, T Lim, M Clarke, J Park, A Pang, L Lai, DW Karakunnel, J Robbins, P Narwal, R Venhaus, R AF Reardon, David A. Dietrich, Jorg Kaley, Thomas Gan, Hui Dunn, Gavin P. Cloughesy, Timothy Lim, Michael Clarke, Jennifer Park, Andrew Pang, Linda Lai, Domenic W. Karakunnel, Joyson Robbins, Paul Narwal, Rajesh Venhaus, Ralph TI Phase 2 study to evaluate the clinical efficacy and safety of MEDI4736 in patients with glioblastoma (GBM) SO CANCER IMMUNOLOGY RESEARCH LA English DT Meeting Abstract C1 [Reardon, David A.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Dietrich, Jorg] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Kaley, Thomas] Mem Sloan Kettering Canc Ctr, 1275 York Ave, New York, NY 10021 USA. [Gan, Hui] Austin Hosp, Melbourne, Vic 3084, Australia. [Dunn, Gavin P.] Washington Univ, St Louis, MO USA. [Cloughesy, Timothy] Ronald Reagan UCLA Med Ctr, Los Angeles, CA USA. [Lim, Michael] Johns Hopkins Univ Hosp, Baltimore, MD 21287 USA. [Clarke, Jennifer] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Park, Andrew; Pang, Linda; Venhaus, Ralph] Ludwig Inst Canc Res, New York, NY USA. [Lai, Domenic W.; Karakunnel, Joyson; Robbins, Paul; Narwal, Rajesh] MedImmune, Gaithersburg, MD 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 2326-6066 EI 2326-6074 J9 CANCER IMMUNOL RES JI Cancer Immunol. Res. PD JAN PY 2016 VL 4 IS 1 SU S MA A046 DI 10.1158/2326-6074.CRICIMTEATIAACR15-A046 PG 2 WC Oncology; Immunology SC Oncology; Immunology GA DL2SB UT WOS:000375484400041 ER PT J AU Tanne, A Muniz, L Ting, D Levine, A Bhardwaj, N Greenbaum, B AF Tanne, Antoine Muniz, Luciana Ting, David Levine, Arnold Bhardwaj, Nina Greenbaum, Benjamin TI Unraveling predicted immunomodulatory effects of novel cancer associated noncoding RNAs SO CANCER IMMUNOLOGY RESEARCH LA English DT Meeting Abstract C1 [Tanne, Antoine; Muniz, Luciana; Bhardwaj, Nina; Greenbaum, Benjamin] Mt Sinai Sch Med, Tisch Canc Inst, New York, NY USA. [Ting, David] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Levine, Arnold] IAS, Simmons Ctr Syst Biol, Princeton, NJ 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 2326-6066 EI 2326-6074 J9 CANCER IMMUNOL RES JI Cancer Immunol. Res. PD JAN PY 2016 VL 4 IS 1 SU S MA A077 DI 10.1158/2326-6074.CRICIMTEATIAACR15-A077 PG 2 WC Oncology; Immunology SC Oncology; Immunology GA DL2SB UT WOS:000375484400162 ER PT J AU Tyler, P Servos, M Dougan, SK AF Tyler, Paul Servos, Mariah Dougan, Stephanie K. TI Quality of initial activation of CD8 T cells specific for TRP1 determines long-term antitumor immunity SO CANCER IMMUNOLOGY RESEARCH LA English DT Meeting Abstract C1 [Tyler, Paul; Servos, Mariah; Dougan, Stephanie K.] 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 2326-6066 EI 2326-6074 J9 CANCER IMMUNOL RES JI Cancer Immunol. Res. PD JAN PY 2016 VL 4 IS 1 SU S MA A067 DI 10.1158/2326-6074.CRICIMTEATIAACR15-A067 PG 1 WC Oncology; Immunology SC Oncology; Immunology GA DL2SB UT WOS:000375484400103 ER PT J AU Liang, AC Mandeville, ET Maki, T Shindo, A Som, AT Egawa, N Itoh, K Chuang, TT McNeish, JD Holder, JC Lok, J Lo, EH Arai, K AF Liang, Anna C. Mandeville, Emiri T. Maki, Takakuni Shindo, Akihiro Som, Angel T. Egawa, Naohiro Itoh, Kanako Chuang, Tsu Tshen McNeish, John D. Holder, Julie C. Lok, Josephine Lo, Eng H. Arai, Ken TI Effects of Aging on Neural Stem/Progenitor Cells and Oligodendrocyte Precursor Cells After Focal Cerebral Ischemia in Spontaneously Hypertensive Rats SO CELL TRANSPLANTATION LA English DT Article; Proceedings Paper 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 DE Neural stem cells; Oligodendrocyte precursor cells (OPCs); Middle cerebral artery occlusion; Stroke; Spontaneously hypertensive rat (SHR); Aging ID AGE-RELATED DECREASE; BONE-MARROW; NESTIN EXPRESSION; ARTERY OCCLUSION; STEM-CELLS; STROKE; BRAIN; OUTCOMES; MATTER; PROLIFERATION AB Aging and vascular comorbidities such as hypertension comprise critical cofactors that influence how the brain responds to stroke. Ischemic stress induces neurogenesis and oligodendrogenesis in younger brains. However, it remains unclear whether these compensatory mechanisms can be maintained even under pathologically hypertensive and aged states. To clarify the age-related remodeling capacity after stroke under hypertensive conditions, we assessed infarct volume, behavioral outcomes, and surrogate markers of neurogenesis and oligodendrogenesis in acute and subacute phases after transient focal cerebral ischemia in 3- and 12-month-old spontaneously hypertensive rats (SI-IRs). Hematoxylin and eosin staining showed that 3- and 12-month-old SHRs exhibited similar infarction volumes at both 3 and 14 days after focal cerebral ischemia. However, recovery of behavioral deficits (neurological score assessment and adhesive removal test) was significantly less in 12-month-old SHRs compared to 3-month-old SHRs. Concomitantly, numbers of nestin(+) neural stem/progenitor cells (NSPCs) near the infarct border area or subventricular zone in 12-month-old SHRs were lower than 3-month-old SHRs at day 3. Similarly, numbers of PDGFR-alpha(+) oligodendrocyte precursor cells (OPCs) in the corpus callosum were lower in 12-month-old SHRs at day 3. Lower levels of NSPC and OPC numbers were accompanied by lower expression levels of phosphorylated CREB. By day 14 postischemia, NSPC and OPC numbers in 12-month-old SHRs recovered to similar levels as in 3-month-old SHRs, but the numbers of proliferating NSPCs (Ki-67(+)nestin(+) cells) and proliferating OPCs (Ki-67+PDGFR-alpha(+) cells) remained lower in the older brains even at day 14. Taken together, these findings suggest that aging may also decrease poststroke compensatory responses for neurogenesis and oligodendrogenesis even under hypertensive conditions. C1 [Liang, Anna C.; Mandeville, Emiri T.; Maki, Takakuni; Shindo, Akihiro; Som, Angel T.; Egawa, Naohiro; Itoh, Kanako; Lok, Josephine; Lo, Eng H.; Arai, Ken] Massachusetts Gen Hosp, Dept Radiol, Neuroprotect Res Lab, Boston, MA USA. [Liang, Anna C.; Mandeville, Emiri T.; Maki, Takakuni; Shindo, Akihiro; Som, Angel T.; Egawa, Naohiro; Itoh, Kanako; Lok, Josephine; Lo, Eng H.; Arai, Ken] Massachusetts Gen Hosp, Dept Neurol, Neuroprotect Res Lab, Boston, MA 02114 USA. [Liang, Anna C.; Mandeville, Emiri T.; Maki, Takakuni; Shindo, Akihiro; Som, Angel T.; Egawa, Naohiro; Itoh, Kanako; Lok, Josephine; Lo, Eng H.; Arai, Ken] Harvard Univ, Sch Med, Boston, MA USA. [Chuang, Tsu Tshen; McNeish, John D.] GlaxoSmithKline, Regenerat Med Discovery Performance Unit, Boston, MA USA. [Holder, Julie C.] GlaxoSmithKline, Regenerat Med Discovery Performance Unit, Stevenage, Herts, England. RP Lo, EH; Arai, K (reprint author), Neuroprotect Res Lab, 13th St,MGH East 149-2401, Charlestown, MA 02129 USA. EM lo@helix.mgh.harvard.edu; karai@partners.org FU NINDS NIH HHS [R01 NS065089, P01 NS055104, P01-NS55104, R01-NS065089] NR 38 TC 1 Z9 1 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 2016 VL 25 IS 4 BP 705 EP 714 DI 10.3727/096368916X690557 PG 10 WC Cell & Tissue Engineering; Medicine, Research & Experimental; Transplantation SC Cell Biology; Research & Experimental Medicine; Transplantation GA DK2BB UT WOS:000374718500009 PM 26811151 ER PT J AU Egawa, N Shindo, A Xing, C Liang, AC Sudo, R Lo, EH Arai, K AF Egawa, N. Shindo, A. Xing, C. Liang, A. C. Sudo, R. Lo, E. H. Arai, K. TI Accessibility to Neighboring Cells Modulates Cell Viability and Lineage Decision of Oligodendrocyte Precursor Cells in a Novel Three-Dimensional Culture System SO CELL TRANSPLANTATION LA English DT Meeting Abstract CT 23rd Annual Meeting of the American-Society-for-Neural-Therapy-and-Repair (ASNTR) CY APR 29-30, 2016 CL Clearwater, FL SP Amer Soc Neural Therapy & Repair C1 [Egawa, N.; Shindo, A.; Xing, C.; Liang, A. C.; Lo, E. H.; Arai, K.] Massachusetts Gen Hosp, Dept Radiol, Neuroprotect Res Lab, Charlestown, MA USA. [Egawa, N.; Shindo, A.; Xing, C.; Liang, A. C.; Lo, E. H.; Arai, K.] Massachusetts Gen Hosp, Dept Neurol, Neuroprotect Res Lab, Charlestown, MA USA. [Egawa, N.; Shindo, A.; Xing, C.; Liang, A. C.; Lo, E. H.; Arai, K.] Harvard Univ, Sch Med, Charlestown, MA USA. [Sudo, R.] Keio Univ, Dept Syst Design Engn, Yokohama, Kanagawa 223, 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 2016 VL 25 IS 4 BP 755 EP 756 PG 2 WC Cell & Tissue Engineering; Medicine, Research & Experimental; Transplantation SC Cell Biology; Research & Experimental Medicine; Transplantation GA DK2BB UT WOS:000374718500035 ER PT J AU Jiang, X Pu, H Mao, L Xia, J Wang, G Zhang, H Wu, Y Shi, Y Hu, X Gao, Y Chen, J AF Jiang, X. Pu, H. Mao, L. Xia, J. Wang, G. Zhang, H. Wu, Y. Shi, Y. Hu, X. Gao, Y. Chen, J. TI Poststroke EPA/DHA Treatment Combined With Dietary Supplementation of Omega-3 Polyunsaturated Fatty Acids Promotes Long-Term Neurological Recovery After Transient Cerebral Ischemia SO CELL TRANSPLANTATION LA English DT Meeting Abstract CT 23rd Annual Meeting of the American-Society-for-Neural-Therapy-and-Repair (ASNTR) CY APR 29-30, 2016 CL Clearwater, FL SP Amer Soc Neural Therapy & Repair C1 [Jiang, X.; Pu, H.; Mao, L.; Xia, J.; Wang, G.; Zhang, H.; Wu, Y.; Shi, Y.; Hu, X.; Chen, J.] Univ Pittsburgh, Sch Med, Ctr Cerebrovasc Dis Res, Pittsburgh, PA USA. [Jiang, X.; Pu, H.; Wang, G.; Hu, X.; Gao, Y.; Chen, J.] Fudan Univ, State Key Lab Med Neurobiol, Shanghai 200433, Peoples R China. [Jiang, X.; Pu, H.; Wang, G.; Hu, X.; Gao, Y.; Chen, J.] Fudan Univ, Inst Brain Sci, Shanghai 200433, Peoples R China. [Hu, X.; Chen, J.] Vet Affairs Pittsburgh Hlth Care Syst, Ctr Geriatr Res Educ & Clin, Pittsburgh, PA USA. RI Gao, Yanqin/I-6790-2016 OI Gao, Yanqin/0000-0002-4915-9819 NR 0 TC 0 Z9 0 U1 0 U2 1 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 2016 VL 25 IS 4 BP 762 EP 763 PG 2 WC Cell & Tissue Engineering; Medicine, Research & Experimental; Transplantation SC Cell Biology; Research & Experimental Medicine; Transplantation GA DK2BB UT WOS:000374718500056 ER PT J AU Shi, Y Zhang, L Pu, H Mao, L Hu, X Jiang, X Xu, N Stetler, RA Lealc, RK Keep, RF Chen, J AF Shi, Y. Zhang, L. Pu, H. Mao, L. Hu, X. Jiang, X. Xu, N. Stetler, R. A. Lealc, R. K. Keep, R. F. Chen, J. TI Rapid Endothelial Cytoskeletal Reorganization Enables Early Blood Brain Barrier Disruption and Long-Term Ischemic/Reperfusion Brain Injury SO CELL TRANSPLANTATION LA English DT Meeting Abstract CT 23rd Annual Meeting of the American-Society-for-Neural-Therapy-and-Repair (ASNTR) CY APR 29-30, 2016 CL Clearwater, FL SP Amer Soc Neural Therapy & Repair C1 [Shi, Y.; Zhang, L.; Pu, H.; Mao, L.; Hu, X.; Jiang, X.; Xu, N.; Stetler, R. A.; Chen, J.] Univ Pittsburgh, Sch Med, Ctr Cerebrovasc Dis Res, Pittsburgh, PA USA. [Shi, Y.; Zhang, L.; Hu, X.; Stetler, R. A.; Chen, J.] Vet Affairs Pittsburgh Hlth Care Syst, Geriatr Res Educ & Clin Ctr, Pittsburgh, PA USA. [Lealc, R. K.] Duquesne Univ, Mylan Sch Pharm, Div Pharmaceut Sci, Pittsburgh, PA 15219 USA. [Keep, R. F.] Univ Michigan, Dept Neurosurg, Ann Arbor, MI 48109 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 2016 VL 25 IS 4 BP 772 EP 772 PG 1 WC Cell & Tissue Engineering; Medicine, Research & Experimental; Transplantation SC Cell Biology; Research & Experimental Medicine; Transplantation GA DK2BB UT WOS:000374718500086 ER PT J AU Zeng, X Ropper, AE Anderson, JE Aljuboori, Z Lee, HJ Snyder, EY Sidmang, RL Kim, SU Teng, YD AF Zeng, X. Ropper, A. E. Anderson, J. E. Aljuboori, Z. Lee, H. J. Snyder, E. Y. Sidmang, R. L. Kim, S. U. Teng, Y. D. TI Engineered Human Neural Stem Cells for Treating Spinal Cord Gliomas: A Neurobiology-Based Approach SO CELL TRANSPLANTATION LA English DT Meeting Abstract CT 23rd Annual Meeting of the American-Society-for-Neural-Therapy-and-Repair (ASNTR) CY APR 29-30, 2016 CL Clearwater, FL SP Amer Soc Neural Therapy & Repair C1 [Zeng, X.; Ropper, A. E.; Anderson, J. E.; Aljuboori, Z.; Teng, Y. D.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Neurosurg, Boston, MA 02115 USA. [Zeng, X.; Ropper, A. E.; Anderson, J. E.; Aljuboori, Z.; Teng, Y. D.] Vet Affairs Boston Healthcare Syst, Div SCI Res, Boston, MA USA. [Lee, H. J.; Kim, S. U.] Chung Ang Univ, Coll Med, Med Res Inst, Seoul 156756, South Korea. [Snyder, E. Y.] Sanford Burnham Med Res Inst, Ctr Stem Cells & Regenerat Med, La Jolla, CA USA. [Sidmang, R. L.] Harvard Univ, Sch Med, BIDMC, Dept Neurol, Boston, MA USA. [Teng, Y. D.] Harvard Univ, Sch Med, Spaulding Rehabil Hosp, Dept PM&R, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU COGNIZANT COMMUNICATION CORP PI PUTNAM VALLEY PA 18 PEEKSKILL HOLLOW RD, PO BOX 37, PUTNAM VALLEY, NY 10579 USA SN 0963-6897 EI 1555-3892 J9 CELL TRANSPLANT JI Cell Transplant. PY 2016 VL 25 IS 4 BP 778 EP 778 PG 1 WC Cell & Tissue Engineering; Medicine, Research & Experimental; Transplantation SC Cell Biology; Research & Experimental Medicine; Transplantation GA DK2BB UT WOS:000374718500104 ER PT J AU Prywes, N Michaels, YS Pal, A Oh, SS Szostak, JW AF Prywes, Noam Michaels, Yale S. Pal, Ayan Oh, Seung Soo Szostak, Jack W. TI Thiolated uridine substrates and templates improve the rate and fidelity of ribozyme-catalyzed RNA copying SO CHEMICAL COMMUNICATIONS LA English DT Article ID IN-VITRO SELECTION; EXTREME THERMOPHILE; PRIMER EXTENSION; 2-THIOURIDINE; EFFICIENCY; POLYMERIZATION; 4-THIOURIDINE; RIBOTHYMIDINE; TRANSCRIPTION; CLEAVAGE AB Ribozyme-catalyzed RNA polymerization is inefficient and error prone. Here we demonstrate that two alternative bases, 2-thio-uridine (s(2)U) and 2-thio-ribo-thymidine (s(2)T), improve the rate and fidelity of ribozyme catalyzed nucleotide addition as NTP substrates and as template bases. We also demonstrate the functionality of s(2)U and s(2)T-containing ribozymes. C1 [Prywes, Noam; Michaels, Yale S.; Pal, Ayan; Oh, Seung Soo; Szostak, Jack W.] Massachusetts Gen Hosp, Howard Hughes Med Inst, Dept Mol Biol, 185 Cambridge St, Boston, MA 02114 USA. [Prywes, Noam; Michaels, Yale S.; Pal, Ayan; Oh, Seung Soo; Szostak, Jack W.] Massachusetts Gen Hosp, Ctr Computat & Integrat Biol, 185 Cambridge St, Boston, MA 02114 USA. [Prywes, Noam; Szostak, Jack W.] Harvard Univ, Dept Chem & Biol Chem, 12 Oxford St, Cambridge, MA 02138 USA. [Michaels, Yale S.] Univ Oxford, Radcliffe Dept Med, Weatherall Inst Mol Med, Oxford OX3 9DS, England. [Pal, Ayan; Oh, Seung Soo; Szostak, Jack W.] Harvard Univ, Sch Med, Dept Genet, 77 Ave Louis Pasteur, Boston, MA 02115 USA. RP Szostak, JW (reprint author), Massachusetts Gen Hosp, Howard Hughes Med Inst, Dept Mol Biol, 185 Cambridge St, Boston, MA 02114 USA.; Szostak, JW (reprint author), Massachusetts Gen Hosp, Ctr Computat & Integrat Biol, 185 Cambridge St, Boston, MA 02114 USA.; Szostak, JW (reprint author), Harvard Univ, Dept Chem & Biol Chem, 12 Oxford St, Cambridge, MA 02138 USA.; Szostak, JW (reprint author), Harvard Univ, Sch Med, Dept Genet, 77 Ave Louis Pasteur, Boston, MA 02115 USA. EM szostak@molbio.mgh.harvard.edu RI Oh, Seung Soo/N-6315-2016 OI Oh, Seung Soo/0000-0001-8045-080X NR 32 TC 1 Z9 1 U1 7 U2 11 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 2016 VL 52 IS 39 BP 6529 EP 6532 DI 10.1039/c6cc02692c PG 4 WC Chemistry, Multidisciplinary SC Chemistry GA DL4RN UT WOS:000375625000006 PM 27109314 ER PT J AU Matthews, AM Fu, RW Dana, T Chou, R AF Matthews, Annette M. Fu, Rongwei Dana, Tracy Chou, Roger TI Intranasal or transdermal nicotine for the treatment of postoperative pain SO COCHRANE DATABASE OF SYSTEMATIC REVIEWS LA English DT Review ID SYSTEMATIC REVIEWS; MANAGEMENT; PATCH; ANALGESIA; SMOKING; NAUSEA; TRIAL; METAANALYSIS; EXPERIENCES; SURGERY AB Background Acute pain frequently occurs after surgical procedures. Nicotine has been explored as an adjunctive medication for management of postoperative pain. Objectives To assess the effect of transdermal or intranasal nicotine administration on postoperative pain, opioid analgesic use, and opioid-related adverse events. Search methods We searched MEDLINE (1966 to 20 March 2014), the Cochrane Central Register of Controlled Trials (CENTRAL; 2014, Issue 3), EMBASE (1980 to 20 March 2014), and also databases of ongoing trials (www.controlled-trials.com/ and http://clinicaltrials.gov/). We re-ran the search on 28 April 2015. We will assess the one study of interest when we update the review. Selection criteria We included randomized, placebo-controlled clinical trials that evaluated the effects of perioperative (pre-, intra-, or postoperative) administration of nicotine on postoperative pain, opioid use, and opioid-related adverse events. We excluded all other studies. Data collection and analysis Two authors independently screened all titles and abstracts for eligibility and documented reasons for exclusion. In case of disagreement, a third author decided on the inclusion or exclusion of a trial report. When additional information was needed in order to decide if a trial should be included, one of the authors contacted the corresponding author of the trial in question. Main results Nine trials (666 participants) evaluated nicotine for postoperative pain. Nicotine may reduce postoperative pain scores at 24 hours by a small amount compared with placebo (eight trials, mean difference -0.88 on a 0 to 10 scale, 95% confidence interval (CI) -1.58 to 0.18; low quality evidence). The effect on pain at one hour and 12 hours postoperatively was less certain (very low quality evidence). Statistical heterogeneity was substantial and not adequately explained by stratification of trials according to type of surgical procedure, smoking status, mode of nicotine administration, timing of administration, or assessed risk of bias. Excluding one trial at high risk of bias resulted in similar findings. The effect of nicotine on postoperative opioid use was uncertain due to small number of participants in the studies. Nicotine probably increases the risk of postoperative nausea (seven trials, RR 1.24, 95% CI 1.03 to 1.50; moderate quality evidence). Three trials assessed sedation but the effect is very uncertain due to the very low quality of evidence. We found no evidence that nicotine increased the risk of vomiting (seven studies, risk difference (RD) 0.03, 95% CI -0.04 to 0.09; low quality evidence). The results from one single small trial were insufficient to establish whether nicotine led to an earlier hospital discharge (very low quality evidence). Authors' conclusions Based on evidence of generally low quality, nicotine may reduce postoperative pain at 24 hours compared with placebo, but the effects were relatively small (less than 1 point on a 10 point pain scale) and there was substantial heterogeneity in the results of our analyses. Nicotine does not appear to reduce postoperative use of opioids or opioid-related adverse events but probably increases the risk of nausea. More research is needed to determine the effectiveness of nicotine for postoperative pain and to understand the optimal timing, dose, and method of delivery of nicotine. C1 [Matthews, Annette M.] Portland VA Med Ctr, Dept Behav Hlth & Neurosci, 3710 SW US Vet Hosp Rd, Portland, OR 97207 USA. [Matthews, Annette M.] Oregon Hlth & Sci Univ, Dept Psychiat, Portland, OR 97201 USA. [Matthews, Annette M.; Dana, Tracy; Chou, Roger] Oregon Hlth & Sci Univ, Dept Med Informat & Clin Epidemiol, Portland, OR 97201 USA. [Fu, Rongwei] Oregon Hlth & Sci Univ, Dept Publ Hlth, Portland, OR 97201 USA. [Fu, Rongwei] Oregon Hlth & Sci Univ, Dept Prevent Med, Portland, OR 97201 USA. [Fu, Rongwei] Oregon Hlth & Sci Univ, Dept Emergency Med, Portland, OR 97201 USA. [Chou, Roger] Oregon Hlth & Sci Univ, Dept Internal Med, Portland, OR 97201 USA. RP Matthews, AM (reprint author), Portland VA Med Ctr, Dept Behav Hlth & Neurosci, 3710 SW US Vet Hosp Rd, Portland, OR 97207 USA. EM Annette.Matthews@va.gov FU Oregon Health & Science University Human Investigations Program, USA; National Center for Research Resources/National Center for Advancing Translational Sciences (NCRR/NCATS) [UL1RR024140]; Veterans Affairs Clinical Sciences Research and Development (CSR&D) Career Development Award, USA FX Internal sources; Oregon Health & Science University Human Investigations Program, USA.; A draft of this protocol was first developed as part of a course on systematic reviews that was sponsored by National Center for Research Resources/National Center for Advancing Translational Sciences (NCRR/NCATS)-funded Clinical and Translational Science Award (CTSA) grant (UL1RR024140).; External sources; Veterans Affairs Clinical Sciences Research and Development (CSR&D) Career Development Award, USA. Awarded to Annette M. Matthews, MD. NR 38 TC 0 Z9 0 U1 0 U2 0 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 2016 IS 1 AR CD009634 DI 10.1002/14651858.CD009634.pub2 PG 125 WC Medicine, General & Internal SC General & Internal Medicine GA DJ7PV UT WOS:000374404200040 PM 26756459 ER PT J AU Berman, NC Tung, ES Matheny, N Cohen, IG Wilhelm, S AF Berman, Noah Chase Tung, Esther S. Matheny, Natalie Cohen, I. Glenn Wilhelm, Sabine TI Clinical decision making regarding suicide risk: Effect of patient and clinician age SO DEATH STUDIES LA English DT Article ID PERSONALITY-DISORDER; DIAGNOSIS; CARE; STRATEGIES; GUIDELINES; ATTITUDES; BEHAVIOR; HEALTH; BIAS; RACE AB To ascertain how patient age influences suicide risk assessment, clinicians (N=262) read an ambiguous vignette about Bill (aged either 39 or 79 years old) and subsequently rated Bill's suicide risk and hospitalization needs. Suicide-risk ratings varied greatly and young clinicians rated Bill's suicide risk and hospitalization needs higher when he was elderly (79 years old); whereas, older clinicians rated Bill's suicide risk and need for hospitalization higher when he was younger (39 years old). The interaction between patient and clinician age may reflect a similarity bias, such that clinicians perceive those who are different (i.e., younger or older) to be at elevated risk. C1 [Berman, Noah Chase; Tung, Esther S.; Matheny, Natalie; Wilhelm, Sabine] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. [Cohen, I. Glenn] Harvard Univ, Sch Law, Cambridge, MA 02114 USA. RP Berman, NC (reprint author), Massachusetts Gen Hosp, Dept Psychiat, 185 Cambridge St,Suite 2000, Boston, MA 02114 USA.; Berman, NC (reprint author), Harvard Univ, Sch Med, 185 Cambridge St,Suite 2000, Boston, MA 02114 USA. EM nberman@mgh.harvard.edu NR 32 TC 0 Z9 0 U1 2 U2 5 PU ROUTLEDGE JOURNALS, TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXFORDSHIRE, ENGLAND SN 0748-1187 EI 1091-7683 J9 DEATH STUD JI Death Stud. PY 2016 VL 40 IS 5 BP 269 EP 274 DI 10.1080/07481187.2015.1128498 PG 6 WC Psychology, Multidisciplinary; Social Issues; Social Sciences, Biomedical SC Psychology; Social Issues; Biomedical Social Sciences GA DK1HK UT WOS:000374662900001 PM 26677913 ER PT J AU Tourville, TW Shultz, SJ Vacek, PM Knudsen, EJ Bernstein, IM Tourville, KJ Hardy, DM Johnson, RJ Slauterbeck, JR Beynnon, BD AF Tourville, Timothy W. Shultz, Sandra J. Vacek, Pamela M. Knudsen, Emily J. Bernstein, Ira M. Tourville, Kelly J. Hardy, Daniel M. Johnson, Robert J. Slauterbeck, James R. Beynnon, Bruce D. TI Evaluation of an Algorithm to Predict Menstrual-Cycle Phase at the Time of Injury SO JOURNAL OF ATHLETIC TRAINING LA English DT Article DE anterior cruciate ligament injury; risk factors; validation ID CRUCIATE LIGAMENT INJURIES; TEAM HANDBALL; KNEE LAXITY; WOMEN; RISK; ASSOCIATION; DEFICIENCY; PREVENTION; PROFILES; LENGTH AB Context: Women are 2 to 8 times more likely to sustain an anterior cruciate ligament (ACL) injury than men, and previous studies indicated an increased risk for injury during the preovulatory phase of the menstrual cycle (MC). However, investigations of risk rely on retrospective classification of MC phase, and no tools for this have been validated. Objective: To evaluate the accuracy of an algorithm for retrospectively classifying MC phase at the time of a mock injury based on MC history and salivary progesterone (P4) concentration. Design: Descriptive laboratory study. Setting: Research laboratory. Participants: Thirty-one healthy female collegiate athletes (age range, 18-24 years) provided serum or saliva (or both) samples at 8 visits over 1 complete MC. Main Outcome Measure(s): Self-reported MC information was obtained on a randomized date (1-45 days) after mock injury, which is the typical timeframe in which researchers have access to ACL-injured study participants. The MC phase was classified using the algorithm as applied in a stand-alone computational fashion and also by 4 clinical experts using the algorithm and additional subjective hormonal history information to help inform their decision. To assess algorithm accuracy, phase classifications were compared with the actual MC phase at the time of mock injury (ascertained using urinary luteinizing hormone tests and serial serum P4 samples). Clinical expert and computed classifications were compared using kappa statistics. Results: Fourteen participants (45%) experienced anovulatory cycles. The algorithm correctly classified MC phase for 23 participants (74%): 22 (76%) of 29 who were preovulatory/anovulatory and 1 (50%) of 2 who were postovulatory. Agreement between expert and algorithm classifications ranged from 80.6% (kappa = 0.50) to 93% (kappa = 0.83). Classifications based on same-day saliva sample and optimal P4 threshold were the same as those based on MC history alone (87.1% correct). Algorithm accuracy varied during the MC but at no time were both sensitivity and specificity levels acceptable. Conclusions: These findings raise concerns about the accuracy of previous retrospective MC-phase classification systems, particularly in a population with a high occurrence of anovulatory cycles. C1 [Tourville, Timothy W.; Tourville, Kelly J.] Univ Vermont, Dept Rehabil & Movement Sci, Burlington, VT 05405 USA. [Shultz, Sandra J.] Univ N Carolina, Dept Kinesiol, Greensboro, NC 27412 USA. [Vacek, Pamela M.] Univ Vermont, Med Biostat Unit, Burlington, VT 05405 USA. [Knudsen, Emily J.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Bernstein, Ira M.] Univ Vermont, Dept Obstet Gynecol & Reprod Sci, Burlington, VT 05405 USA. [Hardy, Daniel M.] Texas Tech Univ, Dept Cell Biol & Biochem, Lubbock, TX 79409 USA. [Johnson, Robert J.; Slauterbeck, James R.; Beynnon, Bruce D.] Univ Vermont, Dept Orthopaed & Rehabil, Stafford Hall,4th Floor,95 Carrigan Dr, Burlington, VT 05405 USA. RP Beynnon, BD (reprint author), Univ Vermont, Dept Orthopaed & Rehabil, Stafford Hall,4th Floor,95 Carrigan Dr, Burlington, VT 05405 USA. EM bruce.beynnon@uvm.edu FU National Institute of Arthritis and Musculoskeletal and Skin Diseases of the National Institutes of Health [R01-AR050421] FX Funding for this investigation was provided by research grant R01-AR050421 from the National Institute of Arthritis and Musculoskeletal and Skin Diseases of the National Institutes of Health (Dr Beynnon). NR 35 TC 0 Z9 0 U1 0 U2 3 PU NATL ATHLETIC TRAINERS ASSOC INC PI DALLAS PA 2952 STEMMONS FREEWAY, DALLAS, TX 75247 USA SN 1062-6050 EI 1938-162X J9 J ATHL TRAINING JI J. Athl. Train. PD JAN PY 2016 VL 51 IS 1 BP 47 EP 56 DI 10.4085/1062-6050-51.3.01 PG 10 WC Sport Sciences SC Sport Sciences GA DK2OT UT WOS:000374755000006 PM 26807868 ER PT J AU Mehrtash, A Gupta, SN Shanbhag, D Miller, JV Kapur, T Fennessy, FM Kikinis, R Fedorov, A AF Mehrtash, Alireza Gupta, Sandeep N. Shanbhag, Dattesh Miller, James V. Kapur, Tina Fennessy, Fiona M. Kikinis, Ron Fedorov, Andriy TI Bolus arrival time and its effect on tissue characterization with dynamic contrast-enhanced magnetic resonance imaging SO JOURNAL OF MEDICAL IMAGING LA English DT Article DE bolus arrival time; dynamic contrast-enhanced magnetic resonance imaging; Tofts model; pharmacokinetic analysis; reproducibly; quantitative imaging ID SINGULAR-VALUE DECOMPOSITION; DCE-MRI DATA; PROSTATE-CANCER; PHARMACOKINETIC PARAMETERS; MYOCARDIAL-PERFUSION; TRACER KINETICS; TUMOR RESPONSE; REPRODUCIBILITY; THERAPY; TRACKING AB Matching the bolus arrival time (BAT) of the arterial input function (AIF) and tissue residue function (TRF) is necessary for accurate pharmacokinetic (PK) modeling of dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI). We investigated the sensitivity of volume transfer constant (K-trans) and extravascular extracellular volume fraction (v(e)) to BAT and compared the results of four automatic BAT measurement methods in characterization of prostate and breast cancers. Variation in delay between AIF and TRF resulted in a monotonous change trend of Ktrans and ve values. The results of automatic BAT estimators for clinical data were all comparable except for one BAT estimation method. Our results indicate that inaccuracies in BAT measurement can lead to variability among DCE-MRI PK model parameters, diminish the quality of model fit, and produce fewer valid voxels in a region of interest. Although the selection of the BAT method did not affect the direction of change in the treatment assessment cohort, we suggest that BAT measurement methods must be used consistently in the course of longitudinal studies to control measurement variability. (C) 2016 Society of Photo-Optical Instrumentation Engineers (SPIE) C1 [Mehrtash, Alireza; Kapur, Tina; Fennessy, Fiona M.; Kikinis, Ron; Fedorov, Andriy] Brigham & Womens Hosp, Dept Radiol, Surg Planning Lab, ASBI, L1-050,75 Francis St, Boston, MA 02115 USA. [Mehrtash, Alireza; Kapur, Tina; Fennessy, Fiona M.; Kikinis, Ron; Fedorov, Andriy] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Gupta, Sandeep N.; Shanbhag, Dattesh; Miller, James V.] Gen Elect Global Res, Niskayuna, NY 12309 USA. [Fennessy, Fiona M.] Dana Farber Canc Inst, Dept Radiol, Boston, MA 02115 USA. RP Mehrtash, A (reprint author), Brigham & Womens Hosp, Dept Radiol, Surg Planning Lab, ASBI, L1-050,75 Francis St, Boston, MA 02115 USA. EM mehrtash@bwh.harvard.edu OI Fedorov, Andrey/0000-0003-4806-9413 FU NCI NIH HHS [R01 CA111288, U01 CA151261, U24 CA180918]; NIBIB NIH HHS [P41 EB015902, P41 EB015898] NR 44 TC 0 Z9 0 U1 2 U2 5 PU SPIE-SOC PHOTO-OPTICAL INSTRUMENTATION ENGINEERS PI BELLINGHAM PA 1000 20TH ST, PO BOX 10, BELLINGHAM, WA 98225 USA SN 2329-4302 EI 2329-4310 J9 J MED IMAGING JI J. Med. Imaging PD JAN-MAR PY 2016 VL 3 IS 1 AR 014503 DI 10.1117/1.JMI.3.1.014503 PG 16 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA DJ5HA UT WOS:000374236300024 PM 26989759 ER PT J AU Kaiser, AP Seligowski, A Spiro, A Chopra, M AF Kaiser, Anica Pless Seligowski, Antonia Spiro, Avron, III Chopra, Mohit TI Health status and treatment-seeking stigma in older adults with trauma and posttraumatic stress disorder SO JOURNAL OF REHABILITATION RESEARCH AND DEVELOPMENT LA English DT Article DE aging; comorbidity; health-related quality of life; linear mixed modeling; mental health; physical health; post traumatic; stress disorder; stigma; trauma; treatment-seeking ID QUALITY-OF-LIFE; INTERNATIONAL NEUROPSYCHIATRIC INTERVIEW; PRIMARY-CARE CLINICS; WAR VETERANS; RISK-FACTORS; DSM-IV; PTSD; MILITARY; METAANALYSIS; PREVALENCE AB This study compared health status across four trauma/posttraumatic stress disorder (PTSD) groups of older adults with depression, anxiety, and/or at -risk drinking who attended primary care appointments (N = 1,199; mean age = 73.5 yr), mostly at Department of Veterans Affairs hospitals. The trauma and PTSD categories were PTSD (n = 81), partial PTSD (n = 127), trauma only (n = 323), and no trauma (n = 668). Physical and mental health-related quality of life (HQL), indices of social and economic impairment and stigma regarding treatment -seeking were compared among groups. Group differences were found for several indicators of functional impairment; the PTSD group had fewer close friends and higher treatment -seeking stigma beliefs related to having a disorder. Linear mixed modeling examined associations between trauma/PTSD group and HQL. After accounting for covariates, the trauma/PTSD groups differed across the Medical Outcome Study Short Form -36 scales and component scores (indicated by significant group by scale interaction). Differences among groups were confined to mental health measures; those with PTSD had worse HQL. Post hoc analyses examined the number of comorbid psychiatric diagnoses by trauma/PTSD. group. Overall, findings indicate that mental HQL varies among older adults with trauma and PTSD and that although treatment related stigma does not differ among groups, it does affect HQL. C1 [Kaiser, Anica Pless; Seligowski, Antonia] VA Boston Healthcare Syst, Dept Vet Affairs VA Natl Ctr PTSD, Boston, MA USA. [Kaiser, Anica Pless; Spiro, Avron, III; Chopra, Mohit] Boston Univ, Sch Med, Dept Psychiat, Boston, MA 02118 USA. [Spiro, Avron, III] VA Boston Healthcare Syst, Massachusetts Vet Epidemiol Res & Informat Ctr, Boston, MA USA. [Spiro, Avron, III] Boston Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA USA. [Chopra, Mohit] Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA. RP Kaiser, AP (reprint author), VA Boston Healthcare Syst, VA Natl Ctr PTSD, 150 S Huntington Ave 116-B2, Boston, MA 02130 USA. EM anica.plesskaiser@va.gov FU National Institute of Aging [R24-AG039343]; VA Senior Research Career Scientist Award from VA Clinical Science Research and Development Service; Substance Abuse and Mental Health Services Administration, the VA; Centers for Medicare and Medicaid Services FX This material was based on work supported by the National Institute of Aging (grant R24-AG039343) and a VA Senior Research Career Scientist Award to Dr. Spiro from the VA Clinical Science Research and Development Service. The PRISM-E was funded jointly by the Substance Abuse and Mental Health Services Administration, the VA, and the Centers for Medicare and Medicaid Services. This work was supported with resources and the use of facilities at the VA Boston Healthcare System. NR 37 TC 0 Z9 0 U1 5 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 2016 VL 53 IS 3 BP 391 EP 402 PG 12 WC Rehabilitation SC Rehabilitation GA DL6EF UT WOS:000375731700009 ER PT J AU Gruionu, G Bazou, D Maimon, N Onita-Lenco, M Gruionu, LG Huang, PG Munn, LL AF Gruionu, Gabriel Bazou, Despina Maimon, Nir Onita-Lenco, Mara Gruionu, Lucian G. Huang, Peigen Munn, Lance L. TI Implantable tissue isolation chambers for analyzing tumor dynamics in vivo SO LAB ON A CHIP LA English DT Article ID INTERSTITIAL FLUID PRESSURE; ORIENTED COLLAGEN GELS; BLOOD-VESSEL FORMATION; CONTACT GUIDANCE; MICROVASCULAR ARCHITECTURE; VASCULAR-PERMEABILITY; EXTRACELLULAR-MATRIX; CELL-MIGRATION; SOLID STRESS; ANGIOGENESIS AB Recruitment of new blood vessels from the surrounding tissue is central to tumor progression and involves a fundamental transition of the normal, organized vasculature into a dense disarray of vessels that infiltrates the tumor. At present, studying the co-development of the tumor and recruited normal tissue is experimentally challenging because many of the important events occur rapidly and over short length scales in a dense three-dimensional space. To overcome these experimental limitations, we partially confined tumors within biocompatible and optically clear tissue isolation chambers (TICs) and implanted them in mice to create a system that is more amenable to microscopic analysis. Our goal was to integrate the tumor into a recruited host tissue complete with vasculature -and demonstrate that the system recapitulates relevant features of the tumor microenvironment. We show that the TICs allow clear visualization of the cellular events associated with tumor growth and progression at the host-tumor interface including cell infiltration, matrix remodeling and angiogenesis. The tissue within the chamber is viable for more than a month, and the process is robust in both the skin and brain. Treatment with losartan, an angiotensin II receptor antagonist, decreased the collagen density and fiber length in the TIC, consistent with the known activity of this drug. We further show that collagen fibers display characteristic tumor signatures and play a central role in angiogenesis, guiding the migration of tethered endothelial sprouts. The methodology combines accessible methods of microfabrication with animal models and will enable more informative studies of the cellular mechanisms of tumor progression. C1 [Gruionu, Gabriel; Bazou, Despina; Maimon, Nir; Onita-Lenco, Mara; Huang, Peigen; Munn, Lance L.] Massachusetts Gen Hosp, Edwin L Steele Labs Tumor Biol, Dept Radiat Oncol, Boston, MA 02114 USA. [Gruionu, Gabriel; Bazou, Despina; Maimon, Nir; Onita-Lenco, Mara; Huang, Peigen; Munn, Lance L.] Harvard Univ, Sch Med, Boston, MA USA. [Gruionu, Gabriel] Massachusetts Gen Hosp, Dept Surg, Div Trauma Emergency Surg & Surg Crit Care, Boston, MA 02114 USA. [Gruionu, Gabriel; Gruionu, Lucian G.] Medinsys SRL, Craiova, Romania. [Gruionu, Lucian G.] Univ Craiova, Fac Mech, Craiova, Romania. RP Munn, LL (reprint author), Massachusetts Gen Hosp, Edwin L Steele Labs Tumor Biol, Dept Radiat Oncol, Boston, MA 02114 USA.; Munn, LL (reprint author), Harvard Univ, Sch Med, Boston, MA USA. EM munn@steele.mgh.harvard.edu RI Gruionu, Lucian/F-6121-2011; Munn, Lance/L-3950-2016 OI Gruionu, Lucian/0000-0002-4526-0864; Munn, Lance/0000-0003-0698-7232 FU National Institutes of Health [R01HL106584, R01CA149285]; European Economic Area (EEA) Financial Mechanism [EEA-JRP-RO-NO-2013-1-0123, 3SEE/30.06.2014]; Executive Agency for Higher Education, Research, Development and Innovation Funding (UEFISCDI), Romania [12/2014, PN-II-PT-PCCA-2013-4-1105] FX The authors would like to acknowledge funding from the National Institutes of Health (R01HL106584 and R01CA149285), the European Economic Area (EEA) Financial Mechanism 2009-2014 (Project EEA-JRP-RO-NO-2013-1-0123, contract no. 3SEE/30.06.2014) and the Executive Agency for Higher Education, Research, Development and Innovation Funding (UEFISCDI), Romania (Contract No. 12/2014, Code PN-II-PT-PCCA-2013-4-1105). We thank Julia Khan, Sylvie Roberge and the Cox-7 animal facility staff from the Edwin L. Steele Laboratories for Tumor Biology, Massachusetts General Hospital for chamber implantations and their excellent animal caretaking. NR 56 TC 2 Z9 2 U1 2 U2 6 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 2016 VL 16 IS 10 BP 1840 EP 1851 DI 10.1039/c6lc00237d PG 12 WC Biochemical Research Methods; Chemistry, Multidisciplinary; Nanoscience & Nanotechnology SC Biochemistry & Molecular Biology; Chemistry; Science & Technology - Other Topics GA DL6CC UT WOS:000375724800009 PM 27128791 ER PT J AU Chang, DK Kurella, VB Biswas, S Avnir, Y Sui, JH Wang, XQ Sun, JS Wang, YY Panditrao, M Peterson, E Tallarico, A Fernandes, S Goodall, M Zhu, Q Brown, JR Jefferis, R Marasco, WA AF Chang, De-Kuan Kurella, Vinodh B. Biswas, Subhabrata Avnir, Yuval Sui, Jianhua Wang, Xueqian Sun, Jiusong Wang, Yanyan Panditrao, Madhura Peterson, Eric Tallarico, Aimee Fernandes, Stacey Goodall, Margaret Zhu, Quan Brown, Jennifer R. Jefferis, Roy Marasco, Wayne A. TI Humanized mouse G6 anti-idiotypic monoclonal antibody has therapeutic potential against IGHV1-69 germline gene-based B-CLL SO MABS LA English DT Article DE B-cell chronic lymphocytic leukemia; cytotoxicity; GTL mice; humanization; immunotherapy; monoclonal antibody; precision medicine ID CHRONIC LYMPHOCYTIC-LEUKEMIA; CELL LYMPHOMA; SOMATIC HYPERMUTATION; ANTIGEN RECEPTORS; PATHOGENETIC IMPLICATIONS; IMMUNE-RESPONSES; XENOGRAFT MODELS; FORCE-FIELD; BLT MICE; T-CELLS AB In 10-20% of the cases of chronic lymphocytic leukemia of B-cell phenotype (B-CLL), the IGHV1-69 germline is utilized as VH gene of the B cell receptor (BCR). Mouse G6 (MuG6) is an anti-idiotypic monoclonal antibody discovered in a screen against rheumatoid factors (RFs) that binds with high affinity to an idiotope expressed on the 51p1 alleles of IGHV1-69 germline gene encoded antibodies (G6-id(+)). The finding that unmutated IGHV1-69 encoded BCRs are frequently expressed on B-CLL cells provides an opportunity for anti-idiotype monoclonal antibody immunotherapy. In this study, we first showed that MuG6 can deplete B cells encoding IGHV1-69 BCRs using a novel humanized GTL mouse model. Next, we humanized MuG6 and demonstrated that the humanized antibodies (HuG6s), especially HuG6.3, displayed similar to 2-fold higher binding affinity for G6-id(+) antibody compared to the parental MuG6. Additional studies showed that HuG6.3 was able to kill G6-id(+) BCR expressing cells and patient B-CLL cells through antibody-dependent cell-mediated cytotoxicity (ADCC) and complement-dependent cytotoxicity (CDC). Finally, both MuG6 and HuG6.3 mediate in vivo depletion of B-CLL cells in NSG mice. These data suggest that HuG6.3 may provide a new precision medicine to selectively kill IGHV1-69-encoding G6-id(+) B-CLL cells. C1 [Chang, De-Kuan; Kurella, Vinodh B.; Biswas, Subhabrata; Avnir, Yuval; Sui, Jianhua; Wang, Xueqian; Sun, Jiusong; Wang, Yanyan; Panditrao, Madhura; Peterson, Eric; Tallarico, Aimee; Zhu, Quan; Marasco, Wayne A.] Dana Farber Canc Inst, Dept Canc Immunol & Virol, Boston, MA 02115 USA. [Chang, De-Kuan; Kurella, Vinodh B.; Biswas, Subhabrata; Avnir, Yuval; Sui, Jianhua; Wang, Xueqian; Sun, Jiusong; Tallarico, Aimee; Zhu, Quan; Marasco, Wayne A.] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. [Fernandes, Stacey; Brown, Jennifer R.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Goodall, Margaret; Jefferis, Roy] Univ Birmingham, Sch Med, Div Immun & Infect, Birmingham, W Midlands, England. [Chang, De-Kuan] AbVitro Inc, Boston, MA 02210 USA. [Kurella, Vinodh B.] Intrexon Corp, Immunooncol Div, Germantown, MD 20876 USA. [Sui, Jianhua] Natl Inst Biol Sci, Beijing, Peoples R China. RP Marasco, WA (reprint author), Dana Farber Canc Inst, Dept Canc Immunol & Virol, Boston, MA 02115 USA.; Marasco, WA (reprint author), Harvard Univ, Sch Med, Dept Med, Boston, MA USA. EM wayne_marasco@dfci.harvard.edu OI SUI, JIANHUA/0000-0002-1272-9662 FU Defense Advanced Research Projects Agency's "7-Day Biodefense" program [W911NF-10-1-0266] FX This work was also funded by the Defense Advanced Research Projects Agency's "7-Day Biodefense" program under contract # W911NF-10-1-0266 to WAM. NR 71 TC 0 Z9 0 U1 0 U2 0 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 530 WALNUT STREET, STE 850, PHILADELPHIA, PA 19106 USA SN 1942-0862 EI 1942-0870 J9 MABS-AUSTIN JI mAbs PY 2016 VL 8 IS 4 BP 787 EP 798 DI 10.1080/19420862.2016.1159365 PG 12 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA DL7XT UT WOS:000375854400013 PM 26963739 ER PT J AU Macakova, M Bohuslavova, B Vochozkova, P Pavlok, A Sedlackova, M Vidinska, D Vochyanova, K Liskova, I Valekova, L Baxa, M Ellederova, Z Klima, J Juhas, S Juhasova, J Klouckova, J Haluzik, M Klempir, J Hansikova, H Spacilova, J Collins, R Blumenthal, I Talkowski, M Gusella, JF Howland, DS DiFiglia, M Motlik, J AF Macakova, Monika Bohuslavova, Bozena Vochozkova, Petra Pavlok, Antonin Sedlackova, Miroslava Vidinska, Daniela Vochyanova, Klara Liskova, Irena Valekova, Lvona Baxa, Monika Ellederova, Zdenka Klima, Jiri Juhas, Stefan Juhasova, Jana Klouckova, Jana Haluzik, Martin Klempir, Jiri Hansikova, Hana Spacilova, Jana Collins, Ryan Blumenthal, Ian Talkowski, Michael Gusella, James F. Howland, David S. DiFiglia, Marian Motlik, Jan TI Mutated Huntingtin Causes Testicular Pathology in Transgenic Minipig Boars SO NEURODEGENERATIVE DISEASES LA English DT Article DE Huntington's disease; Pig model; Mutant huntingtin; Spermatozoa; Testes; Degeneration ID YAC128 MOUSE MODEL; MUTANT HUNTINGTIN; NEURODEGENERATIVE DISORDERS; CELLULAR TOXICITY; MINIATURE PIG; HUMAN BRAIN; DISEASE; LENGTH; REPEAT; MICE AB Background: Huntington's disease is induced by CAG expansion in a single gene coding the huntingtin protein. The mutated huntingtin (mtHtt) primarily causes degeneration of neurons in the brain, but it also affects peripheral tissues, including testes. Objective: We studied sperm and testes of transgenic boars expressing the N-terminal region of human mtHtt. Methods: In this study, measures of reproductive parameters and electron microscopy (EM) images of spermatozoa and testes of transgenic (TgHD) and wild-type (WT) boars of Fl (24-48 months old) and F2 (12-36 months old) generations were compared. In addition, immunofluorescence, immunohistochemistry, Western blot, hormonal analysis and whole-genome sequencing were done in order to elucidate the effects of mtHtt. Results: Evidence for fertility failure of both TgHD generations was observed at the age of 13 months. Reproductive parameters declined and progressively worsened with age. EM revealed numerous pathological features in sperm tails and in testicular epithelium from 24- and 36-month-old TgHD boars. Moreover, innmunohistochemistry confirmed significantly lower proliferation activity of spermatogonia in transgenic testes. mtHtt was highly expressed in spermatozoa and testes of TgHD boars and localized in all cells of seminiferous tubules. Levels of fertility-related hormones did not differ in TgHD and WT siblings. Genome analysis confirmed that insertion of the lentiviral construct did not interrupt any coding sequence in the pig genome. Conclusions: The sperm and testicular degeneration of TgHD boars is caused by gain-of-function of the highly expressed mtHtt. (C) 2016 S. Karger AG, Basel C1 [Macakova, Monika; Bohuslavova, Bozena; Vochozkova, Petra; Pavlok, Antonin; Vidinska, Daniela; Vochyanova, Klara; Liskova, Irena; Valekova, Lvona; Baxa, Monika; Ellederova, Zdenka; Klima, Jiri; Juhas, Stefan; Juhasova, Jana; Motlik, Jan] Acad Sci Czech Republic, Inst Anim Physiol & Genet, Lab Cell Regenerat & Plast, Libechov, Czech Republic. [Sedlackova, Miroslava] Masaryk Univ, Fac Med, Dept Histol & Embryol, Brno, Czech Republic. [Macakova, Monika; Bohuslavova, Bozena; Vochozkova, Petra; Vidinska, Daniela; Vochyanova, Klara; Valekova, Lvona; Baxa, Monika] Charles Univ Prague, Fac Sci, Dept Cell Biol, Prague, Czech Republic. [Liskova, Irena; Klempir, Jiri] Charles Univ Prague, Fac Med 1, Dept Neurol, Prague, Czech Republic. [Liskova, Irena; Klempir, Jiri] Charles Univ Prague, Fac Med 1, Ctr Clin Neurosci, Prague, Czech Republic. [Klouckova, Jana; Haluzik, Martin] Charles Univ Prague, Fac Med 1, Dept Med 3, Dept Endocrinol & Metab, Prague, Czech Republic. [Hansikova, Hana; Spacilova, Jana] Charles Univ Prague, Fac Med 1, Dept Pediat & Adolescent Med, Lab Study Mitochondrial Disorders, Prague, Czech Republic. [Hansikova, Hana; Spacilova, Jana] Gen Univ Hosp, Prague, Czech Republic. [Collins, Ryan; Blumenthal, Ian; Talkowski, Michael; Gusella, James F.] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA. [DiFiglia, Marian] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. [Howland, David S.] CHDI Fdn, Princeton, NY USA. RP Motlik, J (reprint author), Inst Anim Physiol & Genet, Lab Cell Regenerat & Plast, Rumburska 89, CZ-27721 Libechov, Czech Republic. EM motlik@iapg.cas.cz RI Krizova, Jana/E-8721-2017; OI Krizova, Jana/0000-0003-1841-7341; Collins, Ryan/0000-0003-1268-9995 FU CHDI Foundation [A-5378]; project EXAM from the European Regional Development Fund [CZ.1.05/2.1.00/03.0124]; RVO [67985904]; Norwegian Financial Mechanism; Ministry of Education, Youth and Sports [MSMT-28477/2014]; Charles University [SVV 260083]; National Sustainability Programme [LO1609] FX This work was supported by the CHDI Foundation (A-5378), the project EXAM from the European Regional Development Fund (CZ.1.05/2.1.00/03.0124), RVO 67985904, the Norwegian Financial Mechanism 2009-2014, the Ministry of Education, Youth and Sports (project contract MSMT-28477/2014) and Charles University (grant SVV 260083), and National Sustainability Programme No. LO1609 (MEYS CR). NR 39 TC 1 Z9 1 U1 4 U2 9 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 1660-2854 EI 1660-2862 J9 NEURODEGENER DIS JI Neurodegener. Dis. PY 2016 VL 16 IS 3-4 BP 245 EP 259 DI 10.1159/000443665 PG 15 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA DJ9CV UT WOS:000374512500015 PM 26959244 ER PT J AU Benmansour, S Adeniji, OS Privratsky, AA Frazer, A AF Benmansour, Saloua Adeniji, Opeyemi S. Privratsky, Anthony A. Frazer, Alan TI Effects of Long-Term Treatment with Estradiol and Estrogen Receptor Subtype Agonists on Serotonergic Function in Ovariectomized Rats SO NEUROENDOCRINOLOGY LA English DT Article DE Estradiol; Estrogen receptor agonists; Antidepressant; Forced swim test; Signaling pathways ID CENTRAL-NERVOUS-SYSTEM; FORCED SWIM TEST; OBJECT MEMORY CONSOLIDATION; DEPRESSIVE-LIKE BEHAVIOR; SIGNAL-REGULATED KINASE; BETA MESSENGER-RNA; ER-BETA; ANTIDEPRESSANT TREATMENTS; HIPPOCAMPAL-FORMATION; SYNAPTIC PLASTICITY AB Acute estradiol treatment was reported to slow the clearance of serotonin via activation of estrogen receptors (ER)beta and/or GPR30 and to block the ability of a selective serotonin reuptake inhibitor (SSRI) to slow serotonin clearance via activation of ER alpha. In this study, the behavioral consequences of longer-term treatments with estradiol or ER subtype-selective agonists and/or an SSRI were examined in the forced swim test (FST). Ovariectomized rats were administered the following for 2 weeks: estradiol, ER beta agonist (diarylpropionitrile, DPN), GPR30 agonist (G1), ER alpha agonist (PPT), and/or the SSRI sertraline. Similar to sertraline, longer-term treatment with estradiol, DPN or G1 induced an antidepressant-like effect. By contrast, PPT did not, even though it blocked the antidepressant-like effect of sertraline. Uterus weights, used as a peripheral measure of estrogenic activity, were increased by estradiol and PPT but not DPN or G1 treatment. A second part of this study investigated, using Western blot analyses in homogenates from hippocampus, whether these behavioral effects are accompanied by changes in the activation of specific signaling pathways and/or TrkB. Estradiol and G1 increased phosphorylation of Akt, ERK and TrkB. These effects were similar to those obtained after treatment with sertraline. Treatment with DPN increased phosphorylation of ERK and TrkB, but it did not alter that of Akt. Treatment with PPT increased phosphorylation of Akt and ERK without altering that of TrkB. In conclusion, activation of at least TrkB and possibly ERK may be involved in the antidepressant- like effect of estradiol, ER beta and GPR30 agonists whereas Akt activation may not be necessary. (C) 2015 S. Karger AG, Basel C1 [Benmansour, Saloua; Adeniji, Opeyemi S.; Privratsky, Anthony A.; Frazer, Alan] Univ Texas Hlth Sci Ctr San Antonio, Dept Pharmacol MC 7764, 7703 Floyd Curl Dr, San Antonio, TX 78229 USA. [Frazer, Alan] South Texas Vet Hlth Care Syst, San Antonio, TX USA. RP Benmansour, S (reprint author), Univ Texas Hlth Sci Ctr San Antonio, Dept Pharmacol MC 7764, 7703 Floyd Curl Dr, San Antonio, TX 78229 USA. EM benmansour@uthscsa.edu FU NARSAD; Department of Veterans Affairs; National Institute of Mental Health [MH090386] FX This research was supported by funds from NARSAD, the Department of Veterans Affairs and the National Institute of Mental Health (MH090386). NR 75 TC 3 Z9 3 U1 4 U2 4 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0028-3835 EI 1423-0194 J9 NEUROENDOCRINOLOGY JI Neuroendocrinology PY 2016 VL 103 IS 3-4 BP 269 EP 281 DI 10.1159/000437268 PG 13 WC Endocrinology & Metabolism; Neurosciences SC Endocrinology & Metabolism; Neurosciences & Neurology GA DL6RO UT WOS:000375766500009 PM 26159182 ER PT J AU Chen, RC Hoffman, KE Sher, DJ Showalter, TN Morrell, R Chen, AB Benda, R Nguyen, PL Movsas, B Hardenbergh, P AF Chen, Ronald C. Hoffman, Karen E. Sher, David J. Showalter, Timothy N. Morrell, Rosalyn Chen, Aileen B. Benda, Rashmi Nguyen, Paul L. Movsas, Benjamin Hardenbergh, Patricia TI Development of a standard survivorship care plan template for radiation oncologists SO PRACTICAL RADIATION ONCOLOGY LA English DT Article ID RANDOMIZED CONTROLLED-TRIAL; CANCER SURVIVORS; BREAST-CANCER AB Purpose: In response to a need expressed by members of the American Society for Radiation Oncology (ASTRO), the ASTRO Board of Directors approved an initiative to create a radiation oncology-specific survivorship care plan (SCP) template. Methods and Materials: Members of the ASTRO Health Services Research Committee (which was subsequently renamed the Clinical, Translational, and Basic Science Advisory Committee) were charged with this task. Creation of the ASTRO SCP template was informed by existing SCP templates published by other organizations and modified to add radiation treatment details felt to be important by committee members. An emphasis was placed on describing diagnostic and treatment details in ways that patients and referring physicians can understand. The resulting template subsequently underwent ASTRO committee review, public comment, and was ultimately approved by the ASTRO Board of Directors. Results: The standardized template includes 2 components: the first 2 pages represent an SCP that is to be given to the patient and referring physicians, whereas page 3 includes additional technical radiation therapy details which are usually included in a traditional radiation treatment summary. That is, the template serves two purposes-obviating the need for radiation oncologists to create an SCP for patients and a separate treatment completion note. Conclusions: The standardized ASTRO SCP template serves an immediate need of practicing radiation oncologists to have a template that is radiation-specific and meets current requirements for SCP and radiation treatment summary. Potential future work may include development of disease-specific templates that will include more granular details regarding expected toxicities and follow-up care recommendations and working with electronic medical record system vendors to facilitate autocreation of SCP documents to reduce the burden on physicians and other staff. These future developments can make this intervention more helpful to patients, and further reduce the burden of creating SCPs. (C) 2016 American Society for Radiation Oncology. Published by Elsevier Inc. All rights reserved. C1 [Chen, Ronald C.] Univ N Carolina, Dept Radiat Oncol, CB 7512, Chapel Hill, NC 27599 USA. [Hoffman, Karen E.] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. [Sher, David J.] UT Southwestern Med Ctr, Dept Radiat Oncol, Dallas, TX USA. [Showalter, Timothy N.] Univ Virginia, Charlottesville, VA USA. [Morrell, Rosalyn] Adv Radiat Ctr Beverly Hills, Beverly Hills, CA USA. [Chen, Aileen B.] Dana Farber Brigham & Womens Canc Inst, Boston, MA USA. [Benda, Rashmi] Boca Raton Reg Hosp, Lynn Canc Inst, Dept Radiat Oncol, Boca Raton, FL USA. [Nguyen, Paul L.] Harvard Univ, Sch Med, Dana Farber Brigham & Womens Canc Ctr, Boston, MA USA. [Movsas, Benjamin] Henry Ford Hosp, Dept Radiat Oncol, Detroit, MI 48202 USA. [Hardenbergh, Patricia] Univ Colorado, Shaw Reg Canc Ctr, Edwards, CO USA. RP Chen, RC (reprint author), Univ N Carolina, Dept Radiat Oncol, CB 7512, Chapel Hill, NC 27599 USA. EM Ronald_chen@med.unc.edu NR 15 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1879-8500 J9 PRACT RADIAT ONCOL JI Pract. Radiat. Oncol. PD JAN-FEB PY 2016 VL 6 IS 1 BP 57 EP 65 DI 10.1016/j.prro.2015.10.001 PG 9 WC Oncology SC Oncology GA DK1JC UT WOS:000374667300013 PM 26778795 ER PT J AU Han, ZH Bondeson, JC Lewis, JH Mannarino, EG Friesen, SA Wagar, MM Balboni, TA Alexander, BM Arvold, ND Sher, DJ Hacker, FL AF Han, Zhaohui Bondeson, John C. Lewis, John H. Mannarino, Edward G. Friesen, Scott A. Wagar, Matthew M. Balboni, Tracy A. Alexander, Brian M. Arvold, Nils D. Sher, David J. Hacker, Fred L. TI Evaluation of initial setup accuracy and intrafraction motion for spine stereotactic body radiation therapy using stereotactic body frames SO PRACTICAL RADIATION ONCOLOGY LA English DT Article ID BEAM COMPUTED-TOMOGRAPHY; LOCALIZATION ACCURACY; SAFE PRACTICE; RADIOTHERAPY; METASTASES; IMMOBILIZATION; RADIOSURGERY; IMPACT AB Purpose: The purposes of this study were (1) to evaluate the initial setup accuracy and intrafraction motion for spine stereotactic body radiation therapy (SBRT) using stereotactic body frames (SBFs) and (2) to validate an in-house-developed SBF using a commercial SBF as a benchmark. Methods and materials: Thirty-two spine SBRT patients (34 sites, 118 fractions) were immobilized with the Elekta and in-house (BHS) SBFs. All patients were set up with the Brainlab ExacTrac system, which includes infrared and stereoscopic kilovoltage x-ray-based positioning. Patients were initially positioned in the frame with the use of skin tattoos and then shifted to the treatment isocenter based on infrared markers affixed to the frame with known geometry relative to the isocenter. ExacTrac kV imaging was acquired, and automatic 6D (6 degrees of freedom) bony fusion was performed. The resulting translations and rotations gave the initial setup accuracy. These translations and rotations were corrected for by use of a robotic couch, and verification imaging was acquired that yielded residual setup error. The imaging/fusion process was repeated multiple times during treatment to provide intrafraction motion data. Results: The BHS SBF had greater initial setup errors (mean +/- SD): -3.9 +/- 5.5 mm (0.2 +/- 0.9 degrees), -1.6 +/- 6.0 mm (0.5 +/- 1.4 degrees), and 0.0 +/- 5.3 mm (0.8 +/- 1.0 degrees), respectively, in the vertical (VRT), longitudinal (LNG), and lateral (LAT) directions. The corresponding values were 0.6 +/- 2.7 mm (0.2 +/- 0.6 degrees), 0.9 +/- 5.3 mm (-0.2 +/- 0.9 degrees), and -0.9 +/- 3.0 mm (0.3 +/- 0.9 degrees) for the Elekta SBF. The residual setup errors were essentially the same for both frames and were -0.1 +/- 0.4 mm (0.1 +/- 0.5 degrees), -0.2 +/- 0.4 mm (0.0 +/- 0.4 degrees), and 0.0 +/- 0.4 mm (0.0 +/- 0.4 degrees), respectively, in VRT, LNG, and LAT. The intrafraction shifts in VRT, LNG, and LAT were 0.0 +/- 0.4 mm (0.0 +/- 0.3 degrees), 0.0 +/- 0.5 mm (0.0 +/- 0.4 degrees), and 0.0 +/- 0.4 mm (0.0 +/- 0.3 degrees), with no significant difference observed between the 2 frames. Conclusions: These results showed that the combination of the ExacTrac system with either SBF was highly effective in achieving both setup accuracy and intrafraction stability, which were on parwith that of mask-based cranial radiosurgery. (C) 2016 American Society for Radiation Oncology. Published by Elsevier Inc. All rights reserved. C1 [Han, Zhaohui; Bondeson, John C.; Lewis, John H.; Mannarino, Edward G.; Friesen, Scott A.; Wagar, Matthew M.; Balboni, Tracy A.; Alexander, Brian M.; Arvold, Nils D.; Hacker, Fred L.] Brigham & Womens Hosp, Dept Radiat Oncol, 75 Francis St,ASBI L2, Boston, MA 02115 USA. [Han, Zhaohui; Bondeson, John C.; Lewis, John H.; Mannarino, Edward G.; Friesen, Scott A.; Wagar, Matthew M.; Balboni, Tracy A.; Alexander, Brian M.; Arvold, Nils D.; Hacker, Fred L.] Dana Farber Canc Inst, 75 Francis St,ASBI L2, Boston, MA 02115 USA. [Han, Zhaohui; Bondeson, John C.; Lewis, John H.; Mannarino, Edward G.; Friesen, Scott A.; Wagar, Matthew M.; Balboni, Tracy A.; Alexander, Brian M.; Arvold, Nils D.; Hacker, Fred L.] Harvard Univ, Sch Med, Boston, MA USA. [Sher, David J.] Rush Univ, Med Ctr, Dept Radiat Oncol, Chicago, IL 60612 USA. RP Hacker, FL (reprint author), Brigham & Womens Hosp, Dept Radiat Oncol, 75 Francis St,ASBI L2, Boston, MA 02115 USA.; Hacker, FL (reprint author), Dana Farber Canc Inst, 75 Francis St,ASBI L2, Boston, MA 02115 USA. EM fhacker@lroc.harvard.edu NR 23 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 1879-8500 J9 PRACT RADIAT ONCOL JI Pract. Radiat. Oncol. PD JAN-FEB PY 2016 VL 6 IS 1 BP E17 EP E24 DI 10.1016/j.prro.2015.08.009 PG 8 WC Oncology SC Oncology GA DK1JC UT WOS:000374667300003 PM 26603596 ER PT J AU Niska, JR Keane, FK Wolfgang, JA Hahn, PF Wo, JY Zhu, AX Hong, TS AF Niska, Joshua R. Keane, Florence K. Wolfgang, John A. Hahn, Peter F. Wo, Jennifer Y. Zhu, Andrew X. Hong, Theodore S. TI Impact of intravenous contrast enhancement phase on target definition for hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (IHC): Observations from patients enrolled on a prospective phase 2 trial SO PRACTICAL RADIATION ONCOLOGY LA English DT Article ID PROTON-BEAM THERAPY; PERIPHERAL CHOLANGIOCARCINOMA; RADIATION-THERAPY; DYNAMIC CT; LIVER; RADIOTHERAPY; PATTERNS; THROMBUS AB Background: The safety and efficacy of radiation therapy for hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (IHC) depend on accurate definition of gross tumor volume (GTV), but GTV often varies between phases of multiphasic computed tomography (CT) imaging. Methods: We contoured GTVs on arterial, portal venous, and delayed phases of multiphasic CT scans for 32 patients treated on an institutional review board-approved prospective trial of proton therapy for primary liver tumors and determined which phase provided optimal GTV visualization. We assessed agreement between individual phase GTVs to determine if GTV for each phase was encompassed in a 5-mm expansion of either the smallest or the best-visualized GTV. Results: There were 19 HCC lesions and 14 IHC lesions. HCC lesions were best identified on the arterial phase in 42% (n = 8), portal venous phase in 32% (n = 6), and delayed phase in 26% (n = 5). IHC lesions were best identified on portal venous phase in 64% (n = 9) and the arterial phase in 29% (n = 4), with 1 case equally visualized on arterial and portal venous phases. In all 33 lesions, a 5-mm expansion around the smallest GTV failed to cover GTVs defined on other available phases. A 5-mm expansion around the best-visualized GTV provided satisfactory coverage of all available phases' GTVs in 6/18 HCC cases and 2/9 IHC cases. Conclusions: Variability between GTVs on multiphasic CT scans could not be overcome with a 5-mm expansion of either the smallest GTV or the best-visualized GTV. Assessment of all available intravenous contrast phases is essential to accurately define the GTV. (C) 2016 American Society for Radiation Oncology. Published by Elsevier Inc. All rights reserved. C1 [Niska, Joshua R.] Mayo Clin, Dept Radiat Oncol, Phoenix, AZ USA. [Keane, Florence K.; Wolfgang, John A.; Wo, Jennifer Y.; Hong, Theodore S.] Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. [Hahn, Peter F.] Massachusetts Gen Hosp, Dept Radiol, Boston, MA USA. [Zhu, Andrew X.] Massachusetts Gen Hosp, Dept Med, Div Hematol Oncol, Boston, MA 02114 USA. RP Hong, TS (reprint author), Massachusetts Gen Hosp, 100 Blossom St,Cox 3, Boston, MA 02459 USA. EM tshong1@mgh.harvard.edu NR 25 TC 0 Z9 0 U1 1 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1879-8500 J9 PRACT RADIAT ONCOL JI Pract. Radiat. Oncol. PD JAN-FEB PY 2016 VL 6 IS 1 BP E9 EP E16 DI 10.1016/j.prro.2015.08.005 PG 8 WC Oncology SC Oncology GA DK1JC UT WOS:000374667300002 PM 26598907 ER PT J AU Minikel, E Lek, M Samocha, KE Karczewski, KJ Marshall, JL Armean, I Ware, J Daly, MJ MacArthur, DG AF Minikel, Eric Lek, Monkol Samocha, Kaitlin E. Karczewski, Konrad J. Marshall, Jamie L. Armean, Irina Ware, James Daly, Mark J. MacArthur, Daniel G. CA Exome Aggregation Consortium TI An early glimpse of saturation mutagenesis in humans: Insights from protein-coding genetic variation in 60,706 people SO PRION LA English DT Meeting Abstract C1 [Minikel, Eric] Broad Inst, Cambridge, MA USA. [Minikel, Eric] Harvard Univ, Sch Med, Cambridge, MA 02138 USA. [Minikel, Eric; Lek, Monkol; Samocha, Kaitlin E.; Karczewski, Konrad J.; Marshall, Jamie L.; Armean, Irina; Daly, Mark J.; MacArthur, Daniel G.; Exome Aggregation Consortium] Broad Inst, Program Med & Populat Genet, Cambridge, MA USA. [Minikel, Eric; Lek, Monkol; Samocha, Kaitlin E.; Karczewski, Konrad J.; Marshall, Jamie L.; Armean, Irina; Daly, Mark J.; MacArthur, Daniel G.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Minikel, Eric; Samocha, Kaitlin E.] Harvard Univ, Sch Med, Program Biol & Biomed Sci, Boston, MA USA. [Ware, James] Univ London Imperial Coll Sci Technol & Med, London, England. NR 0 TC 0 Z9 0 U1 0 U2 0 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 530 WALNUT STREET, STE 850, PHILADELPHIA, PA 19106 USA SN 1933-6896 EI 1933-690X J9 PRION JI Prion PY 2016 VL 10 SU 1 MA P-137 BP S107 EP S107 PG 1 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA DK1EW UT WOS:000374656300151 ER PT J AU Soule, MC Beale, EE Suarez, L Beach, SR Mastromauro, CA Celano, CM Moore, SV Huffman, JC AF Soule, Michael C. Beale, Eleanor E. Suarez, Laura Beach, Scott R. Mastromauro, Carol A. Celano, Christopher M. Moore, Shannon V. Huffman, Jeff C. TI Understanding motivations to participate in an observational research study: Why do patients enroll? SO SOCIAL WORK IN HEALTH CARE LA English DT Article DE Cardiac; motivation; observational; recruitment; research participation ID LIFE-STYLE INTERVENTION; ACUTE CORONARY EVENTS; HEALTH-BELIEF MODEL; GRATITUDE RESEARCH; INFORMED-CONSENT; CLINICAL-TRIALS; QUESTIONNAIRE; ATTITUDES; VALIDITY; DISEASE AB By understanding common motivations for participating in observational research studies, clinicians may better understand the perceived benefits of research participation from their clients' perspective. We enrolled 164 cardiac patients in a study about the effects of gratitude and optimism. Two weeks post-enrollment, participants completed a four-item questionnaire regarding motivations for study enrollment. Altruistic motivation ranked highest, while intellectual, health-related, and financial motivations rated lower. Four subgroups of participants emerged, each with distinct characteristics and different priorities for participating. These findings may help front-line clinicians to understand which motivations for participation apply to their clients who enroll in non-treatment-based research projects. C1 [Soule, Michael C.; Beale, Eleanor E.; Suarez, Laura; Beach, Scott R.; Mastromauro, Carol A.; Celano, Christopher M.; Moore, Shannon V.; Huffman, Jeff C.] Massachusetts Gen Hosp, Dept Psychiat, 55 Fruit St,Blake 11, Boston, MA 02114 USA. [Beach, Scott R.; Celano, Christopher M.; Huffman, Jeff C.] Harvard Univ, Dept Psychiat, Sch Med, Boston, MA 02115 USA. RP Huffman, JC (reprint author), Massachusetts Gen Hosp, Dept Psychiat, 55 Fruit St,Blake 11, Boston, MA 02114 USA. EM jhuffman@partners.org FU Expanding the Science and Practice of Gratitude Project run by UC Berkeley's Greater Good Science Center; UC Davis; John Templeton Foundation [15627]; NIH [R01HL113272] FX This research and analysis time were funded by the Expanding the Science and Practice of Gratitude Project run by UC Berkeley's Greater Good Science Center in partnership with UC Davis with funding from the John Templeton Foundation ( grant ID 15627) to JH. Analysis and editing time was also supported by NIH grant R01HL113272 to JH. The content is solely the responsibility of the authors and does not represent the official views of the funders. NR 54 TC 1 Z9 1 U1 1 U2 1 PU ROUTLEDGE JOURNALS, TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXFORDSHIRE, ENGLAND SN 0098-1389 EI 1541-034X J9 SOC WORK HEALTH CARE JI Soc. Work Health Care PY 2016 VL 55 IS 3 BP 231 EP 246 DI 10.1080/00981389.2015.1114064 PG 16 WC Social Work SC Social Work GA DL4LF UT WOS:000375606900004 PM 26933943 ER PT J AU Moy, MP Sauk, J Gee, MS AF Moy, Matthew P. Sauk, Jenny Gee, Michael S. TI The Role of MR Enterography in Assessing Crohn's Disease Activity and Treatment Response SO GASTROENTEROLOGY RESEARCH AND PRACTICE LA English DT Review ID INFLAMMATORY-BOWEL-DISEASE; SUPERPARAMAGNETIC IRON-OXIDE; MAGNETIC-RESONANCE ENTEROGRAPHY; DIFFUSION-WEIGHTED MRI; COMPUTED-TOMOGRAPHY ENTEROGRAPHY; CHRONIC KIDNEY-DISEASE; CONTRAST-ENHANCED MRI; MULTIPLE-SCLEROSIS; RADIATION-EXPOSURE; CT ENTEROGRAPHY AB MR enterography (MRE) has become the primary imaging modality in the assessment of Crohn's disease (CD) in both children and adults at many institutions in the United States and worldwide, primarily due to its noninvasiveness, superior soft tissue contrast, and lack of ionizing radiation. MRE technique includes distention of the small bowel with oral contrast media with the acquisition of T2-weighted, balanced steady-state free precession, and multiphase T1-weighted fat suppressed gadolinium contrast-enhanced sequences. With the introduction of molecule-targeted biologic agents into the clinical setting for CD and their potential to reverse the inflammatory process, MRE is increasingly utilized to evaluate disease activity and response to therapy as an imaging complement to clinical indices or optical endoscopy. New and emerging MRE techniques, such as diffusion-weighted imaging (DWI), magnetization transfer, ultrasmall superparamagnetic iron oxide-(USPIO-) enhanced MRI, and PET-MR, offer the potential for an expanded role of MRI in detecting occult disease activity, evaluating early treatment response/resistance, and differentiating inflammatory from fibrotic strictures. Familiarity with MR enterography is essential for radiologists and gastroenterologists as the technique evolves and is further incorporated into the clinical management of CD. C1 [Moy, Matthew P.; Gee, Michael S.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Abdominal Imaging, Boston, MA 02138 USA. [Moy, Matthew P.; Gee, Michael S.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Pediat Imaging, Boston, MA 02138 USA. [Sauk, Jenny] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Gastroenterol, Boston, MA 02138 USA. RP Sauk, J (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Gastroenterol, Boston, MA 02138 USA. EM jsauk@partners.org NR 123 TC 0 Z9 0 U1 2 U2 3 PU HINDAWI LTD PI LONDON PA ADAM HOUSE, 3RD FLR, 1 FITZROY SQ, LONDON, WIT 5HE, ENGLAND SN 1687-6121 EI 1687-630X J9 GASTROENT RES PRACT JI Gastroenterol. Res. Pract. PY 2016 AR 8168695 DI 10.1155/2016/8168695 PG 13 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA DC0VA UT WOS:000368934700001 ER PT J AU Richter, JM Arshi, NK Oster, G AF Richter, James M. Arshi, Nabeela K. Oster, Gerry TI Oral 5-Aminosalicylate, Mesalamine Suppository, and Mesalamine Enema as Initial Therapy for Ulcerative Proctitis in Clinical Practice with Quality of Care Implications SO CANADIAN JOURNAL OF GASTROENTEROLOGY AND HEPATOLOGY LA English DT Article ID PRACTICE GUIDELINES; MEDICAL-MANAGEMENT; COLITIS; MESALAZINE; ADULTS AB Background. Ulcerative proctitis (UP) is typically treated initially with oral 5-aminosalicylate ("5-ASA"), mesalamine suppository, or mesalamine enema ("UP Rx"). Little is known about their effectiveness in practice. Methods. Using a US health insurance database, we identified new-onset UP patients between January 1, 2005, and December 31, 2007, based on the following: (1) initiation of UP Rx; (2) endoscopy in prior 30 days resulting in diagnosis of UP; and (3) no prior encounters for ulcerative colitis or Crohn's disease. We examined the incidence of therapy escalation and total costs in relation to initial UP Rx. Results. We identified 548 patients: 327 received mesalamine suppository, 138 received oral 5-ASA, and 83 received mesalamine enema, as initial UP Rx. One-third receiving oral 5-ASA experienced therapy escalation over 12 months, 21% for both mesalamine suppository and enema. Mean cumulative total cost of UP Rx over 12 months was $1552, $996, and $986 for patients beginning therapy with oral 5-ASA, mesalamine enema, and mesalamine suppository, respectively. Contrary to expert recommendations the treatments were often not continued prophylactically. Conclusions. Treatment escalation was common, and total costs of therapy were higher, in patients who initiated treatment with oral 5-ASA. Further study is necessary to assess the significance of these observations. C1 [Richter, James M.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Richter, James M.] Harvard Univ, Sch Med, Boston, MA 02114 USA. [Arshi, Nabeela K.; Oster, Gerry] Policy Anal Inc, Brookline, MA 02445 USA. RP Richter, JM (reprint author), Massachusetts Gen Hosp, Boston, MA 02114 USA.; Richter, JM (reprint author), Harvard Univ, Sch Med, Boston, MA 02114 USA. EM jrichter@mgh.harvard.edu FU Aptalis, Birmingham, AL FX This study was funded in full by Aptalis (formerly, Axcan), Birmingham, AL, under a research contract. NR 14 TC 0 Z9 0 U1 0 U2 0 PU HINDAWI PUBLISHING CORP PI NEW YORK PA 410 PARK AVENUE, 15TH FLOOR, #287 PMB, NEW YORK, NY 10022 USA SN 2291-2797 J9 CAN J GASTROENTEROL JI Can. J. Gastroenterol. Hepatol. PY 2016 AR 6928710 DI 10.1155/2016/6928710 PG 7 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA DK3WP UT WOS:000374848400001 ER PT J AU Castillo, JJ Treon, SP Davids, MS AF Castillo, Jorge J. Treon, Steven P. Davids, Matthew S. TI Inhibition of the Bruton Tyrosine Kinase Pathway in B-Cell Lymphoproliferative Disorders SO CANCER JOURNAL LA English DT Review DE Bruton tyrosine kinase; chronic lymphocytic leukemia; ibrutinib; mantle cell lymphoma; Waldenstrom macroglobulinemia ID CHRONIC LYMPHOCYTIC-LEUKEMIA; L265P SOMATIC MUTATION; NON-HODGKIN-LYMPHOMA; WALDENSTROMS MACROGLOBULINEMIA; MYD88 L265P; TREATMENT-NAIVE; PHASE 1B/2; IBRUTINIB; MALIGNANCIES; BTK AB Activation of the Bruton tyrosine kinase (BTK) pathway plays an important role in the pathophysiology of a number of B-cell lymphoproliferative disorders (LPDs). A number of preclinical studies support inhibiting BTK as a mechanism to treat LPDs. Clinically, BTK inhibitors, specifically ibrutinib, have shown to be safe and effective on treating patients with indolent B-cell lymphomas and chronic lymphocytic leukemia (CLL). Ibrutinib has recently gained approval for the treatment of patients with mantle cell lymphoma, Waldenstrom macroglobulinemia, and CLL. Ongoing clinical trials are investigating ibrutinib and other BTK inhibitors alone or in combination for the treatment of mantle cell lymphoma, Waldenstrom macroglobulinemia, CLL, activated B-cell-type diffuse large B-cell lymphoma, and follicular lymphoma, among others. The objective of this review is to succinctly summarize the current body of evidence on BTK inhibition in patients with B-cell LPDs. C1 Harvard Univ, Sch Med, Bing Ctr Waldenstroms Macroglobulinemia, Boston, MA 02115 USA. Harvard Univ, Sch Med, Div Hematol Malignancies, Dana Farber Canc Inst, Boston, MA 02115 USA. RP Castillo, JJ (reprint author), 450 Brookline Ave, Boston, MA 02215 USA. EM jorgej_castillo@dfci.harvard.edu OI Castillo, Jorge/0000-0001-9490-7532 NR 42 TC 4 Z9 4 U1 1 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 1528-9117 EI 1540-336X J9 CANCER J JI Cancer J. PD JAN-FEB PY 2016 VL 22 IS 1 BP 34 EP 39 PG 6 WC Oncology SC Oncology GA DL1MJ UT WOS:000375395900008 PM 26841015 ER PT J AU Moghadam-Kia, S Oddis, CV Aggarwal, R AF Moghadam-Kia, Siamak Oddis, Chester V. Aggarwal, Rohit TI Approach to asymptomatic creatine kinase elevation SO CLEVELAND CLINIC JOURNAL OF MEDICINE LA English DT Article ID HYPER-CK-EMIA; STATIN-INDUCED MYOPATHY; MUSCLE BIOPSY; IDIOPATHIC HYPERCKEMIA; PERSISTENT HYPERCKEMIA; LARGE POPULATION; RHABDOMYOLYSIS; HYPOTHYROIDISM; DYSTROPHY; MUTATION AB How to manage a patient who has an elevated serum creatine kinase (CK) level but no or insignificant muscle-related signs and symptoms is a clinical conundrum. The authors provide a systematic approach, including repeat testing after a period of rest, defining higher thresholds over which pursuing a diagnosis is worthwhile, and evaluating for a variety of nonneuromuscular causes. They also outline a workup for neuromuscular causes. C1 [Moghadam-Kia, Siamak; Oddis, Chester V.] Univ Pittsburgh, Sch Med, Div Rheumatol & Clin Immunol, Pittsburgh, PA 15261 USA. [Moghadam-Kia, Siamak] VA Pittsburgh Healthcare Syst, Pittsburgh, PA USA. [Aggarwal, Rohit] Univ Pittsburgh, Sch Med, Div Rheumatol & Clin Immunol, Med, Pittsburgh, PA 15261 USA. RP Aggarwal, R (reprint author), Univ Pittsburgh, Dept Med, Div Rheumatol & Clin Immunol, 3601 5th Ave,Suite 2B, Pittsburgh, PA 15261 USA. EM aggarwalr@upmc.edu FU NIAID NIH HHS [T32 AI089443] NR 37 TC 0 Z9 1 U1 0 U2 1 PU CLEVELAND CLINIC PI CLEVELAND PA 9500 EUCLID AVE, CLEVELAND, OH 44106 USA SN 0891-1150 EI 1939-2869 J9 CLEV CLIN J MED JI Clevel. Clin. J. Med. PD JAN PY 2016 VL 83 IS 1 BP 37 EP 42 DI 10.3949/ccjm.83a.14120 PG 6 WC Medicine, General & Internal SC General & Internal Medicine GA DK3TL UT WOS:000374840200010 PM 26760521 ER PT J AU Wylie, KP Smucny, J Legget, KT Tregellas, JR AF Wylie, Korey P. Smucny, Jason Legget, Kristina T. Tregellas, Jason R. TI Targeting Functional Biomarkers in Schizophrenia with Neuroimaging SO CURRENT PHARMACEUTICAL DESIGN LA English DT Article DE Biomarkers; functional magnetic resonance imaging; fMRI; nicotine; alpha7 nicotinic receptor; functional connectivity; SPEM ID PURSUIT EYE-MOVEMENTS; DEFAULT-MODE NETWORK; CNS DRUG DEVELOPMENT; ACETYLCHOLINE-RECEPTOR; PHARMACOLOGICAL FMRI; TRACKING DYSFUNCTION; NICOTINIC RECEPTORS; LEADING SACCADES; BRAIN NETWORKS; MOUSE MODEL AB Many of the most debilitating symptoms for psychiatric disorders such as schizophrenia remain poorly treated. As such, the development of novel treatments is urgently needed. Unfortunately, the costs associated with high failure rates for investigational compounds as they enter clinical trials has led to pharmaceutical companies downsizing or eliminating research programs needed to develop these drugs. One way of increasing the probability of success for investigational compounds is to incorporate alternative methods of identifying biological targets in order to more effectively screen new drugs. A promising method of accomplishing this goal for psychiatric drugs is to use functional magnetic resonance imaging (fMRI). fMRI investigates neural circuits, shedding light on the biology that generates symptoms such as hallucinations. Once identified, relevant neural circuits can be targeted with pharmacologic interventions and the response to these drugs measured with fMRI. This review describes the early use of fMRI in this context, and discusses the alpha7 nicotinic receptor agonist 3-(2,4-dimethoxybenzylidene) anabaseine (DMXB-A), as an example of the potential value of fMRI for psychiatric drug development. C1 [Wylie, Korey P.; Smucny, Jason; Legget, Kristina T.; Tregellas, Jason R.] Univ Colorado Anschutz Med Campus, Dept Psychiat, Denver, CO USA. [Smucny, Jason] Univ Colorado Anschutz Med Campus, Neurosci Program, Denver, CO USA. [Tregellas, Jason R.] Denver Vet Affairs Med Ctr, Res Serv, Denver, CO USA. RP Wylie, KP (reprint author), Anschutz Med Campus, Dept Psychiat, Bldg 500,Mail Stop F546,13001 East 17th Pl, Aurora, CO 80045 USA. EM Korey.Wylie@ucdenver.edu OI Smucny, Jason/0000-0001-5656-7987; Legget, Kristina/0000-0002-2948-506X FU Veterans Administration Biomedical Laboratory and Clinical Science Research and Development Service; National Institutes of Health [R01MH102224, R01DK103691, K01DK100445]; Brain and Behavior Research Foundation FX This work was supported by the Veterans Administration Biomedical Laboratory and Clinical Science Research and Development Service, the National Institutes of Health grants R01MH102224, R01DK103691, K01DK100445 and the Brain and Behavior Research Foundation. NR 80 TC 1 Z9 1 U1 3 U2 6 PU BENTHAM SCIENCE PUBL LTD PI SHARJAH PA EXECUTIVE STE Y-2, PO BOX 7917, SAIF ZONE, 1200 BR SHARJAH, U ARAB EMIRATES SN 1381-6128 EI 1873-4286 J9 CURR PHARM DESIGN JI Curr. Pharm. Design PY 2016 VL 22 IS 14 BP 2117 EP 2123 DI 10.2174/1381612822666160127113912 PG 7 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA DK7ZV UT WOS:000375146900014 PM 26818860 ER PT J AU Sasaki, H Hirai, K Martins, CM Furusho, H Battaglino, R Hashimoto, K AF Sasaki, Hajime Hirai, Kimito Martins, Christine M. Furusho, Hisako Battaglino, Ricardo Hashimoto, Koshi TI Interrelationship Between Periapical Lesion and Systemic Metabolic Disorders SO CURRENT PHARMACEUTICAL DESIGN LA English DT Article DE Periapical lesion; metabolic disorders; type 2 diabetes; hypertension; NAFLD; cytokines; inflammation; immunity ID FATTY LIVER-DISEASE; GAMMA-GLUTAMYL-TRANSFERASE; BONE-MINERAL DENSITY; II-INDUCED HYPERTENSION; RECEPTOR 4-DEFICIENT MICE; TYPE-2 DIABETIC SUBJECTS; CORONARY-ARTERY-DISEASE; TUMOR-NECROSIS-FACTOR; C-REACTIVE PROTEIN; HUMAN DENTAL-PULP AB Background: Periapical periodontitis, also known as periapical lesion, is a common dental disease, along with periodontitis (gum disease). Periapical periodontitis is a chronic inflammatory disease, caused by endodontic infection, and its development is regulated by the host immune/inflammatory response. Metabolic disorders, which are largely dependent on life style such as eating habits, have been interpreted as a "metabolically-triggered" low-grade systemic inflammation and may interact with periapical periodontitis by triggering immune modulation. The host immune system is therefore considered the common fundamental mechanism of both disease conditions. Method: We have reviewed >200 articles to discuss the interrelationship between periapical lesions and metabolic disorders including type 2 diabetes mellitus, hypertension, and non-alcoholic fatty liver diseases (NAFLD), and their common pathological background in immunology/osteoimmunology and cytokine biology. Results: An elevated inflammatory state caused by metabolic disorders can impact the clinical outcome of periapical lesions and interfere with wound healing after endodontic treatment. Although additional well-designed clinical studies are needed, periapical lesions appear to affect insulin sensitivity and exacerbate non-alcoholic steatohepatitis. Conclusion: Immune regulatory cytokines produced by various cell types, including immune cells and adipose tissue, play an important role in this interrelationship. C1 [Sasaki, Hajime; Hirai, Kimito; Martins, Christine M.] Forsyth Inst, Dept Immunol & Infect Dis, 245 First St, Cambridge, MA 02142 USA. [Sasaki, Hajime] Harvard Univ, Sch Dent Med, Dept Oral Med Infect & Immun, 188 Longwood Ave, Boston, MA 02115 USA. [Martins, Christine M.] Univ Estadual Paulista, UNESP, Dept Restorat Dent, Aracatuba Dent Sch, 1193 Jose Bonifacio, BR-16015050 Aracatuba, PR, Brazil. [Furusho, Hisako] Hiroshima Univ, Inst Biomed & Hlth Sci, Dept Oral & Maxillofacial Pathobiol, Minami Ku, 1-2-3 Kasumi, Hiroshima 7348553, Japan. [Battaglino, Ricardo] Forsyth Inst, Dept Mineralized Tissue Biol, Cambridge, MA USA. [Hashimoto, Koshi] Tokyo Med & Dent Univ, Grad Sch Med & Dent Sci, Dept Preempt Med & Metab, Bunkyo Ku, 1-5-45 Yushima, Tokyo 1138510, Japan. RP Sasaki, H (reprint author), Forsyth Inst, Dept Immunol & Infect Dis, 245 First St, Cambridge, MA 02142 USA. EM hsasaki@forsyth.org FU National Institute of Dental & Craniofacial Research of the National Institutes of Health [R21DE023178, R01DE024796] FX Authors thank Drs. Ana Cristina Andrada (Harvard School of Dental Medicine) and Nobuyuki Kawashima (Department of Pulp Biology and Endodontics, Division of Oral Health Sciences, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University) for their helpful comments on this manuscript. We are grateful to Ms. Moira Cahan for her assistance on the preparation of the manuscript. This work was supported by the National Institute of Dental & Craniofacial Research of the National Institutes of Health under R21DE023178 and R01DE024796 (both H.S). NR 207 TC 1 Z9 1 U1 8 U2 8 PU BENTHAM SCIENCE PUBL LTD PI SHARJAH PA EXECUTIVE STE Y-2, PO BOX 7917, SAIF ZONE, 1200 BR SHARJAH, U ARAB EMIRATES SN 1381-6128 EI 1873-4286 J9 CURR PHARM DESIGN JI Curr. Pharm. Design PY 2016 VL 22 IS 15 BP 2204 EP 2215 DI 10.2174/1381612822666160216145107 PG 12 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA DK8AE UT WOS:000375147900003 PM 26881444 ER PT J AU Sima, C Van Dyke, TE AF Sima, Corneliu Van Dyke, Thomas E. TI Therapeutic Targets for Management of Periodontitis and Diabetes SO CURRENT PHARMACEUTICAL DESIGN LA English DT Article DE Diabetes mellitus; periodontitis; inflammation; lipid mediators; pro-resolution therapeutics ID TUMOR-NECROSIS-FACTOR; PRORESOLVING LIPID MEDIATORS; N-3 FATTY-ACIDS; MONOCYTE CHEMOATTRACTANT PROTEIN-1; VASCULAR-DISEASE EPIDEMIOLOGY; ADIPOSE-TISSUE INFLAMMATION; NONSTEROIDAL ANTIINFLAMMATORY DRUGS; IMPAIRED NEUTROPHIL CHEMOTAXIS; ENDOPLASMIC-RETICULUM STRESS; INDUCED INSULIN-RESISTANCE AB The increasing incidence of diabetes mellitus (DM) and chronic periodontitis (CP) worldwide imposes a rethinking of individualized therapy for patients with both conditions. Central to bidirectional links between DM and CP is deregulated systemic inflammation and dysfunctional immune responses to altered-self and non-self. Control of blood glucose levels and metabolic imbalances associated with hyperglycemia in DM, and disruption of pathogenic subgingival biofilms in CP are currently the main therapeutic approaches for these conditions. Mounting evidence suggests the need to integrate immune modulatory therapeutics in treatment regimens that address the unresolved inflammation associated with DM and CP. The current review discusses the pathogenesis of DM and CP with emphasis on deregulated inflammation, current therapeutic approaches and the novel pro-resolution lipid mediators derived from Omega-3 polyunsaturated fatty acids. C1 [Sima, Corneliu; Van Dyke, Thomas E.] Forsyth Inst, Dept Appl Oral Sci, Cambridge, MA USA. [Van Dyke, Thomas E.] Harvard Univ, Sch Dent Med, Dept Oral Med Infect & Immun, 188 Longwood Ave, Boston, MA 02115 USA. RP Sima, C (reprint author), 245 First St,Room 5145, Cambridge, MA 02142 USA. EM csima@forsyth.org OI Van Dyke, Thomas/0000-0003-0568-124X FU National Institute of Dental and Craniofacial Research through USPHS grants [K99DE024575, DE25030] FX Supported in part by the National Institute of Dental and Craniofacial Research through USPHS grants K99DE024575 (CS) and DE25030 (TVD). NR 243 TC 1 Z9 1 U1 2 U2 6 PU BENTHAM SCIENCE PUBL LTD PI SHARJAH PA EXECUTIVE STE Y-2, PO BOX 7917, SAIF ZONE, 1200 BR SHARJAH, U ARAB EMIRATES SN 1381-6128 EI 1873-4286 J9 CURR PHARM DESIGN JI Curr. Pharm. Design PY 2016 VL 22 IS 15 BP 2216 EP 2237 DI 10.2174/1381612822666160216150338 PG 22 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA DK8AE UT WOS:000375147900004 PM 26881443 ER PT J AU Accordino, RE Kidd, C Politte, LC Henry, CA McDougle, CJ AF Accordino, Robert E. Kidd, Christen Politte, Laura C. Henry, Charles A. McDougle, Christopher J. TI Psychopharmacological interventions in autism spectrum disorder SO EXPERT OPINION ON PHARMACOTHERAPY LA English DT Review DE Antidepressants; atypical antipsychotics; autism; autism spectrum disorder; mood stabilizers; oxytocin; pervasive developmental disorders; psychopharmacology; stimulants ID PERVASIVE DEVELOPMENTAL DISORDERS; PLACEBO-CONTROLLED TRIAL; ATTENTION-DEFICIT/HYPERACTIVITY DISORDER; OPEN-LABEL TRIAL; SEROTONIN REUPTAKE INHIBITORS; CONTROLLED-RELEASE MELATONIN; ABERRANT BEHAVIOR CHECKLIST; GUANFACINE EXTENDED-RELEASE; N-ACETYL CYSTEINE; DEFICIT HYPERACTIVITY DISORDER AB Introduction: Individuals with autism spectrum disorder (ASD) commonly present for treatment of emotional and behavioral disturbances associated with ASD's "core" symptoms. Psychotropic medications are widely utilized in alleviating associated emotional and behavioral symptoms. Areas covered: Emotional and behavioral disturbances associated with ASD include irritability/severely disruptive behavior, which comprises the heaviest symptom burden; hyperactivity and other Attention-Deficit-Hyperactivity-Disorder (ADHD)-type symptoms; repetitive/stereotyped behaviors; and social withdrawal. Existing evidence for medications for each of these symptom clusters will be examined in this review. Expert opinion: Psychopharmacological treatment of core and associated symptoms in ASD is challenging, in large part because of the heterogeneity in the presentation of ASD. Furthermore, children and adolescents with ASD are more vulnerable to the side effects of psychopharmacological intervention than their age-matched, typically developing counterparts. Currently, risperidone and aripiprazole are the only medications that have been (relatively) reliably shown to help treat certain symptom clusters associated with ASD, namely severely disruptive behavior and hyperactivity. Recent studies have begun to look at medications with mechanisms that are novel in the treatment of ASD and that may address underlying pathophysiology and/or core symptoms such as glutamate-modulating agents. Overall, randomized, placebo-controlled studies of medications for the treatment of ASD are scarce. C1 [Accordino, Robert E.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Accordino, Robert E.] McLean Hosp, Boston, MA USA. [Accordino, Robert E.] Yawkey Outpatient Care Ctr, Child & Adolescent Psychiat Serv, Boston, MA USA. [Kidd, Christen] New York Presbyterian Hosp, Weill Cornell Med Ctr, Payne Whitney Clin, New York, NY USA. [Politte, Laura C.] Univ N Carolina, Sch Med, Carolina Inst Dev Disabil, Carrboro, NC USA. [Henry, Charles A.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Yawkey Outpatient Care Ctr,Child & Adolescent Psy, Boston, MA USA. [McDougle, Christopher J.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Lurie Ctr Autism, Lexington, MA USA. RP McDougle, CJ (reprint author), Lurie Ctr Autism, One Maguire Rd, Lexington, MA 02421 USA. EM cmcdougle@mgh.harvard.edu NR 156 TC 2 Z9 2 U1 7 U2 13 PU TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND SN 1465-6566 EI 1744-7666 J9 EXPERT OPIN PHARMACO JI Expert Opin. Pharmacother. PY 2016 VL 17 IS 7 BP 937 EP 952 DI 10.1517/14656566.2016.1154536 PG 16 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA DK5ZG UT WOS:000374999200006 PM 26891879 ER PT J AU Xiong, L Davidsdottir, S Reijmer, YD Shoamanesh, A Roongpiboonsopit, D Thanprasertsuk, S Martinez-Ramirez, S Charidimou, A Ayres, AM Fotiadis, P Gurol, E Blacker, DL Greenberg, SM Viswanathan, A AF Xiong, Li Davidsdottir, Sigurros Reijmer, Yael D. Shoamanesh, Ashkan Roongpiboonsopit, Duangnapa Thanprasertsuk, Sekh Martinez-Ramirez, Sergi Charidimou, Andreas Ayres, Alison M. Fotiadis, Panagiotis Gurol, Edip Blacker, Deborah L. Greenberg, Steven M. Viswanathan, Anand TI Cognitive Profile and its Association with Neuroimaging Markers of Non-Demented Cerebral Amyloid Angiopathy Patients in a Stroke Unit SO JOURNAL OF ALZHEIMERS DISEASE LA English DT Article DE Brain atrophy; cerebral amyloid angiopathy; cerebral microbleeds; clinical neuropsychology; cognitive impairment; hippocampal atrophy; intracranial hemorrhage; white matter hyperintensities ID SMALL-VESSEL DISEASE; INTRACEREBRAL HEMORRHAGE; ALZHEIMERS-DISEASE; VASCULAR DEMENTIA; IMPAIRMENT; MICROBLEEDS; HIPPOCAMPAL; POPULATION; PREVALENCE; ATROPHY AB Background: Cerebral amyloid angiopathy (CAA) is increasingly recognized as a cause of cognitive impairment in the elderly, but the cognitive profile in patients with the disease has not been well characterized. Objective: To characterize the neuropsychological profile of CAA patients without dementia and to determine the association between cognitive performance in different domains and neuroimaging lesions characteristic of CAA. Methods: Fifty-eight non-demented CAA patients were compared to 138 cognitively normal subjects using a standard neuropsychological test battery. Total brain volume (TBV), white matter hyperintensities, number of lobar cerebral microbleeds, hippocampal volume, and cortical superficial siderosis in all CAA patients were assessed. The association between these neuroimaging markers and neuropsychological performance in different cognitive domains in the CAA group were analyzed. Results: Patients with CAA had significantly worse performance on all individual neuropsychological domains tested, when compared to the cognitive normal group. The cognitive decline of CAA patients was most noticeable in tests for processing speed with a Z score of -1.92 +/- 1.56 (mean +/- SD), then followed by executive function (-0.93 +/- 1.01), episodic memory (-0.87 +/- 1.29), semantic fluency (-0.73 +/- 1.06), and attention (-0.42 +/- 0.98). TBV of the CAA patients was correlated with processing speed (beta = 0.335, p = 0.03) and executive function (beta = 0.394, p = 0.01). Conclusions: Non-demented patients with CAA had cognitive deficits in multiple areas. Lower TBV was related to slower processing speed and worse executive function. C1 [Xiong, Li; Reijmer, Yael D.; Roongpiboonsopit, Duangnapa; Martinez-Ramirez, Sergi; Charidimou, Andreas; Ayres, Alison M.; Fotiadis, Panagiotis; Gurol, Edip; Greenberg, Steven M.; Viswanathan, Anand] Harvard Univ, Sch Med, Dept Neurol, Massachusetts Gen Hosp, Boston, MA 02115 USA. [Xiong, Li] Wuhan Univ, Zhongnan Hosp, Dept Neurol, Wuhan 430072, Peoples R China. [Davidsdottir, Sigurros; Blacker, Deborah L.] Harvard Univ, Sch Med, Dept Psychiat, Massachusetts Gen Hosp, Boston, MA 02115 USA. [Shoamanesh, Ashkan] McMaster Univ, Populat Hlth Res Inst, Dept Neurol, Hamilton, ON L8S 4L8, Canada. [Roongpiboonsopit, Duangnapa] Naresuan Univ, Dept Med, Phitsanulok, Thailand. [Thanprasertsuk, Sekh] Chulalongkorn Univ, Dept Med, Bangkok, Thailand. RP Xiong, L (reprint author), 175 Cambridge St,Suite 300, Boston, MA 02114 USA. EM lxiong2@partners.org RI Gurol, Edip/J-2279-2014 OI Gurol, Edip/0000-0002-2169-4457 FU NIH [R01AG047975, R01AG026484, P50AG005134, K23AG028726] FX This work was supported by the NIH (grants R01AG047975, R01AG026484, P50AG005134, and K23AG028726). NR 44 TC 2 Z9 2 U1 4 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 2016 VL 52 IS 1 BP 171 EP 178 DI 10.3233/JAD-150890 PG 8 WC Neurosciences SC Neurosciences & Neurology GA DK6CK UT WOS:000375008500016 PM 27060947 ER PT J AU Ahmed, R Rifat, AA Yetisen, AK Yun, SH Khan, S Butt, H AF Ahmed, Rajib Rifat, Ahmmed A. Yetisen, Ali K. Yun, Seok Hyun Khan, Safyan Butt, Haider TI Mode-multiplexed waveguide sensor SO JOURNAL OF ELECTROMAGNETIC WAVES AND APPLICATIONS LA English DT Article DE Multi-mode waveguides; mode multiplexing; directional couplers; optical sensing; sensors ID RING RESONATORS; MICRORING RESONATOR; PHOTONIC CRYSTAL; METAMATERIAL SENSOR; DESIGN; OPTIMIZATION; SIMULATION; BIOSENSOR AB Optical sensors enable quantification of analyte concentrations non-invasively without being affected from electromagnetic fields. The development of single-mode waveguides (WGs) is simple approach; however, limitations in the spatial distribution of the refractive index and the inability to sense multiple samples at the same time. Here, we demonstrate a multi-mode WG model and matrix inversion method (MIM) to improve spatial information in at least one dimension. This method is used to optimize and estimate three external stimulus properties in TE00, TE01 and TM00 multiplexed modes for a semi-triangular ring resonator configuration. The multi-mode WG and MIM may have applications in the development of biosensors for multi-analyte detection. C1 [Ahmed, Rajib; Butt, Haider] Univ Birmingham, Sch Mech Engn, Nanotechnol Lab, Birmingham B15 2TT, W Midlands, England. [Rifat, Ahmmed A.] Univ Malaya, Integrated Lightwave Res Grp, Fac Engn, Elect Engn, Kuala Lumpur 50603, Malaysia. [Yetisen, Ali K.; Yun, Seok Hyun] Harvard Univ, Sch Med, 65 Landsdowne St, Cambridge, MA 02139 USA. [Yetisen, Ali K.; Yun, Seok Hyun] Massachusetts Gen Hosp, Wellman Ctr Photomed, 65 Landsdowne St, Cambridge, MA 02139 USA. [Yun, Seok Hyun] MIT, Harvard Mit Div Hlth Sci & Technol, Cambridge, MA 02139 USA. [Khan, Safyan] King Fahd Univ Petr & Minerals, Ctr Excellence Nanotechnol, Dhahran 34464, Saudi Arabia. RP Ahmed, R (reprint author), Univ Birmingham, Sch Mech Engn, Nanotechnol Lab, Birmingham B15 2TT, W Midlands, England. EM RXA448@bham.ac.uk RI engineering, @UM-2016/I-9329-2016; Khan, Safyan/B-8520-2015; OI Khan, Safyan/0000-0002-7759-7066; Butt, Haider/0000-0003-2434-9525 FU Leverhulme Trust FX The authors thank Dr. Matthias Jager, Dr. Michael Stich, Prof. Zahirul Hoque Mozumder, I. K. Alam Bhuiyan, Areej Badar, and Prof. Dr.-Ing Klaus Petermann for their valuable suggestions, comments, and fruitful discussions. Dr. Haider Butt thanks the Leverhulme Trust for research funding. NR 24 TC 5 Z9 5 U1 5 U2 10 PU TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND SN 0920-5071 EI 1569-3937 J9 J ELECTROMAGNET WAVE JI J. Electromagn. Waves Appl. PY 2016 VL 30 IS 4 BP 444 EP 455 DI 10.1080/09205071.2015.1117025 PG 12 WC Engineering, Electrical & Electronic; Physics, Applied SC Engineering; Physics GA DL2MM UT WOS:000375469100004 ER PT J AU Dai, XM Busby-Whitehead, J Forman, DE Alexander, KP AF Dai, Xuming Busby-Whitehead, Jan Forman, Daniel E. Alexander, Karen P. TI Stable ischemic heart disease in the older adults SO JOURNAL OF GERIATRIC CARDIOLOGY LA English DT Article DE Aging; Coronary artery disease; Older adults; Risk assessment; Stable ischemic heart disease ID CORONARY-ARTERY-DISEASE; ELDERLY-PATIENTS; ASSOCIATION; TIME; OCTOGENARIANS; TRIAL C1 [Dai, Xuming] Univ N Carolina, Div Cardiol, Chapel Hill, NC USA. [Busby-Whitehead, Jan] Univ N Carolina, Ctr Aging & Hlth, Div Geriatr Med, Chapel Hill, NC USA. [Forman, Daniel E.] Univ Pittsburgh, Sect Geriatr Cardiol, VA Pittsburgh Healthcare Syst, Med Ctr,Geriatr Res Educ & Clin Ctr, Pittsburgh, PA USA. [Alexander, Karen P.] Duke Univ, Med Ctr, Div Cardiol, Durham, NC 27710 USA. RP Alexander, KP (reprint author), Duke Univ, Med Ctr, Div Cardiol, Durham, NC 27710 USA. EM karen.alexander@duke.edu NR 20 TC 0 Z9 0 U1 1 U2 1 PU SCIENCE PRESS PI BEIJING PA 16 DONGHUANGCHENGGEN NORTH ST, BEIJING 100717, PEOPLES R CHINA SN 1671-5411 J9 J GERIATR CARDIOL JI J. Geriatr. Cardiol. PY 2016 VL 13 IS 2 BP 109 EP 114 PG 6 WC Cardiac & Cardiovascular Systems; Geriatrics & Gerontology SC Cardiovascular System & Cardiology; Geriatrics & Gerontology GA DK2WV UT WOS:000374776000002 PM 27168734 ER PT J AU Silva, CGDE Franklin, BA Forman, DE Araujo, CGS AF de Souza e Silva, Christina G. Franklin, Barry A. Forman, Daniel E. Araujo, Claudio Gil S. TI Influence of age in estimating maximal oxygen uptake SO JOURNAL OF GERIATRIC CARDIOLOGY LA English DT Article DE Aging; Cardiopulmonary exercise testing; Error of measurement ID CYCLE ERGOMETRY EQUATION; ALL-CAUSE MORTALITY; HEALTHY-MEN; CARDIAC REHABILITATION; EXERCISE; HEART; EFFICIENCY; DISEASE; WOMEN; METAANALYSIS AB Objective To assess the influence of age on the error of estimate (EE) of maximal oxygen uptake (VO(2)max) using sex and population specific-equations in cycle ergometer exercise testing, since estimated VO(2)max is associated with a substantial EE, often exceeding 20%, possibly due to intrinsic variability of mechanical efficiency. Methods 1850 adults (68% men), aged 18 to 91 years, underwent maximal cycle ergometer cardiopulmonary exercise testing. Cardiorespiratory fitness (CRF) was assessed relative to sex and age [younger (18 to 35 years), middle-aged (36 to 60 years) and older (>60 years)]. VO(2)max [mL.(kg.min)(-1)] was directly measured by assessment of gas exchange and estimated using sex and population specific-equations. Measured and estimated values of VO(2)max and related EE were compared among the three age-and sex-specific groups. Results Directly measured VO(2)max of men and women were 29.5 +/- 10.5 mL.(kg.min)(-1) and 24.2 +/- 9.0 mL.(kg.min)(-1) (P < 0.01). EE [mL.(kg.min)(-1)] and percent errors (%E) for men and women had similar values, 0.5 +/- 3.2 and 0.4 +/- 2.9 mL.(kg.min)(-1), and -0.8 +/- 13.1% and -1.7 +/- 15.4% (P > 0.05), respectively. EE and %E for each age-group were, respectively, for men: younger = 1.9 +/- 4.1 mL.(kg.min)(-1) and 3.8 +/- 10.5%, middle-aged = 0.6 +/- 3.1 mL.(kg.min)(-1) and 0.4 +/- 10.3%, older = -0.2 +/- 2.7 mL.(kg.min)(-1) and -4.2 +/- 16.6% (P < 0.01); and for women: younger = 1.2 +/- 3.1 mL.(kg.min)(-1) and 2.7 +/- 10.0%, middle-aged = 0.7 +/- 2.8 mL.(kg.min)(-1) and 0.5 +/- 11.1%, older = -0.8 +/- 2.3 mL.(kg.min)(-1) and -9.5 +/- 22.4% (P < 0.01). Conclusion VO(2)max were underestimated in younger age-groups and were overestimated in older age groups. Age significantly influences the magnitude of the EE of VO(2)max in both men and women and should be considered when CRF is estimated using population specific equations, rather than directly measured. C1 [de Souza e Silva, Christina G.; Araujo, Claudio Gil S.] Univ Fed Rio de Janeiro, Heart Inst Edson Saad & Med Sch, Rio De Janeiro, RJ, Brazil. [de Souza e Silva, Christina G.; Araujo, Claudio Gil S.] CLINIMEX, Exercise Med Clin, Rua Siqueira Campos 93-101, BR-22031070 Rio De Janeiro, RJ, Brazil. [Franklin, Barry A.] William Beaumont Hosp, Prevent Cardiol & Cardiac Rehabil, Royal Oak, MI 48072 USA. [Forman, Daniel E.] Univ Pittsburgh, Sect Geriatr Cardiol, Geriatr Res Educ & Clin Ctr, Med Ctr,VA Pittsburgh Healthcare Syst, Pittsburgh, PA USA. RP Araujo, CGS (reprint author), CLINIMEX, Exercise Med Clin, Rua Siqueira Campos 93-101, BR-22031070 Rio De Janeiro, RJ, Brazil. EM cgaraujo@iis.com.br RI Araujo, Claudio/A-7027-2008 OI Araujo, Claudio/0000-0001-6679-6695 FU CNPq; FAPERJ FX Partial financial support for this study was provided by CNPq and FAPERJ. NR 37 TC 1 Z9 1 U1 0 U2 1 PU SCIENCE PRESS PI BEIJING PA 16 DONGHUANGCHENGGEN NORTH ST, BEIJING 100717, PEOPLES R CHINA SN 1671-5411 J9 J GERIATR CARDIOL JI J. Geriatr. Cardiol. PY 2016 VL 13 IS 2 BP 126 EP 131 PG 6 WC Cardiac & Cardiovascular Systems; Geriatrics & Gerontology SC Cardiovascular System & Cardiology; Geriatrics & Gerontology GA DK2WV UT WOS:000374776000005 ER PT J AU Mitra, D Catalano, PJ Cimbak, N Damato, AL Muto, MG Viswanathan, AN AF Mitra, Devarati Catalano, Paul J. Cimbak, Nicole Damato, Antonio L. Muto, Michael G. Viswanathan, Akita N. TI The risk of lymphedema after postoperative radiation therapy in endometrial cancer SO JOURNAL OF GYNECOLOGIC ONCOLOGY LA English DT Article DE Endometrial Neoplasms; Lymphedema; Positive Lymph Nodes ID LOWER-LIMB LYMPHEDEMA; COMPLEX DECONGESTIVE PHYSIOTHERAPY; QUALITY-OF-LIFE; EXTREMITY LYMPHEDEMA; PNEUMATIC COMPRESSION; GYNECOLOGICAL CANCER; ELASTIC STOCKINGS; NODE DISSECTION; LYMPHADENECTOMY; CARCINOMA AB Objective: Lower extremity lymphedema adversely affects quality of life by causing discomfort, impaired mobility and increased risk of infection. The goal of this study is to investigate factors that influence the likelihood of lymphedema in patients with endometrial cancer who undergo adjuvant radiation with or without chemotherapy. Methods: A retrospective chart review identified all stage endometrial cancer patients who had a hysterectomy with or without complete staging lymphadenectomy and adjuvant radiation therapy between January 2006 and February 2013. Patients with new-onset lymphedema after treatment were identified. Logistic regression was used to find factors that influenced lymphedema risk. Results: Of 212 patients who met inclusion criteria, 15 patients (7.1%) developed new-onset lymphedema. Lymphedema was associated with lymph-node dissection (odds ratio [OR], 5.6; 95% CI, 1.01 to 105.5; p=0.048) and with the presence of pathologically positive lymph nodes (OR, 4.1; 95% CI, 1.4 to 12.3; p=0.01). Multivariate logistic regression confirmed the association with lymph-node positivity (OR, 3.2; 95% CI, 1.0007 to 10.7; p=0.0499) when controlled for lymph-node dissection. Median time to lymphedema onset was 8 months (range, 1 to 58 months) with resolution or improvement in eight patients (53.3%) after a median of 10 months. Conclusion: Lymph-node positivity was associated with an increased risk of lymphedema in endometrial cancer patients who received adjuvant radiation. Future studies are needed to explore whether node-positive patients may benefit from early lymphedema-controlling interventions. C1 [Mitra, Devarati; Cimbak, Nicole; Damato, Antonio L.; Viswanathan, Akita N.] Dana Farber Canc Inst, Dept Radiat Oncol, Boston, MA 02115 USA. [Mitra, Devarati; Cimbak, Nicole; Damato, Antonio L.; Muto, Michael G.; Viswanathan, Akita N.] Brigham & Womens Hosp, 75 Francis St, Boston, MA 02115 USA. [Catalano, Paul J.] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA. [Catalano, Paul J.] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. [Muto, Michael G.] Dana Farber Canc Inst, Dept Gynecol Oncol, Boston, MA 02115 USA. RP Mitra, D (reprint author), Brigham & Womens Hosp, Dept Radiat Oncol, 75 Francis St, Boston, MA 02115 USA. EM dmitra1@partners.org FU National Institutes of Health [R21167800] FX Dr. Viswanathan receives funding from National Institutes of Health R21167800. NR 28 TC 2 Z9 2 U1 1 U2 2 PU KOREAN SOC GYNECOLOGY ONCOLOGY & COLPOSCOPY PI SEOUL PA 102-HO, 55-5, NONHYEON-DONG, GANGNAM-GU, SEOUL, 135-010, SOUTH KOREA SN 2005-0380 EI 2005-0399 J9 J GYNECOL ONCOL JI J. Gynecol. Oncol. PD JAN PY 2016 VL 27 IS 1 AR e4 DI 10.3802/jgo.2016.27.e4 PG 11 WC Oncology; Obstetrics & Gynecology SC Oncology; Obstetrics & Gynecology GA DJ6XC UT WOS:000374355500002 PM 26463430 ER PT J AU Yurgil, KA Clifford, RE Risbrough, VB Geyer, MA Huang, MX Barkauskas, DA Vasterling, JJ Baker, DG AF Yurgil, Kate A. Clifford, Royce E. Risbrough, Victoria B. Geyer, Mark A. Huang, Mingxiong Barkauskas, Donald A. Vasterling, Jennifer J. Baker, Dewleen G. TI Prospective Associations Between Traumatic Brain Injury and Postdeployment Tinnitus in Active-Duty Marines SO JOURNAL OF HEAD TRAUMA REHABILITATION LA English DT Article DE blast; combat; military; posttraumatic stress disorder; PTSD; TBI; tinnitus; traumatic brain injury ID POSTTRAUMATIC-STRESS-DISORDER; OPERATION IRAQI FREEDOM; ADMINISTERED PTSD SCALE; ENDURING FREEDOM; HEARING PROBLEMS; ACOUSTIC TRAUMA; SCORING RULES; UNITED-STATES; HEAD-INJURY; DEPRESSION AB Objective: To examine whether cause, severity, and frequency of traumatic brain injury (TBI) increase risk of postdeployment tinnitus when accounting for comorbid posttraumatic stress disorder. Design: Self-report and clinical assessments were done before and after an "index" deployment to Iraq or Afghanistan. Setting, Participants, and Measures: Assessments took place on Marine Corps bases in southern California and the VA San Diego Medical Center. Participants were 1647 active-duty enlisted Marine and Navy servicemen who completed pre- and postdeployment assessments of the Marine Resiliency Study. The main outcome was the presence of tinnitus at 3 months postdeployment. Results: Predeployment TBI increased the likelihood of new-onset postdeployment tinnitus (odds ratio [OR] = 1.86; 95% confidence interval [CI], 1.28-2.70). Deployment-related TBIs increased the likelihood of postdeployment tinnitus (OR = 2.65; 95% CI, 1.19-5.89). Likelihood of new-onset postdeployment tinnitus was highest for those who were blast-exposed (OR = 2.93; 95% CI, 1.82-6.17), who reported moderate-severe TBI symptoms (OR = 2.22; 95% CI, 1.22-3.40), and who sustained multiple TBIs across study visits (OR = 2.27; 95% CI, 1.44-4.24). Posttraumatic stress disorder had no effect on tinnitus outcome. Conclusions: Participants who were blast-exposed, sustained multiple TBIs, and reported moderate-severe TBI symptoms were most at risk for new-onset tinnitus. C1 [Yurgil, Kate A.; Risbrough, Victoria B.; Geyer, Mark A.; Baker, Dewleen G.] VA San Diego Healthcare Syst, San Diego, CA USA. [Yurgil, Kate A.; Risbrough, Victoria B.; Baker, Dewleen G.] VA Ctr Excellence Stress & Mental Hlth, San Diego, CA USA. [Yurgil, Kate A.] Loyola Univ, Dept Psychol Sci, New Orleans, LA 70118 USA. [Clifford, Royce E.] Naval Med Ctr San Diego, San Diego, CA USA. [Clifford, Royce E.] Harvard Univ, Sch Publ Hlth, 665 Huntington Ave, Boston, MA 02115 USA. [Risbrough, Victoria B.; Geyer, Mark A.; Baker, Dewleen G.] Univ Calif San Diego, Dept Psychiat, La Jolla, CA 92093 USA. [Huang, Mingxiong] Univ Calif San Diego, Dept Radiol, La Jolla, CA 92093 USA. [Barkauskas, Donald A.] Univ So Calif, Keck Sch Med, Dept Prevent Med, Los Angeles, CA 90033 USA. [Vasterling, Jennifer J.] VA Boston Healthcare Syst, Boston, MA USA. [Vasterling, Jennifer J.] VA Natl Ctr PTSD, Boston, MA USA. [Vasterling, Jennifer J.] Boston Univ, Sch Med, Dept Psychiat, Boston, MA 02118 USA. RP Baker, DG (reprint author), VA Ctr Stress & Mental Hlth 116A, 3350 La Jolla Village Dr, San Diego, CA 92161 USA. EM dgbaker@ucsd.edu FU VA Health Service Research and Development [SDR 09-0128]; Marine Corps; Navy Bureau of Medicine and Surgery FX This work was supported by VA Health Service Research and Development project no. SDR 09-0128, the Marine Corps, and the Navy Bureau of Medicine and Surgery. The authors acknowledge all MRS coinvestigators, as well as administrative core, of the MRS Team, including logistic coordinators, clinician-interviewers, and data collection staff listed in the Methods article (Baker et al, Prev Chronic Dis. 2012;9(10):E97). The authors also thank the Marine and Navy Corpsmen volunteers for military service and participation in this study. NR 73 TC 0 Z9 0 U1 4 U2 6 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0885-9701 EI 1550-509X J9 J HEAD TRAUMA REHAB JI J. Head Trauma Rehabil. PD JAN-FEB PY 2016 VL 31 IS 1 BP 30 EP 39 DI 10.1097/HTR.0000000000000117 PG 10 WC Clinical Neurology; Rehabilitation SC Neurosciences & Neurology; Rehabilitation GA DK9CN UT WOS:000375228000011 PM 25699623 ER PT J AU Kearns, WD Fozard, JL Ray, RD Scott, S Jasiewicz, JM Craighead, JD Pagano, CV AF Kearns, William D. Fozard, James L. Ray, Roger D. Scott, Steven Jasiewicz, Jan M. Craighead, Jeffrey D. Pagano, Craig V. TI Movement Path Tortuosity Predicts Compliance With Therapeutic Behavioral Prompts in Patients With Traumatic Brain Injury SO JOURNAL OF HEAD TRAUMA REHABILITATION LA English DT Article DE location aware technology; memory prompting and spatial disorientation; movement path tortuosity; traumatic brain injury ID PAGING SYSTEM; MEMORY; PEOPLE; TRIAL; ADULTS AB Objective: Rehabilitation of patients with traumatic brain injury typically includes therapeutic prompts for keeping appointments and adhering to medication regimens. Level of cognitive impairment may significantly affect a traumatic brain injury victim's ability to benefit from text-based prompting. We tested the hypothesis that spatial disorientation as measured by movement path tortuosity during ambulation would be associated with poorer compliance with automated prompts by veterans actively being treated for traumatic brain injury. Setting: Clinical polytrauma center. Participants: Ten (1 female) veteran patients mean age = 35.4 (SD = 12.4) years. Design: Small group correlational study without random assignment. Main Measures: Fractal Dimension, a measure of movement path tortuosity derived from a GPS logging device used to record casual outdoor ambulation at the start of the study. Compliance with smart home machine-generated therapeutic prompts received during rehabilitation at the James A. Haley Veterans Administration Hospital Polytrauma Transitional Rehabilitation Program. A patient was compliant with a prompt if they transited from where the prompt was presented to the prescribed destination (both within the Polytrauma Transitional Rehabilitation Program) within 30 minutes. Noncompliance was failure to appear at the destination within the allotted time. Results: Fractal dimension was significantly inversely related to overall prompt compliance (r = -0.603, n = 10, P = .032; 1-tailed). Conclusions: The findings support the hypothesis that increased spatial disorientation adversely impacts compliance with automated prompts throughout therapy. The results are consistent with previous studies linking elevated path tortuosity to cognitive impairment and increased risk for falls in assisted living facility residents. C1 [Kearns, William D.] Univ S Florida, Coll Behav & Community Sci, Dept Rehabil & Mental Hlth Counseling, 13301 N Bruce B Downs Blvd,MHC 1601, Tampa, FL 33612 USA. [Fozard, James L.] Univ S Florida, Coll Behav & Community Sci, Sch Aging Studies, Tampa, FL 33612 USA. [Ray, Roger D.] Rollins Coll, Dept Psychol, Winter Pk, FL 32789 USA. [Scott, Steven; Pagano, Craig V.] US Dept Vet Affairs, James A Haley Vet Adm Hosp, Phys Med & Rehabil Serv, Tampa, FL USA. [Jasiewicz, Jan M.; Craighead, Jeffrey D.] US Dept Vet Affairs, James A Haley Vet Adm Hosp, Ctr Innovat Disabil & Rehabil Res CINDRR, Tampa, FL USA. RP Kearns, WD (reprint author), Univ S Florida, Coll Behav & Community Sci, Dept Rehabil & Mental Hlth Counseling, 13301 N Bruce B Downs Blvd,MHC 1601, Tampa, FL 33612 USA. EM Kearns@usf.edu RI Kearns, William/F-9810-2015 OI Kearns, William/0000-0002-0241-814X FU US Department of Defense [W81XWH-11-1-0634] FX This research was supported by the US Department of Defense under award number W81XWH-11-1-0634 to Dr Paul Sanberg "Battlefield-Related Injury Translational Research, Post-Traumatic Disease, and Disability Veterans Injury Translational Research, Post-Traumatic Disease, and Disability Veterans Re-Integration." NR 23 TC 1 Z9 1 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0885-9701 EI 1550-509X J9 J HEAD TRAUMA REHAB JI J. Head Trauma Rehabil. PD JAN-FEB PY 2016 VL 31 IS 1 BP E20 EP E27 DI 10.1097/HTR.0000000000000126 PG 8 WC Clinical Neurology; Rehabilitation SC Neurosciences & Neurology; Rehabilitation GA DK9CN UT WOS:000375228000003 PM 25931182 ER PT J AU Sparrow, D DeAngelis, TR Hendron, K Thomas, CA Saint-Hilaire, M Ellis, T AF Sparrow, David DeAngelis, Tamara R. Hendron, Kathryn Thomas, Cathi A. Saint-Hilaire, Marie Ellis, Terry TI Highly Challenging Balance Program Reduces Fall Rate in Parkinson Disease SO JOURNAL OF NEUROLOGIC PHYSICAL THERAPY LA English DT Article DE balance; exercise; falls; Parkinson disease; postural control; rehabilitation ID RANDOMIZED CONTROLLED-TRIAL; POSTURAL RESPONSES; PREVENTION TRIALS; MINI-BESTEST; EXERCISE; PEOPLE; GAIT; MOTOR; RECOMMENDATIONS; INTERVENTION AB Background and Purpose: There is a paucity of effective treatment options to reduce falls in Parkinson disease (PD). Although a variety of rehabilitative approaches have been shown to improve balance, evidence of a reduction in falls has been mixed. Prior balance trials suggest that programs with highly challenging exercises had superior outcomes. We investigated the effects of a theory-driven, progressive, highly challenging group exercise program on fall rate, balance, and fear of falling. Methods: Twenty-three subjects with PD participated in this randomized cross-over trial. Subjects were randomly allocated to 3 months of active balance exercises or usual care followed by the reverse. During the active condition, subjects participated in a progressive, highly challenging group exercise program twice weekly for 90 minutes. Outcomes included a change in fall rate over the 3-month active period and differences in balance (Mini-Balance Evaluation Systems Test [Mini-BESTest]), and fear of falling (Falls Efficacy Scale-International [FES-I]) between active and usual care conditions. Results: The effect of time on falls was significant (regression coefficient = -0.015 per day, P < 0.001). The estimated rate ratio comparing incidence rates at time points 1 month apart was 0.632 (95% confidence interval, 0.524-0.763). Thus, there was an estimated 37% decline in fall rate per month (95% confidence interval, 24%-48%). Improvements were also observed on the Mini-BESTest (P = 0.037) and FES-I (P = 0.059). Discussion and Conclusions: The results of this study show that a theory-based, highly challenging, and progressive exercise program was effective in reducing falls, improving balance, and reducing fear of falling in PD. Video Abstract available for more insights from the authors (see Supplemental Digital Content 1, http://links.lww.com/JNPT/A120). C1 [Sparrow, David] Boston Univ, Sch Med, VA Boston Healthcare Syst, 635 Commonwealth Ave, Boston, MA 02215 USA. [Sparrow, David] Boston Univ, Sch Med, Dept Med, 635 Commonwealth Ave, Boston, MA 02215 USA. [DeAngelis, Tamara R.; Hendron, Kathryn; Ellis, Terry] Boston Univ, Coll Hlth & Rehabil Sci Sargent, Ctr Neurorehabil, Dept Phys Therapy & Athlet Training, 635 Commonwealth Ave, Boston, MA 02215 USA. [Thomas, Cathi A.; Saint-Hilaire, Marie] Boston Univ, Dept Neurol, Boston Univ Med Campus,635 Commonwealth Ave, Boston, MA 02215 USA. RP Ellis, T (reprint author), Boston Univ, Coll Hlth & Rehabil Sci Sargent, 635 Commonwealth Ave, Boston, MA 02215 USA. EM tellis@bu.edu FU Boston Claude D. Pepper Older Americans Independence Center [NIH 5P30AG031679]; American Parkinson Disease Association (ADPA); ADPAMA Chapter FX This study was funded by the Boston Claude D. Pepper Older Americans Independence Center (NIH 5P30AG031679). Additional support was provided by the American Parkinson Disease Association (ADPA); ADPAMA Chapter. NR 35 TC 2 Z9 2 U1 3 U2 8 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 1557-0576 EI 1557-0584 J9 J NEUROL PHYS THER JI J. Neurol. Phys. Ther. PD JAN PY 2016 VL 40 IS 1 BP 24 EP 30 DI 10.1097/NPT.0000000000000111 PG 7 WC Clinical Neurology; Rehabilitation SC Neurosciences & Neurology; Rehabilitation GA DK9CY UT WOS:000375229200005 PM 26655100 ER PT J AU Steensma, DP AF Steensma, David P. TI The Farid Fata Medicare Fraud Case and Misplaced Incentives in Oncology Care SO JOURNAL OF ONCOLOGY PRACTICE LA English DT Editorial Material C1 [Steensma, David P.] Dana Farber Canc Inst, 450 Brookline Ave,D2037, Boston, MA 02115 USA. [Steensma, David P.] Harvard Univ, Sch Med, Boston, MA USA. RP Steensma, DP (reprint author), Dana Farber Canc Inst, 450 Brookline Ave,D2037, Boston, MA 02115 USA. EM david_steensma@dfci.harvard.edu NR 7 TC 0 Z9 0 U1 1 U2 1 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 1554-7477 EI 1935-469X J9 J ONCOL PRACT JI J. Oncol. Pract. PD JAN PY 2016 VL 12 IS 1 BP 51 EP U100 DI 10.1200/JOP.2015.008557 PG 5 WC Health Care Sciences & Services SC Health Care Sciences & Services GA DJ6LR UT WOS:000374325200019 PM 26733620 ER PT J AU Goodman, LM Moeller, MB Azzouqa, AG Guthrie, AE Dalby, CK Earl, MA Cheng, C Pennell, NA Shapiro, M Velcheti, V Stevenson, LP AF Goodman, Lindsey Martin Moeller, Machette B. Azzouqa, Abdel-Ghani Guthrie, Amy E. Dalby, Carole K. Earl, Marc A. Cheng, Connie Pennell, Nathan A. Shapiro, Marc Velcheti, Vamsidhar Stevenson, Lames P. TI Reduction of Inappropriate Prophylactic Peplated Granulocyte Colony-Stimulating Factor Use for Patients With Non Small-Cell Lung Cancer Who Receive Chemotherapy: An ASCO Quality Training Program Project of the Cleveland Clinic Taussig Cancer Institute SO JOURNAL OF ONCOLOGY PRACTICE LA English DT Article ID FEBRILE NEUTROPENIA; GUIDELINE; UPDATE AB Purpose Routine prophylactic pegylated granulocyte colony-stimulating factor (pGCSF) administration for patients receiving chemotherapy regimens associated with low risk (< 10%) for neutropenic fever (LRNF) is not recommended. Inappropriate use of pGCSF increases patient morbidity and health care costs. Methods A multidisciplinary team reviewed the charts of patients with non-small-cell lung cancer (NSCLC) at the Taussig Cancer Institute in whom a new chemotherapy regimen was initiated from April through November 2013. pGCSF use was identified and deemed appropriate if prescribed for chemotherapy associated with high risk of neutropenic fever (> 20%) or intermediate risk (10% to 20%) if other risk factors for neutropenic fever were present. Use with LRNF chemotherapy was recorded as inappropriate. Results One hundred eighty patients with NSCLC received a new chemotherapy regimen during the specified time period. Thirty-four of 119 patients (28%) treated with LRNF chemotherapy received pGCSF. Each patient received an average of 2.6 doses of pGCSF (total, 89 doses). We implemented three plan-do-study-act cycles: education of providers, development of Taussig Cancer Institute consensus guidelines for pGCSF in NSCLC, and removal of standing pGCSF orders from LRNF chemotherapy in the electronic medical record. Analysis during the change period revealed 4% of patients with NSCLC treated with LRNF chemotherapy received pGCSF. Cost analysis showed an 84% decrease in billed charges per month. No increase in neutropenic fever admissions was found. Conclusion pGCSF was excessively prescribed for patients with NSCLC. Factors contributing to inappropriate use included provider lack of familiaritywith guidelines and knowledge with regard to the risk of neutropenicfever for individual chemotherapy regimens, and electronic medical record chemotherapy templates that contain standing GCSF orders. Interventions to address these gaps quickly produced improved compliance with guidelines and led to significant cost savings. C1 Cleveland Clin, Cleveland, OH 44106 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. RP Goodman, LM (reprint author), Cleveland Clin, Taussig Canc Inst, Dept Hematol & Med Oncol, 9500 Euclid Ave,R35, Cleveland, OH 44195 USA. EM goodmal2@ccf.org NR 6 TC 0 Z9 0 U1 0 U2 1 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 1554-7477 EI 1935-469X J9 J ONCOL PRACT JI J. Oncol. Pract. PD JAN PY 2016 VL 12 IS 1 BP E101 EP E107 DI 10.1200/JOP.2015.006502 PG 7 WC Health Care Sciences & Services SC Health Care Sciences & Services GA DJ6LR UT WOS:000374325200006 PM 26759474 ER PT J AU Ma, L Donohue, C DeNofrio, T Pedulla, LV Haddad, RI Rabinowits, G AF Ma, Laura Donohue, Caitlin DeNofrio, Tina Pedulla, Lillian Vitale Haddad, Robert I. Rabinowits, Guilherme TI Optimizing Tobacco Cessation Resource Awareness Among Patients and Providers SO JOURNAL OF ONCOLOGY PRACTICE LA English DT Article ID NECK-CANCER; HEAD; SMOKING AB Purpose Despite receiving a cancer diagnosis, many patients continue to use tobacco during treatment, negatively affecting their outcomes. We hypothesized that limited tobacco cessation (TC) discussion among patients and providers was partially the result of providers' lack of awareness of current TC resources available. Methods We surveyed the head and neck oncology providers (HNOPs) at Dana -Farber Cancer Institute to evaluate their awareness of existing TC resources within the community and performed a 6 -month medical record review of active tobacco users (ATUs) to evaluate the frequency of documented TC discussions in clinic. We educated the HNOPs about available TC resources, developed a TC resource teaching sheet, placed a provider alert page in examination rooms as a reminder of TC discussions, and built a TC discussion template to ease documentation. Four weeks postintervention, we resurveyed providers and again performed medical record reviews of ATUs. Results Preintervention, 13% of HNOPs were aware of TC resources available, and TC discussion documentation was 28%. Postintervention, 100% of HNOPs became aware of the TC resources available, and documentations increased to 56% at 5 months. Identification of ATUs increased from six to 13 per month to 17 to 33 per month post intervention. Eighty-eight percent of HNOPs felt the intervention prompted TC discussions in clinicwith their ATUs. Conclusion The limited number of TC discussions among patients and providers was at least partially the result of unawareness of TC resources available within the community. Educating HNOPs and alerting them to ATUs at their clinic visits successfully prompted TC discussions in clinic. C1 [Rabinowits, Guilherme] Dana Farber Canc Inst, 450 Brookline Ave, Boston, MA 02215 USA. Brigham & Womens Hosp, 75 Francis St, Boston, MA 02115 USA. RP Rabinowits, G (reprint author), Dana Farber Canc Inst, 450 Brookline Ave, Boston, MA 02215 USA. EM guilherme_rabinowits@dfci.harvard.edu NR 13 TC 0 Z9 0 U1 1 U2 2 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 1554-7477 EI 1935-469X J9 J ONCOL PRACT JI J. Oncol. Pract. PD JAN PY 2016 VL 12 IS 1 BP E77 EP E82 DI 10.1200/JOP.2015.005124 PG 6 WC Health Care Sciences & Services SC Health Care Sciences & Services GA DJ6LR UT WOS:000374325200002 PM 26330532 ER PT J AU Moriarty, HJ Robinson, JP Bunting-Perry, L Bradway, CW AF Moriarty, Helene J. Robinson, Joanne P. Bunting-Perry, Lisette Bradway, Christine W. TI Cognitive, Affective, and Behavioral Dimensions of the Lower Urinary Tract Symptom Experience in Men With Parkinson's Disease SO JOURNAL OF WOUND OSTOMY AND CONTINENCE NURSING LA English DT Article DE lower urinary tract symptoms; military veterans; Parkinson's disease; symptom experience; urinary incontinence ID QUALITY-OF-LIFE; VOIDING DYSFUNCTION; INCONTINENCE; DEPRESSION; MANAGEMENT; IMPACT; ADULTS; WOMEN; STATE AB OBJECTIVE: Lower urinary tract symptoms (LUTS) in persons with Parkinson's disease (PD) have received little research attention. To address this gap in our knowledge, we examined the LUTS experience in men with PD, guided by The Theory of Unpleasant Symptoms. METHODS: A qualitative design was used to explore the LUTS experience in this population. Participants were recruited from a Veterans' Affairs PD Center. Maximum variation sampling was used to select diverse participants for audiotaped open-ended interviews. Additional data sources included field notes collected during interviews and observation of a PD support group. The template organizing analytic approach was used to code transcribed interviews and field notes. RESULTS: Cognitive, affective, and behavioral dimensions of the LUTS experience were identified. Participants attributed LUTS to aging, medications, and effects of motor symptoms on their ability to respond to the urge to void. There was little awareness of the neurologic contributions of PD to LUTS, and most viewed LUTS as "something that you have to put up with." Negative effects of LUTS on self-identity were noted, which jeopardized relationships, intimacy, participation in social activities, and travel. Affective responses to LUTS, particularly embarrassment, had a profound impact on quality of life. Behavioral strategies to manage LUTS focused on "being prepared to go when you need to go" and consisted mostly of trial-and-error efforts. CONCLUSION: Misconceptions about LUTS among men with PD may result in underreporting, missed opportunities for professional assistance, and diminished health-related quality of life. Future research should focus on developing and testing nursing interventions to address cognitive, affective, and behavioral aspects of the LUTS experience in men with PD. C1 [Moriarty, Helene J.] Villanova Univ, Coll Nursing, 800 Lancaster Ave, Villanova, PA 19085 USA. [Moriarty, Helene J.] Dept Vet Affairs Med Ctr, Nursing Serv, Philadelphia, PA 19104 USA. [Robinson, Joanne P.] Rutgers State Univ, Sch Nursing, Camden, NJ 08102 USA. [Bunting-Perry, Lisette] Univ Delaware, Sch Nursing, Newark, DE 19716 USA. [Bunting-Perry, Lisette] Dept Vet Affairs Med Ctr, Parkinsons Dis Res Educ & Clin Ctr, Philadelphia, PA 19104 USA. [Bradway, Christine W.] Univ Penn, Sch Nursing, Philadelphia, PA 19104 USA. RP Moriarty, HJ (reprint author), Villanova Univ, Coll Nursing, 800 Lancaster Ave, Villanova, PA 19085 USA. EM Helene.moriarty@villanova.edu FU Hollister Grant for Continence Nursing from the Wound Ostomy Continence Nursing Society's Center for Clinical Investigation FX The project described was funded by the Hollister Grant for Continence Nursing, from the Wound Ostomy Continence Nursing Society's Center for Clinical Investigation. The research team thanks the veterans with Parkinson's disease who gave of themselves and their time to share their stories and take part in this study. NR 43 TC 2 Z9 2 U1 1 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 1071-5754 EI 1528-3976 J9 J WOUND OSTOMY CONT JI J. Wound Ostomy Cont. Nurs. PD JAN-FEB PY 2016 VL 43 IS 1 BP 80 EP 87 DI 10.1097/WON.0000000000000165 PG 8 WC Nursing SC Nursing GA DK9EO UT WOS:000375233800012 PM 26727686 ER PT J AU Milburn, E Warren, T Dickey, MW AF Milburn, Evelyn Warren, Tessa Dickey, Michael Walsh TI World knowledge affects prediction as quickly as selectional restrictions: evidence from the visual world paradigm SO LANGUAGE COGNITION AND NEUROSCIENCE LA English DT Article DE Language comprehension; plausibility; eye tracking; sentence processing; prediction ID ANTICIPATORY EYE-MOVEMENTS; LANGUAGE COMPREHENSION; EVENT KNOWLEDGE; TIME-COURSE; INTEGRATION; VERBS; VIOLATIONS; MODELS AB There has been considerable debate regarding the question of whether linguistic knowledge and world knowledge are separable and used differently during processing or not (Hagoort et al, 2004). Integration of word meaning and world knowledge in language comprehension (Matsuki et al, 2011). Event-based plausibility immediately influences on-line language comprehension (Paczynski et al, 2012). Multiple influences of semantic memory on sentence processing: Distinct effects of semantic relatedness on violations of real-world event/state knowledge and animacy selection restrictions (Warren et al, 2007). Investigating effects of selectional restriction violations and plausibility violation severity on eye movements in reading. Previous investigations into this question have provided mixed evidence as to whether violations of selectional restrictions are detected earlier than violations of world knowledge. We report a visual world eye-tracking study comparing the timing of facilitation contributed by selectional restrictions vs. world knowledge. College-aged adults (n=36) viewed photographs of natural scenes while listening to sentences. Participants anticipated upcoming direct objects similarly regardless of whether facilitation was provided by only world knowledge or a combination of selectional restrictions and world knowledge. These results suggest that selectional restrictions are not available earlier in comprehension than world knowledge. C1 [Milburn, Evelyn; Warren, Tessa] Univ Pittsburgh, Dept Psychol, Pittsburgh, PA 15260 USA. [Milburn, Evelyn; Warren, Tessa] Univ Pittsburgh, Learning Res & Dev Ctr, Pittsburgh, PA USA. [Dickey, Michael Walsh] Univ Pittsburgh, Dept Commun Sci & Disorders, Pittsburgh, PA USA. [Dickey, Michael Walsh] VA Pittsburgh Healthcare Syst, Pittsburgh, PA USA. RP Milburn, E (reprint author), Univ Pittsburgh, Dept Psychol, Pittsburgh, PA 15260 USA.; Milburn, E (reprint author), Univ Pittsburgh, Learning Res & Dev Ctr, Pittsburgh, PA USA. EM eam115@pitt.edu FU National Institutes of Health [R01DC011520] FX This research was supported by the National Institutes of Health under grant R01DC011520 to the second and third authors. NR 29 TC 0 Z9 0 U1 2 U2 4 PU ROUTLEDGE JOURNALS, TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXFORDSHIRE, ENGLAND SN 2327-3798 EI 2327-3801 J9 LANG COGN NEUROSCI JI Lang. Cogn. Neurosci. PY 2016 VL 31 IS 4 BP 536 EP 548 DI 10.1080/23273798.2015.1117117 PG 13 WC Audiology & Speech-Language Pathology; Behavioral Sciences; Linguistics; Psychology, Experimental SC Audiology & Speech-Language Pathology; Behavioral Sciences; Linguistics; Psychology GA DK5VO UT WOS:000374989100017 PM 27148555 ER PT J AU Brunner, AM Hobbs, G Jalbut, MM Neuberg, DS Fathi, AT AF Brunner, Andrew M. Hobbs, Gabriela Jalbut, Marla M. Neuberg, Donna S. Fathi, Amir T. TI A population-based analysis of second malignancies among patients with myeloproliferative neoplasms in the SEER database SO LEUKEMIA & LYMPHOMA LA English DT Letter ID ACUTE MYELOID-LEUKEMIA; TERM-FOLLOW-UP; POLYCYTHEMIA-VERA; ESSENTIAL THROMBOCYTHEMIA; MYELODYSPLASTIC SYNDROMES; RISK; CANCERS C1 [Brunner, Andrew M.; Hobbs, Gabriela; Jalbut, Marla M.; Fathi, Amir T.] Massachusetts Gen Hosp, Zero Emerson Pl,Suite 118, Boston, MA 02114 USA. [Brunner, Andrew M.; Neuberg, Donna S.] Dana Farber Canc Inst, Boston, MA 02115 USA. RP Fathi, AT (reprint author), Massachusetts Gen Hosp, Zero Emerson Pl,Suite 118, Boston, MA 02114 USA. EM afathi@partners.org OI Hobbs, Gabriela/0000-0002-0199-9333 FU NCI NIH HHS [P30 CA006516, T32 CA 71345-18, 5P30 CA 006516, T32 CA071345, K12 CA087723] NR 15 TC 1 Z9 1 U1 0 U2 0 PU TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND SN 1042-8194 EI 1029-2403 J9 LEUKEMIA LYMPHOMA JI Leuk. Lymphoma PY 2016 VL 57 IS 5 BP 1197 EP 1200 DI 10.3109/10428194.2015.1071490 PG 4 WC Oncology; Hematology SC Oncology; Hematology GA DK6IS UT WOS:000375027000031 PM 26155828 ER PT J AU Ni, A Yang, T Mesnard-Hoaglin, NA Gutierrez, R Stubbs, EB McGuire, SO Sanders, VM Jones, KJ Foecking, EM Xin, JP AF Ni, Allen Yang, Tao Mesnard-Hoaglin, Nichole A. Gutierrez, Rafael Stubbs, Evan B., Jr. McGuire, Susan O. Sanders, Virginia M. Jones, Kathryn J. Foecking, Eileen M. Xin, Junping TI Th17 Cell Response in SOD1(G93A) Mice following Motor Nerve Injury SO MEDIATORS OF INFLAMMATION LA English DT Article ID AMYOTROPHIC-LATERAL-SCLEROSIS; REGULATORY T-LYMPHOCYTES; MEDIATE NEUROPROTECTION; THERAPEUTIC-STRATEGIES; ALS; INFLAMMATION; AXOTOMY; SERUM AB An increased risk of ALS has been reported for veterans, varsity athletes, and professional football players. The mechanism underlying the increased risk in these populations has not been identified; however, it has been proposed that motor nerve injury may trigger immune responses which, in turn, can accelerate the progression of ALS. Accumulating evidence indicates that abnormal immune reactions and inflammation are involved in the pathogenesis of ALS, but the specific immune cells involved have not been clearly defined. To understand how nerve injury and immune responses may contribute to ALS development, we investigated responses of CD4(+) T cell after facial motor nerve axotomy (FNA) at a presymptomatic stage in a transgenic mouse model of ALS (B6SJL SOD1(G93A)). SOD1(G93A) mice, compared with WT mice, displayed an increase in the basal activation state of CD4(+) T cells and higher frequency of Th17 cells, which were further enhanced by FNA. In conclusion, SOD1(G93A) mice exhibit abnormal CD4(+) T cell activation with increased levels of Th17 cells prior to the onset of neurological symptoms. Motor nerve injury exacerbates Th17 cell responses and may contribute to the development of ALS, especially in those who carry genetic susceptibility to this disease. C1 [Ni, Allen; Gutierrez, Rafael; Xin, Junping] Loyola Univ Chicago, Oncol Res Inst, Maywood, IL 60153 USA. [Ni, Allen; Mesnard-Hoaglin, Nichole A.; Stubbs, Evan B., Jr.; McGuire, Susan O.; Foecking, Eileen M.; Xin, Junping] US Dept Vet Affairs, Vet Affairs Edward Hines Jr Hosp, Res Serv, Roosevelt Rd & 5th Ave, Hines, IL 60141 USA. [Yang, Tao] Gansu Prov Chinese Tradit Med Hosp, Dept Brain Dis, Lanzhou 730050, Gansu, Peoples R China. [Stubbs, Evan B., Jr.] Loyola Univ Chicago, Stritch Sch Med, Dept Ophthalmol, Maywood, IL 60153 USA. [Sanders, Virginia M.] Ohio State Univ, Coll Med, Dept Mol Virol Immunol & Med Genet, Columbus, OH 43210 USA. [Jones, Kathryn J.] Indiana Univ, Sch Med, Dept Anat & Cell Biol, Indianapolis, IN 46202 USA. [Jones, Kathryn J.] Roudebush VA Hosp, Res & Dev Serv, Indianapolis, IN 46202 USA. [Foecking, Eileen M.] Loyola Univ, Ctr Med, Dept Otolaryngol, Maywood, IL 60153 USA. [Xin, Junping] Loyola Univ Chicago, Dept Mol Pharmacol & Therapeut, Maywood, IL 60153 USA. RP Xin, JP (reprint author), Loyola Univ Chicago, Oncol Res Inst, Maywood, IL 60153 USA.; Xin, JP (reprint author), US Dept Vet Affairs, Vet Affairs Edward Hines Jr Hosp, Res Serv, Roosevelt Rd & 5th Ave, Hines, IL 60141 USA.; Xin, JP (reprint author), Loyola Univ Chicago, Dept Mol Pharmacol & Therapeut, Maywood, IL 60153 USA. EM researchtreg@gmail.com FU Muscular Dystrophy Association [MDA202906]; NIH [NIH 40433, R21-CA181970]; Leukemia Research Foundation; Gansu Chinese Medicine Administration [GZK-2014-11] FX This work was supported by a grant from Muscular Dystrophy Association (MDA202906 to Junping Xin) and partially by NIH grant (NIH 40433 to Kathryn J. Jones and Virginia M. Sanders). Junping Xin was also supported in part by grants from NIH (R21-CA181970) and the Leukemia Research Foundation (New Investigator Award, 8th Annual George Richard Memorial Grant). Tao Yang was supported by a grant from Gansu Chinese Medicine Administration (GZK-2014-11). The authors thank Ms. Patricia Simms and Ms. Ashley Hess for assistance with FACS analysis and Drs. Jiwang Zhang, James Walter, Gwendolyn L. Kartje, William Wolf, Keith Fargo, Haiyan Chen, and Cynthia Pervan for ongoing professional support and collaborations, as well as scientific suggestions and discussions. NR 16 TC 0 Z9 0 U1 0 U2 0 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 2016 AR 6131234 DI 10.1155/2016/6131234 PG 7 WC Cell Biology; Immunology SC Cell Biology; Immunology GA DL0GN UT WOS:000375310500001 ER PT J AU Detappe, A Lux, F Tillement, O AF Detappe, Alexandre Lux, Francois Tillement, Olivier TI Pushing radiation therapy limitations with theranostic nanoparticles SO NANOMEDICINE LA English DT Editorial Material DE clinical trial; gadolinium; image-guided radiation therapy; radiosensitizer; theranostic nanoparticles ID GADOLINIUM-BASED NANOPARTICLES; GOLD NANOPARTICLES; RADIOTHERAPY C1 [Detappe, Alexandre; Lux, Francois; Tillement, Olivier] Univ Lyon 1, CNRS, Inst Lumiere Matiere, UMR 5306, F-69365 Lyon, France. [Detappe, Alexandre] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Radiat Oncol, 44 Binney St, Boston, MA 02115 USA. RP Tillement, O (reprint author), Univ Lyon 1, CNRS, Inst Lumiere Matiere, UMR 5306, F-69365 Lyon, France. EM olivier.tillement@univ-lyon1.fr OI Detappe, Alexandre/0000-0001-9364-1621 NR 12 TC 1 Z9 1 U1 1 U2 10 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 2016 VL 11 IS 9 BP 997 EP 999 DI 10.2217/nnm.16.38 PG 3 WC Biotechnology & Applied Microbiology; Nanoscience & Nanotechnology SC Biotechnology & Applied Microbiology; Science & Technology - Other Topics GA DK2UU UT WOS:000374770700004 PM 27074108 ER PT J AU Piantoni, G Halgren, E Cash, SS AF Piantoni, Giovanni Halgren, Eric Cash, Sydney S. TI The Contribution of Thalamocortical Core and Matrix Pathways to Sleep Spindles SO NEURAL PLASTICITY LA English DT Review ID EYE-MOVEMENT SLEEP; GENERALIZED PENICILLIN EPILEPSY; CORTICOTHALAMIC FEEDBACK; MEMORY CONSOLIDATION; SLOW WAVES; BRAIN RHYTHMS; HUMAN CORTEX; OSCILLATIONS; MECHANISMS; EEG AB Sleep spindles arise from the interaction of thalamic and cortical neurons. Neurons in the thalamic reticular nucleus (TRN) inhibit thalamocortical neurons, which in turn excite the TRN and cortical neurons. A fundamental principle of anatomical organization of the thalamocortical projections is the presence of two pathways: the diffuse matrix pathway and the spatially selective core pathway. Cortical layers are differentially targeted by these two pathways with matrix projections synapsing in superficial layers and core projections impinging on middle layers. Based on this anatomical observation, we propose that spindles can be classified into two classes, those arising from the core pathway and those arising from the matrix pathway, although this does not exclude the fact that some spindles might combine both pathways at the same time. We find evidence for this hypothesis in EEG/MEG studies, intracranial recordings, and computational models that incorporate this difference. This distinction will prove useful in accounting for the multiple functions attributed to spindles, in that spindles of different types might act on local and widespread spatial scales. Because spindle mechanisms are often hijacked in epilepsy and schizophrenia, the classification proposed in this review might provide valuable information in defining which pathways have gone awry in these neurological disorders. C1 [Piantoni, Giovanni; Cash, Sydney S.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Piantoni, Giovanni; Cash, Sydney S.] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Halgren, Eric] Univ Calif San Diego, La Jolla, CA 92093 USA. RP Piantoni, G (reprint author), Massachusetts Gen Hosp, Boston, MA 02114 USA.; Piantoni, G (reprint author), Harvard Univ, Sch Med, Boston, MA 02115 USA. EM gio@gpiantoni.com FU BIAL Foundation [220/12]; ONR [N00014-13-1-0672]; NIH [R01 EB009282, R01 MH099645] FX This work was supported by BIAL Foundation 220/12, ONR N00014-13-1-0672, NIH R01 EB009282, and NIH R01 MH099645. NR 93 TC 2 Z9 2 U1 2 U2 2 PU HINDAWI PUBLISHING CORP 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 2016 AR 3024342 DI 10.1155/2016/3024342 PG 10 WC Neurosciences SC Neurosciences & Neurology GA DK3YE UT WOS:000374852500001 ER PT J AU Hashimoto, N Bautista, PA Haneishi, H Snuderl, M Yagi, Y AF Hashimoto, Noriaki Bautista, Pinky A. Haneishi, Hideaki Snuderl, Matija Yagi, Yukako TI Development of a 2D Image Reconstruction and Viewing System for Histological Images from Multiple Tissue Blocks: Towards High-Resolution Whole-Organ 3D Histological Images SO PATHOBIOLOGY LA English DT Article DE 2D image reconstruction; Histology image; Whole organ ID SECTIONS; REGISTRATION; PATHOLOGY; CLASSIFICATION; VALIDATION; MICROSCOPE; PROGNOSIS; QUALITY; DESIGN AB High-resolution 3D histology image reconstruction of the whole brain organ starts from reconstructing the high-resolution 2D histology images of a brain slice. In this paper, we introduced a method to automatically align the histology images of thin tissue sections cut from the multiple paraffin embedded tissue blocks of a brain slice. For this method, we employed template matching and incorporated an optimization technique to further improve the accuracy of the 2D reconstructed image. In the template matching, we used the gross image of the brain slice as a reference to the reconstructed 2D histology image of the slice, while in the optimization procedure, we utilized the Jaccard index as the metric of the reconstruction accuracy. The results of our experiment on the initial 3 different whole-brain tissue slices showed that while the method works, it is also constrained by tissue deformations introduced during the tissue processing and slicing. The size of the reconstructed high-resolution 2D histology image of a brain slice is huge, and designing an image viewer that makes particularly efficient use of the computing power of a standard computer used in our laboratories is of interest. We also present the initial implementation of our 2D image viewer system in this paper. (C) 2016 S. Karger AG, Basel C1 [Hashimoto, Noriaki; Haneishi, Hideaki] Chiba Univ, Ctr Frontier Med Engn, Chiba, Japan. [Bautista, Pinky A.; Yagi, Yukako] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Yagi, Yukako] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. [Snuderl, Matija] NYU, Langone Med Ctr, New York, NY USA. RP Yagi, Y (reprint author), Massachusetts Gen Hosp, Pathol Imaging & Commun Technol Ctr, 101 Merrimac St,Suite 820, Boston, MA 02114 USA. EM YYAGI@mgh.harvard.edu RI Haneishi, Hideaki/E-4162-2017; OI Haneishi, Hideaki/0000-0001-7157-4309; Snuderl, Matija/0000-0003-0752-0917 NR 30 TC 1 Z9 1 U1 0 U2 1 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 1015-2008 EI 1423-0291 J9 PATHOBIOLOGY JI Pathobiology PY 2016 VL 83 IS 2-3 BP 127 EP 139 DI 10.1159/000443278 PG 13 WC Cell Biology; Pathology SC Cell Biology; Pathology GA DK6IE UT WOS:000375025100009 PM 27100217 ER PT J AU Senter-Zapata, M Patel, K Bautista, PA Griffin, M Michaelson, J Yagi, Y AF Senter-Zapata, Michael Patel, Kunal Bautista, Pinky A. Griffin, Molly Michaelson, James Yagi, Yukako TI The Role of Micro-CT in 3D Histology Imaging SO PATHOBIOLOGY LA English DT Article DE 3D reconstruction; 3D Slicer; High-resolution 3D histology; ImageJ; Micro-CT; Volume measurements ID TISSUE; SYSTEM AB Objectives: 3D histology tissue modeling is a useful analytical technique for understanding anatomy and disease at the cellular level. However, the current accuracy of 3D histology technology is largely unknown, and errors, misalignment and missing information are common in 3D tissue reconstruction. We used micro-CT imaging technology to better understand these issues and the relationship between fresh tissue and its 3D histology counterpart. Methods: We imaged formalin-fixed and 2% Lugol-stained mouse brain, human uterus and human lung tissue with micro-CT. We then conducted image analyses on the tissues before and after paraffin embedding using 3D Slicer and ImageJ software to understand how tissue changes between the fixation and embedding steps. Results: We found that all tissue samples decreased in volume by 19.2-61.5% after embedding, that micro-CT imaging can be used to assess the integrity of tissue blocks, and that micro-CT analysis can help to design an optimized tissue-sectioning protocol. Conclusions: Micro-CT reference data help to identify where and to what extent tissue was lost or damaged during slide production, provides valuable anatomical information for reconstructing missing parts of a 3D tissue model, and aids in correcting reconstruction errors when fitting the image information in vivo and ex vivo. (C) 2016 S. Karger AG, Basel C1 [Senter-Zapata, Michael; Patel, Kunal; Bautista, Pinky A.; Griffin, Molly; Michaelson, James; Yagi, Yukako] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Michaelson, James; Yagi, Yukako] Harvard Univ, Sch Med, Dept Pathol, Boston, MA USA. RP Yagi, Y (reprint author), Massachusetts Gen Hosp, Pathol Imaging & Commun Technol Ctr, 101 Merrimac St,Suite 820, Boston, MA 02114 USA. EM YYAGI@mgh.harvard.edu OI Griffin, Molly/0000-0002-1615-2645 NR 14 TC 0 Z9 0 U1 3 U2 3 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 1015-2008 EI 1423-0291 J9 PATHOBIOLOGY JI Pathobiology PY 2016 VL 83 IS 2-3 BP 140 EP 147 DI 10.1159/000442387 PG 8 WC Cell Biology; Pathology SC Cell Biology; Pathology GA DK6IE UT WOS:000375025100010 PM 27100885 ER PT J AU Nachega, JB Skinner, D Jennings, L Magidson, JF Altice, FL Burke, JG Lester, RT Uthman, OA Knowlton, AR Cotton, MF Anderson, JR Theron, GB AF Nachega, Jean B. Skinner, Donald Jennings, Larissa Magidson, Jessica F. Altice, Frederick L. Burke, Jessica G. Lester, Richard T. Uthman, Olalekan A. Knowlton, Amy R. Cotton, Mark F. Anderson, Jean R. Theron, Gerhard B. TI Acceptability and feasibility of mHealth and community-based directly observed antiretroviral therapy to prevent mother-to-child HIV transmission in South African pregnant women under Option B plus : an exploratory study SO PATIENT PREFERENCE AND ADHERENCE LA English DT Article DE HIV; AIDS; pregnancy; short messaging system; social support ID SUB-SAHARAN AFRICA; IMPROVE ADHERENCE; CONTROLLED-TRIAL; SOCIAL SUPPORT; CARE; INTERVENTIONS; ADULTS; COUNTRIES; KENYA AB Objective: To examine the acceptability and feasibility of mobile health (mHealth)/short message service (SMS) and community-based directly observed antiretroviral therapy (cDOT) as interventions to improve antiretroviral therapy (ART) adherence for preventing mother-to-child human immunodeficiency virus (HIV) transmission (PMTCT). Design and methods: A mixed-method approach was used. Two qualitative focus group discussions with HIV-infected pregnant women (n=20) examined the acceptability and feasibility of two ART adherence interventions for PMTCT: 1) SMS text messaging and 2) patient-nominated cDOT supporters. Additionally, 109 HIV-infected, pregnant South African women (18-30 years old) receiving PMTCT services under single-tablet antiretroviral therapy regimen during pregnancy and breastfeeding and continuing for life ("Option B+") were interviewed about mobile phone access, SMS use, and potential treatment supporters. Setting: A community primary care clinic in Cape Town, South Africa. Participants: HIV-infected pregnant women. Main outcomes: Acceptability and feasibility of mHealth and cDOT interventions. Results: Among the 109 women interviewed, individual mobile phone access and SMS use were high (>90%), and 88.1% of women were interested in receiving SMS ART adherence support messages such as reminders, motivation, and medication updates. Nearly all women (95%) identified at least one person close to them to whom they had disclosed their HIV status and would nominate as a cDOT supporter. Focus group discussions revealed that cDOT supporters and adherence text messages were valued, but some concerns regarding supporter time availability and risk of unintended HIV status disclosure were expressed. Conclusion: mHealth and/or cDOT supporter as interventions to improve ART adherence are feasible in this setting. However, safe HIV status disclosure to treatment supporters and confidentiality of text messaging content about HIV and ART were deemed crucial. C1 [Nachega, Jean B.] Univ Pittsburgh, Grad Sch Publ Hlth, Dept Epidemiol, 130 DeSoto St, Pittsburgh, PA 15261 USA. [Nachega, Jean B.] Univ Stellenbosch, Fac Med & Hlth Sci, Ctr Infect Dis, Dept Med, Cape Town, South Africa. [Nachega, Jean B.] Univ Stellenbosch, Fac Med & Hlth Sci, ACTG Clin Trial Unit CTU, Family Clin Res Unit FAMCRU, Cape Town, South Africa. [Skinner, Donald] Univ Stellenbosch, Fac Med & Hlth Sci, Dept Interdisciplinary Hlth Studies, Res Hlth & Soc, Cape Town, South Africa. [Jennings, Larissa] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Int Hlth, Social & Behav Intervent Program, Baltimore, MD USA. [Magidson, Jessica F.] Harvard Univ, Sch Med, Dept Psychiat, Massachusetts Gen Hosp, Boston, MA 02115 USA. [Altice, Frederick L.] Yale Univ, Sch Med, AIDS Program, Div Infect Dis, New Haven, CT USA. [Burke, Jessica G.] Univ Pittsburgh, Grad Sch Publ Hlth, Dept Behav & Community Hlth, Pittsburgh, PA 15261 USA. [Lester, Richard T.] Univ British Columbia, Dept Med, Div Infect Dis, Vancouver, BC, Canada. [Uthman, Olalekan A.] Univ Warwick, Warwick Med Sch, Div Hlth Sci, WCAHRD, Coventry CV4 7AL, W Midlands, England. [Uthman, Olalekan A.] Univ Stellenbosch, Fac Med & Hlth Sci, Ctr Evidence Based Hlth Care, Cape Town, South Africa. [Knowlton, Amy R.] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Hlth Behav & Soc, Baltimore, MD USA. [Cotton, Mark F.] Univ Stellenbosch, Fac Med & Hlth Sci, Dept Pediat & Child Hlth, Cape Town, South Africa. [Anderson, Jean R.] Johns Hopkins Univ, Sch Med, Dept Obstet & Gynecol, Baltimore, MD 21205 USA. [Theron, Gerhard B.] Univ Stellenbosch, Fac Med & Hlth Sci, Dept Obstet & Gynecol, Cape Town, South Africa. RP Nachega, JB (reprint author), Univ Pittsburgh, Grad Sch Publ Hlth, Dept Epidemiol, 130 DeSoto St, Pittsburgh, PA 15261 USA. EM jbn16@pitt.edu RI Emchi, Karma/Q-1952-2016 FU National Institutes of Health/National Institutes for Allergy and Infectious Disease; AIDS Clinical Trial Group (ACTG)/Stellenbosch University Clinical Trial Unit [2UM1AI069521-08]; US President Emergency Plan for AIDS Relief (PEPFAR) [T84HA21652-01-00]; European Developing Countries Clinical Trial Partnership Senior Fellowship Award [TA-08-40200-021]; Wellcome Trust Southern Africa Consortium for Research Excellence [WT087537MA]; National Institute on Drug Abuse [R01-DA10186, R01 DA13805, R01 DA017072, K24 DA017072]; National Institutes of Health/National Institutes for Mental Health [R01-MH09755]; Michael Smith Foundation for Health Research; Grand Challenges Canada; FAS Marie Curie International PostDoc [2012-0064]; National Institute of Mental Health [T32MH093310] FX Dr Nachega receives research grant support from the National Institutes of Health/National Institutes for Allergy and Infectious Disease, the AIDS Clinical Trial Group (ACTG)/Stellenbosch University Clinical Trial Unit (2UM1AI069521-08); the US President Emergency Plan for AIDS Relief (PEPFAR; T84HA21652-01-00) for Medical Education Partnership Initiative; the European Developing Countries Clinical Trial Partnership Senior Fellowship Award (TA-08-40200-021); and the Wellcome Trust Southern Africa Consortium for Research Excellence (WT087537MA). Professor Altice is funded by the National Institute on Drug Abuse for research (R01-DA10186, R01 DA13805, and R01 DA017072) and career development (K24 DA017072). Dr Lester is supported in part by research grants from the National Institutes of Health/National Institutes for Mental Health (R01-MH09755), the Michael Smith Foundation for Health Research, and Grand Challenges Canada. Dr Uthman acknowledges support from the FAS Marie Curie International PostDoc (2012-0064). Dr Magidson acknowledges support from the National Institute of Mental Health (T32MH093310). NR 40 TC 1 Z9 1 U1 1 U2 1 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 2016 VL 10 BP 683 EP 690 DI 10.2147/PPA.S100002 PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA DK7AT UT WOS:000375077900001 PM 27175068 ER PT J AU Ingelfinger, JR Kalantar-Zadeh, K Schaefer, F AF Ingelfinger, Julie R. Kalantar-Zadeh, Kamyar Schaefer, Franz CA World Kidney Day Steering Comm TI Editorial: World Kidney Day 2016: Averting the Legacy of Kidney Disease-Focus on Childhood SO SEMINARS IN NEPHROLOGY LA English DT Editorial Material DE Pediatric nephrology; chronic kidney disease; pediatrics; congenital anomalies of the kidney and urinary tract (CAKUT); developmental origins of health and disease (DoHAD) ID NEPHROLOGY ASSOCIATION IPNA; RENAL REPLACEMENT THERAPY; LOW-BIRTH-WEIGHT; NONCOMMUNICABLE DISEASES; INTERNATIONAL SOCIETY; CONSENSUS STATEMENT; PROSPECTIVE COHORT; BLOOD-PRESSURE; GLOBAL HEALTH; CHILDREN AB World Kidney Day 2016 focuses on kidney disease in childhood and the antecedents of adult kidney disease that can begin in earliest childhood. Chronic kidney disease (CKD) in childhood differs from that in adults, as the largest diagnostic group among children includes congenital anomalies and inherited disorders, with glomerulopathies and kidney disease in the setting of diabetes being relatively uncommon. In addition, many children with acute kidney injury will ultimately develop sequelae that may lead to hypertension and CKD in later childhood or in adult life. Children born early or who are small-for-date newborns have a relatively increased risk for the development of CKD later in life. Persons with a high-risk birth and early childhood history should be watched closely to help detect early signs of kidney disease in time to provide effective prevention or treatment. Successful therapy is feasible for advanced CKD in childhood; there is evidence that children fare better than adults if they receive kidney replacement therapy including dialysis and transplantation, although only a minority of children may require this ultimate intervention. Because there are disparities in access to care, effort is needed so that those children with kidney disease, wherever they live, may be treated effectively, irrespective of their geographic or economic circumstances. Our hope is that World Kidney Day will inform the general public, policy makers, and caregivers about the needs and possibilities surrounding kidney disease in childhood. (C) 2016 Published by Elsevier Inc. C1 [Ingelfinger, Julie R.] Harvard Univ, Sch Med, Boston, MA USA. [Ingelfinger, Julie R.] Massachusetts Gen Hosp, MassGen Hosp Children, Boston, MA 02114 USA. [Kalantar-Zadeh, Kamyar] Heidelberg Univ, Ctr Pediat & Adolescent Med, Div Pediat Nephrol, Heidelberg, Germany. [Kalantar-Zadeh, Kamyar] Univ Calif Irvine, Sch Med, Div Nephrol & Hypertens Pediat & Publ Hlth, Irvine, CA 92717 USA. [Schaefer, Franz] Vet Affairs VA Long Beach Healthcare Syst, Long Beach, CA USA. [Schaefer, Franz] UCLA Fielding Sch Publ Hlth, Dept Epidemiol, Los Angeles, CA USA. RP Ingelfinger, JR (reprint author), ISN Global Operat Ctr, Rues Fabr 1, B-1000 Brussels, Belgium. OI Kalantar-Zadeh, Kamyar/0000-0002-8666-0725 NR 34 TC 0 Z9 0 U1 1 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 0270-9295 EI 1558-4488 J9 SEMIN NEPHROL JI Semin. Nephrol. PD JAN PY 2016 VL 36 IS 1 BP 1 EP 6 DI 10.1016/j.semnephrol.2016.01.010 PG 6 WC Urology & Nephrology SC Urology & Nephrology GA DK4TZ UT WOS:000374914500001 PM 27085729 ER PT J AU Weisbord, SD Palevsky, PM AF Weisbord, Steven D. Palevsky, Paul M. TI Design of Clinical Trials in Acute Kidney Injury: Lessons from the Past and Future Directions SO SEMINARS IN NEPHROLOGY LA English DT Review DE Acute kidney injury; clinical trial; prevention; treatment ID CONTRAST-INDUCED NEPHROPATHY; ACUTE-RENAL-FAILURE; ATRIAL-NATRIURETIC-PEPTIDE; GROWTH-FACTOR-I; RADIOCONTRAST-INDUCED NEPHROPATHY; RANDOMIZED-CONTROLLED-TRIAL; CRITICALLY-ILL PATIENTS; ACUTE TUBULAR-NECROSIS; PERCUTANEOUS CORONARY INTERVENTION; MELANOCYTE-STIMULATING HORMONE AB Acute kidney injury (AKI) is a common condition with multiple etiologies and variable clinical findings and pathologic manifestations. AKI is associated with serious adverse clinical outcomes, including the development of de novo chronic kidney disease, accelerated progression of pre-existing chronic kidney disease, end-stage kidney disease, and increased mortality. Past research has advanced our understanding of the pathophysiology, epidemiology, and outcomes of AKI significantly, however, little progress has been made in the development of evidence-based interventions for its prevention and treatment. In this review, we discuss key considerations in the design of clinical trials in AKI and highlight significant methodologic limitations that precluded many past studies from determining the effectiveness of preventive and therapeutic strategies for this common and serious condition. Published by Elsevier Inc. C1 [Weisbord, Steven D.; Palevsky, Paul M.] Univ Pittsburgh, Sch Med, Dept Med, Renal Sect,VA Pittsburgh Healthcare Syst,Renal El, Pittsburgh, PA 15213 USA. RP Weisbord, SD (reprint author), VA Pittsburgh Healthcare Syst, Dept Med, Renal Sect, Renal Electrolyte Div, 7 East,Room 120 111F-U,Univ Dr Div, Pittsburgh, PA 15240 USA. EM weisbordsd@upmc.edu OI Palevsky, Paul/0000-0002-7334-5400 NR 89 TC 1 Z9 1 U1 2 U2 3 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0270-9295 EI 1558-4488 J9 SEMIN NEPHROL JI Semin. Nephrol. PD JAN PY 2016 VL 36 IS 1 BP 42 EP 52 DI 10.1016/j.semnephrol.2016.01.004 PG 11 WC Urology & Nephrology SC Urology & Nephrology GA DK4TZ UT WOS:000374914500006 PM 27085734 ER PT J AU Binagwaho, A Wagner, CM Farmer, PE AF Binagwaho, Agnes Wagner, Claire M. Farmer, Paul E. TI A Vision for Global Cancer Medicine: Pursuing the Equity of Chance SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Review ID WESTERN KENYA; ABANDONMENT; EXPERIENCES; THERAPY; RWANDA AB At the turn of the century, some claimed that HIV/AIDS was a disease that could not be managed in low-income settings. It was argued that "poor people would not comply with treatment," and that treatment was too expensive and too complicated to deliver. But over the past two decades, data on outcomes have thoroughly disproved this myth. Similar arguments have more recently been made about cancer treatment: chemotherapy was said to be too toxic and too costly and that it required administration expertise beyond that available in low-income settings. We argue that these claims are similarly rooted in ideology rather than evidence. Fortunately, such claims are starting to be refuted by a diverse set of global cancer partnerships around the world that are documenting progress and positive results. In this review article, we provide examples of programs that can give us reason to hope that the treatment playing field is being leveled such that birthplace does not determine survival prognosis. We believe that through strong collaborative efforts and solidarity, the equity of chance can be achieved for patients with cancer worldwide. (C) 2015 by American Society of Clinical Oncology C1 [Binagwaho, Agnes] Minist Hlth Rwanda, Kigali, Rwanda. [Binagwaho, Agnes] Harvard Univ, Sch Med, Boston, MA USA. [Binagwaho, Agnes] Dartmouth Coll, Geisel Sch Med, Hanover, NH 03755 USA. [Wagner, Claire M.] Dana Farber Canc Inst, Ctr Global Canc Med, Boston, MA 02115 USA. [Wagner, Claire M.] Union Int Canc Control, Geneva, Switzerland. [Farmer, Paul E.] Harvard Univ, Sch Med, Partners Hlth, Boston, MA USA. [Farmer, Paul E.] Brigham & Womens Hosp, 75 Francis St, Boston, MA 02115 USA. RP Binagwaho, A (reprint author), Minist Hlth Rwanda, Off Minister, POB 84, Kigali, Rwanda. EM agnes_binagwaho@hms.harvard.edu FU National Cancer Institute's Center for Global Cancer Medicine FX Supported by the National Cancer Institute's Center for Global Cancer Medicine. NR 13 TC 2 Z9 2 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 2016 VL 34 IS 1 BP 3 EP + DI 10.1200/JCO.2015.62.4395 PG 5 WC Oncology SC Oncology GA DJ6MD UT WOS:000374326500002 PM 26578610 ER PT J AU Nelson, AM Milner, DA Rebbeck, TR Iliyasu, Y AF Nelson, Ann M. Milner, Danny A. Rebbeck, Timothy R. Iliyasu, Yawale TI Oncologic Care and Pathology Resources in Africa: Survey and Recommendations SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Review ID SUB-SAHARAN AFRICA; CHILDHOOD-CANCER; DIAGNOSIS; HIV; CHILDREN; DISEASE; UGANDA; TUMORS AB The connection of a clinician who identifies a patient with signs and symptoms of malignancy to an oncologist who has the tools to treat a patient's cancer requires a diagnostic pathology laboratory to receive, process, and diagnose the tumor. Without an accurate classification, nothing is known of diagnosis, prognosis, or treatment by the clinical team, and most important, the patient is left scared, confused, and without hope. The vast majority of deaths frommalignancies occur in sub-Saharan Africa primarily as a result of lack of public awareness of cancer and how it is diagnosed and treated in the setting of a severe lack of resources (physical and personnel) to actually diagnose tumors. To correct this massive health disparity, a plan of action is required across the continent of Africa to bring diagnostic medicine into the modern era and connect patients with the care they desperately need. We performed a survey of resources in Africa for tissue diagnosis of cancer and asked quantitative questions about tools, personnel, and utilization. We identified a strong correlation between pathology staffing and capacity to provide pathology services. On the basis of this survey and through a congress of concerned pathologists, we propose strategies that will catapult the continent into an era of high-quality pathology services with resultant improvement in cancer outcomes. (C) 2015 by American Society of Clinical Oncology C1 [Nelson, Ann M.] Joint Pathol Ctr, Silver Spring, MD USA. [Milner, Danny A.] Harvard Univ, Sch Med, Boston, MA USA. [Milner, Danny A.] Harvard Univ, Sch Publ Hlth, 665 Huntington Ave, Boston, MA 02115 USA. [Rebbeck, Timothy R.] Univ Penn, Perelman Sch Med, Philadelphia, PA 19104 USA. [Iliyasu, Yawale] Ahmadu Bello Univ, Zaria, Nigeria. RP Rebbeck, TR (reprint author), Dana Farber Canc Inst, 1101 Dana Bldg,450 Brookline Ave, Boston, MA 02115 USA. EM timothy_rebbeck@dfci.harvard.edu NR 24 TC 8 Z9 8 U1 1 U2 1 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 2016 VL 34 IS 1 BP 20 EP + DI 10.1200/JCO.2015.61.9767 PG 9 WC Oncology SC Oncology GA DJ6MD UT WOS:000374326500005 PM 26578619 ER PT J AU Efstathiou, JA Heunis, M Karumekayi, T Makufa, R Bvochora-Nsingo, M Gierga, DP Suneja, G Grover, S Kasese, J Mmalane, M Moffat, H von Paleske, A Makhema, J Dryden-Peterson, S AF Efstathiou, Jason A. Heunis, Magda Karumekayi, Talkmore Makufa, Remigio Bvochora-Nsingo, Memory Gierga, David P. Suneja, Gita Grover, Surbhi Kasese, Joseph Mmalane, Mompati Moffat, Howard von Paleske, Alexander Makhema, Joseph Dryden-Peterson, Scott TI Establishing and Delivering Quality Radiation Therapy in Resource-Constrained Settings: The Story of Botswana SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Review ID MIDDLE-INCOME COUNTRIES; ATOMIC-ENERGY AGENCY; DOSE-RATE BRACHYTHERAPY; GLOBAL ACCESS; RADIOTHERAPY; CANCER; ONCOLOGY; INFRASTRUCTURE; IMPLEMENTATION; GUIDELINES AB There is a global cancer crisis, and it is disproportionately affecting resource-constrained settings, especially in low- and middle-income countries (LMICs). Radiotherapy is a critical and cost-effective component of a comprehensive cancer control plan that offers the potential for cure, control, and palliation of disease in greater than 50% of patients with cancer. Globally, LMICs do not have adequate access to quality radiation therapy and this gap is particularly pronounced in sub-Saharan Africa. Although there are numerous challenges in implementing a radiation therapy program in a low-resource setting, providing more equitable global access to radiotherapy is a responsibility and investment worth prioritizing. We outline a systems approach and a series of key questions to direct strategy toward establishing quality radiation services in LMICs, and highlight the story of private-public investment in Botswana from the late 1990s to the present. After assessing the need and defining the value of radiation, we explore core investments required, barriers that need to be overcome, and assets that can be leveraged to establish a radiation program. Considerations addressed include infrastructure; machine choice; quality assurance and patient safety; acquisition, development, and retention of human capital; governmental engagement; public-private partnerships; international collaborations; and the need to critically evaluate the program to foster further growth and sustainability. (C) 2015 by American Society of Clinical Oncology C1 [Efstathiou, Jason A.; Gierga, David P.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. [Dryden-Peterson, Scott] Brigham & Womens Hosp, 75 Francis St, Boston, MA 02115 USA. [Heunis, Magda] Univ Stellenbosch, Cape Town, South Africa. [Heunis, Magda] Tygerberg Hosp, Cape Town, South Africa. [Karumekayi, Talkmore; Makufa, Remigio; Bvochora-Nsingo, Memory] Gaborone Private Hosp, Gaborone, Botswana. [Kasese, Joseph] Bokamoso Private Hosp, Gaborone, Botswana. [Mmalane, Mompati; Makhema, Joseph; Dryden-Peterson, Scott] Botswana Harvard AIDS Inst, Gaborone, Botswana. [Moffat, Howard] Botswana Minist Hlth, Gaborone, Botswana. [Suneja, Gita] Univ Utah, Sch Med, Huntsman Canc Hosp, Salt Lake City, UT USA. [Grover, Surbhi] Univ Penn, Perelman Sch Med, Philadelphia, PA 19104 USA. [von Paleske, Alexander] Univ Zimbabwe, Mpilo Hosp, Bulawayo, Zimbabwe. RP Efstathiou, JA (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Radiat Oncol, 100 Blossom St,Cox 3, Boston, MA 02114 USA. EM jefstathiou@partners.org FU NIAID NIH HHS [K23 AI091434] NR 47 TC 4 Z9 4 U1 2 U2 3 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 2016 VL 34 IS 1 BP 27 EP + DI 10.1200/JCO.2015.62.8412 PG 10 WC Oncology SC Oncology GA DJ6MD UT WOS:000374326500006 PM 26578607 ER PT J AU Tapela, NM Mpunga, T Karema, N Nzayisenga, I Fadelu, T Uwizeye, FR Hirschhorn, LR Muhimpundu, MA Balinda, JP Amoroso, C Wagner, CM Binagwaho, A Shulman, LN AF Tapela, Neo M. Mpunga, Tharcisse Karema, Nadine Nzayisenga, Ignace Fadelu, Temidayo Uwizeye, Frank R. Hirschhorn, Lisa R. Muhimpundu, Marie Aimee Balinda, Jean Paul Amoroso, Cheryl Wagner, Claire M. Binagwaho, Agnes Shulman, Lawrence N. TI Implementation Science for Global Oncology: The Imperative to Evaluate the Safety and Efficacy of Cancer Care Delivery SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Review ID MIDDLE-INCOME COUNTRIES; SUB-SAHARAN AFRICA; RESOURCE-LIMITED SETTINGS; MULTIDRUG-RESISTANT TUBERCULOSIS; WILMS-TUMOR; HIV TREATMENT; RADIATION-THERAPY; BREAST-CANCER; ANTIRETROVIRAL THERAPY; PATHOLOGY SERVICES AB Purpose The development of cancer care treatment facilities in resource-constrained settings represents a challenge for many reasons. Implementation science-the assessment of how services are set up and delivered; contextual factors that affect delivery, treatment safety, toxicity, and efficacy; and where adaptations are needed-is essential if we are to understand the performance of a treatment program, know where the gaps in care exist, and design interventions in care delivery models to improve outcomes for patients. Methods The field of implementation science in relation to cancer care delivery is reviewed, and the experiences of the integrated implementation science program at the Butaro Cancer Center of Excellence in Rwanda are described as a practical application. Implementation science of HIV and tuberculosis care delivery in similar challenging settings offers some relevant lessons. Results Integrating effective implementation science into cancer care in resource-constrained settings presents many challenges, which are discussed. However, with carefully designed programs, it is possible to perform this type of research, on regular and ongoing bases, and to use the results to develop interventions to improve quality of care and patient outcomes and provide evidence for effective replication and scale-up. Conclusion Implementation science is both critical and feasible in evaluating, improving, and supporting effective expansion of cancer care in resource-limited settings. In ideal circumstances, it should be a prospective program, established early in the lifecycle of a new cancer treatment program and should be an integrated and continual process. (C) 2015 by American Society of Clinical Oncology C1 [Tapela, Neo M.; Fadelu, Temidayo] Brigham & Womens Hosp, 75 Francis St, Boston, MA 02115 USA. [Tapela, Neo M.; Fadelu, Temidayo; Hirschhorn, Lisa R.; Binagwaho, Agnes] Harvard Univ, Sch Med, Boston, MA USA. [Hirschhorn, Lisa R.] Ariadne Labs, Boston, MA USA. [Wagner, Claire M.; Shulman, Lawrence N.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Mpunga, Tharcisse; Binagwaho, Agnes] Rwandan Minist Hlth, Kigali, Rwanda. [Muhimpundu, Marie Aimee; Balinda, Jean Paul] Rwanda Biomed Ctr, Kigali, Rwanda. [Tapela, Neo M.; Karema, Nadine; Nzayisenga, Ignace; Fadelu, Temidayo; Uwizeye, Frank R.; Amoroso, Cheryl] Partners Hlth Inshuti Mu Buzima, Rwinkwavu, Rwanda. [Wagner, Claire M.] Union Int Canc Control, Geneva, Switzerland. [Binagwaho, Agnes] Dartmouth Coll, Geisel Sch Med, Hanover, NH 03755 USA. [Shulman, Lawrence N.] Abramson Canc Ctr, Philadelphia, PA USA. RP Tapela, NM (reprint author), Brigham & Womens Hosp, Div Global Hlth Equ, 75 Francis St, Boston, MA 02115 USA. EM ntapela@gmail.com NR 85 TC 2 Z9 2 U1 1 U2 1 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 2016 VL 34 IS 1 BP 43 EP + DI 10.1200/JCO.2015.61.7738 PG 11 WC Oncology SC Oncology GA DJ6MD UT WOS:000374326500008 PM 26578617 ER PT J AU Shulman, LN Wagner, CM Barr, R Lopes, G Longo, G Robertson, J Forte, G Torode, J Magrini, N AF Shulman, Lawrence N. Wagner, Claire M. Barr, Ronald Lopes, Gilberto Longo, Giuseppe Robertson, Jane Forte, Gilles Torode, Julie Magrini, Nicola TI Proposing Essential Medicines to Treat Cancer: Methodologies, Processes, and Outcomes SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Review ID CELL LUNG-CANCER; MIDDLE-INCOME COUNTRIES; SUB-SAHARAN AFRICA; PEDIATRIC-ONCOLOGY; RANDOMIZED-TRIALS; ESSENTIAL DRUGS; CHEMOTHERAPY; SURVIVAL; HEALTH; METAANALYSES AB Purpose A great proportion of the world's cancer burden resides in low- and middle-income countries where cancer care infrastructure is often weak or absent. Although treatment of cancer is multidisciplinary, involving surgery, radiation, systemic therapies, pathology, radiology, and other specialties, selection of medicines that have impact and are affordable has been particularly challenging in resource-constrained settings. In 2014, at the invitation of the WHO, the Union for International Cancer Control convened experts to develop an approach to propose essential cancer medicines to be included in the WHO Model Essential Medicines Lists (EML) for Adults and for Children, as well as a resulting new list of cancer medicines. Methods Experts identified 29 cancer types with potential for maximal treatment impact, on the basis of incidence and benefit of systemic therapies. More than 90 oncology experts from all continents drafted and reviewed disease-based documents outlining epidemiology, diagnostic needs, treatment options, and benefits and toxicities. Results Briefing documents were created for each disease, along with associated standard treatment regimens, resulting in a list of 52 cancer medicines. A comprehensive application was submitted as a revision to the existing cancer medicines on the WHO Model Lists. In May 2015, the WHO announced the addition of 16 medicines to the Adult EML and nine medicines to the Children's EML. Conclusion The list of medications proposed, and the ability to link each recommended medicine to specific diseases, should allow public officials to apply resources most effectively in developing and supporting nascent or growing cancer treatment programs. (C) 2015 by American Society of Clinical Oncology C1 [Shulman, Lawrence N.; Wagner, Claire M.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Shulman, Lawrence N.] Partners Hlth, Boston, MA USA. [Wagner, Claire M.; Torode, Julie] Union Int Canc Control, Geneva, Switzerland. [Robertson, Jane; Forte, Gilles; Magrini, Nicola] WHO, CH-1211 Geneva, Switzerland. [Barr, Ronald] McMaster Univ, Hamilton, ON, Canada. [Lopes, Gilberto] Ctr Paulista Oncol & Hcor Onco, Sao Paulo, Brazil. [Lopes, Gilberto] Johns Hopkins Univ, Baltimore, MD USA. [Longo, Giuseppe] Azienda Osped Univ Policlin Modena, Modena, Italy. RP Shulman, LN (reprint author), Univ Penn, Abramson Canc Ctr, Ctr Global Canc Med, 3400 Civ Ctr Blvd, Philadelphia, PA 19104 USA. EM lawrence.shulman@uphs.upenn.edu FU Center for Global Health of the National Cancer Institute, National Institutes of Health FX Supported by the Center for Global Health of the National Cancer Institute, National Institutes of Health. NR 57 TC 6 Z9 7 U1 1 U2 3 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 2016 VL 34 IS 1 BP 69 EP + DI 10.1200/JCO.2015.61.8736 PG 8 WC Oncology SC Oncology GA DJ6MD UT WOS:000374326500011 PM 26578613 ER PT J AU Tanboon, J Williams, EA Louis, DN AF Tanboon, Jantima Williams, Erik A. Louis, David N. TI The Diagnostic Use of Immunohistochemical Surrogates for Signature Molecular Genetic Alterations in Gliomas SO JOURNAL OF NEUROPATHOLOGY AND EXPERIMENTAL NEUROLOGY LA English DT Review DE Astrocytoma; Glioblastoma; Glioma; Immunohistochemistry; Molecular markers; Neuropathology; Oligodendroglioma ID HIGH-GRADE ASTROCYTOMAS; BRAF V600E MUTATION; ISOCITRATE DEHYDROGENASE 1; ELEMENT-BINDING PROTEIN-1; MGMT PROMOTER METHYLATION; INTRINSIC PONTINE GLIOMAS; CENTRAL-NERVOUS-SYSTEM; IDH1 MUTATION; GENOMIC ANALYSIS; DIFFUSE GLIOMAS AB A number of key mutations that affect treatment and prognosis have been identified in human gliomas. Two major ways to identify these mutations in a tumor sample are direct interrogation of the mutated DNA itself and immunohistochemistry to assess the effects of the mutated genes on proteins. Immunohistochemistry is an affordable, robust, and widely available technology that has been in place for decades. For this reason, the use of immunohistochemical approaches to assess molecular genetic changes has become an essential component of state-of-the-art practice. In contrast, even though DNA sequencing technologies are undergoing rapid development, many medical centers do not have access to such methodologies and may be thwarted by the relatively high costs of sending out such tests to reference laboratories. This review summarizes the current experience using immunohistochemistry of glioma samples to identify mutations in IDH1, TP53, ATRX, histone H3 genes, BRAF, EGFR, MGMT, CIC, and FUBP1 as well as guidelines for prudent use of DNA sequencing as a supplemental method. C1 [Tanboon, Jantima; Williams, Erik A.; Louis, David N.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02115 USA. [Tanboon, Jantima] Mahidol Univ, Siriraj Hosp, Dept Pathol, Bangkok 10700, Thailand. RP Louis, DN (reprint author), Massachusetts Gen Hosp, CS Kubik Lab Neuropathol, Warren Bldg 225,55 Fruit St, Boston, MA 02114 USA. EM dlouis@mgh.harvard.edu NR 138 TC 8 Z9 9 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0022-3069 J9 J NEUROPATH EXP NEUR JI J. Neuropathol. Exp. Neurol. PD JAN PY 2016 VL 75 IS 1 BP 4 EP 18 DI 10.1093/jnen/nlv009 PG 15 WC Clinical Neurology; Neurosciences; Pathology SC Neurosciences & Neurology; Pathology GA DK9DJ UT WOS:000375230400002 PM 26671986 ER PT J AU Kanaan, NM Cox, K Alvarez, VE Stein, TD Poncil, S Mckee, AC AF Kanaan, Nicholas M. Cox, Kristine Alvarez, Victor E. Stein, Thor D. Poncil, Sharra Mckee, Ann C. TI Characterization of Early Pathological Tau Conformations and Phosphorylation in Chronic Traumatic Encephalopathy SO JOURNAL OF NEUROPATHOLOGY AND EXPERIMENTAL NEUROLOGY LA English DT Article DE Alzheimer disease; Chronic traumatic encephalopathy; Dementia; Oligomers; Phosphatase-activating domain; Tauopathy; Traumatic brain injury ID PROGRESSIVE SUPRANUCLEAR PALSY; DEPENDENT AXONAL-TRANSPORT; MILD COGNITIVE IMPAIRMENT; REPETITIVE HEAD-INJURY; ALZHEIMERS-DISEASE; NEUROFIBRILLARY TANGLES; BRAIN-INJURY; POTENTIAL TARGETS; CASPASE-CLEAVAGE; NEURODEGENERATIVE DISORDERS AB Chronic traumatic encephalopathy (CTE) is a neurodegenerative tauopathy that develops after repetitive head injury. Several lines of evidence in other tauopathies suggest that tau oligomer formation induces neurotoxicity and that tau oligomer-mediated neurotoxicity involves induction of axonal dysfunction through exposure of an N-terminal motif in tau, the phosphatase-activating domain (PAD). Additionally, phosphorylation at serine 422 in tau occurs early and correlates with cognitive decline in patients with Alzheimer disease (AD). We performed immunohistochemistry and immunofluorescence on fixed brain sections and biochemical analysis of fresh brain extracts to characterize the presence of PAD-exposed tau (TNT1 antibody), tau oligomers (TOC1 antibody), tau phosphorylated at S422 (pS422 antibody), and tau truncated at D421 (TauC3 antibody) in the brains of 9-11 cases with CTE and cases of nondemented aged controls and AD (Braak VI) (n = 6, each). All 3 early tau markers (ie, TNT1, TOC1, and pS422) were present in CTE and displayed extensive colocalization in perivascular tau lesions that are considered diagnostic for CTE. Notably, the TauC3 epitope, which is abundant in AD, was relatively sparse in CTE. Together, these results provide the first description of PAD exposure, TOC1 reactive oligomers, phosphorylation of S422, and TauC3 truncation in the tau pathology of CTE. C1 [Kanaan, Nicholas M.; Cox, Kristine; Poncil, Sharra] Michigan State Univ, Coll Human Med, Dept Translat Sci & Mol Med, 333 Bostwick Ave NE, Grand Rapids, MI 49503 USA. [Kanaan, Nicholas M.] Mercy Hlth St Marys, Hauenstein Neurosci Ctr, Grand Rapids, MI USA. [Alvarez, Victor E.; Stein, Thor D.; Mckee, Ann C.] VA Boston Healthcare Syst, Boston, MA USA. [Alvarez, Victor E.; Stein, Thor D.; Mckee, Ann C.] Boston Univ, Sch Med, CTE Program, Alzheimers Dis Ctr, Boston, MA 02215 USA. [Stein, Thor D.] Dept Vet Affairs Med Ctr, Bedford, MA USA. [Stein, Thor D.; Mckee, Ann C.] Boston Univ, Sch Med, Dept Pathol & Lab Med, Boston, MA 02215 USA. RP Kanaan, NM (reprint author), Michigan State Univ, Coll Human Med, Dept Translat Sci & Mol Med, 333 Bostwick Ave NE, Grand Rapids, MI 49503 USA. EM Nicholas.kanaan@hc.msu.edu FU NIH [R01 AG044372, R01 NS082730]; BrightFocus Foundation [A2013364S]; Department of Veterans Affairs; National Institute of Neurological Diseases and Stroke [1U01NS086659-01]; National Institute of Aging Boston University Alzheimer's Disease Center [P30AG13846, 0572063345-5]; National Institute of Aging Boston University Framingham Heart Study [AG1649]; Alzheimer's Association [NIRG-305779]; Sports Legacy Institute; National Operating Committee on Standards for Athletic Equipment; Veterans Affairs Biorepository [CSP 501]; Translational Research Center for Traumatic Brain Injury and Stress Disorders (TRACTS) Veterans Affairs Rehabilitation Research and Development Traumatic Brain Injury Center of Excellence [B6796-C]; National Institute of Neurological Disorders and Stroke (National Brain and Tissue Resource for Parkinson's Disease and Related Disorders) [U24 NS072026]; National Institute on Aging (Arizona Alzheimer's Disease Core Center) [P30 AG19610]; Arizona Department of Health Services (Arizona Alzheimer's Research Center) [211002]; Arizona Biomedical Research Commission [4001, 0011, 05-901, 1001]; Michael J. Fox Foundation for Parkinson's Research; Alzheimer's Disease Core Center grant from the National Institute on Aging [P30 AG013854] FX This work was supported by NIH grants R01 AG044372 and R01 NS082730 (NMK), the BrightFocus Foundation (A2013364S, NMK), the Department of Veterans Affairs (ACM); National Institute of Neurological Diseases and Stroke 1U01NS086659-01 (ACM), National Institute of Aging Boston University Alzheimer's Disease Center [P30AG13846; supplement 0572063345-5, ACM]; National Institute of Aging Boston University Framingham Heart Study R01 [AG1649, ACM]; Alzheimer's Association (NIRG-305779, TDS); Sports Legacy Institute (ACM); National Operating Committee on Standards for Athletic Equipment (ACM); the Veterans Affairs Biorepository (CSP 501, ACM); Translational Research Center for Traumatic Brain Injury and Stress Disorders (TRACTS) Veterans Affairs Rehabilitation Research and Development Traumatic Brain Injury Center of Excellence (B6796-C, ACM), unrestricted gifts from the National Football League, the Andlinger Foundation and the World Wrestling Entertainment, Inc. (WWE) (ACM), the Brain and Body Donation Program is supported by the National Institute of Neurological Disorders and Stroke (U24 NS072026 National Brain and Tissue Resource for Parkinson's Disease and Related Disorders), the National Institute on Aging (P30 AG19610 Arizona Alzheimer's Disease Core Center), the Arizona Department of Health Services (contract 211002, Arizona Alzheimer's Research Center), the Arizona Biomedical Research Commission (contracts 4001, 0011, 05-901, and 1001 to the Arizona Parkinson's Disease Consortium), the Michael J. Fox Foundation for Parkinson's Research, and the Alzheimer's Disease Core Center grant (P30 AG013854) from the National Institute on Aging to Northwestern University, Chicago Illinois. NR 72 TC 8 Z9 8 U1 5 U2 8 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0022-3069 J9 J NEUROPATH EXP NEUR JI J. Neuropathol. Exp. Neurol. PD JAN PY 2016 VL 75 IS 1 BP 19 EP 34 DI 10.1093/jnen/nlv001 PG 16 WC Clinical Neurology; Neurosciences; Pathology SC Neurosciences & Neurology; Pathology GA DK9DJ UT WOS:000375230400003 PM 26671985 ER PT J AU Hossein-nezhad, A Fatemi, RP Ahmad, R Peskind, ER Zabetian, CP Hu, SC Shi, M Wahlestedt, C Zhang, J Faghihi, MA AF Hossein-nezhad, Arash Fatemi, Roya Pedram Ahmad, Rili Peskind, Elaine R. Zabetian, Cyrus P. Hu, Shu-Ching Shi, Min Wahlestedt, Claes Zhang, Jing Faghihi, Mohammad Ali TI Transcriptomic Profiling of Extracellular RNAs Present in Cerebrospinal Fluid Identifies Differentially Expressed Transcripts in Parkinson's Disease SO JOURNAL OF PARKINSONS DISEASE LA English DT Article DE Parkinson disease; RNA sequencing; cerebrospinal fluid; biomarkers; long noncoding RNA ID LARGE GENE LISTS; ALPHA-SYNUCLEIN; NONCODING RNAS; BIOMARKERS; SUSCEPTIBILITY; GENERATION; NDUFV2; MIRNA AB Background: Parkinson's disease (PD) is a debilitating neurological disorder for which prognostic and diagnostic biomarkers are lacking. Cerebrospinal fluid (CSF) is an accessible body fluid that comes into direct contact with the central nervous system (CNS) and acts as a nuclease-free repository where RNA transcripts shed by brain tissues can reside for extended periods of time. Objective: We studied the RNA species present in the CSF of PD patients to identify novel diagnostic biomarkers. Methods: Small volumes of CSF from 27 PD patients and 30 healthy age-and sex-matched controls were used for RNA extraction followed by next-generation sequencing (RNA-seq) using the Illumina platform. CSF contains a number of fragmented RNA species that were individually sequenced and analyzed. Comparing PD to control subjects, we observed a pool of dysregulated sequencing tags that were further analyzed and validated by quantitative real-time PCR (qRT-PCR). Results: A total of 201 differentially expressed sequencing tags (DETs), including 92 up-regulated and 109 down-regulated DETs were identified. We validated the following DETs by real time PCR in the patient samples: Dnmt1, Ezh2, CCR3, SSTR5, PTPRC, UBC, NDUFV2, BMP7, SCN9, SCN9 antisense (AC010127.3), and long noncoding RNAs AC079630 and UC001lva. 4 (close to the LRRK2 gene locus), as potential PD biomarkers. Conclusions: The CSF is a unique environment that contains many species of RNA. Our work demonstrates that CSF can potentially be used to identify biomarkers for the detection and tracking of disease progression and evaluation of therapeutic outcomes. C1 [Hossein-nezhad, Arash; Fatemi, Roya Pedram; Ahmad, Rili; Wahlestedt, Claes; Faghihi, Mohammad Ali] Univ Miami, Miller Sch Med, Dept Psychiat & Behav Sci, Miami, FL 33136 USA. [Faghihi, Mohammad Ali] Univ Miami, Miller Sch Med, John P Hussman Inst Human Genom, Miami, FL 33136 USA. [Peskind, Elaine R.] Univ Washington, Sch Med, Dept Psychiat & Behav Sci, Seattle, WA USA. [Peskind, Elaine R.] Vet Affairs Puget Sound Hlth Care Syst, Mental Illness Res Educ & Clin Ctr, Seattle, WA USA. [Zabetian, Cyrus P.; Hu, Shu-Ching] Vet Affairs Puget Sound Hlth Care Syst, Geriatr Res Educ & Clin Ctr, Seattle, WA USA. [Zabetian, Cyrus P.; Hu, Shu-Ching] Vet Affairs Puget Sound Hlth Care Syst, Parkinsons Dis Res Educ & Clin Ctr, Seattle, WA USA. [Zabetian, Cyrus P.; Hu, Shu-Ching] Univ Washington, Sch Med, Dept Neurol, Seattle, WA USA. [Shi, Min; Zhang, Jing] Univ Washington, Sch Med, Dept Pathol, Seattle, WA 98195 USA. RP Faghihi, MA (reprint author), 1501 NW 10th Ave,Biomed Res Bldg,Room 508, Miami, FL 33136 USA. EM mfaghihi@med.miami.edu OI Hossein-nezhad, Arash/0000-0003-2847-4737 FU NIH [P50NS071674, U01 NS082137, P50 NS062684, P50 NIA AG05136] FX NIH grants P50NS071674 supporting AH and part of MAF as well as sequencing costs, U01 NS082137 (to JZ), P50 NS062684 (PANUC), and P50 NIA AG05136 (to EP). NR 39 TC 2 Z9 2 U1 1 U2 3 PU IOS PRESS PI AMSTERDAM PA NIEUWE HEMWEG 6B, 1013 BG AMSTERDAM, NETHERLANDS SN 1877-7171 EI 1877-718X J9 J PARKINSON DIS JI J. Parkinsons Dis. PY 2016 VL 6 IS 1 BP 109 EP 117 DI 10.3233/JPD-150737 PG 9 WC Neurosciences SC Neurosciences & Neurology GA DK0YL UT WOS:000374638600011 PM 26889637 ER PT J AU Lebwohl, B Murray, JA Verdu, EF Crowe, SE Dennis, M Fasano, A Green, PHR Guandalini, S Khosla, C AF Lebwohl, Benjamin Murray, Joseph A. Verdu, Elena F. Crowe, Sheila E. Dennis, Melinda Fasano, Alessio Green, Peter H. R. Guandalini, Stefano Khosla, Chaitan TI Gluten Introduction, Breastfeeding, and Celiac Disease: Back to the Drawing Board SO AMERICAN JOURNAL OF GASTROENTEROLOGY LA English DT Article ID RISK; CHILDREN; AUTOIMMUNITY; PREVALENCE; PREGNANCY; CHILDHOOD; INFANTS; DIET; MILK AB This commentary by the leadership of the North American Society for the Study of Celiac Disease (NASSCD) concerns recent research findings regarding infant feeding practices. Celiac disease has increased markedly in recent decades, and seroprevalence studies indicate that this is a true rise, rather than one due to increased awareness and testing. Prior studies have suggested that infant feeding practices and timing of initial gluten exposure are central to the development of celiac disease. Two recent multicenter randomized trials tested strategies of early or delayed gluten introduction in infants, and neither strategy appeared to influence celiac disease risk. These studies also found that breastfeeding did not protect against the development of celiac disease. While disappointing, these results should spur the study of wider environmental risk factors beyond infant feeding, such as intrauterine and perinatal exposures as well as environmental influences later in life, including drug exposure, microbial infections, and the microbiome. Given that celiac disease can develop at any age, it is imperative to study these proposed triggers so as to elucidate the loss of tolerance to gluten and to develop future intervention strategies. C1 [Lebwohl, Benjamin; Green, Peter H. R.] Columbia Univ, Dept Med, Med Ctr, Celiac Dis Ctr, New York, NY USA. [Murray, Joseph A.] Mayo Clin, Div Gastroenterol & Hepatol, 200 1st St SW, Rochester, MN 55905 USA. [Verdu, Elena F.] McMaster Univ, Dept Med, Div Gastroenterol, Hamilton, ON, Canada. [Verdu, Elena F.] McMaster Univ, Farncombe Family Digest Hlth Res Inst, Hamilton, ON, Canada. [Crowe, Sheila E.] Univ Calif San Diego, Div Gastroenterol, La Jolla, CA 92093 USA. [Dennis, Melinda] Beth Israel Deaconess Med Ctr, Celiac Ctr, Boston, MA 02215 USA. [Fasano, Alessio] MassGen Hosp Children, Ctr Celiac Res, Div Pediat Gastroenterol & Nutr, Boston, MA USA. [Guandalini, Stefano] Univ Chicago, Celiac Dis Ctr, Pediat Gastroenterol Hepatol & Nutr, Chicago, IL 60637 USA. [Khosla, Chaitan] Stanford Univ, Dept Chem, Sch Engn, Stanford, CA 94305 USA. RP Murray, JA (reprint author), Mayo Clin, Div Gastroenterol & Hepatol, 200 1st St SW, Rochester, MN 55905 USA. EM murray.joseph@mayo.edu FU National Center for Advancing Translational Sciences, National Institutes of Health [UL1 TR000040]; National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health [R01 DK063158] FX BL: The National Center for Advancing Translational Sciences, National Institutes of Health (UL1 TR000040). C Khosla: The National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health (R01 DK063158). NR 22 TC 0 Z9 1 U1 5 U2 10 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 2016 VL 111 IS 1 BP 12 EP 14 DI 10.1038/ajg.2015.219 PG 3 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA DJ5OM UT WOS:000374258500005 PM 26259710 ER PT J AU Pandhi, N Schumacher, JR Thorpe, CT Smith, MA AF Pandhi, Nancy Schumacher, Jessica R. Thorpe, Carolyn T. Smith, Maureen A. TI Cross-sectional study examining whether the extent of first-contact access to primary care differentially benefits those with certain personalities to receive preventive services SO BMJ OPEN LA English DT Article DE PRIMARY CARE; PREVENTIVE MEDICINE ID 5-FACTOR MODEL; INFLUENZA VACCINATION; UNITED-STATES; OLDER-ADULTS; PREDICTORS; MAMMOGRAPHY; VALIDATION; OBSERVERS; TRAITS; HEALTH AB Objective The extent of first-contact access to primary care (ie, easy availability when needed) is associated with receiving recommended preventive services. Whether this access benefits patients at risk of preventive services underutilisation, such as those with certain personality characteristics, is unclear. Setting Secondary analysis of the 2003-2006 round of the Wisconsin Longitudinal Study. Participants 6975 respondents who reported a usual provider whose specialty was internal medicine or family medicine. Those reporting not visiting a medical provider in the past 12months, and those who were uninsured were excluded. Primary outcome measures Receiving mammography, cholesterol testing and influenza vaccination. Adjusted predicted probabilities (aPP) of receiving these services were analysed stratified by personality characteristics overall, and if significant, then interacted with first-contact access. Results Lower conscientiousness as compared with higher conscientiousness predicted less of all 3 preventive services; mammography (aPP 80%; 95% CI (77% to 83%) vs aPP 85%; (95% CI 82% to 87%)), cholesterol testing (88%; (85% to 90%) vs 93% (91% to 94%), and influenza vaccination (62%; (59% to 64%) vs 66%; (63% to 68%)). Lower agreeableness as compared with higher agreeableness predicted less mammography (77%; (73% to 81%) vs 84%; (82% to 87%)) and less influenza vaccination (59%; (56% to 62%) vs 65%; (63% to 68%)). Lower extraversion predicted less cholesterol testing (88%; (86% to 91%) vs (92%; (90% to 94%)). Lower openness to experience predicted less influenza vaccination (59%; (56% to 63%) vs (68%; (65% to 70%)). For agreeableness, these differences in receiving preventive services did not persist when first-contact access to primary care was present. Conclusions Certain personality characteristics predicted receiving less preventive care services. For those with less agreeableness, improved first-contact access to primary care mitigated this effect. If these results are replicated in other studies, primary care offices seeking to improve population health through receiving preventive services should prioritise increasing their first-contact accessibility. C1 [Pandhi, Nancy; Smith, Maureen A.] Univ Wisconsin, Sch Med & Publ Hlth, Dept Family Med & Community Hlth, Madison, WI USA. [Pandhi, Nancy; Smith, Maureen A.] Univ Wisconsin, Sch Med & Publ Hlth, Hlth Innovat Program, Dept Populat Hlth Sci, Madison, WI USA. [Schumacher, Jessica R.; Smith, Maureen A.] Univ Wisconsin, Sch Med & Publ Hlth, Dept Surg, Madison, WI USA. [Thorpe, Carolyn T.] Univ Pittsburgh, Sch Pharm, Dept Pharm & Therapeut, Philadelphia, PA USA. [Thorpe, Carolyn T.] Vet Affairs Pittsburgh Healthcare Syst, Hlth Serv Res & Dev, Pittsburgh, PA USA. [Smith, Maureen A.] Univ Wisconsin, Sch Med & Publ Hlth, Dept Populat Hlth Sci, Madison, WI USA. RP Pandhi, N (reprint author), Univ Wisconsin, Sch Med & Publ Hlth, Dept Family Med & Community Hlth, Madison, WI USA.; Pandhi, N (reprint author), Univ Wisconsin, Sch Med & Publ Hlth, Hlth Innovat Program, Dept Populat Hlth Sci, Madison, WI USA. EM nancy.pandhi@fammed.wisc.edu FU Clinical and Translational Science Award (CTSA) programme; National Center for Research Resources (NCRR) [1UL1RR025011]; National Center for Advancing Translational Sciences (NCATS) [9U54TR000021]; National Institute on Aging Mentored Clinical Scientist Research Career Development Award [1 K08 AG029527]; University of Wisconsin Carbone Cancer Center (UWCCC) Support Grant from the National Cancer Institute [P30 CA014520]; UW School of Medicine and Public Health from the Wisconsin Partnership Program FX This work was supported by the Clinical and Translational Science Award (CTSA) programme, previously through the National Center for Research Resources (NCRR) grant 1UL1RR025011, and now by the National Center for Advancing Translational Sciences (NCATS), grant 9U54TR000021. The content is solely the responsibility of the authors, and does not necessarily represent the official views of the NIH, the Department of Veterans Affairs or the USA government. In addition, NP was supported by a National Institute on Aging Mentored Clinical Scientist Research Career Development Award, grant number 1 K08 AG029527. This project was also supported by the University of Wisconsin Carbone Cancer Center (UWCCC) Support Grant from the National Cancer Institute, grant number P30 CA014520. Additional support was provided by the UW School of Medicine and Public Health from the Wisconsin Partnership Program. NR 38 TC 0 Z9 0 U1 0 U2 0 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 2016 VL 6 IS 3 AR e009738 DI 10.1136/bmjopen-2015-009738 PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA DJ2RH UT WOS:000374052300039 PM 26951211 ER PT J AU Gray, NE Zweig, JA Kawamoto, C Quinn, JF Copenhaver, PF AF Gray, Nora E. Zweig, Jonathan A. Kawamoto, Colleen Quinn, Joseph F. Copenhaver, Philip F. TI STX, a Novel Membrane Estrogen Receptor Ligand, Protects Against Amyloid-beta Toxicity SO JOURNAL OF ALZHEIMERS DISEASE LA English DT Article DE Amyloid-beta toxicity; mitochondrial dysfunction; neuroprotection; selective estrogen receptor modulator ID TRANSGENIC MOUSE MODEL; INDUCED NEURONAL DEATH; ALZHEIMERS-DISEASE; SYNAPTIC PLASTICITY; PRECURSOR PROTEIN; OXIDATIVE STRESS; CELL-DEATH; MITOCHONDRIAL DYSFUNCTION; BIOENERGETIC DEFICITS; COGNITIVE IMPAIRMENT AB Because STX is a selective ligand for membrane estrogen receptors, it may be able to confer the beneficial effects of estrogen without eliciting the deleterious side effects associated with activation of the nuclear estrogen receptors. This study evaluates the neuroprotective properties of STX in the context of amyloid-beta (A beta) exposure. MC65 and SH-SY5Y neuroblastoma cell lines, as well as primary hippocampal neurons from wild type (WT) and Tg2576 mice, were used to investigate the ability of STX to attenuate cell death, mitochondrial dysfunction, dendritic simplification, and synaptic loss induced by A beta. STX prevented A beta-induced cell death in both neuroblastoma cell lines; it also normalized the decrease in ATP and mitochondrial gene expression caused by A beta in these cells. Notably, STX also increased ATP content and mitochondrial gene expression in control neuroblastoma cells (in the absence of A beta). Likewise in primary neurons, STX increased ATP levels and mitochondrial gene expression in both genotypes. In addition, STX treatment enhanced dendritic arborization and spine densities in WT neurons and prevented the diminished outgrowth of dendrites caused by A beta exposure in Tg2576 neurons. These data suggest that STX can act as an effective neuroprotective agent in the context of A beta toxicity, improving mitochondrial function as well as dendritic growth and synaptic differentiation. In addition, since STX also improved these endpoints in the absence of A beta, this compound may have broader therapeutic value beyond Alzheimer's disease. C1 [Gray, Nora E.; Quinn, Joseph F.] Oregon Hlth & Sci Univ, Dept Neurol, 3181 SW Sam Jackson Pk Rd, Portland, OR 97201 USA. [Zweig, Jonathan A.; Kawamoto, Colleen; Copenhaver, Philip F.] 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 Department of Veterans Affairs Merit Review grant; NIH [NS078363, AG025525, P30 NS061800]; OHSU School of Medicine Faculty Innovation Fund FX This work was funded by a Department of Veterans Affairs Merit Review grant awarded to J. Quinn, and by NIH grants NS078363 and AG025525 awarded to P. Copenhaver. The authors thank Dr. Martin Kelly for providing his expertise and the STX used in this study, and Dr. Gary Banker and Ms. Barbara Smoody for their support of our experiments with primary hippocampal neurons. We also wish to thank Ms. Jenna Fisk for her assistance with image acquisition in some of our studies. Dr. Doris Kretzschmar provided critical input on this manuscript. We gratefully acknowledge Dr. Stefanie Kaech and Ms. Aurelie Snyder for their invaluable assistance with the confocal imaging analysis that was performed in the Advanced Light Microscopy Core, Jungers Center, OHSU. Confocal imaging was supported in part by NIH P30 NS061800, and by the OHSU School of Medicine Faculty Innovation Fund (to P. Copenhaver). MC65 cells were generously provided by Randy Woltjer, MD, PhD. NR 92 TC 0 Z9 1 U1 3 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 2016 VL 51 IS 2 BP 391 EP 403 DI 10.3233/JAD-150756 PG 13 WC Neurosciences SC Neurosciences & Neurology GA DJ5IJ UT WOS:000374240000007 PM 26890746 ER PT J AU Gurubhagavatula, I Patil, S Meoli, A Olson, R Sullivan, S Berneking, M Watson, NF AF Gurubhagavatula, Indira Patil, Susheel Meoli, Amy Olson, Ryan Sullivan, Shannon Berneking, Michael Watson, Nathaniel F. CA Amer Acad Sleep Med TI Sleep Apnea Evaluation of Commercial Motor Vehicle Operators SO JOURNAL OF CLINICAL SLEEP MEDICINE LA English DT Editorial Material C1 [Gurubhagavatula, Indira] Univ Penn, Med Ctr, Div Sleep Med, Occupat Sleep Med, Philadelphia, PA 19104 USA. [Gurubhagavatula, Indira] Philadelphia VA Med Ctr, Sleep Med Clin, Philadelphia, PA USA. [Patil, Susheel] Johns Hopkins Univ, Sch Med, Baltimore, MD USA. [Meoli, Amy] Penn State Hershey Sleep Res & Treatment Ctr, Hummelstown, PA USA. [Olson, Ryan] Oregon Hlth & Sci Univ, Portland, OR 97201 USA. [Sullivan, Shannon] Stanford Univ, Div Sleep Med, Dept Psychiat, Palo Alto, CA 94304 USA. [Berneking, Michael] Concentra, Grand Rapids, MI USA. [Watson, Nathaniel F.] Univ Washington, UW Med Sleep Ctr, Seattle, WA 98195 USA. Amer Acad Sleep Med, Sleep & Transportat Safety Awareness Task Force, Darien, IL 60561 USA. RP Gurubhagavatula, I (reprint author), Amer Acad Sleep Med, Sleep & Transportat Safety Awareness Task Force, 2510 N Frontage Rd, Darien, IL 60561 USA. NR 11 TC 0 Z9 0 U1 2 U2 3 PU AMER ACAD SLEEP MEDICINE PI WESTCHESTER PA ONE WESTBROOK CORPORATE CTR, STE 920, WESTCHESTER, IL 60154 USA SN 1550-9389 EI 1550-9397 J9 J CLIN SLEEP MED JI J. Clin. Sleep Med. PY 2016 VL 12 IS 3 BP 285 EP 286 AR PII jc-00060-16 DI 10.5664/jcsm.5560 PG 2 WC Clinical Neurology SC Neurosciences & Neurology GA DJ3XI UT WOS:000374139600001 PM 26857051 ER PT J AU Budhiraja, R Kushida, CA Nichols, DA Walsh, JK Simon, RD Gottlieb, DJ Quan, SF AF Budhiraja, Rohit Kushida, Clete A. Nichols, Deborah A. Walsh, James K. Simon, Richard D. Gottlieb, Daniel J. Quan, Stuart F. TI Impact of Randomization, Clinic Visits, and Medical and Psychiatric Cormorbidities on Continuous Positive Airway Pressure Adherence in Obstructive Sleep Apnea SO JOURNAL OF CLINICAL SLEEP MEDICINE LA English DT Article DE adherence; age; comorbid; compliance; continuous positive airway pressure; CPAP; medical disorders; obstructive sleep apnea; psychiatric disorders; race; sex; sleep disordered breathing ID CPAP USE; NASAL; THERAPY; OFFICE AB Study Objectives: To evaluate factors associated with continuous positive airway pressure (CPAP) adherence in patients with obstructive sleep apnea (OSA) in the Apnea Positive Pressure Long-term Efficacy Study (APPLES) cohort. Methods: The data from a prospective 6-mo multicenter randomized controlled trial with 558 subjects randomized to active CPAP and 547 to sham CPAP were analyzed to assess adherence to CPAP during first 2 mo (early period) and during months 5-6 (late period). Results: Participants randomized to active CPAP had higher hours of nightly adherence compared to the sham CPAP group at both 2 (4.9 +/- 2.0 h versus 4.07 +/- 2.14 h, p < 0.001) and 6 mo (4.70 +/- 2.08 h versus 3.41 +/- 2.19 h, p < 0.001). Those assigned to sham CPAP were more likely to correctly identify their treatment group (70.0% versus 55.2%, p < 0.001). Irrespective of treatment group assignment, those who believed they were receiving active CPAP had higher hours of adherence than those who thought they were in the sham CPAP group at both 2 mo (4.91 +/- 2.01 versus 4.17 +/- 2.17, p < 0.001) and 6 mo (4.65 +/- 2.10 versus 3.65 +/- 2.22, p < 0.001). Among those randomized to active CPAP, older age was significantly related to CPAP use > 4 h per night. Presence of cardiovascular disorders was associated with higher hours of CPAP use, whereas presence of anxiety was associated with a trend toward lower hours of CPAP use. Presence of nasal congestion was associated with a decrease in mean daily CPAP use between the early and the late adherence period. The adherence during the week prior to a clinic visit was higher than the average adherence during the 2-mo period prior to the visit. Conclusions: Randomization to active therapy, belief that one is in the active treatment group, older age, and possibly presence of cardiovascular disorders are positively linked to CPAP adherence. Nasal congestion and anxiety are negatively associated with CPAP adherence. CPAP nightly usage increases as clinic visits approach. C1 [Budhiraja, Rohit; Gottlieb, Daniel J.; Quan, Stuart F.] Brigham & Womens Hosp, Div Sleep & Circadian Disorders, 221 Longwood Ave,Suite 438, Boston, MA 02115 USA. [Budhiraja, Rohit; Gottlieb, Daniel J.; Quan, Stuart F.] Harvard Univ, Sch Med, Div Sleep Med, Boston, MA USA. [Kushida, Clete A.; Nichols, Deborah A.] Stanford Univ, Sleep Clin, Redwood City, CA USA. [Kushida, Clete A.; Nichols, Deborah A.] Ctr Human Sleep Res, Redwood City, CA USA. [Walsh, James K.] St Lukes Hosp, Sleep Med & Res Ctr, Chesterfield, MO USA. [Simon, Richard D.] Providence St Mary Med Ctr, Walla Walla, WA USA. [Gottlieb, Daniel J.] VA Boston Healthcare Syst, Boston, MA USA. [Quan, Stuart F.] Univ Arizona, Arizona Resp Ctr, Tucson, AZ USA. RP Budhiraja, R (reprint author), Brigham & Womens Hosp, Div Sleep & Circadian Disorders, 221 Longwood Ave,Suite 438, Boston, MA 02115 USA. EM budhi3@gmail.com FU National Heart, Lung and Blood Institute [5UO1-HL-068060]; American Academy of Sleep Medicine; National Institute of Neurological Disorders and Stroke [N44-NS-002394]; Sleep Medicine Education and Research Foundation FX The Apnea Positive Pressure Long-term Efficacy Study (APPLES) study was funded by contract 5UO1-HL-068060 from the National Heart, Lung and Blood Institute. The APPLES pilot studies were supported by grants from the American Academy of Sleep Medicine and the Sleep Medicine Education and Research Foundation to Stanford University and by the National Institute of Neurological Disorders and Stroke (N44-NS-002394) to SAM Technology. In addition, APPLES investigators gratefully recognize the vital input and support of Dr. Sylvan Green, who died before the results of this trial were analyzed, but was instrumental in its design and conduct. NR 25 TC 2 Z9 2 U1 0 U2 2 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 2016 VL 12 IS 3 BP 333 EP 341 DI 10.5664/jcsm.5578 PG 9 WC Clinical Neurology SC Neurosciences & Neurology GA DJ3XI UT WOS:000374139600010 PM 26518698 ER PT J AU Primeau, M Gershon, A Talbot, L Cotto, I Lotspeich, L Hardan, A Hallmayer, J O'Hara, R AF Primeau, Michelle Gershon, Anda Talbot, Lisa Cotto, Isabelle Lotspeich, Linda Hardan, Antonio Hallmayer, Joachim O'Hara, Ruth TI Individuals with Autism Spectrum Disorders Have Equal Success Rate But Require Longer Periods of Systematic Desensitization than Control Patients to Complete Ambulatory Polysomnography SO JOURNAL OF CLINICAL SLEEP MEDICINE LA English DT Article DE autism spectrum disorder; polysomnography; pediatric; methodology ID RESPIRATORY INDICATIONS; PRACTICE PARAMETERS; YOUNG-CHILDREN; SLEEP-APNEA; FEASIBILITY; EVENTS; BRAIN AB Study Objectives: Polysomnography (PSG) is the gold standard for the assessment of sleep, yet the extensive apparatus required for monitoring with PSG can be difficult to tolerate, particularly in children. Clinical populations, such as those with anxiety or tactile sensitivity, may have even greater difficulty tolerating the PSG equipment. This study evaluated an innovative protocol for obtaining full PSG in individuals diagnosed autism spectrum disorders (ASD) or developmental delay (DD), as well as typically developing controls (TD). The primary aim was to assess whether this protocol was equally successful for obtaining PSG between these groups. Methods: One hundred sixty-one individuals were recruited for participation; 93 with a diagnosis of ASD, 23 with a diagnosis of DD, and 45 TD. The participants and families were instructed on a procedure of systematic desensitization to the ambulatory PSG equipment; PSG was performed in the home of the participant. Results: PSG was successfully attained in 144 (89.4%) participants. There was no difference in completion rate by diagnosis (p = 0.1), though younger age (p = 0.018) and duration of desensitization (p = 0.024) did predict PSG failure. Further, it was found that individuals with ASD took longer to desensitize to the equipment (16.08 d), than those with DD (8.04 d) or TD (0.98 d). Conclusions: Systematic desensitization to PSG equipment, in combination with PSG completed in the home, allows for individuals with ASD to be equally successful in completing PSG, though they do take longer to acclimate to the equipment. C1 [Primeau, Michelle] Palo Alto Med Fdn, Dept Sleep Med, Sunnyvale, CA 94087 USA. [Primeau, Michelle; Gershon, Anda; Cotto, Isabelle; Lotspeich, Linda; Hardan, Antonio; Hallmayer, Joachim; O'Hara, Ruth] Stanford Univ, Dept Psychiat & Behav Sci, Stanford, CA 94305 USA. [Talbot, Lisa; O'Hara, Ruth] San Francisco VA Med Ctr, San Francisco, CA USA. [Hardan, Antonio; Hallmayer, Joachim] Stanford Univ, Dept Psychiat & Behav Sci, Child & Adolescent Psychiat, Stanford, CA 94305 USA. [O'Hara, Ruth] Dept Vet Affairs, MIRECC, VISN Sierra Pacific Network 21, Palo Alto, CA USA. RP Primeau, M (reprint author), Palo Alto Med Fdn, 1309 S Mary Ave Ste 200, Sunnyvale, CA 94087 USA. EM primeamm@pamf.org FU Roche FX This was not an industry supported study. Dr. Hardan has recieved research support from Roche and has consulted for Integragen. The other authors have indicated no financial conflicts of interest. NR 32 TC 0 Z9 0 U1 2 U2 2 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 2016 VL 12 IS 3 BP 357 EP 362 AR PII jc-00448-14 DI 10.5664/jcsm.5584 PG 6 WC Clinical Neurology SC Neurosciences & Neurology GA DJ3XI UT WOS:000374139600013 PM 26564388 ER PT J AU Moro, M Westover, MB Kelly, J Bianchi, MT AF Moro, Marilyn Westover, M. Brandon Kelly, Jessica Bianchi, Matt T. TI Decision Modeling in Sleep Apnea: The Critical Roles of Pretest Probability, Cost of Untreated Obstructive Sleep Apnea, and Time Horizon SO JOURNAL OF CLINICAL SLEEP MEDICINE LA English DT Article DE cost; effectiveness; home sleep test; obstructive sleep apnea; PSG ID POSITIVE AIRWAY PRESSURE; ECONOMIC-ANALYSIS; DIAGNOSIS; MODERATE; TRIAL; CPAP; EPIDEMIOLOGY; MANAGEMENT; HYPOPNEA; THERAPY AB Study Objectives: Obstructive sleep apnea (OSA) is associated with increased morbidity and mortality, and treatment with positive airway pressure (PAP) is cost-effective. However, the optimal diagnostic strategy remains a subject of debate. Prior modeling studies have not consistently supported the widely held assumption that home sleep testing (HST) is cost-effective. Methods: We modeled four strategies: (1) treat no one; (2) treat everyone empirically; (3) treat those testing positive during in-laboratory polysomnography (PSG) via in-laboratory titration; and (4) treat those testing positive during HST with auto-PAP. The population was assumed to lack independent reasons for in-laboratory PSG (such as insomnia, periodic limb movements in sleep, complex apnea). We considered the third-party payer perspective, via both standard (quality-adjusted) and pure cost methods. Results: The preferred strategy depended on three key factors: pretest probability of OSA, cost of untreated OSA, and time horizon. At low prevalence and low cost of untreated OSA, the treat no one strategy was favored, whereas empiric treatment was favored for high prevalence and high cost of untreated OSA. In-laboratory backup for failures in the at-home strategy increased the preference for the at-home strategy. Without laboratory backup in the at-home arm, the in-laboratory strategy was increasingly preferred at longer time horizons. Conclusion: Using a model framework that captures a broad range of clinical possibilities, the optimal diagnostic approach to uncomplicated OSA depends on pretest probability, cost of untreated OSA, and time horizon. Estimating each of these critical factors remains a challenge warranting further investigation. C1 [Moro, Marilyn; Westover, M. Brandon; Kelly, Jessica; Bianchi, Matt T.] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. [Bianchi, Matt T.] Harvard Univ, Sch Med, Div Sleep Med, Boston, MA USA. RP Bianchi, MT (reprint author), Massachusetts Gen Hosp, Wang Neurol 7, 55 Fruit St, Boston, MA 02114 USA. EM mtbianchi@partners.org FU Department of Neurology, Massachusetts General Hospital; Center for Integration of Medicine and Innovative Technology; Department of Defense; Milton Family Foundation; MC10, Inc.; Servier; NIH-NINDS [1K23NS090900-01]; Andrew David Heitman Neuroendovascular Research Fund; Rappaport Foundation FX This was not an industry supported study. Dr. Bianchi receives funding from the Department of Neurology, Massachusetts General Hospital, the Center for Integration of Medicine and Innovative Technology, the Department of Defense, the Milton Family Foundation, and MC10, Inc. Dr. Bianchi has a patent pending on a home sleep monitoring device. Dr. Bianchi has received travel funding from Servier, serves on the advisory board of Foramis, and has provided expert testimony in sleep medicine. Dr. Westover receives funding from NIH-NINDS (1K23NS090900-01), the Andrew David Heitman Neuroendovascular Research Fund, and the Rappaport Foundation. The other authors have indicated no financial conflicts of interest. NR 41 TC 0 Z9 0 U1 1 U2 1 PU AMER ACAD SLEEP MEDICINE PI WESTCHESTER PA ONE WESTBROOK CORPORATE CTR, STE 920, WESTCHESTER, IL 60154 USA SN 1550-9389 EI 1550-9397 J9 J CLIN SLEEP MED JI J. Clin. Sleep Med. PY 2016 VL 12 IS 3 BP 409 EP 418 AR PII jc-00083-15 DI 10.5664/jcsm.5596 PG 10 WC Clinical Neurology SC Neurosciences & Neurology GA DJ3XI UT WOS:000374139600019 PM 26518699 ER PT J AU Kuhn, E Weiss, BJ Taylor, KL Hoffman, JE Ramsey, KM Manber, R Gehrman, P Crowley, JJ Ruzek, JI Trockel, M AF Kuhn, Eric Weiss, Brandon J. Taylor, Katherine L. Hoffman, Julia E. Ramsey, Kelly M. Manber, Rachel Gehrman, Philip Crowley, Jill J. Ruzek, Josef I. Trockel, Mickey TI CBT-I Coach: A Description and Clinician Perceptions of a Mobile App for Cognitive Behavioral Therapy for Insomnia SO JOURNAL OF CLINICAL SLEEP MEDICINE LA English DT Article DE Cognitive behavioral therapy for insomnia; Diffusion of Innovations; mobile apps; sleep problems ID RANDOMIZED CONTROLLED-TRIAL; COMPARATIVE METAANALYSIS; PERSISTENT INSOMNIA; BREAST-CANCER; DISSEMINATION; INTERVENTIONS; RESTRICTION; EFFICACY; OUTCOMES; MHEALTH AB Study Objectives: This paper describes CBT-I Coach, a patient-facing smartphone app designed to enhance cognitive behavioral therapy for insomnia (CBT-I). It presents findings of two surveys of U. S. Department of Veterans Affairs (VA) CBT-I trained clinicians regarding their perceptions of CBT-I Coach before it was released (n = 138) and use of it two years after it was released (n = 176). Methods: VA-trained CBT-I clinicians completed web-based surveys before and two years after CBT-I Coach was publicly released. Results: Prior to CBT-I Coach release, clinicians reported that it was moderately to very likely that the app could improve care and a majority (87.0%) intended to use it if it were available. Intention to use the app was predicted by smartphone ownership (beta = 0.116, p < 0.05) and perceptions of relative advantage to existing CBT-I practices (beta = 0.286, p < 0.01), compatibility with their own needs and values (beta = 0.307, p < 0.01), and expectations about the complexity of the app (beta = 0.245, p < 0.05). Two years after CBT-I Coach became available, 59.9% of participants reported using it with patients and had favorable impressions of its impact on homework adherence and outcomes. Conclusions: Findings suggest that before release, CBT-I Coach was perceived to have potential to enhance CBT-I and address common adherence issues and clinicians would use it. These results are reinforced by findings two years after it was released suggesting robust uptake and favorable perceptions of its value. C1 [Kuhn, Eric; Weiss, Brandon J.; Taylor, Katherine L.; Hoffman, Julia E.; Ramsey, Kelly M.; Crowley, Jill J.; Ruzek, Josef I.] VA Palo Alto Hlth Care Syst, Palo Alto, CA USA. [Kuhn, Eric; Weiss, Brandon J.; Manber, Rachel; Ruzek, Josef I.; Trockel, Mickey] Stanford Univ, Stanford, CA 94305 USA. [Gehrman, Philip] Philadelphia VA Med Ctr, Philadelphia, PA USA. [Gehrman, Philip] Univ Penn, Philadelphia, PA 19104 USA. RP Kuhn, E (reprint author), VA Natl Ctr PTSD, D&T Div, 795 Willow Rd, Menlo Pk, CA 94025 USA. EM Eric.Kuhn@va.gov RI Emchi, Karma/Q-1952-2016 FU Merck Inc. FX This was not an industry supported study. Julia E. Hoffman is a consultant to Otsuka Pharmaceuticals. Rachel Manber receives royalties from New Harbinger Press. Philip Gehrman has received grant/research support from Merck Inc. The other authors have indicated no financial conflicts of interest. The contents do not represent the views of the U.S. Department of Veterans Affairs or the United States Government. NR 41 TC 2 Z9 2 U1 2 U2 11 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 2016 VL 12 IS 4 BP 597 EP 606 AR PII jc-00087-15 DI 10.5664/jcsm.5700 PG 10 WC Clinical Neurology SC Neurosciences & Neurology GA DJ3XM UT WOS:000374140000019 PM 26888586 ER PT J AU Liu, WZ Pfister, EL Kennington, LA Chase, KO Mueller, C DiFiglia, M Aronin, N AF Liu, Wanzhao Pfister, Edith L. Kennington, Lori A. Chase, Kathryn O. Mueller, Christian DiFiglia, Marian Aronin, Neil TI Does the Mutant CAG Expansion in Huntingtin mRNA Interfere with Exonucleolytic Cleavage of its First Exon? SO JOURNAL OF HUNTINGTONS DISEASE LA English DT Article DE Huntington's disease; RNAi; mRNA degradation; CAG repeats ID REPEAT LENGTH; DISEASE; GENE; PATHOGENESIS; ARABIDOPSIS; EXPRESSION; TURNOVER; MODEL; MICE; HTT AB Background: Silencing mutant huntingtin mRNA by RNA interference (RNAi) is a therapeutic strategy for Huntington's disease. RNAi induces specific endonucleolytic cleavage of the target HTT mRNA, followed by exonucleolytic processing of the cleaved mRNA fragments. Objectives: We investigated the clearance of huntingtin mRNA cleavage products following RNAi, to find if particular huntingtin mRNA sequences persist. We especially wanted to find out if the expanded CAG increased production of a toxic mRNA species by impeding degradation of human mutant huntingtin exon 1 mRNA. Methods: Mice expressing the human mutant HTT transgene with 128 CAG repeats (YAC128 mice) were injected in the striatum with self-complementary AAV9 vectors carrying a miRNA targeting exon 48 of huntingtin mRNA (scAAV-U6-miRNA-HTT-GFP). Transgenic huntingtin mRNA levels were measured in striatal lysates after two weeks. For qPCR, we used species specific primer-probe combinations that together spanned 6 positions along the open reading frame and untranslated regions of the human huntingtin mRNA. Knockdown was also measured in the liver following tail vein injection. Results: Two weeks after intrastriatal administration of scAAV9-U6-miRNA-HTT-GFP, we measured transgenic mutant huntingtin in striatum using probes targeting six different sites along the huntingtin mRNA. Real time PCR showed a reduction of 29% to 36% in human HTT. There was no significant difference in knockdown measured at any of the six sites, including exon 1. In liver, we observed a more pronounced HTT mRNA knockdown of 70% to 76% relative to the untreated mice, and there were also no significant differences among sites. Conclusions: Our results demonstrate that degradation is equally distributed across the human mutant huntingtin mRNA following RNAi-induced cleavage. C1 [Liu, Wanzhao; Pfister, Edith L.; Kennington, Lori A.; Chase, Kathryn O.; Aronin, Neil] Univ Massachusetts, Sch Med, RNA Therapeut Inst, Worcester, MA 01605 USA. [Liu, Wanzhao; Pfister, Edith L.; Kennington, Lori A.; Chase, Kathryn O.; Aronin, Neil] Univ Massachusetts, Sch Med, Dept Med, Worcester, MA 01605 USA. [Mueller, Christian] Univ Massachusetts, Sch Med, Gene Therapy Ctr, Worcester, MA 01605 USA. [DiFiglia, Marian] Massachusetts Gen Hosp, Mass Gen Inst Neurodegenerat Dis, Charlestown, MA USA. RP Aronin, N (reprint author), Univ Massachusetts, Sch Med, RNA Therapeut Inst, Worcester, MA 01605 USA.; Aronin, N (reprint author), Univ Massachusetts, Sch Med, Dept Med, Worcester, MA 01605 USA. EM Neil.Aronin@umassmed.edu FU NINDS NIH HHS [R01 NS038194, NS 38194] NR 20 TC 0 Z9 0 U1 4 U2 4 PU IOS PRESS PI AMSTERDAM PA NIEUWE HEMWEG 6B, 1013 BG AMSTERDAM, NETHERLANDS SN 1879-6397 EI 1879-6400 J9 J HUNTINGTONS DIS JI J. Huntingtons Dis. PY 2016 VL 5 IS 1 BP 33 EP 38 DI 10.3233/JHD-150183 PG 6 WC Neurosciences SC Neurosciences & Neurology GA DJ3PV UT WOS:000374118800004 PM 27003665 ER PT J AU Im, H Park, YI Pathania, D Castro, CM Weissleder, R Lee, H AF Im, Hyungsoon Park, Yong Il Pathania, Divya Castro, Cesar M. Weissleder, Ralph Lee, Hakho TI Digital diffraction detection of protein markers for avian influenza SO LAB ON A CHIP LA English DT Article ID SMARTPHONE; PLATFORM; ASSAYS; CHIP AB Rapid pathogen testing is expected to play a critical role in infection control and in limiting epidemics. Smartphones equipped with state-of-the-art computing and imaging technologies have emerged as new point-of-use (POU) sensing platforms. We herein report a new assay format for fast, sensitive and portable detection of avian influenza-associated antibodies. C1 [Im, Hyungsoon; Park, Yong Il; Pathania, Divya; Castro, Cesar M.; Weissleder, Ralph; Lee, Hakho] Massachusetts Gen Hosp, Ctr Syst Biol, 185 Cambridge St,CPZN 5206, Boston, MA 02114 USA. [Im, Hyungsoon; Pathania, Divya; Weissleder, Ralph; Lee, Hakho] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. [Castro, Cesar M.] Harvard Univ, Sch Med, Dept Med, Massachusetts Gen Hosp, Boston, MA 02114 USA. [Weissleder, Ralph] Harvard Univ, Sch Med, Dept Syst Biol, 200 Longwood Ave, Boston, MA 02115 USA. [Park, Yong Il] Chonnam Natl Univ, Sch Appl Chem Engn, 77 Yongbong Ro, Gwangju 61186, South Korea. RP Weissleder, R (reprint author), Massachusetts Gen Hosp, Ctr Syst Biol, 185 Cambridge St,CPZN 5206, Boston, MA 02114 USA.; Weissleder, R (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA.; Weissleder, R (reprint author), Harvard Univ, Sch Med, Dept Syst Biol, 200 Longwood Ave, Boston, MA 02115 USA. EM rweissleder@mgh.harvard.edu RI Im, Hyungsoon/A-3178-2009 OI Im, Hyungsoon/0000-0002-0626-1346 FU US NIH [R01-HL113156, R01-EB010011, R01-EB00462605A1, T32CA79443, K12CA087723-11 A1, 1K99CA201248-01]; Massachusetts General Hospital Physician Scientist Development Award; National Heart, Lung, and Blood Institute [HHSN268201000044C]; Department of Defense Ovarian Cancer Research Program [W81XWH-14-1-0279] FX The authors would like to thank Hojun Suk for technical assistance in assay development. This work was supported in part by US NIH Grants R01-HL113156 (to H. L.), R01-EB010011 (to R. W.), R01-EB00462605A1 (to R. W.), T32CA79443 (to R. W.), K12CA087723-11 A1 (to C. M. C.) and 1K99CA201248-01 (to H. I.), the Massachusetts General Hospital Physician Scientist Development Award (to C. M. C.), National Heart, Lung, and Blood Institute Contract HHSN268201000044C (to R. W.) and the Department of Defense Ovarian Cancer Research Program Award W81XWH-14-1-0279 (to H. L.). NR 19 TC 1 Z9 1 U1 2 U2 5 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 2016 VL 16 IS 8 BP 1340 EP 1345 DI 10.1039/c5lc01558h PG 6 WC Biochemical Research Methods; Chemistry, Multidisciplinary; Nanoscience & Nanotechnology SC Biochemistry & Molecular Biology; Chemistry; Science & Technology - Other Topics GA DJ5CR UT WOS:000374224900005 PM 26980325 ER PT B AU Olson, CK AF Olson, Cheryl K. BE Kowert, R Quandt, T TI ARE ELECTRONIC GAMES HEALTH HAZARDS OR HEALTH PROMOTERS? SO VIDEO GAME DEBATE: UNRAVELLING THE PHYSICAL, SOCIAL, AND PSYCHOLOGICAL EFFECTS OF DIGITAL GAMES LA English DT Article; Book Chapter ID VIDEO GAME; PHYSICAL-ACTIVITY; ATTENTION PROBLEMS; BEHAVIOR-CHANGE; PLAY; METAANALYSIS; ADOLESCENTS; DEPRESSION; CHILDREN; TRIAL C1 [Olson, Cheryl K.] Massachusetts Gen Hosp, Ctr Mental Hlth & Media, Boston, MA 02114 USA. NR 58 TC 0 Z9 0 U1 0 U2 0 PU ROUTLEDGE PI ABINGDON PA 2 PARK SQ, MILTON PARK, ABINGDON OX14 4RN, OXFORD, ENGLAND BN 978-1-138-83163-6; 978-1-315-73649-5; 978-1-138-83160-5 PY 2016 BP 39 EP 53 PG 15 WC Communication; Psychology, Multidisciplinary SC Communication; Psychology GA BE4SR UT WOS:000372114100003 ER PT J AU Tong, GE Kumar, S Chong, KC Shah, N Wong, MJ Zimmet, JM Wang, ZJ Yee, J Fu, YJ Yeh, BM AF Tong, Gregory E. Kumar, Sant Chong, Karen C. Shah, Nikita Wong, Margaret J. Zimmet, Jeffrey M. Wang, Zhen Jane Yee, Judy Fu, Yanjun Yeh, Benjamin M. TI Risk of contrast-induced nephropathy for patients receiving intravenous vs. intra-arterial iodixanol administration SO ABDOMINAL RADIOLOGY LA English DT Article DE Contrast-induced nephropathy; Intra-arterial; Intravenous; Renal; CT; Cardiac catheterization ID ACUTE KIDNEY INJURY; PERCUTANEOUS CORONARY INTERVENTIONS; INDUCED NEPHROTOXICITY; METAANALYSIS; OSMOLALITY; FREQUENCY; ANEMIA; MEDIA AB Purpose: To compare the incidence of contrast-induced nephropathy (CIN) for intravenous vs. intra-arterial administration of iodixanol, compared to non-administration. Methods: We retrospectively identified 650 patients who had intravenous iodixanol-enhanced CT, 695 with intra-arterial iodixanol cardiac catheterization, 651 with unenhanced CT, and those who also had baseline and follow-up serum creatinine within 5 days of the exam. From the medical records, we recorded the gender, age, baseline and follow-up serum creatinine/eGFR; underlying renal injury risk factors; indication for imaging; contrast material administration volume, concentration, and route of administration; and use of pre-imaging prophylactic measures for CIN. Univariate and multivariate models were used to determine predictors of CIN. Results: Baseline eGFR was lower for patients undergoing unenhanced CT than intravenous or intra-arterial patients (68 vs. 74.6 and 72.2, respectively, p < 0.01) and not different between intravenous and intra-arterial patients (p = 0.735). Simple logistic regression did not show a difference in the rate of CIN in patients who received intravenous vs. intra-arterial iodixanol (28 of 650, 4%, vs. 28 of 695, 4%, respectively, p = 0.798), nor a higher rate of CIN than seen with unenhanced CT (45 of 651, 7%, p = 0.99 and p = 0.98 by one-sided t test). Multivariate regression modeling showed that only elevated baseline creatinine or decreased eGFR and low hematocrit/hemoglobin were associated with CIN incidence (odds ratio 1.28 and 2.5; p < 0.023 and < 0.006, respectively). Conclusions: Elevation in serum creatinine due to intravenous and intra-arterial iodixanol administration is infrequent and is not more common than after unenhanced CT scans. C1 [Tong, Gregory E.; Kumar, Sant; Chong, Karen C.; Shah, Nikita; Wong, Margaret J.; Wang, Zhen Jane; Yee, Judy; Fu, Yanjun; Yeh, Benjamin M.] Univ Calif San Francisco, Dept Radiol & Biomed Imaging, Box 0628,M-372,505 Parnassus Ave, San Francisco, CA 94143 USA. [Zimmet, Jeffrey M.] San Francisco VA Med Ctr, Div Cardiol, 4150 Clement Ave, San Francisco, CA 94121 USA. RP Yeh, BM (reprint author), Univ Calif San Francisco, Dept Radiol & Biomed Imaging, Box 0628,M-372,505 Parnassus Ave, San Francisco, CA 94143 USA. EM ben.yeh@ucsf.edu FU General Electric Healthcare; NIH [1R21EB013816, 1R01EB015476]; National Center for Advancing Translational Sciences, National Institutes of Health, through UCSF-CTSI [UL1 TR000004] FX This study was supported by grants from General Electric Healthcare, NIH Grant Numbers 1R21EB013816 and 1R01EB015476, and the National Center for Advancing Translational Sciences, National Institutes of Health, through UCSF-CTSI Grant Number UL1 TR000004. Its contents are solely the responsibility of the authors and do not necessarily represent the official views of General Electric Healthcare or the NIH. NR 22 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 2366-004X EI 2366-0058 J9 ABDOM RADIOL JI Abdom. Radiol. PD JAN PY 2016 VL 41 IS 1 BP 91 EP 99 DI 10.1007/s00261-015-0611-9 PG 9 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA DJ3MK UT WOS:000374109400012 PM 26830615 ER PT J AU Misra, M Klibanski, A AF Misra, Madhusmita Klibanski, Anne TI Anorexia Nervosa and Its Associated Endocrinopathy in Young People SO HORMONE RESEARCH IN PAEDIATRICS LA English DT Review DE Bone; Cortisol; Eating disorders; Estrogen; Cortisol; Growth hormone; Insulin-like growth factor 1 ID BONE-MINERAL DENSITY; PHYSIOLOGICAL ESTROGEN REPLACEMENT; PEDIATRIC OFFICIAL POSITIONS; NORMAL-WEIGHT WOMEN; ADOLESCENT GIRLS; GROWTH-HORMONE; BULIMIA-NERVOSA; HEALTHY ADOLESCENTS; SECRETORY DYNAMICS; BODY-COMPOSITION AB Anorexia nervosa (AN) is a condition of severe undernutrition associated with adaptive changes in many endocrine axes. These changes include hypogonadotropic hypogonadism, acquired growth hormone resistance with low insulin-like growth factor 1 (IGF-1) levels, hypercortisolemia, altered secretion of adipokines and appetite-regulating hormones, and low bone mineral density (BMD). Bone health is impaired subsequent to a low body mass index, decreased lean mass, and the endocrine changes described above. In addition to low areal BMD, AN is characterized by a decrease in volumetric BMD, changes in bone geometry, and reductions in strength estimates, leading to an increased risk for fracture. Weight restoration is essential for restoration of normal endocrine function; however, hypercortisolemia, high peptide YY levels, and ghrelin dynamics may not completely normalize. In some patients, hypogonadotropic hypogonadism persists despite weight restoration. Weight gain and menstrual recovery are critical for improving bone health in AN; however, residual deficits may persist. Physiologic estrogen replacement using transdermal, but not oral, estrogen increases bone accrual in adolescents with AN, while bisphosphonates improve BMD in adults. Recombinant human IGF-1 and teriparatide have been used in a few studies as bone anabolic therapies. More data are necessary to determine the optimal therapeutic strategies for low BMD in AN. (C) 2016 S. Karger AG, Basel C1 [Misra, Madhusmita; Klibanski, Anne] Massachusetts Gen Hosp, Neuroendocrine Unit, Boston, MA 02114 USA. [Misra, Madhusmita; Klibanski, Anne] Harvard Univ, Sch Med, Boston, MA USA. [Misra, Madhusmita] Massachusetts Gen Hosp Children, Pediat Endocrine Unit, Room 539,175 Cambridge St, Boston, MA 02114 USA. RP Misra, M (reprint author), Massachusetts Gen Hosp Children, Pediat Endocrine Unit, Room 539,175 Cambridge St, Boston, MA 02114 USA. EM mmisra@mgh.harvard.edu FU NIH [2 R01 DK062249, 1 K24 HD071843, 1R01MH103402] FX This work was possible in part because of the following NIH grants: 2 R01 DK062249, 1 K24 HD071843, and 1R01MH103402. NR 101 TC 1 Z9 2 U1 1 U2 8 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 1663-2818 EI 1663-2826 J9 HORM RES PAEDIAT JI Horm. Res. Paediatr. PY 2016 VL 85 IS 3 BP 147 EP 157 DI 10.1159/000443735 PG 11 WC Endocrinology & Metabolism; Pediatrics SC Endocrinology & Metabolism; Pediatrics GA DJ0XA UT WOS:000373926500001 PM 26863308 ER PT J AU Russo, K Bianchi, MT AF Russo, Kathryn Bianchi, Matt T. TI How Reliable Is Self-Reported Body Position during Sleep? SO JOURNAL OF CLINICAL SLEEP MEDICINE LA English DT Article DE body position; supine; sleep apnea; self-report ID APNEA AB Many patients with obstructive sleep apnea (OSA) exhibit worsening event indices while supine. Positional therapy is an option if indices normalize in non-supine sleep. Although several methods are available for patients choosing positional therapy, monitoring adherence remains challenging in part because the reliability of self-reported sleep position is uncertain. We analyzed self-reported sleep position in a sample of 300 patients who underwent clinical polysomnography (PSG) in our center. We found a broad range of discrepancy with objective body position, which was not correlated with demographics, PSG metrics, or confidence in the self-report. The results suggest that objective position monitoring can be an important complement to self-report in the management of patients opting for positional therapy. C1 [Russo, Kathryn; Bianchi, Matt T.] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. [Bianchi, Matt T.] Harvard Univ, Sch Med, Div Sleep Med, Boston, MA USA. RP Bianchi, MT (reprint author), Massachusetts Gen Hosp, Wang Neurol 7, 55 Fruit St, Boston, MA 02114 USA. EM mtbianchi@partners.org FU Department of Neurology, Massachusetts General Hospital; Center for Integration of Medicine and Innovative Technology; Milton Family Foundation; MGH-MIT Grand Challenge; Servier; GrandRounds FX This was not an industry supported study. Dr. Bianchi receives funding from the Department of Neurology, Massachusetts General Hospital, the Center for Integration of Medicine and Innovative Technology, the Milton Family Foundation, and the MGH-MIT Grand Challenge. Dr Bianchi has a patent pending on a home sleep monitoring device. Dr. Bianchi received travel funding from Servier, has consulting agreements with Foramis, MC10, and GrandRounds, and has provided expert testimony in sleep medicine. NR 6 TC 1 Z9 1 U1 0 U2 2 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 2016 VL 12 IS 1 BP 127 EP 128 AR PII jc-00335-15 DI 10.5664/jcsm.5410 PG 2 WC Clinical Neurology SC Neurosciences & Neurology GA DJ3VW UT WOS:000374135800017 PM 26518704 ER PT J AU Ustun, B Westover, B Rudin, C Bianchi, MT AF Ustun, Berk Westover, Brandon Rudin, Cynthia Bianchi, Matt T. TI Clinical Prediction Models for Sleep Apnea: The Importance of Medical History over Symptoms SO JOURNAL OF CLINICAL SLEEP MEDICINE LA English DT Article DE sleep apnea; electronic health records; medical scoring systems; machine learning; sparsity in predictive models ID HEART HEALTH; RISK-FACTORS; EPIDEMIOLOGY; QUESTIONNAIRES; ASSOCIATION; SEVERITY; HYPOPNEA; PRESSURE; DISEASE; STROKE AB Study Objective: Obstructive sleep apnea (OSA) is a treatable contributor to morbidity and mortality. However, most patients with OSA remain undiagnosed. We used a new machine learning method known as SLIM (Supersparse Linear Integer Models) to test the hypothesis that a diagnostic screening tool based on routinely available medical information would be superior to one based solely on patient-reported sleep-related symptoms. Methods: We analyzed polysomnography (PSG) and self-reported clinical information from 1,922 patients tested in our clinical sleep laboratory. We used SLIM and 7 state-of-the-art classification methods to produce predictive models for OSA screening using features from: (i) self-reported symptoms; (ii) self-reported medical information that could, in principle, be extracted from electronic health records (demographics, comorbidities), or (iii) both. Results: For diagnosing OSA, we found that model performance using only medical history features was superior to model performance using symptoms alone, and similar to model performance using all features. Performance was similar to that reported for other widely used tools: sensitivity 64.2% and specificity 77%. SLIM accuracy was similar to state-of-the-art classification models applied to this dataset, but with the benefit of full transparency, allowing for hands-on prediction using yes/no answers to a small number of clinical queries. Conclusion: To predict OSA, variables such as age, sex, BMI, and medical history are superior to the symptom variables we examined for predicting OSA. SLIM produces an actionable clinical tool that can be applied to data that is routinely available in modern electronic health records, which may facilitate automated, rather than manual, OSA screening. Commentary: A commentary on this article appears in this issue on page 159. C1 [Ustun, Berk] MIT, Elect Engn & Comp Sci, 77 Massachusetts Ave, Cambridge, MA 02139 USA. [Westover, Brandon; Bianchi, Matt T.] Massachusetts Gen Hosp, Dept Neurol, Sleep Div, Boston, MA 02114 USA. [Rudin, Cynthia] MIT, Sloan Sch Management & Comp Sci, 77 Massachusetts Ave, Cambridge, MA 02139 USA. [Rudin, Cynthia] MIT, Artificial Intelligence Lab, Cambridge, MA 02139 USA. [Bianchi, Matt T.] Harvard Univ, Sch Med, Div Sleep Med, Boston, MA USA. RP Bianchi, MT (reprint author), Massachusetts Gen Hosp, Wang Neurol 7, 55 Fruit St, Boston, MA 02114 USA. EM mtbianchi@partners.org FU Servier; department of Neurology, Massachusetts General Hospital; Young Clinician Award from the Center for Integration of Medicine and Innovative Technology; Harvard Catalyst KL2 Medical Research Investigator Fellowship; Milton Foundation; Department of Defense; MGH-MIT Grand Challenge; Wistron; Siemens; Ford; MIT Big Data Initiative; National Science Foundation; NIH-NINDS [1K23NS090900-01]; Andrew David Heitman Neuroendovascular Research Fund FX This was not an industry supported study. Dr. Bianchi is co-inventor on pending patent related to a sleep monitoring device, has consulting agreements with GrandRounds, is on the Advisory Board of Foramis, has received travel funds from Servier, and provides expert witness testimony. Dr. Bianchi has received support from the department of Neurology, Massachusetts General Hospital, the Young Clinician Award from the Center for Integration of Medicine and Innovative Technology, the Harvard Catalyst KL2 Medical Research Investigator Fellowship, the Milton Foundation, the Department of Defense, and the MGH-MIT Grand Challenge. Dr. Rudin acknowledges support from Wistron, Siemens, Ford, the MIT Big Data Initiative and the National Science Foundation. Dr. Westover has received support from NIH-NINDS (1K23NS090900-01), and from the Andrew David Heitman Neuroendovascular Research Fund. Mr. Ustun has indicated no financial conflicts of interest. NR 33 TC 3 Z9 3 U1 1 U2 1 PU AMER ACAD SLEEP MEDICINE PI WESTCHESTER PA ONE WESTBROOK CORPORATE CTR, STE 920, WESTCHESTER, IL 60154 USA SN 1550-9389 EI 1550-9397 J9 J CLIN SLEEP MED JI J. Clin. Sleep Med. PY 2016 VL 12 IS 2 BP 161 EP 168 DI 10.5664/jcsm.5476 PG 8 WC Clinical Neurology SC Neurosciences & Neurology GA DJ3XB UT WOS:000374138900004 PM 26350602 ER PT J AU Dzierzewski, JM Wallace, DM Wohlgemuth, WK AF Dzierzewski, Joseph M. Wallace, Douglas M. Wohlgemuth, William K. TI Adherence to Continuous Positive Airway Pressure in Existing Users: Self-Efficacy Enhances the Association between Continuous Positive Airway Pressure and Adherence SO JOURNAL OF CLINICAL SLEEP MEDICINE LA English DT Article DE adherence; continuous positive airway pressure; CPAP; moderation; self-efficacy; sleep apnea ID OBSTRUCTIVE SLEEP-APNEA; QUALITY-OF-LIFE; CPAP ADHERENCE; US VETERANS; THERAPY; RISK; POPULATION; DEPRESSION; DISORDER; GENDER AB Study Objectives: Obstructive sleep apnea-hypopnea syndrome (OSAHS) is a common sleep disorder associated with a myriad of sequelae. OSAHS is effectively treated with continuous positive airway pressure (CPAP) therapy. However, fewer than 50% of patients are compliant with their CPAP therapy prescriptions. The current study sought to explore an integrated, biopsychological approach to CPAP adherence among experienced CPAP users. Methods: We performed a retrospective, cross-sectional analysis of a cohort of veterans with a diagnosis of OSAHS (n = 191) who were prescribed CPAP therapy and returned for adherence download at the Miami VA Sleep Clinic. The relationships between biomedical characteristics (e.g., CPAP pressure, self-reported sleepiness, and change in sleep efficiency) and psychological factors (e.g., self-efficacy beliefs and psychological diagnoses) and objectively measured CPAP use were examined to determine whether psychological factors moderated the relationships between biomedical characteristics and CPAP adherence. Results: Hierarchical regression analyses predicting CPAP adherence (adjusting for time since CPAP prescription, age, education, prescribed CPAP pressure, daytime sleepiness, changes in sleep efficiency with CPAP, and psychiatric conditions) revealed the following: (1) CPAP self-efficacy and CPAP pressure were positively related to adherence, and (2) CPAP self-efficacy moderates the relationship between CPAP pressure and CPAP adherence. Conclusions: There was no relationship between CPAP pressure and adherence in individuals with low self-efficacy beliefs. However, for individuals with high self-efficacy beliefs, there was a significant positive relationship between CPAP pressure and adherence. Self-efficacy beliefs appear to be a prime target for focused interventions aimed at improving CPAP adherence among those individuals with higher pressure prescriptions. C1 [Dzierzewski, Joseph M.] Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90095 USA. [Dzierzewski, Joseph M.] VA Greater Los Angeles Healthcare Syst, Geriatr Res Educ & Clin Ctr, 16111 Plummer St 11E, North Hills, CA 91343 USA. [Wallace, Douglas M.; Wohlgemuth, William K.] Univ Miami, Miller Sch Med, Sleep Med Div, Dept Neurol, Miami, FL 33136 USA. [Wallace, Douglas M.] Bruce W Carter VA Med Ctr, Neurol Serv, Miami, FL USA. RP Dzierzewski, JM (reprint author), Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90095 USA.; Dzierzewski, JM (reprint author), VA Greater Los Angeles Healthcare Syst, Geriatr Res Educ & Clin Ctr, 16111 Plummer St 11E, North Hills, CA 91343 USA. EM Joseph.Dzierzewski@va.gov FU UCLA Claude Pepper Center [5P30AG028748]; UCLA CTSI [UL1TR000124]; VA Advanced Geriatrics Fellowship FX This work was performed at the Bruce W. Carter VA Medical Center. Joseph M Dzierzewski was supported by UCLA Claude Pepper Center (5P30AG028748), UCLA CTSI (UL1TR000124), and VA Advanced Geriatrics Fellowship. The authors have indicated no financial conflicts of interest. NR 44 TC 1 Z9 1 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 2016 VL 12 IS 2 BP 169 EP 176 DI 10.5664/jcsm.5478 PG 8 WC Clinical Neurology SC Neurosciences & Neurology GA DJ3XB UT WOS:000374138900005 PM 26350607 ER PT J AU Batool-Anwar, S Li, YP De Vito, K Malhotra, A Winkelman, J Gao, X AF Batool-Anwar, Salma Li, Yanping De Vito, Katerina Malhotra, Atul Winkelman, John Gao, Xiang TI Lifestyle Factors and Risk of Restless Legs Syndrome: Prospective Cohort Study SO JOURNAL OF CLINICAL SLEEP MEDICINE LA English DT Article DE behavioral modifications; epidemiology; lifestyle factors; restless legs syndrome; risk factors ID FOOD FREQUENCY QUESTIONNAIRE; GENERAL-POPULATION; PHYSICAL-ACTIVITY; US WOMEN; DISEASE; PREVALENCE; HEALTH; REPRODUCIBILITY; EPIDEMIOLOGY; VALIDITY AB Study Objectives: To examine the association between modifiable lifestyle factors, and the risk of developing restless legs syndrome (RLS). Methods: This is a Prospective Cohort study of population including 12,812 men participating in Health Professionals Follow-up Study and 42,728 women participating in the Nurses' Health study II. The participants were free of RLS at baseline (2002 for the HPFS and 2005 for the NHS II) and free of diabetes and arthritis through follow-up. RLS was assessed via a set of questions recommended by International Restless Legs Syndrome Study group. The Information was collected on height, weight, level of physical activity, dietary intake, and smoking status via questionnaires. Results: During 4-6 years of follow-up, we identified 1,538 incident RLS cases. Participants with normal weight, and who were physically active, non-smoker, and had some alcohol consumption had a lower risk of developing RLS. When we combined the effects of these four factors together, we observed a dose response relationship between the increased number of healthy lifestyle factors and a low risk of RLS: after adjusting for potential confounders the pooled odds ratio was 0.67 (95% CI: 0.47-0.97) for 4 vs. 0 healthy factors (p trend < 0.001). In contrast, we did not observe significant associations between caffeine consumption or diet quality as assessed by the Alternate Healthy Eating Index, and altered RLS risk in men and women. Conclusions: Several modifiable lifestyle factors may play an important role in RLS risk. C1 [Batool-Anwar, Salma] Brigham & Womens Hosp, Dept Med SB, Div Sleep Med, 75 Francis St, Boston, MA 02115 USA. [Li, Yanping; De Vito, Katerina; Gao, Xiang] Harvard Univ, Sch Med, Channing Div Network Med, Boston, MA USA. [Winkelman, John] Massachusetts Gen Hosp, Dept Psychiat Sleep Med, Boston, MA 02114 USA. [Li, Yanping; Gao, Xiang] Brigham & Womens Hosp, Dept Med, 75 Francis St, Boston, MA 02115 USA. [Li, Yanping; Gao, Xiang] Harvard Univ, Sch Med, Boston, MA USA. [Li, Yanping; Gao, Xiang] Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA. [Malhotra, Atul] Univ Calif San Diego, Div Pulm Crit Care & Sleep Med, La Jolla, CA 92093 USA. [Gao, Xiang] Penn State Univ, Dept Nutr Sci, 109 Chandlee Lab, University Pk, PA 16802 USA. RP Gao, X (reprint author), Penn State Univ, Dept Nutr Sci, 109 Chandlee Lab, University Pk, PA 16802 USA.; Batool-Anwar, S (reprint author), Harvard Univ, Sch Med, Brigham & Womens Hosp, Div Sleep Med,Med, 221 Longwood Ave,BL1044, Boston, MA 02115 USA. EM sbatool@bics.bwh.harvard.edu; xxg14@psu.edu FU UCB Pharma; Xenoport; Sunovion; Impax Laboratories; Impax Pharmaceuticals; GlaxoSmithKline; NHSII [UM1 CA176726]; HPFS [UM1 CA167552]; [5R01NS062879-02] FX This was not an industry supported study. Funding was provided by government grant: 5R01NS062879-02 (PI: Xiang Gao) NHSII: UM1 CA176726 and HPFS: UM1 CA167552. Dr. Winkelman has received consulting fees from UCB Pharma, Xenoport, Sunovion, and Impax Laboratories. He has provided expert testimony for Axinn Veltrop Harkrider, and received grant support from Impax Pharmaceuticals, GlaxoSmithKline, and UCB Pharma. The other authors have indicated no financial conflicts of interest. NR 35 TC 1 Z9 1 U1 0 U2 2 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 2016 VL 12 IS 2 BP 187 EP 194 AR PII jc-00049-15 DI 10.5664/jcsm.5482 PG 8 WC Clinical Neurology SC Neurosciences & Neurology GA DJ3XB UT WOS:000374138900007 PM 26446243 ER PT J AU Bomar, L Brugger, SD Yost, BH Davies, SS Lemon, KP AF Bomar, Lindsey Brugger, Silvio D. Yost, Brian H. Davies, Sean S. Lemon, Katherine P. TI Corynebacterium accolens Releases Antipneumococcal Free Fatty Acids from Human Nostril and Skin Surface Triacylglycerols SO MBIO LA English DT Article ID INVASIVE PNEUMOCOCCAL DISEASE; UPPER RESPIRATORY-TRACT; RESISTANT STAPHYLOCOCCUS-AUREUS; COMPLETE GENOME SEQUENCE; PROPIONIBACTERIUM-ACNES; STREPTOCOCCUS-PNEUMONIAE; CONJUGATE VACCINE; MICROBIAL COMMUNITIES; MYCOBACTERIUM-SMEGMATIS; ANTIBACTERIAL ACTIVITY AB Bacterial interspecies interactions play clinically important roles in shaping microbial community composition. We observed that Corynebacterium spp. are overrepresented in children free of Streptococcus pneumoniae (pneumococcus), a common pediatric nasal colonizer and an important infectious agent. Corynebacterium accolens, a benign lipid-requiring species, inhibits pneumococcal growth during in vitro cocultivation on medium supplemented with human skin surface triacylglycerols (TAGs) that are likely present in the nostrils. This inhibition depends on LipS1, a TAG lipase necessary for C. accolens growth on TAGs such as triolein. We determined that C. accolens hydrolysis of triolein releases oleic acid, which inhibits pneumococcus, as do other free fatty acids (FFAs) that might be released by LipS1 from human skin surface TAGs. Our results support a model in which C. accolens hydrolyzes skin surface TAGS in vivo releasing antipneumococcal FFAs. These data indicate that C. accolens may play a beneficial role in sculpting the human microbiome. IMPORTANCE Little is known about how harmless Corynebacterium species that colonize the human nose and skin might impact pathogen colonization and proliferation at these sites. We show that Corynebacterium accolens, a common benign nasal bacterium, modifies its local habitat in vitro as it inhibits growth of Streptococcus pneumoniae by releasing antibacterial free fatty acids from host skin surface triacylglycerols. We further identify the primary C. accolens lipase required for this activity. We postulate a model in which higher numbers of C. accolens cells deter/limit S. pneumoniae nostril colonization, which might partly explain why children without S. pneumoniae colonization have higher levels of nasal Corynebacterium. This work narrows the gap between descriptive studies and the needed in-depth understanding of the molecular mechanisms of microbe-microbe interactions that help shape the human microbiome. It also lays the foundation for future in vivo studies to determine whether habitat modification by C. accolens could be promoted to control pathogen colonization. C1 [Bomar, Lindsey; Brugger, Silvio D.; Yost, Brian H.; Lemon, Katherine P.] Forsyth Inst, Dept Microbiol, Cambridge, MA USA. [Bomar, Lindsey; Brugger, Silvio D.] Harvard Univ, Sch Dent Med, Dept Oral Med Infect & Immun, 188 Longwood Ave, Boston, MA 02115 USA. [Davies, Sean S.] Vanderbilt Univ, Dept Pharmacol, Div Clin Pharmacol, Nashville, TN USA. [Lemon, Katherine P.] Harvard Univ, Sch Med, Boston Childrens Hosp, Div Infect Dis, Boston, MA USA. RP Lemon, KP (reprint author), Forsyth Inst, Dept Microbiol, Cambridge, MA USA.; Lemon, KP (reprint author), Harvard Univ, Sch Med, Boston Childrens Hosp, Div Infect Dis, Boston, MA USA. EM klemon@forsyth.org FU Swiss Society for Microbiology Encouragement Award; Swiss National Science Foundation; Swiss Foundation for Grants in Biology and Medicine [P3SMP3_155315]; Boston Children's Hospital Career Development Grant; HHS \ NIH \ National Institute of Allergy and Infectious Diseases (NIAID) [AI101018, AI066304]; HHS \ NIH \ National Institute of Dental and Craniofacial Research (NIDCR) [DE007327, DE020751]; HHS \ NIH \ National Center for Complementary and Integrative Health (NCCIH) [AT007830]; Harvard Catalyst Pilot Grant under NIH [1 UL1 RR 025758-02] FX Swiss Society for Microbiology Encouragement Award provided funding to Silvio D. Brugger. The Swiss National Science Foundation and Swiss Foundation for Grants in Biology and Medicine provided funding to Silvio D. Brugger under grant number P3SMP3_155315. Boston Children's Hospital Career Development Grant provided funding to Katherine P. Lemon. HHS vertical bar NIH vertical bar National Institute of Allergy and Infectious Diseases (NIAID) provided funding to Katherine P. Lemon under grant number AI101018. HHS vertical bar NIH vertical bar National Institute of Dental and Craniofacial Research (NIDCR) provided funding to Lindsey Bomar under grant number DE007327. HHS vertical bar NIH vertical bar National Institute of Dental and Craniofacial Research (NIDCR) provided funding to Katherine P. Lemon under grant number DE020751. HHS vertical bar NIH vertical bar National Center for Complementary and Integrative Health (NCCIH) provided funding to Sean S. Davies under grant number AT007830.; HHS vertical bar NIH vertical bar National Institute of Allergy and Infectious Diseases (NIAID) provided funding to collect pediatric nasopharyngeal swabs under grant number AI066304 to Jonathan A. Finkelstein. These funders did not have any role in study design, data collection, data analysis, or the decision to submit the work for publication. Harvard Catalyst Pilot Grant provided funding to Katherine P. Lemon under grant number NIH grant 1 UL1 RR 025758-02 and financial contributions from participating institutions. NR 96 TC 8 Z9 8 U1 2 U2 4 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 2150-7511 J9 MBIO JI mBio PD JAN-FEB PY 2016 VL 7 IS 1 AR e01725-15 DI 10.1128/mBio.01725-15 PG 13 WC Microbiology SC Microbiology GA DJ0ZO UT WOS:000373933100007 PM 26733066 ER PT J AU Mahiti, M Toyoda, M Jia, XF Kuang, XMT Mwimanzi, F Mwimanzi, P Walker, BD Xiong, Y Brumme, ZL Brockman, MA Ueno, T AF Mahiti, Macdonald Toyoda, Mako Jia, Xiaofei Kuang, Xiaomei T. Mwimanzi, Francis Mwimanzi, Philip Walker, Bruce D. Xiong, Yong Brumme, Zabrina L. Brockman, Mark A. Ueno, Takamasa TI Relative Resistance of HLA-B to Downregulation by Naturally Occurring HIV-1 Nef Sequences SO MBIO LA English DT Article ID IMMUNODEFICIENCY-VIRUS TYPE-1; CYTOTOXIC T-LYMPHOCYTES; I CYTOPLASMIC TAIL; ANTIVIRAL ACTIVITY; ELITE CONTROLLERS; IMMUNE EVASION; DYNAMIC-RANGE; COMPLEX; INFECTION; MOLECULES AB HIV-1 Nef binds to the cytoplasmic region of HLA-A and HLA-B and downregulates these molecules from the surface of virus-infected cells, thus evading immune detection by CD8(+) T cells. Polymorphic residues within the HLA cytoplasmic region may affect Nef's downregulation activity. However, the effects of HLA polymorphisms on recognition by primary Nef isolates remain elusive, as do the specific Nef regions responsible for downregulation of HLA-A versus HLA-B. Here, we examined 46 Nef clones isolated from chronically HIV-1 subtype B-infected subjects for their ability to downregulate various HLA-A, HLA-B, and HLA-C molecules on the surface of virus-infected cells. Overall, HLA-B exhibited greater resistance to Nef-mediated downregulation than HLA-A, regardless of the cell type examined. As expected, no Nef clone downregulated HLA-C. Importantly, the differential abilities of patient-derived Nef clones to downregulate HLA-A and HLA-B correlated inversely with the sensitivities of HIV-infected target cells to recognition by effector cells expressing an HIV-1 Gag-specific T cell receptor. Nef codon function analysis implicated amino acid variation at position 202 (Nef-202) in differentially affecting the ability to downregulate HLA-A and HLA-B, an observation that was subsequently confirmed by experiments using Nef mutants constructed by site-directed mutagenesis. The in silico and mutagenesis analyses further suggested that Nef-202 may interact with the C-terminal Cys-Lys-Val residues of HLA-A, which are absent in HLA-B. Taken together, the results show that natural polymorphisms within Nef modulate its interaction with natural polymorphisms in the HLA cytoplasmic tails, thereby affecting the efficiency of HLA downregulation and consequent recognition by HIV-specific T cells. These results thus extend our understanding of this complex pathway of retroviral immune evasion. IMPORTANCE Recognition of genetically diverse pathogens by the adaptive immune system represents a primary strategy for host defense; however, pathogens such as HIV-1 can evade these responses to achieve persistent infection. The HIV-1 nef gene and the HLA class I locus rank among the most diverse genes of virus and host, respectively. The HIV-1 Nef protein interacts with the cytoplasmic region of HLA-A and HLA-B and downregulates these molecules to evade cellular immunity. By combining molecular, genetic, and in silico analyses, we demonstrate that patient-derived Nef clones downregulate HLA-A more effectively than HLA-B molecules. This in turn modulates the ability of HIV-specific T cells to recognize HIV-infected cells. We also identify a naturally polymorphic site at Nef codon 202 and HLA cytoplasmic motifs (GG(314,315) and CKV339-341) that contribute to differential HLA downregulation by Nef. Our results highlight new interactions between HIV-1 and the human immune system that may contribute to pathogenesis. C1 [Mahiti, Macdonald; Toyoda, Mako; Mwimanzi, Francis; Mwimanzi, Philip; Ueno, Takamasa] Kumamoto Univ, Ctr AIDS Res, Kumamoto, Japan. [Mahiti, Macdonald; Ueno, Takamasa] Kumamoto Univ, Int Res Ctr Med Sci, Kumamoto, Japan. [Jia, Xiaofei; Xiong, Yong] Yale Univ, Dept Mol Biophys & Biochem, New Haven, CT USA. [Kuang, Xiaomei T.; Mwimanzi, Philip; Brumme, Zabrina L.; Brockman, Mark A.] Simon Fraser Univ, Burnaby, BC V5A 1S6, Canada. [Walker, Bruce D.] MIT, Ragon Inst MGH, Boston, MA USA. [Walker, Bruce D.] Harvard Univ, Boston, MA 02115 USA. [Walker, Bruce D.] Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA. [Walker, Bruce D.] Howard Hughes Med Inst, Chevy Chase, MD USA. [Brumme, Zabrina L.; Brockman, Mark A.] British Columbia Ctr Excellence HIV AIDS, Vancouver, BC, Canada. RP Ueno, T (reprint author), Kumamoto Univ, Ctr AIDS Res, Kumamoto, Japan.; Ueno, T (reprint author), Kumamoto Univ, Int Res Ctr Med Sci, Kumamoto, Japan. EM uenotaka@kumamoto-u.ac.jp RI Ueno, Takamasa/F-5788-2013; OI Ueno, Takamasa/0000-0003-4852-4236; Brockman, Mark/0000-0001-6432-1426 FU HHS \ National Institutes of Health (NIH) [AI102778]; Japan Agency for Medical Research and Development (AMED); AIDS International Collaborative Research grant from the Ministry of Education, Science Sports, and Culture (MEXT) of Japan; Imai Memorial Trust for AIDS Research; Waksman Foundation of Japan FX HHS vertical bar National Institutes of Health (NIH) provided funding to Yong Xiong under grant number AI102778.; This study was supported by a grant from Japan Agency for Medical Research and Development (AMED) (Research Program on HIV/AIDS), an AIDS International Collaborative Research grant from the Ministry of Education, Science Sports, and Culture (MEXT) of Japan, the Imai Memorial Trust for AIDS Research, the Waksman Foundation of Japan (to T.U.). NR 48 TC 0 Z9 0 U1 2 U2 2 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 2150-7511 J9 MBIO JI mBio PD JAN-FEB PY 2016 VL 7 IS 1 AR e01516-15 DI 10.1128/mBio.01516-15 PG 12 WC Microbiology SC Microbiology GA DJ0ZO UT WOS:000373933100046 PM 26787826 ER PT J AU Grob, SR Finn, A Papakostas, TD Eliott, D AF Grob, Seanna R. Finn, Avni Papakostas, Thanos D. Eliott, Dean TI Clinical Trials in Retinal Dystrophies SO MIDDLE EAST AFRICAN JOURNAL OF OPHTHALMOLOGY LA English DT Article DE Cell Therapy; Genetic Therapy; Retinal Dystrophies ID EPITHELIUM-DERIVED FACTOR; LEBERS CONGENITAL AMAUROSIS; EMBRYONIC STEM-CELLS; ENDOTHELIAL GROWTH-FACTOR; MEDIATED GENE-TRANSFER; PIGMENT EPITHELIUM; MACULAR DEGENERATION; CHOROIDAL NEOVASCULARIZATION; RETINITIS-PIGMENTOSA; VISUAL FUNCTION AB Research development is burgeoning for genetic and cellular therapy for retinal dystrophies. These dystrophies are the focus of many research efforts due to the unique biology and accessibility of the eye, the transformative advances in ocular imaging technology that allows for in vivo monitoring, and the potential benefit people would gain from success in the field - the gift of renewed sight. Progress in the field has revealed the immense complexity of retinal dystrophies and the challenges faced by researchers in the development of this technology. This study reviews the current trials and advancements in genetic and cellular therapy in the treatment of retinal dystrophies and also discusses the current and potential future challenges. C1 [Grob, Seanna R.; Finn, Avni; Papakostas, Thanos D.; Eliott, Dean] Harvard Univ, Sch Med, Dept Ophthalmol, Boston, MA USA. [Grob, Seanna R.; Finn, Avni; Papakostas, Thanos D.; Eliott, Dean] Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. [Papakostas, Thanos D.; Eliott, Dean] Massachusetts Eye & Ear Infirm, Retina, Boston, MA 02114 USA. RP Eliott, D (reprint author), Harvard Univ, Sch Med, Dept Ophthalmol, Boston, MA USA.; Eliott, D (reprint author), Massachusetts Eye & Ear Infirm, Retina Serv, Boston, MA 02114 USA. EM dean_eliott@meei.harvard.edu NR 110 TC 1 Z9 1 U1 0 U2 1 PU MEDKNOW PUBLICATIONS & MEDIA PVT LTD PI MUMBAI PA B-9, KANARA BUSINESS CENTRE, OFF LINK RD, GHAKTOPAR-E, MUMBAI, 400075, INDIA SN 0974-9233 EI 0975-1599 J9 MIDDLE EAST AFR J OP JI Middle East Afr. J. Ophthalmol. PD JAN-MAR PY 2016 VL 23 IS 1 BP 49 EP 59 DI 10.4103/0974-9233.173135 PG 11 WC Ophthalmology SC Ophthalmology GA DJ1FS UT WOS:000373949300007 PM 26957839 ER PT J AU Lamba, S Strang, A Edelman, D Navedo, D Soto-Greene, ML Guarino, AJ AF Lamba, Sangeeta Strang, Aimee Edelman, David Navedo, Deborah Soto-Greene, Maria L. Guarino, Anthony J. TI Promoting interprofessionalism: initial evaluation of a master of science in health professions education degree program SO ADVANCES IN MEDICAL EDUCATION AND PRACTICE LA English DT Article DE health professions education; program evaluation; and survey; development; master's degree; interprofessional education; G-theory; faculty development; teacher training ID LEADERS AB This survey study assessed former students' perceptions on the efficacy of how well a newly implemented master's in health professions education degree program achieved its academic aims. These academic aims were operationalized by an author-developed scale to assess the following domains: a) developing interprofessional skills and identity; b) acquiring new academic skills; and c) providing a student-centered environment. The respondents represented a broad range of health care providers, including physicians, nurses, and occupational and physical therapists. Generalizability-theory was applied to partition the variance of the scores. Student's overwhelmingly responded that the program successfully achieved its academic aims. C1 [Lamba, Sangeeta; Soto-Greene, Maria L.] Rutgers State Univ, New Jersey Med Sch, Dept Emergency Med, MSB C 642,185 South Orange Ave, Newark, NJ 07101 USA. [Strang, Aimee] Albany Coll Pharm & Hlth Sci, Dept Pharm Practice, Albany, NY USA. [Edelman, David] Wayne State Univ, Sch Med, Dept Surg, Detroit, MI 48201 USA. [Navedo, Deborah; Guarino, Anthony J.] Massachusetts Gen Hosp, Inst Hlth Profess, Hlth Profess Educ Program, Boston, MA 02114 USA. RP Lamba, S (reprint author), Rutgers State Univ, New Jersey Med Sch, Dept Emergency Med, MSB C 642,185 South Orange Ave, Newark, NJ 07101 USA. EM lambasa@njms.rutgers.edu NR 13 TC 0 Z9 0 U1 3 U2 3 PU DOVE MEDICAL PRESS LTD PI ALBANY PA PO BOX 300-008, ALBANY, AUCKLAND 0752, NEW ZEALAND SN 1179-7258 J9 Adv Med Educ Pract JI Adv. Med. Educ. Pract. PY 2016 VL 7 BP 51 EP 55 DI 10.2147/AMEP.S97482 PG 5 WC Medicine, General & Internal SC General & Internal Medicine GA DI6TM UT WOS:000373633100006 PM 26917985 ER PT J AU Fung, V Price, M Busch, AB Landrum, MB Fireman, B Nierenberg, AA Newhouse, JP Hsu, J AF Fung, Vicki Price, Mary Busch, Alisa B. Landrum, Mary Beth Fireman, Bruce Nierenberg, Andrew A. Newhouse, Joseph P. Hsu, John TI The Introduction of Generic Risperidone in Medicare Part D SO AMERICAN JOURNAL OF MANAGED CARE LA English DT Article ID INCENTIVE-BASED FORMULARIES; BRAND-NAME; MEDICATIONS; BIOEQUIVALENCE; SUBSTITUTION; EXPENDITURES; DRUGS AB Objectives: The introduction of generic second-generation anti-psychotics (SGAs), starting with risperidone in July 2008, could reduce antipsychotic spending and cost-related use barriers. This study examines associations between generic risperidone use and spending and adherence after introduction among Medicare Advantage (MA) beneficiaries. Study Design: Historic cohort study. Methods: The study included MA beneficiaries receiving SGA treatment prior to July 2008. We examined antipsychotic spending using linear models, adherence (proportion of days covered >= 80%) using logistic models, and nonpersistence (time to first gap in antipsychotic use >30 days) in 2009 using Cox proportional hazard models, comparing beneficiaries with versus without generic use, adjusting for individual and plan characteristics. Results: Between July 2008 and December 2009, 22.8% of beneficiaries had >= 1 fill of generic risperidone: 73% of those previously using branded risperidone and 6.7% of those previously using other SGAs. Beneficiaries in private fee-for-service (FFS) versus health maintenance organization (HMO) plans had lower rates of generic use (hazard ratio [HR], 0.73 [95% CI, 0.56-0.96]); however, cost-sharing levels were not associated with generic use. Compared with beneficiaries who continued using other SGAs, those who switched from other SGAs to generic risperidone in 2008 had lower out-of-pocket spending (-$214; 95% CI, -$314 to -$115), higher adherence (odds ratio, 2.34; 95% CI, 1.62-3.40) and lower rates of nonpersistence (HR, 0.56; 95% CI, 0.46-0.69) in 2009. Conclusions: Generic use was concentrated among patients previously using branded risperidone. HMO plans appeared to be more effective at encouraging generic use than unmanaged private FFS plans; however, patient financial incentives had limited influence on switching. Additional opportunity remains to encourage greater generic SGA use, reduce spending, and potentially improve treatment adherence and outcomes. C1 [Nierenberg, Andrew A.] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. [Fung, Vicki; Price, Mary; Hsu, John] Massachusetts Gen Hosp, Mongan Inst Hlth Policy, Boston, MA 02114 USA. [Fung, Vicki; Hsu, John] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. [Busch, Alisa B.; Landrum, Mary Beth; Newhouse, Joseph P.; Hsu, John] Harvard Univ, Sch Med, Dept Hlth Care Policy, Boston, MA 02115 USA. [Nierenberg, Andrew A.] Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA. [Busch, Alisa B.] McLean Hosp, 115 Mill St, Belmont, MA 02178 USA. [Busch, Alisa B.] Partners Psychiat & Mental Hlth, Hlth Serv Res Div, Boston, MA USA. [Fireman, Bruce] Kaiser Permanente No Calif, Div Res, Oakland, CA USA. [Newhouse, Joseph P.] Harvard Univ, Sch Publ Hlth, Dept Hlth Policy & Management, 665 Huntington Ave, Boston, MA 02115 USA. [Newhouse, Joseph P.] Harvard Univ, Harvard Kennedy Sch, Cambridge, MA 02138 USA. RP Fung, V (reprint author), 50 Staniford St,9th Fl, Boston, MA 02114 USA. EM vfung@mgh.harvard.edu FU National Institute of Mental Health [R01MH090284] FX The National Institute of Mental Health (R01MH090284) provided funding for this study. NR 24 TC 0 Z9 0 U1 0 U2 1 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 2016 VL 22 IS 1 BP 41 EP + PG 11 WC Health Care Sciences & Services; Health Policy & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA DI5WH UT WOS:000373570700008 PM 26799124 ER PT J AU Mammoto, T Chen, Z Jiang, A Jiang, E Ingber, DE Mammoto, A AF Mammoto, Tadanori Chen, Zhao Jiang, Amanda Jiang, Elisabeth Ingber, Donald E. Mammoto, Akiko TI Acceleration of Lung Regeneration by Platelet-Rich Plasma Extract through the Low-Density Lipoprotein Receptor-Related Protein 5-Tie2 Pathway SO AMERICAN JOURNAL OF RESPIRATORY CELL AND MOLECULAR BIOLOGY LA English DT Article DE angiogenesis; lung regeneration; platelet-rich plasma extract; LRP5; Tie2 ID CLINICAL-APPLICATIONS; PULMONARY-EDEMA; GROWTH-FACTORS; STEM-CELLS; ADULT LUNG; ANGIOGENESIS; MICE; ALVEOLARIZATION; PNEUMONECTOMY; MECHANISMS AB Angiogenesis, the growth of new blood vessels, plays a key role in organ development, homeostasis, and regeneration. The cooperation of multiple angiogenic factors, rather than a single factor, is required for physiological angiogenesis. Recently, we have reported that soluble platelet-rich plasma (PRP) extract, which contains abundant angiopoietin-1 and multiple other angiogenic factors, stimulates angiogenesis and maintains vascular integrity in vitro and in vivo. In this report, we have demonstrated that mouse PRP extract increases phosphorylation levels of the Wnt coreceptor low-density lipoprotein receptor-related protein 5 (LRP5) and thereby activates angiogenic factor receptor Tie2 in endothelial cells (ECs) and accelerates EC sprouting and lung epithelial cell budding in vitro. PRP extract also increases phosphorylation levels of Tie2 in the mouse lungs and accelerates compensatory lung growth and recovery of exercise capacity after unilateral pneumonectomy in mice, whereas soluble Tie2 receptor or Lrp5 knockdown attenuates the effects of PRP extract. Because human PRP extract is generated from autologous peripheral blood and can be stored at-80 degrees C, our findings may lead to the development of novel therapeutic interventions for various angiogenesis-related lung diseases and to the improvement of strategies for lung regeneration. C1 [Mammoto, Tadanori; Jiang, Amanda; Jiang, Elisabeth; Ingber, Donald E.; Mammoto, Akiko] Boston Childrens Hosp, Dept Surg, Vasc Biol Program, Boston, MA USA. [Mammoto, Tadanori; Chen, Zhao; Jiang, Amanda; Jiang, Elisabeth; Ingber, Donald E.; Mammoto, Akiko] Harvard Univ, Sch Med, Boston, MA USA. [Chen, Zhao] Dana Farber Canc Inst, Dept Med, Boston, MA 02115 USA. [Ingber, Donald E.] Wyss Inst Biol Inspired Engn, Boston, MA USA. [Ingber, Donald E.] Harvard Univ, Sch Engn & Appl Sci, Cambridge, MA 02138 USA. RP Mammoto, T (reprint author), Vasc Biol Program, KFRL11005B,1 Blackfan Circle, Boston, MA 02115 USA. EM tadanori.mammoto@childrens.harvard.edu FU American Heart Association; Boston Children's Hospital Faculty Career Development Fellowship; Department of Defense grant [W81XWH-10-1-0565]; Boston Children's Hospital Intellectual and Developmental Disabilities Research Center grant [P30 HD18655] FX This work was supported by funds from the American Heart Association (A.M.), by a Boston Children's Hospital Faculty Career Development Fellowship (T.M. and A.M.), by Department of Defense grant W81XWH-10-1-0565 (D.E.I.), and by Boston Children's Hospital Intellectual and Developmental Disabilities Research Center grant P30 HD18655. NR 49 TC 1 Z9 1 U1 0 U2 1 PU AMER THORACIC SOC PI NEW YORK PA 25 BROADWAY, 18 FL, NEW YORK, NY 10004 USA SN 1044-1549 EI 1535-4989 J9 AM J RESP CELL MOL JI Am. J. Respir. Cell Mol. Biol. PD JAN PY 2016 VL 54 IS 1 BP 103 EP 113 DI 10.1165/rcmb.2014-0045OC PG 11 WC Biochemistry & Molecular Biology; Cell Biology; Respiratory System SC Biochemistry & Molecular Biology; Cell Biology; Respiratory System GA DI7TP UT WOS:000373705200012 PM 26091161 ER PT J AU Klionsky, DJ Abdelmohsen, K Abe, A Abedin, MJ Abeliovich, H Arozena, AA Adachi, H Adams, CM Adams, PD Adeli, K Adhihetty, PJ Adler, SG Agam, G Agarwal, R Aghi, MK Agnello, M Agostinis, P Aguilar, PV Aguirre-Ghiso, J Airoldi, EM Ait-Si-Ali, S Akematsu, T Akporiaye, ET Al-Rubeai, M Albaiceta, GM Albanese, C Albani, D Albert, ML Aldudo, J Algul, H Alirezaei, M Alloza, I Almasan, A Almonte-Beceril, M Alnemri, ES Alonso, C Altan-Bonnet, N Altieri, DC Alvarez, S Alvarez-Erviti, L Alves, S Amadoro, G Amano, A Amantini, C Ambrosio, S Amelio, I Amer, AO Amessou, M Amon, A An, ZY Anania, FA Andersen, SU Andley, UP Andreadi, CK Andrieu-Abadie, N Anel, A Ann, DK Anoopkumar-Dukie, S Antonioli, M Aoki, H Apostolova, N Aquila, S Aquilano, K Araki, K Arama, E Aranda, A Araya, J Arcaro, A Arias, E Arimoto, H Ariosa, AR Armstrong, JL Arnould, T Arsov, I Asanuma, K Askanas, V Asselin, E Atarashi, R Atherton, SS Atkin, JD Attardi, LD Auberger, P Auburger, G Aurelian, L Autelli, R Avagliano, L Avantaggiati, ML Avrahami, L Awale, S Azad, N Bachetti, T Backer, JM Bae, DH Bae, JS Bae, ON Bae, SH Baehrecke, EH Baek, SH Baghdiguian, S Bagniewska-Zadworna, A Bai, H Bai, J Bai, XY Bailly, Y Balaji, KN Balduini, W Ballabio, A Balzan, R Banerjee, R Banhegyi, G Bao, HJ Barbeau, B Barrachina, MD Barreiro, E Bartel, B Bartolome, A Bassham, DC Bassi, MT Bast, RC Basu, A Batista, MT Batoko, H Battino, M Bauckman, K Baumgarner, BL Bayer, KU Beale, R Beaulieu, JF Beck, GR Becker, C Beckham, JD Bedard, PA Bednarski, PJ Begley, TJ Behl, C Behrends, C Behrens, GMN Behrns, KE Bejarano, E Belaid, A Belleudi, F Benard, G Berchem, G Bergamaschi, D Bergami, M Berkhout, B Berliocchi, L Bernard, A Bernard, M Bernassola, F Bertolotti, A Bess, AS Besteiro, S Bettuzzi, S Bhalla, S Bhattacharyya, S Bhutia, SK Biagosch, C Bianchi, MW Biard-Piechaczyk, M Billes, V Bincoletto, C Bingol, B Bird, SW Bitoun, M Bjedov, I Blackstone, C Blanc, L Blanco, GA Blomhoff, HK Boada-Romero, E Bockler, S Boes, M Boesze-Battaglia, K Boise, LH Bolino, A Boman, A Bonaldo, P Bordi, M Bosch, J Botana, LM Botti, J Bou, G Bouche, M Bouchecareilh, M Boucher, MJ Boulton, ME Bouret, SG Boya, P Boyer-Guittaut, M Bozhkov, PV Brady, N Braga, VMM Brancolini, C Braus, GH Bravo-San Pedro, JM Brennan, LA Bresnick, EH Brest, P Bridges, D Bringer, MA Brini, M Brito, GC Brodin, B Brookes, PS Brown, EJ Brown, K Broxmeyer, HE Bruhat, A Brum, PC Brumell, JH Brunetti-Pierri, N Bryson-Richardson, RJ Buch, S Buchan, AM Budak, H Bulavin, DV Bultman, SJ Bultman, SJ Bumbasirevic, V Burelle, Y Burke, RE Burmeister, M Butikofer, P Caberlotto, L Cadwell, K Cahova, M Cai, DS Cai, JJ Cai, Q Calatayud, S Camougrand, N Campanella, M Campbell, GR Campbell, M Campello, S Candau, R Caniggia, I Cantoni, L Cao, LZ Caplan, AB Caraglia, M Cardinali, C Cardoso, SM Carew, JS Carleton, LA Carlin, CR Carloni, S Carlsson, SR Carmona-Gutierrez, D Carneiro, LAM Carnevali, O Carra, S Carrier, A Carroll, B Casas, C Casas, J Cassinelli, G Castets, P Castro-Obregon, S Cavallini, G Ceccherini, I Cecconi, F Cederbaum, AI Cena, V Cenci, S Cerella, C Cervia, D Cetrullo, S Chaachouay, H Chae, HJ Chagin, AS Chai, CY Chakrabarti, G Chamilos, G Chan, EYW Chan, MTV Chandra, D Chandra, P Chang, CP Chang, RCC Chang, TY Chatham, JC Chatterjee, S Chauhan, S Che, YS Cheetham, ME Cheluvappa, R Chen, CJ Chen, G Chen, GC Chen, GQ Chen, HZ Chen, JW Chen, JK Chen, M Chen, MZ Chen, PW Chen, Q Chen, Q Chen, SD Chen, S Chen, SSL Chen, W Chen, WJ Chen, WQ Chen, WL Chen, XM Chen, YH Chen, YG Chen, Y Chen, YY Chen, YS Chen, YJ Chen, YQ Chen, YJ Chen, Z Chen, Z Cheng, A Cheng, CHK Cheng, H Cheong, HS Cherry, S Chesney, J Cheung, CHA Chevet, E Chi, HC Chi, SG Chiacchiera, F Chiang, HL Chiarelli, R Chiariello, M Chieppa, M Chin, LS Chiong, M Chiu, GNC Cho, DH Cho, SG Cho, WC Cho, YY Cho, YS Choi, AMK Choi, EJ Choi, EK Choi, JY Choi, ME Choi, SI Chou, TF Chouaib, S Choubey, D Choubey, V Chow, KC Chowdhury, K Chu, CT Chuang, TH Chun, T Chung, HW Chung, TJ Chung, YL Chwae, YJ Cianfanelli, V Ciarcia, R Ciechomska, IA Ciriolo, MR Cirone, M Claerhout, S Clague, MJ Claria, J Clarke, PGH Clarke, R Clementi, E Cleyrat, C Cnop, M Coccia, EM Cocco, T Codogno, P Coers, J Cohen, EEW Colecchia, D Coletto, L Coll, NS Colucci-Guyon, E Comincini, S Condello, M Cook, KL Coombs, GH Cooper, CD Cooper, JM Coppens, I Corasaniti, MT Corazzari, M Corbalan, R Corcelle-Termeau, E Cordero, MD Corral-Ramos, C Corti, O Cossarizza, A Costelli, P Costes, S Costes, S Coto-Montes, A Cottet, S Couve, E Covey, LR Cowart, LA Cox, JS Coxon, FP Coyne, CB Cragg, MS Craven, RJ Crepaldi, T Crespo, JL Criollo, A Crippa, V Cruz, MT Cuervo, AM Cuezva, JM Cui, TX Cutillas, PR Czaja, MJ Czyzyk-Krzeska, MF Dagda, RK Dahmen, U 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FY Song, HK Song, JX Song, W Soo, KY Sood, AK Soong, TW Soontornniyomkij, V Sorice, M Sotgia, F Soto-Pantoja, DR Sotthibundhu, A Sousa, MJ Spaink, HP Span, PN Spang, A Sparks, JD Speck, PG Spector, SA Spies, CD Springer, W St Clair, D Stacchiotti, A Staels, B Stang, MT Starczynowski, DT Starokadomskyy, P Steegborn, C Steele, JW Stefanis, L Steffan, J Stellrecht, CM Stenmark, H Stepkowski, TM Stern, ST Stevens, C Stockwell, BR Stoka, V Storchova, Z Stork, B Stratoulias, V Stravopodis, DJ Strnad, P Strohecker, AM Strom, AL Stromhaug, P Stulik, J Su, YX Su, ZL Subauste, CS Subramaniam, S Sue, CM Suh, SW Sui, XB Sukseree, S Sulzer, D Sun, FL Sun, JR Sun, J Sun, SY Sun, Y Sun, Y Sun, YJ Sundaramoorthy, V Sung, J Suzuki, H Suzuki, K Suzuki, N Suzuki, T Suzuki, YJ Swanson, MS Swanton, C Sward, K Swarup, G Sweeney, ST Sylvester, PW Szatmari, Z Szegezdi, E Szlosarek, PW Taegtmeyer, H Tafani, M Taillebourg, E Tait, SWG Takacs-Vellai, K Takahashi, Y Takats, S Takemura, G Takigawa, N Talbot, NJ 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Chai, Chee-Yin Chakrabarti, Gopal Chamilos, Georgios Chan, Edmond Y. W. Chan, Matthew T. V. Chandra, Dhyan Chandra, Pallavi Chang, Chih-Peng Chang, Raymond Chuen-Chung Chang, Ta Yuan Chatham, John C. Chatterjee, Saurabh Chauhan, Santosh Che, Yongsheng Cheetham, Michael E. Cheluvappa, Rajkumar Chen, Chun-Jung Chen, Gang Chen, Guang-Chao Chen, Guoqiang Chen, Hongzhuan Chen, Jeff W. Chen, Jian-Kang Chen, Min Chen, Mingzhou Chen, Peiwen Chen, Qi Chen, Quan Chen, Shang-Der Chen, Si Chen, Steve S-L Chen, Wei Chen, Wei-Jung Chen, Wen Qiang Chen, Wenli Chen, Xiangmei Chen, Yau-Hung Chen, Ye-Guang Chen, Yin Chen, Yingyu Chen, Yongshun Chen, Yu-Jen Chen, Yue-Qin Chen, Yujie Chen, Zhen Chen, Zhong Cheng, Alan Cheng, Christopher H. K. Cheng, Hua Cheong, Heesun Cherry, Sara Chesney, Jason Cheung, Chun Hei Antonio Chevet, Eric Chi, Hsiang Cheng Chi, Sung-Gil Chiacchiera, Fulvio Chiang, Hui-Ling Chiarelli, Roberto Chiariello, Mario Chieppa, Marcello Chin, Lih-Shen Chiong, Mario Chiu, Gigi N. C. 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Gannage, Monique Gao, Fen-Biao Gao, Feng Gao, Jian-Xin Garcia Nannig, Lorena Vescovi, Eleonora Garcia Garcia-Macia, Marina Garcia-Ruiz, Carmen Garg, Abhishek D. Garg, Pramod Kumar Gargini, Ricardo Gassen, Nils Christian Gatica, Damian Gatti, Evelina Gavard, Julie Gavathiotis, Evripidis Ge, Liang Ge, Pengfei Ge, Shengfang Gean, Po-Wu Gelmetti, Vania Genazzani, Armando A. Geng, Jiefei Genschik, Pascal Gerner, Lisa Gestwicki, Jason E. Gewirtz, David A. Ghavami, Saeid Ghigo, Eric Ghosh, Debabrata Giammarioli, Anna Maria Giampieri, Francesca Giampietri, Claudia Giatromanolaki, Alexandra Gibbings, Derrick J. Gibellini, Lara Gibson, Spencer B. Ginet, Vanessa Giordano, Antonio Giorgini, Flaviano Giovannetti, Elisa Girardin, Stephen E. Gispert, Suzana Giuliano, Sandy Gladson, Candece L. Glavic, Alvaro Gleave, Martin Godefroy, Nelly Gogal, Robert M., Jr. Gokulan, Kuppan Goldman, Gustavo H. Goletti, Delia Goligorsky, Michael S. Gomes, Aldrin V. Gomes, Ligia C. Gomez, Hernando Gomez-Manzano, Candelaria Gomez-Sanchez, Ruben Goncalves, Dawit A. P. Goncu, Ebru Gong, Qingqiu Gongora, Celine Gonzalez, Carlos B. Gonzalez-Alegre, Pedro Gonzalez-Cabo, Pilar Ana Gonzalez-Polo, Rosa Goping, Ing Swie Gorbea, Carlos Gorbunov, Nikolai V. Goring, Daphne R. Gorman, Adrienne M. Gorski, Sharon M. Goruppi, Sandro Goto-Yamada, Shino Gotor, Cecilia Gottlieb, Roberta A. Gozes, Illana Gozuacik, Devrim Graba, Yacine Graef, Martin Granato, Giovanna E. Grant, Gary Dean Grant, Steven Gravina, Giovanni Luca Green, Douglas R. Greenhough, Alexander Greenwood, Michael T. Grimaldi, Benedetto Gros, Frederic Grose, Charles Groulx, Jean-Francois Gruber, Florian Grumati, Paolo Grune, Tilman Guan, Jun-Lin Guan, Kun-Liang Guerra, Barbara Guillen, Carlos Gulshan, Kailash Gunst, Jan Guo, Chuanyong Guo, Lei Guo, Ming Guo, Wenjie Guo, Xu-Guang Gust, Andrea A. Gustafsson, Asa B. Gutierrez, Elaine Gutierrez, Maximiliano G. Gwak, Ho-Shin Haas, Albert Haber, James E. Hadano, Shinji Hagedorn, Monica Hahn, David R. Halayko, Andrew J. Hamacher-Brady, Anne Hamada, Kozo Hamai, Ahmed Hamann, Andrea Hamasaki, Maho Hamer, Isabelle Hamid, Qutayba Hammond, Ester M. Han, Feng Han, Weidong Handa, James T. Hanover, John A. Hansen, Malene Harada, Masaru Harhaji-Trajkovic, Ljubica Harper, J. Wade Harrath, Abdel Halim Harris, Adrian L. Harris, James Hasler, Udo Hasselblatt, Peter Hasui, Kazuhisa Hawley, Robert G. Hawley, Teresa S. He, Congcong He, Cynthia Y. He, Fengtian He, Gu He, Rong-Rong He, Xian-Hui He, You-Wen He, Yu-Ying Heath, Joan K. Hebert, Marie-Josee Heinzen, Robert A. Helgason, Gudmundur Vignir Hensel, Michael Henske, Elizabeth P. Her, Chengtao Herman, Paul K. Hernandez, Agustin Hernandez, Carlos Hernandez-Tiedra, Sonia Hetz, Claudio Hiesinger, P. Robin Higaki, Katsumi Hilfiker, Sabine Hill, Bradford G. Hill, Joseph A. Hill, William D. Hino, Keisuke Hofius, Daniel Hofman, Paul Hoeglinger, Guenter U. Hoehfeld, Joerg Holz, Marina K. Hong, Yonggeun Hood, David A. Hoozemans, Jeroen J. M. Hoppe, Thorsten Hsu, Chin Hsu, Chin-Yuan Hsu, Li-Chung Hu, Dong Hu, Guochang Hu, Hong-Ming Hu, Hongbo Hu, Ming Chang Hu, Yu-Chen Hu, Zhuo-Wei Hua, Fang Hua, Ya Huang, Canhua Huang, Huey-Lan Huang, Kuo-How Huang, Kuo-Yang Huang, Shile Huang, Shiqian Huang, Wei-Pang Huang, Yi-Ran Huang, Yong Huang, Yunfei Huber, Tobias B. Huebbe, Patricia Huh, Won-Ki Hulmi, Juha J. Hur, Gang Min Hurley, James H. Husak, Zvenyslava Hussain, Sabah N. A. Hussain, Salik Hwang, Jung Jin Hwang, Seungmin Hwang, Thomas I. S. Ichihara, Atsuhiro Imai, Yuzuru Imbriano, Carol Inomata, Megumi Into, Takeshi Iovane, Valentina Iovanna, Juan L. Iozzo, Renato V. Ip, Nancy Y. Irazoqui, Javier E. Iribarren, Pablo Isaka, Yoshitaka Isakovic, Aleksandra J. Ischiropoulos, Harry Isenberg, Jeffrey S. Ishaq, Mohammad Ishida, Hiroyuki Ishii, Isao Ishmael, Jane E. Isidoro, Ciro Isobe, Ken-ichi Isono, Erika Issazadeh-Navikas, Shohreh Itahana, Koji Itakura, Eisuke Ivanov, Andrei I. Iyer, Anand Krishnan V. Izquierdo, Jose M. Izumi, Yotaro Izzo, Valentina Jaeaettelae, Marja Jaber, Nadia Jackson, Daniel John Jackson, William T. Jacob, Tony George Jacques, Thomas S. Jagannath, Chinnaswamy Jain, Ashish Jana, Nihar Ranjan Jang, Byoung Kuk Jani, Alkesh Janji, Bassam Jannig, Paulo Roberto Jansson, Patric J. Jean, Steve Jendrach, Marina Jeon, Ju-Hong Jessen, Niels Jeung, Eui-Bae Jia, Kailiang Jia, Lijun Jiang, Hong Jiang, Hongchi Jiang, Liwen Jiang, Teng Jiang, Xiaoyan Jiang, Xuejun Jiang, Xuejun Jiang, Ying Jiang, Yongjun Jimenez, Alberto Jin, Cheng Jin, Hongchuan Jin, Lei Jin, Meiyan Jin, Shengkan Jinwal, Umesh Kumar Jo, Eun-Kyeong Johansen, Terje Johnson, Daniel E. Johnson, Gail V. W. Johnson, James D. Jonasch, Eric Jones, Chris Joosten, Leo A. B. Jordan, Joaquin Joseph, Anna-Maria Joseph, Bertrand Joubert, Annie M. Ju, Dianwen Ju, Jingfang Juan, Hsueh-Fen Juenemann, Katrin Juhasz, Gabor Jung, Hye Seung Jung, Jae U. Jung, Yong-Keun Jungbluth, Heinz Justice, Matthew J. Jutten, Barry Kaakoush, Nadeem O. Kaarniranta, Kai Kaasik, Allen Kabuta, Tomohiro Kaeffer, Bertrand Kagedal, Katarina Kahana, Alon Kajimura, Shingo Kakhlon, Or Kalia, Manjula Kalvakolanu, Dhan V. Kamada, Yoshiaki Kambas, Konstantinos Kaminskyy, Vitaliy O. Kampinga, Harm H. Kandouz, Mustapha Kang, Chanhee Kang, Rui Kang, Tae-Cheon Kanki, Tomotake Kanneganti, Thirumala-Devi Kanno, Haruo Kanthasamy, Anumantha G. Kantorow, Marc Kaparakis-Liaskos, Maria Kapuy, Orsolya Karantza, Vassiliki Karim, Md Razaul Karmakar, Parimal Kaser, Arthur Kaushik, Susmita Kawula, Thomas Kaynar, A. Murat Ke, Po-Yuan Ke, Zun-Ji Kehrl, John H. Keller, Kate E. Kemper, Jongsook Kim Kenworthy, Anne K. Kepp, Oliver Kern, Andreas Kesari, Santosh Kessel, David Ketteler, Robin Kettelhut, Isis do Carmo Khambu, Bilon Khan, Muzamil Majid Khandelwal, Vinoth K. M. Khare, Sangeeta Kiang, Juliann G. Kiger, Amy A. Kihara, Akio Kim, Arianna L. Kim, Cheol Hyeon Kim, Deok Ryong Kim, Do-Hyung Kim, Eung Kweon Kim, Hye Young Kim, Hyung-Ryong Kim, Jae-Sung Kim, Jeong Hun Kim, Jin Cheon Kim, Jin Hyoung Kim, Kwang Woon Kim, Michael D. Kim, Moon-Moo Kim, Peter K. Kim, Seong Who Kim, Soo-Youl Kim, Yong-Sun Kim, Yonghyun Kimchi, Adi Kimmelman, Alec C. Kimura, Tomonori King, Jason S. Kirkegaard, Karla Kirkin, Vladimir Kirshenbaum, Lorrie A. Kishi, Shuji Kitajima, Yasuo Kitamoto, Katsuhiko Kitaoka, Yasushi Kitazato, Kaio Kley, Rudolf A. Klimecki, Walter T. Klinkenberg, Michael Klucken, Jochen Knaevelsrud, Helene Knecht, Erwin Knuppertz, Laura Ko, Jiunn-Liang Kobayashi, Satoru Koch, Jan C. Koechlin-Ramonatxo, Christelle Koenig, Ulrich Ko, Young Ho Koehler, Katja Kohlwein, Sepp D. Koike, Masato Komatsu, Masaaki Kominami, Eiki Kong, Dexin Kong, Hee Jeong Konstantakou, Eumorphia G. Kopp, Benjamin T. Korcsmaros, Tamas Korhonen, Laura Korolchuk, Viktor I. Koshkina, Nadya V. Kou, Yanjun Koukourakis, Michael I. Koumenis, Constantinos Kovacs, Attila L. Kovacs, Tibor Kovacs, Werner J. Koya, Daisuke Kraft, Claudine Krainc, Dimitri Kramer, Helmut Kravic-Stevovic, Tamara Krek, Wilhelm Kretz-Remy, Carole Krick, Roswitha Krishnamurthy, Malathi Kriston-Vizi, Janos Kroemer, Guido Kruer, Michael C. Kruger, Rejko Ktistakis, Nicholas T. Kuchitsu, Kazuyuki Kuhn, Christian Kumar, Addanki Pratap Kumar, Anuj Kumar, Ashok Kumar, Deepak Kumar, Dhiraj Kumar, Rakesh Kumar, Sharad Kundu, Mondira Kung, Hsing-Jien Kuno, Atsushi Kuo, Sheng-Han Kuret, Jeff Kurz, Tino Kwok, Terry Kwon, Taeg Kyu Kwon, Yong Tae Kyrmizi, Irene La Spada, Albert R. Lafont, Frank Lahm, Tim Lakkaraju, Aparna Lam, Truong Lamark, Trond Lancel, Steve Landowski, Terry H. Lane, Darius J. R. Lane, Jon D. Lanzi, Cinzia Lapaquette, Pierre Lapierre, Louis R. Laporte, Jocelyn Laukkarinen, Johanna Laurie, Gordon W. Lavandero, Sergio Lavie, Lena LaVoie, Matthew J. Law, Betty Yuen Kwan Law, Helen Ka-wai Law, Kelsey B. Layfield, Robert Lazo, Pedro A. Le Cam, Laurent Le Roch, Karine G. Le Stunff, Herve Leardkamolkarn, Vijittra Lecuit, Marc Lee, Byung-Hoon Lee, Che-Hsin Lee, Erinna F. Lee, Gyun Min Lee, He-Jin Lee, Hsinyu Lee, Jae Keun Lee, Jongdae Lee, Ju-Hyun Lee, Jun Hee Lee, Michael Lee, Myung-Shik Lee, Patty J. Lee, Sam W. Lee, Seung-Jae Lee, Shiow-Ju Lee, Stella Y. Lee, Sug Hyung Lee, Sung Sik Lee, Sung-Joon Lee, Sunhee Lee, Ying-Ray Lee, Yong J. Lee, Young H. Leeuwenburgh, Christiaan Lefort, Sylvain Legouis, Renaud Lei, Jinzhi Lei, Qun-Ying Leib, David A. Leibowitz, Gil Lekli, Istvan Lemaire, Stephane D. Lemasters, John J. Lemberg, Marius K. Lemoine, Antoinette Leng, Shuilong Lenz, Guido Lenzi, Paola Lerman, Lilach O. Barbato, Daniele Lettieri Leu, Julia I-Ju Leung, Hing Y. Levine, Beth Lewis, Patrick A. Lezoualc'h, Frank Li, Chi Li, Faqiang Li, Feng-Jun Li, Jun Li, Ke Li, Lian Li, Min Li, Min Li, Qiang Li, Rui Li, Sheng Li, Wei Li, Wei Li, Xiaotao Li, Yumin Lian, Jiqin Liang, Chengyu Liang, Qiangrong Liao, Yulin Liberal, Joana Liberski, Pawel P. Lie, Pearl Lieberman, Andrew P. Lim, Hyunjung Jade Lim, Kah-Leong Lim, Kyu Lima, Raquel T. Lin, Chang-Shen Lin, Chiou-Feng Lin, Fang Lin, Fangming Lin, Fu-Cheng Lin, Kui Lin, Kwang-Huei Lin, Pei-Hui Lin, Tianwei Lin, Wan-Wan Lin, Yee-Shin Lin, Yong Linden, Rafael Lindholm, Dan Lindqvist, Lisa M. Lingor, Paul Linkermann, Andreas Liotta, Lance A. Lipinski, Marta M. Lira, Vitor A. Lisanti, Michael P. Liton, Paloma B. Liu, Bo Liu, Chong Liu, Chun-Feng Liu, Fei Liu, Hung-Jen Liu, Jianxun Liu, Jing-Jing Liu, Jing-Lan Liu, Ke Liu, Leyuan Liu, Liang Liu, Quentin Liu, Rong-Yu Liu, Shiming Liu, Shuwen Liu, Wei Liu, Xian-De Liu, Xiangguo Liu, Xiao-Hong Liu, Xinfeng Liu, Xu Liu, Xueqin Liu, Yang Liu, Yule Liu, Zexian Liu, Zhe Liuzzi, Juan P. Lizard, Gerard Ljujic, Mila Lodhi, Irfan J. Logue, Susan E. Lokeshwar, Bal L. Long, Yun Chau Lonial, Sagar Loos, Benjamin Lopez-Otin, Carlos Lopez-Vicario, Cristina Lorente, Mar Lorenzi, Philip L. Lorincz, Peter Los, Marek Lotze, Michael T. Lovat, Penny E. Lu, Binfeng Lu, Bo Lu, Jiahong Lu, Qing Lu, She-Min Lu, Shuyan Lu, Yingying Luciano, Federic Luckhart, Shirley Lucocq, John Milton Ludovico, Paula Lugea, Aurelia Lukacs, Nicholas W. Lum, Julian J. Lund, Anders H. Luo, Honglin Luo, Jia Luo, Shouqing Luparello, Claudio Lyons, Timothy Ma, Jianjie Ma, Yi Ma, Yong Ma, Zhenyi Machado, Juliano Machado-Santelli, Glaucia M. Macian, Fernando MacIntosh, Gustavo C. MacKeigan, Jeffrey P. Macleod, Kay F. MacMicking, John D. MacMillan-Crow, Lee Ann Madeo, Frank Madesh, Muniswamy Madrigal-Matute, Julio Maeda, Akiko Maeda, Tatsuya Maegawa, Gustavo Maellaro, Emilia Maes, Hannelore Magarinos, Marta Maiese, Kenneth Maiti, Tapas K. Maiuri, Luigi Maiuri, Maria Chiara Maki, Carl G. Malli, Roland Malorni, Walter Maloyan, Alina Mami-Chouaib, Fathia Man, Na Mancias, Joseph D. Mandelkow, Eva-Maria Mandell, Michael A. Manfredi, Angelo A. Manie, Serge N. Manzoni, Claudia Mao, Kai Mao, Zixu Mao, Zong-Wan Marambaud, Philippe Marconi, Anna Maria Marelja, Zvonimir Marfe, Gabriella Margeta, Marta Margittai, Eva Mari, Muriel Mariani, Francesca V. Marin, Concepcio Marinelli, Sara Marino, Guillermo Markovic, Ivanka Marquez, Rebecca Martelli, Alberto M. Martens, Sascha Martin, Katie R. Martin, Seamus J. Martin, Shaun Martin-Acebes, Miguel A. Martin-Sanz, Paloma Martinand-Mari, Camille Martinet, Wim Martinez, Jennifer Martinez-Lopez, Nuria Martinez-Outschoorn, Ubaldo Martinez-Velazquez, Moises Martinez-Vicente, Marta Martins, Waleska Kerllen Mashima, Hirosato Mastrianni, James A. Matarese, Giuseppe Matarrese, Paola Mateo, Roberto Matoba, Satoaki Matsumoto, Naomichi Matsushita, Takehiko Matsuura, Akira Matsuzawa, Takeshi Mattson, Mark P. Matus, Soledad Maugeri, Norma Mauvezin, Caroline Mayer, Andreas Maysinger, Dusica Mazzolini, Guillermo D. McBrayer, Mary Kate McCall, Kimberly McCormick, Craig McInerney, Gerald M. McIver, Skye C. McKenna, Sharon McMahon, John J. McNeish, Iain A. Mechta-Grigoriou, Fatima Medema, Jan Paul Medina, Diego L. Megyeri, Klara Mehrpour, Maryam Mehta, Jawahar L. Mei, Yide Meier, Ute-Christiane Meijer, Alfred J. Melendez, Alicia Melino, Gerry Melino, Sonia Tenorio de Melo, Edesio Jose Mena, Maria A. Meneghini, Marc D. Menendez, Javier A. Menezes, Regina Meng, Liesu Meng, Ling-hua Meng, Songshu Menghini, Rossella Menko, A. Sue Menna-Barreto, Rubem F. S. Menon, Manoj B. Meraz-Rios, Marco A. Merla, Giuseppe Merlini, Luciano Merlot, Angelica M. Meryk, Andreas Meschini, Stefania Meyer, Joel N. Mi, Man-Tian Miao, Chao-Yu Micale, Lucia Michaeli, Simon Michiels, Carine Migliaccio, Anna Rita Mihailidou, Anastasia Susie Mijaljica, Dalibor Mikoshiba, Katsuhiko Milan, Enrico Miller-Fleming, Leonor Mills, Gordon B. Mills, Ian G. Minakaki, Georgia Minassian, Berge A. Ming, Xiu-Fen Minibayeva, Farida Minina, Elena A. Mintern, Justine D. Minucci, Saverio Miranda-Vizuete, Antonio Mitchell, Claire H. Miyamoto, Shigeki Miyazawa, Keisuke Mizushima, Noboru Mnich, Katarzyna Mograbi, Baharia Mohseni, Simin Moita, Luis Ferreira Molinari, Marco Molinari, Maurizio Moller, Andreas Buch Mollereau, Bertrand Mollinedo, Faustino Monick, Martha M. Monick, Martha M. Montagnaro, Serena Montell, Craig Moore, Darren J. Moore, Michael N. Mora-Rodriguez, Rodrigo Moreira, Paula I. Morel, Etienne Morelli, Maria Beatrice Moreno, Sandra Morgan, Michael J. Moris, Arnaud Moriyasu, Yuji Morrison, Janna L. Morrison, Lynda A. Morselli, Eugenia Moscat, Jorge Moseley, Pope L. Mostowy, Serge Motori, Elisa Mottet, Denis Mottram, Jeremy C. Moussa, Charbel E-H Mpakou, Vassiliki E. Mukhtar, Hasan Levy, Jean M. Mulcahy Muller, Sylviane Munoz-Moreno, Raquel Munoz-Pinedo, Cristina Muenz, Christian Murphy, Maureen E. Murray, James T. Murthy, Aditya Mysorekar, Indira U. Nabi, Ivan R. Nabissi, Massimo Nader, Gustavo A. Nagahara, Yukitoshi Nagai, Yoshitaka Nagata, Kazuhiro Nagelkerke, Anika Nagy, Peter Naidu, Samisubbu R. Nair, Sreejayan Nakano, Hiroyasu Nakatogawa, Hitoshi Nanjundan, Meera Napolitano, Gennaro Naqvi, Naweed I. Nardacci, Roberta Narendra, Derek P. Narita, Masashi Nascimbeni, Anna Chiara Natarajan, Ramesh Navegantes, Luiz C. Nawrocki, Steffan T. Nazarko, Taras Y. Nazarko, Volodymyr Y. Neill, Thomas Neri, Luca M. Netea, Mihai G. Netea-Maier, Romana T. Neves, Bruno M. Ney, Paul A. Nezis, Ioannis P. Nguyen, Hang T. T. Huu Phuc Nguyen Nicot, Anne-Sophie Nilsen, Hilde Nilsson, Per Nishimura, Mikio Nishino, Ichizo Niso-Santano, Mireia Niu, Hua Nixon, Ralph A. Njar, Vincent C. O. Noda, Takeshi Noegel, Angelika A. Nolte, Elsie Magdalena Norberg, Erik Norga, Koenraad K. Noureini, Sakineh Kazemi Notomi, Shoji Notterpek, Lucia Nowikovsky, Karin Nukina, Nobuyuki Nuernberger, Thorsten O'Donnell, Valerie B. O'Donovan, Tracey O'Dwyer, Peter J. Oehme, Ina Oeste, Clara L. Ogawa, Michinaga Ogretmen, Besim Ogura, Yuji Oh, Young J. Ohmuraya, Masaki Ohshima, Takayuki Ojha, Rani Okamoto, Koji Okazaki, Toshiro Oliver, F. Javier Ollinger, Karin Olsson, Stefan Orban, Daniel P. Ordonez, Paulina Orhon, Idil Orosz, Laszlo O'Rourke, Eyleen J. Orozco, Helena Ortega, Angel L. Ortona, Elena Osellame, Laura D. Oshima, Junko Oshima, Shigeru Osiewacz, Heinz D. Otomo, Takanobu Otsu, Kinya Ou, Jing-hsiung James Outeiro, Tiago F. Ouyang, Dong-yun Ouyang, Hongjiao Overholtzer, Michael Ozbun, Michelle A. Ozdinler, P. Hande Ozpolat, Bulent Pacelli, Consiglia Paganetti, Paolo Page, Guylene Pages, Gilles Pagnini, Ugo Pajak, Beata Pak, Stephen C. Pakos-Zebrucka, Karolina Pakpour, Nazzy Palkova, Zdena Palladino, Francesca Pallauf, Kathrin Pallet, Nicolas Palmieri, Marta Paludan, Soren R. Palumbo, Camilla Palumbo, Silvia Pampliega, Olatz Pan, Hongming Pan, Wei Panaretakis, Theocharis Pandey, Aseem Pantazopoulou, Areti Papackova, Zuzana Papademetrio, Daniela L. Papassideri, Issidora Papini, Alessio Parajuli, Nirmala Pardo, Julian Parekh, Vrajesh V. Parenti, Giancarlo Park, Jong-In Park, Junsoo Park, Ohkmae K. Parker, Roy Parlato, Rosanna Parys, Jan B. Parzych, Katherine R. Pasquet, Jean-Max Pasquier, Benoit Pasumarthi, Kishore B. S. Patschan, Daniel Patterson, Cam Pattingre, Sophie Pattison, Scott Pause, Arnim Pavenstaedt, Hermann Pavone, Flaminia Pedrozo, Zully Pena, Fernando J. Penalva, Miguel A. Pende, Mario Peng, Jianxin Penna, Fabio Penninger, Josef M. Pensalfini, Anna Pepe, Salvatore Pereira, Gustavo J. S. Pereira, Paulo C. Perez-de la Cruz, Veronica Esther Perez-Perez, Maria Perez-Rodriguez, Diego Perez-Sala, Dolores Perier, Celine Perl, Andras Perlmutter, David H. Perrotta, Ida Pervaiz, Shazib Pesonen, Maija Pessin, Jeffrey E. Peters, Godefridus J. Petersen, Morten Petrache, Irina Petrof, Basil J. Petrovski, Goran Phang, James M. Piacentini, Mauro Pierdominici, Marina Pierre, Philippe Pierrefite-Carle, Valerie Pietrocola, Federico Pimentel-Muinos, Felipe X. Pinar, Mario Pineda, Benjamin Pinkas-Kramarski, Ronit Pinti, Marcello Pinton, Paolo Piperdi, Bilal Piret, James M. Platanias, Leonidas C. Platta, Harald W. Plowey, Edward D. Poggeler, Stefanie Poirot, Marc Polcic, Peter Poletti, Angelo Poon, Audrey H. Popelka, Hana Popova, Blagovesta Poprawa, Izabela Poulose, Shibu M. Poulton, Joanna Powers, Scott K. Powers, Ted Pozuelo-Rubio, Mercedes Prak, Krisna Prange, Reinhild Prescott, Mark Priault, Muriel Prince, Sharon Proia, Richard L. Proikas-Cezanne, Tassula Prokisch, Holger Promponas, Vasilis J. Przyklenk, Karin Puertollano, Rosa Pugazhenthi, Subbiah Puglielli, Luigi Pujol, Aurora Puyal, Julien Pyeon, Dohun Qi, Xin Qian, Wen-bin Qin, Zheng-Hong Qiu, Yu Qu, Ziwei Quadrilatero, Joe Quinn, Frederick Raben, Nina Rabinowich, Hannah Radogna, Flavia Ragusa, Michael J. Rahmani, Mohamed Raina, Komal Ramanadham, Sasanka Ramesh, Rajagopal Rami, Abdelhaq Randall-Demllo, Sarron Randow, Felix Rao, Hai Rao, V. Ashutosh Rasmussen, Blake B. Rasse, Tobias M. Ratovitski, Edward A. Rautou, Pierre-Emmanuel Ray, Swapan K. Razani, Babak Reed, Bruce H. Reggiori, Fulvio Rehm, Markus Reichert, Andreas S. Rein, Theo Reiner, David J. Reits, Eric Ren, Jun Ren, Xingcong Renna, Maurizio Reusch, Jane E. B. Revuelta, Jose L. Reyes, Leticia Rezaie, Alireza R. Richards, Robert I. Richardson, Des R. Richetta, Clemence Riehle, Michael A. Rihn, Bertrand H. Rikihisa, Yasuko Riley, Brigit E. Rimbach, Gerald Rippo, Maria Rita Ritis, Konstantinos Rizzi, Federica Rizzo, Elizete Roach, Peter J. Robbins, Jeffrey Roberge, Michel Roca, Gabriela Roccheri, Maria Carmela Rocha, Sonia Rodrigues, Cecilia M. P. Rodriguez, Clara I. Rodriguez de Cordoba, Santiago Rodriguez-Muela, Natalia Roelofs, Jeroen Rogov, Vladimir V. Rohn, Troy T. Rohrer, Baerbel Romanelli, Davide Romani, Luigina Silvia Romano, Patricia Roncero, M. Isabel G. Luis Rosa, Jose Rosello, Alicia Rosen, Kirill V. Rosenstiel, Philip Rost-Roszkowska, Magdalena Roth, Kevin A. Roue, Gael Rouis, Mustapha Rouschop, Kasper M. Ruan, Daniel T. Ruano, Diego Rubinsztein, David C. Rucker, Edmund B., III Rudich, Assaf Rudolf, Emil Rudolf, Ruediger Ruegg, Markus A. Ruiz-Roldan, Carmen Ruparelia, Avnika Ashok Rusmini, Paola Russ, David W. Russo, Gian Luigi Russo, Giuseppe Russo, Rossella Rusten, Tor Erik Ryabovol, Victoria Ryan, Kevin M. Ryter, Stefan W. Sabatini, David M. Sacher, Michael Sachse, Carsten Sack, Michael N. Sadoshima, Junichi Saftig, Paul Sagi-Eisenberg, Ronit Sahni, Sumit Saikumar, Pothana Saito, Tsunenori Saitoh, Tatsuya Sakakura, Koichi Sakoh-Nakatogawa, Machiko Sakuraba, Yasuhito Salazar-Roa, Maria Salomoni, Paolo Saluja, Ashok K. Salvaterra, Paul M. Salvioli, Rosa Samali, Afshin Sanchez, Anthony M. J. Sanchez-Alcazar, Jose A. Sanchez-Prieto, Ricardo Sandri, Marco Sanjuan, Miguel A. Santaguida, Stefano Santambrogio, Laura Santoni, Giorgio dos Santos, Claudia Nunes Saran, Shweta Sardiello, Marco Sargent, Graeme Sarkar, Pallabi Sarkar, Sovan Sarrias, Maria Rosa Sarwal, Minnie M. Sasakawa, Chihiro Sasaki, Motoko Sass, Miklos Sato, Ken Sato, Miyuki Satriano, Joseph Savaraj, Niramol Saveljeva, Svetlana Schaefer, Liliana Schaible, Ulrich E. Scharl, Michael Schatzl, Hermann M. Schekman, Randy Scheper, Wiep Schiavi, Alfonso Schipper, Hyman M. Schmeisser, Hana Schmidt, Jens Schmitz, Ingo Schneider, Bianca E. Schneider, E. Marion Schneider, Jaime L. Schon, Eric A. Schoenenberger, Miriam J. 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[Qi, Xin] Case Western Reserve Univ, Sch Med, Dept Physiol & Biophys, Cleveland, OH 44106 USA. [Subauste, Carlos S.] Case Western Reserve Univ, Sch Med, Div Infect Dis & HIV Med, Dept Med, Cleveland, OH 44106 USA. [Vila, Miquel] Catalan Inst Res & Adv Studies ICREA, Barcelona, Spain. [Cho, Yong-Yeon] Catholic Univ Korea, Coll Pharm, Bucheon, South Korea. [Lee, Sug Hyung] Catholic Univ Korea, Seoul, South Korea. [Alves, Sandro] INSERM, CEA DSV BM 12, U1169, Gene Therapy Neurodegenerat Dis, Fontenay Aux Roses, France. [Gottlieb, Roberta A.] Barbra Streisand Womens Heart Ctr, Cedars Sinai Heart Inst, Los Angeles, CA USA. [Seki, Ekihiro] Cedars Sinai Med Ctr, Dept Med, Los Angeles, CA 90048 USA. [Lugea, Aurelia] VAGLAHS UCLA, Cedars Sinai Med Ctr, Pancreat Res Grp, Los Angeles, CA USA. [Jiang, Ying; Lie, Pearl; McBrayer, Mary Kate; Pensalfini, Anna; Sarkar, Pallabi] Nathan S Kline Inst, Ctr Dementia Res, Orangeburg, NY USA. 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[Krick, Roswitha; Thumm, Michael] Univ Gottingen, Inst Cellular Biochem, D-37073 Gottingen, Germany. [Liotta, Lance A.] George Mason Univ, Manassas, VA USA. [Hawley, Robert G.] George Washington Univ, Dept Anat & Regenerat Biol, Washington, DC USA. [Hawley, Teresa S.] George Washington Univ, Flow Cytometry Core Facil, Washington, DC USA. [Moussa, Charbel E-H] Georgetown Univ, Med Ctr, Dept Neurosci, Washington, DC 20007 USA. [Clarke, Robert] Georgetown Univ, Med Ctr, Dept Oncol, Washington, DC 20007 USA. [Suzuki, Yuichiro J.] Georgetown Univ, Dept Physiol & Pharmacol, Washington, DC USA. [Albanese, Chris] Georgetown Univ, Lombardi Comprehens Canc Ctr, Dept Oncol, Washington, DC USA. [Albanese, Chris] Georgetown Univ, Lombardi Comprehens Canc Ctr, Dept Pathol, Washington, DC USA. [Avantaggiati, Maria Laura] Georgetown Univ, Lombardi Comprehens Canc Ctr, Washington, DC USA. [Lokeshwar, Bal L.] Georgia Regents Univ, Ctr Canc, Dept Med, Augusta, GA USA. [Hill, William D.] Georgia Regents Univ, Dept Neurol, Augusta, GA USA. [Hill, William D.] Georgia Regents Univ, Dept Orthopaed Surg, Augusta, GA USA. [Hill, William D.] Georgia Regents Univ, Inst Regenerat & Reparat Med, Augusta, GA USA. [Atherton, Sally S.] Georgia Regents Univ, Med Coll Georgia, Augusta, GA USA. [Chen, Jian-Kang; Dong, Zheng; Hill, William D.; Xu, Jinxian] Georgia Regents Univ, Med Coll Georgia, Dept Cellular Biol & Anat, Augusta, GA USA. [Chen, Jian-Kang; Xu, Jinxian] Georgia Regents Univ, Med Coll Georgia, Dept Med, Augusta, GA USA. [Oehme, Ina] German Canc Res Ctr, Clin Cooperat Unit CCU Pediat Oncol, Heidelberg, Germany. [Hamacher-Brady, Anne] German Canc Res Ctr, Lysosomal Syst Biol, Heidelberg, Germany. [Brady, Nathan] German Canc Res Ctr, Syst Biol Cell Death Mech, Heidelberg, Germany. [Hoeglinger, Guenter U.] German Ctr Neurodegenerat Dis DZNE, Munich, Germany. [Grune, Tilman] German Inst Human Nutr, Dept Mol Toxicol, Nuthetal, Germany. [Vandenabeele, Peter] Univ Ghent, Dept Biomed Mol Biol, Inflammat Res Ctr, VIB,Methusalem Program, B-9000 Ghent, Belgium. [Menendez, Javier A.] ICO, Girona Biomed Res Inst IDIBGI, Catalonia, Spain. [Auburger, Georg; Gispert, Suzana; Klinkenberg, Michael] Goethe Univ, Sch Med, Expt Neurol, Frankfurt, Germany. [Doetsch, Volker; Rogov, Vladimir V.] Goethe Univ Frankfurt, Inst Biophys Chem, D-60054 Frankfurt, Germany. [Dikic, Ivan; Grumati, Paolo] Goethe Univ, Sch Med, Inst Biochem 2, Frankfurt, Germany. [Dikic, Ivan; Grumati, Paolo] Buchmann Inst Mol Life, Frankfurt, Germany. [Schaefer, Liliana] Goethe Univ, Inst Pharmacol & Toxicol, Frankfurt, Germany. [Fulda, Simone] Goethe Univ, Inst Expt Canc Res Pediat, Frankfurt, Germany. [Hamann, Andrea; Knuppertz, Laura; Osiewacz, Heinz D.] Goethe Univ, Inst Mol Biosci, Mol Dev Biol, Frankfurt, Hesse, Germany. [Veras, Patricia S. T.] Fundacao Oswaldo Cruz, FIOCRUZ BA, Goncalo Moniz Res Ctr, Lab Pathol & Biointervent, Salvador, BA, Brazil. [Gwak, Ho-Shin] Grad Sch Canc Sci & Policy, Dept Syst Canc Sci, Goyang, South Korea. [Choi, Eun-Kyoung] Hallym Univ, Grad Sch, Chunchon, Kangwon Do, South Korea. [Anoopkumar-Dukie, Shailendra; Grant, Gary Dean] Griffith Univ, Menzies Hlth Inst Queensland, Nathan, Qld 4111, Australia. [Leng, Shuilong] Guangzhou Med Univ, Dept Human Anat, Sch Basic Sci, Guangzhou, Guangdong, Peoples R China. [Sakakura, Koichi] Gunma Univ, Grad Sch Med, Dept Otolaryngol Head & Neck Surg, Gunma, Japan. [Sato, Miyuki] Gunma Univ, Lab Mol Membrane Biol, Inst Mol & Cellular Regulat, Gunma, Japan. [Sato, Ken] Gunma Univ, Lab Mol Traff, Inst Mol & Cellular Regulat, Gunma, Japan. [Bravo-San Pedro, Jose M.; Galluzzi, Lorenzo; Izzo, Valentina; Pietrocola, Federico; Sica, Valentina] Gustave Roussy Canc Campus, Villejuif, France. [Kroemer, Guido] Gustave Roussy Comprehens Canc Ctr, Villejuif, France. [Chouaib, Salem; Mami-Chouaib, Fathia] Inst Gustave Roussy, Villejuif, France. [Kim, Deok Ryong] Gyeongsang Natl Univ, Sch Med, Dept Biochem & Convergence Med Sci, JinJu, Gyeongsang, South Korea. [Kim, Deok Ryong] Inst Hlth Sci, JinJu, South Korea. [Leibowitz, Gil] Hadassah Hebrew Univ, Med Ctr, Endocrinol & Metab Serv, Dept Med, Jerusalem, Israel. [Kakhlon, Or] Hadassah Hebrew Univ, Med Ctr, Dept Neurol, Jerusalem, Israel. [Kang, Tae-Cheon] Hallym Univ, Dept Anat & Neurobiol, Coll Med, Kangwon Do, South Korea. [Choi, Eun-Kyoung] Hallym Univ, Dept Biomed Gerontol, Chunchon, Kangwon Do, South Korea. [Kim, Yong-Sun] Hallym Univ, Dept Microbiol, Coll Med, Chunchon, Gangwon, South Korea. [Ko, Young Ho] Hallym Univ, Ilsong Inst Life Sci, Chunchon, South Korea. [Suh, Sang Won] Hallym Univ, Sch Med, Dept Physiol, Chunchon, South Korea. [Azad, Neelam; Iyer, Anand Krishnan V.] Hampton Univ, Dept Pharmaceut Sci, Sch Pharm, Hampton, VA 23668 USA. [Yang, Yi] Hangzhou Normal Univ, Dept Pharmacol, Sch Med, Hangzhou, Zhejiang, Peoples R China. [Behrens, Georg M. N.] Hannover Med Sch, Dept Clin Immunol & Rheumotol, Hannover, Germany. [Gaestel, Matthias; Menon, Manoj B.] Hannover Med Sch, Dept Biochem, Hannover, Germany. [Thum, Thomas] Hannover Med Sch, Inst Mol & Translat Therapeut Strategies IMTTS, Hannover, Germany. [Bae, Ok-Nam] Hanyang Univ, Coll Pharm, Ansan, South Korea. [Wang, Dong] Harbin Med Univ, Coll Bioinformat Sci & Technol, Harbin, Heilongjiang, Peoples R China. [Xu, Hongwei] Harbin Med Univ, Dept Immunol, Heilongjiang Prov Key Lab Infect & Immun, Harbin, Peoples R China. [Chou, Tsui-Fen] Harbor UCLA Med Ctr, Torrance, CA 90509 USA. [Chou, Tsui-Fen] Los Angeles Biomed Res Inst, Div Med Genet, Dept Pediat, Torrance, CA USA. [Geng, Jiefei; Xavier, Ramnik J.] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Xavier, Ramnik J.] Broad Inst, Boston, MA USA. [Kang, Chanhee] Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Genet,Div Genet, Boston, MA 02115 USA. [Kimmelman, Alec C.; Mancias, Joseph D.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. [Mancias, Joseph D.] Beth Israel Deaconess Med Ctr, Dept Radiat Oncol, Boston, MA 02215 USA. [Harper, J. Wade; Yuan, Junying] Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA 02115 USA. [Irazoqui, Javier E.] Harvard Univ, Sch Med, Lab Comparat Immunol,Massachusetts Gen Hosp, Ctr Study Inflammatory Bowel Dis,Res Inst, Boston, MA 02115 USA. [Narendra, Derek P.] Harvard Univ, Sch Med, Neurol Residency Program, Brigham & Womens Hosp, Boston, MA 02115 USA. [Narendra, Derek P.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Notomi, Shoji; Vavvas, Demetrios G.] Harvard Univ, Sch Med, Ophthalmol, Boston, MA 02115 USA. [Airoldi, Edoardo M.] Harvard Univ, Dept Stat, Cambridge, MA 02138 USA. [Yuan, Zhi-Min] Harvard Univ, Sch Publ Hlth, Dept Genet & Complex Dis, Boston, MA 02115 USA. [Sarrias, Maria Rosa] Hlth Res Inst Germans Trias Pujol, Badalona, Spain. [Abeliovich, Hagai] Hebrew Univ Jerusalem, Fac Agr Food & Environm Biochem & Food Sci, IL-76100 Rehovot, Israel. [Rasse, Tobias M.] Heidelberg Univ, Deutsch Krebsforschungszentrum, Proteostasis Neurodegenerat Dis B180, CHS Res Grp CellNetworks, Heidelberg, Germany. [Schuck, Sebastian] Heidelberg Univ, Zentrum Mol Biol Univ Heidelberg ZMBH, Heidelberg, Germany. [Ventura, Natascia] Univ Dusseldorf, Inst Clin Chem, Dusseldorf, Germany. [Ventura, Natascia] Diagnost Lab, Fac Med, Dusseldorf, Germany. [Willbold, Dieter] Univ Dusseldorf, Inst Phys Biol, Dusseldorf, Germany. [Stork, Bjoern] Univ Dusseldorf, Inst Mol Med, Dusseldorf, Germany. [Schmitz, Ingo] Helmholtz Ctr Infect Res, Syst Oriented Immunol & Inflammat Res, Braunschweig, Germany. [Korhonen, Laura] Univ Helsinki, Cent Hosp, Fac Med, Div Child Psychiat, Helsinki, Finland. [Screen, Mark] Univ Helsinki, Dept Med Genet, Helsinki, Finland. [Zhou, Guang-Zhou] Henan Univ Technol, Coll Bioengn, Zhengzhou 450000, Henan Province, Peoples R China. [Tanji, Kunikazu] Hirosaki Univ, Grad Sch Med, Hirosaki, Aomori, Japan. [Yamada, Takahiro] Hokkaido Univ, Grad Sch Med, Dept Obstet & Gynecol, Sapporo, Hokkaido, Japan. [Kihara, Akio] Hokkaido Univ, Fac Pharmaceut Sci, Kita 12, Sapporo, Hokkaido 060, Japan. [Ubukata, Makoto] Hokkaido Univ, Res Fac Agr, Sapporo, Hokkaido, Japan. [Li, Min; Song, Ju-Xian] Hong Kong Baptist Univ, Sch Chinese Med, Kowloon, Hong Kong, Peoples R China. [Law, Helen Ka-wai; Siu, Parco M.] Hong Kong Polytech Univ, Dept Hlth Technol & Informat, Fac Hlth & Social Sci, Kowloon, Hong Kong, Peoples R China. [Ip, Nancy Y.] Hong Kong Univ Sci & Technol, Kowloon, Hong Kong, Peoples R China. [Rautou, Pierre-Emmanuel] Hop Beaujon, Paris, France. [Kroemer, Guido] Hop Europeen Georges Pompidou, AP HP, Paris, France. [Cerella, Claudia; Radogna, Flavia] Hop Kirchberg, Lab Biol Mol & Cellulaire Canc, Luxembourg, Luxembourg. [Lemoine, Antoinette] Hop Univ Paris Sud Biochim & Oncogenet, Hop Paul Brousse, Villejuif, France. [Brumell, John H.] Hosp Sick Children, 555 Univ Ave, Toronto, ON M5G 1X8, Canada. [Mena, Maria A.] Hosp Univ Ramon Cajal, CIBERNED, Dept Neurobiol, Madrid, Spain. [Frigo, Daniel E.] Houston Methodist Res Inst, Genom Med Program, Houston, TX USA. [Kang, Chanhee] Howard Hughes Med Inst, Boston, MA 02115 USA. [Levine, Beth] Howard Hughes Med Inst, Dallas, TX USA. [Yan, Xianghua] Huazhong Agr Univ, Coll Anim Sci & Technol, Wuhan, Hubei, Peoples R China. [Jiang, Yongjun; Liu, Xueqin] Huazhong Agr Univ, Dept Aquat Anim Med, Coll Fisheries, Wuhan, Peoples R China. [Liu, Zexian; Xue, Yu] Huazhong Univ Sci & Technol, Dept Biomed Engn, Coll Life Sci & Technol, Wuhan 430074, Hubei, Peoples R China. [Kaparakis-Liaskos, Maria] Ctr Innate Immun & Infect Dis, Hudson Inst Med Res, Melbourne, Vic, Australia. [Shen, Chiung-Chyi] Hungkuang Univ, Dept Phys Therapy, Taichung, Taiwan. [Aranda, Agustin] Inst Agrochem & Food Technol, IATA CSIC, Paterna, Valencia, Spain. [Menezes, Regina; dos Santos, Claudia Nunes] Inst Biol Expt & Tecnol, iBET, Oeiras, Portugal. [Huang, Yong] Icahn Sch Med Mt Sinai, Dept Neurosci, New York, NY 10029 USA. [Cederbaum, Arthur I.] Icahn Sch Med Mt Sinai, Dept Pharmacol & Syst Therapeut, New York, NY 10029 USA. [Gandy, Sam] Icahn Sch Med Mt Sinai, Dept Neurol, Ctr Cognit Hlth, Mt Sinai Alzheimers Dis Res Ctr, New York, NY 10029 USA. [Gandy, Sam] Icahn Sch Med Mt Sinai, Dept Psychiat, Ctr Cognit Hlth, Mt Sinai Alzheimers Dis Res Ctr, New York, NY 10029 USA. [Yue, Zhenyu] Icahn Sch Med Mt Sinai, Friedman Brain Inst, New York, NY 10029 USA. [Wu, Defeng] Icahn Sch Med Mt Sinai, New York, NY 10029 USA. [Le Cam, Laurent] Inst Rech Cancerol Montpellier, ICM, Montpellier, France. [Pujol, Aurora] ICREA Catalan Inst Res & Adv Studies, Catalonia, Spain. [Vaccari, Thomas] FIRC Inst Mol Oncol, IFOM, Milan, Italy. [Sonawane, Avinash] IIT Univ, Sch Biotechnol, Bhubaneswar, Orissa, India. [Barreiro, Esther] Pompeu Fabra Univ, Barcelona Biomed Res Pk, Dept Resp Med, Lung Canc & Muscle Res Grp,IMIM Hosp Mar CIBERES, Barcelona, Spain. [Thurston, Teresa L. M.] Univ London Imperial Coll Sci Technol & Med, MRC Ctr Mol Bacteriol & Infect, London, England. [Braga, Vania M. M.] Univ London Imperial Coll Sci Technol & Med, Natl Heart & Lung Inst, London, England. [de Belleroche, Jackie] Univ London Imperial Coll Sci Technol & Med, Neurogenet Grp, Div Brain Sci, London, England. [Mostowy, Serge] Univ London Imperial Coll Sci Technol & Med, Microbiol Sect, MRC Ctr Mol Bacteriol & Infect, London, England. [Lee, Michael] Incheon Natl Univ, Div Life Siences, Inchon, South Korea. [Balaji, Kithiganahalli Narayanaswamy] Indian Inst Sci, Dept Microbiol & Cell Biol, Bangalore 560012, Karnataka, India. [Somasundaram, Kumaravel] Indian Inst Sci Microbiol & Cell Biol, Bangalore, Karnataka, India. [Dubey, Vikash Kumar] Indian Inst Technol, Dept Biosci & Bioengn, Gauhati, Assam, India. [Maiti, Tapas K.] Indian Inst Technol, Dept Biotechnol, Kharagpur 721302, W Bengal, India. [Justice, Matthew J.] Indiana Univ Sch Med, Biochem & Mol Biol, Denver, CO USA. [Dong, X. Charlie; Roach, Peter J.] Indiana Univ Sch Med, Dept Biochem & Mol Biol, Indianapolis, IN 46202 USA. [Naidu, Samisubbu R.] Indiana Univ Sch Med, Dept Dermatol, Indianapolis, IN 46202 USA. [Broxmeyer, Hal E.] Indiana Univ Sch Med, Dept Microbiol & Immunol, Indianapolis, IN 46202 USA. [Boulton, Michael E.] Indiana Univ Sch Med, Dept Ophthalmol, Indianapolis, IN 46202 USA. [Khambu, Bilon; Yin, Xiao-Ming] Indiana Univ Sch Med, Dept Pathol & Lab Med, Indianapolis, IN 46202 USA. [Lahm, Tim] Indiana Univ Sch Med, Richard L Roudebush VA Med Ctr, Div Pulm, Crit Care Sleep & Occupat Med, Indianapolis, IN 46202 USA. [Hong, Yonggeun] Inje Univ, Dept Rehabil Sci, Coll Biomed Sci & Engn, u HARC, Gimhae, South Korea. [Corazzari, Marco] INMI IRCCS L Spallanzani, Rome, Italy. [Bruhat, Alain] Ctr Clermont Theix, INRA, Nutr Humaine UMR 1019, St Genes Champanelle, France. [Favier, Francois B.] INRA, Dynam Musculaire & Metab UMR866, F-34060 Montpellier, France. [Seiliez, Iban] INRA, UR1067, Nutr Metab Aquaculture, St Pee Sur Nivelle, France. [Luciano, Federic] INSERM, U1065, C3M, Team 2, Nice, France. [Belaid, Amine; Brest, Patrick; Mograbi, Baharia] IRCAN, INSERM, U1081, CNRS UMR7284, Nice, France. [Giuliano, Sandy] Ctr Sci Monaco, Biomed Dept, Monaco, Monaco. [Giuliano, Sandy; Pages, Gilles] Univ Nice Sophia Antipolis, Inst Res Canc & Ageing Nice, CNRS UMR 7284, INSERM U1081, F-06189 Nice, France. [Dupuis, Luc] INSERM, U1118, Mecanismes Cent & Periphet Neurodegenerescence, Strasbourg, France. [Kepp, Oliver; Torriglia, Alicia] INSERM, U1138, Paris, France. [Pallet, Nicolas] INSERM, U1147, Paris, France. [Mechta-Grigoriou, Fatima] Inst Curie, INSERM U830, Stress & Canc Lab, Paris, France. [Benard, Giovanni] INSERM U862, Neuroctr Magendie, Bordeaux, France. [Le Cam, Laurent] INSERM U896, Montpellier, France. [Duran, Raul V.; Villar, Victor H.] Univ Bordeaux, INSERM U916, Inst Europeen Chim & Biol, Pessac, France. [Teixeira-Clerc, Fatima] INSERM U955, Fac Med Creteil, UMR S955, Creteil, France. [Laporte, Jocelyn; Nicot, Anne-Sophie] Univ Strasbourg, INSERM U964, CNRS UMR7104, Dept Translat Med,IGBMC, Illkirch Graffenstaden, France. [Andrieu-Abadie, Nathalie] Ctr Rech Cancerol Toulouse, INSERM UMR1037, Toulouse, France. [Dugail, Isabelle] INSERM UMRS 1166, Unite Rech Malad Cardiovasc Metab & Nutr, Paris, France. [Kroemer, Guido] INSERM, Cordeliers Res Canc, Paris, France. [Bulavin, Dmitry V.] INSERM, UMR CNRS 7284 U1081, Nice, France. [Gatti, Evelina; Pierre, Philippe] INSERM, U1104, Marseille, France. [Corti, Olga] INSERM, U1127, CNRS, UMR 7225, Paris, France. [Bravo-San Pedro, Jose M.; Galluzzi, Lorenzo; Izzo, Valentina; Pietrocola, Federico; Sica, Valentina] INSERM, U1138, Paris, France. [Rautou, Pierre-Emmanuel] INSERM, U970, Paris, France. [Roue, Gael] IDIBAPS, Hemato Oncol Dept, Barcelona, Spain. [Francois, Aurelie] Inst Cancerol Lorraine, Vandoeuvre Les Nancy, France. [Le Cam, Laurent] Inst Canc Montpellier, Montpellier, France. [Fiorito, Filomena] Ist Zooprofilattico Sperimentale Mezzogio, Dept Chem, Naples, Italy. [Echard, Arnaud] Inst Pasteur, CNRS URA2582, Cell Biol & Infect Dept, Membrane Traff & Cell Div Lab, Paris, France. [Lafont, Frank] Univ Lille, Ctr Infect & Immun Lille, Inst Pasteur Lille, CNRS,INSERM,Lille Reg Univ Hosp Ctr, Lille, France. [Colucci-Guyon, Emma] Inst Pasteur, CNRS, URA2578, Unite Macrophages & Dev Immunite,Dept Biol Dev &, Paris, France. [Albert, Matthew L.] Inst Pasteur, Dept Immunol, Paris, France. [Lecuit, Marc] Inst Pasteur, INSERM, Biol Infect Unit, Paris, France. [Papackova, Zuzana] Inst Clin & Expt Med, Ctr Med Expt, Dept Metab & Diabet, Prague, Czech Republic. [Bianchi, Michele Wolfe] Univ Paris Saclay, Inst Integrat Biol Cell, Gif Sur Yvette, France. [Zorzano, Antonio] Barcelona Inst Sci & Technol, Inst Res Biomed IRB Barcelona, Barcelona, Spain. [Triola, Gemma] Spanish Res Council IQAC CSIC, Inst Adv Chem Catalonia, Dept Biomed Chem, Barcelona, Spain. [Ryabovol, Victoria] Inst Biochem & Biophys, Kazan, Russia. [Almonte-Beceril, Maylin] Inst Biomed Invest INIBIC, Inflamat & Regenerat Med, Coruna, Spain. [Jones, Chris] Inst Canc Res, Div Mol Pathol & Canc Therapeut, London SW3 6JB, England. [Zhivotovsky, Boris] Karolinska Inst, Inst Environm Med, Div Toxicol, Stockholm, Sweden. [Chauhan, Santosh] Inst Life Sci, Bhubaneswar, Odisa, India. [Ishaq, Mohammad] Inst Microbial Technol IMTECH, Cell Biol & Immunol Div, Chandigarh, India. [Vachova, Libuse] Inst Microbiol ASCR, Vvi, Prague, Czech Republic. [Penninger, Josef M.] Austrian Acad Sci, IMBA, Inst Mol Biotechnol, A-1010 Vienna, Austria. [Scovassi, A. Ivana] CNR, Inst Mol Genet, Pavia, Italy. [Stulik, Jiri] FMHS UO, Inst Mol Pathol & Biol, Hradec Kralove, Czech Republic. [Stepkowski, Tomasz M.] Ctr Radiobiol & Biol Dosimetry, Inst Nucl Chem & Technol, Dorodna, Poland. [Vescovi, Eleonora Garcia] Inst Biol Mol & Celular Rosario IBR CONICET, Rosario, Argentina. [Lazo, Pedro A.] Hosp Univ Salamanca, Inst Invest Biomed Salamanca IBSAL, Salamanca, Spain. [Martin-Sanz, Paloma] Ctr Invest Biomed Red Enfermedade Hepat & Digest, Inst Invest Biomed Albert Sols, CSIC UAM, Madrid, Spain. [Valverde, Angela M.] CSIC UAM, Inst Invest Biomed Albert Sols, Madrid, Spain. [Fernandez-Checa, Jose C.] CSIC IDI BAPS, Inst Invest Biomed Barcelona, Barcelona, Spain. [Fernandez-Checa, Jose C.] CIBEREHD, ISCIII, Ctr Invest Red Enfermedades Hepat & Digest, Barcelona, Spain. [Oliver, F. Javier] CSIC, IPBLN, Granada, Spain. [Menezes, Regina; dos Santos, Claudia Nunes] Univ Nova Lisboa, Inst Tecnol Quim & Biol Antonio Xavier, P-2780156 Oeiras, Portugal. [Moita, Luis Ferreira] Inst Gulbenkian Ciencias, Oeiras, Portugal. [Garcia-Ruiz, Carmen] Hosp Clin Barcelona IDIBAPS, Inst Invest Biomed Barcelona IIBB CSIC, Liver Unit, Barcelona, Spain. [Garcia-Ruiz, Carmen] CIBEREHD, Barcelona, Spain. [Wappner, Pablo] Inst Leloir, Buenos Aires, DF, Argentina. [Alonso, Covadonga; Galindo, Inmaculada; Munoz-Moreno, Raquel] Inst Nacl Invest & Tecnol Agr & Alimentaria INIA, Dept Biotecnol, Madrid, Spain. [Perez-de la Cruz, Veronica] Inst Nacl Neurol & Neurocirug, Neurochem Unit, Mexico City, DF, Mexico. [Pineda, Benjamin] Inst Nacl Neurol & Neurocirug, Neuroimmunol & Neuro Oncol Unit, Mexico City, DF, Mexico. [Menna-Barreto, Rubem F. S.] Fiocruz MS, Inst Oswaldo Cruz, Lab Biol Celular, BR-21045900 Rio De Janeiro, Brazil. [Chandra, Pallavi; Kumar, Dhiraj] Int Ctr Genet Engn & Biotechnol, Immunol Grp, New Delhi, India. [Kanthasamy, Anumantha G.] Iowa State Univ, Dept Biomed Sci, Iowa Ctr Adv Neurotoxicl, Ames, IA USA. [Bassham, Diane C.] Iowa State Univ, Dept Genet Dev & Cell Biol, Ames, IA USA. [MacIntosh, Gustavo C.] Iowa State Univ, Roy J Carver Dept Biochem Biophys & Mol Biol, Ames, IA USA. [Fusco, Carmela; Merla, Giuseppe; Micale, Lucia] IRCCS Casa Sollievo Sofferenza, Med Genet Unit, San Giovanni Rotondo, FG, Italy. [Fornai, Francesco; Sciarretta, Sebastiano] IRCCS Neuromed, Pozzilli, IS, Italy. [Ferraro, Elisabetta] IRCCS San Raffaele Pisana, Lab Skeletal Muscle Dev & Metab, Rome, Italy. [Cecconi, Francesco; D'Amelio, Marcello; Molinari, Marco; Viscomi, Maria Teresa] IRCCS Santa Lucia Fdn, Rome, Italy. [Campello, Silvia] IRCCS Santa Lucia Fdn, Dept Expt Neurosci, Rome, Italy. [Crippa, Valeria] IRCCS C Mondino Natl Neurol Inst, Expt Neurobiol Lab, Pavia, Italy. [Facchiano, Antonio] IRCCS, Ist Dermopatico Immacolata, Rome, Italy. [Cantoni, Lavinia] IRCCS Ist Ric Farmacol Mario Negri, Dept Mol Biochem & Pharmacol, Milan, Italy. [Albani, Diego] IRCCS Ist Ric Farmacol Mario Negri, Dept Neurosci, Milan, Italy. [Matarese, Giuseppe] IRCCS MultiMed, Milan, Italy. [Marin, Concepcio] Inst Invest Biomed August Pi & Sunyer IDIBAPS, IRCE, Barcelona, Spain. [Gongora, Celine] INSERM, IRCM, Inst Rech Cancerol Montpellier, U896, Montpellier, France. [Pattingre, Sophie] IRCM, Inst Rech Cancerol Montpellier, Montpellier, France. [Cottet, Sandra; Schorderet, Daniel F.] IRO, Inst Res Ophthalmol, Sion, Switzerland. [Chiariello, Mario; Colecchia, David] Ist Fisiol Clin, Siena, Italy. [Bachetti, Tiziana; Ceccherini, Isabella] UOC Med Genet, Ist Giannina Gaslini, Genoa, Italy. [Grimaldi, Benedetto] Ist Italiano Tecnol, Dept Drug Discovery & Dev, Lab Mol Med, Genoa, Italy. [Giovannetti, Elisa] Univ Pisa, AIRC Start UP Unit, Canc Pharmacol Lab, Pisa, Italy. [Merlini, Luciano] Ist Ortopedico Rizzoli IOR IRCCS, Lab Musculoskeletal Cell Biol, Bologna, Italy. [Ortona, Elena; Pierdominici, Marina] Ist Super Sanita, Dept Cell Biol & Neurosci, Viale Regina Elena 299, I-00161 Rome, Italy. [Salvioli, Rosa] Ist Super Sanita, Dept Haematol Oncol & Mol Med, Viale Regina Elena 299, I-00161 Rome, Italy. [Coccia, Eliana M.] Ist Super Sanita, Dept Infect Parasit & Immunomediated Dis, Viale Regina Elena 299, I-00161 Rome, Italy. [Matarrese, Paola] Ist Super Sanita, Dept Therapeut Res & Med, Evaluat Sect Cell Aging Degenerat & Gender Med, Viale Regina Elena 299, I-00161 Rome, Italy. [Giammarioli, Anna Maria; Malorni, Walter] Ist Super Sanita, Viale Regina Elena 299, I-00161 Rome, Italy. [Chiariello, Mario; Colecchia, David] Ist Toscano Tumori, Siena, Italy. [Condello, Maria; Meschini, Stefania] Italian Natl Inst Hlth, Dept Technol & Hlth, Rome, Italy. [Schiavi, Alfonso; Ventura, Natascia] IUF Leibniz Res Inst Environm Med, Dusseldorf, Germany. [Stoka, Veronika; Turk, Boris; Turk, Vito] Jozef Stefan Inst, Dept Biochem & Mol & Struct Biol, Ljubljana, Slovenia. [Karmakar, Parimal] Jadavpur Univ, Life Sci & Biotechnol, Kolkata, W Bengal, India. [Gandy, Sam] James J Peters VA Med Ctr, Bronx, NY USA. [Saran, Shweta] Jawaharlal Nehru Univ, Sch Life Sci, New Delhi 110067, India. [Platanias, Leonidas C.] Jesse Brown VA Med Ctr, Dept Med, Chicago, IL USA. [Song, Wei] McGill Univ, Jewish Gen Hosp, Bloomfield Ctr Res Aging, Lady Davis Inst Med Res, Montreal, PQ H3T 1E2, Canada. [Schipper, Hyman M.] McGill Univ, Jewish Gen Hosp, Dept Neurol & Neurosurg, Dept Med, Montreal, PQ H3T 1E2, Canada. [Topisirovic, Ivan] McGill Univ, Jewish Gen Hosp, Dept Oncol, Montreal, PQ H3T 1E2, Canada. [Yu, Huixin; Zhang, Li] Jiangsu Inst Nucl Med, Wuxi, Jiangsu, Peoples R China. [Su, Zhaoliang] Jiangsu Univ, Dept Immunol, Zhenjiang, Jiangsu, Peoples R China. [Guo, Wenjie] Jiangsu Univ, Sch Pharm, Zhenjiang, Jiangsu, Peoples R China. 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[Kominami, Eiki] Juntendo Univ, Tokyo, Japan. [Hasui, Kazuhisa] Kagoshima Univ, Grad Sch Med & Dent Sci, Div Human Pathol, Dept Oncol,Course Adv Therapeut, Kagoshima 890, Japan. [Setoguchi, Takao] Kagoshima Univ, Near Future Locomoter Organ Med Creat Course, Grad Sch Med & Dent Sci, Kagoshima 890, Japan. [Lee, Gyun Min] Korea Adv Inst Sci & Technol, Dept Biol Sci, Daejon, South Korea. [Okazaki, Toshiro] Kanazawa Med Univ, Dept Med, Kanazawa, Ishikawa, Japan. [Koya, Daisuke] Kanazawa Med Univ, Diabetol & Endocrinol, Kanazawa, Ishikawa, Japan. [Sasaki, Motoko] Kanazawa Univ, Grad Sch Med Sci, Dept Human Pathol, Kanazawa, Ishikawa, Japan. [Wong, Richard W.] Kanagawa Univ, Cell Bion Unit, Dept Biol, Fac Nat Syst,Inst Sci & Engn, Kanagawa, Ishikawa, Japan. [Wong, Richard W.] Kanagawa Univ, Lab Mol & Cellular Biol, Dept Biol, Fac Nat Syst,Inst Sci & Engn, Kanagawa, Ishikawa, Japan. [Lee, Stella Y.; Roelofs, Jeroen] Kansas State Univ, Div Biol, Manhattan, KS 66506 USA. 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[Takigawa, Nagio] Kawasaki Med Univ, Dept Gen Internal Med 4, Okayama, Japan. [Hino, Keisuke] Kawasaki Med Univ, Dept Hepatol & Pancreatol, Kurashiki, Okayama, Japan. [Kwon, Taeg Kyu] Keimyung Univ, Daegu, South Korea. [Jang, Byoung Kuk] Keimyung Univ, Sch Med, Div Gastroenterol & Hepatol, Dept Internal Med, Daegu, South Korea. [Ishii, Isao] Keio Univ, Grad Sch Pharmaceut Sci, Dept Biochem, Tokyo, Japan. [Suzuki, Hidekazu] Keio Univ, Sch Med, Med Educ Ctr, Tokyo, Japan. [Alloza, Iraide] Basque Fdn Sci, KERBASQUE, Bilbao, Spain. [Harrath, Abdel Halim] King Saud Univ, Coll Sci, Dept Zool, Riyadh 11451, Saudi Arabia. [Otsu, Kinya] Kings Coll London, Cardiovasc Div, London WC2R 2LS, England. [Fanto, Manolis; Jungbluth, Heinz] Kings Coll London, Dept Basic & Clin Neurosci, IoPPN, London WC2R 2LS, England. [Jungbluth, Heinz] Kings Coll London, Randall Div Cell & Mol Biophys, Muscle Signalling Sect, London, England. [Shintani, Michiko] Kobe Univ, Grad Sch Hlth Sci, Pathol Lab, Div Med Biophys, Kobe, Hyogo, Japan. [Matsushita, Takehiko] Kobe Univ, Grad Sch Med, Dept Orthopaed Surg, Kobe, Hyogo, Japan. [Voitsekhovskaja, Olga V.] Komarov Bot Inst RAS, Plant Ecol Physiol Lab, St Petersburg, Russia. [Cho, Ssang-Goo] Konkuk Univ, Dept Anim Biotechnol, Seoul, South Korea. [Lim, Hyunjung Jade] Konkuk Univ, Dept Vet Med, Seoul, South Korea. [Chung, Hyewon] Konkuk Univ, Sch Med, Dept Ophthalmol, Seoul, South Korea. [Lee, He-Jin] Konkuk Univ, Sch Med, Dept Anat, Seoul, South Korea. [Kim, Cheol Hyeon] Korea Canc Ctr Hosp, Dept Internal Med, Seoul, South Korea. [Lee, Sung-Joon] Korea Univ, Dept Biotechnol, PLUS Grad Sch Life Sci & Biotechnol BK21, Seoul, South Korea. [Chi, Sung-Gil; Choi, Eui-Ju; Lee, Jae Keun; Wright, Karen L.] Korea Univ, Dept Life Sci & Biotechnol, Seoul, South Korea. [Chun, Taehoon] Korea Univ, Dept Biotechnol, Coll Life Sci & Biotechnol, Seoul, South Korea. [Park, Ohkmae K.; Song, Hyun Kyu] Korea Univ, Div Life Sci, Seoul, South Korea. [Van Den Bosch, Ludo] Katholieke Univ Leuven, Leuven, Belgium. [Van Den Bosch, Ludo] VIB, Vesalius Res Ctr, Neurobiol Lab, Leuven, Belgium. [Gunst, Jan; Van den Berghe, Greet; Vanhorebeek, Ilse] Katholieke Univ Leuven, Clin Div, Leuven, Belgium. [Gunst, Jan; Van den Berghe, Greet; Vanhorebeek, Ilse] Lab Intens Care Med, Dept Cellular & Mol Med, Leuven, Belgium. [Decuypere, Jean-Paul] Katholieke Univ Leuven, Dept Abdominal Transplant Surg, Leuven, Belgium. [Martin, Shaun] Katholieke Univ Leuven, Dept Cellular & Mol Med, Leuven, Belgium. [Soenen, Stefaan J.] Katholieke Univ Leuven, Dept Imaging & Pathol, Leuven, Belgium. [Agostinis, Patrizia; Maes, Hannelore] Katholieke Univ Leuven, Lab Cell Death Res & Therapy, Dept Cellular & Mol Med, Campus Gasthuisberg, Leuven, Belgium. [Bultynck, Geert; Parys, Jan B.] Katholieke Univ Leuven, Lab Mol & Cellular Signaling, Dept Cellular & Mol Med, Leuven, Belgium. [Ohmuraya, Masaki] Kumamoto Univ, Inst Resource Dev & Anal, Kumamoto, Japan. [Agam, Galila] Kunming Univ Sci & Technol, Sch Med, Kunmimg, Yunnan, Peoples R China. [Tanaka, Masaki; Watanabe, Yoshihisa] Kyoto Prefectural Univ Med, Dept Basic Geriatr, Kyoto, Japan. [Matoba, Satoaki] Kyoto Prefectural Univ Med, Dept Cardiovasc Med, Grad Sch Med Sci, Kyoto, Japan. [Nagata, Kazuhiro] Kyoto Sangyo Univ, Dept Life Sci, Kyoto 603, Japan. [Ushioda, Ryo] Kyoto Sangyo Univ, Dept Mol Biosci, Fac Life Sci, Kyoto 603, Japan. [Goto-Yamada, Shino] Kyoto Univ, Dept Bot, Kyoto, Japan. [Shioi, Tetsuo] Kyoto Univ, Dept Cardiovasc Med, Kyoto, Japan. [Asanuma, Katsuhiko] Kyoto Univ, Grad Sch Med, Med Innocat Ctr TMK Project, Kyoto, Japan. [Cho, Dong-Hyung] Kyung Hee Univ, Grad Sch East Wast Med Sci, Seoul, South Korea. [Bae, Jae-Sung] Kyungpook Natl Univ, Dept Physiol, Sch Med, Daegu, South Korea. [Shirabe, Ken] Kyushu Univ, Dept Surg & Sci, Fukuoka 812, Japan. [Fairlie, W. Douglas; Lee, Erinna F.] Olivia Newton John Canc Res Inst, Melbourne, Vic, Australia. [Soo, Kai Y.] La Trobe Univ, Dept Biochem & Genet, La Trobe Inst Mol Sci, Melbourne, Vic, Australia. [Fairlie, W. Douglas; Lee, Erinna F.] La Trobe Univ, Dept Chem & Phys, Melbourne, Vic, Australia. [Fairlie, W. Douglas; Lee, Erinna F.] La Trobe Univ, Sch Canc Med, Melbourne, Vic, Australia. [Paganetti, Paolo] Neurodegenerat Grp, Lab Biomed Neurosci NSI EOC, Torricella Taverne, Switzerland. [Nilsson, Per] RIKEN, Brain Sci Inst, Lab Proteolyt Neurosci, Wako, Saitama, Japan. [Choi, Eun-Kyoung] Ilsong Inst Life Sci, Lab Cellular Aging & Neurodegenerat, Anyang, Gyeonggi Do, South Korea. [Mayer, Andreas] Univ Lancaster, Fac Hlth & Med, Div Biomed & Life Sci, Lancaster, England. [Erenpreisa, Jekaterina] Latvian Biomed Res & Study Ctr, Riga, Latvia. [Spaink, Herman P.] Leiden Univ, Inst Biol, Leiden, Netherlands. [Stern, Stephan T.] Leidos Biomedical Res Inc, Frederick Natl Lab Canc Res, Nanotechnol Characterizat Lab, Canc Res Technol Program, Frederick, MD USA. [Los, Marek] Med Univ Silesia, ENT Dept, Sch Med, Katowice, Poland. [Kagedal, Katarina; Mohseni, Simin; Ollinger, Karin] Linkoping Univ, Dept Clin & Expt Med, Linkoping, Sweden. [Kurz, Tino] Linkoping Univ, Dept Med & Hlth Sci, Linkoping, Sweden. [Boman, Andrea] Linkoping Univ, Expt Pathol, Dept Clin & Expt Med, Fac Hlth Sci, Linkoping, Sweden. [Taylor, Mark J.] Univ Liverpool, Liverpool Sch Trop Med, Dept Parasitol, Liverpool L3 5QA, Merseyside, England. [Shajahan-Haq, Ayesha N.] Georgetown Univ, Med Ctr, Dept Oncol, Lombardi Comprehens Canc Ctr, Washington, DC 20007 USA. [Zhivotovsky, Boris] Lomonosov Moscow State Univ, Fac Basic Med, Moscow, Russia. [Tooze, Sharon A.] Canc Res UK, London Res Inst, London, England. [Swanton, Charles] UCL, Inst Canc, London, England. [Rihn, Bertrand H.] Lorraine Univ, CITHeFOR EA3452, Fac Pharm, Nancy, France. [Adler, Sharon G.] Harbor UCLA Med Ctr, Los Angeles Biomed Res Inst, Torrance, CA 90509 USA. [Huang, Shile] Louisiana State Univ, Hlth Sci Ctr, Dept Biochem & Mol Biol, Shreveport, LA 71105 USA. [Wu, Chunlai] Louisiana State Univ, Hlth Sci Ctr, Neurosci Ctr Excellence, New Orleans, LA 71105 USA. [Lin, Yong] Lovelace Resp Res Inst, Mol Biol & Lung Canc Program, Albuquerque, NM USA. [von Schwarzenberg, Karin] Univ Munich, Dept Pharm, Munich, Germany. [Swaerd, Karl] Lund Univ, Biomed Ctr, Dept Expt Med Sci, Lund, Sweden. [Berchem, Guy] Luxembourg Inst Hlth, Luxembourg, Luxembourg. [Berchem, Guy] Ctr Hosp Luxembourg, Luxembourg, Luxembourg. [Janji, Bassam] Luxembourg Inst Hlth, Lab Expt Hemato Oncol, Dept Oncol, Luxembourg, Luxembourg. [El-Khoury, Victoria] Luxembourg Inst Hlth, Dept Oncol, Luxembourg, Luxembourg. 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[Tan, Mei Lan] Malaysian Inst Pharmaceut & Nutraceuticals, George Town, Malaysia. [Rudolf, Ruediger; Wild, Franziska] Mannheim Univ Appl Sci, Inst Mol & Cell Biol, Mannheim, Germany. [Slaninova, Iva] Masaryk Univ, Dept Biol, Fac Med, Brno, Czech Republic. [Costes, Safia; Mao, Kai] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Costes, Safia] Harvard Univ, Sch Med, Ctr Human Genet Res, Boston, MA USA. [Costes, Safia] Dept Neurol, Boston, MA USA. [Goruppi, Sandro; Lee, Sam W.; Tannous, Bakhos A.] Massachusetts Gen Hosp, Charlestown, MA USA. [Goruppi, Sandro; Lee, Sam W.] Harvard Univ, Sch Med, Cutaneous Biol Res Ctr, Charlestown, MA USA. [Mao, Kai] Harvard Univ, Sch Med, Dept Mol Biol, Dept Genet, Boston, MA 02115 USA. [Tannous, Bakhos A.] Harvard Univ, Sch Med, Expt Therapeut & Mol Imaging Lab, Neurosci Ctr, Charlestown, MA USA. [Vyas, Jatin M.] Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA. [Amon, Angelika; Santaguida, Stefano] MIT, Koch Inst Integrat Canc Res, 77 Massachusetts Ave, Cambridge, MA 02139 USA. [Graef, Martin; Motori, Elisa] Max Planck Inst Biol Ageing, Cologne, Germany. [Storchova, Zuzana] Max Planck Inst Biochem, Grp Maintenance Genome Stabil, Klopferspitz 18A, D-82152 Martinsried, Germany. [Wollert, Thomas] Max Planck Inst Biochem, Mol Membrane & Organelle Biol, Klopferspitz 18A, D-82152 Martinsried, Germany. [Chowdhury, Kamal] Max Planck Inst Biophys Chem, Dept Mol Cell Biol, D-37077 Gottingen, Germany. [Gassen, Nils Christian; Rein, Theo] Max Planck Inst Psychiat, Translat Res Psychiat, Munich, Germany. [Schulze, Ryan J.] Mayo Clin, Dept Biochem, Rochester, MN USA. [Fiesel, Fabienne C.; Springer, Wolfdieter] Mayo Clin, Dept Neurosci, Jacksonville, FL 32224 USA. [Lerman, Lilach O.] Mayo Clin, Div Nephrol & Hypertens, Rochester, MN USA. [Sinicrope, Frank A.; Xu, Xiaolei] Mayo Clin, Rochester, MN USA. 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[Campbell, Matthew] Trinity Coll Dublin, Smurfit Inst Genet, Dublin, Ireland. [Chen, Ye-Guang; Liu, Yule; Wang, Yan] Tsinghua Univ, Sch Life Sci, Beijing 100084, Peoples R China. [Yu, Li] Tsinghua Univ, State Key Lab Biomembrane & Membrane Biotechnol, Tsing Hua Univ, Peking Univ,Joint Ctr Life Sci,Sch Life Sci, Beijing 100084, Peoples R China. [Lei, Jinzhi] Tsinghua Univ, Zhou Pei Yuan Ctr Appl Math, Beijing 100084, Peoples R China. [Taylor, Allen] Tufts Univ, USDA Human Nutr Res Ctr Aging, Boston, MA 02111 USA. [Dash, Srikanta] Tulane Univ, Hlth Sci Ctr, Dept Pathol & Lab Med, New Orleans, LA 70118 USA. [Simak, Jan] US FDA, Ctr Biol Evaluat & Res, Silver Spring, MD USA. [Rao, V. Ashutosh] US FDA, Ctr Drug Evaluat & Res, Silver Spring, MD USA. [Galadari, Sehamuddin] UAE Univ, Cell Signaling Lab, Dept Biochem, Coll Med & Hlth Sci, Abu Dhabi, U Arab Emirates. [Bjedov, Ivana] UCL Canc Inst, London, England. [Salomoni, Paolo] UCL Canc Inst, Samantha Dickson Brain Canc Unit, London, England. [Jacques, Thomas S.] UCL Inst Child Hlth, London, England. [Jacques, Thomas S.] Great Ormond St Hosp Children NHS Fdn Trust, London, England. [Lewis, Patrick A.] UCL Inst Neurol, Dept Mol Neurosci, London, England. [Manzoni, Claudia] UCL Inst Neurol, London, England. [Cheetham, Michael E.] UCL Inst Ophthalmol, London, England. [Guo, Ming] Univ Calif Los Angeles, David Geffen Sch Med, Brain Res Inst, Los Angeles, CA 90095 USA. [Linden, Rafael] Univ Fed Rio de Janeiro, Inst Biofis Carlos Chagas Filho, Rio de Janeiro, Brazil. [Simmet, Thomas] Univ Ulm, Inst Pharmacol Nat Cpds & Clin Pharmacol, D-89069 Ulm, Germany. [Carlsson, Sven R.] Umea Univ, Dept Med Biochem & Biophys, Umea, Sweden. [Kaeffer, Bertrand] UMR 1280, Nantes, France. [Manie, Serge N.] CNRS, INSERM 1052, UMR 5286, Canc Res Ctr Lyon, Lyon, France. [Maiuri, Maria Chiara] Ctr Rech Cordeliers, UMRS 1138, Paris, France. [Gorbunov, Nikolai V.] Uniformed Serv Univ Hlth Sci, Dept Anesthesiol, Bethesda, MD 20814 USA. [Kiang, Juliann G.] Uniformed Serv Univ Hlth Sci, Radiat Combined Injury Program, Armed Forces Radiobiol Res Inst, Bethesda, MD 20814 USA. [Ozpolat, Bulent; Scovassi, A. Ivana; Stellrecht, Christine M.] Univ Texas MD Anderson Canc Ctr, Dept Expt Therapeut, Houston, TX 77030 USA. [Gonzalez, Carlos B.] Univ Austral Chile, Dept Physiol, Valdivia, Chile. [Diaz-Nido, Javier] Univ Autonoma Madrid, Ctr Biol Mol Severo Ochoa, CIBERER, Madrid, Spain. [Gargini, Ricardo] Univ Autonoma Madrid, CNB CSIC, Ctr Biol Mol Severo Ochoa, Dept Biol Mol, Madrid, Spain. [Cuezva, Jose M.] Univ Autonoma Madrid, Dept Biol Mol, Madrid, Spain. [Magarinos, Marta] Univ Autonoma Madrid, Dept Biol, Madrid, Spain. [Guillen, Carlos] Univ Complutense, Sch Pharm, E-28040 Madrid, Spain. [Guillen, Carlos] Inst Salud Carlos III, CIBER Diabet & Enfermedades Metab Olicas Asociada, Madrid, Spain. [Papademetrio, Daniela L.] Univ Buenos Aires, Inmunol, Fac Farm & Bioquim, Buenos Aires, DF, Argentina. [Cena, Valentin] Univ Castilla La Mancha, Albacete, Spain. [Jordan, Joaquin] Univ Castilla La Mancha, Fac Med, Dept Ciencias Med, Albacete, Spain. [Sanchez-Prieto, Ricardo] Univ Castilla La Mancha, Lab Oncol Mol, Ctr Reg Invest Biomed, Albacete, Spain. [Troncoso, Rodrigo] Univ Chile, Adv Ctr Chron Dis ACCDiS, Fac Ciencias Quim & Farmaceut, Santiago, Chile. [Chiong, Mario; Criollo, Alfredo; Lavandero, Sergio] Univ Chile, Adv Ctr Chron Dis ACCDiS, Santiago, Chile. [Diaz-Araya, Guillermo] Univ Chile, Fac Ciencias Quim & Farmaceut, Santiago, Chile. [Glavic, Alvaro] Univ Chile, Fac Ciencias, Dept Biol, Ctr Regulac Genoma, Santiago, Chile. [Troncoso, Rodrigo] Univ Chile, INTA, Santiago, Chile. [Corral-Ramos, Cristina; Di Pietro, Antonio; Roncero, M. Isabel G.; Ruiz-Roldan, Carmen] Univ Cordoba, Campus Excelencia Agroalimentario CeiA3, Dept Genet, Cordoba, Spain. [Mora-Rodriguez, Rodrigo] Univ Costa Rica, CIET, San Jose, Costa Rica. [Fuentes, Jose M.; Gomez-Sanchez, Ruben; Ana Gonzalez-Polo, Rosa; Niso-Santano, Mireia] Univ Extremadura, CIBERNED, Dept Bioquim & Biol Mol & Genent, Fac Enfermeria & Terapia Ocupac, Caceres, Spain. [Fernandez-Lopez, Arsenio; Perez-Rodriguez, Diego] Univ Leon, Area Biol Celular, Inst Biomed, E-24071 Leon, Spain. [Fernandez-Barrena, Maite G.] Univ Navarra, Ctr Invest Med Aplicada, E-31080 Pamplona, Spain. [Albaiceta, Guillermo M.] Univ Oviedo, Dept Biol Func, Oviedo, Spain. [Fernandez, Alvaro F.; Lopez-Otin, Carlos] Univ Oviedo, Inst Univ Oncol, Dept Bioquim & Biol Mol, Oviedo, Spain. [Jimenez, Alberto] Univ Salamanca, Dept Microbiol & Genet, Campus Miguel Unamuno, E-37008 Salamanca, Spain. [Boada-Romero, Emilio; Pimentel-Muinos, Felipe X.] Univ Salamanca, IBMCC, Ctr Invest Canc, Campus Unamuno, Salamanca, Spain. [Miranda-Vizuete, Antonio] Univ Seville, Inst Biomed Sevilla, Hosp Univ Virgen Rocio, Consejo Super Invest Cient, Seville, Spain. [Ruano, Diego] Univ Seville, Inst Biomed Sevilla, Seville, Spain. [Crespo, Jose L.; Esther Perez-Perez, Maria] Univ Seville, CSIC, Inst Bioquim Vegetal & Fotosintesis, Seville, Spain. [Couve, Eduardo] Univ Valparaiso, Inst Biol, Fac Ciencias, Valparaiso, Chile. [Pardo, Julian] Univ Zaragoza Araid, IIS Aragon, Ctr Invest Biomed Aragon, Zaragoza, Spain. [Filippi-Chiela, Eduardo C.; Lenz, Guido; Thome, Marcos P.] Univ Fed Rio Grande do Sul, Dept Biophys, Porto Alegre, RS, Brazil. [Filippi-Chiela, Eduardo C.; Lenz, Guido; Thome, Marcos P.] Ctr Biotechnol, Porto Alegre, RS, Brazil. [Silvia Romano, Patricia] Univ Nacl Cuyo FCM UNCUYO, Inst Histol & Embriol IHEM CONICET, Fac Ciencias Med, Mendoza, Argentina. [Sanchez-Alcazar, Jose A.] Univ Pablo Olavide, CABD, Consejo Super Invest Cient Junta Andalucia, Seville, Spain. [Weis, Simone Nardin] Univ Brasilia, Dept Biol Celular, Brasilia, DF, Brazil. [Rodrigues, Cecilia M. P.] Univ Lisbon, Res Inst Med iMed ULisboa, Fac Pharm, Lisbon, Portugal. [Botana, Luis M.] Univ Santiago Compostela, Dept Farmacol, Fac Vet, Lugo, Spain. [Goldman, Gustavo H.] Univ Sao Paulo, FCFRP, USP, Sao Paulo, Brazil. [Hernandez, Agustin] Univ Sao Paulo, Dept Parasitol, Inst Ciencias Biomed, Sao Paulo, Brazil. [Brito, Glauber C.] Univ Sao Paulo, Inst Canc Estado Sao Paulo, Fac Med, Sao Paulo, SP, Brazil. [Tenorio de Melo, Edesio Jose] Univ Estadual Norte Fluminense, Ctr Biociencias Biotecnol, Lab Biol Celular & Tecidual, Setor Toxicol Celular, Campos Goytacazes, Rio De Janeiro, Brazil. [Rizzo, Elizete] Univ Fed Minas Gerais, Dept Morfol, Inst Ciencias Biol, Belo Horizonte, MG, Brazil. [Bincoletto, Claudia] Univ Fed Sao Paulo UNIFESP, Dept Farmacol, Escola Paulista Med, Sao Paulo, SP, Brazil. [Vieira, Helena L. A.] Univ Nova Lisboa, CEDOC, NOVA Med Sch, Lisbon, Portugal. [Revuelta, Jose L.] Univ Salamanca, Dept Microbiol & Genet, Campus Miguel Unamuno, E-37008 Salamanca, Spain. [Poletti, Angelo; Rusmini, Paola] Univ Milan, Dipartimento Sci Farmacol & Biomol, Milan, Italy. [Carra, Serena] Univ Modena & Reggio Emilia, Dipartimento Sci Biomed Metab & Neurosci, Modena, Italy. [Follo, Carlo; Isidoro, Ciro] Univ Piemonte Orientale, Dipartimento Sci Salute, Novara, Italy. [Genazzani, Armando A.] Univ Piemonte Orientale, Novara, Italy. [Matarese, Giuseppe] Univ Salerno, Dipartimento Med & Chirurg, I-84100 Salerno, Italy. [Rippo, Maria Rita] Univ Politecn Marche, Dept Clin & Mol Sci, Ancona, Italy. [Cenci, Simone; Milan, Enrico] Univ Vita Salute San Raffaele, Milan, Italy. [Casas, Caty] Univ Autonoma Barcelona, Dept Cell Biol Physiol & Immunol, Inst Neurociencies, E-08193 Barcelona, Spain. [Ventura, Salvador] Autonomous Univ Barcelona, Inst Biotecnol & Biomed, Bellaterra, Barcelona, Spain. [Ventura, Salvador] Dept Bioquim & Biol Mol, Bellaterra, Barcelona, Spain. [Zorzano, Antonio] Univ Barcelona, Dept Bioquim & Biol Mol, Fac Biol, Barcelona, Spain. [Luis Rosa, Jose] Univ Barcelona, Hosp Llobregat, Dept Ciencies Fisiol Giques 2, Inst Invest Biomed Bellvitge IDI BELL, Campus Bellvitge, Barcelona, Spain. [Segui-Simarro, Jose M.] Univ Politecn Valencia, COMAV Inst, E-46022 Valencia, Spain. [Reichert, Andreas S.] Univ Klinikum Dusseldorf, Inst Biochem & Mol Biol 1, Dusseldorf, Germany. [Bouchecareilh, Marion; Priault, Muriel] Univ Bordeaux Segalen, Inst Biochim & Genet Cellulaires, CNRS, UMR 5095, Bordeaux, France. [Pasquet, Jean-Max] Univ Bordeaux Segalen, INSERM U1035, Hematopoiese Leucem & Cibles Therapeut, Bordeaux, France. [Duvezin-Caubet, Stephane] Univ Bordeaux, Inst Biochim & Genet Cellulaires, CNRS, UMR 5095, Bordeaux, France. [Lapaquette, Pierre] Univ Bourgogne Franche Comte, Agrosup Dijon, UMR PAM, Equipe Vin Aliment Microbiol, Dijon, France. [Feron, Olivier] Catholic Univ Louvain, IREC, B-1200 Brussels, Belgium. [Batoko, Henri] Catholic Univ Louvain, Inst Sci Vie, Louvain La Neuve, Belgium. [Deldicque, Louise] Catholic Univ Louvain, Inst Neurosci, Louvain La Neuve, Belgium. [Gailly, Philippe] Catholic Univ Louvain, Lab Cell Physiol, B-1200 Brussels, Belgium. [Bruhat, Alain] Univ Clermont 1, UFR Med, Nutr Humaine UMR1019, Clermont Ferrand, France. [Dalmasso, Guillaume; Darfeuille-Michaud, Arlette; Nguyen, Hang T. T.] Univ Auvergne, M2iSH, INSERM UMR 1071, Ctr Biomed Rech & Valorisat,Fac Med, Clermont Ferrand, France. [Djavaheri-Mergny, Mojgan] Univ Bordeaux, INSERM U916, Inst Bergonie, Bordeaux, France. [Dehay, Benjamin] Univ Bordeaux, Inst Malad Neurodegenerat, CNRS UMR 5293, Bordeaux, France. [Camougrand, Nadine] Univ Bordeaux, CNRS, Inst Biochim & Genet Cellulaires, UMR 5095, Bordeaux, France. [Delage-Mourroux, Regis] Univ Franche Comte, UFR Sci & Tech EA3922, SFR IBCT FED 4234, Estrogenes Express Genique & Pathol Syst Nerveux, Besancon, France. [Boyer-Guittaut, Michaeel] Univ Franche Comte, UFR Sci & Tech, Lab Biochim, Besancon, France. [Verdier, Mireille] Univ Limoges, EA 3842, LHCP, Fac Med, Limoges, France. [Kretz-Remy, Carole] Univ Lyon, Lyon, France. [Kretz-Remy, Carole] Univ Lyon 1, Ctr Genet & Physiol Mol & Cellulaire, F-69622 Villeurbanne, France. [Freyssenet, Damien G.] Univ Lyon, Fac Med, Saint Etienne, France. [Faure, Mathias] Univ Lyon, INSERM, CIRI, Ecole Normale Super Lyon,CNRS,UMR 5308,U 111, Lyon, France. [Mollereau, Bertrand] Univ Lyon, CNRS UMR 5239, Mol Cell Biol Lab, Ecole Normale Super Lyon, Lyon, France. [Besteiro, Sebastien] Univ Montpellier, DIMNP, CNRS, UMR 5235, F-34059 Montpellier, France. [Pattingre, Sophie] Univ Montpellier, Inst Reg Canc Montpellier, INSERM, U 1194, F-34059 Montpellier, France. [Favier, Francois B.] Univ Montpellier, F-34059 Montpellier, France. [Bernard, Monique; Hebert, Marie-Josee] Univ Montreal, Dept Med, Montreal, PQ, Canada. [Pacelli, Consiglia] Univ Montreal, Dept Pharmacol, Fac Med, Montreal, PQ H3C 3J7, Canada. [Burelle, Yan] Univ Montreal, Fac Pharm, Montreal, PQ H3C 3J7, Canada. [Knaevelsrud, Helene] Univ Montreal, Inst Res Immunol & Canc, Montreal, PQ H3C 3J7, Canada. [Vallette, Francois] Univ Nantes, CRCNA, UMRINSERM 892, CNRS 6299, Nantes, France. [Chevet, Eric] Univ Rennes 1, OSS, ERL INSERM 440, Ctr Lutte Canc Eugene Marquis, Rennes, France. [Beaulieu, Jean-Francois; Jean, Steve] Univ Sherbrooke, Dept Anat & Cell Biol, Fac Med & Hlth Sci, Sherbrooke, PQ J1K 2R1, Canada. [Dupuis, Luc] Univ Strasbourg, Fac Med, UMRS 1118, Strasbourg, France. [Gros, Frederic] Univ Strasbourg, CNRS UPR3572, Immunopathol & Chim Therapeut, IBMC, Strasbourg, France. [Barbeau, Benoit] Univ Quebec, Dept Sci Biol, Montreal, PQ H3C 3P8, Canada. [Barbeau, Benoit] Ctr Rech BioMed, Montreal, PQ, Canada. [Taillebourg, Emmanuel] Univ Grenoble Alpes, CEA DSV iRTSV BGE GenandChem, INSERM, U1038, Grenoble, France. [Francois, Arnaud] Univ Laval, Neurosci Axis, Quebec City, PQ, Canada. [Cnop, Miriam] Univ Libre Bruxelles, ULB Ctr Diabet Res, Brussels, Belgium. [Palladino, Francesca] Univ Lyon, Ecole Normale Super Lyon, Lyon, France. [Baghdiguian, Stephen] Univ Montpellier 2, Inst Sci Evolut, CNRS, UMR 5554, Montpellier, Languedoc Rouss, France. [Pierrefite-Carle, Valerie] Univ Nice Sophia Antipolis, UMR MATOs CEA iBEB E 4320TIRO, Fac Med, Nice, France. [Kroemer, Guido] Univ Paris 05, Apoptosis Canc & Immun Lab, Team 11, Equipe Labellisee Ligue Canc & Cell Biol & Met Pl, Paris, France. [Tamburini, Jerome] Univ Paris 05, Inst Cochin, Sorbonne Paris Cite, Fac Med, Paris, France. [Pende, Mario] Univ Paris 05, Inst Necker Enfants Malades, INSERM, U1151, Paris, France. [Rautou, Pierre-Emmanuel] Univ Paris 05, Paris, France. [Bravo-San Pedro, Jose M.; Galluzzi, Lorenzo; Izzo, Valentina; Pietrocola, Federico; Sica, Valentina] Univ Paris Descartes Paris V, Paris, France. [Botti, Joelle; Codogno, Patrice; Dupont, Nicolas; Hamai, Ahmed; Mehrpour, Maryam; Morel, Etienne; Nascimbeni, Anna Chiara; Orhon, Idil] Univ Paris 05, Sorbonne Paris Cite, INEM, INSERM U1151,CNRS UMR 5253, Paris, France. [Ait-Si-Ali, Slimane] Univ Paris 05, Sorbonne Paris Cite, Ctr Epigenet & Destin Cellulaire, CNRS,UMR 7216, Paris, France. [Le Stunff, Herve] Univ Paris 05, Unite Biol Fonctionnelle & Adaptat, CNRS UMR 8251, Paris, France. [Bianchi, Michele Wolfe] Univ Paris Est Creteil, Creteil, France. [Teixeira-Clerc, Fatima] Univ Paris Est, Inst Mondor Rech Biomed, Paris, France. [Le Stunff, Herve; Legouis, Renaud] Univ Paris Sud, CEA, CNRS, Inst Integrat Biol Cell, Gif Sur Yvette, France. [Bianchi, Michele Wolfe] Univ Paris Sud, CEA, CNRS, Paris, France. [Deutsch, Eric] Univ Paris Sud, INSERM 1030, Gustave Roussy Canc Campus, Paris, France. [Dokudovskaya, Svetlana] Univ Paris Sud, Inst Gustave Roussy, CNRS UMR 8126, Villejuif, France. [Wiels, Joelle] Univ Paris Sud, Univ Paris Saclay, CNRS UMR 8126, Inst Gustave Roussy, Villejuif, France. [Tan, Mei Lan] Univ Sains Malaysia, Adv Med & Dent Inst, Minist Sci Technol & Innovat, George Town, Malaysia. [D'Orazi, Gabriella] Univ G dAnnunzio, Dept Med Oral & Biotechnol Sci, Chieti, Italy. [Corasaniti, Maria Tiziana] Magna Graecia Univ Catanzaro, Dept Hlth Sci, Catanzaro, Italy. [Isakovic, Aleksandra J.] Univ Belgrade, Sch Med, Belgrade, Serbia. [Lizard, Gerard] Univ Bourgogne Franche Comte, EA 7270, INSERM, Dijon, France. [Fortunato, Franco] Univ Clin Heidelberg, Dept Expt Surg, Heidelberg, Germany. [Rami, Abdelhaq] Univ Clin, Inst Cellular & Mol Anat Anat 3, Frankfurt, Germany. [McKenna, Sharon; O'Donovan, Tracey] Natl Univ Ireland Univ Coll Cork, BioSci Inst Co, Cork Canc Res Ctr, Cork, Ireland. [Waeber, Christian] Natl Univ Ireland Univ Coll Cork, Sch Pharm, Dept Pharmacol & Therapeut, Cork, Ireland. [Al-Rubeai, Mohamed] Univ Coll Dublin, Sch Chem & Bioproc Engn, Dublin 2, Ireland. [Alvarez-Erviti, Lydia; Cooper, J. Mark] UCL, Dept Clin Neurosci, London, England. [Ketteler, Robin; Kriston-Vizi, Janos; Prak, Krisna] UCL, MRC Lab Mol Cell Biol, London, England. [Duchen, Michael R.] UCL, UCL Consortium Mitochondrial Res, London, England. [Duchen, Michael R.] Dept Cell & Dev Biol, London, England. [Clementi, Emilio] Univ Milan, Univ Hosp Luigi Sacco, Clin Pharmacol Unit, Natl Res Council,Inst Neurosci,Dept Biomed & Clin, Milan, Italy. [Strnad, Pavel] Univ Hosp Aachen, IZKF, Aachen, Germany. [Strnad, Pavel] Dept Internal Med III, Aachen, Germany. [Puyal, Julien; Truttmann, Anita C.] Univ Lausanne, Univ Hosp Ctr, Clin Neonatol, Dept Pediat & Pediat Surg, Lausanne, Switzerland. [Bergami, Matteo] Univ Hosp Cologne, CECAD Res Ctr, Cologne, Germany. [Klucken, Jochen; Minakaki, Georgia] Univ Erlangen Nurnberg, Univ Hosp Erlangen, D-91054 Erlangen, Germany. [Hasselblatt, Peter] Univ Hosp Freiburg, Dept Med 2, Freiburg, Germany. [Dahmen, Uta] Univ Hosp Jena, Dept Gen Visceral & Vasc Surg, Expt Transplantat Surg, Jena, Germany. [Bou, German] Univ Hosp La Coruna, Dept Microbiol, La Coruna, Spain. [Pavenstaedt, Hermann] Univ Hosp Muenster, Internal Med D, Dept Nephrol Hypertens & Rheumatol, Albert Schweitzer Campus, Munster, Germany. [Patschan, Daniel] Univ Hosp Gottingen, Dept Nephrol & Rheumatol, Gottingen, Germany. [Duchosal, Michel A.] Univ Hosp Lausanne, Serv & Cent Lab Hematol, Lausanne, Switzerland. [Weide, Thomas] Univ Hosp Muenster, Dept Internal Med D, Mol Nephrol, Munster, Germany. [Schneider, E. Marion] Univ Hosp Ulm, Sekt Expt Anaestesiol, Ulm, Germany. [Scharl, Michael] Univ Hosp Zurich, Div Gastroenterol & Hepatolog, Zurich, Switzerland. [Decuypere, Jean-Paul] Univ Hosp Leuven, Dept Microbiol & Immunol, Lab Abdominal Transplantat, Leuven, Belgium. [Vandenberghe, Wim] Univ Hosp Leuven, Dept Neurol, Leuven, Belgium. [Martinez, Jennifer] Natl Inst Environm Hlth Sci, Immun Inflammat & Dis Lab, Res Triangle Pk, NC USA. [Duez, Helene; Lancel, Steve] Univ Lille, INSERM, CHU Lille, Inst Pasteur Lille,U1011,EGID, Lille, France. [Huber, Tobias B.] Univ Med Ctr Freiburg, Freiburg, Germany. [Vellenga, Edo] Univ Groningen, Univ Med Ctr Groningen, Dept Hematol, Groningen, Netherlands. [Galliciotti, Giovanna] Univ Hamburg, Med Ctr, Inst Neuropathol, Hamburg, Germany. [Behl, Christian] Johannes Gutenberg Univ Mainz, Med Ctr, Inst Pathobiochemi, D-55122 Mainz, Germany. [Mari, Muriel; Reggiori, Fulvio] Univ Groningen, Univ Med Ctr Groningen, Dept Cell Biol, Groningen, Netherlands. [Schmidt, Jens] Univ Gottingen, Med Ctr, Clin Neurol, D-37073 Gottingen, Germany. [Schmidt, Jens] Dept Neuroimmunol, Gottingen, Germany. [Outeiro, Tiago F.] Univ Gottingen, Med Ctr, Dept Neurodegenerat & Restorat Res, D-37073 Gottingen, Germany. [Boes, Marianne] Univ Utrecht, Med Ctr, Lab Translat Immunol, Utrecht, Netherlands. [Boes, Marianne] Univ Hosp Children & Youth, Dept Pediat Immunol, Utrecht, Netherlands. [Koch, Jan C.] Univ Med Gottingen, Dept Neurol, Gottingen, Germany. [Wang, Jing] Univ Montpellier I, INSERM U1051, Montpellier, France. [Vidal, Michel] Univ Montpellier, UMR5235, F-34059 Montpellier, France. [Coxon, Fraser P.] Univ Aberdeen, Div Appl Med, Aberdeen, Scotland. [Ganesan, Swamynathan] Univ Adelaide, Alzheimers Dis Genet Lab, Adelaide, SA, Australia. [Richards, Robert I.] Univ Adelaide, Dept Genet & Evolut, Sch Biol Sci, Adelaide, SA, Australia. [Ramanadham, Sasanka] Univ Alabama Birmingham, Dept Cell Dev & Integrat Biol CDIB, Comprehens Diabet Ctr UCDC, Birmingham, AL USA. [Xu, Zhi-Xiang] Univ Alabama Birmingham, Dept Med, Div Hematol & Oncol, Ctr Comprehens Canc, Birmingham, AL 35294 USA. [Roth, Kevin A.; Shacka, John J.; Zhang, Jianhua] Univ Alabama Birmingham, Dept Pathol, Birmingham, AL 35294 USA. [Darley-Usmar, Victor M.] Univ Alabama Birmingham, Dept Pathol, Ctr Free Radical Biol, Birmingham, AL 35294 USA. [Chatham, John C.] Univ Alabama Birmingham, Div Mol & Cellular Pathol, Dept Pathol, Birmingham, AL USA. [Kim, Yonghyun] Univ Alabama, Dept Chem & Biol Engn, Tuscaloosa, AL USA. [Goping, Ing Swie] Univ Alberta, Dept Biochem, Edmonton, AB, Canada. [Diaz-Laviada, Ines] Univ Alcala De Henares, Dept Syst Biol, Biochem & Mol Biol Unit, Sch Med, Madrid, Spain. [Medema, Jan Paul] Univ Amsterdam, Acad Med Ctr, Lab Expt Oncol & Radiobiol, Meibergdreef 9, NL-1105 AZ Amsterdam, North Holland, Netherlands. [Juenemann, Katrin] Univ Amsterdam, Acad Med Ctr, Dept Cellbiol & Histol, Meibergdreef 9, NL-1105 AZ Amsterdam, Netherlands. [Meijer, Alfred J.] Univ Amsterdam, Acad Med Ctr, Dept Med Biochem, Meibergdreef 9, NL-1105 AZ Amsterdam, Netherlands. [Berkhout, Ben] Univ Amsterdam, Acad Med Ctr, Lab Expt Virol, Ctr Infect & Immun Amsterdam CINIMA, Meibergdreef 9, NL-1105 AZ Amsterdam, Netherlands. [Norga, Koenraad K.] Univ Antwerp, Dept Paediat Oncol, B-2020 Antwerp, Belgium. [De Meyer, Guido R. Y.; Martinet, Wim] Univ Antwerp, Lab Physiopharmacol, B-2020 Antwerp, Belgium. [Landowski, Terry H.] Univ Arizona, Ctr Canc, Dept Med, Tucson, AZ USA. [Kruer, Michael C.] Univ Arizona, Coll Med, Barrow Neurol Inst, Phoenix Childrens Hosp,Dept Child Hlth, Phoenix, AZ USA. [Riehle, Michael A.] Univ Arizona, Dept Entomol, Tucson, AZ USA. [Chen, Yin; Klimecki, Walter T.; Zhang, Donna D.] Univ Arizona, Dept Pharmacol & Toxicol, Coll Pharm, Tucson, AZ 85721 USA. [Ding, Zufeng; Mehta, Jawahar L.] Univ Arkansas Med Sci, Dept Cardiol, Little Rock, AR 72205 USA. [Voth, Daniel E.] Univ Arkansas Med Sci, Dept Microbiol & Immunol, Little Rock, AR 72205 USA. [MacMillan-Crow, Lee Ann; Parajuli, Nirmala] Univ Arkansas Med Sci, Dept Pharmacol Toxicol, Little Rock, AR 72205 USA. [Dridi, Sami] Univ Arkansas, Ctr Excellence Poultry Sci, Fayetteville, AR 72701 USA. [Konstantakou, Eumorphia G.; Stravopodis, Dimitrios J.; Trougakos, Ioannis P.; Velentzas, Athanassios D.] Univ Athens, Dept Cell Biol & Biophys, Fac Biol, Athens, Greece. [Mpakou, Vassiliki E.] Univ Athens, Sch Med, Dept Internal Med 2, Athens, Greece. [Mpakou, Vassiliki E.] Attikon Univ, Gen Hosp, Res Inst, Athens, Greece. [Kampinga, Harm H.] Univ Groningen, Univ Med Ctr Groningen, Dept Cell Biol, Groningen, Netherlands. [Pierre, Philippe] Univ Aveiro, Inst Res Biomed iBiMED, Aveiro Hlth Sci Program, Aveiro, Portugal. [Neves, Bruno M.] Univ Aveiro QOPNA, Dept Chem, Aveiro, Portugal. [Claria, Joan; Lopez-Vicario, Cristina] Univ Barcelona, Dept Biochem & Mol Genet, Hosp Clin, IDIBAPS CIBERehd, Barcelona, Spain. [Ambrosio, Santiago] Univ Barcelona, Sch Med, Campus Bellvitge, Lhospitalet De Llobregat, Spain. [Cocco, Tiziana] Univ Bari Aldo Moro, Dept Basic Med Sci Neurosci & Organs Senses, Bari, Italy. [Tucci, Marco] Univ Bari Aldo Moro, Dept Biomed Sci & Clin Oncol, Bari, Italy. [Simone, Cristiano] Univ Bari Aldo Moro, Div Med Genet, DIMO, Sch Med, Bari, Italy. [Castets, Perrine; Ruegg, Markus A.; Spang, Anne] Univ Basel, Biozentrum, Basel, BS, Switzerland. [Boeckler, Stefan; Westermann, Benedikt] Univ Bayreuth, Cell Biol, Bayreuth, Germany. [Steegborn, Clemens] Univ Bayreuth, Dept Biochem, Bayreuth, Germany. [Harhaji-Trajkovic, Ljubica] Univ Belgrade, Inst Biol Res Sinisa Stankov, Belgrade, Serbia. [Kravic-Stevovic, Tamara] Univ Belgrade, Inst Histol & Embryol, Sch Med, Belgrade, Serbia. [Markovic, Ivanka] Univ Belgrade, Inst Med & Clin Biochem, Fac Med, Belgrade, Serbia. [Trajkovic, Vladimir] Univ Belgrade, Sch Med, Belgrade, Serbia. [Bumbasirevic, Vladimir] Univ Belgrade, Sch Med, Inst Histol & Embryol, Belgrade, Serbia. [Tschan, Mario P.] Univ Bern, Div Expt Pathol, Inst Pathol, Bern, Switzerland. [Arcaro, Alexandre] Univ Bern, Div Pediat Hematol Oncol, Dept Clin Res, Bern, Switzerland. [Buetikofer, Peter] Univ Bern, Inst Biochem & Mol Med, Bern, Switzerland. [Simon, Hans-Uwe] Univ Bern, Inst Pharmacol, Bern, Switzerland. [Sarkar, Sovan; Ward, Carl] Univ Birmingham, Inst Biomed Res, Inst Canc & Genom Sci, Coll Med & Dent Sci, Birmingham, W Midlands, England. [Taylor, Graham S.] Univ Birmingham, Inst Immunol & Immunotherapy, Birmingham, W Midlands, England. [Martelli, Alberto M.] Univ Bologna, Dept Biomed & Neuromotor Sci, Bologna, Italy. [Cetrullo, Silvia; Flamigni, Flavio] Univ Bologna, Dipartimento Sci Biomed & Neuromotorie, Bologna, Italy. [Walter, Jochen] Univ Bonn, Dept Neurol, Bonn, Germany. [Haas, Albert; Hoehfeld, Joerg] Univ Bonn, Inst Cell Biol, Bonn, Germany. [Till, Andreas] Univ Bonn, Inst Reconstruct Neurobiol, Bonn, Germany. [Fanzani, Alessandro] Univ Brescia, Dept Mol & Translat Med, Brescia, Italy. [Lane, Jon D.] Univ Bristol, Sch Biochem, Bristol, Avon, England. [Greenhough, Alexander] Univ Bristol, Sch Cellular & Mol Med, Bristol, Avon, England. [Roberge, Michel; Yip, Calvin K.] Univ British Columbia, Dept Biochem & Mol Biol, Vancouver, BC V5Z 1M9, Canada. [Johnson, James D.; Nabi, Ivan R.] Univ British Columbia, Dept Cellular & Physiol Sci, Vancouver, BC V5Z 1M9, Canada. [Wang, Yu Tian] Univ British Columbia, Dept Med, Vancouver, BC V5Z 1M9, Canada. [Wang, Yu Tian] Brain Res Ctr, Vancouver, BC, Canada. [Luo, Honglin] Univ British Columbia, Dept Pathol & Lab Med, James Hogg Res Ctr, Vancouver, BC V5Z 1M9, Canada. [Shi, Junyan] Univ British Columbia, Dept Pathol & Lab Med, Vancouver, BC V5Z 1M9, Canada. [Toker, Lilach] Univ British Columbia, Dept Psychiat, Vancouver, BC V5Z 1M9, Canada. [Gleave, Martin] Univ British Columbia, Dept Urol Sci, Vancouver, BC V5Z 1M9, Canada. [Jiang, Xiaoyan] Univ British Columbia, Med Genet & BC Canc Agcy, Terry Fox Lab, Vancouver, BC V5Z 1M9, Canada. [Piret, James M.] Univ British Columbia, Michael Smith Labs, Dept Chem & Biol Engn, Vancouver, BC V5Z 1M9, Canada. [Turner, Robin F. B.] Univ British Columbia, Michael Smith Labs, Vancouver, BC V5Z 1M9, Canada. [Blanco, Guillermo A.] Univ Buenos Aires, IDEHU CONICET, Fac Pharm & Biochem, Buenos Aires, DF, Argentina. [Alvarez, Silvia] Univ Buenos Aires, Inst Biochem & Biophys, Sch Pharm & Biochem, Buenos Aires, DF, Argentina. [Vaccaro, Maria I.] Univ Buenos Aires, Natl Council Sci & Tech Res CONICET, Inst Biochem & Mol Med, Dept Pathophysiol,Sch Pharm & Biochem, Buenos Aires, DF, Argentina. [Perrotta, Ida] Univ Calabria, Dept Biol Ecol & Earth Sci, Lab Electron Microscopy, I-87036 Cosenza, Italy. [Aquila, Saveria] Univ Calabria, Dept Pharm Hlth & Nutrit Sci, I-87036 Cosenza, Italy. [Russo, Rossella] Univ Calabria, Dept Pharm Hlth & Nutrit Sci, Sect Preclin & Translat Pharmacol, I-87036 Cosenza, Italy. [Chakrabarti, Gopal] Univ Calcutta, Dept Biotechnol, Dr BC Guha Ctr Genet Engn & Biotechnol, Kolkata, WB, India. [Zheng, Xi-Long] Univ Calgary, Dept Biochem & Mol Biol, Libin Cardiovasc Inst Alberta, Calgary, AB, Canada. [Schatzl, Hermann M.] Univ Calgary, Fac Vet Med, Calgary, AB, Canada. [Hurley, James H.; Thorner, Jeremy] Univ Calif Berkeley, Dept Mol & Cell Biol, Berkeley, CA 94720 USA. [Ge, Liang; Schekman, Randy] Univ Calif Berkeley, Howard Hughes Med Inst, Dept Mol & Cell Biol, Berkeley, CA 94720 USA. [Kung, Hsing-Jien] Univ Calif Davis, Ctr Canc, Davis, CA 95616 USA. [Luckhart, Shirley; Pakpour, Nazzy] Univ Calif Davis, Dept Med Microbiol & Immunol, Sch Med, Davis, CA 95616 USA. [Powers, Ted] Univ Calif Davis, Dept Mol & Cellular Biol, Davis, CA 95616 USA. [Gomes, Aldrin V.] Univ Calif Davis, Dept Neurobiol Physiol & Behav, Davis, CA 95616 USA. [Dinesh-Kumar, Savithrama P.] Univ Calif Davis, Dept Plant Biol, Davis, CA 95616 USA. [Dinesh-Kumar, Savithrama P.] Coll Biol Sci, Genome Ctr, Davis, CA USA. [van Doorn, Wouter G.] Univ Calif Davis, Mann Lab, Dept Plant Sci, Davis, CA 95616 USA. [Edinger, Aimee L.] Univ Calif Irvine, Dept Dev & Cell Biol, Irvine, CA 92717 USA. [Chen, Jeff W.] Univ Calif Irvine, Dept Neurosurg, Irvine, CA USA. [Steffan, Joan] Univ Calif Irvine, Dept Psychiat & Human Behav, Irvine, CA 92717 USA. [Ganesan, Anand K.] Univ Calif Irvine, Irvine, CA USA. [Xia, Tian] Univ Calif Los Angeles, Dept Med, Los Angeles, CA USA. [Costes, Safia] Univ Calif Los Angeles, David Geffen Sch Med, Larry Hillblom Islet Res Ctr, Los Angeles, CA 90095 USA. [Le Roch, Karine G.] Univ Calif Riverside, Dept Cell Biol & Neurosci, Riverside, CA 92521 USA. [Steele, John W.] Univ Calif San Diego, Dept Cellular & Mol Med, La Jolla, CA 92093 USA. [Lee, Jongdae; Satriano, Joseph] Univ Calif San Diego, Dept Med, La Jolla, CA 92093 USA. [Sigurdson, Christina J.] Univ Calif San Diego, Dept Pathol, San Diego, CA 92103 USA. [Spector, Stephen A.] Univ Calif San Diego, Dept Pediat Div Infect Dis, La Jolla, CA 92093 USA. [Campbell, Grant R.; Ordonez, Paulina] Univ Calif San Diego, Dept Pediat, La Jolla, CA 92093 USA. [Guan, Kun-Liang] Univ Calif San Diego, Dept Pharmacol, La Jolla, CA 92093 USA. [Guan, Kun-Liang] Moores Canc Ctr, La Jolla, CA USA. [Miyamoto, Shigeki] Univ Calif San Diego, Dept Pharmacol, La Jolla, CA 92093 USA. [La Spada, Albert R.] Univ Calif San Diego, Dept Cellular & Mol Med, Div Biol Sci, Inst Genom Med, La Jolla, CA 92093 USA. [La Spada, Albert R.] Univ Calif San Diego, Dept Neurosci, Div Biol Sci, Inst Genom Med, La Jolla, CA 92093 USA. [La Spada, Albert R.] Univ Calif San Diego, Dept Pediat, Div Biol Sci, Inst Genom Med, La Jolla, CA 92093 USA. [Kiger, Amy A.] Univ Calif San Diego, Div Biol Sci, La Jolla, CA 92093 USA. [Liu, Jing-Jing; Nazarko, Taras Y.] Univ Calif San Diego, Div Biol Sci, Mol Biol Sect, La Jolla, CA 92093 USA. [Till, Andreas] Univ Calif San Diego, San Diego Ctr Syst Biol, La Jolla, CA 92093 USA. [Cohen, Ezra E. W.] Univ Calif San Diego, Moores Canc Ctr, La Jolla, CA 92093 USA. [Soontornniyomkij, Virawudh] Univ Calif San Diego, Sch Med, Dept Psychiat, La Jolla, CA 92093 USA. [Gustafsson, Asa B.] Univ Calif San Diego, Skaggs Sch Pharm & Pharmaceut Sci, La Jolla, CA 92093 USA. [Cox, Jeffery S.] Univ Calif San Francisco, Dept Microbiol & Immunol, San Francisco, CA 94143 USA. [Aghi, Manish K.] Univ Calif San Francisco, Dept Neurol Surg, San Francisco, CA 94143 USA. [An, Zhenyi] Univ Calif San Francisco, Dept Neurol, San Francisco, CA 94143 USA. [Hetz, Claudio; Matus, Soledad] FONDAP Ctr Gerosci Brain Hlth & Metab, Santiago, Chile. [Gestwicki, Jason E.] Univ Calif San Francisco, Dept Pharmaceut Chem, San Francisco, CA 94143 USA. [Sarwal, Minnie M.] Univ Calif San Francisco, Dept Surg, San Francisco, CA 94143 USA. [Finkbeiner, Steven] Univ Calif San Francisco, Dept Neurol, San Francisco, CA 94143 USA. [Finkbeiner, Steven] Univ Calif San Francisco, Dept Physiol, San Francisco, CA 94143 USA. [Finkbeiner, Steven] Gladstone Inst Neurol Dis, San Francisco, CA USA. [Debnath, Jayanta; Margeta, Marta] Univ Calif San Francisco, Sch Med, Dept Pathol, San Francisco, CA 94143 USA. [Kajimura, Shingo] Univ Calif San Francisco, UCSF Diabet Ctr, Dept Cell & Tissue Biol, San Francisco, CA 94143 USA. [Montell, Craig] Univ Calif Santa Barbara, Dept Mol Cellular & Dev Biol, Santa Barbara, CA 93106 USA. [Kaser, Arthur] Univ Cambridge, Addenbrookes Hosp, Dept Med, Cambridge CB2 2QQ, England. [Rubinsztein, David C.] Univ Cambridge, Addenbrookes Hosp, Cambridge Inst Med Res, Dept Med Genet, Cambridge CB2 2QQ, England. [Floto, R. Andres] Univ Cambridge, Cambridge Inst Med Res, Cambridge, England. [Narita, Masashi] Univ Cambridge, Canc Res UK Cambridge Inst, Li Ka Shing Ctr, Cambridge, England. [Miller-Fleming, Leonor] Univ Cambridge, Dept Biochem, Cambridge, England. [Renna, Maurizio] Univ Cambridge, Dept Med Genet, Cambridge Inst Med Res, Cambridge, England. [Randow, Felix] Univ Cambridge, Dept Med, Addenbrookes Hosp, Cambridge CB2 2QQ, England. [Beale, Rupert] Univ Cambridge, Dept Pathol, Div Virol, Tennis Court Rd, Cambridge CB2 1QP, England. [Amantini, Consuelo] Univ Camerino, Sch Biosci & Vet Med, I-62032 Camerino, Italy. [Nabissi, Massimo] Univ Camerino, Sch Pharm, I-62032 Camerino, Italy. [Santoni, Giorgio] Univ Camerino, Sch Pharm, Sect Expt Med, I-62032 Camerino, MC, Italy. [Ferreira-Halder, Carmen Verissima] Univ Estadual Campinas, Dept Biochem & Tissue Biol, Campinas, SP, Brazil. [Dobson, Renwick C. J.] Univ Canterbury, Biomol Interact Ctr, Sch Biol Sci, Christchurch 1, New Zealand. [Prince, Sharon] Univ Cape Town, Dept Human Biol, ZA-7925 Cape Town, Western Provinc, South Africa. [Davids, Lester M.] Univ Cape Town, Redox Lab, Dept Human Biol, ZA-7925 Cape Town, South Africa. [Zervos, Antonis S.] Univ Cent Florida, Coll Med, Burnett Sch Biomed Sci, Orlando, FL 32816 USA. [He, Yu-Ying] Univ Chicago, Dept Med, Dermatol Sect, Chicago, IL 60637 USA. [Choi, Jayoung; Hwang, Seungmin] Univ Chicago, Dept Pathol, Chicago, IL 60637 USA. [Mastrianni, James A.] Univ Chicago, Pritzker Sch Med, Dept Neurol, Chicago, IL 60637 USA. [Macleod, Kay F.] Univ Chicago, Ben May Dept Canc Res, Chicago, IL 60637 USA. [Corbalan, Ramon; Garcia Nannig, Lorena] Univ Chile, Adv Ctr Chron Dis ACCDiS, Div Cardiovasc Dis, Fac Med, Santiago, Chile. [Pedrozo, Zully] P Catholic Univ Chile, Adv Ctr Chron Dis ACCDiS, Fac Med, Santiago, Chile. [Matus, Soledad] Univ Chile, Biomed Neurosci Inst, Santiago, Chile. [Segura-Aguilar, Juan] Univ Chile, Fac Med, ICBM Mol & Clin Pharmacol, Santiago 7, Chile. [Hetz, Claudio] Univ Chile, Fac Med, Inst Biomed Sci, Ctr Mol Studies Cell,Program Cellular,Mol Biol &, Santiago 7, Chile. [Weaver, Timothy E.] Univ Cincinnati, Coll Med, Cincinnati Childrens Res Fdn, Cincinnati, OH USA. [Weaver, Timothy E.] Dept Pediat, Cincinnati, OH USA. [Czyzyk-Krzeska, Maria F.; Guan, Jun-Lin; Wang, Chenran] Dept Pediat, Coll Med, Dept Canc Biol, Cincinnati, OH USA. [Robbins, Jeffrey] Univ Cincinnati, Cincinnati Childrens Hosp, Cincinnati, OH USA. [Choubey, Divaker] Univ Cincinnati, Cincinnati, OH USA. [Moreira, Paula I.] Univ Coimbra, CNC Ctr Neurosci & Cell Biol, Coimbra, Portugal. [Moreira, Paula I.] Fac Med, Coimbra, Portugal. [Cruz, Maria Teresa; Liberal, Joana] Univ Coimbra, Ctr Neurosci & Cell Biol, Coimbra, Portugal. [Cruz, Maria Teresa; Liberal, Joana] Fac Pharm, Coimbra, Portugal. [Vega-Naredo, Ignacio] Univ Coimbra, CNC Ctr Neurosci & Cell Biol, Cantanhede, Portugal. [Batista, Maria Teresa] Univ Coimbra, Coimbra, Portugal. [Cardoso, Sandra Morais] Univ Coimbra, Fac Med, Ctr Neurosci & Cell Biol, Coimbra, Portugal. [Pereira, Paulo C.] Univ Coimbra, IBILI, Fac Med, Coimbra, Portugal. [Fabri, Mario] Univ Cologne, Dept Dermatol, D-50931 Cologne, Germany. [Hoppe, Thorsten] Univ Cologne, Inst Genet, CECAD Res Ctr, D-50931 Cologne, Germany. [Noegel, Angelika A.] Univ Cologne, Inst Biochem 1, Fac Med, Cologne, Germany. [Eichinger, Ludwig] Univ Cologne, Fac Med, Ctr Biochem, D-50931 Cologne, Germany. [Edelstein, Charles L.] Univ Colorado, Boulder, CO 80309 USA. [Weekes, Colin D.] Univ Colorado, Div Med Oncol, Dept Med, Aurora, CO USA. [Agarwal, Rajesh; Raina, Komal] Univ Colorado, Skaggs Sch Pharm & Pharmaceut Sci, Dept Pharmaceut Sci, Aurora, CO USA. [Jani, Alkesh] Univ Colorado, Denver, CO USA. [Jani, Alkesh] Denver VAMC, Denver, CO USA. [Levy, Jean M. Mulcahy] Univ Colorado, Dept Pediat, Ctr Canc & Blood Disorders, Aurora, CO USA. [Parker, Roy] Univ Colorado, HHMI, Dept Chem & Biochem, Aurora, CO USA. [Pugazhenthi, Subbiah] Univ Colorado, Sch Med, Anschutz Med Campus, Aurora, CO USA. [Reusch, Jane E. B.] Univ Colorado, Sch Med, Aurora, CO USA. [Pyeon, Dohun] Univ Colorado, Sch Med, Dept Immunol & Microbiol, Aurora, CO USA. [Bayer, K. Ulrich; Morgan, Michael J.; Thorburn, Andrew] Univ Colorado, Sch Med, Dept Pharmacol, Aurora, CO USA. [Beckham, J. David] Univ Colorado, Sch Med, Div Infect Dis, Aurora, CO USA. [Frankel, Lisa B.; Issazadeh-Navikas, Shohreh; Lund, Anders H.] Univ Copenhagen, BRIC, Copenhagen, Denmark. [Petersen, Morten] Univ Copenhagen, Dept Biol, Copenhagen, Denmark. [Olsson, Stefan] Univ Copenhagen, Dept Plant & Environm Sci, Sect Genet & Microbiol, Copenhagen, Denmark. [Tavernarakis, Nektarios] Univ Crete, Dept Basic Sci, Fac Med, Iraklion, Greece. [Tavernarakis, Nektarios] Univ Crete, Inst Mol Biol & Biotechnol, Iraklion, Greece. [Chamilos, Georgios; Kyrmizi, Irene] Univ Crete, Sch Med, Dept Infect Dis, Iraklion, Greece. [Promponas, Vasilis J.] Univ Cyprus, Dept Biol Sci, Bioinformat Res Lab, CY-1678 Nicosia, Cyprus. [Fesus, Laszlo] Univ Debrecen, Debrecen, Hungary. [Lekli, Istvan] Univ Debrecen, Fac Pharm, Dept Pharmacol, Debrecen, Hungary. [van Golen, Kenneth L.] Univ Delaware, Dept Biol Sci, Newark, DE USA. [van Golen, Kenneth L.] Univ Delaware, Ctr Translat Canc Res, Newark, DE USA. [Rocha, Sonia] Univ Dundee, Ctr Gene Regulat & Express, Coll Life Sci, Dundee DD1 4HN, Scotland. [Ganley, Ian G.] Univ Dundee, MRC Prot Phosphorylat & Ubiquitylat Unit, Sch Life Sci, Dundee, Scotland. [Wileman, Tom] Univ E Anglia, Norwich Med Sch, Norwich NR4 7TJ, Norfolk, England. [Pesonen, Maija] Univ Eastern Finland, Fac Hlth Sci, Sch Pharm Toxicol, Kuopio, Finland. [Kaarniranta, Kai] Univ Eastern Finland, Kuopio Univ Hosp, Dept Ophthalmol, Kuopio, Finland. [Digard, Paul] Univ Edinburgh, Easter Bush, Roslin Insitute, Edinburgh EH8 9YL, Midlothian, Scotland. [Gammoh, Noor] Univ Edinburgh, Edinburgh Canc Res Ctr, Edinburgh, Midlothian, Scotland. [Wilkinson, Simon] Univ Edinburgh, Edinburgh Canc Res UK Ctr, MRC Inst Genet & Mol Med, Edinburgh, Midlothian, Scotland. [Distler, Joerg H. W.] Univ Erlangen Nurnberg, Dept Internal Med 3, D-91054 Erlangen, Germany. [Moore, Michael N.] Univ Exeter, Sch Med, ECEHH, Truro, Cornwall, England. [Talbot, Nicholas J.] Univ Exeter, Sch Biosci, Exeter, Devon, England. [Pena, Fernando J.; Tapia, Jose A.] Univ Extremadura, Dept Med, Fac Vet Med, Caceres, Spain. [Neri, Luca M.; Pinton, Paolo] Univ Ferrara, Dept Morphol Surg & Expt Med, I-44100 Ferrara, Italy. [Papini, Alessio] Univ Florence, Dept Biol, Florence, Italy. [Dunn, William A., Jr.] Univ Florida, Coll Med, Dept Anat & Cell Biol, Gainesville, FL USA. [Notterpek, Lucia] Univ Florida, Coll Med, Dept Neurosci, Gainesville, FL USA. [Joseph, Anna-Maria] Univ Florida, Dept Aging & Geriatr Res, Gainesville, FL USA. [Wohlgemuth, Stephanie E.] Univ Florida, Dept Anim Sci, IFAS Coll Agr & Life Sci, Gainesville, FL 32611 USA. [Adhihetty, Peter J.; Powers, Scott K.] Univ Florida, Dept Appl Physiol & Kinesiol, Gainesville, FL USA. [Maegawa, Gustavo] Univ Florida, Dept Pediat Genet & Metab, Gainesville, FL USA. [Behrns, Kevin E.] Univ Florida, Dept Surg, Gainesville, FL USA. [Kim, Jae-Sung] Univ Florida, Gainesville, FL USA. [Leeuwenburgh, Christiaan] Univ Florida, Inst Aging, Gainesville, FL USA. [Dengjel, Joern] Univ Freiburg, Dept Dermatol, Med Ctr, Ctr Biol Syst Anal ZBSA, Hugstetter Str 55, D-79106 Freiburg, Germany. [Yang, Zhihong] Univ Fribourg, Dept Med, Div Physiol, Fac Sci, CH-1700 Fribourg, Switzerland. [Ming, Xiu-Fen; Xiong, Yuyan] Univ Fribourg, Dept Med, Div Physiol, CH-1700 Fribourg, Switzerland. [Gannage, Monique] Univ Geneva, Sch Med, Dept Pathol & Immunol, CH-1211 Geneva, Switzerland. [Gogal, Robert M., Jr.] Univ Georgia, Coll Vet Med, Dept Biosci & Diagnost Imaging, Athens, GA 30602 USA. [Quinn, Frederick] Univ Georgia, Dept Infectious Dis, Athens, GA 30602 USA. [Leung, Hing Y.; Ryan, Kevin M.; Tait, Stephen W. G.] Univ Glasgow, Canc Res UK Beatson Inst, Glasgow, Lanark, Scotland. [Leung, Hing Y.; McNeish, Iain A.] Univ Glasgow, Inst Canc Sci, Glasgow, Lanark, Scotland. [Evans, Thomas J.] Univ Glasgow, Inst Infect Immun & Inflammat, Glasgow, Lanark, Scotland. [Helgason, Gudmundur Vignir] Univ Glasgow, Wolfson Wohl Canc Res Ctr, MVLS, Inst Canc Sci, Glasgow, Lanark, Scotland. [Jackson, Daniel John] Univ Gottingen, Dept Geobiol, D-37073 Gottingen, Germany. [Lingor, Paul] Univ Gottingen, Dept Neurol, D-37073 Gottingen, Germany. [Carmona-Gutierrez, Didac; Eisenberg, Tobias; Kohlwein, Sepp D.; Madeo, Frank] Graz Univ, Inst Mol Biosci, BioTechMed Graz, Graz, Austria. [van der Klei, Ida J.; Williams, Chris] Univ Groningen, Mol Cell Biol, Groningen, Netherlands. [Lemberg, Marius K.] Heidelberg Univ, Ctr Mol Biol, Heidelberg, Germany. [Parlato, Rosanna] Heidelberg Univ, Inst Anat & Cell Biol, Heidelberg, Germany. [Lindholm, Dan] Univ Helsinki, Biomedicum, Helsinki, Finland. [Eskelinen, Eeva-Liisa; Stratoulias, Vassilis] Univ Helsinki, Dept Biosci, Helsinki, Finland. [Hulmi, Juha J.] Univ Helsinki, Dept Physiol, Fac Med, Helsinki, Finland. [Wang, Yu] Univ Hong Kong, Dept Pharmacol & Pharm, Hong Kong, Hong Kong, Peoples R China. [Su, Yu-Xiong] Univ Hong Kong, Div Oral & Maxillofacial Surg, Fac Dent, Hong Hom, Hong Kong, Peoples R China. [Feng, Yibin] Univ Hong Kong, Hong Kong, Hong Kong, Peoples R China. [Chang, Raymond Chuen-Chung] Univ Hong Kong, Lab Neurodegenerat Dis, Sch Biomed Sci, LKS Fac Med, Hong Kong, Hong Kong, Peoples R China. [Eriksen, Jason L.; Zhang, Yang] Univ Houston, Coll Pharm Pharmacol & Pharmaceut Sci, Houston, TX USA. [Frigo, Daniel E.] Univ Houston, Dept Biol & Biochem, Ctr Nucl Receptors & Cell Signaling, Houston, TX USA. [Caplan, Allan B.] Univ Idaho, Plant Soil & Entomol Sci, Moscow, ID USA. [Yue, Beatrice Y. J. T.] Univ Illinois, Coll Med, Dept Ophthalmol & Visual Sci, Chicago, IL USA. [Zhou, Guofei] Univ Illinois, Coll Med, Dept Pediat, Chicago, IL USA. [Hu, Guochang] Univ Illinois, Dept Anesthesiol, Chicago, IL USA. [Hu, Guochang] Univ Illinois, Dept Pharmacol, Chicago, IL USA. [Shukla, Deepak] Univ Illinois, Dept Ophthalmol, Chicago, IL 60680 USA. [Shukla, Deepak] Univ Illinois, Dept Microbiol & Immunol, Chicago, IL 60680 USA. [Nazarko, Volodymyr Y.; Segev, Nava] Univ Illinois, Deprtment Biochem & Mol Genet, Chicago, IL USA. [Sun, Jun] Univ Illinois, Div Gastroenterol & Hepatol, Dept Med, Chicago, IL USA. [Kemper, Jongsook Kim] Univ Illinois, Dept Mol & Integrat Physiol, Urbana, IL USA. [Zhang, Guo-Chang] Univ Illinois, Inst Genom Biol, Urbana, IL USA. [Meryk, Andreas] Univ Innsbruck, Inst Biomed Aging Res, A-6020 Innsbruck, Austria. [Romanelli, Davide; Tettamanti, Gianluca] Univ Insubria, Dept Biotechnol & Life Sci, Varese, Italy. [Grose, Charles] Univ Iowa, Childrens Hosp, Iowa City, IA USA. [Lira, Vitor A.] Univ Iowa, Dept Hlth & Human Physiol, Iowa City, IA USA. [Adams, Christopher M.] Univ Iowa, Dept Internal Med, Iowa City, IA 52242 USA. [Monick, Martha M.] Univ Iowa, Dept Med, Iowa City, IA 52242 USA. [Fingert, John H.] Univ Iowa, Dept Ophthalmol & Visual Sci, Iowa City, IA 52242 USA. [Hulmi, Juha J.] Univ Jyvaskyla, Dept Biol Phys Act, SF-40100 Jyvaskyla, Finland. [Marquez, Rebecca; Xu, Liang] Univ Kansas, Lawrence, KS 66045 USA. [Marquez, Rebecca; Xu, Liang] Univ Kansas, Ctr Canc, Dept Mol Biosci, Lawrence, KS 66045 USA. [Marquez, Rebecca; Xu, Liang] Univ Kansas, Ctr Canc, Dept Radiat Oncol, Lawrence, KS 66045 USA. [Chen, Qi; Ding, Wen-Xing] Univ Kansas, Med Ctr, Dept Pharmacol Toxicol & Therapeut, Kansas City, KS 66103 USA. [Hsu, Chin] Univ Kaohsiung, Med Univ, Dept Physiol, Fac Med,Coll Med, Kaohsiung, Taiwan. [Chen, Gang; Luo, Jia] Univ Kentucky, Coll Med, Dept Pharmacol & Nutrit Sci, Lexington, KY USA. [Rucker, Edmund B., III] Univ Kentucky, Dept Biol, Lexington, KY USA. [Dickson, Robert C.] Univ Kentucky, Dept Mol & Cellular Biochem, Lexington, KY USA. [Craven, Rolf J.] Univ Kentucky, Dept Pharmacol & Nutrit Sci, Lexington, KY USA. [St Clair, Daret] Univ Kentucky, Dept Toxicol & Canc Biol, Lexington, KY USA. [Frey, Norbert; Kuhn, Christian] Univ Kiel, Dept Cardiol, Kiel, Germany. [Rosenstiel, Philip] Univ Kiel, Inst Clin Mol Biol, Kiel, Germany. [Huebbe, Patricia; Pallauf, Kathrin; Rimbach, Gerald] Univ Kiel, Inst Human Nutr & Food Sci, Kiel, Germany. [Denizot, Melanie] Univ La Reunion, CYROI, IRG Immunopathol & Infect Res Grouping, Reunion, Reunion. [Gravina, Giovanni Luca] Univ Aquila, Dept Biotechnol & Appl Clin Sci, Div Radiotherapy & Radiobiol, I-67100 Laquila, Italy. [Mayer, Andreas] Univ Lausanne, Dept Biochem, CH-1066 Epalinges, Switzerland. [Clarke, Peter G. H.; Ginet, Vanessa; Puyal, Julien] Univ Lausanne, Dept Fundamental Neurosci, Fac Biol & Med, Lausanne, Switzerland. [Cottet, Sandra; Schorderet, Daniel F.] Univ Lausanne, Dept Ophthalmol, Lausanne, Switzerland. [Noureini, Sakineh Kazemi] Hakim Sabzevari Univ, Dept Biol, Fac Basic Sci, Sabzevar, Iran. [Andreadi, Catherine K.; Brown, Karen] Univ Leicester, Dept Canc Studies, Leicester, Leics, England. [Giorgini, Flaviano] Univ Leicester, Dept Genet, Leicester, Leics, England. [Garg, Abhishek D.] Univ Leuven, Campus Gasthuisberg, Dept Cellular & Mol Med, Lab Cell Death Res & Therapy, Leuven, Belgium. [Vandenberghe, Wim] Univ Leuven, Dept Neurosci, Leuven, Belgium. [Claerhout, Sofie] KU Leuven Univ Leuven, Ctr Human Genet, Leuven, Belgium. [Claerhout, Sofie] VIB Ctr Biol Dis, Leuven, Belgium. [Mottet, Denis] Univ Liege, GIGA Signal Transduct Dept, Prot Signalisat & Interact Lab, Liege, Belgium. [Staels, Bart] Univ Lille, INSERM UMR1011, Inst Pasteur Lille, Lille, France. [Terro, Faraj] Univ Limoges, Dept Histol & Cell Biol, Limoges, France. [Clague, Michael J.] Univ Liverpool, Cellular & Mol Physiol, Inst Translat Med, Liverpool L69 3BX, Merseyside, England. [Erman, Andreja] Univ Ljubljana, Inst Cell Biol, Fac Med, Ljubljana, Slovenia. [Campanella, Michelangelo] Univ London, RVC Dept Comparat Biomed Sci, UCL Consortium Mitochondrial Res, London, England. [Sylvester, Paul W.] Univ Louisiana Monroe, Sch Pharm, Monroe, LA USA. [Cheng, Alan] Univ Louisville, Dept Biochem & Mol Genet, Louisville, KY 40292 USA. [Chesney, Jason; Telang, Sucheta] Univ Louisville, Dept Med Hem Onc, Louisville, KY 40292 USA. [Hill, Bradford G.] Univ Louisville, Dept Med, Inst Mol Cardiol, Diabet & Obes Ctr, Louisville, KY 40292 USA. [Sen, Utpal] Univ Louisville, Dept Physiol, Louisville, KY 40292 USA. [Li, Chi] Univ Louisville, James Graham Brown Canc Ctr, Dept Med, Dept Pharmacol & Toxicol, Louisville, KY 40292 USA. [Kumar, Ashok] Univ Louisville, Sch Med, Dept Anat Sci & Neurobiol, Louisville, KY 40292 USA. [Tyagi, Suresh C.] Univ Louisville, Sch Med, Dept Physiol & Biophys, Louisville, KY 40292 USA. [Kruger, Rejko] Univ Luxembourg, Luxembourg Ctr Syst Biomed, Luxembourg, Luxembourg. [Lu, Jiahong] Univ Macau, State Key Lab Qual Res Chinese Med, Inst Chinese Med Sci, Macau, Peoples R China. [Balzan, Rena] Univ Malta, Dept Physiol & Biochem, Fac Med & Surg, Msida, Malta. [Lisanti, Michael P.] Univ Manchester, Breakthrough Breast Canc Res Unit, Manchester Ctr Cellular Metab, Manchester M13 9PL, Lancs, England. [Tournier, Cathy] Univ Manchester, Fac Life Sci, Manchester, Lancs, England. [Sotgia, Federica] Univ Manchester, Inst Canc Sci, Fac Med & Human Sci, Manchester, Lancs, England. [Gibson, Spencer B.] Univ Manitoba, CancerCare Manitoba, Manitoba Inst Cell Biol, Dept Biochem, Winnipeg, MB, Canada. [Gibson, Spencer B.] Univ Manitoba, Dept Med Genet & Immunol, Winnipeg, MB, Canada. [Ghavami, Saeid] Univ Manitoba, Dept Human Anat & Cell Sci, Winnipeg, MB, Canada. [Halayko, Andrew J.] Univ Manitoba, Dept Physiol & Pathophysiol, Winnipeg, MB, Canada. [Kirshenbaum, Lorrie A.] Univ Manitoba, Inst Cardiovasc Sci, Coll Med, Fac Hlth Sci, Winnipeg, MB, Canada. [Sharma, Shweta] Univ Maryland, Dept Nutr & Food Sci, College Pk, MD 20742 USA. [Zhang, Yanjin] Univ Maryland, Dept Vet Med, College Pk, MD 20742 USA. [Fang, Shengyun] Univ Maryland, Sch Med, Sch Med, Ctr Biomed Engn & Technol,Dept Physiol, Baltimore, MD 21201 USA. [Wu, Junfang] Univ Maryland, Sch Med, Dept Anesthesiol & Ctr Shock, Trauma & Anesthesiol Res STAR,Natl Study Ctr Trau, Baltimore, MD 21201 USA. [Lipinski, Marta M.] Univ Maryland, Sch Med, Dept Anesthesiol, Baltimore, MD 21201 USA. [Njar, Vincent C. O.] Univ Maryland, Sch Med, Dept Chem, Baltimore, MD 21201 USA. [Jackson, William T.; Kalvakolanu, Dhan V.] Univ Maryland, Sch Med, Dept Microbiol & Immunol, Baltimore, MD 21201 USA. [Yang, Peixin] Univ Maryland, Sch Med, Dept Obstet Gynecol & Reprod Sci, Baltimore, MD 21201 USA. [Aurelian, Laure] Univ Maryland, Sch Med, Dept Pharmacol, Baltimore, MD 21201 USA. [Cheng, Hua] Univ Maryland, Sch Med, Inst Human Virol, Baltimore, MD 21201 USA. [Baehrecke, Eric H.; Velentzas, Panagiotis D.] Univ Massachusetts, Sch Med, Dept Mol Cell & Canc Biol, Worcester, MA 01605 USA. [Gao, Fen-Biao] Univ Massachusetts, Sch Med, Dept Neurol, Worcester, MA 01605 USA. [Davis, Roger J.] Univ Massachusetts, Sch Med, Howard Hughes Med Inst, Worcester, MA 01605 USA. [Maiese, Kenneth] Univ Med & Dent New Jersey, Cellular & Mol Signaling, Newark, NJ 07103 USA. [Lindqvist, Lisa M.] Cell Signalling & Cell Death Div, Parkville, Vic, Australia. [Lindqvist, Lisa M.] Univ Melbourne, Walter & Eliza Hall Inst Med Res, Dept Med Biol, Parkville, Vic 3052, Australia. [White, Anthony R.] Univ Melbourne, Dept Pathol, Parkville, Vic 3052, Australia. [Delbridge, Lea M. D.] Univ Melbourne, Dept Physiol, Parkville, Vic 3052, Australia. [Pepe, Salvatore] Univ Melbourne, Murdoch Childrens Res Inst, Dept Paediat, Royal Childrens Hosp, Melbourne, Vic, Australia. [Kim, Michael D.] Univ Miami, Miller Sch Med, Dept Mol & Cellular Pharmacol, Miami, FL 33136 USA. [Man, Na] Univ Miami, Miller Sch Med, Sylvester Comprehens Canc Ctr, Miami, FL 33136 USA. [Soleimanpour, Scott A.] Univ Michigan, Sch Med, Dept Internal Med, Ann Arbor, MI 48109 USA. [Lieberman, Andrew P.; Lukacs, Nicholas W.] Univ Michigan, Sch Med, Dept Pathol, Ann Arbor, MI 48109 USA. [Towns, Roberto] Univ Michigan, Ann Arbor, MI 48109 USA. [Duncan, Mara C.] Univ Michigan, Dept Cell & Dev Biol, Ann Arbor, MI 48109 USA. [Swanson, Michele S.] Univ Michigan, Dept Microbiol & Immunol, Ann Arbor, MI 48109 USA. [Lee, Jun Hee] Univ Michigan, Dept Mol & Integrat Physiol, Ann Arbor, MI 48109 USA. [Klionsky, Daniel J.; Feng, Yuchen; Gatica, Damian; Jin, Meiyan; Kumar, Anuj; Liu, Xu; Orban, Daniel P.; Parzych, Katherine R.; Wen, Xin; Xu, Haoxing; Xu, Ziheng; Yao, Zhiyuan] Univ Michigan, Dept Mol Cellular & Dev Biol, Ann Arbor, MI 48109 USA. [Zacks, David N.] Univ Michigan, Dept Ophthalmol & Visual Sci, Ann Arbor, MI 48109 USA. [Xie, Chuan-Ming] Univ Michigan, Dept Radiat Oncol, Ann Arbor, MI 48109 USA. [Sun, Yi; Zhao, Yongchao] Univ Michigan, Dept Radiat Oncol, Div Radiat & Canc Biol, Ann Arbor, MI 48109 USA. [Klionsky, Daniel J.; Ariosa, Aileen R.; Bernard, Amelie; Delorme-Axford, Elizabeth; Feng, Yuchen; Gatica, Damian; Jin, Meiyan; Liu, Xu; Orban, Daniel P.; Parzych, Katherine R.; Popelka, Hana; Wen, Xin; Xu, Ziheng; Yao, Zhiyuan] Univ Michigan, Inst Life Sci, Ann Arbor, MI 48109 USA. [Burmeister, Margit] Univ Michigan, Mol & Behav Neurosci Inst, Dept Computat Med & Bioinformat, Ann Arbor, MI 48109 USA. [Burmeister, Margit] Univ Michigan, Mol & Behav Neurosci Inst, Dept Psychiat, Ann Arbor, MI 48109 USA. [Burmeister, Margit] Univ Michigan, Mol & Behav Neurosci Inst, Dept Human Genet, Ann Arbor, MI 48109 USA. [Hua, Ya] Univ Michigan, Neurosurg, Ann Arbor, MI 48109 USA. [Kahana, Alon] Univ Michigan, Ophthalmol & Visual Sci, Kellogg Eye Ctr, Ann Arbor, MI 48109 USA. [Liu, Fei] Univ Michigan, Sch Dent, Dept Biol & Mat Sci, Ann Arbor, MI 48109 USA. [Minucci, Saverio] Univ Milan, Dept Expt Oncol, European Inst Oncol, Milan, Italy. [Minucci, Saverio] Dept Biosci, Milan, Italy. [Avagliano, Laura; Marconi, Anna Maria] Univ Milan, Dept Hlth Sci, Milan, Italy. [Vitale, Giovanni] Univ Milan, Ist Auxol Italiano, Dept Clin Sci & Community Hlth, Milan, Italy. [Ludovico, Paula] Univ Minho, Life & Hlth Sci Res Inst ICVS, Sch Hlth Sci, Braga, Portugal. [Sousa, Maria Joao] Univ Minho, Mol & Environm Biol Ctr CBMA, Dept Biol, Braga, Portugal. [Ludovico, Paula] ICVS 3Bs PT Govt Associate Lab, Braga, Portugal. [Kim, Do-Hyung] Univ Minnesota, Dept Biochem Mol Biol & Biophys, Minneapolis, MN USA. [Mauvezin, Caroline] Univ Minnesota, Dept Genet Cell Biol & Dev, Minneapolis, MN USA. [Abedin, Md Joynal] Univ Minnesota, Dept Lab Med & Pathol, Minneapolis, MN 55455 USA. [Karim, Md Razaul] Univ Minnesota, Dept Neurosci, Minneapolis, MN 55455 USA. [Saluja, Ashok K.] Univ Minnesota, Dept Surg, Box 242 UMHC, Minneapolis, MN 55455 USA. [Imbriano, Carol; Pinti, Marcello] Univ Modena & Reggio Emilia, Dept Life Sci, Modena, Italy. [Gibellini, Lara] Univ Modena & Reggio Emilia, Dept Surg Med Dent & Morphol Sci, Modena, Italy. [Cossarizza, Andrea] Univ Modena & Reggio Emilia, Sch Med, Dept Surg Med Dent & Morphol Sci, Modena, Italy. [Koechlin-Ramonatxo, Christelle] Univ Montpellier, INRA, UMR 866, Dynam Musculaire & Metab, F-34059 Montpellier, France. [Candau, Robin] Univ Montpellier, UMR 866, Dynam Musculaire & Metab, F-34059 Montpellier, France. [Godefroy, Nelly; Martinand-Mari, Camille] Univ Montpellier, UMR 5554, F-34059 Montpellier, France. [Valdor, Rut] Univ Murcia, IMIB Virgen Arrixaca Hosp, Human Anat & Psycobiol Dept, Cell Therapy & Hematopoiet Transplantat Unit, Murcia, Spain. [Shidoji, Yoshihiro] Nagasaki Univ, Mol & Cellular Biol, Grad Sch Human Hlth Sci, Nagasaki 852, Japan. [Arnould, Thierry; Michiels, Carine] Univ Namur, Lab Biochem & Cell Biol URBC, Namur Res Inst Life Sci NARILIS, Namur, Belgium. [Hamer, Isabelle] Univ Namur, Res Unit Mol Physiol URPhyM, Namur, Belgium. [Ciarcia, Roberto; De Martino, Luisa; Fiorito, Filomena; Florio, Salvatore; Montagnaro, Serena; Pagnini, Ugo] Univ Naples Federico II, Dept Vet Med & Anim Prod, Naples, Italy. [Donohue, Terrence M., Jr.; Thomes, Paul G.] Univ Nebraska Med Ctr, Dept Internal Med, Omaha, NE USA. [Buch, Shilpa] Univ Nebraska Med Ctr, Omaha, NE USA. [Franco, Rodrigo] Univ Nebraska, Redox Biol Ctr, Lincoln, NE USA. [Franco, Rodrigo] Sch Vet Med & Biomed Sci, Lincoln, NE USA. [Ozbun, Michelle A.] Univ New Mexico, Ctr Comprehens Canc, Dept Mol Genet & Microbiol, Albuquerque, NM 87131 USA. [Dokladny, Karol; Moseley, Pope L.] Univ New Mexico, Dept Internal Med, Albuquerque, NM 87131 USA. [Cleyrat, Cedric] Univ New Mexico, Dept Pathol, Albuquerque, NM 87131 USA. [Cleyrat, Cedric] Canc Res & Treatment Ctr, Albuquerque, NM USA. [Deretic, Vojo; Kimura, Tomonori; Mandell, Michael A.] Univ New Mexico, Hlth Sci Ctr, Dept Mol Genet & Microbiol, Albuquerque, NM 87131 USA. [Cheluvappa, Rajkumar] Univ New S Wales, Inflammat & Infect Res Ctr, Sch Med Sci, Sydney, NSW, Australia. [Kaakoush, Nadeem O.] Univ New S Wales, Sch Biotechnol & Biomol Sci, Sydney, NSW, Australia. [Zhang, Xu Dong] Univ Newcastle, Sch Biomed Sci & Pharm, Newcastle, NSW 2300, Australia. [Jin, Lei] Univ Newcastle, Sch Med & Publ Hlth, Callaghan, NSW 2308, Australia. [Auberger, Patrick] Univ Nice, INSERM U1065, C3M, Nice, France. [Hofman, Paul] Univ Nice Sophia Antipolis, INSERM U1081, CNRS 7284, Fac Med, F-06189 Nice, France. [Bulavin, Dmitry V.] Univ Nice Sophia Antipolis, IRCAN, F-06189 Nice, France. [Vouret-Craviari, Valerie] Univ Nice Sophia Antipolis, IRCAN, F-06189 Nice, France. [Aoki, Hiroshi] Niigata Univ, Dept Neurosurg, Brain Res Inst, Niigata, Japan. [Bultman, Scott J.] Univ N Carolina, Dept Genet, Chapel Hill, NC USA. [Ting, Jenny Pan-yun] Univ N Carolina, Dept Microbiol & Immunol, Chapel Hill, NC USA. [Der, Channing J.] Univ N Carolina, Lineberger Comprehens Canc Ctr, Chapel Hill, NC 27599 USA. [Ting, Jenny Pan-yun] Univ N Carolina, Lineberger Comprehens Canc Ctr, Inst Inflammatory Dis, Ctr Translat Immunol, Chapel Hill, NC 27599 USA. [Kawula, Thomas] Univ N Carolina, Microbiol & Immunol, Chapel Hill, NC USA. [Wu, Min] Univ N Dakota, Dept Biomed Sci, Sch Med & Hlth Sci, Grand Forks, ND 58201 USA. [Basu, Alakananda] Univ N Texas, Hlth Sci Ctr, Dept Mol & Med Genet, Ft Worth, TX USA. [Layfield, Robert] Univ Nottingham, Sch Life Sci, Nottingham NG7 2RD, England. [Adachi, Hiroaki] Univ Occupat & Environm Hlth, Sch Med, Dept Neurol, Fukuoka, Japan. [Harada, Masaru] Univ Occupat & Environm Hlth, Dept Internal Med 3, Kitakyushu, Fukuoka, Japan. [Xu, Jian] Univ Oklahoma, Hlth Sci Ctr, Dept Med, Oklahoma City, OK USA. [Ramesh, Rajagopal; Zhao, Zhizhuang J.] Univ Oklahoma, Hlth Sci Ctr, Dept Pathol, Oklahoma City, OK USA. [Xie, Zhonglin] Univ Oklahoma, Hlth Sci Ctr, Sect Mol Med, Dept Med, Oklahoma City, OK USA. [Jain, Ashish; Rusten, Tor Erik] Univ Oslo, Ctr Canc Biomed, Oslo, Norway. [Seglen, Per O.] Univ Oslo, Ctr Mol Med Norway NCMM, Oslo, Norway. [Torgersen, Maria Lyngaas] Univ Oslo, Dept Biochem, Inst Canc Res, Oslo, Norway. [Mills, Ian G.] Univ Oslo, Dept Mol Oncol, Dept Urol, Oslo, Norway. [Nilsen, Hilde] Univ Oslo, Dept Clin Mol Biol, Oslo, Norway. [Petrovski, Goran] Univ Oslo, Dept Ophthalmol, Oslo, Norway. [Mills, Ian G.] Queens Univ Belfast, Ctr Canc Res & Cell Biol, Lisburn Rd, Belfast, Antrim, North Ireland. [Blomhoff, Heidi Kiil; Simonsen, Anne] Univ Oslo, Inst Basic Med Sci, Oslo, Norway. [Engedal, Nikolai; Gerner, Lisa] Univ Oslo, Oslo Univ Hosp, Ctr Mol Med Norway, Nord EMBL Partnership, Oslo, Norway. [Hensel, Michael] Univ Osnabrueck, Div Microbiol, Osnabruck, Germany. [Ungermann, Christian] Univ Osnabrueck, Fachbereich Biol Chem, Osnabruck, Germany. [Slack, Ruth] Univ Ottawa, Dept Cellular & Mol Med, Fac Med, Ottawa, ON, Canada. [Gibbings, Derrick J.] Univ Ottawa, Dept Cellular & Mol Med, Ottawa, ON, Canada. [Marino, Guillermo] Univ Oviedo, Dept Anim Physiol, Fac Med, Campus Cristo, Oviedo, Spain. [Buchan, Alastair M.] Univ Oxford, Acute Stroke Programme, Radcliffe Dept Med, Oxford, England. [Hammond, Ester M.] Univ Oxford, CRUK MRC Oxford Inst Radiat Oncol, Oxford, England. [Poulton, Joanna] Univ Oxford, Nuffield Dept Obstet & Gynaecol, Oxford, England. [Brini, Marisa; Valle, Luisa Dalla; Scovassi, A. Ivana] Univ Padua, Dept Biol, Padua, Italy. [Bonaldo, Paolo; Chen, Peiwen; Grumati, Paolo] Univ Padua, Dept Mol Med, Padua, Italy. [Viola, Giampietro] Univ Padua, Dept Womans & Childs Hlth, Lab Oncohematol, Padua, Italy. [Monick, Martha M.; Sandri, Marco; Zaglia, Tania] Univ Padua, Venetian Inst Mol Med, Dept Biomed Sci, Padua, Italy. [Agnello, Maria; Chiarelli, Roberto; Luparello, Claudio; Roccheri, Maria Carmela] Univ Palermo, Dipartimento Sci &Tecnol Biol, Chim & Farmaceutiche STEBICEF, Palermo, Italy. [Bettuzzi, Saverio; Rizzi, Federica] Univ Parma, Dept Biomed Biotechnol & Translat Sci, I-43100 Parma, Italy. [Comincini, Sergio; Palumbo, Silvia] Univ Pavia, Dept Biol & Biotechnol, Via Palestro 3, I-27100 Pavia, Italy. [Emanuele, Enzo] Univ Pavia, Dept Hlth Sci, Via Palestro 3, I-27100 Pavia, Italy. [Koumenis, Constantinos] Univ Penn, Perelman Sch Med, Dept Radiat Oncol, Philadelphia, PA 19104 USA. [O'Dwyer, Peter J.; Vogl, Dan T.] Univ Penn, Abramson Canc Ctr, Philadelphia, PA 19104 USA. [Gonzalez-Alegre, Pedro] Univ Penn, Ctr Cell & Mol Therapy, Children Hosp Philadelphia, Dept Neurol,Perelman Sch Med, Philadelphia, PA 19104 USA. [Mitchell, Claire H.] Univ Penn, Dept Anat & Cell Biol, Philadelphia, PA 19104 USA. [Boesze-Battaglia, Kathleen] Univ Penn, Dept Biochem, SDM, Philadelphia, PA 19104 USA. [Cherry, Sara] Univ Penn, Dept Microbiol, Philadelphia, PA 19104 USA. [Zhang, Lin] Univ Penn, Dept Obstet & Gynecol, Philadelphia, PA 19104 USA. [Zhang, Lin] Perelman Sch Med, Philadelphia, PA USA. [Sanchez, Anthony M. J.] Univ Perpignan Via Domitia, Lab Europee Performance St Altitude, EA 4604, Ft Romeu, France. [Romani, Luigina] Univ Perugia, Dept Expt Med, I-06100 Perugia, Italy. [De Tata, Vincenzo; Fornai, Francesco; Lenzi, Paola] Univ Pisa, Dept Translat Res & New Technol Med & Surg, Pisa, Italy. [Cavallini, Gabriella] Univ Pisa, Interdepartmental Res Ctr Biol & Pathol Aging, Pisa, Italy. [Singh, Shivendra V.] Univ Pittsburgh, Inst Canc, Hillman Canc Ctr Res Pavil, Pittsburgh, PA USA. [Johnson, Daniel E.] Univ Pittsburgh, Inst Canc, Pittsburgh, PA USA. [Tsung, Allan] Univ Pittsburgh, Med Ctr, Dept Surg, Pittsburgh, PA USA. [Gomez, Hernando] Univ Pittsburgh, Dept Crit Care Med, Ctr Crit Care Nephrol, Clin Res Invest & Syst Modeling Acute Illness, Pittsburgh, PA USA. [Coyne, Carolyn B.] Univ Pittsburgh, Dept Microbiol & Mol Genet, Pittsburgh, PA USA. [Rabinowich, Hannah] Univ Pittsburgh, Dept Pathol, Pittsburgh, PA USA. [Kang, Rui; Tang, Daolin] Univ Pittsburgh, Dept Surg, Hillman Canc Ctr, Pittsburgh, PA USA. [Fan, Jie; Lee, Yong J.] Univ Pittsburgh, Dept Surg, Pittsburgh, PA USA. [Lotze, Michael T.] Univ Pittsburgh, Dept Surg, Inst Canc, Pittsburgh, PA USA. [Perlmutter, David H.] Univ Pittsburgh, Pittsburgh, PA USA. [Ouyang, Hongjiao] Univ Pittsburgh, Sch Dent Med, Dept Endodont, Pittsburgh, PA USA. [Kaynar, A. Murat] Univ Pittsburgh, Sch Med, Dept Anesthesiol, Pittsburgh, PA USA. [Kaynar, A. Murat] Univ Pittsburgh, Sch Med, Dept Crit Care Med, Pittsburgh, PA USA. [Lu, Binfeng] Univ Pittsburgh, Sch Med, Dept Immunol, Pittsburgh, PA USA. [Chu, Charleen T.] Univ Pittsburgh, Sch Med, Dept Pathol, Pittsburgh, PA USA. [Chu, Charleen T.] Univ Pittsburgh, Ctr Neurosci, Pittsburgh, PA 15260 USA. [Pak, Stephen C.; Silverman, Gary A.] Univ Pittsburgh, Sch Med, Dept Pediat, Pittsburgh, PA 15260 USA. [Zhang, Lin] Univ Pittsburgh, Sch Med, Dept Pharmacol & Chem Biol, Pittsburgh, PA 15260 USA. [Stang, Michael T.] Univ Pittsburgh, Sch Med, Dept Surg, Div Endocrine Surg, Pittsburgh, PA 15260 USA. [Isenberg, Jeffrey S.] Univ Pittsburgh, Vasc Med Inst, Pittsburgh, PA 15260 USA. [Page, Guylene] Univ Poitiers, Mol Targets & Therapeut Alzheimers Dis EA3808, Poitiers, France. [Lima, Raquel T.; Seca, Hugo; Vasconcelos, M. Helena; Xavier, Cristina P. R.] Univ Porto, Canc Drug Resistance Grp, IPA TIMUP, Inst Mol Pathol & Immunol, Rua Campo Alegre 823, P-4100 Oporto, Portugal. [Seca, Hugo; Vasconcelos, M. Helena] Univ Porto, Dept Biol Sci, Fac Pharm, Rua Campo Alegre 823, P-4100 Oporto, Portugal. [Lima, Raquel T.] Univ Porto, Dept Pathol & Oncol, Fac Pharm, Rua Campo Alegre 823, P-4100 Oporto, Portugal. [Lima, Raquel T.; Seca, Hugo; Vasconcelos, M. Helena; Xavier, Cristina P. R.] Univ Porto, i3S, Rua Campo Alegre 823, P-4100 Oporto, Portugal. [Joubert, Annie M.; Nolte, Elsie Magdalena; Theron, Anne E.] Univ Pretoria, Dept Physiol, ZA-0002 Pretoria, Gauteng, South Africa. [Asselin, Eric] Univ Quebec Trois Rivieres, Dept Biol & Med, Trois Rivieres, PQ GA9 5H7, Canada. [Walker, Mark J.] Univ Queensland, Australian Infect Dis Res Ctr, Brisbane, Qld, Australia. [Walker, Mark J.] Sch Chem & Mol Biosci, Brisbane, Qld, Australia. [Wolvetang, Ernst J.] Univ Queensland, AIBN, Brisbane, Qld, Australia. [Manzoni, Claudia] Univ Reading, Sch Pharm, Reading, Berks, England. [Lewis, Patrick A.] Univ Reading, Sch Pharm, Whiteknights, Reading, Berks, England. [Brookes, Paul S.; Johnson, Gail V. W.] Univ Rochester, Med Ctr, Dept Anesthesiol, Rochester, NY 14642 USA. [Sparks, Janet D.] Univ Rochester, Med Ctr, Dept Pathol & Lab Med, Rochester, NY 14642 USA. [Giordano, Antonio] Univ Siena, Dept Med Surg & Neurosci, Via Laterina 8, I-53100 Siena, Italy. [Sciarretta, Sebastiano] Univ Roma La Sapienza, Dept Med Surg Sci & Biotechnol, Latina, Italy. [Aquilano, Katia; Campello, Silvia; Ciriolo, Maria Rosa; Di Bartolomeo, Sabrina; Filomeni, Giuseppe; Barbato, Daniele Lettieri; Piacentini, Mauro] Univ Roma Tor Vergata, Dept Biol, Rome, Italy. [Schiavi, Alfonso] Univ Roma Tor Vergata, Dept Biomed & Prevent, Rome, Italy. [Franco, Rodrigo] Univ Roma Tor Vergata, Dept Chem, Rome, Italy. [Ozbun, Michelle A.] Univ Roma Tor Vergata, Dept Clin Sci & Translat Med, Rome, Italy. [Bernassola, Francesca] Univ Roma Tor Vergata, Dept Expt Med & Surg, Rome, Italy. [Melino, Gerry] Univ Roma Tor Vergata, Dept Surg & Expt Med, Rome, Italy. [Di Daniele, Nicola; Federici, Massimo; Menghini, Rossella] Univ Roma Tor Vergata, Dept Syst Med, Rome, Italy. [Cecconi, Francesco; Corazzari, Marco] Univ Roma Tor Vergata, Dept Biol, Rome, Italy. [Sibirny, Andriy A.] Univ Rzeszow, Inst Biol, Rzeszow, Poland. [Dini, Luciana] Univ Salento, Dept Biol & Environm Sci & Technol, Lecce, Italy. [Fimia, Gian Maria] Univ Salento, Dept Biol & Environm Sci & Technol DiSTeBA, Lecce, Italy. [Iovane, Valentina] Univ Salento, Dept Pharm, Salerno, Italy. [Valente, Enza Maria] Univ Salento, Sect Neurosci, Dept Med & Surg, Salerno, Italy. [Machado-Santelli, Glaucia M.] Univ Sao Paulo, Inst Biomed Sci, Dept Cell & Dev Biol, Sao Paulo, SP, Brazil. [Goncalves, Dawit A. P.; Kettelhut, Isis do Carmo; Machado, Juliano] Univ Sao Paulo, Ribeirao Preto Med Sch, Dept Biochem & Immunol, Ribeirao Preto, SP, Brazil. [Navegantes, Luiz C.; Silveira, Wilian A.] Univ Sao Paulo, Ribeirao Preto Med Sch, Dept Physiol, Ribeirao Preto, SP, Brazil. [Brum, Patricia Chakur; Jannig, Paulo Roberto] Univ Sao Paulo, Sch Phys Educ & Sport, Cellular & Mol Exercise Physiol Lab, Sao Paulo, Brazil. [Man, Na; Wen, Longping; Zhang, Yunjiao] Univ Sci & Technol China, Hefei, Anhui, Peoples R China. [Mei, Yide] Univ Sci & Technol China, CAS Key Lab Innate Immun & Chron Dis, Sch Lifesci, Hefei, Anhui, Peoples R China. [Shi, Qinghua] Univ Sci & Technol China, Sch Life Sci, Hefei, Anhui, Peoples R China. [Shi, Qinghua] Hefei Natl Lab Phys Sci Microscale, Hefei, Anhui, Peoples R China. [Wu, Mian] Univ Sci & Technol China, Sch Life Sci, Hefei, Anhui, Peoples R China. [Daza, Paula] Univ Seville, Dept Cell Biol, Seville, Spain. [Cordero, Mario D.] Univ Seville, Inst Biomed Sevilla IBIS, Dept Oral Med, Seville, Spain. [King, Jason S.] Univ Sheffield, Dept Biomed Sci, Sheffield S10 2TN, S Yorkshire, England. [Boucher, Marie-Josee] Univ Sherbrooke, Fac Med & Sci St, Dept Med, Div Gastroenterol, Sherbrooke, PQ J1K 2R1, Canada. [Del Bello, Barbara; Maellaro, Emilia] Univ Siena, Dept Mol & Dev Med, Via Laterina 8, I-53100 Siena, Italy. [Poprawa, Izabela; Rost-Roszkowska, Magdalena] Univ Silesia, Dept Anim Histol & Embryol, Katowice, Poland. [Tan, Ming] Univ S Alabama, Mitchell Canc Inst, Mobile, AL 36688 USA. [Kumar, Sharad] Univ S Australia, Adelaide, SA 5001, Australia. [Kumar, Sharad] Ctr Canc Biol, SA Pathol, Adelaide, SA, Australia. [Morrison, Janna L.] Univ S Australia, Early Origins Adult Hlth Res Grp, Sch Pharm & Med Sci, Sansom Inst Hlth Res, Adelaide, SA 5001, Australia. [Cui, Taixing; Fan, Daping] Univ S Carolina, Sch Med, Dept Cell Biol & Anat, Columbia, SC 29208 USA. [Ray, Swapan K.] Univ S Carolina, Sch Med, Dept Pathol Microbiol & Immunol, Columbia, SC 29208 USA. [Baumgarner, Bradley L.] Univers South Carolina Upstate, Dept Biol, Div Nat Sci & Engn, Spartanburg, SC USA. [Chatterjee, Saurabh] Univ S Carolina, Environm Hlth & Dis Lab, Dept Environm Hlth Sci, Columbia, SC 29208 USA. [Pattison, Scott] Univ S Dakota, Div Basic Biomed Sci, Vermillion, SD 57069 USA. [Wang, Hongmin] Univ S Dakota, Sanford Sch Med, Div Basic Biomed Sci, Vermillion, SD 57069 USA. [Wang, Xuejun] Univ S Dakota, Vermillion, SD 57069 USA. [Dickey, Chad A.] Univ S Florida, Byrd Alzheimers Inst, Tampa, FL USA. [Nanjundan, Meera] Univ S Florida, Dept Cell Biol Microbiol & Mol Biol, Tampa, FL USA. [Uversky, Vladimir N.] Univ S Florida, Dept Mol Med, Tampa, FL USA. [Zhou, Shu-Feng] Univ S Florida, Dept Pharmaceut Sci, Tampa, FL USA. [Jinwal, Umesh Kumar] Univ S Florida, Dept Pharmaceut Sci, Coll Pharm, Byrd Alzheimers Inst, Tampa, FL USA. 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[Zhang, Long] Zhejiang Univ, Inst Life Sci, Hangzhou, Zhejiang, Peoples R China. [Liu, Wei] Zhejiang Univ, Sch Med, Dept Biochem, Hangzhou 310003, Zhejiang, Peoples R China. [Han, Weidong] Zhejiang Univ, Sir Run Run Shaw Hosp, Coll Med, Hangzhou 310003, Zhejiang, Peoples R China. [Pan, Hongming; Sui, Xinbing] Zhejiang Univ, Sir Run Run Shaw Hosp, Dept Med Oncol, Hangzhou 310003, Zhejiang, Peoples R China. [Chen, Yongshun] Zhengzhou Univ, Affiliated Canc Hosp, Zhengzhou 450052, Peoples R China. RP Klionsky, DJ (reprint author), Univ Michigan, Inst Life Sci, Ann Arbor, MI 48109 USA. 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Cervia, Davide/0000-0002-2727-9449; Li, Rui/0000-0002-7210-8358; Soenen, Stefaan/0000-0003-2390-3133; Tapia, Jose/0000-0002-3614-6867; Wang, Haichao/0000-0002-0211-9000; Duran, Raul/0000-0002-2249-9215; Xue, Yu/0000-0002-9403-6869; Ke, Zun-Ji/0000-0003-4038-2456; Chiong, Mario/0000-0002-5174-6545; Penalva, Miguel A/0000-0002-3102-2806; Pinton, Paolo/0000-0001-7108-6508; xia, tian/0000-0003-0123-1305; Tettamanti, Gianluca/0000-0002-0665-828X; Corazzari, Marco/0000-0002-6246-5968; Neves, Bruno/0000-0001-7391-3124; Yamanaka, Koji/0000-0003-4655-0035; Besteiro, Sebastien/0000-0003-1853-1494; Garcia-Macia, Marina/0000-0002-3908-9060; Lopez-Otin, Carlos/0000-0001-6964-1904; King, Jason/0000-0003-0596-4506; ZHUANG, Xiaohong/0000-0002-2480-8210; Smith, Duncan /0000-0002-6592-9852; Molinari, Marco/0000-0001-9808-9688; Vitale, Giovanni/0000-0003-2478-683X; Piacentini, Mauro/0000-0003-2919-1296; ferraro, elisabetta/0000-0002-9596-4624; Nardacci, Roberta/0000-0002-9209-1207; Chiacchiera, Fulvio/0000-0003-3830-2090; 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Oshima, Shigeru/0000-0003-1186-9177; Mauvezin, Caroline/0000-0003-4220-7272; Gotor, Cecilia/0000-0003-4272-7446; Poletti, Angelo/0000-0002-8883-0468; Liu, Zexian/0000-0001-9698-0610; Szegezdi, Eva/0000-0002-5708-3535; Rodrigues, Cecilia/0000-0002-4829-754X; LEE, Sung Sik/0000-0001-9267-232X; Villar-Rayo, Marga/0000-0003-4172-9079; Mizushima, Noboru/0000-0002-6258-6444; Segui-Simarro, Jose M./0000-0001-7672-4169; Segura-Aguilar, Juan/0000-0002-1018-673X; Viscomi, Maria Teresa/0000-0002-9096-4967; Arimoto, Hirokazu/0000-0002-0086-6117; Jannig, Paulo/0000-0002-2569-4091; Wang, Chengshu/0000-0003-1477-1466; Knavelsrud, Helene/0000-0001-8848-8829; trisciuoglio, Daniela/0000-0002-7007-7914; De Santi, Mauro/0000-0003-2983-8344; Wu, William K.K./0000-0002-5662-5240; GROS, Frederic/0000-0002-6252-4323; Di Renzo, Livia/0000-0003-3807-0760; Clarke, Robert/0000-0002-9278-0854; Morrison, Janna/0000-0002-8602-8519; Poirot, Marc/0000-0002-5711-6624; Van Kaer, Luc/0000-0001-5275-2309; De Meyer, Guido/0000-0003-3848-8702; 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Romani, Luigina/0000-0002-1356-525X; Velasco, Guillermo/0000-0002-1994-2386; Bravo-San Pedro, Jose Manuel/0000-0002-5781-1133; Chieppa, Marcello/0000-0001-9819-0823; Frigo, Daniel/0000-0002-0713-471X; Olsson, Stefan/0000-0003-1931-9081; Cocco, Tiziana/0000-0001-7171-3460; Chang, Chih-Peng/0000-0002-0061-3478; Dikic, Ivan/0000-0001-8156-9511; Norga, Koenraad/0000-0002-9231-0350; Harris, Adrian/0000-0003-1376-8409; Kaminskyy, Vitaliy/0000-0002-8151-5270; Qi, Xin/0000-0002-9578-3890; Shiri-Sverdlov, Ronit/0000-0002-6736-7814; Schiavi, Alfonso/0000-0002-6563-8035; Ketteler, Robin/0000-0002-2786-7291; Salazar, Maria/0000-0001-6784-9541; CRIPPA, VALERIA/0000-0002-3058-5711; Wu, Jian/0000-0001-9933-7364; Hilfiker, Sabine/0000-0002-5167-7682; Hulmi, Juha/0000-0003-3813-2124; Fernandez-Checa, Jose Carlos/0000-0003-3422-2990; Wong, Esther/0000-0003-2421-7346; Chen, Quan/0000-0001-7539-8728; Rudolf, Ruediger/0000-0002-0833-1053; Zhu, Wei-Guo/0000-0001-8385-6581; Winklhofer, Konstanze/0000-0002-7256-8231; Fearnhead, Howard/0000-0002-8054-9794; Sahni, Sumit/0000-0002-2900-8845; Clementi, Emilio/0000-0001-7333-8270; , Carmen/0000-0002-2652-6102; Kalia, Manjula/0000-0002-3376-3659; Cianfanelli, Valentina/0000-0002-3857-9463; Rein, Theo/0000-0003-2850-4289; antonioli, manuela/0000-0002-7568-4713; MacIntosh, Gustavo/0000-0003-1350-1229; Hamann, Andrea/0000-0001-9821-7491; Sigurdsson, Einar/0000-0003-1451-0952 FU BLRD VA [I01 BX001746, I01 BX001969]; Biotechnology and Biological Sciences Research Council [BBS/E/B/000C0413]; Cancer Research UK [11359, 12825, 12918]; Doris Duke Charitable Foundation [2014112]; Medical Research Council [G0300648, G0601891, G0801936, G1000089, G1002186, MC_U105185860, MC_U132670600, MC_UP_A500_1019, MC_UU_12016/4, MC_UU_12022/6, MR/J010448/1, MR/L010933/1, MR/M00869X/1, MR/M019217/1, MR/N004434/1]; NCCIH NIH HHS [R01 AT005076]; NCI NIH HHS [K08 CA164047, K08 CA193982, K22 CA181274, P01 CA163200, P30 CA010815, R01 CA078810, R01 CA089121, R01 CA130893, R01 CA140964, R01 CA142862, R01 CA143811, R01 CA162405, R01 CA184137, R01 CA187305, R01 CA193698, T32 CA009686, U54 CA149147]; NCRR NIH HHS [P20 RR024489]; NEI NIH HHS [R01 EY005681, R01 EY009083, R01 EY010199, R01 EY013434, R01 EY015537, R01 EY018884, R01 EY019643, R01 EY022633, R01 EY023512, R01 EY024327, R01 EY025362, R21 EY026207]; NHLBI NIH HHS [R01 HL107594, P01 HL129941, R01 HL056416, R01 HL059888, R01 HL071158, R01 HL072166, R01 HL072844, R01 HL079669, R01 HL098216, R01 HL117913, R01 HL126711, R01 HL130174, R01 HL130230, R01 HL130845, R56 HL122580]; NIA NIH HHS [K02 AG042095, P01 AG031782, P30 AG028740, R00 AG042494, R00 AG048016, R01 AG020197, R01 AG031867, R01 AG032611, R01 AG038664, R01 AG039756, R01 AG043517, R37 AG021904]; NIAAA NIH HHS [K01 AA019996, R01 AA019954, R01 AA022601]; NIAID NIH HHS [R01 AI042999, R01 AI091968, R01 AI092084, R01 AI103197, R01 AI104928, R01 AI108906, R01 AI111935, R21 AI115286]; NIAMS NIH HHS [R01 AR042527, R01 AR050429, R01 AR060837, R01 AR062030, R21 AR060444]; NICHD NIH HHS [U54 HD090255]; NIDDK NIH HHS [K01 DK075386, K08 DK089117, P01 DK098108, P30 DK020541, P30 DK020572, P30 DK020593, R00 DK094980, R01 DK033823, R01 DK044234, R01 DK061498, R01 DK062092, R01 DK073336, R01 DK076685, R01 DK079879, R01 DK090115, R01 DK097441, R01 DK098331, R01 DK105118, R01 DK107220, R03 DK089010, R03 DK106304, R03 DK106344, R21 DK075494, R56 DK037034, R56 DK108921]; NIEHS NIH HHS [P30 ES006694, P30 ES023512]; NIGMS NIH HHS [GM053396, K12 GM068524, P20 GM103492, P20 GM103554, P20 GM103652, P20 GM104934, R01 GM021841, R01 GM053396, R01 GM060574, R01 GM061766, R01 GM063075, R01 GM101056, R01 GM114840, R01 GM116908]; NINDS NIH HHS [K08 NS083739, K08 NS085324, R01 NS062792, R01 NS073813, R01 NS075685, R01 NS076896, R01 NS077239, R01 NS078072, R01 NS079697, R01 NS085070, R01 NS088192, R01 NS089737, R01 NS091218, R01 NS094527, R03 NS090939, R21 NS091928]; Parkinson's UK [F-1002, H-1201, K-1202]; Wellcome Trust [087518]; Worldwide Cancer Research [14-1328] NR 2174 TC 332 Z9 341 U1 543 U2 915 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 530 WALNUT STREET, STE 850, PHILADELPHIA, PA 19106 USA SN 1554-8627 EI 1554-8635 J9 AUTOPHAGY JI Autophagy PY 2016 VL 12 IS 1 BP 1 EP 222 DI 10.1080/15548627.2015.1100356 PG 222 WC Cell Biology SC Cell Biology GA DI6FU UT WOS:000373595400001 PM 26799652 ER PT J AU Bhuiyan, TR Hoq, MR Nishat, NS Al Mahbuba, D Rashu, R Islam, K Hossain, L Dey, A Harris, JB Ryan, ET Calderwood, SB Svennerholm, AM Qadri, F AF Bhuiyan, Taufiqur Rahman Hoq, Mohammad Rubel Nishat, Naoshin Sharmin Al Mahbuba, Deena Rashu, Rasheduzzaman Islam, Kamrul Hossain, Lazina Dey, Ayan Harris, Jason B. Ryan, Edward T. Calderwood, Stephen B. Svennerholm, Ann-Mari Qadri, Firdausi TI Enumeration of Gut-Homing beta 7-Positive, Pathogen-Specific Antibody-Secreting Cells in Whole Blood from Enterotoxigenic Escherichia coli- and Vibrio cholerae-Infected Patients, Determined Using an Enzyme-Linked Immunosorbent Spot Assay Technique SO CLINICAL AND VACCINE IMMUNOLOGY LA English DT Article ID HUMAN PERIPHERAL-BLOOD; IMMUNE-RESPONSES; COLONIZATION FACTORS; PRODUCTION INVITRO; BANGLADESHI CHILDREN; IMMUNOLOGICAL MEMORY; ENTERIC INFECTIONS; ORAL IMMUNIZATION; O1 INFECTION; VACCINE AB Vibrio cholerae and enterotoxigenic Escherichia coli (ETEC) are noninvasive mucosal pathogens that cause acute watery diarrhea in people in developing countries. Direct assessment of the mucosal immune responses to these pathogens is problematic. Surrogate markers of local mucosal responses in blood are increasingly being studied to determine the mucosal immune responses after infection. However, the volume of blood available in children and infants has limited this approach. We assessed whether an approach that first isolates beta 7-positive cells from a small volume of blood would allow measurement of the antigen-specific immune responses in patients with cholera and ETEC infection. beta 7 is a cell surface marker associated with mucosal homing. We isolated beta 7-expressing cells from blood on days 2, 7, and 30 and used an enzyme-linked immunosorbent spot (ELISPOT) assay to assess the gut-homing antibody-secreting cells (ASCs) specific to pathogen antigens. Patients with ETEC diarrhea showed a significant increase in toxin-specific gut-homing ASCs at day 7 compared to the levels at days 2 and 30 after onset of illness and to the levels in healthy controls. Similar elevations of responses to the ETEC colonization factors (CFs) CS6 and CFA/I were observed in patients infected with CS6- and CFA/I-positive ETEC strains. Antigen-specific gut-homing ASCs to the B subunit of cholera toxin and cholera-specific lipopolysaccharides (LPS) were also observed on day 7 after the onset of cholera using this approach. This study demonstrates that a simple ELISPOT assay can be used to study the mucosal immunity to specific antigens using a cell-sorting protocol to isolate mucosal homing cells, facilitating measurement of mucosal responses in children following infection or vaccination. C1 [Bhuiyan, Taufiqur Rahman; Hoq, Mohammad Rubel; Nishat, Naoshin Sharmin; Al Mahbuba, Deena; Rashu, Rasheduzzaman; Islam, Kamrul; Hossain, Lazina; Qadri, Firdausi] Int Ctr Diarrhoeal Dis Res, Ctr Vaccine Sci, GPO Box 128, Dhaka 1000, Bangladesh. [Dey, Ayan] Int Vaccine Inst, Seoul, South Korea. [Harris, Jason B.; Ryan, Edward T.; Calderwood, Stephen B.] Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA. [Svennerholm, Ann-Mari] Univ Gothenburg, Dept Microbiol & Immunol, Gothenburg, Sweden. RP Qadri, F (reprint author), Int Ctr Diarrhoeal Dis Res, Ctr Vaccine Sci, GPO Box 128, Dhaka 1000, Bangladesh. EM fqadri@icddrb.org FU Commission of the European Communities grant [HEALTH-F3-2010-261472]; Fogarty International Centre [TW005572]; Swedish Collaborative grant SIDA [SWE2009-023]; Swedish SIDA [INT-ICDDR B-HN-01-AV]; HHS \ National Institutes of Health (NIH) [AI106878, AI058935, AI103055]; International Centre for Diarrhoeal Disease Research, Bangladesh (icddr,b) [SIDA-SWE-2009-023, B-HN-01-AV]; National Institutes of Health; National Institute of Allergy and Infectious Diseases [AI106878, AI058935, AI103055]; Fogarty International Center [TW005572] FX Commission of the European Communities grant to STOPENTERICS provided funding to Taufiqur Rahman Bhuiyan, Ann-Mari Svennerholm, and Firdausi Qadri under grant number HEALTH-F3-2010-261472. Fogarty International Centre provided funding to Taufiqur Rahman Bhuiyan, Rasheduzzaman Rashu, and Kamrul Islam under grant number TW005572. Swedish Collaborative grant SIDA provided funding to Mohammad Rubel Hoq, Naoshin Sharmin Nishat, Deena Al Mahbuba, Lazina Hossain, Ann-Mari Svennerholm, and Firdausi Qadri under grant number SWE2009-023. Swedish SIDA provided funding to Ann-Mari Svennerholm and Firdausi Qadri under grant number INT-ICDDR B-HN-01-AV. HHS vertical bar National Institutes of Health (NIH) provided funding to Jason B. Harris, Edward T. Ryan, Stephen B. Calderwood, Firdausi Qadri under grant numbers AI106878, AI058935, and AI103055.; This work was supported by the International Centre for Diarrhoeal Disease Research, Bangladesh (icddr,b), a Swedish Sida (SIDA) grant (INT-ICDDR,B-HN-01-AV), and Swedish collaborative grant SIDA-SWE-2009-023, as well as by the Commission of the European Communities grant to STOPENTERICS (grant HEALTH-F3-2010-261472). This study was also supported by grants from the National Institutes of Health, including grants from the National Institute of Allergy and Infectious Diseases (AI106878 [E.T.R. and F.Q.], AI058935 [S.B.C., E.T.R., and F.Q.], and AI103055 [J.B.H. and F.Q.]), and the Fogarty International Center (training grant in vaccine development and public health TW005572 [T.R.B., R.R., and K.I.]). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 48 TC 0 Z9 0 U1 3 U2 3 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 2016 VL 23 IS 1 BP 27 EP 36 DI 10.1128/CVI.00526-15 PG 10 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA DI4RY UT WOS:000373488200005 ER PT J AU Peak, NJ Overholser, JC Ridley, J Braden, A Fisher, L Bixler, J Chandler, M AF Peak, Nicole J. Overholser, James C. Ridley, Josephine Braden, Abby Fisher, Lauren Bixler, James Chandler, Megan TI Too Much to Bear Psychometric Evidence Supporting the Perceived Burdensomeness Scale SO CRISIS-THE JOURNAL OF CRISIS INTERVENTION AND SUICIDE PREVENTION LA English DT Article DE perceived burdensomeness; assessment; depression; hopelessness; suicide ID INTERPERSONAL-PSYCHOLOGICAL THEORY; INVENTORY-II SCORES; SUICIDAL IDEATION; COLLEGE-STUDENTS; THWARTED BELONGINGNESS; DEPRESSIVE SYMPTOMS; HOPELESSNESS SCALE; MILITARY PERSONNEL; OLDER-ADULTS; RISK-FACTORS AB Background: People who feel they have become a burden on others may become susceptible to suicidal ideation. When people no longer feel capable or productive, they may assume that friends and family members would be better off without them. Aim: The present study was designed to assess preliminary psychometric properties of a new measure, the Perceived Burdensomeness (PBS) Scale. Method: Depressed psychiatric patients (N = 173) were recruited from a veterans affairs medical center. Patients were assessed with a structured diagnostic interview and self-report measures assessing perceived burdensomeness, depression severity, hopelessness, and suicidal ideation. Results: The present study supported preliminary evidence of reliability and concurrent validity of the PBS. Additionally, perceived burdensomeness was significantly associated with higher levels of hopelessness and suicidal ideation. Conclusion: It is hoped that with the aid of the PBS clinicians may be able to intervene more specifically in the treatment of suicidality. C1 [Overholser, James C.] Case Western Reserve Univ, Dept Psychol, Cleveland, OH USA. [Ridley, Josephine] Louis Stokes Cleveland VA Med Ctr, Cleveland, OH USA. [Peak, Nicole J.] Univ Rockies, Sch Profess Psychol, Colorado Springs, CO USA. [Braden, Abby] Univ Calif San Diego, Ctr Hlth Eating & Act Res, San Diego, CA 92103 USA. [Fisher, Lauren] Massachusetts Gen Hosp, Dept Psychiat, Depress Clin & Res Program, Boston, MA 02114 USA. [Bixler, James] Frostburg State Univ, Counseling & Psychol Serv, Frostburg, MD 21532 USA. [Chandler, Megan] Torrance State Hosp, Sexual Responsibil & Treatment Program, Derry, PA USA. RP Peak, NJ (reprint author), Univ Rockies, Sch Profess Psychol, Colorado Springs, CO USA.; Peak, NJ (reprint author), Univ Rockies, 1201 16th St Suite 200, Denver, CO 80202 USA. EM nj.peak@gmail.com NR 53 TC 0 Z9 0 U1 4 U2 6 PU HOGREFE & HUBER PUBLISHERS PI GOTTINGEN PA ROHNSWEG 25, D-37085 GOTTINGEN, GERMANY SN 0227-5910 EI 2151-2396 J9 CRISIS JI Crisis PY 2016 VL 37 IS 1 BP 59 EP 67 DI 10.1027/0227-5910/a000355 PG 9 WC Psychiatry; Psychology, Multidisciplinary SC Psychiatry; Psychology GA DI2TM UT WOS:000373351800008 PM 26620916 ER PT J AU Weiner, MW Gorriz, JM Ramirez, J Castiglioni, I AF Weiner, Michael W. Gorriz, Juan M. Ramirez, Javier Castiglioni, Isabella TI Statistical Signal Processing in the Analysis, Characterization and Detection of Alzheimer's Disease SO CURRENT ALZHEIMER RESEARCH LA English DT Editorial Material C1 [Weiner, Michael W.] Univ Calif San Francisco, San Francisco VA Med Ctr, 4150 Clement St 114M, San Francisco, CA 94121 USA. [Gorriz, Juan M.; Ramirez, Javier] Univ Granada, Dept Signal Theory Networking & Commun, Fuentenueva S-N, E-18071 Granada, Spain. [Castiglioni, Isabella] CNR, Inst Mol Bioimaging & Physiol, Rome, Italy. RP Gorriz, JM; Ramirez, J (reprint author), Univ Granada, Dept Signal Theory Networking & Commun, Fuentenueva S-N, E-18071 Granada, Spain.; Castiglioni, I (reprint author), CNR, Inst Mol Bioimaging & Physiol, Rome, Italy. EM gorriz@ugr.es; javierrp@ugr.es; isabella.castiglioni@ibfm.cnr.it RI Ramirez, Javier/B-1836-2012 OI Ramirez, Javier/0000-0002-6229-2921 NR 23 TC 1 Z9 1 U1 0 U2 3 PU BENTHAM SCIENCE PUBL LTD PI SHARJAH PA EXECUTIVE STE Y-2, PO BOX 7917, SAIF ZONE, 1200 BR SHARJAH, U ARAB EMIRATES SN 1567-2050 EI 1875-5828 J9 CURR ALZHEIMER RES JI Curr. Alzheimer Res. PY 2016 VL 13 IS 5 BP 466 EP 468 DI 10.2174/156720501304160325180321 PG 3 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA DI4GP UT WOS:000373458700001 PM 27025774 ER PT J AU Grundman, M Johnson, KA Lu, M Siderowf, A Dell'Agnello, G Arora, AK Skovronsky, DM Mintun, MA Pontecorvo, MJ AF Grundman, Michael Johnson, Keith A. Lu, Ming Siderowf, Andrew Dell'Agnello, Grazia Arora, Anupa K. Skovronsky, Daniel M. Mintun, Mark A. Pontecorvo, Michael J. CA 18F-AV-45-A17 Study Grp TI Effect of Amyloid Imaging on the Diagnosis and Management of Patients with Cognitive Decline: Impact of Appropriate Use Criteria SO DEMENTIA AND GERIATRIC COGNITIVE DISORDERS LA English DT Article DE Florbetapir; Amyloid imaging; Positron emission tomography; Appropriate use criteria; Alzheimer's disease ID PITTSBURGH COMPOUND-B; FLORBETAPIR F 18; ALZHEIMERS-DISEASE; CLINICAL-DIAGNOSIS; NATIONAL INSTITUTE; DEMENTIA CENTER; BETA PLAQUES; TASK-FORCE; PET; F-18-FLUTEMETAMOL AB Background: Published appropriate use criteria (AUC) describe patients for whom amyloid positron emission tomography (PET) might be most useful. This study compared the impact of amyloid PET on diagnosis and management in subjects likely to either meet or not meet AUC. Methods: Physicians provided a provisional diagnosis and management plan for patients presenting with cognitive decline before and after amyloid PET imaging with florbetapir F 18. Participants were classified as AUC-like or not, based on the prescan diagnosis and demographic features. Results: In all, 125 of 229 participants (55%) were classified as AUC-like. Sixty-two percent of the AUC-like subjects had a change in diagnosis after scanning compared with 45% of the non-AUC subjects (p = 0.011). Both groups demonstrated high rates of change in their management plans after scanning (88.0% for AUC-like cases, 85.6% for non-AUC cases). Conclusions: The impact of amyloid imaging on diagnosis and planned management was maintained and, if anything, amplified in AUC-like patients. (C) 2016 S. Karger AG, Basel C1 [Grundman, Michael] Global R&D Partners LLC, San Diego, CA USA. [Grundman, Michael] Univ Calif San Diego, Dept Neurosci, San Diego, CA 92103 USA. [Johnson, Keith A.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. [Lu, Ming; Siderowf, Andrew; Arora, Anupa K.; Skovronsky, Daniel M.; Mintun, Mark A.; Pontecorvo, Michael J.] Avid Radiopharmaceut Inc, 3711 Market St, Philadelphia, PA 19104 USA. [Dell'Agnello, Grazia] Eli Lilly & Co, Florence, Italy. RP Pontecorvo, MJ (reprint author), Avid Radiopharmaceut Inc, 3711 Market St, Philadelphia, PA 19104 USA. EM pontecorvo@avidrp.com FU Avid Radiopharmaceuticals, a wholly owned subsidiary of Eli Lilly and Company FX This study was sponsored by Avid Radiopharmaceuticals, a wholly owned subsidiary of Eli Lilly and Company. NR 30 TC 1 Z9 1 U1 0 U2 2 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 1420-8008 EI 1421-9824 J9 DEMENT GERIATR COGN JI Dement. Geriatr. Cogn. Disord. PY 2016 VL 41 IS 1-2 BP 80 EP 92 DI 10.1159/000441139 PG 13 WC Geriatrics & Gerontology; Clinical Neurology; Psychiatry SC Geriatrics & Gerontology; Neurosciences & Neurology; Psychiatry GA DI3CO UT WOS:000373376000009 PM 26745445 ER PT J AU Perez, C Leite, J Carvalho, S Fregni, F AF Perez, Carolina Leite, Jorge Carvalho, Sandra Fregni, Felipe TI Transcranial Electrical Stimulation (tES) for the Treatment of Neuropsychiatric Disorders Across Lifespan SO EUROPEAN PSYCHOLOGIST LA English DT Article DE Transcranial electrical stimulation; neuropsychiatric disorders; lifespan ID DORSOLATERAL PREFRONTAL CORTEX; CRANIAL ELECTROTHERAPY STIMULATION; RANDOM NOISE STIMULATION; AUDITORY VERBAL HALLUCINATIONS; NONINVASIVE BRAIN-STIMULATION; CHILDHOOD-ONSET SCHIZOPHRENIA; OBSESSIVE-COMPULSIVE DISORDER; GENERALIZED ANXIETY DISORDER; PULSED CURRENT STIMULATION; MAJOR DEPRESSIVE DISORDER AB Transcranial electrical stimulation (tES) is a safe, painless, and inexpensive noninvasive brain stimulation (NIBS) technique. tES has been shown to reduce symptoms in a variety of neuropsychiatric conditions such as depression, schizophrenia, anxiety, autism, and craving. There are many factors that can influence the effects of tES, such as current intensity, duration, baseline level of activity, gender, and age. Age is a critical variable, since the human brain undergoes several anatomical and functional changes across the lifespan. Therefore, tES-induced effects may not be the same across the lifespan. In this review we summarize the effects of tES, including tDCS, tACS, and tRNS, on clinical outcomes in several neuropsychiatric conditions, using a framework in which studies are organized according to the age of subjects. The use of tES in neuropsychiatric disorders has yielded promising results with mild, if any, adverse effects. Most of the published studies with tES have been conducted with tDCS in adult population. Future studies should focus on interventions guided by surrogate outcomes of neuroplasticity. A better understanding of neuroplasticity across the lifespan will help optimize current tES stimulation parameters, especially for use with children and elderly populations. C1 [Perez, Carolina; Leite, Jorge; Carvalho, Sandra; Fregni, Felipe] Spaulding Rehabil Hosp, Dept Phys Med & Rehabil, Spaulding Neuromodulat Ctr, Boston, MA USA. [Perez, Carolina; Leite, Jorge; Carvalho, Sandra; Fregni, Felipe] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. [Leite, Jorge; Carvalho, Sandra] Univ Minho, CIPsi, Neuropsychophysiol Lab, Sch Psychol EPsi, Braga, Portugal. RP Fregni, F (reprint author), Spaulding Rehabil Ctr, 96 13th St, Charlestown, MA 02129 USA. EM felipe.fregni@ppcr.hms.harvard.edu RI Leite, Jorge/E-4404-2013; OI Leite, Jorge/0000-0002-0323-9012; Carvalho, Sandra/0000-0003-1759-5146 FU Portuguese Foundation for Science and Technology (FCT) [SFRH/BPD/86027/2012, SFRH/BPD/86041/2012]; European Union (FSE-POPH) FX Carolina Perez, Jorge Leite, and Sandra Carvalho share first coauthorship. Jorge Leite (SFRH/BPD/86027/2012) and Sandra Carvalho (SFRH/BPD/86041/2012) are supported by grants from the Portuguese Foundation for Science and Technology (FCT) and European Union (FSE-POPH). The authors wish to thank Melanie French for the editing and proofreading. NR 127 TC 1 Z9 1 U1 4 U2 4 PU HOGREFE & HUBER PUBLISHERS PI KIRKLAND PA PO BOX 2487, KIRKLAND, WA 98083-2487 USA SN 1016-9040 EI 1878-531X J9 EUR PSYCHOL JI Eur. Psychol. PY 2016 VL 21 IS 1 SI SI BP 78 EP 95 DI 10.1027/1016-9040/a000252 PG 18 WC Psychology, Multidisciplinary SC Psychology GA DI2TS UT WOS:000373352400008 ER PT S AU Leachman, SA Cassidy, PB Chen, SC Curiel, C Geller, A Gareau, D Pellacani, G Grichnik, JM Malvehy, J North, J Jacques, SL Petrie, T Puig, S Swetter, SM Tofte, S Weinstock, MA AF Leachman, Sancy A. Cassidy, Pamela B. Chen, Suephy C. Curiel, Clara Geller, Alan Gareau, Daniel Pellacani, Giovanni Grichnik, James M. Malvehy, Josep North, Jeffrey Jacques, Steven L. Petrie, Tracy Puig, Susana Swetter, Susan M. Tofte, Susan Weinstock, Martin A. BE Kaufman, HL Mehnert, JM TI Methods of Melanoma Detection SO MELANOMA SE Cancer Treatment and Research LA English DT Article; Book Chapter DE Melanoma detection; In vivo confocal microscopy; Hyperspectral imaging; Melanoma screening; Dermoscopy; Gene expression profiling; Optical coherence tomography; Melanoma prevention; Atypical nevi; Melanoma digital photography; Optical biopsy; Quantitative real-time PCR (qRT-PCR); Fluorescence in situ hybridization (FISH) ID OPTICAL COHERENCE TOMOGRAPHY; REFLECTANCE CONFOCAL MICROSCOPY; SKIN SELF-EXAMINATION; IN-SITU HYBRIDIZATION; SCANNING LASER MICROSCOPY; TOTAL-BODY PHOTOGRAPHY; BASAL-CELL CARCINOMA; HIGH-RESOLUTION ULTRASOUND; PRIMARY-CARE PHYSICIANS; INTERNATIONAL-DERMOSCOPY-SOCIETY AB Detection and removal of melanoma, before it has metastasized, dramatically improves prognosis and survival. The purpose of this chapter is to (1) summarize current methods of melanoma detection and (2) review state-of-the-art detection methods and technologies that have the potential to reduce melanoma mortality. Current strategies for the detection of melanoma range from population-based educational campaigns and screening to the use of algorithm-driven imaging technologies and performance of assays that identify markers of transformation. This chapter will begin by describing state-of-the-art methods for educating and increasing awareness of at-risk individuals and for performing comprehensive screening examinations. Standard and advanced photographic methods designed to improve reliability and reproducibility of the clinical examination will also be reviewed. Devices that magnify and/or enhance malignant features of individual melanocytic lesions (and algorithms that are available to interpret the results obtained from these devices) will be compared and contrasted. In vivo confocal microscopy and other cellular-level in vivo technologies will be compared to traditional tissue biopsy, and the role of a noninvasive "optical biopsy" in the clinical setting will be discussed. Finally, cellular and molecular methods that have been applied to the diagnosis of melanoma, such as comparative genomic hybridization (CGH), fluorescent in situ hybridization (FISH), and quantitative reverse transcriptase polymerase chain reaction (qRT-PCR), will be discussed. C1 [Leachman, Sancy A.] Oregon Hlth & Sci Univ, Dept Dermatol, 3303 SW Bond Ave,CH16D, Portland, OR 97239 USA. [Leachman, Sancy A.] Oregon Hlth & Sci Univ, Knight Canc Inst, 3303 SW Bond Ave,CH16D, Portland, OR 97239 USA. [Cassidy, Pamela B.] Oregon Hlth & Sci Univ, Dept Dermatol, 3125 SW Sam Jackson Pk Rd,L468R, Portland, OR 97239 USA. [Cassidy, Pamela B.] Oregon Hlth & Sci Univ, Knight Canc Inst, 3125 SW Sam Jackson Pk Rd,L468R, Portland, OR 97239 USA. [Chen, Suephy C.] Emory Univ, Dept Dermatol, Sch Med, 1525 Clifton Rd NE,1st Floor, Atlanta, GA 30322 USA. [Curiel, Clara] Univ Arizona, Dept Dermatol, 1515 N Campbell Ave, Tucson, AZ 85721 USA. [Curiel, Clara] Univ Arizona, Arizona Canc Ctr, 1515 N Campbell Ave, Tucson, AZ 85721 USA. [Geller, Alan] Harvard Univ, Sch Publ Hlth, Dept Dermatol, 401 Pk Dr,3rd Floor East, Boston, MA 02215 USA. [Geller, Alan] Massachusetts Gen Hosp, Landmark Ctr, 401 Pk Dr,3rd Floor East, Boston, MA 02215 USA. [Gareau, Daniel] Rockefeller Univ, Lab Investigat Dermatol, 1230 York Ave, New York, NY 10065 USA. [Pellacani, Giovanni] Univ Modena & Reggio Emilia, Dept Dermatol, Via Pozzo 71, Modena, Italy. [Grichnik, James M.] Univ Miami, Sch Med, Dept Dermatol & Cutaneous Surg, Room 912,BRB R-125,1501 NW 10th Ave, Miami, FL 33136 USA. [Malvehy, Josep; Puig, Susana] Hosp Clin Barcelona, Melanoma Unit, Dept Dermatol, Villarroel 170, Barcelona 08036, Spain. [North, Jeffrey] Univ Calif San Francisco, 1701 Divisadero St,Suite 280, San Francisco, CA 94115 USA. [Jacques, Steven L.] Oregon Hlth & Sci Univ, Dept Biomed Engn & Dermatol, 3303 SW Bond Ave,CH13B, Portland, OR 97239 USA. [Petrie, Tracy] Oregon Hlth & Sci Univ, Dept Biomed Engn, 3303 SW Bond Ave,CH13B, Portland, OR 97239 USA. [Swetter, Susan M.] Stanford Univ, Dept Dermatol Cutaneous Oncol, 900 Blake Wilbur Dr,W3045, Stanford, CA 94305 USA. [Tofte, Susan] Oregon Hlth & Sci Univ, Dept Dermatol, 3303 SW Bond Ave,CH16D, Portland, OR 97239 USA. [Weinstock, Martin A.] Brown Univ, Dept Dermatol, VA Med Ctr 111D, 830 Chalkstone Ave, Providence, RI 02908 USA. [Weinstock, Martin A.] Brown Univ, Dept Epidemiol, VA Med Ctr 111D, 830 Chalkstone Ave, Providence, RI 02908 USA. RP Leachman, SA (reprint author), Oregon Hlth & Sci Univ, Dept Dermatol, 3303 SW Bond Ave,CH16D, Portland, OR 97239 USA.; Leachman, SA (reprint author), Oregon Hlth & Sci Univ, Knight Canc Inst, 3303 SW Bond Ave,CH16D, Portland, OR 97239 USA. EM leachmas@ohsu.edu; cassidyp@ohsu.edu; schen2@emory.edu; ccuriel@email.arizona.edu; ageller@hsph.harvard.edu; daniel.gareau@rockefeller.edu; giovanni.pellacani@unimore.it; grichnik@miami.edu; jmalvehy@clinic.ub.es; jeffrey.north@ucsf.edu; jacquess@ohsu.edu; petrie@ohsu.edu; spuig@clinic.ub.es; sswetter@stanford.edu; toftes@ohsu.edu; maw@brown.edu OI Pellacani, Giovanni/0000-0002-7222-2951; Puig, Susana/0000-0003-1337-9745 NR 214 TC 8 Z9 8 U1 5 U2 13 PU SPRINGER PI DORDRECHT PA PO BOX 17, 3300 AA DORDRECHT, NETHERLANDS SN 0927-3042 BN 978-3-319-22539-5; 978-3-319-22538-8 J9 CANCER TREAT RES JI Canc. Treat. Res. PY 2016 VL 167 BP 51 EP 105 DI 10.1007/978-3-319-22539-5_3 D2 10.1007/978-3-319-22539-5 PG 55 WC Oncology; Dermatology SC Oncology; Dermatology GA BE5XZ UT WOS:000373625700003 PM 26601859 ER PT J AU de Sousa, MVP Ferraresi, C Kawakubo, M Kaippert, B Yoshimura, EM Hamblin, MR AF Pires de Sousa, Marcelo Victor Ferraresi, Cleber Kawakubo, Masayoshi Kaippert, Beatriz Yoshimura, Elisabeth Mateus Hamblin, Michael R. TI Transcranial low-level laser therapy (810 nm) temporarily inhibits peripheral nociception: photoneuromodulation of glutamate receptors, prostatic acid phophatase, and adenosine triphosphate SO NEUROPHOTONICS LA English DT Article DE transcranial low-level laser therapy; photobiomodulation; pain threshold; nociception; Von Frey filaments; tail flick test; cold plate test; formalin injection; adenosine triphosphate; prostatic acid phosphatase; metabotropic glutamate receptor ID TRAUMATIC BRAIN-INJURY; LIGHT THERAPY; CHRONIC PAIN; PATHOLOGICAL PAIN; ISCHEMIC-STROKE; IRRADIATION; MECHANISMS; MODELS; INFLAMMATION; PHOSPHATASE AB Photobiomodulation or low-level light therapy has been shown to attenuate both acute and chronic pain, but the mechanism of action is not well understood. In most cases, the light is applied to the painful area, but in the present study we applied light to the head. We found that transcranial laser therapy (TLT) applied to mouse head with specific parameters (810 nm laser, 300 mW/cm(2), 7.2 or 36 J/cm(2)) decreased the reaction to pain in the foot evoked either by pressure (von Frey filaments), cold, or inflammation (formalin injection) or in the tail (evoked by heat). The pain threshold increasing is maximum around 2 h after TLT, remains up to 6 h, and is finished 24 h after TLT. The mechanisms were investigated by quantification of adenosine triphosphate (ATP), immunofluorescence, and hematoxylin and eosin (H&E) staining of brain tissues. TLT increased ATP and prostatic acid phosphatase (an endogenous analgesic) and reduced the amount of glutamate receptor (mediating a neurotransmitter responsible for conducting nociceptive information). There was no change in the concentration of tubulin, a constituent of the cytoskeleton, and the H&E staining revealed no tissue damage. (C) 2016 Society of Photo-Optical Instrumentation Engineers (SPIE) C1 [Pires de Sousa, Marcelo Victor; Ferraresi, Cleber; Kawakubo, Masayoshi; Kaippert, Beatriz; Hamblin, Michael R.] Massachusetts Gen Hosp, Wellman Ctr Photomed, BAR414,40 Blossom St, Boston, MA 02114 USA. [Pires de Sousa, Marcelo Victor; Yoshimura, Elisabeth Mateus] Univ Sao Paulo, Inst Phys, Lab Radiat Dosimetry & Med Phys, Rua Matao,Travessa R,187,Cidade Univ, Sao Paulo, Brazil. [Pires de Sousa, Marcelo Victor] Bright Photomed Ltd, CIETEC Bldg,2242 Lineu Prestes, BR-05508000 Sao Paulo, Brazil. [Ferraresi, Cleber] Univ Fed Sao Carlos, Dept Phys Therapy, Lab Electrothermophototherapy, St Washington Luis,Km 235, BR-13565905 Sao Paulo, Brazil. [Ferraresi, Cleber] Univ Fed Sao Carlos, Postgrad Program Biotechnol, St Washington Luis,Km 235, BR-13560000 Sao Paulo, Brazil. [Ferraresi, Cleber] Univ Sao Paulo, Opt Grp, Phys Inst Sao Carlos, St Miguel Petroni,146 Jardim Bandeirantes, BR-13560970 Sao Paulo, Brazil. [Kaippert, Beatriz] Univ Fed Rio de Janeiro, 373 Cidade Univ, BR-21941170 Rio De Janeiro, RJ, Brazil. [Hamblin, Michael R.] Harvard Univ, Sch Med, Dept Dermatol, 50 Staniford St 807, Boston, MA 02114 USA. [Hamblin, Michael R.] Harvard MIT, Div Hlth Sci & Technol, 77 Massachusetts Ave,E25-518, Cambridge, MA 02139 USA. RP de Sousa, MVP; Hamblin, MR (reprint author), Massachusetts Gen Hosp, Wellman Ctr Photomed, BAR414,40 Blossom St, Boston, MA 02114 USA.; de Sousa, MVP (reprint author), Univ Sao Paulo, Inst Phys, Lab Radiat Dosimetry & Med Phys, Rua Matao,Travessa R,187,Cidade Univ, Sao Paulo, Brazil.; de Sousa, MVP (reprint author), Bright Photomed Ltd, CIETEC Bldg,2242 Lineu Prestes, BR-05508000 Sao Paulo, Brazil.; Hamblin, MR (reprint author), Harvard Univ, Sch Med, Dept Dermatol, 50 Staniford St 807, Boston, MA 02114 USA.; Hamblin, MR (reprint author), Harvard MIT, Div Hlth Sci & Technol, 77 Massachusetts Ave,E25-518, Cambridge, MA 02139 USA. EM marcelo230786@gmail.com; hamblin@helix.mgh.harvard.edu RI Sao Carlos Institute of Physics, IFSC/USP/M-2664-2016; Yoshimura, Elisabeth/E-8848-2012 FU NIAID NIH HHS [R01 AI050875] NR 44 TC 1 Z9 1 U1 2 U2 3 PU SPIE-SOC PHOTO-OPTICAL INSTRUMENTATION ENGINEERS PI BELLINGHAM PA 1000 20TH ST, PO BOX 10, BELLINGHAM, WA 98225 USA SN 2329-423X EI 2329-4248 J9 NEUROPHOTONICS JI Neurophotonics PD JAN-MAR PY 2016 VL 3 IS 1 AR 015003 DI 10.1117/1.NPh.3.1.015003 PG 9 WC Neurosciences; Optics SC Neurosciences & Neurology; Optics GA DI8SJ UT WOS:000373771200007 PM 26835486 ER PT J AU de Sousa, MVP Ferraresi, C Kawakubo, M Kaippert, B Yoshimura, EM Hamblin, MR AF Pires de Sousa, Marcelo Victor Ferraresi, Cleber Kawakubo, Masayoshi Kaippert, Beatriz Yoshimura, Elisabeth Mateus Hamblin, Michael R. TI Transcranial low-level laser therapy (810 nm) temporarily inhibits peripheral nociception: photoneuromodulation of glutamate receptors, prostatic acid phophatase, and adenosine triphosphate (vol 3, 015003, 2016) SO NEUROPHOTONICS LA English DT Correction C1 [Pires de Sousa, Marcelo Victor; Ferraresi, Cleber; Kawakubo, Masayoshi; Kaippert, Beatriz; Hamblin, Michael R.] Massachusetts Gen Hosp, Wellman Ctr Photomed, BAR414,40 Blossom St, Boston, MA 02114 USA. [Pires de Sousa, Marcelo Victor; Yoshimura, Elisabeth Mateus] Univ Sao Paulo, Inst Phys, Lab Radiat Dosimetry & Med Phys, Rua Matao,Travessa R,187 Cidade Univ, Sao Paulo, Brazil. [Pires de Sousa, Marcelo Victor] Bright Photomed Ltd, CIETEC Bldg, BR-05508000 Sao Paulo, Brazil. [Ferraresi, Cleber] Univ Fed Sao Carlos, Dept Phys Therapy, Lab Electrothermophototherapy, St Washington Luis,Km 235, BR-13565905 Sao Paulo, Brazil. [Ferraresi, Cleber] Univ Fed Sao Carlos, Postgrad Program Biotechnol, St Washington Luis,Km 235, BR-13560000 Sao Paulo, Brazil. [Ferraresi, Cleber] Univ Sao Paulo, Opt Grp, Phys Inst Sao Carlos, St Miguel Petroni,146 Jardim Bandeirantes, BR-13560970 Sao Paulo, Brazil. [Kaippert, Beatriz] Univ Fed Rio de Janeiro, 373 Cidade Univ, BR-21941170 Rio De Janeiro, RJ, Brazil. [Hamblin, Michael R.] Harvard Univ, Sch Med, Dept Dermatol, 50 Staniford St 807, Boston, MA 02114 USA. [Hamblin, Michael R.] Harvard MIT, Div Hlth Sci & Technol, 77 Massachusetts Ave,E25-518, Cambridge, MA 02139 USA. RP de Sousa, MVP (reprint author), Massachusetts Gen Hosp, Wellman Ctr Photomed, BAR414,40 Blossom St, Boston, MA 02114 USA.; de Sousa, MVP (reprint author), Univ Sao Paulo, Inst Phys, Lab Radiat Dosimetry & Med Phys, Rua Matao,Travessa R,187 Cidade Univ, Sao Paulo, Brazil.; de Sousa, MVP (reprint author), Bright Photomed Ltd, CIETEC Bldg, BR-05508000 Sao Paulo, Brazil. RI Sao Carlos Institute of Physics, IFSC/USP/M-2664-2016; Yoshimura, Elisabeth/E-8848-2012 NR 2 TC 0 Z9 0 U1 2 U2 3 PU SPIE-SOC PHOTO-OPTICAL INSTRUMENTATION ENGINEERS PI BELLINGHAM PA 1000 20TH ST, PO BOX 10, BELLINGHAM, WA 98225 USA SN 2329-423X EI 2329-4248 J9 NEUROPHOTONICS JI Neurophotonics PD JAN-MAR PY 2016 VL 3 IS 1 AR 019801 DI 10.1117/1.NPh.3.1.019801 PG 1 WC Neurosciences; Optics SC Neurosciences & Neurology; Optics GA DI8SJ UT WOS:000373771200009 ER PT B AU Dobrev, I Cheng, JT Khaleghi, M Guignard, J Ravicz, ME Rosowski, JJ Furlong, C AF Dobrev, Ivo Cheng, Jeffrey T. Khaleghi, Morteza Guignard, Jeremie Ravicz, Michael E. Rosowski, John J. Furlong, Cosme BE Dirckx, J TI Developments in Opto-Electronic Holography (OEH) for measurement of sound-induced eardrum motion SO OPTICAL MEASUREMENT TECHNIQUES FOR STRUCTURES & SYSTEMS III LA English DT Proceedings Paper CT 6th International Conference on Optical Measurement Techniques for Structures and Systems III (OPTIMESS2015) CY APR 08-09, 2015 CL Univ Antwerp, Antwerp, BELGIUM SP Res Fdn Flanders, Univ Antwerp, Lab Biomed Phys, Univ Antwerp HO Univ Antwerp ID TYMPANIC-MEMBRANE; SURFACE; SHAPE; EARS AB Prior to 2009 the data available to characterize the function of the mammalian eardrum was rather limited and consisted of time-averaged holograms gathered 30 to 40 years previously or laser-vibrometer measurements usually made with low spatial density or over small regions of the eardrum. These few measurements could be compared to the plethora of Finite-Element models of eardrum and middle ear function. More recently, a collaboration between an optics group at the Center for Holographic Studies and Laser micro-mechaTronics at the Worcester Polytechnic Institute in Worcester MA and physiologists and acousticians at the Eaton-Peabody Laboratory at the Massachusetts Eye and Ear Infirmary in Boston MA have applied new computer controlled holographic methods to greatly increase the data describing eardrum function. The techniques and their results include: (1) One-dimensional Stroboscopic Opto-Electronic Holography (OEH) to describe the magnitude (with nanometer resolution) and phase of over 200,000 points on the surface of the eardrum to a broad range of sinusoidal stimuli that led to descriptions of combinations of stationary-wave and traveling-wave like motions on the eardrum surface. (2) Dual-wavelength OEH that produced rapid micron level measurements of the 3D-shape of the eardrum that allowed estimations of the effect of shape on our ID measurements. (3) Three-dimensional OEH that produced high resolution measurements in time and space of the 3D motion of the eardrum surface. The combination of the 3D shape and motion measurements led to assessment of the contribution of in-plane motions to eardrum function, where these motions have been found to be small compared to out-of-plane motions. (4) High-speed OEH (HS-OEH) that allows measurements of the response of the eardrum to acoustic or mechanical transients, where these impulse responses enable continued investigations of the role of stationary and traveling surface waves on eardrum function. Each of these methods will be reviewed and available results summarized. C1 [Dobrev, Ivo] Univ Zurich Hosp, Ramistr 100, CH-8006 Zurich, Switzerland. [Cheng, Jeffrey T.; Guignard, Jeremie; Ravicz, Michael E.; Rosowski, John J.] Massachusett Eye & Ear Infirm, 243 Charles St, Boston, MA 02114 USA. [Khaleghi, Morteza; Furlong, Cosme] Worcester Polytech Inst, Dept Mech Engn, 100 Inst Rd, Worcester, MA 01609 USA. [Cheng, Jeffrey T.; Guignard, Jeremie; Ravicz, Michael E.; Rosowski, John J.] Harvard Univ, Sch Med, 25 Shattuck St, Boston, MA 02115 USA. [Cheng, Jeffrey T.; Guignard, Jeremie; Ravicz, Michael E.; Rosowski, John J.] Worcester Polytech Inst, 100 Inst Rd, Worcester, MA 01609 USA. RP Dobrev, I (reprint author), Univ Zurich Hosp, Ramistr 100, CH-8006 Zurich, Switzerland.; Cheng, JT; Guignard, J; Ravicz, ME; Rosowski, JJ (reprint author), Massachusett Eye & Ear Infirm, 243 Charles St, Boston, MA 02114 USA.; Khaleghi, M; Furlong, C (reprint author), Worcester Polytech Inst, Dept Mech Engn, 100 Inst Rd, Worcester, MA 01609 USA.; Cheng, JT; Guignard, J; Ravicz, ME; Rosowski, JJ (reprint author), Harvard Univ, Sch Med, 25 Shattuck St, Boston, MA 02115 USA.; Cheng, JT; Guignard, J; Ravicz, ME; Rosowski, JJ (reprint author), Worcester Polytech Inst, 100 Inst Rd, Worcester, MA 01609 USA. EM Ivo.Dobreva@usz.ch; tao_cheng@meei.harvard.edu; mkm@wpi.edu; Jeremie_Guignard@meei.harvard.edu; Mike_Ravicz@meei.harvard.edu; John_Rosowski@meei.harvard.edu; cfurlong@wpi.edu NR 12 TC 0 Z9 0 U1 2 U2 2 PU SHAKER PUBLISHING BV PI MAASTRICHT PA ST MAARTENSLAAN 26, MAASTRICHT, 6221 AX, NETHERLANDS BN 978-90-423-0439-0 PY 2016 BP 73 EP 83 PG 11 WC Optics; Physics, Applied; Imaging Science & Photographic Technology SC Optics; Physics; Imaging Science & Photographic Technology GA BE5TM UT WOS:000373413300008 ER PT S AU Nayagam, BA Edge, ASB AF Nayagam, Bryony A. Edge, Albert S. B. BE Dabdoub, A Fritzsch, B Popper, AN Fay, RR TI Stem Cells for the Replacement of Auditory Neurons SO PRIMARY AUDITORY NEURONS OF THE MAMMALIAN COCHLEA SE Springer Handbook of Auditory Research LA English DT Article; Book Chapter DE Cell transplantation; Differentiation; Hair cell; Inner ear; innervation; Regeneration; Spiral ganglion neuron; Synaptogenesis ID SPIRAL GANGLION NEURONS; MARROW STROMAL CELLS; SPINAL-CORD-INJURY; GUINEA-PIG COCHLEA; VESICULAR GLUTAMATE TRANSPORTER-3; SENSORINEURAL HEARING-LOSS; DEVELOPING INNER-EAR; IN-VITRO; HAIR-CELLS; ELECTRICAL-STIMULATION C1 [Nayagam, Bryony A.] Univ Melbourne, Dept Audiol & Speech Pathol, Parkville, Vic 3010, Australia. [Edge, Albert S. B.] Harvard Univ, Sch Med, Eaton Peabody Lab, Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. RP Edge, ASB (reprint author), Harvard Univ, Sch Med, Eaton Peabody Lab, Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. EM b.nayagam@unimelb.edu.au; albert_edge@meei.harvard.edu NR 110 TC 0 Z9 0 U1 1 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013, UNITED STATES SN 0947-2657 BN 978-1-4939-3031-9; 978-1-4939-3030-2 J9 SPRINGER HANDB AUDIT JI Springer Handb. Audit. Res. PY 2016 VL 52 BP 263 EP 286 DI 10.1007/978-1-4939-3031-9_9 D2 10.1007/978-1-4939-3031-9 PG 24 WC Neurosciences; Otorhinolaryngology SC Neurosciences & Neurology; Otorhinolaryngology GA BE5XR UT WOS:000373620100012 ER PT J AU Lee, LK Kilcoyne, A Goldberg-Stein, S Chow, DZ Lee, SI AF Lee, Leslie K. Kilcoyne, Aoife Goldberg-Stein, Shlomit Chow, David Z. Lee, Susanna I. TI FDG PET-CT of Genitourinary and Gynecologic Tumors: Overcoming the Challenges of Evaluating the Abdomen and Pelvis SO SEMINARS IN ROENTGENOLOGY LA English DT Article ID F-18-FDG PET/CT; BENIGN; PITFALLS; INFLAMMATION; ENDOMETRIAL; INFECTION; OVARIAN; CANCER; MASSES C1 [Lee, Leslie K.; Kilcoyne, Aoife; Chow, David Z.; Lee, Susanna I.] Harvard Univ, Sch Med, Dept Radiol, Massachusetts Gen Hosp, Boston, MA 02115 USA. [Goldberg-Stein, Shlomit] Montefiore Med Ctr, Albert Einstein Coll Med, Dept Radiol, Bronx, NY 10467 USA. RP Lee, LK (reprint author), Massachusetts Gen Hosp, Div Nucl Med & Mol Imaging, Dept Radiol, 55 Fruit St,White 427, Boston, MA 02114 USA. EM llee22@partners.org FU Mac Erlaine Scholarship; Academic Radiology Research Trust; St Vincent's Radiology Group, Dublin, Ireland FX Aoife Kilcoyne would like to acknowledge the support of the Mac Erlaine Scholarship, from the Academic Radiology Research Trust, St Vincent's Radiology Group, Dublin, Ireland. NR 28 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0037-198X EI 1558-4658 J9 SEMIN ROENTGENOL JI Semin. Roentgenology PD JAN PY 2016 VL 51 IS 1 BP 2 EP 11 DI 10.1053/j.ro.2015.12.007 PG 10 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA DI5OR UT WOS:000373549000002 PM 27020231 ER PT J AU Gunewardene, N Crombie, D Dottori, M Nayagam, BA AF Gunewardene, Niliksha Crombie, Duncan Dottori, Mirella Nayagam, Bryony A. TI Innervation of Cochlear Hair Cells by Human Induced Pluripotent Stem Cell-Derived Neurons In Vitro SO STEM CELLS INTERNATIONAL LA English DT Article ID SPIRAL GANGLION NEURONS; AUDITORY NEURONS; DIFFERENTIATION; REINNERVATION; PROGENITORS AB Induced pluripotent stem cells (iPSCs) may serve as an autologous source of replacement neurons in the injured cochlea, if they can be successfully differentiated and reconnected with residual elements in the damaged auditory system. Here, we explored the potential of hiPSC-derived neurons to innervate early postnatal hair cells, using established in vitro assays. We compared two hiPSC lines against a well-characterized hESC line. After ten days' coculture in vitro, hiPSC-derived neural processes contacted inner and outer hair cells in whole cochlear explant cultures. Neural processes from hiPSC-derived neurons also made contact with hair cells in denervated sensory epithelia explants and expressed synapsin at these points of contact. Interestingly, hiPSC-derived neurons cocultured with hair cells at an early stage of differentiation formed synapses with a higher number of hair cells, compared to hiPSC-derived neurons cocultured at a later stage of differentiation. Notable differences in the innervation potentials of the hiPSC-derived neurons were also observed and variations existed between the hiPSC lines in their innervation efficiencies. Collectively, these data illustrate the promise of hiPSCs for auditory neuron replacement and highlight the need to develop methods to mitigate variabilities observed amongst hiPSC lines, in order to achieve reliable clinical improvements for patients. C1 [Gunewardene, Niliksha] Harvard Univ, Sch Med, Dept Otol & Laryngol, Boston, MA 02114 USA. [Gunewardene, Niliksha] Massachusetts Eye & Ear Infirm, Eaton Peabody Lab, Boston, MA 02114 USA. [Crombie, Duncan; Nayagam, Bryony A.] Univ Melbourne, Ctr Eye Res Australia, East Melbourne, Vic 3002, Australia. [Dottori, Mirella] Univ Melbourne, Ctr Neural Engn, Parkville, Vic 3010, Australia. [Nayagam, Bryony A.] Univ Melbourne, Dept Audiol & Speech Pathol, Parkville, Vic 3010, Australia. [Nayagam, Bryony A.] Univ Melbourne, Bion Inst, East Melbourne, Vic 3002, Australia. RP Nayagam, BA (reprint author), Univ Melbourne, Ctr Eye Res Australia, East Melbourne, Vic 3002, Australia.; Nayagam, BA (reprint author), Univ Melbourne, Dept Audiol & Speech Pathol, Parkville, Vic 3010, Australia.; Nayagam, BA (reprint author), Univ Melbourne, Bion Inst, East Melbourne, Vic 3002, Australia. EM b.nayagam@unimelb.edu.au OI Crombie, Duncan/0000-0002-4718-1967 NR 28 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 1687-966X EI 1687-9678 J9 STEM CELLS INT JI Stem Cells Int. PY 2016 AR 1781202 DI 10.1155/2016/1781202 PG 10 WC Cell & Tissue Engineering SC Cell Biology GA DI4WT UT WOS:000373500800001 ER PT J AU Grant, M Eisner, B AF Grant, Michael Eisner, Brian TI Percutaneous Nephrolithotomy in Patients With BMI >50: Single Surgeon Outcomes and Feasibility EDITORIAL COMMENT SO UROLOGY LA English DT Editorial Material ID BODY-MASS INDEX; POSITION; OBESITY C1 [Grant, Michael; Eisner, Brian] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Urol, Boston, MA USA. RP Grant, M (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Urol, Boston, MA USA. NR 8 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0090-4295 EI 1527-9995 J9 UROLOGY JI Urology PD JAN PY 2016 VL 87 BP 37 EP 38 DI 10.1016/j.urology.2015.06.072 PG 2 WC Urology & Nephrology SC Urology & Nephrology GA DI4IJ UT WOS:000373463300014 PM 27243082 ER PT J AU Dinh, KT Muralidhar, V Mahal, BA Chen, YW Nezolosky, MD Beard, CJ Choueiri, TK Martin, NE Orio, PF Sweeney, CJ Trinh, QD Nguyen, PL AF Dinh, Kathryn T. Muralidhar, Vinayak Mahal, Brandon A. Chen, Yu-Wei Nezolosky, Michelle D. Beard, Clair J. Choueiri, Toni K. Martin, Neil E. Orio, Peter F. Sweeney, Christopher J. Quoc-Dien Trinh Nguyen, Paul L. TI Occult High-risk Disease in Clinically Low-risk Prostate Cancer with >= 50% Positive Biopsy Cores: Should National Guidelines Stop Calling Them Low Risk? SO UROLOGY LA English DT Article ID BEAM RADIATION-THERAPY; RADICAL PROSTATECTOMY; ACTIVE SURVEILLANCE; GLEASON SCORE; NEEDLE-BIOPSY; PERCENTAGE; STAGE; MORTALITY; SPECIMENS; TUMORS AB OBJECTIVE To identify contemporary, clinically low-risk patients with >= 50% cores positive and compare the risk of upgrading at prostatectomy with other low- or intermediate-risk patients. MATERIALS AND METHODS We studied 14,902 patients with prostate cancer in the Surveillance, Epidemiology, and End Results database in 2010-2011 treated with prostatectomy. Patients were categorized by National Comprehensive Cancer Network clinical risk groups, separating low-risk patients by percent positive biopsy cores (PBC). We measured incidence of pathologic high-risk disease, defined as pT3a-T4 or Gleason 8-10, and multivariable logistic regression was used to determine if patients with clinical low-risk disease and >= 50% PBC were similar to other low- or intermediate-risk patients. This analysis was repeated with favorable and unfavorable intermediate risk. RESULTS At prostatectomy, 9.2% of clinically low-risk patients with <50% PBC, 18.6% of clinically low-risk patients with >= 50% PBC, and 27.6% of clinically intermediate-risk patients had occult, high-risk disease (P < .001). On multivariable logistic regression, low-risk patients with >= 50% PBC were more likely than low-risk patients with <50% PBC to have pathologic high-risk disease (adjusted odds ratio [AOR] 2.28, 95% confidence interval 1.90-2.73, P < .001), had similar risk to favorable intermediate patients overall (AOR 1.09, 0.91-1.31, P = .33), and had higher risk than favorable intermediate patients aged over 60 years (AOR 1.28, 1.00-1.64, P = .04). Low-risk patients with >= 50% PBC had a mean tumor size similar to unfavorable intermediate-risk patients (21.3 vs 21.0 mm, P = .82). CONCLUSION Nearly 1 in 5 clinically low-risk prostate cancer patients with >= 50% PBC harbor occult pT3aT4 or Gleason 8-10, suggesting that national guidelines should not classify low-risk patients with >= 50% cores positive as "low risk," and patients should be made aware of this excess risk if considering active surveillance. (C) 2015 Elsevier Inc. C1 Harvard Univ, Sch Med, Boston, MA USA. Harvard Univ, TH Chan Sch Publ Hlth, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Radiat Oncol, Boston, MA 02115 USA. [Nguyen, Paul L.] Brigham & Womens Hosp, 75 Francis St, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. Harvard Univ, Brigham & Womens Hosp, Sch Med, Boston, MA 02115 USA. Harvard Univ, Brigham & Womens Hosp, Sch Med, Div Urol, Boston, MA 02115 USA. RP Nguyen, PL (reprint author), Brigham & Womens Hosp, 75 Francis St, Boston, MA 02115 USA. EM pnguyen@LROC.harvard.edu FU Prostate Cancer Foundation FX This work is supported by Fitz's Cancer Warriors, David and Cynthia Chapin, the Prostate Cancer Foundation, Hugh Simons in honor of Frank and Anne Simons, Scott Forbes and Gina Ventre, and a grant from an anonymous family foundation. NR 24 TC 5 Z9 5 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0090-4295 EI 1527-9995 J9 UROLOGY JI Urology PD JAN PY 2016 VL 87 BP 125 EP 131 DI 10.1016/j.urology.2015.08.026 PG 7 WC Urology & Nephrology SC Urology & Nephrology GA DI4IJ UT WOS:000373463300036 PM 26391387 ER PT J AU Nguyen, PL AF Nguyen, Paul L. TI Long-term Impact of Androgen-deprivation Therapy on Cardiovascular Morbidity After Radiotherapy for Clinically Localized Prostate Cancer EDITORIAL COMMENT SO UROLOGY LA English DT Editorial Material C1 [Nguyen, Paul L.] Harvard Univ, Dana Farber Brigham & Womens Canc Ctr, Sch Med, Dept Radiat Oncol, Boston, MA USA. RP Nguyen, PL (reprint author), Harvard Univ, Dana Farber Brigham & Womens Canc Ctr, Sch Med, Dept Radiat Oncol, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0090-4295 EI 1527-9995 J9 UROLOGY JI Urology PD JAN PY 2016 VL 87 BP 152 EP 152 DI 10.1016/j.urology.2015.08.030 PG 1 WC Urology & Nephrology SC Urology & Nephrology GA DI4IJ UT WOS:000373463300043 PM 27243087 ER PT J AU Clark, NC Friel, AM Pru, CA Zhang, L Shioda, T Rueda, BR Peluso, JJ Pru, JK AF Clark, Nicole C. Friel, Anne M. Pru, Cindy A. Zhang, Ling Shioda, Toshi Rueda, Bo R. Peluso, John J. Pru, James K. TI Progesterone receptor membrane component 1 promotes survival of human breast cancer cells and the growth of xenograft tumors SO CANCER BIOLOGY & THERAPY LA English DT Article DE Breast cancer; endocrine; PGRMC1; progesterone; TNBC; xenograft ID IMMORTALIZED GRANULOSA-CELLS; ESTROGEN PLUS PROGESTIN; HEALTHY POSTMENOPAUSAL WOMEN; HORMONE REPLACEMENT THERAPY; HEME-1 DOMAIN PROTEIN; MOUSE MAMMARY-GLAND; GENE-EXPRESSION; ANTIAPOPTOTIC ACTION; BINDING-PROTEIN; OVARIAN-CANCER AB Triple negative breast cancers (TNBCs) are highly aggressive and grow in response to sex steroid hormones despite lacking expression of the classical estrogen (E2) and progesterone (P4) receptors. Since P4 receptor membrane component 1 (PGRMC1) is expressed in breast cancer tumors and is known to mediate P4-induced cell survival, this study was designed to determine the expression of PGRMC1 in TNBC tumors and the involvement of PGRMC1 in regulating proliferation and survival of TNBC cells in vitro and the growth of TNBC tumors in vivo. For the latter studies, the MDA-MB-231 (MDA) cell line derived from TNBC was used. These cells express PGRMC1 but lack expression of the classical P4 receptor. A lentiviral-based shRNA approach was used to generate a stably transfected PGRMC1-deplete MDA line for comparison to the PGRMC1-intact MDA line. The present studies demonstrate that PGRMC1: 1) is expressed in TNBC cells; 2) mediates the ability of P4 to suppress TNBC cell mitosis in vitro; 3) is required for P4 to reduce the apoptotic effects of doxorubicin in vitro; and 4) facilitates TNBC tumor formation and growth in vivo. Taken together, these findings indicate that PGRMC1 plays an important role in regulating the growth and survival of TNBC cells in vitro and ultimately in the formation and development of these tumors in vivo. Thus, PGRMC1 may be a therapeutic target for TNBCs. C1 [Clark, Nicole C.; Pru, Cindy A.; Pru, James K.] Washington State Univ, Ctr Reprod Biol, Sch Mol Biosci, Dept Anim Sci, Pullman, WA 99164 USA. [Friel, Anne M.; Zhang, Ling; Rueda, Bo R.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Vincent Ctr Reprod Biol, Boston, MA USA. [Friel, Anne M.; Zhang, Ling; Rueda, Bo R.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Gynecol Oncol,Dept Obstet & Gynecol, Boston, MA USA. [Shioda, Toshi] Massachusetts Gen Hosp, Ctr Canc, Charlestown, MA USA. [Shioda, Toshi] Harvard Univ, Sch Med, Charlestown, MA USA. [Peluso, John J.] Univ Connecticut, Ctr Hlth, Dept Obstet & Gynecol, Farmington, CT USA. [Peluso, John J.] Univ Connecticut, Ctr Hlth, Dept Cell Biol, Farmington, CT USA. RP Pru, JK (reprint author), Washington State Univ, Ctr Reprod Biol, Sch Mol Biosci, Dept Anim Sci, Pullman, WA 99164 USA. EM jpru@wsu.edu FU Vincent Memorial Research Funds; Advanced Medical Research Foundation; NIH [R21-RR030264, R21-OD016564] FX This work was supported by Vincent Memorial Research Funds, the Advanced Medical Research Foundation, and NIH R21-RR030264 and R21-OD016564. NR 75 TC 5 Z9 5 U1 0 U2 2 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. PY 2016 VL 17 IS 3 BP 262 EP 271 DI 10.1080/15384047.2016.1139240 PG 10 WC Oncology SC Oncology GA DH9JI UT WOS:000373112000006 PM 26785864 ER PT J AU Solak, S Acar, YA Uysal, E AF Solak, Suleyman Acar, Yahya Ayhan Uysal, Emin TI Bladder herniation into inguinal canal: an important differential diagnosis of inguinal hernia SO CUKUROVA MEDICAL JOURNAL LA English DT Letter ID URINARY-BLADDER; INGUINOSCROTAL HERNIATION; INCIDENTAL DEMONSTRATION; BONE-SCAN; SCROTUM C1 [Solak, Suleyman; Uysal, Emin] Bagcilar Training & Res Hosp, Dept Emergency Med, Istanbul, Turkey. [Acar, Yahya Ayhan] San Francisco VA Med Ctr, Dept Anaesthesiol, San Francisco, CA USA. RP Acar, YA (reprint author), San Francisco VA Med Ctr, Dept Anaesthesiol, San Francisco, CA USA. EM yahya_acar@yahoo.com NR 19 TC 0 Z9 0 U1 0 U2 0 PU CUKUROVA UNIV, FAC MEDICINE PI ADANA PA YAYIN VE DOKUMENTASYON KURULU, BALCALI, ADANA, 01330, TURKEY SN 0250-5150 J9 CUKUROVA MED J JI Cukurova Med. J. PY 2016 VL 41 IS 1 BP 191 EP 192 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA DH9PS UT WOS:000373128700034 ER PT J AU Feng, MH Tang, BQ Liang, SH Jiang, XF AF Feng, Minghao Tang, Bingqing Liang, Steven H. Jiang, Xuefeng TI Sulfur Containing Scaffolds in Drugs: Synthesis and Application in Medicinal Chemistry SO CURRENT TOPICS IN MEDICINAL CHEMISTRY LA English DT Review DE Sulfur containing drugs; Sulfonamide; Thioether; Sulfones; Sulfur dioxide fixation; Organic synthesis ID FUNGUS EPICOCCUM-NIGRUM; ARYL HALIDES; PHOTOCHEMICAL FORMATION; PROMOTED CYCLIZATIONS; ARYLBORONIC ACIDS; ROOM-TEMPERATURE; ONE-POT; DIOXIDE; SULFONAMIDES; 3-COMPONENT AB The impact of the development of sulfur therapeutics is instrumental to the evolution of the pharmaceutical industry. Sulfur-derived functional groups can be found in a broad range of pharmaceuticals and natural products. For centuries, sulfur continues to maintain its status as the dominating heteroatom integrated into a set of 362 sulfur-containing FDA approved drugs (besides oxygen or nitrogen) through the present. Sulfonamides, thioethers, sulfones and Penicillin are the most common scaffolds in sulfur containing drugs, which are well studied both on synthesis and application during the past decades. In this review, these four moieties in pharmaceuticals and recent advances in the synthesis of the corresponding core scaffolds are presented. C1 [Feng, Minghao; Tang, Bingqing; Jiang, Xuefeng] E China Normal Univ, Sch Chem & Mol Engn, Shanghai Key Lab Green Chem & Chem Proc, Shanghai 200062, Peoples R China. [Liang, Steven H.] Massachusetts Gen Hosp, Dept Radiol, Div Nucl Med & Mol Imaging, Boston, MA USA. [Liang, Steven H.] Harvard Univ, Sch Med, Boston, MA USA. [Jiang, Xuefeng] Nankai Univ, State Key Lab Elementoorgan Chem, Tianjin 300071, Peoples R China. RP Jiang, XF (reprint author), E China Normal Univ, Sch Chem & Mol Engn, Shanghai Key Lab Green Chem & Chem Proc, Shanghai 200062, Peoples R China.; Liang, SH (reprint author), Massachusetts Gen Hosp, Dept Radiol, Div Nucl Med & Mol Imaging, Boston, MA USA.; Liang, SH (reprint author), Harvard Univ, Sch Med, Boston, MA USA. EM Liang.Steven@mgh.harvard.edu; xfjiang@chem.ecnu.edu.cn FU NBRPC [2015CB856600]; NSFC [21472050, 21272075]; NCET [120178]; DFMEC [20130076110023]; Fok Ying Tung Education Foundation [141011]; program for Shanghai Rising Star [15QA1401800]; Shanghai Institutions of Higher Learning; Changjiang Scholar and Innovative Research Team in University FX Financial support was provided by NBRPC (973 Program, 2015CB856600), NSFC (21472050, 21272075), NCET (120178), DFMEC (20130076110023), Fok Ying Tung Education Foundation (141011), the program for Shanghai Rising Star (15QA1401800), Professor of Special Appointment (Eastern Scholar) at Shanghai Institutions of Higher Learning, and the Changjiang Scholar and Innovative Research Team in University. NR 58 TC 10 Z9 10 U1 8 U2 18 PU BENTHAM SCIENCE PUBL LTD PI SHARJAH PA EXECUTIVE STE Y-2, PO BOX 7917, SAIF ZONE, 1200 BR SHARJAH, U ARAB EMIRATES SN 1568-0266 EI 1873-5294 J9 CURR TOP MED CHEM JI Curr. Top. Med. Chem. PY 2016 VL 16 IS 11 BP 1200 EP 1216 DI 10.2174/1568026615666150915111741 PG 17 WC Chemistry, Medicinal SC Pharmacology & Pharmacy GA DH5QV UT WOS:000372847800002 PM 26369815 ER PT J AU Sillesen, NH Greene, ME Nebergall, AK Huddleston, JI Emerson, R Gebuhr, P Troelsen, A Malchau, H AF Sillesen, Nanna H. Greene, Meridith E. Nebergall, Audrey K. Huddleston, James I. Emerson, Roger Gebuhr, Peter Troelsen, Anders Malchau, Henrik TI 3-year follow-up of a long-term registry-based multicentre study on vitamin E diffused polyethylene in total hip replacement SO HIP INTERNATIONAL LA English DT Article DE Hip arthroplasty; Polyethylene; Revisions; Vitamin E ID CROSS-LINKED POLYETHYLENE; ARTHROPLASTY REGISTER; ACETABULAR COMPONENTS; CONTROLLED-TRIALS; TOTAL JOINT; SURFACE; WEAR; OPERATIONS; CHARNLEY; SYSTEMS AB Purpose: Preclinical studies of vitamin E diffused highly cross-linked polyethylene (E-XLPE) has shown enhanced mechanical properties with less wear. The purpose of our study was to document the early clinical outcome of E-XLPE to ensure, for the safety of patients, that there are no unforeseen early adverse events from using this new biomaterial. Methods: The enrolled patients (n = 977) have received either a porous titanium coated or porous plasma sprayed acetabular shell with either a E-XLPE liner or a medium cross-linked (AXL) liner. At each follow-up 5 patient-reported outcome measures (PROMs) were completed: Harris Hip Score, Case Mix Indicator, UCLA Activity Score, SF-36, and EQ-5D. Radiographs were measured for cup and stem position, as well as femoral head penetration into the liner (wear). Postoperative complications and revisions were collected. Results: At 3 years follow-up, there were 13 revisions due to: 4 periprosthetic fractures; 1 sepsis; 6 instabilities; and 2 implant mismatches at surgery. Wear of the hip implant, calculated by software analysis of pelvis x-rays, from the postoperative interval to 3 years showed a liner penetration rate of 0.027 mm/year for AXL and 0.005 mm/year for E-XLPE with no significant difference between the 2 (p = 0.24). Improvement was seen in all PROMs from the preoperative interval to 3 years after surgery (p<0.0001). Conclusions: Early follow-up of the E-XLPE and AXL liners show low penetration. PROMs indicate improvement after total hip arthroplasty in functionality and quality of life across the centers. We have not observed any early in vivo adverse effects from diffusing the liners with vitamin E. C1 [Sillesen, Nanna H.; Greene, Meridith E.; Nebergall, Audrey K.; Malchau, Henrik] Massachusetts Gen Hosp, Harris Orthopaed Lab, 55 Fruit St, Boston, MA 02114 USA. [Huddleston, James I.] Stanford Univ, Med Ctr, Dept Orthopaed Surg, Stanford, CA 94305 USA. [Emerson, Roger] Texas Ctr Joint Replacement, Plano, TX USA. [Gebuhr, Peter; Troelsen, Anders] Copenhagen Univ Hosp Hvidovre, Dept Orthopaed, Clin Orthoped Res Hvidovre, Hvidovre, Denmark. RP Nebergall, AK (reprint author), Massachusetts Gen Hosp, Harris Orthopaed Lab, 55 Fruit St, Boston, MA 02114 USA. EM anebergall@mgh.harvard.edu FU Biomet, Inc. FX Biomet, Inc. provided funding for this study. The institutions and Biomet signed a standard legal study agreement. The agreement stated that the economic support was granted unconditionally and that the manufacturer would have no influence on study design, data analysis or publication. NR 31 TC 0 Z9 1 U1 0 U2 2 PU WICHTIG PUBLISHING PI MILAN PA 72/74 VIA FRIULI, 20135 MILAN, ITALY SN 1120-7000 EI 1724-6067 J9 HIP INT JI Hip Int. PD JAN-FEB PY 2016 VL 26 IS 1 BP 97 EP 103 DI 10.5301/hipint.5000297 PG 7 WC Orthopedics SC Orthopedics GA DI2XD UT WOS:000373361600019 PM 26692248 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 (2015,468704,2015) SO JOURNAL OF DIABETES RESEARCH LA English DT Editorial Material C1 [Mottalib, Adham; Sakr, Mahmoud; Shehabeldin, Mohamed; Hamdy, Osama] Joslin Diabet Ctr, One Joslin Pl, 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 NR 2 TC 0 Z9 0 U1 0 U2 0 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 2016 AR 8708047 DI 10.1155/2016/8708047 PG 2 WC Endocrinology & Metabolism; Medicine, Research & Experimental SC Endocrinology & Metabolism; Research & Experimental Medicine GA DH7RR UT WOS:000372992000001 ER PT J AU Tiedemann, LM Manley, P Smith, ER Dagi, LR AF Tiedemann, Laura M. Manley, Peter Smith, Edward R. Dagi, Linda R. TI Visual Field Loss in a Case of Recurrent Cystic Craniopharyngioma During Concomitant Treatment With Pegylated Interferon alpha-2b SO JOURNAL OF PEDIATRIC HEMATOLOGY ONCOLOGY LA English DT Article DE visual field; pegylated interferon alpha-2b; craniopharyngioma ID ISCHEMIC OPTIC NEUROPATHY; CHRONIC HEPATITIS-C; THERAPY AB A 13-year-old male with suprasellar cystic craniopharyngioma initially controlled with sequential subtotal resections and proton-beam irradiation was later treated with intracystic pegylated interferon alpha-2b due to progression and a lack of further surgical options. After initial successful control of recurrent cyst enlargement and stabilization of the ophthalmic examination, progressive and irreversible visual field loss ensued. Imaging revealed intracranial leakage from the intracystic catheter, and direct administration of interferon alpha-2b was discontinued. Given the recent interest in interferon alpha-2b, oncologists are advised to vigilantly monitor patients for signs of local toxicity that may result from unintended leakage during intracystic delivery. C1 [Tiedemann, Laura M.; Dagi, Linda R.] Boston Childrens Hosp, Dept Ophthalmol, 300 Longwood Ave,Fegan 4, Boston, MA 02115 USA. [Manley, Peter; Smith, Edward R.] Boston Childrens Hosp, Dana Farber Canc Inst, Boston, MA 02115 USA. [Smith, Edward R.] Boston Childrens Hosp, Dept Neurosurg, Boston, MA 02115 USA. RP Dagi, LR (reprint author), Boston Childrens Hosp, Dept Ophthalmol, 300 Longwood Ave,Fegan 4, Boston, MA 02115 USA. EM linda.dagi@childrens.harvard.edu FU Children's Hospital Ophthalmology Foundation Chair FX Supported by endowed chair funds: Children's Hospital Ophthalmology Foundation Chair (L.R.D.). NR 13 TC 0 Z9 0 U1 1 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 1077-4114 EI 1536-3678 J9 J PEDIAT HEMATOL ONC JI J. Pediatr. Hematol. Oncol. PD JAN PY 2016 VL 38 IS 1 BP E26 EP E28 DI 10.1097/MPH.0000000000000468 PG 3 WC Oncology; Hematology; Pediatrics SC Oncology; Hematology; Pediatrics GA DH5OF UT WOS:000372838700007 PM 26558808 ER PT J AU Millstein, RA Hoerster, KD Rosenberg, DE Nelson, KM Reiber, G Saelens, BE AF Millstein, Rachel A. Hoerster, Katherine D. Rosenberg, Dori E. Nelson, Karin M. Reiber, Gayle Saelens, Brian E. TI Individual, Social, and Neighborhood Associations With Sitting Time Among Veterans SO JOURNAL OF PHYSICAL ACTIVITY & HEALTH LA English DT Article DE sedentary behavior; physical functioning; health behaviors; mental health ID PHYSICAL-ACTIVITY QUESTIONNAIRE; TELEVISION VIEWING TIME; SEDENTARY BEHAVIOR; OLDER-ADULTS; US ADULTS; HEALTH; DEPRESSION; WALKABILITY; OUTCOMES; WOMEN AB Background: Sedentary behavior is an increasingly recognized health risk factor, independent of physical activity. Although several correlates of sedentary behavior are known, little research has identified them among U.S. veterans, a population that faces disproportionate chronic disease burden. Methods: A survey was mailed to 1997 randomly selected veterans at a large urban Veterans Affairs medical center in 2012 and remailed in 2013 to nonresponders, resulting in a 40% response rate. We examined individual-, social-, and neighborhood-level factors in association with self-reported sitting time. Factors correlated with sitting time at P < .05 were included in a multiple linear regression model. Results: In the multivariate model, higher depression (B = 7.8), body mass index (B = 5.1), functional impairment (B = 4.2), and self-rated health (B = 68.5) were significantly associated with higher sitting time, and leisure time physical activity (B = -0.10) and being employed (B = -71.3) were significantly associated with lower sitting time. Conclusions: Individual-level, but not social- and neighborhood-level, variables were associated with sitting time in this population. This study identified individual-level targets for reducing sitting time and improving overall health among veterans. C1 [Millstein, Rachel A.] Univ Calif San Diego, San Diego Joint Doctoral Program Clin Psychol, San Diego State Univ, San Diego, CA 92103 USA. [Millstein, Rachel A.; Hoerster, Katherine D.] VA Puget Sound Healthcare Syst, Mental Hlth Serv, Seattle Div, Seattle, WA USA. [Hoerster, Katherine D.; Saelens, Brian E.] Univ Washington, Dept Psychiat & Behav Sci, Seattle, WA 98195 USA. [Rosenberg, Dori E.] Grp Hlth Res Inst, Seattle, WA USA. [Rosenberg, Dori E.] Univ Washington, Sch Publ Hlth, Seattle, WA 98195 USA. [Nelson, Karin M.] VA Puget Sound Healthcare Syst, Hlth Serv Res & Dev & Gen Internal Med Serv, Seattle Div, Seattle, WA USA. [Nelson, Karin M.] Univ Washington, Dept Med, Seattle, WA USA. [Reiber, Gayle] VA Puget Sound Healthcare Syst, Hlth Serv Res & Dev Serv, Seattle Div, Seattle, WA USA. [Reiber, Gayle] Univ Washington, Sch Publ Hlth, Dept Epidemiol, Seattle, WA 98195 USA. [Reiber, Gayle] Univ Washington, Sch Publ Hlth, Dept Hlth Serv, Seattle, WA 98195 USA. [Saelens, Brian E.] Seattle Childrens Res Inst, Seattle, WA USA. RP Millstein, RA (reprint author), Univ Calif San Diego, San Diego Joint Doctoral Program Clin Psychol, San Diego State Univ, San Diego, CA 92103 USA.; Millstein, RA (reprint author), VA Puget Sound Healthcare Syst, Mental Hlth Serv, Seattle Div, Seattle, WA USA. EM rmillstein@gmail.com FU US Department of Veterans Affairs; VA Puget Sound, Seattle Division Mental Illness Research, Education, and Clinical Center (MIRECC); Health Services Research and Development (HSR&D) Center of Excellence FX The authors would like to acknowledge Carol Malte, Linda Guerrero, David Tice, Marie Lutton, and Jeff Rodenbaugh, all from VA Puget Sound Healthcare System, Seattle Division, for their important contributions to this study. Ms Malte identified the survey sample using VA administrative data. Ms Guerrero, Mr Tice, and Ms Lutton helped to coordinate the survey mailing. Ms Lutton performed data entry, and Mr Rodenbaugh performed the study analyses. This material is based upon work supported by the US Department of Veterans Affairs, including local funds from the VA Puget Sound, Seattle Division Mental Illness Research, Education, and Clinical Center (MIRECC) and the Health Services Research and Development (HSR&D) Center of Excellence. NR 41 TC 0 Z9 0 U1 3 U2 5 PU HUMAN KINETICS PUBL INC PI CHAMPAIGN PA 1607 N MARKET ST, PO BOX 5076, CHAMPAIGN, IL 61820-2200 USA SN 1543-3080 EI 1543-5474 J9 J PHYS ACT HEALTH JI J. Phys. Act. Health PD JAN PY 2016 VL 13 IS 1 BP 30 EP 35 DI 10.1123/jpah.2014-0369 PG 6 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA DH4QH UT WOS:000372770000005 PM 25831556 ER PT J AU Seal, KH Bertenthal, D Samuelson, K Maguen, S Kumar, S Vasterling, JJ AF Seal, Karen H. Bertenthal, Daniel Samuelson, Kristin Maguen, Shira Kumar, Sant Vasterling, Jennifer J. TI Association between mild traumatic brain injury and mental health problems and self-reported cognitive dysfunction in Iraq and Afghanistan Veterans SO JOURNAL OF REHABILITATION RESEARCH AND DEVELOPMENT LA English DT Article DE cognitive dysfunction; concussion; depression; mental health; mild traumatic brain injury; population-based screening; postdeployment; posttraumatic stress disorder; primary care; recovery expectations; Veterans ID POSTTRAUMATIC-STRESS-DISORDER; PERSISTENT POSTCONCUSSIVE SYMPTOMS; NEUROPSYCHOLOGICAL OUTCOMES; WAR VETERANS; HEAD-INJURY; COMPLAINTS; PERFORMANCE; DEPLOYMENT; SOLDIERS; CONSEQUENCES AB The Department of Veterans Affairs traumatic brain injury (TBI) screening program is intended to detect and expedite treatment for TBI and postconcussive symptoms. Between April 14, 2007, and May 31, 2012, of 66,089 Iraq and Afghanistan Veterans who screened positive on first-level TBI screening and later completed comprehensive TBI evaluation that includes the Neurobehavioral Symptoms Inventory, 72% reported moderate to very severe cognitive impairment (problems with attention, concentration, memory, etc.) that interfered with daily activities. This included 42% who were found not to have sustained combat-related mild TBI (mTBI). In contrast, 70.0% received a posttraumatic stress disorder (PTSD) diagnosis and 45.8% received a depression diagnosis. Compared with Veterans without mTBI, PTSD, or depression diagnoses, the lowest risk for self-reported cognitive impairment was in Veterans with confirmed mTBI only; a greater risk was found in those with PTSD diagnoses, with the greatest risk in Veterans with PTSD, depression, and confirmed mTBI, suggesting only a weakly additive effect of mTBI. These findings suggest that Veterans with multiple mental health comorbidities, not just those with TBI, report moderate to very severe cognitive impahment. Mental health treatment for conditions such as PTSD and depression (with or without TBI) may result in improvements in cognitive functioning and/or include assessment and support for Veterans experiencing cognitive problems. C1 [Seal, Karen H.; Bertenthal, Daniel; Samuelson, Kristin; Maguen, Shira; Kumar, Sant] San Francisco Dept Vet Affairs VA Hlth Care Syst, San Francisco, CA USA. [Seal, Karen H.; Maguen, Shira] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Samuelson, Kristin] Alliant Int Univ, Calif Sch Profess Psychol, San Francisco, CA USA. [Vasterling, Jennifer J.] VA Boston Healthcare Syst, Boston, MA USA. [Vasterling, Jennifer J.] Boston Univ, Sch Med, Boston, MA 02118 USA. RP Seal, KH (reprint author), San Francisco VA Med Ctr, 4150 Clement St,Box 111A-1, San Francisco, CA 94121 USA. EM Karen.Seal@va.gov FU VA Health Services Research and Development [SDR-08-408] FX This material was based on work supported by VA Health Services Research and Development (award SDR-08-408). NR 41 TC 1 Z9 1 U1 7 U2 13 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 2016 VL 53 IS 2 BP 185 EP 198 DI 10.1682/JRRD.2014.12.0301 PG 14 WC Rehabilitation SC Rehabilitation GA DH4QX UT WOS:000372771600002 PM 27148692 ER PT J AU Ingelfinger, JR Kalantar-Zadeh, K Schaefer, F AF Ingelfinger, Julie R. Kalantar-Zadeh, Kamyar Schaefer, Franz CA World Kidney Day Steering Comm TI Averting the Legacy of Kidney Disease - Focus on Childhood SO NEPHRON LA English DT Article ID NEPHROLOGY ASSOCIATION IPNA; RENAL REPLACEMENT THERAPY; LOW-BIRTH-WEIGHT; NONCOMMUNICABLE DISEASES; INTERNATIONAL SOCIETY; CONSENSUS STATEMENT; PROSPECTIVE COHORT; BLOOD-PRESSURE; GLOBAL HEALTH; CHILDREN AB World Kidney Day 2016 focuses on kidney disease in childhood and the antecedents of adult kidney disease that can begin in earliest childhood. Chronic kidney disease (CKD) in childhood differs from that in adults, as the largest diagnostic group among children includes congenital anomalies and inherited disorders, with glomerulopathies and kidney disease in the setting of diabetes being relatively uncommon. In addition, many children with acute kidney injury will ultimately develop sequelae that may lead to hypertension and CKD in later childhood or in adult life. Children born early or who are small-for-date newborns have relatively increased risk for the development of CKD later in life. Persons with a high-risk birth and early childhood history should be watched closely in order to help detect early signs of kidney disease in time to provide effective prevention or treatment. Successful therapy is feasible for advanced CKD in childhood; there is evidence that children fare better than adults, if they receive kidney replacement therapy including dialysis and transplantation, while only a minority of children may require this ultimate intervention. Because there are disparities in access to care, effort is needed so that those children with kidney disease, wherever they live, may be treated effectively, irrespective of their geographic or economic circumstances. Our hope is that World Kidney Day will inform the general public, policy makers and caregivers about the needs and possibilities surrounding kidney disease in childhood. (C) 2016 S. Karger AG, Basel C1 [Ingelfinger, Julie R.] Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. [Ingelfinger, Julie R.] Massachusetts Gen Hosp, Mass Gen Hosp Children, Pediat Nephrol, Boston, MA 02114 USA. [Ingelfinger, Julie R.] Massachusetts Gen Hosp, Mass Gen Hosp Children, Pediact, Boston, MA 02114 USA. [Kalantar-Zadeh, Kamyar] Univ Calif Irvine, Sch Med, Dept Med, Div Nephrol & Hypertens, Irvine, CA 92717 USA. [Kalantar-Zadeh, Kamyar] Univ Calif Irvine, Sch Med, Div Pediat & Publ Hlth, Irvine, CA 92717 USA. [Kalantar-Zadeh, Kamyar] Vet Affairs Long Beach Healthcare Syst, Long Beach, CA USA. [Kalantar-Zadeh, Kamyar] Univ Calif Los Angeles, Los Angeles Fielding Sch Publ Hlth, Dept Epidemiol, Los Angeles, CA USA. [Schaefer, Franz] Heidelberg Univ, Dept Pediat, Heidelberg, Germany. [Schaefer, Franz] Univ Heidelberg Hosp, Ctr Pediat & Adolescent Med, Div Pediat Nephrol, Heidelberg, Germany. RP Ingelfinger, JR (reprint author), Int Federat Kidney Fdn, Int Soc Nephrol, World Kidney Day, Rues Fabriques, BE-1000 Brussels, Belgium. OI Kalantar-Zadeh, Kamyar/0000-0002-8666-0725 NR 33 TC 1 Z9 1 U1 1 U2 2 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 1660-8151 EI 2235-3186 J9 NEPHRON JI Nephron PY 2016 VL 132 IS 3 BP 161 EP 167 DI 10.1159/000444461 PG 7 WC Urology & Nephrology SC Urology & Nephrology GA DI1ID UT WOS:000373248900001 PM 26926120 ER PT J AU Termsarasab, P Ramdhani, RA Battistella, G Rubien-Thomas, E Choy, M Farwell, IM Velickovic, M Blitzer, A Frucht, SJ Reilly, RB Hutchinson, M Ozelius, LJ Simonyan, K AF Termsarasab, Pichet Ramdhani, Ritesh A. Battistella, Giovanni Rubien-Thomas, Estee Choy, Melissa Farwell, Ian M. Velickovic, Miodrag Blitzer, Andrew Frucht, Steven J. Reilly, Richard B. Hutchinson, Michael Ozelius, Laurie J. Simonyan, Kristina TI Neural correlates of abnormal sensory discrimination in laryngeal dystonia SO NEUROIMAGE-CLINICAL LA English DT Article DE Sensory processing; Endophenotype; Brain imaging ID PRIMARY TORSION DYSTONIA; IDIOPATHIC CERVICAL DYSTONIA; TEMPORAL DISCRIMINATION; SPASMODIC DYSPHONIA; GENERALIZED DYSTONIA; FOCAL DYSTONIA; MATTER CHANGES; RHESUS-MONKEY; BASAL GANGLIA; WRITERS CRAMP AB Aberrant sensory processing plays a fundamental role in the pathophysiology of dystonia; however, its underpinning neural mechanisms in relation to dystonia phenotype and genotype remain unclear. We examined temporal and spatial discrimination thresholds in patients with isolated laryngeal form of dystonia (LD), who exhibited different clinical phenotypes (adductor vs. abductor forms) and potentially different genotypes (sporadic vs. familial forms). We correlated our behavioral findings with the brain gray matter volume and functional activity during resting and symptomatic speech production. We found that temporal but not spatial discrimination was significantly altered across all forms of LD, with higher frequency of abnormalities seen in familial than sporadic patients. Common neural correlates of abnormal temporal discrimination across all forms were found with structural and functional changes in the middle frontal and primary somatosensory cortices. In addition, patients with familial LD had greater cerebellar involvement in processing of altered temporal discrimination, whereas sporadic LD patients had greater recruitment of the putamen and sensorimotor cortex. Based on the clinical phenotype, adductor form-specific correlations between abnormal discrimination and brain changes were found in the frontal cortex, whereas abductor form-specific correlations were observed in the cerebellum and putamen. Our behavioral and neuroimaging findings outline the relationship of abnormal sensory discrimination with the phenotype and genotype of isolated LD, suggesting the presence of potentially divergent pathophysiological pathways underlying different manifestations of this disorder. (C) 2015 The Authors. Published by Elsevier Inc. C1 [Termsarasab, Pichet; Ramdhani, Ritesh A.; Battistella, Giovanni; Rubien-Thomas, Estee; Choy, Melissa; Farwell, Ian M.; Velickovic, Miodrag; Blitzer, Andrew; Frucht, Steven J.; Simonyan, Kristina] Icahn Sch Med Mt Sinai, Dept Neurol, 1 Gustave L Levy Pl,Box 1137, New York, NY 10029 USA. [Simonyan, Kristina] Icahn Sch Med Mt Sinai, Otolaryngol, New York, NY 10029 USA. [Blitzer, Andrew] Head & Neck Surg Grp, New York, NY USA. [Reilly, Richard B.] Trinity Coll Dublin, Trinity Ctr Bioengn, Dublin, Ireland. [Hutchinson, Michael] St Vincents Univ Hosp, Dept Neurol, Dublin 4, Ireland. [Ozelius, Laurie J.] Massachusetts Gen Hosp, Dept Neurol, Charlestown, MA USA. RP Simonyan, K (reprint author), Icahn Sch Med Mt Sinai, Dept Neurol, 1 Gustave L Levy Pl,Box 1137, New York, NY 10029 USA. EM kristina.simonyan@mssm.edu OI Simonyan, Kristina/0000-0001-7444-0437; Reilly, Richard/0000-0001-8578-1245 FU National Institute on Deafness and Other Communication Disorders, National Institutes of Health; Dystonia Medical Research Foundation FX We thank Aisling Fanning, Adriana Dabacan and Robert Whelan for their help with initial TDT setup, Beth Belluscio for her advice on SDT procedures, Amanda Pechman for patient recruitment, and Lazar Fleysher and Heather Alexander for imaging data acquisition. This work was supported by R01DC01180 grant to KS from the National Institute on Deafness and Other Communication Disorders, National Institutes of Health. PT was supported by a clinical fellowship training program from the Dystonia Medical Research Foundation. NR 55 TC 3 Z9 3 U1 1 U2 3 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 2213-1582 J9 NEUROIMAGE-CLIN JI NeuroImage-Clin. PY 2016 VL 10 BP 18 EP 26 DI 10.1016/j.nicl.2015.10.016 PG 9 WC Neuroimaging SC Neurosciences & Neurology GA DI0LX UT WOS:000373189000002 PM 26693398 ER PT J AU Jarcho, JM Feier, NA Labus, JS Naliboff, B Smith, SR Hong, JY Colloca, L Tillisch, K Mandelkern, MA Mayer, EA London, ED AF Jarcho, Johanna M. Feier, Natasha A. Labus, Jennifer S. Naliboff, Bruce Smith, Suzanne R. Hong, Jui-Yang Colloca, Luana Tillisch, Kirsten Mandelkern, Mark A. Mayer, Emeran A. London, Edythe D. TI Placebo analgesia: Self-report measures and preliminary evidence of cortical dopamine release associated with placebo response SO NEUROIMAGE-CLINICAL LA English DT Article DE Placebo effect; Pain; PET; [F-18]fallypride; Ventrolateral prefrontal cortex ID TRANSCRANIAL MAGNETIC STIMULATION; REFERENCE TISSUE MODEL; CHRONIC PAIN; PREFRONTAL CORTEX; PARKINSONS-DISEASE; C-11 RACLOPRIDE; INDIVIDUAL-DIFFERENCES; CLINICAL IMPORTANCE; OPIOID ACTIVITY; HEALTH-CARE AB Placebo analgesia is measured by self-report, yet current, expected, and recalled efficacy may be differentially related to brain function. Here we used a human thermal pain model to compare self-reports of expected, concurrent, and recalled efficacy of a topical placebo analgesic, and tested associations of the three measures of efficacy with changes in dopamine D2/D3 receptor availability in brain using [F-18] fallypride with positron emission tomography (PET). Participants (15 healthy women) were assessed on three test days. The first test day included a laboratory visit, during which the temperature needed to evoke consistent pain was determined, placebo analgesia was induced via verbal and experience-based expectation, and the placebo response was measured. On two subsequent test days, PET scans were performed in Control and Placebo conditions, respectively, in counterbalanced order. During Visit 1, concurrent and recalled placebo efficacy were unrelated; during the Placebo PET visit, expected and recalled efficacy were highly correlated (rho = 0.68, p = 0.005), but concurrent efficacy was unrelated to expected or recalled efficacy. Region of interest analysis revealed dopamine D2/D3 receptor availability was lower in left ventrolateral prefrontal cortex in the Placebo condition (p < 0.001, uncorrected), and greater change in this measure was associated with higher levels of recalled analgesic efficacy (rho = 0.58, p = 0.02). These preliminary findings underscore the need to consider how self-reported symptom improvement is assessed in clinical trials of analgesics and suggest that dopaminergic activity in the ventrolateral prefrontal cortex may promote recalled efficacy of placebo. (C) 2015 The Authors. Published by Elsevier Inc. C1 [Jarcho, Johanna M.; Feier, Natasha A.; Labus, Jennifer S.; Naliboff, Bruce; Smith, Suzanne R.; Hong, Jui-Yang; Tillisch, Kirsten; Mayer, Emeran A.] Univ Calif Los Angeles, David Geffen Sch Med, Gail & Gerald Oppenheimer Family Ctr Neurobiol St, Los Angeles, CA 90095 USA. [Jarcho, Johanna M.] SUNY Stony Brook, Dept Psychol, Stony Brook, NY USA. [Feier, Natasha A.] McGill Univ, Fac Dent, Alan Edwards Ctr Res Pain, Montreal, PQ, Canada. [Labus, Jennifer S.; Naliboff, Bruce; Smith, Suzanne R.; Hong, Jui-Yang; Tillisch, Kirsten; Mayer, Emeran A.] Univ Calif Los Angeles, David Geffen Sch Med, Div Digest Dis, Dept Med, Los Angeles, CA 90095 USA. [Labus, Jennifer S.; Naliboff, Bruce; Smith, Suzanne R.; Hong, Jui-Yang; Tillisch, Kirsten; Mayer, Emeran A.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Psychiat & Biobehav Sci, Los Angeles, CA 90095 USA. [Labus, Jennifer S.; Naliboff, Bruce; Smith, Suzanne R.; Hong, Jui-Yang; Tillisch, Kirsten; Mayer, Emeran A.; London, Edythe D.] Univ Calif Los Angeles, Dept Physiol, Los Angeles, CA 90024 USA. [Labus, Jennifer S.; Naliboff, Bruce; Smith, Suzanne R.; Hong, Jui-Yang; Tillisch, Kirsten; Mayer, Emeran A.] Univ Calif Los Angeles, PAIN, Los Angeles, CA USA. [Colloca, Luana] Univ Maryland, Sch Nursing, Baltimore, MD 21201 USA. [Colloca, Luana] Univ Maryland, Sch Med, Baltimore, MD 21201 USA. [Tillisch, Kirsten; Mandelkern, Mark A.; London, Edythe D.] VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. [London, Edythe D.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Mol & Med Pharmacol, Los Angeles, CA 90095 USA. RP Mayer, EA (reprint author), Univ Calif Los Angeles, David Geffen Sch Med, Div Digest Dis, Gail & Gerald Oppenheimer Family Ctr Neurobiol St, CHS 42-210 MC737818,10833 Le Conte Ave, Los Angeles, CA 90095 USA. EM emayer@ucla.edu OI Jarcho, Johanna/0000-0001-9075-6968 FU Intramural Research Program at National Institute of Mental Health, National Institutes of Health [F31-DA021951, T32-MH017140] FX This work was supported in part by the Intramural Research Program at the National Institute of Mental Health, National Institutes of Health Grants F31-DA021951, T32-MH017140 (JMJ), and endowments from the Thomas P and Katherine K Pike Chair of Addiction Studies (EDL) and an endowment from the Marjorie Green Trust. NR 54 TC 2 Z9 2 U1 1 U2 5 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 2213-1582 J9 NEUROIMAGE-CLIN JI NeuroImage-Clin. PY 2016 VL 10 BP 107 EP 114 DI 10.1016/j.nicl.2015.11.009 PG 8 WC Neuroimaging SC Neurosciences & Neurology GA DI0LX UT WOS:000373189000012 PM 26759785 ER PT J AU Mattfeld, AT Whitfield-Gabrieli, S Biederman, J Spencer, T Brown, A Fried, R Gabrieli, JDE AF Mattfeld, Aaron T. Whitfield-Gabrieli, Susan Biederman, Joseph Spencer, Thomas Brown, Ariel Fried, Ronna Gabrieli, John D. E. TI Dissociation of working memory impairments and attention-deficit/hyperactivity disorder in the brain SO NEUROIMAGE-CLINICAL LA English DT Article DE ADHD; n-Back; fMRI; Longitudinal; Working memory ID DEFICIT HYPERACTIVITY DISORDER; EXECUTIVE FUNCTION DEFICITS; FUNCTIONAL NEUROANATOMY; PREFRONTAL CORTEX; UNITED-STATES; ADHD; CAPACITY; ADULTS; INTELLIGENCE; ACTIVATION AB Prevailing neuropsychological models of attention-deficit/hyperactivity disorder (ADHD) propose that ADHD arises from deficits in executive functions such as working memory, but accumulating clinical evidence suggests a dissociation between ADHD and executive dysfunctions. This study examined whether ADHD and working memory capacity are behaviorally and neurobiologically separable using functional magnetic resonance imaging (fMRI). Participants diagnosed with ADHD in childhood who subsequently remitted or persisted in their diagnosis as adults were characterized at follow-up in adulthood as either impaired or unimpaired in spatial working memory relative to controls who never had ADHD. ADHD participants with impaired spatial working memory performed worse than controls and ADHD participants with unimpaired working memory during an n-back working memory task while being scanned. Both controls and ADHD participants with unimpaired working memory exhibited significant linearly increasing activation in the inferior frontal junction, precuneus, lingual gyrus, and cerebellum as a function of working-memory load, and these activations did not differ significantly between these groups. ADHD participants with impaired working memory exhibited significant hypoactivation in the same regions, which was significantly different than both control participants and ADHD participants with unimpaired working memory. These findings support both a behavioral and neurobiological dissociation between ADHD and working memory capacity. (C) 2016 The Authors. Published by Elsevier Inc. C1 [Mattfeld, Aaron T.; Whitfield-Gabrieli, Susan; Gabrieli, John D. E.] MIT, McGovern Inst Brain Res, 77 Massachusetts Ave, Cambridge, MA 02139 USA. [Mattfeld, Aaron T.; Whitfield-Gabrieli, Susan; Gabrieli, John D. E.] MIT, Dept Brain & Cognit Sci, E25-618, Cambridge, MA 02139 USA. [Mattfeld, Aaron T.] Florida Int Univ, Dept Psychol, 11200 SW 8th St,AHC4-462, Miami, FL 33199 USA. [Biederman, Joseph; Spencer, Thomas; Brown, Ariel; Fried, Ronna] Massachusetts Gen Hosp, Clin & Res Program Pediat Psychopharmacol, Boston, MA 02114 USA. [Biederman, Joseph; Spencer, Thomas; Brown, Ariel; Fried, Ronna; Gabrieli, John D. E.] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. RP Mattfeld, AT (reprint author), Florida Int Univ, Dept Psychol, 11200 SW 8th St,AHC4-462, Miami, FL 33199 USA. EM amattfel@fiu.edu FU Poitras Center for Affective Disorders Research at the McGovern Institute for Brain Research at MIT; Pediatric Psychopharmacology Council Fund at MGH; NIMH [R01 HD036317, R01 MH050657] FX We thank Steve Shannon, Sheeba Arnold, and Christina Triantafyllou for technical assistance. Imaging was performed at the Athinoula A. Martinos Imaging Center at McGovern Institute for Brain Research, MIT. We thank Elana Kagan for assistance in recruitment and data collection. The Poitras Center for Affective Disorders Research at the McGovern Institute for Brain Research at MIT, the Pediatric Psychopharmacology Council Fund at MGH, and the NIMH(J.B., grant numbers R01 HD036317 and R01 MH050657) supported this work. NR 73 TC 2 Z9 2 U1 14 U2 20 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 2213-1582 J9 NEUROIMAGE-CLIN JI NeuroImage-Clin. PY 2016 VL 10 BP 274 EP 282 DI 10.1016/j.nicl.2015.12.003 PG 9 WC Neuroimaging SC Neurosciences & Neurology GA DI0LX UT WOS:000373189000026 PM 26900567 ER PT J AU Bergamino, M Pasternak, O Farmer, M Shenton, ME Hamilton, JP AF Bergamino, Maurizio Pasternak, Ofer Farmer, Madison Shenton, Martha E. Hamilton, J. Paul TI Applying a free-water correction to diffusion imaging data uncovers stress-related neural pathology in depression SO NEUROIMAGE-CLINICAL LA English DT Article DE Diffusion tensor imaging; Free-water corrected DTI; Major depressive disorder; Tract-based spatial statistics; Fractional anisotropy; Axial diffusivity ID WHITE-MATTER; HIPPOCAMPAL VOLUME; CORPUS-CALLOSUM; MRI; BRAIN; METAANALYSIS; DISORDER; AMYGDALA; SCHIZOPHRENIA; DEMYELINATION AB Diffusion tensor imaging (DTI) holds promise for developing our understanding of white-matter pathology in major depressive disorder (MDD). Variable findings in DTI-based investigations ofMDD, however, have thwarted development of this literature. Effects of extra-cellular free-water on the sensitivity of DTI metrics could account for some of this inconsistency. Here we investigated whether applying a free-water correction algorithm to DTI data could improve the sensitivity to detect clinical effects using DTI metrics. Only after applying this correction, we found: a) significantly decreased fractional anisotropy and axial diffusivity (AD) in the left inferior frontooccipital fasciculus (IFOF) in MDD; and b) increased self-reported stress that significantly correlated with decreased IFOF AD in depression. We estimated and confirmed the robustness of differences observed between free-water corrected and uncorrected approaches using bootstrapping. We conclude that applying a free-water correction to DTI data increases the sensitivity of DTI-based metrics to detect clinical effects in MDD. (C) 2015 The Authors. Published by Elsevier Inc. C1 [Bergamino, Maurizio; Farmer, Madison; Hamilton, J. Paul] Laureate Inst Brain Res, 6655 South Yale Ave, Tulsa, OK 74136 USA. [Pasternak, Ofer; Shenton, Martha E.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Psychiat & Radiol, 1249 Boylston St, Boston, MA 02115 USA. [Shenton, Martha E.] VA Boston Healthcare Syst, Boston, MA USA. [Hamilton, J. Paul] Dept Clin & Expt Med, Ctr Social & Affect Neurosci, S-58233 Linkoping, Sweden. RP Hamilton, JP (reprint author), Linkoping Univ, Ctr Social & Affect Neurosci, Dept Clin & Expt Med, S-58183 Linkoping, Sweden. EM mbergamino@laureateinstitute.org; ofer@bwh.har-vard.edu; mfarmer@laureateinstitute.org; shenton@bwh.har-vard.edu; paul.hamilton@cal.berkeley.edu FU Warren Foundation FX The authors gratefully acknowledge the Warren Foundation for funding this investigation (Totts Gap Research Endowment to JPH). NR 46 TC 1 Z9 1 U1 0 U2 1 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 2213-1582 J9 NEUROIMAGE-CLIN JI NeuroImage-Clin. PY 2016 VL 10 BP 336 EP 342 DI 10.1016/j.nicl.2015.11.020 PG 7 WC Neuroimaging SC Neurosciences & Neurology GA DI0LX UT WOS:000373189000033 PM 27006903 ER PT J AU Messamore, E Yao, JK AF Messamore, Erik Yao, Jeffrey K. TI Phospholipid, arachidonate and eicosanoid signaling in schizophrenia SO OCL-OILSEEDS AND FATS CROPS AND LIPIDS LA English DT Review DE Phospholipids; arachidonic acid; eicosanoids; niacin-induced flushing, endophenotype marker; schizophrenia ID NIACIN SKIN FLUSH; CEREBRAL-BLOOD-FLOW; OPTICAL REFLECTION SPECTROSCOPY; MAGNETIC-RESONANCE-SPECTROSCOPY; POLYUNSATURATED FATTY-ACIDS; PLACEBO-CONTROLLED TRIAL; CELL MEMBRANE DYNAMICS; NICOTINIC-ACID; PROSTAGLANDIN D-2; TOPICAL NIACIN AB This paper reviews the potential role of arachidonic acid in the pathophysiology of schizophrenia. We discuss how abnormal levels of arachidonic acid may arise, and how dysregulation of signaling molecules derived from it have the potential to disrupt not only dopamine signaling, but numerous other physiological processes associated with the illness. Pharmacological doses of niacin stimulate the release of arachidonic acid; and arachidonic acid-derived molecules in turn dilate blood vessels in the skin. A blunted skin flush response to niacin is reliably observed among patients with schizophrenia. The niacin response abnormality may thus serve as a biomarker to identify a physiological subtype of schizophrenia associated with defective arachidonic acid-derived signaling. C1 [Messamore, Erik] Univ Cincinnati, Cincinnati, OH USA. [Messamore, Erik] Lindner Ctr Hope, Cincinnati, OH USA. [Yao, Jeffrey K.] VA Pittsburgh Healthcare Syst, Pittsburgh, PA 15240 USA. [Yao, Jeffrey K.] Univ Pittsburgh, Med Ctr, Western Psychiat Inst Clin, Dept Psychiat, Pittsburgh, PA 15213 USA. [Yao, Jeffrey K.] Univ Pittsburgh, Sch Pharm, Dept Pharmaceut Sci, Pittsburgh, PA 15213 USA. RP Yao, JK (reprint author), VA Pittsburgh Healthcare Syst, Pittsburgh, PA 15240 USA.; Yao, JK (reprint author), Univ Pittsburgh, Med Ctr, Western Psychiat Inst Clin, Dept Psychiat, Pittsburgh, PA 15213 USA.; Yao, JK (reprint author), Univ Pittsburgh, Sch Pharm, Dept Pharmaceut Sci, Pittsburgh, PA 15213 USA. EM jkyao@pitt.edu NR 95 TC 0 Z9 0 U1 3 U2 4 PU EDP SCIENCES S A PI LES ULIS CEDEX A PA 17, AVE DU HOGGAR, PA COURTABOEUF, BP 112, F-91944 LES ULIS CEDEX A, FRANCE SN 1258-8210 EI 2257-6614 J9 OCL OILS FAT CROP LI JI OCL Oilseed.Fats Crops Lipids PD JAN-FEB PY 2016 VL 23 IS 1 AR D112 DI 10.1051/ocl/2015054 PG 8 WC Agronomy SC Agriculture GA DH9WB UT WOS:000373145600007 ER PT J AU Chang, DK Peterson, E Sun, J Goudie, C Drapkin, RI Liu, JF Matulonis, U Zhu, Q Marasco, WA AF Chang, De-Kuan Peterson, Eric Sun, Jiusong Goudie, Calum Drapkin, Ronny I. Liu, Joyce F. Matulonis, Ursula Zhu, Quan Marasco, Wayne A. TI Anti-CCR4 monoclonal antibody enhances antitumor immunity by modulating tumor-infiltrating Tregs in an ovarian cancer xenograft humanized mouse model SO ONCOIMMUNOLOGY LA English DT Article DE CCR4; immunotherapy; monoclonal antibody; ovarian cancer; regulatory T cells ID REGULATORY T-CELLS; LYMPHOCYTE-ASSOCIATED ANTIGEN-4; PROTEIN-COUPLED RECEPTORS; LUNG-CANCER; METASTATIC MELANOMA; SOLUBLE CD25; ALPHA-CHAIN; BLOCKADE; THERAPY; CCR4 AB Recent studies have demonstrated that regulatory T cells (Tregs) are recruited to tumor sites where they can suppress antitumor immunity. The chemokine receptor CCR4 is expressed at high levels on functional CD4(+)CD25(+)FoxP3(+) Tregs and production of the CCR4 ligand CCL22 by tumor cells and tumor-associated macrophages is associated with Treg recruitment to the tumor site. Here, we tested IgG1 and IgG4 isotypes of human anti-CCR4 mAb2-3 for their in vitro activity and in vivo capacity in a NSG mouse model bearing CCL22-secreting ovarian cancer (OvCA) xenograft to modulate Tregs and restore antitumor activity. Both mAb2-3 isotypes blocked in vitro chemoattraction of Tregs to CCL22-secreting OvCA cells. However, they differed in their in vivo mode of action with IgG1 causing Treg depletion and IgG4 blocking migration to the tumors. Primary T cells that were primed with OvCA-pulsed dendritic cells (DCs) demonstrated INF secretion that could be enhanced through Treg depletion by mAb2-3. Humanized mice reconstructed with allogeneic tumor-primed T cells (TP-T) were used to evaluate the restoration of OvCA immunity by depletion or blockade of Tregs with mAb2-3. We observed that IgG1 was more potent than IgG4 in inhibiting tumor growth. Mechanism studies demonstrated that mAb2-3 treatment lead to inhibition of IL-2 binding to its receptor. Further studies showed that mAb2-3 induced CD25 shedding (sCD25) from Tregs which lead to a decrease in IL-2-dependent survival. Together, the results demonstrate that mAb2-3 is an agonist antibody that can restore anti-OvCA immunity through modulation of Treg activity. C1 [Chang, De-Kuan; Peterson, Eric; Sun, Jiusong; Goudie, Calum; Matulonis, Ursula; Zhu, Quan; Marasco, Wayne A.] Dana Farber Canc Inst, Dept Canc Immunol & Virol, Boston, MA 02115 USA. [Chang, De-Kuan; Liu, Joyce F.; Zhu, Quan; Marasco, Wayne A.] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. [Drapkin, Ronny I.; Liu, Joyce F.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Drapkin, Ronny I.] Brigham & Womens Hosp, Dept Pathol, 75 Francis St, Boston, MA 02115 USA. [Drapkin, Ronny I.] Univ Penn, Dept Obstet & Gynecol, Ovarian Canc Res Ctr, Perelman Sch Med, Philadelphia, PA 19104 USA. RP Marasco, WA (reprint author), Dana Farber Canc Inst, Dept Canc Immunol & Virol, Boston, MA 02115 USA.; Marasco, WA (reprint author), Harvard Univ, Sch Med, Dept Med, Boston, MA USA. EM wayne_marasco@dfci.harvard.edu FU DFCI Women's Cancer Program grant; Honorable Tina Brozman Foundation; Dr Miriam and Sheldon G. Adelson Medical Research Foundation; NIH [U01 CA-152990]; Robert and Debra First Fund FX This study was supported by grants from DFCI Women's Cancer Program grant (WAM), Honorable Tina Brozman Foundation (RD), the Dr Miriam and Sheldon G. Adelson Medical Research Foundation (RD), NIH U01 CA-152990 (RD) and the Robert and Debra First Fund (RD). NR 67 TC 3 Z9 3 U1 3 U2 5 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 530 WALNUT STREET, STE 850, PHILADELPHIA, PA 19106 USA SN 2162-402X J9 ONCOIMMUNOLOGY JI OncoImmunology PY 2016 VL 5 IS 3 AR e1090075 DI 10.1080/2162402X.2015.1090075 PG 14 WC Oncology; Immunology SC Oncology; Immunology GA DI3GC UT WOS:000373385700021 ER PT J AU Cooper, ZA Reuben, A Spencer, CN Prieto, PA Austin-Breneman, JL Jiang, H Haymaker, C Gopalakrishnan, V Tetzlaff, MT Frederick, DT Sullivan, RJ Amaria, RN Patel, SP Hwu, P Woodman, SE Glitza, IC Diab, A Vence, LM Rodriguez-Canales, J Parra, ER Wistuba, II Coussens, LM Sharpe, AH Flaherty, KT Gershenwald, JE Chin, L Davies, MA Clise-Dwyer, K Allison, JP Sharma, P Wargo, JA AF Cooper, Zachary A. Reuben, Alexandre Spencer, Christine N. Prieto, Peter A. Austin-Breneman, Jacob L. Jiang, Hong Haymaker, Cara Gopalakrishnan, Vancheswaran Tetzlaff, Michael T. Frederick, Dennie T. Sullivan, Ryan J. Amaria, Rodabe N. Patel, Sapna P. Hwu, Patrick Woodman, Scott E. Glitza, Isabella C. Diab, Adi Vence, Luis M. Rodriguez-Canales, Jaime Parra, Edwin R. Wistuba, Ignacio I. Coussens, Lisa M. Sharpe, Arlene H. Flaherty, Keith T. Gershenwald, Jeffrey E. Chin, Lynda Davies, Michael A. Clise-Dwyer, Karen Allison, James P. Sharma, Padmanee Wargo, Jennifer A. TI Distinct clinical patterns and immune infiltrates are observed at time of progression on targeted therapy versus immune checkpoint blockade for melanoma SO ONCOIMMUNOLOGY LA English DT Article DE Immune checkpoint blockade; melanoma; targeted therapy; BRAF; CTLA-4; PD-1 ID RANDOMIZED CONTROLLED-TRIAL; METASTATIC MELANOMA; BRAF INHIBITORS; SURVIVAL; IPILIMUMAB; IMMUNOTHERAPY; DABRAFENIB; RESPONSES; MULTICENTER; VEMURAFENIB AB We have made major advances in the treatment of melanoma through the use of targeted therapy and immune checkpoint blockade; however, clinicians are posed with therapeutic dilemmas regarding timing and sequence of therapy. There is a growing appreciation of the impact of antitumor immune responses to these therapies, and we performed studies to test the hypothesis that clinical patterns and immune infiltrates differ at progression on these treatments. We observed rapid clinical progression kinetics in patients on targeted therapy compared to immune checkpoint blockade. To gain insight into possible immune mechanisms behind these differences, we performed deep immune profiling in tumors of patients on therapy. We demonstrated low CD8(+) T-cell infiltrate on targeted therapy and high CD8(+) T-cell infiltrate on immune checkpoint blockade at clinical progression. These data have important implications, and suggest that antitumor immune responses should be assessed when considering therapeutic options for patients with melanoma. C1 [Cooper, Zachary A.; Reuben, Alexandre; Prieto, Peter A.; Austin-Breneman, Jacob L.; Jiang, Hong; Gopalakrishnan, Vancheswaran; Gershenwald, Jeffrey E.; Wargo, Jennifer A.] Univ Texas MD Anderson Canc Ctr, Dept Surg Oncol, Houston, TX 77030 USA. [Cooper, Zachary A.; Spencer, Christine N.; Chin, Lynda; Wargo, Jennifer A.] Univ Texas MD Anderson Canc Ctr, Genom Med, Houston, TX 77030 USA. [Haymaker, Cara; Amaria, Rodabe N.; Patel, Sapna P.; Hwu, Patrick; Woodman, Scott E.; Glitza, Isabella C.; Diab, Adi; Davies, Michael A.] Univ Texas MD Anderson Canc Ctr, Melanoma Med Oncol, Houston, TX 77030 USA. [Tetzlaff, Michael T.] Univ Texas MD Anderson Canc Ctr, Pathol, Houston, TX 77030 USA. [Frederick, Dennie T.; Sullivan, Ryan J.; Flaherty, Keith T.] Massachusetts Gen Hosp, Div Med Oncol, Boston, MA 02114 USA. [Vence, Luis M.; Allison, James P.; Sharma, Padmanee] Univ Texas MD Anderson Canc Ctr, Immunol, Houston, TX 77030 USA. [Rodriguez-Canales, Jaime; Parra, Edwin R.; Wistuba, Ignacio I.] Univ Texas MD Anderson Canc Ctr, Translat Mol Pathol, Houston, TX 77030 USA. [Coussens, Lisa M.] Oregon Hlth & Sci Univ, Dept Cell Dev & Canc Biol, Portland, OR 97201 USA. [Coussens, Lisa M.] Oregon Hlth & Sci Univ, Knight Canc Inst, Portland, OR 97201 USA. [Sharpe, Arlene H.] Harvard Univ, Sch Med, Div Immunol, Dept Microbiol & Immunobiol, Boston, MA USA. [Clise-Dwyer, Karen] Univ Texas MD Anderson Canc Ctr, Stem Cell Transplantat, Houston, TX 77030 USA. [Sharma, Padmanee] Univ Texas MD Anderson Canc Ctr, Genitourinary Med Oncol, Houston, TX 77030 USA. RP Cooper, ZA; Wargo, JA (reprint author), Univ Texas MD Anderson Canc Ctr, Dept Surg Oncol, Houston, TX 77030 USA.; Cooper, ZA; Wargo, JA (reprint author), Univ Texas MD Anderson Canc Ctr, Genom Med, Houston, TX 77030 USA. EM zcooper@mdanderson.org; jwargo@mdanderson.org OI Cooper, Zachary/0000-0003-1059-0940 FU National Institutes of Health (NIH) [1K08CA160692-01A1]; Melanoma Research Alliance Team Science Award; Kenedy Memorial Foundation [0727030]; NIH [U54CA163125, U54CA163123, T32 CA009599]; MD Anderson South Campus Flow Core Facility - NIH [P30CA16672] FX JAW acknowledges National Institutes of Health (NIH) grants 1K08CA160692-01A1, the Melanoma Research Alliance Team Science Award, the Kenedy Memorial Foundation grant # 0727030 and the generous philanthropic support of several families whose lives have been affected by melanoma. ZAC, JAW, KTF, AHS, LMC acknowledges NIH grants U54CA163125 and U54CA163123. Supported by the philanthropic contributions to The University of Texas MD Anderson Cancer Center Melanoma Moon Shots Program. KCD, ZAC, and JAW acknowledge the support of the MD Anderson South Campus Flow Core Facility which is supported by NIH grant P30CA16672. PAP is supported by NIH grant T32 CA009599. NR 30 TC 6 Z9 6 U1 1 U2 4 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 530 WALNUT STREET, STE 850, PHILADELPHIA, PA 19106 USA SN 2162-402X J9 ONCOIMMUNOLOGY JI OncoImmunology PY 2016 VL 5 IS 3 AR e1136044 DI 10.1080/2162402X.2015.1136044 PG 8 WC Oncology; Immunology SC Oncology; Immunology GA DI3GC UT WOS:000373385700044 PM 27141370 ER PT J AU Handtke, V Wolff, H Williams, BA AF Handtke, Violet Wolff, Hans Williams, Brie A. TI The pains of imprisonment: challenging aspects of pain management in correctional settings SO PAIN MANAGEMENT LA English DT Editorial Material DE ethics; jail; pain; prison; vulnerable patients ID PRISON HEALTH-CARE; PREVALENCE; INMATES C1 [Handtke, Violet] Univ Basel, Inst Biomed Eth, Bernoullistr 28, CH-4056 Basel, Switzerland. [Wolff, Hans] Univ Hosp Geneva, Div Correct Med & Psychiat, Geneva, Switzerland. [Wolff, Hans] Univ Geneva, Fac Med, CH-1211 Geneva 4, Switzerland. [Williams, Brie A.] Univ Calif San Francisco, Div Geriatr, San Francisco, CA 94143 USA. [Williams, Brie A.] San Francisco VA Med Ctr, San Francisco, CA USA. RP Handtke, V (reprint author), Univ Basel, Inst Biomed Eth, Bernoullistr 28, CH-4056 Basel, Switzerland. EM v.handtke@unibas.ch NR 19 TC 0 Z9 0 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 1758-1869 EI 1758-1877 J9 PAIN MANAG JI Pain Manag. PY 2016 VL 6 IS 2 BP 133 EP 136 DI 10.2217/pmt.15.62 PG 4 WC Clinical Neurology SC Neurosciences & Neurology GA DH7TB UT WOS:000372995600008 PM 26915436 ER PT J AU Dicianno, BE Morgan, A Lieberman, J Rosen, L AF Dicianno, Brad E. Morgan, Amy Lieberman, Jenny Rosen, Lauren TI Rehabilitation Engineering & Assistive Technology Society (RESNA) position on the application of wheelchair standing devices: 2013 current state of the literature SO ASSISTIVE TECHNOLOGY LA English DT Article DE mobility limitation; rehabilitation; standing position; wheelchairs ID SPINAL-CORD-INJURY; WHOLE-BODY VIBRATION; SPASTIC CEREBRAL-PALSY; BONE-MINERAL DENSITY; WEIGHT-BEARING; ORTHOSTATIC HYPOTENSION; CHILDREN; PROGRAMS; MOBILITY; INDIVIDUALS AB This article, approved by the Rehabilitation Engineering & Assistive Technology Society of North America Board of Directors on December 23, 2013, shares typical clinical applications and provides evidence from the literature supporting the use of wheelchair standers. C1 [Dicianno, Brad E.] VA Pittsburgh Healthcare Syst, Human Engn Res Labs, 6425 Penn Ave,Suite 400,Bakery Sq, Pittsburgh, PA 15206 USA. [Dicianno, Brad E.] Univ Pittsburgh, Sch Med, Dept PM&R, Pittsburgh, PA USA. [Morgan, Amy] Permobil Inc, Lebanon, TN USA. [Lieberman, Jenny] Mt Sinai Hosp, Dept Rehabil, New York, NY 10029 USA. [Rosen, Lauren] St Josephs Childrens Hosp Tampa, Mot Anal Ctr, Tampa, FL USA. RP Dicianno, BE (reprint author), VA Pittsburgh Healthcare Syst, Human Engn Res Labs, 6425 Penn Ave,Suite 400,Bakery Sq, Pittsburgh, PA 15206 USA. EM dicianno@pitt.edu NR 44 TC 0 Z9 0 U1 3 U2 6 PU R E S N A PRESS PI ARLINGTON PA 1700 MOORE ST, STE 1540, ARLINGTON, VA 22209-1903 USA SN 1040-0435 EI 1949-3614 J9 ASSIST TECHNOL JI Assist. Technol. PY 2016 VL 28 IS 1 BP 57 EP 62 DI 10.1080/10400435.2015.1113837 PG 6 WC Rehabilitation SC Rehabilitation GA DH0KY UT WOS:000372474300009 PM 26910615 ER PT J AU Matthews, LT Bajunirwe, F Kastner, J Sanyu, N Akatukwasa, C Ng, C Rifkin, R Milford, C Moore, L Wilson, IB Bangsberg, DR Smit, JA Kaida, A AF Matthews, Lynn T. Bajunirwe, Francis Kastner, Jasmine Sanyu, Naomi Akatukwasa, Cecilia Ng, Courtney Rifkin, Rachel Milford, Cecilia Moore, Lizzie Wilson, Ira B. Bangsberg, David R. Smit, Jennifer A. Kaida, Angela TI "I Always Worry about What Might Happen Ahead": Implementing Safer Conception Services in the Current Environment of Reproductive Counseling for HIV-Affected Men and Women in Uganda SO BIOMED RESEARCH INTERNATIONAL LA English DT Article ID SOUTH-AFRICA; DISCORDANT COUPLES; FERTILITY DESIRES; INFECTED MEN; PROVIDER COMMUNICATION; DECISION-MAKING; RISK BEHAVIOR; CARE; OPPORTUNITIES; TRANSMISSION AB Background. We explored healthcare provider perspectives and practices regarding safer conception counseling for HIV-affected clients. Methods. We conducted semistructured interviews with 38 providers (medical and clinical officers, nurses, peer counselors, and village health workers) delivering care to HIV-infected clients across 5 healthcare centres in Mbarara District, Uganda. Interview transcripts were analyzed using content analysis. Results. Of 38 providers, 76% were women with median age 34 years (range 24-57). First, we discuss providers' reproductive counseling practices. Emergent themes include that providers (1) assess reproductive goals of HIV-infected female clients frequently, but infrequently for male clients; (2) offer counseling focused on "family planning" and maternal and child health; (3) empathize with the importance of having children for HIV-affected clients; and (4) describe opportunities to counsel HIV-serodiscordant couples. Second, we discuss provider-level challenges that impede safer conception counseling. Emergent themes included the following: (1) providers struggle to translate reproductive rights language into individualized risk reduction given concerns about maternal health and HIV transmission and (2) providers lack safer conception training and support needed to provide counseling. Discussion. Tailored guidelines and training are required for providers to implement safer conception counseling. Such support must respond to provider experiences with adverse HIV-related maternal and child outcomes and a national emphasis on pregnancy prevention. C1 [Matthews, Lynn T.; Rifkin, Rachel; Bangsberg, David R.] Massachusetts Gen Hosp, Ctr Global Hlth, Boston, MA 02114 USA. [Matthews, Lynn T.] Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA. [Bajunirwe, Francis; Sanyu, Naomi; Akatukwasa, Cecilia] Mbarara Univ Sci & Technol, Mbarara, Uganda. [Kastner, Jasmine] McGill Univ, Res Ctr, Montreal, PQ H3H 2R9, Canada. [Ng, Courtney] Harvard Univ, TH Chan Sch Publ Hlth, Boston, MA 02115 USA. [Milford, Cecilia; Moore, Lizzie; Smit, Jennifer A.] Univ Witwatersrand, Maternal Adolescent & Child Hlth MatCH Res, ZA-3629 Durban, Kwazulu Natal, South Africa. [Wilson, Ira B.] Brown Univ, Sch Publ Hlth, Providence, RI 02903 USA. [Kaida, Angela] Simon Fraser Univ, Burnaby, BC V5A 1S6, Canada. RP Matthews, LT (reprint author), Massachusetts Gen Hosp, Ctr Global Hlth, Boston, MA 02114 USA.; Matthews, LT (reprint author), Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA. EM ltmatthews@partners.org FU Canada Sub-Saharan Africa HIV/AIDS Network; NIMH [K23 095655, K24 MH 087227]; NICHD [R03072602] FX The authors gratefully acknowledge the participants and the research team in Mbarara. They also thank Drs. Christina Psaros, Steven Safren, and Abigail Harrison who supported the South Africa version of this study and therefore informed this project. This work was supported by a pilot award from the Canada Sub-Saharan Africa HIV/AIDS Network, NIMH K23 095655, K24 MH 087227, and NICHD R03072602. NR 41 TC 3 Z9 3 U1 1 U2 1 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 2016 AR 4195762 DI 10.1155/2016/4195762 PG 9 WC Biotechnology & Applied Microbiology; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Research & Experimental Medicine GA DH2RY UT WOS:000372635000001 ER PT J AU Basal, E Ayeni, T Zhang, Q Langstraat, C Donahoe, PK Pepin, D Yin, X Leof, E Cliby, W AF Basal, E. Ayeni, T. Zhang, Q. Langstraat, C. Donahoe, P. K. Pepin, D. Yin, X. Leof, E. Cliby, W. TI Patterns of Mullerian Inhibiting Substance Type II and Candidate Type I Receptors in Epithelial Ovarian Cancer SO CURRENT MOLECULAR MEDICINE LA English DT Article DE ALK2; ALK3; ALK6; mullerian inhibiting substance; ovarian cancer ID GROWTH-FACTOR-BETA; CELL-LINES; GYNECOLOGIC CANCERS; EXPRESSION; HORMONE; ALK2; VIVO; MIS AB The MIS pathway is a potential therapeutic target in epithelial ovarian cancer (EOC): signaling requires both type II (T2R) and type I receptors (T1R), and results in growth inhibition. MISR2 is expressed in EOC, but the prevalence and relative contributions of candidate T1R remain unknown. We sought to: a) determine expression of T1R in EOC; b) assess impact of T1R expression with clinical outcomes; c) verify MIS-dependent Smad signaling and growth inhibition in primary EOC cell cultures. Tissue microarrays (TMA) were developed for analysis of T1Rs (ALK2/3/6) and MISR2 expression. Primary cell cultures were initiated from ascites harvested at surgery which were used to characterize response to MIS. TMA's from 311 primary cancers demonstrated the most common receptor combinations were: MISR2+/ALK2+3+6+ (36%); MISR2+/ALK2+3+6- (34%); MISR2-/ALK2+3+6- (18%); and MISR2-/ALK2+3+6+ (6.8%). No differences in overall survival (OS) were noted between combinations. The ALK6 receptor was least often expressed T1R and was associated with lower OS in early stage disease only (p = 0.03). Most primary cell cultures expressed MISR2 (14/22 (63.6%)): 95% of these express ALK 2 and ALK3, whereas 54.5% expressed ALK6. MIS-dependent Smad phosphorylation was seen in the majority of cultures (75%). Treatment with MIS led to reduced cell viability at an average of 71% (range: 57-87%) in primary cultures. MIS signaling is dependent upon the presence of both MISR2 and specific T1R. In the majority of EOC, the T1R required for MIS-dependent signaling are present and such cells demonstrate appropriate response to MIS. C1 [Basal, E.; Ayeni, T.; Zhang, Q.; Langstraat, C.; Cliby, W.] Mayo Clin, Dept Obstet & Gynecol, 200 First St SW, Rochester, MN 55905 USA. [Yin, X.; Leof, E.] Mayo Clin, Thorac Dis Res Unit, 200 First St SW, Rochester, MN 55905 USA. [Donahoe, P. K.; Pepin, D.] Massachusetts Gen Hosp, Pediat Surg Res Labs, 55 Fruit St, Boston, MA 02114 USA. RP Cliby, W (reprint author), Mayo Clin, Dept Obstet & Gynecol, 200 First St SW, Rochester, MN 55905 USA. EM cliby.william@mayo.edu FU National Institute of Health Research Funding [R01CA148747] FX Grant support was provided by the National Institute of Health Research Funding (R01CA148747 to WC). NR 22 TC 1 Z9 1 U1 0 U2 0 PU BENTHAM SCIENCE PUBL LTD PI SHARJAH PA EXECUTIVE STE Y-2, PO BOX 7917, SAIF ZONE, 1200 BR SHARJAH, U ARAB EMIRATES SN 1566-5240 EI 1875-5666 J9 CURR MOL MED JI Curr. Mol. Med. PY 2016 VL 16 IS 3 BP 222 EP 231 DI 10.2174/1566524016666160225151131 PG 10 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA DH1NB UT WOS:000372550400002 PM 26917267 ER PT J AU Zhou, CC Grottkau, BE Zou, SJ AF Zhou, Chenchen Grottkau, Brian E. Zou, Shujuan TI Regulators of Stem Cells Proliferation in Tissue Regeneration SO CURRENT STEM CELL RESEARCH & THERAPY LA English DT Article DE Apoptosis; cell cycle; cell proliferation; dental regeneration; stem cells; tissue regeneration ID SKELETAL-MUSCLE REGENERATION; EMBRYONIC SIGNALING CENTER; FIBROBLAST GROWTH-FACTOR; HUMAN PLATELET LYSATE; HUMAN DENTAL-PULP; BONE-MARROW; SELF-RENEWAL; IN-VITRO; TGF-BETA; SATELLITE CELLS AB This review summarizes recent breakthroughs in studies regarding proliferation of adult stem cells which complement and extend our knowledge to various aspects of cell biology and signal pathways. In recent years, many interesting results and discoveries were achieved regarding the proliferative properties of stem cells. In vitro expansion of stem cells may benefit from high proliferation rates, which can produce a large amount of cells to regenerate tissue defects. Meanwhile, optimizing the culture conditions for stem cell propagation is helpful in maintaining the pluripotency and differentiation potential of stem cells, which are critical for tissue engineering and regenerative medicine. Additionally, understanding the proliferation of stem cells may help us to uncover new mechanisms of drug resistance, since stem cells are believed to play an important role in drug resistance. In this review, we focus on signaling pathways regulating the proliferation of various stem cells isolated from adult tissues. We also emphasize the significance of stem cells proliferation in cell research, as well as rapid propagation of adult stem cells for regenerative medicine. C1 [Grottkau, Brian E.] Harvard Univ, Sch Med, MassGen Hosp Children, Pediat Orthopaed Lab Tissue Engn & Regenerat Med, Boston, MA 02114 USA. [Zhou, Chenchen; Zou, Shujuan] Sichuan Univ, West China Sch Stomatol, State Key Lab Oral Dis, Chengdu 610041, Peoples R China. RP Grottkau, BE (reprint author), Harvard Univ, Sch Med, MassGen Hosp Children, Pediat Orthopaed Lab Tissue Engn & Regenerat Med, Boston, MA 02114 USA.; Zou, SJ (reprint author), Sichuan Univ, West China Sch Stomatol, State Key Lab Oral Dis, Chengdu 610041, Peoples R China. EM bgrottkau@partners.org; shujuanzou@aliyun.com FU National Natural Science Foundation of China [81470777, 81271178]; Anthony and Constance Fund for Pediatric Orthopaedic and Spine Surgery Research at the Massachusetts General Hospital FX This work was funded by National Natural Science Foundation of China (81470777, 81271178) and the Anthony and Constance Fund for Pediatric Orthopaedic and Spine Surgery Research at the Massachusetts General Hospital. NR 139 TC 0 Z9 0 U1 4 U2 9 PU BENTHAM SCIENCE PUBL LTD PI SHARJAH PA EXECUTIVE STE Y-2, PO BOX 7917, SAIF ZONE, 1200 BR SHARJAH, U ARAB EMIRATES SN 1574-888X EI 2212-3946 J9 CURR STEM CELL RES T JI Curr. Stem Cell Res. Ther. PY 2016 VL 11 IS 3 BP 177 EP 187 DI 10.2174/1574888X10666150531172108 PG 11 WC Cell & Tissue Engineering; Cell Biology SC Cell Biology GA DG8KS UT WOS:000372333300002 PM 26027682 ER PT J AU Deutsch, RM Clyman, J AF Deutsch, Robin M. Clyman, Jeremy TI IMPACT OF MENTAL ILLNESS ON PARENTING CAPACITY IN A CHILD CUSTODY MATTER SO FAMILY COURT REVIEW LA English DT Article DE Custody Evaluation; Mental Illness; Parenting; Parenting Capacity; Separation and Divorce; and Substance Abuse ID PSYCHOPATHOLOGY; DISORDER; MOTHERS; DEPRESSION AB Recently, courts have seen an increase in cases where a parent has an alleged or documented mental illness. Understanding whether there is a mental illness and what the symptoms are and determining the meaning of this information for parenting and child functioning present a host of challenges for judges, custody evaluators, and attorneys. We offer an example of a custody evaluator's inquiry and present a functional-contextual model for considering the significant parental capacities and vulnerabilities that impact child functioning, in order to better make decisions about parent access and treatment. Practitioner Keypoints: Understand how to effectively integrate mental health information into matters of custody Identify parenting and co-parenting tasks and behaviors that may be affected by mental illness Identify parenting capacities that are linked to child outcomes Review a step-by-step decision-making process to effectively examine allegations of mental illness during a custody evaluation or dispute C1 [Deutsch, Robin M.] William James Coll, Ctr Excellence Children Families & Law, Newton, MA USA. [Deutsch, Robin M.] Harvard Univ, Sch Med, Psychol, Cambridge, MA 02138 USA. [Deutsch, Robin M.] Massachusetts Gen Hosp, Children & Law Program, Boston, MA 02114 USA. [Deutsch, Robin M.] Assoc Family & Conciliat Courts, Newton, MA USA. [Clyman, Jeremy] William James Coll, Ctr Excellence Children Families & Law, Child & Family Psychol Evaluat Serv, Forens Psychol, Newton, MA 02459 USA. RP Clyman, J (reprint author), William James Coll, Ctr Excellence Children Families & Law, Child & Family Psychol Evaluat Serv, Forens Psychol, Newton, MA 02459 USA. EM clymanj@gmail.com NR 20 TC 0 Z9 0 U1 4 U2 5 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1531-2445 EI 1744-1617 J9 FAM COURT REV JI Fam. Court Rev. PD JAN PY 2016 VL 54 IS 1 SI SI BP 29 EP 38 DI 10.1111/fcre.12201 PG 10 WC Law SC Government & Law GA DH2UZ UT WOS:000372643600004 ER PT J AU Sheth, RA Heidari, P Woods, K Chung, D Chan, AT Mahmood, U AF Sheth, Rahul A. Heidari, Pedram Woods, Kevin Chung, Daniel Chan, Andrew T. Mahmood, Umar TI Pilot Clinical Trial of Indocyanine Green Fluorescence-Augmented Colonoscopy in High Risk Patients SO GASTROENTEROLOGY RESEARCH AND PRACTICE LA English DT Article ID COLORECTAL-CANCER; REAL-TIME; CONFOCAL ENDOMICROSCOPY; ULCERATIVE-COLITIS; ASSOCIATION; ENDOSCOPY; DYSPLASIA; RECEPTOR; LESIONS; MICE AB White light colonoscopy is the current gold standard for early detection and treatment of colorectal cancer, but emerging data suggest that this approach is inherently limited. Even the most experienced colonoscopists, under optimal conditions, miss at least 15-25% of adenomas. There is an unmet clinical need for an adjunctive modality to white light colonoscopy with improved lesion detection and characterization. Optical molecular imaging with exogenously administered organic fluorochromes is a burgeoning imaging modality poised to advance the capabilities of colonoscopy. In this proof-of-principle clinical trial, we investigated the ability of a custom-designed fluorescent colonoscope and indocyanine green, a clinically approved fluorescent blood pool imaging agent, to visualize polyps in high risk patients with polyposis syndromes or known distal colonic masses. We demonstrate (1) the successful performance of real-time, wide-field fluorescence endoscopy using off-the-shelf equipment, (2) the ability of this system to identify polyps as small as 1 mm, and (3) the potential for fluorescence imaging signal intensity to differentiate between neoplastic and benign polyps. C1 [Sheth, Rahul A.; Heidari, Pedram; Mahmood, Umar] Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Boston, MA 02114 USA. [Sheth, Rahul A.] Univ Texas MD Anderson Canc Ctr, Div Diagnost Imaging, Dept Intervent Radiol, Houston, TX 77030 USA. [Woods, Kevin] Souheastern Reg Med Ctr, Canc Treatment Ctr Amer, Atlanta, GA 30265 USA. [Woods, Kevin; Chung, Daniel; Chan, Andrew T.] Massachusetts Gen Hosp, Div Gastroenterol, Boston, MA 02114 USA. [Chan, Andrew T.] Massachusetts Gen Hosp, Clin & Translat Epidemiol Unit, Boston, MA 02114 USA. RP Sheth, RA (reprint author), Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Boston, MA 02114 USA.; Sheth, RA (reprint author), Univ Texas MD Anderson Canc Ctr, Div Diagnost Imaging, Dept Intervent Radiol, Houston, TX 77030 USA. EM rsheth@partners.org FU NIH [P50CA127003] FX This work was supported by NIH P50CA127003. NR 24 TC 0 Z9 0 U1 2 U2 2 PU HINDAWI PUBLISHING CORP PI NEW YORK PA 410 PARK AVENUE, 15TH FLOOR, #287 PMB, NEW YORK, NY 10022 USA SN 1687-6121 EI 1687-630X J9 GASTROENT RES PRACT JI Gastroenterol. Res. Pract. PY 2016 AR 6184842 DI 10.1155/2016/6184842 PG 7 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA DH7YK UT WOS:000373009900001 ER PT J AU Bighamian, R Soleymani, S Reisner, AT Seri, I Hahn, JO AF Bighamian, Ramin Soleymani, Sadaf Reisner, Andrew T. Seri, Istvan Hahn, Jin-Oh TI Prediction of Hemodynamic Response to Epinephrine via Model-Based System Identification SO IEEE JOURNAL OF BIOMEDICAL AND HEALTH INFORMATICS LA English DT Article DE Epinephrine; hemodynamic response; latency-dose-response-cardiovascular model; prediction; system identification; vasopressor-inotrope ID VASOPRESSORS; INOTROPES; DOPAMINE; SHOCK; PHARMACOKINETICS; HYPOTENSION; PRESSURE AB In this study, we present a system identification approach to the mathematical modeling of hemodynamic responses to vasopressor-inotrope agents. We developed a hybrid model called the latency-dose-response-cardiovascular (LDC) model that incorporated 1) a low-order lumped latency model to reproduce the delay associated with the transport of vasopressor-inotrope agent and the onset of physiological effect, 2) phenomenological dose-response models to dictate the steady-state inotropic, chronotropic, and vasoactive responses as a function of vasopressor-inotrope dose, and 3) a physiological cardiovascular model to translate the agent's actions into the ultimate response of blood pressure. We assessed the validity of the LDC model to fit vasopressor-inotrope dose-response data using data collected from five piglet subjects during variable epinephrine infusion rates. The results suggested that the LDC model was viable in modeling the subjects' dynamic responses: After tuning the model to each subject, the r(2) values for measured versus model-predicted mean arterial pressure were consistently higher than 0.73. The results also suggested that intersubject variability in the dose-response models, rather than the latency models, had significantly more impact on the model's predictive capability: Fixing the latency model to population-averaged parameter values resulted in r(2) values higher than 0.57 between measured versus model-predicted mean arterial pressure, while fixing the dose-response model to population-averaged parameter values yielded nonphysiological predictions of mean arterial pressure. We conclude that the dose-response relationship must be individualized, whereas a population-averaged latency-model may be acceptable with minimal loss of model fidelity. C1 [Bighamian, Ramin; Hahn, Jin-Oh] Univ Maryland, Dept Mech Engn, College Pk, MD 20742 USA. [Soleymani, Sadaf; Seri, Istvan] Childrens Hosp Los Angeles, Ctr Fetal & Neonatal Med, Los Angeles, CA 90089 USA. [Soleymani, Sadaf] Univ So Calif, Biomed Engn, Los Angeles, CA 90089 USA. [Reisner, Andrew T.] Massachusetts Gen Hosp, Dept Emergency Med, Boston, MA 02142 USA. [Seri, Istvan] Univ So Calif, Los Angeles, CA 90027 USA. RP Bighamian, R; Hahn, JO (reprint author), Univ Maryland, Dept Mech Engn, College Pk, MD 20742 USA.; Soleymani, S; Seri, I (reprint author), Childrens Hosp Los Angeles, Ctr Fetal & Neonatal Med, Los Angeles, CA 90089 USA.; Soleymani, S (reprint author), Univ So Calif, Biomed Engn, Los Angeles, CA 90089 USA.; Reisner, AT (reprint author), Massachusetts Gen Hosp, Dept Emergency Med, Boston, MA 02142 USA.; Seri, I (reprint author), Univ So Calif, Los Angeles, CA 90027 USA. EM rbighami@umd.edu; ssoleymani@chla.usc.edu; areisner@partners.org; iseri@chla.usc.edu; jhahn12@umd.edu FU Office of Naval Research (ONR) [N000141410591] FX This material is based upon work supported in part by the Office of Naval Research (ONR) under Grant No. N000141410591. Any opinions, findings, and conclusions or recommendations expressed in this material are those of the authors and do not necessarily reflect the views of the ONR. NR 28 TC 0 Z9 0 U1 0 U2 0 PU IEEE-INST ELECTRICAL ELECTRONICS ENGINEERS INC PI PISCATAWAY PA 445 HOES LANE, PISCATAWAY, NJ 08855-4141 USA SN 2168-2194 J9 IEEE J BIOMED HEALTH JI IEEE J. Biomed. Health Inform. PD JAN PY 2016 VL 20 IS 1 BP 416 EP 423 DI 10.1109/JBHI.2014.2371533 PG 8 WC Computer Science, Information Systems; Computer Science, Interdisciplinary Applications; Mathematical & Computational Biology; Medical Informatics SC Computer Science; Mathematical & Computational Biology; Medical Informatics GA DH2PX UT WOS:000372629700044 PM 25420273 ER PT J AU Markovic, S Belz, J Kumar, R Cormack, RA Sridhar, S Niedre, M AF Markovic, Stacey Belz, Jodi Kumar, Rajiv Cormack, Robert A. Sridhar, Srinivas Niedre, Mark TI Near-infrared fluorescence imaging platform for quantifying in vivo nanoparticle diffusion from drug loaded implants SO INTERNATIONAL JOURNAL OF NANOMEDICINE LA English DT Article DE optical imaging; fluorescence; drug delivery; brachytherapy; treatment monitoring ID LOCALIZED PROSTATE-CANCER; MODIFIED SILICA NANOPARTICLES; RADIATION-THERAPY; TISSUE PHANTOM; BRACHYTHERAPY; TRIAL AB Drug loaded implants are a new, versatile technology platform to deliver a localized payload of drugs for various disease models. One example is the implantable nanoplatform for chemo-radiation therapy where inert brachytherapy spacers are replaced by spacers doped with nanoparticles (NPs) loaded with chemotherapeutics and placed directly at the disease site for long-term localized drug delivery. However, it is difficult to directly validate and optimize the diffusion of these doped NPs in in vivo systems. To better study this drug release and diffusion, we developed a custom macroscopic fluorescence imaging system to visualize and quantify fluorescent NP diffusion from spacers in vivo. To validate the platform, we studied the release of free fluorophores, and 30 nm and 200 nm NPs conjugated with the same fluorophores as a model drug, in agar gel phantoms in vitro and in mice in vivo. Our data verified that the diffusion volume was NP size-dependent in all cases. Our near-infrared imaging system provides a method by which NP diffusion from implantable nanoplatform for chemo-radiation therapy spacers can be systematically optimized (eg, particle size or charge) thereby improving treatment efficacy of the platform. C1 [Markovic, Stacey; Niedre, Mark] Northeastern Univ, Dept Elect & Comp Engn, 213B Lake Hall,360 Huntington Ave, Boston, MA 02115 USA. [Belz, Jodi] Northeastern Univ, Dept Bioengn, Boston, MA 02115 USA. [Kumar, Rajiv; Sridhar, Srinivas] Northeastern Univ, Dept Phys, Boston, MA 02115 USA. [Kumar, Rajiv; Cormack, Robert A.; Sridhar, Srinivas] Brigham & Womens Hosp, Dana Farber Canc Inst, Dept Radiat Oncol, 75 Francis St, Boston, MA 02115 USA. [Kumar, Rajiv; Cormack, Robert A.; Sridhar, Srinivas] Harvard Univ, Sch Med, Boston, MA USA. RP Niedre, M (reprint author), Northeastern Univ, Dept Elect & Comp Engn, 213B Lake Hall,360 Huntington Ave, Boston, MA 02115 USA. EM mniedre@ece.neu.edu FU Integrative Graduate Education and Research Traineeship Nanomedicine Science and Technology [NSF-DGE-0965843]; Massachusetts Life Sciences Center New Investigator Award FX This work was supported by Integrative Graduate Education and Research Traineeship Nanomedicine Science and Technology NSF-DGE-0965843 (principal investigator S Sridhar), fellowships to J Belz and S Markovic, and a Massachusetts Life Sciences Center New Investigator Award to M Niedre. The authors report no other conflicts of interest in this work. NR 25 TC 0 Z9 0 U1 1 U2 3 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 2016 VL 11 DI 10.2147/IJN.S93324 PG 11 WC Nanoscience & Nanotechnology; Pharmacology & Pharmacy SC Science & Technology - Other Topics; Pharmacology & Pharmacy GA DH5DN UT WOS:000372805600001 ER PT J AU Salony Sole, X Alves, CP Dey-Guha, I Ritsma, L Boukhali, M Lee, JH Chowdhury, J Ross, KN Haas, W Vasudevan, S Ramaswamy, S AF Salony Sole, Xavier Alves, Cleidson P. Dey-Guha, Ipsita Ritsma, Laila Boukhali, Myriam Lee, Ju H. Chowdhury, Joeeta Ross, Kenneth N. Haas, Wilhelm Vasudevan, Shobha Ramaswamy, Sridhar TI AKT Inhibition Promotes Nonautonomous Cancer Cell Survival SO MOLECULAR CANCER THERAPEUTICS LA English DT Article ID LUNG-CANCER; RNA-SEQ; RESISTANCE; EXPRESSION; GROWTH; ACTIVATION; MECHANISM; ALIGNMENT; PATHWAY; GENOME AB Small molecule inhibitors of AKT (v-akt murine thymoma viral oncogene homolog) signaling are being evaluated in patients with various cancer types, but have so far proven therapeutically disappointing for reasons that remain unclear. Here, we treat cancer cells with subtherapeutic doses of Akti-1/2, an allosteric small molecule AKT inhibitor, in order to experimentally model pharmacologic inhibition of AKT signaling in vitro. We then apply a combined RNA, protein, and metabolite profiling approach to develop an integrated, multiscale, molecular snapshot of this "AKT(low)" cancer cell state. We find that AKT-inhibited cancer cells suppress thousands of mRNA transcripts, and proteins related to the cell cycle, ribosome, and protein translation. Surprisingly, however, these AKT-inhibited cells simultaneously upregulate a host of other proteins and metabolites posttranscriptionally, reflecting activation of their endo-vesiculo-membrane system, secretion of inflammatory proteins, and elaboration of extracellular microvesicles. Importantly, these microvesicles enable rapidly proliferating cancer cells of various types to better withstand different stress conditions, including serum deprivation, hypoxia, or cytotoxic chemotherapy in vitro and xenografting in vivo. These findings suggest a model whereby cancer cells experiencing a partial inhibition of AKT signaling may actually promote the survival of neighbors through non-cell autonomous communication. (C) 2015 AACR. C1 [Salony; Sole, Xavier; Alves, Cleidson P.; Dey-Guha, Ipsita; Ritsma, Laila; Boukhali, Myriam; Lee, Ju H.; Chowdhury, Joeeta; Ross, Kenneth N.; Haas, Wilhelm; Vasudevan, Shobha; Ramaswamy, Sridhar] Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA. [Salony; Sole, Xavier; Alves, Cleidson P.; Dey-Guha, Ipsita; Ritsma, Laila; Boukhali, Myriam; Lee, Ju H.; Chowdhury, Joeeta; Ross, Kenneth N.; Haas, Wilhelm; Vasudevan, Shobha; Ramaswamy, Sridhar] Harvard Univ, Sch Med, Boston, MA USA. [Ramaswamy, Sridhar] Broad Inst Harvard & MIT, Cambridge, MA USA. [Ramaswamy, Sridhar] Harvard Stem Cell Inst, Cambridge, MA USA. [Ramaswamy, Sridhar] Harvard Ludwig Ctr Canc Res, Boston, MA USA. RP Ramaswamy, S (reprint author), Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA.; Ramaswamy, S (reprint author), Massachusetts Gen Hosp, 185 Cambridge St, Boston, MA 02114 USA. EM sridhar@mgh.harvard.edu FU National Cancer Institute [R01 CA 185086, C06 CA 05926]; Howard Hughes Medical Institute (Physician-Scientist Early Career Award); Susan G. Komen for the Cure, and Prostate Cancer Foundation; Stand Up To Cancer Innovative Research Grant [SU2CAACR-IRG0411]; American Association for Cancer Research; scientific partner of SU2C; Bolsa de Ampliacion de Estudios, Instituto de Salud Carlos III, Ministerio de Economia y Competitividad [BA12/00021]; CNPq "Ciencia sem Fronteiras"-Brazil [202620/2012-3]; Rubicon Fellowship from the Netherlands Organization for Scientific Research [NWO] [825.13.016] FX This work was supported by awards from the National Cancer Institute (R01 CA 185086, C06 CA 05926), Howard Hughes Medical Institute (Physician-Scientist Early Career Award), Susan G. Komen for the Cure, and Prostate Cancer Foundation (to S. Ramaswamy). S. Ramaswamy was supported by a Stand Up To Cancer Innovative Research Grant (SU2CAACR-IRG0411). Stand Up To Cancer is a program of the Entertainment Industry Foundation. Research grants are administered by the American Association for Cancer Research, the scientific partner of SU2C. X. Sole was supported by the "Bolsa de Ampliacion de Estudios, Instituto de Salud Carlos III, Ministerio de Economia y Competitividad (BA12/00021)"-Spanish fellowship award. C.P. Alves was supported by an award from CNPq "Ciencia sem Fronteiras"-Brazil (202620/2012-3). L. Ritsma was supported by a Rubicon Fellowship from the Netherlands Organization for Scientific Research ([NWO] 825.13.016). NR 41 TC 1 Z9 1 U1 0 U2 2 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1535-7163 EI 1538-8514 J9 MOL CANCER THER JI Mol. Cancer Ther. PD JAN PY 2016 VL 15 IS 1 BP 142 EP 153 DI 10.1158/1535-7163.MCT-15-0414 PG 12 WC Oncology SC Oncology GA DG3ZR UT WOS:000372010200014 PM 26637368 ER PT S AU Munn, LL AF Munn, Lance L. BE Janmey, P Fletcher, D Gerecht, S Levine, R Mallick, P McCarty, O Munn, L ReinhartKing, C TI Fluid Mechanics and Transport in Tumors SO PHYSICAL SCIENCES AND ENGINEERING ADVANCES IN LIFE SCIENCES AND ONCOLOGY: A WTEC GLOBAL ASSESSMENT SE Science Policy Reports LA English DT Article; Book Chapter ID METASTATIC BREAST-CANCER; INTERSTITIAL FLOW; CELL-MIGRATION; SOLID TUMORS; ANGIOGENESIS; LYMPHATICS; PERMEABILITY; HYPERTENSION; VASCULATURE; SURVIVAL C1 [Munn, Lance L.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Charlestown, MA USA. RP Munn, LL (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Charlestown, MA USA. EM lance@steele.mgh.harvard.edu RI Munn, Lance/L-3950-2016 OI Munn, Lance/0000-0003-0698-7232 NR 37 TC 0 Z9 0 U1 0 U2 2 PU SPRINGER-VERLAG BERLIN PI BERLIN PA HEIDELBERGER PLATZ 3, D-14197 BERLIN, GERMANY SN 2213-1965 BN 978-3-319-17930-8; 978-3-319-17929-2 J9 SCI POL REP PY 2016 BP 73 EP 88 DI 10.1007/978-3-319-17930-8_5 D2 10.1007/978-3-319-17930-8 PG 16 WC Biophysics; Oncology SC Biophysics; Oncology GA BE3LN UT WOS:000370941600008 ER PT J AU Primack, BA Carroll, MV Weiss, PM Shihadeh, AL Shensa, A Farley, ST Fine, MJ Eissenberg, T Nayak, S AF Primack, Brian A. Carroll, Mary V. Weiss, Patricia M. Shihadeh, Alan L. Shensa, Ariel Farley, Steven T. Fine, Michael J. Eissenberg, Thomas Nayak, Smita TI Systematic Review and Meta-Analysis of Inhaled Toxicants from Waterpipe and Cigarette Smoking SO PUBLIC HEALTH REPORTS LA English DT Article ID HIGH-SCHOOL-STUDENTS; POLYCYCLIC AROMATIC-HYDROCARBONS; US UNIVERSITY-STUDENTS; PIPE TOBACCO SMOKING; MAINSTREAM SMOKE; CARBON-MONOXIDE; NARGHILE WATERPIPE; HOOKAH USE; VOLATILE ALDEHYDES; NICOTINE EXPOSURE AB Objective. Waterpipe tobacco smoking (WTS) is an emerging trend worldwide. To inform public health policy and educational programming, we systematically reviewed the biomedical literature to compute the inhaled smoke volume, nicotine, tar, and carbon monoxide (CO) associated with a single WTS session and a single cigarette. Methods. We searched seven biomedical bibliographic databases for controlled laboratory or natural environment studies designed to mimic human tobacco consumption. Included studies quantified the mainstream smoke of a single cigarette and/or single WTS session for smoke volume, nicotine, tar, and/or CO. We conducted meta-analyses to calculate summary estimates for the inhalation of each unique substance for each mode of tobacco consumption. We assessed between-study heterogeneity using chi-squared and I-squared statistics. Results. Sufficient data from 17 studies were available to derive pooled estimates for inhalation of each exposure via each smoking method. Two researchers working independently abstracted measurement of smoke volume in liters, and nicotine, tar, and CO in milligrams. All numbers included in meta analyses matched precisely between the two researchers (100% agreement, Cohen's kappa=1.00). Whereas one WTS session was associated with 74.1 liters of smoke inhalation (95% confidence interval [CI] 38.2, 110.0), one cigarette was associated with 0.6 liters of smoke (95% CI 0.5, 0.7). One WTS session was also associated with higher levels of nicotine, tar, and CO. Conclusions. One WTS session consistently exposed users to larger smoke volumes and higher levels of tobacco toxicants compared with one cigarette. These computed estimates may be valuable to emphasize in prevention programming. C1 [Primack, Brian A.; Shensa, Ariel; Farley, Steven T.] Univ Pittsburgh, Sch Med, 230 McKee Pl,Ste 600, Pittsburgh, PA 15213 USA. [Carroll, Mary V.] Squirrel Hill Hlth Ctr, Pittsburgh, PA USA. [Weiss, Patricia M.] Univ Pittsburgh Hlth Sci Lib Syst, Pittsburgh, PA USA. [Shihadeh, Alan L.] Amer Univ Beirut, Beirut, Lebanon. [Fine, Michael J.] VA Pittsburgh Healthcare Syst, Pittsburgh, PA USA. [Eissenberg, Thomas] Virginia Commonwealth Univ, Richmond, VA USA. [Nayak, Smita] Swedish Ctr Res & Innovat, Swedish Hlth Serv, Seattle, WA USA. RP Primack, BA (reprint author), Univ Pittsburgh, Sch Med, 230 McKee Pl,Ste 600, Pittsburgh, PA 15213 USA. EM bprimack@pitt.edu OI Shihadeh, Alan/0000-0001-6387-8564; Weiss, Patricia/0000-0002-5434-391X FU National Cancer Institute [R01-CA140150] FX The authors acknowledge receipt of funding from the National Cancer Institute (R01-CA140150). The fenders played no role in the conception, data collection, writing, or approval of this manuscript. NR 49 TC 7 Z9 8 U1 4 U2 9 PU ASSOC SCHOOLS PUBLIC HEALTH PI WASHINGTON PA 1900 M ST NW, STE 710, WASHINGTON, DC 20036 USA SN 0033-3549 J9 PUBLIC HEALTH REP JI Public Health Rep. PD JAN-FEB PY 2016 VL 131 IS 1 BP 76 EP 85 PG 10 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA DG9HD UT WOS:000372392500014 PM 26843673 ER PT J AU Denner, J Tonjes, RR Takeuchi, Y Fishman, J Scobie, L AF Denner, Joachim Toenjes, Ralf R. Takeuchi, Yasu Fishman, Jay Scobie, Linda TI First update of the International Xenotransplantation Association consensus statement on conditions for undertaking clinical trials of porcine islet products in type 1 diabetesChapter 5: recipient monitoring and response plan for preventing disease transmission SO XENOTRANSPLANTATION LA English DT Article DE CRISPR; Cas; designated pathogen-free status; disease transmission; hepatitis E virus; infectious disease; islet xenotransplantation; porcine endogenous retrovirus; type 1 diabetes; xenozoonoses ID HEPATITIS-E VIRUS; ENDOGENOUS RETROVIRUSES PERVS; TRANSMEMBRANE ENVELOPE PROTEIN; POTENTIALLY XENOTIC VIRUSES; CROSS-SPECIES TRANSMISSION; NATURALLY INFECTED-PIGS; TRANSGENIC PIGS; NEUTRALIZING ANTIBODIES; TRANSPLANT RECIPIENTS; REVERSE-TRANSCRIPTASE AB Xenotransplantation of porcine cells, tissues, and organs may be associated with the transmission of porcine microorganisms to the human recipient. A previous, 2009, version of this consensus statement focused on strategies to prevent transmission of porcine endogenous retroviruses (PERVs). This version addresses potential transmission of all porcine microorganisms including monitoring of the recipient and provides suggested approaches to the monitoring and prevention of disease transmission. Prior analyses assumed that most microorganisms other than the endogenous retroviruses could be eliminated from donor animals under appropriate conditions which have been called designated pathogen-free (DPF) source animal production. PERVs integrated as proviruses in the genome of all pigs cannot be eliminated in that manner and represent a unique risk. Certain microorganisms are by nature difficult to eliminate even under DPF conditions; any such clinically relevant microorganisms should be included in pig screening programs. With the use of porcine islets in clinical trials, special consideration has to be given to the presence of microorganisms in the isolated islet tissue to be used and also to the potential use of encapsulation. It is proposed that microorganisms absent in the donor animals by sensitive microbiological examination do not need to be monitored in the transplant recipient; this will reduce costs and screening requirements. Valid detection assays for donor and manufacturing-derived microorganisms must be established. Special consideration is needed to preempt potential unknown pathogens which may pose a risk to the recipient. This statement summarizes the main achievements in the field since 2009 and focus on issues and solutions with microorganisms other than PERV. C1 [Denner, Joachim] Robert Koch Inst, Nordufer 20, D-13353 Berlin, Germany. [Toenjes, Ralf R.] Paul Ehrlich Inst, Langen, Germany. [Takeuchi, Yasu] UCL, Div Infect & Immun, London, England. [Fishman, Jay] Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA. [Scobie, Linda] Glasgow Caledonian Univ, Glasgow G4 0BA, Lanark, Scotland. RP Denner, J (reprint author), Robert Koch Inst, Nordufer 20, D-13353 Berlin, Germany. EM DennerJ@rki.de NR 89 TC 7 Z9 7 U1 1 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0908-665X EI 1399-3089 J9 XENOTRANSPLANTATION JI Xenotransplantation PD JAN-FEB PY 2016 VL 23 IS 1 BP 53 EP 59 DI 10.1111/xen.12227 PG 7 WC Medicine, Research & Experimental; Transplantation SC Research & Experimental Medicine; Transplantation GA DH3ZY UT WOS:000372726500007 PM 26918415 ER PT J AU Lasiglie, D Boero, S Bauer, I Morando, S Damonte, P Cea, M Monacelli, F Odetti, P Ballestrero, A Uccelli, A Mostoslavsky, R Poggi, A Nencioni, A AF Lasiglie, Denise Boero, Silvia Bauer, Inga Morando, Sara Damonte, Patrizia Cea, Michele Monacelli, Fiammetta Odetti, Paizio Ballestrero, Alberto Uccelli, Antonio Mostoslavsky, Raul Poggi, Alessandro Nencioni, Alessio TI Sirt6 regulates dendritic cell differentiation, maturation, and function SO AGING-US LA English DT Article DE Sirt6; dendritic cells; TNF-alpha; Toll-like receptor ligands; costimulatory molecules; immunosenescence ID COLONY-STIMULATING FACTOR; MOUSE BONE-MARROW; NECROSIS-FACTOR-ALPHA; TNF-ALPHA; STEADY-STATE; LIFE-SPAN; ACTIVATION; ANTIGEN; GENERATION; INHIBITORS AB Dendritic cells (DCs) are antigen-presenting cells that critically influence decisions about immune activation or tolerance. Impaired DC function is at the core of common chronic disorders and contributes to reduce immunocompetence during aging. Knowledge on the mechanisms regulating DC generation and function is necessary to understand the immune system and to prevent disease and immunosenescence. Here we show that the sirtuin Sirt6, which was previously linked to healthspan promotion, stimulates the development of myeloid, conventional DCs (cDCs). Sirt6-knockout (Sirt6KO) mice exhibit low frequencies of bone marrow cDC precursors and low yields of bone marrow-derived cDCs compared to wild-type (WT) animals. Sirt6KO cDCs express lower levels of class II MHC, of costimulatory molecules, and of the chemokine receptor CCR7, and are less immunostimulatory compared to WT cDCs. Similar effects in terms of differentiation and immunostimulatory capacity were observed in human monocyte-derived DCs in response to SIRT6 inhibition. Finally, while Sirt6KO cDCs show an overall reduction in their ability to produce IL-12, TNF-alpha and IL-6 secretion varies dependent on the stimulus, being reduced in response to CpG, but increased in response to other Toll-like receptor ligands. In conclusion, Sirt6 plays a crucial role in cDC differentiation and function and reduced Sirt6 activity may contribute to immunosenescence. C1 [Lasiglie, Denise; Bauer, Inga; Damonte, Patrizia; Cea, Michele; Monacelli, Fiammetta; Odetti, Paizio; Ballestrero, Alberto; Nencioni, Alessio] Univ Genoa, Dept Internal Med, I-16132 Genoa, Italy. [Boero, Silvia; Monacelli, Fiammetta; Odetti, Paizio; Ballestrero, Alberto; Uccelli, Antonio; Poggi, Alessandro; Nencioni, Alessio] Azienda Osped Univ San Martino, Ist Nazl Ric Canc, Ist Sci Tumori, IRCCS, I-16132 Genoa, Italy. [Morando, Sara; Uccelli, Antonio] Univ Genoa, Dept Neurol Rehabil Ophthalmol Genet Maternal & C, I-16100 Genoa, Italy. [Mostoslavsky, Raul] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Canc, Boston, MA 02114 USA. RP Lasiglie, D; Nencioni, A (reprint author), Univ Genoa, Dept Internal Med, I-16132 Genoa, Italy.; Nencioni, A (reprint author), Azienda Osped Univ San Martino, Ist Nazl Ric Canc, Ist Sci Tumori, IRCCS, I-16132 Genoa, Italy. EM deniselasiglie@gmail.com; alessio.nencioni@unige.it RI Poggi, Alessandro/K-6664-2016 OI Poggi, Alessandro/0000-0002-1860-430X FU Fondazione Italiana Sclerosi Multipla (FISM); Italian Ministry of Health [GR-2008-1135635, GR-2011-02347192]; Associazione Italiana per la Ricerca sul Cancro (AIRC) [6108]; Seventh Framework project PANACREAS [256986]; Seventh Framework project ATHERO-B-CELL [602114]; Compagnia di San Paolo (R.O.L.) [689]; Fondazione Umberto Veronesi; University of Genoa; PO CRO Fondo Sociale Europeo Regione Liguria Asse IV "Capitale Umano" ob. Specifico I/6 FX This work was supported by the Fondazione Italiana Sclerosi Multipla (FISM; to A.N.); Italian Ministry of Health grants GR-2008-1135635 and GR-2011-02347192 (to A.N.); Associazione Italiana per la Ricerca sul Cancro (AIRC, #6108, to A.N.); Seventh Framework project PANACREAS (grant agreement #256986; to A.N.); Seventh Framework project ATHERO-B-CELL (grant agreement #602114; to A.N.); Compagnia di San Paolo (R.O.L. 689, to A.N.), Fondazione Umberto Veronesi (to A.N.); University of Genoa (to A.N.); and by the PO CRO Fondo Sociale Europeo Regione Liguria 2007-2013 Asse IV "Capitale Umano" ob. Specifico I/6 (to S.B. and A.N.). NR 39 TC 2 Z9 2 U1 0 U2 4 PU IMPACT JOURNALS LLC PI ALBANY PA 6211 TIPTON HOUSE, STE 6, ALBANY, NY 12203 USA SN 1945-4589 J9 AGING-US JI Aging-US PD JAN PY 2016 VL 8 IS 1 BP 34 EP 49 PG 16 WC Cell Biology SC Cell Biology GA DG5AV UT WOS:000372085500005 PM 26761436 ER PT J AU Genes, N Kim, MS Thum, FL Rivera, L Beato, R Song, C Soriano, J Kannry, J Baumlin, K Hwang, U AF Genes, Nicholas Kim, Min Soon Thum, Frederick L. Rivera, Laura Beato, Rosemary Song, Carolyn Soriano, Jared Kannry, Joseph Baumlin, Kevin Hwang, Ula TI Usability Evaluation of a Clinical Decision Support System for Geriatric ED Pain Treatment SO APPLIED CLINICAL INFORMATICS LA English DT Article DE Clinical decision support systems; decision support techniques; aged; acute pain; medical record systems; computerized; man-machine systems ID HEALTH INFORMATION-TECHNOLOGY; EMERGENCY-DEPARTMENT PATIENTS; RANDOMIZED-CONTROLLED-TRIAL; POSTOPERATIVE PAIN; ORDER ENTRY; CARE; IMPACT; ADHERENCE; INTERVENTIONS; MEDICATION AB Background: Older adults are at risk for inadequate emergency department (ED) pain care. Unrelieved acute pain is associated with poor outcomes. Clinical decision support systems (CDSS) hold promise to improve patient care, but CDSS quality varies widely, particularly when usability evaluation is not employed. Objective: To conduct an iterative usability and redesign process of a novel geriatric abdominal pain care CDSS. We hypothesized this process would result in the creation of more usable and favorable pain care interventions. Methods: Thirteen emergency physicians familiar with the Electronic Health Record (EHR) in use at the study site were recruited. Over a 10-week period, 17 1-hour usability test sessions were conducted across 3 rounds of testing. Participants were given 3 patient scenarios and provided simulated clinical care using the EHR, while interacting with the CDSS interventions. Quantitative System Usability Scores (SUS), favorability scores and qualitative narrative feedback were collected for each session. Using a multi-step review process by an interdisciplinary team, positive and negative usability issues in effectiveness, efficiency, and satisfaction were considered, prioritized and incorporated in the iterative redesign process of the CDSS. Video analysis was used to determine the appropriateness of the CDS appearances during simulated clinical care. Results: Over the 3 rounds of usability evaluations and subsequent redesign processes, mean SUS progressively improved from 74.8 to 81.2 to 88.9; mean favorability scores improved from 3.23 to 4.29 (1 worst, 5 best). Video analysis revealed that, in the course of the iterative redesign processes, rates of physicians' acknowledgment of CDS interventions increased, however most rates of desired actions by physicians (such as more frequent pain score updates) decreased. Conclusion: The iterative usability redesign process was instrumental in improving the usability of the CDSS; if implemented in practice, it could improve geriatric pain care. The usability evaluation process led to improved acknowledgement and favorability. Incorporating usability testing when designing CDSS interventions for studies may be effective to enhance clinician use. C1 [Genes, Nicholas; Thum, Frederick L.; Rivera, Laura; Beato, Rosemary; Song, Carolyn; Baumlin, Kevin] Icahn Sch Med Mt Sinai, Dept Emergency Med, New York, NY 10029 USA. [Kim, Min Soon] Univ Missouri, Sch Med, Dept Hlth Management & Informat, Columbia, MO USA. [Kim, Min Soon] Univ Missouri, Inst Informat, Columbia, MO USA. [Soriano, Jared; Kannry, Joseph] Mt Sinai Hlth Syst, Informat Technol, New York, NY USA. [Kannry, Joseph] Icahn Sch Med Mt Sinai, Div Gen Internal Med, New York, NY 10029 USA. [Hwang, Ula] Icahn Sch Med Mt Sinai, Brookdale Dept Geriatr & Palliat Med, New York, NY 10029 USA. [Hwang, Ula] James J Peters VAMC, Geriatr Res Educ & Clin Ctr, Bronx, NY USA. RP Genes, N (reprint author), Icahn Sch Med Mt Sinai, Dept Emergency Med, New York, NY 10029 USA. EM nicholas.genes@mountsinai.org NR 35 TC 0 Z9 0 U1 2 U2 3 PU SCHATTAUER GMBH-VERLAG MEDIZIN NATURWISSENSCHAFTEN PI STUTTGART PA HOLDERLINSTRASSE 3, D-70174 STUTTGART, GERMANY SN 1869-0327 J9 APPL CLIN INFORM JI Appl. Clin. Inform. PY 2016 VL 7 IS 1 BP 128 EP 142 DI 10.4338/ACI-2015-08-RA-0108 PG 15 WC Medical Informatics SC Medical Informatics GA DG4SQ UT WOS:000372063200010 PM 27081412 ER PT J AU Henderson, LM Weiss, J Hubbard, RA O'Donoghue, C DeMartini, WB Buist, DSM Kerlikowske, K Goodrich, M Virnig, B Tosteson, ANA Lehman, CD Onega, T AF Henderson, Louise M. Weiss, Julie Hubbard, Rebecca A. O'Donoghue, Cristina DeMartini, Wendy B. Buist, Diana S. M. Kerlikowske, Karla Goodrich, Martha Virnig, Beth Tosteson, Anna N. A. Lehman, Constance D. Onega, Tracy TI Factors Associated with Preoperative Magnetic Resonance Imaging Use among Medicare Beneficiaries with Nonmetastatic Breast Cancer SO BREAST JOURNAL LA English DT Article DE breast magnetic resonance imaging; ductal carcinoma in situ; invasive breast cancer; preoperative ID INVASIVE LOBULAR CARCINOMA; CONTRALATERAL BREAST; COMMUNITY PRACTICE; MRI UTILIZATION; UNITED-STATES; COMICE TRIAL; WOMEN; MAMMOGRAPHY; TRENDS; RECURRENCE AB Preoperative breast magnetic resonance imaging (MRI) use among Medicare beneficiaries with breast cancer has substantially increased from 2005 to 2009. We sought to identify factors associated with preoperative breast MRI use among women diagnosed with ductal carcinoma in situ ( DCIS) or stage I-III invasive breast cancer (IBC). Using Surveillance, Epidemiology, and End Results and Medicare data from 2005 to 2009 we identified women ages 66 and older with DCIS or stage I-III IBC who underwent breast-conserving surgery or mastectomy. We compared preoperative breast MRI use by patient, tumor and hospital characteristics stratified by DCIS and IBC using multivariable logistic regression. From 2005 to 2009, preoperative breast MRI use increased from 5.9% to 22.4% of women diagnosed with DCIS and 7.0% to 24.3% of women diagnosed with IBC. Preoperative breast MRI use was more common among women who were younger, married, lived in higher median income zip codes and had no comorbidities. Among women with IBC, those with lobular disease, smaller tumors (<1 cm) and those with estrogen receptor negative tumors were more likely to receive preoperative breast MRI. Women with DCIS were more likely to receive preoperative MRI if tumors were larger (>2 cm). The likelihood of receiving preoperative breast MRI is similar for women diagnosed with DCIS and IBC. Use of MRI is more common in women with IBC for tumors that are lobular and smaller while for DCIS MRI is used for evaluation of larger lesions. C1 [Henderson, Louise M.] Univ N Carolina, Dept Radiol, CB 7515, Chapel Hill, NC 27599 USA. [Weiss, Julie; Goodrich, Martha] Geisel Sch Med, Dept Community & Family Med, Dartmouth, NS, Canada. [Hubbard, Rebecca A.] Univ Penn, Dept Biostat & Epidemiol, Philadelphia, PA 19104 USA. [Hubbard, Rebecca A.] Univ Washington, Dept Biostat, Seattle, WA 98195 USA. [O'Donoghue, Cristina] Univ S Florida, H Lee Moffitt Canc Ctr, Tampa, FL 33682 USA. [DeMartini, Wendy B.] Univ Wisconsin, Dept Radiol, Madison, WI 53706 USA. [Buist, Diana S. M.] Grp Hlth Res Inst, Seattle, WA USA. [Kerlikowske, Karla] Univ Calif San Francisco, Dept Med, San Francisco, CA 94143 USA. [Kerlikowske, Karla] Univ Calif San Francisco, Dept Biostat & Epidemiol, San Francisco, CA 94143 USA. [Kerlikowske, Karla] Univ Calif San Francisco, Dept Vet Affairs, Gen Internal Med Sect, San Francisco, CA 94143 USA. [Virnig, Beth] Univ Minnesota, Sch Publ Hlth, Div Hlth Policy & Management, Minneapolis, MN USA. [Tosteson, Anna N. A.; Onega, Tracy] Geisel Sch Med Dartmouth, Dartmouth Inst Hlth Policy & Clin Practice, Hanover, NH USA. [Tosteson, Anna N. A.; Onega, Tracy] Geisel Sch Med Dartmouth, Norris Cotton Canc Ctr, Hanover, NH USA. [Lehman, Constance D.] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. RP Henderson, LM (reprint author), Univ N Carolina, Dept Radiol, CB 7515, Chapel Hill, NC 27599 USA. EM louise_henderson@med.unc.edu FU National Institutes of Health, National Cancer Institute [R01 CA149365-01] FX This work was supported by funding from the National Institutes of Health, National Cancer Institute under grant R01 CA149365-01. This study used the linked SEER-Medicare data base. The interpretation and reporting of these data are the sole responsibility of the authors. The authors acknowledge the efforts of the Applied Research Program, NCI; the Office of Research, Development and Information, CMS; Information Management Services (IMS); and the Surveillance, Epidemiology, and End Results (SEER) Program tumor registries in the creation of the SEER-Medicare data base. NR 44 TC 1 Z9 1 U1 0 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1075-122X EI 1524-4741 J9 BREAST J JI Breast J. PD JAN-FEB PY 2016 VL 22 IS 1 BP 24 EP 34 DI 10.1111/tbj.12522 PG 11 WC Oncology; Obstetrics & Gynecology SC Oncology; Obstetrics & Gynecology GA DG5TD UT WOS:000372140700004 PM 26511204 ER PT J AU Nambudiri, VE Vivero, M Watson, AJ Thakuria, M Ng, A Russell, S Rabinowits, G LeBoeuf, NR AF Nambudiri, Vinod E. Vivero, Marina Watson, Alice J. Thakuria, Manisha Ng, Andrea Russell, Sara Rabinowits, Guilherme LeBoeuf, Nicole R. TI Merkel Cell Carcinoma Presenting as Subcutaneous Breast Masses: An Uncommon Presentation of a Rare Neuroendocrine Neoplasm SO BREAST JOURNAL LA English DT Editorial Material C1 [Nambudiri, Vinod E.; Watson, Alice J.; Thakuria, Manisha; LeBoeuf, Nicole R.] Brigham & Womens Hosp, Dept Dermatol, 75 Francis St, Boston, MA 02115 USA. [Nambudiri, Vinod E.; Watson, Alice J.; Thakuria, Manisha; Ng, Andrea; Russell, Sara; LeBoeuf, Nicole R.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Nambudiri, Vinod E.] Brigham & Womens Hosp, Dept Med, 75 Francis St, Boston, MA 02115 USA. [Vivero, Marina] Brigham & Womens Hosp, Dept Pathol, 75 Francis St, Boston, MA 02115 USA. [Ng, Andrea] Brigham & Womens Hosp, Dept Radiat Oncol, 75 Francis St, Boston, MA 02115 USA. [Russell, Sara] Brigham & Womens Hosp, Dept Surg Oncol, 75 Francis St, Boston, MA 02115 USA. [Rabinowits, Guilherme] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. RP LeBoeuf, NR (reprint author), Harvard Univ, Sch Med, Dana Farber Brigham & Womens Canc Ctr, Dept Dermatol, 375 Longwood Ave, Boston, MA 02115 USA. EM nleboeuf@partners.org NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1075-122X EI 1524-4741 J9 BREAST J JI Breast J. PD JAN-FEB PY 2016 VL 22 IS 1 BP 113 EP 115 DI 10.1111/tbj.12534 PG 3 WC Oncology; Obstetrics & Gynecology SC Oncology; Obstetrics & Gynecology GA DG5TD UT WOS:000372140700016 PM 26607182 ER PT J AU Keraliya, AR Krajewski, KM Jagannathan, JP Shinagare, AB Braschi-Amirfarzan, M Tirumani, SH Ramaiya, NH AF Keraliya, Abhishek R. Krajewski, Katherine M. Jagannathan, Jyothi P. Shinagare, Atul B. Braschi-Amirfarzan, Marta Tirumani, Sree H. Ramaiya, Nikhil H. TI Multimodality imaging of osseous involvement In haematological malignancies SO BRITISH JOURNAL OF RADIOLOGY LA English DT Review ID BONE-MARROW INVOLVEMENT; WHOLE-BODY MRI; PEDIATRIC ACUTE-LEUKEMIA; B-CELL LYMPHOMA; MULTIPLE-MYELOMA; FDG-PET/CT; WALDENSTROM MACROGLOBULINEMIA; HODGKINS-LYMPHOMA; F-18-FDG PET/CT; STAGING SYSTEM AB The purpose of this article is to provide a comprehensive review of the imaging features of osseous involvement in haematological malignancies. Osseous involvement can be seen in various haematological malignancies including lymphomas, plasma cell neoplasms, leukaemias and myeloproliferative neoplasms. Imaging plays a crucial role in initial diagnosis, staging and in the assessment of treatment response in these patients. C1 [Keraliya, Abhishek R.; Krajewski, Katherine M.; Jagannathan, Jyothi P.; Shinagare, Atul B.; Braschi-Amirfarzan, Marta; Tirumani, Sree H.; Ramaiya, Nikhil H.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Imaging, 44 Binney St, Boston, MA 02115 USA. [Keraliya, Abhishek R.; Krajewski, Katherine M.; Jagannathan, Jyothi P.; Shinagare, Atul B.; Braschi-Amirfarzan, Marta; Tirumani, Sree H.; Ramaiya, Nikhil H.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Radiol, Boston, MA 02115 USA. RP Keraliya, AR (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Imaging, 44 Binney St, Boston, MA 02115 USA.; Keraliya, AR (reprint author), Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Radiol, Boston, MA 02115 USA. EM akeraliya@partners.org NR 66 TC 0 Z9 0 U1 2 U2 2 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. PY 2016 VL 89 IS 1059 AR 20150980 DI 10.1259/bjr.20150980 PG 12 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA DG6NR UT WOS:000372202900037 PM 26781757 ER PT J AU Zygmanski, P Sajo, E AF Zygmanski, Piotr Sajo, Erno TI Nanoscale radiation transport and clinical beam modeling for gold nanoparticle dose enhanced radiotherapy (GNPT) using X-rays SO BRITISH JOURNAL OF RADIOLOGY LA English DT Review ID MONTE-CARLO-SIMULATION; LOW-ENERGY-ELECTRON; MEGAVOLTAGE PHOTON BEAMS; TRACK-STRUCTURE; CONTRAST AGENTS; LIQUID WATER; THERAPY; IRRADIATION; GEOMETRY; PROTONS AB We review radiation transport and clinical beam modelling for gold nanoparticle dose-enhanced radiotherapy using X-rays. We focus on the nanoscale radiation transport and its relation to macroscopic dosimetry for monoenergetic and clinical beams. Among other aspects, we discuss Monte Carlo and deterministic methods and their applications to predicting dose enhancement using various metrics. C1 [Zygmanski, Piotr] Brigham & Womens Hosp, Dana Farber Canc Inst, Dept Radiat Oncol, 75 Francis St, Boston, MA 02115 USA. [Zygmanski, Piotr] Harvard Univ, Sch Med, Boston, MA USA. [Sajo, Erno] Univ Massachusetts, Med Phys Program, Dept Phys & Appl Phys, Lowell, MA USA. RP Zygmanski, P (reprint author), Brigham & Womens Hosp, Dana Farber Canc Inst, Dept Radiat Oncol, 75 Francis St, Boston, MA 02115 USA. EM pzygmanski@lroc.harvard.edu NR 75 TC 3 Z9 3 U1 6 U2 16 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. PY 2016 VL 89 IS 1059 AR 20150200 DI 10.1259/bjr.20150200 PG 19 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA DG6NR UT WOS:000372202900004 PM 26642305 ER PT J AU Versteeg, R George, RE AF Versteeg, Rogier George, Rani E. TI Targeting ALK: The Ten Lives of a Tumor SO CANCER DISCOVERY LA English DT Editorial Material ID INHIBITOR; NEUROBLASTOMA; PF-06463922; RESISTANCE; MUTATIONS; LYMPHOMA; SPECTRUM; MYCN AB In this issue, Infarinato and colleagues report the results of preclinical testing of a novel ALK/ROS1 inhibitor, PF-06463922, in neuroblastoma. This small-molecule inhibitor was shown to efficiently inhibit the growth of patient-derived and established neuroblastoma xenograft models expressing mutated ALK. Although the in vivo data are impressive and the authors suggest that clinical trials are warranted, the presented data also suggest that it is as yet too early to welcome the new drug as a magic bullet. (C) 2016 AACR. C1 [Versteeg, Rogier] Univ Amsterdam, Acad Med Ctr, Dept Oncogen, Meibergdreef 9, NL-1105 AZ Amsterdam, Netherlands. [George, Rani E.] Dana Farber Canc Inst, Dept Pediat Hematol & Oncol, Boston, MA 02115 USA. [George, Rani E.] Harvard Univ, Sch Med, Boston Childrens Hosp, Boston, MA USA. RP Versteeg, R (reprint author), Univ Amsterdam, Acad Med Ctr, Meibergdreef 15, NL-1105 AZ Amsterdam, Netherlands.; George, RE (reprint author), Dana Farber Canc Inst, Dept Pediat Oncol, Dana 640E,450 Brookline Ave, Boston, MA 02215 USA. EM r.versteeg@amc.nl; Rani_George@DFCI.Harvard.edu FU NCI NIH HHS [R01 CA148688, R01CA148688] NR 10 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 2159-8274 EI 2159-8290 J9 CANCER DISCOV JI Cancer Discov. PD JAN PY 2016 VL 6 IS 1 BP 20 EP 21 DI 10.1158/2159-8290.CD-15-1411 PG 2 WC Oncology SC Oncology GA DG8HA UT WOS:000372322500020 PM 26747894 ER PT J AU Neupane, M Clark, AP Landini, S Birkbak, NJ Eklund, AC Lim, E Culhane, AC Barry, WT Schumacher, SE Beroukhim, R Szallasi, Z Vidal, M Hill, DE Silver, DP AF Neupane, Manish Clark, Allison P. Landini, Serena Birkbak, Nicolai J. Eklund, Aron C. Lim, Elgene Culhane, Aedin C. Barry, William T. Schumacher, Steven E. Beroukhim, Rameen Szallasi, Zoltan Vidal, Marc Hill, David E. Silver, Daniel P. TI MECP2 Is a Frequently Amplified Oncogene with a Novel Epigenetic Mechanism That Mimics the Role of Activated RAS in Malignancy SO CANCER DISCOVERY LA English DT Article ID COPY-NUMBER ALTERATION; AUTISM SPECTRUM DISORDERS; X-CHROMOSOME INACTIVATION; CPG-BINDING PROTEIN-2; RETT-SYNDROME; PTEN MUTATIONS; HUMAN CANCERS; MUTANT MICE; TRANSFORMATION; EXPRESSION AB An unbiased genome-scale screen for unmutated genes that drive cancer growth when overexpressed identified methyl cytosine-guanine dinucleotide (CpG) binding protein 2 (MECP2) as a novel oncogene. MECP2 resides in a region of the X-chromosome that is significantly amplified across 18% of cancers, and many cancer cell lines have amplified, overexpressed MECP2 and are dependent on MECP2 expression for growth. MECP2 copy-number gain and RAS family member alterations are mutually exclusive in several cancer types. The MECP2 splicing isoforms activate the major growth factor pathways targeted by activated RAS, the MAPK and PI3K pathways. MECP2 rescued the growth of a KRAS(G12C) - addicted cell line after KRAS downregulation, and activated KRAS rescues the growth of an MECP2 - addicted cell line after MECP2 downregulation. MECP2 binding to the epigenetic modification 5-hydroxymethylcytosine is required for efficient transformation. These observations suggest that MECP2 is a commonly amplified oncogene with an unusual epigenetic mode of action. SIGNIFICANCE: MECP2 is a commonly amplified oncogene in human malignancies with a unique epigenetic mechanism of action. (C) 2015 AACR. C1 [Neupane, Manish; Clark, Allison P.; Landini, Serena; Schumacher, Steven E.; Beroukhim, Rameen; Vidal, Marc; Hill, David E.; Silver, Daniel P.] Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA. [Neupane, Manish; Clark, Allison P.; Beroukhim, Rameen; Silver, Daniel P.] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. [Birkbak, Nicolai J.; Eklund, Aron C.; Szallasi, Zoltan] Tech Univ Denmark, Ctr Biol Sequence Anal, Dept Syst Biol, DK-2800 Lyngby, Denmark. [Lim, Elgene] St Vincents Hosp, Garvan Inst Med Res, Kinghorn Canc Ctr, Darlinghurst, NSW 2010, Australia. [Culhane, Aedin C.; Barry, William T.] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA. [Culhane, Aedin C.; Barry, William T.] Harvard Univ, Dept Biostat, TH Chan Sch Publ Hlth, Boston, MA 02115 USA. [Schumacher, Steven E.; Beroukhim, Rameen] Broad Inst Harvard & MIT, Cambridge, MA USA. [Beroukhim, Rameen; Silver, Daniel P.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02215 USA. [Szallasi, Zoltan] Harvard MIT Div Hlth Sci & Technol, Childrens Hosp Informat Program, Boston, MA USA. [Szallasi, Zoltan] Harvard Univ, Sch Med, Boston, MA USA. [Vidal, Marc; Hill, David E.; Silver, Daniel P.] Dana Farber Canc Inst, Ctr Canc Syst Biol, Boston, MA 02215 USA. [Vidal, Marc; Hill, David E.] Harvard Univ, Sch Med, Dept Genet, Boston, MA USA. RP Silver, DP (reprint author), Dana Farber Canc Inst, Smith Bldg,Room 868b,450 Brookline Ave, Boston, MA 02215 USA. EM Daniel_Silver@dfci.harvard.edu OI Eklund, Aron Charles/0000-0003-0861-1001 FU Cogan Family Foundation; Dana-Farber Cancer Institute (DFCI); DF/HCC SPORE in breast cancer NIH [P50 CA168504-01A1, U01HG001715]; DFCI Institute; Ellison Foundation, Boston, MA FX This work was supported by a grant from the Cogan Family Foundation (to D.P. Silver), Dana-Farber Cancer Institute (DFCI) startup funds from philanthropic sources (to D.P. Silver), the DF/HCC SPORE in breast cancer NIH P50 CA168504-01A1, a U01HG001715 (to M. Vidal and D.E. Hill), DFCI Institute Sponsored Research (to M. Vidal and D.E. Hill), and the Ellison Foundation, Boston, MA (to M. Vidal and D.E. Hill). NR 70 TC 3 Z9 3 U1 0 U2 7 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 2159-8274 EI 2159-8290 J9 CANCER DISCOV JI Cancer Discov. PD JAN PY 2016 VL 6 IS 1 BP 45 EP 58 DI 10.1158/2159-8290.CD-15-0341 PG 14 WC Oncology SC Oncology GA DG8HA UT WOS:000372322500023 PM 26546296 ER PT J AU Scarbrough, PM Weber, RP Iversen, ES Brhane, Y Amos, CI Kraft, P Hung, RJ Sellers, TA Witte, JS Pharoah, P Henderson, BE Gruber, SB Hunter, DJ Garber, JE Joshi, AD McDonnell, K Easton, DF Eeles, R Kote-Jarai, Z Muir, K Doherty, JA Schildkraut, JM AF Scarbrough, Peter M. Weber, Rachel Palmieri Iversen, Edwin S. Brhane, Yonathan Amos, Christopher I. Kraft, Peter Hung, Rayjean J. Sellers, Thomas A. Witte, John S. Pharoah, Paul Henderson, Brian E. Gruber, Stephen B. Hunter, David J. Garber, Judy E. Joshi, Amit D. McDonnell, Kevin Easton, Doug F. Eeles, Ros Kote-Jarai, Zsofia Muir, Kenneth Doherty, Jennifer A. Schildkraut, Joellen M. TI A Cross-Cancer Genetic Association Analysis of the DNA Repair and DNA Damage Signaling Pathways for Lung, Ovary, Prostate, Breast, and Colorectal Cancer SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID GENOME-WIDE ASSOCIATION; SYSTEMIC-LUPUS-ERYTHEMATOSUS; SUSCEPTIBILITY LOCI; RISK ALLELES; ATAXIA-TELANGIECTASIA; GENOTYPE IMPUTATION; 14Q24.1 RAD51L1; IDENTIFIES 2; METAANALYSIS; VARIANTS AB Background: DNA damage is an established mediator of carcinogenesis, although genome-wide association studies (GWAS) have identified few significant loci. This cross-cancer site, pooled analysis was performed to increase the power to detect common variants of DNA repair genes associated with cancer susceptibility. Methods: We conducted a cross-cancer analysis of 60,297 single nucleotide polymorphisms, at 229 DNA repair gene regions, using data from the NCI Genetic Associations and Mechanisms in Oncology (GAME-ON) Network. Our analysis included data from 32 GWAS and 48,734 controls and 51,537 cases across five cancer sites (breast, colon, lung, ovary, and prostate). Because of the unavailability of individual data, data were analyzed at the aggregate level. Meta-analysis was performed using the Association analysis for SubSETs (ASSET) software. To test for genetic associations that might escape individual variant testing due to small effect sizes, pathway analysis of eight DNA repair pathways was performed using hierarchical modeling. Results: We identified three susceptibility DNA repair genes, RAD51B (P < 5.09 x 10(-6)), MSH5 (P < 5.09 x 10(-6)), and BRCA2 (P = 5.70 x 10(-6)). Hierarchical modeling identified several pleiotropic associations with cancer risk in the base excision repair, nucleotide excision repair, mismatch repair, and homologous recombination pathways. Conclusions: Only three susceptibility loci were identified, which had all been previously reported. In contrast, hierarchical modeling identified several pleiotropic cancer risk associations in key DNA repair pathways. Impact: Results suggest that many common variants in DNA repair genes are likely associated with cancer susceptibility through small effect sizes that do not meet stringent significance testing criteria. (C) 2015 AACR. C1 [Scarbrough, Peter M.; Weber, Rachel Palmieri; Schildkraut, Joellen M.] Duke Univ, Med Ctr, Dept Community & Family Med, Durham, NC 27710 USA. [Scarbrough, Peter M.; Weber, Rachel Palmieri; Schildkraut, Joellen M.] Duke Canc Inst, Canc Prevent Detect & Control Res Program, Durham, NC USA. [Scarbrough, Peter M.] Duke Univ, Sch Med, Dept Pharmacol & Canc Biol, Durham, NC USA. [Iversen, Edwin S.] Duke Univ, Dept Stat Sci, Durham, NC USA. [Brhane, Yonathan; Hung, Rayjean J.] Mt Sinai Hosp, Lunenfeld Tanenbaum Res Inst, Toronto, ON M5G 1X5, Canada. [Amos, Christopher I.; Doherty, Jennifer A.] Dartmouth Coll, Geisel Sch Med, 1 Med Ctr Dr, Lebanon, NH 03756 USA. [Kraft, Peter; Hunter, David J.; Joshi, Amit D.] Harvard Univ, Sch Publ Hlth, Program Genet Epidemiol & Stat Genet, 665 Huntington Ave, Boston, MA 02115 USA. [Sellers, Thomas A.] Univ S Florida, H Lee Moffitt Canc Ctr, Dept Canc Epidemiol, Tampa, FL 33682 USA. [Witte, John S.] Univ Calif San Francisco, Inst Human Genet, San Francisco, CA 94143 USA. [Witte, John S.] Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA. [Pharoah, Paul] Univ Cambridge, Dept Oncol, Cambridge, England. [Pharoah, Paul] Univ Cambridge, Dept Publ Hlth & Primary Care, Cambridge, England. [Henderson, Brian E.; Gruber, Stephen B.; McDonnell, Kevin] Univ So Calif, Keck Sch Med, Dept Prevent Med, Los Angeles, CA 90033 USA. [Henderson, Brian E.; Gruber, Stephen B.; McDonnell, Kevin] Univ So Calif, Kenneth Norris Jr Comprehens Canc Ctr, Los Angeles, CA 90033 USA. [Garber, Judy E.] Dana Farber Canc Inst, Canc Risk & Prevent Clin, Boston, MA 02115 USA. [Easton, Doug F.] Univ Cambridge, Dept Publ Hlth & Primary Care, Ctr Canc Genet Epidemiol, Cambridge, England. [Eeles, Ros; Kote-Jarai, Zsofia] Inst Canc Res, Div Genet & Epidemiol, London SW3 6JB, England. [Eeles, Ros; Kote-Jarai, Zsofia] Royal Marsden NHS Fdn Trust, London, England. [Eeles, Ros; Kote-Jarai, Zsofia] Royal Marsden NHS Fdn Trust, Sutton, Surrey, England. [Muir, Kenneth] Univ Manchester, Inst Populat Hlth, Manchester, Lancs, England. [Muir, Kenneth] Univ Warwick, Warwick Med Sch, Coventry CV4 7AL, W Midlands, England. [Schildkraut, Joellen M.] Univ Virginia, Dept Publ Hlth Sci, Charlottesville, VA 22903 USA. RP Schildkraut, JM (reprint author), Univ Virginia, POB 800765, Charlottesville, VA 22903 USA. EM jms2yf@virginia.edu RI Hung, Rayjean/A-7439-2013; OI Eeles, Rosalind/0000-0002-3698-6241 FU Genetic Associations and Mechanisms in Oncology (GAME-ON): an NCI Cancer Post-GWAS Initiative [U19CA148112, U19CA148127, U19CA148107, U19CA148065, U19CA148537]; National Cancer Institute [R01CA176016, R01CA088164, R25CA126938, P30 CA023108, U01CA127298]; National Institute of General Medical Science [P20GM103534]; Cancer Research UK [C490/A16561, C490/A10124, C490/A10119, C1287/A16563] FX The scientific development and funding for this project were supported by the following: the Genetic Associations and Mechanisms in Oncology (GAME-ON): an NCI Cancer Post-GWAS Initiative, U19CA148112 (T.A. Sellers, J.M. Schildkraut, P. Pharoah), U19CA148127 (C.I. Amos), U19CA148107 (S.B. Gruber), U19CA148065 (D.J. Hunter, P. Kraft, D.F. Easton), U19CA148537 (B.E. Henderson), National Cancer Institute grants R01CA176016 (J.M. Schildkraut), R01CA088164 (J.S. Witte), R25CA126938 (J.M. Schildkraut), P30 CA023108 (C.I. Amos), U01CA127298 (J.S. Witte), National Institute of General Medical Science grant P20GM103534 (C.I. Amos), Cancer Research UK grants C490/A16561 (P. Pharoah), C490/A10124 (P. Pharoah), C490/A10119 (P. Pharoah), and C1287/A16563 (D.F. Easton). NR 58 TC 4 Z9 4 U1 1 U2 3 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 2016 VL 25 IS 1 BP 193 EP 200 DI 10.1158/1055-9965.EPI-15-0649 PG 8 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA DG6DC UT WOS:000372171400025 PM 26637267 ER PT J AU Borgquist, S Tamimi, RM Chen, WY Garber, JE Eliassen, AH Ahern, TP AF Borgquist, Signe Tamimi, Rulla M. Chen, Wendy Y. Garber, Judy E. Eliassen, A. Heather Ahern, Thomas P. TI Statin Use and Breast Cancer Risk in the Nurses' Health Study SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID WOMEN AB Preclinical studies support an anticancer effect of statin drugs, yet epidemiologic evidence remains inconsistent regarding their role in breast cancer primary prevention. Here, we report an updated analysis of the association between statin use and breast cancer incidence in the Nurses' Health Study (NHS) cohort. Postmenopausal NHS participants without a cancer history were followed from 2000 until 2012 (n = 79,518). Data on statin use were retrieved from biennial questionnaires. We fit Cox regression models to estimate associations between longitudinal statin use and breast cancer incidence. Over 823,086 person-years of follow-up, 3,055 cases of invasive breast cancer occurred. Compared with never users, both former and current statin users had similar rates of invasive breast cancer incidence [former users: HRadj, 0.96; 95% confidence interval (CI), 0.82-1.1; current users: HRadj, 1.1; 95% CI, 0.92-1.3]. Associations did not differ by estrogen receptor (ER) status or histology (ductal vs. lobular carcinoma). Statin use was not associated with risk of invasive breast cancer, irrespective of histologic subtype and ER status. Statin drugs do not appear to modify processes involved in breast cancer initiation. (C) 2016 AACR. C1 [Borgquist, Signe; Chen, Wendy Y.; Garber, Judy E.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02215 USA. [Borgquist, Signe] Lund Univ, Dept Clin Sci, Div Oncol & Pathol, Lund, Sweden. [Tamimi, Rulla M.; Chen, Wendy Y.; Eliassen, A. Heather] Brigham & Womens Hosp, Channing Div Network Med, 75 Francis St, Boston, MA 02115 USA. [Tamimi, Rulla M.; Chen, Wendy Y.; Eliassen, A. Heather] Harvard Univ, Sch Med, Boston, MA 02215 USA. [Tamimi, Rulla M.; Eliassen, A. Heather] Harvard Univ, Dept Epidemiol, TH Chan Sch Publ Hlth, Boston, MA 02215 USA. [Ahern, Thomas P.] Univ Vermont, Coll Med, Dept Surg, Burlington, VT USA. [Ahern, Thomas P.] Univ Vermont, Coll Med, Dept Biochem, Burlington, VT 05405 USA. RP Borgquist, S (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, 450 Brookline Ave,Dana 1118, Boston, MA 02215 USA. EM signe.borgquist@med.lu.se FU Swedish Research Council; Swedish Cancer Foundation; Governmental funding of Clinical Research within the Swedish National Health Services (ALF); National Cancer Institute at the National Institutes of Health [UM1 CA186107, P01 CA87969]; Susan G. Komen for the Cure [CCR13264024]; Mary Kay Foundation [003-14] FX S. Borgquist was supported by grants from the Swedish Research Council, The Swedish Cancer Foundation and Governmental funding of Clinical Research within the Swedish National Health Services (ALF). The NHS is supported by the following grants from the National Cancer Institute at the National Institutes of Health: UM1 CA186107 (to W.Y. Chen and R.M. Tamimi), P01 CA87969 (to W.Y. Chen and R.M. Tamimi). T.P. Ahern was supported by Susan G. Komen for the Cure (CCR13264024) and by the Mary Kay Foundation (003-14). NR 14 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 1055-9965 EI 1538-7755 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD JAN PY 2016 VL 25 IS 1 BP 201 EP 206 DI 10.1158/1055-9965.EPI-15-0654 PG 6 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA DG6DC UT WOS:000372171400026 PM 26762806 ER PT J AU Ahmadi, SF Zahmatkesh, G Ahmadi, E Streja, E Rhee, CM Gillen, DL De Nicola, L Minutolo, R Ricardo, AC Kovesdy, CP Kalantar-Zadeh, K AF Ahmadi, Seyed-Foad Zahmatkesh, Golara Ahmadi, Emad Streja, Elani Rhee, Connie M. Gillen, Daniel L. De Nicola, Luca Minutolo, Roberto Ricardo, Ana C. Kovesdy, Csaba P. Kalantar-Zadeh, Kamyar TI Association of Body Mass Index with Clinical Outcomes in Non-Dialysis-Dependent Chronic Kidney Disease: A Systematic Review and Meta-Analysis SO CARDIORENAL MEDICINE LA English DT Review DE Chronic kidney disease; Body mass index; Mortality; End-stage renal disease; Obesity paradox ID ALL-CAUSE MORTALITY; CARDIOVASCULAR RISK-FACTORS; OBESITY PARADOX; PERITONEAL-DIALYSIS; CKD; HEMODIALYSIS; POPULATION; OVERWEIGHT; SURVIVAL; FAILURE AB Background: Previous studies have not shown a consistent link between body mass index (BMI) and outcomes such as mortality and kidney disease progression in non-dialysis-dependent chronic kidney disease (CKD) patients. Therefore, we aimed to complete a systematic review and meta-analysis study on this subject. Methods: We searched MEDLINE, EMBASE, Web of Science, Cumulative Index to Nursing and Allied Health Literature (CINAHL), and Co-chrane Central Register of Controlled Trials (CENTRAL), and screened 7,123 retrieved studies for inclusion. Two investigators independently selected the studies using predefined criteria and assessed each study's quality using the Newcastle-Ottawa quality assessment scale. We meta-analyzed the results based on the BMI classification system by the WHO. Results: We included 10 studies (with a total sample size of 484,906) in the systematic review and 4 studies in the meta-analyses. The study results were generally heterogeneous. However, following reanalysis of the largest reported study and our meta-analyses, we observed that in stage 3-5 CKD, being underweight was associated with a higher risk of death while being overweight or obese class I was associated with a lower risk of death; however, obesity classes II and III were not associated with risk of death. In addition, reanalysis of the largest available study showed that a higher BMI was associated with an incrementally higher risk of kidney disease progression; however, this association was attenuated in our pooled results. For earlier stages of CKD, we could not complete meta-analyses as the studies were sparse and had heterogeneous BMI classifications and/or referent BMI groups. Conclusion: Among the group of patients with stage 3-5 CKD, we found a differential association between obesity classes I-III and mortality compared to the general population, indicating an obesity paradox in the CKD population. (C) 2015 S. Karger AG, Basel C1 [Ahmadi, Seyed-Foad; Zahmatkesh, Golara; Streja, Elani; Rhee, Connie M.; Kalantar-Zadeh, Kamyar] Univ Calif Irvine, Harold Simmons Ctr Kidney Dis Res & Epidemiol, Div Nephrol & Hypertens, Med Ctr, 101 City Dr South,City Tower, Orange, CA 92868 USA. [Ahmadi, Seyed-Foad; Gillen, Daniel L.; Kalantar-Zadeh, Kamyar] Univ Calif Irvine, Dept Populat Hlth & Dis Prevent, Program Publ Hlth, Irvine, CA USA. [Gillen, Daniel L.] Univ Calif Irvine, Donald Bren Sch Informat & Comp Sci, Dept Stat, Irvine, CA USA. [Ahmadi, Emad] Harvard Univ, Sch Med, Dept Radiol, Massachusetts Gen Hosp, Boston, MA 02115 USA. [Streja, Elani; Kalantar-Zadeh, Kamyar] Vet Affairs Long Beach Healthcare Syst, Long Beach, CA USA. [Gillen, Daniel L.; Kalantar-Zadeh, Kamyar] Univ Calif Los Angeles, Sch Publ Hlth, Dept Epidemiol, Los Angeles, CA 90024 USA. [Ricardo, Ana C.] Univ Illinois, Dept Med, Div Nephrol, Chicago, IL USA. [Kovesdy, Csaba P.] Univ Tennessee, Ctr Hlth Sci, Div Nephrol, Memphis, TN 38163 USA. [Kovesdy, Csaba P.] Memphis Vet Affairs Med Ctr, Memphis, TN USA. [De Nicola, Luca; Minutolo, Roberto] Univ Naples 2, Nephrol Div, Naples, Italy. RP Kalantar-Zadeh, K (reprint author), Univ Calif Irvine, Harold Simmons Ctr Kidney Dis Res & Epidemiol, Div Nephrol & Hypertens, Med Ctr, 101 City Dr South,City Tower, Orange, CA 92868 USA. EM kkz@uci.edu OI Kalantar-Zadeh, Kamyar/0000-0002-8666-0725 FU NIDDK NIH HHS [K23 DK094829] NR 37 TC 14 Z9 15 U1 0 U2 2 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 1664-3828 EI 1664-5502 J9 CARDIORENAL MED JI CardioRenal Med. PY 2016 VL 6 IS 1 BP 37 EP 49 DI 10.1159/000437277 PG 13 WC Cardiac & Cardiovascular Systems; Urology & Nephrology SC Cardiovascular System & Cardiology; Urology & Nephrology GA DG2YD UT WOS:000371935800005 PM 27194995 ER PT J AU Taylor, RL Cruickshank, MN Karimi, M Ng, HL Quail, E Kaufman, KM Harley, JB Abraham, LJ Tsao, BP Boackle, SA Ulgiati, D AF Taylor, Rhonda L. Cruickshank, Mark N. Karimi, Mahdad Ng, Han Leng Quail, Elizabeth Kaufman, Kenneth M. Harley, John B. Abraham, Lawrence J. Tsao, Betty P. Boackle, Susan A. Ulgiati, Daniela TI Focused transcription from the human CR2/CD21 core promoter is regulated by synergistic activity of TATA and Initiator elements in mature B cells SO CELLULAR & MOLECULAR IMMUNOLOGY LA English DT Article DE B cells; core promoter; CR2/CD21; molecular biology; transcription factor ID SYSTEMIC-LUPUS-ERYTHEMATOSUS; COMPLEMENT RECEPTOR 2; HUMAN LYMPHOCYTES-B; GENOME-WIDE ANALYSIS; GENE-EXPRESSION; PLASMA-CELL; FACTOR E2A; CR-2 GENE; T-CELLS; C3D AB Complement receptor 2 (CR2/CD21) is predominantly expressed on the surface of mature B cells where it forms part of a coreceptor complex that functions, in part, to modulate B-cell receptor signal strength. CR2/CD21 expression is tightly regulated throughout B-cell development such that CR2/CD21 cannot be detected on pre-B or terminally differentiated plasma cells. CR2/CD21 expression is upregulated at B-cell maturation and can be induced by IL-4 and CD40 signaling pathways. We have previously characterized elements in the proximal promoter and first intron of CR2/CD21 that are involved in regulating basal and tissue-specific expression. We now extend these analyses to the CR2/CD21 core promoter. We show that in mature B cells, CR2/CD21 transcription proceeds from a focused TSS regulated by a non-consensus TATA box, an initiator element and a downstream promoter element. Furthermore, occupancy of the general transcriptional machinery in pre-B versus mature B-cell lines correlate with CR2/CD21 expression level and indicate that promoter accessibility must switch from inactive to active during the transitional B-cell window. C1 [Taylor, Rhonda L.; Ng, Han Leng; Abraham, Lawrence J.; Ulgiati, Daniela] Univ Western Australia, Ctr Genet Origins Hlth & Dis, Sch Pathol & Lab Med, Crawley, WA 6009, Australia. [Taylor, Rhonda L.; Karimi, Mahdad; Quail, Elizabeth] Univ Western Australia, Sch Chem & Biochem, Biochem & Mol Biol, Crawley, WA 6009, Australia. [Cruickshank, Mark N.] Univ Western Australia, Telethon Kids Inst, Crawley, WA 6009, Australia. [Kaufman, Kenneth M.; Harley, John B.] Cincinnati Childrens Hosp Med Ctr, Cincinnati, OH 45229 USA. [Kaufman, Kenneth M.; Harley, John B.] US Dept Vet Affairs, Med Ctr, Cincinnati, OH USA. [Tsao, Betty P.] Univ Calif Los Angeles, Dept Med, Div Rheumatol, Los Angeles, CA 90024 USA. [Boackle, Susan A.] Univ Colorado, Sch Med, Div Rheumatol, Aurora, CO USA. RP Ulgiati, D (reprint author), Univ Western Australia, Sch Pathol & Lab Med, 35 Stirling Highway, Crawley, WA 6009, Australia. EM daniela.ulgiati@uwa.edu.au FU National Health and Medical Research Council of Australia [303206]; Lupus Research Institute; Alliance for Lupus Research; National Institutes of Health [R01AI070983, K24 AI078004, P01AI083194, P01AR049084, R37AI024717, U01HG006828]; US Department of Veterans Affairs FX This study was generously supported by the National Health and Medical Research Council of Australia (303206 to DU and LJA), the Lupus Research Institute (to SAB), the Alliance for Lupus Research (to SAB, DU and BPT), National Institutes of Health (R01AI070983 to SAB, DU and BPT, K24 AI078004 to SAB, and P01AI083194, P01AR049084, R37AI024717 and U01HG006828 to JBH) and the US Department of Veterans Affairs (to JBH). The authors declare that there is no conflict of interest. NR 62 TC 0 Z9 0 U1 0 U2 0 PU CHIN SOCIETY IMMUNOLOGY PI BEING PA 5 DONGDAN SANTIAO, DONGCHEN DISTRICT, BEING, 100005, PEOPLES R CHINA SN 1672-7681 EI 2042-0226 J9 CELL MOL IMMUNOL JI Cell. Mol. Immunol. PD JAN PY 2016 VL 13 IS 1 SI SI BP 119 EP 131 DI 10.1038/cmi.2014.138 PG 13 WC Immunology SC Immunology GA DG3UQ UT WOS:000371996300013 PM 25640655 ER PT J AU Nellore, A Fishman, JA AF Nellore, Anoma Fishman, Jay A. TI The Microbiome, Systemic Immune Function, and Allotransplantation SO CLINICAL MICROBIOLOGY REVIEWS LA English DT Review ID T-CELL EXHAUSTION; EPSTEIN-BARR-VIRUS; BRONCHIOLITIS OBLITERANS SYNDROME; ORTHOTOPIC LIVER-TRANSPLANTATION; CHRONIC VIRAL-INFECTION; HEPATITIS-C; CYTOMEGALOVIRUS-INFECTION; INTESTINAL MICROBIOTA; RENAL-TRANSPLANTATION; ALLOGRAFT-REJECTION AB Diverse effects of the microbiome on solid organ transplantation are beginning to be recognized. In allograft recipients, microbial networks are disrupted by immunosuppression, nosocomial and community-based infectious exposures, antimicrobial therapies, surgery, and immune processes. Shifting microbial patterns, including acute infectious exposures, have dynamic and reciprocal interactions with local and systemic immune systems. Both individual microbial species and microbial networks have central roles in the induction and control of innate and adaptive immune responses, in graft rejection, and in ischemia-reperfusion injury. Understanding the diverse interactions between the microbiome and the immune system of allograft recipients may facilitate clinical management in the future. C1 [Fishman, Jay A.] Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA. Massachusetts Gen Hosp, Transplant Ctr, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. [Nellore, Anoma] Univ Alabama Birmingham, Div Infect Dis, Birmingham, AL USA. RP Fishman, JA (reprint author), Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA. EM jfishman@partners.org NR 103 TC 4 Z9 5 U1 1 U2 2 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0893-8512 EI 1098-6618 J9 CLIN MICROBIOL REV JI Clin. Microbiol. Rev. PD JAN PY 2016 VL 29 IS 1 BP 191 EP 199 DI 10.1128/CMR.00063-15 PG 9 WC Microbiology SC Microbiology GA DG7GB UT WOS:000372251700008 PM 26656674 ER PT J AU Niu, B Xing, ZH Zhao, MM Huo, HZ Huang, GH Chen, FX Su, Q Lu, Y Wang, M Yang, J Chen, L Tang, L Zheng, LF AF Niu, Bing Xing, Zhihao Zhao, Manman Huo, Haizhong Huang, Guohua Chen, Fuxue Su, Qiang Lu, Yin Wang, Meng Yang, Jing Chen, Lei Tang, Ling Zheng, Linfeng TI Study of Drug-Drug Combinations Based on Molecular Descriptors and Physicochemical Properties SO COMBINATORIAL CHEMISTRY & HIGH THROUGHPUT SCREENING LA English DT Article DE Physicochemical properties; mRMR; drug-drug combinations; random forest; feature selection ID ESTROGEN RECEPTOR LIGANDS; BREAST-CANCER; TRASTUZUMAB HERCEPTIN; INDAZOLE ESTROGENS; CHEMICAL DATABASE; FEATURE-SELECTION; RANDOM FORESTS; QSAR ANALYSIS; PREDICTION; TAMOXIFEN AB In the present study, molecular descriptors and physicochemical properties were used to encode drug molecules. Based on this molecular representation method, Random forest was applied to construct a drug-drug combination network. After feature selection, an optimal features subset was built, which described the main factors of drugs in our prediction. As a result, the selected features can be clustered into three categories: elemental analysis, chemistry, and geometric features. And all the three types of features are essential elements of the drug-drug combination network. The final prediction model achieved a Matthew's correlation coefficient (MCC) of 0.5335 and an overall prediction accuracy of 88.79% for the 10-fold cross-validation test. C1 [Niu, Bing; Zhao, Manman; Chen, Fuxue; Su, Qiang] Shanghai Univ, Sch Life Sci, 333 Nanchen Rd, Shanghai 200444, Peoples R China. [Niu, Bing] Harvard Univ, Schepens Eye Res Inst, Dept Ophthalmol, Sch Med, 20 Staniford St, Boston, MA 02114 USA. [Xing, Zhihao; Wang, Meng; Yang, Jing] Shanghai Jiao Tong Univ Sch Med, 225 Chong Qing Nan Rd, Shanghai 200025, Peoples R China. [Huo, Haizhong] Shanghai Jiao Tong Univ, Dept Gen Surg, Shanghai Peoples Hosp 9, Sch Med, Shanghai 200011, Peoples R China. [Huo, Haizhong] Harvard Univ, Massachusetts Gen Hosp, Dept Surg, Sch Med, 20 Staniford St, Boston, MA 02114 USA. [Huang, Guohua] Shanghai Univ, Inst Syst Biol, Inst Hlth Sci, Shanghai Inst Biol Sci, Shanghai 200031, Peoples R China. [Lu, Yin] Shanghai Inst Mat Med, Drug Discovery & Design Ctr, Shanghai, Peoples R China. [Chen, Lei] Shanghai Maritime Univ, Coll Informat Engn, Shanghai 201306, Peoples R China. [Tang, Ling] Cent S Univ, Xiangya Hosp, Deprtment Phamacy, Changsha 410008, Hunan, Peoples R China. [Zheng, Linfeng] Shanghai Jiao Tong Univ, First Peoples Hosp, Dept Radiol, Peoples Hosp 1, Shanghai 200080, Peoples R China. RP Niu, B (reprint author), Shanghai Univ, Sch Life Sci, 333 Nanchen Rd, Shanghai 200444, Peoples R China. EM Bingniu@shu.edu.cn RI Chen, Lei/A-2275-2011 OI Chen, Lei/0000-0003-3068-1583 FU Shanghai Municipal Education Commission; National Natural Science Foundation of China [20973108, 81271384, 61202021, 61373028, 11371008]; Natural Science Foundation of Science and Technology Commission [12ZR1424900]; Shanghai Key Laboratory of Bio-energy Crops [13DZ2272100]; Innovation Program of Shanghai Municipal Education Commission [12YZ120]; Shanghai Educational Development Foundation [12CG55] FX The author would like to thank scholarship from Shanghai Municipal Education Commission, the National Natural Science Foundation of China (20973108, 81271384, 61202021, 61373028 and 11371008), Natural Science Foundation of Science and Technology Commission (12ZR1424900), Shanghai Key Laboratory of Bio-energy Crops (13DZ2272100), Innovation Program of Shanghai Municipal Education Commission (12YZ120) and Shanghai Educational Development Foundation (12CG55) for their financial support. We also acknowledge the ChemAxon for their excellent products. NR 52 TC 1 Z9 1 U1 9 U2 10 PU BENTHAM SCIENCE PUBL LTD PI SHARJAH PA EXECUTIVE STE Y-2, PO BOX 7917, SAIF ZONE, 1200 BR SHARJAH, U ARAB EMIRATES SN 1386-2073 EI 1875-5402 J9 COMB CHEM HIGH T SCR JI Comb. Chem. High Throughput Screen PY 2016 VL 19 IS 2 BP 153 EP 160 DI 10.2174/1386207319666151110122931 PG 8 WC Biochemical Research Methods; Chemistry, Applied; Pharmacology & Pharmacy SC Biochemistry & Molecular Biology; Chemistry; Pharmacology & Pharmacy GA DG5FZ UT WOS:000372103100008 PM 26552439 ER PT J AU Cade, BE Gottlieb, DJ Lauderdale, DS Bennett, DA Buchman, AS Buxbaum, SG De Jager, PL Evans, DS Fulop, T Gharib, SA Johnson, WC Kim, H Larkin, EK Lee, SK Lim, AS Punjabi, NM Shin, C Stone, KL Tranah, GJ Weng, J Yaffe, K Zee, PC Patel, SR Zhu, XF Redline, S Saxena, R AF Cade, Brian E. Gottlieb, Daniel J. Lauderdale, Diane S. Bennett, David A. Buchman, Aron S. Buxbaum, Sarah G. De Jager, Philip L. Evans, Daniel S. Fueloep, Tibor Gharib, Sina A. Johnson, W. Craig Kim, Hyun Larkin, Emma K. Lee, Seung Ku Lim, Andrew S. Punjabi, Naresh M. Shin, Chol Stone, Katie L. Tranah, Gregory J. Weng, Jia Yaffe, Kristine Zee, Phyllis C. Patel, Sanjay R. Zhu, Xiaofeng Redline, Susan Saxena, Richa TI Common variants in DRD2 are associated with sleep duration: the CARe consortium SO HUMAN MOLECULAR GENETICS LA English DT Article ID GENOME-WIDE ASSOCIATION; D2 RECEPTOR GENE; HUMAN-BRAIN; DOPAMINE-RECEPTORS; OSTEOPOROTIC FRACTURES; ADENOSINE A(2A); HUMAN STRIATUM; METAANALYSIS; DESIGN; LOCI AB Sleep duration is implicated in the etiologies of chronic diseases and premature mortality. However, the genetic basis for sleep duration is poorly defined. We sought to identify novel genetic components influencing sleep duration in a multi-ethnic sample. Meta-analyses were conducted of genetic associations with self-reported, habitual sleep duration from seven Candidate Gene Association Resource (CARe) cohorts of over 25 000 individuals of African, Asian, European and Hispanic American ancestry. All individuals were genotyped for similar to 50 000 SNPs from 2000 candidate heart, lung, blood and sleep genes. African-Americans had additional genome-wide genotypes. Four cohorts provided replication. A SNP (rs17601612) in the dopamine D2 receptor gene (DRD2) was significantly associated with sleep duration (P = 9.8 x 10(-7)). Conditional analysis identified a second DRD2 signal with opposite effects on sleep duration. In exploratory analysis, suggestive association was observed for rs17601612 with polysomnographically determined sleep latency (P = 0.002). The lead DRD2 signal was recently identified in a schizophrenia GWAS, and a genetic risk score of 11 additional schizophrenia GWAS loci genotyped on the IBC array was also associated with longer sleep duration (P = 0.03). These findings support a role for DRD2 in influencing sleep duration. Our work motivates future pharmocogenetics research on alerting agents such as caffeine and modafinil that interact with the dopaminergic pathway and further investigation of genetic overlap between sleep and neuro-psychiatric traits. C1 [Cade, Brian E.; Gottlieb, Daniel J.; Weng, Jia; Patel, Sanjay R.; Redline, Susan; Saxena, Richa] Brigham & Womens Hosp, Div Sleep & Circadian Disorders, 75 Francis St, Boston, MA 02115 USA. [De Jager, Philip L.] Brigham & Womens Hosp, Dept Neurol & Psychiat, 75 Francis St, Boston, MA 02115 USA. [Cade, Brian E.; Gottlieb, Daniel J.; Patel, Sanjay R.; Redline, Susan; Saxena, Richa] Harvard Univ, Sch Med, Div Sleep Med, Boston, MA 02115 USA. [Gottlieb, Daniel J.] VA Boston Healthcare Syst, Boston, MA 02132 USA. [Lauderdale, Diane S.] Univ Chicago, Dept Hlth Studies, Chicago, IL 60637 USA. [Bennett, David A.; Buchman, Aron S.] Rush Univ, Med Ctr, Rush Alzheimers Dis Ctr, Chicago, IL 60612 USA. [Buxbaum, Sarah G.] Jackson State Univ, Sch Publ Hlth, Jackson, MS 39217 USA. [Evans, Daniel S.; Stone, Katie L.; Tranah, Gregory J.] Calif Pacific Med Ctr, Res Inst, San Francisco, CA 94107 USA. [Fueloep, Tibor] Univ Mississippi, Dept Internal Med, Med Ctr, Jackson, MS 39216 USA. [Gharib, Sina A.] Univ Washington, Div Pulm & Crit Care Med, UW Med Sleep Ctr, Computat Med Core,Ctr Lung Biol, Seattle, WA 98195 USA. [Johnson, W. Craig] Univ Washington, Dept Biostat, Seattle, WA 98195 USA. [Kim, Hyun; Lee, Seung Ku; Shin, Chol] Korea Univ, Ansan Med Ctr, Inst Human Genom Study, Ansan 465707, South Korea. [Larkin, Emma K.] Vanderbilt Univ, Med Ctr, Div Allergy Pulm & Crit Care, Dept Med, Nashville, TN 37232 USA. [Lim, Andrew S.] Univ Toronto, Sunnybrook Hlth Sci Ctr, Dept Med, Div Neurol, 2075 Bayview Ave, Toronto, ON M4N 3M5, Canada. [Punjabi, Naresh M.] Johns Hopkins Univ, Sch Med, Dept Med, Baltimore, MD 21205 USA. [Shin, Chol] Korea Univ, Ansan Hosp, Dept Internal Med, Div Pulm Sleep & Crit Care Med, Ansan 425707, South Korea. [Yaffe, Kristine] Univ Calif San Francisco, Dept Psychiat, San Francisco, CA 94107 USA. [Yaffe, Kristine] Univ Calif San Francisco, Dept Neurol, San Francisco, CA 94107 USA. [Yaffe, Kristine] Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94107 USA. [Yaffe, Kristine] San Francisco VA Med Ctr, San Francisco, CA 94121 USA. [Zee, Phyllis C.] Northwestern Univ, Dept Neurol, Chicago, IL 60611 USA. [Zee, Phyllis C.] Northwestern Univ, Sleep Med Ctr, Chicago, IL 60611 USA. [Patel, Sanjay R.; Redline, Susan] Beth Israel Deaconess Med Ctr, Div Pulm Crit Care & Sleep Med, Boston, MA 02215 USA. [Zhu, Xiaofeng] Case Western Reserve Univ, Sch Med, Dept Epidemiol & Biostat, Cleveland, OH 44106 USA. [Saxena, Richa] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA. [Saxena, Richa] Massachusetts Gen Hosp, Dept Anesthesia Pain & Crit Care Med, Boston, MA 02114 USA. [Saxena, Richa] Broad Inst, Program Med & Populat Genet, Cambridge, MA 02142 USA. RP Cade, BE (reprint author), Harvard Univ, Sch Med, Brigham & Womens Hosp, Div Sleep & Circadian Disorders, 221 Longwood Ave, Boston, MA 02115 USA. EM bcade@partners.org OI Patel, Sanjay/0000-0002-9142-5172 FU National Institutes of Health [T32-HL007901-16, R01-HL113338-02, N01-HC-65226, HHSN268200625226C, RO1 HL46380-01-16, M01-RR-00080, N01-HC-25195, R01-HL-092577, R01-HL-076784, R01-AG-028321, U01HL064360, R01AG017917, P30AG010161, R01AG015819, R01AG024480, R01NS078009, R01AG036836, R01AG030146]; NIH [R21 HL121728]; National Heart, Lung, and Blood Institute [HHSN268201100005C, HHSN268201100006C, HHSN268201100007C, HHSN268201100008C, HHSN268201100009C, HHSN268201100010C, HHSN268201100011C, HHSN268201100012C]; National Human Genome Research Institute [U01HG004402]; National Institutes of Health and NIH Roadmap for Medical Research [UL1RR025005]; National Institute of Neurological Disorders and Stroke; National Institute on Aging [AG023629, P30AG10161, R01AG15819, R01AG24871, R01AG26147, R01AG26916, P01AG09466, P01AG14449, K08AG00849, K23AG23675, R01 AG005407, R01 AR35582, R01 AR35583, R01 AR35584, R01 AG005394, R01 AG027574, R01 AG027576]; University of Alabama at Birmingham [HHSN268201300025C, HHSN268201300026C]; Northwestern University [HHSN268201300027C]; University of Minnesota [HHSN268201300028C, U01 HL053934]; Kaiser Foundation Research Institute [HHSN268201300029C]; Johns Hopkins University School of Medicine [HHSN268200900041C]; Intramural Research Program of the National Institute on Aging; National Institute on Minority Health and Health Disparities; MESA [N01-HC-95159, N01-HC-95160, N01-HC-95161, N01-HC-95162, N01-HC-95163, N01-HC-95164, N01-HC-95165, N01-HC-95166, N01-HC-95167, N01-HC-95168, N01-HC-95169, CTSA UL1-RR-024156]; Case Western University [U01 HL063463]; University of California, Davis [U01 HL053916]; University of Arizona [U01 HL053938]; University of Pittsburgh [U01 HL077813]; Boston University [U01 HL053941]; MedStar Research Institute [U01 HL063429]; Johns Hopkins University [U01 HL053937]; Korean Genome Analysis Project [4845-301]; Korean Genome and Epidemiology Study [2001-347-6111-221, 2002-347-6111-221]; Korea Biobank Project [4851-307, KBP-2013-25]; Korea Center for Disease Control and Prevention, Republic of Korea; Illinois Department of Public Health; Elsie Heller Brain Bank Endowment Fund; Robert C. Borwell Chair of Neurological Sciences; National Institute of Arthritis and Musculoskeletal and Skin Diseases [RC2ARO58973]; National Center for Research Resources; NIH Roadmap for Medical Research [U01 AR45580, U01 AR45614, U01 AR45632, U01 AR45647, U01 AR45654, U01 AR45583]; [HHSN268201200036C]; [HHSN268200800007C]; [N01 HC55222]; [N01HC85079]; [N01HC85080]; [N01HC85081]; [N01HC85082]; [N01HC85083]; [N01HC85086]; [U01 AG18197]; [U01-AG027810]; [UL1 RR024140]; [R01HL087641]; [R01HL59367]; [R01HL086694]; [HL080295]; [AG0005]; [HHSN268201300046C]; [HHSN268201300047C]; [HHSN268201300048C]; [HHSN268201300049C]; [HHSN268201300050C]; [R01 HL071194]; [R01 HL070848]; [R01 HL070847]; [R01 HL070842]; [R01 HL070841]; [R01 HL070837]; [R01 HL070838]; [R01 HL070839] FX B.E.C. is supported by National Institutes of Health grants (T32-HL007901-16, R01-HL113338-02). R.S. is supported by NIH R21 HL121728. Centralized CARe resources for the following eight cohorts were supported through a National Institutes of Health grant to the Broad Institute (N01-HC-65226).; Atherosclerotic Risk in Communities (ARIC): The Atherosclerosis Risk in Communities Study is carried out as a collaborative study supported by National Heart, Lung, and Blood Institute contracts (HHSN268201100005C, HHSN268201100006C, HHSN268201100007C, HHSN268201100008C, HHSN268201100009C, HHSN268201100010C, HHSN268201100011C, and HHSN268201100012C, R01HL087641, R01HL59367 and R01HL086694); a National Human Genome Research Institute contract (U01HG004402); and National Institutes of Health contract (HHSN268200625226C). Infrastructure was partly supported by Grant Number (UL1RR025005), a component of the National Institutes of Health and NIH Roadmap for Medical Research.; Cardiovascular Health Study (CHS): This research was supported by contracts (HHSN268201200036C, HHSN268200800007C, N01 HC55222, N01HC85079, N01HC85080, N01HC85081, N01HC85082, N01HC85083, N01HC85086) and grant (HL080295) from the National Heart, Lung, and Blood Institute, with additional contribution from the National Institute of Neurological Disorders and Stroke. Additional support was provided by (AG023629) from the National Institute on Aging.; Cleveland Family Study (CFS): National Institutes of Health grants to Case Western Reserve University (RO1 HL46380-01-16, M01-RR-00080).; Coronary Artery Risk in Young Adults (CARDIA): The Coronary Artery Risk Development in Young Adults Study (CARDIA) 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 and an intra-agency agreement between the National Institute on Aging and the National Heart, Lung, and Blood Institute (AG0005).; Framingham Heart Study (FHS): National Institutes of Health grants to Boston University (N01-HC-25195, R01-HL-092577, R01-HL-076784, R01-AG-028321).; Jackson Heart Study (JHS): 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.; Multi-Ethnic Study of Atherosclerosis (MESA): MESA is conducted and supported by the National Heart, Lung, and Blood Institute in collaboration with MESA investigators. Support for MESA is provided by contracts (N01-HC-95159, N01-HC-95160, N01-HC-95161, N01-HC-95162, N01-HC-95163, N01-HC-95164, N01-HC-95165, N01-HC-95166, N01-HC-95167, N01-HC-95168, N01-HC-95169 and CTSA UL1-RR-024156). Funding for CARe genotyping was provided by the National Heart, Lung, and Blood Institute contract (N01-HC-65226).; Sleep Heart Health Study (SHHS): National Institutes of Health grants to Johns Hopkins University (U01HL064360), Case Western University (U01 HL063463), University of California, Davis (U01 HL053916), University of Arizona (U01 HL053938), University of Minnesota (relocated in 2006 to University of Arizona) (U01 HL053934), University of Pittsburgh (U01 HL077813), Boston University (U01 HL053941), MedStar Research Institute (U01 HL063429), Johns Hopkins University (U01 HL053937).; Korean Genome and Epidemiology Study (KoGES): This study was provided with biospecimens and data from the Korean Genome Analysis Project (4845-301), the Korean Genome and Epidemiology Study (2001-347-6111-221, 2002-347-6111-221) and Korea Biobank Project (4851-307, KBP-2013-25) that were supported by the Korea Center for Disease Control and Prevention, Republic of Korea.; Religious Orders Study (ROS): The Religious Orders Study is supported by grants from the National Institute on Aging: P30AG10161, R01AG15819, R01AG24871, R01AG26147, R01AG26916, P01AG09466, P01AG14449; K08AG00849, K23AG23675, the Illinois Department of Public Health, the Elsie Heller Brain Bank Endowment Fund, and the Robert C. Borwell Chair of Neurological Sciences.; Rush Memory and Aging Project (MAP): The Rush Memory and Aging Project is supported by the National Institutes of Health grants R01AG017917, P30AG010161, R01AG015819, R01AG024480, R01NS078009, R01AG036836 and R01AG030146.; Osteoporotic Fractures in Men (MrOS) Study: The Osteoporotic Fractures in Men (MrOS) Study is supported by National Institutes of Health funding. The following institutes provide support: the National Institute of Arthritis and Musculoskeletal and Skin Diseases, the National Institute on Aging, the National Center for Research Resources, and NIH Roadmap for Medical Research under the following grant numbers: (U01 AR45580, U01 AR45614, U01 AR45632, U01 AR45647, U01 AR45654, U01 AR45583, U01 AG18197, U01-AG027810 and UL1 RR024140). The National Heart, Lung, and Blood Institute provides funding for the MrOS Sleep ancillary study 'Outcomes of Sleep Disorders in Older Men' under the following grant numbers: (R01 HL071194, R01 HL070848, R01 HL070847, R01 HL070842, R01 HL070841, R01 HL070837, R01 HL070838 and R01 HL070839). The National Institute of Arthritis and Musculoskeletal and Skin Diseases provides funding for the MrOS ancillary study 'GWAS in MrOS and SOF' under the grant number (RC2ARO58973).; Study of Osteoporotic Fractures (SOF): The Study of Osteoporotic Fractures (SOF) is supported by National Institutes of Health funding. The National Institute on Aging provides support under the following grant numbers: (R01 AG005407, R01 AR35582, R01 AR35583, R01 AR35584, R01 AG005394, R01 AG027574 and R01 AG027576). The SOF Sleep Study is supported by National Institutes of Health funding. The National Institute on Aging provides support under the following grant numbers: (R01 AG005407, R01 AR35582, R01 AR35583, R01 AR35584, R01 AG005394, R01 AG027574, R01 AG027576 and R01 AG026720). NR 92 TC 5 Z9 5 U1 3 U2 7 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 2016 VL 25 IS 1 BP 167 EP 179 DI 10.1093/hmg/ddv434 PG 13 WC Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA DG5VQ UT WOS:000372147800014 PM 26464489 ER PT J AU Horstkotte, K Brooks, M Lindsay, RW AF Horstkotte, Kate Brooks, Michelle Lindsay, Robin W. TI Creation of an Electronic Data Repository for Patients With Nasal Obstruction Undergoing Functional Rhinoplasty SO JAMA FACIAL PLASTIC SURGERY LA English DT Letter ID OUTCOMES C1 [Horstkotte, Kate; Lindsay, Robin W.] Massachusetts Eye & Ear Infirm, Div Facial Plast & Reconstruct Surg, Boston, MA 02114 USA. [Brooks, Michelle] Massachusetts Gen Hosp, Partners Res Informat Serv & Comp, Boston, MA 02114 USA. RP Lindsay, RW (reprint author), Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Div Facial Plast & Reconstruct Surg,Dept Otol & L, 243 Charles St, Boston, MA 02114 USA. EM robin_lindsay@meei.harvard.edu NR 9 TC 1 Z9 1 U1 1 U2 1 PU AMER MEDICAL ASSOC PI CHICAGO PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA SN 2168-6076 EI 2168-6092 J9 JAMA FACIAL PLAST SU JI JAMA Facial Plast. Surg. PD JAN-FEB PY 2016 VL 18 IS 1 BP 73 EP 75 DI 10.1001/jamafacial.2015.1589 PG 3 WC Surgery SC Surgery GA DG5WY UT WOS:000372152000016 PM 26540027 ER PT J AU Zamboanga, BL Tomaso, CC Cloutier, RM Blumenthal, H Kenney, SR Borsari, B AF Zamboanga, Byron L. Tomaso, Cara C. Cloutier, Renee M. Blumenthal, Heidemarie Kenney, Shannon R. Borsari, Brian TI Drinking Game Participation Among High School and Incoming College Students A Narrative Review SO JOURNAL OF ADDICTIONS NURSING LA English DT Review DE college transition; adolescents; incoming college students; drinking games; alcohol use; high school students ID RANDOMIZED CONTROLLED-TRIAL; ILLICIT DRUG-USE; ALCOHOL-USE; HEAVY-DRINKING; MOTIVES; RISK; INTERVENTION; TRANSITION; BEHAVIORS; 1ST-YEAR AB The transition from high school to college has been characterized as a potentially vulnerable period because of decreased parental supervision and increased autonomy. This transition can increase risk for participation in high-risk behaviors such as drinking games (DGs), which are a social drinking activity that encourages intoxication and are associated with negative alcohol-related consequences. To date, there has not been a narrative review of DG research that examines this activity among high schoolers and incoming college students specifically, and thus, the current review bridges this gap. Findings indicate that DG participation is consistently linked to negative consequences (e.g., passing out, becoming sick) and other high-risk behaviors, such as prepartying (drinking before going to a social event). In addition, DG participation is linked to demographic (e.g., age, gender), psychological (e.g., personality, alcohol cognitions), and contextual/cultural factors (e.g., the college drinking culture). These findings have implications for current prevention and intervention efforts and suggest promising directions for future research. C1 [Zamboanga, Byron L.; Tomaso, Cara C.] Smith Coll, Northampton, MA 01063 USA. [Cloutier, Renee M.; Blumenthal, Heidemarie] Univ N Texas, Denton, TX 76203 USA. [Kenney, Shannon R.] Brown Univ, Providence, RI 02912 USA. [Borsari, Brian] San Francisco VA Med Ctr, San Francisco, CA USA. [Borsari, Brian] Univ Calif San Francisco, San Francisco, CA 94143 USA. RP Zamboanga, BL; Tomaso, CC (reprint author), Smith Coll, Dept Psychol, Northampton, MA 01063 USA. EM bzamboan@smith.edu; ctomaso@smith.edu FU National Institute on Alcohol Abuse and Alcoholism [R01-AA017427]; VISN1 Career Development Award [V1CDA2012-18] FX Brian Borsari's contribution to this manuscript was supported by National Institute on Alcohol Abuse and Alcoholism Grant R01-AA017427 and VISN1 Career Development Award V1CDA2012-18. The contents of this manuscript do not represent the views of the National Institute on Alcohol Abuse and Alcoholism, the Department of Veterans Affairs, or the United States Government. Byron L. Zamboanga and Cara C. Tomaso contributed equally to the writing of this manuscript. NR 54 TC 2 Z9 2 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 1088-4602 EI 1548-7148 J9 J ADDICT NURS JI J. Addict. Nurs. PD JAN-MAR PY 2016 VL 27 IS 1 BP 24 EP 31 DI 10.1097/JAN.0000000000000108 PG 8 WC Substance Abuse; Nursing SC Substance Abuse; Nursing GA DG6RV UT WOS:000372214700004 PM 26950839 ER PT J AU Kim, YH Beak, SH Charidimou, A Song, M AF Kim, Yong Hwan Beak, Seung Han Charidimou, Andreas Song, Min TI Discovering New Genes in the Pathways of Common Sporadic Neurodegenerative Diseases: A Bioinformatics Approach SO JOURNAL OF ALZHEIMERS DISEASE LA English DT Article DE Alzheimer's disease; bio-textmining; literature-based discovery; Parkinson's disease ID HUNTINGTONS-DISEASE; MENTAL-RETARDATION; ADHERENS JUNCTIONS; EVENT EXTRACTION; LRRK2; DOMAIN; PRESENILIN-1; EXPRESSION; NETWORKS; SYSTEM AB Late onset Alzheimer's disease (AD) and Parkinson's disease (PD) are mostly "sporadic" age-related neurode-generative disorders, but with a clear genetic component. However, their genetic architecture is complex and heterogeneous, largely remaining a conundrum, with only a handful of well-established genetic risk factors consistently associated with these diseases. It is possible that numerous, yet undiscovered, AD and PD related genes might exist. We focused on the 'gene' as a mediator to find new potential genes that might have a relationship with both disorders using bio-literature mining techniques. Based on Entrez Gene, we extracted the genes and directional gene-gene relation in the entire MEDLINE records and then constructed a directional gene-gene network. We identified common genes associated with two different but related diseases by performing shortest path analysis on the network. With our approach, we were able to identify and map already known genes that have a direct relationship with PD and AD. In addition, we identified 7 genes previously unknown to be a bridge between these two disorders. We confirmed 4 genes, ROS1, FMN1, ATP8A2, and SNORD12C, by biomedical literature and further checked 3 genes, ERVK-10, PRS, and C7orf49, that might have a high possibility to be related with both diseases. Additional experiments were performed to demonstrate the effectiveness of our proposed method. Comparing to the co-occurrence approach, our approach detected 25% more candidate genes and verified 10% more genes that have the relationship between both diseases than the co-occurrence approach did. C1 [Kim, Yong Hwan; Song, Min] Yonsei Univ, Dept Lib & Informat Sci, 50 Yonsei Ro, Seoul 120749, South Korea. [Beak, Seung Han] Yonsei Univ, Inst Convergence, 50 Yonsei Ro, Seoul 120749, South Korea. [Charidimou, Andreas] Harvard Univ, Sch Med, Dept Neurol, Massachusetts Gen Hosp,Stroke Res Ctr, Boston, MA 02115 USA. RP Song, M (reprint author), Yonsei Univ, Dept Lib & Informat Sci, 50 Yonsei Ro, Seoul 120749, South Korea. EM min.song@yonsei.ac.kr FU Bio-Synergy Research Project of the Ministry of Science, ICT, and Future Planning through the National Research Foundation [NRF-2013M3A9C4078138] FX This work was supported by the Bio-Synergy Research Project (NRF-2013M3A9C4078138) of the Ministry of Science, ICT, and Future Planning through the National Research Foundation. NR 53 TC 0 Z9 0 U1 2 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 2016 VL 51 IS 1 BP 293 EP 312 DI 10.3233/JAD-150769 PG 20 WC Neurosciences SC Neurosciences & Neurology GA DG6GO UT WOS:000372181900025 PM 26836166 ER PT J AU Muralidhar, V Xiang, M Orio, PF Martin, NE Beard, CJ Feng, FY Hoffman, KE Nguyen, PL AF Muralidhar, Vinayak Xiang, Michael Orio, Peter F., III Martin, Neil E. Beard, Clair J. Feng, Felix Y. Hoffman, Karen E. Nguyen, Paul L. TI Brachytherapy boost and cancer-specific mortality in favorable high-risk versus other high-risk prostate cancer SO JOURNAL OF CONTEMPORARY BRACHYTHERAPY LA English DT Article DE brachytherapy; favorable high-risk prostate cancer; high-risk prostate cancer; risk stratification ID ANDROGEN DEPRIVATION THERAPY; DOSE-RATE BRACHYTHERAPY; RADICAL PROSTATECTOMY; RANDOMIZED-TRIAL; COMPLICATIONS; FAILURE; DISEASE; MEN AB Purpose: Recent retrospective data suggest that brachytherapy (BT) boost may confer a cancer-specific survival benefit in radiation-managed high-risk prostate cancer. We sought to determine whether this survival benefit would extend to the recently defined favorable high-risk subgroup of prostate cancer patients (T1c, Gleason 4 + 4 = 8, PSA < 10 ng/ml or Tic, Gleason 6, PSA > 20 ng/ml). Material and methods: We identified 45,078 patients in the Surveillance, Epidemiology, and End Results database with cT1c-T3aNOMO intermediate-to high-risk prostate cancer diagnosed 2004-2011 treated with external beam radiation therapy (EBRT) only or EBRT plus BT. We used multivariable competing risks regression to determine differences in the rate of prostate cancer-specific mortality (PCSM) after EBRT + BT or EBRT alone in patients with intermediate-risk, favorable high-risk, or other high-risk disease after adjusting for demographic and clinical factors. Results: EBRT + BT was not associated with an improvement in 5-year PCSM compared to EBRT alone among patients with favorable high-risk disease (1.6% vs. 1.8%; adjusted hazard ratio [AHR]: 0.56; 95% confidence interval [CI]: 0.21-1.52, p = 0.258), and intermediate-risk disease (0.8% vs. 1.0%, AHR: 0.83, 95% CI: 0.59-1.16, p = 0.270). Others with high-risk disease had significantly lower 5-year PCSM when treated with EBRT + BT compared with EBRT alone (3.9% vs. 5.3%; AHR: 0.73; 95% CI: 0.55-0.95; p = 0.022). Conclusions: Brachytherapy boost is associated with a decreased rate of PCSM in some men with high-risk prostate cancer but not among patients with favorable high-risk disease. Our results suggest that the recently-defined "favorable high-risk" category may be used to personalize therapy for men with high-risk disease. C1 [Muralidhar, Vinayak] Harvard Univ, Sch Med, Harvard Mit Div Hlth Sci & Technol, Boston, MA USA. [Xiang, Michael] Stanford Sch Med, Dept Radiat Oncol, Stanford, CA USA. [Orio, Peter F., III; Martin, Neil E.; Beard, Clair J.; Nguyen, Paul L.] Dana Farber Canc Inst, Dept Radiat Oncol, 75 Francis St, Boston, MA 02115 USA. [Orio, Peter F., III; Martin, Neil E.; Beard, Clair J.; Nguyen, Paul L.] Brigham & Womens Hosp, 75 Francis St, Boston, MA 02115 USA. [Feng, Felix Y.] Univ Michigan, Dept Radiat Oncol, Ann Arbor, MI 48109 USA. [Hoffman, Karen E.] Univ Texas MD Anderson Canc Ctr, Dept Radiat Oncol, Houston, TX 77030 USA. RP Nguyen, PL (reprint author), Dana Farber Canc Inst, Dept Radiat Oncol, 75 Francis St, Boston, MA 02115 USA.; Nguyen, PL (reprint author), Brigham & Womens Hosp, 75 Francis St, Boston, MA 02115 USA. EM pnguyen@LROC.harvard.edu NR 26 TC 1 Z9 1 U1 2 U2 2 PU TERMEDIA PUBLISHING HOUSE LTD PI POZNAN PA KLEEBERGA ST 2, POZNAN, 61-615, POLAND SN 1689-832X EI 2081-2841 J9 J CONTEMP BRACHYTHER JI J. Contemp. Brachytherapy PD JAN-FEB PY 2016 VL 8 IS 1 BP 1 EP 6 DI 10.5114/jcb.2016.58080 PG 6 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA DG5SG UT WOS:000372138300001 PM 26985191 ER PT J AU Henderson, E AF Henderson, Elizabeth TI Potentially Dangerous Patients: A Review of the Duty to Warn Response SO JOURNAL OF EMERGENCY NURSING LA English DT Letter C1 [Henderson, Elizabeth] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Henderson, E (reprint author), Massachusetts Gen Hosp, Boston, MA 02114 USA. EM ehenderson102@gmail.com NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0099-1767 EI 1527-2966 J9 J EMERG NURS JI J. Emerg. Nurs. PD JAN PY 2016 VL 42 IS 1 BP 4 EP 5 DI 10.1016/j.jen.2015.09.009 PG 4 WC Emergency Medicine; Nursing SC Emergency Medicine; Nursing GA DG3TI UT WOS:000371992600007 PM 26825501 ER PT J AU Normandin, PA AF Normandin, Patricia A. TI BEHAVIORAL HEALTH EMERGENCIES SO JOURNAL OF EMERGENCY NURSING LA English DT Editorial Material C1 [Normandin, Patricia A.] Tufts Med Ctr, 800 Washington St, Boston, MA 02111 USA. [Normandin, Patricia A.] Northeastern Univ, Boston, MA 02115 USA. [Normandin, Patricia A.] Massachusetts Gen Hosp, Inst Hlth Profess, Boston, MA 02114 USA. RP Normandin, PA (reprint author), Tufts Med Ctr, 800 Washington St, Boston, MA 02111 USA. EM pnormandinrn@aol.com NR 6 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0099-1767 EI 1527-2966 J9 J EMERG NURS JI J. Emerg. Nurs. PD JAN PY 2016 VL 42 IS 1 BP 81 EP 84 DI 10.1016/j.jen.2015.09.013 PG 4 WC Emergency Medicine; Nursing SC Emergency Medicine; Nursing GA DG3TI UT WOS:000371992600024 PM 26825511 ER PT J AU Mihos, CG Santana, O AF Mihos, Christos G. Santana, Orlando TI Mitral valve repair for ischemic mitral regurgitation: lessons from the Cardiothoracic Surgical Trials Network randomized study SO JOURNAL OF THORACIC DISEASE LA English DT Article DE Coronary artery disease; ischemic mitral regurgitation; mitral valve repair; mitral valve replacement; papillary muscle ID ARTERY-BYPASS SURGERY; RING ANNULOPLASTY; HEART-DISEASE; REPLACEMENT; METAANALYSIS; RECURRENCE; MECHANISMS; COMPLEX AB Approximately 30% to 50% of patients will develop ischemic mitral regurgitation (MR) after a myocardial infarction, which is a result of progressive left ventricular remodeling and dysfunction of the subvalvular apparatus, and portends a poor long-term prognosis. Surgical treatment is centered on mitral valve repair utilizing a restrictive annuloplasty, or valve replacement with preservation of the subvalvular apparatus. In the recent Cardiothoracic Surgical Trials Network (CSTN) study, patients with severe ischemic MR were randomized to mitral valve repair with a restrictive annuloplasty versus chordal-sparing valve replacement, and concomitant coronary artery bypass grafting, if indicated. At 2-year follow-up, mitral valve repair was associated with a significantly higher incidence of moderate or greater recurrent MR and heart failure, with no difference in the indices of left ventricular reverse remodeling, as compared with valve replacement. The current appraisal aims to provide insight into the CSTN trial results, and discusses the evidence supporting a pathophysiologic-guided repair strategy incorporating combined annuloplasty and subvalvular repair techniques to optimize the outcomes of mitral valve repair in ischemic MR. C1 [Mihos, Christos G.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Cardiac Ultrasound Lab, 55 Fruit St, Boston, MA 02114 USA. [Santana, Orlando] Columbia Univ, Mt Sinai Heart Inst, Div Cardiol, Miami Beach, FL USA. RP Mihos, CG (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Cardiac Ultrasound Lab, 55 Fruit St, Boston, MA 02114 USA. EM cmihos@mgh.harvard.edu NR 32 TC 3 Z9 3 U1 0 U2 0 PU PIONEER BIOSCIENCE PUBL CO PI HONG KONG PA 9A GOLD SHINE TOWER, 346-348 QUEEN'S RD CENTRAL, SHEUNG WAN, HONG KONG, 00000, PEOPLES R CHINA SN 2072-1439 EI 2077-6624 J9 J THORAC DIS JI J. Thorac. Dis. PD JAN PY 2016 VL 8 IS 1 BP E94 EP E99 DI 10.3978/j.issn.2072-1439.2016.01.27 PG 6 WC Respiratory System SC Respiratory System GA DG5EL UT WOS:000372098000012 PM 26904260 ER PT J AU Yang, QS Lu, Y Xi, Y Cong, WX Kalra, M Wang, G AF Yang, Qingsong Lu, Yang Xi, Yan Cong, Wenxiang Kalra, Mannudeep Wang, Ge TI Sinogram-based attenuation correction in PET/CT SO JOURNAL OF X-RAY SCIENCE AND TECHNOLOGY LA English DT Article DE PET/CT; sinogram; attenuation correction ID COMPUTED-TOMOGRAPHY; INTERIOR TOMOGRAPHY; CT; EMISSION; SCANNER; IMAGES; TISSUE AB In a typical positron emission tomography/computed tomography (PET/CT) system, the attenuation correction is necessary for PET image reconstruction, which involves a transformation from the CT Hounsfield units (HU) to its linear attenuation coefficient (LAC) at 511 keV. This transformation is usually aided by an empirical bilinear function, followed by the forward projection of the transformed attenuation image. In this paper, we propose a direct method that calculates attenuation factors from CT projections, without using a reconstructed CT image. In this method, the human body is considered as a mixture of three distinct components: air, water and bone. Then, we estimate the proportions of these three components along each x-ray path and restore the attenuation factor at 511 keV with the known water and bone LACs. Our numerical results show that the proposed method produces as accurate estimation as the conventional HU mapping method. C1 [Yang, Qingsong; Xi, Yan; Cong, Wenxiang; Wang, Ge] Rensselaer Polytech Inst, Dept Biomed Engn, Troy, NY 12180 USA. [Lu, Yang] United Imaging Healthcare Co Ltd, Mol Imaging Business Unit, Dept Phys & Reconstruct, Shanghai, Peoples R China. [Kalra, Mannudeep] Massachusetts Gen Hosp, Div Thorac Imaging, Boston, MA 02114 USA. [Kalra, Mannudeep] Massachusetts Gen Hosp, Div Cardiac Imaging, Boston, MA 02114 USA. RP Wang, G (reprint author), Rensselaer Polytech Inst, Dept Biomed Engn, Troy, NY 12180 USA. EM wangg6@rpi.edu NR 26 TC 0 Z9 0 U1 1 U2 2 PU IOS PRESS PI AMSTERDAM PA NIEUWE HEMWEG 6B, 1013 BG AMSTERDAM, NETHERLANDS SN 0895-3996 EI 1095-9114 J9 J X-RAY SCI TECHNOL JI J. X-Ray Sci. Technol. PY 2016 VL 24 IS 1 BP 9 EP 22 DI 10.3233/XST-160536 PG 14 WC Instruments & Instrumentation; Optics; Physics, Applied SC Instruments & Instrumentation; Optics; Physics GA DF9ZQ UT WOS:000371721700002 PM 26890905 ER PT J AU Karimi, M Zare, H Nik, AB Yazdani, N Hamrang, M Mohamed, E Zangabad, PS Basri, SMM Bakhtiari, L Hamblin, MR AF Karimi, Mahdi Zare, Hossein Nik, Amirala Bakhshian Yazdani, Narges Hamrang, Mohammad Mohamed, Elmira Zangabad, Parham Sahandi Basri, Seyed Masoud Moosavi Bakhtiari, Leila Hamblin, Michael R. TI Nanotechnology in diagnosis and treatment of coronary artery disease SO NANOMEDICINE LA English DT Review DE atherosclerosis; coronary artery disease; nanocarriers; nanotechnology; restenosis; stent coatings; vulnerable plaque ID MESOPOROUS SILICA NANOPARTICLES; DUAL ANTIPLATELET THERAPY; DRUG-ELUTING STENTS; IN-VIVO; MAGNETIC NANOPARTICLES; ATHEROSCLEROTIC PLAQUES; NEOINTIMAL HYPERPLASIA; NANOCOMPOSITE POLYMER; PLGA NANOPARTICLES; LOCAL-DELIVERY AB Nanotechnology could provide a new complementary approach to treat coronary artery disease (CAD) which is now one of the biggest killers in the Western world. The course of events, which leads to atherosclerosis and CAD, involves many biological factors and cellular disease processes which may be mitigated by therapeutic methods enhanced by nanotechnology. Nanoparticles can provide a variety of delivery systems for cargoes such as drugs and genes that can address many problems within the arteries. In order to improve the performance of current stents, nanotechnology provides different nanomaterial coatings, in addition to controlled-release nanocarriers, to prevent in-stent restenosis. Nanotechnology can increase the efficiency of drugs, improve local and systematic delivery to atherosclerotic plaques and reduce the inflammatory or angiogenic response after intravascular intervention. Nanocarriers have potential for delivery of imaging and diagnostic agents to precisely targeted destinations. This review paper will cover the current applications and future outlook of nanotechnology, as well as the main diagnostic methods, in the treatment of CAD. C1 [Karimi, Mahdi] Iran Univ Med Sci, Dept Med Nanotechnol, Fac Adv Technol Med, Tehran, Iran. [Zare, Hossein; Yazdani, Narges; Hamrang, Mohammad; Mohamed, Elmira; Bakhtiari, Leila] Iran Univ Sci & Technol, Biomat Grp, Mat Sci & Engn Dept, POB 1684613114, Tehran, Iran. [Nik, Amirala Bakhshian] Univ Tehran, Div Biomed Engn, Dept Life Sci Engn, Fac New Sci & Technol, Tehran 1439957131, Iran. [Zangabad, Parham Sahandi] Sharif Univ Technol, Dept Mat Sci & Engn, POB 11365-9466, Tehran 14588, Iran. [Basri, Seyed Masoud Moosavi] Inst Res Fundamental Sci, Sch Comp Sci, Tehran, Iran. [Basri, Seyed Masoud Moosavi] Shahid Beheshti Univ, Civil & Environm Engn Dept, Tehran, Iran. [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 02139 USA. RP Hamblin, MR (reprint author), Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA.; Hamblin, MR (reprint author), Harvard Univ, Sch Med, Dept Dermatol, Boston, MA 02115 USA.; Hamblin, MR (reprint author), Harvard Mit Div Hlth Sci & Technol, Cambridge, MA 02139 USA. EM hamblin@helix.mgh.harvard.edu FU US NIH [R01AI050875] FX MR Hamblin was supported by US NIH grant R01AI050875. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed. NR 110 TC 5 Z9 5 U1 3 U2 16 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 2016 VL 11 IS 5 BP 513 EP 530 DI 10.2217/nnm.16.3 PG 18 WC Biotechnology & Applied Microbiology; Nanoscience & Nanotechnology SC Biotechnology & Applied Microbiology; Science & Technology - Other Topics GA DG5WA UT WOS:000372148800007 PM 26906471 ER PT J AU Bakshi, R Mittal, S Liao, ZX Scherzer, CR AF Bakshi, Rachit Mittal, Shuchi Liao, Zhixiang Scherzer, Clemens R. TI A Feed-Forward Circuit of Endogenous PGC-1 alpha and Estrogen Related Receptor alpha Regulates the Neuronal Electron Transport Chain SO PARKINSONS DISEASE LA English DT Article ID PARKINSONS-DISEASE; MITOCHONDRIAL BIOGENESIS; ERR-ALPHA; MOUSE MODEL; OXIDATIVE-PHOSPHORYLATION; NIGROSTRIATAL SYSTEM; COACTIVATOR PGC-1; NEURODEGENERATION; EXPRESSION; PIOGLITAZONE AB Peroxisome proliferator-activated receptor gamma coactivator 1 alpha (PGC-1 alpha) is a central regulator of cellular and mitochondrial metabolism. Cellular bioenergetics are critically important in "energy-guzzling" neurons, but the components and wiring of the transcriptional circuit through which PGC-1 alpha regulates the neuronal electron transport chain have not been established. This information may be vital for restoring neuronal bioenergetics gene expression that is compromised during incipient Parkinson's neuropathology and in aging-dependent brain diseases. Here we delineate a neuronal transcriptional circuit controlled by endogenous PGC-1 alpha. We show that a feed-forward circuit of endogenous neuronal PGC-1 alpha and the orphan nuclear estrogen-related receptor alpha (ERR alpha) activates the nuclear-encoded mitochondrial electron transport chain. PGC-1 alpha not only trans-activated expression of ERR alpha, but also coactivated ERR alpha target genes in complexes I, II, IV, and V of the neuronal electron transport chain via association with evolutionary conserved ERR alpha promoter binding motifs. Chemical activation of this transcriptional program induced transcription of the neuronal electron transport chain. These data highlight a neuronal transcriptional circuit regulated by PGC-1 alpha that can be therapeutically targeted for Parkinson's and other neurodegenerative diseases. C1 [Bakshi, Rachit; Mittal, Shuchi; Liao, Zhixiang; Scherzer, Clemens R.] Harvard Univ, Sch Med, Neurogen Lab, Cambridge, MA 02139 USA. [Bakshi, Rachit; Mittal, Shuchi; Liao, Zhixiang; Scherzer, Clemens R.] Harvard Univ, Sch Med, Harvard Parkinson Personalized Med Initiat, Cambridge, MA 02139 USA. [Bakshi, Rachit; Mittal, Shuchi; Liao, Zhixiang; Scherzer, Clemens R.] Brigham & Womens Hosp, Cambridge, MA 02139 USA. [Scherzer, Clemens R.] Brigham & Womens Hosp, Dept Neurol, Boston, MA 02115 USA. [Scherzer, Clemens R.] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. [Scherzer, Clemens R.] Harvard NeuroDiscovery Ctr, Biomarkers Program, Boston, MA 02115 USA. RP Scherzer, CR (reprint author), Harvard Univ, Sch Med, Neurogen Lab, Cambridge, MA 02139 USA.; Scherzer, CR (reprint author), Harvard Univ, Sch Med, Harvard Parkinson Personalized Med Initiat, Cambridge, MA 02139 USA.; Scherzer, CR (reprint author), Brigham & Womens Hosp, Cambridge, MA 02139 USA.; Scherzer, CR (reprint author), Brigham & Womens Hosp, Dept Neurol, Boston, MA 02115 USA.; Scherzer, CR (reprint author), Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA.; Scherzer, CR (reprint author), Harvard NeuroDiscovery Ctr, Biomarkers Program, Boston, MA 02115 USA. EM cscherzer@rics.bwh.harvard.edu FU NIH [U01 NS082157]; US Department of Defense; M.E.M.O. Hoffman Foundation FX This work was supported by NIH Grant U01 NS082157, the US Department of Defense, and the M.E.M.O. Hoffman Foundation. NR 46 TC 0 Z9 0 U1 1 U2 1 PU HINDAWI PUBLISHING CORP PI NEW YORK PA 410 PARK AVENUE, 15TH FLOOR, #287 PMB, NEW YORK, NY 10022 USA SN 2090-8083 EI 2042-0080 J9 PARKINSONS DIS-US JI Parkinsons Dis. PY 2016 AR 2405176 DI 10.1155/2016/2405176 PG 9 WC Clinical Neurology SC Neurosciences & Neurology GA DG7QR UT WOS:000372279300001 ER PT J AU Ingelfinger, JR Kalantar-Zadeh, K Schaefer, F AF Ingelfinger, Julie R. Kalantar-Zadeh, Kamyar Schaefer, Franz CA World Kidney Day Steering Comm TI Averting the Legacy of Kidney Disease - Focus on Childhood SO AMERICAN JOURNAL OF NEPHROLOGY LA English DT Article ID NEPHROLOGY ASSOCIATION IPNA; RENAL REPLACEMENT THERAPY; LOW-BIRTH-WEIGHT; NONCOMMUNICABLE DISEASES; INTERNATIONAL SOCIETY; CONSENSUS STATEMENT; PROSPECTIVE COHORT; GLOBAL HEALTH; CHILDREN; EPIDEMIOLOGY AB World Kidney Day 2016 focuses on kidney disease in childhood and the antecedents of adult kidney disease that can begin in earliest childhood. Chronic kidney disease (CKD) in childhood differs from that in adults, as the largest diagnostic group among children includes congenital anomalies and inherited disorders, with glomerulopathies and kidney disease in the setting of diabetes being relatively uncommon. In addition, many children with acute kidney injury will ultimately develop sequelae that may lead to hypertension and CKD in later childhood or in adult life. Children born early or who are small-for date newborns have relatively increased risk for the development of CKD later in life. Persons with a high-risk birth and early childhood history should be watched closely in order to help detect early signs of kidney disease in time to provide effective prevention or treatment. Successful therapy is feasible for advanced CKD in childhood; there is evidence that children fare better than adults, if they receive kidney replacement therapy including dialysis and transplantation, while only a minority of children may require this ultimate intervention. Because there are disparities in access to care, effort is needed so that those children with kidney disease, wherever they live, may be treated effectively, irrespective of their geographic or economic circumstances. Our hope is that World Kidney Day will inform the general public, policy makers and caregivers about the needs and possibilities surrounding kidney disease in childhood. (C) 2016 S. Karger AG, Basel C1 [Ingelfinger, Julie R.] Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. [Ingelfinger, Julie R.] Massachusetts Gen Hosp, Mass Gen Hosp Children, Pediat Nephrol, Boston, MA 02114 USA. [Ingelfinger, Julie R.] Massachusetts Gen Hosp, Mass Gen Hosp Children, Pediactr, Boston, MA 02114 USA. [Kalantar-Zadeh, Kamyar] Univ Calif Irvine, Dept Med, Div Nephrol & Hypertens, Irvine, CA 92717 USA. [Kalantar-Zadeh, Kamyar] Univ Calif Irvine, Sch Med, Div Pediat & Publ Hlth, Irvine, CA 92717 USA. [Kalantar-Zadeh, Kamyar] Vet Affairs Long Beach Healthcare Syst, Long Beach, CA USA. [Kalantar-Zadeh, Kamyar] Univ Calif Los Angeles, Los Angeles Fielding Sch Publ Hlth, Dept Epidemiol, Los Angeles, CA USA. [Schaefer, Franz] Heidelberg Univ, Dept Pediat, Heidelberg, Germany. [Schaefer, Franz] Univ Heidelberg Hosp, Ctr Pediat & Adolescent Med, Div Pediat Nephrol, Heidelberg, Germany. RP Ingelfinger, JR (reprint author), Care Of Fahssis M, Int Soc Nephrol, Rues Fabriques 1B, BE-1000 Brussels, Belgium. OI Kalantar-Zadeh, Kamyar/0000-0002-8666-0725 NR 33 TC 1 Z9 1 U1 0 U2 0 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0250-8095 EI 1421-9670 J9 AM J NEPHROL JI Am. J. Nephrol. PY 2016 VL 43 IS 1 BP 58 EP 64 DI 10.1159/000444509 PG 7 WC Urology & Nephrology SC Urology & Nephrology GA DG0XH UT WOS:000371788800007 PM 26895161 ER PT J AU Kensler, TW Spira, A Garber, JE Szabo, E Lee, JJ Dong, ZG Dannenberg, AJ Hait, WN Blackburn, E Davidson, NE Foti, M Lippman, SM AF Kensler, Thomas W. Spira, Ayrum Garber, Judy E. Szabo, Eva Lee, J. Jack Dong, Zigang Dannenberg, Andrew J. Hait, William N. Blackburn, Elizabeth Davidson, Nancy E. Foti, Margaret Lippman, Scott M. TI Transforming Cancer Prevention through Precision Medicine and Immune-oncology SO CANCER PREVENTION RESEARCH LA English DT Article ID COLORECTAL-CANCER; LUNG-CANCER; ASPIRIN; TUMOR; RISK AB We have entered a transformative period in cancer prevention (including early detection). Remarkable progress in precision medicine and immune-oncology, driven by extraordinary recent advances in genome-wide sequencing, big-data analytics, blood-based technologies, and deep understanding of the tumor immune microenvironment (TME), has provided unprecedented possibilities to study the biology of premalignancy. The pace of research and discovery in precision medicine and immunoprevention has been astonishing and includes the following clinical firsts reported in 2015: driver mutations detected in circulating cell-free DNA in patients with premalignant lesions (lung); clonal hematopoiesis shown to be a premalignant state; molecular selection in chemoprevention randomized controlled trial (RCT; oral); striking efficacy in RCT of combination chemoprevention targeting signaling pathway alterations mechanistically linked to germline mutation (duodenum); molecular markers for early detection validated for lung cancer and showing promise for pancreatic, liver, and ovarian cancer. Identification of HPV as the essential cause of a major global cancer burden, including HPV16 as the single driver of an epidemic of oropharyngeal cancer in men, provides unique opportunities for the dissemination and implementation of public health interventions. Important to immunoprevention beyond viral vaccines, genetic drivers of premalignant progression were associated with increasing immunosuppressive TME; and Kras vaccine efficacy in pancreas genetically engineered mouse (GEM) model required an inhibitory adjuvant (Treg depletion). In addition to developing new (e.g., epigenetic) TME regulators, recent mechanistic studies of repurposed drugs (aspirin, metformin, and tamoxifen) have identified potent immune activity. Just as precision medicine and immune-oncology are revolutionizing cancer therapy, these approaches are transforming cancer prevention. Here, we set out a brief agenda for the immediate future of cancer prevention research (including a "Pre-Cancer Genome Atlas" or " PCGA"), which will involve the inter-related fields of precision medicine and immunoprevention - pivotal elements of a broader domain of personalized public health. (C)2016 AACR. C1 [Kensler, Thomas W.] Univ Pittsburgh, Pittsburgh, PA USA. [Kensler, Thomas W.] Penn & Johns Hopkins Bloomberg Sch Publ Hlth, Baltimore, MD USA. [Spira, Ayrum] Boston Univ, Boston, MA 02215 USA. [Garber, Judy E.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Szabo, Eva] NCI, Div Canc Prevent, Rockville, MD USA. [Lee, J. Jack] Univ Texas Hlth Sci Ctr Houston, Houston, TX 77030 USA. [Dong, Zigang] Univ Minnesota, Hormel Inst, Minneapolis, MN USA. [Dannenberg, Andrew J.] Weill Cornell Med Coll, New York, NY USA. [Hait, William N.] Janssen Res & Dev LLC, Raritan, NJ USA. [Blackburn, Elizabeth] Salk Inst Biol Studies, 10010 N Torrey Pines Rd, La Jolla, CA 92037 USA. [Davidson, Nancy E.] Univ Pittsburgh, Inst Canc, Pittsburgh, PA USA. [Foti, Margaret] Amer Assoc Canc Res, Philadelphia, PA USA. [Lippman, Scott M.] Univ Calif San Diego, Moores Canc Ctr, La Jolla, CA 92093 USA. RP Lippman, SM (reprint author), Univ Calif San Diego, Moores Canc Ctr, La Jolla, CA 92093 USA. EM slippman@ucsd.edu RI Kensler, Thomas/D-8686-2014 OI Kensler, Thomas/0000-0002-6676-261X FU [NIH/NCI P30 CA023100 28] FX This work was supported in part by grant NIH/NCI P30 CA023100 28. NR 101 TC 18 Z9 18 U1 14 U2 26 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1940-6207 EI 1940-6215 J9 CANCER PREV RES JI Cancer Prev. Res. PD JAN PY 2016 VL 9 IS 1 BP 2 EP 10 DI 10.1158/1940-6207.CAPR-15-0406 PG 9 WC Oncology SC Oncology GA DG3XY UT WOS:000372005700002 PM 26744449 ER PT J AU Song, MY Mehta, RS Wu, KN Fuchs, CS Ogino, S Giovannucci, EL Chan, AT AF Song, Mingyang Mehta, Raaj S. Wu, Kana Fuchs, Charles S. Ogino, Shuji Giovannucci, Edward L. Chan, Andrew T. TI Plasma Inflammatory Markers and Risk of Advanced Colorectal Adenoma in Women SO CANCER PREVENTION RESEARCH LA English DT Article ID C-REACTIVE PROTEIN; MACROPHAGE INHIBITORY CYTOKINE-1; NESTED CASE-CONTROL; TGF-BETA SUPERFAMILY; GROWTH-FACTOR-BETA; CANCER-RISK; POSTMENOPAUSAL WOMEN; RANDOMIZED-TRIAL; COLON-CANCER; ASPIRIN USE AB Evidence remains inconclusive about the association of systemic inflammatory markers with colorectal neoplasia. We investigated whether circulating inflammatory markers were associated with risk of advanced colorectal adenoma. We measured plasma macrophage inhibitory cytokine-1 (MIC-1), C-reactive protein (CRP), interleukin-6 (IL6), and soluble TNF receptor 2 (sTNFR-2) in blood samples drawn from 32,826 women in 1989 to 1990 in the Nurses' Health Study. Through 2008, we documented 757 cases of advanced colorectal adenomas (>= 1 cm or any size with advanced histology); each case was matched by age and time of blood draw with one control randomly selected from participants who underwent lower endoscopy and did not have neoplasia. Plasma MIC-1 was associated with higher risk of advanced adenoma (P-trend = 0.04), with an OR of 1.55 (95% confidence interval, 1.03-2.32) comparing extreme quintiles of MIC-1 after adjusting for colorectal cancer-risk factors and other inflammatory markers. Among cases, MIC-1 level was positively associated with the number of adenomas (P < 0.001) and gradually increased from adenomas located in the rectum, distal colon, and up to the proximal colon. There was a strong positive association between MIC-1 and risk of adenomas with multiplicity, >= 1 cm size and location in the proximal colon (all P-trend < 0.05). CRP, IL6, or sTNFR-2 was not associated with adenoma risk. In conclusion, plasma MIC-1 was associated with higher risk of colorectal adenoma, especially multiple, large, and proximal adenomas. Our results provide further support for a role for MIC-1 in carcinogenesis and the potential for MIC-1 as an adjunctive biomarker for detection of advanced colorectal adenoma. (C) 2015 AACR. C1 [Song, Mingyang; Mehta, Raaj S.; Chan, Andrew T.] Massachusetts Gen Hosp, Clin & Translat Epidemiol Unit, Boston, MA 02114 USA. [Song, Mingyang; Mehta, Raaj S.; Ogino, Shuji; Chan, Andrew T.] Harvard Univ, Sch Med, 55 Fruit St, Boston, MA 02114 USA. [Song, Mingyang; Mehta, Raaj S.; Chan, Andrew T.] Massachusetts Gen Hosp, Div Gastroenterol, Boston, MA 02114 USA. [Song, Mingyang; Wu, Kana; Giovannucci, Edward L.] Harvard Univ, TH Chan Sch Publ Hlth, Dept Nutr, Boston, MA USA. [Song, Mingyang; Ogino, Shuji; Giovannucci, Edward L.] Harvard Univ, TH Chan Sch Publ Hlth, Dept Epidemiol, Boston, MA USA. [Fuchs, Charles S.; Giovannucci, Edward L.; Chan, Andrew T.] Harvard Univ, Sch Med, Dept Med, Channing Div Network Med, Boston, MA USA. [Fuchs, Charles S.; Ogino, Shuji] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Ogino, Shuji] Brigham & Womens Hosp, Dept Pathol, 75 Francis St, Boston, MA 02115 USA. RP Chan, AT (reprint author), Harvard Univ, Sch Med, 55 Fruit St, Boston, MA 02114 USA.; Chan, AT (reprint author), Massachusetts Gen Hosp, Boston, MA 02114 USA. EM achan@partners.org FU NIH [R01 CA137178, K24 DK098311, P01 CA87969, UM1 CA186107, R01 CA49449, R35 CA197735, 1U54CA155626] FX This work was supported by the NIH [R01 CA137178 (to A.T. Chan), K24 DK098311 (to A.T. Chan), P01 CA87969 (to M.J. Stampfer), UM1 CA186107 (to M.J. Stampfer), R01 CA49449 (to S.E. Hankinson), R35 CA197735 (to S. Ogino), and 1U54CA155626 (to F.B. Hu)]. NR 56 TC 3 Z9 3 U1 0 U2 3 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1940-6207 EI 1940-6215 J9 CANCER PREV RES JI Cancer Prev. Res. PD JAN PY 2016 VL 9 IS 1 BP 27 EP 34 DI 10.1158/1940-6207.CAPR-15-0307 PG 8 WC Oncology SC Oncology GA DG3XY UT WOS:000372005700005 PM 26511487 ER PT J AU Merrick, DT Gao, DX Miller, YE Keith, RL Baron, AE Feser, W Kennedy, TC Blatchford, PJ Braudrick, S Hirsch, FR Heasley, L Bunn, PA Franklin, WA AF Merrick, Daniel T. Gao, Dexiang Miller, York E. Keith, Robert L. Baron, Anna E. Feser, William Kennedy, Timothy C. Blatchford, Patrick J. Braudrick, Sarah Hirsch, Fred R. Heasley, Lynn Bunn, Paul A., Jr. Franklin, Wilbur A. TI Persistence of Bronchial Dysplasia Is Associated with Development of Invasive Squamous Cell Carcinoma SO CANCER PREVENTION RESEARCH LA English DT Article ID ENDOTHELIAL GROWTH-FACTOR; WHITE-LIGHT BRONCHOSCOPY; LUNG-CANCER; PREINVASIVE LESIONS; AUTOFLUORESCENCE BRONCHOSCOPY; IN-SITU; PRENEOPLASTIC LESIONS; FACTOR RECEPTOR; NATURAL COURSE; FOLLOW-UP AB Bronchial dysplasia (BD), a presumed precursor of pulmonary squamous cell carcinoma (SCC), rarely progresses to invasive cancer. A high-risk cohort at the University of Colorado provided an opportunity to directly sample airway epithelium at mapped sites on successive bronchoscopies. We have hypothesized that persistent dysplastic lesions showing a similar or higher level of dysplasia on follow-up biopsy, are associated with increased risk for the development of SCC. Endoscopic biopsies from 188 high-risk subjects were histologically classified according to the current WHO classification for BD using a numeric histology score ranging from 1 to 8 representing normal bronchial mucosa through invasive lung cancer. Differences in follow-up histology scores were compared between sites classified by clinical, histologic, and immunohistochemical variables. Subjects with a higher frequency of sites that persist or progress to high-grade dysplasia (>37.5% persist/progress, N = 35 versus <37.5% persist/progress, N = 114) show a significant association with development of incident invasive SCC (adjusted HR, 7.84; 95% confidence interval, 1.56-39.39), and those with incident lung SCC have adjusted mean follow-up histology scores 1.55 U higher than in subjects without lung cancer. Current smoking, elevated Ki67 growth fraction, histologic features of angiogenic squamous dysplasia (ASD) and higher histology score in baseline biopsies are significantly associated with increased follow-up histology scores. These results show that persistent BD is associated with the development of invasive SCC. Furthermore, increased expression of Ki67, the presence of angiogenic change and degree of baseline atypia are associated with persistence of BD. (C)2015 AACR. C1 [Merrick, Daniel T.; Hirsch, Fred R.; Franklin, Wilbur A.] Univ Colorado, Dept Pathol, Anschutz Med Campus, Aurora, CO 80045 USA. [Gao, Dexiang; Blatchford, Patrick J.] Univ Colorado, Dept Pediat, Anschutz Med Campus, Aurora, CO 80045 USA. [Miller, York E.; Keith, Robert L.] Denver Vet Affairs Med Ctr, Dept Med, Div Pulm Med, Denver, CO USA. [Miller, York E.; Keith, Robert L.; Kennedy, Timothy C.] Univ Colorado, Dept Med, Div Pulm Med, Anschutz Med Campus, Aurora, CO 80045 USA. [Baron, Anna E.; Feser, William] Colorado Sch Publ Hlth, Dept Biostat & Informat, Aurora, CO USA. [Heasley, Lynn] Univ Colorado, Dept Craniofacial Biol, Anschutz Med Campus, Aurora, CO 80045 USA. [Bunn, Paul A., Jr.] Univ Colorado, Dept Med, Div Med Oncol, Anschutz Med Campus, Aurora, CO 80045 USA. RP Merrick, DT (reprint author), Univ Colorado, Mail Stop 8104,12801 East 17th Ave,Room 5114, Aurora, CO 80045 USA. EM dan.merrick@ucdenver.edu FU Lung Specialized Programs of Research Excellence [P50 CA058187]; Cancer Center Support grant [P30 CA046934] FX This study was supported by Lung Specialized Programs of Research Excellence P50 CA058187 and Cancer Center Support grant P30 CA046934 (all authors received P30 CA046934) NR 36 TC 3 Z9 3 U1 0 U2 1 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1940-6207 EI 1940-6215 J9 CANCER PREV RES JI Cancer Prev. Res. PD JAN PY 2016 VL 9 IS 1 BP 96 EP 104 DI 10.1158/1940-6207.CAPR-15-0305 PG 9 WC Oncology SC Oncology GA DG3XY UT WOS:000372005700013 PM 26542061 ER PT J AU Charidimou, A Ni, J Martinez-Ramirez, S Vashkevich, A Ayres, A Rosand, J Gurol, EM Greenberg, SM Viswanathan, A AF Charidimou, Andreas Ni, Jun Martinez-Ramirez, Sergi Vashkevich, Anastasia Ayres, Alison Rosand, Jonathan Gurol, Edip M. Greenberg, Steven M. Viswanathan, Anand TI Cortical Superficial Siderosis in Memory Clinic Patients: Further Evidence for Underlying Cerebral Amyloid Angiopathy SO CEREBROVASCULAR DISEASES LA English DT Article DE Alzheimer's disease; Mild cognitive impairment; MRI; Cerebral amyloid angiopathy; Cortical superficial siderosis ID MATTER PERIVASCULAR SPACES; SMALL VESSEL DISEASE; COGNITIVE IMPAIRMENT; PREVALENCE; MICROBLEEDS; POPULATION; MARKER; MRI; SPECTRUM; STROKE AB Background: Cerebral amyloid angiopathy (CAA) is associated with many cases of spontaneous symptomatic lobar intracerebral haemorrhage in older individuals and is emerging as an important contributor to cognitive impairment. Cortical superficial siderosis (cSS) is an increasingly recognized haemorrhagic neuroimaging manifestation of CAA. We sought to investigate its prevalence and its association with underlying CAA among memory clinic patients. Methods: We included consecutive eligible patients who presented to the out-patient memory clinic at the Massachusetts General Hospital from 2007 to 2010 and had appropriate MRI, including blood-sensitive sequences. We analyzed the prevalence and topography of cSS according to demographic, clinical, APOE and MRI data. Results: Our cohort consisted of 339 memory clinic patients: Alzheimer's disease (n = 86); mild cognitive impairment (n = 162); vascular dementia/mixed dementia (n = 18); other dementia/undetermined (n = 42); and subjective cognitive complains (n = 31). cSS was detected in 10 patients (3%; 95% CI 1.4-5.4): in 7 cases cSS was focal and in 3 cases, it was disseminated. In multivariable logistic regression analysis, the presence of cSS was associated with lobar microbleeds (OR 1.08; 95% CI 1.03-1.13; p = 0.001, per each additional microbleed) and severe white matter hyperintensities (Fazekas score 5-6, OR 4.43; 95% CI 1.21-26.28; p = 0.028) after adjusting for age. These associations were not influenced by the clinical diagnosis. In patients with APOE data, the APOE epsilon 4/epsilon 4 genotype was over-represented among subjects with vs. without cSS. In the sub-group of patients with probable CAA (n = 68; 9 with cSS) based on the presence of strictly lobar microbleeds, cSS was also associated with a higher prevalence of severe white matter hyperintensities (66.7 vs. 10.2%; p = 0.001), high centrum semiovale perivascular spaces burden (88.9 vs. 52.4%; p = 0.041) and higher counts of lobar microbleeds (median 13; IQR 10-36 vs. median 1; IQR 1-2; p < 0.00001), compared to patients without cSS. Conclusions: Our data provide further evidence supporting the hypothesis that cSS is a manifestation of advanced CAA in memory clinic populations. Future longitudinal studies should explore any direct effect of cSS on cognition or haemorrhage risk and disease progression. (C) 2016 S. Karger AG, Basel C1 [Charidimou, Andreas; Martinez-Ramirez, Sergi; Vashkevich, Anastasia; Ayres, Alison; Rosand, Jonathan; Gurol, Edip M.; Greenberg, Steven M.; Viswanathan, Anand] Massachusetts Gen Hosp, Ctr Stroke Res, Dept Neurol, Hemorrhag Stroke Res Program, Boston, MA 02114 USA. [Viswanathan, Anand] Massachusetts Gen Hosp, Ctr Stroke Res, Massachusetts Alzheimers Dis Res Ctr ADRC, Boston, MA 02114 USA. [Rosand, Jonathan] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Neurocrit Care & Emergency Neurol, Boston, MA USA. [Rosand, Jonathan] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Human Genet Res, Boston, MA USA. [Ni, Jun] Beijing Union Med Coll Hosp, Dept Neurol, Beijing, Peoples R China. RP Viswanathan, A (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, J Kistler Stroke Res Ctr, 175 Cambridge St,Suite 300, Boston, MA 02114 USA. EM aviswanathan1@parters.org RI Gurol, Edip/J-2279-2014 OI Gurol, Edip/0000-0002-2169-4457 FU NIH [5P50AG005134, 5K23AG028726-05, 5R01AG026484-10, 5R01NS070834-05, 1R01AG047975-01] FX The project described was supported by NIH grants 5P50AG005134, 5K23AG028726-05, 5R01AG026484-10, 5R01NS070834-05, 1R01AG047975-01. NR 26 TC 5 Z9 5 U1 2 U2 3 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 1015-9770 EI 1421-9786 J9 CEREBROVASC DIS JI Cerebrovasc. Dis. PY 2016 VL 41 IS 3-4 BP 156 EP 162 DI 10.1159/000442299 PG 7 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA DG0YO UT WOS:000371792300007 PM 26751369 ER PT J AU Karimi, M Ghasemi, A Zangabad, PS Rahighi, R Basri, SMM Mirshekari, H Amiri, M Pishabad, ZS Aslani, A Bozorgomid, M Ghosh, D Beyzavi, A Vaseghi, A Aref, AR Haghani, L Bahrami, S Hamblin, MR AF Karimi, Mahdi Ghasemi, Amir Zangabad, Parham Sahandi Rahighi, Reza Basri, S. Masoud Moosavi Mirshekari, H. Amiri, M. Pishabad, Z. Shafaei Aslani, A. Bozorgomid, M. Ghosh, D. Beyzavi, A. Vaseghi, A. Aref, A. R. Haghani, L. Bahrami, S. Hamblin, Michael R. TI Smart micro/nanoparticles in stimulus-responsive drug/gene delivery systems SO CHEMICAL SOCIETY REVIEWS LA English DT Review ID MESOPOROUS SILICA NANOPARTICLES; CONTROLLED DRUG-DELIVERY; REDUCED GRAPHENE OXIDE; BLOCK-COPOLYMER MICELLES; CROSS-LINKED MICELLES; SEVERE COMBINED IMMUNODEFICIENCY; PEGYLATED LIPOSOMAL DOXORUBICIN; INTRACELLULAR CONTROLLED-RELEASE; TEMPERATURE-SENSITIVE LIPOSOMES; LIGHT-TRIGGERED DISSOCIATION AB New achievements in the realm of nanoscience and innovative techniques of nanomedicine have moved micro/nanoparticles (MNPs) to the point of becoming actually useful for practical applications in the near future. Various differences between the extracellular and intracellular environments of cancerous and normal cells and the particular characteristics of tumors such as physicochemical properties, neovasculature, elasticity, surface electrical charge, and pH have motivated the design and fabrication of inventive "smart'' MNPs for stimulus-responsive controlled drug release. These novel MNPs can be tailored to be responsive to pH variations, redox potential, enzymatic activation, thermal gradients, magnetic fields, light, and ultrasound (US), or can even be responsive to dual or multi-combinations of different stimuli. This unparalleled capability has increased their importance as site-specific controlled drug delivery systems (DDSs) and has encouraged their rapid development in recent years. An in-depth understanding of the underlying mechanisms of these DDS approaches is expected to further contribute to this groundbreaking field of nanomedicine. Smart nanocarriers in the form of MNPs that can be triggered by internal or external stimulus are summarized and discussed in the present review, including pH-sensitive peptides and polymers, redox-responsive micelles and nanogels, thermo-or magnetic-responsive nanoparticles (NPs), mechanical-or electrical-responsive MNPs, light or ultrasound-sensitive particles, and multi-responsive MNPs including dual stimuli-sensitive nanosheets of graphene. This review highlights the recent advances of smart MNPs categorized according to their activation stimulus (physical, chemical, or biological) and looks forward to future pharmaceutical applications. C1 [Karimi, Mahdi; Bahrami, S.] Iran Univ Med Sci, Fac Adv Technol Med, Dept Med Nanotechnol, Tehran, Iran. [Ghasemi, Amir; Zangabad, Parham Sahandi; Amiri, M.; Aslani, A.] Sharif Univ Technol, Dept Mat Sci & Engn, Tehran 113659466, Iran. [Rahighi, Reza] Sharif Ultrahigh Nanotechnologists SUN Co, Dept Res & Dev, POB 13488-96394, Tehran, Iran. [Rahighi, Reza] Res Inst Petr Ind, Nanotechnol Res Ctr, West Entrance Blvd,POB 14857-33111, Tehran, Iran. [Basri, S. Masoud Moosavi] Sharif Univ Technol, Bioenvironm Res Ctr, Tehran, Iran. [Basri, S. Masoud Moosavi] Shahid Beheshti Univ, Civil & Environm Engn Dept, Tehran, Iran. [Mirshekari, H.] Univ Kerala, Dept Biotechnol, Trivandrum 695001, Kerala, India. [Pishabad, Z. Shafaei] Kharazmi Univ, Fac Biol Sci, Dept Cell & Mol Biol, Tehran, Iran. [Bozorgomid, M.] Islamic Azad Univ Tehran, Dept Appl Chem, Cent Branch, Tehran, Iran. [Ghosh, D.] Univ Tehran Med Sci, Sch Adv Technol Med SATiM, Dept Med Nanotechnol, Tehran, Iran. [Vaseghi, A.] Boston Univ, Sch Mech Engn, Boston, MA 02215 USA. [Vaseghi, A.] Fac Adv Sci & Technol Isfahan, Dept Biotechnol, Esfahan, Iran. [Aref, A. R.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Canc Biol,Ctr Canc Syst Biol,Dept Genet, 44 Binney St, Boston, MA 02115 USA. [Haghani, L.] Univ Tehran Med Sci, Sch Med, Int Campus, Tehran, Iran. [Hamblin, Michael R.] Massachusetts Gen Hosp, Wellman Ctr Photomedicine, 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 02139 USA. RP Hamblin, MR (reprint author), Massachusetts Gen Hosp, Wellman Ctr Photomedicine, Boston, MA 02114 USA.; Hamblin, MR (reprint author), Harvard Univ, Sch Med, Dept Dermatol, Boston, MA 02115 USA.; Hamblin, MR (reprint author), Harvard Mit Div Hlth Sci & Technol, Cambridge, MA 02139 USA. EM Hamblin@helix.mgh.harvard.edu OI Sahandi Zangabad, Parham /0000-0001-8316-6732 FU US NIH [R01AI050875] FX Michael R. Hamblin was supported by US NIH grant R01AI050875. NR 543 TC 65 Z9 67 U1 228 U2 444 PU ROYAL SOC CHEMISTRY PI CAMBRIDGE PA THOMAS GRAHAM HOUSE, SCIENCE PARK, MILTON RD, CAMBRIDGE CB4 0WF, CAMBS, ENGLAND SN 0306-0012 EI 1460-4744 J9 CHEM SOC REV JI Chem. Soc. Rev. PY 2016 VL 45 IS 5 BP 1457 EP 1501 DI 10.1039/c5cs00798d PG 45 WC Chemistry, Multidisciplinary SC Chemistry GA DF8JV UT WOS:000371604800014 PM 26776487 ER PT J AU Loewenstein, G Price, J Volpp, K AF Loewenstein, George Price, Joseph Volpp, Kevin TI Habit formation in children: Evidence from incentives for healthy eating SO JOURNAL OF HEALTH ECONOMICS LA English DT Article DE Habit formation; Incentives; School lunch; Field experiments ID INTRINSIC MOTIVATION; EXERCISE; TRIAL AB We present findings from a field experiment conducted at 40 elementary schools involving 8000 children and 400,000 child-day observations, which tested whether providing short-run incentives can create habit formation in children. Over a 3- or 5-week period, students received an incentive for eating a serving of fruits or vegetables during lunch. Relative to an average baseline rate of 39%, providing small incentives doubled the fraction of children eating at least one serving of fruits or vegetables. Two months after the end of the intervention, the consumption rate at schools remained 21% above baseline for the 3 week treatment and 44% above baseline for the 5-week treatment. These findings indicate that short-run incentives can produce changes in behavior that persist after incentives are removed. (C) 2015 Elsevier B.V. All rights reserved. C1 [Loewenstein, George] Carnegie Mellon Univ, Social & Decis Sci, Pittsburgh, PA 15213 USA. [Price, Joseph] Brigham Young Univ, 162 FOB, Provo, UT 84602 USA. [Volpp, Kevin] Philadelphia VA Med Ctr, Philadelphia, PA USA. [Volpp, Kevin] Leonard Davis Inst, Ctr Hlth Incent & Behav Econ, Davis, CA USA. [Volpp, Kevin] Penn Med Ctr Innovat, Philadelphia, PA USA. [Volpp, Kevin] Univ Penn, Perelman Sch Med, 1120 Blockley Hall,423 Guardian Dr, Philadelphia, PA 19104 USA. [Volpp, Kevin] Univ Penn, Wharton Sch, 1120 Blockley Hall,423 Guardian Dr, Philadelphia, PA 19104 USA. RP Price, J (reprint author), Brigham Young Univ, 162 FOB, Provo, UT 84602 USA. EM joseph_price@byu.edu FU USDA Economic Research Service [59-5000-1-0034] FX The authors are grateful to the USDA Economic Research Service for research funding (grant # 59-5000-1-0034) and for the many BYU undergraduates and PTA parents that helped as research assistants on the project. This paper has benefitted from the helpful comments by Sandy Black, Dan Hamermesh, Patrick Nolen, Devin Pope, Bob Slonim, Coady Wing, Jingsan Zhu and seminar participants at the Cornell University, Harris School, University of Illinois at Chicago, University of Sydney, UT-Austin, Iowa State, University of Utah, University of Oregon, University of Iowa, and Brigham Young University. NR 22 TC 1 Z9 1 U1 8 U2 14 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0167-6296 EI 1879-1646 J9 J HEALTH ECON JI J. Health Econ. PD JAN PY 2016 VL 45 BP 47 EP 54 DI 10.1016/j.jhealeco.2015.11.004 PG 8 WC Economics; Health Care Sciences & Services; Health Policy & Services SC Business & Economics; Health Care Sciences & Services GA DG1PU UT WOS:000371840800004 PM 26717440 ER PT J AU Mejia, P Diez-Silva, M Kamena, F Lu, FX Fernandes, SM Seeberger, PH Davis, AE Mitchell, JR AF Mejia, Pedro Diez-Silva, Monica Kamena, Faustin Lu, Fengxin Fernandes, Stacey M. Seeberger, Peter H. Davis, Alvin E., III Mitchell, James R. TI Human C1-Inhibitor Suppresses Malaria Parasite Invasion and Cytoadhesion via Binding to Parasite Glycosylphosphatidylinositol and Host Cell Receptors SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article DE malaria; GPI; C1-inhibitor ID PLASMODIUM-FALCIPARUM MALARIA; EXPERIMENTAL CEREBRAL MALARIA; ANCHORED MEMBRANE-PROTEINS; C1 ESTERASE INHIBITOR; COMPLEMENT ACTIVATION; C1-ESTERASE INHIBITOR; INFECTED ERYTHROCYTES; CHONDROITIN SULFATE; REPERFUSION INJURY; SYNTHETIC GPI AB Plasmodium falciparum-induced severe malaria remains a continuing problem in areas of endemicity, with elevated morbidity and mortality. Drugs targeting mechanisms involved in severe malaria pathology, including cytoadhesion of infected red blood cells (RBCs) to host receptors and production of proinflammatory cytokines, are still necessary. Human C1-inhibitor (C1INH) is a multifunctional protease inhibitor that regulates coagulation, vascular permeability, and inflammation, with beneficial effects in inflammatory disease models, including septic shock. We found that human C1INH, at therapeutically relevant doses, blocks severe malaria pathogenic processes by 2 distinct mechanisms. First, C1INH bound to glycan moieties within P. falciparum glycosylphosphatidylinositol (PfGPI) molecules on the parasite surface, inhibiting parasite RBC invasion and proinflammatory cytokine production by parasite-stimulated monocytes in vitro and reducing parasitemia in a rodent model of experimental cerebral malaria (ECM) in vivo. Second, C1INH bound to host CD36 and chondroitin sulfate A molecules, interfering with cytoadhesion of infected RBCs by competitive binding to these receptors in vitro and reducing sequestration in specific tissues and protecting against ECM in vivo. This study reveals that C1INH is a potential therapeutic antimalarial molecule able to interfere with severe-disease etiology at multiple levels through specific interactions with both parasite PfGPIs and host cell receptors. C1 [Mejia, Pedro; Lu, Fengxin; Fernandes, Stacey M.; Davis, Alvin E., III] Harvard Univ, Immune Dis Inst, Boston, MA 02115 USA. [Mejia, Pedro; Mitchell, James R.] Harvard Univ, Harvard TH Chan Sch Publ Hlth, Dept Genet & Complex Dis, 665 Huntington Ave,Bldg 2,1st Fl,Rm 127, Boston, MA 02115 USA. [Diez-Silva, Monica] MIT, Dept Mat Sci & Engn, Cambridge, MA 02139 USA. [Kamena, Faustin] Max Planck Inst Infekt Biol, Parasitol Unit, Berlin, Germany. [Seeberger, Peter H.] Max Planck Inst Colloids & Interfaces, Dept Biomol Syst, Berlin, Germany. [Kamena, Faustin; Seeberger, Peter H.] Free Univ Berlin, Inst Chem & Biochem, Berlin, Germany. RP Mejia, P (reprint author), Harvard Univ, Harvard TH Chan Sch Publ Hlth, Dept Genet & Complex Dis, 665 Huntington Ave,Bldg 2,1st Fl,Rm 127, Boston, MA 02115 USA. EM pmejia@hsph.harvard.edu FU National Institutes of Health [AI057366, HD22082]; Harvard T. H. Chand School of Public Health; Max-Planck Society; Swiss National Science Foundation [205320-120260]; Infectious Disease Program of the Singapore-MIT Alliance for Research and Technology FX This work was supported by the National Institutes of Health (grants AI057366 and HD22082), the Harvard T. H. Chand School of Public Health (Yerby postdoctoral fellowship to P. M.), the Max-Planck Society (funding to P. H. S. and F. K.), the Swiss National Science Foundation (grant 205320-120260 to P. H. S.), and the Infectious Disease Program of the Singapore-MIT Alliance for Research and Technology (support to M. D.-S.). NR 49 TC 1 Z9 1 U1 2 U2 5 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 2016 VL 213 IS 1 BP 80 EP 89 DI 10.1093/infdis/jiv439 PG 10 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA DF2EG UT WOS:000371152700012 PM 26347576 ER PT J AU Tangutoori, S Spring, BQ Mai, ZM Palanisami, A Mensah, LB Hasan, T AF Tangutoori, Shifalika Spring, Bryan Q. Mai, Zhiming Palanisami, Akilan Mensah, Lawrence B. Hasan, Tayyaba TI Simultaneous delivery of cytotoxic and biologic therapeutics using nanophotoactivatable liposomes enhances treatment efficacy in a mouse model of pancreatic cancer SO NANOMEDICINE-NANOTECHNOLOGY BIOLOGY AND MEDICINE LA English DT Article DE Pancreatic cancer; Liposomes; Combinatorial chemotherapy; Bevacizumab; Benzoporphyrin derivative; Photodynamic therapy; Nanomedicine; Avastin; Nanoparticle ID ENDOTHELIAL GROWTH-FACTOR; ADVANCED SOLID TUMORS; PHASE-I TRIAL; PHOTODYNAMIC THERAPY; ANTIANGIOGENIC TREATMENT; OXALIPLATIN FOLFIRINOX; COMBINATION THERAPY; CATIONIC LIPOSOMES; PROSTATE-CANCER; STRESS-RESPONSE AB A lack of intracellular delivery systems has limited the use of biologics such as monoclonal antibodies (mAb) that abrogate molecular signaling pathways activated to promote escape from cancer treatment. We hypothesized that intracellular co-delivery of the photocytotoxic chromophore benzoporphyrin derivative monoacid A (BPD) and the anti-VEGF mAb bevacizumab in a nanophotoactivatable liposome (nanoPAL) might enhance the efficacy of photodynamic therapy (PDT) combined with suppression of VEGF-mediated signaling pathways. As a proof-of-concept we found that nanoPAL-PDT induced enhanced extra-and intracellular bevacizumab delivery and enhanced acute cytotoxicity in vitro. In an in vivo subcutaneous mouse model of pancreatic ductal adenocarcinoma, nanoPAL-PDT achieved significantly enhanced tumor reduction. We attribute this to the optimal incorporation of insoluble BPD into the lipid bilayer, enhancing photocytotoxicity, and the simultaneous spatiotemporal delivery of bevacizumab, ensuring efficient neutralization of the rapid but transient burst of VEGF following PDT. From the Clinical Editor: Most patients with pancreatic ductal adenocarcinoma (PDAC) by the time present the disease it is very advanced, which unavoidably translates to poor survival. For these patients, use of traditional chemotherapy often becomes ineffective due to tumor resistance to drugs. Photodynamic therapy (PDT) can be an effective modality against chemo-resistant cancers. In this article, the authors investigated the co-delivery of a photocytotoxic agent and anti-VEGF mAb using liposomes. This combination was shown to results in enhanced tumor killing. This method should be applicable to other combination of treatments. (C) 2015 Elsevier Inc. All rights reserved. C1 [Tangutoori, Shifalika; Spring, Bryan Q.; Mai, Zhiming; Palanisami, Akilan; Mensah, Lawrence B.; Hasan, Tayyaba] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Wellman Ctr Photomed, Boston, MA USA. [Hasan, Tayyaba] Harvard Mit Div Hlth Sci & Technol, Boston, MA USA. [Tangutoori, Shifalika] Nemucore Med Innovat Inc, 55 Union St, Worcester, MA 01608 USA. [Mensah, Lawrence B.] MIT, Koch Inst Integrat Canc Res, 77 Massachusetts Ave, Cambridge, MA 02139 USA. RP Hasan, T (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Wellman Ctr Photomed, Boston, MA USA.; Hasan, T (reprint author), Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA. EM thasan@mgh.harvard.edu FU National Institutes of Health (NIH)-National Cancer Institute (NCI) [F32CA144210, RO1CA160998, PO1CA084203] FX This study was supported by the National Institutes of Health (NIH)-National Cancer Institute (NCI) Grants F32CA144210, RO1CA160998 and PO1CA084203. NR 57 TC 4 Z9 4 U1 4 U2 17 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1549-9634 EI 1549-9642 J9 NANOMED-NANOTECHNOL JI Nanomed.-Nanotechnol. Biol. Med. PD JAN PY 2016 VL 12 IS 1 BP 223 EP 234 DI 10.1016/j.nano.2015.08.007 PG 12 WC Nanoscience & Nanotechnology; Medicine, Research & Experimental SC Science & Technology - Other Topics; Research & Experimental Medicine GA DG1BR UT WOS:000371800600021 PM 26390832 ER PT J AU Palumbo, A Offidani, M Pegourie, B De La Rubia, J Garderet, L Laribi, K Bosi, A Marasca, R Laubach, J Mohrbacher, A Carella, AM Singhal, AK Lynch, M Jou, YM Jakubowiak, A AF Palumbo, A. Offidani, M. Pegourie, B. De La Rubia, J. Garderet, L. Laribi, K. Bosi, A. Marasca, R. Laubach, J. Mohrbacher, A. Carella, A. M. Singhal, A. K. Lynch, M. Jou, Y-M Jakubowiak, A. TI Elotuzumab plus bortezomib and dexamethasone (EBd) versus bortezomib and dexamethasone (Bd) in patients (Pts) with relapsed/refractory multiple myeloma (RRMM)-2-year follow-up SO ONCOLOGY RESEARCH AND TREATMENT LA English DT Meeting Abstract C1 [Palumbo, A.] Osped Molinette, AOU San Giovanni Battista Torino, Turin, Italy. [Offidani, M.] AOU Osped Riuniti Ancona, Ancona, Italy. [Pegourie, B.] Hop Albert Michallon, CHU Grenoble, Grenoble, France. [De La Rubia, J.] HUP La Fe, Valencia, Spain. [Garderet, L.] Hop St Antoine, F-75571 Paris, France. [Laribi, K.] Ctr Hosp, Le Mans, France. [Bosi, A.] AOU Careggi, Florence, Italy. [Marasca, R.] AOU Policlin Modena, Modena, Italy. [Laubach, J.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Mohrbacher, A.] Univ So Calif, Norris Comprehens Canc Ctr, Los Angeles, CA USA. [Carella, A. M.] IRCCS San Martino IST, Genoa, Italy. [Singhal, A. K.] AbbVie Biotherapeut Inc ABR, Redwood City, CA USA. [Lynch, M.] Bristol Myers Squibb, Wallingford, Oxon, England. [Jou, Y-M] Bristol Myers Squibb, Hopewell, England. [Jakubowiak, A.] Univ Chicago, Med Ctr, Chicago, IL 60637 USA. RI Marasca, Roberto/I-8072-2013 OI Marasca, Roberto/0000-0002-6431-6878 NR 0 TC 0 Z9 0 U1 0 U2 0 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 2296-5270 EI 2296-5262 J9 ONCOL RES TREAT JI Oncol. Res. Treat. PY 2016 VL 39 SU 1 MA 0410 BP 28 EP 28 PG 1 WC Oncology SC Oncology GA DF4XB UT WOS:000371353700088 ER PT J AU Larkin, J Chiarion-Sileni, V Gonzalez, R Grob, JJ Cowey, CL Lao, CD Wagstaff, J Hogg, D Hill, A Carlino, MS Wolter, P Lebbe, C Schachter, J Thomas, L Hassel, JC Lorigan, P Walker, D Jiang, J Hodi, FS Wolchok, JD AF Larkin, J. Chiarion-Sileni, V. Gonzalez, R. Grob, J. -J. Cowey, C. L. Lao, C. D. Wagstaff, J. Hogg, D. Hill, A. Carlino, M. S. Wolter, P. Lebbe, C. Schachter, J. Thomas, L. Hassel, J. C. Lorigan, P. Walker, D. Jiang, J. Hodi, F. S. Wolchok, J. D. TI Efficacy and safety in key patient subgroups of nivolumab (NIVO) alone or combined with ipilimumab (IPI) versus IPI alone in treatment-naive patients with advanced melanoma (MEL) (CheckMate 067) SO ONCOLOGY RESEARCH AND TREATMENT LA English DT Meeting Abstract C1 [Larkin, J.] Royal Marsden Hosp, London, England. [Chiarion-Sileni, V.] IOV IRCCS, Melanoma Oncol Unit, Padua, Italy. [Gonzalez, R.] Univ Colorado, Ctr Canc, Denver, CO 80202 USA. [Grob, J. -J.] Aix Marseille Univ, Hop La Timone AP, Marseille, France. [Cowey, C. L.] Baylor Charles A Sammons Canc Ctr, Dallas, TX USA. [Lao, C. D.] Univ Michigan, Ann Arbor, MI 48109 USA. [Wagstaff, J.] Singleton Hosp, South West Wales Canc Inst, Swansea SA2 8QA, W Glam, Wales. [Hogg, D.] Univ Toronto, Princess Margaret Hosp, Toronto, ON, Canada. [Hill, A.] Tasman Oncol Res, Southport Gold Coast, Qld, Australia. [Carlino, M. S.] Melanoma Inst Australia, Sydney, NSW, Australia. [Carlino, M. S.] Univ Sydney, Sydney, NSW 2006, Australia. [Wolter, P.] UZ Leuven, Leuven, Belgium. [Lebbe, C.] Univ Paris Diderot, Hop St Louis, Paris, France. [Schachter, J.] Inst Oncol, Tel Hashomer, Israel. [Thomas, L.] Ctr Hosp Lyon Sud, F-69310 Pierre Benite, France. [Hassel, J. C.] Univ Heidelberg Hosp, German Canc Res Ctr, Heidelberg, Germany. [Lorigan, P.] Christie NHS Fdn Trust, Manchester, England. [Walker, D.] Bristol Myers Squibb Co, Princeton, NJ USA. [Jiang, J.] Bristol Myers Squibb, Hopewell, NJ USA. [Hodi, F. S.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Wolchok, J. D.] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. [Wolchok, J. D.] Weill Cornell Med Coll, New York, NY USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 2296-5270 EI 2296-5262 J9 ONCOL RES TREAT JI Oncol. Res. Treat. PY 2016 VL 39 SU 1 MA 0354 BP 40 EP 40 PG 1 WC Oncology SC Oncology GA DF4XB UT WOS:000371353700124 ER PT J AU Happold, C Gorlia, T Chinot, O Gilbert, MR Nabors, LB Wick, W Pugh, SL Hegi, M Cloughesy, T Roth, P Reardon, DA Perry, JR Mehta, MP Stupp, R Weller, M AF Happold, C. Gorlia, T. Chinot, O. Gilbert, M. R. Nabors, L. B. Wick, W. Pugh, S. L. Hegi, M. Cloughesy, T. Roth, P. Reardon, D. A. Perry, J. R. Mehta, M. P. Stupp, R. Weller, M. TI Role of valproic acid or levetiracetam in survival of glioblastoma patients SO ONCOLOGY RESEARCH AND TREATMENT LA English DT Meeting Abstract C1 [Happold, C.; Roth, P.; Weller, M.] Univ Zurich Hosp, Dept Neurol, CH-8091 Zurich, Switzerland. [Gorlia, T.] EORTC Data Ctr, Brussels, Belgium. [Chinot, O.] Aix Marseille Univ, Univ Hosp Timone, Assistance Publ Hop Marseille, Div Neurooncol, Marseille, France. [Gilbert, M. R.] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. [Nabors, L. B.] Univ Alabama Birmingham, Birmingham, AL USA. [Wick, W.] Heidelberg Univ, Neurol Clin, Bergheimer Str 58, D-69115 Heidelberg, Germany. [Wick, W.] German Canc Res Ctr, Heidelberg, Germany. [Pugh, S. L.] NRG Oncol Stat & Data Management Ctr, Philadelphia, PA USA. [Hegi, M.] Univ Lausanne Hosp, Dept Clin Neurosci, Lausanne, Switzerland. [Cloughesy, T.] UCLA Neurooncol Program, Los Angeles, CA USA. [Reardon, D. A.] Dana Farber Canc Inst, Ctr Neurooncol, Boston, MA 02115 USA. [Perry, J. R.] Univ Toronto, Sunnybrook Hlth Sci Ctr, Div Neurol, Toronto, ON, Canada. [Mehta, M. P.] Univ Maryland, Sch Med, Baltimore, MD 21201 USA. [Stupp, R.] Univ Zurich Hosp, Dept Oncol, CH-8091 Zurich, Switzerland. RI Gilbert, Mark/J-7494-2016 OI Gilbert, Mark/0000-0003-2556-9722 NR 0 TC 0 Z9 0 U1 0 U2 0 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 2296-5270 EI 2296-5262 J9 ONCOL RES TREAT JI Oncol. Res. Treat. PY 2016 VL 39 SU 1 MA 0319 BP 61 EP 61 PG 1 WC Oncology SC Oncology GA DF4XB UT WOS:000371353700192 ER PT J AU Sequist, LV Goldman, JW Wakelee, H Camidge, DR Gadgeel, S Yu, HA Varga, A Solomon, B Oxnard, GR Ou, SHI Papadimitrakopoulou, V Liu, SV Reckamp, KL Spira, AI Despain, D Karlovich, CA Yurasov, S Soria, JC AF Sequist, L. V. Goldman, J. W. Wakelee, H. Camidge, D. R. Gadgeel, S. Yu, H. A. Varga, A. Solomon, B. Oxnard, G. R. Ou, S. -H. I. Papadimitrakopoulou, V. Liu, S. V. Reckamp, K. L. Spira, A. I. Despain, D. Karlovich, C. A. Yurasov, S. Soria, J. -C. TI Efficacy of Rociletinib (CO-1686) in Centrally Confirmed T790M-positive and T790M-negative Non-small Cell Lung Cancer (NSCLC) Patients (Pts) SO ONCOLOGY RESEARCH AND TREATMENT LA English DT Meeting Abstract C1 [Sequist, L. V.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Goldman, J. W.] Univ Calif Los Angeles, Med Ctr, Santa Monica, CA USA. [Wakelee, H.] Stanford Univ, Sch Med, Stanford Canc Inst, Stanford, CA 94305 USA. [Camidge, D. R.] Univ Colorado, Ctr Canc, Aurora, CO USA. [Gadgeel, S.] Wayne State Univ, Karmanos Canc Inst, Detroit, MI USA. [Yu, H. A.] Mem Sloan Kettering Canc Ctr, 1275 York Ave, New York, NY 10021 USA. [Varga, A.; Soria, J. -C.] Inst Gustave Roussy, Villejuif, France. [Solomon, B.] Peter MacCallum Canc Ctr, East Melbourne, Vic, Australia. [Oxnard, G. R.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Ou, S. -H. I.] UC Irvine Med Ctr, Chao Family Comprehens Canc Ctr, Orange, CA USA. [Papadimitrakopoulou, V.] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. [Liu, S. V.] Georgetown Univ Hosp, Washington, DC 20007 USA. [Reckamp, K. L.] City Hope Natl Med Ctr, Dept Med Oncol & Therapeut Res, Duarte, CA USA. [Spira, A. I.] US Oncol Res, Virginia Canc Specialists Res Inst, Fairfax, VA USA. [Despain, D.; Karlovich, C. A.; Yurasov, S.] Clovis Oncol Inc, San Francisco, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 2296-5270 EI 2296-5262 J9 ONCOL RES TREAT JI Oncol. Res. Treat. PY 2016 VL 39 SU 1 MA 0443 BP 121 EP 121 PG 1 WC Oncology SC Oncology GA DF4XB UT WOS:000371353700392 ER PT J AU Dimopoulos, M Lonial, S White, D Moreau, P Palumbo, A San Miguel, J Shpilberg, O Anderson, K Grosicki, S Spicka, I Walter-Croneck, A Magen-Nativ, H Mateos, MV Belch, A Reece, D Beksac, M Bleickardt, E Poulart, V Katz, J Singhal, AK Richardson, P AF Dimopoulos, M. Lonial, S. White, D. Moreau, P. Palumbo, A. San Miguel, J. Shpilberg, O. Anderson, K. Grosicki, S. Spicka, I. Walter-Croneck, A. Magen-Nativ, H. Mateos, M. -V Belch, A. Reece, D. Beksac, M. Bleickardt, E. Poulart, V. Katz, J. Singhal, A. K. Richardson, P. TI ELOQUENT-2 Update: A Phase 3, Randomized, Open-Label Study of Elotuzumab in Combination with Lenalidomide/Dexamethasone (ELd) vs Lenalidomide/Dexamethasone (Ld) in Patients (Pts) with Relapsed/Refractory Multiple Myeloma (RRMM)-3-Year Safety and Efficacy Follow-up SO ONCOLOGY RESEARCH AND TREATMENT LA English DT Meeting Abstract C1 [Dimopoulos, M.] Univ Athens, Athens, Greece. [Lonial, S.] Emory Univ, Sch Med, Winship Canc Inst, Atlanta, GA USA. [White, D.] QEII Hlth Sci Ctr, Halifax, NS, Canada. [White, D.] Dalhousie Univ, Halifax, NS, Canada. [Moreau, P.] Univ Hosp, Nantes, France. [Palumbo, A.] AOU San Giovanni Battista Torino, Osped Molinette, Turin, Italy. [San Miguel, J.] Univ Navarra Clin, Pamplona, Spain. [Shpilberg, O.] Assuta Med Ctr, Tel Aviv, Israel. [Anderson, K.; Richardson, P.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Grosicki, S.] Silesian Med Univ, Katowice, Poland. [Spicka, I.] Charles Univ Hosp, Prague, Czech Republic. [Walter-Croneck, A.] Med Univ Lublin, Lublin, Poland. [Magen-Nativ, H.] Rabin Med Ctr, Davidoff Canc Ctr, Petah Tiqwa, Israel. [Magen-Nativ, H.] Tel Aviv Univ, Ramat Aviv, Israel. [Mateos, M. -V] Univ Hosp Salamanca IBSAL, Salamanca, Spain. [Belch, A.] Cross Canc Inst, Edmonton, AB T6G 1Z2, Canada. [Belch, A.] Univ Alberta, Edmonton, AB, Canada. [Reece, D.] Princess Margaret Canc Ctr, Toronto, ON, Canada. [Beksac, M.] Ankara Univ, TR-06100 Ankara, Turkey. [Bleickardt, E.] Bristol Myers Squibb, Wallingford, CT USA. [Poulart, V.] Bristol Myers Squibb, Braine Lalleud, Belgium. [Katz, J.] Bristol Myers Squibb Co, Princeton, NJ USA. [Singhal, A. K.] AbbVie Biotherapeut Inc ABR, Redwood City, CA USA. RI richard, chrystelle/K-8595-2015 NR 0 TC 0 Z9 0 U1 0 U2 2 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 2296-5270 EI 2296-5262 J9 ONCOL RES TREAT JI Oncol. Res. Treat. PY 2016 VL 39 SU 1 MA 0420 BP 122 EP 123 PG 2 WC Oncology SC Oncology GA DF4XB UT WOS:000371353700396 ER PT J AU Kappeler, C Reichardt, P Kong, YK Blay, JY Joensuu, H Schaefer, K Chung, J Wagner, A Cosali, PG Demetri, G AF Kappeler, C. Reichardt, P. Kong, Y. -K. Blay, J. -Y. Joensuu, H. Schaefer, K. Chung, J. Wagner, A. Cosali, P. G. Demetri, G. TI Exploratory analysis of tumor growth rate in patients (pts) with advanced gastrointestinal stromal tumors (GIST) treated with regorafenib (REG) in the GRID phase 3 trial SO ONCOLOGY RESEARCH AND TREATMENT LA English DT Meeting Abstract C1 [Kappeler, C.; Schaefer, K.; Wagner, A.] Bayer Pharma AG, Berlin, Germany. [Reichardt, P.] HELIOS Klinikum Berlin Buch, Berlin, Germany. [Kong, Y. -K.] Asan Med Ctr, Seoul, South Korea. [Blay, J. -Y.] Ctr Leon Berard, F-69373 Lyon, France. [Joensuu, H.] Helsinki Univ Hosp, Helsinki, Finland. [Chung, J.] Bayer HealthCare Pharmaceut, Whippany, NJ USA. [Cosali, P. G.] Ist Nazl Tumori, Via Venezian 1, I-20133 Milan, Italy. [Demetri, G.] Dana Farber Canc Inst, Ludwig Ctr, Boston, MA 02115 USA. [Demetri, G.] Harvard Univ, Sch Med, Boston, MA USA. RI Blay, Jean-Yves/N-3966-2016 OI Blay, Jean-Yves/0000-0001-7190-120X NR 0 TC 0 Z9 0 U1 0 U2 0 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 2296-5270 EI 2296-5262 J9 ONCOL RES TREAT JI Oncol. Res. Treat. PY 2016 VL 39 SU 1 MA 0017 BP 144 EP 145 PG 2 WC Oncology SC Oncology GA DF4XB UT WOS:000371353700470 ER PT J AU Holliday, EB Dieckmann, NF McDonald, TL Hung, AY Thomas, CR Wood, LJ AF Holliday, Emma B. Dieckmann, Nathan F. McDonald, Tasha L. Hung, Arthur Y. Thomas, Charles R., Jr. Wood, Lisa J. TI Relationship between fatigue, sleep quality and inflammatory cytokines during external beam radiation therapy for prostate cancer: A prospective-study SO RADIOTHERAPY AND ONCOLOGY LA English DT Article DE Radiotherapy; Cancer treatment related fatigue; Prosate Cancer; Cytokines; Sleep disturbance ID IMMUNOLOGICALLY MEDIATED FATIGUE; OF-LIFE; CHEMORADIATION THERAPY; SYMPTOM CLUSTER; BREAST-CANCER; LUNG-CANCER; CHEMOTHERAPY; RADIOTHERAPY; IRRADIATION; SURGERY AB Background and purpose: Mechanisms of fatigue reported during radiotherapy are poorly defined but may include inflammatory cytokines and/or sleep disturbances. This prospective, longitudinal, phase II study assessed fatigue, sleep, and serum cytokine levels during radiotherapy for early-stage prostate cancer (PCa). Material and methods: Twenty-eight men undergoing radiotherapy for early-stage PCa wore an Actiwatch Score to record fatigue level, sleep time, onset latency, efficiency and wake after sleep onset. Serum levels of IL-1 alpha, IL-1 beta, TNF-alpha, IL-6, IL-8, IL-10 and VEGF were measured weekly during radiotherapy. Patient reported quality of life (QOL) metrics were collected before and after treatment. Linear mixed effects models examined trajectories across treatment weeks. Results: Fatigue increased across treatment weeks (P < .01), and fatigue was associated with decreased patient-reported QOL. Sleep efficiency increased across treatment weeks (rate of change over time = .29, P = .03), and sleep onset latency decreased (rate of change over time = .86, P = .06). IL-6 tended to increase during treatment (P = 0.09), but none of the cytokine levels or sleep variables were significantly related to fatigue trajectories. Conclusions: Despite increased sleep efficiency across treatment weeks, fatigue significantly increased. Although IL-6 increased during the course of radiotherapy, cytokines levels were not associated with fatigue scores or sleep disturbance. Further studies are needed to define the mechanisms for fatigue during radiotherapy. (C) 2015 Elsevier Ireland Ltd. All rights reserved. C1 [Holliday, Emma B.; Wood, Lisa J.] Univ Texas MD Anderson Canc Ctr, Div Radiat Oncol, Houston, TX 77030 USA. [Dieckmann, Nathan F.] Oregon Hlth & Sci Univ, Sch Nursing, Dept Publ Hlth & Preventat Med, Portland, OR 97201 USA. [Dieckmann, Nathan F.] Oregon Hlth & Sci Univ, Sch Nursing, Dept Psychiat, Portland, OR 97201 USA. [McDonald, Tasha L.; Hung, Arthur Y.; Thomas, Charles R., Jr.] Oregon Hlth & Sci Univ, Dept Radiat Med, Portland, OR 97201 USA. [Wood, Lisa J.] Massachusetts Gen Hosp, Inst Hlth Profess, 79-96 Thirteenth St, Boston, MA 02129 USA. RP Wood, LJ (reprint author), Massachusetts Gen Hosp, Inst Hlth Profess, 79-96 Thirteenth St, Boston, MA 02129 USA. EM ljwood@mghihp.edu FU RSNA Research Resident [RR0730]; National Institute of Nursing Research [5R211NR010363] FX Supported by RSNA Research Resident Grant No. RR0730 (TLM) and National Institute of Nursing Research project no. 5R211NR010363 (LJW). NR 39 TC 3 Z9 3 U1 4 U2 4 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0167-8140 J9 RADIOTHER ONCOL JI Radiother. Oncol. PD JAN PY 2016 VL 118 IS 1 BP 105 EP 111 DI 10.1016/j.radonc.2015.12.015 PG 7 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA DF7PW UT WOS:000371551100016 PM 26743832 ER PT J AU Tang, LX Yuan, DJ Wang, QL Jiang, F Guo, J Tang, YG Zheng, LX Kang, JX AF Tang, Li-Xin Yuan, Dong-Juan Wang, Qi-Ling Jiang, Fang Guo, Jian Tang, Yun-Ge Zheng, Li-Xin Kang, Jing X. TI Association of decreased spermatozoa omega-3 fatty acid levels and increased oxidative DNA damage with varicocele in infertile men: a case control study SO REPRODUCTION FERTILITY AND DEVELOPMENT LA English DT Article DE 8-hydroxy-2-deoxyguanosine; infertility; omega-6 fatty acids ID FATTY-ACID-COMPOSITION; SEMINAL PLASMA; ASTHENOZOOSPERMIC MALES; SPERM; ANTIOXIDANTS; STRESS AB Varicocele is commonly associated with male infertility because it impairs normal sperm morphology and activity. Polyunsaturated fatty acids (PUFA) are important determinants of sperm cell structure and function, but their relationship with varicocele remains unclear. The aim of the present study was to investigate the PUFA composition in spermatozoa of infertile men with varicocele and to evaluate the potential relationship between PUFA and varicocele. This case control study recruited 92 infertile men with varicocele, 99 infertile men without varicocele and 95 fertile male control subjects. Semen morphology and activity parameters were assessed and seminal plasma 8-hydroxy-2-deoxyguanosine (8-OHdG) content was determined by ELISA. Sperm concentrations of omega-3 and omega-6 fatty acids were measured by gas chromatography. Infertile men with varicocele had lower concentrations of omega-3 PUFA, higher omega-6:omega-3 PUFA ratios and greater oxidative DNA damage in spermatozoa compared with infertile men without varicocele and normal subjects. The degree of varicocele and DNA damage was associated with decreased omega-3 PUFA concentrations and semen quality in infertile men with varicocele. The findings suggest that omega-3 PUFA deficiency could be implicated in varicocele-associated infertility, and highlight the need for intervention trials to test the usefulness of omega-3 supplementation in reducing sperm abnormalities in infertile men with varicocele. C1 [Tang, Li-Xin; Wang, Qi-Ling; Jiang, Fang; Tang, Yun-Ge; Zheng, Li-Xin] Natl Hlth & Family Planning Commiss China, Key Lab Male Reprod & Genet, Guangzhou 510000, Guangdong, Peoples R China. [Tang, Li-Xin; Wang, Qi-Ling; Jiang, Fang; Tang, Yun-Ge; Zheng, Li-Xin] Guangdong Family Planning Sci & Technol Inst, Dept Androl, Guangzhou 510030, Guangdong, Peoples R China. [Yuan, Dong-Juan; Guo, Jian] Guangdong Med Coll, Dept Biochem & Mol Biol, Zhanjiang 524023, Peoples R China. [Yuan, Dong-Juan] S China Univ Technol, Sch Light Ind & Food Sci, Guangzhou 510630, Guangdong, Peoples R China. [Kang, Jing X.] Massachusetts Gen Hosp, Lab Lipid Med & Technol, Boston, MA 02129 USA. [Kang, Jing X.] Harvard Univ, Sch Med, Boston, MA 02129 USA. RP Tang, LX (reprint author), Natl Hlth & Family Planning Commiss China, Key Lab Male Reprod & Genet, Guangzhou 510000, Guangdong, Peoples R China.; Kang, JX (reprint author), Massachusetts Gen Hosp, Lab Lipid Med & Technol, Boston, MA 02129 USA.; Kang, JX (reprint author), Harvard Univ, Sch Med, Boston, MA 02129 USA. EM tang-lixin@126.com; kang.jing@mgh.harvard.edu FU Guangdong Province Science and Technology Project of China; Fortune Education Foundation; Sansun Life Sciences FX This study was supported by funding from the Guangdong Province Science and Technology Project of China (to LXT) and from the Fortune Education Foundation and Sansun Life Sciences (both to JXK). The authors are grateful to the study participants and the staff of the infertilitiy clinic, and to Marina Kang for her editorial assistance. NR 22 TC 1 Z9 2 U1 1 U2 1 PU CSIRO PUBLISHING PI CLAYTON PA UNIPARK, BLDG 1, LEVEL 1, 195 WELLINGTON RD, LOCKED BAG 10, CLAYTON, VIC 3168, AUSTRALIA SN 1031-3613 EI 1448-5990 J9 REPROD FERT DEVELOP JI Reprod. Fertil. Dev. PY 2016 VL 28 IS 5 BP 648 EP 654 DI 10.1071/RD14276 PG 7 WC Developmental Biology; Reproductive Biology; Zoology SC Developmental Biology; Reproductive Biology; Zoology GA DF8RS UT WOS:000371626600012 PM 25405715 ER PT J AU Haidar, G Crespo, M Maximous, S Lendermon, E Clancy, CJ Nguyen, MH AF Haidar, G. Crespo, M. Maximous, S. Lendermon, E. Clancy, C. J. Nguyen, M. H. TI Invasive Tracheobronchial Aspergillosis in a Lung Transplant Recipient Receiving Belatacept as Salvage Maintenance Immunosuppression: A Case Report SO TRANSPLANTATION PROCEEDINGS LA English DT Article ID ALLERGIC BRONCHOPULMONARY ASPERGILLOSIS; COSTIMULATION BLOCKADE; PHASE-III; CYCLOSPORINE; REGIMENS; PATIENT; BENEFIT AB Introduction. The association between belatacept, a CD28 costimulation blocker, and invasive mycoses is unclear. Case Report. We describe a patient who initiated belatacept 3 years after lung transplantation and developed invasive tracheobronchial aspergillosis, a disease encountered almost exclusively within the first 6 months after transplantation. Conclusions. Belatacept may have played a causative role. Until more data are available, belatacept should be used cautiously after lung transplantation. C1 [Haidar, G.; Crespo, M.; Maximous, S.; Lendermon, E.; Clancy, C. J.; Nguyen, M. H.] Univ Pittsburgh, Med Ctr, Dept Med, Pittsburgh, PA 15213 USA. [Clancy, C. J.] VA Pittsburgh Healthcare Syst, Pittsburgh, PA USA. RP Haidar, G (reprint author), Univ Pittsburgh, Med Ctr, 3601 Fifth Ave,Suite 3A,Falk Med Bldg, Pittsburgh, PA 15213 USA. EM haidarg@upmc.edu NR 22 TC 0 Z9 0 U1 2 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0041-1345 EI 1873-2623 J9 TRANSPL P JI Transplant. Proc. PD JAN-FEB PY 2016 VL 48 IS 1 BP 275 EP 278 DI 10.1016/j.transproceed.2016.01.003 PG 4 WC Immunology; Surgery; Transplantation SC Immunology; Surgery; Transplantation GA DG1TG UT WOS:000371849800051 PM 26915884 ER PT J AU Alonso, JL Goldmann, WH AF Alonso, Jose Luis Goldmann, Wolfgang H. TI Cellular mechanotransduction SO AIMS BIOPHYSICS LA English DT Review DE integrins; focal adhesions; cell-matrix and cell-cell contacts; mechanosensing; mechanotransduction ID INTEGRIN-MEDIATED MECHANOTRANSDUCTION; FOCAL ADHESION DYNAMICS; MECHANICAL-STRESS; VINCULIN PHOSPHORYLATION; EXTRACELLULAR-MATRIX; SIGNALING PATHWAYS; NUCLEAR MECHANICS; KINASE; CONTRACTILITY; TENSION AB Cell adhesion and cell-cell contacts are pre-requisites for proper metabolism, protein synthesis, cell survival, and cancer metastasis. Major transmembrane receptors are the integrins, which are responsible for cell matrix adhesions, and the cadherins, which are important for cell-cell adhesions. Adherent cells are anchored via focal adhesions (FAs) to the extracellular matrix, while cell-cell contacts are connected via focal adherens junctions (FAJs). Force transmission over considerable distances and stress focusing at these adhesion sites make them prime candidates for mechanosensors. Exactly which protein(s) within FAs and FAJs or which membrane component of ion channels sense, transmit, and respond to mechano-chemical signaling is currently strongly debated and numerous candidates have been proposed. C1 [Alonso, Jose Luis] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Med, Charlestown, MA 02129 USA. [Goldmann, Wolfgang H.] Univ Erlangen Nurnberg, Biophys Grp, D-91052 Erlangen, Germany. RP Alonso, JL (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Med, Charlestown, MA 02129 USA.; Goldmann, WH (reprint author), Univ Erlangen Nurnberg, Biophys Grp, D-91052 Erlangen, Germany. EM jalonso@partners.org; wgoldmann@biomed.uni-erlangen.de NR 66 TC 1 Z9 1 U1 10 U2 15 PU AMER INST MATHEMATICAL SCIENCES-AIMS PI SPRINGFIELD PA PO BOX 2604, SPRINGFIELD, MO 65801-2604 USA SN 2377-9098 J9 AIMS BIOPHYS JI AIMS Biophys. PY 2016 VL 3 IS 1 BP 50 EP 62 DI 10.3934/biophy.2016.1.50 PG 13 WC Biophysics SC Biophysics GA DF8UW UT WOS:000371636400003 ER PT J AU Ahluwalia, SC Schreibeis-Baum, H Prendergast, TJ Reinke, LF Lorenz, KA AF Ahluwalia, Sangeeta C. Schreibeis-Baum, Hannah Prendergast, Thomas J. Reinke, Lynn F. Lorenz, Karl A. TI NURSES AS INTERMEDIARIES: HOW CRITICAL CARE NURSES PERCEIVE THEIR ROLE IN FAMILY MEETINGS SO AMERICAN JOURNAL OF CRITICAL CARE LA English DT Article ID OF-LIFE CARE; PATIENT OUTCOMES; PALLIATIVE CARE; COMMUNICATION; END; UNIT; PHYSICIANS; PERSPECTIVES; ICU; PERCEPTIONS AB Background Nurses' involvement in family meetings in the intensive care unit is central to supporting consistent communication and shared understanding within the care team and with patients and patients' family members. Evidence suggests the existence of major barriers to the effective participation and contribution of nurses during family meetings. Objectives To characterize the nature and extent of nurses' involvement in family meetings in the intensive care unit, including identifying barriers to nurses' participation and opportunities for involvement. Methods Meetings with focus groups of nurses at a Veterans Affairs medical intensive care unit were recorded, transcribed, and qualitatively analyzed by using the constant comparative method. Results Thirty critical care nurses participated in 6 focus groups. Three major themes describing nurses' involvement in family meetings were identified: nurses can play multiple roles in supporting conduct in family meetings, nurses face critical barriers to fully realizing these roles, and nurses end up as intermediaries in family meetings. Subthemes pertained to being well positioned to act as the patient's advocate, yet feeling undervalued and underempowered to contribute important information in family meetings, often resulting in mixed messages about care preferences, prognosis, or goals of care that nurses did not feel able to address during the meeting. Conclusion Nurses are positioned to play essential roles in family meetings, but their full involvement remains unrealized. Communication training and greater attention to nurses' empowerment and to facilitating the nurse-physician relationship in the context of family meetings most likely would increase appropriate involvement of nurses in the meetings. C1 [Ahluwalia, Sangeeta C.] RAND Corp, 1776 Main St, Santa Monica, CA 90401 USA. [Ahluwalia, Sangeeta C.] Univ Calif Los Angeles, Fielding Sch Publ Hlth, Los Angeles, CA 90024 USA. [Schreibeis-Baum, Hannah; Lorenz, Karl A.] Vet Affairs Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. [Prendergast, Thomas J.] Oregon Hlth & Sci Univ, Med, Portland, OR USA. [Prendergast, Thomas J.] Portland VA Med Ctr, Pulm & Crit Care Med, Portland, OR USA. [Reinke, Lynn F.] Vet Affairs Puget Sound Healthcare Syst, Seattle, WA USA. [Reinke, Lynn F.] Univ Washington, Sch Nursing, Seattle, WA 98195 USA. [Lorenz, Karl A.] Univ Calif Los Angeles, Sch Med, Med, Los Angeles, CA 90024 USA. RP Ahluwalia, SC (reprint author), RAND Corp, 1776 Main St, Santa Monica, CA 90401 USA. EM sahluwal@rand.org FU National Palliative Care Research Center; Implementation Research Institute, George Warren Brown School of Social Work, Washington University, St Louis, Missouri, through the National Institute of Mental Health [R25 MH080916-01A2]; Department of Veterans Affairs, Health Services Research and Development Service, Quality Enhancement Research Initiative FX Dr Ahluwalia was supported by a career development award from the National Palliative Care Research Center. The preparation of this article was supported in part by the Implementation Research Institute, George Warren Brown School of Social Work, Washington University, St Louis, Missouri, through the National Institute of Mental Health (R25 MH080916-01A2) and the Department of Veterans Affairs, Health Services Research and Development Service, Quality Enhancement Research Initiative. NR 31 TC 2 Z9 2 U1 3 U2 12 PU AMER ASSOC CRITICAL CARE NURSES PI ALISO VIEJO PA 101 COLUMBIA, ALISO VIEJO, CA 92656 USA SN 1062-3264 EI 1937-710X J9 AM J CRIT CARE JI Am. J. Crit. Care PD JAN 1 PY 2016 VL 25 IS 1 BP 33 EP 38 DI 10.4037/ajcc2016653 PG 6 WC Critical Care Medicine; Nursing SC General & Internal Medicine; Nursing GA DF3FL UT WOS:000371229200011 PM 26724291 ER PT J AU Sumner, JA Powers, A Jovanovic, T Koenen, KC AF Sumner, Jennifer A. Powers, Abigail Jovanovic, Tanja Koenen, Karestan C. TI Genetic Influences on the Neural and Physiological Bases of Acute Threat: A Research Domain Criteria (RDoC) Perspective SO AMERICAN JOURNAL OF MEDICAL GENETICS PART B-NEUROPSYCHIATRIC GENETICS LA English DT Review DE RDoC; acute threat; genetics; neural circuit; physiology ID CATECHOL-O-METHYLTRANSFERASE; POSTTRAUMATIC-STRESS-DISORDER; FEAR-POTENTIATED STARTLE; EARLY-LIFE STRESS; TRYPTOPHAN-HYDROXYLASE ISOFORM; SEROTONIN TRANSPORTER GENE; BDNF VAL66MET POLYMORPHISM; GENOME-WIDE ASSOCIATION; PANIC DISORDER; ACOUSTIC STARTLE AB The NIMH Research Domain Criteria (RDoC) initiative aims to describe key dimensional constructs underlying mental function across multiple units of analysis-from genes to observable behaviors-in order to better understand psychopathology. The acute threat ("fear") construct of the RDoC Negative Valence System has been studied extensively from a translational perspective, and is highly pertinent to numerous psychiatric conditions, including anxiety and trauma-related disorders. We examined genetic contributions to the construct of acute threat at two units of analysis within the RDoC framework: (1) neural circuits and (2) physiology. Specifically, we focused on genetic influences on activation patterns of frontolimbic neural circuitry and on startle, skin conductance, and heart rate responses. Research on the heritability of activation in threat-related frontolimbic neural circuitry is lacking, but physiological indicators of acute threat have been found to be moderately heritable (35-50%). Genetic studies of the neural circuitry and physiology of acute threat have almost exclusively relied on the candidate gene method and, as in the broader psychiatric genetics literature, most findings have failed to replicate. The most robust support has been demonstrated for associations between variation in the serotonin transporter (SLC6A4) and catechol-O-methyltransferase (COMT) genes with threat-related neural activation and physiological responses. However, unbiased genome-wide approaches using very large samples are needed for gene discovery, and these can be accomplished with collaborative consortium-based research efforts, such as those of the Psychiatric Genomics Consortium (PGC) and Enhancing Neuro Imaging Genetics through Meta-Analysis (ENIGMA) Consortium. (C) 2015 Wiley Periodicals, Inc. C1 [Sumner, Jennifer A.] Columbia Univ, Med Ctr, Ctr Behav Cardiovasc Hlth, 622 W 168th St,PH 9-315, New York, NY 10032 USA. [Sumner, Jennifer A.; Koenen, Karestan C.] Harvard Univ, Dept Epidemiol, TH Chan Sch Publ Hlth, Boston, MA USA. [Powers, Abigail; Jovanovic, Tanja] Emory Univ, Sch Med, Dept Psychiat & Behav Sci, Atlanta, GA 30322 USA. [Koenen, Karestan C.] Massachusetts Gen Hosp, Psychiat & Neurodev Genet Unit, Boston, MA 02114 USA. [Koenen, Karestan C.] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. [Koenen, Karestan C.] Broad Inst MIT & Harvard, Stanley Ctr Psychiat Res, Cambridge, MA USA. RP Sumner, JA (reprint author), Columbia Univ, Med Ctr, Ctr Behav Cardiovasc Hlth, 622 W 168th St,PH 9-315, New York, NY 10032 USA. EM js4456@cumc.columbia.edu OI Powers, Abigail/0000-0003-3197-7415 FU National Institutes of Health [R21 MH098212, F32 MH102890] FX Grant sponsor: National Institutes of Health; Grant numbers: R21 MH098212, F32 MH102890. NR 163 TC 2 Z9 2 U1 9 U2 12 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1552-4841 EI 1552-485X J9 AM J MED GENET B JI Am. J. Med. Genet. B PD JAN PY 2016 VL 171 IS 1 SI SI BP 44 EP 64 DI 10.1002/ajmg.b.32384 PG 21 WC Genetics & Heredity; Psychiatry SC Genetics & Heredity; Psychiatry GA DF3LI UT WOS:000371245100002 PM 26377804 ER PT J AU Nakhleh, RE Nose, V Renshaw, A McCrory, D Fatheree, L AF Nakhleh, Raouf E. Nose, Vania Renshaw, Andrew McCrory, Doug Fatheree, Lisa TI Diagnostic Error in Anatomic Pathology Reply SO ARCHIVES OF PATHOLOGY & LABORATORY MEDICINE LA English DT Letter C1 [Nakhleh, Raouf E.] Mayo Clin Florida, Dept Lab Med & Pathol, Jacksonville, FL 32224 USA. [Nose, Vania] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Renshaw, Andrew] Baptist Hosp Miami, Dept Pathol, Miami, FL USA. [McCrory, Doug] Duke Univ, Dept Med, Durham, NC USA. [Fatheree, Lisa] Coll Amer Pathologists, Pathol & Lab Qual Ctr, Northfield, IL USA. RP Nakhleh, RE (reprint author), Mayo Clin Florida, Dept Lab Med & Pathol, Jacksonville, FL 32224 USA.; Nose, V (reprint author), Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA.; Renshaw, A (reprint author), Baptist Hosp Miami, Dept Pathol, Miami, FL USA.; McCrory, D (reprint author), Duke Univ, Dept Med, Durham, NC USA.; Fatheree, L (reprint author), Coll Amer Pathologists, Pathol & Lab Qual Ctr, Northfield, IL USA. NR 1 TC 1 Z9 1 U1 0 U2 0 PU COLL AMER PATHOLOGISTS PI NORTHFIELD PA C/O KIMBERLY GACKI, 325 WAUKEGAN RD, NORTHFIELD, IL 60093-2750 USA SN 0003-9985 EI 1543-2165 J9 ARCH PATHOL LAB MED JI Arch. Pathol. Lab. Med. PD JAN PY 2016 VL 140 IS 1 BP 9 EP 10 DI 10.5858/arpa.2015-0293-LE PG 3 WC Medical Laboratory Technology; Medicine, Research & Experimental; Pathology SC Medical Laboratory Technology; Research & Experimental Medicine; Pathology GA DF3EL UT WOS:000371226600002 PM 26717052 ER PT J AU Crothers, BA Darragh, TM Tambouret, RH Nayar, R Barkan, GA Zhao, CQ Booth, CN Padmanabhan, V Tabatabai, L Souers, RJ Thomas, N Wilbur, DC Moriarty, AT AF Crothers, Barbara A. Darragh, Teresa M. Tambouret, Rosemary H. Nayar, Ritu Barkan, Guliz A. Zhao, Chengquan Booth, Christine Noga Padmanabhan, Vijayalakshmi Tabatabai, Laura Souers, Rhona J. Thomas, Nicole Wilbur, David C. Moriarty, Ann T. TI Trends in Cervical Cytology Screening and Reporting Practices Results From the College of American Pathologists 2011 PAP Education Supplemental Questionnaire SO ARCHIVES OF PATHOLOGY & LABORATORY MEDICINE LA English DT Article ID SQUAMOUS INTRAEPITHELIAL LESION; INCREASING CYTOTECHNOLOGIST WORKLOAD; THINPREP IMAGING-SYSTEM; HUMAN-PAPILLOMAVIRUS; GYNECOLOGIC CYTOLOGY; PAPANICOLAOU TESTS; 100 SLIDES; SPECIMENS; WOMEN; CATEGORY AB Context.-The College of American Pathologists periodically surveys laboratories to determine changes in cytopathology practices. We report the results of a 2011 gynecologic cytology survey. Objective.-To provide a cross-sectional survey of gynecologic cytology practices in 2010. Design.-In 2011, a survey was sent to 1604 laboratories participating in the College of American Pathologists gynecologic cytology interlaboratory comparison education program and proficiency testing programs requesting data from 2010 on the following topics: terminology/reporting, cytotechnologist workload, quality assurance, reagents, and ancillary testing. Results.-Six hundred and twenty-five laboratories (39%) replied to the survey. The nonstandard use of "low-grade squamous intraepithelial lesion cannot exclude high-grade squamous intraepithelial lesion'' is used by most laboratories to report the presence of low-grade squamous intraepithelial lesion with possibility of high-grade squamous intraepithelial lesion. Most laboratories also report the presence or absence of cells from the transformation zone. Most respondents do not limit cytotechnologist screening workload during the work shift. Only about one-third of laboratories (188 of 582; 32%) use image-assisted screening devices. Rapid prescreening as a quality assurance measure is used by only 3.5%(21 of 594) of the laboratories. When used for screening, most laboratories use the imager for retrospective review of slides to detect human locator and interpretive errors. Most laboratories receive both liquid-based cytology samples (mainly ThinPrep, Hologic, Marlborough, Massachusetts) and conventional Papanicolaou tests. Expiration dates of liquid-based cytology test vials are not usually recorded. Conclusions.-The field of gynecologic cytology is evolving rapidly. These survey results offer a snapshot of national gynecologic cytology practices in 2010. C1 [Crothers, Barbara A.] Walter Reed Natl Mil Med Ctr, Dept Pathol & Area Lab Serv, 8901 Wisconsin Ave, Bethesda, MD 20889 USA. [Darragh, Teresa M.] Univ Calif San Francisco, Mt Zion Med Ctr, Pathol Cytol Lab, San Francisco, CA USA. [Tambouret, Rosemary H.; Wilbur, David C.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Nayar, Ritu] Northwestern Univ, Sch Med, Dept Cytopathol, Chicago, IL USA. [Barkan, Guliz A.] Loyola Univ, Med Ctr, Dept Pathol, Maywood, IL 60153 USA. [Zhao, Chengquan] Magee Womens Hosp, Dept Pathol, Pittsburgh, PA 15213 USA. [Booth, Christine Noga] Cleveland Clin Fdn, Dept Anat Pathol, 9500 Euclid Ave, Cleveland, OH 44195 USA. [Padmanabhan, Vijayalakshmi] Dartmouth Hitchcock Med Ctr, Dept Pathol, Lebanon, NH 03766 USA. [Tabatabai, Laura] Univ Calif San Francisco, Dept Pathol, San Francisco, CA 94140 USA. [Tabatabai, Laura] Vet Adm Med Ctr, San Francisco, CA 94121 USA. [Souers, Rhona J.] Coll Amer Pathologists, Dept Biostat, Northfield, IL USA. [Thomas, Nicole] Coll Amer Pathologists, Cytopathol Comm, Northfield, IL USA. [Moriarty, Ann T.] AmeriPath Indiana, Dept Pathol, Indianapolis, IN USA. RP Crothers, BA (reprint author), Walter Reed Natl Mil Med Ctr, Dept Pathol & Area Lab Serv, 8901 Wisconsin Ave, Bethesda, MD 20889 USA. EM Barbara.a.crothers.mil@mail.mil NR 35 TC 1 Z9 1 U1 0 U2 0 PU COLL AMER PATHOLOGISTS PI NORTHFIELD PA C/O KIMBERLY GACKI, 325 WAUKEGAN RD, NORTHFIELD, IL 60093-2750 USA SN 0003-9985 EI 1543-2165 J9 ARCH PATHOL LAB MED JI Arch. Pathol. Lab. Med. PD JAN PY 2016 VL 140 IS 1 BP 13 EP 21 DI 10.5858/arpa.2015-0004-CP PG 9 WC Medical Laboratory Technology; Medicine, Research & Experimental; Pathology SC Medical Laboratory Technology; Research & Experimental Medicine; Pathology GA DF3EL UT WOS:000371226600005 PM 26046490 ER PT J AU Nakhleh, RE Nose, V Colasacco, C Fatheree, LA Lillemoe, TJ McCrory, DC Meier, FA Otis, CN Owens, SR Raab, SS Turner, RR Ventura, CB Renshaw, AA AF Nakhleh, Raouf E. Nose, Vania Colasacco, Carol Fatheree, Lisa A. Lillemoe, Tamera J. McCrory, Douglas C. Meier, Frederick A. Otis, Christopher N. Owens, Scott R. Raab, Stephen S. Turner, Roderick R. Ventura, Christina B. Renshaw, Andrew A. TI Interpretive Diagnostic Error Reduction in Surgical Pathology and Cytology Guideline From the College of American Pathologists Pathology and Laboratory Quality Center and the Association of Directors of Anatomic and Surgical Pathology SO ARCHIVES OF PATHOLOGY & LABORATORY MEDICINE LA English DT Article ID MANDATORY 2ND OPINION; NEEDLE-ASPIRATION-CYTOLOGY; RADICAL PROSTATECTOMY SPECIMENS; SOFT-TISSUE SARCOMAS; GYNECOLOGIC-ONCOLOGY; CLINICAL IMPACT; BREAST-CANCER; INTEROBSERVER REPRODUCIBILITY; 2ND-OPINION PATHOLOGY; BIOPSY INTERPRETATION AB Context.-Additional reviews of diagnostic surgical and cytology cases have been shown to detect diagnostic discrepancies. Objective.-To develop, through a systematic review of the literature, recommendations for the review of pathology cases to detect or prevent interpretive diagnostic errors. Design.-The College of American Pathologists Pathology and Laboratory Quality Center in association with the Association of Directors of Anatomic and Surgical Pathology convened an expert panel to develop an evidence-based guideline to help define the role of case reviews in surgical pathology and cytology. A literature search was conducted to gather data on the review of cases in surgical pathology and cytology. Results.-The panel drafted 5 recommendations, with strong agreement from open comment period participants ranging from 87% to 93%. The recommendations are: (1) anatomic pathologists should develop procedures for the review of selected pathology cases to detect disagreements and potential interpretive errors; (2) anatomic pathologists should perform case reviews in a timely manner to avoid having a negative impact on patient care; (3) anatomic pathologists should have documented case review procedures that are relevant to their practice setting; (4) anatomic pathologists should continuously monitor and document the results of case reviews; and (5) if pathology case reviews show poor agreement within a defined case type, anatomic pathologists should take steps to improve agreement. Conclusions.-Evidence exists that case reviews detect errors; therefore, the expert panel recommends that anatomic pathologists develop procedures for the review of pathology cases to detect disagreements and potential interpretive errors, in order to improve the quality of patient care. C1 [Nakhleh, Raouf E.] Mayo Clin, Dept Lab Med & Pathol, 4500 San Pablo Rd, Jacksonville, FL 32224 USA. [Nose, Vania; Meier, Frederick A.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Colasacco, Carol] Coll Amer Pathologists, Governance, Northfield, IL USA. [Fatheree, Lisa A.; Ventura, Christina B.] Coll Amer Pathologists, Pathol & Lab Qual Ctr, Northfield, IL USA. [Lillemoe, Tamera J.] Abbott NW Hosp, Hosp Pathol Associates, Minneapolis, MN 55407 USA. [McCrory, Douglas C.] Duke Univ, Dept Med, Durham, NC USA. [Meier, Frederick A.] Henry Ford Hlth Syst, Dept Pathol & Lab Med, Detroit, MI USA. [Otis, Christopher N.] Baystate Med Ctr, Dept Pathol, Springfield, MA USA. [Owens, Scott R.] Univ Michigan, Sch Med, Dept Pathol, Ann Arbor, MI USA. [Raab, Stephen S.] Mem Univ Newfoundland Eastern Hlth Author, Dept Pathol, St John, NF, Canada. [Turner, Roderick R.] St Johns Hlth Ctr, Dept Pathol, Santa Monica, CA USA. [Renshaw, Andrew A.] Homestead Hosp, Dept Pathol, Homestead, FL USA. RP Nakhleh, RE (reprint author), Mayo Clin, Dept Lab Med & Pathol, 4500 San Pablo Rd, Jacksonville, FL 32224 USA. EM Nakhleh.Raouf@mayo.edu OI Colasacco, Carol/0000-0001-7856-7531 NR 148 TC 10 Z9 10 U1 4 U2 4 PU COLL AMER PATHOLOGISTS PI NORTHFIELD PA C/O KIMBERLY GACKI, 325 WAUKEGAN RD, NORTHFIELD, IL 60093-2750 USA SN 0003-9985 EI 1543-2165 J9 ARCH PATHOL LAB MED JI Arch. Pathol. Lab. Med. PD JAN PY 2016 VL 140 IS 1 BP 29 EP 40 DI 10.5858/arpa.2014-0511-SA PG 12 WC Medical Laboratory Technology; Medicine, Research & Experimental; Pathology SC Medical Laboratory Technology; Research & Experimental Medicine; Pathology GA DF3EL UT WOS:000371226600007 PM 25965939 ER PT J AU Louis, DN Feldman, M Carter, AB Dighe, AS Pfeifer, JD Bry, L Almeida, JS Saltz, J Braun, J Tomaszewski, JE Gilbertson, JR Sinard, JH Gerber, GK Galli, SJ Golden, JA Becich, MJ AF Louis, David N. Feldman, Michael Carter, Alexis B. Dighe, Anand S. Pfeifer, John D. Bry, Lynn Almeida, Jonas S. Saltz, Joel Braun, Jonathan Tomaszewski, John E. Gilbertson, John R. Sinard, John H. Gerber, Georg K. Galli, Stephen J. Golden, Jeffrey A. Becich, Michael J. TI Computational Pathology A Path Ahead SO ARCHIVES OF PATHOLOGY & LABORATORY MEDICINE LA English DT Article ID SOMATIC MUTATIONS; DATABASE; DEFINITION; HEALTH; SIFT AB Context.-We define the scope and needs within the new discipline of computational pathology, a discipline critical to the future of both the practice of pathology and, more broadly, medical practice in general. Objective.-To define the scope and needs of computational pathology. Data Sources.-A meeting was convened in Boston, Massachusetts, in July 2014 prior to the annual Association of Pathology Chairs meeting, and it was attended by a variety of pathologists, including individuals highly invested in pathology informatics as well as chairs of pathology departments. Conclusions.-The meeting made recommendations to promote computational pathology, including clearly defining the field and articulating its value propositions; asserting that the value propositions for health care systems must include means to incorporate robust computational approaches to implement data-driven methods that aid in guiding individual and population health care; leveraging computational pathology as a center for data interpretation in modern health care systems; stating that realizing the value proposition will require working with institutional administrations, other departments, and pathology colleagues; declaring that a robust pipeline should be fostered that trains and develops future computational pathologists, for those with both pathology and non-pathology backgrounds; and deciding that computational pathology should serve as a hub for data-related research in health care systems. The dissemination of these recommendations to pathology and bioinformatics departments should help facilitate the development of computational pathology. C1 [Louis, David N.; Dighe, Anand S.; Gilbertson, John R.] Massachusetts Gen Hosp, James Homer Wright Pathol Labs, WRN2,55 Fruit St, Boston, MA 02114 USA. [Louis, David N.; Dighe, Anand S.; Bry, Lynn; Gilbertson, John R.; Gerber, Georg K.; Golden, Jeffrey A.] Harvard Univ, Sch Med, Boston, MA USA. [Feldman, Michael] Univ Penn, Dept Pathol & Lab Med, Perelman Sch Med, Philadelphia, PA USA. [Carter, Alexis B.] Emory Univ, Dept Pathol & Lab Med, Atlanta, GA 30322 USA. [Pfeifer, John D.] Washington Univ, Sch Med, Dept Pathol & Immunol, St Louis, MO USA. [Bry, Lynn; Gerber, Georg K.; Golden, Jeffrey A.] Brigham & Womens Hosp, Dept Pathol, 75 Francis St, Boston, MA 02115 USA. [Almeida, Jonas S.; Saltz, Joel] SUNY Stony Brook, Dept Biomed Informat, Stony Brook, NY 11794 USA. [Braun, Jonathan] Univ Calif Los Angeles, David Geffen Sch Med, Dept Pathol & Lab Med, Los Angeles, CA 90095 USA. [Tomaszewski, John E.] SUNY Buffalo, Dept Pathol & Anat Sci, Buffalo, NY 14260 USA. [Sinard, John H.] Yale Univ, Sch Med, Dept Pathol, New Haven, CT 06510 USA. [Galli, Stephen J.] Stanford Univ, Dept Pathol & Lab Med, Palo Alto, CA 94304 USA. [Becich, Michael J.] Univ Pittsburgh, Dept Biomed Informat, Pittsburgh, PA USA. RP Louis, DN (reprint author), Massachusetts Gen Hosp, James Homer Wright Pathol Labs, WRN2,55 Fruit St, Boston, MA 02114 USA. EM louis@helix.mgh.harvard.edu FU NCI NIH HHS [U24 CA180924] NR 43 TC 5 Z9 5 U1 4 U2 5 PU COLL AMER PATHOLOGISTS PI NORTHFIELD PA C/O KIMBERLY GACKI, 325 WAUKEGAN RD, NORTHFIELD, IL 60093-2750 USA SN 0003-9985 EI 1543-2165 J9 ARCH PATHOL LAB MED JI Arch. Pathol. Lab. Med. PD JAN PY 2016 VL 140 IS 1 BP 41 EP 50 DI 10.5858/arpa.2015-0093-SA PG 10 WC Medical Laboratory Technology; Medicine, Research & Experimental; Pathology SC Medical Laboratory Technology; Research & Experimental Medicine; Pathology GA DF3EL UT WOS:000371226600008 PM 26098131 ER PT J AU Jahan-Tigh, RR Chinn, GM Rapini, RP AF Jahan-Tigh, Richard R. Chinn, Garrett M. Rapini, Ronald P. TI A Comparative Study Between Smartphone-Based Microscopy and Conventional Light Microscopy in 1021 Dermatopathology Specimens SO ARCHIVES OF PATHOLOGY & LABORATORY MEDICINE LA English DT Article ID OF-CARE DIAGNOSTICS; GLOBAL BURDEN; TELEDERMATOLOGY; DISEASE; REGIONS; NEEDS; PHONE AB Context.-The incorporation of high-resolution cameras into smartphones has allowed for a variety of medical applications including the use of lens attachments that provide telescopic, macroscopic, and dermatoscopic data, but the feasibility and performance characteristics of such a platform for use in dermatopathology have not been described. Objective.-To determine the diagnostic performance of a smartphone microscope compared to traditional light microscopy in dermatopathology specimens. Design.-A simple smartphone microscope constructed with a 3-mm ball lens was used to prospectively evaluate 1021 consecutive dermatopathology cases in a blinded fashion. Referred, consecutive specimens from the community were evaluated at a single university hospital. The performance characteristics of the smartphone platform were calculated by using conventional light microscopy as the gold standard. The sensitivity and specificity for the diagnosis of melanoma, nonmelanoma skin cancers, and other miscellaneous conditions by the phone microscopy platform, as compared with traditional light microscopy, were calculated. Results.-For basal cell carcinoma (n = 136), the sensitivity and specificity of smartphone microscopy were 95.6% and 98.1%, respectively. The sensitivity and specificity for squamous cell carcinoma (n = 94) were 89.4% and 97.3%, respectively. The lowest sensitivity was found in melanoma (n = 15) at 60%, although the specificity was high at 99.1%. The accuracy of diagnosis of inflammatory conditions and other neoplasms was variable. Conclusions.-Mobile phone-based microscopy has excellent performance characteristics for the inexpensive diagnosis of nonmelanoma skin cancers in a setting where a traditional microscope is not available. C1 [Jahan-Tigh, Richard R.; Rapini, Ronald P.] Univ Texas Houston, Hlth Sci Ctr, Dept Dermatol, 6655 Travis St,Suite 980, Houston, TX 77030 USA. [Jahan-Tigh, Richard R.; Rapini, Ronald P.] Univ Texas Houston, Hlth Sci Ctr, Dept Pathol, 6655 Travis St,Suite 980, Houston, TX 77030 USA. [Chinn, Garrett M.] Massachusetts Gen Hosp, Div Gen Internal Med, Dept Med, Boston, MA 02114 USA. [Chinn, Garrett M.] Harvard Univ, Sch Med, Boston, MA USA. RP Jahan-Tigh, RR (reprint author), Univ Texas Houston, Hlth Sci Ctr, Dept Dermatol, 6655 Travis St,Suite 980, Houston, TX 77030 USA.; Jahan-Tigh, RR (reprint author), Univ Texas Houston, Hlth Sci Ctr, Dept Pathol, 6655 Travis St,Suite 980, Houston, TX 77030 USA. EM Richard.r.jahantigh@uth.tmc.edu NR 18 TC 3 Z9 3 U1 5 U2 16 PU COLL AMER PATHOLOGISTS PI NORTHFIELD PA C/O KIMBERLY GACKI, 325 WAUKEGAN RD, NORTHFIELD, IL 60093-2750 USA SN 0003-9985 EI 1543-2165 J9 ARCH PATHOL LAB MED JI Arch. Pathol. Lab. Med. PD JAN PY 2016 VL 140 IS 1 BP 86 EP 90 DI 10.5858/arpa.2014-0593-OA PG 5 WC Medical Laboratory Technology; Medicine, Research & Experimental; Pathology SC Medical Laboratory Technology; Research & Experimental Medicine; Pathology GA DF3EL UT WOS:000371226600013 PM 26717060 ER PT S AU Fornwald, JA Lu, Q Boyce, FM Ames, RS AF Fornwald, James A. Lu, Quinn Boyce, Frederick M. Ames, Robert S. BE Murhammer, DW TI Gene Expression in Mammalian Cells Using BacMam, a Modified Baculovirus System SO BACULOVIRUS AND INSECT CELL EXPRESSION PROTOCOLS, 3RD EDITION SE Methods in Molecular Biology LA English DT Article; Book Chapter DE BacMam; Modified baculovirus; Mammalian expression; Transient expression; Viral transduction; Co-expression; Pseudotyping; Woodchuck hepatitis virus post-transcriptional regulatory element (WPRE) ID RECOMBINANT BACULOVIRUS; SMOOTHENED RECEPTOR; OSTEOSARCOMA CELLS; PROTEIN EXPRESSION; ESCHERICHIA-COLI; DRUG DISCOVERY; VECTORS; TRANSDUCTION; DELIVERY; TRANSIENT AB BacMams are modified baculoviruses that contain mammalian expression cassettes for gene delivery and expression in mammalian cells. BacMams have become an integral part of the recombinant mammalian gene expression toolbox in research labs worldwide. Construction of transfer vectors is straightforward using basic molecular biology protocols. Virus generation is based on common methods used with the baculovirus insect cell expression system. BacMam transduction of mammalian cells requires minimal modifications to familiar cell culture methods. This chapter highlights the BacMam transfer vector pHTBV. C1 [Fornwald, James A.; Lu, Quinn; Ames, Robert S.] Platform Technol & Sci GlaxoSmithKline, Collegeville, PA USA. [Boyce, Frederick M.] Harvard Univ, Sch Med, Dept Neurol, Massachusetts Gen Hosp, Boston, MA 02115 USA. RP Fornwald, JA (reprint author), Platform Technol & Sci GlaxoSmithKline, Collegeville, PA USA. NR 43 TC 0 Z9 0 U1 3 U2 5 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DR, STE 208, TOTOWA, NJ 07512-1165 USA SN 1064-3745 BN 978-1-4939-3043-2; 978-1-4939-3042-5 J9 METHODS MOL BIOL JI Methods Mol. Biol. PY 2016 VL 1350 BP 95 EP 116 DI 10.1007/978-1-4939-3043-2_5 D2 10.1007/978-1-4939-3043-2 PG 22 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Microbiology SC Biochemistry & Molecular Biology; Microbiology GA BE3TY UT WOS:000371264800006 PM 26820855 ER PT J AU Liu, T Shen, JK Li, ZH Choy, E Hornicek, FJ Duan, ZF AF Liu, Tang Shen, Jacson K. Li, Zhihong Choy, Edwin Hornicek, Francis J. Duan, Zhenfeng TI Development and potential applications of CRISPR-Cas9 genome editing technology in sarcoma SO CANCER LETTERS LA English DT Review DE CRISPR-Cas9; Sarcoma; Cancer modeling; Gene therapy ID SOFT-TISSUE SARCOMA; MOUSE MODEL; COLORECTAL-CANCER; IN-VIVO; PLEOMORPHIC RHABDOMYOSARCOMA; CHROMOSOMAL TRANSLOCATIONS; THERAPEUTIC TARGETS; CRISPR/CAS9 SYSTEM; ANTITUMOR-ACTIVITY; CELLULAR-ORIGINS AB Sarcomas include some of the most aggressive tumors and typically respond poorly to chemotherapy. In recent years, specific gene fusion/mutations and gene over-expression/activation have been shown to drive sarcoma pathogenesis and development. These emerging genomic alterations may provide targets for novel therapeutic strategies and have the potential to transform sarcoma patient care. The RNA guided nuclease CRISPR-Cas9 (Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR)-associated protein-9 nuclease) is a convenient and versatile platform for site-specific genome editing and epigenome targeted modulation. Given that sarcoma is believed to develop as a result of genetic alterations in mesenchymal progenitor/stem cells, CRISPR-Cas9 genome editing technologies hold extensive application potentials in sarcoma models and therapies. We review the development and mechanisms of the CRISPR-Cas9 system in genome editing and introduce its application in sarcoma research and potential therapy in clinic. Additionally, we propose future directions and discuss the challenges faced with these applications, providing concise and enlightening information for readers interested in this area. (C) 2016 Elsevier Ireland Ltd. All rights reserved. C1 [Liu, Tang; Shen, Jacson K.; Choy, Edwin; Hornicek, Francis J.; Duan, Zhenfeng] Massachusetts Gen Hosp, Dept Orthopaed Surg, Sarcoma Biol Lab, 55 Fruit St,Jackson 1115, Boston, MA 02114 USA. [Liu, Tang; Shen, Jacson K.; Choy, Edwin; Hornicek, Francis J.; Duan, Zhenfeng] Harvard Univ, Sch Med, 55 Fruit St,Jackson 1115, Boston, MA 02114 USA. [Liu, Tang; Li, Zhihong] Cent S Univ, Xiangya Hosp 2, Dept Orthopaed, 139 Renmin Rd, Changsha 410011, Hunan, Peoples R China. RP Duan, ZF (reprint author), Massachusetts Gen Hosp, Dept Orthopaed Surg, Sarcoma Biol Lab, 55 Fruit St,Jackson 1115, Boston, MA 02114 USA.; Duan, ZF (reprint author), Harvard Univ, Sch Med, 55 Fruit St,Jackson 1115, Boston, MA 02114 USA. EM zduan@mgh.harvard.edu FU Gattegno and Wechsler funds; Kenneth Stanton Fund; Jennifer Hunter Yates Foundation; Sarcoma Foundation of America (SFA); National Cancer Institute (NCI)/National Institutes of Health (NIH) [U01, CA 151452-01]; Sarcoma SPORE/NIH [5U54 CA168512-02]; Academic Enrichment Fund of MGH Orthopaedics; China Scholarship Council FX This work was supported, in part, by the Gattegno and Wechsler funds, the Kenneth Stanton Fund, and the Jennifer Hunter Yates Foundation. Dr. Duan is supported, in part, through a grant from Sarcoma Foundation of America (SFA), a grant from National Cancer Institute (NCI)/National Institutes of Health (NIH), U01, CA 151452-01, a pilot grant from Sarcoma SPORE/NIH, 5U54 CA168512-02, and a grant from an Academic Enrichment Fund of MGH Orthopaedics. Dr. Liu is supported by a scholarship from the China Scholarship Council. NR 89 TC 4 Z9 4 U1 11 U2 48 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0304-3835 EI 1872-7980 J9 CANCER LETT JI Cancer Lett. PY 2016 VL 373 IS 1 BP 109 EP 118 DI 10.1016/j.canlet.2016.01.030 PG 10 WC Oncology SC Oncology GA DF7PB UT WOS:000371548900012 PM 26806808 ER PT J AU Vodopivec, I Prasad, S AF Vodopivec, Ivana Prasad, Sashank TI Treatment of Susac Syndrome SO CURRENT TREATMENT OPTIONS IN NEUROLOGY LA English DT Review DE Susac syndrome; Treatment; Immunosuppression; Antiplatelet agents ID RETINAL ARTERIAL-OCCLUSION; ANTIENDOTHELIAL CELL ANTIBODIES; RETINOCOCHLEOCEREBRAL VASCULOPATHY; HEARING-LOSS; YOUNG-WOMEN; BRAIN; MICROANGIOPATHY; THERAPY; ENDOTHELIOPATHY; IMPROVEMENT AB Susac syndrome is a microangiopathy of the brain, retina, and cochlea. Several lines of evidence support the concept that this disease is an acquired autoimmune disorder. Prospective, randomized, controlled studies of treatments are not available because the disease is rare. Furthermore, the average period of follow-up in reported cases is short, limiting a complete understanding of the natural history of the disease. Empirical treatment strategies are therefore based upon expert recommendations and anecdotal reports of response to various immunomodulators, and the appropriate duration of therapy is not known. In our opinion, the encephalopathic form of Susac syndrome should be treated early and aggressively to avoid cognitive dysfunction and disability. Induction therapy with pulse methylprednisolone frequently proves to be inadequate. Additional agents, including intravenous immunoglobulins, intravenous cyclophosphamide, or rituximab are often necessary to induce a sustained remission. Maintenance therapy with oral glucocorticoids combined with intravenous immunoglobulins, mycophenolate mofetil, methotrexate, azathioprine, cyclophosphamide, or rituximab is typically necessary to achieve a sustained remission. Aspirin may be used as an adjunctive agent, although evidence showing efficacy is scant. The response to treatment should be closely monitored by frequent clinical examinations, brain MRI, and fluorescein angiography. Once disease remission has been established, it appears prudent to continue maintenance treatment for at least two additional years, although the real long-term risk of future relapses remains unknown. Establishing a multicenter patient registry and biorepository is essential to study the pathogenesis of the disease, further define the duration of disease, identify reliable biomarkers that aid early diagnosis and assess risk of relapse, and develop effective disease-specific therapies. C1 [Vodopivec, Ivana] Massachusetts Eye & Ear Infirm, Neuroophthalmol Serv, 243 Charles St, Boston, MA 02114 USA. [Vodopivec, Ivana; Prasad, Sashank] Brigham & Womens Hosp, Dept Neurol, 75 Francis St, Boston, MA 02115 USA. [Vodopivec, Ivana; Prasad, Sashank] Harvard Univ, Sch Med, Boston, MA USA. RP Vodopivec, I (reprint author), Massachusetts Eye & Ear Infirm, Neuroophthalmol Serv, 243 Charles St, Boston, MA 02114 USA.; Vodopivec, I (reprint author), Brigham & Womens Hosp, Dept Neurol, 75 Francis St, Boston, MA 02115 USA.; Vodopivec, I (reprint author), Harvard Univ, Sch Med, Boston, MA USA. EM ivodopivec@partners.org NR 43 TC 0 Z9 0 U1 5 U2 5 PU CURRENT MEDICINE GROUP PI PHILADELPHIA PA 400 MARKET STREET, STE 700, PHILADELPHIA, PA 19106 USA SN 1092-8480 EI 1534-3138 J9 CURR TREAT OPTION NE JI Curr. Treat. Options Neurol. PD JAN PY 2016 VL 18 IS 1 AR 3 DI 10.1007/s11940-015-0386-x PG 8 WC Clinical Neurology SC Neurosciences & Neurology GA DF5KQ UT WOS:000371391000004 PM 26715396 ER PT J AU Bury, L Falcinelli, E Chiasserini, D Springer, TA Italiano, JE Gresele, P AF Bury, Loredana Falcinelli, Emanuela Chiasserini, Davide Springer, Timothy A. Italiano, Joseph E., Jr. Gresele, Paolo TI Cytoskeletal perturbation leads to platelet dysfunction and thrombocytopenia in variant forms of Glanzmann thrombasthenia SO HAEMATOLOGICA LA English DT Article ID GLYCOPROTEIN-IIB-IIIA; INTEGRIN ALPHA(IIB)BETA(3); PROPLATELET FORMATION; CONGENITAL MACROTHROMBOCYTOPENIA; ALPHA-IIB-BETA-3 RECEPTOR; PEPTIDE IDENTIFICATION; BETA-3; ACTIVATION; FIBRINOGEN; MUTATIONS AB Several patients have been reported to have variant dominant forms of Glanzmann thrombasthenia, associated with macrothrombocytopenia and caused by gain-of-function mutations of ITGB3 or ITGA2B leading to reduced surface expression and constitutive activation of integrin alpha(IIb)beta(3). The mechanisms leading to a bleeding phenotype of these patients have never been addressed. The aim of this study was to unravel the mechanism by which ITGB3 mutations causing activation of alpha(IIb)beta(3) lead to platelet dysfunction and macrothrombocytopenia. Using platelets from two patients carrying the beta(3) del647-686 mutation and Chinese hamster ovary cells expressing different alpha(IIb)beta(3)-activating mutations, we showed that reduced surface expression of alpha(IIb)beta(3) is due to receptor internalization. Moreover, we demonstrated that permanent triggering of alpha(IIb)beta(3)-mediated outside-in signaling causes an impairment of cytoskeletal reorganization arresting actin turnover at the stage of polymerization. The induction of actin polymerization by jasplakinolide, a natural toxin that promotes actin nucleation and prevents depolymerization of stress fibers, in control platelets produced an impairment of platelet function similar to that of patients with variant forms of dominant Glanzmann thrombasthenia. del647-686 beta(3)-transduced murine megakaryocytes generated proplatelets with a reduced number of large tips and asymmetric barbell-proplatelets, suggesting that impaired cytoskeletal rearrangement is the cause of macrothrombocytopenia. These data show that impaired cytoskeletal remodeling caused by a constitutively activated alpha(IIb)beta(3) is the main effector of platelet dysfunction and macrothrombocytopenia, and thus of bleeding, in variant forms of dominant Glanzmann thrombasthenia. C1 [Bury, Loredana; Falcinelli, Emanuela; Gresele, Paolo] Univ Perugia, Sect Internal & Cardiovasc Med, Dept Med, I-06100 Perugia, Italy. [Chiasserini, Davide] Univ Perugia, Neurol Sect, Dept Med, I-06100 Perugia, Italy. [Springer, Timothy A.] Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA. [Springer, Timothy A.] Childrens Hosp, Program Cellular & Mol Med, 300 Longwood Ave, Boston, MA 02115 USA. [Italiano, Joseph E., Jr.] Boston Childrens Hosp, Brigham & Womens Hosp, Vasc Biol Program, Dept Med,Hematol Div, Boston, MA USA. [Italiano, Joseph E., Jr.] Harvard Univ, Sch Med, Boston, MA USA. RP Gresele, P (reprint author), Univ Perugia, Sect Internal & Cardiovasc Med, Dept Med, I-06100 Perugia, Italy. EM paolo.gresele@unipg.it RI Chiasserini, Davide/K-7074-2016 OI Chiasserini, Davide/0000-0002-1169-3258 FU Telethon grant [GGP10155] FX This work was supported by a Telethon grant (GGP10155) to PG. NR 48 TC 7 Z9 7 U1 4 U2 6 PU FERRATA STORTI FOUNDATION PI PAVIA PA VIA GIUSEPPE BELLI 4, 27100 PAVIA, ITALY SN 0390-6078 J9 HAEMATOLOGICA JI Haematologica PD JAN PY 2016 VL 101 IS 1 BP 46 EP 56 DI 10.3324/haematol.2015.130849 PG 11 WC Hematology SC Hematology GA DF3CG UT WOS:000371220700019 PM 26452979 ER PT J AU Nakasone, H Sahaf, B Tian, L Wang, T Haagenson, MD Schoenrock, K Perloff, S Ryan, CE Wu, F Spellman, SR Lee, SJ Ritz, J Miklos, DB AF Nakasone, Hideki Sahaf, Bita Tian, Lu Wang, Tao Haagenson, Michael D. Schoenrock, Kelsi Perloff, Spenser Ryan, Christine E. Wu, Fang Spellman, Stephen R. Lee, Stephanie J. Ritz, Jerome Miklos, David B. CA Ctr Int Blood Marrow TI Presensitization to HY antigens in female donors prior to transplant is not associated with male recipient post-transplant HY antibody development nor with clinical outcomes SO HAEMATOLOGICA LA English DT Letter DE allogeneic hematopoietic transplantation; bone marrow transplantation; graft versus host disease (GVHD); HY antigen; sex mismatch transplantation ID VERSUS-HOST-DISEASE; STEM-CELL TRANSPLANTATION; B-CELLS; IMPACT C1 [Nakasone, Hideki; Sahaf, Bita; Ryan, Christine E.; Wu, Fang; Miklos, David B.] Stanford Univ, Sch Med, Div Blood & Marrow Transplantat, Stanford, CA 94305 USA. [Nakasone, Hideki] Jichi Med Univ, Saitama Med Ctr, Div Hematol, Saitama, Japan. [Tian, Lu] Stanford Univ, Sch Med, Hlth Res & Policy, Stanford, CA 94305 USA. [Wang, Tao; Schoenrock, Kelsi; Perloff, Spenser] Med Coll Wisconsin, Ctr Int Blood & Marrow Transplant Res, Milwaukee, WI 53226 USA. [Wang, Tao; Schoenrock, Kelsi; Perloff, Spenser] Med Coll Wisconsin, Div Biostat, Milwaukee, WI 53226 USA. [Haagenson, Michael D.; Spellman, Stephen R.] Ctr Int Blood & Marrow Transplant Res, Minneapolis, MN USA. [Lee, Stephanie J.] Fred Hutchinson Canc Res Ctr, Ctr Int Blood & Marrow Transplant Res, 1124 Columbia St, Seattle, WA 98104 USA. [Lee, Stephanie J.] Fred Hutchinson Canc Res Ctr, Div Clin Res, 1124 Columbia St, Seattle, WA 98104 USA. [Ritz, Jerome] Harvard Univ, Sch Med, Dana Farber Canc Inst, Div Hematol Malignancies, 44 Binney St, Boston, MA 02115 USA. RP Miklos, DB (reprint author), Stanford Univ, Sch Med, Div Blood & Marrow Transplantat, Stanford, CA 94305 USA. EM dmiklos@stanford.edu FU NCI NIH HHS [P01 CA049605, P01 CA142106, P01CA049605, U24 CA076518, U24-CA76518]; NHLBI NIH HHS [5U01HL069294, K08 HL069132, K08HL69132, R21 HL084318, U01 HL069294]; PHS HHS [HHSH234200637015C] NR 15 TC 0 Z9 0 U1 0 U2 0 PU FERRATA STORTI FOUNDATION PI PAVIA PA VIA GIUSEPPE BELLI 4, 27100 PAVIA, ITALY SN 0390-6078 J9 HAEMATOLOGICA JI Haematologica PD JAN PY 2016 VL 101 IS 1 BP E30 EP E33 DI 10.3324/haematol.2015.134551 PG 4 WC Hematology SC Hematology GA DF3CG UT WOS:000371220700009 PM 26494841 ER PT J AU Messerlian, C Souter, I Gaskins, AJ Williams, PL Ford, JB Chiu, YH Calafat, AM Hauser, R AF Messerlian, Carmen Souter, Irene Gaskins, Audrey J. Williams, Paige L. Ford, Jennifer B. Chiu, Yu-Han Calafat, Antonia M. Hauser, Russ CA Earth Study Team TI Urinary phthalate metabolites and ovarian reserve among women seeking infertility care SO HUMAN REPRODUCTION LA English DT Article DE phthalate metabolites; ovarian reserve; antral follicle count; medically assisted reproduction; assisted reproductive technology; epidemiology ID ENDOCRINE-DISRUPTING CHEMICALS; BISPHENOL-A; REPRODUCTIVE DEVELOPMENT; EXPOSURE; HEALTH; ASSOCIATION; MECHANISMS; FOLLICLES; RATS; LIFE AB Are urinary phthalate metabolites associated with reduced antral follicle growth among women in an infertility setting? Higher urinary concentrations of di(2-ethylhexyl) phthalate (DEHP) metabolites were associated with significant decreases in antral follicle count (AFC) among women seeking infertility care. Experimental animal studies show that DEHP accelerates primordial follicle recruitment and inhibits antral follicle growth. Whether phthalates also reduce the growing antral follicle pool in humans remains unknown. We examined the association between urinary phthalate metabolites and AFC using prospective data from 215 females recruited between 2004 and 2012 in the Environment and Reproductive Health (EARTH) study. We quantified the urinary concentrations of 11 phthalate metabolites. We estimated the geometric mean for all urine samples provided prior to unstimulated day 3 AFC assessment for each woman. We evaluated the association of AFC with aDEHP (molar sum of four DEHP metabolites) and individual phthalate metabolites using Poisson regression, adjusting for age, BMI and smoking. We observed significant decreases in mean AFC for all higher quartiles of aDEHP as compared with the lowest quartile. Compared with women in the first quartile of aDEHP, women in the second, third and fourth quartiles had a -24% (95% confidence interval (CI): -32%, -16%), -19% (95% CI: -27%, -9%), and -14% (95% CI: -23%, -5%) decrease in mean AFC. The absolute mean AFC in the first quartile was 14.2 follicles (95% CI: 13.2, 15.2) compared with 10.7 follicles (95% CI: 9.9, 11.6) in the second quartile. We observed similar trends among the four individual DEHP metabolites. There was no consistent change in AFC among the remaining phthalate metabolite concentrations evaluated. We demonstrated a negative association between DEHP and a well-established marker of ovarian reserve among a subfertile population. However these findings may not be generalizable to women without fertility concerns, and we cannot rule out co-exposure to other chemicals. Environmental chemicals that inhibit the size of the growing antral follicle pool can impair fertility and reduce fecundity. This study suggests evidence in need of further investigation on the impact of phthalates on the human oocyte and follicular development. Work supported by grants ES009718, ES022955, ES000002, and T32ES007069 from the National Institute of Environmental Health Sciences (NIEHS) and grant T32 DK007703-16 from the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK). C.M. was supported by a post-doctoral training award from the Canadian Institutes of Health Research. There are no competing interests to declare. C1 [Messerlian, Carmen; Ford, Jennifer B.; Hauser, Russ] Harvard Univ, TH Sch Publ Hlth, Dept Environm Hlth, Boston, MA 02115 USA. [Souter, Irene; Hauser, Russ] Harvard Univ, Sch Med, Dept Obstet & Gynecol, Fertil Ctr,Massachusetts Gen Hosp, Boston, MA 02115 USA. [Gaskins, Audrey J.; Chiu, Yu-Han] Harvard Univ, TH Chan Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA. [Williams, Paige L.] Harvard Univ, TH Chan Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. [Williams, Paige L.; Hauser, Russ] Harvard Univ, TH Chan Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. [Calafat, Antonia M.] Ctr Dis Control & Prevent, Natl Ctr Environm Hlth, Atlanta, GA USA. RP Messerlian, C (reprint author), Harvard Univ, TH Chan Sch Publ Hlth, 665 Huntington Ave,FXB 102A, Boston, MA USA. EM cmesser@hsph.harvard.edu FU National Institute of Environmental Health Sciences (NIEHS) [ES009718, ES022955, ES000002, T32ES007069]; National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) [T32 DK007703-16]; Canadian Institutes of Health Research FX Work supported by grants ES009718, ES022955, ES000002, and T32ES007069 from the National Institute of Environmental Health Sciences (NIEHS) and grant T32 DK007703-16 from the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK). C.M. was supported by a post-doctoral training award from the Canadian Institutes of Health Research. NR 36 TC 8 Z9 8 U1 2 U2 6 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0268-1161 EI 1460-2350 J9 HUM REPROD JI Hum. Reprod. PD JAN PY 2016 VL 31 IS 1 BP 75 EP 83 DI 10.1093/humrep/dev292 PG 9 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA DF2CY UT WOS:000371148900011 PM 26573529 ER PT J AU Hato, T Zhu, AX Duda, DG AF Hato, Tai Zhu, Andrew X. Duda, Dan G. TI Rationally combining anti-VEGF therapy with checkpoint inhibitors in hepatocellular carcinoma SO IMMUNOTHERAPY LA English DT Review DE CTLA-4; hepatocellular carcinoma; immune checkpoint; LAG-3; PD-1; PD-L1; TIM-3; VEGF; VEGFR2 ID ENDOTHELIAL GROWTH-FACTOR; CHRONIC HEPATITIS-C; DENDRITIC CELL-DIFFERENTIATION; INDUCED IMMUNE SUPPRESSION; NATURAL-KILLER-CELLS; REGULATORY T-CELLS; TUMOR MICROENVIRONMENT; ADENOSINE RECEPTOR; VIRUS-INFECTION; ANTITUMOR IMMUNITY AB Hepatocellular carcinoma (HCC) is a fatal disease with rising incidence in the world. For advanced HCC, sorafenib, a multikinase inhibitor, is the only systemic therapy with proven survival benefits. Sorafenib is a pan-VEGF receptor inhibitor, and thus many studies have focused its antivascular effects. But VEGF also acts as an immunosuppressive molecule. VEGF can inhibit maturation of dendritic cells, promote immune suppressive cell infiltration and enhance immune checkpoint molecules expression. On the other hand, potent VEGF inhibition may increase tumor hypoxia, which could hinder antitumor immunity or immunotherapy. Thus, achieving synergy when combining anti-VEGF therapy with immunotherapy may require proper polarization of the tumor microenvironment by dose titration or combination with other immunomodulating agents. C1 [Hato, Tai; Duda, Dan G.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Edwin L Steele Labs,Dept Radiat Oncol, Boston, MA 02114 USA. [Hato, Tai] Keio Univ, Sch Med, Dept Surg, Tokyo 1608582, Japan. [Zhu, Andrew X.] Harvard Univ, Sch Med, Hematol Oncol, Dept Med,Massachusetts Gen Hosp,Canc Ctr, Boston, MA 02114 USA. RP Duda, DG (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Edwin L Steele Labs,Dept Radiat Oncol, Boston, MA 02114 USA. EM gduda@partners.org FU National Institutes of Health [P01-CA080124, R01-CA159258, R21-CA139168]; National Cancer Institute/Proton Beam Federal Share Program award; American Cancer Society [120733-RSG-11-073-01-TBG] FX This study is supported by the National Institutes of Health (grant nos. P01-CA080124, R01-CA159258 and R21-CA139168), a National Cancer Institute/Proton Beam Federal Share Program award and the American Cancer Society (grant no. 120733-RSG-11-073-01-TBG [to DG Duda]). 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 94 TC 2 Z9 2 U1 3 U2 11 PU FUTURE MEDICINE LTD PI LONDON PA UNITEC HOUSE, 3RD FLOOR, 2 ALBERT PLACE, FINCHLEY CENTRAL, LONDON, N3 1QB, ENGLAND SN 1750-743X EI 1750-7448 J9 IMMUNOTHERAPY-UK JI Immunotherapy PY 2016 VL 8 IS 3 BP 299 EP 313 DI 10.2217/imt.15.126 PG 15 WC Immunology SC Immunology GA DF2FY UT WOS:000371159200008 PM 26865127 ER PT J AU Fan, VS Gharib, SA Martin, TR Wurfel, MM AF Fan, Vincent S. Gharib, Sina A. Martin, Thomas R. Wurfel, Mark M. TI COPD disease severity and innate immune response to pathogen-associated molecular patterns SO INTERNATIONAL JOURNAL OF CHRONIC OBSTRUCTIVE PULMONARY DISEASE LA English DT Article DE chronic obstructive pulmonary disease; innate immunity; inflammation; chronic bronchitis; toll-like receptors ID OBSTRUCTIVE PULMONARY-DISEASE; TOLL-LIKE RECEPTORS; TUMOR-NECROSIS-FACTOR; AIRWAY INFLAMMATION; SYSTEMIC INFLAMMATION; ALVEOLAR MACROPHAGES; BRONCHIAL LAVAGE; HUMAN MONOCYTES; EXPRESSION; CYTOKINES AB The airways of COPD patients are often colonized with bacteria leading to increased airway inflammation. This study sought to determine whether systemic cytokine responses to microbial pathogen-associated molecular patterns (PAMPs) are increased among subjects with severe COPD. In an observational cross-sectional study of COPD subjects, PAMP-induced cytokine responses were measured in whole blood ex vivo. We used PAMPs derived from microbial products recognized by toll-like receptors 1, 2, 4, 5, 6, 7, and 8. Patterns of cytokine response to PAMPs were assessed using hierarchical clustering. One-sided Student's t-tests were used to compare PAMP-induced cytokine levels in blood from patients with and without severe COPD, and for subjects with and without chronic bronchitis. Of 28 male patients, 12 had moderate COPD (FEV1 50%-80%) and 16 severe COPD (FEV1,50%); 27 participants provided data on self-reported chronic bronchitis, of which 15 endorsed chronic bronchitis symptoms and 12 did not. Cytokine responses to PAMPs in severe COPD were generally lower than in subjects with milder COPD. This finding was particularly strong for PAMP-induced interleukin (IL)-10, granulocyte colony stimulating factor, and IL-1 beta. Subjects with chronic bronchitis showed higher PAMP-induced IL-1RA responses to most of the PAMPs evaluated. COPD patients with more severe disease demonstrated a diminished cytokine response to PAMPs, suggesting that chronic colonization with bacteria may dampen the systemic innate immune response. C1 [Fan, Vincent S.; Martin, Thomas R.] VA Puget Sound Hlth Care Syst, Seattle, WA 98108 USA. [Fan, Vincent S.; Gharib, Sina A.; Martin, Thomas R.; Wurfel, Mark M.] Univ Washington, Div Pulm & Crit Care Med, Dept Med, Seattle, WA 98195 USA. [Gharib, Sina A.] Univ Washington, Computat Med Core, Ctr Lung Biol, Seattle, WA 98195 USA. RP Fan, VS (reprint author), VA Puget Sound Hlth Care Syst, Hlth Serv Res & Dev 152, 1660 S Columbian Way, Seattle, WA 98108 USA. EM vfan@u.washington.edu FU United States Department of Veterans Affairs Health Services Research and Development Program [02-170-2]; National Institute of Allergy and Infectious Diseases [U54 AI057141] FX Angela Horn assisted in recruitment, study visits, and data management for the study. This work was supported by Career Development Award, Award # 02-170-2, from the United States Department of Veterans Affairs Health Services Research and Development Program, as well as a grant by the National Institute of Allergy and Infectious Diseases (Award # U54 AI057141). The views expressed in this article are those of the authors and do not necessarily represent the views of the Department of Veterans Affairs. NR 45 TC 3 Z9 3 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 2016 VL 11 BP 467 EP 477 DI 10.2147/COPD.S94410 PG 11 WC Respiratory System SC Respiratory System GA DF5GK UT WOS:000371379600001 PM 27019597 ER PT J AU Peetz, A Salim, A Askari, R De Moya, MA Olufajo, OA Simon, TG Gibbons, FK Christopher, KB AF Peetz, Allan Salim, Ali Askari, Reza De Moya, Marc A. Olufajo, Olubode A. Simon, Tracey G. Gibbons, Fiona K. Christopher, Kenneth B. TI Association of Model for End-Stage Liver Disease Score and Mortality in Trauma Patients With Chronic Liver Disease SO JAMA SURGERY LA English DT Article ID INJURY SEVERITY SCORE; CRITICALLY-ILL; PREDICTIVE ABILITY; INTENSIVE-CARE; ORGAN FAILURE; CIRRHOSIS; EPIDEMIOLOGY; PERFORMANCE; VALIDATION; SELECTION AB IMPORTANCE The Model for End-Stage Liver Disease (MELD) score is predictive of trauma outcomes. OBJECTIVE To determine whether a decrease in MELD score is associated with improved mortality in critically ill trauma patients. DESIGN, SETTING, AND PARTICIPANTS We performed a retrospective registry study of critically ill trauma patients 18 years or older with chronic liver disease treated between August 3, 1998, and January 5, 2012, at 2 level I trauma centers in Boston, Massachusetts. The consecutive sample included 525 patients (male, 373 [71.0%]; white, 399 [76.0%]; mean [SD] age, 55.0[12.4] years). EXPOSURES Change in MELD score from intensive care unit (ICU) admission to 48 to 72 hours later. MAIN OUTCOMES AND MEASURES Thirty-day all-cause mortality. RESULTS The mean (SD) MELD score at ICU admission was 19.3 (9.7). The 30-day mortality was 21.9%. The odds of 30-day mortality with a change in MELD score of less than -2, -2 to -1, +1 to +4, and greater than +4 were 0.23 (95% CI, 0.10-0.51), 0.30 (95% CI, 0.10-0.85), 0.57 (95% CI, 0.27-1.20), and 1.31 (95% CI, 0.58-2.96), respectively, relative to a change in MELD score of 0 and adjusted for age, sex, race, Charlson/Deyo Index, sepsis, number of acute organ failures, International Classification of Diseases, Ninth Revision-based injury severity score, and ICU admission MELD score. CONCLUSIONS AND RELEVANCE A decrease in MELD score within 72 hours of ICU admission is associated with improved mortality. C1 [Peetz, Allan; Salim, Ali; Askari, Reza; Olufajo, Olubode A.] Brigham & Womens Hosp, Dept Surg, Div Trauma Burns & Surg Crit Care, 75 Francis St, Boston, MA 02115 USA. [De Moya, Marc A.] Massachusetts Gen Hosp, Dept Surg, Div Trauma Emergency Surg & Surg Crit Care, Boston, MA 02114 USA. [Simon, Tracey G.] Brigham & Womens Hosp, Dept Med, 75 Francis St, Boston, MA 02115 USA. [Gibbons, Fiona K.] Massachusetts Gen Hosp, Dept Med, Div Pulm & Crit Care Med, Boston, MA 02114 USA. [Christopher, Kenneth B.] Brigham & Womens Hosp, Dept Med, Div Renal, Nathan E Hellman Mem Lab, Boston, MA 02115 USA. RP Christopher, KB (reprint author), Brigham & Womens Hosp, Nathan E Hellman Mem Lab, Div Renal, Dept Med, 75 Francis St,Med Res Bldg 418, Boston, MA 02115 USA. EM kbchristopher@partners.org NR 30 TC 3 Z9 3 U1 0 U2 2 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 2016 VL 151 IS 1 BP 41 EP 48 DI 10.1001/jamasurg.2015.3114 PG 8 WC Surgery SC Surgery GA DF4KD UT WOS:000371315800011 PM 26422817 ER PT J AU Beringer, PM Bensman, TJ Ho, H Agnello, M Denovel, N Nguyen, A Wong-Beringer, A She, R Tran, DQ Moskowitz, SM Selsted, ME AF Beringer, Paul M. Bensman, Timothy J. Ho, Henry Agnello, Melissa Denovel, Nicole Albert Nguyen Wong-Beringer, Annie She, Rosemary Tran, Dat Q. Moskowitz, Samuel M. Selsted, Michael E. TI Rhesus theta-defensin-1 (RTD-1) exhibits in vitro and in vivo activity against cystic fibrosis strains of Pseudomonas aeruginosa SO JOURNAL OF ANTIMICROBIAL CHEMOTHERAPY LA English DT Article ID THETA-DEFENSINS; ANTIMICROBIAL PEPTIDE; POLYMYXIN RESISTANCE; ALPHA-DEFENSINS; BIOFILMS; INFECTION; COLISTIN; SYSTEM; PMRB; MICE AB Objectives:Chronic endobronchial infections with Pseudomonas aeruginosa contribute to bronchiectasis and progressive loss of lung function in patients with cystic fibrosis. This study aimed to evaluate the therapeutic potential of a novel macrocyclic peptide, rhesus theta-defensin-1 (RTD-1), by characterizing its in vitro antipseudomonal activity and in vivo efficacy in a murine model of chronic Pseudomonas lung infection. Methods: Antibacterial testing of RTD-1 was performed on 41 clinical isolates of P. aeruginosa obtained from cystic fibrosis patients. MIC, MBC, time-kill and post-antibiotic effects were evaluated following CLSI-recommended methodology, but using anion-depleted Mueller-Hinton broth. RTD-1 was nebulized daily for 7 days to cystic fibrosis transmembrane conductance regulator (CFTR) F508del-homozygous mice infected using the agar bead model of chronic P. aeruginosa lung infection. In vivo activity was evaluated by change in lung bacterial burden, airway leucocytes and body weight. Results: RTD-1 exhibited potent in vitro bactericidal activity against mucoid and non-mucoid strains of P. aeruginosa (MIC90=8 mg/L). Cross-resistance was not observed when tested against MDR and colistin-resistant isolates. Time-kill studies indicated very rapid, concentration-dependent bactericidal activity of RTD-1 with >= 3 log(10) cfu/mL reductions at concentrations >= 4xMIC. No post-antibiotic effect was observed. In vivo, nebulized treatment with RTD-1 significantly decreased lung P. aeruginosa burden (mean difference of -1.30 log(10) cfu; P=0.0061), airway leucocytes (mean difference of -0.37 log(10); P=0.0012) and weight loss (mean difference of -12.62% at day 7; P < S0.05) when compared with controls. Conclusions: This study suggests that RTD-1 is a promising potential therapeutic agent for cystic fibrosis airway disease. C1 [Beringer, Paul M.; Bensman, Timothy J.; Ho, Henry; Agnello, Melissa; Denovel, Nicole; Albert Nguyen; Wong-Beringer, Annie] Univ So Calif, Sch Pharm, 1985 Zonal Ave, Los Angeles, CA 90033 USA. [She, Rosemary; Tran, Dat Q.; Selsted, Michael E.] Univ So Calif, Keck Sch Med, Dept Pathol & Lab Med, 2011 Zonal Ave, Los Angeles, CA 90033 USA. [Moskowitz, Samuel M.] Massachusetts Gen Hosp, Dept Pediat, 275 Cambridge St, Boston, MA 02114 USA. [Moskowitz, Samuel M.] Harvard Univ, Sch Med, 275 Cambridge St, Boston, MA USA. [Selsted, Michael E.] USC Norris Comprehens Canc Ctr, 1441 Eastlake Ave, Los Angeles, CA USA. RP Beringer, PM (reprint author), Univ So Calif, Sch Pharm, 1985 Zonal Ave, Los Angeles, CA 90033 USA. EM beringer@usc.edu FU Cystic Fibrosis Foundation [BERING14GO]; Cystic Fibrosis Research Inc.; National Institute of Dental and Craniofacial Research [5T90DE021982]; National Institute of General Medicine [F31GM109729, RO1AI22931, R01DE 021341]; National Cancer Institute [P30CA014089] FX Research was supported in part by research grants from the Cystic Fibrosis Foundation (BERING14GO) and Cystic Fibrosis Research Inc. (P. M. B.), the National Institute of Dental and Craniofacial Research (5T90DE021982) and the National Institute of General Medicine (F31GM109729) (T. J. B.), RO1AI22931 and R01DE 021341 (M. E. S.) and the National Cancer Institute (P30CA014089). NR 36 TC 2 Z9 2 U1 1 U2 7 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0305-7453 EI 1460-2091 J9 J ANTIMICROB CHEMOTH JI J. Antimicrob. Chemother. PD JAN PY 2016 VL 71 IS 1 BP 181 EP 188 DI 10.1093/jac/dkv301 PG 8 WC Infectious Diseases; Microbiology; Pharmacology & Pharmacy SC Infectious Diseases; Microbiology; Pharmacology & Pharmacy GA DF3IS UT WOS:000371238100027 PM 26433781 ER PT J AU Fu, JJ Shi, ZZ Li, M Wang, YY Yu, L AF Fu, JingJing Shi, ZhuanZhuan Li, Man Wang, Yangyang Yu, Ling TI Label-Free Detection of Chondroitin Sulphate Proteoglycan 4 by a Polyaniline/Graphene Nanocomposite Functionalized Impedimetric Immunosensor SO JOURNAL OF NANOMATERIALS LA English DT Article ID MELANOMA-ASSOCIATED ANTIGEN; MALIGNANT-MELANOMA; HMW-MAA; CSPG4; CELLS; CANCER; SERUM; IMMUNOTHERAPY; GRAPHENE; SURVIVAL AB The chondroitin sulphate proteoglycan 4 (CSPG4), also known as high molecular weight-melanoma associated antigen (HMW-MAA), is a tumor-associated antigen that is expressed in more than 85% of surgically removed melanoma lesions but has restricted distribution in normal tissues. The diagnostic and therapeutic value of CSPG4 drives a need for sensitive and low-cost detection approaches. To this end, we developed a polyaniline/graphene oxide nanocomposite (PANI@GO) that was electrochemically codeposited on indium tin oxide (ITO) electrode. Glutaraldehyde mediated the covalent immobilization of CSPG4 specific antibody mAbD2.8.5 to construct a CSPG4 immunosensor using cell culture media and cell lysate as samples. The fully assembled impedimetric immunosensor was used to detect CSPG4 in CSPG4-positive cell lines M14/CSPG4 and MV3. No impedance signal changes could be observed from CSPG4-negative cell lines M14 and mAbMk2-23 showing the specificity of the CSPG4-impedimetric immunosensor. This low-cost, simple, and label-free analytical method is an alternative to enzyme-linked immunosorbent assay and flow cytometry in screening of CSPG4 in complex biological samples. C1 [Fu, JingJing; Shi, ZhuanZhuan; Li, Man; Yu, Ling] Chongqing Key Lab Adv Mat & Technol Clean Energie, Chongqing 400715, Peoples R China. [Fu, JingJing; Shi, ZhuanZhuan; Li, Man; Yu, Ling] Southwest Univ, Fac Mat & Energy, Inst Clean Energy & Adv Mat, Chongqing 400715, Peoples R China. [Wang, Yangyang] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA 02114 USA. RP Yu, L (reprint author), Chongqing Key Lab Adv Mat & Technol Clean Energie, Chongqing 400715, Peoples R China.; Yu, L (reprint author), Southwest Univ, Fac Mat & Energy, Inst Clean Energy & Adv Mat, Chongqing 400715, Peoples R China. EM lingyu12@swu.edu.cn RI Yu, Ling/J-4286-2016 FU National Key Scientific Instrument and Equipment Development Projects of China [2013YQ03062909]; National Science Foundation of China [21375108]; Science Foundation of Chongqing [cstc2014jcyjA10070]; Fundamental Research Funds for the Central Universities [XDJK2015B020] FX The authors thank Dr. Soldano Ferrone (Massachusetts General Hospital, Harvard Medical School) for the kind gift of the CSPG4 antibodies and melanoma cell lines. This work is financially supported by the National Key Scientific Instrument and Equipment Development Projects of China under Contract no. 2013YQ03062909, National Science Foundation of China (no. 21375108), Science Foundation of Chongqing (cstc2014jcyjA10070), and Fundamental Research Funds for the Central Universities (XDJK2015B020). NR 20 TC 1 Z9 1 U1 10 U2 26 PU HINDAWI PUBLISHING CORP PI NEW YORK PA 410 PARK AVENUE, 15TH FLOOR, #287 PMB, NEW YORK, NY 10022 USA SN 1687-4110 EI 1687-4129 J9 J NANOMATER JI J. Nanomater. PY 2016 AR 7834657 DI 10.1155/2016/7834657 PG 8 WC Nanoscience & Nanotechnology; Materials Science, Multidisciplinary SC Science & Technology - Other Topics; Materials Science GA DF7FA UT WOS:000371522000001 ER PT J AU Brummel-Smith, K Butler, D Frieder, M Gibbs, N Henry, M Koons, E Loggers, E Porock, D Reuben, DB Saliba, D Scanlon, WJ Tabbush, V Tinetti, M Tumlinson, A Vladeck, BC Kogan, AC Mosqueda, L Wilber, K Goodwin, C Lundebjerg, NE Mikhailovich, A Aiello, SE AF Brummel-Smith, Kenneth Butler, Dawn Frieder, Miryam Gibbs, Nancy Henry, Maureen Koons, Eileen Loggers, Elizabeth Porock, Davina Reuben, David B. Saliba, Debra Scanlon, William J. Tabbush, Victor Tinetti, Mary Tumlinson, Anne Vladeck, Bruce C. Kogan, Alexis Coulourides Mosqueda, Laura Wilber, Kate Goodwin, Carol Lundebjerg, Nancy E. Mikhailovich, Anna Aiello, Susan E. CA Amer Geriatrics Soc Expert Panel TI Person-Centered Care: A Definition and Essential Elements SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Article DE person-centered care; patient-centered care; care delivery; care quality; care coordination AB Improving healthcare safety, quality, and coordination, as well as quality of life, are important aims of caring for older adults with multiple chronic conditions and/or functional limitations. Person-centered care is an approach to meeting these aims, but there are no standardized, agreed-upon parameters for delivering such care. The SCAN Foundation charged a team from the American Geriatrics Society (AGS) in collaboration with a research and clinical team from the Keck School of Medicine of the University of Southern California to provide the evidence base to support a definition of person-centered care and its essential elements. An interprofessional panel of experts in person-centered care principles and practices that the AGS convened developed this statement. C1 [Brummel-Smith, Kenneth] Amer Geriat Soc, 40 Fulton St 18th Floor, New York, NY 10038 USA. [Brummel-Smith, Kenneth] Florida State Univ, Coll Med, Tallahassee, FL 32306 USA. [Butler, Dawn] Indiana Univ, Sch Med, Indianapolis, IN 46204 USA. [Frieder, Miryam] Avalere Hlth, Washington, DC USA. [Gibbs, Nancy] So Calif Permanente Med Grp, Pasadena, CA USA. [Henry, Maureen] NCQA, Washington, DC USA. [Henry, Maureen] Univ Utah, Coll Nursing, Salt Lake City, UT USA. [Koons, Eileen] Huntington Hosp Senior Care Network, Pasadena, CA USA. [Loggers, Elizabeth] Univ Washington, Sch Med, Fred Hutchinson Canc Res Ctr, Seattle, WA 98195 USA. [Loggers, Elizabeth] Seattle Canc Care Alliance, Seattle, WA USA. [Porock, Davina] Lehman Coll, Bronx, NY USA. [Reuben, David B.] Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA USA. [Saliba, Debra] Univ Calif Los Angeles, Jewish Home Borun Ctr Gerontol Res, Los Angeles, CA USA. [Saliba, Debra] VA Greater Angeles Healthcare Syst, Geriat Res, Educ & Clin Ctr, Los Angeles, CA USA. [Saliba, Debra] RAND Hlth, Santa Monica, CA USA. [Scanlon, William J.] Natl Hlth Policy Forum, Washington, DC USA. [Tabbush, Victor] Univ Calif Los Angeles, Anderson Sch Management, Los Angeles, CA USA. [Tinetti, Mary] Yale Univ, Sch Med, New Haven, CT USA. [Tumlinson, Anne] Anne Tumlinson Innovat LLC, Washington, DC USA. [Vladeck, Bruce C.] Nexera Inc, New York, NY USA. [Kogan, Alexis Coulourides; Mosqueda, Laura] Univ So Calif, Family Med & Geriat, Keck Sch Med, Los Angeles, CA USA. [Wilber, Kate] Univ So Calif, Davis Sch Gerontol, Los Angeles, CA USA. [Goodwin, Carol; Lundebjerg, Nancy E.; Mikhailovich, Anna] Writing & Editorial Serv, New York, NY USA. [Goodwin, Carol; Lundebjerg, Nancy E.; Mikhailovich, Anna] Amer Geriat Soc, 40 Fulton St 18th Floor, New York, NY USA. [Aiello, Susan E.] Provided Editorial Serv, Indianapolis, IN USA. RP Goodwin, C (reprint author), Writing & Editorial Serv, New York, NY USA.; Goodwin, C (reprint author), Amer Geriat Soc, 40 Fulton St 18th Floor, New York, NY USA. EM CGoodwin@americangeriatrics.org FU TSF FX This work was supported by a grant from TSF. Gretchen E. Alkema, PhD, Victoria R. Ballesteros, MA, Megan Burke, MSW, Megan Juring, Lynn Palin, MSW, Rene Seidel, Dipl. Soz. Paed. (FH), and Erin Westphal, MS, The SCAN Foundation, Long Beach, CA, and Sean Dryden, PerryUndem Research/Communication, Washington, DC, participated in the expert panel meeting. NR 4 TC 11 Z9 11 U1 1 U2 3 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 2016 VL 64 IS 1 BP 15 EP 18 DI 10.1111/jgs.13866 PG 4 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA DF2FQ UT WOS:000371157900003 ER PT J AU Goto, T Yoshida, K Tsugawa, Y Camargo, CA Hasegawa, K AF Goto, Tadahiro Yoshida, Kazuki Tsugawa, Yusuke Camargo, Carlos A., Jr. Hasegawa, Kohei TI Infectious Disease-Related Emergency Department Visits of Elderly Adults in the United States, 2011-2012 SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Article DE infectious disease; emergency department; hospitalization; mortality; elderly ID PNEUMOCOCCAL POLYSACCHARIDE VACCINE; INFLUENZA VACCINE; OLDER-ADULTS; FREQUENT UTILIZATION; DISPARITIES; POPULATION; COMMUNITY; HOSPITALIZATIONS; CARE AB OBJECTIVES: To investigate the frequency of infectious disease (ID)-related emergency department (ED) visits of elderly adults in the United States. DESIGN: Cross-sectional analysis. SETTING: Nationwide emergency department sample in 2011-12. PARTICIPANTS: Individuals in the ED aged 65 and older with a primary diagnosis of an ID. MEASUREMENTS: ID-related ED visits, hospitalizations, hospital-based mortality. RESULTS: During 2012, a weighted estimate of 3,123,909 ED visits for IDs was calculated in elderly U.S. adults. This accounted for 13.5% (3.1 million visits) of all ED visits of elderly adults; this burden was higher than that for myocardial infarction and congestive heart failure combined. The rate of ID-related ED visits was 7,231 per 100,000 elderly adults. The most-common diagnoses were lower respiratory infections (26.2%; 95% confidence interval (CI) = 25.7-26.6%), urinary tract infections (25.3%, 95% CI = 25.0-25.7%), and septicemia (18.9%, 95% CI = 18.3-19.6%). Of all ID-related ED visits, 1,786,657 (57.2%, 95% CI = 56.6-57.7%) resulted in hospitalization. The leading cause of hospitalization was septicemia, accounting for 32.2% (95% CI = 31.1-33.3%) of all ID-related hospitalizations through EDs, followed by lower respiratory infections (27.8%, 95% CI = 27.2-28.4%). Overall, 123,894 individuals (4.0%, 95% CI = 3.8-4.1%) died during their ED visit or hospitalization. Of these, septicemia was the leading cause of mortality (74.7%, 95% CI = 73.8-75.6%), followed by lower respiratory infections (15.2%, 95% CI = 14.6-15.9%). Analysis of the 2011 data gave similar results for the burden of ID-related ED visits, hospitalizations, and mortality. CONCLUSION: Using a nationally representative sample, it was found that the public health burden of IDs in elderly U.S. adults was substantial, as measured by ED visits, subsequent hospitalizations, and hospital-based mortality. C1 [Goto, Tadahiro] Univ Fukui Hosp, Dept Emergency Med, 23-3 Shimoaiduki, Fukui 9101193, Japan. [Goto, Tadahiro; Camargo, Carlos A., Jr.; Hasegawa, Kohei] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Emergency Med, Boston, MA 02115 USA. [Yoshida, Kazuki; Camargo, Carlos A., Jr.] Harvard Univ, TH Chan Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. [Tsugawa, Yusuke] Harvard Univ, Harvard Interfac Initiat Hlth Policy, Boston, MA 02115 USA. RP Goto, T (reprint author), Univ Fukui Hosp, Dept Emergency Med, 23-3 Shimoaiduki, Fukui 9101193, Japan. EM qq_gto@yahoo.co.jp OI Yoshida, Kazuki/0000-0002-2030-3549 FU Pfizer; Takeda; Bayer; PhRMA; Honjo International Scholarship Foundation (Tokyo, Japan) FX Dr. Yoshida receives tuition support jointly from Japan Student Services Organization and Harvard T. H. Chan School of Public Health (partially supported by training grants from Pfizer, Takeda, Bayer and PhRMA). Dr. Tsugawa is funded by Honjo International Scholarship Foundation (Tokyo, Japan). NR 29 TC 3 Z9 3 U1 1 U2 5 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 2016 VL 64 IS 1 BP 31 EP 36 DI 10.1111/jgs.13836 PG 6 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA DF2FQ UT WOS:000371157900006 PM 26696501 ER PT J AU Schepker, CA Leveille, SG Pedersen, MM Ward, RE Kurlinski, LA Grande, L Kiely, DK Bean, JF AF Schepker, Caroline A. Leveille, Suzanne G. Pedersen, Mette M. Ward, Rachel E. Kurlinski, Laura A. Grande, Laura Kiely, Dan K. Bean, Jonathan F. TI Effect of Pain and Mild Cognitive Impairment on Mobility SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Article DE pain; cognition; mobility; aged ID LATE-LIFE FUNCTION; PHYSICAL PERFORMANCE BATTERY; LOWER-EXTREMITY FUNCTION; VERBAL-LEARNING TEST; OLDER-ADULTS; DISABILITY INSTRUMENT; GAIT SPEED; MUSCULOSKELETAL PAIN; VALIDATION; LIMITATION AB OBJECTIVES: To examine the effect of pain and mild cognitive impairment (MCI)-together and separately-on performance-based and self-reported mobility outcomes in older adults in primary care with mild to moderate self-reported mobility limitations. DESIGN: Cross-sectional analysis. SETTING: Academic community outpatient clinic. PARTICIPANTS: Individuals aged 65 and older in primary care enrolled in the Boston Rehabilitative Impairment Study in the Elderly who were at risk of mobility decline (N = 430). MEASUREMENTS: Participants with an average score greater than three on the Brief Pain Inventory (BPI) were defined as having pain. MCI was defined using age-adjusted scores on a neuropsychological battery. Multivariable linear regression models assessed associations between pain and MCI, together and separately, and mobility performance (habitual gait speed, Short Physical Performance Battery), and self-reports of function and disability in various day-to-day activities (Late Life Function and Disability Instrument). RESULTS: The prevalence of pain was 34% and of MCI was 42%; 17% had pain only, 25% had MCI only, 17% had pain and MCI, and 41% had neither. Participants with pain and MCI performed significantly worse than all others on all mobility outcomes (P < .001). Participants with MCI only or pain only also performed significantly worse on all mobility outcomes than those with neither (P < .001). CONCLUSION: Mild to moderate pain and MCI were independently associated with poor mobility, and the presence of both comorbidities was associated with the poorest status. Primary care practitioners who encounter older adults in need of mobility rehabilitation should consider screening them for pain and MCI to better inform subsequent therapeutic interventions. C1 [Schepker, Caroline A.; Pedersen, Mette M.; Ward, Rachel E.; Kurlinski, Laura A.; Kiely, Dan K.; Bean, Jonathan F.] Spaulding Rehabil Hosp, Boston, MA USA. [Schepker, Caroline A.; Ward, Rachel E.; Bean, Jonathan F.] Harvard Univ, Sch Med, Dept Phys Med & Rehabil, Boston, MA USA. [Schepker, Caroline A.] Touro Univ Calif, Coll Osteopath Med, Vallejo, CA USA. [Leveille, Suzanne G.] Univ Massachusetts, Dept Nursing, Boston, MA 02125 USA. [Leveille, Suzanne G.] Beth Israel Deaconess Med Ctr, Dept Med, Boston, MA 02215 USA. [Leveille, Suzanne G.] Harvard Univ, Sch Med, Boston, MA USA. [Pedersen, Mette M.] Copenhagen Univ Hosp, Clin Res Ctr, Hvidovre, Denmark. [Ward, Rachel E.] Boston Univ, Sch Publ Hlth, Boston, MA USA. [Grande, Laura] VA Boston Healthcare Syst, Psychol Serv, Boston, MA USA. [Grande, Laura] Boston Univ, Sch Med, Dept Psychiat, Boston, MA 02118 USA. [Bean, Jonathan F.] VA Boston Healthcare Syst, New England Geriatr Res Educ & Clin Ctr, Boston, MA USA. RP Schepker, CA (reprint author), Spaulding Ctr Lifelong Hlth & Fitness, 1575 Cambridge St, Cambridge, MA 02139 USA. EM caroline.schepker@gmail.com RI Bean, Jonathan/F-5798-2017 OI Bean, Jonathan/0000-0001-8385-8210 FU CAS's Rehabilitation Research Experience for Medical Students Award FX CAS's Rehabilitation Research Experience for Medical Students Award provided summer stipend support for 8 contiguous weeks of clinical research, with support from a designated mentor and associated clinical research staff. NR 30 TC 1 Z9 2 U1 2 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 2016 VL 64 IS 1 BP 138 EP 143 DI 10.1111/jgs.13869 PG 6 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA DF2FQ UT WOS:000371157900020 PM 26782863 ER PT J AU Lai, ECC Wong, MB Iwata, I Zhang, YH Hsieh, CY Yang, YHK Setoguchi, S AF Lai, Edward Chia-Cheng Wong, Monera B. Iwata, Isao Zhang, Yinghong Hsieh, Cheng-Yang Yang, Yea-Huei Kao Setoguchi, Soko TI PNEUMONIA RISK WITH CHOLINESTERASE INHIBITORS RESPONSE SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Letter C1 [Lai, Edward Chia-Cheng; Zhang, Yinghong; Setoguchi, Soko] Duke Univ, Sch Med, Duke Clin Res Inst, Durham, NC USA. [Lai, Edward Chia-Cheng; Hsieh, Cheng-Yang; Yang, Yea-Huei Kao] Natl Cheng Kung Univ, Sch Pharm, Inst Clin Pharm & Pharmaceut Sci, Tainan 701, Taiwan. [Wong, Monera B.] Massachusetts Gen Hosp, Geriatr Med Unit, Boston, MA 02114 USA. [Iwata, Isao; Yang, Yea-Huei Kao] Natl Cheng Kung Univ, Hlth Outcome Res Ctr, Tainan 701, Taiwan. [Iwata, Isao] Univ N Carolina, Div Geriatr Med, Chapel Hill, NC USA. [Hsieh, Cheng-Yang] Tainan Sin Lau Hosp, Dept Neurol, Tainan, Taiwan. RP Lai, ECC (reprint author), Duke Univ, Sch Med, Duke Clin Res Inst, Durham, NC USA.; Lai, ECC (reprint author), Natl Cheng Kung Univ, Sch Pharm, Inst Clin Pharm & Pharmaceut Sci, Tainan 701, Taiwan. FU Duke Clinical Research Institute; National Center for Advancing Translational Sciences [UL1TR001117] FX The original study was supported internally by the Duke Clinical Research Institute and by Grant UL1TR001117 from the National Center for Advancing Translational Sciences. NR 3 TC 0 Z9 0 U1 1 U2 3 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 2016 VL 64 IS 1 BP 242 EP 243 DI 10.1111/jgs.13916 PG 4 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA DF2FQ UT WOS:000371157900058 PM 26782900 ER PT J AU Rost, NS Bottle, A Lee, JM Randall, M Middleton, S Shaw, L Thijs, V Rinkel, GJE Hemmen, TM AF Rost, Natalia S. Bottle, Alex Lee, Jin-Moo Randall, Marc Middleton, Steven Shaw, Louise Thijs, Vincent Rinkel, Gabriel J. E. Hemmen, Thomas M. CA Global Comparators Stroke GOAL TI Stroke Severity Is a Crucial Predictor of Outcome: An International Prospective Validation Study SO JOURNAL OF THE AMERICAN HEART ASSOCIATION LA English DT Review DE mortality; statistics; stroke; survival ID MODIFIED RANKIN SCALE; ACUTE ISCHEMIC-STROKE; BASE-LINE SEVERITY; HOSPITAL OUTCOMES; GUIDELINES-STROKE; CLINICAL-TRIALS; QUESTIONNAIRE; ASSOCIATION; RELIABILITY; PERFORMANCE AB Background-Stroke is among the leading causes of morbidity and mortality worldwide. Without reliable prediction models and outcome measurements, comparison of care systems is impossible. We analyzed prospectively collected data from 4 countries to explore the importance of stroke severity in outcome prediction. Methods and Results-For 2 months, all acute ischemic stroke patients from the hospitals participating in the Global Comparators Stroke GOAL (Global Outcomes Accelerated Learning) collaboration received a National Institutes of Health Stroke Scale (NIHSS) score on admission and a modified Rankin Scale score at 30 and 90 days. These data were added to the administrative data set, and risk prediction models including age, sex, comorbidity index, and NIHSS were derived for in-hospital death within 7 days, all in-hospital death, and death and good outcome at 30 and 90 days. The relative importance of each variable was assessed using the proportion of explained variation. Of 1034 admissions for acute ischemic stroke, 614 had a full set of NIHSS and both modified Rankin Scale values recorded; of these, 507 patients could be linked to administrative data. The marginal proportion of explained variation was 0.7% to 4.0% for comorbidity index, and 11.3 to 25.0 for NIHSS score. The percentage explained by the model varied by outcome (16.6-29.1%) and was highest for good outcome at 30 and 90 days. There was high agreement between 30-and 90-day modified Rankin Scale scores (weighted kappa= 0.82). Conclusions-In this prospective pilot study, the baseline NIHSS score was essential for prediction of acute ischemic stroke outcomes, followed by age; whereas traditional comorbidity index contributed little to the overall model. Future studies of stroke outcomes between different care systems will benefit from including a baseline NIHSS score. C1 [Rost, Natalia S.] Massachusetts Gen Hosp, Dept Neurol, Stroke Div, Boston, MA 02114 USA. [Bottle, Alex] Univ London Imperial Coll Sci Technol & Med, Dr Foster Unit, London, England. [Lee, Jin-Moo] Washington Univ, Sch Med, Dept Neurol, Stroke Ctr, St Louis, MO 63110 USA. [Lee, Jin-Moo] Washington Univ, Sch Med, Hope Ctr Neurol Disorders, St Louis, MO USA. [Randall, Marc] Sheffield Teaching Hosp NHS Fdn Trust, Sheffield, S Yorkshire, England. [Middleton, Steven] Dr Foster, London, England. [Shaw, Louise] Royal United Hosp Bath NHS Trust, Bath, Avon, England. Univ Hosp Leuven, Dept Neurol, Leuven, Belgium. [Thijs, Vincent] Austin Hlth, Heidelberg, Vic, Australia. [Thijs, Vincent] Univ Melbourne, Florey Inst Neurosci & Mental Hlth, Heidelberg, Vic, Australia. [Rinkel, Gabriel J. E.] Univ Med Ctr, Brain Ctr Rudolf Magnus, Dept Neurol & Neurosurg, Utrecht, Netherlands. [Hemmen, Thomas M.] Univ Calif San Diego Hlth Syst, San Diego, CA USA. RP Rost, NS (reprint author), Massachusetts Gen Hosp, J Philip Kistler Stroke Res Ctr, 175 Cambridge St,Suite 300, Boston, MA 02114 USA. EM nrost@partners.org RI Thijs, Vincent/C-3647-2009 OI Thijs, Vincent/0000-0002-6614-8417 FU National Institutes of Health; Dr Foster Unit at Imperial College from Dr Foster, a private health care information company; National Institute for Health Research; Alzheimer's Association; Hope Center for Neurological Disorders; FWO Flanders FX Dr Rost is funded in part by the National Institutes of Health. Dr Bottle: receives funding through the Dr Foster Unit at Imperial College, which is largely funded by a research grant from Dr Foster, a private health care information company. He also receives grants from the National Institute for Health Research. Dr Jin-Moo Lee is funded by the National Institutes of Health, the Alzheimer's Association, and the Hope Center for Neurological Disorders. Dr Marc Randall has nothing to disclose. Mr Steven Middleton is an employee of Dr Foster. Dr Gabriel Rinkel has nothing to disclose. Dr Thomas Hemmen is in part funded by the National Institutes of Health and is a Consultant for Merck Co. Dr Louise Shaw has nothing to disclose. Dr Vincent Thijs is funded by FWO Flanders. NR 32 TC 6 Z9 6 U1 2 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 2016 VL 5 IS 1 AR e002433 DI 10.1161/JAHA.115.002433 PG 7 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA DF3XV UT WOS:000371282800035 ER PT J AU Wang, W Shen, G Shahar, E Bidulescu, A Kimberly, WT Sheth, KN Campbell, BW Horbal, S Correa, A Griswold, ME AF Wang, Wei Shen, Gui Shahar, Eyal Bidulescu, Aurelian Kimberly, W. Taylor Sheth, Kevin N. Campbell, Brenda W. Horbal, Steven Correa, Adolfo Griswold, Michael E. TI Forced Expiratory Volume in the First Second and Aldosterone as Mediators of Smoking Effect on Stroke in African Americans: The Jackson Heart Study SO JOURNAL OF THE AMERICAN HEART ASSOCIATION LA English DT Article DE aldosterone; lung function; mediation effects; smoking; stroke ID LUNG-FUNCTION; CIGARETTE-SMOKING; SYSTEMIC INFLAMMATION; ATHEROSCLEROSIS RISK; BLOOD-PRESSURE; CHOLESTEROL LEVELS; ISCHEMIC-STROKES; FEV1 DECLINE; FOLLOW-UP; DISEASE AB Background-Cigarette smoking is a risk factor for stroke, but the mechanisms by which smoking contributes to stroke are not well understood. This study aimed to evaluate the roles of lung function (represented by forced expiratory volume in the first second (FEV1)) and aldosterone as potential mediators of the association of smoking with stroke. Methods and Results-The data were derived from 5010 Jackson Heart Study participants who had mean follow-up of 97.9 months. Using the Cox proportional hazards model, we estimated the hazard ratios of smoking for total stroke with and without adjustment for FEV1 and/or aldosterone at baseline after controlling for the confounders. The hazard ratio for current smoking (versus never smoking) was 2.70 (95% CI 1.71 to 4.25) for total stroke after adjustment for the confounders. Additional adjustment for FEV1 and aldosterone reduced the hazard ratio to 2.32 (95% CI 1.42 to 3.79), suggesting that 22.4% of the excess risk of current smoking for total stroke is mediated by these factors. FEV1 and aldosterone account for 13.1% and 12.1%, respectively, of the excess risk. The hazard ratio for FEV1 increased (0.61 versus 0.65) after including systemic inflammatory marker C-reactive protein, and the hazard ratios for aldosterone were comparable for the models that included all confounders and smoking status with or without different blood pressure measurements. Conclusions-Our findings suggest that the difference in stroke risk between current and never smokers may develop partially through pathways involving lung function and aldosterone and that the mediation effect through aldosterone is independent of blood pressure. C1 [Wang, Wei; Griswold, Michael E.] Univ Mississippi, Med Ctr, Ctr Biostat & Bioinformat, 2500 North State St, Jackson, MS 39216 USA. [Correa, Adolfo] Univ Mississippi, Med Ctr, Jackson Heart Study, Dept Med, Jackson, MS 39216 USA. [Shen, Gui] Mississippi State Univ, Dept Math & Stat, Mississippi State, MS 39762 USA. [Shahar, Eyal] Univ Arizona, Mel & Enid Zuckerman Coll Publ Hlth, Dept Epidemiol & Biostat, Tucson, AZ USA. [Bidulescu, Aurelian; Horbal, Steven] Indiana Univ, Sch Publ Hlth, Dept Epidemiol & Biostat, Bloomington, IN USA. [Kimberly, W. Taylor] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. [Sheth, Kevin N.] Yale Univ, Sch Med, Div Neurocrit Care & Emergency Neurol, New Haven, CT USA. [Campbell, Brenda W.] Jackson State Univ, Jackson, MS USA. RP Wang, W (reprint author), Univ Mississippi, Med Ctr, Ctr Biostat & Bioinformat, 2500 North State St, Jackson, MS 39216 USA. EM wwang@umc.edu FU National Heart, Lung, and Blood Institute [HHSN268201300046C, HHSN268201300047C, HHSN268201300048C, HHSN268201300049C, HHSN268201300050C]; National Institute on Minority Health and Health Disparities FX The Jackson Heart Study 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. NR 53 TC 0 Z9 0 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 2016 VL 5 IS 1 AR e002689 DI 10.1161/JAHA.115.002689 PG 8 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA DF3XV UT WOS:000371282800048 ER PT J AU Chan, JCY Shek, SYN Kono, T Yeung, CK Chan, HHL AF Chan, Johnny Chun-yin Shek, Samantha Yee-nam Kono, Taro Yeung, Chi Keung Chan, Henry Hin-lee TI A Retrospective Analysis on the Management of Pigmented Lesions Using a Picosecond 755-nm Alexandrite Laser in Asians SO LASERS IN SURGERY AND MEDICINE LA English DT Article DE skin pigmentation; pigment; Alexandrite laser; picosecond laser; Asian; Nevus of Ota ID ACQUIRED BILATERAL NEVUS; INTENSE PULSED-LIGHT; SWITCHED RUBY-LASER; OTA-LIKE MACULES; ND-YAG LASERS; TRIAL; COMPLICATIONS; LENTIGINES; EFFICACY; FRECKLES AB Background and objectives: Photo-aging in Chinese often presents with benign pigmentary lesions. Q-switched lasers for pigmentary lesions in Asians had reported a risk of post-inflammatory hyperpigmentation (PIH) up to 25%. Longer pulse widths in the millisecond domains were advocated with reduced risk of PIH. Recently, picosecond lasers of various wavelengths were introduced with proven efficacy in tattoo removal. The objective of this study is to assess the efficacy and safety of a novel picosecond 755-nm alexandrite laser for the treatment of benign pigmented lesions in Asians retrospectively. Methods: A list of all patients who received picosecond 755-nm alexandrite laser treatment at a private dermatology center in Hong Kong was included. Those who had any other laser or topical treatment during the period of picosecond laser treatment were excluded. The age, skin phototype, type of pigmentary lesion, number of treatments performed was recorded. The baseline and most recent standardized photographs were assessed by trained physicians for comparison. A score of 0-4, representing poor 0-24%, fair 25-49%, good 50-74%, excellent 75-95%, and complete 95%+ improvement was given. Adverse events associated with the laser treatment were also recorded. All patients were followed up until 6 months after the last laser session. Results: A total of 13 subjects were included in the present study. The number of treatment sessions received ranged from one to seven. The benign pigmentary lesions consist of Nevus of Ota, cafe-au-lait patches, lentigines, Becker's nevus, Hori's macules, and nevus spilus. Among patients with Nevus of Ota, one patient achieved complete clearance after four treatments and two other patients had excellent clearance after three and four sessions, respectively. Patients with cafe-au-lait had fair to good clearance after one to seven treatment sessions. One patient who has Hori's macules was resistant to laser treatments and a fair response was achieved after eight treatments. In the present series, two patients (4.8%) developed transient hypopigmentation, which had improved upon subsequent follow-up in both cases and none had post-inflammatory hyperpigmentation. Conclusions: The novel picosecond 755-nm alexandrine laser is effective for the treatment of benign pigmentary lesions in Chinese, especially for the clearance of Nevus of Ota. Picosecond laser appears to be associated with a much lower risk of PIH for treatment of pigmentary lesions in Asians. (C) 2015 Wiley Periodicals, Inc. C1 [Chan, Johnny Chun-yin; Shek, Samantha Yee-nam; Yeung, Chi Keung; Chan, Henry Hin-lee] Univ Hong Kong, Dept Med, Div Dermatol, Hong Kong, Hong Kong, Peoples R China. [Kono, Taro] Tokai Univ, Dept Plast Surg, Kanagawa 2591100, Japan. [Chan, Henry Hin-lee] Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA. RP Chan, JCY (reprint author), Queen Mary Hosp, Room 303,New Clin Bldg, Hong Kong, Hong Kong, Peoples R China. EM johnny7241980@gmail.com NR 26 TC 5 Z9 6 U1 0 U2 1 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 2016 VL 48 IS 1 BP 23 EP 29 DI 10.1002/lsm.22443 PG 7 WC Dermatology; Surgery SC Dermatology; Surgery GA DF6YX UT WOS:000371505600003 PM 26696500 ER PT J AU Hong, JX Xu, JJ Cao, WJ Ji, J Sun, XH AF Hong, Jiaxu Xu, Jianjiang Cao, Wenjun Ji, Jian Sun, Xinghuai TI Actinobacillus actinomycetemcomitans Keratitis After Glaucoma Infiltration Surgery A Clinical Report and Literature Review SO MEDICINE LA English DT Article ID ENDOGENOUS ENDOPHTHALMITIS; FUNGAL KERATITIS; CROSS-LINKING; PERIODONTITIS AB Actinobacillus actinomycetemcomitans infection is a rare and easily misdiagnosed ocular disease. In this article, the authors report a chronic, purulent, and difficult-to-treat case of A actinomycetemcomitans keratitis following a glaucoma infiltration surgery. A 56-year-old man with a long-standing history of open-angle glaucoma in both eyes presented with a 12-week history of ocular pain, redness, and blurred vision in his right eye. He underwent a glaucoma infiltration surgery in his right eye 6 months ago. Three months postoperatively, he developed peripheral corneal stromal opacities associated with a white, thin, cystic bleb, and conjunctival injection. These opacities grew despite topical treatment with topical tobramycin, levofloxacin, natamycin, amikacin, and metronidazole eye drops. Multiple corneal scrapings revealed no organisms, and no organisms grew on aerobic, anaerobic, fungal, or mycobacterial cultures. The patient's right eye developed a severe purulent corneal ulcer with a dense hypopyon and required a corneal transplantation. Histopathologic analysis and 16S ribosomalribonucleic acid polymerase chain reaction sequencing revealed A actinomycetemcomitans as the causative organism. Postoperatively, treatment was initiated with topical levofloxacin and cyclosporine, as well as oral levofloxacin and cyclosporine. Graft and host corneal transparency were maintained at the checkup 1 month after surgery. Although it is a rare cause of corneal disease, A actinomycetemcomitans should be suspected in patients with keratitis refractory to topical antibiotic therapy. Delay in diagnosis and appropriate treatment can result in vision loss. C1 [Hong, Jiaxu; Xu, Jianjiang; Cao, Wenjun; Ji, Jian; Sun, Xinghuai] Fudan Univ, Eye & Ear Nose & Throat Hosp E, Shanghai Med Coll, Dept Ophthalmol & Visual Sci, Shanghai 200031, Peoples R China. [Hong, Jiaxu] Xiamen Univ, Sch Life Sci, Fujian Prov Key Lab Ophthalmol & Visual Sci, Xiamen, Fujian, Peoples R China. [Hong, Jiaxu] Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Boston, MA USA. [Sun, Xinghuai] Inst Brain Sci, China State Key Lab Med Neurobiol, Shanghai, Peoples R China. [Sun, Xinghuai] Natl Hlth & Family Planning Commiss, Key Lab Myopia, Shanghai, Peoples R China. RP Sun, XH (reprint author), Fudan Univ, Eye Ear Nose & Throat Hosp, Sch Shanghai Med, Dept Ophthalmol & Visual Sci, 83 Fenyang Rd, Shanghai 200031, Peoples R China. EM xhsuneent@163.com FU Ministry of Health, China [201302015]; Ministry of Science and Technology, China [2012BAI08B01]; National Natural Science Foundation of China [81170817, 81200658, 81300735, 81270978, U1205025, 81330022]; Science and Technology Commission of Shanghai Municipality, Shanghai [13441900900, 13430720400]; Chinese Postdoctoral Fund [XMU135890]; New Technology Joint Research Project in Shanghai Hospitals [SHDC12014114] FX The authors were supported by grants from the Key Clinic Medicine Research Program, the Ministry of Health, China (201302015); the National Science and Technology Research Program, the Ministry of Science and Technology, China (2012BAI08B01); the National Natural Science Foundation of China (81170817, 81200658, 81300735, 81270978, U1205025, and 81330022); the Scientific Research Program, Science and Technology Commission of Shanghai Municipality, Shanghai (13441900900, 13430720400); the Chinese Postdoctoral Fund (XMU135890); and the New Technology Joint Research Project in Shanghai Hospitals (SHDC12014114). NR 18 TC 0 Z9 0 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0025-7974 EI 1536-5964 J9 MEDICINE JI Medicine (Baltimore) PD JAN PY 2016 VL 95 IS 3 BP 1 EP 4 AR e2608 DI 10.1097/MD.0000000000002608 PG 4 WC Medicine, General & Internal SC General & Internal Medicine GA DE4AJ UT WOS:000370571300001 PM 26817919 ER PT J AU Wen, PY AF Wen, Patrick Y. TI Untitled SO NEURO-ONCOLOGY LA English DT Editorial Material C1 [Wen, Patrick Y.] Harvard Univ, Sch Med, Neurooncol, Cambridge, MA 02138 USA. [Wen, Patrick Y.] Harvard Univ, Sch Med, Neurol, Cambridge, MA 02138 USA. [Wen, Patrick Y.] Dana Farber Brigham & Womens Canc Ctr, Ctr Neurooncol, Boston, MA 02138 USA. RP Wen, PY (reprint author), Harvard Univ, Sch Med, Neurooncol, Cambridge, MA 02138 USA.; Wen, PY (reprint author), Harvard Univ, Sch Med, Neurol, Cambridge, MA 02138 USA.; Wen, PY (reprint author), Dana Farber Brigham & Womens Canc Ctr, Ctr Neurooncol, Boston, MA 02138 USA. NR 0 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 2016 VL 18 IS 1 BP 1 EP 1 DI 10.1093/neuonc/nov309 PG 1 WC Oncology; Clinical Neurology SC Oncology; Neurosciences & Neurology GA DF3GU UT WOS:000371232900001 PM 26667135 ER PT J AU van der Vos, KE Abels, ER Zhang, X Lai, C Carrizosa, E Oakley, D Prabhakar, S Mardini, O Crommentuijn, MHW Skog, J Krichevsky, AM Stemmer-Rachamimov, A Mempel, TR El Khoury, J Hickman, SE Breakefield, XO AF van der Vos, Kristan E. Abels, Erik R. Zhang, Xuan Lai, Charles Carrizosa, Esteban Oakley, Derek Prabhakar, Shilpa Mardini, Osama Crommentuijn, Matheus H. W. Skog, Johan Krichevsky, Anna M. Stemmer-Rachamimov, Anat Mempel, Thorsten R. El Khoury, Joseph Hickman, Suzanne E. Breakefield, Xandra O. TI Directly visualized glioblastoma-derived extracellular vesicles transfer RNA to microglia/macrophages in the brain SO NEURO-ONCOLOGY LA English DT Article DE brain tumors; exosomes; extracellular vesicles; microglia; microRNA ID RECIPIENT CELLS; TUMOR PROGRESSION; HUMAN GLIOMA; CANCER; MICRORNAS; PHENOTYPE; MICROGLIA; GENE; MICROENVIRONMENT; MECHANISMS AB To understand the ability of gliomas to manipulate their microenvironment, we visualized the transfer of vesicles and the effects of tumor-released extracellular RNA on the phenotype of microglia in culture and in vivo. Extracellular vesicles (EVs) released from primary human glioblastoma (GBM) cells were isolated and microRNAs (miRNAs) were analyzed. Primary mouse microglia were exposed to GBM-EVs, and their uptake and effect on proliferation and levels of specific miRNAs, mRNAs, and proteins were analyzed. For in vivo analysis, mouse glioma cells were implanted in the brains of mice, and EV release and uptake by microglia and monocytes/macrophages were monitored by intravital 2-photon microscopy, immunohistochemistry, and fluorescence activated cell sorting analysis, as well as RNA and protein levels. Microglia avidly took up GBM-EVs, leading to increased proliferation and shifting of their cytokine profile toward immune suppression. High levels of miR-451/miR-21 in GBM-EVs were transferred to microglia with a decrease in the miR-451/miR-21 targetc-Myc mRNA. In in vivo analysis, we directly visualized release of EVs from glioma cells and their uptake by microglia and monocytes/macrophages in brain. Dissociated microglia and monocytes/macrophages from tumor-bearing brains revealed increased levels of miR-21 and reduced levels of c-Myc mRNA. Intravital microscopy confirms the release of EVs from gliomas and their uptake into microglia and monocytes/macrophages within the brain. Our studies also support functional effects of GBM-released EVs following uptake into microglia, associated in part with increased miRNA levels, decreased target mRNAs, and encoded proteins, presumably as a means for the tumor to manipulate its environs. C1 [van der Vos, Kristan E.; Abels, Erik R.; Zhang, Xuan; Lai, Charles; Prabhakar, Shilpa; Mardini, Osama; Crommentuijn, Matheus H. W.; Skog, Johan; Breakefield, Xandra O.] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. [van der Vos, Kristan E.; Abels, Erik R.; Zhang, Xuan; Lai, Charles; Prabhakar, Shilpa; Mardini, Osama; Crommentuijn, Matheus H. W.; Skog, Johan; Breakefield, Xandra O.] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. [van der Vos, Kristan E.; Abels, Erik R.; Zhang, Xuan; Lai, Charles; Prabhakar, Shilpa; Mardini, Osama; Crommentuijn, Matheus H. W.; Skog, Johan; Breakefield, Xandra O.] Harvard Univ, Sch Med, NeuroDiscovery Ctr, Boston, MA 02115 USA. [Carrizosa, Esteban; Mempel, Thorsten R.; El Khoury, Joseph; Hickman, Suzanne E.] Massachusetts Gen Hosp, Ctr Immunol & Inflammatory Dis, Boston, MA 02114 USA. [Oakley, Derek; Stemmer-Rachamimov, Anat] Massachusetts Gen Hosp, Neuropathol Serv, Boston, MA 02114 USA. [Oakley, Derek; Stemmer-Rachamimov, Anat] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. [Krichevsky, Anna M.] Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Neurol, Boston, MA 02115 USA. [van der Vos, Kristan E.] Netherlands Canc Inst, Div Mol Carcinogenesis, Amsterdam, Netherlands. [Breakefield, Xandra O.] Mol Neurogenet Unit, MGH East,13th St,Bldg 149, Charlestown, MA USA. [Skog, Johan] Ctr Immunol & Inflammatory Dis, Neuroimmunol & Innate Immun Lab, MGH East,13th St,Bldg 149, Charlestown, MA USA. [Skog, Johan] Exosome Diagnost Inc, Boston, MA 02139 USA. RP Breakefield, XO (reprint author), Netherlands Canc Inst, Div Mol Carcinogenesis, Amsterdam, Netherlands.; Breakefield, XO (reprint author), Mol Neurogenet Unit, MGH East,13th St,Bldg 149, Charlestown, MA USA.; Hickman, SE (reprint author), Ctr Immunol & Inflammatory Dis, Neuroimmunol & Innate Immun Lab, MGH East,13th St,Bldg 149, Charlestown, MA USA. EM shickman@partners.org; breakefield@hms.harvard.edu RI Lai, Charles/D-5442-2017; OI Crommentuijn, Matheus/0000-0001-8217-5370 FU Dutch Scientific Organisation (NWO-Rubicon); NIH Common Fund through the Office of Strategic Coordination/Office of the NIH Director [U19 CA179563]; NIH/NCI [P01 CA069246, R01 CA150975, CA179563]; Voices Against Brain Cancer; Richard Floor Biorepository Fund; Canadian Institute of Health Research; NIH/NINDS/NIA [R01 NS059005, U24 AI082660] FX This work was supported by the Dutch Scientific Organisation (NWO-Rubicon) (KvdV), U19 CA179563 (supported by the NIH Common Fund through the Office of Strategic Coordination/Office of the NIH Director [X.O.B., A.M.K., T.R.M.]), NIH/NCI P01 CA069246 (X.O.B.), Voices Against Brain Cancer (X.O.B., C.P.L.), the Richard Floor Biorepository Fund (X.O.B.), and NIH/NCI grants R01 CA150975 and CA179563 (T.R.M.). Vectors were generated through the NIH/NINDS P30 core facility, NS045776. C.P.L. was supported by the Canadian Institute of Health Research. This work was also supported by NIH/NINDS/NIA grants R01 NS059005 and U24 AI082660 (J.E.K.). NR 42 TC 12 Z9 12 U1 8 U2 12 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 2016 VL 18 IS 1 BP 58 EP 69 DI 10.1093/neuonc/nov244 PG 12 WC Oncology; Clinical Neurology SC Oncology; Neurosciences & Neurology GA DF3GU UT WOS:000371232900009 PM 26433199 ER PT J AU Goldstein, RD Trachtenberg, FL Sens, MA Harty, BJ Kinney, HC AF Goldstein, Richard D. Trachtenberg, Felicia L. Sens, Mary Ann Harty, Brian J. Kinney, Hannah C. TI Overall Postneonatal Mortality and Rates of SIDS SO PEDIATRICS LA English DT Article ID INFANT-DEATH-SYNDROME; UNITED-STATES; SLEEP POSITION; SUDDEN; RISK; TRENDS; CLASSIFICATION; ABNORMALITIES; MARKER AB BACKGROUND: Reductions in sudden infant death syndrome (SIDS) are commonly attributed to modifications in infant sleep environments. Approaches to diagnosis in sudden infant death, death scene investigations, the prevalence of intrinsic risk factors for SIDS, and the potential influence of treatment-related factors on infant vulnerability have also changed. Understanding all contributory factors may help reduce residual SIDS rates. METHODS: We analyzed US Mortality Multiple Causes Records for 1983 to 2012 to compare SIDS postneonatal mortality rates with a projection applying non-SIDS mortality changes, using those changes as a proxy measure for alterations in intrinsic risk. Composites of neglect-related, unknown, and circumstantial respiratory diagnoses were measured, as was a cumulative composite of unexplained infant death diagnoses. Cluster analysis with leading causes of postneonatal mortality and SIDS mortality rates for low birth weight infants were also examined. RESULTS: SIDS and non-SIDS postneonatal mortality rates were concordant over time. Important variance was seen 1994 to 1996, coinciding with Back-to-Sleep initiation. Other variance, eliminated in the cumulative composite, appeared related to differences in diagnostic practices. Changes in SIDS rates resembled changes in mortality from congenital malformations, respiratory distress of the newborn, and diseases of the circulatory system. SIDS rates for low birth weight infants followed broader postneonatal trends. CONCLUSIONS: SIDS mortality followed trends in overall postneonatal mortality, including effects of changes in the infant sleep environment and diagnostic classification. Preventing asphyxia risk in the sleep environment must be coupled with efforts to understand intrinsic biological pathways, some potentially associated with other categories of infant and perinatal mortality. C1 [Goldstein, Richard D.] Dana Farber Boston Childrens Canc & Blood Disord, Boston, MA USA. [Goldstein, Richard D.; Kinney, Hannah C.] Harvard Univ, Sch Med, Boston, MA USA. [Trachtenberg, Felicia L.; Harty, Brian J.] New England Res Inst, 9 Galen St, Watertown, MA 02172 USA. [Sens, Mary Ann] Univ N Dakota, Dept Pathol, Grand Forks, ND 58201 USA. [Kinney, Hannah C.] Boston Childrens Hosp, Dept Pathol, Boston, MA USA. RP Goldstein, RD (reprint author), Dana Farber Canc Inst, Dana 2008,450 Brookline Ave, Boston, MA 02115 USA. EM richard_goldstein@dfci.harvard.edu FU Barrett Tallman Memorial Fund; Robert's Program on Sudden Unexpected Death in Pediatrics FX Supported by the Barrett Tallman Memorial Fund and Robert's Program on Sudden Unexpected Death in Pediatrics. NR 44 TC 2 Z9 2 U1 3 U2 10 PU AMER ACAD PEDIATRICS PI ELK GROVE VILLAGE PA 141 NORTH-WEST POINT BLVD,, ELK GROVE VILLAGE, IL 60007-1098 USA SN 0031-4005 EI 1098-4275 J9 PEDIATRICS JI Pediatrics PD JAN PY 2016 VL 137 IS 1 AR e20152298 DI 10.1542/peds.2015-2298 PG 10 WC Pediatrics SC Pediatrics GA DF5KJ UT WOS:000371390300028 ER PT J AU Zou, L Li, L AF Zou, Lee Li, Lei TI The 2015 Albert Lasker Basic Medical Research Award: An exhilarating journey to the DNA damage checkpoint SO SCIENCE CHINA-LIFE SCIENCES LA English DT Editorial Material ID YEAST C1 [Zou, Lee] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02129 USA. [Zou, Lee] Harvard Univ, Sch Med, Dept Pathol, Massachusetts Gen Hosp, Boston, MA 02114 USA. [Li, Lei] Univ Texas MD Anderson Canc Ctr, Dept Expt Radiat Oncol, Houston, TX 77030 USA. RP Zou, L (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02129 USA.; Zou, L (reprint author), Harvard Univ, Sch Med, Dept Pathol, Massachusetts Gen Hosp, Boston, MA 02114 USA.; Li, L (reprint author), Univ Texas MD Anderson Canc Ctr, Dept Expt Radiat Oncol, Houston, TX 77030 USA. EM zou.lee@mgh.harvard.edu; leili@mdanderson.org FU NCI NIH HHS [P30 CA016672] NR 14 TC 1 Z9 1 U1 0 U2 1 PU SCIENCE PRESS PI BEIJING PA 16 DONGHUANGCHENGGEN NORTH ST, BEIJING 100717, PEOPLES R CHINA SN 1674-7305 EI 1869-1889 J9 SCI CHINA LIFE SCI JI Sci. China-Life Sci. PD JAN PY 2016 VL 59 IS 1 BP 103 EP 105 DI 10.1007/s11427-015-4984-3 PG 3 WC Biology SC Life Sciences & Biomedicine - Other Topics GA DF3XI UT WOS:000371281300016 PM 26668018 ER PT J AU Johnson, KA Schultz, A Betensky, RA Becker, JA Sepulcre, J Rentz, D Mormino, E Chhatwal, J Amariglio, R Papp, K Marshall, G Albers, M Mauro, S Pepin, L Alverio, J Judge, K Philiossaint, M Shoup, T Yokell, D Dickerson, B Gomez-Isla, T Hyman, B Vasdev, N Sperling, R AF Johnson, Keith A. Schultz, Aaron Betensky, Rebecca A. Becker, J. Alex Sepulcre, Jorge Rentz, Dorene Mormino, Elizabeth Chhatwal, Jasmeer Amariglio, Rebecca Papp, Kate Marshall, Gad Albers, Mark Mauro, Samantha Pepin, Lesley Alverio, Jonathan Judge, Kelly Philiossaint, Marlie Shoup, Timothy Yokell, Daniel Dickerson, Bradford Gomez-Isla, Teresa Hyman, Bradley Vasdev, Neil Sperling, Reisa TI Tau Positron Emission Tomographic Imaging in Aging and Early Alzheimer Disease SO ANNALS OF NEUROLOGY LA English DT Article ID NATIONAL INSTITUTE; NEUROFIBRILLARY TANGLES; ASSOCIATION WORKGROUPS; DIAGNOSTIC GUIDELINES; AMYLOID BURDEN; PET; PATHOLOGY; PLAQUES; RECOMMENDATIONS; INDIVIDUALS AB Objective: Detection of focal brain tau deposition during life could greatly facilitate accurate diagnosis of Alzheimer disease (AD), staging and monitoring of disease progression, and development of disease-modifying therapies. Methods: We acquired tau positron emission tomography (PET) using F-18 T807 (AV1451), and amyloid-beta PET using C-11 Pittsburgh compound B (PiB) in older clinically normal individuals, and symptomatic patients with mild cognitive impairment or mild AD dementia. Results: We found abnormally high cortical F-18 T807 binding in patients with mild cognitive impairment and AD dementia compared to clinically normal controls. Consistent with the neuropathology literature, the presence of elevated neocortical F-18 T807 binding particularly in the inferior temporal gyrus was associated with clinical impairment. The association of cognitive impairment was stronger with inferior temporal F-18 T807 than with mean cortical C-11 PIB. Regional F-18 T807 was correlated with mean cortical C-11 PiB among both impaired and control subjects. Interpretation: These findings suggest that F-18 T807 PET could have value as a biomarker that reflects both the progression of AD tauopathy and the emergence of clinical impairment. C1 [Johnson, Keith A.; Schultz, Aaron; Becker, J. Alex; Sepulcre, Jorge; Mauro, Samantha; Pepin, Lesley; Alverio, Jonathan; Judge, Kelly; Philiossaint, Marlie; Shoup, Timothy; Yokell, Daniel; Dickerson, Bradford; Vasdev, Neil] Massachusetts Gen Hosp, Div Nucl Med & Mol Imaging, 55 Fruit St, Boston, MA 02114 USA. [Johnson, Keith A.; Rentz, Dorene; Mormino, Elizabeth; Chhatwal, Jasmeer; Amariglio, Rebecca; Papp, Kate; Marshall, Gad; Albers, Mark; Dickerson, Bradford; Gomez-Isla, Teresa; Hyman, Bradley; Sperling, Reisa] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. [Johnson, Keith A.; Becker, J. Alex; Sepulcre, Jorge; Mauro, Samantha; Pepin, Lesley; Alverio, Jonathan; Judge, Kelly; Philiossaint, Marlie; Shoup, Timothy; Yokell, Daniel; Vasdev, Neil] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. [Johnson, Keith A.; Schultz, Aaron; Rentz, Dorene; Mormino, Elizabeth; Chhatwal, Jasmeer; Amariglio, Rebecca; Papp, Kate; Marshall, Gad; Sperling, Reisa] Brigham & Womens Hosp, Dept Neurol, Ctr Alzheimer Res & Treatment, 75 Francis St, Boston, MA 02115 USA. [Johnson, Keith A.; Sepulcre, Jorge; Rentz, Dorene; Chhatwal, Jasmeer; Amariglio, Rebecca; Papp, Kate; Marshall, Gad; Albers, Mark; Yokell, Daniel; Dickerson, Bradford; Gomez-Isla, Teresa; Hyman, Bradley; Vasdev, Neil; Sperling, Reisa] Harvard Univ, Sch Med, Boston, MA USA. [Schultz, Aaron; Sepulcre, Jorge; Dickerson, Bradford; Sperling, Reisa] Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Boston, MA 02114 USA. [Betensky, Rebecca A.] Massachusetts Gen Hosp, Dept Med, Biostat Ctr, Boston, MA 02114 USA. [Betensky, Rebecca A.] Harvard Univ, Sch Publ Hlth, 665 Huntington Ave, Boston, MA 02115 USA. RP Johnson, KA (reprint author), Massachusetts Gen Hosp, Div Nucl Med & Mol Imaging, 55 Fruit St, Boston, MA 02114 USA. EM kajohnson@pet.mgh.harvard.edu FU NIH National Institute on Aging [R01 AG046396, P01 AG036694, P50 AG00513421]; Fidelity Biosciences; Harvard Neurodiscovery Center; Alzheimer's Association FX This study was supported by the NIH National Institute on Aging (R01 AG046396 to K.A.J., P01 AG036694 to R.A.S. and K.A.J., P50 AG00513421 to K.A.J. and R.A.S.), Fidelity Biosciences, Harvard Neurodiscovery Center, and Alzheimer's Association. NR 34 TC 60 Z9 61 U1 12 U2 21 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 2016 VL 79 IS 1 BP 110 EP 119 DI 10.1002/ana.24546 PG 10 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA DE5AM UT WOS:000370642600011 PM 26505746 ER PT J AU Fulciniti, M Amodio, N Cea, M Maiso, P Azab, AK AF Fulciniti, Mariateresa Amodio, Nicola Cea, Michele Maiso, Patricia Azab, Abdel Kareem TI Biological Insights into Myeloma and Other B Cell Malignancies SO BIOMED RESEARCH INTERNATIONAL LA English DT Editorial Material ID MULTIPLE-MYELOMA; THERAPEUTIC IMPLICATIONS; PATHOGENESIS; DISEASE C1 [Fulciniti, Mariateresa] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02215 USA. [Amodio, Nicola] Magna Graecia Univ Catanzaro, Dept Expt & Clin Med, Catanzaro, Italy. [Cea, Michele] Univ Genoa, Genoa, Italy. [Maiso, Patricia] Univ Navarra, E-31080 Pamplona, Spain. [Azab, Abdel Kareem] Washington Univ, St Louis, MO 63108 USA. RP Fulciniti, M (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02215 USA. EM mariateresa_fulciniti@dfci.harvard.edu NR 12 TC 0 Z9 0 U1 1 U2 1 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 2016 AR 5218093 DI 10.1155/2016/5218093 PG 3 WC Biotechnology & Applied Microbiology; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Research & Experimental Medicine GA DF2UZ UT WOS:000371201200001 ER PT S AU Wang, M Huang, YY Sperandio, FF Huang, LY Sharma, SK Mroz, P Hamblin, MR Chiang, LY AF Wang, Min Huang, Yingying Sperandio, Felipe F. Huang, Liyi Sharma, Sulbha K. Mroz, Pawel Hamblin, Michael R. Chiang, Long Y. BE Zhang, M Naik, RR Dai, L TI Photodynamic Therapy with Water-Soluble Cationic Fullerene Derivatives SO CARBON NANOMATERIALS FOR BIOMEDICAL APPLICATIONS SE Springer Series in Biomaterials Science and Engineering LA English DT Article; Book Chapter ID PHOTOINDUCED ELECTRON-TRANSFER; GRAM-POSITIVE BACTERIA; CARCINOMA-CELL LINE; SINGLET OXYGEN; NEGATIVE BACTERIA; MALONIC-ACID; IN-VITRO; PHOTOSENSITIZED OXIDATION; FUNCTIONALIZED FULLERENES; PHOTOPHYSICAL PROPERTIES C1 [Wang, Min; Chiang, Long Y.] Univ Massachusetts, Dept Chem, Inst Nanosci Engn Technol, Lowell, MA 01854 USA. [Huang, Yingying; Sperandio, Felipe F.; Huang, Liyi; Sharma, Sulbha K.; Mroz, Pawel; Hamblin, Michael R.] Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA. [Huang, Yingying; Mroz, Pawel; Hamblin, Michael R.] Harvard Univ, Sch Med, Dept Dermatol, Boston, MA 02115 USA. [Sperandio, Felipe F.] Univ Fed Alfenas, Inst Ciencias Biomed, BR-37130000 Alfenas, MG, Brazil. [Huang, Liyi] Guangxi Med Univ, Affiliated Coll & Hosp 1, Dept Infect Dis, Nanning 530021, Peoples R China. [Hamblin, Michael R.] Harvard MIT Div Hlth Sci & Technol, Cambridge, MA 02139 USA. RP Chiang, LY (reprint author), Univ Massachusetts, Dept Chem, Inst Nanosci Engn Technol, Lowell, MA 01854 USA. EM Long_Chiang@uml.edu NR 197 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER-VERLAG BERLIN PI BERLIN PA HEIDELBERGER PLATZ 3, D-14197 BERLIN, GERMANY SN 2195-0644 BN 978-3-319-22861-7; 978-3-319-22860-0 J9 SPRING SER BIOMAT S PY 2016 VL 5 BP 145 EP 200 DI 10.1007/978-3-319-22861-7_5 D2 10.1007/978-3-319-22861-7 PG 56 WC Engineering, Biomedical; Materials Science, Biomaterials SC Engineering; Materials Science GA BE2AA UT WOS:000368845100005 ER PT J AU Izgu, EC Oh, SS Szostak, JW AF Izgu, Enver Cagri Oh, Seung Soo Szostak, Jack W. TI Synthesis of activated 3 '-amino-3 '-deoxy-2-thio-thymidine, a superior substrate for the nonenzymatic copying of nucleic acid templates SO CHEMICAL COMMUNICATIONS LA English DT Article ID PHOSPHORAMIDATE DNA; PRIMER EXTENSION; RNA; OLIGOMERIZATION; DERIVATIVES; RIBONUCLEOTIDES AB We present a scalable synthesis of 3'-amino-3'-deoxy-2-thio-thymidine-5'-phosphoro-2-methylimidazolide, an activated monomer that can copy adenosine residues in nucleic acid templates rapidly without a polymerase. The sulfur atom substitution enhances the rate of template copying by 5-fold compared with the 3'-amino-3'-deoxy-T monomer, while the 3'-amino monomers exhibit a 2- to 3'-fold enhancement compared with their ribonucleotide counterparts. C1 [Izgu, Enver Cagri; Oh, Seung Soo; Szostak, Jack W.] Massachusetts Gen Hosp, Howard Hughes Med Inst, Dept Mol Biol, 185 Cambridge St, Boston, MA 02114 USA. [Izgu, Enver Cagri; Oh, Seung Soo; Szostak, Jack W.] Massachusetts Gen Hosp, Howard Hughes Med Inst, Ctr Computat & Integrat Biol, 185 Cambridge St, Boston, MA 02114 USA. [Izgu, Enver Cagri; Oh, Seung Soo; Szostak, Jack W.] Harvard Univ, Sch Med, Dept Genet, 77 Ave Louis Pasteur, Boston, MA 02115 USA. [Szostak, Jack W.] Harvard Univ, Dept Chem & Chem Biol, 12 Oxford St, Cambridge, MA 02138 USA. RP Szostak, JW (reprint author), Massachusetts Gen Hosp, Howard Hughes Med Inst, Dept Mol Biol, 185 Cambridge St, Boston, MA 02114 USA.; Szostak, JW (reprint author), Massachusetts Gen Hosp, Howard Hughes Med Inst, Ctr Computat & Integrat Biol, 185 Cambridge St, Boston, MA 02114 USA.; Szostak, JW (reprint author), Harvard Univ, Sch Med, Dept Genet, 77 Ave Louis Pasteur, Boston, MA 02115 USA.; Szostak, JW (reprint author), Harvard Univ, Dept Chem & Chem Biol, 12 Oxford St, Cambridge, MA 02138 USA. EM szostak@molbio.mgh.harvard.edu RI Oh, Seung Soo/N-6315-2016 OI Oh, Seung Soo/0000-0001-8045-080X FU Simons Foundation [290363] FX We thank Dr Shao-Liang Zheng (Harvard) for help with X-ray data collection and structure determination, and Prof. Mohammad Movassaghi (MIT) and Dr Justin Kim (MIT) for their guidance in performing safe hydrogen sulfide experiments. We also thank Dr Lijun Zhou and Ms Moriana Haj for technical assistance and Dr Albert C. Fahrenbach, Dr Victor S. Lelyveld, Mr Tony Z. Jia, and Mr Chun Pong Tam for helpful discussions. J. W. S. is an Investigator of the Howard Hughes Medical Institute. This work was supported in part by a grant (290363) from the Simons Foundation to J. W. S. NR 17 TC 0 Z9 0 U1 7 U2 15 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 2016 VL 52 IS 18 BP 3684 EP 3686 DI 10.1039/c5cc10317g PG 3 WC Chemistry, Multidisciplinary SC Chemistry GA DF0DF UT WOS:000371008500021 PM 26857159 ER PT J AU Singh, JA Ramachandran, R AF Singh, Jasvinder A. Ramachandran, Rekha TI Time trends in total ankle arthroplasty in the USA: a study of the National Inpatient Sample SO CLINICAL RHEUMATOLOGY LA English DT Article DE Ankle arthroplasty; Outcomes; Sex; Time trends; Utilization ID UNITED-STATES; KNEE ARTHROPLASTY; SHOULDER ARTHROPLASTY; TOTAL HIP; OPEN APPENDECTOMY; NIS DATABASE; FOLLOW-UP; OUTCOMES; REPLACEMENT; SURGERY AB The objective of this study was to assess the time trends in utilization, clinical characteristics, and outcomes of patients undergoing total ankle arthroplasty (TAA) in the USA. We used the Nationwide Inpatient Sample (NIS) data from 1998 to 2010 to examine time trends in the utilization rates of TAA. We used the Cochran Armitage test for trend to assess time trends across the years and the analysis of variance (ANOVA), Wilcoxon test, or chi-squared test (as appropriate) to compare the first (1998-2000) and the last time periods (2009-2010). TAA utilization rate increased significant from 1998 to 2010: 0.13 to 0.84 per 100,000 overall, 0.14 to 0.88 per 100,000 in females, and from 0.11 to 0.81 per 100,000 in males (p<0.0001 for each comparison for time trends). Compared to the 1998-2000 period, those undergoing TAA in 2009-2010 were older (41 % fewer patients <50 years, p<0.0001), less likely to have rheumatoid arthritis as the underlying diagnosis (55 % fewer patients, p=0.0001), more likely to have Deyo-Charlson index of 2 or more (197 % more, p=0.0010), and had a shorter length of stay at 2.5 days (17 % reduction, p<0.0001). Mortality was rare ranging from 0 to 0.6 % and discharge to inpatient facility ranged 12.6-14.1 %; we noted no significant time trends in either (p>0.05). The utilization rate of TAA increased rapidly in the USA from 1998 to 2010, but post-arthroplasty mortality rate was stable. Underlying diagnosis and medical comorbidity changed over time and both can impact outcomes after TAA. Further studies should examine how the outcomes and complications of TAA have evolved over time. C1 [Singh, Jasvinder A.] Birmingham VA Med Ctr, Birmingham, AL USA. [Singh, Jasvinder A.; Ramachandran, Rekha] Univ Alabama Birmingham, Sch Med, Dept Med, Fac Off Tower 805B,510 20th St S, Birmingham, AL 35294 USA. [Singh, Jasvinder A.; Ramachandran, Rekha] Univ Alabama Birmingham, Div Epidemiol, Sch Publ Hlth, Fac Off Tower 805B,510 20th St S, Birmingham, AL 35294 USA. [Singh, Jasvinder A.] Mayo Clin, Coll Med, Dept Orthoped Surg, Rochester, MN USA. RP Singh, JA (reprint author), Mayo Clin, Coll Med, Dept Orthoped Surg, Rochester, MN USA. EM Jasvinder.md@gmail.com FU Agency for Health Quality and Research Center for Education and Research on Therapeutics (AHRQ CERTs) [U19 HS021110]; National Institute of Arthritis, Musculoskeletal and Skin Diseases (NIAMS) [P50 AR060772, U34 AR062891]; National Institute of Aging (NIA) [U01 AG018947]; National Cancer Institute (NCI) [U10 CA149950]; Patient Centered Outcomes Research Institute (PCORI) [CE-1304-6631]; VA Medical Center at Birmingham, AL, USA FX JAS is supported by grants from the Agency for Health Quality and Research Center for Education and Research on Therapeutics (AHRQ CERTs) U19 HS021110; the National Institute of Arthritis, Musculoskeletal and Skin Diseases (NIAMS) P50 AR060772 and U34 AR062891; the National Institute of Aging (NIA) U01 AG018947; the National Cancer Institute (NCI) U10 CA149950; and research contract CE-1304-6631 from Patient Centered Outcomes Research Institute (PCORI). JAS is also supported through the use of resources and facilities at the VA Medical Center at Birmingham, AL, USA. NR 25 TC 4 Z9 4 U1 0 U2 0 PU SPRINGER LONDON LTD PI LONDON PA 236 GRAYS INN RD, 6TH FLOOR, LONDON WC1X 8HL, ENGLAND SN 0770-3198 EI 1434-9949 J9 CLIN RHEUMATOL JI Clin. Rheumatol. PD JAN PY 2016 VL 35 IS 1 BP 239 EP 245 DI 10.1007/s10067-014-2703-2 PG 7 WC Rheumatology SC Rheumatology GA DE7MM UT WOS:000370821000029 PM 24907036 ER PT J AU Faez, S Lobo, AM Unizony, SH Stone, JH Papaliodis, GN Sobrin, L AF Faez, Sepideh Lobo, Ann-Marie Unizony, Sebastian H. Stone, John H. Papaliodis, George N. Sobrin, Lucia TI Ocular inflammatory disease in patients with polymyalgia rheumatica: A case series and review of the literature SO CLINICAL RHEUMATOLOGY LA English DT Review DE Episcleritis; Ocular inflammatory disease; Polymyalgia rheumatica; Scleritis; Uveitis ID GIANT-CELL ARTERITIS; TEMPORAL ARTERITIS; REFRACTORY UVEITIS; PRESENTING FEATURE; VITREOUS FLUID; IFN-GAMMA; TOCILIZUMAB; SCLERITIS; INTERLEUKIN-6; T(H)17 AB Scleritis and uveitis are potentially blinding conditions that can be associated with systemic inflammatory diseases. Polymyalgia rheumatica (PMR) is a common rheumatic disorder of the elderly of uncertain etiology. Although there are a few published reports of scleritis and uveitis in PMR patients, the association of PMR to ocular inflammation has not been well established. The aim of this study is to report a series of PMR patients with scleritis and/or uveitis and review the prior published reports of this potential association. We retrospectively reviewed the medical charts of patients with PMR and scleritis or uveitis who were examined in the Ocular Immunology Service of Massachusetts Eye and Ear Infirmary. We also performed a systematic literature search (PubMed; January 1990 until January 2014) to identify earlier published reports. Seven PMR patients with ocular inflammatory disease (OID) were included in our study: two with scleritis, three with anterior uveitis, and two with panuveitis. The onset of PMR preceded the occurrence of OID in six patients, and in one patient uveitis developed 2 months prior to PMR. Five patients demonstrated a temporal association between flares of PMR and OID. In four patients, OID flares developed during tapering of systemic prednisone prescribed for PMR. Four of the five patients who had relapsing PMR had recurrent or persistent uveitis over the course of follow-up. PMR may be associated with both scleritis and uveitis and should be considered as a possible underlying cause of OID. C1 [Faez, Sepideh; Lobo, Ann-Marie; Papaliodis, George N.; Sobrin, Lucia] Harvard Univ, Dept Ophthalmol, Massachusetts Eye & Ear Infirm, Sch Med,Ocular Immunol & Uveitis Serv, 243 Charles St, Boston, MA 02114 USA. [Unizony, Sebastian H.; Stone, John H.] Massachusetts Gen Hosp, Dept Internal Med, Div Rheumatol Allergy & Immunol, 55 Fruit St, Boston, MA 02114 USA. [Sobrin, Lucia] Harvard Univ, Massachusetts Eye & Ear Infirm, Dept Ophthalmol, Sch Med,Retina Div, 243 Charles St, Boston, MA 02114 USA. RP Sobrin, L (reprint author), Harvard Univ, Massachusetts Eye & Ear Infirm, Dept Ophthalmol, Sch Med,Retina Div, 243 Charles St, Boston, MA 02114 USA. EM Lucia_Sobrin@meei.harvard.edu NR 48 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER LONDON LTD PI LONDON PA 236 GRAYS INN RD, 6TH FLOOR, LONDON WC1X 8HL, ENGLAND SN 0770-3198 EI 1434-9949 J9 CLIN RHEUMATOL JI Clin. Rheumatol. PD JAN PY 2016 VL 35 IS 1 BP 251 EP 258 DI 10.1007/s10067-014-2558-6 PG 8 WC Rheumatology SC Rheumatology GA DE7MM UT WOS:000370821000031 PM 24696366 ER PT J AU Ransohoff, RM El Khoury, J AF Ransohoff, Richard M. El Khoury, Joseph TI Microglia in Health and Disease SO COLD SPRING HARBOR PERSPECTIVES IN BIOLOGY LA English DT Article ID CENTRAL-NERVOUS-SYSTEM; EXPERIMENTAL AUTOIMMUNE ENCEPHALOMYELITIS; ALZHEIMERS-DISEASE; FRACTALKINE RECEPTOR; MOUSE MODEL; IN-VIVO; CHEMOKINE FRACTALKINE; CELL-ADHESION; MYELOID CELLS; IMMUNOHISTOCHEMICAL LOCALIZATION AB Microglia, the major myeloid cells of the central nervous system (CNS) are implicated in physiologic processes and in the pathogenesis of several CNS disorders. Since their initial description early in the 20th century, our ability to identify and isolate microglia has significantly improved and new research is providing insight into the functions of these cells in sickness and in health. Here, we review recent advances in our understanding of the role of microglia in physiological and pathological processes of the CNS with a focus on multiple sclerosis and Alzheimer's disease. Because of the prominent roles CX3CR1 and its ligand fractalkine played in bringing about these advances, we discuss the physiological and pathological roles of microglia as viewed from the CX3CR1-fractalkine perspective, providing a unique viewpoint. Based on the most recent studies of molecular profiling of microglia, we also propose a molecular and functional definition of microglia that incorporates the properties attributed to these cells in recent years. C1 [Ransohoff, Richard M.] Cleveland Clin, Lerner Res Inst, Dept Neurosci, Neuroinflammat Res Ctr, Cleveland, OH 44195 USA. [El Khoury, Joseph] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Div Infect Dis, Charlestown, MA 02129 USA. [El Khoury, Joseph] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Immunol & Inflammatory Dis, Charlestown, MA 02129 USA. RP Ransohoff, RM (reprint author), Cleveland Clin, Lerner Res Inst, Dept Neurosci, Neuroinflammat Res Ctr, Cleveland, OH 44195 USA.; El Khoury, J (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Div Infect Dis, Charlestown, MA 02129 USA.; El Khoury, J (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Immunol & Inflammatory Dis, Charlestown, MA 02129 USA. EM ransohr@ccf.org; Jelkhoury@mgh.harvard.edu NR 107 TC 5 Z9 5 U1 4 U2 8 PU COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT PI COLD SPRING HARBOR PA 1 BUNGTOWN RD, COLD SPRING HARBOR, NY 11724 USA SN 1943-0264 J9 CSH PERSPECT BIOL JI Cold Spring Harbor Perspect. Biol. PD JAN PY 2016 VL 8 IS 1 AR a020560 DI 10.1101/cshperspect.a020560 PG 15 WC Cell Biology SC Cell Biology GA DF2NQ UT WOS:000371181000004 ER PT J AU Miedema, MD Huguelet, J Virani, SS AF Miedema, Michael D. Huguelet, Joseph Virani, Salim S. TI Aspirin for the Primary Prevention of Cardiovascular Disease: In Need of Clarity SO CURRENT ATHEROSCLEROSIS REPORTS LA English DT Review DE Aspirin; Primary prevention; Cardiovascular disease ID LOW-DOSE ASPIRIN; RANDOMIZED-CONTROLLED-TRIALS; ACUTE MYOCARDIAL-INFARCTION; PLACEBO-CONTROLLED TRIAL; RISK-FACTORS; EVENTS; CORONARY; METAANALYSIS; SECONDARY; STROKE AB Aspirin remains one of the most extensively studied cardiovascular medications in the history of medicine. However, despite multiple, well-designed, large randomized controlled trials evaluating the potential of aspirin to prevent cardiovascular events in individuals without known cardiovascular disease (CVD), the role of aspirin in primary prevention is currently unclear. The initial aspirin trials included largely low-risk individuals with primary outcomes mostly focused on myocardial infarction (MI) and stroke, and showed a significant reduction in these CVD outcomes, especially MI. The more recently conducted trials have focused on older, higher CVD risk populations with high rates of lipid-lowering and antihypertensive medications use. These studies have used broader CVD outcomes as their primary end points and have failed to show a significant benefit of aspirin therapy in primary prevention. The exact reasons for the lack of efficacy in these recent trials are unclear but may be related to low rate of atherothrombotic events relative to other CVD events in the populations studied. Four large randomized controlled trials are currently underway which should provide some clarity in determining the optimal use of aspirin in the primary prevention of CVD. C1 [Miedema, Michael D.] Minneapolis Heart Inst, Minneapolis, MN USA. [Miedema, Michael D.] Minneapolis Heart Inst Fdn, 920 E 28th St, Minneapolis, MN 55414 USA. [Huguelet, Joseph] Abbott NW Hosp, Minneapolis, MN 55407 USA. [Virani, Salim S.] Baylor Coll Med, Michael E DeBakey Vet Affairs Med Ctr, Houston, TX 77030 USA. [Virani, Salim S.] Baylor Coll Med, Sect Cardiovasc Res, Houston, TX 77030 USA. RP Miedema, MD (reprint author), Minneapolis Heart Inst, Minneapolis, MN USA.; Miedema, MD (reprint author), Minneapolis Heart Inst Fdn, 920 E 28th St, Minneapolis, MN 55414 USA. EM mdm307@mail.harvard.edu OI Virani, Salim/0000-0001-9541-6954 NR 38 TC 0 Z9 0 U1 0 U2 1 PU CURRENT MEDICINE GROUP PI PHILADELPHIA PA 400 MARKET STREET, STE 700, PHILADELPHIA, PA 19106 USA SN 1523-3804 EI 1534-6242 J9 CURR ATHEROSCLER REP JI Curr. Atheroscleros. Rep. PD JAN PY 2016 VL 18 IS 1 AR 4 DI 10.1007/s11883-015-0555-0 PG 6 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA DE7JF UT WOS:000370811300003 PM 26753770 ER PT S AU Liberman, MC AF Liberman, M. Charles BE Popper, AN Hawkins, A TI Noise-Induced Hearing Loss: Permanent Versus Temporary Threshold Shifts and the Effects of Hair Cell Versus Neuronal Degeneration SO EFFECTS OF NOISE ON AQUATIC LIFE II SE Advances in Experimental Medicine and Biology LA English DT Article; Proceedings Paper CT 3rd International Conference on the Effects of Noise on Aquatic Life CY AUG, 2013 CL Budapest, HUNGARY SP Fisheries Joint Management Comm, Natl Oceanog & Atmospher Adm, Natl Sci Fdn, NAVFAC, Off Naval Res, Off Naval Res Global, Acoust Soc Amer, Aquat Noise Trust, Discovery Sound Sea, Co Biologists, Univ Maryland, Coll Chem & Life Sci, Ctr Comparat & Evolutionary Biol Hearing DE Neuropathy; Cochlear nerve; Noise exposure ID AUDITORY-NERVE; FREQUENCY MAP; COCHLEA; DAMAGE; CAT; FIBERS; STEREOCILIA; INJURY; REPAIR; MOUSE AB For decades, research on permanent noise-induced hearing loss has concentrated on the death of sensory hair cells and the associated threshold elevations. Recent work has shown that cochlear neurons are actually more vulnerable to noise, and even after exposures causing only temporary threshold elevation and no loss of hair cells, there is a rapid and irreversible loss of synaptic connections between cochlear neurons and hair cells followed by a slow degeneration of cochlear nerve cell bodies and central axons. Although this noise-induced neuropathy does not affect the audiogram, it likely reduces performance on more complex auditory tasks such as speech discrimination in noise. C1 [Liberman, M. Charles] Harvard Univ, Sch Med, Dept Otol & Laryngol, Boston, MA 02115 USA. [Liberman, M. Charles] Massachusetts Eye & Ear Infirm, Eaton Peabody Labs, 243 Charles St, Boston, MA 02114 USA. RP Liberman, MC (reprint author), Harvard Univ, Sch Med, Dept Otol & Laryngol, Boston, MA 02115 USA.; Liberman, MC (reprint author), Massachusetts Eye & Ear Infirm, Eaton Peabody Labs, 243 Charles St, Boston, MA 02114 USA. EM Charles_Liberman@meei.harvard.edu FU National Institute on Deafness and Other Communicative Disorders, National Institutes of Health [R01-DC-0188, P30-DC-05209] FX The research was supported by Grants R01-DC-0188 and P30-DC-05209 from the National Institute on Deafness and Other Communicative Disorders, National Institutes of Health. NR 33 TC 0 Z9 1 U1 8 U2 18 PU SPRINGER-VERLAG BERLIN PI BERLIN PA HEIDELBERGER PLATZ 3, D-14197 BERLIN, GERMANY SN 0065-2598 BN 978-1-4939-2981-8; 978-1-4939-2980-1 J9 ADV EXP MED BIOL JI Adv.Exp.Med.Biol. PY 2016 VL 875 BP 1 EP 7 DI 10.1007/978-1-4939-2981-8_1 PG 7 WC Environmental Sciences; Marine & Freshwater Biology SC Environmental Sciences & Ecology; Marine & Freshwater Biology GA BE2TA UT WOS:000370000900002 PM 26610938 ER PT S AU Ketten, DR Arruda, J Cramer, S Yamato, M AF Ketten, D. R. Arruda, J. Cramer, S. Yamato, M. BE Popper, AN Hawkins, A TI Great Ears: Low-Frequency Sensitivity Correlates in Land and Marine Leviathans SO EFFECTS OF NOISE ON AQUATIC LIFE II SE Advances in Experimental Medicine and Biology LA English DT Article; Proceedings Paper CT 3rd International Conference on the Effects of Noise on Aquatic Life CY AUG, 2013 CL Budapest, HUNGARY SP Fisheries Joint Management Comm, Natl Oceanog & Atmospher Adm, Natl Sci Fdn, NAVFAC, Off Naval Res, Off Naval Res Global, Acoust Soc Amer, Aquat Noise Trust, Discovery Sound Sea, Co Biologists, Univ Maryland, Coll Chem & Life Sci, Ctr Comparat & Evolutionary Biol Hearing DE Low frequency; Hearing; Whales; Impacts ID COCHLEA; COILING; LENGTH; CALLS AB Like elephants, baleen whales produce low-frequency (LF) and even infrasonic (IF) signals, suggesting they may be particularly susceptible to underwater anthropogenic sound impacts. Analyses of computerized tomography scans and histologies of the ears in five baleen whale and two elephant species revealed that LF thresholds correlate with basilar membrane thickness/width and cochlear radii ratios. These factors are consistent with high-mass, low-stiffness membranes and broad spiral curvatures, suggesting that Mysticeti and Proboscidea evolved common inner ear adaptations over similar time scales for processing IF/LF sounds despite operating in different media. C1 [Ketten, D. R.; Arruda, J.; Cramer, S.] Woods Hole Oceanog Inst, Dept Biol, Woods Hole, MA 02543 USA. [Ketten, D. R.] Harvard Univ, Sch Med, Boston, MA 02114 USA. [Ketten, D. R.] Curtin Univ, Perth, WA 6845, Australia. [Arruda, J.] Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. [Yamato, M.] Smithsonian Inst, Natl Museum Nat Hist, Washington, DC 20004 USA. RP Ketten, DR (reprint author), Woods Hole Oceanog Inst, Dept Biol, Woods Hole, MA 02543 USA.; Ketten, DR (reprint author), Harvard Univ, Sch Med, Boston, MA 02114 USA.; Ketten, DR (reprint author), Curtin Univ, Perth, WA 6845, Australia. EM dketten@whoi.edu; jarruda@whoi.edu; scramer@whoi.edu; YamatoM@si.edu FU Office of Naval Research; National Institutes of Health (NIH); International Association of Oil and Gas Producers (OGP) Joint Industry Programme; National Institute of Deafness and Communication Disorders (NIDCD), NIH FX This work was supported by the Office of Naval Research, the National Institutes of Health (NIH), the International Association of Oil and Gas Producers (OGP) Joint Industry Programme, and the National Institute of Deafness and Communication Disorders (NIDCD), NIH. We are grateful to Jennifer O'Malley, Barbara Burgess, and Diane DeLeo Jones for assistance with the histology and to Clarinda Northrup, the Cape Cod Stranding Network, and the International Fund for Animal Welfare (IFAW) for providing specimens. Above all, we acknowledge the mentorship and inspiration of our colleague Hezy Shoshani, who was a giant among his beloved leviathans and colleagues. He died in defense of his life's work and is sorely missed. NR 16 TC 1 Z9 1 U1 7 U2 10 PU SPRINGER-VERLAG BERLIN PI BERLIN PA HEIDELBERGER PLATZ 3, D-14197 BERLIN, GERMANY SN 0065-2598 BN 978-1-4939-2981-8; 978-1-4939-2980-1 J9 ADV EXP MED BIOL JI Adv.Exp.Med.Biol. PY 2016 VL 875 BP 529 EP 538 DI 10.1007/978-1-4939-2981-8_64 PG 10 WC Environmental Sciences; Marine & Freshwater Biology SC Environmental Sciences & Ecology; Marine & Freshwater Biology GA BE2TA UT WOS:000370000900065 PM 26611001 ER PT S AU Lyamin, OI Korneva, SM Rozhnov, VV Mukhametov, LM AF Lyamin, Oleg I. Korneva, Svetlana M. Rozhnov, Viatcheslav V. Mukhametov, Lev M. BE Popper, AN Hawkins, A TI Cardiorespiratory Responses to Acoustic Noise in Belugas SO EFFECTS OF NOISE ON AQUATIC LIFE II SE Advances in Experimental Medicine and Biology LA English DT Article; Proceedings Paper CT 3rd International Conference on the Effects of Noise on Aquatic Life CY AUG, 2013 CL Budapest, HUNGARY SP Fisheries Joint Management Comm, Natl Oceanog & Atmospher Adm, Natl Sci Fdn, NAVFAC, Off Naval Res, Off Naval Res Global, Acoust Soc Amer, Aquat Noise Trust, Discovery Sound Sea, Co Biologists, Univ Maryland, Coll Chem & Life Sci, Ctr Comparat & Evolutionary Biol Hearing DE Noise; Beluga; Heart rate; Breathing; Stress ID DOLPHIN TURSIOPS-TRUNCATUS AB To date, most research on the adverse effects of anthropogenic noise on marine mammals has focused on auditory and behavioral responses. Other responses have received little attention and are often ignored. In this study, the effect of acoustic noise on heart rate was examined in captive belugas. The data suggest that (1) heart rate can be used as a measure of physiological response (including stress) to noise in belugas and other cetaceans, (2) cardiac response is influenced by parameters of noise and adaptation to repeated exposure, and (3) cetacean calves are more vulnerable to the adverse effect of noise than adults. C1 [Lyamin, Oleg I.; Rozhnov, Viatcheslav V.; Mukhametov, Lev M.] Russian Acad Sci, AN Severtsov Inst Ecol & Evolut, Moscow 119071, Russia. [Lyamin, Oleg I.; Korneva, Svetlana M.; Mukhametov, Lev M.] Utrish Dolphinarium Ltd, Moscow 119071, Russia. [Lyamin, Oleg I.] Sepulveda Res Corp, VA Greater Los Angeles Healthcare Syst, Neurobiol Res 15A03, 16111 Plummer St, North Hills, CA 91343 USA. RP Lyamin, OI (reprint author), Russian Acad Sci, AN Severtsov Inst Ecol & Evolut, Moscow 119071, Russia.; Lyamin, OI (reprint author), Utrish Dolphinarium Ltd, Moscow 119071, Russia.; Lyamin, OI (reprint author), Sepulveda Res Corp, VA Greater Los Angeles Healthcare Syst, Neurobiol Res 15A03, 16111 Plummer St, North Hills, CA 91343 USA. EM olyamin@ucla.edu; s_korneva@list.ru; rozhnov.v@gmail.com; lev.mukhametov@gmail.com RI Varghese, Ann/P-7833-2016 FU Russian Geographical Society; Utrish Dolphinarium Ltd. FX The study was funded by the Russian Geographical Society and supported by Utrish Dolphinarium Ltd. We thank the colleagues from Dr. A. Supin's laboratory (A. N. Severtsov Institute of Ecology and Evolutions, Moscow, Russia) for assistance with the presentation of noises and Dr. P. Kosenko (Utrish Dolphinarium Ltd., Moscow, Russia) for technical support. NR 14 TC 0 Z9 0 U1 9 U2 13 PU SPRINGER-VERLAG BERLIN PI BERLIN PA HEIDELBERGER PLATZ 3, D-14197 BERLIN, GERMANY SN 0065-2598 BN 978-1-4939-2981-8; 978-1-4939-2980-1 J9 ADV EXP MED BIOL JI Adv.Exp.Med.Biol. PY 2016 VL 875 BP 665 EP 672 DI 10.1007/978-1-4939-2981-8_80 PG 8 WC Environmental Sciences; Marine & Freshwater Biology SC Environmental Sciences & Ecology; Marine & Freshwater Biology GA BE2TA UT WOS:000370000900081 PM 26611017 ER PT J AU Jaoude, WA Tiu, B Strieter, N Maloney, JD AF Jaoude, Wassim Abi Tiu, Brian Strieter, Nicole Maloney, James D. TI Thoracoscopic native lung pneumonectomy after single lung transplant: initial experience with 2 cases SO EUROPEAN JOURNAL OF CARDIO-THORACIC SURGERY LA English DT Editorial Material CT CHEST Annual Meeting CY OCT 29, 2013 CL Chicago, IL DE Lung-other; Experimental thoracic surgery ID COMPLICATIONS AB Single lung transplants (SLTs) leave in place a diseased lung, a potential source of complications. Native lung pneumonectomy is occasionally indicated. We present 2 cases of native lung complications (NLCs) managed with video-assisted thoracoscopic surgery (VATS) pneumonectomy at our institution, a procedure never reported in this context before. Case 1 involves a 59-year old gentleman with refractory, invasive pulmonary aspergillosis of the native lung, 5 years after SLT for idiopathic pulmonary fibrosis. Case 2 involves a 66-year old gentleman with alpha-1 antitrypsin deficiency who developed severe haemoptysis and intraparenchymal haemorrhage in the native lung 12 years after SLT. AVATS pneumonectomy was performed in both cases because we believed it would facilitate wound healing and hasten recovery in immunosuppressed patients. Our short-term results align with this hypothesis. We conclude that VATS pneumonectomy is a feasible, adequate and safe procedure in this patient population; larger series are needed to draw definitive conclusions. C1 [Jaoude, Wassim Abi; Maloney, James D.] Univ Wisconsin Hosp & Clin, Div Cardiothorac Surg, Thorac Surg Sect, Madison, WI 53792 USA. [Tiu, Brian] Suny Downstate Med Ctr, Dept Surg, 450 Clarkson Ave, Brooklyn, NY 11203 USA. [Strieter, Nicole; Maloney, James D.] William S Middleton Mem Vet Adm Med Ctr, Div Cardiothorac Surg, Thorac Surg Sect, Madison, WI USA. RP Tiu, B (reprint author), Suny Downstate Med Ctr, Dept Surg, 450 Clarkson Ave, Brooklyn, NY 11203 USA. EM brian.tiu@downstate.edu NR 5 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 1010-7940 EI 1873-734X J9 EUR J CARDIO-THORAC JI Eur. J. Cardio-Thorac. Surg. PD JAN PY 2016 VL 49 IS 1 BP 352 EP 354 DI 10.1093/ejcts/ezv075 PG 3 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery SC Cardiovascular System & Cardiology; Respiratory System; Surgery GA DE9SR UT WOS:000370979800095 ER PT J AU Kim, W Fricke, N Conery, AL Fuchs, BB Rajamuthiah, R Jayamani, E Vlahovska, PM Ausubel, FM Mylonakis, E AF Kim, Wooseong Fricke, Nico Conery, Annie L. Fuchs, Beth Burgwyn Rajamuthiah, Rajmohan Jayamani, Elamparithi Vlahovska, Petia M. Ausubel, Frederick M. Mylonakis, Eleftherios TI NH125 kills methicillin-resistant Staphylococcus aureus persisters by lipid bilayer disruption SO FUTURE MEDICINAL CHEMISTRY LA English DT Article DE antibiotics; giant unilamellar vesicle; MRSA; NH125; two-component system ID HISTIDINE KINASE; RESPONSE REGULATOR; BACILLUS-SUBTILIS; IN-VITRO; DETERGENT SOLUBILIZATION; PSEUDOMONAS-AERUGINOSA; DIRECT VISUALIZATION; BACTERICIDAL ACTION; 2-COMPONENT SYSTEM; VIRULENCE FACTORS AB Background: NH125, a known WalK inhibitor kills MRSA persisters. However, its precise mode of action is still unknown. Methods & results: The mode of action of NH125 was investigated by comparing its spectrum of antimicrobial activity and its effects on membrane permeability and giant unilamellar vesicles (GUVs) with walrycin B, a WalR inhibitor and benzyldimethylhexadecylammonium chloride (16-BAC), a cationic surfactant. NH125 killed persister cells of a variety of Staphylococcus aureus strains. Similar to 16-BAC, NH125 killed MRSA persisters by inducing rapid membrane permeabilization and caused the rupture of GUVs, whereas walrycin B did not kill MRSA persisters or induce membrane permeabilization and did not affect GUVs. Conclusion: NH125 kills MRSA persisters by interacting with and disrupting membranes in a detergent-like manner. C1 [Kim, Wooseong; Fuchs, Beth Burgwyn; Rajamuthiah, Rajmohan; Jayamani, Elamparithi; Mylonakis, Eleftherios] Brown Univ, Rhode Isl Hosp, Alpert Med Sch, Div Infect Dis, Providence, RI 02912 USA. [Fricke, Nico; Vlahovska, Petia M.] Brown Univ, Sch Engn, Providence, RI 02912 USA. [Conery, Annie L.; Rajamuthiah, Rajmohan; Jayamani, Elamparithi; Ausubel, Frederick M.] Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. [Conery, Annie L.; Ausubel, Frederick M.] Harvard Univ, Sch Med, Dept Genet, Boston, MA USA. RP Mylonakis, E (reprint author), Brown Univ, Rhode Isl Hosp, Alpert Med Sch, Div Infect Dis, Providence, RI 02912 USA. EM eleftherios_mylonakis@brown.edu RI Kim, Wooseong/A-9256-2017 OI Kim, Wooseong/0000-0002-4597-8374 FU NIH [P01 AI083214] FX This study was supported by NIH grant P01 AI083214 to EE Mylonakis and FM Ausubel. 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 72 TC 1 Z9 1 U1 0 U2 4 PU FUTURE SCI LTD PI LONDON PA UNITED HOUSE, 2 ALBERT PL, LONDON, N3 1QB, ENGLAND SN 1756-8919 EI 1756-8927 J9 FUTURE MED CHEM JI Future Med. Chem. PY 2016 VL 8 IS 3 BP 257 EP 269 DI 10.4155/fmc.15.189 PG 13 WC Chemistry, Medicinal SC Pharmacology & Pharmacy GA DF0XN UT WOS:000371062800004 PM 26910612 ER PT J AU Boneschansker, L Inoue, Y Oklu, R Irimia, D AF Boneschansker, Leo Inoue, Yoshitaka Oklu, Rahmi Irimia, Daniel TI Capillary plexuses are vulnerable to neutrophil extracellular traps SO INTEGRATIVE BIOLOGY LA English DT Article ID DEEP-VEIN THROMBOSIS; LUNG INJURY; MICE; PLATELETS; KIDNEY; SEPSIS AB Capillary plexuses are commonly regarded as reliable networks for blood flow and robust oxygen delivery to hypoxia sensitive tissues. They have high levels of redundancy to assure adequate blood supply when one or more of the capillaries in the network are blocked by a clot. However, despite having extensive capillary plexuses, many vital organs are often subject to secondary organ injury in patients with severe inflammation. Recent studies have suggested that neutrophils play a role in this pathology, even though their precise contribution remains elusive. Here we investigate the effect of chromatin fibres released from overly-activated neutrophils (neutrophil extracellular traps, NETs) on the flow of blood through microfluidic networks of channels replicating geometrical features of capillary plexuses. In an in vitro setting, we show that NETs can decouple the traffic of red blood cells from that of plasma in microfluidic networks. The effect is astonishingly disproportionate, with NETs from less than 200 neutrophils resulting in more than half of a 0.6 mm(2) microfluidic network to become void of red blood cell traffic. Importantly, the NETs are able to perturb the blood flow in capillary networks despite the presence of anti-coagulants. If verified to occur in vivo, this finding could represent a novel mechanism for tissue hypoxia and secondary organ injury during severe inflammation in patients already receiving antithrombotic and anticoagulant therapies. C1 [Boneschansker, Leo; Inoue, Yoshitaka; Irimia, Daniel] Harvard Univ, Sch Med, Massachusetts Gen Hosp, BioMEMS Resource Ctr,Dept Surg,Shriners Burns Hos, Boston, MA 02129 USA. [Boneschansker, Leo] Boston Childrens Hosp, Transplant Res Program, Boston, MA 02115 USA. [Oklu, Rahmi] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Intervent Radiol, Boston, MA 02129 USA. [Oklu, Rahmi] Mayo Clin, Div Intervent Radiol, Scottsdale, AZ 85258 USA. RP Irimia, D (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, BioMEMS Resource Ctr,Dept Surg,Shriners Burns Hos, Boston, MA 02129 USA. EM dirimia@hms.harvard.edu FU National Institutes of Health [AG051082, GM092804, EB002503]; [T32AI007529] FX We thank Dr David Briscoe for stimulating discussions. This work was supported in part by the National Institutes of Health (grants no. AG051082, GM092804, and EB002503). LB was supported by training grant T32AI007529. NR 20 TC 1 Z9 1 U1 2 U2 4 PU ROYAL SOC CHEMISTRY PI CAMBRIDGE PA THOMAS GRAHAM HOUSE, SCIENCE PARK, MILTON RD, CAMBRIDGE CB4 0WF, CAMBS, ENGLAND SN 1757-9694 EI 1757-9708 J9 INTEGR BIOL-UK JI Integr. Biol. PY 2016 VL 8 IS 2 BP 149 EP 155 DI 10.1039/c5ib00265f PG 7 WC Cell Biology SC Cell Biology GA DE8HQ UT WOS:000370877300002 PM 26797289 ER PT J AU Calverley, PM Postma, DS Anzueto, AR Make, BJ Eriksson, G Peterson, S Jenkins, CR AF Calverley, Peter M. Postma, Dirkje S. Anzueto, Antonio R. Make, Barry J. Eriksson, Goeran Peterson, Stefan Jenkins, Christine R. TI Early response to inhaled bronchodilators and corticosteroids as a predictor of 12-month treatment responder status and COPD exacerbations SO INTERNATIONAL JOURNAL OF CHRONIC OBSTRUCTIVE PULMONARY DISEASE LA English DT Article DE anti-inflammatories; bronchodilator effect; chronic obstructive pulmonary disease; predictors; risk assessment; risk factors ID OBSTRUCTIVE PULMONARY-DISEASE; METERED-DOSE INHALER; LUNG-FUNCTION; FLUTICASONE PROPIONATE; CLINICAL-TRIAL; HEALTH-STATUS; SALMETEROL; EFFICACY; OUTCOMES; BUDESONIDE/FORMOTEROL AB Background: Early treatment response markers, for example, improvement in forced expiratory volume in 1 second (FEV1) and St George's Respiratory Questionnaire (SGRQ) total score, may help clinicians to better manage patients with chronic obstructive pulmonary disease (COPD). We investigated the prevalence of clinically important improvements in FEV1 and SGRQ scores after 2-month budesonide/formoterol or formoterol treatment and whether such improvements predict subsequent improvements and exacerbation rates. Methods: This post hoc analysis is based on data from three double-blind, randomized studies in patients with moderate-to-very-severe COPD receiving twice-daily budesonide/formoterol or formoterol alone for 6 or 12 months. Prebronchodilator FEV1 and SGRQ total score were measured before treatment and at 2 and 12 months; COPD exacerbation rates were measured during months 2-12. Responders were defined by >= 100 mL improvement in prebronchodilator FEV1 and >= 4-point decrease in SGRQ total score. Results: Overall, 2,331 and 1,799 patients were included in the 0-2- and 0-12-month responder analyses, respectively, and 2,360 patients in the 2-12-month exacerbation rate analysis. At 2 months, 35.1% of patients were FEV1 responders and 44.3% were SGRQ responders. The probability of response was significantly greater with budesonide/formoterol than with formoterol or placebo for both parameters. Two-month responders had a greater chance of 12-month response than 2-month nonresponders for both FEV1 (odds ratio, 5.57; 95% confidence interval, 4.14-7.50) and SGRQ (odds ratio, 3.87; 95% confidence interval, 2.83-5.31). Two-month response in FEV1 (P<0.001), but not SGRQ (P=0.11), was associated with greater reductions in exacerbation risk. Conclusion: Early FEV1 and SGRQ treatment responses relate to their changes at 12 months. FEV1 response, but not SGRQ response, at 2 months predicts the risk of a future COPD exacerbation in some, but not all patients. This is potentially useful in clinical practice, although more sensitive and specific markers of favorable treatment response are required. C1 [Calverley, Peter M.] Aintree Univ Hosp NHS Fdn Trust, Pulm & Rehabil Res Grp, Liverpool L9 7AL, Merseyside, England. [Postma, Dirkje S.] Univ Groningen, Univ Med Ctr Groningen, Gronigen Res Inst Asthma, Dept Pulm Med & TB, Groningen, Netherlands. [Postma, Dirkje S.] Univ Groningen, Univ Med Ctr Groningen, COPD, Groningen, Netherlands. [Anzueto, Antonio R.] Univ Texas Hlth Sci Ctr San Antonio, Sch Med, Div Pulm Dis & Crit Care Med, San Antonio, TX 78229 USA. [Anzueto, Antonio R.] South Texas Vet Hlth Care Syst, San Antonio, TX USA. [Make, Barry J.] Univ Colorado, Natl Jewish Hlth, Div Pulm Sci & Crit Care Med, Denver, CO 80202 USA. [Eriksson, Goeran] Univ Hosp, Dept Resp Med & Allergol, Lund, Sweden. [Peterson, Stefan] StatMind AB, Lund, Sweden. [Jenkins, Christine R.] Univ Sydney, Concord Clincal Sch, George Inst Global Hlth, Sydney, NSW 2006, Australia. RP Calverley, PM (reprint author), Aintree Univ Hosp NHS Fdn Trust, Inst Ageing & Chron Dis, Dept Clin Sci, Lower Lane, Liverpool L9 7AL, Merseyside, England. EM pmacal@liverpool.ac.uk FU AstraZeneca FX This analysis was funded by AstraZeneca. Anna Mett and Shaun Foley of in Science Communications, Springer Healthcare, provided medical writing assistance, funded by AstraZeneca. The authors thank Malin Fageras of AstraZeneca R&D, Gothenburg, Sweden, and Thomas Similowski, of Groupe Hospitalier Pitie-Salpetriere, Paris, France, for their assistance with the development of this manuscript. Anders Persson of AstraZeneca R&D, Gothenburg, Sweden, performed additional statistical analyses. NR 30 TC 1 Z9 1 U1 0 U2 3 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 2016 VL 11 BP 381 EP 390 DI 10.2147/COPD.S93303 PG 10 WC Respiratory System SC Respiratory System GA DE9RK UT WOS:000370975600001 PM 26952309 ER PT J AU Ligibel, JA Winer, E Hudis, CA Barry, WT AF Ligibel, Jennifer A. Winer, Eric Hudis, Clifford A. Barry, William T. TI RE: Body Mass Index, PAM50 Subtype, and Outcomes in Node-Positive Breast Cancer: CALGB 9741 RESPONSE SO JNCI-JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Letter ID CHEMOTHERAPY; DIAGNOSIS; RISK C1 [Ligibel, Jennifer A.; Winer, Eric] Dana Farber Canc Inst, Boston, MA 02115 USA. [Hudis, Clifford A.] Mem Sloan Kettering Canc Ctr, 1275 York Ave, New York, NY 10021 USA. [Barry, William T.] Dana Farber Canc Inst, Alliance Stat & Data Ctr, Boston, MA 02115 USA. RP Ligibel, JA (reprint author), 450 Brookline Ave,Yawkey 1234, Boston, MA 02215 USA. EM jligibel@partners.org NR 7 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 2016 VL 108 IS 1 AR djv334 DI 10.1093/jnci/djv334 PG 2 WC Oncology SC Oncology GA DF2EV UT WOS:000371154700017 ER PT J AU Odejide, OO Cronin, AM Earle, CC LaCasce, AS Abel, GA AF Odejide, Oreofe O. Cronin, Angel M. Earle, Craig C. LaCasce, Ann S. Abel, Gregory A. TI Hospice Use Among Patients With Lymphoma: Impact of Disease Aggressiveness and Curability SO JNCI-JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Article ID END-OF-LIFE; B-CELL LYMPHOMA; PALLIATIVE CARE; LUNG-CANCER; TREATMENT PREFERENCES; ELDERLY-PATIENTS; OVARIAN-CANCER; MENTAL-HEALTH; NEAR-DEATH; CHOP AB Background: Little is known about factors that influence hospice use for patients with blood cancers. We aimed to characterize hospice enrollment in a large population of patients with B-cell non-Hodgkin lymphoma (NHL) and assess the impact of disease characteristics such as aggressiveness and curability. Methods: Using the Surveillance, Epidemiology, and End Results-Medicare database, we identified patients age 65 years and older who were diagnosed with indolent NHL, aggressive NHL, or mantle cell lymphoma (MCL, which is aggressive and incurable) and died between 1999 and 2009. We determined the prevalence of hospice use and predictors thereof, using multivariable logistic regression. All statistical tests were two-sided. Results: Of 18 777 patients, 9645 had indolent NHL, 8226 had aggressive NHL, and 906 had MCL. Of the total cohort, 41.6% enrolled in hospice, and 34.3% enrolled three or more days before death. Compared with patients with indolent NHL, those with MCL were more likely to enroll (adjusted odds ratio [AOR] = 1.72, 95% confidence interval [CI] = 1.49 to 1.98), followed by patients with aggressive NHL (AOR = 1.41, 95% CI = 1.32 to 1.50). Other factors statistically significantly associated with hospice use included older age, female sex, white race, high socioeconomic status, and later year of death. Conclusions: In this large cohort of patients with lymphoma, hospice use was substantially lower than the national average for all cancers, suggesting either the need for improvement in enrollment or that the current hospice model is not meeting this population's end-of-life needs. Moreover, the fact that patients with MCL were most likely to enroll suggests that the end-of-life phase may be more easily determined in the context of cancers that are both aggressive and incurable. C1 [Odejide, Oreofe O.; Cronin, Angel M.; Abel, Gregory A.] Dana Farber Canc Inst, Div Populat Sci, Dept Med Oncol, Boston, MA 02215 USA. [Odejide, Oreofe O.; LaCasce, Ann S.] Dana Farber Canc Inst, Ctr Lymphoma, Dept Med Oncol, Boston, MA 02215 USA. [Abel, Gregory A.] Dana Farber Canc Inst, Ctr Leukemia, Dept Med Oncol, Boston, MA 02215 USA. [Earle, Craig C.] Ontario Inst Canc Res, Toronto, ON, Canada. RP Odejide, OO (reprint author), Dana Farber Canc Inst, 450 Brookline Ave, Boston, MA 02215 USA. EM oreofe_odejide@dfci.harvard.edu FU Lymphoma Research Foundation; Conquer Cancer Foundation FX This research was supported by a Lymphoma Research Foundation Postdoctoral Fellow Award (OO) and a Conquer Cancer Foundation Young Investigator Award (OO). These study sponsors had no role in the design of the study, the collection, analysis, or interpretation of the data, the writing of the manuscript, nor the decision to submit the manuscript for publication. NR 45 TC 1 Z9 1 U1 1 U2 1 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 2016 VL 108 IS 1 AR djv280 DI 10.1093/jnci/djv280 PG 8 WC Oncology SC Oncology GA DF2EV UT WOS:000371154700022 ER PT J AU Burgess, DJ Gravely, AA Nelson, DB Bair, MJ Kerns, RD Higgins, DM Farmer, MM Partin, MR AF Burgess, Diana J. Gravely, Amy A. Nelson, David B. Bair, Matthew J. Kerns, Robert D. Higgins, Diana M. Farmer, Melissa M. Partin, Melissa R. TI Association between pain outcomes and race and opioid treatment: Retrospective cohort study of Veterans SO JOURNAL OF REHABILITATION RESEARCH AND DEVELOPMENT LA English DT Article DE blacks; chronic pain; Department of Veterans Affairs; disparities; opioids; pain outcomes; pain treatment effectiveness; race; survey; Veterans ID CHRONIC NONCANCER PAIN; UNITED-STATES; PRIMARY-CARE; RACIAL-DIFFERENCES; HEALTH-CARE; PATIENT SATISFACTION; AFRICAN-AMERICAN; POPULATION; OSTEOARTHRITIS; MANAGEMENT AB We examined whether pain outcomes (pain interference, perceived pain treatment effectiveness) vary by race and then whether opioid use moderates these associations. These analyses are part of a retrospective cohort study among 3,505 black and 46,203 non-Hispanic, white Department of Veterans Affairs (VA) patients with diagnoses of chronic musculoskeletal pain who responded to the 2007 VA Survey of Healthcare Experiences of Patients (SHEP). We used electronic medical record data to identify prescriptions for pharmacologic pain treatments in the year after diagnosis (Pain Diagnosis index visit) and before the SHEP index visit (the visit that made one eligible to complete the SHEP); pain outcomes came from the SHEP. We found no significant associations between race and pain interference or perceived effectiveness of pain treatment. VA patients with opioid prescriptions between the Pain Diagnosis index visit and the SHEP index visit reported greater pain interference on the SHEP than those without opioid prescriptions during that period. Opioid prescriptions were not associated with perceived treatment effectiveness for most patients. Findings raise questions about benefits of opioids for musculoskeletal pain and point to the need for alternative treatments for addressing chronic noncancer pain. C1 [Burgess, Diana J.; Gravely, Amy A.; Nelson, David B.; Partin, Melissa R.] Minneapolis Dept Vet Affairs VA Hlth Care Syst, Ctr Chron Dis Outcomes Res, Minneapolis, MN USA. [Burgess, Diana J.; Nelson, David B.; Partin, Melissa R.] Univ Minnesota, Sch Med, Dept Med, Minneapolis, MN 55455 USA. [Bair, Matthew J.] Richard L Roudebush VA Med Ctr, VA Hlth Serv Res & Dev, Ctr Hlth Informat & Commun, Indianapolis, IN USA. [Bair, Matthew J.] Indiana Univ Sch Med, Indianapolis, IN 46202 USA. [Bair, Matthew J.] Regenstrief Inst Inc, Indianapolis, IN USA. [Kerns, Robert D.; Higgins, Diana M.] VA Connecticut Healthcare Syst, West Haven, CT USA. [Kerns, Robert D.; Higgins, Diana M.] Yale Univ, Sch Med, New Haven, CT USA. [Higgins, Diana M.; Farmer, Melissa M.] VA Greater Angeles Healthcare Syst, Ctr Study Healthcare Innovat Implementat & Policy, VA Hlth Serv Res & Dev Serv, Sepulveda, CA USA. RP Higgins, DM (reprint author), Minneapolis VA Hlth Care Syst, Ctr Chron Dis Outcomes Res, One Vet Dr, Minneapolis, MN 55419 USA. EM Diana.Burgess@va.gov FU VA Health Services Research and Development Service (HSRD) [IIR 07-071]; VA HSR&D Research Career Scientist [RCS 10-185]; Merit Review Entry Program award MRP [04-41-1] FX This material was based on work supported by three awards from VA Health Services Research and Development Service (HSR&D): investigator initiated research IIR 07-071 (D.J.B.), VA HSR&D Research Career Scientist award RCS 10-185 (M.R.P.), and Merit Review Entry Program award MRP 04-41-1 (D.J.B.). NR 48 TC 0 Z9 0 U1 1 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 2016 VL 53 IS 1 BP 13 EP 24 DI 10.1682/JRRD.2014.10.0252 PG 12 WC Rehabilitation SC Rehabilitation GA DE9WS UT WOS:000370991200005 PM 26933921 ER PT J AU Higgins, DM Buta, E Dorflinger, L Masheb, RM Ruser, CB Goulet, JL Heapy, AA AF Higgins, Diana M. Buta, Eugenia Dorflinger, Lindsey Masheb, Robin M. Ruser, Christopher B. Goulet, Joseph L. Heapy, Alicia A. TI Prevalence and correlates of painful conditions and multimorbidity in national sample of overweight/obese Veterans SO JOURNAL OF REHABILITATION RESEARCH AND DEVELOPMENT LA English DT Article DE arthritis; back pain; BMI; chronic pain; comorbidities; multimorbidity; obesity; overweight; Veterans; weight management ID POSTTRAUMATIC-STRESS-DISORDER; OPERATIONS ENDURING FREEDOM; WEIGHT-MANAGEMENT PROGRAM; KNEE OSTEOARTHRITIS; PERSISTENT PAIN; IRAQI FREEDOM; PRIMARY-CARE; OBESITY; ADULTS; COMORBIDITY AB Chronic pain and overweight/obesity are prevalent public health concerns and occur at particularly high rates among Veterans. This study examined the prevalence and correlates of two common painful conditions (back pain and arthritis/joint pain) among overweight/obese Veterans in Veterans Health Administration (VHA) care. Participants (N = 45,477) completed the MOVE!23, a survey intended to tailor treatment for Veterans in VHA's MOVE! weight-management program. Overall, 72% of the sample reported painful conditions, with 10% reporting back pain, 26% reporting arthritis/joint pain, and 35% reporting both. We used multinomial logistic regression with "no pain" as the reference category to examine the association between painful conditions and participant characteristics. After multivariable adjustment, female Veterans had higher odds of reporting arthritis/joint pain and combined back and arthritis/ joint pain than no pain. Participants with higher body mass index had higher odds of reporting arthritis/joint pain and both back and arthritis/joint pain. The likelihood of painful conditions was higher in Veterans with comorbidities (hypertension, hyperlipidemia, lung disease, depression, anxiety, or posttraumatic stress disorder) and generally increased with the number of comorbidities reported (i.e., 5 or more). Overweight/obese Veterans frequently report painful conditions and, among those with pain, often have multiple comorbidities. These factors may increase the complexity of clinical management and necessitate refinements to weight-management programs. C1 [Higgins, Diana M.] Dept Vet Affairs VA Boston Healthcare Syst, Boston, MA USA. [Higgins, Diana M.] Boston Univ, Sch Med, Dept Psychiat, Boston, MA 02118 USA. [Buta, Eugenia; Dorflinger, Lindsey; Masheb, Robin M.; Ruser, Christopher B.; Goulet, Joseph L.; Heapy, Alicia A.] VA Connecticut Healthcare Syst, West Haven, CT USA. [Buta, Eugenia] Yale Univ, Dept Epidemiol, Sch Publ Hlth, New Haven, CT USA. [Dorflinger, Lindsey; Masheb, Robin M.; Ruser, Christopher B.; Goulet, Joseph L.; Heapy, Alicia A.] Yale Univ, Sch Med, New Haven, CT USA. RP Higgins, DM (reprint author), VA Boston Healthcare Syst, 150 South Huntington Ave,116B-2, Boston, MA 02130 USA. EM diana.higgins2@va.gov OI Goulet, Joseph/0000-0002-0842-804X NR 41 TC 1 Z9 1 U1 0 U2 2 PU JOURNAL REHAB RES & DEV PI BALTIMORE PA DEPT OF VETERANS AFFAIRS REHABIL RES & DEVELOP CTR 103 SOUTH GAY STREET, BALTIMORE, MD 21202-4051 USA SN 0748-7711 EI 1938-1352 J9 J REHABIL RES DEV JI J. Rehabil. Res. Dev. PY 2016 VL 53 IS 1 BP 71 EP 82 DI 10.1682/JRRD.2014.10.0251 PG 12 WC Rehabilitation SC Rehabilitation GA DE9WS UT WOS:000370991200010 PM 26933823 ER PT J AU Scioli-Salter, E Forman, DE Otis, JD Tun, C Allsup, K Marx, CE Hauger, RL Shipherd, MC Higgins, DM Tyzik, A Rasmusson, AM AF Scioli-Salter, Erica Forman, Daniel E. Otis, John D. Tun, Carlos Allsup, Kelly Marx, Christine E. Hauger, Richard L. Shipherd, Milian C. Higgins, Diana M. Tyzik, Anna Rasmusson, Ann M. TI Potential neurobiological benefits of exercise in chronic pain and posttraumatic stress disorder: Pilot study SO JOURNAL OF REHABILITATION RESEARCH AND DEVELOPMENT LA English DT Article DE ALLO; biomarkers; cardiorespiratory fitness; chronic pain; exercise; neurosteroids; NPY; pain sensitivity; PTSD; VO2 ID PLASMA NEUROPEPTIDE-Y; COMORBID CHRONIC PAIN; DEHYDROEPIANDROSTERONE-SULFATE; ANXIETY SENSITIVITY; OBESITY PREVALENCE; MUTUAL MAINTENANCE; METABOLIC SYNDROME; BASE-LINE; VETERANS; SYMPTOMS AB This pilot study assessed the effects of cardiopulmonary exercise testing and cardiorespiratory fitness on plasma neuropeptide Y (NPY), allopregnanolone and pregnanolone (ALLO), cortisol, and dehydroepiandrosterone (DHEA), and their association with pain sensitivity. Medication-free trauma exposed participants were either healthy (n = 7) or experiencing comorbid chronic pain/posttraumatic stress disorder (PTSD) (11 = 5). Peak oxygen consumption (VO2) during exercise testing was used to characterize cardiorespiratory fitness. Peak VO2 correlated with baseline and peak NPY levels (r = 0.66, p < 0.05 and r = 0.69, p < 0.05, respectively), as well as exercise -induced changes in ALLO (r = 0.89, p < 0.001) and peak ALLO levels (r= 0.71, p < 0.01). NPY levels at the peak of exercise correlated with.pain threshold 30 min after exercise (r = 0.65, p < 0.05), while exercise-induced increases in ALLO correlated with pain tolerance 30 min after exercise (r = 0.64, p < 0.05). In contrast, exercise-induced changes in cortisol and DHEA levels were inversely correlated with pain tolerance after exercise (r = -0.69, p < 0.05 and r =-0.58, p < 0.05, respectively). These data suggest that cardiorespiratory fitness is associated with higher plasma NPY levels and increased ALLO responses to exercise, which in turn relate to pain sensitivity. Future work will examine whether progressive exercise training increases cardiorespiratory fitness in association with increases in NPY and ALLO and reductions in pain sensitivity in chronic pain patients with PTSD. C1 [Scioli-Salter, Erica; Shipherd, Milian C.; Tyzik, Anna; Rasmusson, Ann M.] Dept Vet Affairs VA Boston Healthcare Syst, Womens Hlth Sci Div, Natl Ctr Posttraumat Stress Disorder, Boston, MA USA. [Scioli-Salter, Erica; Otis, John D.; Allsup, Kelly; Shipherd, Milian C.; Higgins, Diana M.] Dept Vet Affairs VA Boston Healthcare Syst, Res Serv, Boston, MA USA. [Scioli-Salter, Erica; Otis, John D.; Shipherd, Milian C.; Higgins, Diana M.; Rasmusson, Ann M.] Boston Univ, Sch Med, Dept Psychiat, Boston, MA 02118 USA. [Forman, Daniel E.; Allsup, Kelly] VA Pittsburgh Healthcare Syst, Geriatr Res Educ & Clin Ctr, Pittsburgh, PA USA. [Forman, Daniel E.] VA Boston Healthcare Syst, Div Cardiovasc Med, Boston, MA 02130 USA. [Forman, Daniel E.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Div Cardiovasc Med, Boston, MA 02115 USA. [Otis, John D.] Boston Univ, Dept Psychol & Brain Sci, Boston, MA 02215 USA. [Tun, Carlos] Harvard Univ, Sch Med, Div Rehabilitat Med, Boston, MA USA. [Tun, Carlos] VA Boston Healthcare Syst, Div Rehabilitat Med, Boston, MA 02130 USA. [Marx, Christine E.] Duke Univ, Sch Med, Durham VA Med Ctr, Durham, NC USA. [Marx, Christine E.] VA Midatlanti Mental Illness Res Educ & Clin Ctr, Durham, NC USA. [Marx, Christine E.] VA San Diego Healthcare Syst, Ctr Excellence Stress & Mental Hlth, San Diego, CA USA. [Hauger, Richard L.] Univ Calif San Diego, Sch Med, Dept Psychiat, 9500 Gillman Dr, La Jolla, CA 92093 USA. RP Scioli-Salter, E (reprint author), VA Boston Healthcare Syst, Div Res, 150 South Huntington Ave,116B-3, Boston, MA 02130 USA. EM Ericarose.scioli@va.gov FU VA Rehabilitation Research and Development Service [11K2RX000704-01A2]; Women's Health Sciences Division, National Center for PTSD; National Institute of Aging [RO1 AG050595-01]; VA Merit Review [CAMM-001-125]; VA Center of Excellence for Stress and Mental Health; Durham VA Medical Center FX This material was based on work supported in part by the VA Rehabilitation Research and Development Service (award 11K2RX000704-01A2); the Women's Health Sciences Division, National Center for PTSD; the National Institute of Aging (grant RO1 AG050595-01); VA Merit Review (award CAMM-001-125); the VA Center of Excellence for Stress and Mental Health; and the Durham VA Medical Center. The Stress Neuroendocrinology Core of the VA San Diego Healthcare System Research Service, directed by Dr. Hauger, performed the NPY and DHEA(S) immunoassays for this study. The Interventions and Metabolomics Laboratory of the VA Mid-Atlantic Mental Illness Research, Education and Clinical Center, directed by Dr. Marx, quantified neurosteroid levels via gas chromatography/mass spectrometry. NR 59 TC 1 Z9 1 U1 2 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 2016 VL 53 IS 1 BP 95 EP 106 DI 10.1682/JRRD.2014.10.0267 PG 12 WC Rehabilitation SC Rehabilitation GA DE9WS UT WOS:000370991200012 PM 27006290 ER PT J AU van der Hulle, T den Exter, PL Planquette, B Meyer, G Soler, S Monreal, M Jimenez, D Portillo, AK O'Connell, C Liebman, HA Shteinberg, M Adir, Y Tiseo, M Bersanelli, M Abdel-Razeq, HN Mansour, AH Donnelly, OG Radhakrishna, G Ramasamy, S Bozas, G Maraveyas, A Shinagare, AB Hatabu, H Nishino, M Huisman, MV Klok, FA AF van der Hulle, T. den Exter, P. L. Planquette, B. Meyer, G. Soler, S. Monreal, M. Jimenez, D. Portillo, A. K. O'Connell, C. Liebman, H. A. Shteinberg, M. Adir, Y. Tiseo, M. Bersanelli, M. Abdel-Razeq, H. N. Mansour, A. H. Donnelly, O. G. Radhakrishna, G. Ramasamy, S. Bozas, G. Maraveyas, A. Shinagare, A. B. Hatabu, H. Nishino, M. Huisman, M. V. Klok, F. A. TI Risk of recurrent venous thromboembolism and major hemorrhage in cancer-associated incidental pulmonary embolism among treated and untreated patients: a pooled analysis of 926 patients SO JOURNAL OF THROMBOSIS AND HAEMOSTASIS LA English DT Article DE hemorrhage; incidental finding; prognosis; pulmonary embolism; venous thromboembolism ID MANAGEMENT; THROMBOSIS; METAANALYSIS; PREVALENCE; GUIDELINES; MORTALITY; SURVIVAL; CHEST AB Background: Incidental pulmonary embolism (IPE) is defined as pulmonary embolism (PE) diagnosed on computed tomography scanning not performed for suspected PE. IPE has been estimated to occur in 3.1% of all cancer patients and is a growing challenge for clinicians and patients. Nevertheless, knowledge about the treatment and prognosis of cancer-associated IPE is scarce. We aimed to provide the best available evidence on IPE management. Methods: Incidence rates of symptomatic recurrent venous thromboembolism (VTE), major hemorrhage, and mortality during 6-month follow-up were pooled using individual patient data from studies identified by a systematic literature search. Subgroup analyses based on cancer stage, thrombus localization, and management were performed. Results: In 926 cancer patients with IPE from 11 cohorts, weighted pooled 6-month risks of recurrent VTE, major hemorrhage and mortality were 5.8% (95% confidence interval [CI] 3.7-8.3%), 4.7% (95% CI 3.0-6.8%), and 37% (95% CI 28-47%). VTE recurrence risk was comparable under low molecular weight heparins (LMWH) and vitamin K antagonists (VKAs) (6.2% vs. 6.4%; hazard ratio [HR] 0.9; 95% CI 0.3-3.1), while 12% in untreated patients (HR 2.6; 95% CI 0.91-7.3). Risk of major hemorrhage was higher under VKAs than under LMWH (13% vs. 3.9%; HR 3.9; 95% CI 1.6-10). VTE recurrence risk was comparable in patients with an subsegmental IPE and those with a more proximally localized IPE (HR 1.1; 95% CI 0.50-2.4). Conclusion: These results support the current recommendation to anticoagulate cancer-associated IPE with LMWH and argue against different management of subsegmental IPE. C1 [van der Hulle, T.; den Exter, P. L.; Huisman, M. V.; Klok, F. A.] Leiden Univ, Med Ctr, Dept Thrombosis & Hemostasis, Albinusdreef 2,POB 9600, NL-2300 RC Leiden, Netherlands. [Planquette, B.; Meyer, G.] Univ Paris 05, Hop Europeen Georges Pompidou, Dept Resp & Intens Care Med, INSERM U965, Paris, France. [Soler, S.] Hosp St Jaume, Dept Internal Med, Olot, Gerona, Spain. [Monreal, M.] Hosp Badalona Germans Trias & Pujol, Dept Internal Med, Barcelona, Spain. [Jimenez, D.; Portillo, A. K.] Hosp Ramon & Cajal, Resp Dept, IRYCIS, E-28034 Madrid, Spain. [Jimenez, D.; Portillo, A. K.] Univ Alcala de Henares, Madrid, Spain. [O'Connell, C.; Liebman, H. A.] Univ So Calif, Keck Sch Med, Jane Anne Nohl Div Hematol, Los Angeles, CA 90033 USA. [Shteinberg, M.; Adir, Y.] Technion Israel Inst Technol, Carmel Med Ctr, Fac Med, Pulmonol Inst, Haifa, Israel. [Shteinberg, M.] Technion Israel Inst Technol, Carmel Med Ctr, Fac Med, CF Ctr, Haifa, Israel. [Tiseo, M.; Bersanelli, M.] Univ Hosp Parma, Med Oncol Unit, Parma, Italy. [Abdel-Razeq, H. N.; Mansour, A. H.] King Hussein Canc Ctr, Dept Internal Med, Amman, Jordan. [Abdel-Razeq, H. N.; Mansour, A. H.] King Hussein Canc Ctr, Dept Radiol, Amman, Jordan. [Donnelly, O. G.] Univ Leeds, Leeds Inst Canc & Pathol, Leeds, W Yorkshire, England. [Donnelly, O. G.; Radhakrishna, G.; Ramasamy, S.] St James Inst Oncol, Leeds, W Yorkshire, England. [Bozas, G.; Maraveyas, A.] Hull & East Yorkshire Hosp NHS Trust, Queens Ctr Oncol & Haematol, Castle Hill Hosp, Cottingham, Yorks, England. [Maraveyas, A.] Hull York Med Sch, Cottingham, Yorks, England. [Shinagare, A. B.; Hatabu, H.; Nishino, M.] Brigham & Womens Hosp, Dept Radiol, 75 Francis St, Boston, MA 02115 USA. [Shinagare, A. B.; Hatabu, H.; Nishino, M.] Dana Farber Canc Inst, Boston, MA 02115 USA. RP van der Hulle, T (reprint author), Leiden Univ, Med Ctr, Dept Thrombosis & Hemostasis, Albinusdreef 2,POB 9600, NL-2300 RC Leiden, Netherlands. EM t.van_der_hulle@lumc.nl FU National Institutes of Health [1K23CA157631] FX M. Nishino was supported by a National Institutes of Health grant (1K23CA157631). NR 34 TC 11 Z9 11 U1 1 U2 3 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1538-7933 EI 1538-7836 J9 J THROMB HAEMOST JI J. Thromb. Haemost. PD JAN PY 2016 VL 14 IS 1 BP 105 EP 113 DI 10.1111/jth.13172 PG 9 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA DE5HD UT WOS:000370661100012 PM 26469193 ER PT J AU Tandon, V Kang, WS Robbins, TA Spencer, AJ Kim, ES McKenna, MJ Kujawa, SG Fiering, J Pararas, EEL Mescher, MJ Sewell, WF Borenstein, JT AF Tandon, Vishal Kang, Woo Seok Robbins, Tremaan A. Spencer, Abigail J. Kim, Ernest S. McKenna, Michael J. Kujawa, Sharon G. Fiering, Jason Pararas, Erin E. L. Mescher, Mark J. Sewell, William F. Borenstein, Jeffrey T. TI Microfabricated reciprocating micropump for intracochlear drug delivery with integrated drug/fluid storage and electronically controlled dosing SO LAB ON A CHIP LA English DT Article ID GUINEA-PIG COCHLEA; SENSORINEURAL HEARING-LOSS; HAIR CELL; INTRATYMPANIC DEXAMETHASONE; EVOKED-POTENTIALS; SYSTEMIC THERAPY; AUDITORY-NERVE; ROUND WINDOW; PRESSURE; TRANSMISSION AB The anatomical and pharmacological inaccessibility of the inner ear is a major challenge in drug-based treatment of auditory disorders. This also makes pharmacokinetic characterization of new drugs with systemic delivery challenging, because efficacy is coupled with how efficiently a drug can reach its target. Direct delivery of drugs to cochlear fluids bypasses pharmacokinetic barriers and helps to minimize systemic toxicity, but anatomical barriers make administration of multiple doses difficult without an automated delivery system. Such a system may be required for hair-cell regeneration treatments, which will likely require timed delivery of several drugs. To address these challenges, we have developed a micropump for controlled, automated inner-ear drug delivery with the ultimate goal of producing a long-term implantable/wearable delivery system. The current pump is designed to be used with a head mount for guinea pigs in preclinical drug characterization experiments. In this system, we have addressed several microfluidic challenges, including maintaining controlled delivery at safe, low flow rates and delivering drug without increasing the volume of fluid in the cochlea. By integrating a drug reservoir and all fluidic components into the microfluidic structure of the pump, we have made the drug delivery system robust compared to previous systems that utilized separate, tubing-connected components. In this study, we characterized the pump's unique infuse-withdraw and on-demand dosing capabilities on the bench and in guinea pig animal models. For the animal experiments, we used DNQX, a glutamate receptor antagonist, as a physiological indicator of drug delivery. DNQX suppresses compound action potentials (CAPs), so we were able to infer the distribution and spreading of the DNQX over time by measuring the changes in CAPs in response to stimuli at several characteristic frequencies. C1 [Tandon, Vishal; Kang, Woo Seok; McKenna, Michael J.; Kujawa, Sharon G.; Sewell, William F.] Massachusetts Eye & Ear Infirm, Dept Otol & Laryngol, 243 Charles St, Boston, MA 02139 USA. [Tandon, Vishal; Kang, Woo Seok; McKenna, Michael J.; Kujawa, Sharon G.; Sewell, William F.] Harvard Univ, Sch Med, Boston, MA 02139 USA. [Robbins, Tremaan A.; Spencer, Abigail J.; Kim, Ernest S.; Fiering, Jason; Pararas, Erin E. L.; Mescher, Mark J.; Borenstein, Jeffrey T.] Charles Stark Draper Lab Inc, Mat Engn & Microfabricat Directorate, 555 Technol Sq, Cambridge, MA 02139 USA. RP Borenstein, JT (reprint author), Charles Stark Draper Lab Inc, Mat Engn & Microfabricat Directorate, 555 Technol Sq, Cambridge, MA 02139 USA. EM William_Sewell@meei.harvard.edu; jborenstein@draper.com RI Tandon, Vishal/F-5699-2016 OI Tandon, Vishal/0000-0002-6618-7846 FU NIH NIDCD [5 R01 DC006848-08] FX This work was supported by NIH NIDCD Grant 5 R01 DC006848-08. NR 44 TC 1 Z9 1 U1 8 U2 22 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 2016 VL 16 IS 5 BP 829 EP 846 DI 10.1039/c5lc01396h PG 18 WC Biochemical Research Methods; Chemistry, Multidisciplinary; Nanoscience & Nanotechnology SC Biochemistry & Molecular Biology; Chemistry; Science & Technology - Other Topics GA DF0DR UT WOS:000371009700004 PM 26778829 ER PT B AU Petersen, TJ Sprich, SE Wilhelm, S AF Petersen, Timothy J. Sprich, Susan E. Wilhelm, Sabine BE Petersen, TJ Sprich, SE Wilhelm, S TI The Massachusetts General Hospital Handbook of Cognitive Behavioral Therapy Introduction SO MASSACHUSETTS GENERAL HOSPITAL HANDBOOK OF COGNITIVE BEHAVIORAL THERAPY SE Current Clinical Psychiatry LA English DT Editorial Material; Book Chapter ID DEPRESSION; EFFICACY; DISORDER C1 [Petersen, Timothy J.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Psychiat, 101 Merrimac St,10th Floor, Boston, MA 02114 USA. [Sprich, Susan E.] Massachusetts Gen Hosp, Cognit Behav Therapy Program, Dept Psychiat, One Bowdoin Sq,7th Floor, Boston, MA 02114 USA. [Wilhelm, Sabine] Harvard Univ, Massachusetts Gen Hosp, Sch Med, OCD & Related Disorders Program, 185 Cambridge St,Suite 2000, Boston, MA 02114 USA. RP Petersen, TJ (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Psychiat, 101 Merrimac St,10th Floor, Boston, MA 02114 USA. EM tpetersen@partners.org; ssprich@mgh.harvard.edu; swilhelm@mgh.harvard.ed OI Peterson, Tarla Rai/0000-0002-2864-0013 NR 35 TC 0 Z9 0 U1 0 U2 0 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DR, STE 208, TOTOWA, NJ 07512-1165 USA BN 978-1-4939-2605-3; 978-1-4939-2604-6 J9 CURR CLIN PSYCHIAT PY 2016 BP 1 EP 4 DI 10.1007/978-1-4939-2605-3_1 D2 10.1007/978-1-4939-2605-3 PG 4 WC Primary Health Care; Psychiatry SC General & Internal Medicine; Psychiatry GA BE1RR UT WOS:000368436700002 ER PT B AU Calkins, AW Park, JM Wilhelm, S Sprich, SE AF Calkins, Amanda W. Park, Jennifer M. Wilhelm, Sabine Sprich, Susan E. BE Petersen, TJ Sprich, SE Wilhelm, S TI Basic Principles and Practice of Cognitive Behavioral Therapy SO MASSACHUSETTS GENERAL HOSPITAL HANDBOOK OF COGNITIVE BEHAVIORAL THERAPY SE Current Clinical Psychiatry LA English DT Article; Book Chapter ID METAANALYSIS; RELIABILITY; DEPRESSION; INVENTORY; ANXIETY C1 [Calkins, Amanda W.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Psychiat, One Bowdoin Sq,6th Floor, Boston, MA 02114 USA. [Park, Jennifer M.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Child CBT Program, 1st Merrimac St,3rd Floor, Boston, MA 02114 USA. [Wilhelm, Sabine] Harvard Univ, Massachusetts Gen Hosp, Sch Med, OCD & Related Disorders Program, 185 Cambridge St,Suite 2000, Boston, MA 02114 USA. [Sprich, Susan E.] Massachusetts Gen Hosp, Dept Psychiat, Cognit Behav Therapy Program, One Bowdoin Sq,7th Floor, Boston, MA 02114 USA. RP Calkins, AW (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Psychiat, One Bowdoin Sq,6th Floor, Boston, MA 02114 USA. EM acalkins@mgh.harvard.edu; jpark12@mgh-harvard.edu; swilhelm@mgh.harvard.edu; ssprich@mgh.harvard.edu NR 17 TC 0 Z9 0 U1 0 U2 0 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DR, STE 208, TOTOWA, NJ 07512-1165 USA BN 978-1-4939-2605-3; 978-1-4939-2604-6 J9 CURR CLIN PSYCHIAT PY 2016 BP 5 EP 14 DI 10.1007/978-1-4939-2605-3_2 D2 10.1007/978-1-4939-2605-3 PG 10 WC Primary Health Care; Psychiatry SC General & Internal Medicine; Psychiatry GA BE1RR UT WOS:000368436700003 ER PT B AU Rosenbaum, JF AF Rosenbaum, Jerrold F. BE Petersen, TJ Sprich, SE Wilhelm, S TI The Massachusetts General Hospital Handbook of Cognitive Behavioral Therapy Foreword SO MASSACHUSETTS GENERAL HOSPITAL HANDBOOK OF COGNITIVE BEHAVIORAL THERAPY SE Current Clinical Psychiatry LA English DT Editorial Material; Book Chapter C1 [Rosenbaum, Jerrold F.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. RP Rosenbaum, JF (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DR, STE 208, TOTOWA, NJ 07512-1165 USA BN 978-1-4939-2605-3; 978-1-4939-2604-6 J9 CURR CLIN PSYCHIAT PY 2016 BP V EP V D2 10.1007/978-1-4939-2605-3 PG 1 WC Primary Health Care; Psychiatry SC General & Internal Medicine; Psychiatry GA BE1RR UT WOS:000368436700001 ER PT B AU Fisher, LB Sprich, SE AF Fisher, Lauren B. Sprich, Susan E. BE Petersen, TJ Sprich, SE Wilhelm, S TI Cognitive Techniques SO MASSACHUSETTS GENERAL HOSPITAL HANDBOOK OF COGNITIVE BEHAVIORAL THERAPY SE Current Clinical Psychiatry LA English DT Article; Book Chapter ID RANDOMIZED CONTROLLED-TRIAL; DIALECTICAL BEHAVIOR-THERAPY; HOMEWORK ASSIGNMENTS; DISORDER; PSYCHOTHERAPY; DEPRESSION; ANXIETY; MINDFULNESS; ACCEPTANCE C1 [Fisher, Lauren B.] Massachusetts Gen Hosp, Dept Psychiat, One Bowdoin Sq,6th Floor, Boston, MA 02114 USA. [Fisher, Lauren B.; Sprich, Susan E.] Massachusetts Gen Hosp, Dept Psychiat, Cognit Behav Therapy Program, One Bowdoin Sq,7th Floor, Boston, MA 02114 USA. RP Fisher, LB (reprint author), Massachusetts Gen Hosp, Dept Psychiat, One Bowdoin Sq,6th Floor, Boston, MA 02114 USA. EM lbfisher@mgh.harvard.edu; ssprich@mgh.harvard.edu NR 49 TC 0 Z9 0 U1 0 U2 0 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DR, STE 208, TOTOWA, NJ 07512-1165 USA BN 978-1-4939-2605-3; 978-1-4939-2604-6 J9 CURR CLIN PSYCHIAT PY 2016 BP 15 EP 32 DI 10.1007/978-1-4939-2605-3_3 D2 10.1007/978-1-4939-2605-3 PG 18 WC Primary Health Care; Psychiatry SC General & Internal Medicine; Psychiatry GA BE1RR UT WOS:000368436700004 ER PT B AU Chosak, A Baer, L AF Chosak, Anne Baer, Lee BE Petersen, TJ Sprich, SE Wilhelm, S TI Behavioral Strategies SO MASSACHUSETTS GENERAL HOSPITAL HANDBOOK OF COGNITIVE BEHAVIORAL THERAPY SE Current Clinical Psychiatry LA English DT Article; Book Chapter ID ANTIDEPRESSANT MEDICATION; MAJOR DEPRESSION; RANDOMIZED-TRIAL; ACTIVATION; THERAPY; DISORDER C1 [Chosak, Anne] Massachusetts Gen Hosp, Obsess Compuls Disorders Unit, 185 Cambridge St,2nd Floor, Boston, MA 02114 USA. [Baer, Lee] Massachusetts Gen Hosp, Dept Psychiat, 15 Parkman St,Wang Bldg,Suite 812, Boston, MA 02114 USA. RP Chosak, A (reprint author), Massachusetts Gen Hosp, Obsess Compuls Disorders Unit, 185 Cambridge St,2nd Floor, Boston, MA 02114 USA. EM ACHOSAK@BICS.BWH.HARVARD.EDU; lbaer@partners.org NR 15 TC 0 Z9 0 U1 0 U2 0 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DR, STE 208, TOTOWA, NJ 07512-1165 USA BN 978-1-4939-2605-3; 978-1-4939-2604-6 J9 CURR CLIN PSYCHIAT PY 2016 BP 33 EP 41 DI 10.1007/978-1-4939-2605-3_4 D2 10.1007/978-1-4939-2605-3 PG 9 WC Primary Health Care; Psychiatry SC General & Internal Medicine; Psychiatry GA BE1RR UT WOS:000368436700005 ER PT B AU Ellard, KK Chronopoulos, A AF Ellard, Kristen K. Chronopoulos, Antonia BE Petersen, TJ Sprich, SE Wilhelm, S TI Cognitive Behavioral Therapy for Anxiety Disorders SO MASSACHUSETTS GENERAL HOSPITAL HANDBOOK OF COGNITIVE BEHAVIORAL THERAPY SE Current Clinical Psychiatry LA English DT Article; Book Chapter ID COMORBIDITY SURVEY REPLICATION; DSM-IV DISORDERS; PANIC DISORDER; SOCIAL PHOBIA; ATTENTIONAL BIAS; CLINICAL-SAMPLE; EXPOSURE; WORRY; QUESTIONNAIRE; PREVALENCE C1 [Ellard, Kristen K.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Bipolar Clin,Dept Psychiat, 50 Staniford St,Suite 580, Boston, MA 02144 USA. [Ellard, Kristen K.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Res Program,Dept Psychiat, 50 Staniford St,Suite 580, Boston, MA 02144 USA. [Chronopoulos, Antonia] Massachusetts Gen Hosp, Dept Psychiat, 15 Parkman St, Boston, MA 02114 USA. RP Ellard, KK (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Bipolar Clin,Dept Psychiat, 50 Staniford St,Suite 580, Boston, MA 02144 USA.; Ellard, KK (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Res Program,Dept Psychiat, 50 Staniford St,Suite 580, Boston, MA 02144 USA. EM kellard@mgh.harvard.edu; ACHRONOPOULOS@mgh.harvard.edu NR 37 TC 0 Z9 0 U1 1 U2 1 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DR, STE 208, TOTOWA, NJ 07512-1165 USA BN 978-1-4939-2605-3; 978-1-4939-2604-6 J9 CURR CLIN PSYCHIAT PY 2016 BP 43 EP 61 DI 10.1007/978-1-4939-2605-3_5 D2 10.1007/978-1-4939-2605-3 PG 19 WC Primary Health Care; Psychiatry SC General & Internal Medicine; Psychiatry GA BE1RR UT WOS:000368436700006 ER PT B AU Nyer, MB Fisher, LB Farabaugh, A AF Nyer, Maren B. Fisher, Lauren B. Farabaugh, Amy BE Petersen, TJ Sprich, SE Wilhelm, S TI Cognitive Behavioral Therapy for Depression SO MASSACHUSETTS GENERAL HOSPITAL HANDBOOK OF COGNITIVE BEHAVIORAL THERAPY SE Current Clinical Psychiatry LA English DT Article; Book Chapter ID COLLABORATIVE RESEARCH-PROGRAM; MENTAL-HEALTH TREATMENT; MAJOR DEPRESSION; ANTIDEPRESSANT MEDICATION; ACTIVATION TREATMENT; NATIONAL-INSTITUTE; RANDOMIZED-TRIAL; TERM TREATMENT; RATING-SCALE; ANXIETY C1 [Nyer, Maren B.; Fisher, Lauren B.; Farabaugh, Amy] Massachusetts Gen Hosp, Dept Psychiat, DCRP, One Bowdoin Sq,6th Floor, Boston, MA 02114 USA. RP Nyer, MB (reprint author), Massachusetts Gen Hosp, Dept Psychiat, DCRP, One Bowdoin Sq,6th Floor, Boston, MA 02114 USA. EM mnyer@partners.org NR 88 TC 0 Z9 0 U1 0 U2 1 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DR, STE 208, TOTOWA, NJ 07512-1165 USA BN 978-1-4939-2605-3; 978-1-4939-2604-6 J9 CURR CLIN PSYCHIAT PY 2016 BP 63 EP 86 DI 10.1007/978-1-4939-2605-3_6 D2 10.1007/978-1-4939-2605-3 PG 24 WC Primary Health Care; Psychiatry SC General & Internal Medicine; Psychiatry GA BE1RR UT WOS:000368436700007 ER PT B AU Deckersbach, T Eisner, L Sylvia, L AF Deckersbach, Thilo Eisner, Lori Sylvia, Louisa BE Petersen, TJ Sprich, SE Wilhelm, S TI Cognitive Behavioral Therapy for Bipolar Disorder SO MASSACHUSETTS GENERAL HOSPITAL HANDBOOK OF COGNITIVE BEHAVIORAL THERAPY SE Current Clinical Psychiatry LA English DT Article; Book Chapter ID TREATMENT ENHANCEMENT PROGRAM; RANDOMIZED CONTROLLED-TRIAL; INTERNATIONAL NEUROPSYCHIATRIC INTERVIEW; OBSESSIVE-COMPULSIVE DISORDER; MAJOR DEPRESSIVE-DISORDERS; WEEKLY SYMPTOMATIC STATUS; STEP-BD; MOOD DISORDERS; MEDICAL BURDEN; TRANSDIAGNOSTIC TREATMENT C1 [Deckersbach, Thilo; Sylvia, Louisa] Massachusetts Gen Hosp, Dept Psychiat, Bipolar Clin, 50 Staniford St,Suite 580, Boston, MA 02114 USA. [Deckersbach, Thilo; Sylvia, Louisa] Massachusetts Gen Hosp, Dept Psychiat, Res Program, 50 Staniford St,Suite 580, Boston, MA 02114 USA. [Eisner, Lori] Massachusetts Gen Hosp, Dept Psychiat, 15 Parkman St,WAC812, Boston, MA 02114 USA. RP Deckersbach, T (reprint author), Massachusetts Gen Hosp, Dept Psychiat, Bipolar Clin, 50 Staniford St,Suite 580, Boston, MA 02114 USA.; Deckersbach, T (reprint author), Massachusetts Gen Hosp, Dept Psychiat, Res Program, 50 Staniford St,Suite 580, Boston, MA 02114 USA. EM tdeckersbach@mgh.harvard.edu; leisner@mgh.harvard.edu; lsylvia2@partners.org NR 94 TC 0 Z9 0 U1 3 U2 3 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DR, STE 208, TOTOWA, NJ 07512-1165 USA BN 978-1-4939-2605-3; 978-1-4939-2604-6 J9 CURR CLIN PSYCHIAT PY 2016 BP 87 EP 103 DI 10.1007/978-1-4939-2605-3_7 D2 10.1007/978-1-4939-2605-3 PG 17 WC Primary Health Care; Psychiatry SC General & Internal Medicine; Psychiatry GA BE1RR UT WOS:000368436700008 ER PT B AU Berman, NC Elliott, CM Wilhelm, S AF Berman, Noah Chase Elliott, Corinna M. Wilhelm, Sabine BE Petersen, TJ Sprich, SE Wilhelm, S TI Cognitive Behavioral Therapy for Obsessive-Compulsive Disorder: Theory, Assessment, and Treatment SO MASSACHUSETTS GENERAL HOSPITAL HANDBOOK OF COGNITIVE BEHAVIORAL THERAPY SE Current Clinical Psychiatry LA English DT Article; Book Chapter ID RESPONSE PREVENTION; CONTROLLED-TRIAL; EXPOSURE; SCALE; COMBINATION; VALIDATION; INVENTORY; VERSION; FAMILY C1 [Berman, Noah Chase; Elliott, Corinna M.] Massachusetts Gen Hosp, Dept Psychiat, OCD & Related Disorders Program, 185 Cambridge St,Suite 2000, Boston, MA 02114 USA. [Berman, Noah Chase; Elliott, Corinna M.] Harvard Univ, Sch Med, 185 Cambridge St,Suite 2000, Boston, MA 02114 USA. [Wilhelm, Sabine] Harvard Univ, Sch Med, Massachusetts Gen Hosp, OCD & Related Disorders Program, 185 Cambridge St,Suite 2000, Boston, MA 02114 USA. RP Berman, NC (reprint author), Massachusetts Gen Hosp, Dept Psychiat, OCD & Related Disorders Program, 185 Cambridge St,Suite 2000, Boston, MA 02114 USA. EM nberman@mgh.harvard.edu NR 42 TC 0 Z9 0 U1 1 U2 3 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DR, STE 208, TOTOWA, NJ 07512-1165 USA BN 978-1-4939-2605-3; 978-1-4939-2604-6 J9 CURR CLIN PSYCHIAT PY 2016 BP 105 EP 115 DI 10.1007/978-1-4939-2605-3_8 D2 10.1007/978-1-4939-2605-3 PG 11 WC Primary Health Care; Psychiatry SC General & Internal Medicine; Psychiatry GA BE1RR UT WOS:000368436700009 ER PT B AU Keuthen, NJ Usmani, A AF Keuthen, Nancy J. Usmani, Aisha BE Petersen, TJ Sprich, SE Wilhelm, S TI Cognitive Behavioral Treatment for Trichotillomania (Hair-Pulling Disorder) and Excoriation (Skin-Picking) Disorder SO MASSACHUSETTS GENERAL HOSPITAL HANDBOOK OF COGNITIVE BEHAVIORAL THERAPY SE Current Clinical Psychiatry LA English DT Article; Book Chapter ID HABIT-REVERSAL; PSYCHOMETRIC PROPERTIES; MILWAUKEE INVENTORY; EXPERIENTIAL AVOIDANCE; MATTER ABNORMALITIES; INITIAL DEVELOPMENT; COMMITMENT THERAPY; COMMUNITY SAMPLE; CONTROLLED-TRIAL; PREVALENCE C1 [Keuthen, Nancy J.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Psychiat,OCD & Related Disorders Clin, 185 Cambridge St,Simches Bldg,Fl 2, Boston, MA 02114 USA. [Usmani, Aisha] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Psychiat,OCD & Related Disorders Clin, 15 Parkman St,WACC 815, Boston, MA 02114 USA. RP Keuthen, NJ (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Psychiat,OCD & Related Disorders Clin, 185 Cambridge St,Simches Bldg,Fl 2, Boston, MA 02114 USA. EM nkeuthen@partners.org NR 47 TC 0 Z9 0 U1 1 U2 3 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DR, STE 208, TOTOWA, NJ 07512-1165 USA BN 978-1-4939-2605-3; 978-1-4939-2604-6 J9 CURR CLIN PSYCHIAT PY 2016 BP 117 EP 130 DI 10.1007/978-1-4939-2605-3_9 D2 10.1007/978-1-4939-2605-3 PG 14 WC Primary Health Care; Psychiatry SC General & Internal Medicine; Psychiatry GA BE1RR UT WOS:000368436700010 ER PT B AU Reese, HE Usmani, A AF Reese, Hannah E. Usmani, Aisha BE Petersen, TJ Sprich, SE Wilhelm, S TI Behavior Therapy for Tourette Syndrome and Chronic Tic Disorder SO MASSACHUSETTS GENERAL HOSPITAL HANDBOOK OF COGNITIVE BEHAVIORAL THERAPY SE Current Clinical Psychiatry LA English DT Article; Book Chapter ID HABIT REVERSAL TREATMENT; COMPETING RESPONSES; CHILDREN; SEVERITY; TRIAL C1 [Reese, Hannah E.] Bowdoin Coll, Dept Psychol, 6900 Coll Stn, Brunswick, ME 04011 USA. [Reese, Hannah E.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Psychiat, 185 Cambridge St,Suite 2000, Boston, MA 02114 USA. [Usmani, Aisha] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Psychiat, 15 Parkman St,WACC 815, Boston, MA 02114 USA. RP Reese, HE (reprint author), Bowdoin Coll, Dept Psychol, 6900 Coll Stn, Brunswick, ME 04011 USA. EM hreese@bowdoin.edu NR 26 TC 0 Z9 0 U1 0 U2 0 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DR, STE 208, TOTOWA, NJ 07512-1165 USA BN 978-1-4939-2605-3; 978-1-4939-2604-6 J9 CURR CLIN PSYCHIAT PY 2016 BP 131 EP 140 DI 10.1007/978-1-4939-2605-3_10 D2 10.1007/978-1-4939-2605-3 PG 10 WC Primary Health Care; Psychiatry SC General & Internal Medicine; Psychiatry GA BE1RR UT WOS:000368436700011 ER PT B AU Greenberg, JL Blashill, AJ Ragan, J Fang, A AF Greenberg, Jennifer L. Blashill, Aaron J. Ragan, Jennifer Fang, Angela BE Petersen, TJ Sprich, SE Wilhelm, S TI Cognitive Behavioral Therapy for Body Dysmorphic Disorder SO MASSACHUSETTS GENERAL HOSPITAL HANDBOOK OF COGNITIVE BEHAVIORAL THERAPY SE Current Clinical Psychiatry LA English DT Article; Book Chapter ID RANDOMIZED CONTROLLED-TRIAL; POPULATION-BASED SURVEY; SKIN PICKING; CLINICAL CHARACTERISTICS; ANXIETY DISORDERS; PREVALENCE; INDIVIDUALS; INFORMATION; COMORBIDITY; RELIABILITY C1 [Greenberg, Jennifer L.; Blashill, Aaron J.; Ragan, Jennifer; Fang, Angela] Massachusetts Gen Hosp, Dept Psychiat, 185 Cambridge St, Boston, MA 02114 USA. RP Greenberg, JL (reprint author), Massachusetts Gen Hosp, Dept Psychiat, 185 Cambridge St, Boston, MA 02114 USA. EM jlgreenberg@mgh.harvard.edu NR 65 TC 0 Z9 0 U1 0 U2 0 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DR, STE 208, TOTOWA, NJ 07512-1165 USA BN 978-1-4939-2605-3; 978-1-4939-2604-6 J9 CURR CLIN PSYCHIAT PY 2016 BP 141 EP 153 DI 10.1007/978-1-4939-2605-3_11 D2 10.1007/978-1-4939-2605-3 PG 13 WC Primary Health Care; Psychiatry SC General & Internal Medicine; Psychiatry GA BE1RR UT WOS:000368436700012 ER PT B AU Gray, EK Thomas, JJ AF Gray, Emily K. Thomas, Jennifer J. BE Petersen, TJ Sprich, SE Wilhelm, S TI Transdiagnostic Cognitive Behavioral Therapy for Eating Disorders SO MASSACHUSETTS GENERAL HOSPITAL HANDBOOK OF COGNITIVE BEHAVIORAL THERAPY SE Current Clinical Psychiatry LA English DT Article; Book Chapter ID RANDOMIZED CONTROLLED-TRIAL; ANOREXIA-NERVOSA; BULIMIA-NERVOSA; IMPAIRMENT; PREVALENCE; COMMUNITY C1 [Gray, Emily K.; Thomas, Jennifer J.] Massachusetts Gen Hosp, Eating Disorders Clin & Res Program, 2 Longfellow Pl,Suite 200, Boston, MA 02114 USA. RP Gray, EK (reprint author), Massachusetts Gen Hosp, Eating Disorders Clin & Res Program, 2 Longfellow Pl,Suite 200, Boston, MA 02114 USA. EM ekgray@mgh.harvard.edu NR 20 TC 0 Z9 0 U1 1 U2 2 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DR, STE 208, TOTOWA, NJ 07512-1165 USA BN 978-1-4939-2605-3; 978-1-4939-2604-6 J9 CURR CLIN PSYCHIAT PY 2016 BP 155 EP 169 DI 10.1007/978-1-4939-2605-3_12 D2 10.1007/978-1-4939-2605-3 PG 15 WC Primary Health Care; Psychiatry SC General & Internal Medicine; Psychiatry GA BE1RR UT WOS:000368436700013 ER PT B AU Sprich, SE Safren, SA AF Sprich, Susan E. Safren, Steven A. BE Petersen, TJ Sprich, SE Wilhelm, S TI Cognitive Behavioral Therapy for Adult Attention-Deficit Hyperactivity Disorder SO MASSACHUSETTS GENERAL HOSPITAL HANDBOOK OF COGNITIVE BEHAVIORAL THERAPY SE Current Clinical Psychiatry LA English DT Article; Book Chapter ID MEDICATION-TREATED ADULTS; ADHD; SYMPTOMS; CHILDREN C1 [Sprich, Susan E.] Massachusetts Gen Hosp, Dept Psychiat, Cognit Behav Therapy Program, 1 Bowdoin Sq,7th Floor, Boston, MA 02114 USA. [Safren, Steven A.] Massachusetts Gen Hosp, Dept Psychiat Behav Med, 1 Bowdoin Sq,7th Floor, Boston, MA 02114 USA. RP Sprich, SE (reprint author), Massachusetts Gen Hosp, Dept Psychiat, Cognit Behav Therapy Program, 1 Bowdoin Sq,7th Floor, Boston, MA 02114 USA. EM ssprich@mgh.harvard.edu; ssafren@partners.org NR 25 TC 0 Z9 0 U1 2 U2 2 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DR, STE 208, TOTOWA, NJ 07512-1165 USA BN 978-1-4939-2605-3; 978-1-4939-2604-6 J9 CURR CLIN PSYCHIAT PY 2016 BP 171 EP 182 DI 10.1007/978-1-4939-2605-3_13 D2 10.1007/978-1-4939-2605-3 PG 12 WC Primary Health Care; Psychiatry SC General & Internal Medicine; Psychiatry GA BE1RR UT WOS:000368436700014 ER PT B AU Marcus, PH Cather, C AF Marcus, Peter H. Cather, Corinne BE Petersen, TJ Sprich, SE Wilhelm, S TI Cognitive Behavioral Approaches for Schizophrenia and Other Psychotic Disorders SO MASSACHUSETTS GENERAL HOSPITAL HANDBOOK OF COGNITIVE BEHAVIORAL THERAPY SE Current Clinical Psychiatry LA English DT Article; Book Chapter ID HIGH-RISK; AUDITORY HALLUCINATIONS; 1ST-EPISODE PSYCHOSIS; DEPRESSIVE SYMPTOMS; SPECTRUM DISORDERS; NEGATIVE SYMPTOMS; STRESS MODEL; THERAPY; VULNERABILITY; DELUSIONS C1 [Marcus, Peter H.; Cather, Corinne] Massachusetts Gen Hosp, Dept Psychiat, 15 Parkman St,WACC 812, Boston, MA 02114 USA. RP Cather, C (reprint author), Massachusetts Gen Hosp, Dept Psychiat, 15 Parkman St,WACC 812, Boston, MA 02114 USA. EM ccather@partners.org NR 77 TC 0 Z9 0 U1 2 U2 3 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DR, STE 208, TOTOWA, NJ 07512-1165 USA BN 978-1-4939-2605-3; 978-1-4939-2604-6 J9 CURR CLIN PSYCHIAT PY 2016 BP 183 EP 195 DI 10.1007/978-1-4939-2605-3_14 D2 10.1007/978-1-4939-2605-3 PG 13 WC Primary Health Care; Psychiatry SC General & Internal Medicine; Psychiatry GA BE1RR UT WOS:000368436700015 ER PT B AU Yeterian, JD Labbe, AK Kelly, JF AF Yeterian, Julie D. Labbe, Allison K. Kelly, John F. BE Petersen, TJ Sprich, SE Wilhelm, S TI Cognitive Behavioral Approaches for Substance Use Disorders SO MASSACHUSETTS GENERAL HOSPITAL HANDBOOK OF COGNITIVE BEHAVIORAL THERAPY SE Current Clinical Psychiatry LA English DT Article; Book Chapter ID IV ALCOHOL DEPENDENCE; RELAPSE PREVENTION; FOLLOW-UP; RECOVERY; ADDICTION; OUTCOMES; REMISSION; COCAINE; MODEL; SCALE C1 [Yeterian, Julie D.; Kelly, John F.] Massachusetts Gen Hosp, Dept Psychiat, Ctr Addict Med, 151 Merrimac St, Boston, MA 02114 USA. [Labbe, Allison K.] Massachusetts Gen Hosp, Dept Psychiat, Ctr Addict Med, 151 Merrimac St, Boston, MA 02114 USA. [Labbe, Allison K.] Massachusetts Gen Hosp, Dept Psychiat, Behav Med Serv, One Bowdoin Sq,7th Floor, Boston, MA 02114 USA. RP Kelly, JF (reprint author), Massachusetts Gen Hosp, Dept Psychiat, Ctr Addict Med, 151 Merrimac St, Boston, MA 02114 USA. EM jyeterian@mgh.harvard.edu; aklabbe@mgh.harvard.edu; jkelly11@mgh.harvard.edu NR 45 TC 0 Z9 0 U1 0 U2 0 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DR, STE 208, TOTOWA, NJ 07512-1165 USA BN 978-1-4939-2605-3; 978-1-4939-2604-6 J9 CURR CLIN PSYCHIAT PY 2016 BP 197 EP 210 DI 10.1007/978-1-4939-2605-3_15 D2 10.1007/978-1-4939-2605-3 PG 14 WC Primary Health Care; Psychiatry SC General & Internal Medicine; Psychiatry GA BE1RR UT WOS:000368436700016 ER PT B AU Goetter, EM Marques, L AF Goetter, Elizabeth M. Marques, Luana BE Petersen, TJ Sprich, SE Wilhelm, S TI Cognitive Behavioral Therapy for Posttraumatic Stress Disorder SO MASSACHUSETTS GENERAL HOSPITAL HANDBOOK OF COGNITIVE BEHAVIORAL THERAPY SE Current Clinical Psychiatry LA English DT Article; Book Chapter ID EYE-MOVEMENT DESENSITIZATION; QUALITY-OF-LIFE; NATIONAL COMORBIDITY SURVEY; PROLONGED EXPOSURE THERAPY; PLACEBO-CONTROLLED TRIAL; SEXUAL ASSAULT VICTIMS; PROCESSING THERAPY; ANXIETY DISORDERS; RAPE VICTIMS; DOUBLE-BLIND C1 [Goetter, Elizabeth M.; Marques, Luana] Massachusetts Gen Hosp, Dept Psychiat, One Bowdoin Sq,6th Floor, Boston, MA 02114 USA. RP Goetter, EM (reprint author), Massachusetts Gen Hosp, Dept Psychiat, One Bowdoin Sq,6th Floor, Boston, MA 02114 USA. EM egoetter@mgh.harvard.edu; lmarques@mgh.harvard.edu NR 75 TC 0 Z9 0 U1 0 U2 0 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DR, STE 208, TOTOWA, NJ 07512-1165 USA BN 978-1-4939-2605-3; 978-1-4939-2604-6 J9 CURR CLIN PSYCHIAT PY 2016 BP 211 EP 225 DI 10.1007/978-1-4939-2605-3_16 D2 10.1007/978-1-4939-2605-3 PG 15 WC Primary Health Care; Psychiatry SC General & Internal Medicine; Psychiatry GA BE1RR UT WOS:000368436700017 ER PT B AU Harley, R Eisner, L Prairie, E Jacobo, M AF Harley, Rebecca Eisner, Lori Prairie, Ellen Jacobo, Michelle BE Petersen, TJ Sprich, SE Wilhelm, S TI Treatment of Borderline Personality Disorder SO MASSACHUSETTS GENERAL HOSPITAL HANDBOOK OF COGNITIVE BEHAVIORAL THERAPY SE Current Clinical Psychiatry LA English DT Article; Book Chapter ID DIALECTICAL BEHAVIOR-THERAPY; FOLLOW-UP; WOMEN; MINDFULNESS; SUICIDALITY; TRIAL C1 [Harley, Rebecca; Eisner, Lori; Prairie, Ellen; Jacobo, Michelle] Massachusetts Gen Hosp, Dept Psychiat, WACC 812,15 Parkman St, Boston, MA 02114 USA. RP Harley, R (reprint author), Massachusetts Gen Hosp, Dept Psychiat, WACC 812,15 Parkman St, Boston, MA 02114 USA. EM rharley@mgh.harvard.edu; leisner@mgh.harvard.edu; eprairie@partners.org NR 38 TC 0 Z9 0 U1 1 U2 3 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DR, STE 208, TOTOWA, NJ 07512-1165 USA BN 978-1-4939-2605-3; 978-1-4939-2604-6 J9 CURR CLIN PSYCHIAT PY 2016 BP 227 EP 242 DI 10.1007/978-1-4939-2605-3_17 D2 10.1007/978-1-4939-2605-3 PG 16 WC Primary Health Care; Psychiatry SC General & Internal Medicine; Psychiatry GA BE1RR UT WOS:000368436700018 ER PT B AU Vranceanu, AM Gordon, JR Gorman, MJ Safren, SA AF Vranceanu, Ana-Maria Gordon, Janna R. Gorman, Mark J. Safren, Steven A. BE Petersen, TJ Sprich, SE Wilhelm, S TI Behavioral Medicine Strategies in Outpatient Psychiatric Settings SO MASSACHUSETTS GENERAL HOSPITAL HANDBOOK OF COGNITIVE BEHAVIORAL THERAPY SE Current Clinical Psychiatry LA English DT Article; Book Chapter ID RANDOMIZED CONTROLLED-TRIAL; DEPRESSION CBT-AD; HIV MEDICATION ADHERENCE; TREATMENT NONADHERENCE; CARDIAC MORTALITY; ANXIETY DISORDERS; CHRONIC ILLNESS; RISK-FACTOR; INTERVENTIONS; METAANALYSIS C1 [Vranceanu, Ana-Maria; Gordon, Janna R.; Gorman, Mark J.; Safren, Steven A.] Massachusetts Gen Hosp, Dept Psychiat, Behav Med Serv, 1 Bowdoin Sq,7th Floor, Boston, MA 02114 USA. [Vranceanu, Ana-Maria; Gordon, Janna R.; Gorman, Mark J.; Safren, Steven A.] Harvard Univ, Sch Med, 1 Bowdoin Sq,7th Floor, Boston, MA USA. [Gordon, Janna R.] SDSU UC San Diego Joint Doctoral Program Clin Psy, San Diego, CA USA. RP Vranceanu, AM (reprint author), Massachusetts Gen Hosp, Dept Psychiat, Behav Med Serv, 1 Bowdoin Sq,7th Floor, Boston, MA 02114 USA.; Vranceanu, AM (reprint author), Harvard Univ, Sch Med, 1 Bowdoin Sq,7th Floor, Boston, MA USA. EM avranceanu@partners.org; janna.r.gordon@gmail.com; ssafren@partners.org NR 72 TC 0 Z9 0 U1 2 U2 2 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DR, STE 208, TOTOWA, NJ 07512-1165 USA BN 978-1-4939-2605-3; 978-1-4939-2604-6 J9 CURR CLIN PSYCHIAT PY 2016 BP 243 EP 257 DI 10.1007/978-1-4939-2605-3_18 D2 10.1007/978-1-4939-2605-3 PG 15 WC Primary Health Care; Psychiatry SC General & Internal Medicine; Psychiatry GA BE1RR UT WOS:000368436700019 ER PT B AU Henin, A Micco, JA Schoeller, M Boudreaux, A Hirshfeld-Becker, D AF Henin, Aude Micco, Jamie A. Schoeller, Melissa Boudreaux, Alexandra Hirshfeld-Becker, Dina BE Petersen, TJ Sprich, SE Wilhelm, S TI Cognitive Behavioral Therapy with Children and Adolescents SO MASSACHUSETTS GENERAL HOSPITAL HANDBOOK OF COGNITIVE BEHAVIORAL THERAPY SE Current Clinical Psychiatry LA English DT Article; Book Chapter ID RANDOMIZED CLINICAL-TRIAL; OBSESSIVE-COMPULSIVE DISORDER; TREATING ANXIETY DISORDERS; TERM-FOLLOW-UP; CHILDHOOD ANXIETY; ANXIOUS CHILDREN; DEPRESSIVE-DISORDERS; AGGRESSIVE BOYS; FRIENDS PROGRAM; INTERVENTION C1 [Henin, Aude; Micco, Jamie A.; Schoeller, Melissa; Boudreaux, Alexandra; Hirshfeld-Becker, Dina] Massachusetts Gen Hosp, Dept Psychiat, Child Cognit Behav Therapy Program, 151 Merrimac St,3rd Floor, Boston, MA 02114 USA. RP Henin, A (reprint author), Massachusetts Gen Hosp, Dept Psychiat, Child Cognit Behav Therapy Program, 151 Merrimac St,3rd Floor, Boston, MA 02114 USA. EM ahenin@mgh.harvard.edu; jmicco@mgh.harvard.edu; mschoeller@partners.org; aboudreaux@partners.org; dhirshfeld@partners.org NR 90 TC 0 Z9 0 U1 0 U2 1 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DR, STE 208, TOTOWA, NJ 07512-1165 USA BN 978-1-4939-2605-3; 978-1-4939-2604-6 J9 CURR CLIN PSYCHIAT PY 2016 BP 259 EP 275 DI 10.1007/978-1-4939-2605-3_19 D2 10.1007/978-1-4939-2605-3 PG 17 WC Primary Health Care; Psychiatry SC General & Internal Medicine; Psychiatry GA BE1RR UT WOS:000368436700020 ER PT B AU Charney, ME Calkins, AW Hallion, LS Simon, NM AF Charney, Meredith E. Calkins, Amanda W. Hallion, Lauren S. Simon, Naomi M. BE Petersen, TJ Sprich, SE Wilhelm, S TI Evaluating Strategies for Combining Pharmacotherapy with Cognitive Behavioral Therapy SO MASSACHUSETTS GENERAL HOSPITAL HANDBOOK OF COGNITIVE BEHAVIORAL THERAPY SE Current Clinical Psychiatry LA English DT Article; Book Chapter ID RANDOMIZED CONTROLLED-TRIAL; POSTTRAUMATIC-STRESS-DISORDER; SOCIAL ANXIETY DISORDER; PROLONGED EXPOSURE THERAPY; D-CYCLOSERINE ENHANCEMENT; BINGE-EATING DISORDER; RESIDUAL SYMPTOMS; PANIC DISORDER; PSYCHOSOCIAL INTERVENTIONS; PHARMACOLOGICAL-TREATMENTS C1 [Charney, Meredith E.; Simon, Naomi M.] Massachusetts Gen Hosp, Dept Psychiat, One Bowdoin Sq,6th Floor, Boston, MA 02114 USA. [Charney, Meredith E.; Simon, Naomi M.] Harvard Univ, Sch Med, Boston, MA 02114 USA. [Calkins, Amanda W.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Psychiat, One Bowdoin Sq,6th Floor, Boston, MA 02114 USA. [Hallion, Lauren S.] Harvard Univ, Sch Med, Anxiety Disorders Ctr, Ctr CBT,Inst Living, 200 Retreat Ave, Hartford, CT 06106 USA. RP Charney, ME (reprint author), Massachusetts Gen Hosp, Dept Psychiat, One Bowdoin Sq,6th Floor, Boston, MA 02114 USA.; Charney, ME (reprint author), Harvard Univ, Sch Med, Boston, MA 02114 USA. EM mecharney@partners.org; acalkins@mgh.harvard.edu; lauren.hallion@hhchealth.org; nsimon@partners.org NR 67 TC 0 Z9 0 U1 1 U2 1 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DR, STE 208, TOTOWA, NJ 07512-1165 USA BN 978-1-4939-2605-3; 978-1-4939-2604-6 J9 CURR CLIN PSYCHIAT PY 2016 BP 289 EP 299 DI 10.1007/978-1-4939-2605-3_21 D2 10.1007/978-1-4939-2605-3 PG 11 WC Primary Health Care; Psychiatry SC General & Internal Medicine; Psychiatry GA BE1RR UT WOS:000368436700022 ER PT B AU Matthews, JD Doorley, J AF Matthews, John D. Doorley, James BE Petersen, TJ Sprich, SE Wilhelm, S TI Cognitive Behavioral Therapies for Chronic Depression SO MASSACHUSETTS GENERAL HOSPITAL HANDBOOK OF COGNITIVE BEHAVIORAL THERAPY SE Current Clinical Psychiatry LA English DT Article; Book Chapter ID RANDOMIZED CONTROLLED-TRIAL; ANALYSIS SYSTEM; COMMITMENT THERAPY; PARTIAL REMISSION; PSYCHOTHERAPY; ACCEPTANCE; COMBINATION; NEFAZODONE; DISORDERS; ANXIETY C1 [Matthews, John D.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. [Doorley, James] George Mason Univ, Dept Psychol, 1 David King Hall,4400 Univ Dr,MSN 3F5, Fairfax, VA 22030 USA. RP Matthews, JD (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. EM jmatthews@partners.org; jdoorley@gmu.edu NR 71 TC 0 Z9 0 U1 0 U2 2 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DR, STE 208, TOTOWA, NJ 07512-1165 USA BN 978-1-4939-2605-3; 978-1-4939-2604-6 J9 CURR CLIN PSYCHIAT PY 2016 BP 301 EP 317 DI 10.1007/978-1-4939-2605-3_22 D2 10.1007/978-1-4939-2605-3 PG 17 WC Primary Health Care; Psychiatry SC General & Internal Medicine; Psychiatry GA BE1RR UT WOS:000368436700023 ER PT J AU Zygmanski, P Sajo, E AF Zygmanski, Piotr Sajo, Erno TI A self-powered thin-film radiation detector using intrinsic high-energy current SO MEDICAL PHYSICS LA English DT Article DE radiation detection; electron current; high energy current; direct conversion; Auger; photocurrent; self-powered; thin-film ID GEOMETRY AB Purpose: The authors introduce a radiation detection method that relies on high-energy current (HEC) formed by secondary charged particles in the detector material, which induces conduction current in an external readout circuit. Direct energy conversion of the incident radiation powers the signal formation without the need for external bias voltage or amplification. The detector the authors consider is a thin-film multilayer device, composed of alternating disparate electrically conductive and insulating layers. The optimal design of HEC detectors consists of microscopic or nanoscopic structures. Methods: Theoretical and computational developments are presented to illustrate the salient properties of the HEC detector and to demonstrate its feasibility. In this work, the authors examine single-sandwiched and periodic layers of Cu and Al, and Au and Al, ranging in thickness from 100 nm to 300 mu m and separated by similarly sized dielectric gaps, exposed to 120 kVp x-ray beam (half-value thickness of 4.1 mm of Al). The energy deposition characteristics and the high-energy current were determined using radiation transport computations. Results: The authors found that in a dual-layer configuration, the signal is in the measurable range. For a defined total detector thickness in a multilayer structure, the signal sharply increases with decreasing thickness of the high-Z conductive layers. This paper focuses on the computational results while a companion paper reports the experimental findings. Conclusions: Significant advantages of the device are that it does not require external power supply and amplification to create a measurable signal; it can be made in any size and geometry, including very thin (sub-millimeter to submicron) flexible curvilinear forms, and it is inexpensive. Potential applications include medical dosimetry (both in vivo and external), radiation protection, and other settings where one or more of the above qualities are desired. (C) 2016 American Association of Physicists in Medicine. C1 [Zygmanski, Piotr] Brigham & Womens Hosp, Dana Farber Canc Inst, Dept Radiat Oncol, 75 Francis St, Boston, MA 02115 USA. [Zygmanski, Piotr] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Sajo, Erno] Univ Massachusetts, Dept Phys & Appl Phys, Med Phys Program, Lowell, MA 01854 USA. RP Zygmanski, P (reprint author), Brigham & Womens Hosp, Dana Farber Canc Inst, Dept Radiat Oncol, 75 Francis St, Boston, MA 02115 USA.; Zygmanski, P (reprint author), Harvard Univ, Sch Med, Boston, MA 02115 USA.; Sajo, E (reprint author), Univ Massachusetts, Dept Phys & Appl Phys, Med Phys Program, Lowell, MA 01854 USA. EM pzygmanski@LROC.HARVARD.EDU; Erno_Sajo@uml.edu FU Air Force Civil Engineer Center-East, Tyndall AFB, FL [FA8051-15P-0010] FX This work was supported in part by contract FA8051-15P-0010 from the Air Force Civil Engineer Center-East, Tyndall AFB, FL. The authors wish to express their gratitude to Andrew Karellas for many useful discussions. NR 24 TC 2 Z9 2 U1 1 U2 5 PU AMER ASSOC PHYSICISTS MEDICINE AMER INST PHYSICS PI MELVILLE PA STE 1 NO 1, 2 HUNTINGTON QUADRANGLE, MELVILLE, NY 11747-4502 USA SN 0094-2405 J9 MED PHYS JI Med. Phys. PD JAN PY 2016 VL 43 IS 1 BP 4 EP 15 DI 10.1118/1.4935531 PG 12 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA DE7XO UT WOS:000370850600001 PM 26745894 ER PT J AU Zygmanski, P Shrestha, S Briovio, D Karellas, A Sajo, E AF Zygmanski, Piotr Shrestha, Suman Briovio, Davide Karellas, Andrew Sajo, Erno TI Prototypes of self-powered radiation detectors employing intrinsic high-energy current SO MEDICAL PHYSICS LA English DT Article DE radiation detection; electron current; Auger; photocurrent; self-powered; thin-film AB Purpose: The authors experimentally investigate the effect of direct energy conversion of x-rays via selfpowered Auger- and photocurrent, potentially suitable to practical radiation detection and dosimetry in medical applications. Experimental results are compared to computational predictions. The detector the authors consider is a thin-film multilayer device, composed of alternating disparate electrically conductive and insulating layers. This paper focuses on the experiments while a companion paper introduces the fundamental concepts of high-energy current (HEC) detectors. Methods: The energy of ionizing radiation is directly converted to detector signal via electric current induced by high-energy secondary electrons generated in the detector material by the incident primary radiation. The HEC electrons also ionize the dielectric and the resultant charge carriers are selfcollected due to the contact potential of the disparate electrodes. Thus, an electric current is induced in the conductors in two different ways without the need for externally applied bias voltage or amplification. Thus, generated signal in turn is digitized by a data acquisition system. To determine the fundamental properties of the HEC detector and to demonstrate its feasibility for medical applications, the authors used a planar geometry composed of multilayer microstructures. Various detectors with up to seven conducting layers with different combinations of materials (250 mu m Al, 35 mu m Cu, 100 mu m Pb) and air gaps (100 mu m) were exposed to nearly plane-parallel 60-120 kVp x-ray beams. For the experimental design and verification, the authors performed coupled electron-photon radiation transport computations. The detector signal was measured using a commercial data acquisition system with 24 bits dynamic range, 0.4 fC sensitivity, and 0.9 ms sampling time. Results: Measured signals for the prototype detector varied depending on the number of layers, material type, and incident photon energy, and it was in the range of 30-150 nA/cm(2) for unit air kerma (1 Gy), which is viable for practical applications. The experiments had an excellent agreement with the computations. Within the examined range of 60-120 kVp, the energy dependence of the HEC (normalized to the x-ray tube output) was relatively small. Conclusions: Based on the experimental results for 100 ms sampling time, it would be possible to measure the time dependence of x-ray beams for x-ray tube current of 0.1 mA or higher. Significant advantages of the HEC device are that generation of its signal does not require external power supply, it can be made in any size and shape, including flexible curvilinear forms, and it is inexpensive. It remains to be determined, which of the potential applications in medical dosimetry (both in vivo and external), or radiation protection would benefit from such selfpowered detectors. (C) 2016 American Association of Physicists in Medicine. C1 [Zygmanski, Piotr; Briovio, Davide] Brigham & Womens Hosp, Dana Farber Canc Inst, Dept Radiat Oncol, 75 Francis St, Boston, MA 02115 USA. [Zygmanski, Piotr; Briovio, Davide] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Shrestha, Suman; Karellas, Andrew] Univ Massachusetts, Sch Med, Dept Radiol, Worcester, MA 01655 USA. [Sajo, Erno] Univ Massachusetts, Dept Phys & Appl Phys, Med Phys Program, Lowell, MA 01854 USA. RP Zygmanski, P (reprint author), Brigham & Womens Hosp, Dana Farber Canc Inst, Dept Radiat Oncol, 75 Francis St, Boston, MA 02115 USA.; Zygmanski, P (reprint author), Harvard Univ, Sch Med, Boston, MA 02115 USA. EM pzygmanski@LROC.HARVARD.EDU RI Brivio, Davide/R-1330-2016 OI Brivio, Davide/0000-0002-4127-9955 FU Air Force Civil Engineer Center-East, Tyndall AFB, FL [FA8051-15-P-0010] FX This work was supported in part by contract FA8051-15-P-0010 from the Air Force Civil Engineer Center-East, Tyndall AFB, FL. NR 18 TC 2 Z9 2 U1 0 U2 0 PU AMER ASSOC PHYSICISTS MEDICINE AMER INST PHYSICS PI MELVILLE PA STE 1 NO 1, 2 HUNTINGTON QUADRANGLE, MELVILLE, NY 11747-4502 USA SN 0094-2405 J9 MED PHYS JI Med. Phys. PD JAN PY 2016 VL 43 IS 1 BP 16 EP 22 DI 10.1118/1.4935532 PG 7 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA DE7XO UT WOS:000370850600002 PM 26745895 ER PT J AU Berbeco, RI Detappe, A Tsiamas, P Parsons, D Yewondwossen, M Robar, J AF Berbeco, Ross I. Detappe, Alexandre Tsiamas, Panogiotis Parsons, David Yewondwossen, Mammo Robar, James TI Low Z target switching to increase tumor endothelial cell dose enhancement during gold nanoparticle-aided radiation therapy SO MEDICAL PHYSICS LA English DT Article DE radiation therapy; nanoparticle; dose enhancement; vascular disruption ID CANCER STEM-CELLS; MEGAVOLTAGE PHOTON BEAMS; 5,6-DIMETHYLXANTHENONE-4-ACETIC ACID; MONTE-CARLO; RADIOTHERAPY; CONTRAST; VASCULATURE; DISRUPTION; GENERATION; AGENTS AB Purpose: Previous studies have introduced gold nanoparticles as vascular-disrupting agents during radiation therapy. Crucial to this concept is the low energy photon content of the therapy radiation beam. The authors introduce a new mode of delivery including a linear accelerator target that can toggle between low Z and high Z targets during beam delivery. In this study, the authors examine the potential increase in tumor blood vessel endothelial cell radiation dose enhancement with the low Z target. Methods: The authors use Monte Carlo methods to simulate delivery of three different clinical photon beams: (1) a 6 MV standard (Cu/W) beam, (2) a 6 MV flattening filter free (Cu/W), and (3) a 6 MV (carbon) beam. The photon energy spectra for each scenario are generated for depths in tissue-equivalent material: 2, 10, and 20 cm. The endothelial dose enhancement for each target and depth is calculated using a previously published analytic method. Results: It is found that the carbon target increases the proportion of low energy (<150 keV) photons at 10 cm depth to 28% from 8% for the 6 MV standard (Cu/W) beam. This nearly quadrupling of the low energy photon content incident on a gold nanoparticle results in 7.7 times the endothelial dose enhancement as a 6 MV standard (Cu/W) beam at this depth. Increased surface dose from the low Z target can be mitigated by well-spaced beam arrangements. Conclusions: By using the fast-switching target, one can modulate the photon beam during delivery, producing a customized photon energy spectrum for each specific situation. (C) 2016 American Association of Physicists in Medicine. C1 [Berbeco, Ross I.; Detappe, Alexandre] Brigham & Womens Hosp, Dana Farber Canc Inst, Dept Radiat Oncol, 75 Francis St, Boston, MA 02115 USA. [Berbeco, Ross I.; Detappe, Alexandre] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Tsiamas, Panogiotis] St Jude Childrens Res Hosp, Dept Radiat Oncol, 332 N Lauderdale, Memphis, TN 38105 USA. [Parsons, David; Yewondwossen, Mammo; Robar, James] Dalhousie Univ, Dept Radiat Oncol, Halifax, NS B3H 1V7, Canada. [Parsons, David; Yewondwossen, Mammo; Robar, James] Dalhousie Univ, Dept Phys & Atmospher Sci, Halifax, NS B3H 1V7, Canada. RP Berbeco, RI (reprint author), Brigham & Womens Hosp, Dana Farber Canc Inst, Dept Radiat Oncol, 75 Francis St, Boston, MA 02115 USA.; Berbeco, RI (reprint author), Harvard Univ, Sch Med, Boston, MA 02115 USA. EM rberbeco@partners.org OI Detappe, Alexandre/0000-0001-9364-1621 FU Varian Medical Systems, Inc.; National Cancer Institute of the National Institutes of Health [R03CA164645, R21CA188833] FX This project was supported, in part, by a grant from Varian Medical Systems, Inc. (J.R.) and the National Cancer Institute of the National Institutes of Health under Award Nos. R03CA164645 and R21CA188833 (R.I.B.). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Cancer Institute or the National Institutes of Health. NR 44 TC 3 Z9 3 U1 2 U2 9 PU AMER ASSOC PHYSICISTS MEDICINE AMER INST PHYSICS PI MELVILLE PA STE 1 NO 1, 2 HUNTINGTON QUADRANGLE, MELVILLE, NY 11747-4502 USA SN 0094-2405 EI 2473-4209 J9 MED PHYS JI Med. Phys. PD JAN PY 2016 VL 43 IS 1 BP 436 EP 442 DI 10.1118/1.4938410 PG 7 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA DE7XO UT WOS:000370850600031 PM 26745936 ER PT J AU Hosseini, MP Nazem-Zadeh, MR Pompili, D Jafari-Khouzani, K Elisevich, K Soltanian-Zadeh, H AF Hosseini, Mohammad-Parsa Nazem-Zadeh, Mohammad-Reza Pompili, Dario Jafari-Khouzani, Kourosh Elisevich, Kost Soltanian-Zadeh, Hamid TI Comparative performance evaluation of automated segmentation methods of hippocampus from magnetic resonance images of temporal lobe epilepsy patients SO MEDICAL PHYSICS LA English DT Article DE medical imaging; image processing; segmentation; hippocampus; temporal lobe epilepsy; magnetic resonance imaging (MRI) ID MULTI-ATLAS SEGMENTATION; BRAIN MRI; COGNITIVE IMPAIRMENT; ALZHEIMERS-DISEASE; GRAPH-CUTS; REGISTRATION; MODELS; ALGORITHM; PROTOCOLS; TEMPLATE AB Purpose: Segmentation of the hippocampus from magnetic resonance (MR) images is a key task in the evaluation of mesial temporal lobe epilepsy (mTLE) patients. Several automated algorithms have been proposed although manual segmentation remains the benchmark. Choosing a reliable algorithm is problematic since structural definition pertaining to multiple edges, missing and fuzzy boundaries, and shape changes varies among mTLE subjects. Lack of statistical references and guidance for quantifying the reliability and reproducibility of automated techniques has further detracted from automated approaches. The purpose of this study was to develop a systematic and statistical approach using a large dataset for the evaluation of automated methods and establish a method that would achieve results better approximating those attained by manual tracing in the epileptogenic hippocampus. Methods: A template database of 195 (81 males, 114 females; age range 32-67 yr, mean 49.16 yr) MR images of mTLE patients was used in this study. Hippocampal segmentation was accomplished manually and by two well-known tools (FreeSurfer and HAMMER) and two previously published methods developed at their institution [ Automatic brain structure segmentation (ABSS) and LocalInfo]. To establish which method was better performing for mTLE cases, several voxel-based, distance-based, and volume-based performance metrics were considered. Statistical validations of the results using automated techniques were compared with the results of benchmark manual segmentation. Extracted metrics were analyzed to find the method that provided a more similar result relative to the benchmark. Results: Among the four automated methods, ABSS generated the most accurate results. For this method, the Dice coefficient was 5.13%, 14.10%, and 16.67% higher, Hausdorff was 22.65%, 86.73%, and 69.58% lower, precision was 4.94%, -4.94%, and 12.35% higher, and the root mean square (RMS) was 19.05%, 61.90%, and 65.08% lower than LocalInfo, FreeSurfer, and HAMMER, respectively. The Bland-Altman similarity analysis revealed a low bias for the ABSS and LocalInfo techniques compared to the others. Conclusions: The ABSS method for automated hippocampal segmentation outperformed other methods, best approximating what could be achieved by manual tracing. This study also shows that four categories of input data can cause automated segmentation methods to fail. They include incomplete studies, artifact, low signal-to-noise ratio, and inhomogeneity. Different scanner platforms and pulse sequences were considered as means by which to improve reliability of the automated methods. Other modifications were specially devised to enhance a particular method assessed in this study. (C) 2016 American Association of Physicists in Medicine. C1 [Hosseini, Mohammad-Parsa; Pompili, Dario] Rutgers State Univ, Dept Elect & Comp Engn, New Brunswick, NJ 08854 USA. [Hosseini, Mohammad-Parsa; Nazem-Zadeh, Mohammad-Reza; Soltanian-Zadeh, Hamid] Henry Ford Hlth Syst, Med Image Anal Lab, Dept Radiol, Detroit, MI 48202 USA. [Hosseini, Mohammad-Parsa; Nazem-Zadeh, Mohammad-Reza; Soltanian-Zadeh, Hamid] Henry Ford Hlth Syst, Med Image Anal Lab, Dept Res Adm, Detroit, MI 48202 USA. [Jafari-Khouzani, Kourosh] Harvard Univ, Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Dept Radiol,Med Sch, Boston, MA 02129 USA. [Elisevich, Kost] Spectrum Hlth Syst, Dept Clin Neurosci, Grand Rapids, MI 49503 USA. [Elisevich, Kost] Michigan State Univ, Coll Human Med, Div Neurosurg, Grand Rapids, MI 49503 USA. [Soltanian-Zadeh, Hamid] Univ Tehran, CIPCE, Sch Elect & Comp Engn, Tehran 1439957131, Iran. [Soltanian-Zadeh, Hamid] Inst Studies Theoret Phys & Math IPM, Sch Cognit Sci, Tehran 1954856316, Iran. RP Soltanian-Zadeh, H (reprint author), Henry Ford Hlth Syst, Med Image Anal Lab, Dept Radiol, Detroit, MI 48202 USA.; Soltanian-Zadeh, H (reprint author), Henry Ford Hlth Syst, Med Image Anal Lab, Dept Res Adm, Detroit, MI 48202 USA.; Soltanian-Zadeh, H (reprint author), Univ Tehran, CIPCE, Sch Elect & Comp Engn, Tehran 1439957131, Iran.; Soltanian-Zadeh, H (reprint author), Inst Studies Theoret Phys & Math IPM, Sch Cognit Sci, Tehran 1954856316, Iran. EM hamids@rad.hfh.edu RI Soltanian-Zadeh, Hamid/K-2903-2016; OI Soltanian-Zadeh, Hamid/0000-0002-7302-6856; Hosseini, Mohammad-Parsa/0000-0002-0611-7520 FU NIH [R01-EB013227] FX This work was supported in part by NIH Grant No. R01-EB013227. NR 63 TC 1 Z9 1 U1 2 U2 9 PU AMER ASSOC PHYSICISTS MEDICINE AMER INST PHYSICS PI MELVILLE PA STE 1 NO 1, 2 HUNTINGTON QUADRANGLE, MELVILLE, NY 11747-4502 USA SN 0094-2405 J9 MED PHYS JI Med. Phys. PD JAN PY 2016 VL 43 IS 1 BP 538 EP 553 DI 10.1118/1.4938411 PG 16 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA DE7XO UT WOS:000370850600032 PM 26745947 ER PT J AU Gonzalez-Heydrich, J Enlow, MB D'Angelo, E Seidman, LJ Gumlak, S Kim, A Woodberry, KA Rober, A Tembulkar, S O'Donnell, K Hamoda, HM Kimball, K Rotenberg, A Oberman, LM Pascual-Leone, A Keshavan, MS Duffy, FH AF Gonzalez-Heydrich, Joseph Enlow, Michelle Bosquet D'Angelo, Eugene Seidman, Larry J. Gumlak, Sarah Kim, April Woodberry, Kristen A. Rober, Ashley Tembulkar, Sahil O'Donnell, Kyle Hamoda, Hesham M. Kimball, Kara Rotenberg, Alexander Oberman, Lindsay M. Pascual-Leone, Alvaro Keshavan, Matcheri S. Duffy, Frank H. TI N100 Repetition Suppression Indexes Neuroplastic Defects in Clinical High Risk and Psychotic Youth SO NEURAL PLASTICITY LA English DT Article ID MISMATCH NEGATIVITY; SYNAPTIC PLASTICITY; ONSET SCHIZOPHRENIA; DEFICITS; AGE; ENDOPHENOTYPE; PERSPECTIVES; 1ST-EPISODE; INDIVIDUALS; TRANSITION AB Highly penetrant mutations leading to schizophrenia are enriched for genes coding for N-methyl-D-aspartate receptor signaling complex (NMDAR-SC), implicating plasticity defects in the disease's pathogenesis. The importance of plasticity in neurodevelopment implies a role for therapies that target these mechanisms in early life to prevent schizophrenia. Testing such therapies requires noninvasive methods that can assess engagement of target mechanisms. The auditory N100 is an obligatory cortical response whose amplitude decreases with tone repetition. This adaptation may index the health of plasticity mechanisms required for normal development. We exposed participants aged 5 to 17 years with psychosis (n = 22), at clinical high risk (CHR) for psychosis (n = 29), and healthy controls (n = 17) to an auditory tone repeated 450 times and measured N100 adaptation (mean amplitude during first 150 tones - mean amplitude during last 150 tones). N100 adaptation was reduced in CHR and psychosis, particularly among participants <13 years old. Initial N100 blunting partially accounted for differences. Decreased change in the N100 amplitude with tone repetition may be a useful marker of defects in neuroplastic mechanisms measurable early in life. C1 [Gonzalez-Heydrich, Joseph; Enlow, Michelle Bosquet; D'Angelo, Eugene; Gumlak, Sarah; Kim, April; Rober, Ashley; Tembulkar, Sahil; O'Donnell, Kyle; Hamoda, Hesham M.; Kimball, Kara; Rotenberg, Alexander; Duffy, Frank H.] Boston Childrens Hosp, 300 Longwood Ave, Boston, MA 02115 USA. [Gonzalez-Heydrich, Joseph; Enlow, Michelle Bosquet; D'Angelo, Eugene; Seidman, Larry J.; Woodberry, Kristen A.; Hamoda, Hesham M.; Keshavan, Matcheri S.] Harvard Univ, Sch Med, Dept Psychiat, 401 Pk Dr, Boston, MA 02215 USA. [Seidman, Larry J.; Woodberry, Kristen A.; Pascual-Leone, Alvaro; Keshavan, Matcheri S.] Beth Israel Deaconess Med Ctr, Dept Psychiat, Commonwealth Res Ctr, 75 Fenwood Rd, Boston, MA 02115 USA. [Seidman, Larry J.] Massachusetts Gen Hosp, Dept Psychiat, 55 Fruit St, Boston, MA 02114 USA. [Rotenberg, Alexander; Pascual-Leone, Alvaro; Duffy, Frank H.] Harvard Univ, Sch Med, Dept Neurol, 25 Shattuck St, Boston, MA 02115 USA. [Oberman, Lindsay M.] Brown Univ, Neuroplast & Autism Spectrum Disorder Program, 1011 Vet Mem Pkwy, East Providence, RI 02915 USA. [Oberman, Lindsay M.] Brown Univ, Dept Psychiat & Human Behav, EP Bradley Hosp, 1011 Vet Mem Pkwy, East Providence, RI 02915 USA. [Oberman, Lindsay M.] Brown Univ, Warren Alpert Med Sch, 1011 Vet Mem Pkwy, East Providence, RI 02915 USA. RP Gonzalez-Heydrich, J (reprint author), Boston Childrens Hosp, 300 Longwood Ave, Boston, MA 02115 USA.; Gonzalez-Heydrich, J (reprint author), Harvard Univ, Sch Med, Dept Psychiat, 401 Pk Dr, Boston, MA 02215 USA. EM joseph.gonzalez-heydrich@childrens.harvard.edu FU Tommy Fuss Fund; National Institute of Mental Health [1R01MH100186]; Simons Foundation; Nancy Lurie Marks Family Foundation; Boston Children's Hospital; Program for Behavioral Science in the Department of Psychiatry at Boston Children's Hospital; NAPLS-2 grant [U01 MH08198-06A1] FX This work was supported by the Tommy Fuss Fund (Joseph Gonzalez-Heydrich, Michelle Bosquet Enlow, Eugene D'Angelo, Sarah Gumlak, April Kim, Ashley Rober, Sahil Tembulkar, Kyle O'Donnell, Kara Kimball, and Frank H. Duffy). During preparation of this paper, the authors were supported by the National Institute of Mental Health (1R01MH100186, Lindsay Oberman), the Simons Foundation (Lindsay Oberman), the Nancy Lurie Marks Family Foundation (Lindsay Oberman), a Faculty Development Fellowship from Boston Children's Hospital (Hesham M. Hamoda), and the Program for Behavioral Science in the Department of Psychiatry at Boston Children's Hospital (Michelle Bosquet Enlow). Some participants were referred by the NAPLS-2 grant (U01 MH08198-06A1, Larry J. Seidman). The authors thank the patients and families whose generous donation of time made this project possible. NR 60 TC 0 Z9 0 U1 2 U2 5 PU HINDAWI LTD PI LONDON PA ADAM HOUSE, 3RD FLR, 1 FITZROY SQ, LONDON, WIT 5HE, ENGLAND SN 2090-5904 EI 1687-5443 J9 NEURAL PLAST JI Neural. Plast. PY 2016 AR 4209831 DI 10.1155/2016/4209831 PG 11 WC Neurosciences SC Neurosciences & Neurology GA DF0VI UT WOS:000371056900001 ER PT J AU Ivkovic, V Fisher, S Paloski, WH AF Ivkovic, Vladimir Fisher, Stanley Paloski, William H. TI Smartphone-based tactile cueing improves motor performance in Parkinson's disease SO PARKINSONISM & RELATED DISORDERS LA English DT Article DE Smartphone; Tactile; Cueing; Movement; Parkinson's ID EXTERNAL RHYTHMICAL CUES; BASAL GANGLIA; AUDITORY CUES; GAIT; WALKING; TASK; INDIVIDUALS; VARIABILITY; PARAMETERS; PEOPLE AB Introduction: Visual and auditory cueing improve functional performance in Parkinson's disease (PD) patients. However, audiovisual processing shares many cognitive resources used for attention-dependent tasks such as communication, spatial orientation, and balance. Conversely, tactile cues (TC) may be processed faster, with minimal attentional demand, and may be more efficient means for modulating motor-cognitive performance. In this study we aimed to investigate the efficacy and limitations of TC for modulating simple (heel tapping) and more complex (walking) motor tasks (1) over a range of cueing intervals, (2) with/without a secondary motor task (holding tray with cups of water). Methods: Ten PD patients (71 9 years) and 10 healthy controls (69 7 years) participated in the study. TCs was delivered through a smart phone attached to subjects' dominant arm and were controlled by a custom-developed Android application. Results: PD patients and healthy controls were able to use TC to modulate heel tapping (F(3.8,1866.1) = 1008.1, p < 0.001), and partially modulate walking (F(3.5,1448.7) = 187.5, p < 0.001) tasks. In the walking task, PD patients modulated performance over a narrower range of cueing intervals (R-2 = 0.56) than healthy controls (R-2 = 0.84; group difference F(3.5,1448.7) = 8.6, p < 0.001). TC diminished synchronization error associated with performance of secondary motor task during walking in PD patients and healthy controls (main effect of Task (F(1,494) = 0.4; p = 0.527), Task X Group interaction (F(1,494) = 0.5; p = 0.493)). Conclusion: This study expands modalities of TC usage for movement modulation and motor-cognitive integration in PD patients. The smartphone TC application was validated as a user-friendly movement modulation aid. (C) 2015 Elsevier Ltd. All rights reserved. C1 [Ivkovic, Vladimir; Fisher, Stanley; Paloski, William H.] Univ Houston, Ctr Neuromotor & Biomech Res, Natl Ctr Human Performance, 2450 Holcombe Blvd, Houston, TX 77021 USA. [Fisher, Stanley] Methodist Neurol Inst, Movement Disorders & Neurorehabilitat Ctr, 6560 Fannin St,Suite 802, Houston, TX 77030 USA. [Ivkovic, Vladimir] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Psychiat,Neural Syst Grp, 149 13th St,Rm 2651, Charlestown, MA 02129 USA. [Fisher, Stanley] St Lukes Marion Bloch Neurosci Inst, 4401 Wornall Rd,Suite 1708, Kansas City, MO 64111 USA. RP Ivkovic, V (reprint author), Univ Houston, Ctr Neuromotor & Biomech Res, Natl Ctr Human Performance, 2450 Holcombe Blvd, Houston, TX 77021 USA.; Ivkovic, V (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Psychiat,Neural Syst Grp, 149 13th St,Rm 2651, Charlestown, MA 02129 USA. EM vivkovic@nmr.mgh.harvard.edu; stafisher@saint-lukes.org; whpalosk@central.uh.edu OI Ivkovic, Vladimir/0000-0002-0698-9396 FU University of Houston, Center for Neuromotor and Biomechanics Research Scholarship FX This study was performed with the financial support from the University of Houston, Center for Neuromotor and Biomechanics Research Scholarship. NR 30 TC 0 Z9 0 U1 1 U2 9 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 1353-8020 EI 1873-5126 J9 PARKINSONISM RELAT D JI Parkinsonism Relat. Disord. PD JAN PY 2016 VL 22 BP 42 EP 47 DI 10.1016/j.parkreldis.2015.11.006 PG 6 WC Clinical Neurology SC Neurosciences & Neurology GA DE8JU UT WOS:000370883100007 PM 26589004 ER PT J AU Lo, RY Figueroa, KP Pulst, SM Perlman, S Wilmot, G Gomez, C Schmahmann, J Paulson, H Shakkottai, VG Ying, S Zesiewicz, T Bushara, K Geschwind, M Xia, GB Yu, JT Lee, LE Ashizawa, T Subramony, SH Kuo, SH AF Lo, Raymond Y. Figueroa, Karla P. Pulst, Stefan M. Perlman, Susan Wilmot, George Gomez, Christopher Schmahmann, Jeremy Paulson, Henry Shakkottai, Vikram G. Ying, Sarah Zesiewicz, Theresa Bushara, Khalaf Geschwind, Michael Xia, Guangbin Yu, Jui-Tsen Lee, Lue-En Ashizawa, Tetsuo Subramony, S. H. Kuo, Sheng-Han TI Depression and clinical progression in spinocerebellar ataxias SO PARKINSONISM & RELATED DISORDERS LA English DT Article DE Depression; Cerebellum; Spinocerebellar ataxias; Suicide; Neurodegeneration ID MACHADO-JOSEPH-DISEASE; COGNITIVE-AFFECTIVE SYNDROME; PARKINSONS-DISEASE; SYMPTOMS; IMPAIRMENTS; VALIDITY; FEATURES; TYPE-1; PHQ-9; MOTOR AB Background: Depression is a common comorbidity in spinocerebellar ataxias (SCAs) but its association with ataxia progression is not well understood. Objectives: To study the prevalence and influence of depressive symptoms in SCAs. Methods: We studied 300 participants with SCA 1, 2, 3 and 6 from the Clinical Research Consortium for Spinocerebellar Ataxias (CRC-SCA) and repeatedly measured depressive symptoms by the 9-item Patient Health Questionnaire (PHQ-9) along with other clinical features including ataxia, functional status, and quality of life every 6 months for 2 years. We employed regression models to study the effects of depressive symptoms on clinical progression indexed by Scale for Assessment and Rating of Ataxia (SARA), Unified Huntington's Disease Rating Scale Part IV (UHDRS-IV) and EQ5D after adjusting for age, sex and pathological CAG repeats. Results: Comorbid depression is common in SCAs (26%). Although the baseline prevalence of depression was similar among different SCA types, suicidal ideation was more frequently reported in SCA3 (65%). Depressive symptoms were associated with SARA scores but did not significantly progress over time within 2 years or deteriorate by increased numbers of pathological CAG repeats. The effects of depression on ataxia progression varied across different SCA types. Nevertheless, depression had consistently negative and significant impact on functional status and quality of life in all SCAs, even after accounting for ataxia progression. Conclusions: Depressive symptoms are not simply the consequence of motor disability in SCAs. Comorbid depression per se contributes to different health outcomes and deserves more attention when caring patients with SCAs. (C) 2015 Elsevier Ltd. All rights reserved. C1 [Lo, Raymond Y.] Buddhist Tzu Chi Gen Hosp, Dept Neurol, Hualien, Taiwan. [Lo, Raymond Y.] Tzu Chi Univ, Hualien, Taiwan. [Figueroa, Karla P.; Pulst, Stefan M.] Univ Utah, Dept Neurol, Salt Lake City, UT USA. [Perlman, Susan] Univ Calif Los Angeles, Dept Neurol, Los Angeles, CA USA. [Wilmot, George] Emory Univ, Dept Neurol, Atlanta, GA 30322 USA. [Gomez, Christopher] Univ Chicago, Dept Neurol, Chicago, IL 60637 USA. [Schmahmann, Jeremy] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02115 USA. [Paulson, Henry; Shakkottai, Vikram G.] Univ Michigan, Dept Neurol, Ann Arbor, MI 48109 USA. [Ying, Sarah] Johns Hopkins Univ, Dept Neurol, Baltimore, MD 21218 USA. [Zesiewicz, Theresa] Univ S Florida, Dept Neurol, Tampa, FL 33620 USA. [Bushara, Khalaf] Univ Minnesota, Dept Neurol, Minneapolis, MN 55455 USA. [Geschwind, Michael] Univ Calif San Francisco, Dept Neurol, San Francisco, CA 94143 USA. [Xia, Guangbin; Ashizawa, Tetsuo; Subramony, S. H.] Univ Florida, Dept Neurol, Gainesville, FL USA. [Xia, Guangbin; Ashizawa, Tetsuo; Subramony, S. H.] Univ Florida, McKnight Brain Inst, Gainesville, FL USA. [Yu, Jui-Tsen; Lee, Lue-En; Kuo, Sheng-Han] Columbia Univ, Coll Phys & Surg, Dept Neurol, New York, NY USA. RP Kuo, SH (reprint author), 650 West 168th St,Room 305, New York, NY 10032 USA. EM sk3295@columbia.edu FU NINDS [K08 NS083738]; Louis V. Gerstner Jr. Scholarship; American Brain Research Training Fellowship; Parkinson Disease Foundation; American Parkinson's Disease Association; Rare Disease Clinical Research Network (RDCRN) [RC1NS068897]; International Essential Tremor Foundation; NIEHS pilot grant [ES009089]; Smart Foundation; [R37NSNS033123] FX NINDS K08 NS083738, Louis V. Gerstner Jr. Scholarship, American Brain Research Training Fellowship, Parkinson Disease Foundation, American Parkinson's Disease Association, Rare Disease Clinical Research Network (RDCRN) (RC1NS068897), International Essential Tremor Foundation, and NIEHS pilot grant ES009089, the Smart Foundation, and R37NSNS033123. NR 35 TC 2 Z9 2 U1 0 U2 5 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 1353-8020 EI 1873-5126 J9 PARKINSONISM RELAT D JI Parkinsonism Relat. Disord. PD JAN PY 2016 VL 22 BP 87 EP 92 DI 10.1016/j.parkreldis.2015.11.021 PG 6 WC Clinical Neurology SC Neurosciences & Neurology GA DE8JU UT WOS:000370883100014 PM 26644294 ER PT J AU Costa-Mallen, P Zabetian, CP Agarwal, P Hu, SC Yearout, D Samii, A Leverenz, JB Roberts, JW Checkoway, H AF Costa-Mallen, Paola Zabetian, Cyrus P. Agarwal, Pinky Hu, Shu-Ching Yearout, Dora Samii, Ali Leverenz, James B. Roberts, John W. Checkoway, Harvey TI Response to the letter "Haptoglobin phenotype and Parkinson disease risk" by Delanghe et al. SO PARKINSONISM & RELATED DISORDERS LA English DT Letter DE Haptoglobin polymorphism; Parkinson disease; Heterosis C1 [Costa-Mallen, Paola] Bastyr Univ, Res Inst, 14500 Juanita Dr NE, Kenmore, WA USA. [Zabetian, Cyrus P.; Yearout, Dora; Samii, Ali] Vet Affairs Puget Sound Hlth Care Syst, Seattle, WA USA. [Zabetian, Cyrus P.; Hu, Shu-Ching; Samii, Ali] Univ Washington, Sch Med, Dept Neurol, Seattle, WA USA. [Agarwal, Pinky] Evergreen Hlth, Booth Gardner Parkinsons Care Ctr, Kirkland, WA USA. [Leverenz, James B.] Cleveland Clin, Neurol Inst, Lou Ruvo Ctr Brain Hlth, Cleveland, OH 44106 USA. [Roberts, John W.] Virginia Mason Med Ctr, Seattle, WA 98101 USA. [Checkoway, Harvey] Univ Calif San Diego, Dept Family & Prevent Med, La Jolla, CA 92093 USA. RP Costa-Mallen, P (reprint author), Bastyr Univ, Res Inst, 14500 Juanita Dr NE, Kenmore, WA USA. EM pcostamallen@bastyr.edu FU BLRD VA [I01 BX000531]; NIEHS NIH HHS [R01 ES010750]; NINDS NIH HHS [R21 NS070202, P50 NS062684, R01 NS065070] NR 5 TC 1 Z9 1 U1 0 U2 2 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 1353-8020 EI 1873-5126 J9 PARKINSONISM RELAT D JI Parkinsonism Relat. Disord. PD JAN PY 2016 VL 22 BP 110 EP 111 DI 10.1016/j.parkreldis.2015.10.021 PG 2 WC Clinical Neurology SC Neurosciences & Neurology GA DE8JU UT WOS:000370883100020 PM 26708126 ER PT S AU Zawadzka, M Mikulchyk, T Cody, D Martin, S Yetisen, AK Martinez-Hurtado, JL Butt, H Mihaylova, E Awala, H Mintova, S Yun, SH Naydenova, I AF Zawadzka, Monika Mikulchyk, Tatsiana Cody, Dervil Martin, Suzanne Yetisen, Ali Kemal Martinez-Hurtado, Juan Leonardo Butt, Haider Mihaylova, Emilia Awala, Hussein Mintova, Svetlana Yun, Seok Hyun Naydenova, Izabela BE Serpe, MJ Kang, Y Zhang, QM TI Photonic Materials for Holographic Sensing SO PHOTONIC MATERIALS FOR SENSING, BIOSENSING AND DISPLAY DEVICES SE Springer Series in Materials Science LA English DT Article; Book Chapter ID ACRYLAMIDE-BASED PHOTOPOLYMER; GAS SENSORS; OPTICAL-PROPERTIES; LASER-ABLATION; RECORDING MATERIAL; SILVER NANOPARTICLES; AQUEOUS-SOLUTION; MECHANISM; TEMPERATURE; HUMIDITY AB Holography is a practical approach to fabricating optical sensors for applications in the detection of chemical analytes and physical changes. Holographic sensors incorporate diffraction gratings within functionalized polymers or natural organic polymer matrices, that allow indirect optical measurements of physical and chemical stimuli. The advantages of holographic sensors over other optical sensors are the ability to produce three-dimensional (3D) images and amenability to mass manufacturing at low-cost. The aim of this chapter is to (1) describe the principle of operation of holographic sensors (2) describe the holographic recording techniques used for their fabrication (3) discuss approaches to preparing recording media and overview strategies of their functionalization in order to obtain stimuli responsive devices, and (4) highlight emerging applications in environmental sensing and point-of-care diagnostics. Particular emphasis is put on the photonic materials used for holographic sensors recording and the different approaches used for their functionalization with the view of how this can be used to improve sensors sensitivity, selectivity and response time. The main challenges in holographic sensors research and possible solutions to these challenges are outlined. C1 [Zawadzka, Monika; Mikulchyk, Tatsiana; Cody, Dervil; Martin, Suzanne; Mihaylova, Emilia; Naydenova, Izabela] Dublin Inst Technol, Coll Sci & Hlth, Sch Phys, Ctr Ind & Engn Opt, Dublin 8, Ireland. [Yetisen, Ali Kemal; Yun, Seok Hyun] Harvard Univ, Sch Med, 50 Blossom St, Boston, MA 02114 USA. [Yetisen, Ali Kemal; Yun, Seok Hyun] Massachusetts Gen Hosp, Wellman Ctr Photomed, 50 Blossom St, Boston, MA 02114 USA. [Martinez-Hurtado, Juan Leonardo] Univ Cambridge, Dept Chem Engn & Biotechnol, Tennis Court Rd, Cambridge CB2 1QT, England. [Butt, Haider] Univ Birmingham, Sch Mech Engn, Birmingham B15 2TT, W Midlands, England. [Mihaylova, Emilia] Univ Agr, Dept Math Informat & Phys, 12 Mendeleev St, Plovdiv 4000, Bulgaria. [Awala, Hussein; Mintova, Svetlana] Univ Caen, LCS, 7CRISMAT, 6 Blvd Marechal Juin, F-14050 Caen, France. RP Naydenova, I (reprint author), Dublin Inst Technol, Coll Sci & Hlth, Sch Phys, Ctr Ind & Engn Opt, Dublin 8, Ireland.; Yetisen, AK (reprint author), Harvard Univ, Sch Med, 50 Blossom St, Boston, MA 02114 USA. EM ayetisen@mgh.harvard.edu; izabela.naydenova@dit.ie OI Butt, Haider/0000-0003-2434-9525 NR 135 TC 3 Z9 3 U1 1 U2 3 PU SPRINGER-VERLAG BERLIN PI BERLIN PA HEIDELBERGER PLATZ 3, D-14197 BERLIN, GERMANY SN 0933-033X BN 978-3-319-24990-2; 978-3-319-24988-9 J9 SPRINGER SER MATER S PY 2016 VL 229 BP 315 EP 359 DI 10.1007/978-3-319-24990-2_11 D2 10.1007/978-3-319-24990-2 PG 45 WC Optics; Physics, Applied SC Optics; Physics GA BE2DE UT WOS:000369069700012 ER PT B AU Warner, JJP Dilisio, MF Parada, SA AF Warner, Jon J. P. Dilisio, Matthew F. Parada, Stephen A. BE Ryu, RKN Angelo, RL Abrams, JS TI Arthroscopic Panlabral Repair SO SHOULDERS: AANA ADVANCED ARTHROSCOPIC SURGICAL TECHNIQUES LA English DT Article; Book Chapter ID ANTERIOR SHOULDER INSTABILITY; SUPERIOR LABRAL ANTERIOR; GLENOID LABRUM; CIRCUMFERENTIAL LESIONS; POSTERIOR LESIONS; AMERICAN BOARD; BANKART REPAIR; SLAP LESIONS; OUTCOMES; MANAGEMENT C1 [Warner, Jon J. P.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston Shoulder Inst, Boston, MA USA. [Dilisio, Matthew F.] Creighton Univ, Orthopaed CHI Hlth Shoulder Ctr, Orthopaed Surg, Omaha, NE 68178 USA. [Parada, Stephen A.] Eisenhower Army Med Ctr, Shoulder Surg, Ft Gordon, GA USA. [Parada, Stephen A.] Eisenhower Army Med Ctr, Ft Gordon, GA USA. [Parada, Stephen A.] Uniformed Serv Univ Hlth Sci, Bethesda, MD 20814 USA. RP Warner, JJP (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston Shoulder Inst, Boston, MA USA. NR 27 TC 0 Z9 0 U1 0 U2 0 PU SLACK INC PI THOROFARE PA 6900 GROVE ROAD, THOROFARE, NJ 08086-9447 USA BN 978-1-63091-002-0 PY 2016 BP 285 EP 295 PG 11 WC Surgery SC Surgery GA BE1BX UT WOS:000367697500024 ER PT J AU Hetzenecker, A Escourrou, P Kuna, ST Series, F Lewis, K Birner, C Pfeifer, M Arzt, M AF Hetzenecker, Andrea Escourrou, Pierre Kuna, Samuel T. Series, Frederic Lewis, Keir Birner, Christoph Pfeifer, Michael Arzt, Michael TI Treatment of sleep apnea in chronic heart failure patients with auto-servo ventilation improves sleep fragmentation: a randomized controlled trial SO SLEEP MEDICINE LA English DT Article DE Heart failure; Sleep disordered breathing; Auto-servo ventilation; Sleep quality; NT-pro BNP ID POSITIVE AIRWAY PRESSURE; CHEYNE-STOKES RESPIRATION; PROGNOSTIC IMPACT; ADAPTIVE SERVOVENTILATION; HYPOPNEA SYNDROME; WRIST ACTIGRAPHY; PREVALENCE; DIAGNOSIS; SYMPTOMS; EPIDEMIC AB Background: Impaired sleep efficiency is independently associated with worse prognosis in patients with chronic heart failure (CHF). Therefore, a test was conducted on whether auto-servo ventilation (ASV, biphasic positive airway pressure [BiPAP]-ASV, Philips Respironics) reduces sleep fragmentation and improves sleep efficiency in CHF patients with central sleep apnea (CSA) or obstructive sleep apnea (OSA). Methods: In this multicenter, randomized, parallel group trial, a study was conducted on 63 CHF patients (age 64 +/- 10 years; left ventricular ejection fraction 29 +/- 7%) with CSA or OSA (apnea-hypopnea Index, AHI 47 +/- 18/h; 46% CSA) referred to sleep laboratories of the four participating centers. Participants were randomized to either ASV (n = 32) or optimal medical treatment alone (control, n = 31). Results: Polysomnography (PSG) and actigraphy at home (home) with centralized blinded scoring were obtained at baseline and 12 weeks. ASV significantly reduced sleep fragmentation (total arousal indexpsc: -16.4 +/- 20.6 vs.-0.6 13.2/h, p = 0.001; sleep fragmentation index(home):-7.6 +/- 15.6 versus 4.3 +/- 13.9/h, p = 0.003, respectively) and significantly increased sleep efficiency assessed by actigraphy (SEhome) compared to controls (2.3 +/- 10.1 vs.-2.1 +/- 6.9%, p = 0.002). Effects of ASV on sleep fragmentation and efficiency were similar in patients suffering from OSA and CSA. Conclusions: At home, ASV treatment modestly improves sleep fragmentation as well as sleep efficiency in CHF patients having either CSA or OSA. (C) 2015 Elsevier B.V. All rights reserved. C1 [Hetzenecker, Andrea; Birner, Christoph; Pfeifer, Michael; Arzt, Michael] Univ Hosp Regensburg, Dept Internal Med 2, Regensburg, Germany. [Hetzenecker, Andrea; Pfeifer, Michael] Donaustauf Hosp, Ctr Pneumol, Donaustauf, Germany. [Escourrou, Pierre] Hop Antoine Beclere, Ctr Med Sommeil, Clamart, France. [Kuna, Samuel T.] Univ Penn, Perleman Sch Med, Dept Med, Philadelphia, PA 19104 USA. [Kuna, Samuel T.] Philadelphia Vet Affairs Med Ctr, Philadelphia, PA USA. [Series, Frederic] Univ Laval, IUCPQ, Ctr Rech, Quebec City, PQ, Canada. [Lewis, Keir] Prince Philip Hosp, Dept Resp Med, Llanelli, Wales. [Lewis, Keir] Swansea Coll Med, Swansea, W Glam, Wales. [Pfeifer, Michael] Hosp Order St John God Regensburg, Clin Pulmonol, Regensburg, Germany. RP Arzt, M (reprint author), Univ Hosp Regensburg, Ctr Sleep Med, Dept Internal Med 2, Franz Josef Strauss Allee 11, D-93053 Regensburg, Germany. EM michael.arzt@ukr.de NR 41 TC 2 Z9 2 U1 0 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1389-9457 EI 1878-5506 J9 SLEEP MED JI Sleep Med. PD JAN PY 2016 VL 17 BP 25 EP 31 DI 10.1016/j.sleep.2015.08.020 PG 7 WC Clinical Neurology SC Neurosciences & Neurology GA DE8OX UT WOS:000370897100006 PM 26847970 ER PT J AU Foldager, CB Toh, WS Christensen, BB Lind, M Gomoll, AH Spector, M AF Foldager, Casper Bindzus Toh, Wei Seong Christensen, Bjorn Borsoe Lind, Martin Gomoll, Andreas H. Spector, Myron TI Collagen Type IV and Laminin Expressions during Cartilage Repair and in Late Clinically Failed Repair Tissues from Human Subjects SO CARTILAGE LA English DT Article DE collagen type IV; laminin; articular cartilage; cartilage repair ID CHONDROCYTE PERICELLULAR MATRIX; BASEMENT-MEMBRANE COMPONENTS; MESENCHYMAL STEM-CELLS; ARTICULAR-CARTILAGE; OSTEOARTHRITIC CHANGES; HYPOXIC CONDITIONS; ANGIOGENESIS; CHONDROGENESIS; IDENTIFICATION; REGENERATION AB Objective To identify the collagen type IV (Col4) isoform in articular cartilage and to evaluate the expressions of Col4 and laminin in the pericellular matrix (PCM) in damaged cartilage and during cartilage repair. Design The Col4 isoform was determined in chondrocytes isolated from 6 patients cultured up to 6 days and in 21% O-2 or 1% O-2, and the gene expression of Col4 -chains was investigated. The distribution of Col4 and laminin in traumatically damaged cartilage (n = 7) and clinically failed cartilage repair (microfracture, TruFit, autologous chondrocyte implantation; n = 11) were investigated using immunohistochemistry. Normal human cartilage was used as control (n = 8). The distribution during clinical cartilage repair procedures was investigated in a minipig model with 6-month follow-up (untreated chondral, untreated osteochondral, microfracture, autologous chondrocyte implantation; n = 10). Results The Col4 isoform in articular cartilage was characterized as 112, which is an isoform containing antiangiogenic domains in the NC1-terminals (arresten and canstatin). In normal cartilage, laminin and Col4 was exclusively found in the PCM. High amounts (>50%) of Col4 in the PCM significantly decreased in damaged cartilage (P = 0.004) and clinically failed repair tissue (P < 0.001). Laminin was only found with high expression (>50%) in 4/8 of the normal samples, which was not statistically significantly different from damaged cartilage (P = 0.15) or failed cartilage repair (P = 0.054). Conclusions Col4 in cartilage contain antiangiogenic domains and may play a role in the hypoxic environment in articular cartilage. Col4 and laminin was not found in the PCM of damaged and clinically failed repair. C1 [Foldager, Casper Bindzus; Toh, Wei Seong; Spector, Myron] Harvard Univ, Sch Med, Dept Orthoped Surg, Brigham & Womens Hosp, Boston, MA 02115 USA. [Foldager, Casper Bindzus; Toh, Wei Seong; Spector, Myron] VA Boston Healthcare Syst, Tissue Engn Labs, Boston, MA USA. [Foldager, Casper Bindzus; Christensen, Bjorn Borsoe] Aarhus Univ Hosp, Orthopaed Res Lab, Norrebrogade 44,Bldg 1A, DK-8000 Aarhus C, Denmark. [Toh, Wei Seong] Natl Univ Singapore, Fac Dent, Discipline Oral Sci, Singapore 117548, Singapore. [Lind, Martin] Aarhus Univ Hosp, Dept Orthopaed, Sports Trauma Clin, DK-8000 Aarhus C, Denmark. [Gomoll, Andreas H.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Cartilage Repair Ctr, Boston, MA 02115 USA. RP Foldager, CB (reprint author), Aarhus Univ Hosp, Orthopaed Res Lab, Norrebrogade 44,Bldg 1A, DK-8000 Aarhus C, Denmark. EM foldager@clin.au.dk RI Toh, Wei Seong/K-7720-2013 OI Toh, Wei Seong/0000-0001-9147-6423 FU U.S. Department of Veterans Affairs, Veterans Health Administration, Rehabilitation Research and Development Service; Danish National Research Foundation; Elite Research Scholarship from the Danish Minister of Science, Technology and Innovation FX The authors would like to acknowledge their funding sources and technical assistance from the laboratory technicians at the Orthopaedic Research Laboratory, Aarhus University Hospital. The research reported here was supported by the U.S. Department of Veterans Affairs, Veterans Health Administration, Rehabilitation Research and Development Service, and a postdoctoral research grant from the Danish National Research Foundation. A postdoctoral research fellowship for CBF was awarded by an Elite Research Scholarship from the Danish Minister of Science, Technology and Innovation. The funding sources did not play a role in the investigation. NR 35 TC 1 Z9 1 U1 0 U2 0 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 1947-6035 EI 1947-6043 J9 CARTILAGE JI Cartilage PD JAN PY 2016 VL 7 IS 1 BP 52 EP 61 DI 10.1177/1947603515604022 PG 10 WC Orthopedics SC Orthopedics GA DE5WC UT WOS:000370702700005 PM 26958317 ER PT J AU George, MD Baker, JF AF George, Michael D. Baker, Joshua F. TI y The Obesity Epidemic and Consequences for Rheumatoid Arthritis Care SO CURRENT RHEUMATOLOGY REPORTS LA English DT Article DE Rheumatoid arthritis; Obesity; Adiposity ID BODY-MASS INDEX; RADIOGRAPHIC JOINT DAMAGE; TUMOR-NECROSIS-FACTOR; LONG-TERM CHANGES; RISK-FACTORS; DISEASE-ACTIVITY; AUTOIMMUNE-DISEASES; CARDIOVASCULAR RISK; ALCOHOL-CONSUMPTION; GENERAL-POPULATION AB With the prevalence of obesity increasing dramatically worldwide over the past several decades, an increasing body of literature has examined the impact of obesity in the context of rheumatoid arthritis (RA). Epidemiologic studies suggest that obesity may be associated with a modestly increased risk for the development of RA, although these studies have shown conflicting results. Among patients with established RA, obesity has been observed to be associated with greater subjective measures of disease activity and poor treatment response, but also with a decreased risk of joint damage and lower mortality. A comprehensive evaluation of the influence of obesity on the measurement of disease, response to therapies, and long-term prognosis is critical in order to understand these observations. This review therefore focuses on recent observations, potential explanations for these findings, and implications for clinicians and investigators caring for and studying patients with RA. C1 [George, Michael D.; Baker, Joshua F.] Univ Penn, Div Rheumatol, Philadelphia, PA 19104 USA. [Baker, Joshua F.] Philadelphia VA Med Ctr, Philadelphia, PA USA. [Baker, Joshua F.] Univ Penn, Ctr Clin Epidemiol & Biostat, Philadelphia, PA 19104 USA. RP George, MD (reprint author), Univ Penn, Div Rheumatol, Philadelphia, PA 19104 USA. EM michael.george@uphs.upenn.edu FU Veterans Affairs Clinical Science Research & Development Career Development Award [IK2 CX000955] FX Dr. Baker would like to acknowledge funding through a Veterans Affairs Clinical Science Research & Development Career Development Award (IK2 CX000955). The contents of this work do not represent the views of the Department of the Veterans Affairs or the United States Government. NR 78 TC 1 Z9 1 U1 2 U2 2 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1523-3774 EI 1534-6307 J9 CURR RHEUMATOL REP JI Curr. Rheumatol. Rep. PD JAN PY 2016 VL 18 IS 1 AR 6 DI 10.1007/s11926-015-0550-z PG 9 WC Rheumatology SC Rheumatology GA DD9HE UT WOS:000370235500006 PM 26739963 ER PT J AU Ghossein, C Varga, J Fenves, AZ AF Ghossein, Cybele Varga, John Fenves, Andrew Z. TI Recent Developments in the Classification, Evaluation, Pathophysiology, and Management of Scleroderma Renal Crisis SO CURRENT RHEUMATOLOGY REPORTS LA English DT Article DE Scleroderma renal crisis (SRC); Systemic sclerosis; Immune dysregulation; Diffuse cutaneous disease (dcSSc); Renal biopsy; Angiotensin-converting enzyme inhibitor (ACEI); Malignant hypertension; Thrombotic microangiopathy ID LONG-TERM OUTCOMES; SYSTEMIC-SCLEROSIS; ENDOTHELIN AXIS; ACE-INHIBITORS; RISK-FACTORS; DISEASE; INVOLVEMENT; BLOCKADE; FAILURE; PATIENT AB Scleroderma renal crisis (SRC) is an uncommon complication of systemic sclerosis. Despite the advent of angiotensin-converting inhibitor therapy, SRC remains a life-threatening complication. Recent studies have contributed to a better understanding of SRC, but much remains unknown regarding its pathophysiology, risk factors, and optimal management. Genetic studies provide evidence that immune dysregulation might be a contributing factor, providing hope that further research in this direction might illuminate pathogenesis and provide novel predictors for this complication. C1 [Ghossein, Cybele] Northwestern Univ, Feinberg Sch Med, Div Nephrol, Dept Med, 710 North Fairbanks Court,Suite 4500, Chicago, IL 60611 USA. [Varga, John] Northwestern Univ, Feinberg Sch Med, Dept Med, 240 E Huron St McGaw Pavil Rheumatol M300, Chicago, IL 60611 USA. [Varga, John] Northwestern Univ, Feinberg Sch Med, Div Rheumatol, Dept Med, 240 E Huron St McGaw Pavil Rheumatol M300, Chicago, IL 60611 USA. [Fenves, Andrew Z.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Med, 50 Staniford St,Suite 503B, Boston, MA 02114 USA. RP Ghossein, C (reprint author), Northwestern Univ, Feinberg Sch Med, Div Nephrol, Dept Med, 710 North Fairbanks Court,Suite 4500, Chicago, IL 60611 USA. EM c-ghossein@northwestern.edu; j-varga@northwestern.edu; AFENVES@mgh.harvard.edu NR 37 TC 0 Z9 0 U1 0 U2 4 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1523-3774 EI 1534-6307 J9 CURR RHEUMATOL REP JI Curr. Rheumatol. Rep. PD JAN PY 2016 VL 18 IS 1 AR 5 DI 10.1007/s11926-015-0551-y PG 6 WC Rheumatology SC Rheumatology GA DD9HE UT WOS:000370235500005 PM 26711696 ER PT J AU Goodman, DW Mitchell, S Rhodewalt, L Surman, CBH AF Goodman, David W. Mitchell, Sara Rhodewalt, Lauren Surman, Craig B. H. TI Clinical Presentation, Diagnosis and Treatment of Attention-Deficit Hyperactivity Disorder (ADHD) in Older Adults: A Review of the Evidence and its Implications for Clinical Care SO DRUGS & AGING LA English DT Review ID COGNITIVE-BEHAVIORAL THERAPY; OBSTRUCTIVE SLEEP-APNEA; DEFICIT/HYPERACTIVITY DISORDER; LIFE-SPAN; POPULATION; SYMPTOMS; DEMENTIA; SAMPLE; PREVALENCE; TRIAL AB Although previously considered a disorder of childhood, studies in the last decade have demonstrated that attention-deficit hyperactivity disorder (ADHD) continues to impair function into adulthood and responds to pharmacotherapy. Due to age-specific changes in roles and challenges, it is possible that presentation and response to intervention may differ between older and younger adults. A literature search for papers that identified older adults with ADHD, including papers describing its epidemiology, manifestation, and treatment, was the basis for this paper. There is a paucity of data on ADHD in older adults; however, small observational studies have characterized the presence, impact, and treatment of ADHD in adults over the age of 50 years, and larger epidemiologic studies have demonstrated that ADHD symptoms exist in older adulthood. Optimal criteria for diagnosis of ADHD and methods of treating ADHD in older individuals have not been systematically explored. In light of the limited data, this review discusses considerations for differential diagnosis and safe pharmacotherapy of ADHD in older adults. C1 [Goodman, David W.] Johns Hopkins Sch Med, Dept Psychiat & Behav Sci, Baltimore, MD 21205 USA. [Goodman, David W.] Adult Attent Deficit Disorder Ctr Maryland, Lutherville Timonium, MD 21093 USA. [Goodman, David W.] Suburban Psychiat Associates LLC, Johns Hopkins Green Spring Stn, 10751 Falls Rd,Suite 306, Baltimore, MD 21093 USA. [Mitchell, Sara] Massachusetts Gen Hosp, Dept Neurol, 15 Parkman St,WAC 815, Boston, MA 02114 USA. [Rhodewalt, Lauren; Surman, Craig B. H.] Massachusetts Gen Hosp, Clin & Res Program ADHD & Related Disorders, 55 Fruit St,Warren 631, Boston, MA 02114 USA. [Surman, Craig B. H.] Harvard Univ, Sch Med, 25 Shattuck St, Boston, MA 02115 USA. RP Goodman, DW (reprint author), Johns Hopkins Sch Med, Dept Psychiat & Behav Sci, Baltimore, MD 21205 USA.; Goodman, DW (reprint author), Adult Attent Deficit Disorder Ctr Maryland, Lutherville Timonium, MD 21093 USA. EM dgoodma4@jhmi.edu FU WebMD; Medscape; Temple University; American Professional Society of ADHD and Related Disorders; Neuroscience Education Institute; Children and Adults with ADHD Association; McNeil; Teva Pharmaceuticals; Lundbeck; Janssen (US); Janssen (Canada); OptumInsight (Ingenix Pharmaceutical Services, Inc.); Sunovion; Otsuka Pharmaceuticals; Novartis; Iron-shore Pharmaceuticals; Rhodes Pharmaceuticals; Neos Therapeutics; Thomson Reuters; GuidePoint Global; Med-IQ; Avacat; Pontifax; Healthequity Corporation; American Physician Institute for Advanced Professional Studies; LLC; Prescriber's Letter; Consumer Reports; Major League Baseball; National Football League; Nutricia; Pfizer; Rhodes; Shire; Somaxon; Takeda; Alcobra; Janssen; Janssen-Ortho; Reed/MGH Academy FX Dr. David W. Goodman has received consulting fees and honorarium from WebMD, Medscape, Temple University, American Professional Society of ADHD and Related Disorders, Neuroscience Education Institute, Children and Adults with ADHD Association, McNeil, Teva Pharmaceuticals, Lundbeck, Janssen (US and Canada), OptumInsight (Ingenix Pharmaceutical Services, Inc.), Sunovion, Otsuka Pharmaceuticals, Novartis, Iron-shore Pharmaceuticals, Rhodes Pharmaceuticals, Neos Therapeutics, Thomson Reuters, GuidePoint Global, Med-IQ, Avacat, Pontifax, Healthequity Corporation, American Physician Institute for Advanced Professional Studies, LLC, Prescriber's Letter, Consumer Reports, Major League Baseball, and National Football League.; Dr. Craig Surman has received, in his lifetime, consulting fees or honorarium from McNeil, Nutricia, Pfizer, Rhodes, Shire, Somaxon, and Takeda. He has also received payments for lectures from Alcobra, McNeil, Janssen, Janssen-Ortho, Novartis, Shire, and Reed/MGH Academy (funded by multiple companies). Royalties have been given to Dr. Surman from Berkeley/Penguin for FASTMINDS: How to Thrive if You Have ADHD (or Think you Might) and from Humana/Springer for ADHD in Adults: A Practical Guide to Evaluation and Management. Additionally, Dr. Surman has conducted clinical research at Massachusetts General Hospital with Abbott, Cephalon, the Hilda and Preston Davis Foundation, Eli Lilly, Magceutics, Johnson & Johnson/McNeil, Lundbeck, Merck, Nordic Naturals, Nutricia, Pamlab, Pfizer, Organon, Shire, and Takeda. NR 59 TC 0 Z9 0 U1 7 U2 19 PU ADIS INT LTD PI NORTHCOTE PA 5 THE WAREHOUSE WAY, NORTHCOTE 0627, AUCKLAND, NEW ZEALAND SN 1170-229X EI 1179-1969 J9 DRUG AGING JI Drugs Aging PD JAN PY 2016 VL 33 IS 1 BP 27 EP 36 DI 10.1007/s40266-015-0327-0 PG 10 WC Geriatrics & Gerontology; Pharmacology & Pharmacy SC Geriatrics & Gerontology; Pharmacology & Pharmacy GA DE1JE UT WOS:000370382300004 PM 26659731 ER PT J AU Garcia-Albeniz, X Hsu, J Lipsitch, M Logan, RW Hernandez-Diaz, S Hernan, MA AF Garcia-Albeniz, Xabier Hsu, John Lipsitch, Marc Logan, Roger W. Hernandez-Diaz, Sonia Hernan, Miguel A. TI Infective endocarditis and cancer in the elderly SO EUROPEAN JOURNAL OF EPIDEMIOLOGY LA English DT Article DE Infective endocarditis; Colorectal cancer; SEER; Medicare ID STREPTOCOCCUS-GALLOLYTICUS INFECTION; COLORECTAL-CANCER; UNITED-STATES; BOVIS ENDOCARDITIS; SUBSP GALLOLYTICUS; ASSOCIATION; NEOPLASIA; METAANALYSIS; BACTEREMIA; OUTCOMES AB Little is known about the magnitude of the association between infective endocarditis and cancer, and about the natural history of cancer patients with concomitant diagnosis of infective endocarditis. We used the SEER-Medicare linked database to identify individuals aged 65 years or more diagnosed with colorectal, lung, breast, or prostate cancer, and without any cancer diagnosis (5 % random Medicare sample from SEER areas) between 1992 and 2009. We identified infective endocarditis from the ICD-9 diagnosis of each admission recorded in the Medpar file and its incidence rate 90 days around cancer diagnosis. We also estimated the overall survival and CRC-specific survival after a concomitant diagnosis of infective endocarditis. The peri-diagnostic incidence of infective endocarditis was 19.8 cases per 100,000 person-months for CRC, 5.7 cases per 100,000 person-months for lung cancer, 1.9 cases per 100,000 person-months for breast cancer, 4.1 cases per 100,000 person-months for prostate cancer and 2.4 cases per 100,000 person-months for individuals without cancer. Two-year overall survival was 46.4 % (95 % CI 39.5, 54.5 %) for stage I-III CRC patients with concomitant endocarditis and 73.1 % (95 % CI 72.9, 73.3 %) for those without it. In this elderly population, the incidence of infective endocarditis around CRC diagnosis was substantially higher than around the diagnosis of lung, breast and prostate cancers. A concomitant diagnosis of infective endocarditis in patients with CRC diagnosis is associated with shorter survival. C1 [Garcia-Albeniz, Xabier; Lipsitch, Marc; Logan, Roger W.; Hernandez-Diaz, Sonia; Hernan, Miguel A.] Harvard Univ, Dept Epidemiol, TH Chan Sch Publ Hlth, 677 Huntington Ave, Boston, MA 02115 USA. [Garcia-Albeniz, Xabier; Hsu, John] Massachusetts Gen Hosp, Mongan Inst Hlth Policy, Boston, MA 02114 USA. [Hsu, John] Harvard Univ, Sch Med, Dept Hlth Care Policy, Boston, MA 02115 USA. [Lipsitch, Marc] Harvard Univ, TH Chan Sch Publ Hlth, Dept Immunol & Infect, Boston, MA 02115 USA. [Hernan, Miguel A.] Harvard Univ, Dept Biostat, TH Chan Sch Publ Hlth, Boston, MA 02115 USA. [Hernan, Miguel A.] Harvard Mit Div Hlth Sci & Technol, Boston, MA USA. RP Garcia-Albeniz, X (reprint author), Harvard Univ, Dept Epidemiol, TH Chan Sch Publ Hlth, 677 Huntington Ave, Boston, MA 02115 USA.; Garcia-Albeniz, X (reprint author), Massachusetts Gen Hosp, Mongan Inst Hlth Policy, Boston, MA 02114 USA. EM xabi@post.harvard.edu FU California Department of Public Health as part of the statewide cancer reporting program [103885]; National Cancer Institute's Surveillance, Epidemiology and End Results Program [N01-PC-35136, N01-PC-35139, N02-PC-15105]; Centers for Disease Control and Prevention's National Program of Cancer Registries [U55/CCR921930-02]; NIH [P01-CA134294, R01CA164023, R01HS023128]; Raymond P. Lavietes Foundation FX The authors acknowledge the efforts of the Applied Research Program, NCI; the Office of Research, Development and Information, CMS; Information Management Services (IMS), Inc.; and the Surveillance, Epidemiology, and End Results (SEER) Program tumor registries in the creation of the SEER-Medicare database. The interpretation and reporting of these data are the sole responsibility of the authors. The collection of the California cancer incidence data used in this study was supported by the California Department of Public Health as part of the statewide cancer reporting program mandated by California Health and Safety Code Section 103885; the National Cancer Institute's Surveillance, Epidemiology and End Results Program under contract N01-PC-35136 awarded to the Northern California Cancer Center, contract N01-PC-35139 awarded to the University of Southern California, and contract N02-PC-15105 awarded to the Public Health Institute; and the Centers for Disease Control and Prevention's National Program of Cancer Registries, under agreement #U55/CCR921930-02 awarded to the Public Health Institute. The ideas and opinions expressed herein are those of the author(s) and endorsement by the State of California, Department of Public Health the National Cancer Institute, and the Centers for Disease Control and Prevention or their Contractors and Subcontractors is not intended nor should be inferred. This work was partly funded by NIH Grants P01-CA134294, R01CA164023, R01HS023128. XGA is a recipient of a Grant from the Raymond P. Lavietes Foundation. NR 27 TC 1 Z9 1 U1 2 U2 3 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0393-2990 EI 1573-7284 J9 EUR J EPIDEMIOL JI Eur. J. Epidemiol. PD JAN PY 2016 VL 31 IS 1 BP 41 EP 49 DI 10.1007/s10654-015-0111-9 PG 9 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA DE1HB UT WOS:000370376600005 PM 26683995 ER PT J AU Nadal, R Bellmunt, J AF Nadal, Rosa Bellmunt, Joaquim TI The evolving role of enzalutamide on the treatment of prostate cancer SO FUTURE ONCOLOGY LA English DT Article DE castration-resistant prostate cancer; enzalutamide; hormone-sensitive prostate cancer; prostate cancer; STRIVE ID OPEN-LABEL; ANTITUMOR-ACTIVITY; RESISTANCE; ABIRATERONE; CHEMOTHERAPY; DOCETAXEL; MDV3100; MONOTHERAPY; INHIBITOR; EFFICACY AB The field of prostate cancer has witnessed incredible progress in the last decade, owing to the approval of multiple survival-prolonging treatments for metastatic castration-resistant prostate cancer (mCRPC). Enzalutamide is a nonsteroidal androgen receptor inhibitor that targets multiple steps in the androgen receptor signaling axis. It has been approved for the treatment of mCRPC both in the postdocetaxel and in the chemotherapy-naive settings. We summarize the milestones in the development of enzalutamide in patients with prostate cancer. Special focus is placed on the results of the STRIVE Phase II clinical trial comparing head to head enzalutamide and bicalutamide in patients with nonmetastatic and mCRPC who have failed androgen deprivation and in other ongoing trials in the same setting and in earlier disease phases. C1 [Nadal, Rosa] NCI, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. [Bellmunt, Joaquim] Dana Farber Canc Inst, Boston, MA 02115 USA. [Bellmunt, Joaquim] Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Nadal, R (reprint author), NCI, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.; Bellmunt, J (reprint author), Dana Farber Canc Inst, Boston, MA 02115 USA.; Bellmunt, J (reprint author), Harvard Univ, Sch Med, Boston, MA 02115 USA. EM rosa.nadalrios@nih.gov; Joaquim_bellmunt@dfci.harvard.edu FU Pierre Fabre; Astellas Pharma; Pfizer; Takeda/Millennium FX J Bellmunt has received consultancy and lecture fees from Pierre Fabre, Astellas Pharma and Pfizer and research funding from Takeda/Millennium. 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 28 TC 0 Z9 0 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 2016 VL 12 IS 5 BP 607 EP 616 DI 10.2217/fon.15.351 PG 10 WC Oncology SC Oncology GA DE5TQ UT WOS:000370695600007 PM 26839021 ER PT J AU May, P Garrido, MM Cassel, JB Kelley, AS Meier, DE Normand, C Stefanis, L Smith, TJ Morrison, RS AF May, Peter Garrido, Melissa M. Cassel, J. Brian Kelley, Amy S. Meier, Diane E. Normand, Charles Stefanis, Lee Smith, Thomas J. Morrison, R. Sean TI Palliative Care Teams' Cost-Saving Effect Is Larger For Cancer Patients With Higher Numbers Of Comorbidities SO HEALTH AFFAIRS LA English DT Article ID OF-LIFE DISCUSSIONS; RESEARCH PRIORITIES; AMERICAN SOCIETY; CONSULTATION; HEALTH; PREFERENCES; DEATH; END; BENEFICIARIES; OUTCOMES AB Patients with multiple serious conditions account for a high proportion of health care spending. Such spending is projected to continue to grow substantially as a result of increased insurance eligibility, the ever-rising cost of care, the continued use of nonbeneficial high-intensity treatments at the end of life, and demographic changes. We evaluated the impact of palliative care consultation on hospital costs for adults with advanced cancer, excluding those with dementia. We found that compared to usual care, the receipt of a palliative care consultation within two days of admission was associated with 22 percent lower costs for patients with a comorbidity score of 2-3 and with 32 percent lower costs for those with a score of 4 or higher. Earlier consultation was also found to be systematically associated with a larger cost-saving effect for all subsamples defined by multimorbidity. Given ongoing workforce shortages, targeting early specialist palliative care to hospitalized patients with advanced cancer and higher numbers of serious concurrent conditions could improve care while complementing strategies to curb the growth of health spending. C1 [May, Peter] Univ Dublin Trinity Coll, Ctr Hlth Policy & Management, Dublin, Ireland. [May, Peter; Garrido, Melissa M.; Kelley, Amy S.; Meier, Diane E.; Morrison, R. Sean] Icahn Sch Med Mt Sinai, Geriatr & Palliat Med, New York, NY 10029 USA. [Garrido, Melissa M.; Stefanis, Lee] James J Peters Vet Affairs VA Med Ctr, Bronx, NY USA. [Cassel, J. Brian] Virginia Commonwealth Univ, Hematol Oncol & Palliat Care, Richmond, VA 23284 USA. [Meier, Diane E.] Icahn Sch Med Mt Sinai, Ctr Adv Palliat Care, New York, NY 10029 USA. [Normand, Charles] Univ Dublin Trinity Coll, Hlth Policy & Management, Dublin, Ireland. [Smith, Thomas J.] Johns Hopkins Univ, Sidney Kimmel Comprehens Canc Ctr, Palliat Med, Baltimore, MD USA. [Morrison, R. Sean] Icahn Sch Med Mt Sinai, Natl Palliat Care Res Ctr, New York, NY 10029 USA. RP May, P (reprint author), Univ Dublin Trinity Coll, Ctr Hlth Policy & Management, Dublin, Ireland. EM mayp2@tcd.ie RI May, Peter/B-2107-2017 OI May, Peter/0000-0001-8501-6500 FU National Cancer Institute (NCI); National Institute of Nursing Research [5R01CA116227-04]; health economics fellowship from the Health Research Board of Ireland; NCI [P30 CA 006973]; Veterans Affairs Health Services Research and Development Career Development Award [CDA 11-201/CDP 12-255]; National Institute on Aging (NIA) [1K23AG040774-01A1]; National Institutes of Health [5K24AG022345]; NIA; Claude D. Pepper Older Americans Independence Center at the Icahn School of Medicine at Mount Sinai [5P30AG028741]; National Palliative Care Research Center FX An early version of these results was presented at the Annual Assembly of the American Academy of Hospice and Palliative Medicine and the Hospice and Palliative Nurses Association, Philadelphia, Pennsylvania, February 26, 2015. The study was funded by the National Cancer Institute (NCI) and the National Institute of Nursing Research (Project No. 5R01CA116227-04). The study sponsors had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; and preparation, review, or approval of the manuscript. All authors are independent of the study sponsors. Peter May is sponsored by a health economics fellowship from the Health Research Board of Ireland and by the NCI. Melissa Garrido is supported by a Veterans Affairs Health Services Research and Development Career Development Award (Award No. CDA 11-201/CDP 12-255). Amy Kelley was supported by the National Institute on Aging (NIA; Grant No. 1K23AG040774-01A1). Thomas Smith is supported by a grant from the NCI to the Sidney Kimmel Comprehensive Cancer Center at the Johns Hopkins University (Grant No. P30 CA 006973). Sean Morrison received a Midcareer Investigator Award in Patient-Oriented Research from the National Institutes of Health (Award No. 5K24AG022345) during the course of this work. This work was supported by the NIA, the Claude D. Pepper Older Americans Independence Center at the Icahn School of Medicine at Mount Sinai (Grant No. 5P30AG028741), and the National Palliative Care Research Center. 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. The authors thank Robert Arnold, Phil Santa Emma, Mary Beth Happ, Tim Smith, and David Weissman for their contributions to the Palliative Care for Cancer project. NR 42 TC 5 Z9 5 U1 3 U2 5 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 2016 VL 35 IS 1 BP 44 EP 53 DI 10.1377/hlthaff.2015.0752 PG 10 WC Health Care Sciences & Services; Health Policy & Services SC Health Care Sciences & Services GA DD1PV UT WOS:000369694700007 PM 26733700 ER PT J AU Al-Qurayshi, Z Robins, R Hauch, A Randolph, GW Kandil, E AF Al-Qurayshi, Zaid Robins, Russell Hauch, Adam Randolph, Gregory W. Kandil, Emad TI Association of Surgeon Volume With Outcomes and Cost Savings Following Thyroidectomy A National Forecast SO JAMA OTOLARYNGOLOGY-HEAD & NECK SURGERY LA English DT Article ID ACADEMIC MEDICAL-CENTERS; SHORT-TERM OUTCOMES; HOSPITAL VOLUME; UNITED-STATES; TRENDS; MORTALITY; IMPACT; CANCER; PANCREATICODUODENECTOMY; EXPERIENCE AB IMPORTANCE Incidence of thyroidectomies is continuing to increase. Identifying factors associated with favorable outcomes can lead to cost savings. OBJECTIVE To assess the association of surgeon volume with clinical outcomes and costs of thyroidectomy. DESIGN, SETTING, AND PARTICIPANTS Cross-sectional analysis performed in October of 2014 of adult (>= 18 years) inpatients in US community hospitals using the Nationwide Inpatient Sample for the years 2003 through 2009. EXPOSURES Thyroidectomy. MAIN OUTCOMES AND MEASURES Complications, length of stay, and cost following thyroidectomy in relation to surgeon volume. Surgeon volumes were stratified into low (1-3 thyroidectomies per year), intermediate (4-29 thyroidectomies per year), and high (>= 30 thyroidectomies per year). RESULTS A total of 77 863 patients were included. Procedures performed by low-volume surgeons were associated with a higher risk of postoperative complications compared with high-volume surgeons (15.8% vs 7.7%; OR, 1.55 [95% CI, 1.19-2.03]; P = .001). Mean (SD) hospital cost was significantly associated with surgeon volume (high volume, $6662.69 [$409.31]; intermediate volume, $6912.41 [$137.20]; low volume, $10 396.21 [$345.17]; P < .001). During the study period, if all operations performed by low-volume surgeons had been selectively referred to intermediate- or high-volume surgeons, savings of 11.2% or 12.2%, respectively, would have been incurred. On the basis of the cost growth rate, greater savings are forecasted for high-volume surgeons. With a conservative assumption of 150 000 thyroidectomies per year in the United States, referral of all patients to intermediate- or high-volume surgeons would produce savings of $2.08 billion or $3.11 billion, respectively, over a span of 14 years. CONCLUSIONS AND RELEVANCE A surgeon's expertise (measured by surgical volume of procedures per year) is associated with favorable clinical as well as financial outcomes. Our model estimates that considerable cost savings are attainable if higher-volume surgeons perform thyroid procedures in the United States. C1 [Al-Qurayshi, Zaid; Hauch, Adam; Kandil, Emad] Tulane Univ, Sch Med, Dept Surg, 1430 Tulane Ave,SL-22, New Orleans, LA 70112 USA. [Robins, Russell] Tulane Univ, AB Freeman Sch Business, New Orleans, LA 70112 USA. [Randolph, Gregory W.] Massachusetts Eye & Ear Infirm, Div Thyroid & Parathyroid Endocrine Surg, Boston, MA 02114 USA. RP Kandil, E (reprint author), Tulane Univ, Sch Med, Dept Surg, 1430 Tulane Ave,SL-22, New Orleans, LA 70112 USA. EM ekandil@tulane.edu OI Al-Qurayshi, Zaid/0000-0002-3534-7253 NR 32 TC 6 Z9 6 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA SN 2168-6181 EI 2168-619X J9 JAMA OTOLARYNGOL JI JAMA Otolaryngol-Head Neck Surg. PD JAN PY 2016 VL 142 IS 1 BP 32 EP 39 DI 10.1001/jamaoto.2015.2503 PG 8 WC Otorhinolaryngology; Surgery SC Otorhinolaryngology; Surgery GA DE5RN UT WOS:000370689500006 PM 26561736 ER PT J AU Kobraei, EM Lentz, AK Eberlin, KR Hachach-Haram, N Hamdan, US AF Kobraei, Edward M. Lentz, Ashley K. Eberlin, Kyle R. Hachach-Haram, Nadine Hamdan, Usama S. TI Macrostomia: A Practical Guide for Plastic and Reconstructive Surgeons SO JOURNAL OF CRANIOFACIAL SURGERY LA English DT Article DE Macrostomia; Tessier cleft number 7; transverse facial cleft ID FACIAL CLEFTS; CONGENITAL MACROSTOMIA; SURGICAL REPAIR; W-PLASTY; CLASSIFICATION; CLOSURE; FLAPS AB Macrostomia is a rare and debilitating congenital anomaly with incompletely understood etiopathogenesis. Despite the phenotypic variability in macrostomia, plastic surgeons should demonstrate competence in the diagnosis and management of this condition. The anatomy, embryology, classification, and clinical presentation of macrostomia are reviewed in this manuscript. A historical overview of surgical repair is presented that forms the basis for understanding modern techniques of repair. Finally, an effective method of macrostomia repair is presented along with review of 5-year results. It is our intent that this guide serve as a reference for plastic and reconstructive surgeons to accomplish safe, functional, and aesthetic macrostomia reconstruction. C1 [Kobraei, Edward M.; Eberlin, Kyle R.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Plast & Reconstruct Surg, Boston, MA USA. [Lentz, Ashley K.] Univ Florida, Coll Med, Hlth Sci Ctr, Div Plast & Reconstruct Surg, Gainesville, FL USA. [Hachach-Haram, Nadine] Guys & St Thomas Hosp, Dept Plast Surg, London SE1 9RT, England. [Hamdan, Usama S.] Harvard Univ, Sch Med, Tufts Univ, Global Smile Fdn, Boston, MA USA. [Hamdan, Usama S.] Boston Univ, Sch Med, Otolaryngol, Boston, MA 02118 USA. RP Kobraei, EM (reprint author), Massachusetts Gen Hosp, Div Plast & Reconstruct Surg, 55 Fruit St, Boston, MA 02214 USA. EM ekobraei@partners.org NR 42 TC 0 Z9 0 U1 2 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 1049-2275 EI 1536-3732 J9 J CRANIOFAC SURG JI J. Craniofac. Surg. PD JAN PY 2016 VL 27 IS 1 BP 118 EP 123 DI 10.1097/SCS.0000000000002294 PG 6 WC Surgery SC Surgery GA DD7AJ UT WOS:000370075700025 PM 26703052 ER PT J AU Kufta, K Peacock, ZS Chuang, SK Inverso, G Levin, LM AF Kufta, Kenneth Peacock, Zachary S. Chuang, Sung-Kiang Inverso, Gino Levin, Lawrence M. TI Components of Patient Satisfaction After Orthognathic Surgery SO JOURNAL OF CRANIOFACIAL SURGERY LA English DT Article DE Bilaterally sagittal split osteotomy; Le Fort I osteotomy; orthognathic surgery; patient satisfaction ID FOLLOW-UP; PERCEPTIONS; IMPACT; IMPROVEMENT AB The purpose of this study was to compare overall patient satisfaction after orthognathic surgery with the following specific categories: appearance, functional ability, general health, sociability, and patient-clinician communication. A 16-question survey was developed and administered to include patients at either 6 or 12 months after orthognathic surgery between June 2013 and June 2014 at the University of Pennsylvania and Massachusetts General Hospital. The predictor variables included age, sex, type of procedure, medical comorbidities, intra-or postoperative complications, and presence of paresthesia. The outcome variable was patient satisfaction overall and in each category based on a Likert scale (0: not satisfied at all to 5: very satisfied). A total of 37 patients completed the survey and had a high overall rate of satisfaction (100% of responses were 4 or 5 on Likert scale). Overall satisfaction had the highest correlation with appearance (rho = 0.52, P = 0.0009) followed by sociability (rho = 0.47, P = 0.004), patient-clinician communication (rho = 0.38, P = 0.02) functionality (rho = 0.19, P = 0.26), and general health (rho = -0.11, P = 0.51). Patients had high satisfaction scores for orthognathic surgery. Satisfaction with postoperative appearance had the strongest correlation with overall satisfaction. C1 [Kufta, Kenneth; Peacock, Zachary S.] Harvard Univ, Sch Dent Med, 55 Fruit St,Warren Bldg,Suite 1201, Boston, MA 02114 USA. [Peacock, Zachary S.; Chuang, Sung-Kiang] Massachusetts Gen Hosp, Harvard Dent Ctr, Oral & Maxillofacial Surg Serv, Boston, MA 02114 USA. [Inverso, Gino] Hosp Univ Penn, Dept Oral & Maxillofacial Surg, 3400 Spruce St, Philadelphia, PA 19104 USA. [Levin, Lawrence M.] Univ Penn, Childrens Hosp Philadelphia, Div Oral & Maxillofacial Surg, Div Dent, Philadelphia, PA 19104 USA. RP Peacock, ZS (reprint author), Harvard Univ, Sch Dent Med, 55 Fruit St,Warren Bldg,Suite 1201, Boston, MA 02114 USA.; Peacock, ZS (reprint author), Massachusetts Gen Hosp, Oral & Maxillofacial Surg, 55 Fruit St,Warren Bldg,Suite 1201, Boston, MA 02114 USA. EM zpeacock@partners.org NR 19 TC 0 Z9 0 U1 2 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 1049-2275 EI 1536-3732 J9 J CRANIOFAC SURG JI J. Craniofac. Surg. PD JAN PY 2016 VL 27 IS 1 BP E102 EP E105 DI 10.1097/SCS.0000000000002318 PG 4 WC Surgery SC Surgery GA DD7AU UT WOS:000370076800037 PM 26703058 ER PT J AU Li, CQ Pastila, RK Lin, CP AF Li, Chunqiang Pastila, Riikka K. Lin, Charles P. TI Label-free imaging immune cells and collagen in atherosclerosis with two-photon and second harmonic generation microscopy SO JOURNAL OF INNOVATIVE OPTICAL HEALTH SCIENCES LA English DT Article DE Two-photon microscopy; mast cells; atherosclerosis ID MAST-CELLS; IN-VIVO; FLUORESCENCE; PLAQUES; RUPTURE; DISEASE AB Atherosclerosis has been recognized as a chronic inflammation disease, in which many types of cells participate in this process, including lymphocytes, macrophages, dendritic cells (DCs), mast cells, vascular smooth muscle cells (SMCs). Developments in imaging technology provide the capability to observe cellular and tissue components and their interactions. The knowledge of the functions of immune cells and their interactions with other cell and tissue components will facilitate our discovery of biomarkers in atherosclerosis and prediction of the risk factor of rupture-prone plaques. Nonlinear optical microscopy based on two-photon excited autofluorescence and second harmonic generation (SHG) were developed to image mast cells, SMCs and collagen in plaque ex vivo using endogenous optical signals. Mast cells were imaged with two-photon tryptophan autofluorescence, SMCs were imaged with two-photon NADH autofluorescence, and collagen were imaged with SHG. This development paves the way for further study of mast cell degranulation, and the effects of mast cell derived mediators such as induced synthesis and activation of matrix metalloproteinases (MMPs) which participate in the degradation of collagen. C1 [Li, Chunqiang] Univ Texas El Paso, Dept Phys, El Paso, TX 79968 USA. [Pastila, Riikka K.; Lin, Charles P.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Wellman Ctr Photomed, 185 Cambridge St, Boston, MA 02114 USA. [Pastila, Riikka K.; Lin, Charles P.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Syst Biol, 185 Cambridge St, Boston, MA 02114 USA. [Pastila, Riikka K.] STUK Radiat & Nucl Safety Author, Laippatie 4, FI-00880 Helsinki, Finland. RP Li, CQ (reprint author), Univ Texas El Paso, Dept Phys, El Paso, TX 79968 USA. EM cli@utep.edu FU United States NIH [P41 EB015903-02S1] FX This study was supported by United States NIH P41 EB015903-02S1 grant awarded to CPL. We would like to thank Drs. Crystal M. Ripplinger and Farouc A. Jaffer for their help on the mouse model of atherosclerotic plaque. NR 27 TC 0 Z9 0 U1 6 U2 13 PU WORLD SCIENTIFIC PUBL CO PTE LTD PI SINGAPORE PA 5 TOH TUCK LINK, SINGAPORE 596224, SINGAPORE SN 1793-5458 EI 1793-7205 J9 J INNOV OPT HEAL SCI JI J. Innov. Opt. Health Sci. PD JAN PY 2016 VL 9 IS 1 SI SI AR 1640003 DI 10.1142/S1793545816400034 PG 8 WC Optics; Radiology, Nuclear Medicine & Medical Imaging SC Optics; Radiology, Nuclear Medicine & Medical Imaging GA DE0DR UT WOS:000370295600005 ER PT J AU Wang, J Li, PY Chen, XY Wu, MX AF Wang, Ji Li, Peiyu Chen, Xinyuan Wu, Mei X. TI Laser facilitates vaccination SO JOURNAL OF INNOVATIVE OPTICAL HEALTH SCIENCES LA English DT Review DE Laser; vaccine delivery; adjuvant ID RANDOMIZED CONTROLLED SAFETY; INFLUENZA VACCINATION; INTRADERMAL DELIVERY; IMMUNOGENICITY TRIAL; SKIN VACCINATION; DENDRITIC CELLS; VACCINES; INNATE; RESPONSES; ADJUVANT AB Development of novel vaccine deliveries and vaccine adjuvants is of great importance to address the dilemma that the vaccine field faces: to improve vaccine efficacy without compromising safety. Harnessing the specific effects of laser on biological systems, a number of novel concepts have been proposed and proved in recent years to facilitate vaccination in a safer and more efficient way. The key advantage of using laser technology in vaccine delivery and adjuvantation is that all processes are initiated by physical effects with no foreign chemicals administered into the body. Here, we review the recent advances in using laser technology to facilitate vaccine delivery and augment vaccine efficacy as well as the underlying mechanisms. C1 [Wang, Ji; Li, Peiyu] Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA. [Wang, Ji] Harvard Univ, Sch Med, Dept Dermotol, Boston, MA 02114 USA. [Chen, Xinyuan] Univ Rhode Isl, Biomed & Pharmaceut Sci, Coll Pharm, Kingston, RI 02881 USA. RP Wang, J (reprint author), Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA.; Wang, J (reprint author), Harvard Univ, Sch Med, Dept Dermotol, Boston, MA 02114 USA. EM jwang10@mgh.harvard.edu FU National Institutes of Health [AI089779, AI070785, AI097696, DA028378, DA033371, AI107678] FX This work is supported in part by the National Institutes of Health grants AI089779, AI070785, AI097696 and DA028378 (to M.X.W.) and the National Institutes of Health grants DA033371, AI107678 (to X.Y.C). NR 49 TC 1 Z9 1 U1 1 U2 5 PU WORLD SCIENTIFIC PUBL CO PTE LTD PI SINGAPORE PA 5 TOH TUCK LINK, SINGAPORE 596224, SINGAPORE SN 1793-5458 EI 1793-7205 J9 J INNOV OPT HEAL SCI JI J. Innov. Opt. Health Sci. PD JAN PY 2016 VL 9 IS 1 SI SI AR 1630003 DI 10.1142/S1793545816300032 PG 9 WC Optics; Radiology, Nuclear Medicine & Medical Imaging SC Optics; Radiology, Nuclear Medicine & Medical Imaging GA DE0DR UT WOS:000370295600002 ER PT J AU Yu, C Avci, P Canteenwala, T Chiang, LY Chen, BJ Hamblin, MR AF Yu, Chi Avci, Pinar Canteenwala, Taizoon Chiang, Long Y. Chen, Bao J. Hamblin, Michael R. TI Photodynamic Therapy with Hexa(sulfo-n-butyI)[60]Fullerene Against Sarcoma In Vitro and In Vivo SO JOURNAL OF NANOSCIENCE AND NANOTECHNOLOGY LA English DT Article DE Hydrophilic Hexa(sulfo-n-butyl)[60]Fullerene (FC4S); Photodynamic Therapy; Reactive Oxygen Species; S180 Murine Sarcoma; ICR Mice ID SINGLET OXYGEN; FULLERENE; C-60; CELLS; TOXICITY; PHOTOSENSITIZERS; PROTOPORPHYRIN; INFECTIONS; SURVIVAL; LEUKEMIA AB The hydrophilic molecular micellar hexa(sulfo-n-butyl)[60]fullerene (FC4S), first synthesized in 1998 as a photosensitizer (PS) has been reported to exhibit high efficacy for singlet oxygen generation and antimicrobial photodynamic inactivation. The purpose of this study was to investigate the effects of photoactivated FC4S for free radical generation and to mediate photodynamic therapy (PDT) of cancer in vitro and in vivo. The results demonstrated that following light irradiation, FC4S produced singlet oxygen, but after addition of electron donors such as ferrocytochrome c or NADH, FC4S also produced superoxide. The combination of FC4S with light irradiation was able to induce cytotoxicity to human fibrosarcoma cells and murine sarcoma 180 cells in vitro. Cell-killing was proportional to fluence as well as FC4S concentration. Photoirradiation by argon-ion laser after intraperitoneal injection of FC4S also resulted in inhibition of S180 tumor growth in vivo (up to 80% reduction of tumor volume). Hematological and blood biochemistry parameters of the cancer-bearing mice were improved by PDT. Based on these findings, we conclude that FC4S has a great potential as a nanomedicine in PDT for cancer. C1 [Yu, Chi] Natl Pingtung Univ Sci & Technol, Dept Anim Sci, Pingtung 91201, Taiwan. [Avci, Pinar; Hamblin, Michael R.] Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA. [Avci, Pinar; Hamblin, Michael R.] Harvard Univ, Dept Dermatol, Sch Med, Boston, MA 02115 USA. [Avci, Pinar] Semmelweis Univ Sch Med, Dept Dermatol Dermatooncol & Venerol, H-1085 Budapest, Hungary. [Canteenwala, Taizoon; Chiang, Long Y.] Univ Massachusetts, Dept Chem, Lowell, MA 01854 USA. [Chen, Bao J.] Natl Taiwan Univ, Dept Anim Sci, Taipei 10672, Taiwan. [Hamblin, Michael R.] Harvard MIT Div Hlth Sci & Technol, Cambridge, MA 02139 USA. RP Yu, C (reprint author), Natl Pingtung Univ Sci & Technol, Dept Anim Sci, Pingtung 91201, Taiwan.; Hamblin, MR (reprint author), Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA.; Hamblin, MR (reprint author), Harvard Univ, Dept Dermatol, Sch Med, Boston, MA 02115 USA.; Hamblin, MR (reprint author), Harvard MIT Div Hlth Sci & Technol, Cambridge, MA 02139 USA. FU US NIH [R01CA137108, R01AI050875] FX The authors are grateful to US NIH for grant support (R01CA137108 to LYC and R01AI050875 to MRH). NR 43 TC 2 Z9 2 U1 7 U2 9 PU AMER SCIENTIFIC PUBLISHERS PI VALENCIA PA 26650 THE OLD RD, STE 208, VALENCIA, CA 91381-0751 USA SN 1533-4880 EI 1533-4899 J9 J NANOSCI NANOTECHNO JI J. Nanosci. Nanotechnol. PD JAN PY 2016 VL 16 IS 1 BP 171 EP 181 DI 10.1166/jnn.2016.10652 PG 11 WC Chemistry, Multidisciplinary; Nanoscience & Nanotechnology; Materials Science, Multidisciplinary; Physics, Applied; Physics, Condensed Matter SC Chemistry; Science & Technology - Other Topics; Materials Science; Physics GA DD1KK UT WOS:000369680400013 PM 27398442 ER PT J AU Weingarden, H Renshaw, KD Tangney, JR Wilhelm, S AF Weingarden, Hilary Renshaw, Keith D. Tangney, June R. Wilhelm, Sabine TI Development and validation of the Body-Focused Shame and Guilt Scale SO JOURNAL OF OBSESSIVE-COMPULSIVE AND RELATED DISORDERS LA English DT Article DE Shame; Body shame; Body dysmorphic disorder; Measurement ID OBSESSIVE-COMPULSIVE SCALE; DYSMORPHIC DISORDER; TREATMENT STRATEGIES; DEPRESSIVE SYMPTOMS; VALIDITY; VERSION; RELIABILITY; ADOLESCENTS; DASS AB Body shame is described as central in clinical literature on body dysmorphic disorder (BDD). However, empirical investigations of body shame within BDD are rare. One potential reason for the scarcity of such research may be that existing measures of body shame focus on eating and weight-based content. Within BDD, however, body shame likely focuses more broadly on shame felt in response to perceived appearance flaws in one's body parts. We describe the development and validation of the Body-Focused Shame and Guilt Scale (BF-SGS), a measure of BDD-relevant body shame, across two studies: a two time point study of undergraduates, and a follow-up study in two Internet-recruited clinical samples (BDD, obsessive compulsive disorder) and healthy controls. Across both studies, the BF-SGS shame subscale demonstrated strong reliability and construct validity, with Study 2 providing initial clinical norms. (C) 2015 Elsevier Inc. All rights reserved. C1 [Weingarden, Hilary; Renshaw, Keith D.; Tangney, June R.] George Mason Univ, Dept Psychol, 4400 Univ Dr, Fairfax, VA 22030 USA. [Weingarden, Hilary; Wilhelm, Sabine] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Psychiat, Boston, MA 02114 USA. RP Weingarden, H (reprint author), George Mason Univ, Dept Psychol, 4400 Univ Dr, Fairfax, VA 22030 USA. EM hweingar@masonlive.gmu.edu FU NIMH of the National Institutes of Health [1F31MH100845-01A1] FX Study 2 of this article was supported by the NIMH of the National Institutes of Health under award number 1F31MH100845-01A1. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. NR 29 TC 0 Z9 0 U1 3 U2 7 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 2211-3649 J9 J OBSESS-COMPULS REL JI J. Obsessive-Compuls. Relat. Disord. PD JAN PY 2016 VL 8 BP 9 EP 20 DI 10.1016/j.jocrd.2015.11.001 PG 12 WC Psychiatry SC Psychiatry GA DE6UN UT WOS:000370769200002 PM 26640760 ER PT J AU Reese, HE Pollard, CA Szymanski, J Berman, N Crowe, K Rosenfield, E Wilhelm, S AF Reese, Hannah E. Pollard, C. Alec Szymanski, Jeff Berman, Noah Crowe, Katherine Rosenfield, Elizabeth Wilhelm, Sabine TI The Behavior Therapy Training Institute for OCD: A preliminary report SO JOURNAL OF OBSESSIVE-COMPULSIVE AND RELATED DISORDERS LA English DT Article DE Obsessive compulsive disorder; Cognitive behavior therapy; Treatment; Dissemination; Training ID OBSESSIVE-COMPULSIVE DISORDER; THEORY-PRACTICE GAP; QUALITY-OF-LIFE; ANXIETY DISORDERS; EXPOSURE THERAPY; PSYCHOLOGICAL TREATMENTS; DISSEMINATION TRIAL; RANDOMIZED-TRIAL; IMPLEMENTATION; SCALE AB Despite decades of research demonstrating the efficacy of Cognitive Behavioral Therapy (CBT) for obsessive compulsive disorder (OCD), many clinicians have not adopted it into their practice. In an effort to increase the number of trained clinicians, the International OCD Foundation (IOCDF) developed a riationwide intensive training program, the Behavior Therapy Training Institute (BTTI). We report the first data on the BTTI. We emailed a 30-item online survey to all clinicians (N=350) who attended one of twelve BTTI workshops between 2008 and 2011. One hundred and sixty one individuals (53%) responded. Participants reported more than moderate use of all BTTI skills. Expert phone consultation and peer consultation after the training were associated with greater skills use. The most commonly reported barrier to skill use was difficulty integrating the techniques into their practice because of time or an inability to leave the office. The majority of participants also reported an increase in OCD-related referrals after the BTTI. Limitations of this work, suggestions for improvement, and the implications of our findings for broader dissemination efforts are discussed. (C) 2015 Elsevier Inc. All rights reserved. C1 [Reese, Hannah E.; Berman, Noah; Crowe, Katherine; Rosenfield, Elizabeth; Wilhelm, Sabine] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Reese, Hannah E.; Berman, Noah; Crowe, Katherine; Rosenfield, Elizabeth; Wilhelm, Sabine] Harvard Univ, Sch Med, Cambridge, MA 02138 USA. [Reese, Hannah E.] Bowdoin Coll, Brunswick, ME 04011 USA. [Pollard, C. Alec] St Louis Univ, Sch Med, St Louis, MO 63103 USA. [Szymanski, Jeff] Int OCD Fdn, Boston, MA USA. [Crowe, Katherine] Fordham Univ, Bronx, NY 10458 USA. [Rosenfield, Elizabeth] Univ Miami, Coral Gables, FL 33124 USA. RP Reese, HE (reprint author), Bowdoin Coll, Dept Psychol, 6900 Coll Stn, Brunswick, ME 04011 USA. EM hreese@bowdoin.edu NR 39 TC 1 Z9 1 U1 2 U2 3 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 2211-3649 J9 J OBSESS-COMPULS REL JI J. Obsessive-Compuls. Relat. Disord. PD JAN PY 2016 VL 8 BP 79 EP 85 DI 10.1016/j.jocrd.2015.12.005 PG 7 WC Psychiatry SC Psychiatry GA DE6UN UT WOS:000370769200011 ER PT J AU Khan, NM Jentes, ES Brown, C Han, P Rao, SR Kozarsky, P Hagmann, SHF LaRocque, RC Ryan, ET AF Khan, Nomana M. Jentes, Emily S. Brown, Clive Han, Pauline Rao, Sowmya R. Kozarsky, Phyllis Hagmann, Stefan H. F. LaRocque, Regina C. Ryan, Edward T. CA Global TravEpiNet Consortium GTEN TI Pre-Travel Medical Preparation of Business and Occupational Travelers An Analysis of the Global TravEpiNet Consortium, 2009 to 2012 SO JOURNAL OF OCCUPATIONAL AND ENVIRONMENTAL MEDICINE LA English DT Article ID GEOSENTINEL SURVEILLANCE NETWORK; INTERNATIONAL TRAVELERS; CORPORATE TRAVELER; AIRPORT SURVEY; HEPATITIS-A; RISK; KNOWLEDGE; ATTITUDES; HEALTH; DESTINATIONS AB Objectives: The aim of the study was to understand more about pre-travel preparations and itineraries of business and occupational travelers. Methods: De-identified data from 18 Global TravEpiNet clinics from January 2009 to December 2012 were analyzed. Results: Of 23,534 travelers, 61% were non-occupational and 39% occupational. Business travelers were more likely to be men, had short times to departure and shorter trip durations, and commonly refused influenza, meningococcal, and hepatitis B vaccines. Most business travelers indicated that employers suggested the pre-travel health consultation, whereas non-occupational travelers sought consultations because of travel health concerns. Conclusions: Sub-groups of occupational travelers have characteristic profiles, with business travelers being particularly distinct. Employers play a role in encouraging business travelers to seek pre-travel consultations. Such consultations, even if scheduled immediately before travel, can identify vaccination gaps and increase coverage. C1 [Khan, Nomana M.; Jentes, Emily S.; Brown, Clive; Han, Pauline; Kozarsky, Phyllis] Ctr Dis Control & Prevent, Div Global Migrat & Quarantine, 1600 Clifton Rd,MS E-03, Atlanta, GA 30329 USA. [Rao, Sowmya R.] Univ Massachusetts, Sch Med, Dept Quantitat Hlth Sci, Worcester, MA USA. [Rao, Sowmya R.] Bedford VA Med Ctr, Ctr Hlth Qual, Outcomes & Econ Res, Bedford, MA USA. [Hagmann, Stefan H. F.] Bronx Lebanon Hosp Ctr, Div Pediat Infect Dis, Bronx, NY 10456 USA. [Hagmann, Stefan H. F.] Albert Einstein Coll Med, Dept Pediat, Bronx, NY 10467 USA. [LaRocque, Regina C.; Ryan, Edward T.] Massachusetts Gen Hosp, Travelers Advice & Immunizat Ctr, Boston, MA 02114 USA. [LaRocque, Regina C.; Ryan, Edward T.] Harvard Univ, Sch Med, Boston, MA USA. RP Jentes, ES (reprint author), Ctr Dis Control & Prevent, Div Global Migrat & Quarantine, 1600 Clifton Rd,MS E-03, Atlanta, GA 30329 USA. EM efj8@cdc.gov FU US Centers for Disease Control and Prevention [U19CI000514, U01CK000175] FX This work was supported by US Centers for Disease Control and Prevention Grants U19CI000514 and U01CK000175. NR 27 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 1076-2752 EI 1536-5948 J9 J OCCUP ENVIRON MED JI J. Occup. Environ. Med. PD JAN PY 2016 VL 58 IS 1 BP 76 EP 82 DI 10.1097/JOM.0000000000000602 PG 7 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA DD8VC UT WOS:000370204000013 PM 26479857 ER PT J AU Townsend, RR Rosendorff, C Nichols, WW Edwards, DG Chirinos, JA Fernhall, B Cushman, WC AF Townsend, Raymond R. Rosendorff, Clive Nichols, Wilmer W. Edwards, David G. Chirinos, Julio A. Fernhall, Bo Cushman, William C. TI American Society of Hypertension position paper: central blood pressure waveforms in health and disease SO JOURNAL OF THE AMERICAN SOCIETY OF HYPERTENSION LA English DT Article DE Augmentation index; central arterial pressure; pulse pressure augmentation; pulse wave analysis ID CENTRAL AORTIC PRESSURE; LEFT-VENTRICULAR AFTERLOAD; CENTRAL PULSE PRESSURE; ARTERY FUNCTION EVALUATION; MOVING AVERAGE METHOD; SYSTOLIC PRESSURE; NONINVASIVE EVALUATION; CARDIOVASCULAR EVENTS; REFLECTION MAGNITUDE; AUGMENTATION INDEX AB A number of devices are available which noninvasively estimate central aortic blood pressure using a variety of approaches such as tonometry or oscillometry. In this position paper, we discuss how the central pressure waveform is generated and measured, how central pressure waveforms appear in health and disease, the predictive value of central blood pressure measurements, the effects of interventions on waveforms, and areas of future need in this field of clinical and research endeavor. (C) 2016 American Society of Hypertension. All rights reserved. C1 [Townsend, Raymond R.; Chirinos, Julio A.] Univ Penn, Sch Med, Dept Med, Philadelphia, PA 19104 USA. [Rosendorff, Clive] Icahn Sch Med Mt Sinai, Dept Med, New York, NY 10029 USA. [Rosendorff, Clive] James J Peters VA Med Ctr, Dept Med, Bronx, NY USA. [Nichols, Wilmer W.] Univ Florida, Coll Med, Dept Med, Div Med, Gainesville, FL USA. [Nichols, Wilmer W.] Univ Florida, Dept Med, Div Cardiovasc Med, Gainesville, FL USA. [Edwards, David G.] Univ Delaware, Coll Hlth Sci, Dept Kinesiol & Appl Physiol, Newark, DE USA. [Fernhall, Bo] Univ Illinois, Coll Appl Hlth Sci, Dept Kinesiol & Nutr, Chicago, IL USA. [Cushman, William C.] Univ Tennessee, Coll Med, Vet Affairs Med Ctr, Dept Med Serv, Memphis, TN USA. RP Townsend, RR (reprint author), Univ Penn, Renal Electrolyte & Hypertens Div, Perelman Sch Med, 122 Founders Bldg,3400 Spruce St, Philadelphia, PA 19104 USA. EM townsend@exchange.upenn.edu FU NIH; Fukuda Denshi; American College of Radiology Network; Department of Homeland Security; National Multiple Sclerosis Society; Merck; Eli Lilly FX R.R.T. received grants from NIH and Fukuda Denshi. D.G.E. received grants from NIH. J.A.C. received grants from NIH, American College of Radiology Network, and Fukuda Denshi. B.F. received grants from NIH, Department of Homeland Security, and the National Multiple Sclerosis Society. W.C.C. received grants from NIH, Merck, and Eli Lilly. NR 83 TC 2 Z9 2 U1 2 U2 5 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1933-1711 EI 1878-7436 J9 J AM SOC HYPERTENS JI J. Am. Soc. Hypertens. PD JAN PY 2016 VL 10 IS 1 BP 22 EP 33 DI 10.1016/j.jash.2015.10.012 PG 12 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA DE2OM UT WOS:000370466600007 PM 26612106 ER PT J AU Yu, RC Bo, H Villani, V Spencer, PJ Fu, P AF Yu, Ruichao Bo, Hong Villani, Vincenzo Spencer, Philip J. Fu, Ping TI The Inhibitory Effect of Rapamycin on Toll Like Receptor 4 and Interleukin 17 in the Early Stage of Rat Diabetic Nephropathy SO KIDNEY & BLOOD PRESSURE RESEARCH LA English DT Article DE Diabetic nephropathy (DN); Toll-like receptor 4 (TLR4); Interleukin-17 (IL-17); Rapamycin ID TUBULAR EPITHELIAL-CELLS; ACTIVATED PROTEIN-KINASE; DENDRITIC CELLS; T-CELLS; TH17 CELLS; C-FOS; INFLAMMATORY DISEASE; GLOMERULAR INJURY; IMMUNE-RESPONSE; KIDNEY-DISEASE AB Background/Aims: There is increasing evidence showing that innate immune responses and inflammatory processes play an important role in the development and progression of diabetic nephropathy (DN). The potential effect of innate immunity in the early stage of DN is still unclear. Toll-Like-Receptor 4 (TLR4) is vigorously involved in the progress of kidney diseases in a sterile environment. The activation of the interleukin 17 (IL-17) pathway produces inflammatory cytokines, appearing in various kidney diseases. Unfortunately the relationship between TLR4 and IL-17 has not been investigated in diabetic nephropathy to date. The aim of this study is to investigate whether mammalian target of rapamycin (mTOR) inhibition may be dependent on TLR4 signaling and the pro-inflammatory factor IL-17 to delay the progression of DN. Methods: Streptozotocin (STZ)-induced diabetic rats were randomly assigned to 3 experimental groups: a diabetic nephropathy group (DN, n = 6); and a diabetic nephropathy treated with rapamycin group (Rapa, n = 6) and a control group (Control, n = 6). Body weight, fasting blood sugar, and 24h urine albumin were assessed at week 2, week 4 and week 8. Renal tissues were harvested for H&E, PAS staining, as well as an immunohistochemistry assay for TLR4 and IL-17. TLR4 quantitative expression was measured by Western-Blot analysis and RT-PCR. Results: Our results demonstrated that the expression of both TLR4 and IL-17 were upregulated in early stage DN and reduced by rapamycin. TLR4 and IL-17 both increased and positively related to 24h urinary albumin and kidney/weight ratio. However, neither TLR4 nor IL-17 made a significant difference on fasting blood sugar. Conclusions: Taken together, our results confirm and extend previous studies identifying the significance of the TLR4 and Th17 pathways in development of early stage DN. Furthermore, we suggest this overexpression of TLR4 might be involved in the immunopathogenesis of DN through activation of Th17 cells. Rapamycin may attenuate DN via reduction of the TLR4 signaling pathway and Th17 cells signaling. Although the underlying mechanisms need to be explored, the observed increase of TLR4 and IL-17 during the early stages of DN and their suppression with rapamycin treatment suggest the importance of TLR4 and IL-17 in DN pathophysiology. (C) 2016 The Author(s) Published by S. Karger AG, Basel C1 [Yu, Ruichao; Fu, Ping] Sichuan Univ, West China Hosp, Dept Nephrolog, Chengdu 610041, Sichuan, Peoples R China. [Yu, Ruichao] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Transplantat Sci, Boston, MA 02114 USA. [Bo, Hong] Sichuan Univ, Dept Intens Care Unit, West China Hosp, Chengdu 610041, Sichuan, Peoples R China. [Villani, Vincenzo; Spencer, Philip J.] Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. RP Yu, RC (reprint author), Care of Huang SM, Sichuan Univ, West China Hosp, Dept Nephrol, 37 Guoxue Xiang,Bldg 3,Floor 5, Chengdu 610041, Sichuan, Peoples R China. EM songminhuanghx@gmail.com FU National Natural Science Foundation of China [30771005] FX This study was funded by National Natural Science Foundation of China (Funding number: 30771005) NR 66 TC 3 Z9 3 U1 3 U2 4 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 1420-4096 EI 1423-0143 J9 KIDNEY BLOOD PRESS R JI Kidney Blood Pressure Res. PY 2016 VL 41 IS 1 BP 55 EP 69 DI 10.1159/000368547 PG 15 WC Physiology; Urology & Nephrology; Peripheral Vascular Disease SC Physiology; Urology & Nephrology; Cardiovascular System & Cardiology GA DD8ES UT WOS:000370158800007 PM 26849067 ER PT J AU Kilbaugh, TJ Karlsson, M Duhaime, AC Hansson, MJ Elmer, E Margulies, SS AF Kilbaugh, Todd J. Karlsson, Michael Duhaime, Ann-Christine Hansson, Magnus J. Elmer, Eskil Margulies, Susan S. TI Mitochondrial response in a toddler-aged swine model following diffuse non-impact traumatic brain injury SO MITOCHONDRION LA English DT Article DE Pediatric brain injury; Traumatic brain injury; Mitochondria; In vivo studies; Large animal model of injury ID MATURATION-DEPENDENT RESPONSE; IMMATURE BRAIN; HEAD-INJURY; RAT-BRAIN; AXONAL INJURY; DYSFUNCTION; PIGLETS; METABOLISM; SEVERITY; NEUROPROTECTION AB Traumatic brain injury (TBI) is an important health problem, and a leading cause of death in children worldwide. Mitochondrial dysfunction is a critical component of the secondary TBI cascades. Mitochondrial response in the pediatric brain has limited investigation, despite evidence that the developing brain's response differs from that of the adult, especially in diffuse non-impact TBI. We performed a detailed evaluation of mitochondrial bioenergetics using high-resolution respirometry in a swine model of diffuse TBI (rapid non-impact rotational injury: RNR), and examined the cortex and hippocampus. A substrate-uncoupler-inhibitor-titration protocol examined the role of the individual complexes as well as the uncoupled maximal respiration. Respiration per mg of tissue was also related to citrate synthase activity (CS) as an attempt to control for variability in mitochondrial content following injury. Diffuse RNR stimulated increased complex II-driven respiration relative to mitochondrial content in the hippocampus compared to shams. LEAK (State 40) respiration increased in both regions, with decreased respiratory ratios of convergent oxidative phosphorylation through complex I and II, compared to sham animals, indicating uncoupling of oxidative phosphorylation at 24 h. The study suggests that proportionately, complex I contribution to convergent mitochondrial respiration was reduced in the hippocampus after RNR, with a simultaneous increase in complex-II driven respiration. Mitochondrial respiration 24 h after diffuse TBI varies by location within the brain. We concluded that significant uncoupling of oxidative phosphorylation and alterations in convergent respiration through complex I- and complex II-driven respiration reveals therapeutic opportunities for the injured at-risk pediatric brain. (C) 2015 Elsevier B.V. and Mitochondria Research Society. All rights reserved. C1 [Kilbaugh, Todd J.] Univ Penn, Perelman Sch Med, Childrens Hosp Philadelphia, Dept Anesthesiol & Crit Care Med, 3401 Civ Ctr Blvd, Philadelphia, PA 19104 USA. [Karlsson, Michael; Hansson, Magnus J.; Elmer, Eskil] Lund Univ, Dept Clin Sci, Mitochondrial Med, BMC A13, SE-22184 Lund, Sweden. [Duhaime, Ann-Christine] Univ Penn, Dept Bioengn, 210 South 33rd St, Philadelphia, PA 19104 USA. [Margulies, Susan S.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Neurosurg, 15 Parkman St, Boston, MA 02114 USA. [Duhaime, Ann-Christine] 15 Parkman St, Boston, MA 02114 USA. [Margulies, Susan S.] 240 Skirkanich Hall,210 South 33rd St, Philadelphia, PA 19104 USA. RP Kilbaugh, TJ (reprint author), Childrens Hosp Philadelphia, Dept Anesthesiol & Crit Care Med, 34th & Civ Ctr Blvd, Philadelphia, PA 19104 USA. EM kilbaugh@chop.edu; michael.karlsson@med.lu.se; aduhaime@partners.org; magnus.hansson@med.lu.se; eskil.elmer@med.lu.se; margulie@seas.upenn.edu RI Elmer, Eskil/F-9341-2014; OI Elmer, Eskil/0000-0001-7901-1826; Kilbaugh, Todd/0000-0002-4959-3092 FU NIH [UO1 NS069545] FX The authors would like to thank Melissa Byro, Ashley Bebee, Jill Ralston, Sarah Sullivan, Albana Shahini, and Saori Morota for their invaluable technical support. The Oroboros Oxygraph used in the study was a loan from NeuroVive Pharmaceutical AB, Lund Sweden. Studies were supported by the NIH UO1 NS069545. NR 47 TC 3 Z9 3 U1 1 U2 4 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 1567-7249 EI 1872-8278 J9 MITOCHONDRION JI Mitochondrion PD JAN PY 2016 VL 26 BP 19 EP 25 DI 10.1016/j.mito.2015.11.001 PG 7 WC Cell Biology; Genetics & Heredity SC Cell Biology; Genetics & Heredity GA DE6UC UT WOS:000370768100003 PM 26549476 ER PT J AU McClatchey, PM Keller, AC Bouchard, R Knaub, LA Reusch, JEB AF McClatchey, P. Mason Keller, Amy C. Bouchard, Ron Knaub, Leslie A. Reusch, Jane E. B. TI Fully automated software for quantitative measurements of mitochondrial morphology SO MITOCHONDRION LA English DT Article DE Mitochondria; Morphology; Microscopy; Image processing ID CELL-DEATH; DYNAMICS; FISSION; NEURONS; DISEASE; CALCIUM; FIBROBLASTS; DYSFUNCTION; ACTIVATION; INCREASES AB Mitochondria undergo dynamic changes in morphology in order to adapt to changes in nutrient and oxygen availability, communicate with the nucleus, and modulate intracellular calcium dynamics. Many recent papers have been published assessing mitochondrial morphology endpoints. Although these studies have yielded valuable insights, contemporary assessment of mitochondrial morphology is typically subjective and qualitative, precluding direct comparison of outcomes between different studies and likely missing many subtle effects. In this paper, we describe a novel software technique for measuring the average length, average width, spatial density, and intracellular localization of mitochondria from a fluorescent microscope image. This method was applied to distinguish baseline characteristics of Human Umbilical Vein Endothelial Cells (HUVECs), primary Goto-Kakizaki rat aortic smooth muscle cells (GK SMCs), primary Wistar rat aortic smooth muscle cells (Wistar SMCs), and SH-SY5Ys (human neuroblastoma cell line). Consistent with direct observation, our algorithms found SH-SY5Ys to have the greatest mitochondria] density, while HUVECs were found to have the longest mitochondria. Mitochondrial morphology responses to temperature, nutrient, and oxidative stressors were characterized to test algorithm performance. Large morphology changes recorded by the software agreed with direct observation, and subtle but consistent morphology changes were found that would not otherwise have been detected. Endpoints were consistent between experimental repetitions (R = 0.93 for length, R = 0.93 for width, R = 0.89 for spatial density, and R = 0.74 for localization), and maintained reasonable agreement even when compared to images taken with compromised microscope resolution or in an alternate imaging plane. These results indicate that the automated software described herein allows quantitative and objective characterization of mitochondrial morphology from fluorescent microscope images. Published by Elsevier B.V. and Mitochondria Research Society. C1 [McClatchey, P. Mason; Keller, Amy C.; Knaub, Leslie A.; Reusch, Jane E. B.] Univ Colorado Anschutz Med Campus, Div Endocrinol, Aurora, CO USA. [McClatchey, P. Mason; Keller, Amy C.; Bouchard, Ron; Knaub, Leslie A.; Reusch, Jane E. B.] Denver VA Med Ctr, Dept Med, Denver, CO USA. [McClatchey, P. Mason; Reusch, Jane E. B.] Univ Colorado Anschutz Med Campus, Dept Bioengn, Aurora, CO USA. [Reusch, Jane E. B.] Univ Colorado, Sch Med, Ctr Womens Hlth Res, Aurora, CO USA. RP Reusch, JEB (reprint author), Univ Colorado Anschutz Med Campus, Div Endocrinol, Aurora, CO USA. EM jane.reusch@ucdenver.edu FU VA Merit, Denver Research Institute [NIH-5T32HL007171, NIH-5P01HL014985, CCTSI-UL1RR025780]; Center for Women's Health Research; Department of Bioengineering; National Cancer Institute Cancer Center Support Grant [P30CA046934] FX Sources of funding for this study were provided by VA Merit, Denver Research Institute, NIH-5T32HL007171 (ACK), NIH-5P01HL014985 (ACK), CCTSI-UL1RR025780 (JEBR), the Center for Women's Health Research (JEBR), and the Department of Bioengineering (PMM). Flow Cytometry is supported through a National Cancer Institute Cancer Center Support Grant (P30CA046934). NR 41 TC 2 Z9 2 U1 1 U2 3 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 1567-7249 EI 1872-8278 J9 MITOCHONDRION JI Mitochondrion PD JAN PY 2016 VL 26 BP 58 EP 71 DI 10.1016/j.mito.2015.12.003 PG 14 WC Cell Biology; Genetics & Heredity SC Cell Biology; Genetics & Heredity GA DE6UC UT WOS:000370768100007 PM 26688338 ER PT J AU Duong, TQ Watts, LT AF Duong, Timothy Q. Watts, Lora T. TI A brief report on MRI investigation of experimental traumatic brain injury SO NEURAL REGENERATION RESEARCH LA English DT Article DE MRI; traumatic brain injury; magnetic resonance imaging; diffusion tensor imaging; cerebral blood flow ID VETERANS AB Traumatic brain injury is a major cause of death and disability. This is a brief report based on a symposium presentation to the 2014 Chinese Neurotrauma Association Meeting in San Francisco, USA. It covers the work from our laboratory in applying multimodal MRI to study experimental traumatic brain injury in rats with comparisons made to behavioral tests and histology. MRI protocols include structural, perfusion, manganese-enhanced, diffusion-tensor MRI, and MRI of blood-brain barrier integrity and cerebrovascular reactivity. C1 [Duong, Timothy Q.] Univ Texas Hlth Sci Ctr San Antonio, South Texas Vet Hlth Care Syst, Res Imaging Inst, Dept Cellular & Struct Biol, San Antonio, TX 78229 USA. Univ Texas Hlth Sci Ctr San Antonio, South Texas Vet Hlth Care Syst, Res Imaging Inst, Dept Ophthalmol, San Antonio, TX 78229 USA. RP Duong, TQ (reprint author), Univ Texas Hlth Sci Ctr San Antonio, South Texas Vet Hlth Care Syst, Res Imaging Inst, Dept Cellular & Struct Biol, San Antonio, TX 78229 USA. EM duongt@uthscsa.edu NR 17 TC 1 Z9 1 U1 0 U2 0 PU MEDKNOW PUBLICATIONS & MEDIA PVT LTD PI MUMBAI PA B-9, KANARA BUSINESS CENTRE, OFF LINK RD, GHAKTOPAR-E, MUMBAI, 400075, INDIA SN 1673-5374 EI 1876-7958 J9 NEURAL REGEN RES JI Neural Regen. Res. PD JAN PY 2016 VL 11 IS 1 BP 15 EP 17 DI 10.4103/1673-5374.169604 PG 3 WC Cell Biology; Neurosciences SC Cell Biology; Neurosciences & Neurology GA DD7ZF UT WOS:000370142800003 PM 26981069 ER PT J AU Fujikawa, DG Pais, ES Aviles, ER Hsieh, KC Bashir, MT AF Fujikawa, Denson G. Pais, Emil S. Aviles, Ernesto R., Jr. Hsieh, Kung-Chiao Bashir, Muhammad Tariq TI Methamphetamine-induced neuronal necrosis: the role of electrographic seizure discharges SO NEUROTOXICOLOGY LA English DT Article DE Electrographic seizures; Excitotoxicity; Methamphetamine; Mouse; Necrosis; Apoptosis ID INTERNUCLEOSOMAL DNA CLEAVAGE; ELECTRON-MICROSCOPIC FINDINGS; INDUCED STATUS EPILEPTICUS; HYPOGLYCEMIC BRAIN-DAMAGE; TEMPORAL EVOLUTION; APOPTOTIC NEURODEGENERATION; RAT-BRAIN; DEATH; DEGENERATION; FRAGMENTATION AB We have evidence that methamphetamine (METH)-induced neuronal death is morphologically necrotic, not apoptotic, as is currently believed, and that electrographic seizures may be responsible. We administered 40 mg/kg i.p. to 12 male C57BL/6 mice and monitored EEGs continuously and rectal temperatures every 15 min, keeping rectal temperatures <41.0 degrees C. Seven of the 12 mice had repetitive electrographic seizure discharges (RESDs) and 5 did not. The RESDs were often not accompanied by behavioral signs of seizures-i.e., they were often not accompanied by clonic forelimb movements. The 7 mice with RESDs had acidophilic neurons (the H&E light-microscopic equivalent of necrotic neurons by ultrastructural examination) in all of 7 brain regions (hippocampal CA1, CA2, CA3 and hilus, amygdala, piriform cortex and entorhinal cortex), the same brain regions damaged following generalized seizures, 24 h after METH administration. The 5 mice without RESDs had a few acidophilic neurons in 4 of the 7 brain regions, but those with RESDs had significantly more in 6 of the 7 brain regions. Maximum rectal temperatures were comparable in mice with and without RESDs, so that cannot explain the difference between the two groups with respect to METH-induced neuronal death. Our data show that METH-induced neuronal death is morphologically necrotic, that EEGs must be recorded to detect electrographic seizure activity in rodents without behavioral evidence of seizures, and that RESDs may be responsible for METH-induced neuronal death. Published by Elsevier Inc. C1 [Fujikawa, Denson G.; Pais, Emil S.; Aviles, Ernesto R., Jr.; Hsieh, Kung-Chiao; Bashir, Muhammad Tariq] VA Greater Los Angeles Healthcare Syst, Sepulveda VA Ambulatory Care Ctr & Nursing Home, Expt Neurol Lab, North Hills, CA USA. [Fujikawa, Denson G.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Neurol, Los Angeles, CA 90095 USA. [Fujikawa, Denson G.] Univ Calif Los Angeles, David Geffen Sch Med, Brain Res Inst, Los Angeles, CA 90095 USA. RP Fujikawa, DG (reprint author), VA Greater Los Angeles Healthcare Syst, Mail Code 151B4,16111 Plummer St, North Hills, CA 91343 USA. EM dfujikaw@ucla.edu FU VA Merit Review grant [I01-BX001858]; VA Greater Los Angeles Research and Development Service; Sepulveda Research Corporation Various Donors Fund; UCLA Department of Neurology Academic Enrichment Fund FX Our study was supported by a VA Merit Review grant (I01-BX001858), the VA Greater Los Angeles Research and Development Service, the Sepulveda Research Corporation Various Donors Fund and the UCLA Department of Neurology Academic Enrichment Fund. Dr. Jeffrey Gornbein, a UCLA biomathematical statistician, provided expert assistance in the statistical analysis of data. NR 28 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0161-813X EI 1872-9711 J9 NEUROTOXICOLOGY JI Neurotoxicology PD JAN PY 2016 VL 52 BP 84 EP 88 DI 10.1016/j.neuro.2015.11.001 PG 5 WC Neurosciences; Pharmacology & Pharmacy; Toxicology SC Neurosciences & Neurology; Pharmacology & Pharmacy; Toxicology GA DE6TW UT WOS:000370767500009 PM 26562800 ER PT J AU Soleymani, T Daniel, S Garvey, WT AF Soleymani, T. Daniel, S. Garvey, W. T. TI Weight maintenance: challenges, tools and strategies for primary care physicians SO OBESITY REVIEWS LA English DT Review DE Maintenance; obesity; primary care; weight loss ID DIABETES-PREVENTION-PROGRAM; LIFE-STYLE INTERVENTION; RANDOMIZED CONTROLLED-TRIAL; CONTROLLED-RELEASE PHENTERMINE/TOPIRAMATE; COMPLICATIONS-CENTRIC APPROACH; CARDIOVASCULAR RISK-FACTORS; OBSTRUCTIVE SLEEP-APNEA; ALL-CAUSE MORTALITY; BARIATRIC SURGERY; CONTROL REGISTRY AB Obesity is recognized as a chronic disease and one of the major healthcare challenges facing us today. Weight loss can be achieved via lifestyle, pharmacological and surgical interventions, but weight maintenance remains a lifetime challenge for individuals with obesity. Guidelines for the management of obesity have highlighted the role of primary care providers (PCPs). This review examines the long-term outcomes of clinical trials to identify effective weight maintenance strategies that can be utilized by PCPs. Because of the broad nature of the topic, a structured PubMed search was conducted to identify relevant research articles, peer-reviewed reviews, guidelines and articles published by regulatory bodies. Trials have demonstrated the benefit of sustained weight loss in managing obesity and its comorbidities. Maintaining 5-10% weight loss for >= 1 year is known to ameliorate many comorbidities. Weight maintenance with lifestyle modification although challenging - is possible but requires long-term support to reinforce diet, physical activity and behavioural changes. The addition of pharmacotherapy to lifestyle interventions promotes greater and more sustained weight loss. Clinical evidence and recently approved pharmacotherapy has given PCPs improved strategies to support their patients with maintenance of weight loss. Further studies are needed to assess the translation of these strategies into clinical practice. C1 [Soleymani, T.; Daniel, S.; Garvey, W. T.] Univ Alabama Birmingham, Dept Nutr Sci, 1720 Second Ave South, Birmingham, AL 35294 USA. [Soleymani, T.; Garvey, W. T.] Birmingham Vet Affairs Med Ctr, Birmingham, AL USA. RP Garvey, WT (reprint author), Univ Alabama Birmingham, Dept Nutr Sci, 1720 Second Ave South, Birmingham, AL 35294 USA. EM garveyt@uab.edu FU Novo Nordisk A/S; Diabetes Research Center at the University of Alabama at Birmingham - National Institutes of Health [DK-079626] FX WTG acts as guarantor and takes responsibility for the content of the article. Editorial assistance was provided by Dr Ian Seymour from AXON Communications, and funded by Novo Nordisk A/S. The authors acknowledge the support of the Diabetes Research Center at the University of Alabama at Birmingham, funded by an award from the National Institutes of Health (DK-079626). NR 129 TC 1 Z9 1 U1 7 U2 17 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1467-7881 EI 1467-789X J9 OBES REV JI Obes. Rev. PD JAN PY 2016 VL 17 IS 1 BP 81 EP 93 DI 10.1111/obr.12322 PG 13 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA DD8EZ UT WOS:000370159500007 PM 26490059 ER PT J AU Little, EC Camp, ER Wang, C Watson, PM Watson, DK Cole, DJ AF Little, E. C. Camp, E. R. Wang, C. Watson, P. M. Watson, D. K. Cole, D. J. TI The CaSm (LSm1) oncogene promotes transformation, chemoresistance and metastasis of pancreatic cancer cells SO ONCOGENESIS LA English DT Article ID EPITHELIAL-MESENCHYMAL TRANSITION; ACTIVATOR RECEPTOR UPAR; SM-LIKE PROTEIN; HIGH-RISK GROUP; PLASMINOGEN-ACTIVATOR; DUCTAL ADENOCARCINOMA; GENE-EXPRESSION; LUNG-CANCER; STEM-CELLS; GEMCITABINE AB The cancer-associated Sm-like (CaSm) oncogene is overexpressed in 87% of human pancreatic tumor samples and CaSm knockdown has demonstrated therapeutic efficacy in murine models of pancreatic cancer. Evidence indicates that CaSm modulates messenger RNA degradation; however, its target genes and the mechanisms by which CaSm promotes pancreatic cancer remain largely unknown. Here, we demonstrate that the CaSm overexpression alters several hallmarks of cancer-including transformation, proliferation, chemoresistance and metastasis. Doxycycline-induced CaSm expression enhanced proliferation and both anchorage-dependent and -independent growth of the human Panc-1 cells in vitro. CaSm induction decreased gemcitabine-induced cytotoxicity and altered the expression of apoptotic regulation genes, including Bad, E2F1 and Bcl-X-L. CaSm-overexpressing Panc-1 cells were twofold more migratory and fourfold more invasive than the driver controls and demonstrated characteristics of epithelial-to-mesenchymal transition such as morphological changes and decreased E-cadherin expression. CaSm induction resulted in changes in RNA expression of metastasis-associated genes such as MMP1, SerpinB5, uPAR and Slug. Using a murine model of metastatic pancreatic cancer, injection of CaSm-induced Panc-1 cells resulted in a higher abundance of hepatic metastatic lesions. Overall, CaSm overexpression contributed to a more aggressive cancer phenotype in Panc-1 cells, further supporting the use of CaSm as a therapeutic target against pancreatic cancer. C1 [Little, E. C.; Cole, D. J.] Med Univ S Carolina, Dept Microbiol & Immunol, Charleston, SC 29425 USA. [Little, E. C.; Camp, E. R.; Wang, C.; Watson, P. M.; Watson, D. K.; Cole, D. J.] Med Univ S Carolina, Hollings Canc Ctr, Charleston, SC 29425 USA. [Camp, E. R.; Wang, C.; Cole, D. J.] Med Univ S Carolina, Dept Surg, 114 Doughty St,BM 241,MSC 295, Charleston, SC 29425 USA. [Camp, E. R.] Ralph H Johnson VA Med Ctr, Charleston, SC USA. [Watson, P. M.; Watson, D. K.] Med Univ S Carolina, Dept Pathol & Lab Med, Charleston, SC 29425 USA. [Watson, D. K.] Med Univ S Carolina, Dept Biochem & Mol Biol, Charleston, SC 29425 USA. RP Camp, ER (reprint author), Med Univ S Carolina, Dept Surg, 114 Doughty St,BM 241,MSC 295, Charleston, SC 29425 USA. EM campe@musc.edu FU National Institutes of Health [R01CA123159, K08CA142904]; South Carolina Clinical and Translational Research through NIH [UL1TR000062]; Hollings Cancer Center Medical University of South Carolina [POCA138313] FX This work was supported by funding from the National Institutes of Health (R01CA123159 (DJC, DKW) and K08CA142904 (ERC)) and the South Carolina Clinical and Translational Research through NIH grant number UL1TR000062. We thank the MUSC Hollings Cancer Center Tissue Biorepository and the Flow Cytometry core facilities for their assistance. The shared resources are supported in part by the Hollings Cancer Center Medical University of South Carolina Support Grant (POCA138313) NR 42 TC 0 Z9 0 U1 1 U2 2 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 2157-9024 J9 ONCOGENESIS JI Oncogenesis PD JAN PY 2016 VL 5 AR e182 DI 10.1038/oncsis.2015.45 PG 10 WC Oncology SC Oncology GA DE2TP UT WOS:000370480200003 PM 26751936 ER PT J AU Mihos, CG Krishna, RK Kherada, N Larrauri-Reyes, M Tolentino, A Santana, O AF Mihos, Christos G. Krishna, Rama K. Kherada, Nisharahmed Larrauri-Reyes, Maiteder Tolentino, Alfonso Santana, Orlando TI The use of ranolazine in non-anginal cardiovascular disorders: A review of current data and ongoing randomized clinical trials SO PHARMACOLOGICAL RESEARCH LA English DT Review DE Cardiovascular effects; Non-anginal; Ranolazine; Randomized trials ID ONSET ATRIAL-FIBRILLATION; PERCUTANEOUS CORONARY INTERVENTION; LATE SODIUM CURRENT; LATE NA+ CURRENT; LATE I-NA; ANTIANGINAL AGENT; HEART-FAILURE; ION CHANNELS; CASE SERIES; AMIODARONE AB Ranolazine has characteristic properties of a selective inhibitor of the inward sodium current. It is primarily indicated as an anti-anginal agent in patients with coronary artery disease and chronic stable angina. Recently, ranolazine has been noted to possibly impart beneficial effects in various other cardiac conditions, including new-onset, paroxysmal, and chronic atrial fibrillation, post-operative atrial fibrillation, ventricular arrhythmias, post-revascularization coronary artery disease, chemotherapeutic cardiotoxicity, and diastolic and microvascular dysfunction. Herein, we present a review of the current clinical evidence describing the adjunctive or synergistic effects of ranolazine in non-angina related cardiovascular disorders, and include a discussion of the ongoing randomized trials investigating the therapeutic potential of ranolazine in a variety of cardiovascular diseases. (C) 2015 Elsevier Ltd. All rights reserved. C1 [Mihos, Christos G.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Cardiac Ultrasound Lab, Boston, MA USA. [Krishna, Rama K.; Kherada, Nisharahmed; Larrauri-Reyes, Maiteder; Tolentino, Alfonso; Santana, Orlando] Columbia Univ, Div Cardiol, Mt Sinai Heart Inst, Miami Beach, FL USA. RP Santana, O (reprint author), Columbia Univ, Div Cardiol, Mt Sinai Heart Inst, Echocardiog Lab, 4300 Alton Rd, Miami Beach, FL 33140 USA. EM osantana@msmc.com NR 62 TC 2 Z9 2 U1 2 U2 4 PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 1043-6618 J9 PHARMACOL RES JI Pharmacol. Res. PD JAN PY 2016 VL 103 BP 49 EP 55 DI 10.1016/j.phrs.2015.10.018 PG 7 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA DE2KV UT WOS:000370457100005 PM 26546970 ER PT J AU Janke-Stedronsky, SR Greenawalt, DS Stock, EM Tsan, JY MacCarthy, AA MacCarthy, DJ Copeland, LA AF Janke-Stedronsky, Shonda R. Greenawalt, David S. Stock, Eileen M. Tsan, Jack Y. MacCarthy, Andrea A. MacCarthy, Daniel J. Copeland, Laurel A. TI Association of Parental Status and Diagnosis of Posttraumatic Stress Disorder Among Veterans of Operations Iraqi and Enduring Freedom SO PSYCHOLOGICAL TRAUMA-THEORY RESEARCH PRACTICE AND POLICY LA English DT Article DE posttraumatic stress disorder; parenting; gender; veterans ID MALE VIETNAM VETERANS; MENTAL-HEALTH; OEF/OIF VETERANS; RISK-FACTORS; DEPLOYMENT; PTSD; COMBAT; AFGHANISTAN; RESILIENCE; FEMALE AB Research indicates that concerns about disruption of family relationships during military service may be associated with greater posttraumatic stress symptomatology. The current study sought to extend previous findings by examining the relative odds of a posttraumatic stress disorder (PTSD) diagnosis among Operations Enduring and Iraqi Freedom (OEF/OIF) veterans with dependent children versus veterans without dependent children. Administrative databases were queried to identify 36,334 OEF/OIF veterans with dependent children seeking care in the Veterans Health Administration (VA) during fiscal years 2006-2009. These veterans were matched 1: 1 on age, gender, and demobilization date to veterans without dependent children (N = 72,668). In unconditional analyses, OEF/OIF veterans with dependent children versus those without were significantly more likely to incur a PTSD diagnosis (44% vs. 28%). After controlling for demographic variables, mental health utilization, and other serious mental illness, OEF/OIF veterans with dependent children were about 40% more likely to carry a diagnosis of PTSD. The association was stronger for men than for women. It may be of value for clinicians to consider parental status when assessing and treating veterans with PTSD. In-depth study of OEF/OIF veterans is needed to determine whether disruption of family relationships leads to increased psychological stress or parents are more likely than nonparents to seek VA mental health services for PTSD symptoms. C1 [Janke-Stedronsky, Shonda R.] Univ Texas Austin, Southwestern Residency Programs, Seton Healthcare Network, Dept Psychiat, Austin, TX 78712 USA. [Greenawalt, David S.] Albany Stratton Vet Affairs Med Ctr, Albany, NY USA. [Stock, Eileen M.] Texas A&M Hlth Sci Ctr, Coll Med, Dept Internal Med, Temple, TX USA. [Stock, Eileen M.; Copeland, Laurel A.] Cent Texas Vet Hlth Care Syst, Ctr Appl Hlth Res, Temple, TX USA. [Stock, Eileen M.; Copeland, Laurel A.] Baylor Scott & White Hlth, Temple, TX USA. [Tsan, Jack Y.] Cent Texas Vet Hlth Care Syst, Psychol Serv, Austin, TX USA. [MacCarthy, Andrea A.; MacCarthy, Daniel J.] South Texas Vet Hlth Care Syst, Res Serv, San Antonio, TX USA. [Copeland, Laurel A.] Texas A&M Hlth Sci Ctr, Coll Med, Internal Med, Temple, TX USA. RP Copeland, LA (reprint author), Ctr Appl Hlth Res, 2102 Birdcreek Dr, Temple, TX 76502 USA. EM LaurelACopeland@gmail.com OI Copeland, Laurel/0000-0002-9478-0209 FU Department of Veterans Affairs; Central Texas Veterans Health Care System; VHA HSRD [IIR-09-335]; Baylor Scott & White Health, Temple, Texas FX This research was supported by Department of Veterans Affairs, Central Texas Veterans Health Care System, and VHA HSR&D Award IIR-09-335 (Laurel A. Copeland, PI), with additional support from Baylor Scott & White Health, Temple, Texas. The views are those of the authors and do not necessarily represent the views of the Department of Veterans Affairs. NR 43 TC 1 Z9 1 U1 1 U2 4 PU EDUCATIONAL PUBLISHING FOUNDATION-AMERICAN PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST, NE, WASHINGTON, DC 20002-4242 USA SN 1942-9681 EI 1942-969X J9 PSYCHOL TRAUMA-US JI Psychol. Trauma PD JAN PY 2016 VL 8 IS 1 BP 72 EP 79 DI 10.1037/tra0000014 PG 8 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA DD8KW UT WOS:000370176400010 PM 25793320 ER PT J AU Marques, L Eustis, EH Dixon, L Valentine, SE Borba, CPC Simon, N Kaysen, D Wiltsey-Stirman, S AF Marques, Luana Eustis, Elizabeth H. Dixon, Louise Valentine, Sarah E. Borba, Christina P. C. Simon, Naomi Kaysen, Debra Wiltsey-Stirman, Shannon TI Delivering Cognitive Processing Therapy in a Community Health Setting: The Influence of Latino Culture and Community Violence on Posttraumatic Cognitions SO PSYCHOLOGICAL TRAUMA-THEORY RESEARCH PRACTICE AND POLICY LA English DT Article DE PTSD; CPT; Latino; culture; community violence ID UNITED-STATES; STRESS-DISORDER; PTSD; ADAPTATION; DEPRESSION; ETHNICITY; REFUGEES; VICTIMS; IMPACT AB Despite the applicability of cognitive processing therapy (CPT) for posttraumatic stress disorder (PTSD) to addressing sequelae of a range of traumatic events, few studies have evaluated whether the treatment itself is applicable across diverse populations. The present study examined differences and similarities among non-Latino, Latino Spanish-speaking, and Latino English-speaking clients in rigid beliefs-or "stuck points"-associated with PTSD symptoms in a sample of community mental health clients. We utilized the procedures of content analysis to analyze stuck point logs and impact statements of 29 participants enrolled in a larger implementation trial for CPT. Findings indicated that the content of stuck points was similar across Latino and non-Latino clients, although fewer total stuck points were identified for Latino clients compared to non-Latino clients. Given that identification of stuck points is central to implementing CPT, difficulty identifying stuck points could pose significant challenges for implementing CPT among Latino clients and warrants further examination. Thematic analysis of impact statements revealed the importance of family, religion, and the urban context (e.g., poverty, violence exposure) in understanding how clients organize beliefs and emotions associated with trauma. Clinical recommendations for implementing CPT in community settings and the identification of stuck points are provided. C1 [Marques, Luana; Dixon, Louise; Valentine, Sarah E.; Borba, Christina P. C.; Simon, Naomi] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. [Marques, Luana; Valentine, Sarah E.; Borba, Christina P. C.; Simon, Naomi] Harvard Univ, Sch Med, Boston, MA USA. [Eustis, Elizabeth H.] Univ Massachusetts, Boston, MA 02125 USA. [Kaysen, Debra] Univ Washington, Dept Psychiat & Behav Sci, Dept Psychol, Dept Global Hlth, Boston, MA USA. [Wiltsey-Stirman, Shannon] Natl Ctr PTSD, Womens Hlth Sci Div, Boston, MA USA. [Wiltsey-Stirman, Shannon] VA Boston Healthcare Syst, Boston, MA USA. [Wiltsey-Stirman, Shannon] Boston Univ, Dept Psychiat, Boston, MA 02215 USA. RP Marques, L (reprint author), Massachusetts Gen Hosp, Dept Psychiat, Community Psychiat PRIDE, 70 Everett Ave,Suite 516, Chelsea, MA 02150 USA. EM lmarques@mgh.harvard.edu OI Wiltsey Stirman, Shannon/0000-0001-9917-5078 FU National Institutes of Health [NIMH K23 MH096029-01A1] FX This study was funded by a grant from the National Institutes of Health (NIMH K23 MH096029-01A1) awarded to Luana Marques. The authors express sincere gratitude to the study providers and to the project's research assistants. NR 30 TC 1 Z9 1 U1 3 U2 7 PU EDUCATIONAL PUBLISHING FOUNDATION-AMERICAN PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST, NE, WASHINGTON, DC 20002-4242 USA SN 1942-9681 EI 1942-969X J9 PSYCHOL TRAUMA-US JI Psychol. Trauma PD JAN PY 2016 VL 8 IS 1 BP 98 EP 106 DI 10.1037/tra0000044 PG 9 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA DD8KW UT WOS:000370176400013 PM 25961865 ER PT J AU Gutner, CA Gallagher, MW Baker, AS Sloan, DM Resick, PA AF Gutner, Cassidy A. Gallagher, Matthew W. Baker, Aaron S. Sloan, Denise M. Resick, Patricia A. TI Time Course of Treatment Dropout in Cognitive-Behavioral Therapies for Posttraumatic Stress Disorder SO PSYCHOLOGICAL TRAUMA-THEORY RESEARCH PRACTICE AND POLICY LA English DT Article DE treatment dropout; posttraumatic stress disorder; cognitive-behavioral therapy ID ADMINISTERED PTSD SCALE; PROLONGED EXPOSURE; MENTAL-HEALTH; PROCESSING THERAPY; METAANALYSIS; VICTIMS; PSYCHOTHERAPY; CLINICS; TRIAL AB A substantial minority of people drop out of cognitive-behavioral therapies (CBTs) for posttraumatic stress disorder (PTSD). There has been considerable research investigating who drops out of PTSD treatment; however, the question of when dropout occurs has received far less attention. The purpose of the current study was to examine when individuals drop out of CBT for PTSD. Women participants (N = 321) were randomized to 1 of several PTSD treatment conditions. The conditions included prolonged exposure (PE), cognitive processing therapy (CPT), CPT-cognitive only (CPT-C), and written accounts (WA). Survival analysis was used to examine temporal pattern of treatment dropout. Thirty-nine percent of participants dropped out of treatment, and those who dropped out tended to do so by midtreatment. Moreover, the pattern of treatment dropout was consistent across CBT conditions. Additional research is needed to examine if treatment dropout patterns are consistent across treatment modalities and settings. C1 [Gutner, Cassidy A.; Gallagher, Matthew W.; Sloan, Denise M.] VA Boston Healthcare Syst, Natl Ctr PTSD, Boston, MA USA. [Gutner, Cassidy A.; Gallagher, Matthew W.; Baker, Aaron S.; Sloan, Denise M.] Boston Univ, Sch Med, Dept Psychiat, Boston, MA 02215 USA. [Baker, Aaron S.] Univ LaVerne, Dept Psychol, La Verne, CA 91750 USA. [Resick, Patricia A.] Duke Univ, Dept Psychiat, Durham, NC 27706 USA. RP Sloan, DM (reprint author), VA Natl Ctr PTSD, 150 South Huntington Ave, Boston, MA 02130 USA. EM denise.sloan@va.gov FU National Institute of Mental Health [NIH-1 R01-MH51509, NIH-2 R01-MH51509, T32MH019836-15A2, 1K23MH103396-01A1] FX This work was supported by National Institute of Mental Health Grant NIH-1 R01-MH51509 and National Institute of Mental Health Grant NIH-2 R01-MH51509 awarded to Patricia A. Resick while at the University of Missouri-St. Louis. Cassidy A. Gutner and Aaron S. Baker were supported by a National Institute of Mental Health grant (T32MH019836-15A2) awarded to Terence M. Keane. Cassidy A. Gutner was also supported by a National Institute of Mental Health grant (1K23MH103396-01A1) awarded to this author. NR 27 TC 4 Z9 4 U1 4 U2 4 PU EDUCATIONAL PUBLISHING FOUNDATION-AMERICAN PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST, NE, WASHINGTON, DC 20002-4242 USA SN 1942-9681 EI 1942-969X J9 PSYCHOL TRAUMA-US JI Psychol. Trauma PD JAN PY 2016 VL 8 IS 1 BP 115 EP 121 DI 10.1037/tra0000062 PG 7 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA DD8KW UT WOS:000370176400015 PM 26098737 ER PT J AU Otrakji, A Digumarthy, SR Lo Gullo, R Flores, EJ Shepard, JAO Kalra, MK AF Otrakji, Alexi Digumarthy, Subba R. Lo Gullo, Roberto Flores, Efren J. Shepard, Jo-Anne O. Kalra, Mannudeep K. TI Dual-Energy CT: Spectrum of Thoracic Abnormalities SO RADIOGRAPHICS LA English DT Article ID THROMBOEMBOLIC PULMONARY-HYPERTENSION; COMPUTED-TOMOGRAPHY; INITIAL-EXPERIENCE; IMAGE QUALITY; ONCOLOGIC APPLICATIONS; CLINICAL-APPLICATIONS; ADDITIONAL VALUE; METAL ARTIFACTS; ANGIOGRAPHY; LUNG AB Recent studies have demonstrated that dual-energy computed tomography (CT) can provide useful information in several chest-related clinical indications. Compared with single-energy CT, dual-energy CT of the chest is feasible with the use of a radiation-dose-neutral scanning protocol. This article highlights the different types of images that can be generated by using dual-energy CT protocols such as virtual monochromatic, virtual unenhanced (ie, water), and pulmonary blood volume (ie, iodine) images. The physical basis of dual-energy CT and material decomposition are explained. The advantages of the use of virtual low-monochromatic images include reduced volume of intravenous contrast material and improved contrast resolution of images. The use of virtual high-monochromatic images can reduce beam hardening and contrast streak artifacts. The pulmonary blood volume images can help differentiate various parenchymal abnormalities, such as infarcts, atelectasis, and pneumonias, as well as airway abnormalities. The pulmonary blood volume images allow quantitative and qualitative assessment of iodine distribution. The estimation of iodine concentration (quantitative assessment) provides objective analysis of enhancement. The advantages of virtual unenhanced images include differentiation of calcifications, talc, and enhanced thoracic structures. Dual-energy CT has applications in oncologic imaging, including diagnosis of thoracic masses, treatment planning, and assessment of response to treatment. Understanding the concept of dual-energy CT and its clinical application in the chest are the goals of this article. (C)RSNA, 2016 C1 [Otrakji, Alexi; Digumarthy, Subba R.; Lo Gullo, Roberto; Flores, Efren J.; Shepard, Jo-Anne O.; Kalra, Mannudeep K.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Div Thorac Imaging,Dept Radiol, 55 Fruit St,Founders 213, Boston, MA 02114 USA. RP Otrakji, A (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Div Thorac Imaging,Dept Radiol, 55 Fruit St,Founders 213, Boston, MA 02114 USA. EM aotrakji@partners.org NR 42 TC 0 Z9 0 U1 2 U2 5 PU RADIOLOGICAL SOC NORTH AMERICA PI OAK BROOK PA 820 JORIE BLVD, OAK BROOK, IL 60523 USA SN 0271-5333 J9 RADIOGRAPHICS JI Radiographics PD JAN-FEB PY 2016 VL 36 IS 1 BP 38 EP 52 DI 10.1148/rg.2016150081 PG 15 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA DE0TD UT WOS:000370336700004 PM 26761530 ER PT J AU Singh, AK Ditkofsky, NG York, JD Abujudeh, HH Avery, LA Brunner, JF Sodickson, AD Lev, MH AF Singh, Ajay K. Ditkofsky, Noah G. York, John D. Abujudeh, Hani H. Avery, Laura A. Brunner, John F. Sodickson, Aaron D. Lev, Michael H. TI Blast Injuries: From Improvised Explosive Device Blasts to the Boston Marathon Bombing SO RADIOGRAPHICS LA English DT Article ID TRAUMATIC BRAIN-INJURY; TERRORIST BOMBINGS; THORACIC TRAUMA; FOREIGN-BODIES; EXPERIENCE; PATTERN; MECHANISM; SYSTEM; INCIDENTS; HOSPITALS AB Although most trauma centers have experience with the imaging and management of gunshot wounds, in most regions blast wounds such as the ones encountered in terrorist attacks with the use of improvised explosive devices (IEDs) are infrequently encountered outside the battlefield. As global terrorism becomes a greater concern, it is important that radiologists, particularly those working in urban trauma centers, be aware of the mechanisms of injury and the spectrum of primary, secondary, tertiary, and quaternary blast injury patterns. Primary blast injuries are caused by barotrauma from the initial increased pressure of the explosive detonation and the rarefaction of the atmosphere immediately afterward. Secondary blast injuries are caused by debris carried by the blast wind and most often result in penetrating trauma from small shrapnel. Tertiary blast injuries are caused by the physical displacement of the victim and the wide variety of blunt or penetrating trauma sustained as a result of the patient impacting immovable objects such as surrounding cars, walls, or fences. Quaternary blast injuries include all other injuries, such as burns, crush injuries, and inhalational injuries. Radiography is considered the initial imaging modality for assessment of shrapnel and fractures. Computed tomography is the optimal test to assess penetrating chest, abdominal, and head trauma. The mechanism of blast injuries and the imaging experience of the victims of the Boston Marathon bombing are detailed, as well as musculoskeletal, neurologic, gastrointestinal, and pulmonary injury patterns from blast injuries. (C) RSNA, 2016. C1 [Singh, Ajay K.; Abujudeh, Hani H.; Avery, Laura A.; Lev, Michael H.] Massachusetts Gen Hosp, Dept Radiol, 55 Fruit St,FND-210, Boston, MA 02114 USA. [Ditkofsky, Noah G.] Univ Toronto, Sunnybrook Hlth Sci Ctr, Dept Med Imaging, Toronto, ON, Canada. [York, John D.] Naval Med Ctr, Dept Radiol, Portsmouth, VA USA. [Brunner, John F.] Univ So Calif, Dept Radiol, Los Angeles, CA USA. [Sodickson, Aaron D.] Brigham & Womens Hosp, Dept Radiol, 75 Francis St, Boston, MA 02115 USA. RP Singh, AK (reprint author), Massachusetts Gen Hosp, Dept Radiol, 55 Fruit St,FND-210, Boston, MA 02114 USA. EM mghpartners@yahoo.com FU GE Healthcare; Millennium Pharmaceuticals FX M.H.L. Activities related to the present article: disclosed no relevant relationships. Activities not related to the present article: institutional grant and personal fees from GE Healthcare; personal fees from Millennium Pharmaceuticals. Other activities: disclosed no relevant relationships. NR 65 TC 0 Z9 0 U1 5 U2 11 PU RADIOLOGICAL SOC NORTH AMERICA PI OAK BROOK PA 820 JORIE BLVD, OAK BROOK, IL 60523 USA SN 0271-5333 J9 RADIOGRAPHICS JI Radiographics PD JAN-FEB PY 2016 VL 36 IS 1 BP 295 EP 307 DI 10.1148/rg.2016150114 PG 13 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA DE0TD UT WOS:000370336700020 PM 26761543 ER PT B AU Iaccarino, MA Bhatnagar, S Zafonte, R AF Iaccarino, Mary Alexis Bhatnagar, Saurabha Zafonte, Ross BE Brashear, A TI Management of Brain Injury Related Spasticity SO SPASTICITY: DIAGNOSIS AND MANAGEMENT, SECOND EDITION LA English DT Article; Book Chapter ID UPPER-LIMB SPASTICITY; INTRATHECAL BACLOFEN THERAPY; TOXIN TYPE-A; CONTROLLED-TRIAL; BOTULINUM-TOXIN; DOUBLE-BLIND; TIZANIDINE HYDROCHLORIDE; MULTIPLE-SCLEROSIS; SPINAL SPASTICITY; VEGETATIVE STATE C1 [Iaccarino, Mary Alexis] Harvard Univ, Sch Med, Dept Phys Med & Rehabil, Brain Injury Med, Boston, MA USA. [Iaccarino, Mary Alexis; Bhatnagar, Saurabha; Zafonte, Ross] Spaulding Rehabil Hosp, Boston, MA USA. [Bhatnagar, Saurabha] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Phys Med & Rehabil,Phys Med & Rehabil Reside, Boston, MA USA. [Zafonte, Ross] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Phys Med & Rehabil, Boston, MA USA. RP Iaccarino, MA (reprint author), Harvard Univ, Sch Med, Dept Phys Med & Rehabil, Brain Injury Med, Boston, MA USA. NR 75 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 978-1-62070-072-3 PY 2016 BP 413 EP 428 PG 16 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA BE1AP UT WOS:000367632500026 ER PT J AU Singh, P Yoon, SS Kuo, B AF Singh, Prashant Yoon, Sonia S. Kuo, Braden TI Nausea: a review of pathophysiology and therapeutics SO THERAPEUTIC ADVANCES IN GASTROENTEROLOGY LA English DT Review DE autonomic nervous system; central nervous system; diagnostics; nausea; neuroendocrine; pathogenesis; therapeutics; vomiting ID CHEMOTHERAPY-INDUCED NAUSEA; GASTRIC ELECTRICAL-STIMULATION; CYCLIC VOMITING SYNDROME; RECEIVING CANCER-CHEMOTHERAPY; SLOW-WAVE DYSRHYTHMIAS; MOTION SICKNESS; TRICYCLIC ANTIDEPRESSANTS; DIABETIC GASTROPARESIS; MYOELECTRICAL ACTIVITY; RECEPTOR ANTAGONIST AB The sensation of nausea is a common occurrence with diverse causes and a significant disease burden. Nausea is considered to function as a protective mechanism, warning the organism to avoid potential toxic ingestion. Less adaptive circumstances are also associated with nausea, including post-operative nausea, chemotherapy-induced nausea, and motion sickness. A common definition of nausea identifies the symptom as a precursor to the act of vomiting. The interaction, though present, does not appear to be a simple relationship. Nausea is unfortunately the 'neglected symptom', with current accepted therapy generally directed at improving gastrointestinal motility or acting to relieve emesis. Improved understanding of the pathophysiological basis of nausea has important implications for exploiting novel mechanisms or developing novel therapies for nausea relief. C1 [Kuo, Braden] Massachusetts Gen Hosp, GI Unit, 55 Fruit St,Blake 4, Boston, MA 02114 USA. [Singh, Prashant] Massachusetts Gen Hosp, Dept Med, Div Gastroenterol, Boston, MA 02114 USA. [Yoon, Sonia S.] Weill Cornell Med Coll, Div Gastroenterol, New York, NY USA. RP Kuo, B (reprint author), Massachusetts Gen Hosp, GI Unit, 55 Fruit St,Blake 4, Boston, MA 02114 USA. EM bkuo@partners.org FU Takeda; Furiex Pharmaceuticals; Genova Diagnostics FX Dr Braden Kuo has received fees for serving as a consultant for Takeda, Furiex Pharmaceuticals and Genova Diagnostics, and received research funding from Furiex Pharmaceuticals. NR 94 TC 5 Z9 5 U1 2 U2 7 PU SAGE PUBLICATIONS LTD PI LONDON PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND SN 1756-283X EI 1756-2848 J9 THER ADV GASTROENTER JI Ther. Adv. Gastroenterol. PD JAN PY 2016 VL 9 IS 1 BP 98 EP 112 DI 10.1177/1756283X15618131 PG 15 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA DE1VT UT WOS:000370415300010 PM 26770271 ER PT J AU Smith, CJ Saftlas, AF Spracklen, CN Triche, EW Bjonnes, A Keating, B Saxena, R Breheny, PJ Dewan, AT Robinson, JG Hoh, J Ryckman, KK AF Smith, Caitlin J. Saftlas, Audrey F. Spracklen, Cassandra N. Triche, Elizabeth W. Bjonnes, Andrew Keating, Brendan Saxena, Richa Breheny, Patrick J. Dewan, Andrew T. Robinson, Jennifer G. Hoh, Josephine Ryckman, Kelli K. TI Genetic Risk Score for Essential Hypertension and Risk of Preeclampsia SO AMERICAN JOURNAL OF HYPERTENSION LA English DT Article DE blood pressure; genetic epidemiology; genetic predisposition to disease; hypertension; maternal; preeclampsia; pregnancy ID GENOME-WIDE ASSOCIATION; MEAN ARTERIAL-PRESSURE; CARDIOVASCULAR-DISEASE; BLOOD-PRESSURE; LATER LIFE; METAANALYSIS; PREGNANCY; GENOTYPE; PREDICTION; VARIANTS AB BACKGROUND Preeclampsia is a hypertensive complication of pregnancy characterized by novel onset of hypertension after 20 weeks gestation, accompanied by proteinuria. Epidemiological evidence suggests that genetic susceptibility exists for preeclampsia; however, whether preeclampsia is the result of underlying genetic risk for essential hypertension has yet to be investigated. Based on the hypertensive state that is characteristic of preeclampsia, we aimed to determine if established genetic risk scores (GRSs) for hypertension and blood pressure are associated with preeclampsia. METHODS Subjects consisted of 162 preeclamptic cases and 108 normotensive pregnant controls, all of Iowa residence. Subjects' DNA was extracted from buccal swab samples and genotyped on the Affymetrix Genome-wide Human SNP Array 6.0 (Affymetrix, Santa Clara, CA). Missing genotypes were imputed using MaCH and Minimac software. GRSs were calculated for hypertension, systolic blood pressure (SBP), diastolic blood pressure (DBP), and mean arterial pressure (MAP) using established genetic risk loci for each outcome. Regression analyses were performed to determine the association between GRS and risk of preeclampsia. These analyses were replicated in an independent US population of 516 cases and 1,097 controls of European ancestry. RESULTS GRSs for hypertension, SBP, DBP, and MAP were not significantly associated with risk for preeclampsia (P > 0.189). The results of the replication analysis also yielded nonsignificant associations. CONCLUSIONS GRSs for hypertension and blood pressure are not associated with preeclampsia, suggesting that an underlying predisposition to essential hypertension is not on the causal pathway of preeclampsia. C1 [Smith, Caitlin J.; Saftlas, Audrey F.; Spracklen, Cassandra N.; Robinson, Jennifer G.; Ryckman, Kelli K.] Univ Iowa, Dept Epidemiol, Coll Publ Hlth, Iowa City, IA USA. [Spracklen, Cassandra N.] Univ N Carolina, Dept Genet, Chapel Hill, NC USA. [Triche, Elizabeth W.] Brown Univ, Sch Publ Hlth, Dept Epidemiol, Providence, RI 02912 USA. [Bjonnes, Andrew; Saxena, Richa] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA. [Bjonnes, Andrew; Saxena, Richa] Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, Boston, MA 02114 USA. [Bjonnes, Andrew; Saxena, Richa] Broad Inst, Program Med & Populat Genet, Cambridge, MA USA. [Keating, Brendan] Univ Penn, Dept Surg, Penn Transplant Inst, Perelman Sch Med, Philadelphia, PA 19104 USA. [Keating, Brendan] Childrens Hosp Philadelphia, Ctr Appl Genom, Abramson Res Ctr, Philadelphia, PA 19104 USA. [Breheny, Patrick J.] Univ Iowa, Coll Publ Hlth, Dept Biostat, Iowa City, IA USA. [Dewan, Andrew T.] Yale Univ, Sch Publ Hlth, Dept Chron Dis Epidemiol, New Haven, CT USA. [Hoh, Josephine] Yale Univ, Sch Publ Hlth, Dept Environm Hlth Sci, New Haven, CT USA. RP Ryckman, KK (reprint author), Univ Iowa, Dept Epidemiol, Coll Publ Hlth, Iowa City, IA USA. EM kelli-ryckman@uiowa.edu FU National Institute of Child Health and Human Development, National Institutes of Health [R01 HD32579]; Verto Institute; Gertie Marx Grant from the Society for Obstetric Anesthesia and Perinatology FX The SOPHIA study was supported by the National Institute of Child Health and Human Development, National Institutes of Health (R01 HD32579), and the Verto Institute. The replication study was funded in part by a Gertie Marx Grant from the Society for Obstetric Anesthesia and Perinatology. We acknowledge contribution of samples for IBC array genotyping by preeclampsia investigators from Boston (B. Bateman and S.A. Karumanchi), Iowa (J. Murray), USC (M.L. Wilson), and Yale (E. Norwitz) as well as contribution of genotype data from the preeclampsia CARe IBC study.30 NR 30 TC 1 Z9 2 U1 1 U2 5 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0895-7061 EI 1941-7225 J9 AM J HYPERTENS JI Am. J. Hypertens. PD JAN PY 2016 VL 29 IS 1 BP 17 EP 24 DI 10.1093/ajh/hpv069 PG 8 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA DD5WV UT WOS:000369996400005 PM 26002928 ER PT J AU McLeish, AC Luberto, CM O'Bryan, EM AF McLeish, Alison C. Luberto, Christina M. O'Bryan, Emily M. TI Anxiety Sensitivity and Reactivity to Asthma-Like Sensations Among Young Adults With Asthma SO BEHAVIOR MODIFICATION LA English DT Article DE anxiety; anxiety sensitivity; asthma; lung function; reactivity ID QUALITY-OF-LIFE; PANIC DISORDER; CIGARETTE-SMOKING; HEALTH; PREVENTION; DEPRESSION; COMMUNITY; CARE; VULNERABILITY; VALIDATION AB Anxiety sensitivity, particularly the physical concerns domain, is associated with more problematic asthma symptoms and greater functional limitations. It has been theorized that anxiety sensitivity fosters greater reactivity to asthma-related physical sensations; however, this theory has yet to be empirically tested. Thus, the present investigation sought to examine the role of anxiety sensitivity-physical concerns in terms of affective and physical reactivity to asthma-like symptoms. Participants were 101 undergraduates with asthma (76.2% female, M-age = 19.69 years, SD = 3.77 years, range = 18-49 years) who completed self-report measures and a straw-breathing task. Results indicated that after controlling for the effects of gender, asthma control (i.e., how well one's asthma symptoms are managed or controlled), and negative affectivity, greater levels of anxiety sensitivity-physical concerns significantly predicted greater anxiety (4.7% unique variance) and asthma symptoms (6.9% unique variance) and lower levels of lung function (4.4% unique variance) after the straw-breathing task. These findings suggest that individuals with asthma who are fearful of physiological arousal are a particularly at-risk population for poor asthma outcomes because of this greater reactivity and could benefit from interventions targeting anxiety sensitivity. C1 [McLeish, Alison C.] Univ Cincinnati, Dept Psychol, POB 210376, Cincinnati, OH 45221 USA. [Luberto, Christina M.] Univ Cincinnati, Cincinnati, OH 45221 USA. [O'Bryan, Emily M.] Univ Cincinnati, Clin Psychol Doctoral Program, Cincinnati, OH 45221 USA. [Luberto, Christina M.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Boston, MA 02115 USA. RP McLeish, AC (reprint author), Univ Cincinnati, Dept Psychol, POB 210376, Cincinnati, OH 45221 USA. EM alison.mcleish@uc.edu FU University Research Council at the University of Cincinnati FX The author(s) disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: This research was supported, in part, by a Graduate Student Research Fellowship grant awarded to the second author (C.M.L.) from the University Research Council at the University of Cincinnati. NR 36 TC 3 Z9 3 U1 0 U2 1 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0145-4455 EI 1552-4167 J9 BEHAV MODIF JI Behav. Modificat. PD JAN-MAR PY 2016 VL 40 IS 1-2 SI SI BP 164 EP 177 DI 10.1177/0145445515607047 PG 14 WC Psychology, Clinical SC Psychology GA DD5ZC UT WOS:000370002500009 PM 26405256 ER PT J AU Baird, SO Hopkins, LB Medina, JL Rosenfield, D Powers, MB Smits, JAJ AF Baird, Scarlett O. Hopkins, Lindsey B. Medina, Johnna L. Rosenfield, David Powers, Mark B. Smits, Jasper A. J. TI Distress Tolerance as a Predictor of Adherence to a Yoga Intervention: Moderating Roles of BMI and Body Image SO BEHAVIOR MODIFICATION LA English DT Article DE yoga; adherence; intervention; distress tolerance; predictors ID PERCEIVED STRESS QUESTIONNAIRE; REDUCING ANXIETY SENSITIVITY; PHYSICAL-ACTIVITY; PANIC DISORDER; DISCOMFORT INTOLERANCE; SHAPE QUESTIONNAIRE; FUTURE-RESEARCH; EXERCISE; WOMEN; EFFICACY AB This study tested whether distress tolerance, body image, and body mass index (BMI) predicted adherence to a yoga intervention. Participants were 27 women who participated in a yoga intervention as part of a randomized controlled trial. Attendance and distress tolerance were assessed weekly, and body image and BMI were measured at baseline. Multilevel modeling revealed a three-way interaction of distress tolerance, BMI, and body image (p < .001). For participants with few body image concerns, distress tolerance was positively associated with adherence regardless of BMI (p = .009). However, for those with poor body image, increases in distress tolerance were associated with increases in adherence among overweight participants (p < .001) but lower adherence among obese participants (p = .007). Distress tolerance may be implicated in adherence to a yoga intervention, although its effects may be dependent on body image concerns, BMI, and their interaction. Research and clinical implications are discussed. C1 [Baird, Scarlett O.] Univ Texas Austin, Clin Psychol Program, Austin, TX 78712 USA. [Baird, Scarlett O.; Medina, Johnna L.; Powers, Mark B.; Smits, Jasper A. J.] Univ Texas Austin, Austin, TX 78712 USA. [Powers, Mark B.] Univ Texas Austin, Dept Psychol, Austin, TX 78712 USA. [Hopkins, Lindsey B.] San Francisco VA Med Ctr, San Francisco, CA USA. [Rosenfield, David] So Methodist Univ, Fac, Dallas, TX 75275 USA. RP Baird, SO (reprint author), Univ Texas Austin, Mental Hlth Res Inst, Dept Psychol, Austin, TX 78712 USA. EM scarlett.baird@utexas.edu OI Hopkins, Lindsey/0000-0002-0577-2961 FU Pure Action, Inc., Austin, Texas, USA FX The author(s) disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: Portions of this research were funded by a grant from Pure Action, Inc., Austin, Texas, USA, a 501c3 nonprofit organization. NR 54 TC 1 Z9 1 U1 5 U2 11 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0145-4455 EI 1552-4167 J9 BEHAV MODIF JI Behav. Modificat. PD JAN-MAR PY 2016 VL 40 IS 1-2 SI SI BP 199 EP 217 DI 10.1177/0145445515612401 PG 19 WC Psychology, Clinical SC Psychology GA DD5ZC UT WOS:000370002500011 PM 26530475 ER PT J AU Kawano, T Nishiyama, K Morita, H Yamamura, O Hiraide, A Hasegawa, K AF Kawano, Takahisa Nishiyama, Kei Morita, Hiroshi Yamamura, Osamu Hiraide, Atsuchi Hasegawa, Kohei TI Association between shelter crowding and incidence of sleep disturbance among disaster evacuees: a retrospective medical chart review study SO BMJ OPEN LA English DT Review ID POSTTRAUMATIC-STRESS-DISORDER; PSYCHIATRIC MORBIDITY; 1999 EARTHQUAKE; MENTAL-HEALTH; JAPAN; SYMPTOMS; SURVIVORS; BEHAVIOR; KATRINA; ADULTS AB Objectives: We determined whether crowding at emergency shelters is associated with a higher incidence of sleep disturbance among disaster evacuees and identified the minimum required personal space at shelters. Design: Retrospective review of medical charts. Setting: 30 shelter-based medical clinics in Ishinomaki, Japan, during the 46 days following the Great Eastern Japan Earthquake and Tsunami in 2011. Participants: Shelter residents who visited eligible clinics. Outcome measures: Based on the result of a locally weighted scatter-plot smoothing technique assessing the relationship between the mean space per evacuee and cumulative incidence of sleep disturbance at the shelter, eligible shelters were classified into crowded and non-crowded shelters. The cumulative incidence per 1000 evacuees was compared between groups, using a Mann-Whitney U test. To assess the association between shelter crowding and the daily incidence of sleep disturbance per 1000 evacuees, quasi-least squares method adjusting for potential confounders was used. Results: The 30 shelters were categorised as crowded (mean space per evacuee <5.0 m(2), 9 shelters) or non-crowded (>= 5.0 m(2), 21 shelters). The study included 9031 patients. Among the eligible patients, 1079 patients (11.9%) were diagnosed with sleep disturbance. Mean space per evacuee during the study period was 3.3 m(2) (SD, 0.8 m(2)) at crowded shelters and 8.6 m(2) (SD, 4.3 m(2)) at non-crowded shelters. The median cumulative incidence of sleep disturbance did not differ between the crowded shelters (2.3/1000 person-days (IQR, 1.6-5.4)) and non-crowded shelters (1.9/1000 person-days (IQR, 1.0-2.8); p=0.20). In contrast, after adjusting for potential confounders, crowded shelters had an increased daily incidence of sleep disturbance (2.6 per 1000 person-days; 95% CI 0.2 to 5.0/1000 person-days, p=0.03) compared to that at non-crowded shelters. Conclusions: Crowding at shelters may exacerbate sleep disruptions in disaster evacuees; therefore, appropriate evacuation space requirements should be considered. C1 [Kawano, Takahisa; Nishiyama, Kei] Kyoto Univ, Grad Sch Med, Dept Primary Care & Emergency Med, Kyoto, Kyoto 6068501, Japan. [Hiraide, Atsuchi] Kinki Univ, Fac Med, Dept Acute Med, Higashiosaka, Osaka 577, Japan. [Hasegawa, Kohei] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Emergency Med, Boston, MA 02115 USA. RP Kawano, T (reprint author), Kyoto Univ, Grad Sch Med, Dept Primary Care & Emergency Med, Kyoto, Kyoto 6068501, Japan. EM kawano@u-fukui.ac.jp FU Daiwa Securities Health Foundation [2479134]; Ministry of Education, Culture, Sports, Science and Technology, Japan FX This study was funded by the Daiwa Securities Health Foundation, a Grant-in-Aid for Young Scientist (B) of Japan Society for the Promotion of Science (Number 2479134) and Ministry of Education, Culture, Sports, Science and Technology, Japan. The sponsors had no role in data collection, management, analysis, or interpretation. NR 33 TC 0 Z9 0 U1 1 U2 5 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 2016 VL 6 IS 1 AR e009711 DI 10.1136/bmjopen-2015-009711 PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA DD5VX UT WOS:000369993900121 PM 26769785 ER PT J AU Kim, D Kubzansky, LD Baccarelli, A Sparrow, D Spiro, A Tarantini, L Cantone, L Vokonas, P Schwartz, J AF Kim, Daniel Kubzansky, Laura D. Baccarelli, Andrea Sparrow, David Spiro, Avron, III Tarantini, Letizia Cantone, Laura Vokonas, Pantel Schwartz, Joel TI Psychological factors and DNA methylation of genes related to immune/inflammatory system markers: the VA Normative Aging Study SO BMJ OPEN LA English DT Article ID CORONARY-HEART-DISEASE; CELL-ADHESION MOLECULES; SMOOTH-MUSCLE-CELLS; GLUCOCORTICOID-RECEPTOR; LEUKOCYTE TRANSMIGRATION; PSYCHOSOCIAL PREDICTORS; MATERNAL-BEHAVIOR; MOOD DISORDERS; ICAM-1; ATHEROSCLEROSIS AB Objectives: Although psychological factors have been associated with chronic diseases such as coronary heart disease (CHD), the underlying pathways for these associations have yet to be elucidated. DNA methylation has been posited as a mechanism linking psychological factors to CHD risk. In a cohort of community-dwelling elderly men, we explored the associations between positive and negative psychological factors with DNA methylation in promoter regions of multiple genes involved in immune/ inflammatory processes related to atherosclerosis. Design: Prospective cohort study. Setting: Greater Boston, Massachusetts area. Participants: Samples of 538 to 669 men participating in the Normative Aging Study cohort with psychological measures and DNA methylation measures, collected on 1-4 visits between 1999 and 2006 (mean age=72.7 years at first visit). Outcome measures: We examined anxiety, depression, hostility and life satisfaction as predictors of leucocyte gene-specific DNA methylation. We estimated repeated measures linear mixed models, controlling for age, smoking, education, history of heart disease, stroke or diabetes, % lymphocytes, % monocytes and plasma folate. Results: Psychological distress measured by anxiety, depression and hostility was positively associated, and happiness and life satisfaction were inversely associated with average Intercellular Adhesion Molecule-1 (ICAM-1) and coagulation factor III (F3) promoter methylation levels. There was some evidence that hostility was positively associated with toll-like receptor 2 (TLR-2) promoter methylation, and that life satisfaction was inversely associated with TLR-2 and inducible nitric oxide synthase (iNOS) promoter methylation. We observed less consistent and significant associations between psychological factors and average methylation for promoters of the genes for glucocorticoid receptor (NR3C1), interferon-gamma (IFN-gamma) and interleukin 6 (IL-6). Conclusions: These findings suggest that positive and negative psychological factors affect DNA methylation of selected genes involved in chronic immune/inflammatory processes and inflammation-related endothelial dysfunction. Such epigenetic changes may represent biological pathways that mediate the effects of psychological factors on CHD. C1 [Kim, Daniel] Northeastern Univ, Dept Hlth Sci, Boston, MA 02115 USA. [Kim, Daniel; Kubzansky, Laura D.] Harvard Univ, Sch Publ Hlth, Dept Social & Behav Sci, Boston, MA 02115 USA. [Kim, Daniel] EHESP French Sch Publ Hlth, Dept Human & Social Sci, Rennes, France. [Baccarelli, Andrea; Schwartz, Joel] Harvard Univ, Sch Publ Hlth, Dept Environm Hlth, Boston, MA 02115 USA. [Sparrow, David] Boston Univ, Sch Med, Boston, MA 02215 USA. [Sparrow, David; Spiro, Avron, III; Vokonas, Pantel] VA Boston Healthcare Syst, VA Normat Aging Study, Boston, MA USA. [Spiro, Avron, III; Vokonas, Pantel] Boston Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02215 USA. [Spiro, Avron, III] Boston Univ, Sch Med, Dept Psychiat, Boston, MA 02215 USA. [Tarantini, Letizia; Cantone, Laura] Univ Milan, Milan, Italy. [Tarantini, Letizia] IRCCS Maggiore Policlin Hosp, Milan, Italy. [Schwartz, Joel] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. RP Kim, D (reprint author), Northeastern Univ, Dept Hlth Sci, Boston, MA 02115 USA. EM dkim@neu.edu OI Cantone, Laura/0000-0003-3660-129X FU National Institutes of Health [ES05257-06A1, ES014663, ES15172, ES00002, P20-MD000501, R01 ES07821, P42-ES05947, R01-AG02237, R29-AG07465, R01-AG08436]; National Center for Research Resources General Clinical Research Centers programme [M01RR02635]; US Environmental Protection Agency [R832416]; Cooperative Studies Programme/ERIC of the US Department of Veterans Affairs; Massachusetts Veterans Epidemiology Research and Information Center (MAVERIC); VA Research Career Scientist award; National Heart, Lung, and Blood Institute of the National Institutes of Health [R00 HL089459]; National Institute of Environmental Health Sciences [ES000002] FX This research was supported by the National Institutes of Health (ES05257-06A1, ES014663, ES15172, ES00002, P20-MD000501, R01 ES07821, P42-ES05947, R01-AG02237, R29-AG07465, R01-AG08436) and the National Center for Research Resources General Clinical Research Centers programme (M01RR02635); by the US Environmental Protection Agency (R832416); by the Cooperative Studies Programme/ERIC of the US Department of Veterans Affairs; and is a component of the Massachusetts Veterans Epidemiology Research and Information Center (MAVERIC); and by a VA Research Career Scientist award to David Sparrow. Daniel Kim was supported by a career development Pathway to Independence Award through the National Heart, Lung, and Blood Institute of the National Institutes of Health (grant R00 HL089459); Andrea Baccarelli is supported by National Institute of Environmental Health Sciences grant ES000002. NR 62 TC 3 Z9 3 U1 4 U2 9 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 2016 VL 6 IS 1 AR e009790 DI 10.1136/bmjopen-2015-009790 PG 10 WC Medicine, General & Internal SC General & Internal Medicine GA DD5VX UT WOS:000369993900128 PM 26733571 ER PT J AU Mashamba-Thompson, TP Sartorius, B Thabane, L Shi, CX Drain, PK AF Mashamba-Thompson, T. P. Sartorius, B. Thabane, L. Shi, C. X. Drain, P. K. TI Impact of point-of-care diagnostics on maternal outcomes in HIV-infected women: systematic review and meta-analysis protocol SO BMJ OPEN LA English DT Review ID DEVELOPING-WORLD; SOUTH-AFRICA; MORTALITY AB Introduction: Studies indicate substandard diagnostic care, delayed and missed diagnosis as some of the contributing factors to maternal mortality. The clinical impact of point-of-care (POC) diagnostics has been shown in the monitoring and treatment of a variety of infectious diseases, including HIV/AIDS and tuberculosis. The objective of this systematic review is to investigate the impact of POC diagnostics on maternal outcomes for HIV-infected women. Methods: We will conduct a systematic review to evaluate the impact of POC diagnostics for improving desired healthcare outcomes for HIV-infected women. The search strategy will involve electronic databases including: Cochrane Infectious Disease Group Specialised Register; Cochrane Central Register of Control Trials, published in The Cochrane Library; PubMed; EBSCOhost and LILACS. The studies will be mapped in 2 stages: stage 1 will map studies descriptively by focus and method; stage 2 will involve additional inclusion criteria, quality assessment and data extraction undertaken by 2 reviewers in parallel. Evidence will be synthesised using relevant systematic research tools: meta-analysis and subgroup analysis will be conducted using RevMan and Stata 13 will be used for meta-regressions. We will follow recommendations described in the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement and the Cochrane Handbook for Intervention Reviews. Ethics and dissemination: We anticipate finding a large number of studies on POC diagnostic interventions on maternal outcomes in HIV-infected women, which, once summarised, will be useful to guide future diagnostic interventions. The protocol for the systematic review has been registered in PROSPERO. The study will be disseminated electronically and in print. It will also be presented to conferences related to HIV/AIDS, POC diagnostics and maternal health. C1 [Mashamba-Thompson, T. P.; Sartorius, B.] Univ KwaZulu Natal, Sch Nursing & Publ Hlth, Discipline Publ Hlth, Durban, South Africa. [Thabane, L.] St Josephs Healthcare, Biostat Unit FSORC, Hamilton, ON, Canada. [Thabane, L.] McMaster Univ, Dept Clin Epidemiol & Biostat, Hamilton, ON, Canada. [Shi, C. X.] Yale Univ, Sch Publ Hlth, Dept Epidemiol Microbial Dis, New Haven, CT USA. [Drain, P. K.] Univ Washington, Dept Global Hlth, Int Clin Res Ctr, Seattle, WA 98195 USA. [Drain, P. K.] Univ Washington, Dept Med, Div Infect Dis, Seattle, WA 98195 USA. [Drain, P. K.] Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. RP Mashamba-Thompson, TP (reprint author), Univ KwaZulu Natal, Sch Nursing & Publ Hlth, Discipline Publ Hlth, Durban, South Africa. EM Mashamba-Thompson@ukzn.ac.za FU College of Health Sciences, University of KwaZulu Natal; Department of Clinical Epidemiology and Biostatistics of McMaster University; Medical Practice Evaluation Center, Department of Medicine of Massachusetts General Hospital; Harvard Medical School; South African Centre for Epidemiological Modelling and Analysis; African Population Health Research Centre FX The authors would like to thank the College of Health Sciences, University of KwaZulu Natal, Department of Clinical Epidemiology and Biostatistics of McMaster University and Medical Practice Evaluation Center, Department of Medicine of Massachusetts General Hospital, Harvard Medical School and South African Centre for Epidemiological Modelling and Analysis, and African Population Health Research Centre, for their support, and for providing them with resources to help with setting up and conducting this research study. NR 36 TC 2 Z9 2 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 2016 VL 6 IS 1 AR e008002 DI 10.1136/bmjopen-2015-008002 PG 6 WC Medicine, General & Internal SC General & Internal Medicine GA DD5VX UT WOS:000369993900014 PM 26817633 ER PT J AU Pendleton, AA Natarajan, A Ahn, R Nelson, BD Eckardt, MJ Burke, TF AF Pendleton, Anna Alaska Natarajan, Abirami Ahn, Roy Nelson, Brett D. Eckardt, Melody J. Burke, Thomas F. TI A qualitative assessment of the impact of a uterine balloon tamponade package on decisions regarding the role of emergency hysterectomy in women with uncontrolled postpartum haemorrhage in Kenya and Senegal SO BMJ OPEN LA English DT Article ID MANAGEMENT; DEATH AB Objectives: To assess the impact of a every second matters for mothers and babies uterine balloon tamponade package (ESM-UBT) on provider decisions regarding emergency hysterectomy in cases of uncontrolled postpartum haemorrhage (PPH). Design: Qualitative assessment and analysis of a subgroup extracted from a larger database that contains all UBT device uses among ESM-UBT trained health providers. Setting: Health facilities in Kenya and Senegal with ESM-UBT training and capable of performing emergency hysterectomies. Participants: All medical doctors who had placed a UBT for uncontrolled PPH subsequent to implementation of ESM-UBT at their facility, and who also had the capabilities of performing emergency hysterectomies. Primary outcome measures: The impact of ESM-UBT on decisions regarding emergency hysterectomy in cases of uncontrolled PPH. Results: 30 of the 31 medical doctors (97%) who fulfilled the inclusion criteria were independently interviewed. Collectively the interviewed medical doctors had placed over 80 UBT devices for uncontrolled PPH since ESM-UBT implementation. All 30 responded that UBT devices immediately controlled haemorrhage and prevented women from being taken to emergency hysterectomy. All 30 would continue to use UBT devices in future cases of uncontrolled PPH. Conclusions: These preliminary data suggest that following ESM-UBT implementation, emergency hysterectomy for uncontrolled PPH may be averted by use of uterine balloon tamponade. C1 [Pendleton, Anna Alaska; Natarajan, Abirami; Ahn, Roy; Nelson, Brett D.; Eckardt, Melody J.; Burke, Thomas F.] Massachusetts Gen Hosp, Dept Emergency Med, Div Global Hlth & Human Rights, Boston, MA 02114 USA. [Pendleton, Anna Alaska; Natarajan, Abirami; Ahn, Roy; Nelson, Brett D.; Burke, Thomas F.] Harvard Univ, Sch Med, Boston, MA USA. RP Burke, TF (reprint author), Massachusetts Gen Hosp, Dept Emergency Med, Div Global Hlth & Human Rights, Boston, MA 02114 USA.; Burke, TF (reprint author), Harvard Univ, Sch Med, Boston, MA USA. EM tfburke@partners.org FU Izumi Foundation; Ujenzi Charitable Trust; Harvard Medical School; USA Agency for International Development (USAID); Government of Norway; Bill & Melinda Gates Foundation; Grand Challenges Canada; UK Government FX The Every Second Matters for Mothers and Babies Uterine Balloon Tamponade research program (ESM-UBT) is made possible through the generous support of the Izumi Foundation, the Ujenzi Charitable Trust, Harvard Medical School and the Saving Lives at Birth partners: the USA Agency for International Development (USAID), the Government of Norway, the Bill & Melinda Gates Foundation, Grand Challenges Canada, and the UK Government. This manuscript was prepared by the authors and does not necessarily reflect the views of the funding partners. NR 10 TC 0 Z9 0 U1 1 U2 2 PU BMJ PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 2044-6055 J9 BMJ OPEN JI BMJ Open PY 2016 VL 6 IS 1 AR e010083 DI 10.1136/bmjopen-2015-010083 PG 5 WC Medicine, General & Internal SC General & Internal Medicine GA DD5VX UT WOS:000369993900168 PM 26747039 ER PT J AU Shin, CH Zaremba, S Devine, S Nikolov, M Kurth, T Eikermann, M AF Shin, Christina H. Zaremba, Sebastian Devine, Scott Nikolov, Milcho Kurth, Tobias Eikermann, Matthias TI Effects of obstructive sleep apnoea risk on postoperative respiratory complications: protocol for a hospital-based registry study SO BMJ OPEN LA English DT Article ID NEUROMUSCULAR-BLOCKING-AGENTS; NEGATIVE PHARYNGEAL PRESSURE; GENIOGLOSSUS MUSCLE-ACTIVITY; UPPER AIRWAY; SURGICAL-PATIENTS; PASSIVE PHARYNX; ROC CURVE; DECREASES COLLAPSIBILITY; MECHANICAL VENTILATION; NEOSTIGMINE REVERSAL AB Introduction: Obstructive sleep apnoea (OSA), the most common type of sleep-disordered breathing, is associated with significant immediate and long-term morbidity, including fragmented sleep and impaired daytime functioning, as well as more severe consequences, such as hypertension, impaired cognitive function and reduced quality of life. Perioperatively, OSA occurs frequently as a consequence of pre-existing vulnerability, surgery and drug effects. The impact of OSA on postoperative respiratory complications (PRCs) needs to be better characterised. As OSA is associated with significant comorbidities, such as obesity, pulmonary hypertension, myocardial infarction and stroke, it is unclear whether OSA or its comorbidities are the mechanism of PRCs. This project aims to (1) develop a novel prediction score identifying surgical patients at high risk of OSA, (2) evaluate the association of OSA risk on PRCs and (3) evaluate if pharmacological agents used during surgery modify this association. Methods: Retrospective cohort study using hospital-based electronic patient data and perioperative data on medications administered and vital signs. We will use data from Partners Healthcare clinical databases, Boston, Massachusetts. First, a prediction model for OSA will be developed using OSA diagnostic codes and polysomnography procedural codes as the reference standard, and will be validated by medical record review. Results of the prediction model will be used to classify patients in the database as high, medium or low risk of OSA, and we will investigate the effect of OSA on risk of PRCs. Finally, we will test whether the effect of OSA on PRCs is modified by the use of intraoperative pharmacological agents known to increase upper airway instability, including neuromuscular blockade, neostigmine, opioids, anaesthetics and sedatives. Ethics and dissemination: The Partners Human Research Committee approved this study (protocol number: 2014P000218). Study results will be made available in the form of manuscripts for publication and presentations at national and international meetings. C1 [Shin, Christina H.; Zaremba, Sebastian; Nikolov, Milcho; Eikermann, Matthias] Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, Boston, MA 02114 USA. [Shin, Christina H.; Kurth, Tobias; Eikermann, Matthias] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Zaremba, Sebastian] Univ Bonn, Univ Hosp Bonn, Dept Neurol, Dept Sleep Med, Bonn, Germany. [Devine, Scott] Merck & Co Inc, Ctr Observat & Real World Effectiveness US Outcom, Boston, MA USA. [Kurth, Tobias] Charite, Inst Publ Hlth, D-13353 Berlin, Germany. RP Eikermann, M (reprint author), Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, Boston, MA 02114 USA.; Eikermann, M (reprint author), Harvard Univ, Sch Med, Boston, MA 02115 USA. EM meikermann@partners.org RI Kurth, Tobias/A-9243-2012 OI Kurth, Tobias/0000-0001-7169-2620 FU Merck [224941] FX This work is supported by Merck (grant number 224941). NR 77 TC 2 Z9 2 U1 1 U2 6 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 2016 VL 6 IS 1 AR e008436 DI 10.1136/bmjopen-2015-008436 PG 14 WC Medicine, General & Internal SC General & Internal Medicine GA DD5VX UT WOS:000369993900021 PM 26769778 ER PT J AU Sheu, JS Divito, SJ Enamandram, M Merola, JF AF Sheu, Johanna S. Divito, Sherrie J. Enamandram, Monica Merola, Joseph F. TI Dapsone Therapy for Pustular Psoriasis: Case Series and Review of the Literature SO DERMATOLOGY LA English DT Review DE Pustular psoriasis; Palmoplantar pustular psoriasis; Dapsone; Glucose-6-phosphate dehydrogenase ID PALMOPLANTAR PUSTULOSIS; DERMATITIS-HERPETIFORMIS; INDUCED METHEMOGLOBINEMIA; VITAMIN-E; CIMETIDINE; MYELOPEROXIDASE; DERMATOLOGY; INHIBITION; HEMOLYSIS; EFFICACY AB Background: Pustular psoriasis is an uncommon psoriasis variant, clinically characterized as small sterile pustules on an erythematous base. Evidence for therapy is lacking, and many currently employed systemic therapeutics carry risks of significant side effects, without specifically targeting disease etiology which includes the aggregation of neutrophils. Observations: We report therapy with the anti-neutrophil agent dapsone in 5 patients with pustular psoriasis and provide a brief review of the literature. Four patients responded to oral dapsone and 1 to topical dapsone therapy. All 5 patients had previously failed multiple topical and systemic treatments. In 2 cases, oral dapsone allowed for the discontinuation of other systemic agents. One patient stopped oral dapsone due to a side effect of sleep disturbance. Conclusion: Dapsone has a much safer side effect profile and may target the pathophysiology of pustular psoriasis more directly than many other systemic agents. As such, dapsone should be considered for the treatment of patients with pustular psoriasis. (C) 2015 S. Karger AG, Basel C1 [Sheu, Johanna S.; Divito, Sherrie J.; Merola, Joseph F.] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Sheu, Johanna S.] Massachusetts Gen Hosp, Dept Pediat, Boston, MA 02114 USA. [Divito, Sherrie J.; Merola, Joseph F.] Brigham & Womens Hosp, Dept Dermatol, 75 Francis St, Boston, MA 02115 USA. [Merola, Joseph F.] Brigham & Womens Hosp, Dept Med, Div Rheumatol, 75 Francis St, Boston, MA 02115 USA. [Enamandram, Monica] Stanford Med Ctr, Dept Dermatol, Palo Alto, CA USA. RP Merola, JF (reprint author), Harvard Univ, Sch Med, Dept Dermatol, 221 Longwood Ave, Boston, MA 02115 USA.; Merola, JF (reprint author), Harvard Univ, Brigham & Womens Hosp, Sch Med, Div Rheumatol,Dept Med, 221 Longwood Ave, Boston, MA 02115 USA. EM jfmerola@partners.org FU Biogen IDEC FX Dr. Merola serves as an investigator for Amgen, Pfizer and Biogen IDEC, a consultant to Biogen IDEC, receives research funding from Biogen IDEC, has served on a Scientific Advisory Board for Amgen, Eli Lilly and Novartis and is a speaker for Abbvie. Ms. Sheu, Dr. Divito and Dr. Enamandram have no financial disclosures. This study was not supported by any outside funding sources. NR 38 TC 1 Z9 1 U1 1 U2 1 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 1018-8665 EI 1421-9832 J9 DERMATOLOGY JI Dermatology PY 2016 VL 232 IS 1 BP 97 EP 101 DI 10.1159/000431171 PG 5 WC Dermatology SC Dermatology GA DD8CA UT WOS:000370150600017 PM 26465742 ER PT J AU Williams, JS Lynch, CP Voronca, D Egede, LE AF Williams, Joni S. Lynch, Cheryl P. Voronca, Delia Egede, Leonard E. TI Health locus of control and cardiovascular risk factors in veterans with type 2 diabetes SO ENDOCRINE LA English DT Article DE Health locus of control; Diabetes; Diabetes outcomes; Cardiovascular disease risk factors; Quality of life; Veterans ID QUALITY-OF-LIFE; PERCEIVED CONTROL; SELF-MANAGEMENT; VALIDATION; DISEASE; RELIABILITY; POPULATION; DEPRESSION; ADHERENCE; VALIDITY AB Perceptions of control impact outcomes in veterans with chronic disease. The purpose of this study was to examine the association between control orientation and clinical and quality of life (QOL) outcomes in male veterans with type 2 diabetes (T2DM). Cross-sectional study of 283 male veterans from a primary care clinic in the southeastern US. Health locus of control (LOC) was the main predictor and assessed using the Multidimensional Health LOC Scale. Clinical outcomes were glycosylated hemoglobin A1c (HbA1c), systolic and diastolic blood pressure, and low-density lipoprotein cholesterol (LDL-C). Physical (PCS) and mental (MCS) health component scores for QOL were assessed using the Veterans RAND 12-Item Health Survey. Unadjusted and adjusted multivariate analyses were performed to assess associations between LOC and outcomes. Unadjusted analyses showed internal LOC associated with HbA1c (beta = 0.036; 95 % CI 0.001, 0.071), external LOC: powerful others inversely associated with LDL-C (beta = -0.794; 95 % CI -1.483, -0.104), and external LOC: chance inversely associated with MCS QOL (beta = -0.418; 95 % CI -0.859, -0.173). These associations remained significant when adjusting for relevant covariates. Adjusted analyses also demonstrated a significant relationship between external LOC: chance and PCS QOL (beta = 0.308; 95 % CI 0.002, 0.614). In this sample of male veterans with T2DM, internal LOC was significantly associated with glycemic control, and external was significantly associated with QOL and LDL-C, when adjusting for relevant covariates. Assessments of control orientation should be performed to understand the perceptions of patients, thus better equipping physicians with information to maximize care opportunities for veterans with T2DM. C1 [Lynch, Cheryl P.; Egede, Leonard E.] Vet Affairs Med Ctr, Ralph H Johnson Dept, HEROIC, Charleston, SC 29403 USA. [Williams, Joni S.; Lynch, Cheryl P.; Voronca, Delia; Egede, Leonard E.] Med Univ S Carolina, Dept Med, Div Gen Internal Med & Geriatr, Charleston, SC 29425 USA. RP Egede, LE (reprint author), Vet Affairs Med Ctr, Ralph H Johnson Dept, HEROIC, Charleston, SC 29403 USA.; Egede, LE (reprint author), Med Univ S Carolina, Dept Med, Div Gen Internal Med & Geriatr, Charleston, SC 29425 USA. EM stromjl@musc.edu; lynchcp@musc.edu; voronca@musc.edu; egedel@musc.edu FU VHA Health Services Research and Development (HSRD) program [TRP 04-038] FX This study was supported by Grant #TRP 04-038 (PI: Leonard Egede) funded by the VHA Health Services Research and Development (HSR&D) program. NR 37 TC 1 Z9 1 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1355-008X EI 1559-0100 J9 ENDOCRINE JI Endocrine PD JAN PY 2016 VL 51 IS 1 BP 83 EP 90 DI 10.1007/s12020-015-0677-8 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA DD6WH UT WOS:000370064800011 PM 26148703 ER PT J AU Milanesi, A Lee, JW Kim, NH Liu, YY Yang, A Sedrakyan, S Kahng, A Cervantes, V Tripuraneni, N Cheng, SY Perin, L Brent, GA AF Milanesi, Anna Lee, Jang-Won Kim, Nam-Ho Liu, Yan-Yun Yang, An Sedrakyan, Sargis Kahng, Andrew Cervantes, Vanessa Tripuraneni, Nikita Cheng, Sheue-yann Perin, Laura Brent, Gregory A. TI Thyroid Hormone Receptor alpha Plays an Essential Role in Male Skeletal Muscle Myoblast Proliferation, Differentiation, and Response to Injury SO ENDOCRINOLOGY LA English DT Article ID GROWTH-PLATE CHONDROCYTES; INSULIN-RESISTANCE; SATELLITE CELLS; SOLEUS MUSCLE; GENE; MYOD; MICE; EXPRESSION; MUTATION; MOUSE AB Thyroid hormone plays an essential role in myogenesis, the process required for skeletal muscle development and repair, although the mechanisms have not been established. Skeletal muscle develops from the fusion of precursor myoblasts into myofibers. We have used the C2C12 skeletal muscle myoblast cell line, primary myoblasts, and mouse models of resistance to thyroid hormone (RTH) alpha and beta, to determine the role of thyroid hormone in the regulation of myoblast differentiation. T-3, which activates thyroid hormone receptor (TR) alpha and beta, increased myoblast differentiation whereas GC1, a selective TR beta agonist, was minimally effective. Genetic approaches confirmed that TR alpha plays an important role in normal myoblast proliferation and differentiation and acts through the Wnt/beta-catenin signaling pathway. Myoblasts with TR alpha knockdown, or derived from RTH-TR alpha PV (a frame-shift mutation) mice, displayed reduced proliferation and myogenic differentiation. Moreover, skeletal muscle from the TR alpha 1PV mutant mouse had impaired in vivo regeneration after injury. RTH-TR beta PV mutant mouse model skeletal muscle and derived primary myoblasts did not have altered proliferation, myogenic differentiation, or response to injury when compared with control. In conclusion, TR alpha plays an essential role in myoblast homeostasis and provides a potential therapeutic target to enhance skeletal muscle regeneration. C1 [Milanesi, Anna; Liu, Yan-Yun; Yang, An; Brent, Gregory A.] Univ Calif Los Angeles, Vet Affairs Greater Los Angeles Healthcare Syst, Dept Med, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, David Geffen Sch Med, Dept Med, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, David Geffen Sch Med, Dept Physiol, Los Angeles, CA 90073 USA. [Lee, Jang-Won; Kim, Nam-Ho; Kahng, Andrew; Cervantes, Vanessa] Cedars Sinai Med Ctr, Dept Neurosurg, Los Angeles, CA 90048 USA. [Sedrakyan, Sargis; Tripuraneni, Nikita; Perin, Laura] Univ So Calif, Childrens Hosp Los Angeles, Dept Urol, Los Angeles, CA 90027 USA. [Cheng, Sheue-yann] NCI, Bethesda, MD 20892 USA. RP Milanesi, A; Brent, GA (reprint author), VA Greater Angeles Healthcare Syst, Dept Med, 111,11301 Wilshire Blvd, Los Angeles, CA 90073 USA. EM amilanesi@mednet.ucla.edu; gbrent@mednet.ucla.edu FU National Institutes of Health (NIH) Grant [1K08DK097295]; NIH [RO1DK98576]; NIH/National Center for Advancing Translational Science University of California, Los Angeles, Clinical and Translational Science Institute [UL1TR000124] FX This work was supported by National Institutes of Health (NIH) Grant No. 1K08DK097295 (to A.M.), and NIH RO1DK98576 (to G.A.B.). The research described was supported by NIH/National Center for Advancing Translational Science University of California, Los Angeles, Clinical and Translational Science Institute Grant No. UL1TR000124. NR 61 TC 3 Z9 3 U1 2 U2 4 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 2016 VL 157 IS 1 BP 4 EP 15 DI 10.1210/en.2015-1443 PG 12 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA DD5KM UT WOS:000369962600002 PM 26451739 ER PT J AU Tascau, L Gardner, T Anan, H Yongpravat, C Cardozo, CP Bauman, WA Lee, FY Oh, DS Tawfeek, HA AF Tascau, Liana Gardner, Thomas Anan, Hussein Yongpravat, Charlie Cardozo, Christopher P. Bauman, William A. Lee, Francis Y. Oh, Daniel S. Tawfeek, Hesham A. TI Activation of Protein Kinase A in Mature Osteoblasts Promotes a Major Bone Anabolic Response SO ENDOCRINOLOGY LA English DT Article ID ENGINEERED G(S)-COUPLED RECEPTOR; PARATHYROID-HORMONE RESISTANCE; SYMPATHETIC-NERVOUS-SYSTEM; MESSENGER-RNA EXPRESSION; MCCUNE-ALBRIGHT-SYNDROME; ELEMENT-BINDING PROTEIN; HUMAN FIBROUS DYSPLASIA; MESENCHYMAL STEM-CELLS; OSTEOCLAST DIFFERENTIATION; POSTMENOPAUSAL WOMEN AB Protein kinase A(PKA) regulates osteoblast cell function in vitro and is activated by important bone mass modulating agents. We determined whether PKA activation in osteoblasts is sufficient to mediate a bone anabolic response. Thus, a mouse model conditionally expressing a constitutively active PKA (CA-PKA) in osteoblasts (CA-PKA-OB mouse) was developed by crossing a 2.3-kb alpha 1 (I)-collagen promoter-Cre mouse with a floxed-CA-PKA mouse. Primary osteoblasts from the CA-PKA-OB mice exhibited higher basal PKA activity than those from control mice. Microcomputed tomographic analysis revealed that CA-PKA-OB female mice hadan 8.6-fold increase in femoral but only 1.16-fold increase in lumbar 5 vertebral bone volume/total volume. Femur cortical thickness and volume were also higher in the CA-PKA-OB mice. In contrast, alterations in many femoral microcomputed tomographic parameters in male CA-PKA-OB mice were modest. Interestingly, the 3-dimensional structure model index was substantially lower both in femur and lumbar 5 of male and female CA-PKA-OB mice, reflecting an increase in the plate to rod-like structure ratio. In agreement, femurs from female CA-PKA-OB mice had greater load to failure and were stiffer compared with those of control mice. Furthermore, the CA-PKA-OB mice had higher levels of serum bone turnover markers and increased osteoblast and osteoclast numbers per total tissue area compared with control animals. In summary, constitutive activation of PKA in osteoblasts is sufficient to increase bone mass and favorably modify bone architecture and improve mechanical properties. PKA activation in mature osteoblasts is, therefore, an important target for designing anabolic drugs for treating diseases with bone loss. C1 [Cardozo, Christopher P.; Bauman, William A.; Tawfeek, Hesham A.] James J Peters VA Med Ctr, Natl Ctr Med Consequences Spinal Cord Injury, 130 West Kingsbridge Rd,Room 3F-12, Bronx, NY 10468 USA. [Gardner, Thomas; Yongpravat, Charlie; Lee, Francis Y.] Columbia Univ, Ctr Orthopaed Res, New York, NY 10029 USA. [Oh, Daniel S.] Columbia Univ, Coll Dent Med, New York, NY 10029 USA. [Tascau, Liana] Columbia Univ, Dept Mol Med, New York, NY 10029 USA. [Cardozo, Christopher P.; Bauman, William A.; Tawfeek, Hesham A.] Icahn Sch Med Mt Sinai, Dept Med, New York, NY 10029 USA. [Cardozo, Christopher P.; Bauman, William A.] Icahn Sch Med Mt Sinai, Dept Rehabil Med, New York, NY 10029 USA. [Cardozo, Christopher P.] Icahn Sch Med Mt Sinai, Dept Pharmacol & Syst Therapeut, New York, NY 10029 USA. [Anan, Hussein] Temple Univ, Sacred Heart Hosp, Allentown, PA 16102 USA. RP Tawfeek, HA (reprint author), James J Peters VA Med Ctr, Natl Ctr Med Consequences Spinal Cord Injury, 130 West Kingsbridge Rd,Room 3F-12, Bronx, NY 10468 USA. EM HeshamA.Tawfeek@va.gov FU Department of Veterans Affairs Rehabilitation Research and Development Service [B9212C] FX This work was supported in part by the Department of Veterans Affairs Rehabilitation Research and Development Service Grant B9212C (to W.A.B.). NR 93 TC 1 Z9 1 U1 1 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 2016 VL 157 IS 1 BP 112 EP 126 DI 10.1210/en.2015-1614 PG 15 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA DD5KM UT WOS:000369962600018 PM 26488807 ER PT J AU Hattersley, G Dean, T Corbin, BA Bahar, H Gardella, TJ AF Hattersley, Gary Dean, Thomas Corbin, Braden A. Bahar, Hila Gardella, Thomas J. TI Binding Selectivity of Abaloparatide for PTH-Type-1-Receptor Conformations and Effects on Downstream Signaling SO ENDOCRINOLOGY LA English DT Article ID PARATHYROID-HORMONE PTH; (PTH)/PTH-RELATED PROTEIN-RECEPTOR; ERK1/2 ACTIVATION; LIGAND-BINDING; BIASED AGONISM; OSTEOPOROSIS; MECHANISMS; PATHWAYS; STATES; CAMP AB The PTH receptor type 1 (PTHR1) mediates the actions of two endogenous polypeptide ligands, PTH and PTHrP, and thereby plays key roles in bone biology. Based on its capacity to stimulate bone formation, the peptide fragment PTH (1-34) is currently in use as therapy for osteoporosis. Abaloparatide (ABL) is a novel synthetic analog of human PTHrP (1-34) that holds promise as a new osteoporosis therapy, as studies in animals suggest that it can stimulate bone formation with less of the accompanying bone resorption and hypercalcemic effects that can occur with PTH (1-34). Recent studies in vitro suggest that certain PTH or PTHrP ligand analogs can distinguish between two high-affinity PTHR1 conformations, R-0 and RG, and that efficient binding to R-0 results in prolonged signaling responses in cells and prolonged calcemic responses in animals, whereas selective binding to RG results in more transient responses. As intermittent PTH ligand action is known to favor the bone-formation response, whereas continuous ligand action favors the net bone-resorption/calcemic response, we hypothesized that ABL binds more selectively to the RG vs the R-0 PTHR1 conformation than does PTH (1-34), and thus induces more transient signaling responses in cells. We show that ABL indeed binds with greater selectivity to the RG conformation than does PTH (1-34), and as a result of this RG bias, ABL mediates more transient cAMP responses in PTHR1-expressing cells. The findings provide a plausible mechanism (ie, transient signaling via RG-selective binding) that can help account for the favorable anabolic effects that ABL has on bone. C1 [Hattersley, Gary; Bahar, Hila] Radius Hlth Inc, Waltham, MA 02451 USA. [Dean, Thomas; Corbin, Braden A.; Gardella, Thomas J.] Massachusetts Gen Hosp, Endocrine Unit, Thier 10,50 Blossom St, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Gardella, TJ (reprint author), Massachusetts Gen Hosp, Endocrine Unit, Thier 10,50 Blossom St, Boston, MA 02114 USA. EM gardella@helix.mgh.harvard.edu FU National Institutes of Health [DK-11794, AR066261] FX This work was supported by the National Institutes of Health Grants DK-11794 (PO1) and AR066261 (P30). NR 28 TC 14 Z9 14 U1 2 U2 6 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 2016 VL 157 IS 1 BP 141 EP 149 DI 10.1210/en.2015-1726 PG 9 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA DD5KM UT WOS:000369962600020 PM 26562265 ER PT J AU Gruionu, LG Saftoiu, A Gruionu, G AF Gruionu, Lucian Gheorghe Saftoiu, Adrian Gruionu, Gabriel TI A novel fusion imaging system for endoscopic ultrasound SO ENDOSCOPIC ULTRASOUND LA English DT Article DE Electromagnetic (EM) guidance; endoscopic ultrasound (EUS); fusion imaging (FI); hybrid imaging; pancreatic lesions ID GASTROINTESTINAL ENDOSCOPY; FEASIBILITY; MODEL; VIVO; EUS AB Background and Objective: Navigation of a flexible endoscopic ultrasound (EUS) probe inside the gastrointestinal (GI) tract is problematic due to the small window size and complex anatomy. The goal of the present study was to test the feasibility of a novel fusion imaging (FI) system which uses electromagnetic (EM) sensors to co-register the live EUS images with the pre-procedure computed tomography (CT) data with a novel navigation algorithm and catheter. Methods: An experienced gastroenterologist and a novice EUS operator tested the FI system on a GI tract bench top model. Also, the experienced gastroenterologist performed a case series of 20 patients during routine EUS examinations. Results: On the bench top model, the experienced and novice doctors reached the targets in 67 +/- 18 s and 150 +/- 24 s with a registration error of 6 +/- 3 mm and 11 +/- 4 mm, respectively. In the case series, the total procedure time was 24.6 +/- 6.6 min, while the time to reach the clinical target was 8.7 +/- 4.2 min. Conclusions: The FI system is feasible for clinical use, and can reduce the learning curve for EUS procedures and improve navigation and targeting in difficult anatomic locations. C1 [Gruionu, Lucian Gheorghe] Univ Med & Pharm Craiova, Div Trauma Emergency Surg & Surg Clin Care, Dept Surg, Craiova, Romania. [Saftoiu, Adrian] Univ Med & Pharm Craiova, Res Ctr Gastroenterol & Hepatol Craiova, Craiova, Romania. [Saftoiu, Adrian] Copenhagen Univ Hosp, Dept Endoscopy, Copenhagen, Denmark. [Gruionu, Gabriel] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Gruionu, Gabriel] Harvard Univ, Sch Med, Boston, MA USA. RP Gruionu, G (reprint author), Massachusetts Gen Hosp, Boston, MA 02114 USA.; Gruionu, G (reprint author), Harvard Univ, Sch Med, Boston, MA USA. EM ggruionu@mgh.harvard.edu RI Saftoiu, Adrian/C-2792-2011; Gruionu, Lucian/F-6121-2011 OI Gruionu, Lucian/0000-0002-4526-0864 FU ANCS-CNDI-UEFISCDI "PNII - Joint Applied Research Projects" program [87/2012, PN-II-PT-PCCA-2011-3.2-0482]; European Social Fund for Regional Development; National Agency for Scientific Research from Romania [285/16.12.2010, 983 Cod SMIS-CSNR 19782]; SC MEDINSYS SRL FX This work was sponsored by the ANCS-CNDI-UEFISCDI "PNII - Joint Applied Research Projects" program, contract number 87/2012, code PN-II-PT-PCCA-2011-3.2-0482, by the European Social Fund for Regional Development and National Agency for Scientific Research from Romania, contract number 285/16.12.2010, ID nr 983 Cod SMIS-CSNR 19782, and by SC MEDINSYS SRL. Conflicts of Interest: Dr. Lucian Gruionu is the CEO and director of R&D of SC Medinsys SRL and holds equity in the company. Dr. Saftoiu holds equity in SC Medinsys SRL. Dr. Gabriel Gruionu serves as a consultant for SC Medinsys SRL and holds equity in Restore Surgical LLC. NR 18 TC 1 Z9 1 U1 0 U2 1 PU MEDKNOW PUBLICATIONS & MEDIA PVT LTD PI MUMBAI PA B-9, KANARA BUSINESS CENTRE, OFF LINK RD, GHAKTOPAR-E, MUMBAI, 400075, INDIA SN 2303-9027 EI 2226-7190 J9 ENDOSC ULTRASOUND JI Endosc. Ultrasound PD JAN-FEB PY 2016 VL 5 IS 1 BP 35 EP 42 DI 10.4103/2303-9027.175882 PG 8 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA DD2CT UT WOS:000369730800007 PM 26879165 ER PT J AU Smith, K Firth, K Smeeding, S Wolever, R Kaufman, J Delgado, R Bellanti, D Xenalcis, L AF Smith, Katherine Firth, Kimberly Smeeding, Sandra Wolever, Ruth Kaufman, Joanna Delgado, Roxana Bellanti, Dawn Xenalcis, Lea TI GUIDELINES FOR CREATING, IMPLEMENTING, AND EVALUATING MIND-BODY PROGRAMS IN A MILITARY HEALTHCARE SETTING SO EXPLORE-THE JOURNAL OF SCIENCE AND HEALING LA English DT Article DE Mind-body skills; Empowerment; Guidelines; Program evaluation; Healthcare; Military healthcare ID POSTTRAUMATIC-STRESS-DISORDER; RANDOMIZED CONTROLLED-TRIAL; TRAUMATIC BRAIN-INJURY; CENTERED MEDICAL HOME; ALTERNATIVE MEDICINE; MINDFULNESS MEDITATION; VETERANS-IMPLICATIONS; INTEGRATIVE MEDICINE; PEER SUPPORT; CHRONIC PAIN AB Research suggests that the development of mind-body skills can improve individual and family resilience, particularly related to the stresses of illness, trauma, and caregiving. To operationalize the research evidence that mind body skills help with health and recovery, Samueli Institute, in partnership with experts in mind body programming, created a set of guidelines for developing and evaluating mind-body programs for service members, veterans, and their families. The Guidelines for Creating, Implementing, and Evaluating Mind-Body Programs in a Military Healthcare Setting outline key strategies and issues to consider when developing, implementing, and evaluating a mind body focused family empowerment approach in a military healthcare setting. Although these guidelines were developed specifically for a military setting, most of the same principles can be applied to the development of programs in the civilian setting as well. The guidelines particularly address issues unique to mind-body programs, such as choosing evidence-based modalities, licensure and credentialing, safety and contraindications, and choosing evaluation measures that capture the holistic nature of these types of programs. The guidelines are practical, practice-based guidelines, developed by experts in the fields of program development and evaluation, mind-body therapies, patient- and family-centered care, as well as, experts in military and veteran's health systems. They provide a flexible framework to create mind body family empowerment programs and describe important issues that program developers and evaluators are encouraged to address to ensure the development of the most impactful, successful, evidence-supported programs possible. C1 [Smith, Katherine; Firth, Kimberly; Delgado, Roxana; Bellanti, Dawn; Xenalcis, Lea] Samueli Inst, Optimal Healing Environm, 1737 King St,Suite 600, Alexandria, VA 22314 USA. [Firth, Kimberly] NIA, NIH, Bethesda, MD 20892 USA. [Smeeding, Sandra] San Francisco VA Med Ctr, San Francisco, CA USA. [Wolever, Ruth] Duke Sch Med, Dept Psychiat & Behav Sci, Durham, NC USA. [Wolever, Ruth] Duke Integrat Med, Durham, NC USA. [Wolever, Ruth] Vanderbilt Hlth Coaching, Osher Ctr Integrat Med Vanderbilt, Nashville, TN USA. [Wolever, Ruth] Vanderbilt Univ Sch Med, Phys Med & Rehabil, Nashville, TN USA. [Wolever, Ruth] Vanderbilt Univ Sch Med, Dept Psychiat, Nashville, TN USA. [Wolever, Ruth] Vanderbilt Sch Nursing, Nashville, TN USA. [Kaufman, Joanna] Inst Patient & Family Centered Care, Bethesda, MD USA. [Smeeding, Sandra] Salt Lake City VA Healthcare Syst, Integrat Hlth Clin & Program, Salt Lake City, UT USA. [Wolever, Ruth] Duke Sch Med, Durham, NC USA. [Wolever, Ruth] Duke Integrat Med, Durham, NC USA. RP Smith, K (reprint author), Samueli Inst, Optimal Healing Environm, 1737 King St,Suite 600, Alexandria, VA 22314 USA. EM ksmith@siib.org FU US Army Medical Research and Materiel Command, United States [W81XWH-11-1-0759] FX This work is supported by the US Army Medical Research and Materiel Command, United States, under Award no. W81XWH-11-1-0759. The views, opinions and/or findings contained in this report are those of the author(s) and should not be construed as an official Department of the Army position, policy or decision unless so designated by other documentation. NR 102 TC 0 Z9 0 U1 6 U2 12 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1550-8307 EI 1878-7541 J9 EXPLORE-NY JI Explore-J Sci. Heal. PD JAN-FEB PY 2016 VL 12 IS 1 BP 18 EP 33 DI 10.1016/j.explore.2015.10.002 PG 16 WC Integrative & Complementary Medicine SC Integrative & Complementary Medicine GA DD1LG UT WOS:000369682600007 PM 26686476 ER PT J AU Nomura, A Tada, H Teramoto, R Konno, T Hodatsu, A Won, HH Kathiresan, S Ino, H Fujino, N Yamagishi, M Hayashi, K AF Nomura, Akihiro Tada, Hayato Teramoto, Ryota Konno, Tetsuo Hodatsu, Akihiko Won, Hong-Hee Kathiresan, Sekar Ino, Hidekazu Fujino, Noboru Yamagishi, Masakazu Hayashi, Kenshi TI Whole exome sequencing combined with integrated variant annotation prediction identifies a causative myosin essential light chain variant in hypertrophic cardiomyopathy SO JOURNAL OF CARDIOLOGY LA English DT Article DE Hypertrophic cardiomyopathy; Myosin essential light chain; Whole exome sequencing; Bioinformatics ID MOLECULAR-GENETIC DIAGNOSIS; TROPONIN-I GENE; CLINICAL-FEATURES; AMERICAN-COLLEGE; OF-CARDIOLOGY; MUTATION; ASSOCIATION; GUIDELINES; FRAMEWORK; DISEASE AB Background: The development of candidate gene approaches to enable molecular diagnosis of hypertrophic cardiomyopathy (HCM) has required extensive and prolonged efforts. Whole exome sequencing (WES) technologies have already accelerated genetic studies of Mendelian disorders, yielding approximately 30% diagnostic success. As a result, there is great interest in extending the use of WES to any of Mendelian diseases. This study investigated the potential of WES for molecular diagnosis of HCM. Methods: WES was performed on seven relatives from a large HCM family with a clear HCM phenotype (five clinically affected and two unaffected) in the Kanazawa University Hypertrophic Cardiomyopathy Registry. Serial bioinformatics filtering methods as well as using combined annotation dependent depletion (CADD) score and high heart expression (HHE) gene data were applied to detect the causative variant. Moreover, additional carriers of the variant were investigated in the HCM registry, and clinical characteristics harboring the variant were collected and evaluated. Results: WES detected 60020 rare variants in the large HCM family. Of those, 3439 were missense, nonsense, splice-site, or frameshift variants. After genotype phenotype matching, 13 putative variants remained. Using CADD score and HHE gene data, the number of candidates was reduced to one, a variant in the myosin essential light chain (MYL3, NM_000258.2:c.281G>A, p.Arg94His) that was shared by the five affected subjects. Additional screening of the HCM registry (n = 600) identified two more subjects with this variant. Serial assessments of the variant carriers revealed the following phenotypic characteristics: (1) disease-penetrance of 88%; (2) all clinically affected carriers exhibited asymmetric septal hypertrophy with a substantial maximum left ventricular wall thickness of 18 3 mm without any obstruction. Conclusions: WES combined with CADD score and HHE gene data may be useful even in HCM. Furthermore, the MYL3 Arg94His variant was associated with high disease penetrance and substantial interventricular septal hypertrophy. (C) 2015 Japanese College of Cardiology. Published by Elsevier Ltd. All rights reserved. C1 [Nomura, Akihiro; Tada, Hayato; Teramoto, Ryota; Konno, Tetsuo; Hodatsu, Akihiko; Ino, Hidekazu; Fujino, Noboru; Yamagishi, Masakazu; Hayashi, Kenshi] Kanazawa Univ, Div Cardiovasc Med, Grad Sch Med Sci, Kanazawa, Ishikawa 9208641, Japan. [Nomura, Akihiro; Won, Hong-Hee; Kathiresan, Sekar] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA. [Nomura, Akihiro; Won, Hong-Hee; Kathiresan, Sekar] Broad Inst, Program Med & Populat Genet, Cambridge, MA USA. [Nomura, Akihiro; Won, Hong-Hee; Kathiresan, Sekar] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. [Konno, Tetsuo] Kanazawa Univ, Res & Educ Ctr Innovat & Prevent Med, 13-1 Takaramachi, Kanazawa, Ishikawa 9208641, Japan. [Won, Hong-Hee; Kathiresan, Sekar] Massachusetts Gen Hosp, Cardiovasc Res Ctr, Boston, MA 02114 USA. RP Konno, T (reprint author), Kanazawa Univ, Res & Educ Ctr Innovat & Prevent Med, 13-1 Takaramachi, Kanazawa, Ishikawa 9208641, Japan. EM konnokontetsu@staff.kanazawa-u.ac.jp FU JSPS KAKENHI [19590807, 22590808, 25460648, 26460742]; Kanazawa University Hospital; Yoshida Scholarship Foundation FX This study was supported by JSPS KAKENHI Grant Numbers 19590807, 22590808, 25460648, and 26460742. Noboru Fujino was funded by a grant for innovative research from Kanazawa University Hospital. Akihiro Nomura was also funded by a research grant from Yoshida Scholarship Foundation. NR 45 TC 2 Z9 2 U1 1 U2 4 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 2016 VL 67 IS 1-2 BP 133 EP 139 DI 10.1016/j.jjcc.2015.09.003 PG 7 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA DD8YF UT WOS:000370212100025 PM 26443374 ER PT J AU Groen, SC Humphrey, PT Chevasco, D Ausubel, FM Pierce, NE Whiteman, NK AF Groen, Simon C. Humphrey, Parris T. Chevasco, Daniela Ausubel, Frederick M. Pierce, Naomi E. Whiteman, Noah K. TI Pseudomonas syringae enhances herbivory by suppressing the reactive oxygen burst in Arabidopsis SO JOURNAL OF INSECT PHYSIOLOGY LA English DT Article DE Arabidopsis thaliana; Drosophila melanogaster; Pseudomonas syringae; Scaptomyza; Herbivore; Plant defense; Reactive oxygen species ID APOPLASTIC OXIDATIVE BURST; NADPH OXIDASE RBOHD; SALICYLIC-ACID; PLANT DEFENSE; GENE-EXPRESSION; JASMONIC ACID; DISEASE RESISTANCE; INSECT HERBIVORE; DROSOPHILA-MELANOGASTER; PHYTOCHELATIN SYNTHASE AB Plant-herbivore interactions have evolved in the presence of plant-colonizing microbes. These microbes can have important third-party effects on herbivore ecology, as exemplified by drosophilid flies that evolved from ancestors feeding on plant-associated microbes. Leaf-mining flies in the genus Scaptomyza, which is nested within the paraphyletic genus Drosophila, show strong associations with bacteria in the genus Pseudomonas, including Pseudomonas syringae. Adult females are capable of vectoring these bacteria between plants and larvae show a preference for feeding on P. syringae-infected leaves. Here we show that Scaptomyza flava larvae can also vector P. syringae to and from feeding sites, and that they not only feed more, but also develop faster on plants previously infected with P. syringae. Our genetic and physiological data show that P. syringae enhances S. flava feeding on infected plants at least in part by suppressing anti-herbivore defenses mediated by reactive oxygen species. (C) 2015 Elsevier Ltd. All rights reserved. C1 [Groen, Simon C.; Humphrey, Parris T.; Whiteman, Noah K.] Univ Arizona, Dept Ecol & Evolutionary Biol, Tucson, AZ 85721 USA. [Groen, Simon C.; Chevasco, Daniela; Pierce, Naomi E.; Whiteman, Noah K.] Harvard Univ, Dept Organism & Evolutionary Biol, Cambridge, MA 02138 USA. [Ausubel, Frederick M.] Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA. [Ausubel, Frederick M.] Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. RP Groen, SC; Whiteman, NK (reprint author), Univ Arizona, Dept Ecol & Evolutionary Biol, Tucson, AZ 85721 USA.; Groen, SC; Whiteman, NK (reprint author), Harvard Univ, Dept Organism & Evolutionary Biol, Cambridge, MA 02138 USA. EM scgroen@email.arizona.edu; pth@email.arizona.edu; daniela578@gmail.com; ausubel@molbio.mgh.harvard.edu; npierce@oeb.harvard.edu; whiteman@e-mail.arizona.edu RI Groen, Simon/G-2443-2012 FU Kirschstein National Research Service Award (NRSA) from the National Institutes of Health [F32AI069732]; National Geographic Society [9097-12]; University of Arizona (Faculty Seed Grant, Center for Insect Science Seed Grant, and laboratory set-up Grant); National Science Foundation [MCB-0519898, MS 0929226, DEB-1256758]; National Institutes of Health [R37, GM48707]; NSF [DEB-1309493]; Harvard University's Provost Fund for Interfaculty Collaboration; Harvard University Science and Engineering Committee Seed Fund for Interdisciplinary Science; John Templeton Foundation [41855] FX We thank Jennifer Bush and Andrew Gloss for providing Arabidopsis and B. vulgaris plants and adult S. flava, Hoon Pyon for assistance with experiments, and Paul Nabity for advice on conducting DAB staining. We are grateful to Andrew Gloss, Tim O'Connor, Philippe Reymond and Sophie Zaaijer for valuable feedback on manuscript drafts and members of the Whiteman, Ausubel and Pierce laboratories for enlightening discussions. We acknowledge Matthew Velazquez for allowing the use of still images from his documentary about the Whiteman laboratory. NKW was supported by a Kirschstein National Research Service Award (NRSA) from the National Institutes of Health (F32AI069732 to NKW), the National Geographic Society (Grant 9097-12 to NKW), and the University of Arizona (Faculty Seed Grant, Center for Insect Science Seed Grant, and laboratory set-up Grant to NKW). FMA and NKW were supported by Grants from the National Science Foundation (Grants MCB-0519898 and MS 0929226 to FMA, and Grant DEB-1256758 to NKW), and FMA was supported by an R37 grant from the National Institutes of Health (Grant GM48707 to FMA). PTH and NKW were supported by the NSF (Grant DEB-1309493 to PTH and NKW). NKW, SCG, FMA and NEP were supported by a Grant from the Harvard University's Provost Fund for Interfaculty Collaboration, and a Grant from the Harvard University Science and Engineering Committee Seed Fund for Interdisciplinary Science. NKW and SCG were supported by the John Templeton Foundation (Grant ID #41855 to NKW). The funding sources had no involvement in the study design; the collection, analysis and interpretation of data; the writing of the report; or in the decision to submit the article for publication. Data accessibility: all raw data have been deposited in the Dryad data repository (http://dx.doi.org/10.5061/dryad.7q37f). NR 127 TC 2 Z9 2 U1 4 U2 11 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0022-1910 EI 1879-1611 J9 J INSECT PHYSIOL JI J. Insect Physiol. PD JAN PY 2016 VL 84 SI SI BP 90 EP 102 DI 10.1016/j.jinsphys.2015.07.011 PG 13 WC Entomology; Physiology; Zoology SC Entomology; Physiology; Zoology GA DD7MO UT WOS:000370108800010 PM 26205072 ER PT J AU Imamura, M Takahashi, A Yamauchi, T Hara, K Yasuda, K Grarup, N Zhao, W Wang, X Huerta-Chagoya, A Hu, C Moon, S Long, J Kwak, SH Rasheed, A Saxena, R Ma, RCW Okada, Y Iwata, M Hosoe, J Shojima, N Iwasaki, M Fujita, H Suzuki, K Danesh, J Jorgensen, T Jorgensen, ME Witte, DR Brandslund, I Christensen, C Hansen, T Mercader, JM Flannick, J Moreno-Macias, H Burtt, NP Zhang, R Kim, YJ Zheng, W Singh, JR Tam, CHT Hirose, H Maegawa, H Ito, C Kaku, K Watada, H Tanaka, Y Tobe, K Kawamori, R Kubo, M Cho, YS Chan, JCN Sanghera, D Kawamori, R Kubo, M Cho, YS Chan, JCN Sanghera, D Frossard, P Park, KS Shu, XO Kim, BJ Florez, JC Tusie-Luna, T Jia, WP Tai, ES Pedersen, O Saleheen, D Maeda, S Kadowaki, T AF Imamura, Minako Takahashi, Atsushi Yamauchi, Toshimasa Hara, Kazuo Yasuda, Kazuki Grarup, Niels Zhao, Wei Wang, Xu Huerta-Chagoya, Alicia Hu, Cheng Moon, Sanghoon Long, Jirong Kwak, Soo Heon Rasheed, Asif Saxena, Richa Ma, Ronald C. W. Okada, Yukinori Iwata, Minoru Hosoe, Jun Shojima, Nobuhiro Iwasaki, Minaka Fujita, Hayato Suzuki, Ken Danesh, John Jorgensen, Torben Jorgensen, Marit E. Witte, Daniel R. Brandslund, Ivan Christensen, Cramer Hansen, Torben Mercader, Josep M. Flannick, Jason Moreno-Macias, Hortensia Burtt, Noel P. Zhang, Rong Kim, Young Jin Zheng, Wei Singh, Jai Rup Tam, Claudia H. T. Hirose, Hiroshi Maegawa, Hiroshi Ito, Chikako Kaku, Kohei Watada, Hirotaka Tanaka, Yasushi Tobe, Kazuyuki Kawamori, Ryuzo Kubo, Michiaki Cho, Yoon Shin Chan, Juliana C. N. Sanghera, Dharambir Kawamori, Ryuzo Kubo, Michiaki Cho, Yoon Shin Chan, Juliana C. N. Sanghera, Dharambir Frossard, Philippe Park, Kyong Soo Shu, Xiao-Ou Kim, Bong-Jo Florez, Jose C. Tusie-Luna, Teresa Jia, Weiping Tai, E. Shyong Pedersen, Oluf Saleheen, Danish Maeda, Shiro Kadowaki, Takashi TI Genome-wide association studies in the Japanese population identify seven novel loci for type 2 diabetes SO NATURE COMMUNICATIONS LA English DT Article ID SUSCEPTIBILITY LOCI; COMPREHENSIVE RESOURCE; PANCREATIC DEVELOPMENT; GENETIC ARCHITECTURE; GLUCOSE-HOMEOSTASIS; THERAPEUTIC TARGET; INSULIN-RESISTANCE; GLYCEMIC TRAITS; DRUG DISCOVERY; BETA-CELLS AB Genome-wide association studies (GWAS) have identified more than 80 susceptibility loci for type 2 diabetes (T2D), but most of its heritability still remains to be elucidated. In this study, we conducted a meta-analysis of GWAS for T2D in the Japanese population. Combined data from discovery and subsequent validation analyses (23,399 T2D cases and 31,722 controls) identify 7 new loci with genome-wide significance (P<5 x 10(-8)), rs1116357 near CCDC85A, rs147538848 in FAM60A, rs1575972 near DMRTA1, rs9309245 near ASB3, rs67156297 near ATP8B2, rs7107784 near MIR4686 and rs67839313 near INAFM2. Of these, the association of 4 loci with T2D is replicated in multi-ethnic populations other than Japanese (up to 65,936 T2Ds and 158,030 controls, P<0.007). These results indicate that expansion of single ethnic GWAS is still useful to identify novel susceptibility loci to complex traits not only for ethnicity-specific loci but also for common loci across different ethnicities. C1 [Imamura, Minako; Maeda, Shiro] RIKEN Ctr Integrat Med Sci, Lab Endocrinol Metab & Kidney Dis, Yokohama, Kanagawa 2300045, Japan. [Takahashi, Atsushi; Okada, Yukinori] RIKEN Ctr Integrat Med Sci, Lab Stat Anal, Yokohama, Kanagawa 2300045, Japan. [Takahashi, Atsushi] Natl Cerebral & Cardiovasc Ctr, Lab Omics Informat Omics Res Ctr, Suita, Osaka 5658565, Japan. [Yamauchi, Toshimasa; Hara, Kazuo; Hosoe, Jun; Shojima, Nobuhiro; Iwasaki, Minaka; Fujita, Hayato; Suzuki, Ken; Kadowaki, Takashi] Univ Tokyo, Dept Diabet & Metab Dis, Grad Sch Med, Tokyo 1130033, Japan. [Hara, Kazuo] Tokyo Med Univ, Dept Diabet Endocrinol Metab & Rheumatol, Tokyo 1600023, Japan. [Yasuda, Kazuki] Natl Ctr Global Hlth & Med, Dept Metab Disorder, Diabet Res Ctr, Res Inst, Tokyo 1628655, Japan. [Grarup, Niels; Hansen, Torben; Pedersen, Oluf] Univ Copenhagen, Novo Nordisk Fdn Ctr Basic Metab Res, Fac Hlth & Med Sci, DK-2200 Copenhagen, Denmark. [Zhao, Wei; Saleheen, Danish] Univ Penn, Dept Biostat & Epidemiol, Philadelphia, PA 19104 USA. [Wang, Xu; Tai, E. Shyong] Natl Univ Singapore, Saw Swee Hock Sch Publ Hlth, Singapore 138672, Singapore. [Huerta-Chagoya, Alicia; Tusie-Luna, Teresa] Univ Nacl Autonoma Mexico, Unidad Biologi Mol & Med Genom, Inst Invest Biomed, Inst Nacl Ciencias Med & Nutr Salvador Zubiran, Mexico City 14000, DF, Mexico. [Hu, Cheng; Zhang, Rong; Jia, Weiping] Shanghai Jiao Tong Univ, Affiliated Peoples Hosp 6, Shanghai Diabet Inst, Dept Endocrinol & Metab,Shanghai Key Lab Diabet M, Shanghai 200233, Peoples R China. [Moon, Sanghoon; Kim, Young Jin; Kim, Bong-Jo] Ctr Genome Sci, Natl Inst Hlth, Div Struct & Funct Gen, Chungcheongbuk Do 28159, South Korea. [Long, Jirong; Zheng, Wei; Shu, Xiao-Ou] Vanderbilt Univ, Vanderbilt Epidemiol Ctr, Vanderbilt Ingram Canc Ctr, Div Epidemiol,Dept Med,Sch Med, Nashville, TN 37203 USA. [Kwak, Soo Heon; Park, Kyong Soo] Seoul Natl Univ Hosp, Dept Internal Med, Seoul 03080, South Korea. [Rasheed, Asif; Frossard, Philippe; Saleheen, Danish] Ctr Non Communicable Dis, Karachi, Pakistan. [Saxena, Richa] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA. [Ma, Ronald C. W.; Tam, Claudia H. T.; Chan, Juliana C. N.] Chinese Univ Hong Kong, Dept Med & Therapeut, Hong Kong, Hong Kong, Peoples R China. [Ma, Ronald C. W.] Chinese Univ Hong Kong, Hong Kong Inst Diabet & Obes, Hong Kong, Hong Kong, Peoples R China. [Ma, Ronald C. W.] Chinese Univ Hong Kong, Li Ka Shing Inst Hlth Sci, Hong Kong, Hong Kong, Peoples R China. [Okada, Yukinori] Tokyo Med & Dent Univ, Dept Human Genet & Dis Div, Grad Sch Med & Dent Sci, Tokyo 1138510, Japan. [Iwata, Minoru; Tobe, Kazuyuki] Toyama Univ, Dept Internal Med 1, Toyama 9300194, Japan. [Iwata, Minoru] Toyama Univ, Hlth Adm Ctr, Toyama 9300194, Japan. [Danesh, John] Univ Cambridge, Dept Publ Hlth & Primary Care, Cambridge CB1 8RN, England. [Danesh, John] Wellcome Trust Genome Campus Hinxton, Wellcome Trust Sanger Inst, Cambridge CB10 1RQ, England. [Danesh, John] Univ Cambridge, NIHR Blood & Transplant Res Unit Donor Hlth & Gen, Dept Publ Hlth & Primary Care, Cambridge CB1 8RN, England. [Jorgensen, Torben] Capital Reg Denmark, Res Ctr Prevent & Hlth, DK-2600 Glostrup, Denmark. [Jorgensen, Torben] Univ Copenhagen, Fac Hlth & Med Sci, Dept Publ Hlth, DK-2200 Copenhagen, Denmark. [Jorgensen, Torben] Aalborg Univ, Fac Med, DK-9220 Aalborg, Denmark. [Jorgensen, Marit E.] Steno Diabet Ctr, DK-2820 Gentofte, Denmark. [Witte, Daniel R.] Aarhus Univ, Dept Publ Hlth, DK-8000 Aarhus, Denmark. [Witte, Daniel R.] Danish Diabet Acad, DK-5000 Odense, Denmark. [Brandslund, Ivan] Lillebaelt Hosp, Dept Clin Biochem, DK-7100 Vejle, Denmark. [Brandslund, Ivan] Univ Southern Denmark, Inst Reg Hlth Res, DK-5230 Odense, Denmark. [Christensen, Cramer] Lillebaelt Hosp, Dept Med, DK-7100 Vejle, Denmark. [Mercader, Josep M.; Flannick, Jason; Burtt, Noel P.; Florez, Jose C.] Broad Inst Harvard, Program Med & Populat Genet, Cambridge, MA 02142 USA. [Mercader, Josep M.; Flannick, Jason; Burtt, Noel P.; Florez, Jose C.] MIT, Cambridge, MA 02142 USA. [Mercader, Josep M.] Barcelona Supercomputing Ctr, Joint BSC CRG IRB Res Program Computat Biol, Barcelona 08034, Spain. [Mercader, Josep M.; Florez, Jose C.] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA. [Mercader, Josep M.; Florez, Jose C.] Massachusetts Gen Hosp, Diabet Res Ctr, Diabet Unit, Boston, MA 02114 USA. [Flannick, Jason] Harvard Univ, Dept Mol Biol, Sch Med, Boston, MA 02115 USA. [Moreno-Macias, Hortensia] Univ Autonomas Metropolitana, Mexico City 09340, DF, Mexico. [Singh, Jai Rup] Cent Univ Punjab, Bathinda 151001, Punjab, India. [Hirose, Hiroshi] Keio Univ, Ctr Hlth, Tokyo 1608582, Japan. [Maegawa, Hiroshi] Shiga Univ Med Sci, Dept Med, Otsu, Shiga 5202192, Japan. [Ito, Chikako] Grand Tower Med Court Life Care Clin, Hiroshima 7300012, Japan. [Kaku, Kohei] Kawasaki Med Univ, Dept Internal Med, Kurashiki, Okayama 7010192, Japan. [Watada, Hirotaka] Juntendo Univ, Dept Endocrinol & Metab, Grad Sch Med, Tokyo 1138421, Japan. [Watada, Hirotaka; Kawamori, Ryuzo] Juntendo Univ, Sportol Ctr, Grad Sch Med, Tokyo 1130034, Japan. [Tanaka, Yasushi] St Marianna Univ, Div Endocrinol & Metab, Dept Internal Med, Sch Med, Kawasaki, Kanagawa 2168511, Japan. [Kubo, Michiaki] RIKEN Ctr Integrat Med Sci, Yokohama, Kanagawa 2300045, Japan. [Cho, Yoon Shin] Hallym Univ, Dept Biomed Sci, Chunchon 24252, Gangwon Do, South Korea. [Sanghera, Dharambir] Univ Oklahoma, Dept Pediat, Hlth Sci Ctr, Oklahoma City, OK 73104 USA. Univ Oklahoma, Dept Pharmaceut Sci, Hlth Sci Ctr, Oklahoma City, OK 73104 USA. [Park, Kyong Soo] Seoul Natl Univ, Dept Internal Med, Coll Med, Seoul 03080, South Korea. [Park, Kyong Soo] Seoul Natl Univ, Dept Mol Med & Biopharmaceut Sci, Grad Sch Convergence Sci & Technol, Seoul 03080, South Korea. [Florez, Jose C.] Harvard Univ, Dept Med, Sch Med, Boston, MA 02115 USA. [Tai, E. Shyong] Natl Univ Singapore, Yong Loo Lin Sch Med, Singapore 119228, Singapore. [Tai, E. Shyong] Duke Natl Univ Singapore, Grad Sch, Singapore 169857, Singapore. [Maeda, Shiro] Univ Ryukyus, Grad Sch Med, Dept Adv Genom & Lab Med, Nishihara, Okinawa 9030215, Japan. [Maeda, Shiro] Univ Ryukyus Hosp, Div Clin Lab & Blood Transfus, Nishihara, Okinawa 9030215, Japan. RP Maeda, S (reprint author), RIKEN Ctr Integrat Med Sci, Lab Endocrinol Metab & Kidney Dis, Yokohama, Kanagawa 2300045, Japan.; Kadowaki, T (reprint author), Univ Tokyo, Dept Diabet & Metab Dis, Grad Sch Med, Tokyo 1130033, Japan.; Maeda, S (reprint author), Univ Ryukyus, Grad Sch Med, Dept Adv Genom & Lab Med, Nishihara, Okinawa 9030215, Japan.; Maeda, S (reprint author), Univ Ryukyus Hosp, Div Clin Lab & Blood Transfus, Nishihara, Okinawa 9030215, Japan. EM smaeda@med.u-ryukyu.ac.jp; kadowaki-3im@h.u-tokyo.ac.jp RI Hu, Cheng/C-3346-2008; Chan, Juliana /B-7918-2016; Grarup, Niels/K-2807-2015; Zheng, Wei/O-3351-2013; Ma, Ronald/C-2788-2009; Park, Kyong Soo/C-2265-2008; OI Zhao, Wei/0000-0002-8301-9297; Shojima, Nobuhiro/0000-0002-4078-3308; Jorgensen, Torben/0000-0001-9453-2830; Tai, E Shyong/0000-0003-2929-8966; Chan, Juliana /0000-0003-1325-1194; Grarup, Niels/0000-0001-5526-1070; Zheng, Wei/0000-0003-1226-070X; Ma, Ronald/0000-0002-1227-803X; Park, Kyong Soo/0000-0003-3597-342X; Mercader, Josep M/0000-0001-8494-3660; Witte, Daniel/0000-0002-0769-2922 FU Leading Project of Ministry of Education, Culture, Sports, Science and Technology-Japan; National 973 Program [2011CB504001]; 863 Program [2012AA02A509]; National Science Foundation of China [81322010]; Hong Kong Foundation for Research and Development in Diabetes; Innovation and Technology Fund [ITS/088/08, ITS/487/09FP]; Research Grants Council Theme-based Research Scheme [T12-402/13-N]; US National Institutes of Health [R37CA070867, R01CA124558, R01CA64277, UL1 RR024975]; Department of Defense Idea Award [BC050791]; Vanderbilt Ingram professorship funds; Allen Foundation Fund; Korean Genome Analysis Project [4845-301]; Korean Genome and Epidemiology Study [4851-302]; Korea Biobank Project [4851-307, KBP-2013-11, KBP-2014-68]; Korea Center for Disease Control and Prevention, Republic of Korea; Korea National Institute of Health, Republic of Korea [2014-NI73001-00]; Korea Health Technology R&D Project, Ministry of Health and Welfare, Republic of Korea [HI14C0060]; Novo Nordisk Foundation; Lundbeck Foundation; National Institute of Health - Fogarty International Center [KO1TW006087]; National Institute of Diabetes and Digestive and Kidney Diseases [R01DK082766]; University of Oklahoma Health Sciences Center, Oklahoma City, USA; CONACyT-Mexico; Sara Borrell Fellowship from Instituto Carlos III [SEV-2011-00067]; EMBO short-term fellowship; EFSD/Lilly research fellowship; Beatriu de Pinos fellowship from Agency for Management of University and Research Grants (AGAUR); Slim Foundation; National Research Foundation of Korea (NRF) grant - Korea government (MEST) [2012R1A2A1A03006155]; British Heart Foundation; UK Medical Research Council [G0800270]; Wellcome Trust; EU Framework 6; Pfizer; Novartis and Merck; British Heart Foundation [SP/09/002]; UK National Institute for Health Research Cambridge Biomedical Research Centre; European Research Council [268834]; European Commission Framework Programme 7 [HEALTH-F2-2012-279233] FX The Mexican/Latino association data were provided by SIGMA T2D Consortium (see Supplementary Note for the contributors list). Data on glycaemic traits in European populations have been contributed by MAGIC investigators and have been downloaded from www.magicinvestigators.org/. Data on GWAS meta-analysis for T2D in European populations have been contributed by DIAGRAM consortium and have been downloaded from http://diagram-consortium.org/. This work was partly supported by a grant from the Leading Project of Ministry of Education, Culture, Sports, Science and Technology-Japan. The work of the Shanghai Jiao Tong University was supported from grants from the National 973 Program (2011CB504001), 863 Program (2012AA02A509) and National Science Foundation of China (81322010). R.C.W.M. and J.C.N.C. acknowledge support from the Hong Kong Foundation for Research and Development in Diabetes, established under the auspices of the Chinese University of Hong Kong, the Innovation and Technology Fund (ITS/088/08 and ITS/487/09FP)), and the Research Grants Council Theme-based Research Scheme (T12-402/13-N). The work by the Shanghai Diabetes Genetic Study (SDGS) was supported in part by the US National Institutes of Health grants R37CA070867, R01CA124558, R01CA64277 and UL1 RR024975, the Department of Defense Idea Award BC050791, Vanderbilt Ingram professorship funds and the Allen Foundation Fund. We thank the dedicated investigators and staff members from research teams at Vanderbilt University, Shanghai Cancer Institute and the Shanghai Institute of Preventive Medicine, and especially the study participants for their contributions in the studies. This study was provided with data from the Korean Genome Analysis Project (4845-301), the Korean Genome and Epidemiology Study (4851-302) and Korea Biobank Project (4851-307, KBP-2013-11 and KBP-2014-68) that were supported by the Korea Center for Disease Control and Prevention, Republic of Korea. This research was supported by an intramural grant from the Korea National Institute of Health (2014-NI73001-00), Republic of Korea. This study was supported by a grant of the Korea Health Technology R&D Project, Ministry of Health and Welfare, Republic of Korea (HI14C0060). 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). The Danish studies, Inter99 and Health2006, were partly 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 Asian Indian Diabetic Heart Study/Sikh Diabetes Study (AIDHS/SDS) was supported by the National Institute of Health grants KO1TW006087 funded by the Fogarty International Center, R01DK082766 funded by National Institute of Diabetes and Digestive and Kidney Diseases, and a seed grant from University of Oklahoma Health Sciences Center, Oklahoma City, USA. We thank the research participants for their contribution and support for making this study possible. A.H.C. was supported by a fellowship from CONACyT-Mexico. J.M.M. was supported by Sara Borrell Fellowship from the Instituto Carlos III, grant SEV-2011-00067 of Severo Ochoa Program and EMBO short-term fellowship, EFSD/Lilly research fellowship and Beatriu de Pinos fellowship from the Agency for Management of University and Research Grants (AGAUR). SIGMA study was supported by the Slim Foundation. Y.S.C.; acknowledges support from the National Research Foundation of Korea (NRF) grant funded by the Korea government (MEST) (2012R1A2A1A03006155). Field-work, genotyping and standard clinical chemistry assays in PROMIS were principally supported by grants awarded to the University of Cambridge from the British Heart Foundation, UK Medical Research Council, Wellcome Trust, EU Framework 6-funded Bloodomics Integrated Project, Pfizer, Novartis and Merck. J.D. acknowledges that this work was funded by the UK Medical Research Council (G0800270), British Heart Foundation (SP/09/002), UK National Institute for Health Research Cambridge Biomedical Research Centre, European Research Council (268834) and European Commission Framework Programme 7 (HEALTH-F2-2012-279233). NR 65 TC 9 Z9 9 U1 2 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 2016 VL 7 AR 10531 DI 10.1038/ncomms10531 PG 12 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA DC2CL UT WOS:000369024700002 PM 26818947 ER PT J AU Gomperts, SN Marquie, M Locascio, JJ Bayer, S Johnson, KA Growdon, JH AF Gomperts, Stephen N. Marquie, Marta Locascio, Joseph J. Bayer, Stephen Johnson, Keith A. Growdon, John H. TI PET Radioligands Roveal the Basis of Demetia in Parkinson's Disease and Dementia with Lewy Bodies SO NEURODEGENERATIVE DISEASES LA English DT Article; Proceedings Paper CT 12th International Conference on Alzheimer's and Parkinson's Diseases and Related Neurological Disorders (AD/PD (TM)) CY MAR 18-22, 2015 CL Nice, FRANCE DE Amyloid; Cognitive impairment; Dementia; Dementia with Lewy bodies; Dopamine transporter; Dopaminergic neurons; Neuroimaging; Parkinson's disease; Positron emission tomography; Tau protein ID COGNITIVE DECLINE; BODY DISEASES; DIAGNOSIS; PATHOLOGY; BIOMARKERS; ALTROPANE; DLB AB Background: Effective therapies for dementia with Lewy bodies (DLB) and Parkinson's disease (PD) dementia will require accurate diagnosis and an understanding of the contribution of distinct molecular pathologies to these diseases. We seek to use imaging biomarkers to improve diagnostic accuracy and to clarify the contribution of molecular species to cognitive impairment in DLB and PD. Summary: We have performed cross-sectional and prospective cohort studies in subjects with DLB, PD with normal cognition, PD with mild cognitive impairment and PD with dementia, contrasted with Alzheimer's disease (AD) and healthy control subjects (HCS). Subjects underwent formal neurological examination, detailed neuropsychological assessments, MRI and PET scans with the radioligands altropane (a dopamine transporter, DAT) and Pittsburgh compound B (PiB; (3-amyloid). Putamen DAT concentrations were similar in DLB and PD and differentiated them from HCS and AD. Decreased caudate DAT concentration related to functional impairment in DLB but not PD. PiB uptake was greatest in DLB. However, cortical PiB retention was common in PD and predicted cognitive decline. PET imaging of tau aggregates holds promise both to clarify the contribution of tau to cognitive decline in these diseases and to differentiate DLB and PD from the parkinsonian tauopathies. Key Messages: Together, DAT and amyloid PET imaging discriminate DLB from PD and from other disease groups and identify pathological processes that contribute to their course. Multimodal PET imaging has the potential to increase the diagnostic accuracy of DLB and PD in the clinic, improve cohort uniformity for clinical trials, and serve as biomarkers for targeted molecular therapies. (C) 2015 S. Karger AG, Basel C1 [Gomperts, Stephen N.; Marquie, Marta; Locascio, Joseph J.; Bayer, Stephen; Johnson, Keith A.; Growdon, John H.] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. [Johnson, Keith A.] Massachusetts Gen Hosp, Dept Radiol, Boston, MA USA. RP Gomperts, SN (reprint author), Massachusetts Gen Hosp, Dept Neurol, 114 16th St,Room 2004, Charlestown, MA 02129 USA. EM sgomperts@partners.org OI Gomperts, Stephen/0000-0002-0083-0077 FU NIA NIH HHS [U01 AG016976, 5 U01 AG016976-11, P01 AG036694, P50 AG005134, R01 AG046396]; NINDS NIH HHS [R21 NS090243] NR 23 TC 7 Z9 7 U1 6 U2 12 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 1660-2854 EI 1660-2862 J9 NEURODEGENER DIS JI Neurodegener. Dis. PY 2016 VL 16 IS 1-2 BP 118 EP 124 DI 10.1159/000441421 PG 7 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA DD2UP UT WOS:000369778000016 PM 26655867 ER PT J AU Steward, J Holt, CL Pollio, DE Austin, EL Johnson, N Gordon, AJ Kertesz, SG AF Steward, Jocelyn Holt, Cheryl L. Pollio, David E. Austin, Erika L. Johnson, Nancy Gordon, Adam J. Kertesz, Stefan G. TI Priorities in the primary care of persons experiencing homelessness: convergence and divergence in the views of patients and provider/experts SO PATIENT PREFERENCE AND ADHERENCE LA English DT Article DE homeless persons; patient-centered care; primary care; provider perspectives ID DECISION-MAKING; PATIENTS WANT; PREFERENCES; QUALITY AB Purpose: Homeless individuals face unique challenges in health care. Several US initiatives seeking to advance patient-centered primary care for homeless persons are more likely to succeed if they incorporate the priorities of the patients they are to serve. However, there has been no prior research to elicit their priorities in primary care. This study sought to identify aspects of primary care important to persons familiar with homelessness based on personal experience or professional commitment, and to highlight where the priorities of patients and professionals dedicated to their care converge or diverge. Methods: This qualitative exercise asked 26 homeless patients and ten provider/experts to rank 16 aspects of primary care using a card sort. Patient-level respondents (n= 26) were recruited from homeless service organizations across all regions of the USA and from an established board of homeless service users. Provider/expert-level respondents (n= 10) were recruited from veteran and non-veteran-focused homeless health care programs with similar geographic diversity. Results: Both groups gave high priority to accessibility, evidence-based care, coordination, and cooperation. Provider/experts endorsed patient control more strongly than patients. Patients ranked information about their care more highly than provider/experts. Conclusion: Accessibility and the perception of care based on medical evidence represent priority concerns for homeless patients and provider/experts. Patient control, a concept endorsed by experts, is not strongly endorsed by homeless patients. Understanding how to assure fluid communication, coordination, and team member cooperation could represent more worthy targets for research and quality improvement in this domain. C1 [Steward, Jocelyn] Clayton State Univ, Dept Hlth Care Management, Morrow, GA USA. [Holt, Cheryl L.] Univ Maryland, Dept Psychol, College Pk, MD 20742 USA. [Pollio, David E.] Univ Alabama Birmingham, Dept Social Work, Birmingham, AL USA. [Austin, Erika L.; Johnson, Nancy; Kertesz, Stefan G.] Birmingham VA Med Ctr, Birmingham, AL USA. [Austin, Erika L.] Univ Alabama Birmingham, Sch Publ Hlth, Dept Biostat, Birmingham, AL USA. [Gordon, Adam J.] VA Pittsburgh Hlth Care Syst, Pittsburgh, PA USA. [Gordon, Adam J.] Univ Pittsburgh, Sch Med, Pittsburgh, PA USA. [Kertesz, Stefan G.] Univ Alabama Birmingham, Sch Med, Dept Med, Birmingham, AL USA. Birmingham VA Med Ctr, Hlth Serv Res & Dev Program, Birmingham, AL 35233 USA. RP Kertesz, SG (reprint author), Birmingham VA Med Ctr, Hlth Serv Res & Dev Program, 700 South 19th St, Birmingham, AL 35233 USA. EM skertesz@uabmc.edu FU Department of Veterans Affairs, Health Services Research and Development Branch, Merit Award [07-969] FX This study is sponsored by the Department of Veterans Affairs, Health Services Research and Development Branch, Merit Award 07-969. Opinions expressed within this manuscript are those of the authors alone and do not represent positions of the Veterans Health Administration or any entity within the US federal government. NR 21 TC 0 Z9 0 U1 3 U2 4 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 2016 VL 10 BP 153 EP 158 DI 10.2147/PPA.S75477 PG 6 WC Medicine, General & Internal SC General & Internal Medicine GA DD7EA UT WOS:000370085300001 PM 26929607 ER PT J AU Patorno, E Wang, SV Schneeweiss, S Liu, J Bateman, BT AF Patorno, Elisabetta Wang, Shirley V. Schneeweiss, Sebastian Liu, Jun Bateman, Brian T. TI Initiation patterns of statin therapy among adult patients undergoing intermediate to high-risk non-cardiac surgery SO PHARMACOEPIDEMIOLOGY AND DRUG SAFETY LA English DT Article DE statins; non-cardiac surgery; ischemic heart disease; patterns of drug utilization; pharmacoepidemiology ID AORTIC-ANEURYSM SURGERY; LIPID-LOWERING THERAPY; VASCULAR-SURGERY; PERIOPERATIVE MORTALITY; CAROTID-ENDARTERECTOMY; CARDIOVASCULAR EVENTS; MYOCARDIAL-INFARCTION; NONVASCULAR SURGERY; ATRIAL-FIBRILLATION; BETA-BLOCKERS AB Background A growing body of literature has been produced on the potential role of statins in reducing perioperative cardiac events in patients undergoing non-cardiac surgery. However, evidence remains inconsistent, and little is known about the patterns of perioperative statin use in routine care. Objectives The objective of this study was to examine patterns of perioperative statin initiation among adults undergoing non-cardiac elective surgery in the USA. Methods Using data from a large US healthcare insurer, we identified patients aged = 18 years who underwent moderate-risk to high-risk non-cardiac elective surgery between 2003 and 2012 and initiated statins within 30 days before surgery. We evaluated temporal trends of statin initiation and patient characteristics. In a matched analysis, we assessed the effect of temporal proximity to surgery on the likelihood of statin initiation. Results Of 460,154 patients undergoing surgery, 5628 (12 per 1000 patients) initiated a statin within 30 days before surgery. Statin initiation increased from 8 per 1000 patients in 2003 to 15 in 2012 (p = 0.0022). The increase was more pronounced among patients undergoing vascular surgery (149 initiators per 1000 patients by the end of 2012) and with Revised Cardiac Risk Index (RCRI) score = 2 (72 per 1000 patients). Proximity to surgery, in particular vascular surgery, was predictive of statin initiation. Conclusions Despite the lack of robust evidence, perioperative statin initiation progressively increased from 2003 to 2012, particularly among patients undergoing major vascular surgery and with higher RCRI score. These trends were largely attributable to the initiation of statins in anticipation of non-cardiac surgery rather than routine dyslipidemia treatment. Copyright (C) 2015 John Wiley & Sons, Ltd. C1 [Patorno, Elisabetta; Wang, Shirley V.; Schneeweiss, Sebastian; Liu, Jun; Bateman, Brian T.] Harvard Univ, Brigham & Womens Hosp, Div Pharmacoepidemiol & Pharmacoecon, Dept Med,Med Sch, 1620 Tremont St,Suite 3030, Boston, MA 02120 USA. [Bateman, Brian T.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Anesthesia Crit Care & Pain Med, Boston, MA 02120 USA. RP Patorno, E (reprint author), Harvard Univ, Brigham & Womens Hosp, Div Pharmacoepidemiol & Pharmacoecon, Dept Med,Med Sch, 1620 Tremont St,Suite 3030, Boston, MA 02120 USA. EM epatorno@partners.org RI Schneeweiss, Sebastian/C-2125-2013 FU AHRQ HHS [K99 HS022193, R00 HS022193]; NICHD NIH HHS [K08 HD075831] NR 34 TC 0 Z9 0 U1 0 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1053-8569 EI 1099-1557 J9 PHARMACOEPIDEM DR S JI Pharmacoepidemiol. Drug Saf. PD JAN PY 2016 VL 25 IS 1 BP 64 EP 72 DI 10.1002/pds.3892 PG 9 WC Public, Environmental & Occupational Health; Pharmacology & Pharmacy SC Public, Environmental & Occupational Health; Pharmacology & Pharmacy GA DD6TI UT WOS:000370057000009 PM 26494361 ER PT J AU Aldelaijan, S Alzorkany, F Moftah, B Buzurovic, I Seuntjens, J Tomic, N Devic, S AF Aldelaijan, Saad Alzorkany, Faisal Moftah, Belal Buzurovic, Ivan Seuntjens, Jan Tomic, Nada Devic, Slobodan TI Use of a control film piece in radiochromic film dosimetry SO PHYSICA MEDICA-EUROPEAN JOURNAL OF MEDICAL PHYSICS LA English DT Article DE Film; Dosimetry; Radiotherapy ID MODEL GAFCHROMIC(TM) FILM; RADIATION; SPECTRA; BEAMS AB Purpose: Radiochromic films change their color upon irradiation due to polymerization of the sensitive component embedded within the sensitive layer. However, agents, other than monitored radiation, can lead to a change in the color of the sensitive layer (temperature, humidity, UV light) that can be considered as a background signal and can be removed from the actual measurement by using a control film piece. In this work, we investigate the impact of the use of control film pieces on both accuracy and uncertainty of dose measured using radiochromic film based reference dosimetry protocol. Methods: We irradiated "control" film pieces (EBT3 GafChromic (TM) film model) to known doses in a range of 0.05-1 Gy, and five film pieces of the same size to 2, 5, 10, 15 and 20 Gy, considered to be "unknown" doses. Depending on a dose range, two approaches to incorporating control film piece were investigated: signal and dose corrected method. Results: For dose values greater than 10 Gy, the increase in accuracy of 3% led to uncertainty loss of 5% by using dose corrected approach. At lower doses and signals of the order of 5%, we observed an increase in accuracy of 10% with a loss of uncertainty lower than 1% by using the corrected signal approach. Conclusions: Incorporation of the signal registered by the control film piece into dose measurement analysis should be a judgment call of the user based on a tradeoff between deemed accuracy and acceptable uncertainty for a given dose measurement. (C) 2015 Associazione Italiana di Fisica Medica. Published by Elsevier Ltd. All rights reserved. C1 [Aldelaijan, Saad; Alzorkany, Faisal; Moftah, Belal] King Faisal Specialist Hosp & Res Ctr, Dept Biomed Phys, Radiat Phys Sect, Riyadh 11211, Saudi Arabia. [Buzurovic, Ivan] Harvard Univ, Sch Med, Dana Farber Brigham Womens Canc Ctr, Med Phys & Biophys Div,Dept Radiat Oncol, Boston, MA USA. [Moftah, Belal; Seuntjens, Jan; Tomic, Nada; Devic, Slobodan] McGill Univ, Med Phys Unit, Montreal, PQ, Canada. [Tomic, Nada; Devic, Slobodan] SMBD Jewish Gen Hosp, Dept Radiat Oncol, Montreal, PQ, Canada. RP Devic, S (reprint author), SMBD Jewish Gen Hosp, 3755 Chemin Cote St Catherine, Montreal, PQ H3T 1E2, Canada. EM slobodan.devic@mcgill.ca RI Buzurovic, Ivan/C-8036-2011; Grams, Michael/G-5197-2011 OI Buzurovic, Ivan/0000-0001-9632-3434; FU Natural Sciences and Engineering Research Council of Canada [386009]; Fonds de Recherche du Quebec - Sante (FRSQ) [26856] FX The work was supported in part by the Natural Sciences and Engineering Research Council of Canada contract No. 386009. S.D. is a Research Scientist supported by the Fonds de Recherche du Quebec - Sante (FRSQ) contract No. 26856. NR 12 TC 5 Z9 5 U1 0 U2 2 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 1120-1797 EI 1724-191X J9 PHYS MEDICA JI Phys. Medica PD JAN PY 2016 VL 32 IS 1 BP 202 EP 207 DI 10.1016/j.ejmp.2015.12.004 PG 6 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA DD0YK UT WOS:000369647300025 PM 26740474 ER PT S AU Fernandez-Godino, R Pierce, EA Garland, DL AF Fernandez-Godino, Rosario Pierce, Eric A. Garland, Donita L. BE Rickman, CB LaVail, MM Anderson, RE Grimm, C Hollyfield, J Ash, J TI Extracellular Matrix Alterations and Deposit Formation in AMD SO RETINAL DEGENERATIVE DISEASES: MECHANISMS AND EXPERIMENTAL THERAPY SE Advances in Experimental Medicine and Biology LA English DT Article; Proceedings Paper CT 16th International Symposium on Retinal Degeneration (RD) CY JUL 13-18, 2014 CL Pacific Grove, CA DE AMD; Extracellular matrix; basal deposits; RPE; Drusen; Complement system; Inflammation; MMP ID AGE-RELATED MACULOPATHY; HUMAN BRUCHS MEMBRANE; SUB-RPE DEPOSITS; MACULAR DEGENERATION; METALLOPROTEINASE ACTIVITY; RETINITIS-PIGMENTOSA; TISSUE INHIBITOR; HUMAN EYES; DRUSEN; INFLAMMATION AB Age related macular degeneration (AMD) is the primary cause of vision loss in the western world (Friedman et al., Arch Ophthalmol 122: 564-572, 2004). The first clinical indication of AMD is the presence of drusen. However, with age and prior to the formation of drusen, extracellular basal deposits accumulate between the retinal pigment epithelium (RPE) and Bruch's membrane (BrM). Many studies on the molecular composition of the basal deposits and drusen have demonstrated the presence of extracellular matrix (ECM) proteins, complement components and cellular debris. The evidence reviewed here suggests that alteration in RPE cell function might be the primary cause for the accumulation of ECM and cellular debri found in basal deposits. Further studies are obviously needed in order to unravel the specific pathways that lead to abnormal formation of ECM and complement activation. C1 [Fernandez-Godino, Rosario; Pierce, Eric A.; Garland, Donita L.] Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Ocular Genom Inst, Boston, MA 02114 USA. RP Fernandez-Godino, R (reprint author), Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Ocular Genom Inst, Boston, MA 02114 USA. EM rosario_godino@meei.harvard.edu OI Pierce, Eric/0000-0002-2354-4102 NR 59 TC 3 Z9 3 U1 2 U2 14 PU SPRINGER INT PUBLISHING AG PI CHAM PA GEWERBESTRASSE 11, CHAM, CH-6330, SWITZERLAND SN 0065-2598 BN 978-3-319-17121-0; 978-3-319-17120-3 J9 ADV EXP MED BIOL JI Adv.Exp.Med.Biol. PY 2016 VL 854 BP 53 EP 58 DI 10.1007/978-3-319-17121-0_8 PG 6 WC Medicine, Research & Experimental; Ophthalmology SC Research & Experimental Medicine; Ophthalmology GA BE2OL UT WOS:000369715400008 PM 26427393 ER PT S AU Marneros, AG AF Marneros, Alexander G. BE Rickman, CB LaVail, MM Anderson, RE Grimm, C Hollyfield, J Ash, J TI VEGF-A and the NLRP3 Inflammasome in Age-Related Macular Degeneration SO RETINAL DEGENERATIVE DISEASES: MECHANISMS AND EXPERIMENTAL THERAPY SE Advances in Experimental Medicine and Biology LA English DT Article; Proceedings Paper CT 16th International Symposium on Retinal Degeneration (RD) CY JUL 13-18, 2014 CL Pacific Grove, CA DE VEGF-A; NLRP3 inflammasome; Age-related macular degeneration; AMD; Macrophages; Oxidative stress ID RETINAL-PIGMENT EPITHELIUM; VISUAL FUNCTION; CELLS; RPE; CHORIOCAPILLARIS; EXPRESSION AB The pathomechanisms that lead to age-related macular degeneration (AMD) are only partially understood. The NLRP3 inflammasome has been shown to be activated in the retinal pigment epithelium (RPE) in eyes with AMD. However, it is not known whether inflammasome activation is a cause or consequence of pathologic changes in AMD. A roadblock to defining the role of inflammasome activation and pathways that regulate it for AMD has been the lack of a mouse model that forms AMD-like pathologies in an age-dependent manner in which the role of the inflammasome can be investigated using genetic studies. We have recently identified such a mouse model, in which increased VEGF-A levels result in early degenerative changes of the RPE, followed by cardinal features of both nonexudative and neovascular AMD. Importantly, higher VEGF-A levels lead to increased oxidative damage and a sub-retinal inflammatory infiltrate that are associated with NLRP3 inflammasome activation in the RPE. Targeting the NLRP3 inflammasome inhibited AMD-like pathologies in these mice. These findings suggest that inhibiting the NLRP3 inflammasome or pathways that regulate it may provide novel therapeutic approaches for the treatment of both forms of AMD. C1 [Marneros, Alexander G.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Dermatol,Cutaneous Biol Res Ctr, Charlestown, MA 02129 USA. RP Marneros, AG (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Dermatol,Cutaneous Biol Res Ctr, Charlestown, MA 02129 USA. EM amarneros@mgh.harvard.edu NR 19 TC 2 Z9 2 U1 1 U2 3 PU SPRINGER INT PUBLISHING AG PI CHAM PA GEWERBESTRASSE 11, CHAM, CH-6330, SWITZERLAND SN 0065-2598 BN 978-3-319-17121-0; 978-3-319-17120-3 J9 ADV EXP MED BIOL JI Adv.Exp.Med.Biol. PY 2016 VL 854 BP 79 EP 85 DI 10.1007/978-3-319-17121-0_12 PG 7 WC Medicine, Research & Experimental; Ophthalmology SC Research & Experimental Medicine; Ophthalmology GA BE2OL UT WOS:000369715400012 PM 26427397 ER PT S AU Pujol-Lereis, LM Schafer, N Kuhn, LB Rohrer, B Pauly, D AF Pujol-Lereis, Luciana M. Schaefer, Nicole Kuhn, Laura B. Rohrer, Baerbel Pauly, Diana BE Rickman, CB LaVail, MM Anderson, RE Grimm, C Hollyfield, J Ash, J TI Interrelation Between Oxidative Stress and Complement Activation in Models of Age-Related Macular Degeneration SO RETINAL DEGENERATIVE DISEASES: MECHANISMS AND EXPERIMENTAL THERAPY SE Advances in Experimental Medicine and Biology LA English DT Article; Proceedings Paper CT 16th International Symposium on Retinal Degeneration (RD) CY JUL 13-18, 2014 CL Pacific Grove, CA DE Oxidative stress; Complement system; Age-related macular degeneration; Oxidation-specific epitopes; Alternative pathway; Cigarette smoke model; Light-damage model; CEP-immunization model; Sodium iodate-treatment model; Knock-out mice models ID RETINAL-PIGMENT EPITHELIUM; FACTOR-H DEFICIENCY; CHOROIDAL NEOVASCULARIZATION; PHOTORECEPTOR DEGENERATION; REGULATORY PROTEINS; CIGARETTE-SMOKE; RPE CELLS; MICE; EXPRESSION; COMPONENT AB Millions of individuals older than 50-years suffer from age-related macular degeneration (AMD). Associated with this multifactorial disease are polymorphisms of complement factor genes and a main environmental risk factoroxidative stress. Until now the linkage between these risk factors for AMD has not been fully understood. Recent studies, integrating results on oxidative stress, complement activation, epidemiology and ocular pathology suggested the following sequence in AMD-etiology: initially, chronic oxidative stress results in modification of proteins and lipids in the posterior of the eye; these tissue alterations trigger chronic inflammation, involving the complement system; and finally, invasive immune cells facilitate pathology in the retina. Here, we summarize the results for animal studies which aim to elucidate this molecular interplay of oxidative events and tissue-specific complement activation in the eye. C1 [Schaefer, Nicole; Pauly, Diana] Univ Hosp Regensburg, Dept Ophthalmol, Franz Josef Strauss Allee 11, D-93053 Regensburg, Germany. [Rohrer, Baerbel] Med Univ S Carolina, Ralph H Johnson VA Med Ctr, Dept Ophthalmol, Charleston, SC 29401 USA. [Rohrer, Baerbel] Res Serv, Charleston, SC 29401 USA. [Pujol-Lereis, Luciana M.; Kuhn, Laura B.] Univ Regensburg, Inst Human Genet, Franz Josef Strauss Allee 11, D-93053 Regensburg, Germany. RP Pauly, D (reprint author), Univ Hosp Regensburg, Dept Ophthalmol, Franz Josef Strauss Allee 11, D-93053 Regensburg, Germany. EM Luciana.pujol@klinik.uni-regensburg.de; Nicole.schafer@klinik.uni-regensburg.de; laura.kuhn@stud.uni-regensburg.de; rohrer@musc.edu; Diana.Pauly@klinik.uni-regensburg.de OI Pujol Lereis, Luciana Mercedes/0000-0002-7009-2743 NR 33 TC 4 Z9 4 U1 5 U2 14 PU SPRINGER INT PUBLISHING AG PI CHAM PA GEWERBESTRASSE 11, CHAM, CH-6330, SWITZERLAND SN 0065-2598 BN 978-3-319-17121-0; 978-3-319-17120-3 J9 ADV EXP MED BIOL JI Adv.Exp.Med.Biol. PY 2016 VL 854 BP 87 EP 93 DI 10.1007/978-3-319-17121-0_13 PG 7 WC Medicine, Research & Experimental; Ophthalmology SC Research & Experimental Medicine; Ophthalmology GA BE2OL UT WOS:000369715400013 PM 26427398 ER PT S AU Carvalho, LS Vandenberghe, LH AF Carvalho, Livia S. Vandenberghe, Luk H. BE Rickman, CB LaVail, MM Anderson, RE Grimm, C Hollyfield, J Ash, J TI Understanding Cone Photoreceptor Cell Death in Achromatopsia SO RETINAL DEGENERATIVE DISEASES: MECHANISMS AND EXPERIMENTAL THERAPY SE Advances in Experimental Medicine and Biology LA English DT Article; Proceedings Paper CT 16th International Symposium on Retinal Degeneration (RD) CY JUL 13-18, 2014 CL Pacific Grove, CA DE Achromatopsia; Cone dystrophies; Cone photoreceptors; Cell death; Cone degeneration; Apoptosis ID RETINITIS-PIGMENTOSA; CHANNEL DEFICIENCY; GENE-THERAPY; CNG CHANNELS; MICE LACKING; DEGENERATION; MOUSE; MUTATIONS; MUTANT AB Colour vision is only achieved in the presence of healthy and functional cone photoreceptors found in the retina. It is an essential component of human vision and usually the first complaint patients undergoing vision degeneration have is the loss of daylight colour vision. Therefore, an understanding of the biology and basic mechanisms behind cone death under the degenerative state of retinal dystrophies and how the activation of the apoptotic pathway is triggered will provide valuable knowledge. It will also have broader applications for a spectrum of visual disorders and will be critical for future advances in translational research. C1 [Carvalho, Livia S.; Vandenberghe, Luk H.] Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Ophthalmol,Ocular Genom Inst,Schepens Eye Re, 20 Staniford St, Boston, MA 02114 USA. RP Carvalho, LS (reprint author), Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Ophthalmol,Ocular Genom Inst,Schepens Eye Re, 20 Staniford St, Boston, MA 02114 USA. EM livia_carvalho@meei.harvard.edu OI Carvalho, Livia/0000-0002-3909-5778 NR 29 TC 0 Z9 0 U1 2 U2 15 PU SPRINGER INT PUBLISHING AG PI CHAM PA GEWERBESTRASSE 11, CHAM, CH-6330, SWITZERLAND SN 0065-2598 BN 978-3-319-17121-0; 978-3-319-17120-3 J9 ADV EXP MED BIOL JI Adv.Exp.Med.Biol. PY 2016 VL 854 BP 231 EP 236 DI 10.1007/978-3-319-17121-0_31 PG 6 WC Medicine, Research & Experimental; Ophthalmology SC Research & Experimental Medicine; Ophthalmology GA BE2OL UT WOS:000369715400031 PM 26427416 ER PT S AU Beeson, C Lindsey, C Nasarre, C Bandyopadhyay, M Perron, N Rohrer, B AF Beeson, Craig Lindsey, Chris Nasarre, Cecile Bandyopadhyay, Mausumi Perron, Nathan Rohrer, Baerbel BE Rickman, CB LaVail, MM Anderson, RE Grimm, C Hollyfield, J Ash, J TI Small Molecules that Protect Mitochondrial Function from Metabolic Stress Decelerate Loss of Photoreceptor Cells in Murine Retinal Degeneration Models SO RETINAL DEGENERATIVE DISEASES: MECHANISMS AND EXPERIMENTAL THERAPY SE Advances in Experimental Medicine and Biology LA English DT Article; Proceedings Paper CT 16th International Symposium on Retinal Degeneration (RD) CY JUL 13-18, 2014 CL Pacific Grove, CA DE Mitochondria; Respirometry; Glycolysis; Neuroprotectant; ATP ID OXIDATIVE STRESS; RETINITIS-PIGMENTOSA; MECHANISMS; DEATH; APOPTOSIS; SURVIVAL; ENERGY; OXYGEN AB One feature common to many of the pathways implicated in retinal degeneration is increased metabolic stress leading to impaired mitochondrial function. We found that exposure of cells to calcium ionophores or oxidants as metabolic stressors diminish maximal mitochondrial capacity. A library of 50,000 structurally diverse "drug-like" molecules was screened for protection against loss of calcium-induced loss of mitochondrial capacity in 661W rod-derived cells and C6 glioblastomas. Initial protective hits were then tested for protection against IBMX-induced loss of mitochondrial capacity as measured via respirometry. Molecules that protected mitochondria were then evaluated for protection of rod photoreceptor cells in retinal explants from rd1 mice. Two of the molecules attenuated loss of photoreceptor cells in the rd1 model. In the 661W cells, exposure to calcium ionophore or tert-butylhydroperoxide caused mitochondrial fragmentation that was blocked with the both compounds. Our studies have identified molecules that protect mitochondria and attenuate loss of photoreceptors in models of retinal degeneration suggesting that they could be good leads for development of therapeutic drugs for treatment of a wide variety of retinal dystrophies. C1 [Beeson, Craig; Lindsey, Chris] MitoChem Therapeut Inc, 280 Calhoun St,MSC140, Charleston, SC 29403 USA. [Beeson, Craig; Lindsey, Chris] Med Univ S Carolina, Dept Drug Discovery, Charleston, SC 29425 USA. [Beeson, Craig; Lindsey, Chris] Med Univ S Carolina, Dept Biomed Sci, Charleston, SC 29425 USA. [Nasarre, Cecile; Bandyopadhyay, Mausumi; Perron, Nathan; Rohrer, Baerbel] Med Univ S Carolina, Dept Ophthalmol, 171 Ashley Ave, Charleston, SC 29425 USA. [Rohrer, Baerbel] Ralph H Johnson VA Med Ctr, Div Res, Charleston, SC 29401 USA. RP Beeson, C (reprint author), MitoChem Therapeut Inc, 280 Calhoun St,MSC140, Charleston, SC 29403 USA.; Beeson, C (reprint author), Med Univ S Carolina, Dept Drug Discovery, Charleston, SC 29425 USA.; Beeson, C (reprint author), Med Univ S Carolina, Dept Biomed Sci, Charleston, SC 29425 USA. EM beesonc@musc.edu; lindseyc@musc.edu; nassarre@musc.edu; e-bandyom@musc.edu; perron@musc.edu; rohrer@musc.edu NR 15 TC 0 Z9 0 U1 0 U2 5 PU SPRINGER INT PUBLISHING AG PI CHAM PA GEWERBESTRASSE 11, CHAM, CH-6330, SWITZERLAND SN 0065-2598 BN 978-3-319-17121-0; 978-3-319-17120-3 J9 ADV EXP MED BIOL JI Adv.Exp.Med.Biol. PY 2016 VL 854 BP 449 EP 454 DI 10.1007/978-3-319-17121-0_60 PG 6 WC Medicine, Research & Experimental; Ophthalmology SC Research & Experimental Medicine; Ophthalmology GA BE2OL UT WOS:000369715400060 PM 26427445 ER PT S AU Taub, DG Liu, Q AF Taub, Daniel G. Liu, Qin BE Rickman, CB LaVail, MM Anderson, RE Grimm, C Hollyfield, J Ash, J TI The Role of Intraflagellar Transport in the Photoreceptor Sensory Cilium SO RETINAL DEGENERATIVE DISEASES: MECHANISMS AND EXPERIMENTAL THERAPY SE Advances in Experimental Medicine and Biology LA English DT Article; Proceedings Paper CT 16th International Symposium on Retinal Degeneration (RD) CY JUL 13-18, 2014 CL Pacific Grove, CA DE Inherited retinal degeneration; Intraflagellar transport (IFT); Cilia; Photoreceptor; Protein transport ID ASPHYXIATING THORACIC DYSTROPHY; BARDET-BIEDL-SYNDROME; VERTEBRATE PHOTORECEPTORS; KINESIN-II; CAENORHABDITIS-ELEGANS; IFT PARTICLES; OUTER SEGMENT; MUTATIONS; RETROGRADE; PROTEIN AB The photoreceptor is a complex specialized cell in which a major component responsible for visual transduction is the photoreceptor sensory cilium (PSC). Building and maintenance of the PSC requires the transport of large proteins along microtubules that extend from the inner segments to the outer segments. A key process, termed intraflagellar transport (IFT), has been recognized as an essential phenomenon for photoreceptor development and maintenance, and exciting new studies have highlighted its importance in retinal and cilia related diseases. This review focuses on the important roles of IFT players, including motor proteins, IFT proteins, and photoreceptor-specific cargos in photoreceptor sensory cilium. In addition, specific IFT components that are involved in inherited human diseases are discussed. C1 [Taub, Daniel G.; Liu, Qin] Harvard Univ, Sch Med, Ocular Genom Inst, 243 Charles St,5th Floor,563C, Boston, MA 02114 USA. [Taub, Daniel G.; Liu, Qin] Harvard Univ, Sch Med, Massachusetts Eye & Ear Infirm, Berman Gund Lab Study Retinal Degenerat,Dept Opht, 243 Charles St,5th Floor,563C, Boston, MA 02114 USA. RP Liu, Q (reprint author), Harvard Univ, Sch Med, Ocular Genom Inst, 243 Charles St,5th Floor,563C, Boston, MA 02114 USA.; Liu, Q (reprint author), Harvard Univ, Sch Med, Massachusetts Eye & Ear Infirm, Berman Gund Lab Study Retinal Degenerat,Dept Opht, 243 Charles St,5th Floor,563C, Boston, MA 02114 USA. EM dtaub1230@gmail.com; qin_liu@meei.harvard.edu NR 29 TC 0 Z9 0 U1 1 U2 4 PU SPRINGER INT PUBLISHING AG PI CHAM PA GEWERBESTRASSE 11, CHAM, CH-6330, SWITZERLAND SN 0065-2598 BN 978-3-319-17121-0; 978-3-319-17120-3 J9 ADV EXP MED BIOL JI Adv.Exp.Med.Biol. PY 2016 VL 854 BP 627 EP 633 DI 10.1007/978-3-319-17121-0_83 PG 7 WC Medicine, Research & Experimental; Ophthalmology SC Research & Experimental Medicine; Ophthalmology GA BE2OL UT WOS:000369715400083 PM 26427468 ER PT S AU Rohrer, B Bandyopadhyay, M Beeson, C AF Rohrer, Baebel Bandyopadhyay, Mausumi Beeson, Craig BE Rickman, CB LaVail, MM Anderson, RE Grimm, C Hollyfield, J Ash, J TI Reduced Metabolic Capacity in Aged Primary Retinal Pigment Epithelium (RPE) is Correlated with Increased Susceptibility to Oxidative Stress SO RETINAL DEGENERATIVE DISEASES: MECHANISMS AND EXPERIMENTAL THERAPY SE Advances in Experimental Medicine and Biology LA English DT Article; Proceedings Paper CT 16th International Symposium on Retinal Degeneration (RD) CY JUL 13-18, 2014 CL Pacific Grove, CA DE Retinal pigment epithelium; Mitochondria; ATP production; Oxidative stress ID MACULAR DEGENERATION; CELLS; COMPLEMENT AB One of the affected tissues in age-related macular degeneration (AMD) is the retinal pigment epithelium (RPE), a tissue that consists of terminally differentiated cells and that accumulates damage over time. In all tissues, mitochondria (mt), which play an essential role in both cell health (energy) and death (initiator of apoptosis), undergo an aging process through the accumulation of mtDNA damage, changes in mitochondrial dynamics, a reduction in biogenesis, and mitophagy, leading to an overall reduction in mitochondrial energy production and other non-energy-related functions. Here we have compared energy metabolism in primary human RPE cells isolated from aborted fetus or aged donor eyes and grown as stable monolayers. H2O2 treatment resulted in the generation of reactive oxygen species and superoxide, an effect that was significantly augmented by age. Mitochondrial metabolism, as analyzed by Seahorse respirometry, revealed reduced mitochondrial oxygen consumption (ATP production) at baseline and a complete loss of reserve capacity in aged cells. Likewise, glycolysis was blunted in aged cells. Taken together, these studies showed that RPE cells derived from aged donor eyes are more susceptible to oxidative stress, and exhibit a loss in mitochondrial respiratory reserve capacity and a reduction in glycolysis. These data suggest that while old cells may have sufficient energy at rest, they cannot mount a stress response requiring additional ATP and reducing agents. In summary, these data support the hypothesis that mitochondria or energy metabolism is a valid target for therapy in AMD. C1 [Rohrer, Baebel; Bandyopadhyay, Mausumi] Med Univ S Carolina, Dept Ophthalmol, 167 Ashley Ave,SEI614, Charleston, SC 29425 USA. [Beeson, Craig] Med Univ S Carolina, Dept Drug Discovery & Biomed Sci, 167 Ashley Ave,SEI614, Charleston, SC 29425 USA. [Rohrer, Baebel] Ralph H Johnson VA Med Ctr, Res Serv, Charleston, SC USA. RP Rohrer, B (reprint author), Med Univ S Carolina, Dept Ophthalmol, 167 Ashley Ave,SEI614, Charleston, SC 29425 USA. EM rohrer@musc.edu FU National Institutes of Health [R01EY019320]; Veterans Affairs [I01 RX000444]; Foundation Fighting Blindness; Research to Prevent Blindness FX This work was supported in part by the National Institutes of Health (R01EY019320), Veterans Affairs (I01 RX000444), Foundation Fighting Blindness, and an unrestricted grant to MUSC from Research to Prevent Blindness. The authors have no financial conflicts of interest. NR 12 TC 5 Z9 5 U1 0 U2 3 PU SPRINGER INT PUBLISHING AG PI CHAM PA GEWERBESTRASSE 11, CHAM, CH-6330, SWITZERLAND SN 0065-2598 BN 978-3-319-17121-0; 978-3-319-17120-3 J9 ADV EXP MED BIOL JI Adv.Exp.Med.Biol. PY 2016 VL 854 BP 793 EP 798 DI 10.1007/978-3-319-17121-0_106 PG 6 WC Medicine, Research & Experimental; Ophthalmology SC Research & Experimental Medicine; Ophthalmology GA BE2OL UT WOS:000369715400106 PM 26427491 ER PT S AU Medarova, Z AF Medarova, Zdravka BE Medarova, Z TI RNA Imaging Methods and Protocols Preface SO RNA IMAGING: METHODS AND PROTOCOLS SE Methods in Molecular Biology LA English DT Editorial Material; Book Chapter C1 [Medarova, Zdravka] Massachusetts Gen Hosp, Mol Imaging Lab, MGH MIT HMS Athinoula A Martinos Ctr Biomed Imagi, Charlestown, MA USA. [Medarova, Zdravka] Harvard Univ, Sch Med, Charlestown, MA USA. [Medarova, Zdravka] Massachusetts Gen Hosp, Dept Radiol, Charlestown, MA USA. RP Medarova, Z (reprint author), Massachusetts Gen Hosp, Mol Imaging Lab, MGH MIT HMS Athinoula A Martinos Ctr Biomed Imagi, Charlestown, MA USA.; Medarova, Z (reprint author), Harvard Univ, Sch Med, Charlestown, MA USA.; Medarova, Z (reprint author), Massachusetts Gen Hosp, Dept Radiol, Charlestown, MA USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DR, STE 208, TOTOWA, NJ 07512-1165 USA SN 1064-3745 BN 978-1-4939-3148-4; 978-1-4939-3147-7 J9 METHODS MOL BIOL JI Methods Mol. Biol. PY 2016 VL 1372 BP V EP V D2 10.1007/978-1-4939-3148-4 PG 1 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Radiology, Nuclear Medicine & Medical Imaging SC Biochemistry & Molecular Biology; Radiology, Nuclear Medicine & Medical Imaging GA BE2US UT WOS:000370129400001 ER PT S AU Wang, P Moore, A AF Wang, Ping Moore, Anna BE Medarova, Z TI In Vivo Magnetic Resonance Imaging of Small Interfering RNA Nanodelivery to Pancreatic Islets SO RNA IMAGING: METHODS AND PROTOCOLS SE Methods in Molecular Biology LA English DT Article; Book Chapter DE Pancreatic islet; Small interfering RNA; Molecular imaging; Magnetic nanoparticles; Diabetes ID IMMUNE REJECTION; SIRNA DELIVERY; TRANSPLANTATION; THERAPY AB Pancreatic islet transplantation is a promising therapeutic approach for type 1 diabetes. However, recent advances in islet transplantation are limited by significant graft loss after transplantation. Multiple immunological and nonimmunological factors contribute to this loss. Novel therapies that could target the core reasons for the islet graft loss are desperately needed. Small interfering RNA can be used to inhibit the expression of virtually any gene with single-nucleotide specificity including genes responsible for islet damage. Applying adequate delivery of siRNA molecules to pancreatic islets prior to transplantation holds a great potential for improving the survival of islet grafts. Noninvasive imaging provides means for monitoring the survival of transplanted islets in real time. Here, we summarize the approach that has been developed to deliver siRNA to pancreatic islets in conjunction with tracking of the graft outcome by in vivo magnetic resonance imaging (MRI). We synthesize a nano-sized theranostic agent consisting of magnetic nanoparticles (MN), a reporter for MRI, labeled with Cy5.5 dye for near infrared fluorescence (NIRF) imaging, and conjugated to siRNA molecule targeting genes that are harmful to islet grafts. Pre-labeling of islets by MN-Cy5.5-siRNA allowed us to monitor the survival of transplanted islet grafts by MRI and NIRF imaging and resulted in efficient silencing of the target genes in vivo. This novel approach combines a therapeutic effect provided by RNA interference technology with in vivo MR imaging and is expected to significantly improve the outcome of islet transplantation in patients with type 1 diabetes. C1 [Wang, Ping; Moore, Anna] Harvard Univ, Sch Med, Mol Imaging Lab, MGH MIT HMS Athinoula A Martinos Ctr Biomed Imagi, Charlestown, MA USA. [Wang, Ping; Moore, Anna] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Radiol, Charlestown, MA USA. RP Wang, P (reprint author), Harvard Univ, Sch Med, Mol Imaging Lab, MGH MIT HMS Athinoula A Martinos Ctr Biomed Imagi, Charlestown, MA USA. OI Wang, Ping/0000-0001-6712-8939 NR 12 TC 0 Z9 0 U1 1 U2 10 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DR, STE 208, TOTOWA, NJ 07512-1165 USA SN 1064-3745 BN 978-1-4939-3148-4; 978-1-4939-3147-7 J9 METHODS MOL BIOL JI Methods Mol. Biol. PY 2016 VL 1372 BP 25 EP 36 DI 10.1007/978-1-4939-3148-4_2 D2 10.1007/978-1-4939-3148-4 PG 12 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Radiology, Nuclear Medicine & Medical Imaging SC Biochemistry & Molecular Biology; Radiology, Nuclear Medicine & Medical Imaging GA BE2US UT WOS:000370129400003 PM 26530912 ER PT S AU Kavishwar, A Medarova, Z AF Kavishwar, Amol Medarova, Zdravka BE Medarova, Z TI Sensing miRNA: Signal Amplification by Cognate RISC for Intracellular Detection of miRNA in Live Cells SO RNA IMAGING: METHODS AND PROTOCOLS SE Methods in Molecular Biology LA English DT Article; Book Chapter DE miRNA; Sensor; RISC; Intracellular detection; Fluorescence; Turn on; Live cells AB The ability to detect miRNA expression in live cells would leave these cells available for further manipulation or culture. Here, we describe the design of a miRNA sensor oligonucleotide whose sequence mimics the target mRNA. The sensor has a fluorescent label on one end of the oligo and a quencher on the other. When inside the cell, the sensor is recognized by its cognate miRNA-RISC and gets cleaved, setting the fluorophore free from its quencher. This results in fluorescence "turn on." Since cleavage by the RISC complex is an enzymatic process, the described approach has a very high level of sensitivity (nM). The rate of nonspecific cleavage of the sensor is very slow permitting the collection of meaningful signal over a long period of time. C1 [Kavishwar, Amol] Harvard Univ, Sch Med, Massachusetts Gen Hosp,Dept Radiol, Mol Imaging Lab,MGH MIT HMS Athinoula A Martinos, Charlestown, MA USA. [Medarova, Zdravka] Massachusetts Gen Hosp, Mol Imaging Lab, MGH MIT HMS Athinoula A Martinos Ctr Biomed Imagi, Charlestown, MA USA. [Medarova, Zdravka] Harvard Univ, Sch Med, Charlestown, MA USA. [Medarova, Zdravka] Massachusetts Gen Hosp, Dept Radiol, Charlestown, MA USA. RP Kavishwar, A (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp,Dept Radiol, Mol Imaging Lab,MGH MIT HMS Athinoula A Martinos, Charlestown, MA USA. FU NCI NIH HHS [1R01CA163461-01A1, R00CA129070] NR 5 TC 0 Z9 0 U1 2 U2 7 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DR, STE 208, TOTOWA, NJ 07512-1165 USA SN 1064-3745 BN 978-1-4939-3148-4; 978-1-4939-3147-7 J9 METHODS MOL BIOL JI Methods Mol. Biol. PY 2016 VL 1372 BP 121 EP 127 DI 10.1007/978-1-4939-3148-4_10 D2 10.1007/978-1-4939-3148-4 PG 7 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Radiology, Nuclear Medicine & Medical Imaging SC Biochemistry & Molecular Biology; Radiology, Nuclear Medicine & Medical Imaging GA BE2US UT WOS:000370129400011 PM 26530920 ER PT S AU Medarova, Z Balcioglu, M Yigit, MV AF Medarova, Zdravka Balcioglu, Mustafa Yigit, Mehmet V. BE Medarova, Z TI Controlling RNA Expression in Cancer Using Iron Oxide Nanoparticles Detectable by MRI and In Vivo Optical Imaging SO RNA IMAGING: METHODS AND PROTOCOLS SE Methods in Molecular Biology LA English DT Article; Book Chapter DE Contrast agent; MRI; Fluorescence; Optical imaging; Tumor; Nanoparticle; miRNA; siRNA; Antisense oligonucleotide; Iron oxide; Oncogene ID SMALL INTERFERING RNA; THERAPY; NANODRUG; DELIVERY; CELLS AB Herein, we describe a protocol for the preparation of iron oxide nanoparticle-based contrast agents and drug delivery vehicles for noninvasive cancer imaging and therapy. In the first part of the chapter we describe the details of the contrast agent synthesis, functionalization, and characterization. In the second part we describe the methods for tumor imaging using the synthesized particles with noninvasive T2-weighted magnetic resonance imaging (MRI) and in vivo near infrared optical imaging. C1 [Medarova, Zdravka] Massachusetts Gen Hosp, Mol Imaging Lab, MGH MIT HMS Athinoula A Martinos Ctr Biomed Imagi, Charlestown, MA USA. [Medarova, Zdravka] Harvard Univ, Sch Med, Charlestown, MA USA. [Medarova, Zdravka] Massachusetts Gen Hosp, Dept Radiol, Charlestown, MA USA. [Balcioglu, Mustafa; Yigit, Mehmet V.] SUNY Albany, Dept Chem, Albany, NY 12222 USA. [Yigit, Mehmet V.] SUNY Albany, RNA Inst, Albany, NY 12222 USA. RP Medarova, Z (reprint author), Massachusetts Gen Hosp, Mol Imaging Lab, MGH MIT HMS Athinoula A Martinos Ctr Biomed Imagi, Charlestown, MA USA.; Medarova, Z (reprint author), Harvard Univ, Sch Med, Charlestown, MA USA.; Medarova, Z (reprint author), Massachusetts Gen Hosp, Dept Radiol, Charlestown, MA USA. NR 13 TC 0 Z9 0 U1 1 U2 12 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DR, STE 208, TOTOWA, NJ 07512-1165 USA SN 1064-3745 BN 978-1-4939-3148-4; 978-1-4939-3147-7 J9 METHODS MOL BIOL JI Methods Mol. Biol. PY 2016 VL 1372 BP 163 EP 179 DI 10.1007/978-1-4939-3148-4_13 D2 10.1007/978-1-4939-3148-4 PG 17 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Radiology, Nuclear Medicine & Medical Imaging SC Biochemistry & Molecular Biology; Radiology, Nuclear Medicine & Medical Imaging GA BE2US UT WOS:000370129400014 PM 26530923 ER PT S AU Sepulcre, J Masdeu, JC AF Sepulcre, Jorge Masdeu, Joseph C. BE Castrillo, JI Oliver, SG TI Advanced Neuroimaging Methods Towards Characterization of Early Stages of Alzheimer's Disease SO SYSTEMS BIOLOGY OF ALZHEIMER'S DISEASE SE Methods in Molecular Biology LA English DT Article; Book Chapter DE Alzheimer's disease; Neuroimaging; Network analysis; Amyloid; Graph theory; Early stages; Functional connectivity magnetic resonance imaging (fcMRI); Positron emission tomography (PET) ID MILD COGNITIVE IMPAIRMENT; INTRINSIC FUNCTIONAL CONNECTIVITY; AMYLOID-BETA DEPOSITION; COMPLEX BRAIN NETWORKS; PITTSBURGH COMPOUND-B; A-BETA; NEURITIC PLAQUES; NEURODEGENERATIVE DISEASES; NEUROFIBRILLARY TANGLES; CASCADE HYPOTHESIS AB In the past 5 years, imaging network properties in the brain of patients with Alzheimer's disease (AD) has revolutionized our understanding of this disorder. Postmortem data had already suggested that the damage spreads along functional neural networks, but postmortem studies do not provide information on the temporal evolution of the damage in the same patient, essential to determine spreading. These data can be provided by functional and structural neuroimaging, which allow for the visualization over time of the progressive damage inflicted by AD. Functional networks can be mapped by determining the synchrony across brain regions of the blood oxygenation level dependence (BOLD) signal on functional magnetic resonance imaging (MRI) during quiet wakefulness. Other less extensively used techniques are also useful. For instance, amyloid deposition can be imaged and its progression mapped to determine whether it follows brain networks, and, if so, which are affected earliest. Network patterns of neurobiological changes, including tau deposition, may prove critical to our understanding of the neurobiology of AD and therefore open the way for therapeutic interventions. C1 [Sepulcre, Jorge] Massachusetts Gen Hosp, Dept Radiol, Div Nucl Med & Mol Imaging, Boston, MA USA. [Sepulcre, Jorge] Harvard Univ, Sch Med, Boston, MA USA. [Sepulcre, Jorge] Athinioula A Martinos Ctr Biomed Imaging Charlest, Charlestown, MA USA. [Masdeu, Joseph C.] Cornell Univ, Weill Med Coll, Nantz Natl Alzheimer Ctr & Neuroimaging, Houston Methodist Neurol Inst, Houston, TX USA. [Masdeu, Joseph C.] NIMH, Sect Integrat Neuroimaging, Clin Brain Disorders Branch, NIH, Bethesda, MD 20892 USA. RP Sepulcre, J (reprint author), Massachusetts Gen Hosp, Dept Radiol, Div Nucl Med & Mol Imaging, Boston, MA USA.; Sepulcre, J (reprint author), Harvard Univ, Sch Med, Boston, MA USA.; Sepulcre, J (reprint author), Athinioula A Martinos Ctr Biomed Imaging Charlest, Charlestown, MA USA.; Sepulcre, J (reprint author), Cornell Univ, Weill Med Coll, Nantz Natl Alzheimer Ctr & Neuroimaging, Houston Methodist Neurol Inst, Houston, TX USA. NR 69 TC 0 Z9 0 U1 1 U2 34 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DR, STE 208, TOTOWA, NJ 07512-1165 USA SN 1064-3745 BN 978-1-4939-2627-5; 978-1-4939-2626-8 J9 METHODS MOL BIOL JI Methods Mol. Biol. PY 2016 VL 1303 BP 509 EP 519 DI 10.1007/978-1-4939-2627-5_31 D2 10.1007/978-1-4939-2627-5 PG 11 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Clinical Neurology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA BE2UR UT WOS:000370127800032 PM 26235088 ER PT J AU Kovacs, R Baggish, AL AF Kovacs, Richard Baggish, Aaron L. TI Cardiovascular adaptation in athletes SO TRENDS IN CARDIOVASCULAR MEDICINE LA English DT Article DE Athlete's heart; Sports cardiology; Exercise; Athlete; Cardiomyopathy; Hypertrophy ID LEFT-VENTRICULAR HYPERTROPHY; EARLY REPOLARIZATION PATTERN; HEAVY-RESISTANCE EXERCISE; ANDROGENIC STEROID USE; BLOOD-PRESSURE; CARDIAC STRUCTURE; HEART; ENDURANCE; SPORTS; IMPACT AB Millions of athletes train for and participate in competitive athletics each year. Many of these athletes will present to a cardiovascular specialist with signs or symptoms that might indicate heart disease and these athletes/patients will ask for advice on their ability to continue to train and compete safely. By virtue of their training, athletes' hearts may undergo significant structural and electrical change, presenting a special challenge for the cardiovascular specialist. It is important to understand normal adaptive changes in order to separate normal physiology from pathology. C1 [Kovacs, Richard] Indiana Univ Sch Med, Krannert Inst Cardiol, Indianapolis, IN 46202 USA. [Baggish, Aaron L.] Massachusetts Gen Hosp, Cardiovasc Performance Ctr, Boston, MA 02114 USA. RP Kovacs, R (reprint author), Indiana Univ Sch Med, Krannert Inst Cardiol, Indianapolis, IN 46202 USA. EM rikovacs@iu.edu FU University Health/Indiana University School of Medicine Strategic Research Initiative FX Supported in part by the University Health/Indiana University School of Medicine Strategic Research Initiative (R.J.K.). NR 42 TC 4 Z9 4 U1 6 U2 23 PU ELSEVIER SCIENCE LONDON PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 1050-1738 J9 TRENDS CARDIOVAS MED JI Trends Cardiovasc. Med. PD JAN PY 2016 VL 26 IS 1 BP 46 EP 52 DI 10.1016/j.tcm.2015.04.003 PG 7 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA DD1JW UT WOS:000369679000009 PM 25976477 ER PT J AU Mahanna, E Edwards, DA Tarante, N Rahman, M Petersen, JW Bihorac, A AF Mahanna, Elizabeth Edwards, David A. Tarante, Nicki Rahman, Maryam Petersen, John W. Bihorac, Azra TI Variant Neurogenic Stunned Myocardium in a Young Female After Subarachnoid Hemorrhage SO A & A CASE REPORTS LA English DT Article ID TAKO-TSUBO CARDIOMYOPATHY; TAKOTSUBO CARDIOMYOPATHY; ELECTROCARDIOGRAPHIC ABNORMALITIES; VENTRICULAR DYSFUNCTION; AMPULLA CARDIOMYOPATHY; EMOTIONAL-STRESS; BETA-BLOCKERS; HEART AB Neurogenic stunned myocardium is a significant complication of subarachnoid hemorrhage. Diagnosis of neurogenic stunned myocardium is complicated by variable presentation. We present a case of a 23-year-old woman admitted with a subarachnoid hemorrhage from an arteriovenous malformation and associated aneurysm. Postoperatively, she developed pulmonary edema and mildly elevated cardiac biomarkers. Echocardiography showed hypokinesis of the basal left ventricular segments and normal contraction of the apical left ventricular segments consistent with a variant form of neurogenic stunned myocardium. We describe characteristics and outcomes of neurogenic stunned myocardium in this young patient with arteriovenous malformation-associated aneurysmal subarachnoid hemorrhage. C1 [Mahanna, Elizabeth] Ochsner Med Ctr, Dept Neurocrit Care & Anesthesiol, New Orleans, LA USA. [Edwards, David A.; Tarante, Nicki; Bihorac, Azra] Univ Florida, Dept Anesthesiol, Gainesville, FL 32610 USA. [Rahman, Maryam] Univ Florida, Dept Neurosurg, Gainesville, FL 32610 USA. [Petersen, John W.] Univ Florida, Dept Med, Gainesville, FL 32610 USA. [Edwards, David A.] Harvard Univ, Massachusetts Gen Hosp, Dept Anesthesiol Crit Care & Pain Med, Boston, MA 02115 USA. [Tarante, Nicki] Dept Anesthesiol & Crit Care, Portsmouth, VA USA. RP Bihorac, A (reprint author), Univ Florida, Coll Med, Dept Anesthesiol, 1600 SW Archer Rd,POB 100254, Gainesville, FL 32610 USA. EM abihorac@anest.ufl.edu NR 28 TC 1 Z9 1 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 2325-7237 J9 A A CASE REP JI A A Case Rep. PD JAN 1 PY 2016 VL 6 IS 1 BP 10 EP 13 DI 10.1213/XAA.0000000000000172 PG 4 WC Anesthesiology SC Anesthesiology GA DC7VR UT WOS:000369429200004 PM 26422453 ER PT J AU Nicklas, TA Kleinman, RE Storey, ML AF Nicklas, Theresa A. Kleinman, Ronald E. Storey, Maureen L. TI Supplement-Science and Policy: Adopting a Fruitful Vegetable Encounter for Our Children Foreword SO ADVANCES IN NUTRITION LA English DT Editorial Material ID INFANTS C1 [Nicklas, Theresa A.] Baylor Coll Med, Dept Pediat, USDA ARS, Childrens Nutr Res Ctr, Houston, TX 77030 USA. [Kleinman, Ronald E.] Massachusetts Gen Hosp, Dept Pediat, Boston, MA 02114 USA. [Storey, Maureen L.] Alliance Potato Res & Educ, Mclean, VA USA. RP Nicklas, TA (reprint author), Baylor Coll Med, Dept Pediat, USDA ARS, Childrens Nutr Res Ctr, Houston, TX 77030 USA. EM tnicklas@bcm.edu NR 5 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC NUTRITION-ASN PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 2161-8313 EI 2156-5376 J9 ADV NUTR JI Adv. Nutr. PD JAN PY 2016 VL 7 IS 1 BP 209S EP 210S DI 10.3945/an.115.011098 PG 2 WC Nutrition & Dietetics SC Nutrition & Dietetics GA DC3HX UT WOS:000369111500021 PM 26773028 ER PT J AU Kelly, JD Weiser, SD Tsai, AC AF Kelly, J. Daniel Weiser, Sheri D. Tsai, Alexander C. TI Proximate Context of HIV Stigma and Its Association with HIV Testing in Sierra Leone: A Population-Based Study SO AIDS AND BEHAVIOR LA English DT Article DE HIV stigma; HIV testing; Sub-Saharan Africa; Population-based; Sierra Leone ID RURAL UGANDA; AFRICA AB The extent to which HIV stigma at the community level remains a barrier to greater uptake in HIV testing services is poorly understood. We used nationally representative data from the 2008 Sierra Leone Demographic and Health Survey. The primary outcome was HIV testing (past 12 months). Our explanatory variable was HIV stigmatizing attitudes (5-item scale). After multivariable adjustment, HIV testing had an inverse association with HIV stigmatizing attitudes measured at the individual [adjusted odds ratio (AOR) 0.94; 95 % CI 0.87-1.01] and community level (AOR 0.70; 95 % CI 0.58-0.85). HIV stigma had a stronger negative association with HIV testing when modeled at the community rather than individual level. C1 [Kelly, J. Daniel] Univ Calif San Francisco, Div Infect Dis, Dept Med, 513 Parnassus Ave,S-380, San Francisco, CA 94117 USA. [Weiser, Sheri D.] Univ Calif San Francisco, San Francisco Gen Hosp, Div HIV AIDS, Dept Med, San Francisco, CA 94117 USA. [Tsai, Alexander C.] Massachusetts Gen Hosp, MD Div Global Psychiat, Ctr Global Hlth & Chester M Pierce, Boston, MA 02114 USA. [Tsai, Alexander C.] Harvard Univ, Sch Med, Boston, MA USA. [Tsai, Alexander C.] Mbarara Univ Sci & Technol, Mbarara, Uganda. RP Kelly, JD (reprint author), Univ Calif San Francisco, Div Infect Dis, Dept Med, 513 Parnassus Ave,S-380, San Francisco, CA 94117 USA. EM dan.kelly@ucsf.edu OI Tsai, Alexander/0000-0001-6397-7917 FU U.S. National Institutes of Health [K23MH096620]; Robert Wood Johnson Health and Society Scholars Program; Hellman Family Foundation; Burke Family Foundation FX We would like to thank Measure DHS for access and authorization to the 2008 Sierra Leone Demographic Health Survey data files for research purposes. The authors received no specific funding for this study. ACT acknowledges salary support through the U.S. National Institutes of Health K23MH096620 and the Robert Wood Johnson Health and Society Scholars Program. SDW acknowledges salary support through the Hellman Family Foundation and Burke Family Foundation. NR 15 TC 4 Z9 4 U1 1 U2 2 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 2016 VL 20 IS 1 BP 65 EP 70 DI 10.1007/s10461-015-1035-9 PG 6 WC Public, Environmental & Occupational Health; Social Sciences, Biomedical SC Public, Environmental & Occupational Health; Biomedical Social Sciences GA DC9DH UT WOS:000369520800007 PM 25771909 ER PT J AU Obata, Y Adachi, YU Suzuki, K Itagaki, T Kato, H Satomoto, M Nakajima, Y AF Obata, Yukako Adachi, Yushi U. Suzuki, Katsumi Itagaki, Taiga Kato, Hiromi Satomoto, Maiko Nakajima, Yoshiki TI The Influence of Differences in Solvents and Concentration on the Efficacy of Propofol at Induction of Anesthesia SO ANESTHESIOLOGY RESEARCH AND PRACTICE LA English DT Article ID PHARMACODYNAMICS; INFUSION; PHARMACOKINETICS; FORMULATION; GENDER AB Background. Propofol is a popular intravenous anesthetic and varieties of formulations were produced from different laboratories. The present study compared efficacy of propofol of different laboratories and different concentrations (1 and 2%) during induction of anesthesia. Methods. Seventy-five scheduled surgical patients were randomly allocated into three groups. The patients of group D1 received AstraZeneca Diprivan 1% (Osaka, Japan) at a rate of 40mg kg(-1) h(-1). Group M1 was given 1% Maruishi (Maruishi Pharmaceutical, Osaka, Japan) and group M2 was given 2% formulation at the same rate of propofol. Achieving hypnosis was defined as failure to open their eyes in response to a verbal command and the venous blood sample was withdrawn. Results. The hypnotic doses of M2 were significantly larger (D1: 91.4 +/- 30.9, M1: 90.7 +/- 26.7, andM2: 118.4 +/- 40.2 mg, resp. (mean +/- SD). p < 0.005). Age and gender were selected as statistically significant covariates using general linear model-ANOVA. The blood concentration showed no significant difference among the groups (3.73 +/- 2.34, 4.10 +/- 3.04, and 4.70 +/- 2.12 mu gmL(-1), resp.). Conclusion. The required dose of propofol was different among the formulations; however, the serum concentration showed no significant difference. This trial is registered with UMIN Clinical Trial Registry: UMIN000019925. C1 [Obata, Yukako; Kato, Hiromi; Nakajima, Yoshiki] Hamamatsu Univ Sch Med, Dept Intens Care Unit, Higashi Ku, 1-20-1 Handayama, Hamamatsu, Shizuoka 4313192, Japan. [Adachi, Yushi U.] Tokyo Med & Dent Univ, Hosp Med, Dept Intens Care Med, Tokyo, Japan. [Suzuki, Katsumi] Enshu Hosp, Dept Anesthesia, Hamamatsu, Shizuoka, Japan. [Itagaki, Taiga] Massachusetts Gen Hosp, Pulm & Crit Care Med, Boston, MA 02114 USA. [Satomoto, Maiko] Tokyo Med & Dent Univ, Grad Sch Med & Dent Sci, Dept Anesthesiol, Tokyo, Japan. RP Adachi, YU (reprint author), Tokyo Med & Dent Univ, Hosp Med, Dept Intens Care Med, Tokyo, Japan. OI Satomoto, Maiko/0000-0003-2768-7482 NR 15 TC 0 Z9 0 U1 0 U2 2 PU HINDAWI LTD PI LONDON PA ADAM HOUSE, 3RD FLR, 1 FITZROY SQ, LONDON, WIT 5HE, ENGLAND SN 1687-6962 EI 1687-6970 J9 ANESTHESIOL RES PRAC JI Anesthesiol. Res. Pract. PY 2016 AR UNSP 9178523 DI 10.1155/2016/9178523 PG 4 WC Anesthesiology SC Anesthesiology GA DC6NG UT WOS:000369336100001 ER PT J AU Fulciniti, M Amodio, N Bandi, RL Cagnetta, A Samur, MK Acharya, C Prabhala, R D'Aquila, P Bellizzi, D Passarino, G Adamia, S Neri, A Hunter, ZR Treon, SP Anderson, KC Tassone, P Munshi, NC AF Fulciniti, M. Amodio, N. Bandi, R. L. Cagnetta, A. Samur, M. K. Acharya, C. Prabhala, R. D'Aquila, P. Bellizzi, D. Passarino, G. Adamia, S. Neri, A. Hunter, Z. R. Treon, S. P. Anderson, K. C. Tassone, P. Munshi, N. C. TI miR-23b/SP1/c-myc forms a feed-forward loop supporting multiple myeloma cell growth SO BLOOD CANCER JOURNAL LA English DT Editorial Material ID TRANSCRIPTION FACTORS; WALDENSTROM MACROGLOBULINEMIA; THERAPEUTIC IMPLICATIONS; SP1 TRANSACTIVATION; MIR-23B EXPRESSION; ANTITUMOR-ACTIVITY; TUMOR-SUPPRESSOR; CANCER; GENE; FAMILY AB Deregulated microRNA (miR)/transcription factor (TF)-based networks represent a hallmark of cancer. We report here a novel c-Myc/miR-23b/Sp1 feed-forward loop with a critical role in multiple myeloma (MM) and Waldenstrom's macroglobulinemia (WM) cell growth and survival. We have found miR-23b to be downregulated in MM and WM cells especially in the presence of components of the tumor bone marrow milieu. Promoter methylation is one mechanism of miR-23b suppression in myeloma. In gain-of-function studies using miR-23b mimics-transfected or in miR-23b-stably expressing MM and WM cell lines, we observed a significant decrease in cell proliferation and survival, along with induction of caspase-3/7 activity over time, thus supporting a tumor suppressor role for miR-23b. At the molecular level, miR-23b targeted Sp1 3'UTR and significantly reduced Sp1-driven nuclear factor-kappa B activity. Finally, c-Myc, an important oncogenic transcription factor known to stimulate MM cell proliferation, transcriptionally repressed miR-23b. Thus MYC-dependent miR-23b repression in myeloma cells may promote activation of oncogenic Sp1-mediated signaling, representing the first feed-forward loop with critical growth and survival role in myeloma. C1 [Fulciniti, M.; Bandi, R. L.; Cagnetta, A.; Samur, M. K.; Acharya, C.; Prabhala, R.; Adamia, S.; Hunter, Z. R.; Treon, S. P.; Anderson, K. C.; Munshi, N. C.] Harvard Univ, Sch Med, Dana Farber Canc Inst, 44 Binney St, Boston, MA 02115 USA. [Amodio, N.; Tassone, P.] Magna Graecia Univ Catanzaro, Dept Expt & Clin Med, Salvatore Venuta Campus, Catanzaro, Italy. [Prabhala, R.; Munshi, N. C.] Harvard Univ, Sch Med, VA Boston Healthcare Syst, Boston, MA 02115 USA. [D'Aquila, P.; Bellizzi, D.; Passarino, G.] Univ Calabria, Dept Biol Ecol & Earth Sci DiBEST, I-87036 Cosenza, Italy. [Neri, A.] Univ Milan, IRCCS Policlin Fdn, Hematol 1, Dept Med Sci, Milan, Italy. RP Munshi, NC (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Med Oncol, 44 Binney St, Boston, MA 02115 USA. EM nikhil_munshi@dfci.harvard.edu OI Acharya, Chirag/0000-0001-8767-5905; Hunter, Zachary/0000-0002-1689-1691 FU NCI NIH HHS [P50 CA100707]; PHS HHS [P01-155258, P01-78378, P50-100707] NR 39 TC 2 Z9 2 U1 1 U2 2 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 2044-5385 J9 BLOOD CANCER J JI Blood Cancer J. PD JAN PY 2016 VL 6 AR e380 DI 10.1038/bcj.2015.106 PG 8 WC Oncology SC Oncology GA DC6AN UT WOS:000369302100004 PM 26771806 ER PT J AU Raje, N Vadhan-Raj, S Willenbacher, W Terpos, E Hungria, V Spencer, A Alexeeva, Y Facon, T Stewart, AK Feng, A Braun, A Balakumaran, A Roodman, GD AF Raje, N. Vadhan-Raj, S. Willenbacher, W. Terpos, E. Hungria, V. Spencer, A. Alexeeva, Y. Facon, T. Stewart, A. K. Feng, A. Braun, A. Balakumaran, A. Roodman, G. D. TI Evaluating results from the multiple myeloma patient subset treated with denosumab or zoledronic acid in a randomized phase 3 trial SO BLOOD CANCER JOURNAL LA English DT Editorial Material ID STEM-CELL TRANSPLANTATION; BONE METASTASES; DOUBLE-BLIND; CHEMOTHERAPY; SURVIVAL; PREDNISONE; MELPHALAN; CANCER AB In a phase 3 trial of denosumab vs zoledronic acid in patients (n= 1776) with bone metastases and solid tumors or multiple myeloma, denosumab was superior to zoledronic acid for the primary end point of prevention of skeletal-related events. There was no difference in overall survival between the two groups; however, an ad hoc overall survival analysis in the multiple myeloma subset of patients (n= 180) favored zoledronic acid (hazard ratio (HR) 2.26; 95% confidence interval (CI) 1.13-4.50; P = 0.014). In the present analysis, we found imbalances between the groups with respect to baseline risk characteristics. HRs with two-sided 95% CIs were estimated using the Cox model. After adjustment in a covariate analysis, the CI crossed unity (HR 1.86; 95% CI 0.90-3.84; P = 0.0954). Furthermore, we found a higher rate of early withdrawals for the reasons of lost to follow-up and withdrawal of consent in the zoledronic acid group; after accounting for these, the HR was 1.31 (95% CI 0.80-2.15; P = 0.278). In conclusion, the survival results in multiple myeloma patients in this trial were confounded and will eventually be resolved by an ongoing phase 3 trial. C1 [Raje, N.] Massachusetts Gen Hosp, Ctr Canc, Ctr Multiple Myeloma, Boston, MA 02114 USA. [Vadhan-Raj, S.] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. [Willenbacher, W.] Med Univ Innsbruck, Internal Med Haematol & Oncol 5, A-6020 Innsbruck, Austria. [Terpos, E.] Univ Athens, Sch Med, Dept Clin Therapeut, Athens 11528, Greece. [Hungria, V.] Irmandade Santa Casa Misericordia Sao Paulo, Sao Paulo, Brazil. [Spencer, A.] Alfred Hosp, Melbourne, Vic, Australia. [Alexeeva, Y.] City Hosp 31, St Petersburg, Russia. [Facon, T.] Hop Claude Huriez, Lille, France. [Stewart, A. K.] Mayo Clin, Scottsdale, AZ USA. [Feng, A.; Braun, A.] Amgen Inc, Thousand Oaks, CA 91320 USA. [Balakumaran, A.; Roodman, G. D.] Indiana Univ Sch Med, Indianapolis, IN 46202 USA. RP Raje, N (reprint author), Massachusetts Gen Hosp, Ctr Canc, Ctr Multiple Myeloma, Boston, MA 02114 USA. EM nraje@partners.org RI FACON, THIERRY/M-9736-2014 OI FACON, THIERRY/0000-0001-7705-8460 NR 20 TC 2 Z9 2 U1 2 U2 4 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 2044-5385 J9 BLOOD CANCER J JI Blood Cancer J. PD JAN PY 2016 VL 6 AR e378 DI 10.1038/bcj.2015.96 PG 5 WC Oncology SC Oncology GA DC6AN UT WOS:000369302100002 PM 26745852 ER PT J AU Stewart, A Parashar, B Patel, M O'Farrell, D Biagioli, M Devlin, P Mutyala, S AF Stewart, A. Parashar, B. Patel, M. O'Farrell, D. Biagioli, M. Devlin, P. Mutyala, S. TI American Brachytherapy Society consensus guidelines for thoracic brachytherapy for lung cancer SO BRACHYTHERAPY LA English DT Article DE Endobronchial brachytherapy; Interstitial seed brachytherapy; Iodine seeds; Cesium seeds; Lung cancer; Thoracic tumors ID DOSE-RATE BRACHYTHERAPY; INTRAOPERATIVE I-125 BRACHYTHERAPY; RATE ENDOBRONCHIAL BRACHYTHERAPY; PLUS CESIUM-131 BRACHYTHERAPY; ACOSOG Z4032 ALLIANCE; INTERSTITIAL BRACHYTHERAPY; SUBLOBAR RESECTION; RANDOMIZED-TRIAL; WEDGE RESECTION; PROSTATE BRACHYTHERAPY AB PURPOSE: To update brachytherapy recommendations for pretreatment evaluation, treatment, and dosimetric issues for thoracic brachytherapy for lung cancer. METHODS AND MATERIALS: Members of the American Brachytherapy Society with expertise in thoracic brachytherapy updated recommendations for thoracic brachytherapy based on literature review and clinical experience. RESULTS: The American Brachytherapy Society consensus guidelines recommend the use of endobronchial brachytherapy for disease palliation in patients with central obstructing lesions, particularly in patients who have previously received external beam radiotherapy. The use of interstitial implants after incomplete resection may improve outcomes and provide enhanced palliation. Early reports support the use of CT-guided intratumoral volume implants within clinical studies. The use of brachytherapy routinely after sublobar resection is not generally recommended, unless within the confines of a clinical trial or a registry. CONCLUSIONS: American Brachytherapy Society recommendations for thoracic brachytherapy are provided. Practitioners are encouraged to follow these guidelines and to develop further clinical trials to examine this treatment modality to increase the evidence base for its use. (C) 2016 American Brachytherapy Society. Published by Elsevier Inc. All rights reserved. C1 [Stewart, A.] Royal Surrey Cty Hosp, St Lukes Canc Ctr, Egerton Rd, Guildford GU2 9NY, Surrey, England. [Stewart, A.] Univ Surrey, Guildford GU2 5XH, Surrey, England. [Parashar, B.] Weill Cornell Med Coll, Dept Stich Radiat Oncol, New York, NY USA. [Patel, M.] Baylor Scott & White Hlth, Dept Radiat Oncol, Temple, TX USA. [O'Farrell, D.; Devlin, P.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dana Faber Canc Ctr, Boston, MA 02115 USA. [Biagioli, M.] Univ S Florida, H Lee Moffitt Canc Ctr, Dept Radiat Oncol, Florida Hosp Canc Inst, Tampa, FL 33682 USA. [Mutyala, S.] Univ Arizona Canc Ctr Dign Hlth, St Josephs Hosp & Med Ctr, Dept Radiat Med, Phoenix, AZ USA. RP Stewart, A (reprint author), Royal Surrey Cty Hosp, St Lukes Canc Ctr, Egerton Rd, Guildford GU2 9NY, Surrey, England. EM Alexandra.stewart@nhs.net NR 81 TC 2 Z9 3 U1 1 U2 8 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1538-4721 EI 1873-1449 J9 BRACHYTHERAPY JI Brachytherapy PD JAN-FEB PY 2016 VL 15 IS 1 BP 1 EP 11 DI 10.1016/j.brachy.2015.09.006 PG 11 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA DD2UZ UT WOS:000369779000001 PM 26561277 ER PT J AU Harkenrider, MM Grover, S Erickson, BA Viswanathan, AN Small, C Kliethermes, S Small, W AF Harkenrider, Matthew M. Grover, Surbhi Erickson, Beth A. Viswanathan, Akila N. Small, Christina Kliethermes, Stephanie Small, William, Jr. TI Vaginal brachytherapy for postoperative endometrial cancer: 2014 Survey of the American Brachytherapy Society SO BRACHYTHERAPY LA English DT Article DE Vaginal brachytherapy; Endometrial cancer; Vaginal cuff brachytherapy; Vaginal cylinder; Vaginal cuff ID HIGH-DOSE-RATE; GYNECOLOGIC-ONCOLOGY-GROUP; PELVIC RADIATION-THERAPY; PHASE-III TRIAL; STAGE-I; CUFF BRACHYTHERAPY; RANDOMIZED-TRIAL; CARCINOMA; IRRADIATION; RADIOTHERAPY AB PURPOSE: Report current practice patterns for postoperative endometrial cancer emphasizing vaginal brachytherapy (VBT). METHODS AND MATERIALS: A 38-item survey was e-mailed to 1,598 American Brachytherapy Society (ABS) members and 4,329 US radiation oncologists in 2014 totaling 5,710 recipients. Responses of practitioners who had delivered VBT in the previous 12 months were included in the analysis. Responses were tabulated to determine relative frequency distributions. chi(2) analysis was used to compare current results with those from the 2003 ABS survey. RESULTS: A total of 331 respondents initiated the VBT survey, of whom 289 (87.3%) administered VBT in the prior 12 months. Lymph node dissection and number of nodes removed influenced treatment decisions for 90.5% and 69.8%, respectively. High-dose-rate was used by 96.2%. The most common vaginal length treated was 4 cm (31.0%). Three-dimensional planning was used by 83.2% with 73.4% of those for the first fraction only. Doses to normal tissues were reported by 79.8%. About half optimized to the location of dose specification and/or normal tissues. As monotherapy, the most common prescriptions were 7 Gy for three fractions to 0.5-cm depth and 6 Gy for five fractions to the surface. As a boost, the most common prescriptions were 5 Gy for three fractions to 0.5-cm depth and 6 Gy for three fractions to the vaginal surface. Optimization points were placed at the apex and lateral vagina by 73.1%. Secondary quality assurance checks were performed by 98.9%. CONCLUSIONS: VBT is a common adjuvant therapy for endometrial cancer patients, most commonly with HDR. Fractionation and planning processes are variable but generally align with ABS recommendations. (C) 2016 American Brachytherapy Society. Published by Elsevier Inc. All rights reserved. C1 [Harkenrider, Matthew M.; Small, William, Jr.] Loyola Univ Chicago, Stritch Sch Med, Dept Radiat Oncol, 2160 S First Ave,Maguire Bldg,Room 2944, Maywood, IL 60153 USA. [Grover, Surbhi] Univ Penn, Perelman Sch Med, Dept Radiat Oncol, Philadelphia, PA 19104 USA. [Erickson, Beth A.] Med Coll Wisconsin, Froedtert Mem Lutheran Hosp, Dept Radiat Oncol, Milwaukee, WI 53226 USA. [Erickson, Beth A.] Med Coll Wisconsin, Milwaukee, WI 53226 USA. [Viswanathan, Akila N.] Brigham & Womens Hosp, Dana Farber Canc Inst, Dept Radiat Oncol, 75 Francis St, Boston, MA 02115 USA. [Small, Christina; Kliethermes, Stephanie] Loyola Univ Chicago, Stritch Sch Med, Dept Publ Hlth Sci, Maywood, IL USA. RP Harkenrider, MM (reprint author), Loyola Univ Chicago, Stritch Sch Med, Dept Radiat Oncol, 2160 S First Ave,Maguire Bldg,Room 2944, Maywood, IL 60153 USA. EM mharkenrider@lumc.edu FU National Institutes of Health/National Cancer Institute [R21 167800] FX ANV receives support through National Institutes of Health/National Cancer Institute R21 167800. NR 32 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 1538-4721 EI 1873-1449 J9 BRACHYTHERAPY JI Brachytherapy PD JAN-FEB PY 2016 VL 15 IS 1 BP 23 EP 29 DI 10.1016/j.brachy.2015.09.012 PG 7 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA DD2UZ UT WOS:000369779000003 PM 26620818 ER PT J AU Da Silva, N Barton, CR AF Da Silva, Nicolas Barton, Claire R. TI Macrophages and dendritic cells in the post-testicular environment SO CELL AND TISSUE RESEARCH LA English DT Review DE Antigen-presenting cells; Dendritic cells; Epididymis; Macrophages; Peripheral tolerance; Sperm maturation; Spermatozoa ID TISSUE-RESIDENT MACROPHAGES; SPERM QUALITY-CONTROL; MURINE EPIDIDYMIS; BASAL-CELLS; MOUSE EPIDIDYMIS; LUMINAL ACIDIFICATION; MAMMALIAN EPIDIDYMIS; EXCURRENT DUCTS; GENE-EXPRESSION; BETA-DEFENSINS AB Macrophages (MF) and dendritic cells (DCs) are heterogeneous families of functionally and developmentally related immune cells that play crucial roles in tissue homeostasis and the regulation of immune responses. During the past 5 years, immunologists have generated a considerable amount of data that challenge dogmas about the ontogeny and functions of these highly versatile cells. The male excurrent duct system plays a critical role in the establishment of fertility by allowing sperm maturation, transport and storage. In addition, it is challenged by pathogens and must establish a protective and tolerogenic environment for a continuous flow of autoantigenic spermatozoa. The post-testicular environment and, in particular, the epididymis contain an intricate network of DCs and MF; however, the immunophysiology of this intriguing and highly specialized mucosal system is poorly understood. This review summarizes the current trends in mouse MF and DC biology and speculates about their roles in the steady-state epididymis. Unraveling immune cell functions in the male reproductive tract is an essential prerequisite for the design of innovative strategies aimed at controlling male fertility and treating infertility. C1 [Da Silva, Nicolas; Barton, Claire R.] Massachusetts Gen Hosp, Res Inst, Div Nephrol, Ctr Syst Biol, 185 Cambridge St,CPZN 8-218, Boston, MA 02114 USA. [Da Silva, Nicolas; Barton, Claire R.] Massachusetts Gen Hosp, Res Inst, Program Membrane Biol, 185 Cambridge St,CPZN 8-218, Boston, MA 02114 USA. [Da Silva, Nicolas; Barton, Claire R.] Harvard Univ, Sch Med, 185 Cambridge St,CPZN 8-218, Boston, MA 02114 USA. RP Da Silva, N (reprint author), Massachusetts Gen Hosp, Res Inst, Div Nephrol, Ctr Syst Biol, 185 Cambridge St,CPZN 8-218, Boston, MA 02114 USA.; Da Silva, N (reprint author), Massachusetts Gen Hosp, Res Inst, Program Membrane Biol, 185 Cambridge St,CPZN 8-218, Boston, MA 02114 USA.; Da Silva, N (reprint author), Harvard Univ, Sch Med, 185 Cambridge St,CPZN 8-218, Boston, MA 02114 USA. EM dasilva.nicolas@mgh.harvard.edu FU NICHD NIH HHS [R01 HD069623] NR 73 TC 1 Z9 1 U1 0 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0302-766X EI 1432-0878 J9 CELL TISSUE RES JI Cell Tissue Res. PD JAN PY 2016 VL 363 IS 1 BP 97 EP 104 DI 10.1007/s00441-015-2270-0 PG 8 WC Cell Biology SC Cell Biology GA DC6IE UT WOS:000369322500009 PM 26337514 ER PT J AU Byrne, T Montgomery, AE Fargo, JD AF Byrne, Thomas Montgomery, Ann Elizabeth Fargo, Jamison D. TI Unsheltered Homelessness Among Veterans: Correlates and Profiles SO COMMUNITY MENTAL HEALTH JOURNAL LA English DT Article DE Homelessness; Veterans; Serious mental illness; Substance use disorders; Latent class analysis ID STREET OUTREACH; HEALTH; CARE; INDIVIDUALS; SERVICES; ACCESS; ADULTS AB We identified correlates of unsheltered status among Veterans experiencing homelessness and described distinct subgroups within the unsheltered homeless Veteran population using data from a screening instrument for homelessness that is administered to all Veterans accessing outpatient care at a Veterans Health Administration (VHA) facility. Correlates of unsheltered homelessness included male gender, white race, older age, lower levels of VHA eligibility, substance use disorders, frequent use of VHA inpatient and infrequent use of VHA outpatient services, and residing in the West. We identified six distinct subgroups of unsheltered Veterans; the tri-morbid frequent users represented the highest need group, but the largest group was comprised of Veterans who made highly infrequent use of VHA healthcare services. Differences between sheltered and unsheltered Veterans and heterogeneity within the unsheltered Veteran population should be considered in targeting housing and other interventions. C1 [Byrne, Thomas] Boston Univ, Sch Social Work, 264 Bay State Rd, Boston, MA 02215 USA. [Byrne, Thomas; Montgomery, Ann Elizabeth; Fargo, Jamison D.] US Dept Vet Affairs, Natl Ctr Homelessness Vet, 4100 Chester Ave,Suite 201, Philadelphia, PA 19104 USA. [Fargo, Jamison D.] Utah State Univ, Dept Psychol, 2810 Old Main Hill, Logan, UT 84322 USA. RP Byrne, T (reprint author), Boston Univ, Sch Social Work, 264 Bay State Rd, Boston, MA 02215 USA.; Byrne, T (reprint author), US Dept Vet Affairs, Natl Ctr Homelessness Vet, 4100 Chester Ave,Suite 201, Philadelphia, PA 19104 USA. EM tbyrne@bu.edu; Ann.montgomery@va.gov; Jamison.fargo@usu.edu NR 22 TC 1 Z9 1 U1 2 U2 6 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0010-3853 EI 1573-2789 J9 COMMUNITY MENT HLT J JI Community Ment. Health J. PD JAN PY 2016 VL 52 IS 2 BP 148 EP 157 DI 10.1007/s10597-015-9922-0 PG 10 WC Health Policy & Services; Public, Environmental & Occupational Health; Psychiatry SC Health Care Sciences & Services; Public, Environmental & Occupational Health; Psychiatry GA DC7UX UT WOS:000369427100004 PM 26289119 ER PT J AU De Luca, SM Blosnich, JR Hentschel, EAW King, E Amen, S AF De Luca, Susan M. Blosnich, John R. Hentschel, Elizabeth A. W. King, Erika Amen, Sally TI Mental Health Care Utilization: How Race, Ethnicity and Veteran Status are Associated with Seeking Help SO COMMUNITY MENTAL HEALTH JOURNAL LA English DT Article DE Veteran; Mental health; Mental health treatment utilization; Racial/ethnic disparities ID AFGHANISTAN VETERANS; CLINICAL-OUTCOMES; SERVICES; IRAQ; DIAGNOSES; ATTITUDES; MILITARY; BARRIERS; SOLDIERS; MEMBERS AB As veterans disproportionately experience higher rates of mental illness than civilians, conflicting results surround the impact of race/ethnicity on treatment utilization. This study utilized the CDC's Texas Behavioral Risk Factor Surveillance System data, a random-digit dialed telephone survey of non-institutionalized adults. A subset of Texas respondents (n = 8563) were asked questions related to mental health treatment, stigma, help-seeking attitudes and emotional support. While no differences were found in health care utilization between non-Hispanic white veterans and non-veterans, there were distinct patterns among racial/ethnic minority veterans and non-veterans. Black and Latino non-veterans reported significantly lower health care utilization compared to non-Hispanic white non-veterans. Among veterans, there were no differences in reported utilization rates comparing non-Hispanic whites and Latinos and also non-Hispanic whites and Blacks. Our study adds to the literature by examining health care utilization among a diverse group of veterans by focusing on Veterans Administration (VA) and non-VA services to veterans. C1 [De Luca, Susan M.; King, Erika] Univ Texas Austin, Sch Social Work, 1925 San Jacinto Blvd,Stop D3500, Austin, TX 78712 USA. [Blosnich, John R.] VA Pittsburgh Healthcare Syst, Ctr Hlth Equ Res & Promot, Hlth Serv Res, Univ Dr C 151C-U,Bldg 30, Pittsburgh, PA 15240 USA. [Hentschel, Elizabeth A. W.] Univ Texas Austin, Coll Educ, Dept Educ Psychol, Counseling Psychol, 1 Univ Stn D5800, Austin, TX 78712 USA. [Amen, Sally] Univ Texas Austin, Dept Stat & Data Sci, 2317 Speedway D9800, Austin, TX 78712 USA. RP De Luca, SM (reprint author), Univ Texas Austin, Sch Social Work, 1925 San Jacinto Blvd,Stop D3500, Austin, TX 78712 USA. EM sdeluca@austin.utexas.edu; John.blosnich@va.gov; elizwilson@gmail.com; sally.amen@austin.utexas.edu NR 27 TC 0 Z9 0 U1 3 U2 16 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0010-3853 EI 1573-2789 J9 COMMUNITY MENT HLT J JI Community Ment. Health J. PD JAN PY 2016 VL 52 IS 2 BP 174 EP 179 DI 10.1007/s10597-015-9964-3 PG 6 WC Health Policy & Services; Public, Environmental & Occupational Health; Psychiatry SC Health Care Sciences & Services; Public, Environmental & Occupational Health; Psychiatry GA DC7UX UT WOS:000369427100007 PM 26659853 ER PT J AU Johnson, RS Stolar, AG McGuire, JF Clark, S Coonan, LA Hausknecht, P Graham, DP AF Johnson, R. Scott Stolar, Andrea G. McGuire, James F. Clark, Sean Coonan, Loretta A. Hausknecht, Paul Graham, David P. TI US Veterans' Court Programs: An Inventory and Analysis of National Survey Data SO COMMUNITY MENTAL HEALTH JOURNAL LA English DT Article DE Veteran; Court; VA; Recidivism ID OUTCOMES; DRUG AB This study used data from a phone survey inventory of US veterans' courts to provide descriptive information on the current status of their various elements. To identify which items were most predictive of a court's percentage of subjects terminated from their program, a linear regression was performed. The following were associated with higher rates of termination from the veterans' court (VC) program: (a) programs that offered phase progression based on measurable goals, (b) programs that conduct frequent drug and alcohol testing, and (c) programs for which sanctions are more severe for failing immediate goals (sobriety) versus long-term ones (completion of training). The following were associated with lower rates of termination from the VC program: (a) programs in which later phases permit less stringent testing, (b) programs utilizing behavioral contracts, (c) programs utilizing brief incarcerations. This inventory provides nationwide empirical data that may be used in the development of veterans' courts. C1 [Johnson, R. Scott] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA 02114 USA. [Stolar, Andrea G.; Coonan, Loretta A.; Graham, David P.] Michael E DeBakey Vet Affairs VA Med Ctr, Mental Hlth Care Line, Houston, TX USA. [Stolar, Andrea G.; Hausknecht, Paul; Graham, David P.] Baylor Coll Med, Menninger Dept Psychiat & Behav Sci, Houston, TX 77030 USA. [Stolar, Andrea G.] Vet Court Treatment Program, Houston, TX USA. [Graham, David P.] Michael E DeBakey VA Med Ctr, Neurorehabil Neurons Networks Traumat Brain Injur, Houston, TX USA. [Graham, David P.] South Cent Mental Illness Res Educ & Clin Ctr MIR, Dept Vet Affairs, Houston, TX USA. RP Johnson, RS (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA 02114 USA. EM rscottjohnson3@gmail.com NR 15 TC 1 Z9 1 U1 0 U2 0 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0010-3853 EI 1573-2789 J9 COMMUNITY MENT HLT J JI Community Ment. Health J. PD JAN PY 2016 VL 52 IS 2 BP 180 EP 186 DI 10.1007/s10597-015-9972-3 PG 7 WC Health Policy & Services; Public, Environmental & Occupational Health; Psychiatry SC Health Care Sciences & Services; Public, Environmental & Occupational Health; Psychiatry GA DC7UX UT WOS:000369427100008 PM 26797760 ER PT J AU Sheldon, S Farb, N Palombo, DJ Levine, B AF Sheldon, Signy Farb, Norman Palombo, Daniela J. Levine, Brian TI Intrinsic medial temporal lobe connectivity relates to individual differences in episodic autobiographical remembering SO CORTEX LA English DT Article DE Memory; Functional connectivity; Individual differences ID DEFAULT MODE NETWORK; FUNCTIONAL CONNECTIVITY; PREFRONTAL CORTEX; BRAIN ACTIVITY; SEMANTIC RETRIEVAL; EXECUTIVE CONTROL; MEMORY RETRIEVAL; FUTURE EVENTS; ACTIVATIONS; RECOLLECTION AB People vary in how they remember the past: some recall richly detailed episodes; others more readily access the semantic features of events. The neural correlates of such trait-like differences in episodic and semantic remembering are unknown. We found that self reported individual differences in how one recalls the past were related to predictable intrinsic connectivity patterns of the medial temporal lobe (MTL) memory system. A pattern of MTL connectivity to posterior brain regions supporting visual-perceptual processing (occipital/parietal cortices) was related to the endorsement of episodic memory based remembering (recalling spatiotemporal event information), whereas MTL connectivity to inferior and middle prefrontal cortical regions was related to the endorsement of semantic memory-based remembering (recalling facts). These findings suggest that the tendency to engage in episodic autobiographical remembering is associated with accessing and constructing detailed images of a past event in memory, while the tendency to engage in semantic autobiographical remembering is associated with organizing and integrating higher-order conceptual information. More broadly, these findings suggest that differences in how people naturally use memory are instantiated though distinct patterns of MTL functional connectivity. (C) 2015 The Authors. Published by Elsevier Ltd. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). C1 [Sheldon, Signy] McGill Univ, Dept Psychol, Montreal, PQ H3A 1B1, Canada. [Farb, Norman] Univ Toronto, Dept Psychol, Mississauga, ON L5L 1C6, Canada. [Palombo, Daniela J.] Boston Univ, Sch Med, VA Boston Healthcare Syst, Dept Psychiat,Memory Disorders Res Ctr, Boston, MA 02118 USA. [Levine, Brian] Baycrest Hlth Sci, Rotman Res Inst, Toronto, ON M6A 2E1, Canada. [Levine, Brian] Univ Toronto, Dept Psychol, Toronto, ON M5S 1A1, Canada. RP Sheldon, S (reprint author), McGill Univ, Stewart Biol Bldg,1205 Dr Penfield Ave, Montreal, PQ H3A 1B1, Canada.; Levine, B (reprint author), Baycrest Hlth Sci, 3560 Bathurst St, Toronto, ON M6A 2E1, Canada. EM signy.sheldon@mcgill.ca; blevine@research.baycrest.org OI Levine, Brian/0000-0003-4343-811X FU Canadian Institutes of Health Research (CIHR) [MOP-62963] FX The work reported was supported by a Canadian Institutes of Health Research (CIHR) grant award (MOP-62963) to B. Levine. We would like to thank Drs. W. Dale Stevens, Endel Tulving, and Bradley Buchsbaum for their helpful comments on earlier drafts on this manuscript as well as Dr. Craig Stark and Aurora LePort for providing SAM questionnaire data for the HSAM cases. We have no conflicts of interest to report. NR 62 TC 2 Z9 2 U1 2 U2 8 PU ELSEVIER MASSON PI MILANO PA VIA PALEOCAPA 7, 20121 MILANO, ITALY SN 0010-9452 EI 1973-8102 J9 CORTEX JI Cortex PD JAN PY 2016 VL 74 BP 206 EP 216 DI 10.1016/j.cortex.2015.11.005 PG 11 WC Behavioral Sciences; Neurosciences SC Behavioral Sciences; Neurosciences & Neurology GA DC8GS UT WOS:000369458500016 PM 26691735 ER PT J AU Pittig, A van den Berg, L Vervliet, B AF Pittig, Andre van den Berg, Linda Vervliet, Bram TI The key role of extinction learning in anxiety disorders: behavioral strategies to enhance exposure-based treatments SO CURRENT OPINION IN PSYCHIATRY LA English DT Review DE anxiety disorders; enhancement strategies; exposure therapy; fear extinction; inhibitory learning ID POSTTRAUMATIC-STRESS-DISORDER; RECONSOLIDATION-UPDATE MECHANISMS; VENTROMEDIAL PREFRONTAL CORTEX; OBSESSIVE-COMPULSIVE DISORDER; REINSTATEMENT FEAR RELEVANCE; D-CYCLOSERINE AUGMENTATION; LONG-TERM OUTCOMES; SLOW-WAVE SLEEP; CONDITIONED FEAR; MEMORY RECONSOLIDATION AB Purpose of reviewExtinction learning is a major mechanism for fear reduction by means of exposure. Current research targets innovative strategies to enhance fear extinction and thereby optimize exposure-based treatments for anxiety disorders. This selective review updates novel behavioral strategies that may provide cutting-edge clinical implications.Recent findingsRecent studies provide further support for two types of enhancement strategies. Procedural enhancement strategies implemented during extinction training translate to how exposure exercises may be conducted to optimize fear extinction. These strategies mostly focus on a maximized violation of dysfunctional threat expectancies and on reducing context and stimulus specificity of extinction learning. Flanking enhancement strategies target periods before and after extinction training and inform optimal preparation and post-processing of exposure exercises. These flanking strategies focus on the enhancement of learning in general, memory (re-)consolidation, and memory retrieval.SummaryBehavioral strategies to enhance fear extinction may provide powerful clinical applications to further maximize the efficacy of exposure-based interventions. However, future replications, mechanistic examinations, and translational studies are warranted to verify long-term effects and naturalistic utility. Future directions also comprise the interplay of optimized fear extinction with (avoidance) behavior and motivational antecedents of exposure. C1 [Pittig, Andre; van den Berg, Linda] Tech Univ Dresden, Inst Clin Psychol & Psychotherapy, D-01062 Dresden, Germany. [Vervliet, Bram] Harvard Univ, Sch Med, Dept Psychiat, Massachusetts Gen Hosp, Boston, MA 02115 USA. [Vervliet, Bram] Katholieke Univ Leuven, Ctr Excellence Generalizat Hlth & Psychopathol, Leuven, Belgium. RP Pittig, A (reprint author), Tech Univ Dresden, Inst Clin Psychol & Psychotherapy, D-01062 Dresden, Germany. EM andre.pittig@tu-dresden.de RI Pittig, Andre/L-1570-2016 OI Pittig, Andre/0000-0003-3787-9576 FU German Federal Ministry of Education and Research [FKZ 01EE1402B]; Federal Ministry of Education and Research (BMBF); Marie Curie International Outgoing Fellowship within 7th European Community Framework Programme; PROTECT-AD FX The work was supported by the research consortium on anxiety disorders, PROTECT-AD, funded by the German Federal Ministry of Education and Research (FKZ 01EE1402B). PROTECT-AD ('Providing Tools for Effective Care and Treatment of Anxiety Disorders') is one out of nine research consortia in the German Federal research program 'Forschungsnetz zu psychischen Erkrankungen' (2015-2019), funded by the Federal Ministry of Education and Research (BMBF; www.fzpe.de). PROTECT-AD comprises six projects; the presented work was derived in project P1 (PI: Hans-Ulrich Wittchen, Technische Universitat Dresden) and P7 (PI Jurgen Hoyer, Technische Universitat Dresden). This research was further supported by a Marie Curie International Outgoing Fellowship within the 7th European Community Framework Programme (Vervliet). NR 114 TC 4 Z9 4 U1 2 U2 16 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0951-7367 EI 1473-6578 J9 CURR OPIN PSYCHIATR JI Curr. Opin. Psychiatr. PD JAN PY 2016 VL 29 IS 1 BP 39 EP 47 DI 10.1097/YCO.0000000000000220 PG 9 WC Psychiatry SC Psychiatry GA DD0ZF UT WOS:000369649700007 PM 26575298 ER PT J AU Koenig, AM Arnold, SE Streim, JE AF Koenig, Aaron M. Arnold, Steven E. Streim, Joel E. TI Agitation and Irritability in Alzheimer's Disease: Evidenced-Based Treatments and the Black-Box Warning SO CURRENT PSYCHIATRY REPORTS LA English DT Review DE Alzheimer's disease; Neuropsychiatric symptoms; Pharmacological approaches; Non-pharmacological approaches; Black-box warning ID MILD COGNITIVE IMPAIRMENT; PLACEBO-CONTROLLED TRIALS; NEUROPSYCHIATRIC SYMPTOMS; PSYCHOLOGICAL SYMPTOMS; PSYCHOTROPIC-DRUGS; INFORMED-CONSENT; RANDOMIZED-TRIAL; DEMENTIA; ANTIPSYCHOTICS; MANAGEMENT AB More than five million Americans suffer from Alzheimer's disease (AD), and this number is expected to triple by 2050. While impairments in cognition, particularly memory, are typically the defining features of the clinical syndrome, behavioral symptoms are extremely common, affecting up to 90% of patients. Behavioral symptoms in AD can be difficult to manage and may require a combination of non-pharmacological and pharmacological approaches. The latter is complicated by FDA "black-box warnings" for the medication classes most often used to target these symptoms, and currently there are initiatives in place to limit their use. In this review, we describe common behavioral symptoms of AD-with a particular focus on the challenging symptoms of "agitation" and "irritability"- and discuss evidence-based approaches to their management. Ultimately, multidimensional approaches must be tailored to the patient and their environment, though evidence-based practices should define the treatment of agitation and irritability in AD. C1 [Koenig, Aaron M.] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. [Koenig, Aaron M.] Harvard Univ, TH Chan Sch Publ Hlth, Dept Epidemiol, Boston, MA USA. [Arnold, Steven E.] MassGeneral Inst Neurodegenerat Dis, Boston, MA USA. [Arnold, Steven E.] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. [Streim, Joel E.] Univ Penn, Dept Psychiat, Philadelphia, PA 19104 USA. [Streim, Joel E.] Corporal Michael J Crescenz VA Med Ctr, Behav Hlth Serv, Philadelphia, PA USA. RP Koenig, AM (reprint author), Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA.; Koenig, AM (reprint author), Harvard Univ, TH Chan Sch Publ Hlth, Dept Epidemiol, Boston, MA USA. EM amkoenig@mgh.harvard.edu FU National Institutes of Health [T32 MH1711929] FX This work was supported, in part, by National Institutes of Health grant T32 MH1711929 (AMK). NR 63 TC 0 Z9 0 U1 7 U2 10 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1523-3812 EI 1535-1645 J9 CURR PSYCHIAT REP JI Curr. Psychiatry Rep. PD JAN PY 2016 VL 18 IS 1 AR 3 DI 10.1007/s11920-015-0640-7 PG 10 WC Psychiatry SC Psychiatry GA DC5NM UT WOS:000369267700003 PM 26695173 ER PT J AU Jensen, DM Ohning, GV Kovacs, TOG Ghassemi, KA Jutabha, R Dulai, GS Machicado, GA AF Jensen, Dennis M. Ohning, Gordon V. Kovacs, Thomas O. G. Ghassemi, Kevin A. Jutabha, Rome Dulai, Gareth S. Machicado, Gustavo A. TI Doppler endoscopic probe as a guide to risk stratification and definitive hemostasis of peptic ulcer bleeding SO GASTROINTESTINAL ENDOSCOPY LA English DT Article ID RANDOMIZED-TRIAL; ADRENALINE INJECTION; VISIBLE VESSEL; HEATER PROBE; HEMORRHAGE; MANAGEMENT; THERAPY; COAGULATION; ULTRASOUND; CONSENSUS AB Background and Aims: For more than 4 decades endoscopists have relied on ulcer stigmata for risk stratification and as a guide to hemostasis. None used arterial blood flow underneath stigmata to predict outcomes. For patients with severe peptic ulcer bleeding (PUB), we used a Doppler endoscopic probe (DEP) for (1) detection of blood flow underlying stigmata of recent hemorrhage (SRH), (2) quantitating rates of residual arterial blood flow under SRH after visually directed standard endoscopic treatment, and (3) comparing risks of rebleeding and actual 30-day rebleed rates for spurting arterial bleeding (Forrest [F] IA) and oozing bleeding (F IB). Methods: Prospective cohort study of 163 consecutive patients with severe PUB and different SRH. Results: All blood flow detected by the DEP was arterial. Detection rates were 87.4% in major SRH-spurting arterial bleeding (F IA), non-bleeding visible vessel (F IIA), clot (F IIB)-and were significantly lower at 42.3% (P <.0001) for an intermediate group of oozing bleeding (F IB) or flat spot (F IIC). For spurting bleeding (F IA) versus oozing (F IB), baseline DEP arterial flow was 100% versus 46.7%, residual blood flow detected after endoscopic hemostasis was 35.7% versus 0%, and 30-day rebleed rates were 28.6% versus 0% (all P <.05). Conclusions: (1) For major SRH versus oozing or spot, the arterial blood flow detection rate by the DEP was significantly higher, indicating a higher rebleed risk. (2) Before and after endoscopic treatment, spurting (F IA) PUB had significantly higher rates of blood flow detection than oozing (F IB) PUB and a significantly higher 30-day rebleed rate. (3) The DEP is recommended as a new endoscopic guide with SRH to improve risk stratification and potentially definitive hemostasis for PUB. C1 [Jensen, Dennis M.; Ohning, Gordon V.; Kovacs, Thomas O. G.; Ghassemi, Kevin A.; Jutabha, Rome; Dulai, Gareth S.; Machicado, Gustavo A.] Univ Calif Los Angeles, Div Digest Dis, CURE Digest Dis Res Ctr, CURE Hemostasis Res Grp, Los Angeles, CA USA. [Jensen, Dennis M.; Ohning, Gordon V.; Kovacs, Thomas O. G.; Ghassemi, Kevin A.; Jutabha, Rome; Dulai, Gareth S.; Machicado, Gustavo A.] Univ Calif Los Angeles, David Geffen Sch Med, Ronald Reagan Univ Calif Los Angeles, Dept Med,Med Ctr, Los Angeles, CA 90095 USA. [Jensen, Dennis M.; Ohning, Gordon V.; Kovacs, Thomas O. G.; Dulai, Gareth S.; Machicado, Gustavo A.] West Los Angeles Vet Adm Med Ctr, Los Angeles, CA USA. RP Jensen, DM (reprint author), Vet Affairs Greater Los Angeles Healthcare Syst, CURE DDRC, Bldg 115,Room 318,11301 Wilshire Blvd, Los Angeles, CA 90073 USA. FU AstraZeneca; NIH CURE DDRC [41301]; VA Clinical Merit Review Grant; AstraZeneca USA; Vascular Technology Inc (VTI) FX D. Jensen is a consultant for Vascular Technology Incorporated and received an equipment grant for endoscopic Doppler control units to partially support this study. He was a consultant for AstraZeneca and received an investigator-initiated research grant from AstraZeneca, which partially supported a preliminary study. All other authors disclosed no financial relationships relevant to this publication. This study was partially funded by NIH CURE DDRC Grant 41301 (Human Studies Core), a VA Clinical Merit Review Grant (to Dr Jensen, PI), an Investigator Initiated Grant from AstraZeneca USA, and an equipment grant from Vascular Technology Inc (VTI). NR 37 TC 5 Z9 5 U1 1 U2 2 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0016-5107 EI 1097-6779 J9 GASTROINTEST ENDOSC JI Gastrointest. Endosc. PD JAN PY 2016 VL 83 IS 1 BP 129 EP 136 DI 10.1016/j.gie.2015.07.012 PG 8 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA DC5AA UT WOS:000369230900019 PM 26318834 ER PT J AU Jones, M Zheng, ZL Wang, J Dudley, J Albanese, E Kadayifci, A Dias-Santagata, D Le, L Brugge, WR Fernandez-del Castillo, C Mino-Kenudson, M Iafrate, AJ Pitman, MB AF Jones, Martin Zheng, Zongli Wang, Jessica Dudley, Jonathan Albanese, Emily Kadayifci, Abdurrahman Dias-Santagata, Dora Le, Long Brugge, William R. Fernandez-del Castillo, Carlos Mino-Kenudson, Mari Iafrate, A. John Pitman, Martha B. TI Impact of next-generation sequencing on the clinical diagnosis of pancreatic cysts SO GASTROINTESTINAL ENDOSCOPY LA English DT Article ID PAPILLARY MUCINOUS NEOPLASMS; INTRAEPITHELIAL NEOPLASIA; INTEROBSERVER AGREEMENT; PREOPERATIVE DIAGNOSIS; MOLECULAR ANALYSIS; EPITHELIAL ATYPIA; FLUID ANALYSIS; ADDS VALUE; MANAGEMENT; LESIONS AB Background and Aims: The value of next-generation sequencing (NGS) of pancreatic cyst fluid relative to the clinical and imaging impression has not been well-studied. The aim of this study was to assess the impact of NGS on the clinical diagnosis from imaging and carcinoembryonic antigen (CEA) and thus the management of pancreatic cysts. Methods: Ninety-two pancreatic cyst fluids from 86 patients were analyzed by cytology, CEA, and targeted NGS. Cysts were classified by imaging as nonmucinous, mucinous, or not specified. NGS results were compared with the imaging impression stratified by CEA and cytology. Results: NGS impacted the clinical diagnosis by defining a cyst as mucinous in 48% of cysts without elevated CEA levels. The VHL gene in 2 intraductal papillary mucinous neoplasms (IPMNs) supported a serous cystadenoma. Twenty percent of cysts that were nonmucinous by imaging were mucinous by NGS. Of the 14 not-specific cysts, CEA levels were not elevated in 12 (86%), and NGS established a mucinous etiology in 3 (25%). A KRAS or GNAS mutation supported an IPMN with nonmucinous CEA in 71%. A KRAS mutation reclassified 19% of nonneoplastic cysts with nonmucinous CEA as mucinous. Seven cyst fluids (8%) had either a TP53 mutation or loss of CDKN2A or SMAD4 in addition to KRAS and/or GNAS mutations; 5 of 7 (71%) were clinically malignant, and high-grade cytology was detected in all 5. Overall, CEA was more specific for a mucinous etiology (100%), but NGS was more sensitive (86% vs 57%). Conclusions: NGS of pancreatic cyst fluid impacts clinical diagnosis and patient management by defining, supporting, or changing the clinical diagnosis based on imaging and CEA. NGS was most valuable in identifying mucinous cysts with nonmucinous CEA. An added benefit is the potential to detect mutations late in the progression to malignancy that may increase the risk classification of the cyst based on imaging and cytology. C1 [Jones, Martin; Zheng, Zongli; Wang, Jessica; Dudley, Jonathan; Albanese, Emily; Dias-Santagata, Dora; Le, Long; Mino-Kenudson, Mari; Iafrate, A. John; Pitman, Martha B.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Pathol, Boston, MA 02114 USA. [Kadayifci, Abdurrahman; Brugge, William R.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Med, Boston, MA 02114 USA. [Fernandez-del Castillo, Carlos] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Surg, Boston, MA 02114 USA. RP Pitman, MB (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, 55 Fruit St,Warren 105, Boston, MA 02114 USA. EM mpitman@partners.org RI Zheng, Zongli/B-2917-2011; OI Zheng, Zongli/0000-0003-4849-4903; Jones, Martin/0000-0001-7386-7658 NR 53 TC 11 Z9 11 U1 1 U2 3 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0016-5107 EI 1097-6779 J9 GASTROINTEST ENDOSC JI Gastrointest. Endosc. PD JAN PY 2016 VL 83 IS 1 BP 140 EP 148 DI 10.1016/j.gie.2015.06.047 PG 9 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA DC5AA UT WOS:000369230900021 PM 26253016 ER PT J AU Kane, SV Ananthakrishnan, AN AF Kane, Sunanda V. Ananthakrishnan, Ashwin N. TI Toward reducing bias in clinical trials: central readers for endoscopic endpoints SO GASTROINTESTINAL ENDOSCOPY LA English DT Editorial Material ID CROHNS-DISEASE; ULCERATIVE-COLITIS; VALIDATION C1 [Kane, Sunanda V.] Mayo Clin, Div Gastroenterol & Hepatol, Rochester, MN USA. [Ananthakrishnan, Ashwin N.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Gastroenterol, Boston, MA USA. RP Kane, SV (reprint author), Mayo Clin, Div Gastroenterol & Hepatol, Rochester, MN USA. FU NIDDK NIH HHS [K23 DK097142] NR 14 TC 0 Z9 0 U1 1 U2 1 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0016-5107 EI 1097-6779 J9 GASTROINTEST ENDOSC JI Gastrointest. Endosc. PD JAN PY 2016 VL 83 IS 1 BP 198 EP 200 DI 10.1016/j.gie.2015.06.053 PG 3 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA DC5AA UT WOS:000369230900031 PM 26706305 ER PT J AU Sanduleanu, S Kaltenbach, T Barkun, A McCabe, RP Velayos, F Picco, MF Laine, L Soetikno, R McQuaid, KR AF Sanduleanu, Silvia Kaltenbach, Tonya Barkun, Alan McCabe, Robert P. Velayos, Fernando Picco, Michael F. Laine, Loren Soetikno, Roy McQuaid, Kenneth R. TI A roadmap to the implementation of chromoendoscopy in inflammatory bowel disease colonoscopy surveillance practice SO GASTROINTESTINAL ENDOSCOPY LA English DT Editorial Material ID INTERNATIONAL CONSENSUS STATEMENT; DEPRESSED COLORECTAL NEOPLASMS; STANDING ULCERATIVE-COLITIS; QUALITY INDICATORS; METHYLENE-BLUE; DNA-DAMAGE; CANCER; DYSPLASIA; RISK; ENDOSCOPY C1 [Sanduleanu, Silvia] Maastricht Univ, Med Ctr, Dept Med, Div Gastroenterol, NL-6200 MD Maastricht, Netherlands. [Sanduleanu, Silvia] Maastricht Univ, Med Ctr, GROW Sch Oncol & Dev Biol, NL-6200 MD Maastricht, Netherlands. [Kaltenbach, Tonya; Soetikno, Roy] Stanford Univ, Palo Alto, CA 94304 USA. [Kaltenbach, Tonya; Soetikno, Roy] VA Palo Alto Healthcare Syst, Palo Alto, CA USA. [Barkun, Alan] McGill Univ, Ctr Hlth, Div Gastroenterol, Montreal, PQ, Canada. [McCabe, Robert P.] Minnesota Gastroenterol, Minneapolis, MN USA. [Velayos, Fernando] Univ Calif San Francisco, Dept Med, San Francisco, CA USA. [Picco, Michael F.] Mayo Clin, Dept Med, Div Gastroenterol, Jacksonville, FL 32224 USA. [Laine, Loren] Yale Univ, Sch Med, West Haven, CT 06516 USA. [Laine, Loren] VA Connecticut Healthcare Syst, West Haven, CT USA. [McQuaid, Kenneth R.] Univ Calif San Francisco, San Francisco, CA 94143 USA. [McQuaid, Kenneth R.] San Francisco VA Med Ctr, San Francisco, CA USA. RP Sanduleanu, S (reprint author), Maastricht Univ, Med Ctr, GROW Sch Oncol & Dev Biol, Div Gastroenterol & Hepatol,Dept Internal Med, Postbox 5800, NL-6202 AZ Maastricht, Netherlands. NR 50 TC 3 Z9 3 U1 0 U2 0 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0016-5107 EI 1097-6779 J9 GASTROINTEST ENDOSC JI Gastrointest. Endosc. PD JAN PY 2016 VL 83 IS 1 BP 213 EP 222 DI 10.1016/j.gie.2015.08.076 PG 10 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA DC5AA UT WOS:000369230900034 PM 26364967 ER PT J AU Ren, J Chen, YI Liu, CH Chen, PC Prentice, H Wu, JY Liu, PK AF Ren, J. Chen, Y. I. Liu, C. H. Chen, P-C Prentice, H. Wu, J-Y Liu, P. K. TI Noninvasive tracking of gene transcript and neuroprotection after gene therapy SO GENE THERAPY LA English DT Article ID COLONY-STIMULATING FACTOR; FACTOR G-CSF; FOCAL CEREBRAL-ISCHEMIA; CARDIAC-ARREST; IN-VIVO; LIVING BRAINS; MOUSE MODEL; CELL-DEATH; MICE; MRI AB Gene therapy holds exceptional potential for translational medicine by improving the products of defective genes in diseases and/or providing necessary biologics from endogenous sources during recovery processes. However, validating methods for the delivery, distribution and expression of the exogenous genes from such therapy can generally not be applicable to monitor effects over the long term because they are invasive. We report here that human granulocyte colony-stimulating factor (hG-CSF) complimentary DNA (cDNA) encoded in self-complementary adeno-associated virus-type 2 adeno-associated virus, as delivered through eye drops at multiple time points after cerebral ischemia using bilateral carotid occlusion for 60 min (BCAO-60) led to significant reduction in mortality rates, cerebral atrophy and neurological deficits in C57black6 mice. Most importantly, we validated hG-CSF cDNA expression using translatable magnetic resonance imaging (MRI) in living brains. This noninvasive approach for monitoring exogenous gene expression in the brains has potential for great impact in the area of experimental gene therapy in animal models of heart attack, stroke, Alzheimer's dementia, Parkinson's disorder and amyotrophic lateral sclerosis, and the translation of such techniques to emergency medicine. C1 [Ren, J.; Chen, Y. I.; Liu, C. H.; Liu, P. K.] Massachusetts Gen Hosp, Dept Radiol, Athinoula A Martinos Ctr Biomed Imaging, CNY149 13th St, Charlestown, MA 02129 USA. [Ren, J.; Chen, Y. I.; Liu, C. H.; Liu, P. K.] Harvard Univ, Sch Med, CNY149 13th St, Charlestown, MA 02129 USA. [Chen, P-C; Prentice, H.; Wu, J-Y] Florida Atlantic Univ, Charles E Schmidt Coll Med, Dept Biomed Sci, Boca Raton, FL 33431 USA. RP Liu, PK (reprint author), Massachusetts Gen Hosp, Dept Radiol, Athinoula A Martinos Ctr Biomed Imaging, CNY149 13th St, Charlestown, MA 02129 USA.; Liu, PK (reprint author), Harvard Univ, Sch Med, CNY149 13th St, Charlestown, MA 02129 USA.; Liu, PK (reprint author), Massachusetts Gen Hosp, Dept Radiol, CNY149 13th St, Charlestown, MA 02129 USA. EM philipl@nmr.mgh.harvard.edu OI Liu, Christina/0000-0002-5723-177X FU NIH [R01DA029889, R01EB013768, 1S10RR025563]; Boston Area Diabetes Endocrinology Research Center [P30DK057521-14, NS045776]; Wellcome Trust [1012722]; State of Florida [09KW-11] FX We thank Dr Sean I Savitz (University of Texas Houston Medical School, Houston, TX, USA) for demonstration of the corner tests; Dr Jarek Aronowski (UTHMS, TX, USA) for sharing the hypothermia treatment protocol; Dr Charng-Ming Liu for synthesizing all sODN and Dr JS Yang for conducting real time-PCR. This project was supported by NIH grants R01DA029889 and R01EB013768, as well as by a pilot grant from the Boston Area Diabetes Endocrinology Research Center (P30DK057521-14 (J Avruch)) to PKL, NS045776 to the MGH Neuroscience Center). The MR systems used for this work were funded by NIH Shared Instrumentation Grants (1S10RR025563) awarded to the Athinoula A Martinos Center for Biomedical Imaging. The B Wellcome Trust (No. 1012722) to HP, State of Florida (09KW-11) to JYW also supported this research. NR 41 TC 1 Z9 1 U1 3 U2 7 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0969-7128 EI 1476-5462 J9 GENE THER JI Gene Ther. PD JAN PY 2016 VL 23 IS 1 BP 1 EP 9 DI 10.1038/gt.2015.81 PG 9 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA DC9ND UT WOS:000369547400001 PM 26207935 ER PT J AU Li, G Chen, C Laing, SD Ballard, C Biju, KC Reddick, RL Clark, RA Li, S AF Li, G. Chen, C. Laing, S. D. Ballard, C. Biju, K. C. Reddick, R. L. Clark, R. A. Li, S. TI Hematopoietic knockdown of PPAR delta reduces atherosclerosis in LDLR-/- mice SO GENE THERAPY LA English DT Article ID ACTIVATED-RECEPTOR-DELTA; PREVENTS ENDOTHELIAL DYSFUNCTION; NF-KAPPA-B; METABOLIC SYNDROME; MOLECULAR-MECHANISMS; GENE-THERAPY; BETA/DELTA; EXPRESSION; DISEASE; INFLAMMATION AB PPAR(delta) (peroxisome proliferator-activated receptor delta) mediates inflammation in response to lipid accumulation. Systemic administration of a PPAR(delta) agonist can ameliorate atherosclerosis. Paradoxically, genetic deletion of PPAR(delta) in hematopoietic cells led to a reduction of atherosclerosis in murine models, suggesting that downregulation of PPAR(delta) expression in these cells may mitigate atherogenesis. To advance this finding forward to potential clinical translation through hematopoietic stem cell transplantation-based gene therapy, we employed a microRNA (miRNA) approach to knock down PPAR(delta) expression in bone marrow cells followed by transplantation of the cells into LDLR-/- mice. We found that knockdown of PPARd expression in the hematopoietic system caused a dramatic reduction in aortic atherosclerotic lesions. In macrophages, a key component in atherogenesis, knockdown of PPAR(delta) led to decreased expression of multiple pro-inflammatory factors, including monocyte chemoattractant protein-1 (MCP-1), interleukin (IL)-1 beta and IL-6. Expression of CCR2, a receptor for MCP-1, was also decreased. The downregulation of pro-inflammatory factors is consistent with significant reduction of macrophage presence in the lesions, which may also be attributable to elevation of ABCA1 (ATP-binding cassette, subfamily A, member 1) and depression of adipocyte differentiate-related protein. Furthermore, the abundance of both MCP-1 and matrix metalloproteinase-9 proteins was reduced in plaque areas. Our results demonstrate that miRNA-mediated PPAR delta knockdown in hematopoietic cells is able to ameliorate atherosclerosis. C1 [Li, G.; Chen, C.; Laing, S. D.; Ballard, C.; Biju, K. C.; Clark, R. A.; Li, S.] Univ Texas Hlth Sci Ctr San Antonio, Dept Med, 7703 Floyd Curl Dr, San Antonio, TX 78229 USA. [Li, G.; Chen, C.; Laing, S. D.; Ballard, C.; Biju, K. C.; Clark, R. A.; Li, S.] South Texas Vet Hlth Care Syst, Audie L Murphy Div, San Antonio, TX USA. [Reddick, R. L.] Univ Texas Hlth Sci Ctr San Antonio, Dept Pathol, 7703 Floyd Curl Dr, San Antonio, TX 78229 USA. [Li, S.] Univ Texas Hlth Sci Ctr San Antonio, Dept Pharmacol, 7703 Floyd Curl Dr, San Antonio, TX 78229 USA. RP Li, S (reprint author), Univ Texas Hlth Sci Ctr San Antonio, Dept Med, 7703 Floyd Curl Dr, San Antonio, TX 78229 USA.; Li, S (reprint author), South Texas Vet Hlth Care Syst, Audie L Murphy Div, San Antonio, TX USA.; Li, S (reprint author), Univ Texas Hlth Sci Ctr San Antonio, Dept Pharmacol, 7703 Floyd Curl Dr, San Antonio, TX 78229 USA. EM lis1@uthscsa.edu FU Research Division of the Department of Veterans Affairs; William and Ella Owens Medical Research Foundation; Clinical and Translational Science Award from the National Institutes of Health [TR001120]; US Veterans Health Administration FX We thank Xiaoling Xue and Qiong Zhang for excellent laboratory assistance. This study was supported by a Merit Review grant from the Research Division of the Department of Veterans Affairs and by a grant from William and Ella Owens Medical Research Foundation awarded to SL. RAC is supported by Clinical and Translational Science Award TR001120 from the National Institutes of Health. This study was supported by a grant from the US Veterans Health Administration. NR 52 TC 1 Z9 1 U1 1 U2 1 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0969-7128 EI 1476-5462 J9 GENE THER JI Gene Ther. PD JAN PY 2016 VL 23 IS 1 BP 78 EP 85 DI 10.1038/gt.2015.78 PG 8 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA DC9ND UT WOS:000369547400009 PM 26204499 ER PT J AU Lewiecki, EM Baron, R Bilezikian, JP Gagel, RE Leonarc, MB Leslie, WD McClung, MR Miller, PD AF Lewiecki, E. Michael Baron, Roland Bilezikian, John P. Gagel, Robert E. Leonarc, Mary B. Leslie, William D. McClung, Michael R. Miller, Paul D. TI Proceedings of the 2015 Santa Fe Bone Symposium: Clinical Applications of Scientific Advances in Osteoporosis and Metabolic Bone Disease SO JOURNAL OF CLINICAL DENSITOMETRY LA English DT Article DE Bone Health ECHO; emerging; osteoporosis; Project ECHO; treatment ID ISCD OFFICIAL POSITIONS; QUANTITATIVE COMPUTED-TOMOGRAPHY; RANDOMIZED CONTROLLED-TRIAL; JUVENILE IDIOPATHIC ARTHRITIS; CHILDHOOD NEPHROTIC SYNDROME; ATYPICAL FEMORAL FRACTURES; PEDIATRIC CROHNS-DISEASE; FINITE-ELEMENT-ANALYSIS; INCIDENT VERTEBRAL FRACTURES; INFLAMMATORY-BOWEL-DISEASE AB The 2015 Santa Fe Bone Symposium was a venue for healthcare professionals and clinical researchers to present and discuss the clinical relevance of recent advances in the science of skeletal disorders, with a focus on osteoporosis and metabolic bone disease. Symposium topics included new developments in the translation of basic bone science to improved patient care, osteoporosis treatment duration, pediatric bone disease, update of fracture risk assessment, cancer treatment-related bone loss, fracture liaison services, a review of the most significant studies of the past year, and the use of telementoring with Bone Health Extension for Community Healthcare Outcomes, a force multiplier to improve the care of osteoporosis in underserved communities. C1 [Lewiecki, E. Michael] New Mexico Clin Res & Osteoporosis Ctr, 300 Oak St NE, Albuquerque, NM 87106 USA. [Baron, Roland] Harvard Univ, Sch Med, Boston, MA USA. [Baron, Roland] Harvard Univ, Sch Dent Med, Massachusetts Gen Hosp, 188 Longwood Ave, Boston, MA 02115 USA. [Bilezikian, John P.] Columbia Univ Coll Phys & Surg, 630 W 168th St, New York, NY 10032 USA. [Gagel, Robert E.] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. [Leonarc, Mary B.] Stanford Sch Med, Stanford, CA USA. [Leslie, William D.] Univ Manitoba, Dept Internal Med, Winnipeg, MB, Canada. [McClung, Michael R.] Oregon Osteoporosis Ctr, Portland, OR USA. [Miller, Paul D.] Colorado Ctr Bone Res, Lakewood, CO USA. RP Lewiecki, EM (reprint author), New Mexico Clin Res & Osteoporosis Ctr, 300 Oak St NE, Albuquerque, NM 87106 USA. EM mlewiecki@gmail.com FU NPS; Novartis; Amgen; Genzyme; Eli Lilly; Merck; Lilly; Merck Serono; Boehringer Ingelheim; Roche Diagnostics; Takeda; University of Alabama FX Roland Baron, DDS, PhD: Honorarium/Ad Board: Lilly, Bone Therapeutics; Honorarium/Consultant: Daiichi Sankyo, Asari Sankyo; Honorarium/Speaker, AD Board: Merck, Amgen; Grant/Investigator: Merck; Honorarium/Consultant, AD Board: Radius Health; John P. Bilezikian, MD: Honorarium/Consultant: Merck, Amgen, NPS, Lilly; Research Grant: Investigator: NPS; Robert E. Gagel, MD: no financial relationships to disclose; Mary B. Leonard, MD: Consulting Fees/DSMB Member: Novartis; Consulting Fees/Advisory Committee Member: Amgen; William Leslie, MD: Honorarium/Speaker: Amgen, Eli Lilly, Novartis; Research Grants/Researcher: Amgen, Genzyme; E. Michael Lewiecki, MD: Research Grant Support: Amgen, Eli Lilly, Merck; Consultant: Amgen, Eli Lilly, Merck, Radius Health, AgNovos Health care, Theranova, Alexion, NPS, AbbVie; Michael R. McClung, MD: Honorarium and Consultant Fees/Consultant and Speaker: Merck, Amgen; Honorarium/Speaker: GSK; Consulting Fees/Consultant: Lilly; Paul D. Miller, MD: Honorarium and Research Grants/Speaker, Primary Investigator, AD Board Member; Scientific Advisory Board: Amgen, Lilly, Merck; Research Grant(s)/Primary Investigator: Merck Serono, Boehringer Ingelheim; Novartis, Roche Diagnostics, Takeda, University of Alabama; Honorarium/Scientific Advisory Board: Alexion, Radius Pharma; Honorarium/Scientific Board: AgNovos. NR 160 TC 1 Z9 1 U1 1 U2 4 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1094-6950 EI 1559-0747 J9 J CLIN DENSITOM JI J. Clin. Densitom. PD JAN-MAR PY 2016 VL 19 IS 1 BP 102 EP 116 DI 10.1016/j.jocd.2015.11.003 PG 15 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA DC6UA UT WOS:000369353900016 PM 26750746 ER PT J AU Tse, JY Walls, BE Pomerantz, H Yoon, CH Buchbinder, EI Werchniak, AE Dong, F Lian, CG Granter, SR AF Tse, Julie Y. Walls, Brooke E. Pomerantz, Hyemin Yoon, Charles H. Buchbinder, Elizabeth I. Werchniak, Andrew E. Dong, Fei Lian, Christine G. Granter, Scott R. TI Melanoma arising in a nevus of Ito: novel genetic mutations and a review of the literature on cutaneous malignant transformation of dermal melanocytosis SO JOURNAL OF CUTANEOUS PATHOLOGY LA English DT Article DE congenital nevus cells; melanocytic lesions; melanoma; molecular pathology ID CELLULAR BLUE NEVUS; OCULODERMAL MELANOCYTOSIS; CHOROIDAL MELANOMA; BLACK PATIENT; INTRACRANIAL MELANOMA; OCULAR MELANOSIS; INVASIVE NEVUS; DURAL MELANOMA; OTA; TUMORS AB Dermal melanocytosis refers to a spectrum of benign melanocytic proliferations that includes Mongolian spot, nevus of Ota and nevus of Ito. These lesions most commonly occur in persons of Asian or African descent and are often present at birth or develop during childhood. Very rarely, dermal melanocytoses undergo malignant transformation. There have been only 13 reports in the literature of primary cutaneous melanoma arising in dermal melanocytoses. We report a case of a Chinese woman with melanoma arising in a congenital nevus of Ito. We performed targeted next-generation sequencing of the tumor which revealed mutations of GNAQ and BAP1, suggesting that alterations in these two genes led to malignant transformation of the nevus of Ito. We also provide a summary of reports in the literature regarding primary cutaneous melanoma arising in the context of dermal melanocytosis. C1 [Tse, Julie Y.] Massachusetts Gen Hosp, Dept Pathol, 55 Fruit St,Warren 219, Boston, MA 02114 USA. [Walls, Brooke E.; Pomerantz, Hyemin; Werchniak, Andrew E.] Brigham & Womens Hosp, Dept Dermatol, 75 Francis St, Boston, MA 02115 USA. [Yoon, Charles H.] Brigham & Womens Hosp, Dept Surg, 75 Francis St, Boston, MA 02115 USA. [Buchbinder, Elizabeth I.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Dong, Fei; Lian, Christine G.; Granter, Scott R.] Brigham & Womens Hosp, Dept Pathol, 75 Francis St, Boston, MA 02115 USA. RP Tse, JY (reprint author), Massachusetts Gen Hosp, Dept Pathol, 55 Fruit St,Warren 219, Boston, MA 02114 USA. EM JTSE@mgh.harvard.edu NR 66 TC 0 Z9 0 U1 1 U2 2 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 2016 VL 43 IS 1 BP 57 EP 63 DI 10.1111/cup.12568 PG 7 WC Dermatology; Pathology SC Dermatology; Pathology GA DC6BC UT WOS:000369303700010 PM 26260725 ER PT J AU Bratcher, PE Rowe, SM Reeves, G Roberts, T Szul, T Harris, WT Tirouvanziam, R Gaggar, A AF Bratcher, Preston E. Rowe, Steven M. Reeves, Ginger Roberts, Tambra Szul, Tomasz Harris, William T. Tirouvanziam, Rabindra Gaggar, Amit TI Alterations in blood leukocytes of G551D-bearing cystic fibrosis patients undergoing treatment with ivacaftor SO JOURNAL OF CYSTIC FIBROSIS LA English DT Article DE CFTR; G551D; Ivacaftor; VX-770; Leukocyte; Blood ID HUMAN NEUTROPHILS; CFTR POTENTIATOR; G551D MUTATION; EXPRESSION; RECEPTORS; DISEASE; CELLS AB Background: Ivacaftor improves clinical outcome by potentiation of mutant G551D CFTR. Due to the presence of CFTR in monocytes and polymorphonuclear neutrophils (PMNs), we hypothesized that ivacaftor may impact leukocyte activation. Methods: We examined blood leukocytes from G551D CF subjects prior to and at one and six months after receiving ivacaftor. Blood leukocytes from ivacaftor-naive G551D, F508del, and healthy controls were also treated with ivacaftor ex vivo to assess mutation-specific effects. Results: Compared to healthy controls, G551D CF subjects had significantly higher expression of active CD11b on PMNs and of CD63 on monocytes, which were normalized by in vivo ivacaftor treatment. Ex vivo exposure to ivacaftor of blood cells from G551D, but not F508del and healthy subjects, resulted in changes in CXCR2 and CD16 expression on PMNs. Conclusions: In vivo and ex vivo exposure of G551D CF leukocytes to ivacaftor resulted in an altered activation profile, suggesting mutation specific leukocyte modulation. Published by Elsevier B.V. on behalf of European Cystic Fibrosis Society. C1 [Bratcher, Preston E.; Rowe, Steven M.; Szul, Tomasz; Gaggar, Amit] Univ Alabama Birmingham, Dept Med, 424 THT,1900 Univ Blvd, Birmingham, AL 35294 USA. [Bratcher, Preston E.; Rowe, Steven M.; Szul, Tomasz; Gaggar, Amit] Univ Alabama Birmingham, Div Pulm Allergy & Crit Care Med, 424 THT,1900 Univ Blvd, Birmingham, AL 35294 USA. [Rowe, Steven M.; Reeves, Ginger; Roberts, Tambra; Harris, William T.; Gaggar, Amit] Univ Alabama Birmingham, Gregory Fleming James Cyst Fibrosis Res Ctr, MCLM 790,1918 Univ Blvd, Birmingham, AL 35294 USA. [Rowe, Steven M.; Gaggar, Amit] Univ Alabama Birmingham, UAB Lung Hlth Ctr, 526 20th St South, Birmingham, AL 35294 USA. [Gaggar, Amit] US Dept Vet Affairs, Med Serv, Med Ctr, 700 19th St S, Birmingham, AL 35233 USA. [Rowe, Steven M.; Reeves, Ginger; Roberts, Tambra; Harris, William T.] Univ Alabama Birmingham, Dept Pediat Childrens Alabama, 1600 7th Ave South, Birmingham, AL 35233 USA. [Rowe, Steven M.] Dept Cell Dev & Integrat Biol, THT 926,1720 2nd Ave South, Birmingham, AL 35294 USA. [Bratcher, Preston E.; Szul, Tomasz; Harris, William T.; Tirouvanziam, Rabindra; Gaggar, Amit] Univ Alabama Birmingham, Program Protease & Matrix Biol, MCLM 760,1918 Univ Blvd, Birmingham, AL 35294 USA. [Tirouvanziam, Rabindra] Emory Univ, Dept Pediat, 2015 Uppergate Dr,Room 344, Atlanta, GA 30322 USA. [Tirouvanziam, Rabindra] Childrens Healthcare Atlanta, Ctr Cyst Fibrosis & Airway Dis Res, 2015 Uppergate Dr,Room 344, Atlanta, GA 30322 USA. RP Gaggar, A (reprint author), 1918 Univ Blvd,McCallum Room 760, Birmingham, AL 35294 USA. EM bratcher@uab.edu; smrowe@uab.edu; greeves@peds.uab.edu; troberts@peds.uab.edu; szultom@uab.edu; tharris@peds.uab.edu; tirouvanziam@emory.edu; agaggar1@uab.edu FU National Institutes of Health [HL102371, 5T32HL105346-02, P30 DK072482, UL1 TR000165]; Cystic Fibrosis Foundation [GAGGAR07, GOAL13K1, TIROUV13, Harris12Q0]; Ismail Moustafa Scholar Award; Emory Children's Center FX Funding: This work is supported by the National Institutes of Health (HL102371 to AG, 5T32HL105346-02 to PEB, P30 DK072482 to SMR, UL1 TR000165 to SMR), the Cystic Fibrosis Foundation (GAGGAR07 to AG, GOAL13K1 to SMR, TIROUV13 to RT, Harris12Q0 to WTH), the Ismail Moustafa Scholar Award (to AG) and by a faculty start-up from the Emory Children's Center (RT). NR 27 TC 6 Z9 6 U1 0 U2 3 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1569-1993 EI 1873-5010 J9 J CYST FIBROS JI J. Cyst. Fibros PD JAN PY 2016 VL 15 IS 1 BP 67 EP 73 DI 10.1016/j.jcf.2015.02.010 PG 7 WC Respiratory System SC Respiratory System GA DC8HT UT WOS:000369461200012 PM 25769931 ER PT J AU Linnemann, RW O'Malley, PJ Friedman, D Georgiopoulos, AM Buxton, D Altstein, LL Sicilian, L Lapey, A Sawicki, GS Moskowitz, SM AF Linnemann, Rachel W. O'Malley, Patricia J. Friedman, Deborah Georgiopoulos, Anna M. Buxton, David Altstein, Lily L. Sicilian, Leonard Lapey, Allen Sawicki, Gregory S. Moskowitz, Samuel M. TI Development and evaluation of a palliative care curriculum for cystic fibrosis healthcare providers SO JOURNAL OF CYSTIC FIBROSIS LA English DT Article DE Cystic fibrosis; Education; End-of-life care; Palliative care ID QUALITY-OF-LIFE; END; ADULTS; PAIN; DEPRESSION; ADHERENCE; ASSOCIATION; SYMPTOMS; OUTCOMES; ANXIETY AB Background: Primary palliative care refers to basic skills that all healthcare providers can employ to improve quality of life for patients at any stage of disease. Training in these core skills is not commonly provided to clinicians caring for cystic fibrosis (CF) patients. The objective of this study was to assess change in comfort with core skills among care team members after participation in CF-specific palliative care training focused on management of burdensome symptoms and difficult conversations. Methods: A qualitative needs assessment was performed to inform the development of an 18-hour curriculum tailored to the chronicity and complexity of CF care. A 32-question pre- and post-course survey assessed CF provider comfort with the targeted palliative care skills in 5 domains using a 5-point Likert scale (1 = very uncomfortable, 3 = neutral, 5 = very comfortable). Results: Among course participants (n = 16), mean overall comfort score increased by 0.9, from 3 (neutral) to 3.9 (comfortable) (p < 0.001). Mean comfort level increased significantly (range 0.8 to 1.4) in each skill domain: use of supportive care resources, pain management, non-pain symptom management, communication, and psychosocial skills. Conclusions: CF-specific palliative care training was well received by participants and significantly improved self-assessed comfort with core skills. (C) 2015 European Cystic Fibrosis Society. Published by Elsevier B.V. All rights reserved. C1 [Linnemann, Rachel W.; O'Malley, Patricia J.; Lapey, Allen; Moskowitz, Samuel M.] Massachusetts Gen Hosp, Dept Pediat, Boston, MA 02114 USA. [Linnemann, Rachel W.; O'Malley, Patricia J.; Lapey, Allen; Sawicki, Gregory S.; Moskowitz, Samuel M.] Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. [Friedman, Deborah; Georgiopoulos, Anna M.; Buxton, David] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. [Friedman, Deborah; Georgiopoulos, Anna M.; Buxton, David] Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA. [Altstein, Lily L.] Massachusetts Gen Hosp, Dept Biostat, Boston, MA USA. [Sicilian, Leonard] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. [Sicilian, Leonard] Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. [Sawicki, Gregory S.] Boston Childrens Hosp, Dept Med, Boston, MA USA. RP Moskowitz, SM (reprint author), Massachusetts Gen Hosp, Div Pediat Pulm Med, 275 Cambridge St, Boston, MA 02114 USA. EM smoskowitz@mgh.harvard.edu FU Cystic Fibrosis Foundation [MOSKOW13A0, LINNEM14A0] FX This project was supported through research grant MOSKOW13A0 and clinical fellowship grant LINNEM14A0 from the Cystic Fibrosis Foundation. NR 31 TC 5 Z9 5 U1 2 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1569-1993 EI 1873-5010 J9 J CYST FIBROS JI J. Cyst. Fibros PD JAN PY 2016 VL 15 IS 1 BP 90 EP 95 DI 10.1016/j.jcf.2015.03.005 PG 6 WC Respiratory System SC Respiratory System GA DC8HT UT WOS:000369461200016 PM 25817162 ER PT J AU Baizano, J Fresenius, A Walker, P Berdella, M Portenoy, RK Bookbinder, M Glajchen, M Plachta, A Langfelder-Schwind, E Chen, J Dhingra, L AF Baizano, Julie Fresenius, Ashley Walker, Patricia Berdella, Maria Portenoy, Russell K. Bookbinder, Marilyn Glajchen, Myra Plachta, Amy Langfelder-Schwind, Elinor Chen, Jack Dhingra, Lara TI Web-based symptom screening in cystic fibrosis patients: A feasibility study SO JOURNAL OF CYSTIC FIBROSIS LA English DT Article DE Cystic fibrosis; Telehealth; Web-based monitoring; Symptom screening; Symptom burden; Advance care planning ID QUALITY-OF-LIFE; ADULT PATIENTS; DISTRESS; CANCER; SCALE AB Background: Cystic fibrosis (CF) causes high illness burden. Screening may identify patients who could potentially benefit from interventions for symptoms or other sources of distress. We evaluated the feasibility of a web-based system for routine monitoring. Methods: Adult CF patients enrolled in a study of palliative care service delivery completed web-based assessments every 30 days on global distress, physical and psychological symptom distress, and the perceived benefits of discussing advance care planning (ACP) with CF clinicians. Feasibility was assessed by the rate of survey completion, survey reminders, and missed surveys during a 9-month rolling enrollment period. Results: Of 74 participants (47.3% women, 94.4% white), 36.7% had comorbid diabetes, and 56.9% had an FEV1% predicted score of 40-69. In total, patients completed 456 (80.6%) of 566surveys every 30 days over the assessment period. Sixty-five (87.8%) completed 405 (79.7%) of 508 surveys online and 9 (12.2%) completed 51 (88.0%) of 58 surveys using a combination of online, telephone, and mail-based methods. Many surveys were completed without reminders (online: 261 [64.4%] of 405; combined methods: 29 [56.9%] of 51), with 166 (36.4%) surveys requiring 1 or more reminders. Further, 23.0% (17) of patients noted elevated global distress; 20.3% (15) endorsed physical symptom distress, 12.2% (9) had psychological distress, and 58.1% (43) reported that discussing ACP would be beneficial. Conclusions: Repeated web-based screening for symptom distress and ACP preferences is feasible in adult CF patients. Future studies should assess the system's generalizability and staff resources when implementing reminders and non-web methods of completion. (C) 2015 European Cystic Fibrosis Society. Published by Elsevier B.V. All rights reserved. C1 [Baizano, Julie] James J Peters VA Med Ctr, 130 West Kingsbridge Rd, Bronx, NY 10468 USA. [Fresenius, Ashley; Walker, Patricia; Berdella, Maria; Plachta, Amy; Langfelder-Schwind, Elinor] Mt Sinai Beth Israel, Dept Pulm Med, Cyst Fibrosis Ctr, First Ave,16th St, New York, NY 10003 USA. [Portenoy, Russell K.; Bookbinder, Marilyn; Glajchen, Myra; Chen, Jack; Dhingra, Lara] MJHS Inst Innovat Palliat Care, 39 Broadway,3rd Floor, New York, NY 10006 USA. RP Dhingra, L (reprint author), MJHS Inst Innovat Palliat Care, 39 Broadway,3rd Floor, New York, NY 10006 USA. EM LDhingra@mjhs.org FU Cystic Fibrosis Therapeutics, Inc. [PORTEN13A0] FX This research was supported by a grant from Cystic Fibrosis Therapeutics, Inc. (PORTEN13A0). None of the authors have any conflict of interest associated with this research. NR 19 TC 0 Z9 0 U1 2 U2 3 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1569-1993 EI 1873-5010 J9 J CYST FIBROS JI J. Cyst. Fibros PD JAN PY 2016 VL 15 IS 1 BP 102 EP 108 DI 10.1016/j.jcf.2015.11.001 PG 7 WC Respiratory System SC Respiratory System GA DC8HT UT WOS:000369461200018 ER PT J AU Terrelonge, M Marder, KS Weintraub, D Alcalay, RN AF Terrelonge, Mark, Jr. Marder, Karen S. Weintraub, Daniel Alcalay, Roy N. TI CSF beta-Amyloid 1-42 Predicts Progression to Cognitive Impairment in Newly Diagnosed Parkinson Disease SO JOURNAL OF MOLECULAR NEUROSCIENCE LA English DT Article DE CSF beta-amyloid 1-42; Cognitive impairment; Parkinson's disease; PPMI ID CEREBROSPINAL-FLUID; DEMENTIA; TAU; A-BETA(42); ASSOCIATION; PERFORMANCE; BIOMARKERS; GUIDELINES; AUTOPSY AB Low CSF beta-amyloid 1-42 has been associated with cognitive decline in advanced Parkinson's disease; data from a single cohort suggest beta-amyloid 1-42 may be an early marker of cognitive impairment. Newly diagnosed Parkinson's participants (mean duration, 6.9 months) in the Parkinson's Progression Markers Initiative (n = 341) were assessed at baseline (untreated state) and followed for 2 years. CSF beta-amyloid 1-42, alpha-synuclein, total tau, and tau phosphorylated at threonine 181 were collected at baseline. Participants were classified as having cognitive impairment (CI) if scores on two of six cognitive tests were 1.5 standard deviations below the standardized mean based on published norms in healthy controls. Multivariable regression analyses were used to determine the association between baseline CSF markers with cognitive impairment, defined by neuropsychological testing performance at 2-year follow-up. Fifty-five participants (16.1 %) had CI at baseline and were not included in further analyses. Thirty-seven of the 286 participants without CI at baseline (12.9 %) developed CI at 2 years. Participants with CI at 2 years had significantly lower mean baseline CSF beta-amyloid 1-42 levels than non-CI participants (343.8 vs. 380.4 pg/mL, p < 0.01); no significant difference was seen for alpha-synuclein, T-tau, or P-tau 181. In a regression model of 286 participants without baseline CI adjusted for age, gender, disease duration, education, motor severity, and depression status, lower baseline beta-amyloid 1-42 levels were associated with higher odds of CI at 2 years. (OR10pg/mL = 1.04, 95 % CI 1.01-1.08, p < 0.05). CSF beta-amyloid 1-42 level at disease onset is an independent predictor of cognitive impairment in early Parkinson's disease. C1 [Terrelonge, Mark, Jr.; Marder, Karen S.; Alcalay, Roy N.] Columbia Univ, Dept Neurol, 710 W 168th St, New York, NY 10032 USA. [Weintraub, Daniel] Univ Penn, Dept Psychiat, Perelman Sch Med, Philadelphia, PA 19104 USA. [Weintraub, Daniel] Univ Penn, Dept Neurol, Perelman Sch Med, Philadelphia, PA 19104 USA. [Weintraub, Daniel] Philadelphia Vet Affairs Med Ctr, Philadelphia, PA USA. RP Alcalay, RN (reprint author), Columbia Univ, Dept Neurol, 710 W 168th St, New York, NY 10032 USA. EM RNA2104@COLUMBIA.EDU FU NIH [NS036630, 1UL1 RR024156-01, PO412196- G, PO412196-G]; Parkinson disease Foundation; MJ Fox Foundation; Michael J. Fox Foundation for Parkinson's Research; National Institutes of Health; Novartis Pharmaceuticals; Department of Veterans Affairs; Alzheimer's Disease Cooperative Study; University of Pennsylvania; Parkinson's Disease Foundation; National Institutes of Health [NS036630, K02NS080915, UL1 TR000040, UL1 RR024156]; Brookdale Foundation; [U01NS052592] FX Dr. Marder reports grants from NIH [#NS036630 (PI), 1UL1 RR024156-01(Director PCIR), PO412196- G (Co-I), and PO412196-G (Co-I)], grants from steering committee for U01NS052592, grants from Parkinson disease Foundation, and grants from MJ Fox Foundation and research funds from Teva Pharmaceuticals outside the submitted work. Dr. Weintraub received research funding from the Michael J. Fox Foundation for Parkinson's Research, National Institutes of Health, Novartis Pharmaceuticals, Department of Veterans Affairs, and Alzheimer's Disease Cooperative Study; honoraria from Teva Pharmaceuticals, Lundbeck Inc., Pfizer, Avanir Pharmaceuticals, Merck & Co., UCB, Bristol-Myers Squibb Company, Novartis Pharmaceuticals, Eli Lilly and Company, Clintrex LLC, Theravance, Medivation, CHDI Foundation, and Alzheimer's Disease Cooperative Study; license fee payments from the University of Pennsylvania for the QUIP and QUIP-RS; and fees for testifying in court case related to impulse controls disorders in Parkinson's disease (March 2013). Dr. Alcalay is supported by the Parkinson's Disease Foundation, the National Institutes of Health (K02NS080915, NS036630, and UL1 TR000040, formerly the National Center for Research Resources, Grant Number UL1 RR024156), and the Brookdale Foundation. He consulted for Genzyme/Sanofi and Prophase. NR 24 TC 8 Z9 8 U1 1 U2 4 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DRIVE SUITE 208, TOTOWA, NJ 07512 USA SN 0895-8696 EI 1559-1166 J9 J MOL NEUROSCI JI J. Mol. Neurosci. PD JAN PY 2016 VL 58 IS 1 BP 88 EP 92 DI 10.1007/s12031-015-0647-x PG 5 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA DC5RF UT WOS:000369277400010 PM 26330275 ER PT J AU Dahan, H Shir, Y Nicolau, B Keith, D Allison, P AF Dahan, Haissam Shir, Yoram Nicolau, Belinda Keith, David Allison, Paul TI Self-Reported Migraine and Chronic Fatigue Syndrome Are More Prevalent in People with Myofascial vs Nonmyofascial Temporomandibular Disorders SO JOURNAL OF ORAL & FACIAL PAIN AND HEADACHE LA English DT Article DE central sensitivity syndrome; comorbidity; myofascial pain; overlapping conditions; temporomandibular disorders ID RESTLESS LEGS SYNDROME; CENTRAL SENSITIVITY SYNDROMES; MUSCULOSKELETAL PAIN SITES; OVERLAPPING CONDITIONS; DIAGNOSTIC-CRITERIA; OROFACIAL PAIN; RISK-FACTORS; SYMPTOMS; FIBROMYALGIA; VALIDATION AB Aims: To compare the number of comorbidities and the prevalence of five specific comorbidities in people who have temporomandibular disorders (TMD) with or without myofascial pain. Methods: This cross-sectional study included 180 patients seeking TMD treatment in Boston and Montreal hospitals. A self-administered questionnaire was used to collect information on sociodemographic and behavioral factors, as well as the presence of the following five comorbidities: migraine, chronic fatigue syndrome, irritable bowel syndrome, interstitial cystitis, and restless leg syndrome. TMD was diagnosed using the Research Diagnostic Criteria for TMD. Chi-square and Student t tests were used for categorical and continuous variables, respectively, to test for differences between myofascial (n = 121) and nonmyofascial (n = 59) TMD groups. Multiple logistic regression analysis was used to compare the type and number of self-reported comorbidities in both groups, controlling for confounding variables. Results: The following were found to be significantly higher in the myofascial TMD group than in the nonmyofascial TMD group: self-reported migraine (55% vs 28%, P =.001), chronic fatigue syndrome (19% vs 5%, P =.01), and the mean total number of comorbidities (1.30 vs 0.83, P =.01). Conclusion: Individuals with myofascial TMD had a higher prevalence of self-reported migraine and chronic fatigue syndrome than those with nonmyofascial TMD. C1 [Dahan, Haissam; Nicolau, Belinda; Allison, Paul] McGill Univ, Fac Dent, Div Oral Hlth & Soc, 2001 McGill Coll, Montreal, PQ H3A 1G1, Canada. [Shir, Yoram] McGill Univ, Ctr Hlth, Alan Edwards Pain Management Unit, Montreal Gen Hosp Campus, Montreal, PQ H3A 1G1, Canada. [Keith, David] Massachusetts Gen Hosp, Dept Oral & Maxillofacial Surg, Boston, MA 02114 USA. RP Dahan, H (reprint author), McGill Univ, Fac Dent, Div Oral Hlth & Soc, 2001 McGill Coll, Montreal, PQ H3A 1G1, Canada. EM haissam.dahan@mail.mcgill.ca FU Louise and Alan Edwards Foundation FX The authors acknowledge the Louise and Alan Edwards Foundation for its generous financial support of this study. The authors report no conflicts of interest. NR 50 TC 3 Z9 3 U1 1 U2 3 PU QUINTESSENCE PUBLISHING CO INC PI HANOVER PARK PA 4350 CHANDLER DRIVE, HANOVER PARK, IL 60133 USA SN 2333-0384 EI 2333-0376 J9 J ORAL FACIAL PAIN H JI J. Oral Facial Pain Headache PY 2016 VL 30 IS 1 BP 7 EP 13 PG 7 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA DC6QL UT WOS:000369344600002 PM 26817027 ER PT J AU Winter, HS AF Winter, Harland S. TI Commentary on "The Use of Placebo in Pediatric Inflammatory Bowel Diseases'' SO JOURNAL OF PEDIATRIC GASTROENTEROLOGY AND NUTRITION LA English DT Editorial Material ID ULCERATIVE-COLITIS; CROHNS-DISEASE; MAINTENANCE; INFLIXIMAB; CHILDREN; THERAPY C1 [Winter, Harland S.] MassGen Hosp Children, Pediat IBD Program, 175 Cambridge St,CRPZ 5-560, Boston, MA 02114 USA. RP Winter, HS (reprint author), MassGen Hosp Children, Pediat IBD Program, 175 Cambridge St,CRPZ 5-560, Boston, MA 02114 USA. EM hwinter@mgh.harvard.edu NR 5 TC 0 Z9 0 U1 1 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0277-2116 EI 1536-4801 J9 J PEDIATR GASTR NUTR JI J. Pediatr. Gastroenterol. Nutr. PD JAN PY 2016 VL 62 IS 1 BP 5 EP 7 DI 10.1097/MPG.0000000000001047 PG 3 WC Gastroenterology & Hepatology; Nutrition & Dietetics; Pediatrics SC Gastroenterology & Hepatology; Nutrition & Dietetics; Pediatrics GA DC5ZN UT WOS:000369299400003 PM 26704668 ER PT J AU Wu, H Hu, C Wang, A Weisberg, EL Chen, Y Yun, CH Wang, W Liu, Y Liu, X Tian, B Wang, J Zhao, Z Liang, Y Li, B Wang, L Wang, B Chen, C Buhrlage, SJ Qi, Z Zou, F Nonami, A Li, Y Fernandes, SM Adamia, S Stone, RM Galinsky, IA Wang, X Yang, G Griffin, JD Brown, JR Eck, MJ Liu, J Gray, NS Liu, Q AF Wu, H. Hu, C. Wang, A. Weisberg, E. L. Chen, Y. Yun, C-H Wang, W. Liu, Y. Liu, X. Tian, B. Wang, J. Zhao, Z. Liang, Y. Li, B. Wang, L. Wang, B. Chen, C. Buhrlage, S. J. Qi, Z. Zou, F. Nonami, A. Li, Y. Fernandes, S. M. Adamia, S. Stone, R. M. Galinsky, I. A. Wang, X. Yang, G. Griffin, J. D. Brown, J. R. Eck, M. J. Liu, J. Gray, N. S. Liu, Q. TI Discovery of a BTK/MNK dual inhibitor for lymphoma and leukemia SO LEUKEMIA LA English DT Article ID BRUTONS TYROSINE KINASE; MANTLE-CELL LYMPHOMA; CHRONIC LYMPHOCYTIC-LEUKEMIA; X-LINKED AGAMMAGLOBULINEMIA; ACUTE MYELOID-LEUKEMIA; CANCER-THERAPY; TARGETING BTK; IBRUTINIB; TRANSLATION; EIF4E AB Bruton's tyrosine kinase (BTK) kinase is a member of the TEC kinase family and is a key regulator of the B-cell receptor (BCR)-mediated signaling pathway. It is important for B-cell maturation, proliferation, survival and metastasis. Pharmacological inhibition of BTK is clinically effective against a variety of B-cell malignances, such as mantle cell lymphoma, chronic lymphocytic leukemia (CLL), acute myeloid leukemia (AML) and activated B-cell-diffuse large B-cell lymphoma. MNK kinase is one of the key downstream regulators in the RAF-MEK-ERK signaling pathway and controls protein synthesis via regulating the activity of eIF4E. Inhibition of MNK activity has been observed to moderately inhibit the proliferation of AML cells. Through a structure-based drug-design approach, we have discovered a selective and potent BTK/MNK dual kinase inhibitor (QL-X-138), which exhibits covalent binding to BTK and noncovalent binding to MNK. Compared with the BTK kinase inhibitor (PCI-32765) and the MNK kinase inhibitor (cercosporamide), QL-X-138 enhanced the antiproliferative efficacies in vitro against a variety of B-cell cancer cell lines, as well as AML and CLL primary patient cells, which respond moderately to BTK inhibitor in vitro. The agent can effectively arrest the growth of lymphoma and leukemia cells at the G0-G1 stage and can induce strong apoptotic cell death. These primary results demonstrate that simultaneous inhibition of BTK and MNK kinase activity might be a new therapeutic strategy for B-cell malignances. C1 [Wu, H.; Hu, C.; Wang, A.; Chen, Y.; Wang, W.; Liu, X.; Zhao, Z.; Li, B.; Wang, L.; Wang, B.; Chen, C.; Qi, Z.; Zou, F.; Liu, J.; Liu, Q.] Chinese Acad Sci, High Magnet Field Lab, 350 Shushanhu Rd,Mailbox 1110, Hefei 230031, Anhui, Peoples R China. [Wu, H.; Wang, A.; Liu, X.; Liu, Q.] Univ Sci & Technol China, Hefei 230026, Anhui, Peoples R China. [Weisberg, E. L.; Liu, Y.; Nonami, A.; Li, Y.; Fernandes, S. M.; Adamia, S.; Stone, R. M.; Galinsky, I. A.; Yang, G.; Griffin, J. D.; Brown, J. R.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, 44 Binney St, Boston, MA 02115 USA. [Yun, C-H; Wang, J.; Liang, Y.; Buhrlage, S. J.; Eck, M. J.; Gray, N. S.] Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, 250 Longwood Ave,SGM 628, Boston, MA 02115 USA. [Tian, B.] Capital Med Univ, Beijing Tongren Hosp, Beijing Ophthalmol & Visual Sci Key Lab, Beijing Tongren Eye Ctr, Beijing, Peoples R China. [Wang, X.] Tianjin Med Univ Canc Inst & Hosp, Natl Clin Res Ctr Canc, Key Lab Canc Prevent & Therapy, Dept Lymphoma SinoUS Ctr Lymphoma & Leukemia, Tianjin, Peoples R China. [Liu, Q.] Chinese Acad Sci, Hefei Sci Ctr, Hefei, Anhui, Peoples R China. RP Liu, J; Liu, Q (reprint author), Chinese Acad Sci, High Magnet Field Lab, 350 Shushanhu Rd,Mailbox 1110, Hefei 230031, Anhui, Peoples R China.; Gray, NS (reprint author), Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, 250 Longwood Ave,SGM 628, Boston, MA 02115 USA. EM jingliu@hmfl.ac.cn; Nathanael_Gray@dfci.harvard.edu; qsliu97@hmfl.ac.cn OI liu, jing/0000-0001-9513-3591 FU Chinese Academy of Sciences; Anhui Province Natural Science Foundation Annual Key Program [1301023011]; Scientific Research Grant of Hefei Science Center of CAS (SRG-HSC) [2015SRG-HSC022] FX WW, JL and QL are supported by the grant of 'Cross-disciplinary Collaborative Teams Program for Science, Technology and Innovation (2014-2016)' from Chinese Academy of Sciences. ZZ is supported by Anhui Province Natural Science Foundation Annual Key Program (grant number: 1301023011). We thank China 'Thousand Talents Program' support for QL and 'Hundred Talents Program' of The Chinese Academy of Sciences support for JL and WW. We thank Scientific Research Grant of Hefei Science Center of CAS (SRG-HSC # 2015SRG-HSC022) for supporting of QL. NR 42 TC 3 Z9 4 U1 3 U2 18 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0887-6924 EI 1476-5551 J9 LEUKEMIA JI Leukemia PD JAN PY 2016 VL 30 IS 1 BP 173 EP 181 DI 10.1038/leu.2015.180 PG 9 WC Oncology; Hematology SC Oncology; Hematology GA DC8PK UT WOS:000369481600020 PM 26165234 ER PT J AU Etchin, J Montero, J Berezovskaya, A Le, BT Kentsis, A Christie, AL Conway, AS Chen, WC Reed, C Mansour, MR Ng, CEL Adamia, S Rodig, SJ Galinsky, IA Stone, RM Klebanov, B Landesman, Y Kauffman, M Shacham, S Kung, AL Wang, JCY Letai, A Look, AT AF Etchin, J. Montero, J. Berezovskaya, A. Le, B. T. Kentsis, A. Christie, A. L. Conway, A. S. Chen, W. C. Reed, C. Mansour, M. R. Ng, C. E. L. Adamia, S. Rodig, S. J. Galinsky, I. A. Stone, R. M. Klebanov, B. Landesman, Y. Kauffman, M. Shacham, S. Kung, A. L. Wang, J. C. Y. Letai, A. Look, A. T. TI Activity of a selective inhibitor of nuclear export, selinexor (KPT-330), against AML-initiating cells engrafted into immunosuppressed NSG mice SO LEUKEMIA LA English DT Article ID ACUTE MYELOID-LEUKEMIA; STRUCTURAL BASIS; STEM-CELL; CRM1; CANCER; SIGNAL; EXPRESSION; PROGNOSIS; HIERARCHY; XPO1/CRM1 AB Currently available combination chemotherapy for acute myeloid leukemia (AML) often fails to result in long-term remissions, emphasizing the need for novel therapeutic strategies. We reasoned that targeted inhibition of a prominent nuclear exporter, XPO1/CRM1, could eradicate self-renewing leukemia-initiating cells (LICs) whose survival depends on timely XPO1-mediated transport of specific protein and RNA cargoes. Using an immunosuppressed mouse model bearing primary patient-derived AML cells, we demonstrate that selinexor (KPT-330), an oral antagonist of XPO1 that is currently in clinical trials, has strong activity against primary AML cells while sparing normal stem and progenitor cells. Importantly, limiting dilution transplantation assays showed that this cytotoxic activity is not limited to the rapidly proliferating bulk population of leukemic cells but extends to the LICs, whose inherent drug resistance and unrestricted self-renewal capacity has been implicated in the difficulty of curing AML patients with conventional chemotherapy alone. C1 [Etchin, J.; Berezovskaya, A.; Le, B. T.; Christie, A. L.; Conway, A. S.; Reed, C.; Mansour, M. R.; Ng, C. E. L.; Look, A. T.] Harvard Univ, Sch Med, Dept Pediat Oncol, Dana Farber Canc Inst, Mayer Bldg,Room 630,450 Brookline Ave, Boston, MA 02115 USA. [Etchin, J.; Berezovskaya, A.; Le, B. T.; Christie, A. L.; Conway, A. S.; Reed, C.; Mansour, M. R.; Ng, C. E. L.; Look, A. T.] Harvard Univ, Sch Med, Childrens Hosp Boston, Div Hematol Oncol, Boston, MA 02115 USA. [Etchin, J.; Look, A. T.] Childrens Hosp, Div Hematol Oncol, 300 Longwood Ave, Boston, MA 02115 USA. [Montero, J.; Adamia, S.; Galinsky, I. A.; Stone, R. M.; Letai, A.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Montero, J.; Adamia, S.; Galinsky, I. A.; Stone, R. M.; Letai, A.] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Kentsis, A.] Mem Sloan Kettering Canc Ctr, 1275 York Ave, New York, NY 10021 USA. [Chen, W. C.; Wang, J. C. Y.] Univ Hlth Network, Princess Margaret Canc Ctr, Toronto, ON, Canada. [Chen, W. C.; Wang, J. C. Y.] Univ Toronto, Dept Med, Toronto, ON, Canada. [Mansour, M. R.] UCL, UCL Canc Inst, Dept Haematol, London, England. [Rodig, S. J.] Brigham & Womens Hosp, Dept Pathol, 75 Francis St, Boston, MA 02115 USA. [Klebanov, B.; Landesman, Y.; Kauffman, M.; Shacham, S.] Karyopharm Therapeut, Natick, MA USA. [Kung, A. L.] Columbia Univ, Med Ctr, Div Pediat Hematol Oncology Stem Cell Transplanta, New York, NY USA. RP Look, AT (reprint author), Harvard Univ, Sch Med, Dept Pediat Oncol, Dana Farber Canc Inst, Mayer Bldg,Room 630,450 Brookline Ave, Boston, MA 02115 USA. EM thomas_look@dfci.harvard.edu OI Kentsis, Alex/0000-0002-8063-9191; Kung, Andrew/0000-0002-9091-488X FU William Lawrence; Blanche Hughes Foundation; Leukemia and Lymphoma Society's Translational research grant; Alex's Lemonade Stand Foundation's Young Research Investigator grant; Luck2Tuck Foundation; Claudia Adams Barr Innovative Basic Science Research grant; Lady Tata Memorial Trust FX We thank the patients for their cooperation in providing bone marrow samples for this study; Ilene Galinsky for providing the patient samples used to generate mouse PDX models of human AML; Nancy Kohl, Paul Kirschmeier and Prafulla Gokhale for assistance in guiding in vivo studies at the Lurie Family Imaging Center; John Gilbert for his editorial review and critical reading of the manuscript; and John Daley and the flow cytometry team for their valuable advice. This research was supported by William Lawrence and Blanche Hughes Foundation (to ATL), Leukemia and Lymphoma Society's Translational research grant (to ATL), Alex's Lemonade Stand Foundation's Young Research Investigator grant (to JE), Luck2Tuck Foundation (to JE), Claudia Adams Barr Innovative Basic Science Research grant (to MRM) and Lady Tata Memorial Trust (to CELN). NR 43 TC 9 Z9 9 U1 0 U2 5 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0887-6924 EI 1476-5551 J9 LEUKEMIA JI Leukemia PD JAN PY 2016 VL 30 IS 1 BP 190 EP 199 DI 10.1038/leu.2015.194 PG 10 WC Oncology; Hematology SC Oncology; Hematology GA DC8PK UT WOS:000369481600022 PM 26202935 ER PT J AU Akahane, K Sanda, T Mansour, MR Radimerski, T DeAngelo, DJ Weinstock, DM Look, AT AF Akahane, K. Sanda, T. Mansour, M. R. Radimerski, T. DeAngelo, D. J. Weinstock, D. M. Look, A. T. TI HSP90 inhibition leads to degradation of the TYK2 kinase and apoptotic cell death in T-cell acute lymphoblastic leukemia SO LEUKEMIA LA English DT Article ID BREAST-CANCER MODELS; CLINICAL DEVELOPMENT; INDUCTION FAILURE; BCL-2; HEAT-SHOCK-PROTEIN-90; RESISTANCE; PATHWAY; ABT-199; HOMEOSTASIS; MECHANISMS AB We previously found that tyrosine kinase 2 (TYK2) signaling through its downstream effector phospho-STAT1 acts to upregulate BCL2, which in turn mediates aberrant survival of T-cell acute lymphoblastic leukemia (T-ALL) cells. Here we show that pharmacologic inhibition of heat shock protein 90 (HSP90) with a small-molecule inhibitor, NVP-AUY922 (AUY922), leads to rapid degradation of TYK2 and apoptosis in T-ALL cells. STAT1 protein levels were not affected by AUY922 treatment, but phospho-STAT1 (Tyr-701) levels rapidly became undetectable, consistent with a block in signaling downstream of TYK2. BCL2 expression was downregulated after AUY922 treatment, and although this effect was necessary for AUY922-induced apoptosis, it was not sufficient because many T-ALL cell lines were resistant to ABT-199, a specific inhibitor of BCL2. Unlike ABT-199, AUY922 also upregulated the proapoptotic proteins BIM and BAD, whose increased expression was required for AUY922-induced apoptosis. Thus, the potent cytotoxicity of AUY922 involves the synergistic combination of BCL2 downregulation coupled with upregulation of the proapoptotic proteins BIM and BAD. This two-pronged assault on the mitochondrial apoptotic machinery identifies HSP90 inhibitors as promising drugs for targeting the TYK2-mediated prosurvival signaling axis in T-ALL cells. C1 [Akahane, K.; Sanda, T.; Mansour, M. R.; Look, A. T.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Pediat Oncol, 450 Brookline Ave,Mayer 630, Boston, MA 02115 USA. [Sanda, T.] Natl Univ Singapore, Canc Sci Inst Singapore, Singapore 117548, Singapore. [Sanda, T.] Natl Univ Singapore, Yong Loo Lin Sch Med, Dept Med, Singapore 117548, Singapore. [Mansour, M. R.] UCL, UCL Canc Inst, Dept Haematol, London, England. [Radimerski, T.] Novartis Inst BioMed Res, Dis Area Oncol, Basel, Switzerland. [DeAngelo, D. J.; Weinstock, D. M.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Look, A. T.] Childrens Hosp, Div Hematol Oncol, 300 Longwood Ave, Boston, MA 02115 USA. RP Look, AT (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Pediat Oncol, 450 Brookline Ave,Mayer 630, Boston, MA 02115 USA. EM thomas_look@dfci.harvard.edu OI Sanda, Takaomi/0000-0003-1621-4954 FU Leukemia & Lymphoma Society [CDP5014-14]; Lauri Strauss Leukemia Foundation; NPO Corporation the Gold Ribbon Network of the Japan; Alex's Lemonade Stand Foundation; National Cancer Institute [5R01CA176746, 5P01CA109901]; Claudia Adams Barr Innovative Basic Science Research Program; Kay Kendall Leukaemia Trust of the UK; National Research Foundation, Prime Minister's Office, Singapore under its NRF Fellowship Programme [NRF-NRFF2013-02]; Leukemia & Lymphoma Society FX We thank Dr Anthony Letai for helpful discussions and critical review. We also thank John R Gilbert for critical review of the manuscript and editorial suggestions, and Drs Julia Etchin and Cherry Ng-Dombrowsky for helpful advice and assistance. This research was supported by fellowships and grants from the Leukemia & Lymphoma Society (CDP5014-14; KA), the Lauri Strauss Leukemia Foundation (2013 Discovery research grant; KA) and NPO Corporation the Gold Ribbon Network of the Japan (KA), Bridge grant from Alex's Lemonade Stand Foundation, and grants from the National Cancer Institute (5R01CA176746 and 5P01CA109901) (ATL). MRM is funded by the Claudia Adams Barr Innovative Basic Science Research Program and the Kay Kendall Leukaemia Trust of the UK. TS is supported by a grant from the National Research Foundation, Prime Minister's Office, Singapore under its NRF Fellowship Programme (Award No. NRF-NRFF2013-02). DMW is supported by a Translational Research Program award from the Leukemia & Lymphoma Society. We also thank Novartis for the compound NVP-AUY922. NR 35 TC 3 Z9 3 U1 1 U2 3 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0887-6924 EI 1476-5551 J9 LEUKEMIA JI Leukemia PD JAN PY 2016 VL 30 IS 1 BP 219 EP 228 DI 10.1038/leu.2015.222 PG 10 WC Oncology; Hematology SC Oncology; Hematology GA DC8PK UT WOS:000369481600025 PM 26265185 ER PT J AU Gettinger, SN Bazhenova, LA Salgia, R Langer, CJ Gold, K Rosell, R Shaw, AT Weiss, GJ Dorer, DJ Rivera, VM Kerstein, D Camidge, DR AF Gettinger, S. N. Bazhenova, L. A. Salgia, R. Langer, C. J. Gold, K. Rosell, R. Shaw, A. T. Weiss, G. J. Dorer, D. J. Rivera, V. M. Kerstein, D. Camidge, D. R. TI Efficacy and safety of brigatinib (AP26113) in ALK+ NSCLC: phase 1/2 trial results SO LUNG CANCER LA English DT Meeting Abstract C1 [Gettinger, S. N.] Yale Canc Ctr, Med Oncol, New Haven, CT USA. [Bazhenova, L. A.] Univ Calif San Diego, Moores Canc Ctr, Med Oncol, La Jolla, CA 92093 USA. [Salgia, R.] Univ Chicago Med, Biomed Sci, Chicago, IL USA. [Langer, C. J.] Univ Penn, Abramson Canc Ctr, Thorac Oncol, Philadelphia, PA 19104 USA. [Gold, K.] Univ Texas MD Anderson Canc Ctr, Thorac Head & Neck Med Oncol, Houston, TX 77030 USA. [Rosell, R.] Catalan Inst Oncol, Med Oncol, Barcelona, Spain. [Shaw, A. T.] Massachusetts Gen Hosp, Dept Med, Ctr Canc, Boston, MA 02114 USA. [Weiss, G. J.] Canc Treatment Ctr Amer, Western Reg Med Ctr, Goodyear, AZ USA. [Dorer, D. J.] ARIAD Pharmaceut Inc, Biostat, Cambridge, MA 02139 USA. [Rivera, V. M.] ARIAD Pharmaceut Inc, Preclin & Translat Res, Cambridge, MA 02139 USA. [Kerstein, D.] ARIAD Pharmaceut Inc, Clin Res, Cambridge, MA 02139 USA. [Camidge, D. R.] Univ Colorado, Ctr Canc, Med Oncol, Aurora, CO USA. NR 0 TC 0 Z9 0 U1 7 U2 8 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 2016 VL 91 SU 1 MA 56 BP S20 EP S21 PG 2 WC Oncology; Respiratory System SC Oncology; Respiratory System GA DC8GP UT WOS:000369458200056 ER PT J AU Chahine, LM Weintraub, D Hawkins, KA Siderowf, A Eberly, S Oakes, D Seibyl, J Stern, MB Marek, K Jennings, D AF Chahine, Lama M. Weintraub, Daniel Hawkins, Keith A. Siderowf, Andrew Eberly, Shirley Oakes, David Seibyl, John Stern, Matthew B. Marek, Kenneth Jennings, Danna CA PARS Investigators TI Cognition in individuals at risk for Parkinson's: Parkinson associated risk syndrome (PARS) study findings SO MOVEMENT DISORDERS LA English DT Article DE Parkinson's; cognition; prodromal; dopaminergic deficit; hyposmia ID SLEEP BEHAVIOR DISORDER; EXECUTIVE DYSFUNCTION; DOPAMINE TRANSPORTERS; PRODROMAL FEATURES; DISEASE; DEPRESSION; IMPAIRMENT; CARE AB ObjectivesThe Parkinson Associated Risk Syndrome Study identified a cohort of healthy adults with hyposmia and dopamine transporter binding reduction to characterize individuals at risk for Parkinson's disease (PD). We describe the cognitive profile of this cohort. MethodsIndividuals older than 50 y without PD were recruited. Two hundred twenty-five completed cognitive testing and were included in the final analysis. A neuropsychological test battery was administered and normative scores created for global cognition, memory, executive function/working memory, processing speed/attention, visuospatial abilities, and language domains. Other non-motor symptoms (constipation, depression, anxiety, and rapid eye movement sleep behavior disorder) were assessed through questionnaires. ResultsIndividuals with both hyposmia and reduced dopamine transporter binding (n=38) had lower mean scores for global cognition, executive function/working memory, and memory compared with all other participants (n=187). In separate multivariate logistic regression models, lower global cognition (odds ratio, 1.97, P=0.004), and specifically executive function/working memory (odds ratio, 1.84, P=0.004) scores were associated with membership in the hyposmia with dopamine transporter reduction group. Combining hyposmia with relative impairment on specific cognitive domains increased the odds of dopamine transporter binding reduction compared with hyposmia alone, with the greatest increase in odds for hyposmia plus executive function/working memory relative impairment (68% increase in odds from 4.14 to 6.96). ConclusionChanges in global cognitive abilities, and specifically executive function/working memory, are present in individuals at risk for PD. Combining non-motor features, including cognition, improves prediction of dopamine transporter binding reduction. (c) 2015 International Parkinson and Movement Disorder Society C1 [Chahine, Lama M.; Weintraub, Daniel; Stern, Matthew B.] Univ Penn, Dept Neurol, Perelman Sch Med, Philadelphia, PA 19104 USA. [Weintraub, Daniel] Univ Penn, Dept Psychiat, Perelman Sch Med, Philadelphia, PA 19104 USA. [Weintraub, Daniel] Philadelphia Vet Affairs Med Ctr, Educ & Clin Ctr, PD Res, Philadelphia, PA USA. [Hawkins, Keith A.] Yale Univ, Sch Med, Dept Psychiat, New Haven, CT USA. [Siderowf, Andrew] Avid Radiopharmaceut, Philadelphia, PA USA. [Eberly, Shirley; Oakes, David] Univ Rochester, Sch Med, Dept Biostat, Rochester, NY USA. [Seibyl, John; Marek, Kenneth; Jennings, Danna] Inst Neurodegenerat Disorders, New Haven, CT USA. RP Weintraub, D (reprint author), 3615 Chestnut St,330, Philadelphia, PA 19104 USA. EM Daniel.Weintraub@uphs.upenn.edu FU Department of Defense [W81XWH-06-067] FX Support for this study is provided by the Department of Defense award number W81XWH-06-067 NR 43 TC 13 Z9 13 U1 2 U2 10 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0885-3185 EI 1531-8257 J9 MOVEMENT DISORD JI Mov. Disord. PD JAN PY 2016 VL 31 IS 1 BP 86 EP 94 DI 10.1002/mds.26373 PG 9 WC Clinical Neurology SC Neurosciences & Neurology GA DC7WL UT WOS:000369431300017 PM 26293177 ER PT J AU Mata, IF Leverenz, JB Weintraub, D Trojanowski, JQ Chen-Plotkin, A Van Deerlin, VM Ritz, B Rausch, R Factor, SA Wood-Siverio, C Quinn, JF Chung, KA Peterson-Hiller, AL Goldman, JG Stebbins, GT Bernard, B Espay, AJ Revilla, FJ Devoto, J Rosenthal, LS Dawson, TM Albert, MS Tsuang, D Huston, H Yearout, D Hu, SC Cholerton, BA Montine, TJ Edwards, KL Zabetian, CP AF Mata, Ignacio F. Leverenz, James B. Weintraub, Daniel Trojanowski, John Q. Chen-Plotkin, Alice Van Deerlin, Vivianna M. Ritz, Beate Rausch, Rebecca Factor, Stewart A. Wood-Siverio, Cathy Quinn, Joseph F. Chung, Kathryn A. Peterson-Hiller, Amie L. Goldman, Jennifer G. Stebbins, Glenn T. Bernard, Bryan Espay, Alberto J. Revilla, Fredy J. Devoto, Johnna Rosenthal, Liana S. Dawson, Ted M. Albert, Marilyn S. Tsuang, Debby Huston, Haley Yearout, Dora Hu, Shu-Ching Cholerton, Brenna A. Montine, Thomas J. Edwards, Karen L. Zabetian, Cyrus P. TI GBA Variants are associated with a distinct pattern of cognitive deficits in Parkinson's disease SO MOVEMENT DISORDERS LA English DT Article DE cognition; GBA; neuropsychological tests; visuospatial; working memory ID APOLIPOPROTEIN-E GENOTYPE; GAUCHER-DISEASE; GLUCOCEREBROSIDASE MUTATIONS; DEMENTIA; RISK; PERFORMANCE; IMPAIRMENT; INCIDENT; ONSET; GENE AB BackgroundLoss-of-function mutations in the GBA gene are associated with more severe cognitive impairment in PD, but the nature of these deficits is not well understood and whether common GBA polymorphisms influence cognitive performance in PD is not yet known. MethodsWe screened the GBA coding region for mutations and the E326K polymorphism in 1,369 PD patients enrolled at eight sites from the PD Cognitive Genetics Consortium. Participants underwent assessments of learning and memory (Hopkins Verbal Learning Test-Revised), working memory/executive function (Letter-Number Sequencing Test and Trail Making Test A and B), language processing (semantic and phonemic verbal fluency), visuospatial abilities (Benton Judgment of Line Orientation), and global cognitive function (MoCA). We used linear regression to test for association between genotype and cognitive performance with adjustment for important covariates and accounted for multiple testing using Bonferroni's corrections. ResultsMutation carriers (n=60; 4.4%) and E326K carriers (n=65; 4.7%) had a higher prevalence of dementia (mutations, odds ratio=5.1; P=9.7x10(-6); E326K, odds ratio=6.4; P=5.7x10(-7)) and lower performance on Letter-Number Sequencing (mutations, corrected P[P-c]=9.0x10(-4); E326K, P-c=0.036), Trail Making B-A (mutations, P-c=0.018; E326K, P-c=0.018), and Benton Judgment of Line Orientation (mutations, P-c=0.0045; E326K, P-c=0.0013). ConclusionsBoth GBA mutations and E326K are associated with a distinct cognitive profile characterized by greater impairment in working memory/executive function and visuospatial abilities in PD patients. The discovery that E326K negatively impacts cognitive performance approximately doubles the proportion of PD patients we now recognize are at risk for more severe GBA-related cognitive deficits. (c) 2015 International Parkinson and Movement Disorder Society C1 [Mata, Ignacio F.; Tsuang, Debby; Huston, Haley; Yearout, Dora; Hu, Shu-Ching; Cholerton, Brenna A.; Zabetian, Cyrus P.] Vet Affairs Puget Sound Hlth Care Syst, Seattle, WA USA. [Mata, Ignacio F.; Huston, Haley; Yearout, Dora; Hu, Shu-Ching; Zabetian, Cyrus P.] Univ Washington, Sch Med, Dept Neurol, Seattle, WA USA. [Leverenz, James B.] Cleveland Clin, Lou Ruvo Ctr Brain Hlth, Neurol Inst, Cleveland, OH 44106 USA. [Weintraub, Daniel; Chen-Plotkin, Alice] Univ Penn, Dept Neurol, Philadelphia, PA 19104 USA. [Weintraub, Daniel] Univ Penn, Dept Psychiat, Philadelphia, PA 19104 USA. [Weintraub, Daniel] Philadelphia Vet Affairs Med Ctr, Philadelphia, PA USA. [Trojanowski, John Q.; Van Deerlin, Vivianna M.] Univ Penn, Dept Pathol & Lab Med, Philadelphia, PA USA. [Trojanowski, John Q.] Univ Penn, Inst Aging, Philadelphia, PA 19104 USA. [Ritz, Beate] Univ Calif Los Angeles, Sch Publ Hlth, Dept Epidemiol, Los Angeles, CA 90024 USA. [Ritz, Beate] Univ Calif Los Angeles, Sch Publ Hlth, Dept Environm Hlth Sci, Los Angeles, CA 90024 USA. [Ritz, Beate; Rausch, Rebecca] Univ Calif Los Angeles, Dept Neurol, Los Angeles, CA 90024 USA. [Factor, Stewart A.; Wood-Siverio, Cathy] Emory Univ, Sch Med, Dept Neurol, Atlanta, GA 30322 USA. [Quinn, Joseph F.; Chung, Kathryn A.; Peterson-Hiller, Amie L.] Portland VA Med Ctr, Portland, OR USA. [Quinn, Joseph F.; Chung, Kathryn A.; Peterson-Hiller, Amie L.] Oregon Hlth & Sci Univ, Dept Neurol, Portland, OR 97201 USA. [Goldman, Jennifer G.; Stebbins, Glenn T.; Bernard, Bryan] Rush Univ, Med Ctr, Dept Neurol Sci, Chicago, IL 60612 USA. [Espay, Alberto J.; Revilla, Fredy J.; Devoto, Johnna] Univ Cincinnati, Dept Neurol & Rehabil Med, Cincinnati, OH USA. [Revilla, Fredy J.] Cincinnati Vet Affairs Med Ctr, Cincinnati, OH USA. [Rosenthal, Liana S.; Dawson, Ted M.; Albert, Marilyn S.] Johns Hopkins Univ, Sch Med, Dept Neurol, Baltimore, MD 21205 USA. [Dawson, Ted M.] Johns Hopkins Univ, Sch Med, Inst Cell Engn, Neuroregenerat & Stem Cell Programs, Baltimore, MD USA. [Dawson, Ted M.] Johns Hopkins Univ, Sch Med, Solomon H Snyder Dept Neurosci, Baltimore, MD USA. [Dawson, Ted M.] Johns Hopkins Univ, Sch Med, Dept Pharmacol & Mol Sci, Baltimore, MD 21205 USA. [Tsuang, Debby; Cholerton, Brenna A.] Univ Washington, Sch Med, Dept Psychiat & Behav Sci, Seattle, WA 98195 USA. [Montine, Thomas J.] Univ Washington, Sch Med, Dept Pathol, Seattle, WA 98195 USA. [Edwards, Karen L.] Univ Calif Irvine, Sch Med, Dept Epidemiol, Irvine, CA 92717 USA. RP Zabetian, CP (reprint author), VA Puget Sound Hlth Care Syst, GRECC S-182,1660 South Columbian Way, Seattle, WA 98108 USA. EM zabetian@u.washington.edu RI Tsuang, Debby/L-7234-2016 OI Tsuang, Debby/0000-0002-4716-1894 FU National Institutes of Health [K23 NS060949, P01 AG017586, P01 ES016732, P30 AG010124, P50 AG005136, P50 NS038367, P50 NS038377, P50 NS053488, P50 NS062684, R01 ES010544, R01 NS065070, U01 NS082133, U54 ES012078]; Department of Veterans Affairs [1I01BX000531]; Consolidated Anti-Aging Foundation; Dolsen Foundation; Jane and Lee Seidman Fund; Nancy and Buster Alvord Endowment; Parkinson's Disease Foundation; Sartain Lanier Family Foundation; Office of Research and Development Medical Research Service, Department of Veterans Affairs FX This work was supported by grants from the National Institutes of Health (K23 NS060949, P01 AG017586, P01 ES016732, P30 AG010124, P50 AG005136, P50 NS038367, P50 NS038377, P50 NS053488, P50 NS062684, R01 ES010544, R01 NS065070, U01 NS082133, and U54 ES012078), the Department of Veterans Affairs (1I01BX000531), the Consolidated Anti-Aging Foundation, the Dolsen Foundation, the Jane and Lee Seidman Fund, the Nancy and Buster Alvord Endowment, the Parkinson's Disease Foundation, and the Sartain Lanier Family Foundation. This material is based upon work supported, in part, by the Office of Research and Development Medical Research Service, Department of Veterans Affairs. NR 41 TC 16 Z9 16 U1 0 U2 12 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0885-3185 EI 1531-8257 J9 MOVEMENT DISORD JI Mov. Disord. PD JAN PY 2016 VL 31 IS 1 BP 95 EP 102 DI 10.1002/mds.26359 PG 8 WC Clinical Neurology SC Neurosciences & Neurology GA DC7WL UT WOS:000369431300018 PM 26296077 ER PT J AU Brennan, L Siderowf, A Rubright, JD Rick, J Dahodwala, N Duda, JE Hurtig, H Stern, M Xie, SX Rennert, L Karlawish, J Shea, JA Trojanowski, JQ Weintraub, D AF Brennan, Laura Siderowf, Andrew Rubright, Jonathan D. Rick, Jacqueline Dahodwala, Nabila Duda, John E. Hurtig, Howard Stern, Matthew Xie, Sharon X. Rennert, Lior Karlawish, Jason Shea, Judy A. Trojanowski, John Q. Weintraub, Daniel TI Development and initial testing of the Penn Parkinson's Daily Activities Questionnaire SO MOVEMENT DISORDERS LA English DT Article DE Parkinson's disease; instrumental activities of daily living; cognition; item response theory ID MILD COGNITIVE IMPAIRMENT; SOCIETY TASK-FORCE; INSTRUMENTAL ACTIVITIES; ALZHEIMERS-DISEASE; RATING-SCALE; DEMENTIA; RIVASTIGMINE; AGREEMENT; PATIENT AB ObjectiveThe aim of this work was to describe the development and psychometric analysis of the Penn Parkinson's Daily Activities Questionnaire. The questionnaire is an item response theory-based tool for rating cognitive instrumental activities of daily living in PD. MethodsCandidate items for the Penn Parkinson's Daily Activities Questionnaire were developed through literature review and focus groups of patients and knowledgeable informants. Item selection and calibration of item-response theory parameters were performed using responses from a cohort of PD patients and knowledgeable informants (n = 388). In independent cohorts of PD patients and knowledgeable informants, assessments of test-retest reliability (n = 50), and construct validity (n = 68) of the questionnaire were subsequently performed. Construct validity was assessed by correlating questionnaire scores with measures of motor function, cognition, an existing activities of daily living measure, and directly observed daily function. ResultsFifty items were retained in the final questionnaire item bank. Items were excluded owing to redundancy, difficult reading level, and when item-response theory parameters could not be calculated. Test-retest reliability was high (intraclass correlation coefficient = 0.97; P < 0.001). The questionnaire correlated strongly with cognition (r = 0.68; P < 0.001) and directly observed daily function (r = 0.87; P < 0.001), but not with motor impairment (r = 0.08; P = 0.53). The questionnaire score accurately discriminated between PD patients with and without dementia (receiver operating characteristic curve = 0.91; 95% confidence interval: 0.85-0.97). ConclusionsThe Penn Parkinson's Daily Activities Questionnaire shows strong evidence of reliability and validity. Item response theory-based psychometric analysis suggests that this questionnaire can discriminate across a range of daily functions. (c) 2015 International Parkinson and Movement Disorder Society C1 [Brennan, Laura; Weintraub, Daniel] Univ Penn, Sch Med, Dept Psychiat, 3615 Chestnut St,330, Philadelphia, PA 19104 USA. [Brennan, Laura; Duda, John E.; Weintraub, Daniel] Philadelphia Vet Affairs Med Ctr, Philadelphia, PA USA. [Siderowf, Andrew] Avid Radiopharmaceut, Philadelphia, PA USA. [Rubright, Jonathan D.] Amer Inst Certified Publ Accountants, Ewing, NJ USA. [Rick, Jacqueline; Dahodwala, Nabila; Duda, John E.; Hurtig, Howard; Stern, Matthew; Trojanowski, John Q.; Weintraub, Daniel] Univ Penn, Sch Med, Dept Neurol, Philadelphia, PA 19104 USA. [Xie, Sharon X.; Rennert, Lior] Univ Penn, Sch Med, Dept Biostat & Epidemiol, Philadelphia, PA 19104 USA. [Karlawish, Jason] Univ Penn, Sch Med, PENN CMU Roybal Ctr Behav Econ & Hlth, LDI Ctr Hlth Incent,Dept Med Eth, Philadelphia, PA 19104 USA. [Karlawish, Jason] Univ Penn, Sch Med, PENN CMU Roybal Ctr Behav Econ & Hlth, Dept Med,LDI Ctr Hlth Incent, Philadelphia, PA 19104 USA. [Karlawish, Jason] Univ Penn, Sch Med, Alzheimers Dis Ctr, Philadelphia, PA 19104 USA. [Shea, Judy A.] Univ Penn, Sch Med, Dept Med, Philadelphia, PA 19104 USA. RP Weintraub, D (reprint author), Univ Penn, Sch Med, Dept Psychiat, 3615 Chestnut St,330, Philadelphia, PA 19104 USA. EM daniel.weintraub@uphs.upenn.edu FU Morris K. Udall Parkinson's Disease Research Center of Excellence grant from the National Institute of Neurological Disorders and Stroke [NS-053488]; Department of Health of the Commonwealth of Pennsylvania from the Tobacco Master Settlement Agreement [SAP4100027296, Act 2001-77] FX This study was funded by a Morris K. Udall Parkinson's Disease Research Center of Excellence grant from the National Institute of Neurological Disorders and Stroke (NS-053488) and by SAP4100027296, a health research grant awarded by the Department of Health of the Commonwealth of Pennsylvania from the Tobacco Master Settlement Agreement under Act 2001-77. NR 36 TC 2 Z9 2 U1 3 U2 4 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0885-3185 EI 1531-8257 J9 MOVEMENT DISORD JI Mov. Disord. PD JAN PY 2016 VL 31 IS 1 BP 126 EP 134 DI 10.1002/mds.26339 PG 9 WC Clinical Neurology SC Neurosciences & Neurology GA DC7WL UT WOS:000369431300022 PM 26249849 ER PT J AU Clark, MA Gorelick, JJ Sicks, JD Park, ER Graham, AL Abrams, DB Gareen, IF AF Clark, Melissa A. Gorelick, Jeremy J. Sicks, JoRean D. Park, Elyse R. Graham, Amanda L. Abrams, David B. Gareen, Ilana F. TI The Relations Between False Positive and Negative Screens and Smoking Cessation and Relapse in the National Lung Screening Trial: Implications for Public Health SO NICOTINE & TOBACCO RESEARCH LA English DT Article ID COMPUTED-TOMOGRAPHY SCANS; UNITED-STATES; TEACHABLE MOMENT; FOLLOW-UP; CANCER; ABSTINENCE; DIAGNOSIS; SMOKERS; PARTICIPANTS; GUIDELINES AB Introduction: Lung screening is an opportunity for smoking cessation and relapse prevention, but smoking behaviors may differ across screening results. Changes in smoking were evaluated among 18 840 current and former smokers aged 55-74 scheduled to receive three annual lung screenings. Methods: Participants were randomized to low-dose computed tomography or single-view chest radiography in the American College of Radiology/National Lung Screening Trial. Outcome measures included point and sustained (6-month) abstinence and motivation to quit among smokers; and relapse among smokers who quit during follow-up, recent quitters (quit < 6 months), and long-term former smokers (quit >= 6 months). Results: During five years of follow-up, annual point prevalence quit rates ranged from 11.6%-13.4%; 48% of current smokers reported a quit attempt and 7% of long-term former smokers relapsed. Any false positive screening result was associated with subsequent increased point (multivariable hazard ratio HR = 1.23, 95% CI = 1.13, 1.35) and sustained (HR = 1.28, 95% CI = 1.15, 1.43) abstinence among smokers. Recent quitters with >= 1 false positive screen were less likely to relapse (HR = 0.72, 95% CI = 0.54, 0.96). Screening result was not associated with relapse among long-term former smokers or among baseline smokers who quit during follow-up. Conclusions: A false positive screen was associated with increased smoking cessation and less relapse among recent quitters. Consistently negative screens were not associated with greater relapse among long-term former smokers. Given the Affordable Care Act requires most health plans to cover smoking cessation and lung screening, the impact and cost-effectiveness of lung screening could be further enhanced with the addition of smoking cessation interventions. C1 [Clark, Melissa A.; Gareen, Ilana F.] Brown Univ, Sch Publ Hlth, Dept Epidemiol, Box G-121-6, Providence, RI 02912 USA. [Clark, Melissa A.] Brown Univ, Ctr Populat Hlth & Clin Epidemiol, Providence, RI 02912 USA. [Gorelick, Jeremy J.; Sicks, JoRean D.; Gareen, Ilana F.] Brown Univ, Sch Publ Hlth, Ctr Stat Sci, Providence, RI 02912 USA. [Park, Elyse R.] Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA. [Park, Elyse R.] Harvard Univ, Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA. [Park, Elyse R.] Harvard Univ, Massachusetts Gen Hosp, Mongan Inst Hlth Policy, Boston, MA USA. [Graham, Amanda L.; Abrams, David B.] Amer Legacy Fdn, Schroeder Inst Tobacco Res & Policy Studies, Washington, DC USA. [Graham, Amanda L.; Abrams, David B.] Georgetown Univ, Med Ctr, Canc Control Program, Dept Oncol,Lombardi Comprehens Canc Ctr, Washington, DC 20007 USA. [Abrams, David B.] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Hlth Behav & Soc, Baltimore, MD USA. RP Clark, MA (reprint author), Brown Univ, Sch Publ Hlth, Dept Epidemiol, Box G-121-6, Providence, RI 02912 USA. EM Melissa_Clark@brown.edu FU Cancer Imaging Program, Division of Cancer Treatment and Diagnosis [U01-CA-80098, U01-CA-79778] FX The American College of Radiology Imaging Network component of the National Lung Screening Trial (NLST) was funded through grants (U01-CA-80098 and U01-CA-79778) under a cooperative agreement with the Cancer Imaging Program, Division of Cancer Treatment and Diagnosis. The funders had no role in the analysis and interpretation of the data; or the preparation, review, or approval of the manuscript. Trial Registration: National Lung Screening Trial http://ClinicalTrials.gov number, NCT00047385. NR 39 TC 3 Z9 3 U1 1 U2 3 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1462-2203 EI 1469-994X J9 NICOTINE TOB RES JI Nicotine Tob. Res. PD JAN PY 2016 VL 18 IS 1 BP 17 EP 24 DI 10.1093/ntr/ntv037 PG 8 WC Substance Abuse; Public, Environmental & Occupational Health SC Substance Abuse; Public, Environmental & Occupational Health GA DC9HY UT WOS:000369533300004 PM 25746779 ER PT J AU Regan, S Reid, ZZ Kelley, JHK Reyen, M Korotkin, M Japuntich, SJ Viana, JC Levy, DE Rigotti, NA AF Regan, Susan Reid, Zachary Z. Kelley, Jennifer H. K. Reyen, Michele Korotkin, Molly Japuntich, Sandra J. Viana, Joseph C. Levy, Douglas E. Rigotti, Nancy A. TI Smoking Status Confirmation by Proxy: Validation in a Smoking Cessation Trial SO NICOTINE & TOBACCO RESEARCH LA English DT Article ID RANDOMIZED-TRIAL; HOSPITALIZED SMOKERS; SELF-REPORT; RELIABILITY; PREVALENCE AB Introduction: Biochemical confirmation (BC) of self-report is the gold standard of evidence for abstinence in smoking cessation research, but difficulty in obtaining samples may bias estimates of quit rates. Proxy confirmation (PC) has not been validated in cessation trials. We assessed the feasibility and validity of PC in a cessation trial for hospitalized smokers. Methods: We enrolled 402 daily cigarette smokers during a hospital admission. At enrollment, participants provided demographics, smoking history, and named proxies to confirm their smoking status at follow-up. Participants provided self-reported (SR) 7-day tobacco abstinence by telephone at 6 months post-discharge. SR quitters were asked to mail a saliva sample for BC. Incentives were offered for survey completion ($ 20) and returned samples ($ 50). We called proxies for all those with SR to obtain PC. Quit rates were calculated with missing data indicating smoking. We assessed associations of nonresponse with baseline characteristics using chi-squared tests and logistic regression. We calculated the sensitivity and specificity of PC in detecting smokers as determined by BC. Results: All patients named at least one proxy. Response rates were 82% for SR, 84% for PC, and 69% for BC. Observed participant characteristics were unrelated to provision of sample for BC. Estimated quit rates were 35% for SR, 27% for SR + PC, 21% for SR + BC and 27% for SR + BC or PC. Sensitivity of PC was not higher than SR (73% vs. 77%); specificity was lower (84% vs. 100%). Conclusion: PC was feasible but not superior to self-report in a cessation trial. C1 [Regan, Susan; Reid, Zachary Z.; Kelley, Jennifer H. K.; Reyen, Michele; Korotkin, Molly; Japuntich, Sandra J.; Viana, Joseph C.; Levy, Douglas E.; Rigotti, Nancy A.] Massachusetts Gen Hosp, Tobacco Res & Treatment Ctr, Boston, MA 02114 USA. [Regan, Susan; Levy, Douglas E.; Rigotti, Nancy A.] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. [Kelley, Jennifer H. K.; Korotkin, Molly; Levy, Douglas E.; Rigotti, Nancy A.] Massachusetts Gen Hosp, Mongan Inst Hlth Policy, Boston, MA 02114 USA. [Japuntich, Sandra J.] VA Boston Healthcare Syst, Natl Ctr PTSD, Boston, MA USA. [Viana, Joseph C.] Univ Calif Los Angeles, Dept Hlth Policy & Management, Los Angeles, CA USA. RP Regan, S (reprint author), Massachusetts Gen Hosp, Div Gen Internal Med, 50 Staniford St,9th Floor, Boston, MA 02114 USA. EM sregan@partners.org FU National Institutes of Health/National Heart, Lung, and Blood Institute [RC1 HL099668, K24 HL004440]; US Department of Veterans Affairs Clinical Sciences Research and Development Service career development award [1IK2CX000918-01A1] FX This work was supported by the National Institutes of Health/National Heart, Lung, and Blood Institute (RC1 HL099668 and K24 HL004440). SJJ's time was supported in part by the US Department of Veterans Affairs Clinical Sciences Research and Development Service career development award (1IK2CX000918-01A1). 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 15 TC 2 Z9 2 U1 1 U2 1 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1462-2203 EI 1469-994X J9 NICOTINE TOB RES JI Nicotine Tob. Res. PD JAN PY 2016 VL 18 IS 1 BP 34 EP 40 DI 10.1093/ntr/ntv073 PG 7 WC Substance Abuse; Public, Environmental & Occupational Health SC Substance Abuse; Public, Environmental & Occupational Health GA DC9HY UT WOS:000369533300006 PM 25847290 ER PT J AU Ganapati, S Zavalij, PY Eikermann, M Isaacs, L AF Ganapati, Shweta Zavalij, Peter Y. Eikermann, Matthias Isaacs, Lyle TI In Vitro selectivity of an acyclic cucurbit[n]uril molecular container towards neuromuscular blocking agents relative to commonly used drugs SO ORGANIC & BIOMOLECULAR CHEMISTRY LA English DT Article ID BIOCHEMICAL PATHWAYS; AQUEOUS-SOLUTION; DRIVING-FORCE; ROCURONIUM; REVERSAL; CUCURBITURIL; SUGAMMADEX; COMPLEXES; AFFINITY; BINDING AB An acyclic cucurbit[n] uril (CB[n]) based molecular container (2, a. k. a. Calabadion 2) binds to both amino-steroidal and benzylisoquinolinium type neuromuscular blocking agents (NMBAs) in vitro, and reverses the effect of these drugs in vivo displaying faster recovery times than placebo and the.-cyclodextrin (CD) based and clinically used reversal agent Sugammadex. In this study we have assessed the potential for other drugs commonly used during and after surgery (e.g. antibiotics, antihistamines, and antiarrhythmics) to interfere with the ability of 2 to bind NMBAs rocuronium and cisatracurium in vitro. We measured the binding affinities (K-a, M-1) of twenty seven commonly used drugs towards 2 and simulated the equilibrium between 2, NMBA, and drug based on their standard clinical dosages to calculate the equilibrium concentration of 2 . NMBA in the presence of the various drugs. We found that none of the 27 drugs studied possess the combination of a high enough binding affinity with 2 and a high enough standard dosage to be able to promote the competitive dissociation (a. k. a. displacement interactions) of the 2 . NMBA complex with the formation of the 2 . drug complex. Finally, we used the simulations to explore how the potential for displacement interactions is affected by a number of factors including the K-a of the 2 . NMBA complex, the K-a of the AChR . NMBA complex, the K-a of the 2 . drug complex, and the dosage of the drug. C1 [Ganapati, Shweta; Zavalij, Peter Y.; Isaacs, Lyle] Univ Maryland, Dept Chem & Biochem, College Pk, MD 20742 USA. [Eikermann, Matthias] Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, Boston, MA 02114 USA. [Eikermann, Matthias] Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Isaacs, L (reprint author), Univ Maryland, Dept Chem & Biochem, College Pk, MD 20742 USA.; Eikermann, M (reprint author), Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, Boston, MA 02114 USA.; Eikermann, M (reprint author), Harvard Univ, Sch Med, Boston, MA 02115 USA. EM meikermann@partners.org; lisaacs@umd.edu RI Zavalij, Peter/H-3817-2012; Isaacs, Lyle/B-4472-2009 OI Zavalij, Peter/0000-0001-5762-3469; Isaacs, Lyle/0000-0002-4079-332X FU Maryland Technology Development Corporation; National Institutes of Health [CA168365]; Department of Anesthesia, Critical Care, and Pain Medicine; University of Maryland FX L. I. thanks the Maryland Technology Development Corporation and the National Institutes of Health (CA168365 to L. I.) for financial support. M. E. thanks the Department of Anesthesia, Critical Care, and Pain Medicine financial support. S. G. thanks the University of Maryland for the Gary and Sue Christian Graduate Award. NR 58 TC 0 Z9 0 U1 5 U2 17 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 2016 VL 14 IS 4 BP 1277 EP 1287 DI 10.1039/c5ob02356d PG 11 WC Chemistry, Organic SC Chemistry GA DD0ER UT WOS:000369593700016 PM 26648135 ER PT J AU Manchikanti, L Hammer, MJ Boswell, MV Kaye, AD Hirsch, JA AF Manchikanti, Laxmaiah Hammer, Marvel J. Boswell, Mark V. Kaye, Alan D. Hirsch, Joshua A. TI A Seamless Navigation to ICD-10-CM for Interventional Pain Physicians: Is a Rude Awakening Avoidable? SO PAIN PHYSICIAN LA English DT Review DE ICD-9-CM (International Classification of Diseases, Ninth revision, Clinical Modification); ICD-10; ICD-10-CM (International Classification of Diseases, 10th Revision); Health Insurance Portability and Accountability Act (HIPAA); Health Information Technology (HIT) ID CHRONIC SPINAL PAIN; EPIDURAL CORTICOSTEROID INJECTIONS; SUSTAINABLE GROWTH-RATE; LONG-TERM RELIEF; DIAGNOSTIC-ACCURACY; JOINT INTERVENTIONS; UNITED-STATES; STICK POLICY; DOUBLE-BLIND; METAANALYSIS AB Since October 1, 2015, the International Classification of Diseases, 10th Revision, Clinical Modification (ICD-10-CM) was integrated into U.S. medical practices. This monumental transition seemingly occurred rather unceremoniously, despite significant opposition and reservations having been expressed by the provider community. In prior publications, we have described various survival strategies for interventional pain physicians. The regulators and beneficiaries of system - CMS, consultants, and health information technology industry are congratulating themselves for a job well done. Nonetheless, this transition comes at an immeasurable financial and psychological drain on providers. However, a rude awakening may be making its way with expiration of initial concessions from government and private payers. This manuscript provides a template for interventional pain management professionals with multiple steps for seamless navigation, including descriptions of the most commonly used codes, navigation through ICD-10-CM manual, steps for correct coding, and finally, detailed coding descriptions for various interventional techniques. C1 [Manchikanti, Laxmaiah] Pain Management Ctr Paducah, Paducah, KY USA. [Manchikanti, Laxmaiah] Univ Louisville, Anesthesiol & Perioperat Med, Louisville, KY 40292 USA. [Hammer, Marvel J.] MJH Consulting, Denver, CO USA. [Boswell, Mark V.] Univ Louisville, Dept Anesthesiol & Perioperat Med, Louisville, KY 40292 USA. [Kaye, Alan D.] LSU Hlth Sci Ctr, Dept Anesthesia, New Orleans, LA USA. [Hirsch, Joshua A.] Massachusetts Gen Hosp, Intervent Care, Boston, MA 02114 USA. [Hirsch, Joshua A.] Massachusetts Gen Hosp, NeuroIntervent Spine, Boston, MA 02114 USA. [Hirsch, Joshua A.] Massachusetts Gen Hosp, Intervent Radiol, Boston, MA 02114 USA. [Hirsch, Joshua A.] Massachusetts Gen Hosp, Intervent & Endovasc Neuroradiol, Boston, MA 02114 USA. [Hirsch, Joshua A.] Harvard Univ, Sch Med, Boston, MA USA. RP Manchikanti, L (reprint author), 2831 Lone Oak Rd, Paducah, KY 42003 USA. EM drlm@thepainmd.com NR 66 TC 5 Z9 5 U1 0 U2 0 PU AM SOC INTERVENTIONAL PAIN PHYSICIANS PI PADUCAH PA 81 LAKEVIEW DR, PADUCAH, KY 42001 USA SN 1533-3159 J9 PAIN PHYSICIAN JI Pain Physician PD JAN PY 2016 VL 19 IS 1 BP E1 EP E14 PG 14 WC Anesthesiology; Clinical Neurology SC Anesthesiology; Neurosciences & Neurology GA DC1QH UT WOS:000368990800001 PM 26752478 ER PT J AU Manchikanti, L Hammer, MJ Benyamin, RM Hirsch, JA AF Manchikanti, Laxmaiah Hammer, Marvel J. Benyamin, Ramsin M. Hirsch, Joshua A. TI Physician Quality Reporting System (PQRS) for Interventional Pain Management Practices: Challenges and Opportunities SO PAIN PHYSICIAN LA English DT Review DE Value-based modifier; Medicare Access and CHIP Reauthorization Act of 2015 (MACRA); alternative payment models (APMs); merit based payment systems; negative payments; bonuses ID MEDICARE BENEFICIARIES; ORGANIZATION PROGRAM; PRIMARY-CARE; OF-CARE; ICD-10; PERFORMANCE; POLICY; INITIATIVES; SERVICES; LESSONS AB Basing their rationale on multiple publications from Institute of Medicine (IOM), specifically Crossing the Quality Chasm, policy makers have focused on a broad range of issues, including assessment of the influence of medical practice organization structures on quality performance and development of quality measures. The 2006 Tax Relief and Health Care Act established the Physician Quality Reporting System (PQRS), to enable eligible professionals to report health care quality and health outcome information that cannot be obtained from standard Medicare claims. However, the Patient Protection and Affordable Care Act (ACA) of 2010 required the Centers for Medicare and Medicaid Services (CMS) to incorporate a combination of cost and quality into the payment systems for health care as a precursor to value-based payments. The final change to PQRS pending initiation after 2018, is based on the Medicare Access and CHIP Reauthorization Act of 2015 (MACRA) which has incorporated alternative payment models and merit-based payment systems. Recent publication of quality performance scores by CMS has been less than optimal. When voluntary participation began in July 2007, providers were paid a bonus for reporting quality measures from 2008 through 2014, ranging from 0.5% to 2% of the Medicare Part B allowed charges furnished during the reporting period. Starting in 2015, penalties started for nonparticipation. Eligible professionals and group practices that failed to satisfactorily report data on quality measures during 2014 are subject to a 2% reduction in Medicare fee-for-service amounts for services furnished by the eligible professional or group practice during 2016. The CMS proposed rule for 2016 physician payments contained a number of provisions with proposed updates to the PQRS and Physician Value-Based Payment Modifier among other changes. The proposed rule is the first release since MACRA repealed the sustainable growth rate formula. CMS proposed to continue many existing policies regarding PQRS from 2015 to 2016. In addition, 2016 will be the year that is utilized to determine the 2018 PQRS payment adjustment. However, after 2018 the PQRS payment adjustment will be transitioned to the Merit-Based Incentive Payment System (MIPS), as required by MACRA. Overall, there will be over 280 measures in the 2016 PQRS. Readers might be surprised to find out that despite the cost intensity including time requirements personnel, the negative payment adjustments, are only the tip of the iceberg of cost. Indeed, all of the above may only be one-third or one-fourth of the cost to completely implement the PQRS system. Thus far, data across all specialties shows participation to be around 50%. In addition, penalties for lack of reporting of PQRS measures stands to be controversial to the Supreme Court ruling that unfunded mandates must not be permitted and also lack of significant relationships with improvement in quality in the overall analysis in multiple publications. C1 [Manchikanti, Laxmaiah] Pain Management Ctr Paducah, Paducah, KY USA. [Manchikanti, Laxmaiah] Univ Louisville, Anesthesiol & Perioperat Med, Louisville, KY 40292 USA. [Hammer, Marvel J.] MJH Consulting, Denver, CO USA. [Benyamin, Ramsin M.] Millennium Pain Ctr, Bloomington, IL USA. [Benyamin, Ramsin M.] Univ Illinois, Coll Med, Surg, Urbana, IL 61801 USA. [Hirsch, Joshua A.] Massachusetts Gen Hosp, Intervent Care, Boston, MA 02114 USA. [Hirsch, Joshua A.] Massachusetts Gen Hosp, NeuroIntervent Spine, Boston, MA 02114 USA. [Hirsch, Joshua A.] Massachusetts Gen Hosp, Intervent Radiol, Boston, MA 02114 USA. [Hirsch, Joshua A.] Massachusetts Gen Hosp, Intervent & Endovasc Neuroradiol, Boston, MA 02114 USA. [Hirsch, Joshua A.] Harvard Univ, Sch Med, Boston, MA USA. RP Manchikanti, L (reprint author), 2831 Lone Oak Rd, Paducah, KY 42003 USA. EM drlm@thepainmd.com NR 73 TC 9 Z9 9 U1 1 U2 1 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 PY 2016 VL 19 IS 1 BP E15 EP E32 PG 18 WC Anesthesiology; Clinical Neurology SC Anesthesiology; Neurosciences & Neurology GA DC1QH UT WOS:000368990800002 PM 26752483 ER PT J AU Lohmer, LL Clay, MR Naegeli, KM Chi, QY Ziel, JW Hagedorn, EJ Park, JE Jayadev, R Sherwood, DR AF Lohmer, Lauren L. Clay, Matthew R. Naegeli, Kaleb M. Chi, Qiuyi Ziel, Joshua W. Hagedorn, Elliott J. Park, Jieun E. Jayadev, Ranjay Sherwood, David R. TI A Sensitized Screen for Genes Promoting Invadopodia Function In Vivo: CDC-42 and Rab GDI-1 Direct Distinct Aspects of Invadopodia Formation SO PLOS GENETICS LA English DT Article ID ANCHOR-CELL INVASION; BASEMENT-MEMBRANE; CAENORHABDITIS-ELEGANS; C. ELEGANS; N-WASP; TUMOR-CELLS; METASTASIS; CANCER; IDENTIFICATION; PROTEINS AB Invadopodia are specialized membrane protrusions composed of F-actin, actin regulators, signaling proteins, and a dynamically trafficked invadopodial membrane that drive cell invasion through basement membrane (BM) barriers in development and cancer. Due to the challenges of studying invasion in vivo, mechanisms controlling invadopodia formation in their native environments remain poorly understood. We performed a sensitized genome-wide RNAi screen and identified 13 potential regulators of invadopodia during anchor cell (AC) invasion into the vulval epithelium in C. elegans. Confirming the specificity of this screen, we identified the Rho GTPase cdc-42, which mediates invadopodia formation in many cancer cell lines. Using live-cell imaging, we show that CDC-42 localizes to the AC-BM interface and is activated by an unidentified vulval signal(s) that induces invasion. CDC-42 is required for the invasive membrane localization of WSP-1 (N-WASP), a CDC-42 effector that promotes polymerization of F-actin. Loss of CDC-42 or WSP-1 resulted in fewer invadopodia and delayed BM breaching. We also characterized a novel invadopodia regulator, gdi-1 (Rab GDP dissociation inhibitor), which mediates membrane trafficking. We show that GDI-1 functions in the AC to promote invadopodia formation. In the absence of GDI-1, the specialized invadopodial membrane was no longer trafficked normally to the invasive membrane, and instead was distributed to plasma membrane throughout the cell. Surprisingly, the pro-invasive signal(s) from the vulval cells also controls GDI-1 activity and invadopodial membrane trafficking. These studies represent the first in vivo screen for genes regulating invadopodia and demonstrate that invadopodia formation requires the integration of distinct cellular processes that are coordinated by an extracellular cue. C1 [Lohmer, Lauren L.; Clay, Matthew R.; Naegeli, Kaleb M.; Chi, Qiuyi; Ziel, Joshua W.; Park, Jieun E.; Jayadev, Ranjay; Sherwood, David R.] Duke Univ, Dept Biol, Durham, NC USA. [Hagedorn, Elliott J.] Boston Childrens Hosp, Stem Cell Program, Boston, MA USA. [Hagedorn, Elliott J.] Boston Childrens Hosp, Div Hematol Oncol, Boston, MA USA. [Hagedorn, Elliott J.] Harvard Univ, Sch Med, Howard Hughes Med Inst, Dana Farber Canc Inst,Harvard Stem Cell Inst, Boston, MA 02115 USA. RP Sherwood, DR (reprint author), Duke Univ, Dept Biol, Durham, NC USA. EM david.sherwood@duke.edu FU National Institutes of Health [GM100083, GM079329]; Pew Scholars Program in Biomedical Sciences; Damon Runyon Cancer Foundation [DRG-2225-15]; NIH Office of Research Infrastructure Programs [P40 OD010440] FX This work was funded by the National Institutes of Health through grants GM100083 and GM079329 to DRS. Further, this work was supported by the Pew Scholars Program in Biomedical Sciences to DRS and the Damon Runyon Cancer Foundation grant DRG-2225-15 to MRC. The Caenorhabditis Genetics Center also provided strains, which is funded by NIH Office of Research Infrastructure Programs (P40 OD010440). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 80 TC 5 Z9 5 U1 1 U2 6 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 2016 VL 12 IS 1 AR e1005786 DI 10.1371/journal.pgen.1005786 PG 29 WC Genetics & Heredity SC Genetics & Heredity GA DC6ZN UT WOS:000369368200027 PM 26765257 ER PT J AU Tsai, AC Tomlinson, M Comulada, WS Rotheram-Borus, MJ AF Tsai, Alexander C. Tomlinson, Mark Comulada, W. Scott Rotheram-Borus, Mary Jane TI Intimate Partner Violence and Depression Symptom Severity among South African Women during Pregnancy and Postpartum: Population-Based Prospective Cohort Study SO PLOS MEDICINE LA English DT Article ID RANDOMIZED-CONTROLLED-TRIAL; STRESSFUL LIFE EVENTS; GENDER-BASED VIOLENCE; SUB-SAHARAN AFRICA; ATTENDING ANTENATAL CLINICS; IDENTIFICATION TEST AUDIT; COMMON MENTAL-DISORDERS; DOMESTIC VIOLENCE; ALCOHOL-USE; POSTNATAL DEPRESSION AB Background Violence against women by intimate partners remains unacceptably common worldwide. The evidence base for the assumed psychological impacts of intimate partner violence (IPV) is derived primarily from studies conducted in high-income countries. A recently published systematic review identified 13 studies linking IPV to incident depression, none of which were conducted in sub-Saharan Africa. To address this gap in the literature, we analyzed longitudinal data collected during the course of a 3-y cluster-randomized trial with the aim of estimating the association between IPV and depression symptom severity. Methods and Findings We conducted a secondary analysis of population-based, longitudinal data collected from 1,238 pregnant women during a 3-y cluster-randomized trial of a home visiting intervention in Cape Town, South Africa. Surveys were conducted at baseline, 6 mo, 18 mo, and 36 mo (85% retention). The primary explanatory variable of interest was exposure to four types of physical IPV in the past year. Depression symptom severity was measured using the Xhosa version of the ten-item Edinburgh Postnatal Depression Scale. In a pooled cross-sectional multivariable regression model adjusting for potentially confounding time-fixed and time-varying covariates, lagged IPV intensity had a statistically significant association with depression symptom severity (regression coefficient b = 1.04; 95% CI, 0.61-1.47), with estimates from a quantile regression model showing greater adverse impacts at the upper end of the conditional depression distribution. Fitting a fixed effects regression model accounting for all time-invariant confounding (e.g., history of childhood sexual abuse) yielded similar findings (b = 1.54; 95% CI, 1.13-1.96). The magnitudes of the coefficients indicated that a one-standard-deviation increase in IPV intensity was associated with a 12.3% relative increase in depression symptom severity over the same time period. The most important limitations of our study include exposure assessment that lacked measurement of sexual violence, which could have caused us to underestimate the severity of exposure; the extended latency period in the lagged analysis, which could have caused us to underestimate the strength of the association; and outcome assessment that was limited to the use of a screening instrument for depression symptom severity. Conclusions In this secondary analysis of data from a population-based, 3-y cluster-randomized controlled trial, IPV had a statistically significant association with depression symptom severity. The estimated associations were relatively large in magnitude, consistent with findings from high-income countries, and robust to potential confounding by time-invariant factors. Intensive health sector responses to reduce IPV and improve women's mental health should be explored. C1 [Tsai, Alexander C.] Massachusetts Gen Hosp, MGH Global Hlth, Boston, MA 02114 USA. [Tsai, Alexander C.] Harvard Ctr Populat & Dev Studies, Cambridge, MA USA. [Tsai, Alexander C.] Mbarara Univ Sci & Technol, Mbarara, Uganda. [Tomlinson, Mark] Univ Stellenbosch, ZA-7600 Stellenbosch, South Africa. [Comulada, W. Scott; Rotheram-Borus, Mary Jane] Univ Calif Los Angeles, Ctr HIV Identificat Prevent & Treatment Serv, Los Angeles, CA USA. [Comulada, W. Scott; Rotheram-Borus, Mary Jane] Univ Calif Los Angeles, Semel Inst Neurosci & Human Behav, Dept Psychiat & Biobehav Sci, Los Angeles, CA USA. RP Tsai, AC (reprint author), Massachusetts Gen Hosp, MGH Global Hlth, Boston, MA 02114 USA.; Tsai, AC (reprint author), Harvard Ctr Populat & Dev Studies, Cambridge, MA USA.; Tsai, AC (reprint author), Mbarara Univ Sci & Technol, Mbarara, Uganda. EM actsai@partners.org OI Tsai, Alexander/0000-0001-6397-7917 FU U.S. National Institutes of Health (NIH) [R01AA017104]; Center for HIV Identification, Prevention, and Treatment Services [R24AA022919, P30MH058107]; UCLA Center for AIDS Research [P30AI028697]; National Center for Advancing Translational Science through the UCLA Clinical and Translational Science Institute [UL1TR000124]; National Research Foundation of South Africa; [K23MH096620] FX This study was funded by U.S. National Institutes of Health (NIH) R01AA017104 and supported by R24AA022919, P30MH058107 (Center for HIV Identification, Prevention, and Treatment Services), P30AI028697 (UCLA Center for AIDS Research), and UL1TR000124 (National Center for Advancing Translational Science through the UCLA Clinical and Translational Science Institute). The authors also acknowledge salary support through K23MH096620 (ACT) and the National Research Foundation of South Africa (MT). MT is a lead investigator with the Centre of Excellence in Human Development, University of Witwatersrand, South Africa. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 110 TC 2 Z9 2 U1 10 U2 16 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1549-1676 J9 PLOS MED JI PLos Med. PD JAN PY 2016 VL 13 IS 1 AR e1001943 DI 10.1371/journal.pmed.1001943 PG 22 WC Medicine, General & Internal SC General & Internal Medicine GA DC7AL UT WOS:000369370600010 PM 26784110 ER PT S AU Edwards, A Haas, W AF Edwards, Amanda Haas, Wilhelm BE Reinders, J TI Multiplexed Quantitative Proteomics for High-Throughput Comprehensive Proteome Comparisons of Human Cell Lines SO PROTEOMICS IN SYSTEMS BIOLOGY: METHODS AND PROTOCOLS SE Methods in Molecular Biology LA English DT Article; Book Chapter DE Quantitative proteomics; Multiplexing; Isobaric labels; TMT ID MASS-SPECTROMETRY; ENABLES ACCURATE; EXPRESSION; QUANTIFICATION; ANEUPLOIDY; MIXTURES; STRATEGY; REVEALS; CANCER; DRAFT AB The proteome is the functional entity of the cell, and perturbations of a cellular system almost always cause changes in the proteome. These changes are a molecular fingerprint, allowing characterization and a greater understanding of the effect of the perturbation on the cell as a whole. Monitoring these changes has therefore given great insight into cellular responses to stress and disease states, and analytical platforms to comprehensively analyze the proteome are thus extremely important tools in biological research. Mass spectrometry has evolved as the most relevant technology to characterize proteomes in a comprehensive way. However, due to a lack of throughput capacity of mass spectrometry-based proteomics, researchers frequently use measurement of mRNA levels to approximate proteome changes. Growing evidence of substantial differences between mRNA and protein levels as well as recent improvements in mass spectrometry-based proteomics are heralding an increased use of mass spectrometry for comprehensive proteome mapping. Here we describe the use of multiplexed quantitative proteomics using isobaric labeling with tandem mass tags (TMT) for the simultaneous quantitative analysis of five cancer cell proteomes in biological duplicates in one mass spectrometry experiment. C1 [Edwards, Amanda; Haas, Wilhelm] Massachusetts Gen Hosp, Ctr Canc Res, Charlestown, MA USA. [Edwards, Amanda; Haas, Wilhelm] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. RP Edwards, A (reprint author), Massachusetts Gen Hosp, Ctr Canc Res, Charlestown, MA USA.; Edwards, A (reprint author), Harvard Univ, Sch Med, Dept Med, Boston, MA USA. NR 31 TC 0 Z9 0 U1 1 U2 2 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DR, STE 208, TOTOWA, NJ 07512-1165 USA SN 1064-3745 BN 978-1-4939-3341-9; 978-1-4939-3339-6 J9 METHODS MOL BIOL JI Methods Mol. Biol. PY 2016 VL 1394 BP 1 EP 13 DI 10.1007/978-1-4939-3341-9_1 D2 10.1007/978-1-4939-3341-9 PG 13 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA BE2HD UT WOS:000369235200002 PM 26700037 ER PT B AU Marshansky, V Futai, M Gruber, G AF Marshansky, Vladimir Futai, Masamitsu Grueber, Gerhard BE Chakraborti, S Dhalla, NS TI Eukaryotic V-ATPase and Its Super complexes: From Structure and Function to Disease and Drug Targeting SO REGULATION OF CA2+-ATPASES, V-ATPASES AND F-ATPASES SE Advances in Biochemistry in Health and Disease LA English DT Article; Book Chapter DE Eukaryotic V-ATPase; Holoenzyme; Acidification; pH-sensing-Receptor signaling; Super-complex; Vesicular trafficking; Human diseases-Drug targeting ID VACUOLAR H+-ATPASE; BREAST-CANCER CELLS; MICROVASCULAR ENDOTHELIAL-CELLS; PROTON-TRANSLOCATING ATPASE; NUCLEOTIDE EXCHANGE FACTORS; KIDNEY PROXIMAL TUBULES; N-TERMINUS DOMAIN; SACCHAROMYCES-CEREVISIAE; SUBUNIT ISOFORMS; PLASMA-MEMBRANE AB The eukaryotic vacuolar-type ATPase (V-ATPase) is a multi -subunit membrane protein complex, which is evolutionarily conserved from yeast to human. It is also functionally conserved and operates as a rotary proton pumping nano motor. In the first part of this chapter we discuss the structure and function of the yeast V-ATPase (ViVo) holoenzyme, We focus on the structural features of its subunits forming both catalytic V1 and proton conducting Vo sectors. Particularly, the recently solved structure of DF-subunit complex is discussed in relation to the energy coupling and regulation of yeast V-ATPase. It is noteworthy that the structure could contribute to understanding the function and regulation of V-ATPases of eukaryotes including human, leading to the rational design of specific inhibitors for medical applications. In addition to the well characterized role as proton pump, V-ATPases have acquired alternative cellular functions during evolution. In the second part we analyze novel roles of V-ATPase in function, signaling, and vesicular trafficking of cellular receptors. Our recent studies have uncovered that V-ATPase itself functions as an evolutionarily conserved pH-sensing and signaling receptor, which forms super-complex with aldolase/cytohesin-2/Arf1,6 small GTPases in early endosomes. On the other hand, V-ATPase forms a super-complex with mTORC1/Ragulator/Rag/Rheb small GTPases in late endosome/lysosomes and is involved in amino -acids sensing and monitoring nutritional state of cells. Finally, we discuss the role of V-ATPase in the development and progression of various diseases including cancer, diabetes, and osteopetrosis among others. We also present emerging approaches and future perspectives for specific drug targeting to V-ATPase and its super -complexes. C1 [Marshansky, Vladimir] Kadmon Corp, Mol Signaling, Alexandria Ctr Life Sci, 450 East 29th St, New York, NY 10016 USA. [Marshansky, Vladimir] Massachusetts Gen Hosp, Ctr Syst Biol, Program Membrane Biol, Boston, MA 02114 USA. [Marshansky, Vladimir] Massachusetts Gen Hosp, Div Nephrol, Simches Res Ctr, Boston, MA 02114 USA. [Marshansky, Vladimir] Harvard Univ, Sch Med, Dept Med, Boston, MA 02114 USA. [Futai, Masamitsu] Iwate Med Univ, Fac Pharmaceut Sci, Dept Biochem, Morioka, Iwate 0283694, Japan. [Futai, Masamitsu] Osaka Univ, Inst Sci & Ind Res, Osaka 5670047, Japan. [Grueber, Gerhard] Nanyang Technol Univ, Sch Biol Sci, 60 Nanyang Dr, Singapore 637551, Singapore. [Grueber, Gerhard] ASTAR, Bioinformat Inst, 30 Biopolis St,07-01 Matrix, Singapore 138671, Singapore. RP Marshansky, V (reprint author), Kadmon Corp, Mol Signaling, Alexandria Ctr Life Sci, 450 East 29th St, New York, NY 10016 USA.; Marshansky, V (reprint author), Massachusetts Gen Hosp, Ctr Syst Biol, Program Membrane Biol, Boston, MA 02114 USA.; Marshansky, V (reprint author), Massachusetts Gen Hosp, Div Nephrol, Simches Res Ctr, Boston, MA 02114 USA.; Marshansky, V (reprint author), Harvard Univ, Sch Med, Dept Med, Boston, MA 02114 USA. EM Vladimir.Marshansky@kadmon.com NR 214 TC 1 Z9 1 U1 7 U2 8 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013, UNITED STATES BN 978-3-319-24780-9; 978-3-319-24778-6 J9 ADV BIOCHEM HEALTH D JI Adv. Biochem. Health Dis. PY 2016 VL 14 BP 301 EP 335 DI 10.1007/978-3-319-24780-9_16 D2 10.1007/978-3-319-24780-9 PG 35 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA BE2IK UT WOS:000369377300017 ER PT J AU Chao, TE Mandigo, M Opoku-Anane, J Maine, R AF Chao, Tiffany E. Mandigo, Morgan Opoku-Anane, Jessica Maine, Rebecca TI Systematic review of laparoscopic surgery in low- and middle-income countries: benefits, challenges, and strategies SO SURGICAL ENDOSCOPY AND OTHER INTERVENTIONAL TECHNIQUES LA English DT Review DE Global Surgery; Laparoscopy; LMIC; Low-resource settings; Training/courses ID SPINAL-ANESTHESIA; DEVELOPING-WORLD; COMPLICATED APPENDICITIS; DIAGNOSTIC LAPAROSCOPY; ABDOMINAL TUBERCULOSIS; CHOLECYSTECTOMY; EXPERIENCE; CARE; APPENDECTOMY; FEASIBILITY AB Background Laparoscopy may prove feasible to address surgical needs in limited-resource settings. However, no aggregate data exist regarding the role of laparoscopy in low-and middle-income countries (LMICs). This study was designed to describe the issues facing laparoscopy in LMICs and to aggregate reported solutions. Methods A search was conducted using Medline, African Index Medicus, the Directory of Open Access Journals, and the LILACS/BIREME/SCIELO database. Included studies were in English, published after 1992, and reported safety, cost, or outcomes of laparoscopy in LMICs. Studies pertaining to arthroscopy, ENT, flexible endoscopy, hysteroscopy, cystoscopy, computer-assisted surgery, pediatrics, transplantation, and bariatrics were excluded. Qualitative synthesis was performed by extracting results that fell into three categories: advantages of, challenges to, and adaptations made to implement laparoscopy in LMICs. PRISMA guidelines for systematic reviews were followed. Results A total of 1101 abstracts were reviewed, and 58 articles were included describing laparoscopy in 25 LMICs. Laparoscopy is particularly advantageous in LMICs, where there is often poor sanitation, limited diagnostic imaging, fewer hospital beds, higher rates of hemorrhage, rising rates of trauma, and single income households. Lack of trained personnel and equipment were frequently cited challenges. Adaptive strategies included mechanical insufflation with room air, syringe suction, homemade endoloops, hand-assisted techniques, extracorporeal knot tying, innovative use of cheaper instruments, and reuse of disposable instruments. Inexpensive laboratory-based trainers and telemedicine are effective for training. Conclusions LMICs face many surgical challenges that require innovation. Laparoscopic surgery may be safe, effective, feasible, and cost-effective in LMICs, although it often remains limited in its accessibility, acceptability, and quality. This study may not capture articles written in languages other than English or in journals not indexed by the included databases. Surgeons, policymakers, and manufacturers should focus on plans for sustainability, training and retention of providers, and regulation of efforts to develop laparoscopy in LMICs. C1 [Chao, Tiffany E.] Massachusetts Gen Hosp, Dept Surg, 55 Fruit St, Boston, MA 02114 USA. [Chao, Tiffany E.; Mandigo, Morgan; Maine, Rebecca] Harvard Univ, Sch Med, Program Global Surg & Social Change, Boston, MA USA. [Mandigo, Morgan] Univ Miami, Miller Sch Med, Miami, FL 33136 USA. [Opoku-Anane, Jessica] George Washington Univ, Sch Med & Hlth Sci, Dept Obstet & Gynecol, Washington, DC 20052 USA. [Maine, Rebecca] Univ Calif San Francisco, Dept Surg, San Francisco, CA USA. RP Chao, TE (reprint author), Massachusetts Gen Hosp, Dept Surg, 55 Fruit St, Boston, MA 02114 USA.; Chao, TE (reprint author), Harvard Univ, Sch Med, Program Global Surg & Social Change, Boston, MA USA. EM tchao@mgh.harvard.edu NR 67 TC 1 Z9 1 U1 2 U2 7 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0930-2794 EI 1432-2218 J9 SURG ENDOSC JI Surg. Endosc. PD JAN PY 2016 VL 30 IS 1 BP 1 EP 10 DI 10.1007/s00464-015-4201-2 PG 10 WC Surgery SC Surgery GA DC6MR UT WOS:000369334600001 PM 25875087 ER PT J AU Hashimoto, DA Phitayakorn, R Fernandez-del Castillo, C Meireles, O AF Hashimoto, Daniel A. Phitayakorn, Roy Fernandez-del Castillo, Carlos Meireles, Ozanan TI A blinded assessment of video quality in wearable technology for telementoring in open surgery: the Google Glass experience SO SURGICAL ENDOSCOPY AND OTHER INTERVENTIONAL TECHNIQUES LA English DT Article DE Telementoring; Surgical education; Wearable technology; Open surgery AB Background The goal of telementoring is to recreate face-to-face encounters with a digital presence. Open-surgery telementoring is limited by lack of surgeon's point-of-view cameras. Google Glass is a wearable computer that looks like a pair of glasses but is equipped with wireless connectivity, a camera, and viewing screen for video conferencing. This study aimed to assess the safety of using Google Glass by assessing the video quality of a telementoring session. Methods Thirty-four (n = 34) surgeons at a single institution were surveyed and blindly compared via video captured with Google Glass versus an Apple iPhone 5 during the open cholecystectomy portion of a Whipple. Surgeons were asked to evaluate the quality of the video and its adequacy for safe use in telementoring. Results Thirty-four of 107 invited surgical attendings (32 %) responded to the anonymous survey. A total of 50 % rated the Google Glass video as fair with the other 50 % rating it as bad to poor. A total of 52.9 % of respondents rated the Apple iPhone video as good. A significantly greater proportion of respondents felt Google Glass video quality was inadequate for telementoring versus the Apple iPhone's (82.4 vs 26.5 %, p < 0.0001). Intraclass correlation coefficient was 0.924 (95 % CI 0.660-0.999, p < 0.001). Conclusion While Google Glass provides a great breadth of functionality as a wearable device with two-way communication capabilities, current hardware limitations prevent its use as a telementoring device in surgery as the video quality is inadequate for safe telementoring. As the device is still in initial phases of development, future iterations or competitor devices may provide a better telementoring application for wearable devices. C1 [Hashimoto, Daniel A.; Phitayakorn, Roy; Fernandez-del Castillo, Carlos; Meireles, Ozanan] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Surg, 55 Fruit St,GRB425, Boston, MA 02114 USA. RP Hashimoto, DA (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Surg, 55 Fruit St,GRB425, Boston, MA 02114 USA. EM dahashimoto@partners.org OI Phitayakorn, Roy/0000-0002-8327-1484 NR 21 TC 4 Z9 4 U1 1 U2 3 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0930-2794 EI 1432-2218 J9 SURG ENDOSC JI Surg. Endosc. PD JAN PY 2016 VL 30 IS 1 BP 372 EP 378 DI 10.1007/s00464-015-4178-x PG 7 WC Surgery SC Surgery GA DC6MR UT WOS:000369334600050 PM 25829065 ER PT J AU Lee, MY Lee, C Jung, HS Jeon, M Kim, KS Yun, SH Kim, C Hahnft, SK AF Lee, Min-Young Lee, Changho Jung, Ho Sang Jeon, Mansik Kim, Ki Su Yun, Seok Hyun Kim, Chulhong Hahnft, Sei Kwang TI Biodegradable Photonic Melanoidin for Theranostic Applications SO ACS NANO LA English DT Article DE melanoidin; biodegradable; photoacoustic; photothermal; theranostics ID CONTRAST AGENTS; IN-VIVO; LIVING MICE; NANOPARTICLES; NANOVESICLES; GLYCATION; PRODUCTS; PROBES AB Light-absorbing nanoparticles for localized heat generation in tissues have various biomedical applications in diagnostic imaging, surgery, and therapies. Although numerous plasmonic and carbon-based nano particles with strong optical absorption have been developed, their clearance, potential cytotoxicity, and long-term safety issues remain unresolved. Here, we show that "generally regarded as safe (GRAS)" melanoidins prepared from glucose and amino acid offer a high light-to heat conversion efficiency, biocompatibility, biodegradability, nonmutagenicity, and efficient renal clearance, as well as a low cost for synthesis. We exhibit a wide range of biomedical photonic applications of melanoidins, including in vivo photoacoustic mapping of sentinel lymph nodes, photoacoustic tracking of gastrointestinal tracts, photothermal cancer therapy, and photothermal lipolysis. The biodegradation rate and renal clearance of melanoidins are controllable by design. Our results confirm the feasibility of biodegradable melanoidins for various photonic applications to theranostic nanomedicines. C1 [Lee, Min-Young; Jung, Ho Sang; Hahnft, Sei Kwang] Pohang Univ Sci & Technol POSTECH, Dept Mat Sci & Engn, 77 Cheongam Ro, Pohang 790784, Gyeongbuk, South Korea. [Jeon, Mansik; Kim, Chulhong; Hahnft, Sei Kwang] Pohang Univ Sci & Technol POSTECH, Dept Creat IT Engn, 77 Cheongam Ro, Pohang 790784, Gyeongbuk, South Korea. [Lee, Min-Young] Samsung Elect Co Ltd, SAIT, Samsung Biomed Res Inst, Med Device Res Ctr, Seoul 135710, South Korea. [Kim, Ki Su; Yun, Seok Hyun] Harvard Univ, Sch Med, Wellman Ctr Photomed, 65 Landsdowne St UP-5, Cambridge, MA 02139 USA. [Kim, Ki Su; Yun, Seok Hyun] Massachusetts Gen Hosp, 65 Landsdowne St UP-5, Cambridge, MA 02139 USA. [Jeon, Mansik] Kyungpook Natl Univ, Sch Elect Engn, 80 Daehak Ro, Taegu 702701, South Korea. RP Hahnft, SK (reprint author), Pohang Univ Sci & Technol POSTECH, Dept Mat Sci & Engn, 77 Cheongam Ro, Pohang 790784, Gyeongbuk, South Korea.; Kim, C; Hahnft, SK (reprint author), Pohang Univ Sci & Technol POSTECH, Dept Creat IT Engn, 77 Cheongam Ro, Pohang 790784, Gyeongbuk, South Korea. EM chulhong@postech.ac.kr; skhanb@postech.ac.kr FU MSIP (Ministry of Science, ICT and Future Planning), Korea, under the "ICT Consilience Creative Program" [IITP-2015-R0346-15-1007]; Bio & Medical Technology Development Program [2012M3A9C6049791]; Engineering Research Center of the National Research Foundation (NRF) [NRF-2011-0030075]; Korean Health Technology R&D Project, Ministry of Health and Welfare, Korea [HI14C1658] FX This research was supported by the MSIP (Ministry of Science, ICT and Future Planning), Korea, under the "ICT Consilience Creative Program" (IITP-2015-R0346-15-1007) supervised by the IITP (Institute for Information & Communications Technology Promotion). This research was supported by the Bio & Medical Technology Development Program (No. 2012M3A9C6049791) and Engineering Research Center Grant (NRF-2011-0030075) of the National Research Foundation (NRF). This research was supported by a grant of the Korean Health Technology R&D Project, Ministry of Health and Welfare, Korea (HI14C1658). NR 30 TC 8 Z9 8 U1 8 U2 27 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 1936-0851 EI 1936-086X J9 ACS NANO JI ACS Nano PD JAN PY 2016 VL 10 IS 1 BP 822 EP 831 DI 10.1021/acsnano.5b05931 PG 10 WC Chemistry, Multidisciplinary; Chemistry, Physical; Nanoscience & Nanotechnology; Materials Science, Multidisciplinary SC Chemistry; Science & Technology - Other Topics; Materials Science GA DC3JO UT WOS:000369115800089 PM 26623481 ER PT J AU Hanlon, CA Owens, MM Joseph, JE Zhu, X George, MS Brady, KT Hartwell, KJ AF Hanlon, Colleen A. Owens, Max M. Joseph, Jane E. Zhu, Xun George, Mark S. Brady, Kathleen T. Hartwell, Karen J. TI Lower subcortical gray matter volume in both younger smokers and established smokers relative to non-smokers SO ADDICTION BIOLOGY LA English DT Article DE Gray matter; nicotine; smoking; voxel-based morphometry ID CIGARETTE-SMOKING; HUMAN-BRAIN; COGNITIVE PERFORMANCE; VISUAL-ATTENTION; RECEPTOR-BINDING; NICOTINE; TOBACCO; DEPENDENCE; AGE; MORPHOMETRY AB Although established adult smokers with long histories of nicotine dependence have lower neural tissue volume than non-smokers, it is not clear if lower regional brain volume is also observed in younger, less established smokers. The primary goal of this study was to investigate neural tissue volume in a large group of smokers and non-smokers, with a secondary goal of measuring the impact of age on these effects. We used voxel-based morphometry to compare regional gray matter volume in 118 individuals (59 smokers, 59 age- and gender-matched non-smokers). Younger smokers had significantly lower gray matter volume in the left thalamus and the left amygdala than their non-smoking peers (family-wise error-corrected clusters, P<0.05). There was no correlation between smoking use variables and tissue volume among younger smokers. Established smokers had significantly lower gray matter volume than age-matched non-smokers in the insula, parahippocampal gyrus and pallidum. Medial prefrontal cortex gray matter volume was negatively correlated with pack-years of smoking among the established smokers, but not the younger smokers. These data reveal that regional tissue volume differences are not limited exclusively to established smokers. Deficits in young adults indicate that cigarette smoking may either be deleterious to the thalamus and amygdala at an earlier age than previously reported, or that pre-existing differences in these areas may predispose individuals to the development of nicotine dependence. C1 [Hanlon, Colleen A.; Owens, Max M.; Hartwell, Karen J.] Med Univ S Carolina, Dept Psychiat, 67 President St, Charleston, SC 29425 USA. [Hanlon, Colleen A.; Joseph, Jane E.; Zhu, Xun] Med Univ S Carolina, Dept Neurosci, Charleston, SC 29425 USA. [Joseph, Jane E.] Univ Kentucky, Lexington, KY USA. [George, Mark S.; Brady, Kathleen T.] Med Univ S Carolina, Clin Neurosci Div, Charleston, SC 29425 USA. [George, Mark S.; Brady, Kathleen T.; Hartwell, Karen J.] Ralph H Johnson VA Med Ctr, Charleston, SC USA. RP Hanlon, CA (reprint author), Med Univ S Carolina, Dept Psychiat, 67 President St, Charleston, SC 29425 USA.; Hanlon, CA (reprint author), Med Univ S Carolina, Dept Neurosci, 67 President St, Charleston, SC 29425 USA. EM hanlon@musc.edu FU GRAND [GA30523K]; NICHD [K12HD055885, UL1 RR029882]; [K01DA027756]; [DA036085-03]; [5R21DA026085-02] FX Funding was provided by K01DA027756 (CAH), R33 (DA036085-03), GRAND (GA30523K), 5R21DA026085-02, NICHD K12HD055885 and UL1 RR029882 NR 47 TC 5 Z9 5 U1 0 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1355-6215 EI 1369-1600 J9 ADDICT BIOL JI Addict. Biol. PD JAN PY 2016 VL 21 IS 1 BP 185 EP 195 DI 10.1111/adb.12171 PG 11 WC Biochemistry & Molecular Biology; Substance Abuse SC Biochemistry & Molecular Biology; Substance Abuse GA DC2ST UT WOS:000369067300016 PM 25125263 ER PT J AU Dias-Santagata, D Su, YH Hoang, MP AF Dias-Santagata, Dora Su, Yuhua Hoang, Mai P. TI Inununohistochemical Detection of NRASQ61R Mutation in Diverse Tumor Types SO AMERICAN JOURNAL OF CLINICAL PATHOLOGY LA English DT Article DE NRAS; Immunohistochemistry; Melanoma; Thyroid carcinoma; Colorectal carcinoma ID METASTATIC COLORECTAL-CANCER; PAPILLARY THYROID-CARCINOMA; FOLLICULAR VARIANT; RAS MUTATIONS; MELANOMA; BRAF; IMMUNOHISTOCHEMISTRY AB Objectives: Testing for NRAS mutation at codon Q61 is of therapeutic, prognostic, and diagnostic importance for metastatic melanoma, thyroid carcinoma, and colorectal carcinoma. Immunohistochemistry for NRASQ6IR, the most common NRAS mutation, offers several practical advantages over current molecular diagnostic techniques. Methods: We investigated the sensitivity and specificity of NRASQ61R in a series of 149 tumors with known NRAS genotype (72 malignant melanomas, 13 melanocytic nevi, 28 thyroid carcinomas, 25 gastrointestinal carcinomas, and 11 other malignancies). Results: Thirty-five cases harbored the NRASQ61R mutation (19 malignant melanomas, one melanocytic nevus, 10 thyroid carcinomas, two gastrointestinal carcinomas, and three other malignancies). In this series, the concordance rate between immunohistochemistry and mutational analyses was 100%. The sensitivity and specificity were 100% and 100%, respectively. However, lower staining intensity was observed for thyroid carcinomas in comparison to melanomas and other tumors. Conclusions: Our studies confirmed that immunohistochemistry provides excellent sensitivity and specificity for detecting the NRASQ61R mutation in a variety of tumor types in a clinical setting. C1 [Hoang, Mai P.] Massachusetts Gen Hosp, Dept Pathol, 55 Fruit St Warren 820, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Hoang, MP (reprint author), Massachusetts Gen Hosp, Dept Pathol, 55 Fruit St Warren 820, Boston, MA 02114 USA. EM mhoang@mgh.harvard.edu NR 24 TC 8 Z9 8 U1 0 U2 3 PU AMER SOC CLINICAL PATHOLOGY PI CHICAGO PA 2100 W HARRISON ST, CHICAGO, IL 60612 USA SN 0002-9173 EI 1943-7722 J9 AM J CLIN PATHOL JI Am. J. Clin. Pathol. PD JAN PY 2016 VL 145 IS 1 BP 29 EP 34 DI 10.1093/AJCP/AQV015 PG 6 WC Pathology SC Pathology GA DC1GO UT WOS:000368965000004 PM 26712868 ER PT J AU Toufaily, MH Roberts, DJ Westgate, MN Holmes, LB AF Toufaily, M. Hassan Roberts, Drucilla J. Westgate, Marie-Noel Holmes, Lewis B. TI Triploidy Variation of Phenotype SO AMERICAN JOURNAL OF CLINICAL PATHOLOGY LA English DT Article DE Triploidy; Partial hydatidiform mole; Non-molar placenta; Phenotype; Congenital malformations; Syndactyly ID PARTIAL HYDATIDIFORM MOLE; DIAGNOSIS; FEATURES AB Objectives: Triploidy (69, XXX; 69, XXY; 69, XYY) accounts for 1% of conceptions, but the affected fetus often does not survive past the first trimester. Fetal development in triploidy is rare. A consecutive series was used to describe the fetal and placental phenotypes and compare them with previous publications. Methods: Fifty-four triploid fetuses were identified in the Active Malformations Surveillance Program between 1972 and 2012 at Brigham and Women's Hospital in Boston. The phenotype was described from prenatal imaging and autopsy findings. Results: The diagnosis was confirmed by chromosome analysis in 53 of the 54 fetuses. Twenty-seven (50%) of the affected fetuses were identified during pregnancy. The abnormalities identified by prenatal ultrasound included renal malformations, heart defects, hydrocephalus, holoprosencephaly, and myelomeningocele. At autopsy, syndactyly, usually between fingers 3 and 4, was identified in 37 (69%) of the fetuses. Thirteen (24%) of the infants had the histologic features of a partial hydatidiform mole in the placenta. Conclusions: The presence of major malformations and growth restriction during pregnancy makes triploidy a potential diagnosis. There are no obligate clinical features in triploidy. Syndactyly, especially 3-4 syndactyly of the hands, is a distinctive feature. Cystic changes in the placenta can be seen by ultrasound during pregnancy. There was no difference in the phenotype between triploid infants associated with partial moles and those with nonmolar placentas. C1 [Toufaily, M. Hassan; Westgate, Marie-Noel; Holmes, Lewis B.] Harvard Univ, Sch Med, MassGen Hosp Children, Med Genet Unit, Boston, MA USA. [Toufaily, M. Hassan; Westgate, Marie-Noel; Holmes, Lewis B.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Pediat Newborn Med, Boston, MA 02115 USA. [Roberts, Drucilla J.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Pathol, Boston, MA USA. RP Toufaily, MH (reprint author), MassGen Hosp Children, Med Genet Unit, 175 Cambridge St,Fifth Floor, Boston, MA 02114 USA. EM htoufaily@mgh.harvard.edu FU Birth,Defects Registry of the Massachusetts Department of Public Health FX The Active Malformations Surveillance Program was supported by funds provided by the Birth,Defects Registry of the Massachusetts Department of Public Health, which is part of the National Birth Defects Prevention Study, a project of the Birth Defects and Developmental Disabilities Center of the Centers for Disease Control and Prevention, Atlanta, GA. NR 20 TC 0 Z9 0 U1 1 U2 3 PU AMER SOC CLINICAL PATHOLOGY PI CHICAGO PA 2100 W HARRISON ST, CHICAGO, IL 60612 USA SN 0002-9173 EI 1943-7722 J9 AM J CLIN PATHOL JI Am. J. Clin. Pathol. PD JAN PY 2016 VL 145 IS 1 BP 86 EP 95 DI 10.1093/AJCP/AQV012 PG 10 WC Pathology SC Pathology GA DC1GO UT WOS:000368965000012 PM 26712875 ER PT J AU Breton, S Ruan, YC Park, YJ Kim, B AF Breton, Sylvie Ruan, Ye Chun Park, Yoo-Jin Kim, Bongki TI Regulation of epithelial function, differentiation, and remodeling in the epididymis SO ASIAN JOURNAL OF ANDROLOGY LA English DT Review DE basal cells; clear cells; principal cells; pseudostratified epithelia; transepithelial transport ID MALE REPRODUCTIVE-TRACT; CONGENITAL BILATERAL ABSENCE; TRANSMEMBRANE CONDUCTANCE REGULATOR; TRANSCRIPTION FACTOR FOXI1; VAS-DEFERENS EPITHELIA; RAT EPIDIDYMIS; CYSTIC-FIBROSIS; V-ATPASE; CLEAR CELLS; GENE-EXPRESSION AB The epididymis is a single convoluted tubule lined by a pseudostratified epithelium. Specialized epididymal epithelial cells, the so-called principal, basal, narrow, and clear cells, establish a unique luminal environment for the maturation and storage of spermatozoa. The epididymis is functionally and structurally divided into several segments and sub-segments that create regionally distinct luminal environments. This organ is immature at birth, and epithelial cells acquire their fully differentiated phenotype during an extended postnatal period, but the factors involved in this complex process remain incompletely characterized. In the adult epididymis, the establishment of an acidic luminal pH and low bicarbonate concentration in the epididymis contributes to preventing premature activation of spermatozoa during their maturation and storage. Clear cells are proton-secreting cells throughout the epididymis, but principal cells have distinct acid/base transport properties, depending on their localization within the epididymis. Basal cells are located in all epididymal segments, but they have a distinct morphology depending on the segment and species examined. How this structural plasticity of basal cells is regulated is discussed here. Also, the role of luminal factors and androgens in the regulation of epithelial cells is reviewed in relation to their respective localization in the proximal versus distal regions of the epididymis. Finally, we describe a novel role for CFTR in tubulogenesis and epithelial cell differentiation. C1 [Breton, Sylvie; Ruan, Ye Chun; Park, Yoo-Jin; Kim, Bongki] Massachusetts Gen Hosp, Div Nephrol, Program Membrane Biol, Ctr Syst Biol, Boston, MA 02114 USA. [Breton, Sylvie; Ruan, Ye Chun; Park, Yoo-Jin; Kim, Bongki] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Ruan, Ye Chun] Chinese Univ Hong Kong, Sch Biomed Sci, Epithelial Cell Biol Res Ctr, Fac Med, Hong Kong, Hong Kong, Peoples R China. RP Breton, S (reprint author), Massachusetts Gen Hosp, Div Nephrol, Program Membrane Biol, Ctr Syst Biol, Boston, MA 02114 USA.; Breton, S (reprint author), Harvard Univ, Sch Med, Boston, MA 02115 USA. EM breton.sylvie@mgh.harvard.edu FU NIH [RO1HD040793, RO1DK097124]; Lalor Foundation; Charles and Ann Sanders Research Scholar Award at MGH FX This work was supported by NIH grants RO1HD040793 and RO1DK097124 (to S.B.) and by postdoctoral fellowships from the Lalor Foundation (to Y.C.R and Y.J.P.). The Microscopy Core facility of the MGH Program in Membrane Biology receives support from the Boston Area Diabetes and Endocrinology Research Center (DK57521) and the Center for the Study of Inflammatory Bowel Disease (DK43351). S.B. is a recipient of the Charles and Ann Sanders Research Scholar Award at MGH. NR 96 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 1008-682X EI 1745-7262 J9 ASIAN J ANDROL JI Asian J. Androl. PD JAN PY 2016 VL 18 IS 1 BP 3 EP 9 DI 10.4103/1008-682X.165946 PG 7 WC Andrology; Urology & Nephrology SC Endocrinology & Metabolism; Urology & Nephrology GA DA5MJ UT WOS:000367846900001 PM 26585699 ER PT J AU Lee, AP Roth, MY Nya-Ngatchou, JJ Lin, K Walsh, TJ Page, ST Matsumoto, AM Bremner, WJ Amory, JK Anawalt, BD AF Lee, Ada P. Roth, Mara Y. Nya-Ngatchou, Jean-Jacques Lin, Kat Walsh, Thomas J. Page, Stephanie T. Matsumoto, Alvin M. Bremner, William J. Amory, John K. Anawalt, Bradley D. TI Testicular fine-needle aspiration for the assessment of intratesticular hormone concentrations SO ASIAN JOURNAL OF ANDROLOGY LA English DT Article DE male contraception; physiology; reproductive and urinary; testis ID TESTOSTERONE CONCENTRATIONS; NONOBSTRUCTIVE AZOOSPERMIA; GONADOTROPIN SUPPRESSION; SPERM ASPIRATION; HUMAN TESTIS; NORMAL MEN; BIOPSY AB Measurement of intratesticular sex steroid concentrations in men informs both the development of male hormonal contraceptives and the understanding of male infertility. Given the challenges of using invasive techniques to measure testicular hormone physiology, our group has used a minimally-invasive fine-needle aspiration technique to measure intratesticular hormones in normal healthy men. Herein, we present a post-hoc analysis of the safety and efficacy of testicular fine-needle aspiration (FNA) completed as part of six clinical trials. From 2001 through 2011, a total of 404 procedures were conducted among 163 research volunteers, 85.9% of which were successful in obtaining sufficient fluid for the measurement of intratesticular steroid concentrations. Pain was the most common side effect, with 36.8% of procedures associated with moderate procedural pain and 4.7% with severe procedural pain. Postprocedural pain was uncommon and abated within a few days. Mild local bruising occurred with 14.9% of procedures. Two serious adverse events (0.5%) required surgical intervention. The risk of an adverse event was not associated with age, body mass index, testicular size, or the volume of fluid aspirated. Testicular FNA to obtain fluid for measurement of intratesticular steroid concentrations frequently causes mild to moderate procedural pain, but serious adverse events occur rarely. Testicular FNA has been instrumental for defining human intratesticular hormone physiology and is a minimally-invasive, safe, effective method for obtaining fluid for research on testicular physiology and pathology. C1 [Lee, Ada P.] Univ Calif San Francisco, Dept Med, San Francisco, CA USA. [Roth, Mara Y.; Nya-Ngatchou, Jean-Jacques; Page, Stephanie T.; Matsumoto, Alvin M.; Bremner, William J.; Amory, John K.; Anawalt, Bradley D.] Univ Washington, Dept Med, Seattle, WA USA. [Roth, Mara Y.; Nya-Ngatchou, Jean-Jacques; Page, Stephanie T.; Matsumoto, Alvin M.; Bremner, William J.; Amory, John K.; Anawalt, Bradley D.] Univ Washington, Ctr Res Reprod & Contracept, Seattle, WA 98195 USA. [Lin, Kat] Univ Washington, Dept Obstet & Gynecol, Seattle, WA 98195 USA. [Walsh, Thomas J.] Univ Washington, Dept Urol, Seattle, WA 98195 USA. [Matsumoto, Alvin M.] VA Puget Sound Hlth Care Syst, Dept Med, Geriatr Res Educ & Clin Ctr, Seattle, WA USA. [Lin, Kat] Univ Washington, Seattle, WA 98195 USA. RP Anawalt, BD (reprint author), Univ Washington, Dept Med, Seattle, WA USA.; Anawalt, BD (reprint author), Univ Washington, Ctr Res Reprod & Contracept, Seattle, WA 98195 USA. EM banawalt@medicine.washington.edu FU Eunice Kennedy Shriver National Institute of Child Health and Human Development grants [U54 HD-42454]; National Institute of Diabetes and Digestive Kidney Diseases training grant [5T32 DK007247-35, K23 HD073164-02]; Veterans Administration Research and Development FX Funding provided by Eunice Kennedy Shriver National Institute of Child Health and Human Development grants U54 HD-42454 (STP, WJB, JKA, BDA), the National Institute of Diabetes and Digestive Kidney Diseases training grant 5T32 DK007247-35 (JJNN) and K23 HD073164-02 (MYR), and by the Veterans Administration Research and Development (AMM, BDA). NR 17 TC 0 Z9 0 U1 1 U2 2 PU MEDKNOW PUBLICATIONS & MEDIA PVT LTD PI MUMBAI PA B-9, KANARA BUSINESS CENTRE, OFF LINK RD, GHAKTOPAR-E, MUMBAI, 400075, INDIA SN 1008-682X EI 1745-7262 J9 ASIAN J ANDROL JI Asian J. Androl. PD JAN PY 2016 VL 18 IS 1 BP 21 EP 24 DI 10.4103/1008-682X.156637 PG 4 WC Andrology; Urology & Nephrology SC Endocrinology & Metabolism; Urology & Nephrology GA DA5MJ UT WOS:000367846900004 PM 26208394 ER PT J AU Zhang, C Meermeier, NP Terker, AS Blankenstein, KI Singer, JD Hadchouel, J Ellison, DH Yang, CL AF Zhang, Chong Meermeier, Nicholas P. Terker, Andrew S. Blankenstein, Katharina I. Singer, Jeffrey D. Hadchouel, Juliette Ellison, David H. Yang, Chao-Ling TI Degradation by Cullin 3 and effect on WNK kinases suggest a role of KLHL2 in the pathogenesis of Familial Hyperkalemic Hypertension SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article DE Kelch-like protein 2; Cullin 3; WNK kinase; Degradation; Familial Hyperkalemic Hypertension ID PSEUDOHYPOALDOSTERONISM TYPE-II; DISEASE-CAUSING MUTATIONS; NA-CL COTRANSPORTER; UBIQUITINATION; SPAK; HOMEOSTASIS; INTERACTS; COMPLEX; NKCC2; CUL3 AB Mutations in WNK1 and WNK4, and in components of the Cullin-Ring Ligase system, kelch-like 3 (KLHL3) and Cullin 3 (CUL3), can cause the rare hereditary disease, Familial Hyperkalemic Hypertension (FHHt). The disease is characterized by overactivity of the renal sodium chloride cotransporter (NCC), which is phosphorylated and activated by the WNK-stimulated Ste20-type kinases, SPAT( and OSR1. WNK kinases themselves can be targeted for ubiquitination and degradataion by the CUL3-KLHL3 E3 ubiquitin ligase complex. It is unclear, however, why there are significant differences in phenotypic severity among FHHt patients with mutations in different genes. It was reported that kelch-like 2 (KLHL2), a homolog of KLHL3, can also target WNK kinases for ubiquitation and degradation, and may play a special role in the systemic vasculature. Our recent study revealed the disease mutant CUL3 exhibits enhanced degradation of its adaptor protein KLHL3, potentially resulting in accumulation of WNK kinases secondarily. To investigate if KLHL2 plays a role in FHHt, we studied the effect of wild type and FHHt mutant CUL3 on degradation of KLHL2 and WNK kinase proteins in HEK293 cells. Although CUL3 facilitates KLHL2 degradation, the disease mutant CUL3 is more active in this regard. KLHL2 facilitated the degradation of wild type but not disease mutant WNK4 protein. These results suggest that KLHL2 likely plays a role in the pathogenesis of FHHt, and aggravates the phenotype caused by mutations in CUL3 and WNK4. (C) 2015 Elsevier Inc. All rights reserved. C1 [Zhang, Chong] Shanghai Jiao Tong Univ, Sch Med, Xinhua Hosp, Dept Nephrol, Shanghai 200030, Peoples R China. [Meermeier, Nicholas P.; Terker, Andrew S.; Ellison, David H.; Yang, Chao-Ling] Oregon Hlth & Sci Univ, Dept Med, Div Nephrol & Hypertens, Portland, OR 97201 USA. [Blankenstein, Katharina I.] Charite, Inst Vegetat Anat, Campus Charite Mitte, D-13353 Berlin, Germany. [Hadchouel, Juliette] Portland State Univ, Dept Biol, Portland, OR 97207 USA. [Hadchouel, Juliette] Paris Cardiovasc Res Ctr, Paris, France. [Hadchouel, Juliette] Univ Paris 05, Sorbonne Paris Cite, Fac Med, Paris, France. [Ellison, David H.] Portland VA Med Ctr, Portland, OR USA. RP Zhang, C (reprint author), Shanghai Jiao Tong Univ, Sch Med, Xinhua Hosp, Dept Nephrol, Shanghai 200030, Peoples R China.; Yang, CL (reprint author), Oregon Hlth & Sci Univ, Dept Med, Div Nephrol & Hypertens, Portland, OR 97201 USA. EM zhangchongzc@gmail.com; yangch@ohsu.edu RI Hadchouel, Juliette/K-4593-2016 FU National Natural Science Foundation of China [81570634]; Shanghai Municipal Education Commission [15zz054]; NIH [R01 DK51496, 5T32DK067864-10] FX This work was supported by National Natural Science Foundation of China 81570634 and Shanghai Municipal Education Commission 15zz054 (to C. Zhang), and NIH grant R01 DK51496 (to C.-L. Yang and D.H. Ellison). A.S. Terker was supported by NIH 5T32DK067864-10. NR 25 TC 1 Z9 2 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 0006-291X EI 1090-2104 J9 BIOCHEM BIOPH RES CO JI Biochem. Biophys. Res. Commun. PD JAN 1 PY 2016 VL 469 IS 1 BP 44 EP 48 DI 10.1016/j.bbrc.2015.11.067 PG 5 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA DB9WI UT WOS:000368868000007 PM 26607111 ER PT J AU Meimetis, LG Boros, E Carlson, JC Ran, CZ Caravan, P Weissleder, R AF Meimetis, Labros G. Boros, Eszter Carlson, Jonathan C. Ran, Chongzhao Caravan, Peter Weissleder, Ralph TI Bioorthogonal Fluorophore Linked DFO-Technology Enabling Facile Chelator Quantification and Multimodal Imaging of Antibodies SO BIOCONJUGATE CHEMISTRY LA English DT Article ID IMMUNO-PET; IN-VIVO; CANCER; IMMUNOTHERAPY; EXPRESSION; BODIPY; PROBES AB Herein we describe the development and application of a bioorthogonal fluorogenic chelate linker that can be used for facile creation of labeled imaging agents. The chelate linker is based on the trans-cyclooctene(TCO)-tetrazine(Tz) chemistry platform and incorporates deferoxamine (DFO) as a Zr-89 PET tracer and a BODIPY fluorophore for multimodal imaging. The rapid (<3 min) ligation between mAb-TCO and Tz-BODIPY-DFO chelator is monitored using fluorescence and allows for determination of labeling completion. Utilizing BODIPY as the linker between mAb and DFO facilitates in chelator quantification using spectrophotometry, allowing for an alternative to traditional methods (mass and isotope dilution assay). Radiolabeling with Zr-89 to form Zr-89-DFO-BODIPY-trastuzumab was found to be quantitative after incubation at room temperature for 1 h (1.5 mCi/mg specific activity). The cell binding assay using HER2+ (BT474) and HER2- (BT20) cell lines showed significant binding to Zr-89-DFO-BODIPY-trastuzumab (6.45 +/- 1.87% in BT474 versus 1.47 +/- 0.39% in BT20). In vivo PET imaging of mice bearing BT20 or BT474 xenografts with Zr-89-DFO-BODIPY-trastuzumab showed high tumor conspicuity, and biodistribution confirmed excellent, specific probe uptake of 237.3 +/- 14.5% ID/g in BT474 xenografts compared to low, nonspecific probe uptake in BT20 xenografts (16.4 +/- 5.6% ID/g) 96 h p.i. . Ex vivo fluorescence (465ex/520em) of selected tissues confirmed superb target localization and persistence of the fluorescence of Zr-89-DFO-BODIPY-trastuzumab. The described platform is universally adaptable for simple antibody labeling. C1 [Meimetis, Labros G.; Carlson, Jonathan C.; Weissleder, Ralph] Massachusetts Gen Hosp, Ctr Syst Biol, 185 Cambridge St,CPZN 5206, Boston, MA 02114 USA. [Weissleder, Ralph] Harvard Univ, Sch Med, Dept Syst Biol, 200 Longwood Ave, Boston, MA 02115 USA. [Boros, Eszter; Ran, Chongzhao; Caravan, Peter] Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Dept Radiol, 149 Thirteenth St, Charlestown, MA 02129 USA. RP Weissleder, R (reprint author), Massachusetts Gen Hosp, Ctr Syst Biol, 185 Cambridge St,CPZN 5206, Boston, MA 02114 USA.; Weissleder, R (reprint author), Harvard Univ, Sch Med, Dept Syst Biol, 200 Longwood Ave, Boston, MA 02115 USA.; Boros, E (reprint author), Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Dept Radiol, 149 Thirteenth St, Charlestown, MA 02129 USA. EM eboros@nmr.mgh.harvard.edu; rweissleder@mgh.harvard.edu FU NIH [RO1EB010011, RO1EB009062, 2P50A086355, K99HL125728] FX We are grateful to Dr. Ralph Mazitschek for many helpful discussions, Nicholas Rotile for assistance with PET imaging, Shadi Esfahani and Umar Mahmood for assistance with the HER2+ cell line and Brijesh Bhayana for MALDI-TOF acquisition. The authors acknowledge funding by NIH RO1EB010011, RO1EB009062, 2P50A086355, and K99HL125728. NR 22 TC 5 Z9 5 U1 6 U2 18 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 1043-1802 J9 BIOCONJUGATE CHEM JI Bioconjugate Chem. PD JAN PY 2016 VL 27 IS 1 BP 257 EP 263 DI 10.1021/acs.bioconjchem.5b00630 PG 7 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Chemistry, Multidisciplinary; Chemistry, Organic SC Biochemistry & Molecular Biology; Chemistry GA DB6UQ UT WOS:000368651600028 PM 26684717 ER PT J AU Metzger-Filho, O de Azambuja, E Procter, M Krieguer, M Smiths, I Baselga, J Cameron, D Untch, M Jackisch, C Bell, R Gianni, L Goldhirsch, A Piccart, M Gelber, RD AF Metzger-Filho, Otto de Azambuja, Evandro Procter, Marion Krieguer, Magalie Smiths, Ian Baselga, Jose Cameron, David Untch, Michael Jackisch, Christian Bell, Richard Gianni, Luca Goldhirsch, Aron Piccart, Martine Gelber, Richard D. CA HREA Study Team TI Trastuzumab re-treatment following adjuvant trastuzumab and the importance of distant disease-free interval: the HERA trial experience SO BREAST CANCER RESEARCH AND TREATMENT LA English DT Article DE Breast cancer; Disease-free survival; HER2+ ID METASTATIC BREAST-CANCER; CHEMOTHERAPY; PROGRESSION; DOCETAXEL; PERTUZUMAB; EMTANSINE; THERAPY; RELAPSE; PHASE-3; COHORT AB This retrospective analysis conducted using data from patients enrolled onto the Herceptin Adjuvant has two objectives: The first is to evaluate the impact of the time interval between the end of adjuvant trastuzumab and distant recurrence (TDRI) upon overall survival (OS). The second is to describe the duration of trastuzumab-based regimens in the metastatic setting for patients previously treated with adjuvant trastuzumab. The first objective included 187 patients treated with adjuvant trastuzumab and diagnosed with distant recurrence at 4-year median follow-up. The second objective included data from questionnaires sent to investigators retreating patients with trastuzumab upon distant recurrence: 144 of 156 questionnaires were returned (93 %), and 90 patients were selected based on available clinical information and consent for subsequent studies. There was no statistically significant relationship between TDRI following 1 year of adjuvant trastuzumab and OS from distant recurrence: hazard ratio 0.991, p = 0.46. The median OS from distant recurrence was numerically longer among patients with a TDRI of >12 months (n = 103) than <12 months (n = 84) but not statistically significant (23.7 vs. 17.8 months, p = 0.47). The median duration of first-line trastuzumab-based regimens for patients previously treated with adjuvant trastuzumab and diagnosed with distant disease recurrence was 8.8 months (n = 88). This retrospective, exploratory study suggests that TDRI did not impact on OS measured from distant recurrence. We argue that prospective collection of treatment information beyond disease progression should be included in future clinical studies. C1 [Metzger-Filho, Otto] Dana Farber Canc Inst, Dept Med Oncol, 450 Brookline Ave Yawkey, Boston, MA 02215 USA. [de Azambuja, Evandro] Inst Jules Bordet, Dept Med Oncol, B-1000 Brussels, Belgium. [de Azambuja, Evandro; Krieguer, Magalie] Inst Jules Bordet, Breast European Adjuvant Study Team BrEAST, Ctr Data, B-1000 Brussels, Belgium. [de Azambuja, Evandro; Krieguer, Magalie; Piccart, Martine] Univ Libre Bruxelles, Brussels, Belgium. [Procter, Marion] Frontier Sci Scotland Ltd, Kincraig, Kingussie, Scotland. [Smiths, Ian] Royal Marsden Hosp, Breast Unit, London SW3 6JJ, England. [Smiths, Ian] Inst Canc Res, London SW3 6JB, England. [Baselga, Jose] Mem Sloan Kettering Canc Ctr, 1275 York Ave, New York, NY 10021 USA. [Cameron, David] Univ Edinburgh, Western Gen Hosp, Edinburgh Canc Res Ctr, Crewe Rd South, Edinburgh, Midlothian, Scotland. [Untch, Michael] HELIOS Klin, Dept Gynecol & Obstet, Berlin, Germany. [Untch, Michael] HELIOS Klin, Multidisciplinary Breast Canc Ctr, Berlin, Germany. [Jackisch, Christian] Klinikum Off Enbach, Dept Gynecol & Obstet, Off Enbach, Germany. [Bell, Richard] Deakin Univ, Andrew Love Canc Ctr, Dept Med Oncol, Geelong, Vic 3217, Australia. [Gianni, Luca] San Raffaele Inst, Dept Med Oncol, Milan, Italy. [Goldhirsch, Aron] European Inst Oncol, Milan, Italy. [Goldhirsch, Aron] St Anna Clin, Swiss Ctr Breast Hlth, Lugano, Switzerland. [Piccart, Martine] Inst Jules Bordet, Dept Med, B-1000 Brussels, Belgium. [Gelber, Richard D.] Harvard Univ, Sch Med, Dana Farber Canc Inst,IBCSG,Stat Ctr, Dept Biostat & Computat Biol,Harvard Sch Publ Hlt, 44 Binney St, Boston, MA 02115 USA. RP Metzger-Filho, O (reprint author), Dana Farber Canc Inst, Dept Med Oncol, 450 Brookline Ave Yawkey, Boston, MA 02215 USA. EM otto_metzger@dfci.harvard.edu; evandro.azambuja@bordet.be; marion.procter@frontier-science.co.uk; magalie.krieguer@bordet.be; ian.smith@rmh.nhs.uk; baselgaj@mskcc.org; d.cameron@ed.ac.uk; michael.untch@helios-kliniken.de; christian.jackish@klinikum-offenbach.de; richard@barwonhealth.org.au; l.gianni@hsr.it; aron.goldhirsch@ibcsg.org; martine.piccart@bordet.be; gelber@jimmy.harvard.edu FU NCI NIH HHS [P30 CA008748] NR 21 TC 0 Z9 0 U1 1 U2 3 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 2016 VL 155 IS 1 BP 127 EP 132 DI 10.1007/s10549-015-3656-0 PG 6 WC Oncology SC Oncology GA DC1VB UT WOS:000369004200013 PM 26708471 ER PT J AU Freedman, RA Fedewa, SA Punglia, RS Lin, CC Ward, EM Jemal, A Sineshaw, HM AF Freedman, Rachel A. Fedewa, Stacey A. Punglia, Rinaa S. Lin, Chun Chieh Ward, Elizabeth M. Jemal, Ahmedin Sineshaw, Helmneh M. TI Factors associated with radiation therapy incompletion for patients with early-stage breast cancer SO BREAST CANCER RESEARCH AND TREATMENT LA English DT Article DE Breast cancer; Radiation; Incomplete treatment ID LUMPECTOMY PLUS TAMOXIFEN; OLDER WOMEN; ELDERLY-WOMEN; ADJUVANT TRASTUZUMAB; CONSERVATION THERAPY; LOCAL THERAPY; SURGERY; RADIOTHERAPY; MASTECTOMY; AGE AB Purpose The purpose of the study was to examine factors associated with adjuvant radiation treatment (RT) incompletion for women with breast cancer within a large national cancer database. Methods We identified 394,334 women diagnosed with stage I III breast cancer during 2004-2012 in the national cancer database who initiated adjuvant external beam adjuvant RT and examined the proportion of women not completing treatment. We used multivariable logistic regression to examine patient, clinical, and facility factors associated with RT incompletion for those who had breast conserving surgery (BCS), defined as <15 fractions and <3990 centiGray [cGy] (accounting for adoption of hypofractionation), and mastectomy (PMRT, defined as <5000 cGy and <25 fractions), separately. We also examined RT incompletion after BCS using more traditional definitions of <25 fractions and <4500 cGy for diagnosis years <2010. Results Among the 319,003 women who underwent BCS and the 75,331 women who underwent mastectomy and initiated RT, 98.4 and 97.8 % completed radiation, respectively. In adjusted analyses, older age was associated with RT incompletion (odds ratio [O.R.] for age >= 80 = 2.53 for BCS-treated, 95 % confidence interval [CI] 2.19-2.92; O.R. for PMRT incompletion = 2.33, 95 % CI 1.84-2.96; both versus age <50). In addition, those with >2 comorbidities and lower -risk disease had higher odds of RT incompletion. After defining RT completion using more traditional definitions, 94.0 % completed treatment. Conclusions Reassuringly, we found a very low proportion of patients not completing RT, though we observed a higher likelihood for treatment incompletion in some subgroups, most notably older women. Further studies should focus on reasons for treatment discontinuation in populations at risk for suboptimal treatment. C1 [Freedman, Rachel A.; Punglia, Rinaa S.] Dana Farber Canc Inst, 450 Brookline Ave, Boston, MA 02215 USA. [Fedewa, Stacey A.; Lin, Chun Chieh; Ward, Elizabeth M.; Jemal, Ahmedin; Sineshaw, Helmneh M.] Amer Canc Soc, 250 Williams St NW, Atlanta, GA 30303 USA. RP Freedman, RA (reprint author), Dana Farber Canc Inst, 450 Brookline Ave, Boston, MA 02215 USA. EM rafreedman@partners.org FU American Cancer Society Intramural Research; Susan G. Komen for the Cure FX American Cancer Society Intramural Research and Susan G. Komen for the Cure (RAF). NR 41 TC 0 Z9 0 U1 1 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 2016 VL 155 IS 1 BP 187 EP 199 DI 10.1007/s10549-015-3660-4 PG 13 WC Oncology SC Oncology GA DC1VB UT WOS:000369004200020 PM 26683609 ER PT J AU Tuomela, JM Sandholm, JA Kaakinen, M Hayden, KL Haapasaari, KM Jukkola-Vuorinen, A Kauppila, JH Lehenkari, PP Harris, KW Graves, DE Selander, KS AF Tuomela, Johanna M. Sandholm, Jouko A. Kaakinen, Mika Hayden, Katherine L. Haapasaari, Kirsi-Maria Jukkola-Vuorinen, Arja Kauppila, Joonas H. Lehenkari, Petri P. Harris, Kevin W. Graves, David E. Selander, Katri S. TI Telomeric G-quadruplex-forming DNA fragments induce TLR9-mediated and LL-37-regulated invasion in breast cancer cells in vitro SO BREAST CANCER RESEARCH AND TREATMENT LA English DT Article DE Toll-like receptor 9; Invasion; LL-37; Telomeric G-quadruplex DNA; 9-mer hairpin DNA ID TOLL-LIKE RECEPTOR-9; ANTIMICROBIAL PROTEIN HCAP18/LL-37; SUBCELLULAR-LOCALIZATION; HELICOBACTER-PYLORI; NUCLEASE RESISTANCE; CELLULAR INVASION; GENE-EXPRESSION; DENDRITIC CELLS; BACTERIAL-DNA; HUMAN GENOME AB Toll-like receptor 9 (TLR9) is a cellular DNA-receptor widely expressed in cancers. We previously showed that synthetic and self-derived DNA fragments induce TLR9-mediated breast cancer cell invasion in vitro. We investigated here the invasive effects of two nuclease-resistant DNA fragments, a 9-mer hairpin, and a G-quadruplex DNA based on the human telomere sequence, both having native phosphodiester backbone. Cellular uptake of DNAs was investigated with immunofluorescence, invasion was studied with Matrigel-assays, and mRNA and protein expression were studied with qPCR and Western blotting and protease activity with zymograms. TLR9 expression was suppressed through siRNA. Although both DNAs induced TLR9-mediated changes in pro-invasive mRNA expression, only the telomeric G-quadruplex DNA significantly increased cellular invasion. This was inhibited with GM6001 and aprotinin, suggesting MMP- and serine protease mediation. Furthermore, complexing with LL-37, a cathelicidin-peptide present in breast cancers, increased 9-mer hairpin and G-quadruplex DNA uptake into the cancer cells. However, DNA/LL-37 complexes decreased invasion, as compared with DNA-treatment alone. Invasion studies were conducted also with DNA fragments isolated from neoadjuvant chemotherapy-treated breast tumors. Also such DNA induced breast cancer cell invasion in vitro. As with the synthetic DNAs, this invasive effect was reduced by complexing the neoadjuvant tumor-derived DNAs with LL-37. We conclude that 9-mer hairpin and G-quadruplex DNA fragments are nuclease-resistant DNA structures that can act as invasion-inducing TLR9 ligands. Their cellular uptake and the invasive effects are regulated via LL-37. Although such structures may be present in chemotherapy-treated tumors, the clinical significance of this finding requires further studying. C1 [Tuomela, Johanna M.; Sandholm, Jouko A.; Harris, Kevin W.; Selander, Katri S.] Univ Alabama Birmingham, Dept Med, Div Hematol Oncol, Birmingham, AL 35294 USA. [Tuomela, Johanna M.; Sandholm, Jouko A.; Harris, Kevin W.; Graves, David E.; Selander, Katri S.] Univ Alabama Birmingham, Ctr Comprehens Canc, Birmingham, AL 35294 USA. [Tuomela, Johanna M.] Univ Turku, Inst Biomed, Dept Cell Biol & Anat, Turku, Finland. [Sandholm, Jouko A.] Univ Turku, Turku Ctr Biotechnol, Turku, Finland. [Sandholm, Jouko A.] Abo Akad Univ, Turku, Finland. [Kaakinen, Mika; Kauppila, Joonas H.; Lehenkari, Petri P.] Univ Oulu, Dept Anat & Cell Biol, Oulu, Finland. [Kaakinen, Mika] Univ Oulu, Fac Biochem & Mol Med, Oulu Ctr Cell Matrix Res, Bioctr Oulu, Oulu, Finland. [Hayden, Katherine L.; Graves, David E.] Univ Alabama Birmingham, Dept Chem, Birmingham, AL 35294 USA. [Haapasaari, Kirsi-Maria; Kauppila, Joonas H.; Lehenkari, Petri P.] Univ Oulu, Dept Pathol, Oulu, Finland. [Jukkola-Vuorinen, Arja] Univ Hosp Oulu, Dept Oncol, Oulu, Finland. [Lehenkari, Petri P.] Oulu Univ Hosp, Dept Surg, Oulu, Finland. [Harris, Kevin W.] Birmingham Vet Affairs Med Ctr, Birmingham, AL USA. [Selander, Katri S.] Lapland Cent Hosp, Dept Pathol, Rovaniemi, Finland. [Selander, Katri S.] UAB, Dept Chem, CHEM 201 1720 2nd Ave South, Birmingham, AL 35294 USA. RP Selander, KS (reprint author), Univ Alabama Birmingham, Dept Med, Div Hematol Oncol, Birmingham, AL 35294 USA.; Selander, KS (reprint author), Univ Alabama Birmingham, Ctr Comprehens Canc, Birmingham, AL 35294 USA.; Selander, KS (reprint author), Lapland Cent Hosp, Dept Pathol, Rovaniemi, Finland.; Selander, KS (reprint author), UAB, Dept Chem, CHEM 201 1720 2nd Ave South, Birmingham, AL 35294 USA. EM Katriselander@uabmc.edu RI Lehenkari, Petri/O-3009-2016; OI Lehenkari, Petri/0000-0002-0055-5183; Kauppila, Joonas/0000-0001-6740-3726; Tuomela, Johanna/0000-0003-4390-4563 FU Department of Defense [W81XWH-10-1-0308]; Finnish Cancer Organizations; Finnish Cultural Foundation; Maud Kuistila Memorial Foundation; Orion-Farmos Research Foundation; K. Albin Johansson Foundation; Cancer Foundation of South-Western Finland FX This work was funded by grants from the Department of Defense (W81XWH-10-1-0308, K.S.S., D.G.), Finnish Cancer Organizations (J.S.), Finnish Cultural Foundation (J.T.), Maud Kuistila Memorial Foundation (J.T.), Orion-Farmos Research Foundation (J.T.), K. Albin Johansson Foundation (J.T.), and Cancer Foundation of South-Western Finland (J.T). NR 51 TC 2 Z9 2 U1 1 U2 3 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 2016 VL 155 IS 2 BP 261 EP 271 DI 10.1007/s10549-016-3683-5 PG 11 WC Oncology SC Oncology GA DC1US UT WOS:000369003100006 PM 26780557 ER PT J AU Biswas, S Atienza, P Chipman, J Blackford, AL Arun, B Hughes, K Parmigiani, G AF Biswas, Swati Atienza, Philamer Chipman, Jonathan Blackford, Amanda L. Arun, Banu Hughes, Kevin Parmigiani, Giovanni TI A two-stage approach to genetic risk assessment in primary care SO BREAST CANCER RESEARCH AND TREATMENT LA English DT Article DE BRCA1; BRCA2; BRCAPRO; BayesMendel; CancerGene ID CARRIER PROBABILITY ESTIMATION; PREDICTION MODEL BRCAPRO; FAMILY-HISTORY; OVARIAN-CANCER; BREAST; MUTATIONS; SUSCEPTIBILITY; MARKERS; WOMEN AB Genetic risk prediction models such as BRCAPRO are used routinely in genetic counseling for identification of potential BRCA1 and BRCA2 mutation carriers. They require extensive information on the counselee and her family history, and thus are not practical for primary care. To address this gap, we develop and test a two-stage approach to genetic risk assessment by balancing the tradeoff between the amount of information used and accuracy achieved. The first stage is intended for primary care wherein limited information is collected and analyzed using a simplified version of BRCAPRO. If the assessed risk is sufficiently high, more extensive information is collected and the full BRCAPRO is used (stage two: intended for genetic counseling). We consider three first-stage tools: BRCAPROLYTE, BRCAPROLYTE-Plus, and BRCAPROLYTE-Simple. We evaluate the two-stage approach on independent clinical data on probands with family history of breast and ovarian cancers, and BRCA genetic test results. These include population-based data on 1344 probands from Newton-Wellesley Hospital and mostly high-risk family data on 2713 probands from Cancer Genetics Network and MD Anderson Cancer Center. We use discrimination and calibration measures, appropriately modified to evaluate the overall performance of a two-stage approach. We find that the proposed two-stage approach has very limited loss of discrimination and comparable calibration as BRCAPRO. It identifies a similar number of carriers without requiring a full family history evaluation on all probands. We conclude that the two-stage approach allows for practical large-scale genetic risk assessment in primary care. C1 [Biswas, Swati] Univ Texas Dallas, Dept Math Sci, FO 35,800 West Campbell Rd, Dallas, TX 75080 USA. [Atienza, Philamer] Univ N Texas, Hlth Sci Ctr, Sch Publ Hlth, Dept Biostat, Ft Worth, TX USA. [Chipman, Jonathan] Vanderbilt Univ Sch Med, Dept Biostat, Nashville, TN USA. [Blackford, Amanda L.] Johns Hopkins Univ, Sch Med, Div Biostat & Bioinformat, Baltimore, MD USA. [Arun, Banu] Univ Texas MD Anderson Canc Ctr, Dept Breast Med Oncol, Houston, TX 77030 USA. [Arun, Banu] Univ Texas MD Anderson Canc Ctr, Clin Canc Genet, Houston, TX 77030 USA. [Hughes, Kevin] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Hughes, Kevin] Harvard Univ, Sch Med, Boston, MA USA. [Parmigiani, Giovanni] Dana Farber Canc lnst, Dept Biostat & Computat Biol, Boston, MA 02115 USA. [Parmigiani, Giovanni] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. RP Biswas, S (reprint author), Univ Texas Dallas, Dept Math Sci, FO 35,800 West Campbell Rd, Dallas, TX 75080 USA. EM swati.biswas@utdallas.edu FU National Cancer Institute [1R03CA173834-02, 2P30CA006516-47] FX This work was supported in part by the following Grants: 1R03CA173834-02 and 2P30CA006516-47 from the National Cancer Institute. NR 22 TC 0 Z9 0 U1 0 U2 1 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 2016 VL 155 IS 2 BP 375 EP 383 DI 10.1007/s10549-016-3686-2 PG 9 WC Oncology SC Oncology GA DC1US UT WOS:000369003100016 PM 26786860 ER PT S AU Clancy, CJ Nguyen, MH AF Clancy, Cornelius J. Nguyen, M. Hong BE Calderone, R Cihlar, R TI Diagnostic Methods for Detection of Blood-Borne Candidiasis SO CANDIDA SPECIES: METHODS AND PROTOCOLS SE Methods in Molecular Biology LA English DT Article; Book Chapter DE Candidemia; Invasive candidiasis; Intra-abdominal candidiasis; beta-D-glucan; Fungitell; Polymerase chain reaction (PCR); T2Candida; Diagnosis; Bayesian ID PLACEBO-CONTROLLED TRIAL; CRITICALLY-ILL PATIENTS; INTENSIVE-CARE-UNIT; D-GLUCAN ASSAY; INVASIVE CANDIDIASIS; SURGICAL-PATIENTS; FUNGAL-INFECTIONS; DOUBLE-BLIND; FLUCONAZOLE PROPHYLAXIS; HIGH-RISK AB beta-D-glucan (Fungitell) and polymerase chain reaction-based (T2Candida) assays of blood samples are FDA-approved adjuncts to cultures for diagnosing candidemia and other types of invasive candidiasis, but their clinical roles are unclear. In this chapter, we describe laboratory protocols for performing Fungitell and T2Candida assays. We then discuss step-by-step methods for interpreting test results at the bedside using a Bayesian framework, and for incorporating assays into rational patient management strategies. Prior to interpreting results, clinicians must recognize that test performance varies based on the type of invasive candidiasis being diagnosed. In general, the type of invasive candidiasis that is most likely in a given patient can be identifi ed, and the pretest likelihood of disease estimated. From there, positive and negative predictive values (PPV, NPV) for an assay can be calculated. At a population level, tests can be incorporated into screening strategies for antifungal treatment. NPV and PPV thresholds can be defined for discontinuing antifungal prophylaxis or initiating preemptive treatment, respectively. Using the thresholds, it is possible to assign windows of pretest likelihood for invasive candidiasis (and corresponding patient populations) in which tests are most likely to valuable. At the individual patient level, tests may be useful outside of the windows proposed for screening populations. The interpretive and clinical decision-making processes we discuss will be applicable to other diagnostic assays as they enter the clinic, and to existing assays as more data emerge from various populations. C1 [Clancy, Cornelius J.; Nguyen, M. Hong] VA Pittsburgh Healthcare Syst, Pittsburgh, PA USA. [Clancy, Cornelius J.] Univ Pittsburgh, Dept Med, Pittsburgh, PA USA. [Clancy, Cornelius J.] Univ Pittsburgh, Div Infect Dis, Pittsburgh, PA USA. RP Clancy, CJ (reprint author), VA Pittsburgh Healthcare Syst, Pittsburgh, PA USA.; Clancy, CJ (reprint author), Univ Pittsburgh, Dept Med, Pittsburgh, PA USA.; Clancy, CJ (reprint author), Univ Pittsburgh, Div Infect Dis, Pittsburgh, PA USA. NR 36 TC 1 Z9 1 U1 0 U2 2 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DR, STE 208, TOTOWA, NJ 07512-1165 USA SN 1064-3745 BN 978-1-4939-3052-4; 978-1-4939-3051-7 J9 METHODS MOL BIOL JI Methods Mol. Biol. PY 2016 VL 1356 BP 215 EP 238 DI 10.1007/978-1-4939-3052-4_16 D2 10.1007/978-1-4939-3052-4 PG 24 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Microbiology; Mycology SC Biochemistry & Molecular Biology; Microbiology; Mycology GA BE2EJ UT WOS:000369087600017 PM 26519076 ER PT J AU Brennan, JM Sketch, MH Dai, D Trilesskaya, M Al-Hejily, W Rao, SV Brilakis, E Messenger, JC Shaw, RE Anstrom, KJ Peterson, ED Douglas, PS AF Brennan, J. Matthew Sketch, Michael H., Jr. Dai, David Trilesskaya, Marina Al-Hejily, Wesam Rao, Sunil V. Brilakis, Emmanouil Messenger, John C. Shaw, Richard E. Anstrom, Kevin J. Peterson, Eric D. Douglas, Pamela S. TI Safety and Clinical Effectiveness of Drug-Eluting Stents for Saphenous Vein Graft Intervention in Older Individuals: Results From the Medicare-Linked National Cardiovascular Data Registry (R) CathPCI Registry (R) (2005-2009) SO CATHETERIZATION AND CARDIOVASCULAR INTERVENTIONS LA English DT Article DE saphenous vein grafts; drug-eluting stents; bare metal stents; outcomes ID BARE-METAL STENTS; FOLLOW-UP; TRIAL; LESIONS AB Objectives: To evaluate the safety of drug-eluting stents (DES) when treating patients with failing saphenous vein grafts (SVG). Background: DES reduce target vessel revascularization in patients with failing SVGs; however, compared with bare metal stents (BMS), DES have been variably associated with increased mortality. Methods: Clinical records from National Cardiovascular Data Registry (R) CathPCI Registry (R) (49,325 older individuals [>= 65 years] who underwent SVG stenting 2005-2009) were linked to Medicare claims to create a longitudinal record. Death, myocardial infarction (MI), and urgent revascularization with DES versus BMS were evaluated to 3 years using propensity matching (PM). Results were stratified by clinical presentation (acute coronary syndrome [ACS], non-ACS), previous lesion treatment (in-stent, de novo), and graft segment (aortic, body, distal anastomosis). Results: In this older cohort (median age, 75 years), acute presentations were prevalent (ACS, 69%; TIMI flow <3, 45%), and adverse clinical outcomes were common by 3 years (death, 24.5%; MI, 14.6%; urgent revascularization, 29.5%). Among DES patients (n = 31,403), 3-year mortality was lower (vs. BMS) (22.7% vs. 28.0%, P < 0.001; PM hazard ratio [HR] 0.87, 95% confidence interval 0.83-0.91), and no difference was observed in the adjusted risk for MI (PM HR 0.97, 0.91 to 1.03) or urgent revascularization (PM HR 1.04, 0.99-1.08). These findings were independent of clinical presentation, previous lesion treatment, and graft segment (P interaction, ns). Conclusions: In this large SVG PCI cohort, all-cause mortality was lower among those receiving DES, and no difference in MI or urgent revascularization was observed to 3 years. (C) 2015 Wiley Periodicals, Inc. C1 [Brennan, J. Matthew; Sketch, Michael H., Jr.; Dai, David; Al-Hejily, Wesam; Rao, Sunil V.; Anstrom, Kevin J.; Peterson, Eric D.; Douglas, Pamela S.] Duke Univ, Med Ctr, Div Cardiol, Dept Med, Durham, NC 27710 USA. [Trilesskaya, Marina] Calif Pacific Med Ctr, Div Cardiol, Dept Internal Med, San Francisco, CA USA. [Brilakis, Emmanouil] Vet Affairs North Texas Healthcare Syst, Div Cardiol, Dept Internal Med, Dallas, TX USA. [Brilakis, Emmanouil] Univ Texas SW Med Ctr Dallas, Dallas, TX 75390 USA. [Messenger, John C.] Denver Vet Affairs Med Ctr, Div Cardiol, Dept Med, Denver, CO USA. [Shaw, Richard E.] Sutter Pacif Heart Ctr, Div Cardiol, Dept Clin Informat, San Francisco, CA USA. RP Brennan, JM (reprint author), Duke Univ, Med Ctr, Div Cardiol, 2400 Pratt St,Rm 0311 Terrace Level, Durham, NC 27705 USA. EM j.matthew.brennan@dm.duke.edu FU Sanofi; Janssen; St Jude Medical; Terumo; Asahi; Abbott Vascular; Boston Scientific; Guerbet; AstraZeneca; Eli Lilly Company; Medtronic; American College of Cardiology; American Heart Association; Janssen Pharmaceuticals; Society of Thoracic Surgeons FX Dr. Brennan has no relevant disclosures to report. Dr. Sketch has no relevant disclosures to report. Dr. Dai has no relevant disclosures to report. Dr. Trilesskaya has no relevant disclosure to report. Dr. Al-Hejily has no relevant disclosure to report. Dr. Rao has non relevant disclosures to report. Dr. Brilakis reports honoraria/speaker fees from Sanofi (modest), Janssen (modest), St Jude Medical (modest), Terumo (modest), Asahi (significant), Abbott Vascular (modest), and Boston Scientific (significant); research grant from Guerbet (significant); spouse is an employee of Medtronic (significant). Dr. Messenger has no relevant disclosure to report. Dr. Shaw has no relevant disclosures to report. Dr. Anstrom reports research support from AstraZeneca (significant), Eli Lilly & Company (significant), and Medtronic (significant); has served as a consultant for Abbott Vascular (modest), AstraZeneca (modest), Bristol-Meyers Squibb (modest), Gilead (modest), Pfizer (modest), GSK (modest), Promedior (modest), and Ikaria (modest); has served on data monitoring committees for NIH (modest), University of North Carolina (modest), University of Miami (modest), Forest (modest), Pfizer (modest), GSK (modest), and Vertex (modest); and has an equity interest in Biscardia. Dr. Peterson reports research funding for the American College of Cardiology, American Heart Association, Eli Lilly & Company, Janssen Pharmaceuticals, and Society of Thoracic Surgeons (all significant); consulting (including CME) for Merck & Co. (modest), Boehringer Ingelheim, Genentech, Janssen Pharmaceuticals, and Sanofi-Aventis (all significant). Dr. Douglas has no relevant disclosures to report. NR 11 TC 2 Z9 2 U1 0 U2 3 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1522-1946 EI 1522-726X J9 CATHETER CARDIO INTE JI Catheter. Cardiovasc. Interv. PD JAN 1 PY 2016 VL 87 IS 1 BP 43 EP 49 DI 10.1002/ccd.25979 PG 7 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA DB7ML UT WOS:000368699500015 PM 26153480 ER PT J AU Miyamoto, DT Zheng, Y Wittner, BS Lee, RJ Zhu, H Broderick, KT Desai, R Brannigan, BW Arora, KS Dahl, DM Sequist, LV Smith, MR Kapur, R Wu, CL Shioda, T Ramaswamy, S Ting, DT Toner, M Maheswaran, S Haber, DA AF Miyamoto, David T. Zheng, Yu Wittner, Ben S. Lee, Richard J. Zhu, Huili Broderick, Katherine T. Desai, Rushil Brannigan, Brian W. Arora, Kshitij S. Dahl, Douglas M. Sequist, Lecia V. Smith, Matthew R. Kapur, Ravi Wu, Chin-Lee Shioda, Toshi Ramaswamy, Sridhar Ting, David T. Toner, Mehmet Maheswaran, Shyamala Haber, Daniel A. TI Single cell RNA-sequencing of circulating tumor cells SO CLINICAL CANCER RESEARCH LA English DT Meeting Abstract CT Meeting of the American-Association-for-Cancer-Research (AACR) Precision Medicine Series - Integrating Clinical Genomics and Cancer Therapy CY JUN 13-16, 2015 CL Salt Lake, UT SP Amer Assoc Canc Res C1 [Miyamoto, David T.; Zheng, Yu; Wittner, Ben S.; Lee, Richard J.; Zhu, Huili; Broderick, Katherine T.; Desai, Rushil; Brannigan, Brian W.; Arora, Kshitij S.; Dahl, Douglas M.; Sequist, Lecia V.; Smith, Matthew R.; Kapur, Ravi; Wu, Chin-Lee; Shioda, Toshi; Ramaswamy, Sridhar; Ting, David T.; Toner, Mehmet; Maheswaran, Shyamala; Haber, Daniel A.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Charlestown, MA USA. RI bebarta, vikhyat/K-3476-2015 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 1078-0432 EI 1557-3265 J9 CLIN CANCER RES JI Clin. Cancer Res. PD JAN 1 PY 2016 VL 22 SU 1 MA IA09 PG 2 WC Oncology SC Oncology GA DC2XS UT WOS:000369082700007 ER PT J AU Wu, CJ AF Wu, Catherine J. TI The evolutionary landscape of CLL: Therapeutic implications SO CLINICAL CANCER RESEARCH LA English DT Meeting Abstract CT Meeting of the American-Association-for-Cancer-Research (AACR) Precision Medicine Series - Integrating Clinical Genomics and Cancer Therapy CY JUN 13-16, 2015 CL Salt Lake, UT SP Amer Assoc Canc Res C1 [Wu, Catherine J.] Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 EI 1557-3265 J9 CLIN CANCER RES JI Clin. Cancer Res. PD JAN 1 PY 2016 VL 22 SU 1 MA IA03 PG 2 WC Oncology SC Oncology GA DC2XS UT WOS:000369082700003 ER PT J AU Katayama, R Sakashita, T Yanagitani, N Ninomiya, H Horiike, A Friboulet, L Gainor, JF Motoi, N Dobashi, A Sakata, S Tambo, Y Kitazono, S Sato, S Koike, S Iafrate, AJ Mino-Kenudson, M Ishikawa, Y Shaw, AT Engelman, JA Takeuchi, K Nishio, M Fujita, N AF Katayama, Ryohei Sakashita, Takuya Yanagitani, Noriko Ninomiya, Hironori Horiike, Atsushi Friboulet, Luc Gainor, Justin F. Motoi, Noriko Dobashi, Akito Sakata, Seiji Tambo, Yuichi Kitazono, Satoru Sato, Shigeo Koike, Sumie Iafrate, A. John Mino-Kenudson, Mari Ishikawa, Yuichi Shaw, Alice T. Engelman, Jeffrey A. Takeuchi, Kengo Nishio, Makoto Fujita, Naoya TI P-glycoprotein Mediates Ceritinib Resistance in Anaplastic Lymphoma Kinase-rearranged Non-small Cell Lung Cancer SO EBIOMEDICINE LA English DT Article DE ALK; Tyrosine kinase; Resistance; Ceritinib; Crizotinib; P-glycoprotein ID ALK INHIBITOR CRIZOTINIB; SIDE-POPULATION; BREAST-CANCER; MULTIDRUG-RESISTANCE; BRAIN ACCUMULATION; STEM-CELLS; IN-VIVO; MUTATIONS; MS-209; EGFR AB The anaplastic lymphoma kinase (ALK) fusion oncogene is observed in 3%-5% of non-small cell lung cancer (NSCLC). Crizotinib and ceritinib, a next-generation ALK tyrosine kinase inhibitor (TKI) active against crizotinib-refractory patients, are clinically available for the treatment of ALK-rearranged NSCLC patients, and multiple next-generation ALK-TKIs are currently under clinical evaluation. These ALK-TKIs exhibit robust clinical activity in ALK-rearranged NSCLC patients; however, the emergence of ALK-TKI resistance restricts the therapeutic effect. To date, various secondary mutations or bypass pathway activation-mediated resistance have been identified, but large parts of the resistance mechanism are yet to be identified. Here, we report the discovery of p-glycoprotein (P-gp/ABCB1) overexpression as a ceritinib resistance mechanism in ALK-rearranged NSCLC patients. P-gp exported ceritinib and its overexpression conferred ceritinib and crizotinib resistance, but not to PF-06463922 or alectinib, which are next-generation ALK inhibitors. Knockdown of ABCB1 or P-gp inhibitors sensitizes the patient-derived cancer cells to ceritinib, in vitro and in vivo. P-gp overexpression was identified in three out of 11 cases with in ALK-rearranged crizotinib or ceritinib resistant NSCLC patients. Our study suggests that alectinib, PF-06463922, or P-gp inhibitor with ceritinib could overcome the ceritinib or crizotinib resistance mediated by P-gp overexpression. (C) 2015 The Authors. Published by Elsevier B.V. C1 [Katayama, Ryohei; Sakashita, Takuya; Sato, Shigeo; Koike, Sumie; Fujita, Naoya] Japanese Fdn Canc Res, Ctr Canc Chemotherapy, Tokyo 1358550, Japan. [Sakashita, Takuya] Univ Tokyo, Grad Sch Frontier Sci, Dept Med Genome Sci, Tokyo 1088639, Japan. [Yanagitani, Noriko; Horiike, Atsushi; Tambo, Yuichi; Kitazono, Satoru; Nishio, Makoto] Japanese Fdn Canc Res, Canc Inst Hosp, Tokyo 1358550, Japan. [Ninomiya, Hironori; Motoi, Noriko; Dobashi, Akito; Sakata, Seiji; Ishikawa, Yuichi; Takeuchi, Kengo] Japanese Fdn Canc Res, Inst Canc, Tokyo 1358550, Japan. [Friboulet, Luc; Gainor, Justin F.; Shaw, Alice T.; Engelman, Jeffrey A.] Massachusetts Gen Hosp, Ctr Canc, Charlestown, MA 02129 USA. [Iafrate, A. John; Mino-Kenudson, Mari] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. RP Fujita, N (reprint author), Japanese Fdn Canc Res, Ctr Canc Chemotherapy, Tokyo 1358550, Japan.; Nishio, M (reprint author), Japanese Fdn Canc Res, Canc Inst Hosp, Tokyo 1358550, Japan.; Katayama, R (reprint author), Japanese Fdn Canc Res, Ctr Canc Chemotherapy, Koto Ku, 3-8-31 Ariake, Tokyo 1358550, Japan. EM ryohei.katayama@jfcr.or.jp; mnishio@jfcr.or.jp; naoya.fujita@jfcr.or.jp RI Motoi, Noriko/A-9718-2009; friboulet, luc/N-7276-2015 OI Motoi, Noriko/0000-0001-7098-3311; friboulet, luc/0000-0002-1129-4978 NR 44 TC 10 Z9 10 U1 1 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 2352-3964 J9 EBIOMEDICINE JI EBioMedicine PD JAN PY 2016 VL 3 BP 54 EP 66 DI 10.1016/j.ebiom.2015.12.009 PG 13 WC Medicine, General & Internal SC General & Internal Medicine GA DC1ZA UT WOS:000369015800013 PM 26870817 ER PT J AU Richard, J Veillette, M Ding, SL Zoubchenok, D Alsahafi, N Coutu, M Brassard, N Park, J Courter, JR Melillo, B Smith, AB Shaw, GM Hahn, BH Sodroski, J Kaufmann, DE Finzi, A AF Richard, Jonathan Veillette, Maxime Ding, Shilei Zoubchenok, Daria Alsahafi, Nirmin Coutu, Mathieu Brassard, Nathalie Park, Jongwoo Courter, Joel R. Melillo, Bruno Smith, Amos B., III Shaw, George M. Hahn, Beatrice H. Sodroski, Joseph Kaufmann, Daniel E. Finzi, Andres TI Small CD4 Mimetics Prevent HIV-1 Uninfected Bystander CD4+ T Cell Killing Mediated by Antibody-dependent Cell-mediated Cytotoxicity SO EBIOMEDICINE LA English DT Article DE HIV-1; Envelope glycoproteins; gp120; CD4; CD4-bound conformation; Non-neutralizing antibodies; ADCC; CD4-mimetics; Bystander killing ID HUMAN-IMMUNODEFICIENCY-VIRUS; HTLV-III/LAV ENVELOPE; DISEASE PROGRESSION; INFECTED PATIENTS; DENDRITIC CELLS; AIDS PATIENTS; NK CELLS; GLYCOPROTEIN; RECEPTOR; GP120 AB Human immunodeficiency virus type 1 (HIV-1) infection causes a progressive depletion of CD4+ T cells. Despite its importance for HIV-1 pathogenesis, the precise mechanismsunderlying CD4+ T-cell depletion remain incompletely understood. Here we make the surprising observation that antibody-dependent cell-mediated cytotoxicity (ADCC) mediates the death of uninfected bystander CD4+ T cells in cultures of HIV-1-infected cells. While HIV-1-infected cells are protected from ADCC by the action of the viral Vpu and Nef proteins, uninfected bystander CD4+ T cells bind gp120 shed from productively infected cells and are efficiently recognized by ADCC-mediating antibodies. Thus, gp120 shedding represents a viral mechanism to divert ADCC responses towards uninfected bystander CD4+ T cells. Importantly, CD4-mimetic molecules redirect ADCC responses from uninfected bystander cells to HIV-1-infected cells; therefore, CD4-mimetic compounds might have therapeutic utility in new strategies aimed at specifically eliminating HIV-1-infected cells. (C) 2015 The Authors. Published by Elsevier B.V. C1 [Richard, Jonathan; Veillette, Maxime; Ding, Shilei; Zoubchenok, Daria; Alsahafi, Nirmin; Coutu, Mathieu; Brassard, Nathalie; Kaufmann, Daniel E.; Finzi, Andres] Ctr Rech CHUM, Montreal, PQ H2X 0A9, Canada. [Richard, Jonathan; Veillette, Maxime; Ding, Shilei; Zoubchenok, Daria; Coutu, Mathieu; Finzi, Andres] Univ Montreal, Dept Microbiol Infectiol & Immunol, Montreal, PQ H2X 0A9, Canada. [Park, Jongwoo; Courter, Joel R.; Melillo, Bruno; Smith, Amos B., III] Univ Penn, Sch Arts & Sci, Dept Chem, Philadelphia, PA 19104 USA. [Shaw, George M.; Hahn, Beatrice H.] Univ Penn, Perelman Sch Med, Dept Med, Philadelphia, PA 19104 USA. [Shaw, George M.; Hahn, Beatrice H.] Univ Penn, Perelman Sch Med, Dept Microbiol, Philadelphia, PA 19104 USA. [Sodroski, Joseph] Harvard Univ, Sch Med, Dept Canc Immunol & AIDS, Dana Farber Canc Inst, Boston, MA 02115 USA. [Sodroski, Joseph] Harvard Univ, Sch Med, Div Aids, Dept Microbiol & Immunobiol, Boston, MA 02115 USA. [Sodroski, Joseph] Harvard Univ, Sch Publ Hlth, Dept Immunol & Infect Dis, Boston, MA 02115 USA. [Kaufmann, Daniel E.] MIT, Ragon Inst, Massachusetts Gen Hosp, Cambridge, MA 02139 USA. [Kaufmann, Daniel E.] Harvard, Cambridge, MA 02139 USA. [Kaufmann, Daniel E.] Univ Montreal, Dept Med, Montreal, PQ H3C 3T5, Canada. [Kaufmann, Daniel E.] Scripps Res Inst, Ctr HIV AIDS Vaccine Immunol & Immunogen Discover, La Jolla, CA 92037 USA. [Finzi, Andres] McGill Univ, Dept Microbiol & Immunol, Montreal, PQ H3A 2B4, Canada. RP Finzi, A (reprint author), Ctr Rech CHUM, Montreal, PQ H2X 0A9, Canada.; Finzi, A (reprint author), Ctr Rech CHUM, Montreal, PQ H2X 0A9, Canada. EM andres.finzi@umontreal.ca FU Canadian Institutes of Health Research [#119334, #134117, #291485, #29866]; NIAID NIH HHS [NIH AI100645, UM AI100663, UM1 AI100645, UM1 AI100663]; NIGMS NIH HHS [#GM56550, P01 GM056550] NR 90 TC 8 Z9 8 U1 1 U2 4 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 2352-3964 J9 EBIOMEDICINE JI EBioMedicine PD JAN PY 2016 VL 3 BP 122 EP 134 DI 10.1016/j.ebiom.2015.12.004 PG 13 WC Medicine, General & Internal SC General & Internal Medicine GA DC1ZA UT WOS:000369015800020 PM 26870823 ER PT J AU Kita, AE Long, JL AF Kita, Ashley E. Long, Jennifer L. TI Hemangioma SO ENT-EAR NOSE & THROAT JOURNAL LA English DT Editorial Material C1 [Kita, Ashley E.; Long, Jennifer L.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Head & Neck Surg, Los Angeles, CA 90095 USA. [Long, Jennifer L.] VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. RP Kita, AE (reprint author), Univ Calif Los Angeles, David Geffen Sch Med, Dept Head & Neck Surg, Los Angeles, CA 90095 USA. NR 3 TC 0 Z9 0 U1 0 U2 0 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 2016 VL 95 IS 1 BP 19 EP 20 PG 2 WC Otorhinolaryngology SC Otorhinolaryngology GA DB8HS UT WOS:000368758400004 PM 26829680 ER PT J AU Lipton, A Fizazi, K Stopeck, AT Henry, DH Smith, MR Shore, N Martin, M Vadhan-Raj, S Brown, JE Richardson, GE Saad, F Yardley, DA Zhou, K Balakumaran, A Braun, A AF Lipton, A. Fizazi, K. Stopeck, A. T. Henry, D. H. Smith, M. R. Shore, N. Martin, M. Vadhan-Raj, S. Brown, J. E. Richardson, G. E. Saad, F. Yardley, D. A. Zhou, K. Balakumaran, A. Braun, A. TI Effect of denosumab versus zoledronic acid in preventing skeletal-related events in patients with bone metastases by baseline characteristics SO EUROPEAN JOURNAL OF CANCER LA English DT Article DE Denosumab; Zoledronic acid; Bone metastases; Skeletal-related event; Subgroup ID RESISTANT PROSTATE-CANCER; BREAST-CANCER; LUNG-CANCER; SOLID TUMORS; COMPLICATIONS; BISPHOSPHONATES; DISEASE; PREDICTORS AB Background: Analyses of phase III trials showed that denosumab was superior to zoledronic acid (ZA) in preventing skeletal- related events (SREs) irrespective of age, history of SREs, or baseline pain status. This analysis assessed the risk of SREs across additional baseline characteristics. Patients and Methods: Patients (N = 5543) from three phase III trials who had breast cancer, prostate cancer, or other solid tumours and one or more bone metastasis were included. Superiority of denosumab versus ZA in reducing risk of first SRE and first and subsequent SREs was assessed in subgroups defined by the Eastern Cooperative Oncology Group performance status (ECOG PS), bone metastasis location, bone metastasis number, visceral metastasis presence/absence, and urinary N-telopeptide (uNTx) level using Cox proportional hazards and Anderson-Gill models. Subgroups except bone metastasis location were also assessed for each solid tumour type. Results: Compared with ZA, denosumab significantly reduced the risk of first SRE across all subgroups (hazard ratio [HR] ranges: ECOG PS, 0.79-0.84; bone metastasis location, 0.78-0.83; bone metastasis number, 0.78-0.84; visceral metastasis presence/absence, 0.80-0.82; uNTx level, 0.73-0.86) and reduced the risk of first and subsequent SREs in all subgroups (HR ranges: ECOG PS, 0.76-0.83; bone metastasis location, 0.78-0.84; bone metastasis number, 0.79-0.81; visceral metastasis presence/absence, 0.79-0.81; uNTx level, 0.74-0.83). Similar results were observed in subgroups across tumour types. Conclusion: Denosumab was superior to ZA in preventing SREs in patients with bone metastases from advanced cancer, regardless of ECOG PS, bone metastasis number, baseline visceral metastasis presence/absence, and uNTx level. (C) 2015 The Authors. Published by Elsevier Ltd. C1 [Lipton, A.] Penn State Univ, Milton S Hershey Med Ctr, Div Oncol, 500 Univ Dr,Suite CH46, Hershey, PA 17033 USA. [Fizazi, K.] Univ Paris Sud, Inst Gustave Roussy, Dept Med Oncol, Villejuif, France. [Stopeck, A. T.] Stony Brook Canc Ctr, Stony Brook, NY USA. [Henry, D. H.] Penn Hosp, Joan Karnell Canc Ctr, Philadelphia, PA 19107 USA. [Smith, M. R.] Massachusetts Gen Hosp, Ctr Canc, Div Hematol Oncol, Boston, MA USA. [Shore, N.] Carolina Urol Res Ctr, Myrtle Beach, NC USA. [Martin, M.] Univ Complutense, Inst Invest Sanitaria Gregorio Maranon, E-28040 Madrid, Spain. [Vadhan-Raj, S.] Univ Texas MD Anderson Canc Ctr, Dept Sarcoma Med Oncol, Houston, TX 77030 USA. [Brown, J. E.] Univ Sheffield, Acad Unit Clin Oncol, Weston Pk Hosp, Sheffield, S Yorkshire, England. [Richardson, G. E.] Cabrini Med Ctr, Melbourne, Vic, Australia. [Saad, F.] Univ Montreal, Ctr Hosp, Dept Surg, Montreal, PQ, Canada. [Saad, F.] Univ Montreal, Ctr Hosp, Dept Urol, Montreal, PQ, Canada. [Yardley, D. A.] Sarah Cannon Res Inst, Nashville, TN USA. [Yardley, D. A.] Tennessee Oncol, Nashville, TN USA. [Zhou, K.; Balakumaran, A.; Braun, A.] Amgen Inc, Hematol Oncol, Thousand Oaks, CA 91320 USA. [Balakumaran, A.] Merck & Co Inc, Kenilworth, NJ USA. [Braun, A.] Arog Pharmaceut Inc, Dallas, TX USA. RP Lipton, A (reprint author), Penn State Univ, Milton S Hershey Med Ctr, Div Oncol, 500 Univ Dr,Suite CH46, Hershey, PA 17033 USA. EM alipton@hmc.psu.edu FU NCI NIH HHS [P30 CA016672] NR 24 TC 6 Z9 7 U1 2 U2 4 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0959-8049 EI 1879-0852 J9 EUR J CANCER JI Eur. J. Cancer PD JAN PY 2016 VL 53 BP 75 EP 83 DI 10.1016/j.ejca.2015.09.011 PG 9 WC Oncology SC Oncology GA DB8TI UT WOS:000368789100009 PM 26693901 ER PT J AU Ugurel, S Rohmel, J Ascierto, PA Flaherty, KT Grob, JJ Hauschild, A Larkin, J Long, GV Lorigan, P McArthur, GA Ribas, A Robert, C Schadendorf, D Garbe, C AF Ugurel, Selma Roehmel, Joachim Ascierto, Paolo A. Flaherty, Keith T. Grob, Jean Jacques Hauschild, Axel Larkin, James Long, Georgina V. Lorigan, Paul McArthur, Grant A. Ribas, Antoni Robert, Caroline Schadendorf, Dirk Garbe, Claus TI Survival of patients with advanced metastatic melanoma: The impact of novel therapies SO EUROPEAN JOURNAL OF CANCER LA English DT Review DE Melanoma; Therapy; Kinase inhibitors; Immune checkpoint blockers; Survival ID RANDOMIZED CONTROLLED-TRIAL; BRAF-MUTATED MELANOMA; UNTREATED MELANOMA; MEK INHIBITION; CLINICAL-TRIALS; OPEN-LABEL; PHASE-II; IPILIMUMAB; VEMURAFENIB; DABRAFENIB AB The survival of advanced metastatic melanoma has been greatly improved within the past few years. New therapeutic strategies like kinase inhibitors for BRAF-mutant melanoma and immune checkpoint blockers proved to prolong survival times within clinical trials, and many of them have already entered routine clinical use. However, these different treatment modalities have not yet been tested against each other, which complicate therapy decisions. We performed an explorative analysis of survival data from recent clinical trials. Thirty-five Kaplan-Meier survival curves from 17 trials were digitised, re-grouped by matching inclusion criteria and treatment line, and averaged by therapy strategy. Notably, the survival curves grouped by therapy strategy revealed a very high concordance, even if different agents were used. The greatest survival improvement was observed with the combination of BRAF plus MEK inhibitors as well as with Programmed-death-1 (PD1) blockers with or without cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4) blockers, respectively, with these two treatment strategies showing similar survival outcomes. For first-line therapy, averaged survival proportions of patients alive at 12 months were 74.5% with BRAF plus MEK inhibitor treatment versus 71.9% with PD-1 blockade. This explorative comparison shows the kinase inhibitors as similarly effective as immune checkpoint blockers with regard to survival. However, to confirm these first trends for implementation into an individualised treatment of melanoma patients, data from prospective clinical trials comparing the different treatment strategies head-to-head have to be awaited. (C) 2015 Elsevier Ltd. All rights reserved. C1 [Ugurel, Selma; Schadendorf, Dirk] Univ Duisburg Essen, Univ Hosp Essen, Dept Dermatol, D-45122 Essen, Germany. [Ascierto, Paolo A.] Fdn G Pascale, Ist Nazl Tumori, Melanoma Immunotherapy & Innovat Therapy Unit, Naples, Italy. [Flaherty, Keith T.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Grob, Jean Jacques] Timone Hosp, Dept Dermatol, Marseille, France. [Grob, Jean Jacques] Aix Marseille Univ, Marseille, France. [Hauschild, Axel] Univ Hosp Schleswig Holstein, Campus Kiel, D-24105 Kiel, Germany. [Larkin, James] Royal Marsden Hosp NHS Fdn Trust, London, England. [Long, Georgina V.] Melanoma Inst Australia, Sydney, NSW, Australia. [Long, Georgina V.] Univ Sydney, Sydney, NSW 2006, Australia. [Lorigan, Paul] Univ Manchester, Christie NHS Fdn Trust, Manchester, Lancs, England. [McArthur, Grant A.] Peter MacCallum Canc Ctr, East Melbourne, Vic, Australia. [McArthur, Grant A.] Univ Melbourne, Parkville, Vic 3052, Australia. [Ribas, Antoni] Univ Calif Los Angeles, Los Angeles, CA USA. [Robert, Caroline] Gustave Roussy Canc Campus, Villejuif Grand Paris, France. [Garbe, Claus] Univ Tubingen, Dept Dermatol, Ctr Dermatooncol, D-72074 Tubingen, Germany. RP Ugurel, S (reprint author), Univ Hosp Essen, Dept Dermatol, Hufelandstr 55, D-45122 Essen, Germany. EM selma.ugurel@uk-essen.de OI Lorigan, Paul/0000-0002-8875-2164 NR 26 TC 17 Z9 19 U1 4 U2 7 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0959-8049 EI 1879-0852 J9 EUR J CANCER JI Eur. J. Cancer PD JAN PY 2016 VL 53 BP 125 EP 134 DI 10.1016/j.ejca.2015.09.013 PG 10 WC Oncology SC Oncology GA DB8TI UT WOS:000368789100014 PM 26707829 ER EF