FN Thomson Reuters Web of Science™ VR 1.0 PT J AU van den Berk-Clark, C McGuire, J AF van den Berk-Clark, Carissa McGuire, James TI Elderly Homeless Veterans in Los Angeles: Chronicity and Precipitants of Homelessness SO AMERICAN JOURNAL OF PUBLIC HEALTH LA English DT Article ID MINI-MENTAL-STATE; OLDER; PREDICTORS; ILLNESS; ADULTS; ABUSE; WOMEN AB Objectives. We compared the characteristics of chronically homeless and acutely homeless elderly veterans to better understand precipitants of homelessness. Methods. We conducted interviews with 33 chronically and 26 acutely homeless veterans aged 65 years and older receiving transitional housing services in Los Angeles, California, between 2003 and 2005. We asked questions regarding their sociodemographic characteristics and other social status measures. Other precipitants of homelessness were acquired via observation and open-ended and structured questions. Results. Both veterans groups weremore similar than different, with substantial levels of physical, psychiatric, and social impairment. They differed significantly in homelessness history, with chronically homeless veterans having more homelessness episodes and more total time homeless. They were also less educated and had smaller social networks. In response to open-ended questioning, elderly homeless veterans revealed how health and substance use issues interacted with loss of social support and eviction to exacerbate homelessness. Conclusions. Assessment of a range of factors is needed to address risk factors and events leading to homelessness. Further research with larger samples is needed to confirm the characteristics and needs of the elderly homeless veteran population. C1 [van den Berk-Clark, Carissa] US Dept Vet Affairs, St Louis Healthcare Ctr, Washington, DC USA. [McGuire, James] US Dept Vet Affairs, West Los Angles Healthcare Ctr, Washington, DC USA. [van den Berk-Clark, Carissa] Washington Univ, Dept Psychiat, Sch Med, St Louis, MO 63110 USA. RP van den Berk-Clark, C (reprint author), Washington Univ, Dept Psychiat, Sch Med, Med Box 8134, St Louis, MO 63110 USA. EM vandenbc@psychiatry.wustl.edu OI van den Berk-Clark, Carissa/0000-0001-7712-3787 FU Veterans Affairs Greater Los Angeles Healthcare System; National Institute on Drug Abuse Training Grant [T32DA007313] FX The study was supported by the Veterans Affairs Greater Los Angeles Healthcare System; completion of the article was funded by a National Institute on Drug Abuse Training Grant (T32DA007313). NR 35 TC 4 Z9 4 U1 1 U2 13 PU AMER PUBLIC HEALTH ASSOC INC PI WASHINGTON PA 800 I STREET, NW, WASHINGTON, DC 20001-3710 USA SN 0090-0036 EI 1541-0048 J9 AM J PUBLIC HEALTH JI Am. J. Public Health PD DEC PY 2013 VL 103 SU 2 BP S232 EP S238 DI 10.2105/AJPH.2013.301309 PG 7 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA AA4NP UT WOS:000331073100020 PM 24148059 ER PT J AU Nadkarni, SK AF Nadkarni, Seemantini K. TI Optical measurement of arterial mechanical properties: from atherosclerotic plaque initiation to rupture SO JOURNAL OF BIOMEDICAL OPTICS LA English DT Review DE mechanical properties; plaque rupture; atherosclerosis; speckle rheology; microrheology; elastography ID SMOOTH-MUSCLE-CELLS; PARTICLE-TRACKING MICRORHEOLOGY; LOW-COHERENCE INTERFEROMETRY; VULNERABLE CORONARY PLAQUE; ENDOTHELIAL SHEAR-STRESS; SUBSTRATE STIFFNESS; LIVING CELLS; FIBROUS CAP; SIGNAL-TRANSDUCTION; TRACTION STRESSES AB During the pathogenesis of coronary atherosclerosis, from lesion initiation to rupture, arterial mechanical properties are altered by a number of cellular, molecular, and hemodynamic processes. There is growing recognition that mechanical factors may actively drive vascular cell signaling and regulate atherosclerosis disease progression. In advanced plaques, the mechanical properties of the atheroma influence stress distributions in the fibrous cap and mediate plaque rupture resulting in acute coronary events. This review paper explores current optical technologies that provide information on the mechanical properties of arterial tissue to advance our understanding of the mechanical factors involved in atherosclerosis development leading to plaque rupture. The optical approaches discussed include optical microrheology and traction force microscopy that probe the mechanical behavior of single cell and extracellular matrix components, and intravascular imaging modalities including laser speckle rheology, optical coherence elastography, and polarization-sensitive optical coherence tomography to measure the mechanical properties of advanced coronary lesions. Given the wealth of information that these techniques can provide, optical imaging modalities are poised to play an increasingly significant role in elucidating the mechanical aspects of coronary atherosclerosis in the future. (C) The Authors. Published by SPIE under a Creative Commons Attribution 3.0 Unported License. Distribution or reproduction of this work in whole or in part requires full attribution of the original publication, including its DOI. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Wellman Ctr Photomed, Boston, MA 02114 USA. RP Nadkarni, SK (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Wellman Ctr Photomed, Boston, MA 02114 USA. EM snadkarni@mgh.harvard.edu NR 128 TC 6 Z9 7 U1 0 U2 23 PU SPIE-SOC PHOTO-OPTICAL INSTRUMENTATION ENGINEERS PI BELLINGHAM PA 1000 20TH ST, PO BOX 10, BELLINGHAM, WA 98225 USA SN 1083-3668 EI 1560-2281 J9 J BIOMED OPT JI J. Biomed. Opt. PD DEC PY 2013 VL 18 IS 12 DI 10.1117/1.JBO.18.12.121507 PG 10 WC Biochemical Research Methods; Optics; Radiology, Nuclear Medicine & Medical Imaging SC Biochemistry & Molecular Biology; Optics; Radiology, Nuclear Medicine & Medical Imaging GA AB3QY UT WOS:000331706500011 ER PT J AU Samkoe, KS Bryant, A Gunn, JR Pereira, SP Hasan, T Pogue, BW AF Samkoe, Kimberley S. Bryant, Amber Gunn, Jason R. Pereira, Stephen P. Hasan, Tayyaba Pogue, Brian W. TI Contrast enhanced-magnetic resonance imaging as a surrogate to map verteporfin delivery in photodynamic therapy SO JOURNAL OF BIOMEDICAL OPTICS LA English DT Article DE dosimetry; photodynamic therapy; pancreas cancer; verteporfin; magnetic resonance imaging ID PROSTATE AB The use of in vivo contrast-enhanced magnetic resonance (MR) imaging as a surrogate for photosensitizer (verteporfin) dosimetry in photodynamic therapy of pancreas cancer is demonstrated by correlating MR contrast uptake to ex vivo fluorescence images on excised tissue. An orthotopic pancreatic xenograft mouse model was used for the study. A strong correlation (r = 0.57) was found for bulk intensity measurements of T1-weighted gadolinium enhancement and verteporfin fluorescence in the tumor region of interest. The use of contrast-enhanced MR imaging shows promise as a method for treatment planning and photosensitizer dosimetry in human photodynamic therapy (PDT) of pancreas cancer. (C) The Authors. Published by SPIE under a Creative Commons Attribution 3.0 Unported License. Distribution or reproduction of this work in whole or in part requires full attribution of the original publication, including its DOI. C1 [Samkoe, Kimberley S.; Pogue, Brian W.] Dartmouth Coll, Geisel Sch Med, Dept Surg, Lebanon, NH 03756 USA. [Samkoe, Kimberley S.; Bryant, Amber; Gunn, Jason R.; Pogue, Brian W.] Dartmouth Coll, Thayer Sch Engn, Hanover, NH 03755 USA. [Pereira, Stephen P.] UCL, Inst Liver & Digest Hlth, London NW3 2QG, England. [Hasan, Tayyaba] Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA. RP Samkoe, KS (reprint author), Dartmouth Coll, Geisel Sch Med, Dept Surg, 1 Med Ctr Dr, Lebanon, NH 03756 USA. EM Kimberley.S.Samkoe@Dartmouth.edu FU NIH [PO1CA084203] FX This work has been funded by NIH research grant PO1CA084203. NR 11 TC 1 Z9 1 U1 0 U2 3 PU SPIE-SOC PHOTO-OPTICAL INSTRUMENTATION ENGINEERS PI BELLINGHAM PA 1000 20TH ST, PO BOX 10, BELLINGHAM, WA 98225 USA SN 1083-3668 EI 1560-2281 J9 J BIOMED OPT JI J. Biomed. Opt. PD DEC PY 2013 VL 18 IS 12 DI 10.1117/1.JBO.18.12.120504 PG 3 WC Biochemical Research Methods; Optics; Radiology, Nuclear Medicine & Medical Imaging SC Biochemistry & Molecular Biology; Optics; Radiology, Nuclear Medicine & Medical Imaging GA AB3QY UT WOS:000331706500004 PM 24365954 ER PT J AU Byrne, T Munley, EA Fargo, JD Montgomery, AE Culhane, DP AF Byrne, Thomas Munley, Ellen A. Fargo, Jamison D. Montgomery, Ann E. Culhane, Dennis P. TI NEW PERSPECTIVES ON COMMUNITY-LEVEL DETERMINANTS OF HOMELESSNESS SO JOURNAL OF URBAN AFFAIRS LA English DT Article ID NEW-YORK-CITY; RENT CONTROL; RISK-FACTORS; PHILADELPHIA; PREDICTORS; FAMILIES; HEALTH; POLICY AB Understanding the root causes of homelessness is important for developing effective solutions to the problem. This fact has not gone unnoticed by researchers, who have made numerous attempts to identify the underlying structural determinants of homelessness by modeling inter-community variation in the rate of homelessness as a function of community-level variables. Yet, prior studies in this area have a number of serious limitations, principally their reliance on methodologically flawed estimates of the size of the homeless population. The present study addresses this and other limitations by using newly available and more reliable estimates from the U. S. Department of Housing and Urban Development to model variation in the rate of homelessness across a large and diverse sample of communities throughout the United States. In doing so, this study builds on the analysis conducted by Lee, Price-Spratlen, and Kanan (2003), and its findings have implications for policy and future research. C1 [Byrne, Thomas; Munley, Ellen A.; Fargo, Jamison D.; Montgomery, Ann E.; Culhane, Dennis P.] US Dept Vet Affairs, Natl Ctr Homelessness Vet, Washington, DC USA. [Byrne, Thomas; Munley, Ellen A.; Montgomery, Ann E.; Culhane, Dennis P.] Univ Penn, Philadelphia, PA 19104 USA. [Fargo, Jamison D.] Utah State Univ, Logan, UT 84322 USA. RP Byrne, T (reprint author), Natl Ctr Homelessness Vet, 4100 Chester Ave,Suite 201, Philadelphia, PA 19104 USA. EM byrnet@sp2.upenn.edu NR 60 TC 4 Z9 4 U1 7 U2 30 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0735-2166 EI 1467-9906 J9 J URBAN AFF JI J. Urban Aff. PD DEC PY 2013 VL 35 IS 5 BP 607 EP 625 DI 10.1111/j.1467-9906.2012.00643.x PG 19 WC Urban Studies SC Urban Studies GA AA2UT UT WOS:000330950400006 ER PT J AU Fava, MA Choi, CJ El Mollayess, G Melki, SA AF Fava, Mark A. Choi, Catherine J. El Mollayess, George Melki, Samir A. TI Sandwich fibrin glue technique for attachment of conjunctival autograft during pterygium surgery SO CANADIAN JOURNAL OF OPHTHALMOLOGY-JOURNAL CANADIEN D OPHTALMOLOGIE LA English DT Article ID RECURRENT PTERYGIUM; SUTURES; TRANSPLANTATION; ADHESIVE; PASTE; CUT AB Objective: To report the results of a sandwich application of fibrin glue compared with the standard method of using fibrin glue for the attachment of the conjunctival autograft in pterygium surgery. Participants: The study group consisted of 56 consecutive eyes with primary pterygium. Methods: We performed a retrospective analysis comparing the standard method of using fibrin glue for the attachment of the conjunctival autograft during pterygium excision surgery versus the "sandwich technique." In the "sandwich technique," the thrombin component of the fibrin glue was applied after the graft was secured in position over a bed of fibrinogen. Results: Graft dehiscence occurred in 3 eyes in the conventional group only. Recurrence occurred in 2 eyes in the conventional group and 1 eye in the sandwich group. None of the values reached statistical significance. Conclusions: The sandwich technique simplifies conjunctival graft fixation during pterygium surgery with conjunctival autograft by allowing more time to properly position the autograft before fibrin clot formation. C1 [Fava, Mark A.; Choi, Catherine J.; Melki, Samir A.] Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. [Fava, Mark A.; Melki, Samir A.] Harvard Univ, Beth Israel Deaconess Med Ctr, Med Ctr, Boston, MA 02215 USA. [Fava, Mark A.; Melki, Samir A.] Boston Eye Grp, Boston, MA USA. [Choi, Catherine J.] Harvard Univ, Sch Med, Boston, MA USA. [El Mollayess, George] Amer Univ Beirut, Med Ctr, Beirut, Lebanon. RP Melki, SA (reprint author), Massachusetts Eye & Ear Infirm, Cornea & Refract Surg Serv, 243 Charles St, Boston, MA 02114 USA. EM samir_melki@meei.harvard.edu NR 20 TC 0 Z9 0 U1 0 U2 1 PU CANADIAN OPHTHAL SOC PI OTTAWA PA 1525 CARLING AVE SUITE 610, OTTAWA, ONTARIO K1Z 8R9, CANADA SN 0008-4182 EI 1715-3360 J9 CAN J OPHTHALMOL JI Can. J. Opthalmol.-J. Can. Opthalmol. PD DEC PY 2013 VL 48 IS 6 BP 516 EP 520 DI 10.1016/j.jcjo.2013.07.004 PG 5 WC Ophthalmology SC Ophthalmology GA AA5OQ UT WOS:000331149800028 PM 24314414 ER PT J AU Rahimy, E Beardsley, RM Gomez, J Hung, C Sarraf, D AF Rahimy, Ehsan Beardsley, Robert M. Gomez, Jessica Hung, Crystal Sarraf, David TI Grading of posterior staphyloma with spectral-domain optical coherence tomography and correlation with macular disease SO CANADIAN JOURNAL OF OPHTHALMOLOGY-JOURNAL CANADIEN D OPHTALMOLOGIE LA English DT Article ID HIGHLY MYOPIC EYES; RETINAL-DETACHMENT; REFRACTIVE ERRORS; TRACTION MACULOPATHY; VITREORETINAL INTERFACE; ADULT-POPULATION; NATURAL COURSE; UNITED-STATES; AXIAL LENGTH; RISK-FACTORS AB Objective: To develop a novel grading system for posterior staphyloma imaged by spectral-domain optical coherence tomography (SD-OCT) and to correlate the incidence of macular disease (vitreomacular traction, epiretinal membrane, macular schisis, lamellar macular hole, and full-thickness macular hole) with each grade. Design: Retrospective chart review. Participants: A total of 150 eyes from 89 patients with posterior staphylomas were examined at Jules Stein Eye Institute, University of California Los Angeles. Methods: Retrospective analysis of the Cirrus SD-OCT (Carl Zeiss Meditec, Dublin, Calif.) database at a large institution (Jules Stein Eye Institute) was performed and eyes with a posterior staphyloma involving the macula were evaluated for the presence of macular pathology. The radius of each circle was measured and graded, and the incidence of macular pathology was correlated with each staphyloma grade. Statistical analysis was done using Fisher exact and Kruskal-Wallis tests. Results: The overall incidence rate of macular disease was 50.6% (76/150 eyes). The incidence rate of macular schisis was 17.3% (26/150) and was significantly greater with steeper (grade 3 [25.0%] and grade 4 [30.3%] staphyloma) versus shallower grade (grade 1 [5.6%]) staphyloma (p = 0.016). Conclusions: Imaging of staphyloma via SD-OCT is a valuable tool for determining the severity of posterior staphyloma and for determining risk stratification for various macular diseases. C1 [Rahimy, Ehsan; Beardsley, Robert M.; Gomez, Jessica; Hung, Crystal; Sarraf, David] Univ Calif Los Angeles, Jules Stein Eye Inst, David Geffen Sch Med, Los Angeles, CA 90095 USA. [Sarraf, David] Greater Los Angeles VA Healthcare Syst, Los Angeles, CA USA. RP Sarraf, D (reprint author), Univ Calif Los Angeles, Jules Stein Eye Inst, 100 Stein Plaza, Los Angeles, CA 90095 USA. EM dsarraf@ucla.edu FU Karl Kirchgessner Foundation at the Jules Stein Eye Institute FX This study was supported by a grant from the Karl Kirchgessner Foundation at the Jules Stein Eye Institute. NR 36 TC 2 Z9 2 U1 0 U2 1 PU CANADIAN OPHTHAL SOC PI OTTAWA PA 1525 CARLING AVE SUITE 610, OTTAWA, ONTARIO K1Z 8R9, CANADA SN 0008-4182 EI 1715-3360 J9 CAN J OPHTHALMOL JI Can. J. Opthalmol.-J. Can. Opthalmol. PD DEC PY 2013 VL 48 IS 6 BP 539 EP 545 DI 10.1016/j.jcio.2013.07.006 PG 7 WC Ophthalmology SC Ophthalmology GA AA5OQ UT WOS:000331149800033 PM 24314419 ER PT J AU Wang, Q Weisberg, E Zhao, JJ AF Wang, Qi Weisberg, Ellen Zhao, Jean J. TI The gene dosage of class Ia PI3K dictates the development of PTEN hamartoma tumor syndrome SO CELL CYCLE LA English DT Article DE PTEN; PI3K isoforms; PTEN hamartoma tumor syndrome; PI3K inhibitor; skin disease ID TUBEROUS SCLEROSIS COMPLEX; MAMMARY-GLAND DEVELOPMENT; GIANT-CELL ASTROCYTOMAS; P110-ALPHA ISOFORM; COWDEN-SYNDROME; BREAST-CANCER; PATHWAY; DISEASE; TUMORIGENESIS; RAPAMYCIN AB T he PTEN hamartoma tumor syndrome (PHTS) is a complex disorder caused by germline inactivating mutations of the tumor suppressor gene PTEN. Loss of PTEN function leads to unimpeded phosphatidylinositol-3'-kinase (PI3K) activity and PI3K-driven cell division. Individuals with PHTS develop benign hamartomas in various tissues and have an increased risk of developing malignant diseases. Notably, no effective therapy currently exists for this disorder. Using both genetic mouse models and pharmacological approaches, we recently demonstrated that PI3K p110 alpha and p110 beta isoforms play spatially distinct but concerted roles in the skin that are required for the development and maintenance of PHTS. We also show that treatment with a pan-PI3K inhibitor prevents the development of skin PHTS and reverses advanced-stage skin hamartomas in vivo. Here, we report that genetic ablation of only 3 out of 4 p110 alleles is sufficient to block the development of skin hamartomas resulting from the complete loss of Pten in mice. Similar to our findings in skin, we now also show that mammary gland neoplastic lesions can be prevented or reversed upon PI3K inhibition in our PHTS mouse model. Our data suggest a possible route to chemoprevention using reduced doses of PI3K inhibitors for PTEN-deficient carrier patients. C1 [Wang, Qi; Zhao, Jean J.] Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA. [Wang, Qi; Zhao, Jean J.] Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA. [Weisberg, Ellen] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. RP Zhao, JJ (reprint author), Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA. EM jean_zhao@dfci.harvard.edu FU NIH [CA172461-01, 1P50CA168504-01A1]; Stand Up To Cancer [SU2C-AACR-DT0209]; Department of Defense [BC051565] FX We thank T Roberts for scientific discussions. K14Cre mice were generously provided by J Jonkers at the Netherlands Cancer Institute, Netherlands. Floxed Pten mice were generously provided by H Wu at UCLA School of Medicine. This work was supported by NIH grants CA172461-01 (JJZ), 1P50CA168504-01A1 (JJZ), Stand Up To Cancer (SU2C-AACR-DT0209) (JJZ), the Department of Defense (BC051565 to JJZ). NR 40 TC 1 Z9 1 U1 0 U2 0 PU LANDES BIOSCIENCE PI AUSTIN PA 1806 RIO GRANDE ST, AUSTIN, TX 78702 USA SN 1538-4101 EI 1551-4005 J9 CELL CYCLE JI Cell Cycle PD DEC 1 PY 2013 VL 12 IS 23 BP 3589 EP 3593 DI 10.4161/cc.26812 PG 5 WC Cell Biology SC Cell Biology GA 301IQ UT WOS:000330526400009 PM 24131925 ER PT J AU Javaid, S Zhang, JM Anderssen, E Black, JC Wittner, BS Tajima, K Ting, DT Smolen, GA Zubrowski, M Desai, R Maheswaran, S Ramaswamy, S Whetstine, JR Haber, DA AF Javaid, Sarah Zhang, Jianmin Anderssen, Endre Black, Josh C. Wittner, Ben S. Tajima, Ken Ting, David T. Smolen, Gromoslaw A. Zubrowski, Matthew Desai, Rushil Maheswaran, Shyamala Ramaswamy, Sridhar Whetstine, Johnathan R. Haber, Daniel A. TI Dynamic Chromatin Modification Sustains Epithelial-Mesenchymal Transition following Inducible Expression of Snail-1 SO CELL REPORTS LA English DT Article ID TRANSCRIPTION FACTOR SNAIL; E-CADHERIN REPRESSION; STEM-CELLS; MIR-200 FAMILY; CANCER; METASTASIS; PROGRESSION; BREAST; CYCLE; PLURIPOTENCY AB Epithelial-mesenchymal transition (EMT) is thought to contribute to cancer metastasis, but its underlying mechanisms are not well understood. To define early steps in this cellular transformation, we analyzed human mammary epithelial cells with tightly regulated expression of Snail-1, a master regulator of EMT. After Snail-1 induction, epithelial markers were repressed within 6 hr, and mesenchymal genes were induced at 24 hr. Snail-1 binding to its target promoters was transient (6-48 hr) despite continued protein expression, and it was followed by both transient and long-lasting chromatin changes. Pharmacological inhibition of selected histone acetylation and demethylation pathways suppressed the induction as well as the maintenance of Snail-1-mediated EMT. Thus, EMT involves an epigenetic switch that may be prevented or reversed with the use of small-molecule inhibitors of chromatin modifiers. C1 [Javaid, Sarah; Zhang, Jianmin; Anderssen, Endre; Black, Josh C.; Wittner, Ben S.; Tajima, Ken; Ting, David T.; Smolen, Gromoslaw A.; Zubrowski, Matthew; Desai, Rushil; Maheswaran, Shyamala; Ramaswamy, Sridhar; Whetstine, Johnathan R.; Haber, Daniel A.] Massachusetts Gen Hosp, Ctr Canc, Charlestown, MA 02129 USA. [Javaid, Sarah; Zhang, Jianmin; Anderssen, Endre; Black, Josh C.; Wittner, Ben S.; Tajima, Ken; Ting, David T.; Smolen, Gromoslaw A.; Zubrowski, Matthew; Desai, Rushil; Maheswaran, Shyamala; Ramaswamy, Sridhar; Whetstine, Johnathan R.; Haber, Daniel A.] Harvard Univ, Sch Med, Charlestown, MA 02129 USA. [Haber, Daniel A.] Howard Hughes Med Inst, Chevy Chase, MD 20815 USA. RP Haber, DA (reprint author), Massachusetts Gen Hosp, Ctr Canc, Charlestown, MA 02129 USA. EM haber@helix.mgh.harvard.edu RI Black, Joshua/Q-2484-2015; OI Ting, David/0000-0002-3261-2322 FU Howard Hughes Medical Institute; NIH [CA129933]; Susan G. Komen for the Cure; NCI-MGH Federal Share Program; Ellison Medical Foundation [AG-NS-0560-09, CA059267, R01GM097360]; Jane Coffin Childs Memorial Fund for Medical Research FX We thank Laura Libby for expert technical support and members of the Haber, Maheswaran, Whetstine, and Ramaswamy laboratories for helpful discussions. We thank Nick Dyson for discussions and critical reading of the manuscript. This work was supported by the Howard Hughes Medical Institute (D.A.H.), the NIH (grant CA129933 to D.A.H. and S.J.), Susan G. Komen for the Cure (S.M.), the NCI-MGH Federal Share Program (S.M.), the Ellison Medical Foundation (grants AG-NS-0560-09, CA059267, and R01GM097360 to J.R.W.), and the Jane Coffin Childs Memorial Fund for Medical Research (J.C.B.). NR 41 TC 27 Z9 27 U1 2 U2 9 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 2211-1247 J9 CELL REP JI Cell Reports PD DEC PY 2013 VL 5 IS 6 BP 1679 EP 1689 DI 10.1016/j.celrep.2013.11.034 PG 11 WC Cell Biology SC Cell Biology GA AA5PW UT WOS:000331153100018 PM 24360956 ER PT J AU Yu, S Christiani, DC Thompson, BT Bajwa, EK Gong, MN AF Yu, Shun Christiani, David C. Thompson, B. Taylor Bajwa, Ednan K. Gong, Michelle Ng TI Role of Diabetes in the Development of Acute Respiratory Distress Syndrome SO CRITICAL CARE MEDICINE LA English DT Article DE acute lung injury; acute respiratory distress syndrome; diabetes mellitus; hyperglycemia; risk factors ID ACUTE LUNG INJURY; COMMUNITY-ACQUIRED PNEUMONIA; GLYCATION END-PRODUCTS; INTENSIVE-CARE-UNIT; PNEUMOCOCCAL VACCINATION; CLINICAL PREDICTORS; HOSPITALIZED ADULTS; SEVERE SEPSIS; RAT MODEL; INSULIN AB Objectives: Diabetes has been associated with decreased development of acute respiratory distress syndrome in some, but not all, previous studies. Therefore, we examined the relationship between diabetes and development of acute respiratory distress syndrome and whether this association was modified by type of diabetes, etiology of acute respiratory distress syndrome, diabetes medications, or other potential confounders. Design: Observational prospective multicenter study. Setting: Four adult ICUs at two tertiary academic medical centers. Patients: Three thousand eight hundred sixty critically ill patients at risk for acute respiratory distress syndrome from sepsis, pneumonia, trauma, aspiration, or massive transfusion. Interventions: None. Measurements and Main Results: Diabetes history was present in 25.8% of patients. Diabetes was associated with lower rates of developing acute respiratory distress syndrome on univariate (odds ratio, 0.79; 95% CI, 0.66-0.94) and multivariate analysis (adjusted odds ratio, 0.76; 95% CI, 0.61-0.95). After including diabetes medications into the model, diabetes remained protective (adjusted odds ratio, 0.75; 95% CI, 0.59-0.94). Diabetes was associated with decreased development of acute respiratory distress syndrome both in the subgroup of patients with sepsis (adjusted odds ratio, 0.77; 95% CI, 0.61-0.97) and patients with noninfectious etiologies (adjusted odds ratio, 0.30; 95% CI, 0.10-0.90). The protective effect of diabetes on acute respiratory distress syndrome development is not clearly restricted to either type 1 (adjusted odds ratio, 0.50; 95% CI, 0.26-0.99; p = 0.046) or type 2 (adjusted odds ratio, 0.77; 95% CI, 0.60-1.00; p = 0.050) diabetes. Among patients in whom acute respiratory distress syndrome developed, diabetes was not associated with 60-day mortality on univariate (odds ratio, 1.11; 95% CI, 0.80-1.52) or multivariate analysis (adjusted odds ratio, 0.81; 95% CI, 0.56-1.18). Conclusions: Diabetes is associated with a lower rate of acute respiratory distress syndrome development, and this relationship remained after adjusting for clinical differences between diabetics and nondiabetics, such as obesity, acute hyperglycemia, and diabetes-associated medications. In addition, this association was present for type 1 and 2 diabetics and in all subgroups of at-risk patients. C1 [Yu, Shun; Gong, Michelle Ng] Montefiore Med Ctr, Jay B Langner Crit Care Serv, Dept Med, Div Crit Care Med, Bronx, NY 10467 USA. [Christiani, David C.; Thompson, B. Taylor; Bajwa, Ednan K.] Massachusetts Gen Hosp, Dept Med, Pulm & Crit Care Unit, Boston, MA 02114 USA. [Christiani, David C.] Harvard Univ, Sch Publ Hlth, Dept Environm Hlth, Environm & Occupat Med & Epidemiol Program, Boston, MA 02115 USA. [Gong, Michelle Ng] Albert Einstein Coll Med, Dept Epidemiol & Populat Hlth, Bronx, NY 10467 USA. RP Gong, MN (reprint author), Montefiore Med Ctr, Jay B Langner Crit Care Serv, Dept Med, Div Crit Care Med, 111 East 210th St, Bronx, NY 10467 USA. EM mgong@montefiore.org FU National Heart, Lung, and Blood Institute [R01 HL086667, R01 HL060710, U01 HL108712]; NHLBI; NIH FX Supported, in part, by research grants R01 HL086667, R01 HL060710, and U01 HL108712 from the National Heart, Lung, and Blood Institute.; Dr. Christiani received grant support from NHLBI and funding from NIH. Dr. Thompson received grant support from NHLBI and funding from NIH. Dr. Gong received funding from NIH. The remaining authors have disclosed that they do not have any potential conflicts of interest. NR 76 TC 12 Z9 13 U1 2 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0090-3493 EI 1530-0293 J9 CRIT CARE MED JI Crit. Care Med. PD DEC PY 2013 VL 41 IS 12 BP 2720 EP 2732 DI 10.1097/CCM.0b013e318298a2eb PG 13 WC Critical Care Medicine SC General & Internal Medicine GA 301NN UT WOS:000330539100036 PM 23963123 ER PT J AU Deng, XM Elkins, JM Zhang, JW Yang, QK Erazo, T Gomez, N Choi, HG Wang, JH Dzamko, N Lee, JD Sim, T Kim, N Alessi, DR Lizcano, JM Knapp, S Gray, NS AF Deng, Xianming Elkins, Jonathan M. Zhang, Jinwei Yang, Qingkai Erazo, Tatiana Gomez, Nestor Choi, Hwan Geun Wang, Jinhua Dzamko, Nicolas Lee, Jiing-Dwan Sim, Taebo Kim, NamDoo Alessi, Dario R. Lizcano, Jose M. Knapp, Stefan Gray, Nathanael S. TI Structural determinants for ERK5 (MAPK7) and leucine rich repeat kinase 2 activities of benzo[e]pyrimido-[5,4-b]diazepine-6(11H)-ones SO EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY LA English DT Article DE ERK5 inhibitor; Kinase selectivity; Benzo[e]pyrimido-[5,4-b]diazepine-6(11H)-one ID ACTIVATED PROTEIN-KINASE; PROSTATE-CANCER; IN-VIVO; INHIBITOR SELECTIVITY; PARKINSON DISEASE; EXPRESSION; CELLS; LRRK2; POLO-LIKE-KINASE-1; CARCINOMA AB The benzo[e]pyrimido-[5,4-b]diazepine-6(11H)-one core was discovered as a novel ERK5 (also known as MAPK7 and BMK1) inhibitor scaffold, previously. Further structure-activity relationship studies of this scaffold led to the discovery of ERK5-IN-1 (26) as the most selective and potent ERK5 inhibitor reported to date. 26 potently inhibits ERK5 biochemically with an IC50 of 0.162 +/- 0.006 mu M and in cells with a cellular EC50 for inhibiting epidermal growth factor induced ERK5 autophosphorylation of 0.09 +/- 0.03 W. Furthermore, 26 displays excellent selectivity over other kinases with a KINOMEscan selectivity score (S-10) of 0.007, and exhibits exceptional bioavailability (F%) of 90% in mice. 26 will serve as a valuable tool compound to investigate the ERK5 signaling pathway and as a starting point for developing an ERK5 directed therapeutic agent. (C) 2013 Elsevier Masson SAS. All rights reserved. C1 [Deng, Xianming; Choi, Hwan Geun; Wang, Jinhua; Gray, Nathanael S.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA. [Deng, Xianming; Choi, Hwan Geun; Wang, Jinhua; Gray, Nathanael S.] Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA. [Elkins, Jonathan M.; Knapp, Stefan] Univ Oxford, Nuffield Dept Clin Med, Struct Genom Consortium, Oxford, England. [Elkins, Jonathan M.; Knapp, Stefan] Univ Oxford, TDI, Oxford, England. [Zhang, Jinwei; Dzamko, Nicolas; Alessi, Dario R.] Univ Dundee, Coll Life Sci, MRC Prot Phosphorylat Unit, Dundee DD1 5EH, Scotland. [Yang, Qingkai; Lee, Jiing-Dwan] Scripps Res Inst, Dept Immunol & Microbial Sci, La Jolla, CA 92037 USA. [Erazo, Tatiana; Gomez, Nestor; Lizcano, Jose M.] Univ Autonoma Barcelona, Dept Bioquim & Biol Mol, Inst Neurociencies, E-08193 Barcelona, Spain. [Sim, Taebo; Kim, NamDoo] Korea Inst Sci & Technol, Future Convergence Res Div, Seoul 136791, South Korea. RP Gray, NS (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Canc Biol, 250 Longwood Ave,SGM 628, Boston, MA 02115 USA. EM Nathanael_Gray@dfci.harvard.edu RI Lizcano, Jose /E-6080-2010; Gomez, Nestor/I-2522-2015; OI Lizcano, Jose /0000-0002-3154-5383; Gomez, Nestor/0000-0002-1348-2737; Yang, Qingkai/0000-0001-6628-5393; Alessi, Dario/0000-0002-2140-9185; Elkins, Jon/0000-0003-2858-8929; Knapp, Stefan/0000-0001-5995-6494; Dzamko, Nicolas/0000-0002-9121-0294 FU NIH [P41 GM079575-03, CA079871, CA114059]; Medical Research Council; Michael J Fox foundation for Parkinson's disease research; DSTT (AstraZeneca); DSTT (Boehringer-Ingelheim); DSTT (GlaxoSmithKline); DSTT (Merck KgaA); DSTT (Pfizer); Tobacco-Related Disease, Research Program of the University of California [19XT-0084]; Spanish Ministerio de Educacion [BFU2007-60268]; SGC, a registered charity [1097737]; Canadian Institutes for Health Research; Canada Foundation for Innovation; Genome Canada; GlaxoSmithKline; Pfizer; Eli Lilly; Takeda; AbbVie; Novartis Research Foundation; Ontario Ministry of Research and Innovation; Wellcome Trust FX We wish to thank Life Technologies Corporation, SelectScreen Kinase Profiling Service for performing enzymatic biochemical kinase profiling, DiscovRx for performing KINOMEscan profiling. This work was supported by NIH grant P41 GM079575-03 (N. Gray) and the Medical Research Council (D. Alessi), the Michael J Fox foundation for Parkinson's disease research (N. Gray & D. Alessi), the pharmaceutical companies supporting the DSTT (AstraZeneca, Boehringer-Ingelheim, GlaxoSmithKline, Merck KgaA and Pfizer) (D. Alessi), the NIH grant CA079871 and CA114059 (J.-D. Lee) and funds from the Tobacco-Related Disease, Research Program of the University of California, 19XT-0084, (J.-D. Lee), and by the Spanish Ministerio de Educacion grant BFU2007-60268 (J.M. Lizcano). JME, and SK are grateful for financial support by the SGC, a registered charity (number 1097737) that receives funds from the Canadian Institutes for Health Research, the Canada Foundation for Innovation, Genome Canada, GlaxoSmithKline, Pfizer, Eli Lilly, Takeda, AbbVie, the Novartis Research Foundation, the Ontario Ministry of Research and Innovation and the Wellcome Trust. NR 34 TC 8 Z9 8 U1 0 U2 6 PU ELSEVIER FRANCE-EDITIONS SCIENTIFIQUES MEDICALES ELSEVIER PI PARIS PA 23 RUE LINOIS, 75724 PARIS, FRANCE SN 0223-5234 EI 1768-3254 J9 EUR J MED CHEM JI Eur. J. Med. Chem. PD DEC PY 2013 VL 70 BP 758 EP 767 DI 10.1016/j.ejmech.2013.10.052 PG 10 WC Chemistry, Medicinal SC Pharmacology & Pharmacy GA 301TG UT WOS:000330554400071 PM 24239623 ER PT J AU Rapuano, BE MacDonald, DE AF Rapuano, Bruce E. MacDonald, Daniel E. TI Structure-activity relationship of human bone sialoprotein peptides SO EUROPEAN JOURNAL OF ORAL SCIENCES LA English DT Article DE biomimetic; extracellular matrix; integrins; osteoblasts; RGD peptide ID PLASMA GLOW-DISCHARGE; OXIDE NET CHARGE; CELL-ADHESION; TITANIUM-ALLOY; DENTAL IMPLANTS; HUMAN FIBRONECTIN; CRYSTAL-STRUCTURE; INTEGRIN-BINDING; I-TASSER; ATTACHMENT AB In the current study, the relationship between the structure of the RGD-containing human bone sialoprotein (hBSP) peptide 278-293 and its attachment activity toward osteoblast-like (MC3T3) cells was investigated. This goal was accomplished by examining the comparative cell-attachment activities of several truncated forms of peptide 278-293. Computer modeling of the various peptides was also performed to assess the role of secondary structure in peptide bioactivity. Elimination of tyrosine-278 at the N-terminus resulted in a more dramatic loss of cell-attachment activity compared with the removal of either tyrosine-293 or the arg-ala-tyr (291-293) tripeptide. Although replacement of the RGD (arg-gly-asp) peptide moiety with peptide KAE (lys-ala-glu) resulted in a dramatic loss of cell-attachment activity, a peptide containing RGE (arg-gly-glu) in place of RGD retained 70-85% of the parental peptide's attachment activity. These results suggest that the N-terminal RGD-flanking region of hBSP peptide 278-293, in particular the tyrosine-278 residue, represents a second cell-attachment site that stabilizes the RGD-integrin receptor complex. Computer modeling also suggested that a beta-turn encompassing RGD or RGE in some of the hBSP peptides may facilitate its binding to integrins by increasing the exposure of the tripeptide. This knowledge may be useful in the future design of biomimetic peptides which are more effective in promoting the attachment of osteogenic cells to implant surfaces in vivo. C1 [Rapuano, Bruce E.; MacDonald, Daniel E.] Cornell Univ, Weill Med Coll, Hosp Special Surg, New York, NY 10021 USA. [MacDonald, Daniel E.] James J Peters VA Med Ctr, Bronx, NY USA. [MacDonald, Daniel E.] Columbia Univ, Langmuir Ctr Colloids & Interfaces, New York, NY USA. RP MacDonald, DE (reprint author), Hosp Special Surg, 535 E 70th St, New York, NY 10021 USA. EM dem14@columbia.edu FU VA Merit Grant [2894-005]; National Center for Research Resources, NIH [C06-RR12538-01]; [NIH RO1 DE017695] FX This work was supported by VA Merit Grant # 2894-005 and by Grant Number NIH RO1 DE017695 (both awarded to D. E. M.). This material is also the result of work supported with resources and the use of facilities at the James J. Peters VA Medical Center, Bronx, New York. This investigation was also conducted at the HSS research facility constructed with support of Grant C06-RR12538-01 from the National Center for Research Resources, NIH. The authors wish to acknowledge the technical assistance of Christina Silva, Keith Tachibana and Kyle Hackshaw. NR 56 TC 1 Z9 1 U1 0 U2 8 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0909-8836 EI 1600-0722 J9 EUR J ORAL SCI JI Eur. J. Oral Sci. PD DEC PY 2013 VL 121 IS 6 BP 600 EP 609 DI 10.1111/eos.12081 PG 10 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA AA3DO UT WOS:000330973300013 PM 24103036 ER PT J AU Cronin, PR DeCoste, L Kimball, AB AF Cronin, Patrick R. DeCoste, Leah Kimball, Alexa Boer TI A Multivariate Analysis of Dermatology Missed Appointment Predictors SO JAMA DERMATOLOGY LA English DT Letter ID NONATTENDANCE; CARE C1 [Cronin, Patrick R.] Massachusetts Gen Hosp, Practice Improvement Div, Boston, MA 02114 USA. [DeCoste, Leah] Coll Holy Cross, Worcester, MA USA. [Kimball, Alexa Boer] Massachusetts Gen Hosp, Dept Dermatol, Boston, MA 02114 USA. [Kimball, Alexa Boer] Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Kimball, AB (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Dermatol, 50 Staniford St,Suite 240, Boston, MA 02114 USA. EM harvardskinstudies@partners.org NR 6 TC 2 Z9 3 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60654-0946 USA SN 2168-6068 EI 2168-6084 J9 JAMA DERMATOL JI JAMA Dermatol. PD DEC PY 2013 VL 149 IS 12 BP 1435 EP 1437 DI 10.1001/jamadermatol.2013.5771 PG 3 WC Dermatology SC Dermatology GA AA3EW UT WOS:000330976700024 PM 24080767 ER PT J AU Sumino, T Rubash, HE Li, GA AF Sumino, Takanobu Rubash, Harry E. Li, Guoan TI Does cruciate-retaining total knee arthroplasty enhance knee flexion in Western and East Asian patient populations? A meta-analysis SO KNEE LA English DT Article DE Meta-analysis; Total knee arthroplasty; Flexion; Extension; Cruciate retaining designs; CR TKA ID FOLLOW-UP; RANGE; MOTION; PROSTHESES; REPLACEMENT; LIGAMENT; DESIGN; SYSTEM; CEMENTLESS; STANDARD AB Introduction: This study analyzed the published data to examine if CR TKAs can enhance the flexion and functional outcomes of the knee in the Western and East Asian populations using a meta-analysis approach. Materials and methods: A systematic review of literature published through Medline and EMBASE was conducted. The inclusion criteria were: primary TKA, follow up duration greater than one year, a fixed bearing CR prosthesis, and data for maximum pre- and post-operative flexion along with standard deviations or errors. We estimated the weighted mean differences between pre- and post-operative flexion, extension and knee scores (KSS and HSS) via a random effect model. Results: Seventeen articles were selected and reviewed among 1229 studies that included 1090 knees of the Western and 516 knees of the East Asian. No significant difference was noted in maximal knee flexion pre- and post-operatively, when all the studies were pooled together (-0.17 degrees, p = 0.93, post-operative < pre-operative). The mean difference in flexion was -1.87 degrees (p = 02) and 2.03 degrees (p = 0.17), respectively in the both populations. However, the extension angle was significantly improved by -5.49 degrees and -13.05 degrees (p < 0.05), respectively. KSS scores were significantly improved by 46.39 and 51.63, and HSS scores by 36.65 and 30.67 (p < 0.05), respectively in the both populations. Conclusion: The meta-analysis indicated that contemporary CR TKAs have not been shown to enhance post-operative flexion capability in the Western and East Asian. The extension angles of the knee and the knee scores were significantly improved in both populations. (C) 2013 Elsevier B.V. All rights reserved. C1 [Sumino, Takanobu; Rubash, Harry E.; Li, Guoan] Massachusetts Gen Hosp, Dept Orthopaed Surg, Bioengn Lab, Boston, MA 02114 USA. [Sumino, Takanobu; Rubash, Harry E.; Li, Guoan] Harvard Univ, Sch Med, Boston, MA 02114 USA. [Sumino, Takanobu] Nihon Univ, Sch Med, Dept Orthopaed Surg, Tokyo, Japan. RP Li, GA (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Orthopaed Bioengn Lab, 55 Fruit St,GRJ 1215, Boston, MA 02114 USA. EM gli1@partners.org NR 45 TC 5 Z9 5 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0968-0160 EI 1873-5800 J9 KNEE JI Knee PD DEC PY 2013 VL 20 IS 6 BP 376 EP 383 DI 10.1016/j.knee.2013.03.002 PG 8 WC Orthopedics; Sport Sciences; Surgery SC Orthopedics; Sport Sciences; Surgery GA AA0YV UT WOS:000330824200003 PM 23562350 ER PT J AU Hill, MN Bierer, LM Makotkine, I Golier, JA Galea, S McEwen, BS Hillard, CJ Yehuda, R AF Hill, Matthew N. Bierer, Linda M. Makotkine, Iouri Golier, Julia A. Galea, Sandro McEwen, Bruce S. Hillard, Cecilia J. Yehuda, Rachel TI Reductions in circulating endocannabinoid levels in individuals with post-traumatic stress disorder following exposure to the world trade center attacks SO PSYCHONEUROENDOCRINOLOGY LA English DT Article DE Stress; PTSD; Trauma; Endocannabinoid; HPA axis; Cortisol; N-arachidonylethanolamine; Anandamide; 2-Arachidonoylglycerol; Anxiety ID PITUITARY-ADRENAL AXIS; NEUROPEPTIDE-Y CONCENTRATIONS; CONDITIONED FEAR; NERVOUS-SYSTEM; PTSD; INHIBITION; EXTINCTION; ACTIVATION; PLASMA; GLUCOCORTICOIDS AB Endocannabinoid (eCB) signaling has been identified as a modulator of adaptation to stress, and is integral to basal and stress-induced glucocorticoid regulation. Furthermore, interactions between eCBs and glucocorticoids have been shown to be necessary for the regulation of emotional memories, suggesting that eCB function may relate to the development of post-traumatic stress disorder (PTSD). To examine this, plasma eCBs were measured in a sample (n = 46) drawn from a population-based cohort selected for physical proximity to the World Trade Center (WTC) at the time of the 9/11 attacks. Participants received a structured diagnostic interview and were grouped according to whether they met diagnostic criteria for PTSD (no PTSD, n = 22; lifetime diagnosis of PTSD = 24). eCB content (2-arachidonoylglycerol (2-AG) and anandamide (AEA)) and cortisol were measured from 8 a.m. plasma samples. Circulating 2-AG content was significantly reduced among individuals meeting diagnostic criteria for PTSD. The effect of reduced 2-AG content in PTSD remained significant after controlling for the stress of exposure to the WTC collapse, gender, depression and alcohol abuse. There were no significant group differences for AEA or cortisol levels; however, across the whole sample AEA levels positively correlated with circulating cortisol, and AEA levels exhibited a negative relationship with the degree of intrusive symptoms within the PTSD sample. This report shows that PTSD is associated with a reduction in circulating levels of the eCB 2-AG. Given the role of 2-AG in the regulation of the stress response, these data support the hypothesis that deficient eCB signaling may be a component of the glucocorticoid dysregulation associated with PTSD. The negative association between AEA levels and intrusive symptoms is consistent with animal data indicating that reductions in AEA promote retention of aversive emotional memories. Future work will aim to replicate these findings and extend their relevance to clinical pathophysiology, as well as to neuroendocrine and molecular markers of PTSD. (C) 2013 Elsevier Ltd. All rights reserved. C1 [Hill, Matthew N.] Univ Calgary, Hotchkiss Brain Inst, Dept Cell Biol & Anat & Psychiat, Calgary, AB T2N 4N1, Canada. [Hill, Matthew N.; McEwen, Bruce S.] Rockefeller Univ, Neuroendocrinol Lab, New York, NY 10021 USA. [Bierer, Linda M.; Makotkine, Iouri; Golier, Julia A.; Yehuda, Rachel] Mt Sinai Sch Med, Traumat Stress Studies Div, Bronx, NY USA. [Bierer, Linda M.; Makotkine, Iouri; Golier, Julia A.; Yehuda, Rachel] James J Peters Vet Affairs Med Ctr, Bronx, NY USA. [Galea, Sandro] Columbia Mailman Sch Publ Hlth, Dept Epidemiol, New York, NY USA. [Hillard, Cecilia J.] Med Coll Wisconsin, Neurosci Res Ctr, Milwaukee, WI 53226 USA. [Hillard, Cecilia J.] Med Coll Wisconsin, Dept Pharmacol & Toxicol, Milwaukee, WI 53226 USA. RP Hill, MN (reprint author), Univ Calgary, Hotchkiss Brain Inst, 3330 Hosp Dr NW, Calgary, AB T2N 4N1, Canada. EM mnhill@ucalgary.ca FU National Institute of Mental Health (NIMH) [1R56MH077321-01]; NIH [DA026996, MH41256]; Lightfighter Foundation; Canadian Institutes of Health Research; Research and Education Initiative Fund, a component of the Advancing a Healtheir Wisconsin endowment at the Medical College of Wisconsin; National Center for Research Resources [5MO1 RR00071]; Department of Veterans Affairs FX This research was supported by National Institute of Mental Health (NIMH) Innovation Award 1R56MH077321-01 (R.Y.) and NIH Grants DA026996 (C.J.H.) and MH41256 (B.S.M.), operating grants from the Lightfighter Foundation (R.Y. and B.S.M.) and the Canadian Institutes of Health Research (M.N.H.). Partial funding for this study came from the Research and Education Initiative Fund, a component of the Advancing a Healtheir Wisconsin endowment at the Medical College of Wisconsin. Funding was also supported, in part, by 5MO1 RR00071 for the Mount Sinai General Clinical Research Center from the National Center for Research Resources. Support for Dr. Yehuda and Dr. Golier is provided by the Department of Veterans Affairs. The funding bodies had no role in the design of this study, the analysis or interpretation of the data or the composition of this manuscript. NR 57 TC 32 Z9 33 U1 2 U2 25 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0306-4530 J9 PSYCHONEUROENDOCRINO JI Psychoneuroendocrinology PD DEC PY 2013 VL 38 IS 12 BP 2952 EP 2961 DI 10.1016/j.psyneuen.2013.08.004 PG 10 WC Endocrinology & Metabolism; Neurosciences; Psychiatry SC Endocrinology & Metabolism; Neurosciences & Neurology; Psychiatry GA AA0YX UT WOS:000330824400014 PM 24035186 ER PT J AU Guffanti, G Galea, S Yan, LL Roberts, AL Solovieff, N Aiello, AE Smoller, JW De Vivo, I Ranu, H Uddin, M Wildman, DE Purcell, S Koenen, KC AF Guffanti, Guia Galea, Sandro Yan, Lulu Roberts, Andrea L. Solovieff, Nadia Aiello, Allison E. Smoller, Jordan W. De Vivo, Innmaculata Ranu, Hardeep Uddin, Monica Wildman, Derek E. Purcell, Shaun Koenen, Karestan C. TI Genome-wide association study implicates a novel RNA gene, the lincRNA AC068718.1, as a risk factor for post-traumatic stress disorder in women SO PSYCHONEUROENDOCRINOLOGY LA English DT Article DE PTSD; GWAS; lincRNA; Telomere maintenance; Immune system ID ADCYAP1R1 GENOTYPE; NONCODING RNAS; PAC1 RECEPTOR; DEPRESSION; EVOLUTION; COMMUNITY; COMORBIDITY; POPULATION; PREVALENCE; VIOLENCE AB Posttraumatic stress disorder (PTSD) is a common and debilitating mental disorder with a particularly high burden for women. Emerging evidence suggests PTSD may be more heritable among women and evidence from animal models and human correlational studies suggest connections between sex-linked biology and PTSD vulnerability, which may extend to the disorder's genetic architecture. We conducted a genome-wide association study (GWAS) of PTSD in a primarily African American sample of women from the Detroit Neighborhood Health Study (DNHS) and tested for replication in an independent cohort of primarily European American women from the Nurses Health Study II (NHSII). We genotyped 413 DNHS women - 94 PTSD cases and 319 controls exposed to at least one traumatic event - on the Illumina HumanOmniExpress BeadChip for >700,000 markers and tested 578 PTSD cases and 1963 controls from NHSII for replication. We performed a network-based analysis integrating data from GWAS-derived independent regions of association and the Reactome database of functional interactions. We found genome-wide significant association for one marker mapping to a novel RNA gene, lincRNA AC068718.1, for which we found suggestive evidence of replication in NHSII. Our network-based analysis indicates that our top GWAS results were enriched for pathways related to telomere maintenance and immune function. Our findings implicate a novel RNA gene, lincRNA AC068718.1, as risk factor for PTSD in women and add to emerging evidence that non-coding RNA genes may play a crucial role in shaping the landscape of gene regulation with putative pathological effects that lead to phenotypic differences. (C) 2013 Elsevier Ltd. All rights reserved. C1 [Guffanti, Guia] Columbia Univ, Dept Psychiat, New York State Psychiat Inst, New York, NY USA. [Galea, Sandro; Yan, Lulu; Koenen, Karestan C.] Columbia Univ, Dept Epidemiol, Mailman Sch Publ Hlth, New York, NY USA. [Roberts, Andrea L.; De Vivo, Innmaculata] Harvard Univ, Sch Publ Hlth, Dept Soc Human Dev & Hlth, Boston, MA 02115 USA. [Solovieff, Nadia; Smoller, Jordan W.; Purcell, Shaun] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA. [Solovieff, Nadia; Smoller, Jordan W.; Purcell, Shaun] Broad Inst Harvard & MIT, Stanley Ctr Psychiat Res, Cambridge, MA USA. [Solovieff, Nadia; Smoller, Jordan W.; Purcell, Shaun] Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA. [Aiello, Allison E.] Univ Michigan, Sch Publ Hlth, Dept Epidemiol, Ann Arbor, MI 48109 USA. [Ranu, Hardeep] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. [Uddin, Monica] Wayne State Univ, Dept Psychiat & Behav Neurosci, Detroit, MI 48207 USA. [Uddin, Monica; Wildman, Derek E.] Wayne State Univ, Sch Med, Ctr Mol Med & Genet, Detroit, MI USA. [Uddin, Monica; Wildman, Derek E.] Wayne State Univ, Sch Med, Dept Obstet & Gynecol, Detroit, MI 48201 USA. [Purcell, Shaun] Mt Sinai Sch Med, Div Psychiat Genom, New York, NY USA. RP Koenen, KC (reprint author), Columbia Mailman Sch Publ Hlth, 722 West 168th St,Room 720G, New York, NY 10032 USA. EM kck5@cumc.columbia.edu RI Koenen, Karestan/K-5402-2014 OI Roberts, Andrea/0000-0001-5023-4399; Koenen, Karestan/0000-0003-3293-4281 FU National Institute on Mental Health [R01 MH093612, MH078928]; NIH [CA50385]; [DA022720]; [DA 022720-S1]; [MH 088283] FX The Detroit Neighborhood Health Study (PI: Allison Aiello) is funded by DA022720, DA 022720-S1, and MH 088283. Funding for this study was also provided by National Institute on Mental Health awards R01 MH093612, MH078928 to Karestan C. Koenen. The Nurses' Health Study II is funded in part by NIH CA50385. NR 45 TC 29 Z9 29 U1 1 U2 11 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0306-4530 J9 PSYCHONEUROENDOCRINO JI Psychoneuroendocrinology PD DEC PY 2013 VL 38 IS 12 BP 3029 EP 3038 DI 10.1016/j.psyneuen.2013.08.014 PG 10 WC Endocrinology & Metabolism; Neurosciences; Psychiatry SC Endocrinology & Metabolism; Neurosciences & Neurology; Psychiatry GA AA0YX UT WOS:000330824400021 PM 24080187 ER PT J AU Coghlan, G Channick, RN Rubin, LJ Galie, N Perchenet, L Simonneau, G AF Coghlan, G. Channick, R. N. Rubin, L. J. Galie, N. Perchenet, L. Simonneau, G. TI EFFECT OF MACITENTAN ON PULMONARY ARTERIAL HYPERTENSION-RELATED HOSPITALISATIONS: RESULTS FROM THE RANDOMISED CONTROLLED SERAPHIN TRIAL SO THORAX LA English DT Meeting Abstract CT Winter Meeting of the British-Thoracic-Society CY DEC 04-06, 2013 CL London, ENGLAND SP British Thorac Soc C1 [Coghlan, G.] Royal Free Hosp, London NW3 2QG, England. [Channick, R. N.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Rubin, L. J.] Univ Calif San Diego, San Diego, CA 92103 USA. [Galie, N.] Univ Bologna, Bologna, Italy. [Perchenet, L.] Actel Pharmaceut Ltd, Allschwil, Switzerland. [Simonneau, G.] Hop Univ Bicetre, Le Kremlin Bicetre, France. NR 0 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 0040-6376 EI 1468-3296 J9 THORAX JI Thorax PD DEC PY 2013 VL 68 SU 3 BP A143 EP A143 DI 10.1136/thoraxjnl-2013-204457.299 PG 1 WC Respiratory System SC Respiratory System GA 301FR UT WOS:000330518700297 ER PT J AU Taliani, CA Bricker, PL Adelman, AM Cronholm, PF Gabbay, RA AF Taliani, Catherine A. Bricker, Patricia L. Adelman, Alan M. Cronholm, Peter F. Gabbay, Robert A. TI Implementing Effective Care Management in the Patient-Centered Medical Home SO AMERICAN JOURNAL OF MANAGED CARE LA English DT Article ID HEALTH-CARE; DIABETES MANAGEMENT; POSITIVE DEVIANCE; DELIVERY-SYSTEM; OF-CARE; QUALITY; RECORD; MODEL; IMPROVEMENT; DEPRESSION AB Background: There is growing evidence that practice-based care management can improve clinical quality and reduce costly healthcare utilization. Objectives: To explore how a disparate group of patient-centered medical homes (PCMHs) embedded care management in their team care environment to identify best practices. Study Design: A positive deviance approach was used to contrast care management implementation in practices having the greatest and least improvement on clinical measures of diabetes, the initial target disease for a multipayer-supported statewide initiative involving 25 National Committee on Quality Assurance-recognized PCMH practices participating in a regional learning collaborative. Methods: Practices were ranked according to their average absolute percentage point increase from baseline to 18 months on 3 diabetes quality measures. Semistructured interviews were conducted with 136 individuals in 21 of the 25 practices. Interview data were analyzed using grounded theory with NVivo 9.0 software.To develop hypotheses related to care management best practices, we compared and contrasted emerging themes across clinical performance tertiles. Results: Practices with the greatest diabetes improvement described (1) more patient-centered care manager duties, (2) better use of the electronic medical record (EMR) for messaging and patient tracking, and (3) stronger integration of the care manager into the care team compared with practices with the least diabetes improvement. Conclusions: PCMHs may want to ensure that care managers are available to meet with patients during visits, support patient self-management, fully leverage the EMR for team messaging and patient tracking, and ensure integration into the care team with office huddles and ongoing communication. C1 [Adelman, Alan M.] Dept Family & Community Med, Hershey, PA USA. [Taliani, Catherine A.] Penn State Coll Med, Hershey, PA USA. [Bricker, Patricia L.] Penn State Hershey Diabet Inst, Hershey, PA USA. [Gabbay, Robert A.] Univ Penn, Leonard Davis Inst Hlth Econ, Dept Family Med & Community Hlth, Ctr Publ Hlth Initiat, Philadelphia, PA 19104 USA. RP Gabbay, RA (reprint author), Harvard Univ, Sch Med, Joslin Diabet Ctr, Boston, MA 02115 USA. EM Robert.gabbay@joslin.harvard.edu FU Agency for Healthcare Research [R18HS019150]; Aetna Foundation FX This project was supported by grant R18HS019150 from the Agency for Healthcare Research and Quality and by the Aetna Foundation. The content is solely the responsibility of the authors and does not necessarily represent the official views of the Agency for Healthcare Research and Quality or the Aetna Foundation. NR 49 TC 12 Z9 12 U1 2 U2 14 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 DEC PY 2013 VL 19 IS 12 BP 957 EP 964 PG 8 WC Health Care Sciences & Services; Health Policy & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 297PN UT WOS:000330267500001 PM 24512033 ER PT J AU Carbone, L Chin, AS Lee, TA Burns, SP Svircev, JN Hoenig, H Akhigbe, T Thomas, F Bailey, L Weaver, F AF Carbone, Laura Chin, Amy S. Lee, Todd A. Burns, Stephen P. Svircev, Jelena N. Hoenig, Helen Akhigbe, Titilola Thomas, Fridtjof Bailey, Lauren Weaver, Frances TI The Association of Anticonvulsant Use with Fractures in Spinal Cord Injury SO AMERICAN JOURNAL OF PHYSICAL MEDICINE & REHABILITATION LA English DT Article DE Spinal Cord Injury; Anticonvulsants; Fractures; Cox Regression; Survival Analysis ID BONE-MINERAL DENSITY; RANDOMIZED CONTROLLED-TRIAL; ANTIEPILEPTIC DRUGS; HIP-FRACTURES; OLDER MEN; VITAMIN-D; CALCIUM SUPPLEMENTATION; RISK-FACTORS; HEALTH; VETERANS AB Objective: The aim of this study was to determine whether anticonvulsants, including the benzodiazepine subclass, are associated with an increased risk for lower extremity fractures in male patients with spinal cord injury. Design: All male patients with a history of a traumatic spinal cord injury of 2 yrs' duration or longer in the Veterans Affairs Spinal Cord Disease Registry from 2002 to 2007 were included. Incident lower extremity fractures during this period and anticonvulsant use were identified. The association of anticonvulsant use, overall, by type (enzyme inducing, non-enzyme inducing), by number (monotherapy vs. polytherapy), by benzodiazepine subclass, and by individual medication used was determined. Results: In this cohort, 892 veterans sustained a fracture, and 6555 did not. Compared with nonusers of anticonvulsants, there was a significant positive relationship with fractures by overall use of anticonvulsants (HR, 1.17 [95% CI, 1.01-1.36]), by users of the benzodiazepine subclass (HR, 1.28 [95% CI, 1.11-1.47]), and by polytherapy compared with monotherapy (HR, 1.20 [95% CI, 1.00-1.42]) but not by anticonvulsant type (HR, 0.92 [95% CI, 0.58-1.47]). Temazepam (HR, 1.28 [95% CI, 1.01-1.62]), alprazolam (HR, 1.54 [95% CI, 1.04-2.29]), and diazepam (HR, 1.23 [95% CI, 1.06-1.41]) were significantly positively associated with fractures. Conclusions: Attention to fracture prevention is important when anticonvulsants are prescribed in spinal cord injury, particularly when more than one anticonvulsant is used. C1 [Carbone, Laura; Akhigbe, Titilola] Dept Vet Affairs Med Ctr, Memphis, TN USA. [Carbone, Laura; Akhigbe, Titilola] Univ Tennessee, Dept Med, Hlth Sci Ctr, Memphis, TN 38104 USA. [Chin, Amy S.; Lee, Todd A.; Bailey, Lauren; Weaver, Frances] Edward J Hines Jr VA Hosp, Hines, IL USA. [Lee, Todd A.] Univ Illinois, Chicago, IL USA. [Burns, Stephen P.; Svircev, Jelena N.] VA Puget Sound Hlth Care Syst, Seattle, WA USA. [Burns, Stephen P.; Svircev, Jelena N.] Univ Washington, Dept Rehabil Med, Seattle, WA 98195 USA. [Hoenig, Helen] Durham VAMC, Durham, NC USA. [Thomas, Fridtjof] Univ Tennessee, Hlth Sci Ctr, Dept Prevent Med, Memphis, TN USA. [Weaver, Frances] Loyola Univ, Stritch Sch Med, Maywood, IL 60153 USA. RP Carbone, L (reprint author), Georgia Regents Univ, Dept Med, Rheumatol Sect, 1120 15th St,BI 5086, Augusta, GA 30912 USA. FU Department of Veterans Affairs, Veterans Health Administration, Health Services Research and Development [IIR 08-033] FX Supported by the Department of Veterans Affairs, Veterans Health Administration, Health Services Research and Development IIR 08-033. NR 61 TC 3 Z9 3 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0894-9115 EI 1537-7385 J9 AM J PHYS MED REHAB JI Am. J. Phys. Med. Rehabil. PD DEC PY 2013 VL 92 IS 12 BP 1037 EP 1046 DI 10.1097/PHM.0000000000000014 PG 10 WC Rehabilitation; Sport Sciences SC Rehabilitation; Sport Sciences GA 299DN UT WOS:000330375500001 PM 24252933 ER PT J AU Dong, F Yang, P Wang, CF Wu, SL Xiao, Y McDougal, WS Young, RH Wu, CL AF Dong, Fei Yang, Ping Wang, Chaofu Wu, Shulin Xiao, Yu McDougal, W. Scott Young, Robert H. Wu, Chin-Lee TI Architectural Heterogeneity and Cribriform Pattern Predict Adverse Clinical Outcome for Gleason Grade 4 Prostatic Adenocarcinoma SO AMERICAN JOURNAL OF SURGICAL PATHOLOGY LA English DT Article DE prostate cancer; Gleason score; grade; prognosis; metastasis ID 2005 INTERNATIONAL-SOCIETY; INTEROBSERVER REPRODUCIBILITY; RADICAL PROSTATECTOMY; NEEDLE-BIOPSY; CARCINOMA; CANCER; PATHOLOGY; PROGRESSION; TIME AB Gleason grade 4 defines a group of prostatic adenocarcinomas with a variety of architectural patterns, including poorly formed glands, fused glands, and cribriform pattern. To address the relative contribution to clinical prognosis by these distinct patterns, the histology of 241 consecutive radical prostatectomy specimens with the highest Gleason grade of 4 was reviewed. The presence of poorly formed glands, fused glands, and cribriform pattern was recorded for each case, and the types of architectural patterns present were associated with patient outcome. In this population, prostatic adenocarcinomas demonstrated architectural heterogeneity, with 17% of cases exhibiting a single Gleason grade 4 pattern, and 41% of cases exhibiting all 3 morphologic patterns. Patients exhibiting all 3 architectural patterns had lower rates of biochemical disease-free survival (66% vs. 76% at 5 y; log rank P= 0.006). Twenty-two of 165 patients (13.3%) with cribriform pattern adenocarcinoma developed metastasis, whereas 2 of 76 patients (2.6%) without cribriform pattern developed metastasis at a median postoperative follow-up of 10.0 years. The presence of a cribriform pattern was an independent predictor for biochemical recurrence (hazard ratio 2.41; 95% confidence interval, 1.34-4.32; P = 0.003) as well as metastasis after radical prostatectomy (hazard ratio 5.62; 95% confidence interval, 1.29-24.5; P = 0.02). These results suggest that the morphologic sub-classification of distinct Gleason grade 4 architectural patterns provides prognostic information beyond the current Gleason classification system. C1 [Dong, Fei; Yang, Ping; Wang, Chaofu; Wu, Shulin; Xiao, Yu; Young, Robert H.; Wu, Chin-Lee] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [McDougal, W. Scott; Wu, Chin-Lee] Massachusetts Gen Hosp, Dept Urol, Boston, MA 02114 USA. [Yang, Ping] Sun Yat Sen Univ, Dept Pathol, Affiliated Hosp 1, Guangzhou 510275, Guangdong, Peoples R China. RP Wu, CL (reprint author), Massachusetts Gen Hosp, Dept Pathol, Warren Bldg 225,55 Fruit St, Boston, MA 02114 USA. EM cwu2@partners.org NR 22 TC 26 Z9 26 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0147-5185 EI 1532-0979 J9 AM J SURG PATHOL JI Am. J. Surg. Pathol. PD DEC PY 2013 VL 37 IS 12 BP 1855 EP 1861 PG 7 WC Pathology; Surgery SC Pathology; Surgery GA 299YM UT WOS:000330431600009 PM 24145642 ER PT J AU Del Gobbo, A Moltrasio, F Young, RH Rosai, J AF Del Gobbo, Alessandro Moltrasio, Francesca Young, Robert H. Rosai, Juan TI Involvement of the Testis and Related Structures by Rosai-Dorfman Disease Report of 2 New Cases and Review of the Literature SO AMERICAN JOURNAL OF SURGICAL PATHOLOGY LA English DT Article DE Rosai-Dorfman disease; testicular; paratesticular ID LANGERHANS CELL HISTIOCYTOSIS; MASSIVE LYMPHADENOPATHY; SINUS-HISTIOCYTOSIS; LYMPHOMA; PATIENT; ENTITY; INFECTION; DISORDERS AB This report describes 2 new cases of testicular involvement by Rosai-Dorfman disease, also known as sinus histiocytosis with massive lymphadenopathy, and reviews the clinical and pathologic features of the other cases documented in the literature (4 cases) or included in the sinus histiocytosis with massive lymphadenopathy registry (7 cases). Our patients were 42 and 68 years of age, respectively, reflecting the usual middle-age of all the previously reported cases in this location, except for 1, which occurred in a child. Five cases were bilateral, and other sites, such as lymph nodes, kidney, skin, and adrenal gland, were involved in 8 cases. The histories were noteworthy in 2 of the cases, inasmuch as 1 patient had chronic lymphocytic leukemia, and another had a B-cell lymphoma. On gross examination, the testicular masses did not exhibit specific diagnostic features, whereas microscopic examination revealed the typical population of histiocytes, with abundant eosinophilic cytoplasm often exhibiting so-called emperipolesis. The differential diagnosis includes non-neoplastic conditions such as granulomatous orchitis, hematolymphoid disorders, a variety of metastatic tumors, and germ cell tumors. C1 [Del Gobbo, Alessandro] Univ Milan, Dept Pathol, I-20122 Milan, Italy. [Rosai, Juan] Ctr Diagnost Italiano, Milan, Italy. [Moltrasio, Francesca] Univ Milano Bicocca, Dept Pathol, Monza, Italy. [Young, Robert H.] Harvard Univ, Sch Med, Dept Pathol, Massachusetts Gen Hosp, Boston, MA 02115 USA. [Rosai, Juan] Integrated Oncol LabCorp, New York, NY USA. RP Moltrasio, F (reprint author), Univ Milano Bicocca, Dept Pathol, Monza, Italy. EM francescamoltrasio@gmail.com NR 20 TC 5 Z9 5 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0147-5185 EI 1532-0979 J9 AM J SURG PATHOL JI Am. J. Surg. Pathol. PD DEC PY 2013 VL 37 IS 12 BP 1871 EP 1875 PG 5 WC Pathology; Surgery SC Pathology; Surgery GA 299YM UT WOS:000330431600011 PM 24061526 ER PT J AU Ushiku, T Moran, CJ Lauwers, GY AF Ushiku, Tetsuo Moran, Christopher J. Lauwers, Gregory Y. TI Focally Enhanced Gastritis in Newly Diagnosed Pediatric Inflammatory Bowel Disease SO AMERICAN JOURNAL OF SURGICAL PATHOLOGY LA English DT Article DE focally enhanced gastritis; Crohn disease; ulcerative colitis ID CROHNS-DISEASE; ULCERATIVE-COLITIS; INDETERMINATE COLITIS; LYMPHOCYTIC ESOPHAGITIS; CLINICAL-SIGNIFICANCE; MORPHOLOGIC FINDINGS; CHILDREN; GRANULOMAS; ENDOSCOPY; BIOPSY AB Although the significance of focally enhanced gastritis (FEG) as a marker of Crohn disease (CD) in adults has been contested, several studies suggest that it may be more specific of CD in pediatric patients. This study describes the detailed histologic features of FEG in pediatric inflammatory bowel disease (IBD) and clarifies its association with CD. A series of 119 consecutive newly diagnosed IBD patients (62 CD cases, 57 ulcerative colitis [UC] cases) with upper and lower gastrointestinal biopsies were evaluated. The histology of the gastric biopsies was reviewed blinded to final diagnoses and compared with age-matched healthy controls (n = 66). FEG was present in 43% of IBD patients (CD 55% vs. UC 30%, P = 0.0092) and in 5% of controls. Among CD patients, FEG was more common in younger patients (73% in children aged 10 y and below, 43% in children above 10 y of age, P = 0.0358), with the peak in the 5- to 10-year age group (80%). The total number of glands involved in each FEG focus was higher in UC (6.4 +/- 5.1 glands) than in CD (4.0 +/- 3.0 glands, P = 0.0409). Amongst the CD cohort, patients with FEG were more likely than those without FEG to have active ileitis (79% vs. 40%, P = 0.0128) and granulomas elsewhere in the gastrointestinal tract (82% vs. 43%, P = 0.0016). There was no correlation between FEG and other gastrointestinal findings of UC. We demonstrate that differences in FEG seen in pediatric CD and UC relate to not only their frequencies but also the morphology and relationship with other gastrointestinal lesions. Further, FEG is associated with disease activity and the presence of granulomas in pediatric CD. C1 [Ushiku, Tetsuo; Lauwers, Gregory Y.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Ushiku, Tetsuo; Lauwers, Gregory Y.] Massachusetts Gen Hosp, Ctr Study Inflammatory Bowel Dis, Boston, MA 02114 USA. [Ushiku, Tetsuo; Lauwers, Gregory Y.] Harvard Univ, Sch Med, Boston, MA USA. [Moran, Christopher J.] Massachusetts Gen Hosp, Dept Pediat, Div Pediat Gastroenterol Hepatol & Nutr, Boston, MA 02114 USA. RP Ushiku, T (reprint author), Univ Tokyo, Dept Pathol, Bunkyo Ku, 7-3-1 Hongo, Tokyo 1130033, Japan. EM usikut-tky@umin.ac.jp FU Center for the Study of Inflammatory Bowel Disease at Massachusetts General Hospital [DK043351] FX G.Y.L. is supported by the Center for the Study of Inflammatory Bowel Disease (DK043351) at Massachusetts General Hospital. The authors have disclosed that they have no significant relationships with, or financial interest in, any commercial companies pertaining to this article. NR 25 TC 8 Z9 8 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0147-5185 EI 1532-0979 J9 AM J SURG PATHOL JI Am. J. Surg. Pathol. PD DEC PY 2013 VL 37 IS 12 BP 1882 EP 1888 PG 7 WC Pathology; Surgery SC Pathology; Surgery GA 299YM UT WOS:000330431600013 PM 24121177 ER PT J AU Lovich, MA Wakim, MG Wei, A Parker, MJ Maslov, MY Pezone, MJ Tsukada, H Peterfreund, RA AF Lovich, Mark A. Wakim, Matthew G. Wei, Abraham Parker, Michael J. Maslov, Mikhail Y. Pezone, Matthew J. Tsukada, Hisashi Peterfreund, Robert A. TI Drug Infusion System Manifold Dead-Volume Impacts the Delivery Response Time to Changes in Infused Medication Doses In Vitro and Also In Vivo in Anesthetized Swine SO ANESTHESIA AND ANALGESIA LA English DT Article ID DYNAMICS AB BACKGROUND: IV infusion systems can be configured with manifolds connecting multiple drug infusion lines to transcutaneous catheters. Prior in vitro studies suggest that there may be significant lag times for drug delivery to reflect changes in infusion rates set at the pump, especially with low drug and carrier flows and larger infusion system dead-volumes. Drug manifolds allow multiple infusions to connect to a single catheter port but add dead-volume. We hypothesized that the time course of physiological responses to drug infusion in vivo reflects the impact of dead-volume on drug delivery. METHODS: The kinetic response to starting and stopping epinephrine infusion ([3 mL/h] with constant carrier flow [10 mL/h]) was compared for high- and low-dead-volume manifolds in vitro and in vivo. A manifold consisting of 4 sequential stopcocks with drug entering at the most upstream port was contrasted with a novel design comprising a tube with separate coaxial channels meeting at the downstream connector to the catheter, which virtually eliminates the manifold contribution to the dead-volume. The time to 50% (T-50) and 90% (T-90) increase or decrease in drug delivery in vitro or contractile response in a swine model in vivo were calculated for initiation and cessation of drug infusion. RESULTS: The time to steady state after initiation and cessation of drug infusion both in vitro and in vivo was much less with the coaxial low-dead-volume manifold than with the high-volume design. Drug delivery after initiation in vitro reached 50% and 90% of steady state in 1.4 +/- 0.12 and 2.2 +/- 0.42 minutes with the low-dead-volume manifold and in 7.1 +/- 0.58 and 9.8 +/- 1.6 minutes with the high-dead-volume manifold, respectively. The contractility in vivo reached 50% and 90% of the full response after drug initiation in 4.3 +/- 1.3 and 9.9 +/- 3.9 minutes with the low-dead-volume manifold and 11 +/- 1.2 and 17 +/- 2.6 minutes with the high-dead-volume manifold, respectively. Drug delivery in vitro decreased by 50% and 90% after drug cessation in 1.9 +/- 0.17 and 3.5 +/- 0.61 minutes with the low-dead-volume manifold and 10.0 +/- 1.0 and 17.0 +/- 2.8 minutes with the high-dead-volume manifold, respectively. The contractility in vivo decreased by 50% and 90% with drug cessation in 4.1 +/- 1.1 and 14 +/- 5.2 with the low-dead-volume manifold and 12 +/- 2.7 and 23 +/- 5.6 minutes with the high-dead-volume manifold, respectively. CONCLUSIONS: The architecture of the manifold impacts the in vivo biologic response, and the drug delivery rate, to changes in drug infusion rate set at the pump. C1 [Lovich, Mark A.; Wakim, Matthew G.; Wei, Abraham; Maslov, Mikhail Y.; Pezone, Matthew J.] Steward St Elizabeths Med Ctr, Dept Anesthesiol Crit Care & Pain Med, Boston, MA 02135 USA. [Parker, Michael J.] Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Div Pulm Crit Care & Sleep Med,Dept Med, Boston, MA 02215 USA. [Tsukada, Hisashi] Steward St Elizabeths Med Ctr, Dept Med, Div Pulm Crit Care & Sleep Med, Boston, MA 02135 USA. [Peterfreund, Robert A.] Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, Boston, MA 02114 USA. RP Lovich, MA (reprint author), Steward St Elizabeths Med Ctr, Dept Anesthesiol Crit Care & Pain Med, 736 Cambridge St, Boston, MA 02135 USA. EM lovich@steward.org FU Doran International; American Heart Association; Department of Anesthesiology, Critical Care and Pain Medicine, Steward St. Elizabeth's Medical Center, Boston, MA FX In part by Doran International, American Heart Association Scientists Development Grant, and the Department of Anesthesiology, Critical Care and Pain Medicine, Steward St. Elizabeth's Medical Center, Boston, MA. NR 7 TC 10 Z9 10 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0003-2999 EI 1526-7598 J9 ANESTH ANALG JI Anesth. Analg. PD DEC PY 2013 VL 117 IS 6 BP 1313 EP 1318 DI 10.1213/ANE.0b013e3182a76f3b PG 6 WC Anesthesiology SC Anesthesiology GA 300AV UT WOS:000330437700009 PM 24257380 ER PT J AU Hyder, JA Kor, DJ Cima, RR Subramanian, A AF Hyder, Joseph A. Kor, Daryl J. Cima, Robert R. Subramanian, Arun TI How to Improve the Performance of Intraoperative Risk Models: An Example with Vital Signs Using the Surgical Apgar Score SO ANESTHESIA AND ANALGESIA LA English DT Article ID INTEGRATED DISCRIMINATION IMPROVEMENT; PERIOPERATIVE RISK; PREDICTION MODELS; ADVERSE EVENTS; SURGERY; QUALITY; CARE; RECLASSIFICATION; PROGRAM; COMPLICATIONS AB BACKGROUND: Computerized reviews of patient data promise to improve patient care through early and accurate identification of at-risk and well patients. The significance of sampling strategy for patient vital signs data is not known. In the instance of the surgical Apgar score (SAS), we hypothesized that larger sampling intervals would improve the specificity and overall predictive ability of this tool. METHODS: We used electronic intraoperative data from general and vascular surgical patients in a single-institution registry of the American College of Surgeons National Surgical Quality Improvement Program. The SAS, consisting of lowest heart rate, lowest mean arterial blood pressure, and estimated blood loss between incision and skin closure, was calculated using 5 methods: instantaneously and using intervals of of 5 and 10 minutes with and without interval overlap. Major complications including death were assessed at 30 days postoperatively. RESULTS: Among 3000 patients, 272 (9.1%) experienced major complications or death. As the sampling interval increased from instantaneous (shortest) to 10 minutes without overlap (largest), the sensitivity, positive predictive value, and negative predictive value did not change significantly, but significant improvements were noted for specificity (79.5% to 82.9% across methods, P for trend < 0.001) and accuracy (76.0% to 79.3% across methods, P for trend < 0.01). In multivariate modeling, the predictive utility of the SAS as measured by the c-statistic nearly increased from Delta c = +0.012 (P = 0.038) to Delta c = +0.021 (P < 0.002) between the shortest and largest sampling intervals, respectively. Compared with a preoperative risk model, the net reclassification improvement and integrated discrimination improvement for the shortest versus largest sampling intervals of the SAS were net reclassification improvement 0.01 (P = 0.8) vs 0.06 (P = 0.02), and for integrated discrimination improvement, they were 0.008 (P < 0.01) vs 0.015 (P < 0.001). CONCLUSIONS: When vital signs data are recorded in compliance with American Society of Anesthesiologists' standards, the sampling strategy for vital signs significantly influences performance of the SAS. Computerized reviews of patient data are subject to the choice of sampling methods for vital signs and may have the potential to be optimized for safe, efficient patient care. C1 [Hyder, Joseph A.] Mayo Clin, Dept Anesthesiol, Rochester, MN USA. [Kor, Daryl J.; Subramanian, Arun] Mayo Clin, Dept Anesthesiol, Div Crit Care Med, Rochester, MN USA. [Cima, Robert R.] Mayo Clin, Rochester, MN USA. RP Hyder, JA (reprint author), Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, Boston, MA 02114 USA. EM joseph.a.hyder@gmail.com FU Division of Critical Care, Mayo Clinic, Rochester, MN FX This work was supported, in part, by a grant from the Division of Critical Care, Mayo Clinic, Rochester, MN. NR 35 TC 10 Z9 10 U1 1 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0003-2999 EI 1526-7598 J9 ANESTH ANALG JI Anesth. Analg. PD DEC PY 2013 VL 117 IS 6 BP 1338 EP 1346 DI 10.1213/ANE.0b013e3182a46d6d PG 9 WC Anesthesiology SC Anesthesiology GA 300AV UT WOS:000330437700013 PM 24036620 ER PT J AU Mashour, GA Sharifpour, M Freundlich, RE Tremper, KK Shanks, A Nallamothu, BK Vlisides, PE Weightman, A Matlen, L Merte, J Kheterpal, S AF Mashour, George A. Sharifpour, Milad Freundlich, Robert E. Tremper, Kevin K. Shanks, Amy Nallamothu, Brahmajee K. Vlisides, Phillip E. Weightman, Adam Matlen, Lisa Merte, Janna Kheterpal, Sachin TI Perioperative Metoprolol and Risk of Stroke after Noncardiac Surgery SO ANESTHESIOLOGY LA English DT Article ID BETA-BLOCKADE; CARDIAC-SURGERY; ISCHEMIC-STROKE; ASSOCIATION; BLOCKERS; METAANALYSIS; MORTALITY; UPDATE AB Background: Numerous risk factors have been identified for perioperative stroke, but there are conflicting data regarding the role of beta adrenergic receptor blockade in general and metoprolol in particular. Methods: The authors retrospectively screened 57,218 consecutive patients for radiologic evidence of stroke within 30 days after noncardiac procedures at a tertiary care university hospital. Incidence of perioperative stroke within 30 days of surgery and associated risk factors were assessed. Patients taking either metoprolol or atenolol were matched based on a number of risk factors for stroke. Parsimonious logistic regression was used to generate a preoperative risk model for perioperative stroke in the unmatched cohort. Results: The incidence of perioperative stroke was 55 of 57,218 (0.09%). Preoperative metoprolol was associated with an approximately 4.2-fold increase in perioperative stroke (P < 0.001; 95% CI, 2.2-8.1). Analysis of matched cohorts revealed a significantly higher incidence of stroke in patients taking preoperative metoprolol compared with atenolol (P = 0.016). However, preoperative metoprolol was not an independent predictor of stroke in the entire cohort, which included patients who were not taking beta blockers. The use of intraoperative metoprolol was associated with a 3.3-fold increase in perioperative stroke (P = 0.003; 95% CI, 1.4-7.8); no association was found for intraoperative esmolol or labetalol. Conclusions: Routine use of preoperative metoprolol, but not atenolol, is associated with stroke after noncardiac surgery, even after adjusting for comorbidities. Intraoperative metoprolol but not esmolol or labetalol, is associated with increased risk of perioperative stroke. Drugs other than metoprolol should be considered during the perioperative period if beta blockade is required. C1 [Mashour, George A.; Freundlich, Robert E.; Tremper, Kevin K.; Weightman, Adam; Matlen, Lisa; Merte, Janna] Univ Michigan, Sch Med, Dept Anesthesiol, Ann Arbor, MI 48109 USA. [Shanks, Amy] Univ Michigan, Sch Med, Dept Anesthesiol, Stat Core, Ann Arbor, MI 48109 USA. [Nallamothu, Brahmajee K.] Univ Michigan, Sch Med, Dept Internal Med, Ann Arbor, MI 48109 USA. [Sharifpour, Milad; Vlisides, Phillip E.] Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, Boston, MA 02114 USA. [Kheterpal, Sachin] Univ Michigan, Ctr Perioperat Outcomes Res, Dept Anesthesiol, Ann Arbor, MI 48109 USA. RP Mashour, GA (reprint author), Univ Michigan, Sch Med, Dept Anesthesiol, 1500 E Med Ctr Dr, Ann Arbor, MI 48109 USA. EM gmashour@umich.edu FU National Center for Advancing Translational Sciences (Bethesda, Maryland) [UL1RR024986, 2UL1TR000433]; Department of Anesthesiology at the University of Michigan Medical School, Ann Arbor, Michigan FX Supported in part by the National Center for Research Resources, Grant UL1RR024986, which is now at the National Center for Advancing Translational Sciences (Bethesda, Maryland), Grant 2UL1TR000433 and the Department of Anesthesiology at the University of Michigan Medical School, Ann Arbor, Michigan. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. NR 24 TC 28 Z9 29 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0003-3022 EI 1528-1175 J9 ANESTHESIOLOGY JI Anesthesiology PD DEC PY 2013 VL 119 IS 6 BP 1340 EP 1346 DI 10.1097/ALN.0b013e318295a25f PG 7 WC Anesthesiology SC Anesthesiology GA 301JJ UT WOS:000330528300015 PM 23612244 ER PT J AU Harris, RE Napadow, V Huggins, JP Pauer, L Kim, J Hampson, J Sundgren, PC Foerster, B Petrou, M Schmidt-Wilcke, T Clauw, DJ AF Harris, Richard E. Napadow, Vitaly Huggins, John P. Pauer, Lynne Kim, Jieun Hampson, Johnson Sundgren, Pia C. Foerster, Bradley Petrou, Myria Schmidt-Wilcke, Tobias Clauw, Daniel J. TI Pregabalin Rectifies Aberrant Brain Chemistry, Connectivity, and Functional Response in Chronic Pain Patients SO ANESTHESIOLOGY LA English DT Article ID PLACEBO-CONTROLLED TRIAL; GLUTAMATE RELEASE; NEUROPATHIC PAIN; FIBROMYALGIA; GABAPENTIN; INHIBITION; ROBUST; FMRI; REGISTRATION; PLASTICITY AB Background: Chronic pain remains a significant challenge for modern health care as its pathologic mechanisms are largely unknown and preclinical animal models suffer from limitations in assessing this complex subjective experience. However, human brain neuroimaging techniques enable the assessment of functional and neurochemical alterations in patients experiencing chronic pain and how these factors may dynamically change with pharmacologic treatment. Methods: To identify the clinical action of pregabalin, a proven analgesic, the authors performed three complementary brain neuroimaging procedures: (proton magnetic resonance spectroscopy, functional magnetic resonance imaging, and functional connectivity magnetic resonance imaging) in 17 chronic pain patients diagnosed with fibromyalgia. Results: The authors found that pregabalin but not placebo reduces combined glutamate + glutamine levels within the posterior insula (pregabalin P = 0.016; placebo P = 0.71). Interestingly, reductions in clinical pain were associated with reductions in brain connectivity of this structure to brain regions within the default mode network during pregabalin (r = 0.82; P = 0.001) but not placebo (r = -0.13; P = 0.63). Response of default mode network regions to experimental pain was also reduced with pregabalin (P = 0.018) but not placebo (P = 0.182). Perhaps most importantly, baseline values for all three neuroimaging markers predicted subsequent analgesic response to pregabalin but not placebo. Conclusions: The results of this study suggest that pregabalin works in part by reducing insular glutamatergic activity, leading to a reduction of the increased functional connectivity seen between brain regions in chronic pain states. The study also supports a role for human brain imaging in the development, assessment, and personalized use of centralacting analgesics. C1 [Harris, Richard E.; Hampson, Johnson; Clauw, Daniel J.] Univ Michigan, Chron Pain & Fatigue Res Ctr, Dept Anesthesiol, Ann Arbor, MI 48106 USA. [Napadow, Vitaly; Kim, Jieun] Harvard Univ, Sch Med, Martinos Ctr Biomed Imaging, Massachusetts Gen Hosp,Dept Radiol, Boston, MA 02115 USA. [Huggins, John P.; Pauer, Lynne] Pfizer Inc, Groton, CT 06340 USA. [Sundgren, Pia C.; Foerster, Bradley; Petrou, Myria] Univ Michigan, Dept Radiol, Div Neuroradiol, Ann Arbor, MI 48106 USA. [Sundgren, Pia C.] Lund Univ, Dept Diagnost Radiol, Clin Sci Lund, Lund, Sweden. [Foerster, Bradley] Ann Arbor VA Healthcare Syst, Ann Arbor, MI USA. [Schmidt-Wilcke, Tobias] Ruhr Univ Bochum, Dept Neurol, Bergmannsheil, Berufsgenossenschaftliche Univ Klin, Bochum, Germany. RP Harris, RE (reprint author), Univ Michigan, Chron Pain & Fatigue Res Ctr, Dept Anesthesiol, POB 385,24 Frank Lloyd Wright Dr, Ann Arbor, MI 48106 USA. EM reharris@med.umich.edu OI Sundgren, Pia/0000-0001-9237-1236 FU Pfizer Incorporated, Groton Connecticut FX This trial was funded by a grant from Pfizer Incorporated, Groton Connecticut. Both Drs. Harris and Clauw have previously consulted for Pfizer Inc. Also, Drs. Pauer and Huggins were employed by Pfizer and were shareholders at the time that this study was performed. No other authors have competing interests. This work was presented in part at the American College of Rheumatology meeting, Chicago, Illinois, November 10, 2011. The first two authors contributed equally to the writing of this article. NR 46 TC 54 Z9 54 U1 2 U2 13 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0003-3022 EI 1528-1175 J9 ANESTHESIOLOGY JI Anesthesiology PD DEC PY 2013 VL 119 IS 6 BP 1453 EP 1464 DI 10.1097/ALN.0000000000000017 PG 12 WC Anesthesiology SC Anesthesiology GA 301JJ UT WOS:000330528300025 PM 24343290 ER PT J AU Bronshteyn, YS AF Bronshteyn, Yuriy S. TI Value-based Healthcare SO ANESTHESIOLOGY LA English DT Editorial Material C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Bronshteyn, YS (reprint author), Massachusetts Gen Hosp, Boston, MA 02114 USA. EM yuriy.bronshteyn@gmail.com OI Bronshteyn, Yuriy/0000-0002-9250-9490 NR 0 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 0003-3022 EI 1528-1175 J9 ANESTHESIOLOGY JI Anesthesiology PD DEC PY 2013 VL 119 IS 6 BP 1490 EP 1491 DI 10.1097/ALN.0b013e31829996d0 PG 2 WC Anesthesiology SC Anesthesiology GA 301JJ UT WOS:000330528300030 PM 23702816 ER PT J AU Merkow, RP Bentrem, DJ Mulcahy, MF Chung, JW Abbott, DE Kmiecik, TE Stewart, AK Winchester, DP Ko, CY Bilimoria, KY AF Merkow, Ryan P. Bentrem, David J. Mulcahy, Mary F. Chung, Jeanette W. Abbott, Daniel E. Kmiecik, Thomas E. Stewart, Andrew K. Winchester, David P. Ko, Clifford Y. Bilimoria, Karl Y. TI Effect of Postoperative Complications on Adjuvant Chemotherapy Use for Stage III Colon Cancer SO ANNALS OF SURGERY LA English DT Article DE ACS NSQIP; adjuvant chemotherapy; colon cancer; complications; NCDB ID SURGICAL QUALITY IMPROVEMENT; COLORECTAL-CANCER; UNITED-STATES; THERAPY; FLUOROURACIL; LEVAMISOLE; CARCINOMA; SURGERY; PROGRAM; AGE AB Objective: The National Quality Forum has endorsed a quality metric concerning the use of adjuvant chemotherapy administration in stage III colon cancer, yet a substantial treatment gap exists. Our objective was to evaluate the association of postoperative complications on the use of adjuvant therapy after colectomy for cancer. Patients and Methods: Data from the American College of Surgeons National Surgical Quality Improvement Program and National Cancer Data Base were linked to augment cancer registry information with robust clinical data on comorbidities and postoperative complications (2006-2008). The association of complications on adjuvant chemotherapy use was assessed using hierarchical multivariable regression models. Results: From 126 hospitals, 2368 patients underwent resection for stage III colon adenocarcinoma. Overall utilization of adjuvant chemotherapy was 63.2% (1497/2368). Of the 871 patients who did not receive chemotherapy, 652 met National Quality Forum exclusion criteria: death, severe comorbidity, refusal of care, advanced age (>= 80 years), or prior malignancy. Of the remaining 219 patients, 19.1% (42/219) had 1 or more serious postoperative complications (eg, pneumonia, pulmonary failure). After accounting for the aforementioned potential explanations, the utilization rate was 87.2% (1497/1716). The strongest predictors of adjuvant chemotherapy omission were prolonged postoperative ventilation, renal failure, reintubation, and pneumonia (all Ps < 0.05). Superficial surgical site infection did not decrease adjuvant therapy receipt but delayed the time to its use by 3-fold. Serious complications increased time to chemotherapy by 65%. Abscess/anastomotic leak increased time to adjuvant chemotherapy by more than 5-fold. Conclusions: Serious postoperative complications explained nearly 20% of the adjuvant chemotherapy treatment gap for patients with stage III colon cancer. The use of clinical data remains important when judging provider performance. C1 [Merkow, Ryan P.; Stewart, Andrew K.; Winchester, David P.; Ko, Clifford Y.; Bilimoria, Karl Y.] Amer Coll Surg, Div Res & Optimal Patient Care, Chicago, IL 60611 USA. [Merkow, Ryan P.; Bentrem, David J.; Mulcahy, Mary F.; Chung, Jeanette W.; Kmiecik, Thomas E.; Bilimoria, Karl Y.] Northwestern Univ, Feinberg Sch Med, Surg Outcomes & Qual Improvement Ctr, Northwestern Inst Comparat Effectiveness Res Onco, Chicago, IL 60611 USA. [Merkow, Ryan P.; Bentrem, David J.; Mulcahy, Mary F.; Chung, Jeanette W.; Kmiecik, Thomas E.; Bilimoria, Karl Y.] Northwestern Univ, Feinberg Sch Med, Dept Surg, Chicago, IL 60611 USA. [Merkow, Ryan P.] Univ Chicago, Pritzker Sch Med, Dept Surg, Chicago, IL 60637 USA. [Bentrem, David J.] Jesse Brown VAMC, Dept Surg, Chicago, IL USA. [Abbott, Daniel E.] Univ Cincinnati, Dept Surg, Sch Med, Cincinnati, OH 45267 USA. [Ko, Clifford Y.] Univ Calif Los Angeles, Dept Surg, Los Angeles, CA 90024 USA. [Ko, Clifford Y.] VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. RP Merkow, RP (reprint author), Amer Coll Surg, Div Res & Optimal Patient Care, 633 N St Clair St,22nd Floor, Chicago, IL 60611 USA. EM RMerkow@facs.org FU American Cancer Society [280521]; Northwestern Institute for Comparative Effectiveness Research in Oncology FX Supported in part by the American Cancer Society (#280521) to R.P.M. and K.Y.B. and the Northwestern Institute for Comparative Effectiveness Research in Oncology to R.P.M., K.Y.B., and D.J.B. The authors declare no conflicts of interest. NR 32 TC 29 Z9 29 U1 1 U2 6 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0003-4932 EI 1528-1140 J9 ANN SURG JI Ann. Surg. PD DEC PY 2013 VL 258 IS 6 BP 847 EP 853 DI 10.1097/SLA.0000000000000312 PG 7 WC Surgery SC Surgery GA 300MF UT WOS:000330467300002 PM 24169157 ER PT J AU Lawson, EH Ko, CY Adams, JL Chow, WB Hall, BL AF Lawson, Elise H. Ko, Clifford Y. Adams, John L. Chow, Warren B. Hall, Bruce Lee TI Reliability of Evaluating Hospital Quality by Colorectal Surgical Site Infection Type SO ANNALS OF SURGERY LA English DT Article DE colorectal; quality measure; reliability; surgical site infection ID COMPOSITE END-POINTS; RANDOMIZED-TRIALS; WOUND-INFECTION; RISK-FACTORS; MORTALITY; SURGERY; SURVEILLANCE; RESECTION; COLON; CARE AB Objective: To determine whether risk-adjusted colorectal SSI rates are statistically reliable as hospital quality measures. Background: Policymakers use surgical site infections (SSI) for public reporting of hospital quality and pay-for-performance because they are a relatively common and costly cause of patient morbidity. Methods: Patients who underwent a colorectal procedure in 2009 were identified from the American College of Surgeons National Surgical Quality Improvement Program. We developed hierarchical multivariate logistic models for (1) superficial SSI, (2) deep/organ-space SSI, and (3) "any SSI" and compared how each model ranked hospital-level risk-adjusted performance. Statistical reliability of hospital quality measurements was estimated on a scale from 0 to 1; with 0 indicating that apparent variation between a hospital's quality measurement and the average hospital is statistically unreliable, and 1 indicating that any observed variation is due to a real difference in performance. Results: Mean reliability of hospital-level quality measurements was 0.650 for superficial, 0.404 for deep/organ-space, and 0.586 for "any SSI." Lower reliability was accounted for by relatively little variation in risk-adjusted SSI rates between hospitals and insufficient numbers of colorectal cases submitted by individual hospitals. In 2009, we estimate that 22.1% of all US hospitals performed a sufficient number of colorectal cases to report superficial SSI rates at a high standard of statistical reliability and 1.0% did for deep/organ-space SSI. Conclusions: As currently constructed, colorectal SSI quality measures might not meet a high standard of statistical reliability for most hospitals, limiting their ability to confidently differentiate high and low performance. Despite an expectation of improving statistical power, combining superficial and deep/organ-space SSI into an "any SSI" measure worsens reliability. C1 [Lawson, Elise H.; Ko, Clifford Y.; Chow, Warren B.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Surg, Los Angeles, CA 90095 USA. [Lawson, Elise H.; Ko, Clifford Y.; Chow, Warren B.] Amer Coll Surg, Div Res & Optimal Patient Care, Chicago, IL USA. [Ko, Clifford Y.] VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. [Adams, John L.] RAND Corp, Santa Monica, CA USA. [Hall, Bruce Lee] Washington Univ, Sch Med, Dept Surg, Barnes Jewish Hosp,St Louis Vet Affairs Med Ctr, St Louis, MO 63110 USA. [Hall, Bruce Lee] Washington Univ, Ctr Hlth Policy, St Louis, MO USA. [Hall, Bruce Lee] Olin Business Sch, St Louis, MO USA. RP Lawson, EH (reprint author), Univ Calif Los Angeles, David Geffen Sch Med, Dept Surg, 10833 Le Conte Ave,72-215 CHS, Los Angeles, CA 90095 USA. EM elawson@mednet.ucla.edu FU VA Health Services Research and Development program [RWJ 65-020]; American College of Surgeons (ACS) through the Robert Wood Johnson Foundation Clinical Scholars Program (RWJF CSP) FX E.H.L.'s time was supported by the VA Health Services Research and Development program (RWJ 65-020) and the American College of Surgeons (ACS) through the Robert Wood Johnson Foundation Clinical Scholars Program (RWJF CSP). J.L.A. and B.L.H. are each consultants for the ACS, W.B.C. is a Scholar in Residence at the ACS, and C.Y.K. is staff at the ACS. This study received no outside funding. The authors declare no conflicts of interest. NR 26 TC 16 Z9 16 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0003-4932 EI 1528-1140 J9 ANN SURG JI Ann. Surg. PD DEC PY 2013 VL 258 IS 6 BP 994 EP 1000 DI 10.1097/SLA.0b013e3182929178 PG 7 WC Surgery SC Surgery GA 300MF UT WOS:000330467300021 PM 23657082 ER PT J AU Heneghan, AF Pierre, JF Kudsk, KA AF Heneghan, Aaron F. Pierre, Joseph F. Kudsk, Kenneth A. TI IL-25 Improves IgA Levels During Parenteral Nutrition Through the JAK-STAT Pathway SO ANNALS OF SURGERY LA English DT Article DE adaptive immunity; IgA; JAK-STAT; parenteral nutrition; pIgR; small intestine ID POLYMERIC IMMUNOGLOBULIN RECEPTOR; UPPER RESPIRATORY-TRACT; MAJOR ABDOMINAL-TRAUMA; SMOOTH-MUSCLE CELLS; LYMPHOID-TISSUE; SEPTIC MORBIDITY; MUCOSAL IMMUNITY; EOTAXIN RELEASE; RESPONSES; INTERLEUKIN-13 AB Introduction: Parenteral nutrition (PN) impairs mucosal immunity and increases the risk of infection in part via lower IgA levels at mucosal surfaces. Transport of immunoglobulin A (IgA) across the mucosa to the gut lumen depends on the epithelial transport protein, polymeric immunoglobulin receptor (pIgR), which is reduced during PN. In vitro, studies demonstrate that IL-4 up-regulates pIgR production via Janus kinase/signal transducers and activators of transcription (JAK/STAT) signaling. Because IL-4 stimulates IgA and is reduced during PN, we hypothesized that the suppressed pIgR is a result of decreased JAK-1 and STAT-6 phosphorylation. Because IL-4 is mediated by IL-25, we also hypothesized that PN + IL-25 would restore luminal IgA by increasing phosphorylated JAK-1 and STAT-6, resulting in increased tissue pIgR and luminal IgA. Method: Experiment 1: 2 days after intravenous cannulation, male Institute of Cancer Research mice were randomized to chow (n = 11) or PN (n = 9). Experiment 2: 2 days after intravenous cannulation, male Institute of Cancer Research mice were randomized to chow (n = 12), PN (n = 10), or PN + 0.7 mu g of exogenous IL-25 (n = 11) per day. After 5 days, distal ileum tissue was collected, homogenized, and protein extracted for JAK-STAT expression levels using a phospho-specific antibody microarray. Tissue was homogenized to measure pIgR expression via Western blot or fixed in 4% paraformaldehyde to measure pIgR expression via immunohistochemistry. Small intestinal wash fluid was collected and IgA was quantified using enzyme-linked immunosorbent assay. Results: Experiment 1: PN significantly reduced phosphorylated JAK-1 and STAT-6 compared with chow. PN also decreased the tissue levels of the Th2 cytokines, IL-4 and IL-13, as well as pIgR, and luminal IgA compared with chow. Experiment 2: Exogenous administration of PN + IL-25 increased the phosphorylated JAK-1 and STAT-6 compared with PN alone. IL-25 completely restored expression of IL-13 to chow levels. IL-4, pIgR, IgA, and phosphorylated JAK-1 were significantly increased with IL-25 treatment compared with PN but failed to reach levels measured in chow. STAT-6 was significantly increased with IL-25 treatment compared with chow and PN. Conclusions: PN significantly decreases the JAK-STAT pathway by reducing levels of phosphorylated STAT-6 and JAK-1. Consistent with our previous work, sIgA, pIgR, and IL-4 decreased with PN, whereas the addition of IL-25 to PN reversed these decreases and demonstrated the role of the JAK-STAT pathway in vivo during PN. C1 [Heneghan, Aaron F.; Pierre, Joseph F.; Kudsk, Kenneth A.] Univ Wisconsin, Dept Surg, Sch Med & Publ Hlth, Madison, WI USA. [Kudsk, Kenneth A.] William S Middleton Mem Vet Adm Med Ctr, Veteran Adm Surg Serv, Madison, WI USA. RP Kudsk, KA (reprint author), 600 Highland Ave,H4-736, Madison, WI 53792 USA. EM Kudsk@surgery.wisc.edu FU Biomedical Laboratory Research and Development Service of the VA Office of Research and Development [I01BX001672]; National Institute of Health (NIH) [R01 GM53439] FX This project was supported by Award Number I01BX001672 from the Biomedical Laboratory Research and Development Service of the VA Office of Research and Development. This research is supported by National Institute of Health (NIH) Grant R01 GM53439. The contents of this article do not represent the views of the Veterans Affairs or the United States Government. The authors declare no conflicts of interest. NR 47 TC 5 Z9 6 U1 0 U2 7 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0003-4932 EI 1528-1140 J9 ANN SURG JI Ann. Surg. PD DEC PY 2013 VL 258 IS 6 BP 1065 EP 1071 DI 10.1097/SLA.0b013e318277ea9e PG 7 WC Surgery SC Surgery GA 300MF UT WOS:000330467300031 PM 23160152 ER PT J AU Long, CA Boloum, V Albadawi, H Tsai, S Yoo, HJ Oklu, R Goldman, MH Watkins, MT AF Long, Chandler A. Boloum, Valy Albadawi, Hassan Tsai, Shirling Yoo, Hyung-Jin Oklu, Rahmi Goldman, Mitchell H. Watkins, Michael T. TI Poly-ADP-Ribose-Polymerase Inhibition Ameliorates Hind Limb Ischemia Reperfusion Injury in a Murine Model of Type 2 Diabetes SO ANNALS OF SURGERY LA English DT Article DE diabetes; ischemia; reperfusion; skeletal muscle ID SKELETAL-MUSCLE; GLYCERALDEHYDE-3-PHOSPHATE DEHYDROGENASE; RISK-FACTORS; ENDOTHELIAL DYSFUNCTION; ACTIVATION; DISEASE; CELLS; COMPLICATIONS; INFLAMMATION; PATHOGENESIS AB Introduction: Diabetes is known to increase poly-ADP-ribose-polymerase (PARP) activity and posttranslational poly-ADP-ribosylation of several regulatory proteins involved in inflammation and energy metabolism. These experiments test the hypothesis that PARP inhibition will modulate hind limb ischemia reperfusion (IR) in a mouse model of type-II diabetes and ameliorate the ribosylation and the activity/transnuclear localization of the key glycolytic enzyme glyceraldehyde-3-phosphate dehydrogenase (GAPDH). Methods: db/db mice underwent 1.5 hours of hind limb ischemia followed by 1, 7, or 24 hours of reperfusion. The treatment group received the PARP inhibitor PJ34 (PJ34) over a 24-hour period; the untreated group received Lactated Ringer (LR) at the same time points. IR muscles were analyzed for indices of PARP activity, fiber injury, metabolic activity, inflammation, GAPDH activity/intracellular localization, and poly-ADP-ribosylation of GAPDH. Results: PARP activity was significantly lower in the PJ34-treated groups than in the Lactated Ringer group at 7 and 24 hours of reperfusion. There was significantly less muscle fiber injury in the PJ34-treated group than in the Lactated Ringer-treated mice at 24 hours of reperfusion. PJ34 lowered levels of select proinflammatory molecules at 7 hours and 24 hours of IR. There were significant increases in metabolic activity only at 24 hours of IR in the PJ34 group, which temporally correlated with increase in GAPDH activity, decreased GAPDH poly-ADP-ribosylation, and nuclear translocation of GAPDH. Conclusions: PJ34 reduced PARP activity, GAPDH ribosylation, and GAPDH translocation; ameliorated muscle fiber injury; and increased metabolic activity after hind limb IR injury in a murine model of type-II diabetes. PARP inhibition might be a therapeutic strategy after IR in diabetic humans. C1 [Long, Chandler A.; Boloum, Valy; Albadawi, Hassan; Tsai, Shirling; Yoo, Hyung-Jin; Watkins, Michael T.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Vasc & Endovasc Surg, Boston, MA USA. [Long, Chandler A.; Boloum, Valy; Albadawi, Hassan; Tsai, Shirling; Yoo, Hyung-Jin; Watkins, Michael T.] Univ Tennessee, Med Ctr, Knoxville, TN USA. [Long, Chandler A.; Goldman, Mitchell H.] Univ Tennessee, Grad Sch Med, Dept Surg, Knoxville, TN USA. [Boloum, Valy] Sinai Hosp, Dept Surg, Baltimore, MD 21215 USA. [Oklu, Rahmi] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Vasc Imaging & Intervent, Boston, MA USA. [Watkins, Michael T.] Massachusetts Gen Hosp, Div Vasc & Endovasc Surg, Boston, MA 02114 USA. RP Watkins, MT (reprint author), Massachusetts Gen Hosp, Div Vasc & Endovasc Surg, 15 Parkman St,Suite 440, Boston, MA 02114 USA. EM mtwatkins@partners.org FU National Institutes of Health [1R01AR055843]; American Diabetes Association; Pacific Vascular Research Foundation, the Department of Surgery, Division of Vascular and Endovascular Surgery, Massachusetts General Hospital (The Geneen Fund); Department of Surgery, The University of Tennessee, Knoxville; Sinai Hospital, Baltimore, MD FX This study was funded by the National Institutes of Health (1R01AR055843); the American Diabetes Association; the Pacific Vascular Research Foundation, the Department of Surgery, Division of Vascular and Endovascular Surgery, Massachusetts General Hospital (The Geneen Fund); the Department of Surgery, The University of Tennessee, Knoxville; and Sinai Hospital, Baltimore, MD. The authors declare no conflicts of interest. NR 56 TC 8 Z9 8 U1 2 U2 10 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0003-4932 EI 1528-1140 J9 ANN SURG JI Ann. Surg. PD DEC PY 2013 VL 258 IS 6 BP 1087 EP 1095 DI 10.1097/SLA.0b013e31828cced3 PG 9 WC Surgery SC Surgery GA 300MF UT WOS:000330467300034 PM 23549425 ER PT J AU Gupta, PK Sundaram, A MacTaggart, JN Johanning, JM Gupta, H Fang, X Forse, RA Balters, M Longo, GM Sugimoto, JT Lynch, TG Pipinos, II AF Gupta, Prateek K. Sundaram, Abhishek MacTaggart, Jason N. Johanning, Jason M. Gupta, Himani Fang, Xiang Forse, Robert Armour Balters, Marcus Longo, Gernon Matthew Sugimoto, Jeffrey T. Lynch, Thomas G. Pipinos, Iraklis I. TI Preoperative Anemia Is an Independent Predictor of Postoperative Mortality and Adverse Cardiac Events in Elderly Patients Undergoing Elective Vascular Operations SO ANNALS OF SURGERY LA English DT Article DE anemia; endovascular; hemoglobin; outcomes; vascular ID NONCARDIAC SURGERY; BLOOD-TRANSFUSION; EPOETIN-ALPHA; RISK; COHORT; SURVIVAL; OUTCOMES; DISEASE; REPAIR AB Objective: The objective of this study was to assess the impact of preoperative anemia (hematocrit <39%) on postoperative 30-day mortality and adverse cardiac events in patients 65 years or older undergoing elective vascular procedures. Background: Preoperative anemia is associated with adverse outcomes after cardiac surgery, but its association with postoperative outcomes after open and endovascular procedures is not well established. Elderly patients have a decreased tolerance to anemia and are at high risk for complications after vascular procedures. Methods: Patients (N = 31,857) were identified from the American College of Surgeons' 2007-2009 National Surgical Quality Improvement Program-a prospective, multicenter (>250) database maintained across the United States. The primary and secondary outcomes of interest were 30-day mortality and a composite end point of death or cardiac event (cardiac arrest or myocardial infarction), respectively. Results: Forty-seven percent of the study population was anemic. Anemic patients had a postoperative mortality and cardiac event rate of 2.4% and 2.3% in contrast to the 1.2% and 1.2%, respectively, in patients with hematocrit within the normal range (P < 0.0001). On multivariate analysis, we found a 4.2% (95% confidence interval, 1.9-6.5) increase in the adjusted risk of 30-day postoperative mortality for every percentage point of hematocrit decrease from the normal range. Conclusions: The presence and degree of preoperative anemia are independently associated with 30-day death and adverse cardiac events in patients 65 years or older undergoing elective open and endovascular procedures. Identification and treatment of anemia should be important components of preoperative care for patients undergoing vascular operations. C1 [Gupta, Prateek K.] Univ Wisconsin Hosp & Clin, Dept Surg, Madison, WI 53792 USA. [Sundaram, Abhishek; Forse, Robert Armour; Balters, Marcus; Sugimoto, Jeffrey T.] Creighton Univ, Dept Surg, Omaha, NE 68178 USA. [MacTaggart, Jason N.; Johanning, Jason M.; Longo, Gernon Matthew; Lynch, Thomas G.; Pipinos, Iraklis I.] Univ Nebraska Med Ctr, Dept Surg, Omaha, NE 68154 USA. [MacTaggart, Jason N.; Johanning, Jason M.; Longo, Gernon Matthew; Lynch, Thomas G.; Pipinos, Iraklis I.] VA Nebraska & Western Iowa Hlth Care Syst, Omaha, NE USA. [MacTaggart, Jason N.; Johanning, Jason M.; Longo, Gernon Matthew; Lynch, Thomas G.; Pipinos, Iraklis I.] Western Iowa Hlth Care Syst, Omaha, NE USA. [Gupta, Himani] William S Middleton Mem Vet Adm Med Ctr, Dept Med, Madison, WI USA. [Fang, Xiang] Creighton Univ, Biostat Core, Omaha, NE 68178 USA. RP Pipinos, II (reprint author), Univ Nebraska Med Ctr, Dept Surg, Omaha, NE 68154 USA. EM ipipinos@unmc.edu FU NIH [R01AG034995]; American Vascular Association; Charles and Mary Heider Fund for Excellence in Vascular Surgery FX Supported in part by the NIH grant R01AG034995, the William J. von Liebig Award by the American Vascular Association, and the Charles and Mary Heider Fund for Excellence in Vascular Surgery. NR 31 TC 22 Z9 22 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0003-4932 EI 1528-1140 J9 ANN SURG JI Ann. Surg. PD DEC PY 2013 VL 258 IS 6 BP 1096 EP 1102 DI 10.1097/SLA.0b013e318288e957 PG 7 WC Surgery SC Surgery GA 300MF UT WOS:000330467300035 PM 23511839 ER PT J AU Jeschke, MG Finnerty, CC Emdad, F Rivero, HG Kraft, R Williams, FN Gamelli, RL Gibran, NS Klein, MB Arnoldo, BD Tompkins, RG Herndon, DN AF Jeschke, Marc G. Finnerty, Celeste C. Emdad, Fatemeh Rivero, Haidy G. Kraft, Robert Williams, Felicia N. Gamelli, Richard L. Gibran, Nicole S. Klein, Matthew B. Arnoldo, Brett D. Tompkins, Ronald G. Herndon, David N. TI Mild Obesity Is Protective After Severe Burn Injury SO ANNALS OF SURGERY LA English DT Article DE body mass index; burn; inflammation; insulin resistance; obesity ID BODY-MASS INDEX; MULTIPLE ORGAN FAILURE; HEART-FAILURE; MORTALITY; PARADOX; RISK; METAANALYSIS; OVERWEIGHT; TRAUMA; IMPACT AB Objective: To assess the impact of obesity on morbidity and mortality in severely burned patients. Background: Despite the increasing number of people with obesity, little is known about the impact of obesity on postburn outcomes. Methods: A total of 405 patients were prospectively enrolled as part of the multicenter trial Inflammation and the Host Response to Injury Glue Grant with the following inclusion criteria: 0 to 89 years of age, admitted within 96 hours after injury, and more than 20% total body surface area burn requiring at least 1 surgical intervention. Body mass index was used in adult patients to stratify according to World Health Organization definitions: less than 18.5 (underweight), 18.5 to 29.9 (normal weight), 30 to 34.9 (obese I), 35 to 39.9 (obese II), and body mass index more than 40 (obese III). Pediatric patients (2 to <= 18 years of age) were stratified by using the Centers for Disease Control and Prevention and World Health Organization body mass index-for-age growth charts to obtain a percentile ranking and then grouped as underweight (<5th percentile), normal weight (5th percentile to <95th percentile), and obese (>= 95th percentile). The primary outcome was mortality and secondary outcomes were clinical markers of patient recovery, for example, multiorgan function, infections, sepsis, and length of stay. Results: A total of 273 patients had normal weight, 116 were obese, and 16 were underweight; underweight patients were excluded from the analyses because of insufficient patient numbers. There were no differences in primary and secondary outcomes when normal weight patients were compared with obese patients. Further stratification in pediatric and adult patients showed similar results. However, when adult patients were stratified in obesity categories, log-rank analysis showed improved survival in the obese I group and higher mortality in the obese III group compared with obese I group (P < 0.05). Conclusions: Overall, obesity was not associated with increased morbidity and mortality. Subgroup analysis revealed that patients with mild obesity have the best survival, whereas morbidly obese patients have the highest mortality. (NCT00257244) C1 [Jeschke, Marc G.] Univ Toronto, Ross Tilley Burn Ctr, Sunnybrook Hlth Sci Ctr, Toronto, ON M4N 3M5, Canada. [Jeschke, Marc G.] Univ Toronto, Div Plast Surg, Dept Surg, Toronto, ON M4N 3M5, Canada. [Finnerty, Celeste C.; Emdad, Fatemeh; Rivero, Haidy G.; Kraft, Robert; Williams, Felicia N.; Herndon, David N.] Shriners Hosp Children, Galveston, TX 77550 USA. [Finnerty, Celeste C.; Emdad, Fatemeh; Rivero, Haidy G.; Kraft, Robert; Williams, Felicia N.; Herndon, David N.] Univ Texas Med Branch, Dept Surg, Galveston, TX 77555 USA. [Finnerty, Celeste C.] Univ Texas Med Branch, Sealy Ctr Mol Med, Galveston, TX 77555 USA. [Finnerty, Celeste C.] Univ Texas Med Branch, Inst Translat Sci, Galveston, TX 77555 USA. [Gamelli, Richard L.] Loyola Univ, Stritch Sch Med, Dept Surg, Maywood, IL 60153 USA. [Gibran, Nicole S.; Klein, Matthew B.] Univ Washington, Harborview Med Ctr, Sch Med, Dept Surg, Seattle, WA 98104 USA. [Arnoldo, Brett D.] Univ Texas SW Med Ctr Dallas, Dept Surg, Dallas, TX 75390 USA. [Tompkins, Ronald G.] Shriners Hosp Children, Massachusetts Gen Hosp, Dept Surg, Boston, MA USA. [Tompkins, Ronald G.] Harvard Univ, Sch Med, Boston, MA USA. RP Jeschke, MG (reprint author), Univ Toronto, Ross Tilley Burn Ctr, Sunnybrook Hlth Sci Ctr, Sunnybrook Res Inst, Rm D704,2075 Bayview Ave, Toronto, ON M4N 3M5, Canada. EM marc.jeschke@sunnybrook.ca FU Large Scale Collaborative Research Grant from the National Institute of General Medical Sciences [U54 GM-62119]; National Institute of General Medical Sciences [P50 GM-60338, R01 GM-56687, T32 GM-008256, R01 GM-087285]; National Institute on Disability and Rehabilitation Research [H133A120091]; Shriners Hospitals for Children [71008, 84080, 8660]; NIH [KL2RR029875, NIH UL1RR029876] FX Supported in part by a Large Scale Collaborative Research Grant from the National Institute of General Medical Sciences (U54 GM-62119) awarded to Ronald G. Tompkins at the Massachusetts General Hospital, Boston, MA, and in part by research grants awarded to David N. Herndon at the University of Texas Medical Branch, Galveston, TX, by the National Institute of General Medical Sciences (P50 GM-60338, R01 GM-56687, T32 GM-008256), National Institute on Disability and Rehabilitation Research (H133A120091), and the Shriners Hospitals for Children (71008, 84080) and to Marc G. Jeschke by the Shriners Hospitals for Children (8660) and the National Institute of General Medical Sciences (R01 GM-087285). CCF is an Institute for Translational Sciences Career Development Scholar supported, in part, by NIH KL2RR029875 and NIH UL1RR029876. The authors declare no conflicts of interest. NR 33 TC 14 Z9 14 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0003-4932 EI 1528-1140 J9 ANN SURG JI Ann. Surg. PD DEC PY 2013 VL 258 IS 6 BP 1119 EP 1129 DI 10.1097/SLA.0b013e3182984d19 PG 11 WC Surgery SC Surgery GA 300MF UT WOS:000330467300039 PM 23877367 ER PT J AU Navara, CS Hornecker, J Grow, D Chaudhari, S Hornsby, PJ Ichida, JK Eggan, K McCarrey, JR AF Navara, Christopher S. Hornecker, Jacey Grow, Douglas Chaudhari, Shital Hornsby, Peter J. Ichida, Justin K. Eggan, Kevin McCarrey, John R. TI Derivation of Induced Pluripotent Stem Cells from the Baboon: A Nonhuman Primate Model for Preclinical Testing of Stem Cell Therapies SO CELLULAR REPROGRAMMING LA English DT Article ID MARMOSET CALLITHRIX-JACCHUS; LINES; ESTABLISHMENT; BLASTOCYSTS; GENERATION; FIBROBLASTS; MACAQUES; NEURONS; HUMANS; VOLUME AB Development of effective pluripotent stem cell-based therapies will require safety and efficacy testing in a clinically relevant preclinical model such as nonhuman primates (NHPs). Baboons and macaques are equally similar to humans genetically and both have been extensively used for biomedical research. Macaques are preferred for human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS) research whereas baboons are preferred for transplantation studies because of the greater similarity of their anatomy and immunogenetic system to those of humans. We generated four induced pluripotent stem cell (iPSC) lines from skin cells of the olive baboon (Papio anubis). Each line shows the distinct morphology of primate pluripotent stem cells, including flat colonies with well-defined borders and a high nuclear/cytoplasm ratio. Each is positive for the pluripotency markers OCT4, SOX2, NANOG, and SSEA4. Pluripotency was confirmed in two lines by teratoma formation with representative tissues from each germ layer, whereas a third produced cells from all three germ layers following embryoid body differentiation. Three lines have a normal male karyotype and the fourth is missing the short arm of one copy of chromosome 18. This may serve as an in vitro model for the human developmental disorder 18p-, which impacts 1 in 50,000 births/year. These iPSC lines represent the first step toward establishing the baboon as a NHP model for developing stem cell-based therapies. C1 [Navara, Christopher S.; Hornecker, Jacey; Grow, Douglas; Chaudhari, Shital; McCarrey, John R.] Univ Texas San Antonio, Dept Biol, San Antonio, TX 78249 USA. [Hornsby, Peter J.] South Texas Vet Hlth Care Syst, San Antonio, TX 78245 USA. [Hornsby, Peter J.] Univ Texas Hlth Sci Ctr San Antonio, San Antonio, TX 78245 USA. [Ichida, Justin K.; Eggan, Kevin] Harvard Stem Cell Inst, Cambridge, MA 02138 USA. [Eggan, Kevin] Howard Hughes Med Inst, Cambridge, MA 02138 USA. RP Navara, CS (reprint author), Univ Texas San Antonio, Dept Biol, San Antonio, TX 78249 USA. EM Christopher.Navara@utsa.edu RI Navara, Christopher/C-2813-2011 FU National Institutes of Health (NIH) [RR022865, HD046732, GM099117] FX This work was partially supported by National Institutes of Health (NIH) grants RR022865 to J.R.M. and HD046732 and GM099117 to K.E. NR 48 TC 1 Z9 1 U1 0 U2 8 PU MARY ANN LIEBERT, INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 2152-4971 EI 2152-4998 J9 CELL REPROGRAM JI Cell. Reprogramm. PD DEC PY 2013 VL 15 IS 6 BP 495 EP 502 DI 10.1089/cell.2012.0093 PG 8 WC Cell & Tissue Engineering; Biotechnology & Applied Microbiology; Genetics & Heredity SC Cell Biology; Biotechnology & Applied Microbiology; Genetics & Heredity GA 300HC UT WOS:000330454000004 PM 24182315 ER PT J AU Ting, BL Abousayed, MM Holzer, P Cetrulo, CL Kwon, JY AF Ting, Beverlie L. Abousayed, Mostafa M. Holzer, Paul Cetrulo, Curtis L., Jr. Kwon, John Y. TI External Fixator Kickstands for Free Soft Tissue Flap Protection: Case Series and Description of Technique SO FOOT & ANKLE INTERNATIONAL LA English DT Article DE external fixator kickstand; soft tissue flap; lower limbs ID IMMOBILIZATION AB Background: Protected elevation represents a critical component of postoperative care, particularly in posteriorly located flaps, to prevent pressure on the flap's vascular pedicle and ensure a successful skin graft. Although several short case series and technique papers have described kickstand placement to prevent heel ulcers as an adjuvant to fixator placement for fracture management, there remains a paucity of reports describing external fixator placement solely for extremity elevation and pressure alleviation in the postoperative care of flap coverage procedures. Methods: Patients who underwent lower extremity free flap coverage procedures requiring temporary elevation were included. Age, diagnosis, soft tissue procedures performed, type of external fixator placed, duration of frame placement, mode of removal, and complications related to external fixator placement were documented. Patients requiring external fixator placement for fracture management were excluded. Results: Twelve patients with 13 lower limb soft tissue defects were included in our case series. A thin-wire ring external fixator kickstand was applied in 5 limbs while the rest underwent placement of a uniplanar carbon fiber bar type external fixator kickstands. The average time for removal of the frames was 4 weeks. No complications were reported from kickstand placement. Conclusion: The use of external fixator kickstands is an effective and safe adjuvant to soft tissue flap procedures for the lower extremity. Our case series is the largest in the literature and first to address the technical considerations for frame placement, positioning, and removal for external fixator kickstands placed solely for flap coverage procedures. C1 [Ting, Beverlie L.; Abousayed, Mostafa M.; Holzer, Paul; Cetrulo, Curtis L., Jr.; Kwon, John Y.] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Ting, BL (reprint author), Massachusetts Gen Hosp, 55 Fruit St, Boston, MA 02114 USA. EM bting@partners.org NR 10 TC 1 Z9 1 U1 1 U2 3 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 1071-1007 EI 1944-7876 J9 FOOT ANKLE INT JI Foot Ankle Int. PD DEC PY 2013 VL 34 IS 12 BP 1695 EP 1700 DI 10.1177/1071100713500655 PG 6 WC Orthopedics SC Orthopedics GA 297YU UT WOS:000330291800015 PM 23908389 ER PT J AU Buttenheim, AM Asch, DA AF Buttenheim, Alison M. Asch, David A. TI Making vaccine refusal less of a free ride SO HUMAN VACCINES & IMMUNOTHERAPEUTICS LA English DT Article DE vaccine hesitancy; immunization; decision-making; free rider; public good AB Herd immunity against vaccine-preventable diseases is a public good because it is both non-excludable (meaning that there is no way to exclude people from using it) and non-rivalrous (meaning that one person's use does not limit or restrict others' use). Like other public goods, such as lighthouses, street lights and national defense, herd immunity is vulnerable to the "free rider" problem. We discuss four conventional responses to the free rider problem (participation mandates, exclusion, incentives, and social norms) and highlight how a public good perspective can inform the design of interventions to increase vaccine acceptance. C1 [Buttenheim, Alison M.] Univ Penn, Sch Nursing, Dept Family & Community Hlth, Philadelphia, PA 19104 USA. [Buttenheim, Alison M.] Univ Penn, LDI Ctr Hlth Incent & Behav Econ, Philadelphia, PA 19104 USA. [Asch, David A.] Philadelphia VA Med Ctr, Ctr Hlth Equ Res & Promot, Philadelphia, PA USA. [Asch, David A.] Penn Med Ctr Hlth Care Innovat, Philadelphia, PA USA. RP Buttenheim, AM (reprint author), Univ Penn, Sch Nursing, Dept Family & Community Hlth, Philadelphia, PA 19104 USA. EM abutt@nursing.upenn.edu NR 7 TC 3 Z9 3 U1 2 U2 11 PU LANDES BIOSCIENCE PI AUSTIN PA 1806 RIO GRANDE ST, AUSTIN, TX 78702 USA SN 2164-5515 EI 2164-554X J9 HUM VACC IMMUNOTHER JI Human Vaccines Immunother. PD DEC PY 2013 VL 9 IS 12 BP 2674 EP 2675 PG 2 WC Biotechnology & Applied Microbiology; Immunology SC Biotechnology & Applied Microbiology; Immunology GA 299GE UT WOS:000330383200036 PM 24088616 ER PT J AU Separovic, D Breen, P Boppana, NB Van Buren, E Joseph, N Kraveka, JM Rahmaniyan, M Li, L Gudz, TI Bielawska, A Bai, A Bielawski, J Pierce, JS Korbelik, M AF Separovic, Duska Breen, Paul Boppana, Nithin B. Van Buren, Eric Joseph, Nicholas Kraveka, Jacqueline M. Rahmaniyan, Mehrdad Li, Li Gudz, Tatyana I. Bielawska, Alicja Bai, Aiping Bielawski, Jacek Pierce, Jason S. Korbelik, Mladen TI Increased killing of SCCVII squamous cell carcinoma cells after the combination of Pc 4 photodynamic therapy and dasatinib is associated with enhanced caspase-3 activity and ceramide synthase 1 upregulation SO INTERNATIONAL JOURNAL OF ONCOLOGY LA English DT Article DE apoptosis; ceramide; ceramide synthase; ceramidase; dasatinib; PDT; sphingolipids; sphingosine ID APOPTOTIC PHOTOSENSITIZED CELLS; CHRONIC MYELOID-LEUKEMIA; GROWTH-FACTOR RECEPTOR; DE-NOVO SPHINGOLIPIDS; BREAST-CANCER CELLS; HUMAN HEAD; INHIBITOR DASATINIB; OXIDATIVE STRESS; DEATH; KINASE AB Photodynamic therapy (PDT) is not always effective as an anticancer treatment, therefore, PDT is combined with other anticancer agents for improved efficacy. The combination of dasatinib and PDT with the silicone phthalocyanine photosensitizer Pc 4 was assessed for increased killing of SCCVII mouse squamous cell carcinoma cells, a preclinical model of head and neck squamous cell carcinoma, using apoptotic markers and colony formation as experimental end-points. Because each of these treatments regulates the metabolism of the sphingolipid ceramide, their effects on mRNA levels of ceramide synthase, a ceramide-producing enzyme, and the sphingolipid profile were determined. PDT + dasatinib induced an additive loss of clonogenicity. Unlike PDT alone or PDT + dasatinib, dasatinib induced zVAD-fmk-dependent cell killing. PDT or dasatinib-induced caspase-3 activation was potentiated after the combination. PDT alone induced mitochondrial depolarization, and the effect was inhibited after the combination. Annexin V+ and propidium iodide+ cells remained at control levels after treatments. In contrast to PDT alone, dasatinib induced upregulation of ceramide synthase 1 mRNA, and the effect was enhanced after the combination. Dasatinib induced a modest increase in C20:1-and C22-ceramide but had no effect on total ceramide levels. PDT increased the levels of 12 individual ceramides and total ceramides, and the addition of dasatinib did not affect these increases. PDT alone decreased substantially sphingosine levels and inhibited the activity of acid ceramidase, an enzyme that converts ceramide to sphingosine. The data suggest that PDT-induced increases in ceramide levels do not correlate with ceramide synthase mRNA levels but rather with inhibition of ceramidase. Cell killing was zVAD-fmk-sensitive after dasatinib but not after either PDT or the combination and enhanced cell killing after the combination correlated with potentiated caspase-3 activation and upregulation of ceramide synthase 1 mRNA but not the production of ceramide. The data imply potential significance of the combination for cancer treatment. C1 [Separovic, Duska; Breen, Paul; Boppana, Nithin B.; Joseph, Nicholas] Wayne State Univ, Eugene Applebaum Coll Pharm & Hlth Sci, Dept Pharmaceut Sci, Detroit, MI 48201 USA. [Separovic, Duska; Van Buren, Eric] Wayne State Univ, Karmanos Canc Inst, Detroit, MI 48201 USA. [Kraveka, Jacqueline M.; Rahmaniyan, Mehrdad; Li, Li] Med Univ S Carolina, Dept Pediat, Div Hematol Oncol, Charles Darby Childrens Res Inst, Charleston, SC 29425 USA. [Kraveka, Jacqueline M.; Rahmaniyan, Mehrdad; Li, Li] Med Univ S Carolina, Hollings Canc Ctr, Charleston, SC 29425 USA. [Gudz, Tatyana I.] Med Univ S Carolina, Ralph H Johnson Vet Affairs Med Ctr, Charleston, SC 29425 USA. [Gudz, Tatyana I.] Med Univ S Carolina, Dept Neurosci, Charleston, SC 29425 USA. [Bielawska, Alicja; Bai, Aiping; Bielawski, Jacek; Pierce, Jason S.] Med Univ S Carolina, Dept Biochem & Mol Biol, Charleston, SC 29425 USA. [Korbelik, Mladen] British Columbia Canc Agcy, Vancouver, BC V5Z 1L3, Canada. RP Separovic, D (reprint author), Wayne State Univ, Coll Pharm & Hlth Sci, Dept Pharmaceut Sci, 259 Mack Ave, Detroit, MI 48201 USA. EM dseparovic@wayne.edu FU U.S. Public Health Service from the National Cancer Institute (NCI), National Institutes of Health (NIH) [R01 CA77475]; NIH [P20-RR17677]; Rally Foundation for Childhood Cancer Research; Hyundai Hope on Wheels; Monica Kreber Golf Tournament; Chase after a Cure Foundation; Veterans Administration Merit Awards from RRD program; Veterans Administration Merit Awards from BLRD program; (Karmanos Cancer Institute, Wayne State University), NCI [P30 CA22453]; (Medical University of South Carolina), NCI [IPO1CA097132, P30 CA 138313]; NIH/NCRR SC COBRE from the Extramural Research Facilities Program of the National Center for Research Resources [P20 RR017677, C06 RR018823] FX This study was supported by U.S. Public Health Service Grants: to D. S., R01 CA77475 from the National Cancer Institute (NCI), National Institutes of Health (NIH); to J.M.K., P20-RR17677 (NIH), grants from the Rally Foundation for Childhood Cancer Research, Hyundai Hope on Wheels, Monica Kreber Golf Tournament, and Chase after a Cure Foundation; to T. I. G., the Veterans Administration Merit Awards from RR&D and BLRD programs; to the flow cytometry-related work at the Microscopy, Imaging, and Cytometry Resources Core (Karmanos Cancer Institute, Wayne State University), NCI Grant P30 CA22453; to the MS-related work at the Lipidomics Shared Resource (Medical University of South Carolina), NCI Grants IPO1CA097132 and P30 CA 138313, NIH/NCRR SC COBRE Grant P20 RR017677, C06 RR018823 from the Extramural Research Facilities Program of the National Center for Research Resources. NR 37 TC 6 Z9 6 U1 2 U2 10 PU SPANDIDOS PUBL LTD PI ATHENS PA POB 18179, ATHENS, 116 10, GREECE SN 1019-6439 EI 1791-2423 J9 INT J ONCOL JI Int. J. Oncol. PD DEC PY 2013 VL 43 IS 6 BP 2064 EP 2072 DI 10.3892/ijo.2013.2132 PG 9 WC Oncology SC Oncology GA 297AA UT WOS:000330225800039 PM 24126464 ER PT J AU Rannikmae, K Davies, G Devan, W Bevan, S Traylor, M Falcone, G Anderson, C Rost, N Markus, H Rosand, J Van Agtmael, T Sudlow, CLM AF Rannikmaee, K. Davies, G. Devan, W. Bevan, S. Traylor, M. Falcone, G. Anderson, C. Rost, N. Markus, H. Rosand, J. Van Agtmael, T. Sudlow, C. L. M. CA METASTROKE Consortium CHARGE Consortium ISGC TI The contribution of variants in collagen IV genes to common cerebrovascular phenotypes SO INTERNATIONAL JOURNAL OF STROKE LA English DT Meeting Abstract C1 [Rannikmaee, K.; Sudlow, C. L. M.] Univ Edinburgh, Div Clin Neurosci, Edinburgh, Midlothian, Scotland. [Davies, G.] Univ Edinburgh, Dept Psychol, Ctr Cognit Ageing & Cognit Epidemiol, Edinburgh, Midlothian, Scotland. [Devan, W.; Falcone, G.; Anderson, C.; Rost, N.; Rosand, J.] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA. [Bevan, S.; Traylor, M.; Markus, H.] St Georges Univ London, Stroke & Dementia Res Ctr, London, England. [Van Agtmael, T.] Univ Glasgow, Inst Cardiovasc & Med Sci, Glasgow, Lanark, Scotland. [Sudlow, C. L. M.] Univ Glasgow, Inst Genet & Mol Med, Glasgow, Lanark, Scotland. 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 1747-4930 EI 1747-4949 J9 INT J STROKE JI Int. J. Stroke PD DEC PY 2013 VL 8 SU 3 SI SI BP 56 EP 56 PG 1 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 301IV UT WOS:000330526900142 ER PT J AU Rannikmae, K Kalaria, RN Greenberg, SM Chui, HC Schmitt, FA Samarasekera, N Salman, RA Sudlow, CLM AF Rannikmaee, K. Kalaria, R. N. Greenberg, S. M. Chui, H. C. Schmitt, F. A. Samarasekera, N. Salman, Al-Shahi R. Sudlow, C. L. M. TI APOE allele-specific associations with severe CAA-associated vasculopathic changes - collaborative meta-analysis SO INTERNATIONAL JOURNAL OF STROKE LA English DT Meeting Abstract C1 [Rannikmaee, K.; Samarasekera, N.; Salman, Al-Shahi R.; Sudlow, C. L. M.] Univ Edinburgh, Div Clin Neurosci, Edinburgh, Midlothian, Scotland. [Kalaria, R. N.] Newcastle Univ, Inst Ageing & Hlth, Newcastle Upon Tyne NE1 7RU, Tyne & Wear, England. [Greenberg, S. M.] Massachusetts Gen Hosp, Stroke Res Ctr, Boston, MA 02114 USA. [Chui, H. C.] Univ So Calif, Dept Neurol, Los Angeles, CA USA. [Schmitt, F. A.] Univ Kentucky, Sanders Brown Ctr Aging, Lexington, KY 40536 USA. [Sudlow, C. L. M.] Univ Edinburgh, Inst Genet & Mol Med, Edinburgh, Midlothian, Scotland. NR 0 TC 0 Z9 0 U1 0 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1747-4930 EI 1747-4949 J9 INT J STROKE JI Int. J. Stroke PD DEC PY 2013 VL 8 SU 3 SI SI BP 56 EP 56 PG 1 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 301IV UT WOS:000330526900141 ER PT J AU Bayoumi, AM Barnett, PG Joyce, VR Griffin, SC Sun, HY Bansback, NJ Holodniy, M Sanders, G Brown, ST Kyriakides, TC Angus, B Cameron, DW Anis, AH Sculpher, M Owens, DK AF Bayoumi, Ahmed M. Barnett, Paul G. Joyce, Vilija R. Griffin, Susan C. Sun, Huiying Bansback, Nick J. Holodniy, Mark Sanders, Gillian Brown, Sheldon T. Kyriakides, Tassos C. Angus, Brian Cameron, D. William Anis, Aslam H. Sculpher, Mark Owens, Douglas K. TI Cost-Effectiveness of Newer Antiretroviral Drugs in Treatment-Experienced Patients With Multidrug-Resistant HIV Disease SO JAIDS-JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES LA English DT Article DE novel antiretroviral drugs; multidrug-resistant HIV infection; cost-effectiveness analysis; quality of life; health economics ID PLACEBO-CONTROLLED TRIAL; OPTIMIZED BACKGROUND THERAPY; QUALITY-OF-LIFE; PREVIOUSLY TREATED PATIENTS; LONG-TERM EFFICACY; HIV-1-INFECTED PATIENTS; INFECTED PATIENTS; DOUBLE-BLIND; TIPRANAVIR-RITONAVIR; PROTEASE INHIBITORS AB Objective: Newer antiretroviral drugs provide substantial benefits but are expensive. The cost-effectiveness of using antiretroviral drugs in combination for patients with multidrug-resistant HIV disease was determined. Design: A cohort state-transition model was built representing treatment-experienced patients with low CD4 counts, high viral load levels, and multidrug-resistant virus. The effectiveness of newer drugs (those approved in 2005 or later) was estimated from published randomized trials. Other parameters were estimated from a randomized trial and from the literature. The model had a lifetime time horizon and used the perspective of an ideal insurer in the United States. The interventions were combination antiretroviral therapy, consisting of 2 newer drugs and 1 conventional drug, compared with 3 conventional drugs. Outcome measures were life-years, quality-adjusted life-years (QALYs), costs, and incremental cost-effectiveness. Results: Substituting newer antiretroviral drugs increased expected survival by 3.9 years in advanced HIV disease. The incremental cost-effectiveness ratio of newer, compared with conventional, antiretroviral drugs was $75,556/QALY gained. Sensitivity analyses showed that substituting only one newer antiretroviral drug cost $54,559 to $68,732/QALY, depending on assumptions about efficacy. Substituting 3 newer drugs cost $105,956 to $117,477/QALY. Cost-effectiveness ratios were higher if conventional drugs were not discontinued. Conclusions: In treatment-experienced patients with advanced HIV disease, use of newer antiretroviral agents can be cost-effective, given a cost-effectiveness threshold in the range of $50,000 to $75,000 per QALY gained. Newer antiretroviral agents should be used in carefully selected patients for whom less expensive options are clearly inferior. C1 [Bayoumi, Ahmed M.] St Michaels Hosp, Ctr Res Inner City Hlth, Keenan Res Ctr, Li Ka Shing Knowledge Inst, Toronto, ON M5B 1W8, Canada. [Bayoumi, Ahmed M.] Univ Toronto, Dept Med, Toronto, ON, Canada. [Bayoumi, Ahmed M.] Univ Toronto, Inst Hlth Policy Management & Evaluat, Toronto, ON, Canada. [Bayoumi, Ahmed M.] St Michaels Hosp, Div Gen Internal Med, Toronto, ON M5B 1W8, Canada. [Barnett, Paul G.; Joyce, Vilija R.] VA Palo Alto Hlth Care Syst, VA HSR&D Hlth Econ Resource Ctr, VA Cooperat Studies Program Coordinating Ctr, Menlo Pk, CA USA. [Griffin, Susan C.; Sculpher, Mark] Univ York, Ctr Hlth Econ, York YO10 5DD, N Yorkshire, England. [Sun, Huiying] St Pauls Hosp, Ctr Hlth Evaluat & Outcome Sci, Vancouver, BC V6Z 1Y6, Canada. [Sun, Huiying] CIHR Canadian HIV Trials Network, Vancouver, BC, Canada. [Bansback, Nick J.; Anis, Aslam H.] Univ British Columbia, Sch Populat & Publ Hlth, Vancouver, BC V5Z 1M9, Canada. [Holodniy, Mark; Owens, Douglas K.] VA Palo Alto Hlth Care Syst, Palo Alto, CA USA. [Holodniy, Mark; Owens, Douglas K.] Stanford Univ, Dept Med, Stanford, CA 94305 USA. [Sanders, Gillian] Duke Univ, Duke Clin Res Inst, Durham, NC USA. [Brown, Sheldon T.] James J Peters VA Med Ctr, Bronx, NY USA. [Brown, Sheldon T.] Mt Sinai Sch Med, Dept Med, New York, NY USA. [Kyriakides, Tassos C.] VA Cooperat Studies Program Coordinating Ctr, West Haven, CT USA. [Angus, Brian] MRC Clin Trials Unit, London, England. [Angus, Brian] Univ Oxford, Nuffield Dept Med, Oxford, England. [Cameron, D. William] Univ Ottawa, Ottawa Hosp Res Inst, Ottawa, ON, Canada. [Owens, Douglas K.] Stanford Univ, Ctr Primary Care & Outcomes Res, Stanford, CA 94305 USA. [Owens, Douglas K.] Stanford Univ, Ctr Hlth Policy, Stanford, CA 94305 USA. RP Bayoumi, AM (reprint author), St Michaels Hosp, Ctr Res Inner City Hlth, 30 Bond St, Toronto, ON M5B 1W8, Canada. EM ahmed.bayoumi@utoronto.ca OI Cameron, Bill/0000-0002-0090-3539 FU Canadian Institutes of Health Research/Ontario Ministry of Health & Long-Term Care Applied Chair in Health Services and Policy Research; Ontario Ministry of Health and Long-Term Care; US Department of Veterans Affairs Cooperative Studies Program; UK Medical Research Council; Canadian Institutes of Health Research; National Institutes of Health [1RC1AI086927-01, 2 R01 DA15612-016]; Department of Veterans Affairs FX A.M.B is supported by a Canadian Institutes of Health Research/Ontario Ministry of Health & Long-Term Care Applied Chair in Health Services and Policy Research. The Center for Research on Inner City Health is supported in part by a grant from the Ontario Ministry of Health and Long-Term Care. The US Department of Veterans Affairs Cooperative Studies Program, the UK Medical Research Council, and the Canadian Institutes of Health Research funded the OPTIMA trial for Health Research. This work was supported in part by Grants 1RC1AI086927-01 and 2 R01 DA15612-016 from the National Institutes of Health. D.K.O., P. G. B., M. H., S. T. B., and T. C. K. are supported by the Department of Veterans Affairs. NR 50 TC 2 Z9 2 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1525-4135 EI 1077-9450 J9 JAIDS-J ACQ IMM DEF JI JAIDS PD DEC 1 PY 2013 VL 64 IS 4 BP 382 EP 391 PG 10 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 300HE UT WOS:000330454200009 PM 24129369 ER PT J AU Timerman, D Frank, NY AF Timerman, Dmitriy Frank, Natasha Y. TI Novel Double Heterozygous Mutations in MEFV and NLRP3 Genes in a Patient With Familial Mediterranean Fever SO JCR-JOURNAL OF CLINICAL RHEUMATOLOGY LA English DT Article ID CUTTING EDGE; PYRIN; COLCHICINE; DISEASE; HEALTH C1 [Timerman, Dmitriy] Harvard Mit Div Hlth Sci & Technol, Boston, MA USA. [Frank, Natasha Y.] VA Boston Healthcare Syst, Dept Med, Boston, MA 02132 USA. [Frank, Natasha Y.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Div Genet, Boston, MA 02115 USA. RP Frank, NY (reprint author), VA Boston Healthcare Syst, Dept Med, 1400 VFW Pkwy, Boston, MA 02132 USA. EM nfrank@partners.org FU BLRD VA [I01 BX000516]; RRD VA [I01 RX000989] NR 21 TC 3 Z9 3 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1076-1608 EI 1536-7355 J9 JCR-J CLIN RHEUMATOL JI JCR-J. Clin. Rheumatol. PD DEC PY 2013 VL 19 IS 8 BP 452 EP 453 DI 10.1097/RHU.0000000000000044 PG 2 WC Rheumatology SC Rheumatology GA 300KI UT WOS:000330462400008 PM 24263150 ER PT J AU Sarris, J Nierenberg, AA Schweitzer, I Alpert, JE Rosenbaum, JF Iovieno, N Covino, J Fava, M Mischoulon, D AF Sarris, Jerome Nierenberg, Andrew A. Schweitzer, Isaac Alpert, Jonathan E. Rosenbaum, Jerrold F. Iovieno, Nadia Covino, Jennifer Fava, Maurizio Mischoulon, David TI Conditional Probability of Response or Nonresponse of Placebo Compared With Antidepressants or St John's Wort in Major Depressive Disorder SO JOURNAL OF CLINICAL PSYCHOPHARMACOLOGY LA English DT Letter ID METAANALYSIS; FLUOXETINE; PATTERN; TRIAL; RATES C1 [Sarris, Jerome; Schweitzer, Isaac] Univ Melbourne, Dept Psychiat, Melbourne, Vic, Australia. [Sarris, Jerome] Swinburne Univ Technol, Ctr Human Psychopharmacol, Melbourne, Vic, Australia. [Nierenberg, Andrew A.; Alpert, Jonathan E.; Rosenbaum, Jerrold F.; Iovieno, Nadia; Covino, Jennifer; Fava, Maurizio; Mischoulon, David] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Depress Clin & Res Program, Boston, MA USA. RP Sarris, J (reprint author), Univ Melbourne, Dept Psychiat, Melbourne, Vic, Australia. EM jsarris@unimelb.edu.au OI Alpert, Jonathan/0000-0002-4332-908X NR 13 TC 0 Z9 0 U1 0 U2 6 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0271-0749 EI 1533-712X J9 J CLIN PSYCHOPHARM JI J. Clin. Psychopharmacol. PD DEC PY 2013 VL 33 IS 6 BP 827 EP 830 PG 5 WC Pharmacology & Pharmacy; Psychiatry SC Pharmacology & Pharmacy; Psychiatry GA 298TG UT WOS:000330346800021 PM 24091858 ER PT J AU Zou, ZQ Bellenger, S Massey, KA Nicolaou, A Geissler, A Bidu, C Bonnotte, B Pierre, AS Minville-Walz, M Rialland, M Seubert, J Kang, JX Lagrost, L Narce, M Bellenger, J AF Zou, Zuquan Bellenger, Sandrine Massey, Karen A. Nicolaou, Anna Geissler, Audrey Bidu, Celia Bonnotte, Bernard Pierre, Anne-Sophie Minville-Walz, Melaine Rialland, Michael Seubert, John Kang, Jing X. Lagrost, Laurent Narce, Michel Bellenger, Jerome TI Inhibition of the HER2 pathway by n-3 polyunsaturated fatty acids prevents breast cancer in fat-1 transgenic mice SO JOURNAL OF LIPID RESEARCH LA English DT Article DE polyunsaturated fatty acid-derived mediators; xenograft prevention; n-3 tissue enrichment ID RECEPTOR TYROSINE KINASES; TANDEM MASS-SPECTROMETRY; E-CADHERIN; BETA-CATENIN; DOCOSAHEXAENOIC ACID; LIPIDOMIC ANALYSIS; GENE-EXPRESSION; GROWTH; CELLS; ERBB3 AB Overexpression of the tyrosine kinase receptor, ErbB2/HER2/Neu, occurs in 25-30% of invasive breast cancer (BC) with poor patient prognosis. Due to confounding factors, inconsistencies still remain regarding the protective effects of n-3 polyunsaturated fatty acids (PUFAs) on BC. We therefore evaluated whether fat-1 transgenic mice, endogenously synthesizing n-3 PUFAs from n-6 PUFAs, were protected against BC development, and we then aimed to study in vivo a mechanism potentially involved in such protection. E0771 BC cells were implanted into fat-1 and wildtype (WT) mice. After tumorigenesis examination, we analyzed the expression of proteins involved in the HER2 signaling pathway and lipidomic analyses were performed in tumor tissues and plasma. Our results showed that tumors totally disappeared by day 15 in fat-1 mice but continued to grow in WT mice. This prevention can be related in part to significant repression of the HER2/beta-catenin signaling pathway and formation of significant levels of n-3 PUFA-derived bioactive mediators (particularly 15-hydroxyeicosapentaenoic acid, 17-hydroxydocosahexaenoic acid, and prostaglandin E3) in the tumors of fat-1 mice compared with WT mice. All together these data demonstrate an anti-BC effect of n-3 PUFAs through, at least in part, HER2 signaling pathway downregulation, and highlight the importance of gene-diet interactions in BC. C1 [Zou, Zuquan; Bellenger, Sandrine; Bidu, Celia; Pierre, Anne-Sophie; Minville-Walz, Melaine; Rialland, Michael; Narce, Michel; Bellenger, Jerome] Univ Bourgogne, UFR Sci Vie Terre & Environm, Dijon, France. [Zou, Zuquan; Bellenger, Sandrine; Bidu, Celia; Pierre, Anne-Sophie; Minville-Walz, Melaine; Rialland, Michael; Lagrost, Laurent; Narce, Michel; Bellenger, Jerome] Univ Bourgogne, INSERM UMR Lipides Nutr Canc U866, Dijon, France. [Massey, Karen A.; Nicolaou, Anna] Univ Manchester, Sch Pharm, Fac Med & Human Sci, Manchester, Lancs, England. [Geissler, Audrey] Fac Med & Pharm Dijon, Imagerie Cellulaire Histol IFR100, INSERM UMR866, F-21000 Dijon, France. [Bonnotte, Bernard] Univ Bourgogne, UMR1098, Fac Med, IFR100, Dijon, France. [Seubert, John] Univ Alberta, Fac Pharm & Pharmaceut Sci, Edmonton, AB T6G 2N8, Canada. [Kang, Jing X.] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Bellenger, J (reprint author), Univ Bourgogne, UFR Sci Vie Terre & Environm, Dijon, France. EM jerome.bellenger@u-bourgogne.fr OI bonnotte, bernard/0000-0002-1098-4598; Nicolaou, Anna/0000-0002-1314-413X FU French Government under the program "Investissements d'Avenir" [ANR-11-LABX-0021-01-LipSTIC Labex]; Region Bourgogne; La Ligue contre le cancer; Groupe Lipides et Nutrition (GLN) FX This work was supported by a French Government grant managed by the French National Research Agency (ANR) under the program "Investissements d'Avenir" with reference ANR-11-LABX-0021-01-LipSTIC Labex. J.B. acknowledges support from the Region Bourgogne. This work was also partially supported by a grant from La Ligue contre le cancer and the Groupe Lipides et Nutrition (GLN). No potential conflicts of interest relevant to this article have been reported. NR 53 TC 14 Z9 14 U1 1 U2 10 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0022-2275 EI 1539-7262 J9 J LIPID RES JI J. Lipid Res. PD DEC PY 2013 VL 54 IS 12 BP 3453 EP 3463 DI 10.1194/jlr.M042754 PG 11 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 301LX UT WOS:000330534900021 PM 24052576 ER PT J AU Minicocci, I Santini, S Cantisani, V Stitziel, N Kathiresan, S Arroyo, JA Marti, G Pisciotta, L Noto, D Cefalu, AB Maranghi, M Labbadia, G Pigna, G Pannozzo, F Ceci, F Ciociola, E Bertolini, S Calandra, S Tarugi, P Averna, M Arca, M AF Minicocci, Ilenia Santini, Sara Cantisani, Vito Stitziel, Nathan Kathiresan, Sekar Arroyo, Juan Antonio Marti, Gertrudis Pisciotta, Livia Noto, Davide Cefalu, Angelo B. Maranghi, Marianna Labbadia, Giancarlo Pigna, Giovanni Pannozzo, Fabio Ceci, Fabrizio Ciociola, Ester Bertolini, Stefano Calandra, Sebastiano Tarugi, Patrizia Averna, Maurizio Arca, Marcello TI Clinical characteristics and plasma lipids in subjects with familial combined hypolipidemia: a pooled analysis SO JOURNAL OF LIPID RESEARCH LA English DT Article DE ANGPTL3 mutations; angiopoietin-like 3; cardiovascular disease; fatty liver; diabetes mellitus ID ANGIOPOIETIN-LIKE PROTEIN-3; APO-B GENE; LIVER-DISEASE; LIPOPROTEIN-LIPASE; HEPATIC STEATOSIS; ANGPTL3 GENE; FATTY LIVER; IN-VIVO; HYPOBETALIPOPROTEINEMIA; METABOLISM AB Angiopoietin-like 3 (ANGPTL3) regulates lipoprotein metabolism by modulating extracellular lipases. Loss-of function mutations in ANGPTL3 gene cause familial combined hypolipidemia (FHBL2). The mode of inheritance and hepatic and vascular consequences of FHBL2 have not been fully elucidated. To get further insights on these aspects, we reevaluated the clinical and the biochemical characteristics of all reported cases of FHBL2. One hundred fifteen FHBL2 individuals carrying 13 different mutations in the ANGPTL3 gene (14 homozygotes, 8 compound heterozygotes, and 93 heterozygotes) and 402 controls were considered. Carriers of two mutant alleles had undetectable plasma levels of ANGPTL3 protein, whereas heterozygotes showed a reduction ranging from 34% to 88%, according to genotype. Compared with controls, homozygotes as well as heterozygotes showed a significant reduction of all plasma lipoproteins, while no difference in lipoprotein(a) [Lp(a)] levels was detected between groups. The prevalence of fatty liver was not different in FHBL2 subjects compared with controls. Notably, diabetes mellitus and cardiovascular disease were absent among homozygotes. FHBL2 trait is inherited in a codominant manner, and the lipid-lowering effect of two ANGPTL3 mutant alleles was more than four times larger than that of one mutant allele. No changes in Lp(a) were detected in FHBL2. Furthermore, our analysis confirmed that FHBL2 is not associated with adverse clinical sequelae. The possibility that FHBL2 confers lower risk of diabetes and cardiovascular disease warrants more detailed investigation. C1 [Minicocci, Ilenia; Santini, Sara; Maranghi, Marianna; Labbadia, Giancarlo; Pigna, Giovanni; Ciociola, Ester; Arca, Marcello] Univ Roma La Sapienza, Dept Internal Med & Med Specialties, I-00185 Rome, Italy. [Cantisani, Vito] Univ Roma La Sapienza, Dept Radiol Sci, I-00185 Rome, Italy. [Ceci, Fabrizio] Univ Roma La Sapienza, Dept Cellular Biotechnol & Hematol, I-00185 Rome, Italy. [Stitziel, Nathan] Washington Univ, Sch Med, Dept Med, Cardiovasc Div, St Louis, MO 63110 USA. Washington Univ, Sch Med, Div Stat Genom, St Louis, MO USA. [Kathiresan, Sekar] Massachusetts Gen Hosp, Cardiovasc Res Ctr, Boston, MA 02114 USA. [Kathiresan, Sekar] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. [Arroyo, Juan Antonio] Hosp Santa Creu & Sant Pau, Dept Internal Med, Barcelona, Spain. [Marti, Gertrudis] Hosp St Joan de Deu Manresa, Dept Pediat, Barcelona, Spain. [Pisciotta, Livia; Bertolini, Stefano] Univ Genoa, Dept Internal Med, I-16126 Genoa, Italy. [Noto, Davide; Cefalu, Angelo B.; Averna, Maurizio] Univ Palermo, Dept Internal Med & Med Specialties, Palermo, Italy. [Pannozzo, Fabio] Osped S Maria Goretti, Epidemiol Unit, Latina, Italy. [Calandra, Sebastiano] Univ Modena & Reggio Emilia, Dept Biomed Metab & Neural Sci, Modena, Italy. [Tarugi, Patrizia] Univ Modena & Reggio Emilia, Dept Life Sci, Modena, Italy. RP Arca, M (reprint author), Univ Roma La Sapienza, Dept Internal Med & Med Specialties, Piazzale Aldo Moro 5, I-00185 Rome, Italy. EM marcelloarca@libero.it RI Tarugi, Patrizia/D-2179-2015; OI Tarugi, Patrizia/0000-0001-6864-7853; CECI, Fabrizio/0000-0003-4051-4922; Minicocci, Ilenia/0000-0002-9801-4501; CANTISANI, VITO/0000-0003-1525-214X; Noto, Davide/0000-0002-5346-2829; Cefalu', Angelo Baldassare/0000-0003-1259-8284; Averna, Maurizio/0000-0003-3558-9209; Stitziel, Nathan/0000-0002-4963-8211 FU Sapienza University of Rome Grant Progetto Ateneo; National Institutes of Health [K08-HL-114642, R01 HL-107816]; Massachusetts General Hospital (MGH); Donovan Family Foundation; Fondation Leducq Grant FX This work was supported by Sapienza University of Rome Grant Progetto Ateneo 2006 (to M. A.); National Institutes of Health Grant K08-HL-114642 (to N.S.); Massachusetts General Hospital (MGH) Research Scholar Award and Howard Goodman Fellowship (to S. K.); Donovan Family Foundation Grant (to S. K.), National Institutes of Health Grant R01 HL-107816 (to S. K.); and Fondation Leducq Grant (to S.K.). NR 36 TC 9 Z9 9 U1 0 U2 2 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0022-2275 EI 1539-7262 J9 J LIPID RES JI J. Lipid Res. PD DEC PY 2013 VL 54 IS 12 BP 3481 EP 3490 DI 10.1194/jlr.P039875 PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 301LX UT WOS:000330534900024 PM 24058201 ER PT J AU De Genna, NM Feske, U AF De Genna, Natacha M. Feske, Ulrike TI Phenomenology of Borderline Personality Disorder The Role of Race and Socioeconomic Status SO JOURNAL OF NERVOUS AND MENTAL DISEASE LA English DT Article DE Borderline personality disorder; health disparities; women; race; suicide ID AFRICAN-AMERICAN SUICIDE; SUBSTANCE USE-DISORDERS; HISPANIC MEN; SELF-INJURY; DRUG-USE; PREVALENCE; BEHAVIOR; CRITERIA; VIOLENCE; COMORBIDITY AB Little is known about racial differences in borderline personality disorder (BPD) that may influence etiology, phenomenology, and treatment of women with BPD. A total of 83 women with BPD participated in this cross-sectional study: n = 41 white and n = 42 African-American women. Structured interviews were used to assess Axis I and II disorders, and a series of interviews and questionnaires captured internalizing and externalizing symptoms. The white women with BPD reported more severe internalizing symptoms, whereas the African-American women reported more severe externalizing symptoms. Except for the association between race and number of suicide attempts, the relationship between race and internalizing/ externalizing symptoms was mediated by socioeconomic status. In conclusion, African-American women with BPD may present with more severe symptoms of lack of anger control and fewer suicidal behaviors than those of white women with BPD, raising the possibility that they are misdiagnosed and receive treatments that are not optimal for BPD. C1 [De Genna, Natacha M.] Univ Pittsburgh, Dept Psychiat, Sch Med, WPIC, Pittsburgh, PA 15213 USA. [Feske, Ulrike] VA Pittsburgh Healthcare Syst, CHERP, Pittsburgh, PA USA. RP De Genna, NM (reprint author), Univ Pittsburgh, Dept Psychiat, Sch Med, WPIC, 3811 OHara St, Pittsburgh, PA 15213 USA. EM degennan@pitt.edu FU NIH [DA025734, DA020130]; Borderline Personality Disorder Research Foundation FX This work was funded by the NIH (DA025734, PI: De Genna; DA020130, PI: Feske) and the Borderline Personality Disorder Research Foundation (Young Investigator Award, PI: Feske). The authors have no other financial disclosures to report. NR 71 TC 2 Z9 2 U1 3 U2 13 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0022-3018 EI 1539-736X J9 J NERV MENT DIS JI J. Nerv. Ment. Dis. PD DEC PY 2013 VL 201 IS 12 BP 1027 EP 1034 DI 10.1097/NMD.0000000000000053 PG 8 WC Clinical Neurology; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 299EP UT WOS:000330378700003 PM 24284636 ER PT J AU Serrano-Pozo, A Qian, J Monsell, SE Frosch, MP Betensky, RA Hyman, BT AF Serrano-Pozo, Alberto Qian, Jing Monsell, Sarah E. Frosch, Matthew P. Betensky, Rebecca A. Hyman, Bradley T. TI Examination of the Clinicopathologic Continuum of Alzheimer Disease in the Autopsy Cohort of the National Alzheimer Coordinating Center SO JOURNAL OF NEUROPATHOLOGY AND EXPERIMENTAL NEUROLOGY LA English DT Article DE Alzheimer disease; Cerebral amyloid angiopathy; Hippocampal sclerosis; Neuritic plaques; Neurofibrillary tangles; Small-vessel disease ID UNIFORM DATA SET; PURE HIPPOCAMPAL SCLEROSIS; OLIGOMERIC AMYLOID-BETA; RATING-SCALE SUM; A-BETA; SENILE PLAQUES; NEUROFIBRILLARY TANGLES; COGNITIVE FUNCTION; NEUROPATHOLOGIC ASSESSMENT; OLDER PERSONS AB To test the hypothesis that Alzheimer disease (AD) is a clinical and pathologic continuum between normal aging and end-stage dementia, we selected a convenience sample of subjects from the National Alzheimer Coordinating Center 2005 to 2012 autopsy cohort (n = 2,083) with the last clinical evaluation within 2 years before autopsy and no other primary neuropathologic diagnosis. Demographic and neuropathologic characteristics were correlated with the Clinical Dementia Rating-Sum of Boxes in the 835 subjects meeting these criteria. Both neuritic plaques and neurofibrillary tangles independently predicted Clinical Dementia Rating-Sum of Boxes. Severe small-vessel disease, severe amyloid angiopathy, and hippocampal sclerosis were also independently associated with the degree of cognitive impairment. By contrast, education was a strong independent protective factor against cognitive deficits. The cause of mild to moderate dementia remained uncertain in 14% of the patients. Inverse probability weighting suggests the generalizability of these results to nonautopsied cohorts. These data indicate that plaques and tangles independently contribute to cognitive impairment, that concurrent vascular disease strongly correlates with cognitive dysfunction even in a sample selected to represent the AD pathologic continuum, and that education further modifies clinical expression. Thus, multiple concomitant etiologies of brain damage and premorbid characteristics contribute to the uncertainty of AD clinicopathologic correlations based only on tangles and plaques. C1 [Serrano-Pozo, Alberto; Frosch, Matthew P.; Hyman, Bradley T.] Massachusetts Gen Hosp, Massachusetts Alzheimer Dis Res Ctr, Boston, MA 02114 USA. [Qian, Jing; Betensky, Rebecca A.] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. [Qian, Jing] Univ Massachusetts, Div Biostat & Epidemiol, Amherst, MA 01003 USA. [Monsell, Sarah E.] Univ Washington, Natl Alzheimer Coordinating Ctr, Seattle, WA 98195 USA. [Monsell, Sarah E.] Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA. RP Hyman, BT (reprint author), MassGen Inst Neurodegenerat Dis, Alzheimer Res Unit, 16th St,Bldg 114, Charlestown, MA 02129 USA. EM bhyman@partners.org OI SERRANO-POZO, ALBERTO/0000-0003-0899-7530 FU National Institute on Aging Grant [U01 AG016976]; National Institutes of Health Grant [AG05134]; Fundacion Alfonso Martin Escudero (Madrid, Spain); Harvard NeuroDiscovery Center FX The National Alzheimer Coordinating Center database is funded by the National Institute on Aging Grant U01 AG016976. This work was supported by the National Institutes of Health Grant AG05134 (to Bradley Hyman). Alberto Serrano-Pozo was supported by a fellowship from Fundacion Alfonso Martin Escudero (Madrid, Spain). Rebecca Betensky and Jing Qian were supported by the Harvard NeuroDiscovery Center. NR 87 TC 33 Z9 34 U1 0 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0022-3069 EI 1554-6578 J9 J NEUROPATH EXP NEUR JI J. Neuropathol. Exp. Neurol. PD DEC PY 2013 VL 72 IS 12 BP 1182 EP 1192 PG 11 WC Clinical Neurology; Neurosciences; Pathology SC Neurosciences & Neurology; Pathology GA 299ZC UT WOS:000330433200007 PM 24226270 ER PT J AU Nakamoto, BK Shikuma, CM Ogata-Arakaki, D Umaki, T Neuwelt, EA Shiramizu, BT Chow, DC Parikh, NI Kallianpur, KJ Hamilton, BE AF Nakamoto, Beau K. Shikuma, Cecilia M. Ogata-Arakaki, Debra Umaki, Tracie Neuwelt, Edward A. Shiramizu, Bruce T. Chow, Dominic C. Parikh, Nisha I. Kallianpur, Kalpana J. Hamilton, Bronwyn E. TI Feasibility and potential role of ferumoxytol-enhanced neuroimaging in HIV-associated neurocognitive disorder SO JOURNAL OF NEUROVIROLOGY LA English DT Article DE HIV; HIV dementia; MRI; Ferumoxytol ID CENTRAL-NERVOUS-SYSTEM; ANTIRETROVIRAL THERAPY; IMPAIRMENT; INFECTION; AIDS; ERA AB We assessed ferumoxytol-enhanced brain MRI to identify monocyte/macrophage accumulation in HIV-associated neurocognitive disorder (HAND). Four HIV-infected subjects with undetectable HIV RNA levels on antiretroviral therapy, HIV DNA level in CD14+ cells >= 10 copies/10(6) cells, and cognitive impairment underwent ferumoxytol-enhanced brain MRI. On post-ferumoxytol susceptibility-weighted images, all HIV-infected subjects demonstrated a diffuse "tram track" appearance in the perivascular regions of cortical and deep white matter vessels suggesting ferumoxytol uptake in monocytes/macrophages. This finding was not present in an HIV-seronegative control. While ferumoxytol may have potential as an imaging biomarker for monocyte/macrophage accumulation in patients with HAND, future study is needed. C1 [Nakamoto, Beau K.; Shikuma, Cecilia M.; Ogata-Arakaki, Debra; Umaki, Tracie; Shiramizu, Bruce T.; Chow, Dominic C.; Parikh, Nisha I.; Kallianpur, Kalpana J.] Univ Hawaii, Hawaii Ctr AIDS, Honolulu, HI 96822 USA. [Nakamoto, Beau K.] Straub Clin & Hosp, Honolulu, HI USA. [Hamilton, Bronwyn E.] Oregon Hlth & Sci Univ, Dept Radiol, Portland, OR 97201 USA. [Neuwelt, Edward A.] Oregon Hlth & Sci Univ, Dept Neurol, Portland, OR 97201 USA. [Neuwelt, Edward A.] Oregon Hlth & Sci Univ, Dept Neurosurg, Portland, OR 97201 USA. [Neuwelt, Edward A.] Portland VA Med Ctr, Portland, OR USA. [Parikh, Nisha I.] Queens Med Ctr, Dept Cardiol, Honolulu, HI USA. [Nakamoto, Beau K.] Univ Hawaii Manoa, John A Burns Sch Med, Hawaii Ctr AIDS, Honolulu, HI 96816 USA. RP Nakamoto, BK (reprint author), Univ Hawaii Manoa, John A Burns Sch Med, Hawaii Ctr AIDS, 3675 Kilauea Ave,Young Bldg,5th Floor, Honolulu, HI 96816 USA. EM beau_nakamoto@yahoo.com; shikuma@hawaii.edu; ogataara@hawaii.edu; tracieu2@hawaii.edu; neuwelte@ohsu.edu; bshirami@hawaii.edu; dominicc@hawaii.edu; parikh.nisha@gmail.com; kalpana@hawaii.edu; hamiltob@ohsu.edu FU NIH [U54MD007584, U54NS43049, P20RR011091, R01HL095135, R01 CA137488, R01 NS044687, R01 NS053468, R01NS053345, K23 HL088981, U19MH081835]; Pfizer; Merck; Gilead Pharmaceuticals FX Dr. Nakamoto has received research support from NIH (U54MD007584). Dr. Nakamoto declares that there are no conflicts of interest.; Dr. Shikuma has received research support from NIH (U54MD007584, U54NS43049, P20RR011091, and R01HL095135) Pfizer, Merck, and Gilead Pharmaceuticals, and has served on an advisory board for Glaxo Smith Kline. Dr. Shikuma declares that there are no conflicts of interest.; Dr. Neuwelt has received research support from NIH (R01 CA137488, R01 NS044687, R01 NS053468). Dr. Neuwelt declares that there are no conflicts of interest.; Dr. Shiramizu has received research support from NIH (R01NS053345, U54MD007584, U54NS43049). Dr. Shiramizu declares that there are no conflicts of interest.; Dr. Chow has received research support from NIH (K23 HL088981). Dr. Chow declares that there are no conflicts of interest.; Dr. Kallianpur has received research support from NIH (U54MD007584, U19MH081835, U54MD007584). Dr. Kallianpur declares that there are no conflicts of interest. NR 15 TC 2 Z9 2 U1 0 U2 2 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1355-0284 EI 1538-2443 J9 J NEUROVIROL JI J. Neurovirol. PD DEC PY 2013 VL 19 IS 6 BP 601 EP 605 DI 10.1007/s13365-013-0213-7 PG 5 WC Neurosciences; Virology SC Neurosciences & Neurology; Virology GA 296WU UT WOS:000330216900011 PM 24129909 ER PT J AU Caspi, CE Dennerlein, JT Kenwood, C Stoddard, AM Hopcia, K Hashimoto, D Sorensen, G AF Caspi, Caitlin Eicher Dennerlein, Jack T. Kenwood, Christopher Stoddard, Anne M. Hopcia, Karen Hashimoto, Dean Sorensen, Glorian TI Results of a Pilot Intervention to Improve Health and Safety for Health Care Workers SO JOURNAL OF OCCUPATIONAL AND ENVIRONMENTAL MEDICINE LA English DT Article ID LOW-BACK-PAIN; MUSCULOSKELETAL DISORDERS; PHYSICAL-ACTIVITY; REGISTERED NURSES; OCCUPATIONAL INJURIES; COMPENSATION CLAIMS; FOLLOW-UP; SYMPTOMS; DEMANDS; DIRECTIONS AB Objective: To test the feasibility of a multicomponent pilot intervention to improve worker safety and wellness in two Boston hospitals. Methods: A 3-month intervention was conducted on seven hospital units. Pre- (374 workers) and postsurveys (303 workers) assessed changes in safety/ergonomic behaviors and practices, and social support. Wellness outcomes included self-reported pain/aching in specific body areas (musculoskeletal disorders or MSDs) and physical activity (PA). Results: Pain was reported frequently (81%), and PA averaged 4 hours per week. There was a postintervention increase in safe patient handling (P < 0.0001), safety practices (P = 0.0004), ergonomics (P = 0.009), and supervisor support (P = 0.01), but no changes in MSDs or PA. Conclusions: Safe patient handling, ergonomics, and safety practices are good targets for worker safety and wellness interventions; longer intervention periods may reduce the risk of MSDs. C1 [Caspi, Caitlin Eicher] Univ Minnesota, Dept Family Med & Community Hlth, Minneapolis, MN 55414 USA. [Dennerlein, Jack T.] Northeastern Univ, Dept Phys Therapy, Boston, MA 02115 USA. [Kenwood, Christopher; Stoddard, Anne M.] New England Res Inst, Watertown, MA USA. [Hopcia, Karen] Univ Illinois, Coll Nursing, Chicago, IL USA. [Hashimoto, Dean] Partners HealthCare, Dept Occupat Heath, Boston, MA USA. [Sorensen, Glorian] Harvard Univ, Sch Publ Hlth, Dept Soc Human Dev & Hlth, Boston, MA 02115 USA. [Sorensen, Glorian] Dana Farber Canc Inst, Ctr Community Based Res, Boston, MA 02115 USA. RP Caspi, CE (reprint author), Univ Minnesota, Dept Family Med & Community Hlth, 717 Delaware St SE, Minneapolis, MN 55414 USA. EM cecaspi@umn.edu OI Dennerlein, Jack/0000-0001-7703-643X FU National Institute for Occupational Safety and Health [U10 OH008861]; National Cancer Institute by the Harvard Education Program in Cancer Prevention and Control [R25CA057711]; Cancer-Related Health Disparities Education and Career Development Program [R25CA163184] FX This research was supported by a grant from the National Institute for Occupational Safety and Health (U10 OH008861). Funding support for the lead author (Dr Caspi) was also provided through the National Cancer Institute by the Harvard Education Program in Cancer Prevention and Control (R25CA057711) and by the Cancer-Related Health Disparities Education and Career Development Program (R25CA163184). Funding agencies played no role in this study and the contents of this article are solely the responsibility of the authors. The authors declare no conflicts of interests. NR 50 TC 7 Z9 7 U1 3 U2 10 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1076-2752 EI 1536-5948 J9 J OCCUP ENVIRON MED JI J. Occup. Environ. Med. PD DEC PY 2013 VL 55 IS 12 BP 1449 EP 1455 DI 10.1097/JOM.0b013e3182a7e65a PG 7 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 300FK UT WOS:000330449600013 PM 24270297 ER PT J AU Frush, D Denham, CR Goske, MJ Brink, JA Morin, RL Mills, TT Butler, PF McCollough, C Miller, DL AF Frush, Donald Denham, Charles R. Goske, Marilyn J. Brink, James A. Morin, Richard L. Mills, Thalia T. Butler, Priscilla F. McCollough, Cynthia Miller, Donald L. TI Radiation Protection and Dose Monitoring in Medical Imaging: A Journey From Awareness, Through Accountability, Ability and Action ... But Where Will We Arrive? SO JOURNAL OF PATIENT SAFETY LA English DT Review DE CT scan; radiation dose; image gently; computed tomography; children; radiation risk; radiation protection ID CANCER-RISK ESTIMATION; COMPUTED-TOMOGRAPHY; CT; EXPOSURE; CAMPAIGN AB Radiation awareness and protection of patients have been the fundamental responsibilities in diagnostic imaging since the discovery of x-rays late in 1895 and the first reports of radiation injury in 1896. In the ensuing years, there have been significant advancements in equipment that uses either x-rays to form images, such as fluoroscopy or computed tomography (CT), or the types of radiation emitted during nuclear imaging procedures (e.g., positron emission tomography [PET]). These advancements have allowed detailed and indispensable evaluation of a vast array of disorders. In fact, in 2001, CT and MRI were cited by physicians as the most significant medical innovations in the previous 3 decades. Rapid technological advancements in the last decade with CT, especially, have required imaging professionals to keep pace with increasingly complex technology to derive the maximum benefits of improved image acquisition and display techniques, in essence, the improved quality of the examination. It has also been challenging to fulfill the fundamental responsibilities of safety during this period of rapid growth (e.g., radiation protection, management of the risk of additional interventions driven by incidental findings, performing studies that were not indicated). The purpose of this paper is to define critical issues pertinent to ensuring patient safety through the appropriate assessment, recording, monitoring, and reporting of the radiation dose from CT. C1 [Frush, Donald] Duke Univ, Med Ctr, Dept Radiol, Durham, NC 27710 USA. [Denham, Charles R.] TMIT, Austin, TX USA. [Goske, Marilyn J.] Childrens Hosp Med Ctr, Cincinnati, OH USA. [Brink, James A.] Massachusetts Gen Hosp, Dept Diagnost Radiol, Boston, MA 02114 USA. [Morin, Richard L.] Mayo Clin Jacksonville, Dept Radiol, Jacksonville, FL 32224 USA. [Mills, Thalia T.] US FDA, Ctr Devices & Radiol Hlth, Silver Spring, MD USA. [Butler, Priscilla F.] Amer Coll Radiol, Dept Qual & Safety, Reston, VA USA. [Miller, Donald L.] US FDA, Ctr Devices & Radiol Hlth, Silver Spring, MD USA. RP Frush, D (reprint author), Duke Univ, Med Ctr, McGovern Davison Childrens Hlth Ctr 1905, Div Pediat Radiol, Erwin Rd, Durham, NC 27710 USA. EM donald.frush@duke.edu NR 58 TC 7 Z9 8 U1 1 U2 8 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1549-8417 EI 1549-8425 J9 J PATIENT SAF JI J. Patient Saf. PD DEC PY 2013 VL 9 IS 4 BP 232 EP 238 PG 7 WC Health Care Sciences & Services; Health Policy & Services SC Health Care Sciences & Services GA 300GA UT WOS:000330451200008 PM 24257067 ER PT J AU Hwabejire, JO Imam, AM Jin, G Liu, BL Li, YQ Sillesen, M Jepsen, CH Lu, J deMoya, MA Alam, HB AF Hwabejire, John O. Imam, Ayesha M. Jin, Guang Liu, Baoling Li, Yongqing Sillesen, Martin Jepsen, Cecilie H. Lu, Jennifer deMoya, Marc A. Alam, Hasan B. TI Differential effects of fresh frozen plasma and normal saline on secondary brain damage in a large animal model of polytrauma, hemorrhage and traumatic brain injury SO JOURNAL OF TRAUMA AND ACUTE CARE SURGERY LA English DT Article; Proceedings Paper CT 43rd Annual Meeting of the Western-Trauma-Association CY MAR 03-08, 2013 CL Snowmass, CO SP Western Trauma Assoc DE Brain; trauma; hemorrhage; metabolism; swine ID HEAD-INJURY; HYPOTENSION; HYPOXIA; HUMANS AB BACKGROUND: We have previously shown that the extent of traumatic brain injury (TBI) in large animal models can be reduced with early infusion of fresh frozen plasma (FFP), but the precise mechanisms remain unclear. In this study, we investigated whether resuscitation with FFP or normal saline differed in their effects on cerebral metabolism and excitotoxic secondary brain injury in a model of polytrauma, TBI, and hemorrhagic shock. METHODS: Yorkshire swine (n = 10) underwent Grade III liver injury, rib fracture, standardized TBI, and volume-controlled hemorrhage, (40% +/- 5%) and were randomly resuscitated with either FFP or normal saline. Hemodynamic parameters and brain oxygenation were continuously monitored, while microdialysis was used to measure the brain concentrations of pyruvate, lactate, glutamate, and glycerol at baseline; 1 hour and 2 hours after shock; immediate postresuscitation (PR); as well as 2, 4, and 6 hours PR. Cells from the injured hemisphere were separated into mitochondrial and cytosolic fractions and analyzed for activity of the pyruvate dehydrogenase complex (PDH). RESULTS: There were no baseline differences in cerebral perfusion pressure, brain oxygenation, as well as concentrations of pyruvate, lactate, glutamate, and glycerol between the groups. At 2 hours and 4 hours PR, the FFP group had significantly higher cerebral perfusion pressures (52 [5] mm Hg vs. 43 [2] mm Hg, p = 0.016; and 50 [7] mm Hg vs. 37 [1] mm Hg, p = 0.008, respectively). There was a sustained and significant (p < 0.05) drop in the glutamate and glycerol levels in the FFP group, implying a decrease in excitotoxicity and brain damage, respectively. Mitochondrial PDH activity was significantly higher (2,666.2 [638.2] adjusted volume INT x mm(2) vs. 1,293.4 [88.8] adjusted volume INT x mm(2), p = 0.008), and cytosolic PDH activity was correspondingly lower (671.4 [209.2] adjusted volume INT x mm(2) vs. 3070.7 [484.3] adjusted volume INT x mm(2), p < 0.001) in the FFP group, suggesting an attenuation of mitochondrial dysfunction and permeability. CONCLUSION: In this model of TBI, polytrauma, and hemorrhage, FFP resuscitation confers neuroprotection by improving cerebral perfusion, diminishing glutamate-mediated excitotoxic secondary brain injury and reducing mitochondrial dysfunction. (Copyright (C) 2013 by Lippincott Williams & Wilkins) C1 [Hwabejire, John O.; Imam, Ayesha M.; Jin, Guang; Liu, Baoling; Li, Yongqing; Sillesen, Martin; Jepsen, Cecilie H.; Lu, Jennifer; deMoya, Marc A.; Alam, Hasan B.] Massachusetts Gen Hosp, Div Trauma Emergency Surg & Surg Crit Care, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. [Jin, Guang; Liu, Baoling; Alam, Hasan B.] Univ Michigan Hosp, Dept Surg, Ann Arbor, MI 48109 USA. RP Alam, HB (reprint author), Univ Michigan Hosp, Taubman Ctr 5331 2920, 1500 E Med Ctr Dr, Ann Arbor, MI 48109 USA. EM alamh@med.umich.edu NR 18 TC 7 Z9 7 U1 0 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 2163-0755 EI 2163-0763 J9 J TRAUMA ACUTE CARE JI J. Trauma Acute Care Surg. PD DEC PY 2013 VL 75 IS 6 BP 968 EP 974 DI 10.1097/TA.0b013e31829a021a PG 7 WC Critical Care Medicine; Surgery SC General & Internal Medicine; Surgery GA 300IR UT WOS:000330458100008 PM 24256668 ER PT J AU Imam, AM Jin, G Sillesen, M Duggan, M Jepsen, CH Hwabejire, JO Lu, J Liu, BL DeMoya, MA Velmahos, GC Alam, HB AF Imam, Ayesha M. Jin, Guang Sillesen, Martin Duggan, Michael Jepsen, Cecilie H. Hwabejire, John O. Lu, Jennifer Liu, Baoling DeMoya, Marc A. Velmahos, George C. Alam, Hasan B. TI Early treatment with lyophilized plasma protects the brain in a large animal model of combined traumatic brain injury and hemorrhagic shock SO JOURNAL OF TRAUMA AND ACUTE CARE SURGERY LA English DT Article; Proceedings Paper CT 43rd Annual Meeting of the Western-Trauma-Association CY MAR 03-08, 2013 CL Snowmass, CO SP Western Trauma Assoc DE Traumatic brain injury; hemorrhage; edema; swine; shock ID SEVERE HEAD-INJURY; FOCAL CEREBRAL-ISCHEMIA; INTRACRANIAL-PRESSURE; FLUID RESUSCITATION; BLOOD; MORTALITY; AGE; HEMODILUTION; COAGULOPATHY; COAGULATION AB BACKGROUND: Combination of traumatic brain injury (TBI) and hemorrhagic shock (HS) can result in significant morbidity and mortality. We have previously shown that early administration of fresh frozen plasma (FFP) in a large animal model of TBI and HS reduces the size of the brain lesion as well as the associated edema. However, FFP is a perishable product that is not well suited for use in the austere prehospital settings. In this study, we tested whether a shelf-stable, low-volume, lyophilized plasma (LSP) product was as effective as FFP. METHODS: Yorkshire swine (42-50 kg) were instrumented to measure hemodynamic parameters, intracranial pressure, and brain tissue oxygenation. A prototype, computerized, cortical impact device was used to create TBI through a 20-mm craniotomy: 15-mm cylindrical tip impactor at 4 m/s velocity, 100-millisecond dwell time, and 12-mm penetration depth. Volume-controlled hemorrhage was induced (40-45% total blood volume) concurrent with the TBI. After 2 hours of shock, animals were treated with (1) normal saline (NS, n = 5), (2) FFP (n = 5), and (3) LSP (n = 5). The volume of FFP and LSP matched the shed blood volume, whereas NS was 3 times the volume. Six hours after resuscitation, brains were sectioned and stained with TTC (2, 3, 5-Triphenyltetrazolium chloride), and lesion size (mm(3)) and swelling (percent change in volume compared with the contralateral, uninjured side) were measured. RESULTS: This protocol resulted in a highly reproducible brain injury, with clinically relevant changes in blood pressure, cardiac output, tissue hypoperfusion, intracranial pressure, and brain tissue oxygenation. Compared with NS, treatment with LSP significantly (p < 0.05) decreased brain lesion size and swelling (51% and 54%, respectively). CONCLUSION: In a clinically realistic combined TBI + HS model, early administration of plasma products decreases brain lesion size and edema. LSP is as effective as FFP, while offering many logistic advantages. (Copyright (C) 2013 by Lippincott Williams & Wilkins) C1 [Imam, Ayesha M.; Jin, Guang; Sillesen, Martin; Duggan, Michael; Jepsen, Cecilie H.; Hwabejire, John O.; Lu, Jennifer; DeMoya, Marc A.; Velmahos, George C.; Alam, Hasan B.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Trauma Emergency Surg & Surg Crit Care,Dept S, Boston, MA USA. [Jin, Guang; Liu, Baoling; Alam, Hasan B.] Univ Michigan Hosp, Dept Surg, Ann Arbor, MI 48109 USA. RP Alam, HB (reprint author), Univ Michigan Hosp, Taubman Ctr 5331 2920, 1500 E Med Ctr Dr, Ann Arbor, MI 48109 USA. EM alamh@med.umich.edu NR 40 TC 10 Z9 10 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 2163-0755 EI 2163-0763 J9 J TRAUMA ACUTE CARE JI J. Trauma Acute Care Surg. PD DEC PY 2013 VL 75 IS 6 BP 976 EP 983 DI 10.1097/TA.0b013e31829e2186 PG 8 WC Critical Care Medicine; Surgery SC General & Internal Medicine; Surgery GA 300IR UT WOS:000330458100010 PM 24256669 ER PT J AU Kornblith, LZ Kutcher, ME Callcut, RA Redick, BJ Hu, CK Cogbill, TH Baker, CC Shapiro, ML Burlew, CC Kaups, KL DeMoya, MA Haan, JM Koontz, CH Zolin, SJ Gordy, SD Shatz, DV Paul, DB Cohen, MJ AF Kornblith, Lucy Z. Kutcher, Matthew E. Callcut, Rachael A. Redick, Brittney J. Hu, Charles K. Cogbill, Thomas H. Baker, Christopher C. Shapiro, Mark L. Burlew, Clay C. Kaups, Krista L. DeMoya, Marc A. Haan, James M. Koontz, Christopher H. Zolin, Samuel J. Gordy, Stephanie D. Shatz, David V. Paul, Doug B. Cohen, Mitchell J. CA Western Trauma Assoc Study Grp TI Mechanical ventilation weaning and extubation after spinal cord injury: A Western Trauma Association multicenter study SO JOURNAL OF TRAUMA AND ACUTE CARE SURGERY LA English DT Article; Proceedings Paper CT 43rd Annual Meeting of the Western-Trauma-Association CY MAR 03-08, 2013 CL Snowmass, CO SP Western Trauma Assoc DE Spinal cord injury; mechanical ventilation; tracheostomy ID RESPIRATORY COMPLICATIONS; MANAGEMENT; TRACHEOSTOMY; PREDICTORS; OUTCOMES AB BACKGROUND: Respiratory failure after acute spinal cord injury (SCI) is well recognized, but data defining which patients need long-term ventilator support and criteria for weaning and extubation are lacking. We hypothesized that many patients with SCI, even those with cervical SCI, can be successfully managed without long-term mechanical ventilation and its associated morbidity. METHODS: Under the auspices of the Western Trauma Association Multi-Center Trials Group, a retrospective study of patients with SCI at 14 major trauma centers was conducted. Comprehensive injury, demographic, and outcome data on patients with acute SCI were compiled. The primary outcome variable was the need for mechanical ventilation at discharge. Secondary outcomes included the use of tracheostomy and development of acute lung injury and ventilator-associated pneumonia. RESULTS: A total of 360 patients had SCI requiring mechanical ventilation. Sixteen patients were excluded for death within the first 2 days of hospitalization. Of the 344 patients included, 222 (64.5%) had cervical SCI. Notably, 62.6% of the patients with cervical SCI were ventilator free by discharge. One hundred forty-nine patients (43.3%) underwent tracheostomy, and 53.7% of them were successfully weaned from the ventilator, compared with an 85.6% success rate among those with no tracheostomy (p < 0.05). Patients who underwent tracheostomy had significantly higher rates of ventilator-associated pneumonia (61.1% vs. 20.5%, p < 0.05) and acute lung injury (12.8% vs. 3.6%, p < 0.05) and fewer ventilator-free days (1 vs. 24 p < 0.05). When controlled for injury severity, thoracic injury, and respiratory comorbidities, tracheostomy after cervical SCI was an independent predictor of ventilator dependence with an associated 14-fold higher likelihood of prolonged mechanical ventilation (odds ratio, 14.1; 95% confidence interval, 2.78-71.67; p < 0.05). CONCLUSION: While many patients with SCI require short-term mechanical ventilation, the majority can be successfully weaned before discharge. In patients with SCI, tracheostomy is associated with major morbidity, and its use, especially among patients with cervical SCI, deserves further study. Copyright (C) 2013 by Lippincott Williams & Wilkins C1 [Kornblith, Lucy Z.; Kutcher, Matthew E.; Callcut, Rachael A.; Redick, Brittney J.; Cohen, Mitchell J.] Univ Calif San Francisco, San Francisco Gen Hosp, Dept Surg, San Francisco, CA USA. [Kaups, Krista L.] Univ Calif San Francisco, Community Reg Med Ctr, Dept Surg, Fresno, CA USA. [Hu, Charles K.] Scottsdale Healthcare Osborn Med Ctr, Trauma Serv, Scottsdale, AZ USA. [Cogbill, Thomas H.] Gundersen Lutheran Med Fdn, Dept Surg, La Crosse, WI USA. [Baker, Christopher C.] Virginia Tech, Caril Sch Med, Caril Roanoke Mem Hosp, Dept Surg, Roanoke, VA USA. [Shapiro, Mark L.] Duke Univ, Med Ctr, Div Trauma Surg Crit Care & Acute Care Surg, Durham, NC USA. [Burlew, Clay C.] Univ Colorado, Denver Hlth Med Ctr, Dept Surg, Denver, CO 80202 USA. [DeMoya, Marc A.] Massachusetts Gen Hosp, Div Trauma Emergency Surg & Surg Crit Care, Boston, MA 02114 USA. [DeMoya, Marc A.] Harvard Univ, Sch Med, Boston, MA USA. [Haan, James M.] Via Christi Reg Med Ctr, Dept Surg, Wichita, KS USA. [Koontz, Christopher H.] NYU, Dept Surg, Langone Med Ctr, New York, NY 10016 USA. [Zolin, Samuel J.] Univ Pittsburgh, Med Ctr, Dept Gen Surg & Trauma, Pittsburgh, PA USA. [Gordy, Stephanie D.] Oregon Hlth & Sci Univ, Dept Surg, Portland, OR USA. [Shatz, David V.] Univ Calif Davis, Med Ctr, Dept Surg, Davis, CA 95616 USA. [Paul, Doug B.] Grant Med Ctr, Dept Surg, Columbus, OH USA. RP Kornblith, LZ (reprint author), Ward 3A San Francisco Gen Hosp, Dept Surg, 1001 Potrero Ave,Room 3C-38, San Francisco, CA 94110 USA. EM lucy.kornblith@ucsfmedctr.org FU NIGMS NIH HHS [T32 GM-08258-20, T32 GM008258, T32 GM-008258-25, K08 GM085689, GM-085689] NR 23 TC 4 Z9 4 U1 1 U2 8 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 2163-0755 EI 2163-0763 J9 J TRAUMA ACUTE CARE JI J. Trauma Acute Care Surg. PD DEC PY 2013 VL 75 IS 6 BP 1060 EP 1069 DI 10.1097/TA.0b013e3182a74a5b PG 10 WC Critical Care Medicine; Surgery SC General & Internal Medicine; Surgery GA 300IR UT WOS:000330458100029 PM 24256682 ER PT J AU Sotiropoulos, SN Moeller, S Jbabdi, S Xu, J Andersson, JL Auerbach, EJ Yacoub, E Feinberg, D Setsompop, K Wald, LL Behrens, TEJ Ugurbil, K Lenglet, C AF Sotiropoulos, S. N. Moeller, S. Jbabdi, S. Xu, J. Andersson, J. L. Auerbach, E. J. Yacoub, E. Feinberg, D. Setsompop, K. Wald, L. L. Behrens, T. E. J. Ugurbil, K. Lenglet, C. TI Effects of Image Reconstruction on Fiber Orientation Mapping From Multichannel Diffusion MRI: Reducing the Noise Floor Using SENSE SO MAGNETIC RESONANCE IN MEDICINE LA English DT Article DE sum of squares; SENSE; Rician; noncentral-; magnitude image; tractography ID PHASED-ARRAY; SNR; TRACTOGRAPHY AB PurposeTo examine the effects of the reconstruction algorithm of magnitude images from multichannel diffusion MRI on fiber orientation estimation. Theory and MethodsIt is well established that the method used to combine signals from different coil elements in multichannel MRI can have an impact on the properties of the reconstructed magnitude image. Using a root-sum-of-squares approach results in a magnitude signal that follows an effective noncentral- distribution. As a result, the noise floor, the minimum measurable in the absence of any true signal, is elevated. This is particularly relevant for diffusion-weighted MRI, where the signal attenuation is of interest. ResultsIn this study, we illustrate problems that such image reconstruction characteristics may cause in the estimation of fiber orientations, both for model-based and model-free approaches, when modern 32-channel coils are used. We further propose an alternative image reconstruction method that is based on sensitivity encoding (SENSE) and preserves the Rician nature of the single-channel, magnitude MR signal. We show that for the same k-space data, root-sum-of-squares can cause excessive overfitting and reduced precision in orientation estimation compared with the SENSE-based approach. ConclusionThese results highlight the importance of choosing the appropriate image reconstruction method for tractography studies that use multichannel receiver coils for diffusion MRI acquisition. Magn Reson Med 70:1682-1689, 2013. (c) 2013 Wiley Periodicals, Inc. C1 [Sotiropoulos, S. N.; Jbabdi, S.; Andersson, J. L.; Behrens, T. E. J.] Univ Oxford, Ctr Funct Magnet Resonance Imaging Brain, Oxford OX3 9DU, England. [Moeller, S.; Xu, J.; Auerbach, E. J.; Yacoub, E.; Ugurbil, K.; Lenglet, C.] Univ Minnesota, Ctr Magnet Resonance Res, Minneapolis, MN USA. [Feinberg, D.] Adv MRI Technol, Sebastopol, CA USA. [Feinberg, D.] Univ Calif Berkeley, Helen Wills Inst Neurosci, Berkeley, CA 94720 USA. [Setsompop, K.; Wald, L. L.] Massachusetts Gen Hosp, Dept Radiol, Charlestown, MA USA. [Behrens, T. E. J.] UCL, Wellcome Trust Ctr NeuroImaging, London, England. RP Sotiropoulos, SN (reprint author), Univ Oxford, John Radcliffe Hosp, Ctr Funct Magnet Resonance Imaging Brain, Oxford OX3 9DU, England. EM stam@fmrib.ox.ac.uk RI Xu, Junqian/D-2247-2009; Setsompop, Kawin/P-1464-2014; Auerbach, Edward/D-9980-2015; Wald, Lawrence/D-4151-2009; OI Xu, Junqian/0000-0001-8438-2066; Setsompop, Kawin/0000-0003-0455-7634; Auerbach, Edward/0000-0003-4553-1545; Jbabdi, Saad/0000-0003-3234-5639; Sotiropoulos, Stamatios/0000-0003-4735-5776 FU Human Connectome Project [U54MH091657, U01MH093765]; NIH Blueprint for Neuroscience Research; NIH [P41 RR008079, P41 EB015894, P30 NS057091, P30 NS076408] FX Grant sponsor: This study was supported by the Human Connectome Project (grants U54MH091657 and U01MH093765) from the 16 NIH Institutes and Centers that Support the NIH Blueprint for Neuroscience Research. Also by NIH grants P41 RR008079 (NCRR), P41 EB015894 (NIBIB), P30 NS057091, and P30 NS076408. NR 27 TC 35 Z9 35 U1 0 U2 9 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0740-3194 EI 1522-2594 J9 MAGN RESON MED JI Magn. Reson. Med. PD DEC PY 2013 VL 70 IS 6 BP 1682 EP 1689 DI 10.1002/mrm.24623 PG 8 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 296JV UT WOS:000330182100022 PM 23401137 ER PT J AU Sabatini, M AF Sabatini, Mary TI Follicular dynamics: watching the waves SO MENOPAUSE-THE JOURNAL OF THE NORTH AMERICAN MENOPAUSE SOCIETY LA English DT Editorial Material ID NORMAL MENSTRUAL-CYCLE; OVARIAN; FOLLICULOGENESIS C1 Massachusetts Gen Hosp, Fertil Ctr, Obstet & Gynecol Serv, Boston, MA 02114 USA. RP Sabatini, M (reprint author), Massachusetts Gen Hosp, Fertil Ctr, Obstet & Gynecol Serv, Boston, MA 02114 USA. NR 9 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1072-3714 EI 1530-0374 J9 MENOPAUSE JI Menopause-J. N. Am. Menopause Soc. PD DEC PY 2013 VL 20 IS 12 BP 1233 EP 1233 DI 10.1097/gme.0000000000000136 PG 1 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 300LP UT WOS:000330465700003 PM 24193300 ER PT J AU Cohen, LS AF Cohen, Lee S. TI MsFLASH: Do the Findings Guide Clinical Practice? SO MENOPAUSE-THE JOURNAL OF THE NORTH AMERICAN MENOPAUSE SOCIETY LA English DT Meeting Abstract CT 24th Annual Meeting of the North-American-Menopause-Society CY OCT 09-12, 2013 CL Dallas, TX SP N Amer Menopause Soc C1 [Cohen, Lee S.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Cohen, Lee S.] MsFLASH Network, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1072-3714 EI 1530-0374 J9 MENOPAUSE JI Menopause-J. N. Am. Menopause Soc. PD DEC PY 2013 VL 20 IS 12 BP 1315 EP 1315 PG 1 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 300LP UT WOS:000330465700034 ER PT J AU Crawford, S Waetjen, E Crandall, C Derby, C El Khoudary, SR Fischer, M Joffe, H AF Crawford, Sybil Waetjen, Elaine Crandall, Carolyn Derby, Carol El Khoudary, Samar R. Fischer, Mary Joffe, Hadine TI Trends in Exogenous Hormone Therapy Before and After WHI: Data from the Study of Women's Health Across the Nation (SWAN) SO MENOPAUSE-THE JOURNAL OF THE NORTH AMERICAN MENOPAUSE SOCIETY LA English DT Meeting Abstract CT 24th Annual Meeting of the North-American-Menopause-Society CY OCT 09-12, 2013 CL Dallas, TX SP N Amer Menopause Soc C1 [Crawford, Sybil; Fischer, Mary] Univ Massachusetts, Sch Med, Worcester, MA USA. [Waetjen, Elaine] UCDavis Med Ctr, Sacramento, CA USA. [Crandall, Carolyn] Univ Calif Los Angeles, Los Angeles, CA USA. [Derby, Carol] Albert Einstein Coll Med, Bronx, NY 10467 USA. [El Khoudary, Samar R.] Univ Pittsburgh, Pittsburgh, PA USA. [Joffe, Hadine] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1072-3714 EI 1530-0374 J9 MENOPAUSE JI Menopause-J. N. Am. Menopause Soc. PD DEC PY 2013 VL 20 IS 12 BP 1324 EP 1325 PG 2 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 300LP UT WOS:000330465700065 ER PT J AU Looby, S Shifren, JL Corless, I Pedersen, MC Grinspoon, S Joffe, H AF Looby, Sara Shifren, Jan L. Corless, Inge Pedersen, Maria C. Grinspoon, Steven Joffe, Hadine TI Depressive Symptoms in Perimenopausal Women with and without HIV SO MENOPAUSE-THE JOURNAL OF THE NORTH AMERICAN MENOPAUSE SOCIETY LA English DT Meeting Abstract CT 24th Annual Meeting of the North-American-Menopause-Society CY OCT 09-12, 2013 CL Dallas, TX SP N Amer Menopause Soc C1 [Looby, Sara; Pedersen, Maria C.; Grinspoon, Steven] Massachusetts Gen Hosp, Program Nutr Metab, Boston, MA 02114 USA. [Looby, Sara; Pedersen, Maria C.; Grinspoon, Steven] Massachusetts Gen Hosp, Neuroendocrine Unit, Boston, MA 02114 USA. [Looby, Sara; Shifren, Jan L.; Pedersen, Maria C.; Grinspoon, Steven; Joffe, Hadine] Harvard Univ, Sch Med, Boston, MA USA. [Shifren, Jan L.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Corless, Inge] MGH Inst Hlth Profess, Charlestown, MA USA. [Joffe, Hadine] Brigham & Womens Hosp, Dept Psychiat, Boston, MA 02115 USA. [Joffe, Hadine] Dana Farber Canc Inst, Dept Psychosocial Oncol & Palliat Care, Boston, MA 02115 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1072-3714 EI 1530-0374 J9 MENOPAUSE JI Menopause-J. N. Am. Menopause Soc. PD DEC PY 2013 VL 20 IS 12 BP 1341 EP 1341 PG 1 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 300LP UT WOS:000330465700131 ER PT J AU Pinkerton, JV Joffe, H Kazempour, K Mekonnen, H Bhaskar, S Lippman, J AF Pinkerton, JoAnn V. Joffe, Hadine Kazempour, Kazem Mekonnen, Hana Bhaskar, Sailaja Lippman, Joel TI Low-Dose Mesylate Salt of Paroxetine (LDMP) Improved Sleep in Women With Vasomotor Symptoms Due to Menopause SO MENOPAUSE-THE JOURNAL OF THE NORTH AMERICAN MENOPAUSE SOCIETY LA English DT Meeting Abstract CT 24th Annual Meeting of the North-American-Menopause-Society CY OCT 09-12, 2013 CL Dallas, TX SP N Amer Menopause Soc C1 [Pinkerton, JoAnn V.] Univ Virginia, Div Midlife Hlth, Charlottesville, VA USA. [Joffe, Hadine] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. [Kazempour, Kazem; Mekonnen, Hana] Amarex Clin Res, Germantown, MD USA. [Bhaskar, Sailaja; Lippman, Joel] Noven Pharmaceut Inc, New York, NY USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1072-3714 EI 1530-0374 J9 MENOPAUSE JI Menopause-J. N. Am. Menopause Soc. PD DEC PY 2013 VL 20 IS 12 BP 1347 EP 1348 PG 2 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 300LP UT WOS:000330465700152 ER PT J AU Tepper, P Randolph, JF Jones, B Crawford, S Gold, EB El Khoudary, SR Lasley, BL McConnell, DS Joffe, H Zheng, HY Avis, NA Bromberger, JT Brooks, MM Hess, R Ruppert, K Thurston, RC AF Tepper, Ping Randolph, John F. Jones, Bobby Crawford, Sybil Gold, Ellen B. El Khoudary, Samar R. Lasley, Bill L. McConnell, Daniel S. Joffe, Hadine Zheng, Huiyong Avis, Nancy A. Bromberger, Joyce T. Brooks, Maria M. Hess, Rachel Ruppert, Kristine Thurston, Rebecca C. TI Trajectory Patterns of Vasomotor Symptoms over the Menopausal Transition in the Study of Women's Health Across the Nation (SWAN) SO MENOPAUSE-THE JOURNAL OF THE NORTH AMERICAN MENOPAUSE SOCIETY LA English DT Meeting Abstract CT 24th Annual Meeting of the North-American-Menopause-Society CY OCT 09-12, 2013 CL Dallas, TX SP N Amer Menopause Soc C1 [Tepper, Ping; Jones, Bobby; El Khoudary, Samar R.; Bromberger, Joyce T.; Brooks, Maria M.; Hess, Rachel; Ruppert, Kristine; Thurston, Rebecca C.] Univ Pittsburgh, Pittsburgh, PA USA. [Joffe, Hadine] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Crawford, Sybil] Univ Massachusetts, Worcester, MA 01605 USA. [Gold, Ellen B.; Lasley, Bill L.] Univ Calif Davis, Davis, CA 95616 USA. [Randolph, John F.; McConnell, Daniel S.; Zheng, Huiyong] Univ Michigan, Ann Arbor, MI 48109 USA. [Avis, Nancy A.] Wake Forest Univ, Winston Salem, NC 27109 USA. NR 0 TC 1 Z9 1 U1 1 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1072-3714 EI 1530-0374 J9 MENOPAUSE JI Menopause-J. N. Am. Menopause Soc. PD DEC PY 2013 VL 20 IS 12 BP 1356 EP 1356 PG 1 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 300LP UT WOS:000330465700176 ER PT J AU Concha-Benavente, F Srivastava, RM Ferrone, S Ferris, RL AF Concha-Benavente, Fernando Srivastava, Raghvendra M. Ferrone, Soldano Ferris, Robert L. TI EGFR-mediated tumor immunoescape The imbalance between phosphorylated STAT1 and phosphorylated STAT3 SO ONCOIMMUNOLOGY LA English DT Editorial Material DE APM; EGFR; immunoescape; immunotherapy; pSTAT1; pSTAT3; SHP2 ID ANTIGEN-PROCESSING MACHINERY; SQUAMOUS-CELL CARCINOMA; CONSTITUTIVE ACTIVATION; NECK-CANCER; IN-VITRO; HEAD; RECOGNITION; DEFECTS; SYSTEM; SHP2 AB The epidermal growth factor receptor (EGFR) supports the escape of malignant cells from immunosurveillance by inhibiting the activation of signal transducer and activator of transcription 1 (STAT1) while promoting that of STAT3. We have recently demonstrated that protein tyrosine phosphatase, non-receptor type 11 (PTNP11, best known as SHP2), a phosphatase that operates downstream of EGFR, is responsible for the dephosphorylation of active STAT1 and for the inhibition of the antigen-processing machinery (APM), hence favoring tumor immunoescape. Thus, EGFR signaling may skew the tumor microenvironment to suppress cellular immune responses. C1 [Concha-Benavente, Fernando; Ferris, Robert L.] Univ Pittsburgh, Dept Immunol, Pittsburgh, PA 15213 USA. [Srivastava, Raghvendra M.; Ferris, Robert L.] Univ Pittsburgh, Dept Otolaryngol, Pittsburgh, PA 15260 USA. [Ferrone, Soldano] Harvard Univ, Sch Med, Dept Surg, Massachusetts Gen Hosp, Boston, MA 02115 USA. [Ferris, Robert L.] Univ Pittsburgh, Inst Canc, Canc Immunol Program, Pittsburgh, PA USA. RP Ferris, RL (reprint author), Univ Pittsburgh, Dept Immunol, Pittsburgh, PA 15213 USA. EM ferrrl@upmc.edu OI Srivastava, Rakesh/0000-0003-3112-4252; Srivastava, Rakesh/0000-0002-0065-4069 NR 13 TC 9 Z9 9 U1 1 U2 4 PU LANDES BIOSCIENCE PI AUSTIN PA 1806 RIO GRANDE ST, AUSTIN, TX 78702 USA SN 2162-4011 EI 2162-402X J9 ONCOIMMUNOLOGY JI OncoImmunology PD DEC PY 2013 VL 2 IS 12 AR e27091 DI 10.4161/onci.27215 PG 3 WC Oncology; Immunology SC Oncology; Immunology GA 299VZ UT WOS:000330425100018 ER PT J AU Tuomela, J Sandholm, J Kauppila, JH Lehenkari, P Harris, KW Selander, KS AF Tuomela, Johanna Sandholm, Jouko Kauppila, Joonas H. Lehenkari, Petri Harris, Kevin W. Selander, Katri S. TI Chloroquine has tumor-inhibitory and tumor-promoting effects in triple-negative breast cancer SO ONCOLOGY LETTERS LA English DT Article DE chloroquine; hypoxia; toll-like receptor-9; triple-negative breast cancer ID POTENTIAL MEDIATORS; CELLULAR INVASION; CELLS; ACTIVATION; GROWTH; LINES; AKT; P53 AB Toll-like receptor-9 (TLR9) is an intracellular DNA receptor that is widely expressed in breast and other cancers. We previously demonstrated that low tumor TLR9 expression upon diagnosis is associated with significantly shortened disease-specific survival times in patients with triple-negative breast cancer (TNBC). There are no targeted therapies for this subgroup of patients whose prognosis is among the worst in breast cancer. Due to the previously detected in vitro anti-invasive effects of chloroquine in these cell lines, the present study aimed to investigate the in vivo effects of chloroquine against two clinical subtypes of TNBC that differ in TLR9 expression. Chloroquine suppressed matrix metalloproteinase (MMP)-2 and MMP-9 mRNA expression and protein activity, whereas MMP-13 mRNA expression and proteolytic activity were increased. Despite enhancing TLR9 mRNA expression, chloroquine suppressed TLR9 protein expression in vitro. Daily treatment of mice with intraperitoneal (i.p.) chloroquine (80 mg/kg/day) for 22 days, did not inhibit the growth of control siRNA or TLR9 siRNA MDA-MB-231 breast cancer cells. In conclusion, despite the favorable in vitro effects on TNBC invasion and viability, particularly in hypoxic conditions, chloroquine does not prevent the growth of the triple-negative MDA-MB-231 cells with high or low TLR9 expression levels in vivo. This may be explained by the activating effects of chloroquine on MMP-13 expression or by the fact that chloroquine, by suppressing TLR9 expression, permits the activation of currently unknown molecular pathways, which allow the aggressive behavior of TNBC cells with low TLR9 expression in hypoxia. C1 [Tuomela, Johanna; Sandholm, Jouko; Harris, Kevin W.; Selander, Katri S.] Univ Alabama Birmingham, Dept Med, Birmingham, AL 35294 USA. [Tuomela, Johanna] Univ Turku, MediC PET Preclin Imaging, Turku PET Ctr, Turku 20521, Finland. [Sandholm, Jouko] Univ Turku, Turku Ctr Biotechnol, FIN-20520 Turku, Finland. [Sandholm, Jouko] Abo Akad Univ, FIN-20520 Turku, Finland. [Kauppila, Joonas H.; Lehenkari, Petri] Univ Oulu, Dept Anat & Cell Biol, Oulu 90014, Finland. [Kauppila, Joonas H.; Lehenkari, Petri] Univ Hosp Oulu, Dept Surg, Oulu 90020, Finland. [Kauppila, Joonas H.] Univ Hosp Oulu, Dept Pathol, Oulu 90020, Finland. [Harris, Kevin W.] Birmingham Vet Affairs Med Ctr, Birmingham, AL 35233 USA. RP Selander, KS (reprint author), Univ Alabama Birmingham, Dept Med, Div Hematol Oncol, SHEL 514,1825 Univ Blvd, Birmingham, AL 35294 USA. EM Katriselander@uabmc.edu RI Kauppila, Joonas/P-1363-2015; Lehenkari, Petri/O-3009-2016; OI Kauppila, Joonas/0000-0001-6740-3726; Lehenkari, Petri/0000-0002-0055-5183; Tuomela, Johanna/0000-0003-4390-4563 FU Department of Defense [W81XWH-10-1-0308]; Lapland Cultural Foundation; Elsa U. Pardee Foundation; Maud Kuistila Memorial Foundation; Finnish Cultural Foundation; Emil Aaltonen Foundation; Cancer Foundation of Northern Ostrobotnia; Oulu University Research Foundation; Georg C. and Mary Ehrnroot Foundation; Orion-Farmos Research Foundation; Finnish Medical Foundation FX This study was funded by grants from the Department of Defense (W81XWH-10-1-0308, K.S.S.), Lapland Cultural Foundation (K.S.S.), Elsa U. Pardee Foundation (K.S.S.), Maud Kuistila Memorial Foundation (J.T.), Finnish Cultural Foundation (J.S.), Emil Aaltonen Foundation (J.H.K.), Cancer Foundation of Northern Ostrobotnia (J.H.K.), Oulu University Research Foundation (J.H.K.), Georg C. and Mary Ehrnroot Foundation (J.H.K.), Orion-Farmos Research Foundation (J.H.K.) and the Finnish Medical Foundation (J.H.K.). Christine Pressey is acknowledged for providing assistance with the qPCR assays. NR 25 TC 3 Z9 4 U1 0 U2 3 PU SPANDIDOS PUBL LTD PI ATHENS PA POB 18179, ATHENS, 116 10, GREECE SN 1792-1074 EI 1792-1082 J9 ONCOL LETT JI Oncol. Lett. PD DEC PY 2013 VL 6 IS 6 BP 1665 EP 1672 DI 10.3892/ol.2013.1602 PG 8 WC Oncology SC Oncology GA AA0LQ UT WOS:000330787000023 ER PT J AU Seyyedi, M Herrmann, BS Eddington, DK Nadol, JB AF Seyyedi, Mohammad Herrmann, Barbara S. Eddington, Donald K. Nadol, Joseph B., Jr. TI The Pathologic Basis of Facial Nerve Stimulation in Otosclerosis and Multi-Channel Cochlear Implantation SO OTOLOGY & NEUROTOLOGY LA English DT Article DE Cochlear implantation; Facial nerve; Otosclerosis ID SURFACE-POTENTIALS; SYSTEM; EAR AB Hypothesis: Unintentional electrical stimulation of the facial nerve by cochlear implants occurs when advanced otosclerosis invades the endosteum of both the upper basal turn of the cochlea (UBTC) and the facial nerve canal (FNC) and all the bone between these 2 structures. Background: A complication of cochlear implantation is facial nerve stimulation (FNS) known to be more common in otosclerosis. Otosclerotic involvement of the enchondral bone of the otic capsule results in areas of bone resorption, new bone formation, vascular proliferation, and a connective tissue stroma. This may reduce impedance, shunting current to the facial nerve. The cause of FNS has not been fully elucidated, and remarkable differences in FNS rates have been reported using different types of electrode arrays. Methods: Thirteen implanted temporal bones from 11 patients with otosclerosis, 10 with straight, and 3 with perimodiolar electrodes, were histologically processed after death. The data were analyzed using Fisher's exact test. Results: In the straight electrode group (n = 10), only those subjects with temporal bones showing involvement by otosclerosis of the UBTC and of FNC endosteum and the bone between these 2 structures (n = 4; 40%) showed FNS during life (p = 0.005), which was consistent with the location of problematic electrodes during life. None of the cases in the perimodiolar group had FNS even with endosteal involvement by otosclerosis. Conclusion: FNS is a common complication of cochlear implantation in patients with otosclerosis and occurs most commonly with straight electrode implants where the endosteum of both UBTC and FNC and the intervening bone are otosclerotic. C1 [Seyyedi, Mohammad; Herrmann, Barbara S.; Eddington, Donald K.; Nadol, Joseph B., Jr.] Massachusetts Eye & Ear Infirm, Dept Otolaryngol, Boston, MA 02114 USA. [Seyyedi, Mohammad; Eddington, Donald K.; Nadol, Joseph B., Jr.] Harvard Univ, Sch Med, Dept Otol & Laryngol, Boston, MA 02115 USA. [Herrmann, Barbara S.] Massachusetts Eye & Ear Infirm, Dept Audiol, Boston, MA 02114 USA. RP Nadol, JB (reprint author), Massachusetts Eye & Ear Infirm, Dept Otolaryngol, 243 Charles St, Boston, MA 02114 USA. EM joseph_nadol@meei.harvard.edu FU National Institute of Deafness and Other Communication Disorders [R01-DC000152] FX This work was supported by grant R01-DC000152 from the National Institute of Deafness and Other Communication Disorders. NR 33 TC 3 Z9 4 U1 0 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1531-7129 EI 1537-4505 J9 OTOL NEUROTOL JI Otol. Neurotol. PD DEC PY 2013 VL 34 IS 9 BP 1603 EP 1609 PG 7 WC Clinical Neurology; Otorhinolaryngology SC Neurosciences & Neurology; Otorhinolaryngology GA 301HY UT WOS:000330524600014 PM 23928519 ER PT J AU Nakahira, K Kyung, SY Rogers, AJ Gazourian, L Youn, S Massaro, AF Quintana, C Osorio, JC Wang, ZX Zhao, Y Lawler, LA Christie, JD Meyer, NJ Mc Causland, FR Waikar, SS Waxman, AB Chung, RT Bueno, R Rosas, IO Fredenburgh, LE Baron, RM Christiani, DC Hunninghake, GM Choi, AMK AF Nakahira, Kiichi Kyung, Sun-Young Rogers, Angela J. Gazourian, Lee Youn, Sojung Massaro, Anthony F. Quintana, Carolina Osorio, Juan C. Wang, Zhaoxi Zhao, Yang Lawler, Laurie A. Christie, Jason D. Meyer, Nuala J. Mc Causland, Finnian R. Waikar, Sushrut S. Waxman, Aaron B. Chung, Raymond T. Bueno, Raphael Rosas, Ivan O. Fredenburgh, Laura E. Baron, Rebecca M. Christiani, David C. Hunninghake, Gary M. Choi, Augustine M. K. TI Circulating Mitochondrial DNA in Patients in the ICU as a Marker of Mortality: Derivation and Validation SO PLOS MEDICINE LA English DT Article ID INFLAMMATORY RESPONSE SYNDROME; C-REACTIVE PROTEIN; SEVERE SEPSIS; PLASMA NUCLEAR; OUTCOMES; RISK; DISEASE; INJURY; DAMAGE; ARDS AB Background: Mitochondrial DNA (mtDNA) is a critical activator of inflammation and the innate immune system. However, mtDNA level has not been tested for its role as a biomarker in the intensive care unit (ICU). We hypothesized that circulating cell-free mtDNA levels would be associated with mortality and improve risk prediction in ICU patients. Methods and Findings: Analyses of mtDNA levels were performed on blood samples obtained from two prospective observational cohort studies of ICU patients (the Brigham and Women's Hospital Registry of Critical Illness [BWH RoCI, n = 200] and Molecular Epidemiology of Acute Respiratory Distress Syndrome [ME ARDS, n = 243]). mtDNA levels in plasma were assessed by measuring the copy number of the NADH dehydrogenase 1 gene using quantitative real-time PCR. Medical ICU patients with an elevated mtDNA level (>= 3,200 copies/mu l plasma) had increased odds of dying within 28 d of ICU admission in both the BWH RoCI (odds ratio [OR] 7.5, 95% CI 3.6-15.8, p= 1 x 10(-7)) and ME ARDS (OR 8.4, 95% CI 2.9-24.2, p= 9 x 10(-5)) cohorts, while no evidence for association was noted in non-medical ICU patients. The addition of an elevated mtDNA level improved the net reclassification index (NRI) of 28-d mortality among medical ICU patients when added to clinical models in both the BWH RoCI (NRI 79%, standard error 14%, p<1 x 10(-4)) and ME ARDS (NRI 55%, standard error 20%, p = 0.007) cohorts. In the BWH RoCI cohort, those with an elevated mtDNA level had an increased risk of death, even in analyses limited to patients with sepsis or acute respiratory distress syndrome. Study limitations include the lack of data elucidating the concise pathological roles of mtDNA in the patients, and the limited numbers of measurements for some of biomarkers. Conclusions: Increased mtDNA levels are associated with ICU mortality, and inclusion of mtDNA level improves risk prediction in medical ICU patients. Our data suggest that mtDNA could serve as a viable plasma biomarker in medical ICU patients. C1 [Nakahira, Kiichi; Kyung, Sun-Young; Rogers, Angela J.; Gazourian, Lee; Youn, Sojung; Massaro, Anthony F.; Quintana, Carolina; Osorio, Juan C.; Lawler, Laurie A.; Waxman, Aaron B.; Rosas, Ivan O.; Fredenburgh, Laura E.; Baron, Rebecca M.; Hunninghake, Gary M.; Choi, Augustine M. K.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Div Pulm & Crit Care Med,Dept Med, Boston, MA 02115 USA. [Nakahira, Kiichi; Choi, Augustine M. K.] Weill Cornell Med Coll, Dept Med, New York, NY USA. [Kyung, Sun-Young] Gachon Univ, Gil Hosp, Dept Internal Med, Inchon, South Korea. [Rogers, Angela J.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Channing Div Network Med, Boston, MA 02115 USA. [Rogers, Angela J.] Stanford Univ, Dept Med, Div Pulm & Crit Care Med, Stanford, CA 94305 USA. [Wang, Zhaoxi; Zhao, Yang; Christiani, David C.] Harvard Univ, Sch Publ Hlth, Dept Environm Hlth, Boston, MA 02115 USA. [Christie, Jason D.; Meyer, Nuala J.] Univ Penn, Dept Med, Div Pulm Allergy & Crit Care Med, Philadelphia, PA 19104 USA. [Mc Causland, Finnian R.; Waikar, Sushrut S.] Brigham & Womens Hosp, Dept Med, Div Renal, Boston, MA 02115 USA. [Chung, Raymond T.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Gastroenterol,Dept Med, Boston, MA 02115 USA. [Bueno, Raphael] Brigham & Womens Hosp, Dept Surg, Div Thorac Surg, Boston, MA 02115 USA. [Christiani, David C.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Pulm & Crit Care Unit, Boston, MA 02115 USA. [Choi, Augustine M. K.] Sungkyunkwan Univ, Sch Med, Samsung Med Ctr, Seoul, South Korea. RP Nakahira, K (reprint author), Harvard Univ, Brigham & Womens Hosp, Sch Med, Div Pulm & Crit Care Med,Dept Med, Boston, MA 02115 USA. EM amc2056@med.cornell.edu OI Osorio, Juan C/0000-0001-8090-1551 FU Parker B Francis fellowship; [T32 HL007633]; [T32 HL7118]; [T32 HL007680]; [R01 HL087115]; [R01 HL086919]; [K08 GM083207]; [R01 HL091957]; [R01 HL060710]; [ES00002]; [K08 HL092222]; [R01 HL111024]; [P01 HL108801]; [R01 HL079904]; [R01 HL112747] FX KN is supported by T32 HL007633; LG is supported by T32 HL7118 and T32 HL007680; AR is supported by a Parker B Francis fellowship; JC is supported by R01 HL087115 and R01 HL086919; LF is supported by K08 GM083207; RB is supported by R01 HL091957; DC is supported by R01 HL060710 and ES00002; GH is supported by K08 HL092222 and R01 HL111024; and AC is supported by P01 HL108801, R01 HL079904, and R01 HL112747. This paper is subject to the NIH public access policy: http://www.nih.gov/about/publicaccess/Finalpublicaccessimplementation031 505.htm. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 42 TC 59 Z9 61 U1 1 U2 10 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 DEC PY 2013 VL 10 IS 12 AR e1001577 DI 10.1371/journal.pmed.1001577 PG 12 WC Medicine, General & Internal SC General & Internal Medicine GA 301LR UT WOS:000330534300016 PM 24391478 ER PT J AU Melo, MB Nguyen, QP Cordeiro, C Hassan, MA Yang, NH McKell, R Rosowski, EE Julien, L Butty, V Darde, ML Ajzenberg, D Fitzgerald, K Young, LH Saeij, JPJ AF Melo, Mariane B. Nguyen, Quynh P. Cordeiro, Cynthia Hassan, Musa A. Yang, Ninghan McKell, Renee Rosowski, Emily E. Julien, Lindsay Butty, Vincent Darde, Marie-Laure Ajzenberg, Daniel Fitzgerald, Katherine Young, Lucy H. Saeij, Jeroen P. J. TI Transcriptional Analysis of Murine Macrophages Infected with Different Toxoplasma Strains Identifies Novel Regulation of Host Signaling Pathways SO PLOS PATHOGENS LA English DT Article ID TRYPANOSOMA-CRUZI INFECTION; PERSISTENT LCMV INFECTION; I INTERFERON; IFN-BETA; CONGENITAL TOXOPLASMOSIS; INNATE IMMUNITY; UNITED-STATES; CELL CYCLE; GONDII; VIRULENCE AB Most isolates of Toxoplasma from Europe and North America fall into one of three genetically distinct clonal lineages, the type I, II and III lineages. However, in South America these strains are rarely isolated and instead a great variety of other strains are found. T. gondii strains differ widely in a number of phenotypes in mice, such as virulence, persistence, oral infectivity, migratory capacity, induction of cytokine expression and modulation of host gene expression. The outcome of toxoplasmosis in patients is also variable and we hypothesize that, besides host and environmental factors, the genotype of the parasite strain plays a major role. The molecular basis for these differences in pathogenesis, especially in strains other than the clonal lineages, remains largely unexplored. Macrophages play an essential role in the early immune response against T. gondii and are also the cell type preferentially infected in vivo. To determine if non-canonical Toxoplasma strains have unique interactions with the host cell, we infected murine macrophages with 29 different Toxoplasma strains, representing global diversity, and used RNA-sequencing to determine host and parasite transcriptomes. We identified large differences between strains in the expression level of known parasite effectors and large chromosomal structural variation in some strains. We also identified novel strain-specifically regulated host pathways, including the regulation of the type I interferon response by some atypical strains. IFN beta production by infected cells was associated with parasite killing, independent of interferon gamma activation, and dependent on endosomal Toll-like receptors in macrophages and the cytoplasmic receptor retinoic acid-inducible gene 1 (RIG-I) in fibroblasts. C1 [Melo, Mariane B.; Nguyen, Quynh P.; Cordeiro, Cynthia; Hassan, Musa A.; Yang, Ninghan; McKell, Renee; Rosowski, Emily E.; Julien, Lindsay; Butty, Vincent; Saeij, Jeroen P. J.] MIT, Dept Biol, Cambridge, MA 02139 USA. [Cordeiro, Cynthia] Univ Fed Minas Gerais, Sch Med, Dept Internal Med, Belo Horizonte, MG, Brazil. [Cordeiro, Cynthia; Young, Lucy H.] Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Retina Serv,Dept Ophthalmol, Boston, MA USA. [Darde, Marie-Laure; Ajzenberg, Daniel] Ctr Hosp Univ Dupuytren, Toxoplasma Biol Resource Ctr, Ctr Natl Reference Toxoplasmose, Limoges, France. [Darde, Marie-Laure; Ajzenberg, Daniel] Univ Limoges, Fac Med, INSERM, UMR 1094,Lab Parasitol Mycol, Limoges, France. [Fitzgerald, Katherine] Univ Massachusetts, Sch Med, Div Infect Dis & Immunol, Worcester, MA USA. RP Melo, MB (reprint author), MIT, Dept Biol, Cambridge, MA 02139 USA. EM jsaeij@mit.edu RI Melo, Mariane/A-1975-2013; Hassan, Musa/E-8324-2016; OI Hassan, Musa/0000-0002-0371-3300; Saeij, Jeroen/0000-0003-0289-7109 FU National Institutes of Health [R01-AI080621]; NERCE [AIO57159]; Pew Scholars Program in the Biomedical Sciences; Robert A. Swanson Career Development award; Knights Templar Eye Foundation; Welcome Trust-MIT; A*STAR NSS; Pre-Doctoral Grant in the Biological Sciences [5-T32-GM007287-33]; Cleo and Paul Schimmel Fund FX JPJS was supported by National Institutes of Health R01-AI080621, a NERCE developmental grant AIO57159, the Pew Scholars Program in the Biomedical Sciences and a Robert A. Swanson Career Development award; MBM was supported by the Knights Templar Eye Foundation; MAH was supported by a Welcome Trust-MIT postdoctoral fellowship. NY was supported by an A*STAR NSS (PhD) graduate scholarship. ER was supported by Pre-Doctoral Grant in the Biological Sciences 5-T32-GM007287-33. ER was also supported by the Cleo and Paul Schimmel Fund. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 83 TC 17 Z9 17 U1 1 U2 9 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1553-7374 J9 PLOS PATHOG JI PLoS Pathog. PD DEC PY 2013 VL 9 IS 12 AR UNSP e1003779 DI 10.1371/journal.ppat.1003779 PG 17 WC Microbiology; Parasitology; Virology SC Microbiology; Parasitology; Virology GA 301MC UT WOS:000330535400017 PM 24367253 ER PT J AU Yarmand, H Ivy, JS AF Yarmand, Hamed Ivy, Julie S. TI Optimal intervention strategies for an epidemic: A household view SO SIMULATION-TRANSACTIONS OF THE SOCIETY FOR MODELING AND SIMULATION INTERNATIONAL LA English DT Article ID PANDEMIC INFLUENZA; MITIGATION STRATEGIES; UNITED-STATES; INFECTIOUS-DISEASES; COST-EFFECTIVENESS; CONTACT RATES; MODEL; NETWORKS; VACCINATION; SIMULATION C1 [Yarmand, Hamed; Ivy, Julie S.] N Carolina State Univ, Dept Ind & Syst Engn, Raleigh, NC 27695 USA. RP Yarmand, H (reprint author), Harvard Univ, Dept Radiat Oncol, Massachusetts Gen Hosp, Sch Med,Francis H Burr Proton Therapy Ctr, 30 Fruit St, Boston, MA 02114 USA. EM hyarman@ncsu.edu FU CDC [1PO1 TP 000296] FX This research was carried out by the North Carolina Preparedness and Emergency Response Research Center (NCPERRC) which is part of the University of North Carolina (UNC) Center for Public Health Preparedness at UNC at Chapel Hill's Gillings School of Global Public Health and was supported by the CDC Grant 1PO1 TP 000296. NR 77 TC 1 Z9 1 U1 1 U2 5 PU SAGE PUBLICATIONS LTD PI LONDON PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND SN 0037-5497 EI 1741-3133 J9 SIMUL-T SOC MOD SIM JI Simul.-Trans. Soc. Model. Simul. Int. PD DEC PY 2013 VL 89 IS 12 SI SI BP 1505 EP 1522 PG 18 WC Computer Science, Interdisciplinary Applications; Computer Science, Software Engineering SC Computer Science GA 296ZG UT WOS:000330223700009 ER PT J AU Podrasky, AE Javitt, MC Glanc, P Dubinsky, T Harisinghani, MG Harris, RD Khati, NJ Mitchell, DG Pandharipande, PV Pannu, HK Shipp, TD Siegel, CL Simpson, L Wall, DJ Wong-You-Cheong, JJ Zelop, CM AF Podrasky, Ann E. Javitt, Marcia C. Glanc, Phyllis Dubinsky, Theodore Harisinghani, Mukesh G. Harris, Robert D. Khati, Nadia J. Mitchell, Donald G. Pandharipande, Pari V. Pannu, Harpreet K. Shipp, Thomas D. Siegel, Cary Lynn Simpson, Lynn Wall, Darci J. Wong-You-Cheong, Jade J. Zelop, Carolyn M. TI ACR Appropriateness Criteria (R) Second and Third Trimester Bleeding SO ULTRASOUND QUARTERLY LA English DT Article DE Appropriateness Criteria; vaginal bleeding; placenta previa; placenta accreta; vasa previa; placental abruption ID COLOR DOPPLER ULTRASOUND; PLACENTA PREVIA ACCRETA; PRIOR CESAREAN-SECTION; LOW-LYING PLACENTA; VASA-PREVIA; PRENATAL-DIAGNOSIS; ANTENATAL DIAGNOSIS; RISK-FACTORS; SONOGRAPHIC DIAGNOSIS; CERVICAL LENGTH AB Vaginal bleeding occurring in the second or third trimesters of pregnancy can variably affect perinatal outcome, depending on whether it is minor (i.e. a single, mild episode) or major (heavy bleeding or multiple episodes.) Ultrasound is used to evaluate these patients. Sonographic findings may range from marginal subchorionic hematoma to placental abruption. Abnormal placentations such as placenta previa, placenta accreta and vasa previa require accurate diagnosis for clinical management. In cases of placenta accreta, magnetic resonance imaging is useful as an adjunct to ultrasound and is often appropriate for evaluation of the extent of placental invasiveness and potential involvement of adjacent structures. MRI is useful for preplanning for cases of complex delivery, which may necessitate a multi-disciplinary approach for optimal care. The American College of Radiology Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed every two years by a multidisciplinary expert panel. The guideline development and review include an extensive analysis of current medical literature from peer reviewed journals and the application of a well-established consensus methodology (modified Delphi) to rate the appropriateness of imaging and treatment procedures by the panel. In those instances where evidence is lacking or not definitive, expert opinion may be used to recommend imaging or treatment. C1 [Podrasky, Ann E.] Baptist Hosp Miami, South Miami Ctr Women & Infants, Coral Gables, FL 33156 USA. [Javitt, Marcia C.] Walter Reed Natl Mil Med Ctr, Bethesda, MD USA. [Glanc, Phyllis] Sunnybrook Hlth Sci Ctr, Toronto, ON M4N 3M5, Canada. [Dubinsky, Theodore] Univ Washington, Sch Med, Seattle, WA USA. [Harisinghani, Mukesh G.; Pandharipande, Pari V.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Harris, Robert D.] Dartmouth Hitchcock Med Ctr, Lebanon, NH 03766 USA. [Khati, Nadia J.] George Washington Univ Hosp, Washington, DC USA. [Mitchell, Donald G.] Thomas Jefferson Univ Hosp, Philadelphia, PA 19107 USA. [Pannu, Harpreet K.] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. [Shipp, Thomas D.] Brigham & Womens Hosp, Boston, MA 02115 USA. [Siegel, Cary Lynn] Washington Univ, Med Ctr, Mallinckrodt Inst Radiol, St Louis, MO 63110 USA. [Simpson, Lynn] Columbia Univ, New York, NY USA. [Wall, Darci J.] Mayo Clin, Rochester, MN USA. [Wong-You-Cheong, Jade J.] Univ Maryland, Sch Med, Baltimore, MD 21201 USA. [Zelop, Carolyn M.] Valley Hosp, Ridgewood, NJ USA. RP Podrasky, AE (reprint author), Baptist Hosp Miami, South Miami Ctr Women & Infants, 130 Solano Prado, Coral Gables, FL 33156 USA. EM annpo@baptisthealth.net NR 82 TC 4 Z9 4 U1 0 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0894-8771 EI 1536-0253 J9 ULTRASOUND Q JI Ultrasound Q. PD DEC PY 2013 VL 29 IS 4 BP 293 EP 301 PG 9 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 300EP UT WOS:000330447500001 PM 24263752 ER PT J AU Nguyen, MS Ginat, DT Giampoli, EJ O'Connell, AM AF Nguyen, Mike S. Ginat, Daniel T. Giampoli, Ellen J. O'Connell, Avice M. TI Breast Metastases to Thyroid Gland SO ULTRASOUND QUARTERLY LA English DT Article DE thyroid; breast; metastases; ultrasound ID CARCINOMA; BIOPSY; NECK AB Metastases to the thyroid gland are uncommon. We present the sonographic features of metastatic breast adenocarcinoma to the thyroid in a 67-year-old woman. The lesion measured up to 0.9 cm in diameter, contained an echogenic focus with associated ring-down, and was predominantly cystic, thereby resembling a benign nodule. Because of the patient's history of breast adenocarcinoma, the nodule nevertheless underwent fine-needle aspiration. The unusual appearance of the thyroid nodule underscores the importance of considering patient history in deciding whether obtaining tissue diagnosis of thyroid nodules is warranted. C1 [Nguyen, Mike S.; O'Connell, Avice M.] Univ Rochester, Med Ctr, Dept Imaging Sci, Rochester, NY 14642 USA. [Ginat, Daniel T.] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. [Giampoli, Ellen J.] Univ Rochester, Med Ctr, Dept Pathol & Lab Med, Rochester, NY 14642 USA. RP Nguyen, MS (reprint author), Univ Rochester, Med Ctr, Dept Imaging Sci, 601 Elmwood Ave,Box 648, Rochester, NY 14642 USA. EM mike_nguyen@urmc.rochester.edu NR 8 TC 1 Z9 1 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0894-8771 EI 1536-0253 J9 ULTRASOUND Q JI Ultrasound Q. PD DEC PY 2013 VL 29 IS 4 BP 327 EP 328 PG 2 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 300EP UT WOS:000330447500006 PM 24263757 ER PT J AU Nguyen, JT Nguyen, JL Wheatley, MJ Nguyen, TA AF Nguyen, Jesse T. Nguyen, Jenny L. Wheatley, Michael J. Nguyen, Tuan A. TI Muscle hernias of the leg: A case report and comprehensive review of the literature SO CANADIAN JOURNAL OF PLASTIC SURGERY LA English DT Review DE Leg; Muscle hernia; Peroneus brevis; Review ID ANTERIOR TIBIALIS MUSCLE; PERONEAL COMPARTMENT SYNDROME; GASTROCNEMIUS-MUSCLE; FASCIAL DEFECT; LONGUS MUSCLE; DONOR-SITE; REPAIR; NERVE; MESH; COMPLICATION AB A case involving a retired, elderly male war veteran with a symptomatic peroneus brevis muscle hernia causing superficial peroneal nerve compression with chosen surgical management is presented. Symptomatic muscle hernias of the extremities occur most commonly in the leg and are a rare cause of chronic leg pain. Historically, treating military surgeons pioneered the early documentation of leg hernias observed in active military recruits. A focal fascial defect can cause a muscle to herniate, forming a variable palpable subcutaneous mass, and causing pain and potentially neuropathic symptoms with nerve involvement. While the true incidence is not known, the etiology has been classified as secondary to a congenital (or constitutional) fascial weakness, or acquired fascial defect, usually secondary to direct or indirect trauma. The highest occurrence is believed to be in young, physically active males. Involvement of the tibialis anterior is most common, although other muscles have been reported. Dynamic ultrasonography or magnetic resonance imaging is often used to confirm diagnosis and guide treatment. Most symptomatic cases respond successfully to conservative treatment, with surgery reserved for refractory cases. A variety of surgical techniques have been described, ranging from fasciotomy to anatomical repair of the fascial defect, with no consensus on optimal treatment. Clinicians must remember to consider muscle hernias in their repertoire of differential diagnoses for chronic leg pain or neuropathy. A comprehensive review of muscle hernias of the leg is presented to highlight their history, occurrence, presentation, diagnosis and treatment. C1 [Nguyen, Jesse T.] Mayo Clin, Dept Gen Surg, Rochester, MN USA. [Nguyen, Jenny L.] Michigan State Univ, Grand Rapids Med Educ Partners, Dept Plast Surg, Grand Rapids, MI USA. [Wheatley, Michael J.; Nguyen, Tuan A.] Portland VA Med Ctr, Div Plast Surg, Portland, OR USA. RP Nguyen, TA (reprint author), Portland Veteran Affairs Med Ctr, Div Plast Surg, 3710 Southwest,US Vet Hosp Rd, Portland, OR 97239 USA. EM tuan.nguyen6@VA.gov NR 68 TC 6 Z9 7 U1 0 U2 2 PU PULSUS GROUP INC PI OAKVILLE PA 2902 S SHERIDAN WAY, OAKVILLE, ONTARIO L6J 7L6, CANADA SN 1195-2199 J9 CAN J PLAST SURG JI Can. J. Plast. Surg. PD WIN PY 2013 VL 21 IS 4 BP 243 EP 247 PG 5 WC Surgery SC Surgery GA 296NN UT WOS:000330191900009 PM 24497767 ER PT J AU Melman, YF Levy, MS Laham, RJ AF Melman, Yonathan F. Levy, Michael S. Laham, Roger J. TI Intracardiac Echocardiography and Fluoroscopy Guided Percutaneous Left Ventricular Pseudoaneurysm Closure SO CATHETERIZATION AND CARDIOVASCULAR INTERVENTIONS LA English DT Article DE intracardiac echo; peroration; acute coronary syndrome ID FREE-WALL RUPTURE; DEVICE CLOSURE; FALSE ANEURYSM AB Left ventricular (LV) pseudoaneurysm is a rare complication after myocardial infarction and cardiac surgery. Standard treatment remains surgical correction; however, percutaneous closure has been attempted in high risk surgical patients. We report a case of three dimensional echocardiography and cardiac CT defined LV pseudoaneurysm which was closed percutaneously using intracardiac echocardiography (ICE) and fluoroscopy guidance. Appropriate planning and guidance proved essential to the procedure with an excellent outcome. Percutaneous closure of LV pseudoaneurysms is safe and feasible in high risk surgical patients and with appropriate imaging modalities may be an alternative to surgical correction. (C) 2011 Wiley Periodicals, Inc. C1 [Melman, Yonathan F.; Levy, Michael S.; Laham, Roger J.] Harvard Univ, Sch Med, BIDMC, Div Cardiol, Boston, MA 02215 USA. RP Laham, RJ (reprint author), Harvard Univ, Sch Med, BIDMC, 330 Brookline Ave, Boston, MA 02215 USA. EM rlaham@bidmc.harvard.edu FU CIMIT; DeBakey Foundation at Balamand University FX Grant sponsors: CIMIT; DeBakey Foundation at Balamand University. NR 17 TC 1 Z9 1 U1 0 U2 1 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 DEC 1 PY 2013 VL 82 IS 7 BP E915 EP E918 DI 10.1002/ccd.23321 PG 4 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 296JS UT WOS:000330181800014 PM 21954145 ER PT J AU Houde, AA Guay, SP Desgagne, V Hivert, MF Baillargeon, JP St-Pierre, J Perron, P Gaudet, D Brisson, D Bouchard, L AF Houde, Andree-Anne Guay, Simon-Pierre Desgagne, Veronique Hivert, Marie-France Baillargeon, Jean-Patrice St-Pierre, Julie Perron, Patrice Gaudet, Daniel Brisson, Diane Bouchard, Luigi TI Adaptations of placental and cord blood ABCA1 DNA methylation profile to maternal metabolic status SO EPIGENETICS LA English DT Article DE Gestational diabetes; high-density lipoprotein cholesterol; fetal programming; lipid metabolism; epigenetics ID GESTATIONAL DIABETES-MELLITUS; FETAL CHOLESTEROL TRANSPORT; BIRTH-WEIGHT; INTRAUTERINE EXPOSURE; PROMOTER METHYLATION; FAMILIAL HYPERCHOLESTEROLEMIA; HOUSEKEEPING GENES; PREGNANCY OUTCOMES; INSULIN-RESISTANCE; PRENATAL EXPOSURE AB In utero environmental perturbations have been associated with epigenetic changes in the offspring and a lifelong susceptibility to cardiovascular diseases (CVD). DNA methylation at the ATP-binding cassette transporter A1 (ABCA1) gene was previously associated with CVD, but whether these epigenetic marks respond to changes in the maternal environment is unknown. This study was undertaken to assess the associations between the maternal metabolic profile and ABCA1 DNA methylation levels in placenta and cord blood. Placenta and cord blood samples were obtained at delivery from 100 women including 26 with impaired glucose tolerance (IGT) diagnosed following a 75 g-oral glucose tolerance test (OGTT) between week 24 and 28 of gestation. ABCA1 DNA methylation and mRNA levels were measured using bisulfite pyrosequencing and quantitative real-time PCR, respectively. We report that ABCA1 DNA methylation levels on the maternal side of the placenta are correlated with maternal high density lipoprotein cholesterol (HDL-C) levels (r < -0.21; P < 0.04) and glucose levels 2 h post-OGTT (r = 0.25; P = 0.02). On the fetal side of the placenta, ABCA1 DNA methylation levels are associated with cord blood triglyceride levels (r = -0.28; P = 0.01). ABCA1 DNA methylation variability on both sides of the placenta are also associated with ABCA1 mRNA levels (r < -0.35; P = 0.05). As opposed to placenta, cord blood DNA methylation levels are negatively correlated with maternal glucose 2 h post-OGTT (r = -0.26; P = 0.02). In conclusion, the epivariations observed in placenta and cord blood likely contribute to an optimal materno-fetal cholesterol transfer. These in utero epigenetics adaptations may also potentially trigger the long-term susceptibility of the newborn to dyslipidemia and CVD. C1 [Houde, Andree-Anne; Guay, Simon-Pierre; Desgagne, Veronique; Bouchard, Luigi] Univ Sherbrooke, Dept Biochem, Sherbrooke, PQ J1K 2R1, Canada. [Houde, Andree-Anne; Guay, Simon-Pierre; Desgagne, Veronique; St-Pierre, Julie; Perron, Patrice; Gaudet, Daniel; Brisson, Diane; Bouchard, Luigi] Chicoutimi Hosp, ECOGENE 21, Saguenay, PQ, Canada. [Houde, Andree-Anne; Guay, Simon-Pierre; Desgagne, Veronique; St-Pierre, Julie; Perron, Patrice; Gaudet, Daniel; Brisson, Diane; Bouchard, Luigi] Chicoutimi Hosp, Lipid Clin, Saguenay, PQ, Canada. [Hivert, Marie-France; Baillargeon, Jean-Patrice; Perron, Patrice] Univ Sherbrooke, Dept Med, Sherbrooke, PQ J1K 2R1, Canada. [Hivert, Marie-France] Massachusetts Gen Hosp, Div Gen Med, Boston, MA 02114 USA. [St-Pierre, Julie] Chicoutimi Hosp, Dept Pediat, Saguenay, PQ, Canada. [St-Pierre, Julie] Univ Quebec Chicoutimi, Dept Hlth Sci, Saguenay, PQ, Canada. [Gaudet, Daniel; Brisson, Diane] Univ Montreal, Dept Med, Montreal, PQ H3C 3J7, Canada. RP Bouchard, L (reprint author), Univ Sherbrooke, Dept Biochem, Sherbrooke, PQ J1K 2R1, Canada. EM luigi.bouchard@usherbrooke.ca FU Canadian Diabetes Association clinical scientist award; Canadian Institutes for Health and Research (CIHR); FRQS; ECOGENE-21; Canadian Institutes of Health Research (CIHR) [CTP-82941]; FRSQ; Diabete Quebec FX The authors acknowledge the contribution of Cecilia Legare, Sebastien Claveau, MSc; Nadia Mior; Jeanine Landry, RN, and Chantal Aubut, RN from the ECOGENE-21 Clinical Research Center for their dedicated work in this study. The authors also express their gratitude to Celine Belanger, Chicoutimi Hospital, for her thoughtful language revision of the manuscript. Bouchard L and Hivert MF are junior research scholars from the Fonds de la recherche du Quebec en sante (FRQS). Baillargeon JP is senior research scholars from the FRQS. Hivert MF is also supported by a Canadian Diabetes Association clinical scientist award. Bouchard L, Hivert MF, Perron P, and Baillargeon JP are members of the FRQS-funded Centre de recherche clinique Etienne-Le Bel (affiliated to the Centre hospitalier universitaire de Sherbrooke). During this research, Guay SP was the recipient of a doctoral research award from the Canadian Institutes for Health and Research (CIHR) and Houde AA was a recipient of a FRQS doctoral training award. Houde AA and Desgagne V were supported by Diabete Quebec. This project was supported by ECOGENE-21, the Canadian Institutes of Health Research (CIHR team in community genetics [grant #CTP-82941]), FRSQ, and Diabete Quebec. NR 58 TC 19 Z9 19 U1 0 U2 7 PU LANDES BIOSCIENCE PI AUSTIN PA 1806 RIO GRANDE ST, AUSTIN, TX 78702 USA SN 1559-2294 EI 1559-2308 J9 EPIGENETICS-US JI Epigenetics PD DEC 1 PY 2013 VL 8 IS 12 BP 1289 EP 1302 DI 10.4161/epi.26554 PG 14 WC Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA 298DO UT WOS:000330304500006 PM 24113149 ER PT J AU Pulakanti, K Pinello, L Stelloh, C Blinka, S Allred, J Milanovich, S Kiblawi, S Peterson, J Wang, A Yuan, GC Rao, S AF Pulakanti, Kirthi Pinello, Luca Stelloh, Cary Blinka, Steven Allred, Jeremy Milanovich, Samuel Kiblawi, Sid Peterson, Jonathan Wang, Alexander Yuan, Guo-Cheng Rao, Sridhar TI Enhancer transcribed RNAs arise from hypomethylated, Tet-occupied genomic regions SO EPIGENETICS LA English DT Article DE Enhancer Transcribed RNAs (eRNAs); non-coding RNA; DNA methylation; Tet-proteins; transcriptional enhancers ID EMBRYONIC STEM-CELLS; GENE-EXPRESSION; SELF-RENEWAL; PLURIPOTENCY; CHROMATIN; PROMOTERS; NANOG; METHYLATION; DISTINCT; REVEALS AB Enhancers are cis-acting elements capable of regulating transcription in a distance and orientation-independent manner. A subset of enhancers are occupied by RNA polymerase II (RNAP II) and transcribed to produce long non-coding RNAs termed eRNAs. We thoroughly investigated the association between eRNA productivity and various chromatin marks and transcriptional regulators in mouse embryonic stem cells (ESCs) through an integrative approach. We found that eRNA-producing enhancers exhibited elevated levels of the active mark H3K27Ac, decreased DNA methylation, and enrichment for the DNA hydroxylase Tet1. Many eRNA-producing enhancers have recently been characterized as super-enhancers, suggesting an important role in the maintenance of pluripotency. Using experimental methods, we focally investigated a well-characterized enhancer linked to the Nanog locus and confirmed its exclusive eRNA productivity in ESCs. We further demonstrate that the binding of Sall4 and Tet family proteins were required for eRNA productivity at this locus. Collectively, we demonstrate that Tet1 binding and DNA hypomethylation are hallmarks of eRNA production. C1 [Pulakanti, Kirthi; Stelloh, Cary; Kiblawi, Sid; Peterson, Jonathan; Wang, Alexander; Rao, Sridhar] BloodCtr Wisconsin, Blood Res Inst, Milwaukee, WI 53233 USA. [Pinello, Luca; Yuan, Guo-Cheng] Dana Farber Canc Inst, Boston, MA 02115 USA. [Pinello, Luca; Yuan, Guo-Cheng] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. [Blinka, Steven; Allred, Jeremy; Milanovich, Samuel; Rao, Sridhar] Med Coll Wisconsin, Milwaukee, WI 53226 USA. [Blinka, Steven; Rao, Sridhar] Med Coll Wisconsin, Dept Cell Biol, Milwaukee, WI 53226 USA. [Blinka, Steven; Rao, Sridhar] Med Coll Wisconsin, Dept Neurobiol, Milwaukee, WI 53226 USA. [Blinka, Steven; Rao, Sridhar] Med Coll Wisconsin, Dept Anat, Milwaukee, WI 53226 USA. [Milanovich, Samuel; Rao, Sridhar] Med Coll Wisconsin, Dept Pediat, Milwaukee, WI 53226 USA. RP Rao, S (reprint author), BloodCtr Wisconsin, Blood Res Inst, Milwaukee, WI 53233 USA. EM gcyuan@jimmy.harvard.edu; sridhar.rao@bcw.edu FU NHLBI [HL087951]; NHGRI [HG005085]; American Cancer Society [86-004]; Midwest Athletes against Childhood Cancer FX The authors would like to thank all the groups who placed their various datasets into the NCBI database, many of whom provided us with additional information and/or guidance with regards to analysis of their respective datasets. We would like to thank Dr Xiaochun Xu (Univ. of Michigan) for generously providing the anti-Tet2 antibody used in this work. This work is funded in part by NHLBI (HL087951 to Rao S) and NHGRI (HG005085 to Yuan G). In addition, Rao S is supported by a pilot grant from the American Cancer Society (Institutional Research Grant #86-004) and the Midwest Athletes against Childhood Cancer. NR 59 TC 17 Z9 17 U1 0 U2 7 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 530 WALNUT STREET, STE 850, PHILADELPHIA, PA 19106 USA SN 1559-2294 EI 1559-2308 J9 EPIGENETICS-US JI Epigenetics PD DEC 1 PY 2013 VL 8 IS 12 BP 1303 EP 1320 DI 10.4161/epi.26597 PG 18 WC Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA 298DO UT WOS:000330304500007 PM 24135681 ER PT J AU Omer, S Kar, B Cornwell, LD Blaustein, A Levine, GN Ali, N Jneid, H Paniagua, D Atluri, PV Bechara, CF Kougias, P Ruma, M Preventza, O Bozkurt, B Carabello, BA Bakaeen, FG AF Omer, Shuab Kar, Biswajit Cornwell, Lorraine D. Blaustein, Alvin Levine, Glen N. Ali, Nadir Jneid, Hani Paniagua, David Atluri, Prasad V. Bechara, Carlos F. Kougias, Panos Ruma, Maryrose Preventza, Ourania Bozkurt, Biykem Carabello, Blase A. Bakaeen, Faisal G. TI Early Experience of a Transcatheter Aortic Valve Program at a Veterans Affairs Facility SO JAMA SURGERY LA English DT Article ID HIGH-RISK PATIENTS; INOPERABLE PATIENTS; COST-EFFECTIVENESS; EDWARDS-SAPIEN; TRIAL COHORT; HEART-VALVE; REPLACEMENT; IMPLANTATION; STENOSIS; OUTCOMES AB IMPORTANCE The US Food and Drug Administration recently approved the use of a transcatheter aortic valve in patients for whom traditional valve replacement surgery poses a high or prohibitive risk. Our hospital was one of the first Veterans Affairs facilities to launch a transcatheter aortic valve replacement (TAVR) program. OBJECTIVE To evaluate our early experience with transfemoral TAVR. DESIGN AND SETTING We retrospectively reviewed the records of all patients who underwent TAVR during the first year of our program at the Department of Cardiothoracic Surgery, Michael E. DeBakey Veterans Affairs Medical Center. PARTICIPANTS The mean (SD) age of the patients was 77 (9) years, and their mean (SD) Society of Thoracic Surgeons predicted risk of mortality score was 8.8 (10.7). INTERVENTIONS All patients underwent TAVR with the SAPIEN transcutaneous valve. MAIN OUTCOME MEASURES We evaluated operative mortality and major operative morbidity (stroke, myocardial infarction, renal failure necessitating dialysis, and requirement for mechanical circulatory support, as well as vascular complications and requirement for permanent pacemaker), in addition to length of hospital stay and discharge status. RESULTS Between December 21, 2011, and December 13, 2012, a total of 19 transfemoral TAVR procedures were performed at our center. Implantation was successful in all cases. There were no reports of operative (30-day) mortality, prosthetic valve endocarditis, renal failure necessitating dialysis, perioperative myocardial infarction or stroke, or conversion to surgical aortic valve replacement. Seven patients (37%) had mild paravalvular leak, 3 patients (16%) had moderate paravalvular leak, 2 patients (11%) had groin wound complications, 2 patients (11%) required a permanent pacemaker, 1 patient (5%) had a vascular access complication requiring endovascular repair, and 1 patient (5%) required temporary circulatory support (with extracorporeal membrane oxygenation). The mean (SD) length of hospital stay after TAVR was 8.0 (5.9) days. All patients were discharged home. CONCLUSIONS AND RELEVANCE Transcatheter aortic valve replacement can be performed safely and with good outcomes at a Veterans Affairs facility with a committed multidisciplinary team and substantial experience in heart valve and endovascular therapies. C1 [Omer, Shuab; Cornwell, Lorraine D.; Preventza, Ourania] Baylor Coll Med, Michael E DeBakey Dept Surg, Div Cardiothorac Surg, Houston, TX USA. [Omer, Shuab; Kar, Biswajit; Cornwell, Lorraine D.; Blaustein, Alvin; Levine, Glen N.; Ali, Nadir; Jneid, Hani; Paniagua, David; Atluri, Prasad V.; Bechara, Carlos F.; Kougias, Panos; Ruma, Maryrose; Bozkurt, Biykem; Carabello, Blase A.; Bakaeen, Faisal G.] Michael E DeBakey VA Med Ctr, Houston, TX USA. [Kar, Biswajit; Blaustein, Alvin; Levine, Glen N.; Ali, Nadir; Jneid, Hani; Paniagua, David; Bozkurt, Biykem; Carabello, Blase A.] Baylor Coll Med, Dept Cardiol, Houston, TX 77030 USA. [Atluri, Prasad V.] Baylor Coll Med, Dept Anesthesiol, Houston, TX 77030 USA. [Bechara, Carlos F.; Kougias, Panos] Baylor Coll Med, Div Vasc Surg, Michael E DeBakey Dept Surg, Houston, TX 77030 USA. [Preventza, Ourania; Carabello, Blase A.; Bakaeen, Faisal G.] Texas Heart Inst, Houston, TX 77025 USA. RP Omer, S (reprint author), DeBakey Vet Affairs Med Ctr, Mail Code 112,Operat Care Line,2002 Holcombe Blvd, Houston, TX 77030 USA. EM shuab.omer@bcm.edu NR 29 TC 5 Z9 5 U1 1 U2 2 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60654-0946 USA SN 2168-6254 EI 2168-6262 J9 JAMA SURG JI JAMA Surg. PD DEC PY 2013 VL 148 IS 12 BP 1087 EP 1093 DI 10.1001/jamasurg.2013.3743 PG 7 WC Surgery SC Surgery GA 295LD UT WOS:000330116700006 PM 24048246 ER PT J AU Loehrer, AP Song, ZR Auchincloss, HG Hutter, MM AF Loehrer, Andrew P. Song, Zirui Auchincloss, Hugh G. Hutter, Matthew M. TI Massachusetts Health Care Reform and Reduced Racial Disparities in Minimally Invasive Surgery SO JAMA SURGERY LA English DT Article ID LAPAROSCOPIC CHOLECYSTECTOMY; ACUTE CHOLECYSTITIS; INSURANCE STATUS; ACCESS; APPENDECTOMY; PREDICTORS; COVERAGE; RACE AB IMPORTANCE Racial disparities in receipt of minimally invasive surgery (MIS) persist in the United States and have been shown to also be associated with a number of driving factors, including insurance status. However, little is known as to how expanding insurance coverage across a population influences disparities in surgical care. OBJECTIVE To evaluate the impact of Massachusetts health care reform on racial disparities in MIS. DESIGN, SETTING, AND PARTICIPANTS A retrospective cohort study assessed the probability of undergoing MIS vs an open operation for nonwhite patients in Massachusetts compared with 6 control states. All discharges (n = 167 560) of nonelderly white, black, or Latino patients with government insurance (Medicaid or Commonwealth Care insurance) or no insurance who underwent a procedure for acute appendicitis or acute cholecystitis at inpatient hospitals between January 1, 2001, and December 31, 2009, were assessed. Data are from the Hospital Cost and Utilization Project State Inpatient Databases. INTERVENTION The 2006 Massachusetts health care reform, which expanded insurance coverage for government-subsidized, self-pay, and uninsured individuals in Massachusetts. MAIN OUTCOMES AND MEASURES Adjusted probability of undergoing MIS and difference-in-difference estimates. RESULTS Prior to the 2006 reform, Massachusetts nonwhite patients had a 5.21-percentage point lower probability of MIS relative to white patients (P < .001). Nonwhite patients in control states had a 1.39-percentage point lower probability of MIS (P = .007). After reform, nonwhite patients in Massachusetts had a 3.71-percentage point increase in the probability of MIS relative to concurrent trends in control states (P = .01). After 2006, measured racial disparities in MIS resolved in Massachusetts, with nonwhite patients having equal probability of MIS relative to white patients (0.06 percentage point greater; P = .96). However, nonwhite patients in control states without health care reform have a persistently lower probability of MIS relative to white patients (3.19 percentage points lower; P < .001). CONCLUSIONS AND RELEVANCE The 2006 Massachusetts insurance expansion was associated with an increased probability of nonwhite patients undergoing MIS and resolution of measured racial disparities in MIS. C1 [Loehrer, Andrew P.; Auchincloss, Hugh G.; Hutter, Matthew M.] Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. [Song, Zirui] Harvard Univ, Sch Med, FrancisWeld Peabody Soc, Boston, MA USA. [Song, Zirui] Natl Bur Econ Res, Cambridge, MA 02138 USA. RP Loehrer, AP (reprint author), Massachusetts Gen Hosp, Dept Surg, 165 Cambridge St,Ste 403, Boston, MA 02114 USA. EM aloehrer@partners.org FU NIA NIH HHS [F30 AG039175, T32 AG000186] NR 29 TC 17 Z9 17 U1 0 U2 3 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60654-0946 USA SN 2168-6254 EI 2168-6262 J9 JAMA SURG JI JAMA Surg. PD DEC PY 2013 VL 148 IS 12 BP 1116 EP 1122 DI 10.1001/jamasurg.2013.2750 PG 7 WC Surgery SC Surgery GA 295LD UT WOS:000330116700012 PM 24089326 ER PT J AU Jones, TS Dunn, CL Wu, DS Cleveland, JC Kile, D Robinson, TN AF Jones, Teresa S. Dunn, Christina L. Wu, Daniel S. Cleveland, Joseph C., Jr. Kile, Deidre Robinson, Thomas N. TI Relationship Between Asking an Older Adult About Falls and Surgical Outcomes SO JAMA SURGERY LA English DT Article ID GERIATRIC SYNDROMES; ELDERLY-PATIENTS; CARDIAC-SURGERY; FRAILTY; COMPLICATIONS; PREDICTOR; MORBIDITY; MORTALITY; RISK; CARE AB IMPORTANCE More than one-third of all US inpatient operations are performed on patients aged 65 years and older. Existing preoperative risk assessment strategies are not adequate to meet the needs of the aging population. OBJECTIVES To evaluate the relationship of a history of falls (a geriatric syndrome) to postoperative outcomes in older adults undergoing major elective operations. DESIGN, SETTING, AND PARTICIPANTS This prospective, cohort study was conducted at a referral medical center. Persons aged 65 years and older undergoing elective colorectal and cardiac operations were enrolled. The predictor variable was having fallen in the 6 months prior to the operation. MAIN OUTCOMES AND MEASURES Postoperative outcomes measured included 30-day complications, the need for discharge institutionalization, and 30-day readmission. RESULTS There were 235 subjects with a mean (SD) age of 74 (6) years. Preoperative falls occurred in 33%. One or more postoperative complications occurred more frequently in the group with prior falls compared with the nonfallers following both colorectal (59% vs 25%; P = .004) and cardiac (39% vs 15%; P = .002) operations. These findings were independent of advancing chronologic age. The need for discharge to an institutional care facility occurred more frequently in the group that had fallen in comparison with the nonfallers in both the colorectal (52% vs 6%; P < .001) and cardiac (62% vs 32%; P = .001) groups. Similarly, 30-day readmission was higher in the group with prior falls following both colorectal (P = .04) and cardiac (P = .02) operations. CONCLUSIONS AND RELEVANCE A history of 1 or more falls in the 6 months prior to an operation forecasts increased postoperative complications, the need for discharge institutionalization, and 30-day readmission across surgical specialties. Using a history of prior falls in preoperative risk assessment for an older adult represents a shift from current preoperative assessment strategies. C1 [Jones, Teresa S.; Dunn, Christina L.; Wu, Daniel S.; Cleveland, Joseph C., Jr.; Robinson, Thomas N.] Univ Colorado, Sch Med, Dept Surg, Aurora, CO 80045 USA. [Cleveland, Joseph C., Jr.; Robinson, Thomas N.] Denver Vet Affairs Med Ctr, Denver, CO USA. [Kile, Deidre] Univ Colorado, Colorado Hlth Outcomes Program, Aurora, CO 80045 USA. RP Robinson, TN (reprint author), Univ Colorado, Sch Med, MS C313,12631 E 17th Ave, Aurora, CO 80045 USA. EM thomas.robinson@ucdenver.edu FU NHLBI NIH HHS [K24 HL089223]; NIA NIH HHS [K23 AG034632] NR 20 TC 21 Z9 21 U1 1 U2 7 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60654-0946 USA SN 2168-6254 EI 2168-6262 J9 JAMA SURG JI JAMA Surg. PD DEC PY 2013 VL 148 IS 12 BP 1132 EP 1138 DI 10.1001/jamasurg.2013.2741 PG 7 WC Surgery SC Surgery GA 295LD UT WOS:000330116700015 PM 24108317 ER PT J AU Campbell, EG AF Campbell, Eric G. TI Conflicts of Interest and the Future of Medicine: The United States, France and Japan SO JOURNAL OF LAW MEDICINE & ETHICS LA English DT Book Review C1 [Campbell, Eric G.] Massachusetts Gen Hosp, Mongan Inst Hlth Policy, Boston, MA 02129 USA. RP Campbell, EG (reprint author), Massachusetts Gen Hosp, Mongan Inst Hlth Policy, Boston, MA 02129 USA. NR 1 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1073-1105 EI 1748-720X J9 J LAW MED ETHICS JI J. Law Med. Ethics PD DEC PY 2013 VL 41 IS 4 SI SI BP 915 EP 915 DI 10.1111/jlme.12101 PG 1 WC Ethics; Law; Medical Ethics; Medicine, Legal SC Social Sciences - Other Topics; Government & Law; Medical Ethics; Legal Medicine GA 295KS UT WOS:000330115600016 ER PT J AU Greene, SJ Gheorghiade, M Borlaug, BA Pieske, B Vaduganathan, M Burnett, JC Roessig, L Stasch, JP Solomon, SD Paulus, WJ Butler, J AF Greene, Stephen J. Gheorghiade, Mihai Borlaug, Barry A. Pieske, Burkert Vaduganathan, Muthiah Burnett, John C., Jr. Roessig, Lothar Stasch, Johannes-Peter Solomon, Scott D. Paulus, Walter J. Butler, Javed TI The cGMP Signaling Pathway as a Therapeutic Target in Heart Failure With Preserved Ejection Fraction SO JOURNAL OF THE AMERICAN HEART ASSOCIATION LA English DT Review DE cGMP; heart failure; phosphodiesterase 5; preserved ejection fraction; soluble guanylate cyclase ID SOLUBLE GUANYLATE-CYCLASE; NITRIC-OXIDE SYNTHASE; PULMONARY ARTERIAL-HYPERTENSION; IMPROVES EXERCISE CAPACITY; NATRIURETIC PEPTIDE; PHOSPHODIESTERASE-5 INHIBITION; DIASTOLIC DISTENSIBILITY; ENDOTHELIAL DYSFUNCTION; SODIUM-NITROPRUSSIDE; CONTRACTILE RESPONSE C1 [Greene, Stephen J.; Gheorghiade, Mihai] Northwestern Univ, Feinberg Sch Med, Ctr Cardiovasc Innovat, Chicago, IL 60611 USA. [Borlaug, Barry A.; Burnett, John C., Jr.] Mayo Clin & Mayo Fdn, Div Cardiovasc Dis, Rochester, MN USA. [Pieske, Burkert] Med Univ Graz, Dept Cardiol, Graz, Austria. [Vaduganathan, Muthiah] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Med, Boston, MA USA. [Roessig, Lothar] Bayer Pharma AG, Berlin, Germany. [Stasch, Johannes-Peter] Bayer HealthCare, Cardiol Res, Wuppertal, Germany. [Solomon, Scott D.] Brigham & Womens Hosp, Div Cardiovasc, Boston, MA 02115 USA. [Paulus, Walter J.] Vrije Univ Amsterdam, Med Ctr Amsterdam, Dept Physiol, Inst Cardiovasc Res VU, Amsterdam, Netherlands. [Butler, Javed] Emory Univ, Sch Med, Div Cardiol, Atlanta, GA 30322 USA. RP Butler, J (reprint author), Emory Clin Cardiovasc Res Inst, 1462 Clifton Rd NE,Suite 504, Atlanta, GA 30322 USA. EM javed.butler@emory.edu FU Novartis; Bayer; NIH; European Union FX Dr Gheorghiade has been a consultant for Abbott Laboratories, Astellas, AstraZeneca, Bayer HealthCare AG, CorThera, Cytokinetics, DebioPharm S. A., Errekappa Terapeutici, GlaxoSmithKline, Ikaria, Johnson & Johnson, Medtronic, Merck, Novartis Pharma AG, Otsuka Pharmaceuticals, Palatin Technologies, Pericor Therapeutics, Protein Design Laboratories, Sanofi-Aventis, Sigma Tau, Solvay Pharmaceuticals, Takeda Pharmaceutical, and Trevena Therapeutics. Dr Borlaug receives research funding from the NHLBI, AtCor Medical, and Gilead and serves as a consultant for GlaxoSmithKline, Merck, Amgen, CardioKinetix, and Medscape. Dr Roessig is a full-time employee of Bayer Pharma AG. Dr Stasch is an employee of Bayer Pharma AG and holds multiple patent applications related to soluble guanylate cyclase stimulators and activators. Dr Solomon receives research support from Novartis (>$10 000) and consulting support from Novartis and Bayer (<$10 000). Dr Butler reports research support from the NIH and the European Union and is a consultant to Amgen, Bayer, BG Medicine, Celladon, Gambro, GE Healthcare, Harvest, Medtronic, Ono Pharma, Stemedica, and Trevena. The other authors report no conflicts. NR 112 TC 19 Z9 19 U1 0 U2 7 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 DEC PY 2013 VL 2 IS 6 AR e000536 DI 10.1161/JAHA.113.000536 PG 11 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 296IG UT WOS:000330177900016 PM 24334823 ER PT J AU Hong, SN Gona, P Fontes, JD Oyama, N Chan, RH Kenchaiah, S Tsao, CW Yeon, SB Schnabel, RB Keaney, JF O'Donnell, CJ Benjamin, EJ Manning, WJ AF Hong, Susie N. Gona, Philimon Fontes, Joao D. Oyama, Noriko Chan, Raymond H. Kenchaiah, Satish Tsao, Connie W. Yeon, Susan B. Schnabel, Renate B. Keaney, John F. O'Donnell, Christopher J. Benjamin, Emelia J. Manning, Warren J. TI Atherosclerotic Biomarkers and Aortic Atherosclerosis by Cardiovascular Magnetic Resonance Imaging in the Framingham Heart Study SO JOURNAL OF THE AMERICAN HEART ASSOCIATION LA English DT Article DE aorta; atherosclerosis; biomarkers; cardiovascular magnetic resonance imaging ID C-REACTIVE PROTEIN; CORONARY-ARTERY CALCIFICATION; CAROTID ATHEROSCLEROSIS; RISK-FACTORS; INFLAMMATORY BIOMARKERS; DISEASE; ASSOCIATION; MARKERS; MEN; PREDICTOR AB Background-The relations between subclinical atherosclerosis and inflammatory biomarkers have generated intense interest but their significance remains unclear. We sought to determine the association between a panel of biomarkers and subclinical aortic atherosclerosis in a community-based cohort. Methods and Results-We evaluated 1547 participants of the Framingham Heart Study Offspring cohort who attended the 7th examination cycle and underwent both cardiovascular magnetic resonance imaging (CMR) and assays for 10 biomarkers associated with atherosclerosis: high-sensitivity C-reactive protein, fibrinogen, intercellular adhesion molecule-1, interleukin-6, interleukin-18, lipoprotein-associated phospholipase-A2 activity and mass, monocyte chemoattractant protein-1, P-selectin, and tumor necrosis factor receptor-2. In logistic regression analysis, we found no significant association between the biomarker panel and the presence of aortic plaque (global P=0.53). Using Tobit regression with aortic plaque as a continuous variable, we noted a modest association between biomarker panel and aortic plaque volume in age-and sex-adjusted analyses (P=0.003). However, this association was attenuated after further adjustment for clinical covariates (P=0.09). Conclusions-In our community-based cohort, we found no significant association between our multibiomarker panel and aortic plaque. Our results underscore the strengths and limitations of the use of biomarkers for the identification of subclinical atherosclerosis and the importance of traditional risk factors. C1 [Hong, Susie N.; Oyama, Noriko; Chan, Raymond H.; Tsao, Connie W.; Yeon, Susan B.; Manning, Warren J.] Harvard Univ, Beth Israel Deaconess Med Ctr, Div Cardiovasc, Dept Med,Sch Med, Boston, MA 02215 USA. [Manning, Warren J.] Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Dept Radiol, Boston, MA 02215 USA. [Gona, Philimon] Univ Massachusetts, Sch Med, Dept Quantitat Hlth Sci, Div Biostat & Hlth Serv Res, Worcester, MA USA. [Keaney, John F.] Univ Massachusetts, Sch Med, Dept Med, Div Cardiovasc Med, Worcester, MA USA. [Kenchaiah, Satish; Benjamin, Emelia J.] Boston Univ, Sch Med, Whitaker Cardiovasc Inst, Cardiol Sect, Boston, MA 02118 USA. [Kenchaiah, Satish; Benjamin, Emelia J.] Boston Univ, Sch Med, Whitaker Cardiovasc Inst, Prevent Med Sect,Dept Med, Boston, MA 02118 USA. [Benjamin, Emelia J.] Boston Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA USA. [O'Donnell, Christopher J.] Massachusetts Gen Hosp, Dept Med, Div Cardiol, Boston, MA 02114 USA. [Gona, Philimon; Fontes, Joao D.; Kenchaiah, Satish; Tsao, Connie W.; Schnabel, Renate B.; O'Donnell, Christopher J.; Benjamin, Emelia J.] Boston Univ, Natl Heart Lung & Blood Inst, Framingham, MA USA. [Gona, Philimon; Fontes, Joao D.; Kenchaiah, Satish; Tsao, Connie W.; Schnabel, Renate B.; O'Donnell, Christopher J.; Benjamin, Emelia J.] Boston Univ, Framingham Heart Study, Framingham, MA USA. RP Hong, SN (reprint author), Beth Israel Deaconess Med Ctr, Div Cardiovasc, 330 Brookline Ave, Boston, MA 02215 USA. EM snh7311@gmail.com RI Kenchaiah, Satish/A-1519-2016; OI Benjamin, Emelia/0000-0003-4076-2336 FU National Heart, Lung, and Blood Institute's [N01-HC-25195]; National Institutes of Health (NIH) [RO1HL70279]; NIH [RO1 HL064753, HL076784, AG028321] FX The Framingham Heart Study (FHS) is supported by the National Heart, Lung, and Blood Institute's Contract No. N01-HC-25195 and a subcontract from the National Institutes of Health (NIH) (RO1HL70279). Additional funding for this work supported by NIH grants RO1 HL064753, HL076784, and AG028321 to Dr. Benjamin. Lipoprotein-associated phospholipase-A2 activity measurements were provided by Glaxo-SmithKline at no cost to the FHS. The contents of this manuscript are solely the responsibility of the authors and do not necessarily represent the official views of the NIH. NR 31 TC 8 Z9 8 U1 1 U2 6 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 DEC PY 2013 VL 2 IS 6 DI 10.1161/JAHA.113.000307 PG 8 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 296IG UT WOS:000330177900019 ER PT J AU Kalim, S Clish, CB Wenger, J Elmariah, S Yeh, RW Deferio, JJ Pierce, K Deik, A Gerszten, RE Thadhani, R Rhee, EP AF Kalim, Sahir Clish, Clary B. Wenger, Julia Elmariah, Sammy Yeh, Robert W. Deferio, Joseph J. Pierce, Kerry Deik, Amy Gerszten, Robert E. Thadhani, Ravi Rhee, Eugene P. TI A Plasma Long-Chain Acylcarnitine Predicts Cardiovascular Mortality in Incident Dialysis Patients SO JOURNAL OF THE AMERICAN HEART ASSOCIATION LA English DT Article DE cardiovascular disease; dialysis; metabolism; mortality; risk factors ID STAGE RENAL-DISEASE; MAINTENANCE HEMODIALYSIS-PATIENTS; CHRONIC KIDNEY-DISEASE; FATTY-ACID OXIDATION; MYOCARDIAL-INFARCTION; CARNITINE DISORDER; INSULIN-RESISTANCE; RISK-FACTORS; METABOLISM; SURVIVAL AB Background-The marked excess in cardiovascular mortality that results from uremia remains poorly understood. Methods and Results-In 2 independent, nested case-control studies, we applied liquid chromatography-mass spectrometry-based metabolite profiling to plasma obtained from participants of a large cohort of incident hemodialysis patients. First, 100 individuals who died of a cardiovascular cause within 1 year of initiating hemodialysis (cases) were randomly selected along with 100 individuals who survived for at least 1 year (controls), matched for age, sex, and race. Four highly intercorrelated long-chain acylcarnitines achieved the significance threshold adjusted for multiple testing (P<0.0003). Oleoylcarnitine, the long-chain acylcarnitine with the strongest association with cardiovascular mortality in unadjusted analysis, remained associated with 1-year cardiovascular death after multivariable adjustment (odds ratio per SD 2.3 [95% confidence interval, 1.4 to 3.8]; P=0.001). The association between oleoylcarnitine and 1-year cardiovascular death was then replicated in an independent sample (n=300, odds ratio per SD 1.4 [95% confidence interval, 1.1 to 1.9]; P=0.008). Addition of oleoylcarnitine to clinical variables improved cardiovascular risk prediction using net reclassification (NRI, 0.38 [95% confidence interval, 0.20 to 0.56]; P<0.0001). In physiologic profiling studies, we demonstrate that the fold change in plasma acylcarnitine levels from the aorta to renal vein and from pre- to post hemodialysis samples exclude renal or dialytic clearance of long-chain acylcarnitines as confounders in our analysis. Conclusions-Our data highlight clinically meaningful alterations in acylcarnitine homeostasis at the time of dialysis initiation, which may represent an early marker, effector, or both of uremic cardiovascular risk. C1 [Kalim, Sahir; Wenger, Julia; Deferio, Joseph J.; Thadhani, Ravi; Rhee, Eugene P.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Elmariah, Sammy; Yeh, Robert W.; Gerszten, Robert E.] Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. [Gerszten, Robert E.] Massachusetts Gen Hosp, Cardiovasc Res Ctr, Boston, MA 02114 USA. [Clish, Clary B.; Pierce, Kerry; Deik, Amy; Gerszten, Robert E.; Rhee, Eugene P.] Broad Inst, Cambridge, MA USA. RP Kalim, S (reprint author), MGH, Dept Med, Div Nephrol, 165 Cambridge St,Suite 302, Boston, MA 02215 USA. EM skalim@partners.org FU National Kidney Foundation; American Heart Association; NIH [R21-DK-071674, K08-DK-090142] FX These studies were supported by National Kidney Foundation Young Investigator (Dr Kalim), American Heart Association Established Investigator (Dr Gerszten), NIH R21-DK-071674 (Dr Thadhani), and NIH K08-DK-090142 (Dr Rhee) awards. NR 52 TC 25 Z9 25 U1 0 U2 5 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 2047-9980 J9 J AM HEART ASSOC JI J. Am. Heart Assoc. PD DEC PY 2013 VL 2 IS 6 AR e000542 DI 10.1161/JAHA.113.000542 PG 11 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 296IG UT WOS:000330177900022 PM 24308938 ER PT J AU Neilan, TG Farhad, H Dodson, JA Shah, RV Abbasi, SA Bakker, JP Michaud, GF van der Geest, R Blankstein, R Steigner, M John, RM Jerosch-Herold, M Malhotra, A Kwong, RY AF Neilan, Tomas G. Farhad, Hoshang Dodson, John A. Shah, Ravi V. Abbasi, Siddique A. Bakker, Jessie P. Michaud, Gregory F. van der Geest, Rob Blankstein, Ron Steigner, Michael John, Roy M. Jerosch-Herold, Michael Malhotra, Atul Kwong, Raymond Y. TI Effect of Sleep Apnea and Continuous Positive Airway Pressure on Cardiac Structure and Recurrence of Atrial Fibrillation SO JOURNAL OF THE AMERICAN HEART ASSOCIATION LA English DT Article DE atrial fibrillation; cardiac magnetic resonance; sleep apnea ID CARDIOVASCULAR-MAGNETIC-RESONANCE; LATE GADOLINIUM ENHANCEMENT; AMERICAN-HEART-ASSOCIATION; RISK-FACTORS; CATHETER ABLATION; HYPERTENSION; CARDIOLOGY; MANAGEMENT; STROKE; ADULTS AB Background-Sleep apnea (SA) is associated with an increased risk of atrial fibrillation (AF). We sought to determine the effect of SA on cardiac structure in patients with AF, whether therapy for SA was associated with beneficial cardiac structural remodelling, and whether beneficial cardiac structural remodelling translated into a reduced risk of recurrence of AF after pulmonary venous isolation (PVI). Methods and Results-A consecutive group of 720 patients underwent a cardiac magnetic resonance study before PVI. Patients with SA (n=142, 20%) were more likely to be male, diabetic, and hypertensive and have an increased pulmonary artery pressure, right ventricular volume, atrial dimensions, and left ventricular mass. Treated SA was defined as duration of continuous positive airway pressure therapy of >4 hours per night. Treated SA patients (n=71, 50%) were more likely to have paroxysmal AF, a lower blood pressure, lower ventricular mass, and smaller left atrium. During a follow-up of 42 months, AF recurred in 245 patients. The cumulative incidence of AF recurrence was 51% in patients with SA, 30% in patients without SA, 68% in patients with untreated SA, and 35% in patients with treated SA. In a multivariable model, the presence of SA (hazard ratio 2.79, CI 1.97 to 3.94, P<0.0001) and untreated SA (hazard ratio 1.61, CI 1.35 to 1.92, P<0.0001) were highly associated with AF recurrence. Conclusions-Patients with SA have an increased blood pressure, pulmonary artery pressure, right ventricular volume, left atrial size, and left ventricular mass. Therapy with continuous positive airway pressure is associated with lower blood pressure, atrial size, and ventricular mass, and a lower risk of AF recurrence after PVI. C1 [Farhad, Hoshang; Shah, Ravi V.; Abbasi, Siddique A.; Michaud, Gregory F.; Blankstein, Ron; John, Roy M.; Kwong, Raymond Y.] Brigham & Womens Hosp, Div Cardiovasc, Dept Med, Boston, MA 02115 USA. [Dodson, John A.] Brigham & Womens Hosp, Div Aging, Dept Med, Boston, MA 02115 USA. [Bakker, Jessie P.] Brigham & Womens Hosp, Sleep Disorders Res Program, Boston, MA 02115 USA. [Neilan, Tomas G.; Shah, Ravi V.] Massachusetts Gen Hosp, Div Cardiol, Dept Med, Boston, MA 02114 USA. [Neilan, Tomas G.] Massachusetts Gen Hosp, Dept Radiol, Cardiac PET MR CT Program, Boston, MA 02114 USA. [Steigner, Michael; Jerosch-Herold, Michael] Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Radiol, Cambridge, MA 02138 USA. [Malhotra, Atul] Univ Calif San Diego, Pulm & Crit Care Div, La Jolla, CA 92093 USA. [van der Geest, Rob] Leiden Univ, Med Ctr, Dept Radiol, Div Image Proc, Leiden, Netherlands. RP Kwong, RY (reprint author), Brigham & Womens Hosp, Div Cardiovasc, Dept Med, 75 Francis St, Boston, MA 02115 USA. EM rykwong@partners.org FU American Heart Association [12FTF12060588]; National Institutes of Health (NIH) [T32HL09430101A1, T32 AG000158]; NIH [R01HL090634-01A1, R01HL091157] FX This work was supported by an American Heart Association Fellow to Faculty Grant (12FTF12060588, to Dr Neilan), National Institutes of Health (NIH) T32 Training Grants (T32HL09430101A1 to Dr Neilan and T32 AG000158 to Dr Dodson), and NIH project grants (R01HL090634-01A1, to Dr Jerosch-Herold; R01HL091157, to Dr Kwong). NR 39 TC 26 Z9 27 U1 1 U2 4 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 2047-9980 J9 J AM HEART ASSOC JI J. Am. Heart Assoc. PD DEC PY 2013 VL 2 IS 6 AR e000421 DI 10.1161/JAHA.113.000421 PG 10 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 296IG UT WOS:000330177900033 PM 24275628 ER PT J AU Redmond, N Richman, J Gamboa, CM Albert, MA Sims, M Durant, RW Glasser, SP Safford, MM AF Redmond, Nicole Richman, Joshua Gamboa, Christopher M. Albert, Michelle A. Sims, Mario Durant, Raegan W. Glasser, Stephen P. Safford, Monika M. TI Perceived Stress Is Associated With Incident Coronary Heart Disease and All-Cause Mortality in Low- but Not High-Income Participants in the Reasons for Geographic And Racial Differences in Stroke Study SO JOURNAL OF THE AMERICAN HEART ASSOCIATION LA English DT Article DE epidemiology; mortality; myocardial infarction; stress ID MAJOR RISK-FACTORS; SOCIOECONOMIC-STATUS; CARDIOVASCULAR-DISEASE; UNITED-STATES; MYOCARDIAL-INFARCTION; PHYSICAL-ACTIVITY; PSYCHOLOGICAL DISTRESS; ATHEROSCLEROSIS RISK; MULTIPLE IMPUTATION; HEALTH AB Background-Perceived stress may increase risk for coronary heart disease (CHD) and death, but few studies have examined these relationships longitudinally. We sought to determine the association of perceived stress with incident CHD and all-cause mortality. Methods and Results-Data were from a prospective study of 24 443 participants without CHD at baseline from the national Reasons for Geographic And Racial Differences in Stroke (REGARDS) study cohort. Outcomes were expert-adjudicated acute CHD and all-cause mortality. Over a mean follow-up of 4.2 (maximum 6.9) years, there were 659 incident CHD events and 1320 deaths. Analyses were stratified by income level because of significant interactions with stress. For individuals with low income, 3529 (35.4%) reported high stress, and for those with high income, 2524 (22.1%) did so. Compared with reporting no stress, those reporting the highest stress had higher risk for incident CHD if they reported low income (sociodemographic-adjusted HR 1.36, 95% CI: 1.04, 1.78) but not high income (sociodemographic-adjusted HR 0.82, 95% CI: 0.57, 1.16); the finding in low income individuals attenuated with adjustment for clinical and behavioral factors (HR 1.29, 95% CI: 0.99, 1.69, P=0.06). After full adjustment, the highest stress category was associated with higher risk for death among those with low income (HR 1.55, 95% CI: 1.31, 1.82) but not high income (HR 1.13, 95% CI: 0.88, 1.46). Conclusions-High stress was associated with greater risks of CHD and death for individuals with low but not high income. C1 [Redmond, Nicole; Gamboa, Christopher M.; Durant, Raegan W.; Glasser, Stephen P.; Safford, Monika M.] Univ Alabama Birmingham, Div Prevent Med, Birmingham, AL 35294 USA. [Richman, Joshua] Univ Alabama Birmingham, Dept Surg, Birmingham, AL 35294 USA. [Gamboa, Christopher M.] Univ Alabama Birmingham, Dept Epidemiol, Birmingham, AL 35294 USA. [Albert, Michelle A.] Howard Univ, Coll Med, Div Cardiovasc Med, Washington, DC USA. [Sims, Mario] Univ Mississippi, Med Ctr, Dept Med, Jackson, MS 39216 USA. [Durant, Raegan W.] Birmingham Vet Affairs Med Ctr, Birmingham, AL USA. RP Redmond, N (reprint author), Univ Alabama Birmingham, Div Prevent Med, 1717 11th Ave South,Med Towers 610, Birmingham, AL 35294 USA. EM nredmond@uabmc.edu OI Glasser, Stephen/0000-0001-9620-6406 FU National Institute of Neurological Disorders and Stroke (NINDS) [U01NS041588]; National Heart, Lung, and Blood Institute (NHLBI) [R01HL080477, K24HL111154]; NHLBI [R01HL080477-07S1]; Centers for Medicare & Medicaid Services [1CMS331071-01-00, 1CMS331300-01-00]; Amgen Corporation FX REGARDS is supported by cooperative agreement U01NS041588 from the National Institute of Neurological Disorders and Stroke (NINDS, Dr G. Howard, PI). Dr Safford is supported by grants R01HL080477 and K24HL111154 from the National Heart, Lung, and Blood Institute (NHLBI). Dr Redmond is supported by Minority Investigator Research Supplement R01HL080477-07S1 from NHLBI and grants 1CMS331071-01-00 and 1CMS331300-01-00 from the Centers for Medicare & Medicaid Services. Both Drs Safford and Glasser are supported by investigator-initiated grant-in-aid from Amgen Corporation. NR 56 TC 23 Z9 23 U1 5 U2 14 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 DEC PY 2013 VL 2 IS 6 AR e000447 DI 10.1161/JAHA.113.000447 PG 11 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 296IG UT WOS:000330177900040 PM 24356528 ER PT J AU Steinberg, BA Holmes, DN Piccini, JP Ansell, J Chang, P Fonarow, GC Gersh, B Mahaffey, KW Kowey, PR Ezekowitz, MD Singer, DE Thomas, L Peterson, ED Hylek, EM AF Steinberg, Benjamin A. Holmes, DaJuanicia N. Piccini, Jonathan P. Ansell, Jack Chang, Paul Fonarow, Gregg C. Gersh, Bernard Mahaffey, Kenneth W. Kowey, Peter R. Ezekowitz, Michael D. Singer, Daniel E. Thomas, Laine Peterson, Eric D. Hylek, Elaine M. CA Outcomes Registry Better Informed TI Early Adoption of Dabigatran and Its Dosing in US Patients With Atrial Fibrillation: Results From the Outcomes Registry for Better Informed Treatment of Atrial Fibrillation SO JOURNAL OF THE AMERICAN HEART ASSOCIATION LA English DT Article DE anticoagulant; atrial fibrillation; dabigatran; dosing; pharmacoepidemiology ID INTRACRANIAL HEMORRHAGE; RISK FACTOR; WARFARIN; STROKE; XIMELAGATRAN; SAFETY; TRIAL AB Background-Dabigatran is a novel oral anticoagulant approved for thromboprophylaxis in atrial fibrillation. Adoption patterns of this new agent in community practice are unknown. Methods and Results-We studied patterns of dabigatran use among patients enrolled in the Outcomes Registry for Better Informed Treatment of Atrial Fibrillation (ORBIT-AF) Registry between June 2010 and August 2011 and followed for 12 months. Among 9974 atrial fibrillation patients included, 1217 (12%) were treated with dabigatran during the study. Overall, patients receiving dabigatran were younger (median age 72 versus 75 years, P<0.0001), more likely to be white (92% versus 89%, P=0.005), more likely to have private insurance (33% versus 25%, P<0.0001), and less likely to have prior cardiovascular disease (4% versus 33%, P<0.0001). They had more new-onset atrial fibrillation (8.8% versus 4.1%, P<0.0001), lower CHADS(2) scores (estimated risk based on the presence of congestive heart failure, hypertension, aged >= 75 years, diabetes mellitus, and prior stroke or transient ischemic attack; mean 2.0 versus 2.3, P<0.0001), and lower Anticoagulation and Risk Factors in Atrial Fibrillation scores (mean 2.4 versus 2.8, P<0.0001). More than half (n=14/25, 56%) of patients with severe kidney disease were not prescribed reduced dosing, whereas 10% (n=91/920) with preserved renal function received lower dosing. Among patients not on dabigatran at baseline, 8% had dabigatran initiated during follow-up. Patient education was significantly associated with switching from warfarin to dabigatran (adjusted odds ratio for postgraduate 1.73, P=0.007), whereas antiarrhythmic drug use significantly correlated with de novo adoption of dabigatran (adjusted odds ratio 2.4, P<0.0001). Conclusions-Patients receiving dabigatran were younger and at a lower risk of stroke and bleeding. Patients appeared to drive switching from warfarin, whereas clinical characteristics influenced de novo start of dabigatran. These data suggest cautious early uptake of dabigatran, and more careful attention to dosing adjustments is warranted. C1 [Steinberg, Benjamin A.; Piccini, Jonathan P.; Peterson, Eric D.] Duke Univ, Med Ctr, Durham, NC 27710 USA. [Steinberg, Benjamin A.; Holmes, DaJuanicia N.; Piccini, Jonathan P.; Thomas, Laine; Peterson, Eric D.] Duke Clin Res Inst, Durham, NC USA. [Ansell, Jack] NYU, Sch Med, Lenox Hill Hosp, New York, NY USA. [Chang, Paul] Janssen Sci Affairs, Raritan, NJ USA. [Fonarow, Gregg C.] Univ Calif Los Angeles, Div Cardiol, Los Angeles, CA USA. [Gersh, Bernard] Mayo Clin, Rochester, MN USA. [Mahaffey, Kenneth W.] Stanford Univ, Sch Med, Dept Med, Palo Alto, CA 94304 USA. [Kowey, Peter R.] Lankenau Inst Med Res, Wynnewood, PA USA. [Ezekowitz, Michael D.] Thomas Jefferson Med Coll, Lankenau Med Ctr, Wynnewood, PA USA. [Ezekowitz, Michael D.] Cardiovasc Res Fdn, New York, NY USA. [Singer, Daniel E.] Harvard Univ, Sch Med, Boston, MA USA. [Singer, Daniel E.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Hylek, Elaine M.] Boston Univ, Sch Med, Boston, MA 02118 USA. RP Steinberg, BA (reprint author), Duke Univ, Med Ctr, Durham, NC 27710 USA. FU Janssen Scientific Affairs, LLC, Raritan, NJ; National Institutes of Health [5T32HL7101-37] FX The ORBIT-AF registry is sponsored by Janssen Scientific Affairs, LLC, Raritan, NJ. Dr Steinberg was funded by National Institutes of Health T-32 training grant 5T32HL7101-37. NR 24 TC 32 Z9 32 U1 0 U2 5 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 2047-9980 J9 J AM HEART ASSOC JI J. Am. Heart Assoc. PD DEC PY 2013 VL 2 IS 6 AR e000535 DI 10.1161/JAHA.113.000535 PG 12 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 296IG UT WOS:000330177900042 PM 24275632 ER PT J AU Van Dyke, TE Starr, JR AF Van Dyke, Thomas E. Starr, Jacqueline R. TI Unraveling the Link Between Periodontitis and Cardiovascular Disease SO JOURNAL OF THE AMERICAN HEART ASSOCIATION LA English DT Editorial Material DE Editorials; cardiovascular disease; infection; inflammation; periodontitis ID INFLAMMATORY MECHANISMS; INFECTION C1 [Van Dyke, Thomas E.; Starr, Jacqueline R.] Forsyth Inst, Boston, MA USA. RP Van Dyke, TE (reprint author), Ctr Periodontol, Dept Appl Oral Sci, 245 1st St, Cambridge, MA 02142 USA. EM tvandyke@forsyth.org NR 11 TC 1 Z9 1 U1 1 U2 4 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 2047-9980 J9 J AM HEART ASSOC JI J. Am. Heart Assoc. PD DEC PY 2013 VL 2 IS 6 AR e000657 DI 10.1161/JAHA.113.000657 PG 2 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 296IG UT WOS:000330177900045 PM 24342998 ER PT J AU Xanthakis, V Larson, MG Wollert, KC Aragam, J Cheng, S Ho, J Coglianese, E Levy, D Colucci, WS Felker, GM Benjamin, EJ Januzzi, JL Wang, TJ Vasan, RS AF Xanthakis, Vanessa Larson, Martin G. Wollert, Kai C. Aragam, Jayashri Cheng, Susan Ho, Jennifer Coglianese, Erin Levy, Daniel Colucci, Wilson S. Felker, G. Michael Benjamin, Emelia J. Januzzi, James L. Wang, Thomas J. Vasan, Ramachandran S. TI Association of Novel Biomarkers of Cardiovascular Stress With Left Ventricular Hypertrophy and Dysfunction: Implications for Screening SO JOURNAL OF THE AMERICAN HEART ASSOCIATION LA English DT Article DE biomarkers; echocardiography; heart failure; hypertrophy; screening ID GROWTH-DIFFERENTIATION FACTOR-15; ACUTE HEART-FAILURE; HIGHLY SENSITIVE ASSAY; NATRIURETIC PEPTIDE; TROPONIN-T; SYSTOLIC DYSFUNCTION; MYOCARDIAL-INFARCTION; EJECTION FRACTION; CARDIAC TROPONIN; FAMILY-MEMBER AB Background-Currently available screening tools for left ventricular (LV) hypertrophy (LVH) and systolic dysfunction (LVSD) are either expensive (echocardiography) or perform suboptimally (B-type natriuretic peptide [BNP]). It is unknown whether newer biomarkers are associated with LVH and LVSD and can serve as screening tools. Methods and Results-We studied 2460 Framingham Study participants (mean age 58 years, 57% women) with measurements of biomarkers mirroring cardiac biomechanical stress (soluble ST-2 [ST2], growth differentiation factor-15 [GDF-15] and high-sensitivity troponin I [hsTnI]) and BNP. We defined LVH as LV mass/height(2) >= the sex-specific 80th percentile and LVSD as mild/greater impairment of LV ejection fraction (LVEF) or a fractional shortening <0.29. Adjusting for standard risk factors in logistic models, BNP, GDF-15, and hsTnI were associated with the composite echocardiographic outcome (LVH or LVSD), odds ratios (OR) per SD increment in log-biomarker 1.29, 1.14, and 1.18 (95% CI: 1.15 to 1.44, 1.004 to 1.28, and 1.06 to 1.31), respectively. The C-statistic for the composite outcome increased from 0.765 with risk factors to 0.770 adding BNP, to 0.774 adding novel biomarkers. The continuous Net Reclassification Improvement was 0.212 (95% CI: 0.119 to 0.305, P<0.0001) after adding the novel biomarkers to risk factors plus BNP. BNP was associated with LVH and LVSD in multivariable models, whereas GDF-15 was associated with LVSD (OR 1.41, 95% CI: 1.16 to 1.70), and hsTnI with LVH (OR 1.22, 95% CI: 1.09 to 1.36). ST2 was not significantly associated with any outcome. Conclusions-Our community-based investigation suggests that cardiac stress biomarkers are associated with LVH and LVSD but may have limited clinical utility as screening tools. C1 [Xanthakis, Vanessa; Larson, Martin G.; Cheng, Susan; Ho, Jennifer; Levy, Daniel; Benjamin, Emelia J.; Vasan, Ramachandran S.] Framingham Heart Dis Epidemiol Study, Framingham, MA USA. [Xanthakis, Vanessa] Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA USA. [Benjamin, Emelia J.] Boston Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA USA. [Xanthakis, Vanessa; Benjamin, Emelia J.; Vasan, Ramachandran S.] Boston Univ, Sch Med, Sect Prevent Med & Epidemiol, Boston, MA 02118 USA. [Ho, Jennifer; Colucci, Wilson S.; Benjamin, Emelia J.; Vasan, Ramachandran S.] Boston Univ, Sch Med, Cardiol Sect, Boston, MA 02118 USA. [Januzzi, James L.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Cardiol, Boston, MA USA. [Wollert, Kai C.] Hannover Med Sch, Dept Cardiol & Angiol, Div Mol & Translat Cardiol, Hannover, Germany. [Aragam, Jayashri] Vet Adm Hosp, West Roxbury, MA USA. [Aragam, Jayashri; Cheng, Susan] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Med,Div Cardiovasc Med, Boston, MA 02115 USA. [Levy, Daniel] NHLBI, Ctr Populat Studies, Bethesda, MD 20892 USA. [Larson, Martin G.] Boston Univ, Dept Math & Stat, Boston, MA 02215 USA. [Coglianese, Erin] Loyola Univ, Div Cardiol, Chicago, IL 60611 USA. [Felker, G. Michael] Duke Univ, Sch Med, Div Cardiol, Durham, NC USA. [Wang, Thomas J.] Vanderbilt Univ, Div Med, Div Cardiovasc Med, Nashville, TN 37235 USA. RP Xanthakis, V (reprint author), Boston Univ, Sch Med, Dept Med, Sect Prevent Med & Epidemiol, 801 Massachusetts Ave,Suite 470, Boston, MA 02118 USA. EM vanessax@bu.edu OI Ho, Jennifer/0000-0002-7987-4768 FU AHA Clinical Research Program award [13CRP14090010]; German Ministry of Education and Research; Ellison Foundation; Roman W. DeSanctis Clinical Scholar Endowment; [N01-HC-25915]; [R01-HL-08675]; [K99-HL-107642] FX This work was supported by AHA Clinical Research Program award 13CRP14090010 (to Dr Xanthakis), by N01-HC-25915, and R01-HL-08675 and K99-HL-107642. Dr Wollert was supported by the German Ministry of Education and Research, Dr Cheng by the Ellison Foundation, and Dr Januzzi by the Roman W. DeSanctis Clinical Scholar Endowment. NR 49 TC 21 Z9 22 U1 0 U2 4 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 2047-9980 J9 J AM HEART ASSOC JI J. Am. Heart Assoc. PD DEC PY 2013 VL 2 IS 6 AR e000399 DI 10.1161/JAHA.113.000399 PG 10 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 296IG UT WOS:000330177900049 PM 24200688 ER PT J AU Zhang, XC Xu, C Mitchell, RM Zhang, B Zhao, D Li, Y Huang, X Fan, WH Wang, HW Lerma, LA Upton, MP Hay, A Mendez, E Zhao, LP AF Zhang, Xinyi Cindy Xu, Chang Mitchell, Ryan M. Zhang, Bo Zhao, Derek Li, Yao Huang, Xin Fan, Wenhong Wang, Hongwei Lerma, Luisa Angelica Upton, Melissa P. Hay, Ashley Mendez, Eduardo Zhao, Lue Ping TI Tumor Evolution and Intratumor Heterogeneity of an Oropharyngeal Squamous Cell Carcinoma Revealed by Whole-Genome Sequencing SO NEOPLASIA LA English DT Article ID INTRONIC VARIANTS; NECK-CANCER; HEAD; MUTATIONS; METASTASIS; EXPRESSION; THERAPY; PATHWAY; GENE; DNA AB Head and neck squamous cell carcinoma (HNSCC) is characterized by significant genomic instability that could lead to clonal diversity. Intratumor clonal heterogeneity has been proposed as a major attribute underlying tumor evolution, progression, and resistance to chemotherapy and radiation. Understanding genetic heterogeneity could lead to treatments specific to resistant and metastatic tumor cells. To characterize the degree of intratumor genetic heterogeneity within a single tumor, we performed whole-genome sequencing on three separate regions of an human papillomavirus (HPV)-positive oropharyngeal squamous cell carcinoma and two separate regions from one corresponding cervical lymph node metastasis. This approach achieved coverage of approximately 97.9% of the genome across all samples. In total, 5701 somatic point mutations (SPMs) and 4347 small somatic insertions and deletions (indels) were detected in at least one sample. Ninety-two percent of SPMs and 77% of indels were validated in a second set of samples adjacent to the discovery set. All five tumor samples shared 41% of SPMs, 57% of the 1805 genes with SPMs, and 34 of 55 cancer genes. The distribution of SPMs allowed phylogenetic reconstruction of this tumor's evolutionary pathway and showed that the metastatic samples arose as a late event. The degree of intratumor heterogeneity showed that a single biopsy may not represent the entire mutational landscape of HNSCC tumors. This approach may be used to further characterize intratumor heterogeneity in more patients, and their sample-to-sample variations could reveal the evolutionary process of cancer cells, facilitate our understanding of tumorigenesis, and enable the development of novel targeted therapies. C1 [Zhang, Xinyi Cindy; Zhang, Bo; Zhao, Derek; Li, Yao; Huang, Xin; Fan, Wenhong; Wang, Hongwei; Hay, Ashley; Zhao, Lue Ping] Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, Seattle, WA 98109 USA. [Xu, Chang; Mitchell, Ryan M.; Lerma, Luisa Angelica; Mendez, Eduardo] Univ Washington, Sch Med, Dept Otolaryngol Head & Neck Surg, Seattle, WA USA. [Xu, Chang; Mendez, Eduardo] Fred Hutchinson Canc Res Ctr, Div Clin Res, Seattle, WA 98109 USA. [Upton, Melissa P.] Univ Washington, Sch Med, Dept Pathol, Seattle, WA 98195 USA. [Mendez, Eduardo] VA Puget Sound Hlth Care Syst, Surg & Perioperat Care Serv, Seattle, WA USA. [Zhao, Lue Ping] Univ Washington, Sch Publ Hlth, Dept Biostat, Seattle, WA 98195 USA. RP Mendez, E (reprint author), Fred Hutchinson Canc Res Ctr, Div Clin Res, 1100 Fairview Ave N,POB 19024,Mailstop D5-390, Seattle, WA 98109 USA. EM edmendez@u.washington.edu; lzhao@fhcrc.org FU National Institutes of Health, Early Physician-Scientist Career Development Award from the Howard Hughes Medical Institute [CA119225, MH084621, R01MH084621-03S2, R01CA124574-01, 5T32DC000018-29]; American Cancer Society [RSG TBG-123653]; center funds from the Department of Otolaryngology-Head and Neck Surgery, University of Washington and VA Puget Sound Health Care System, Seattle, WA FX This work was supported in part by grants CA119225, MH084621, R01MH084621-03S2, R01CA124574-01, and 5T32DC000018-29 from National Institutes of Health, Early Physician-Scientist Career Development Award from the Howard Hughes Medical Institute, grant RSG TBG-123653 from the American Cancer Society, and center funds from the Department of Otolaryngology-Head and Neck Surgery, University of Washington and VA Puget Sound Health Care System, Seattle, WA. NR 27 TC 24 Z9 25 U1 2 U2 11 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1522-8002 EI 1476-5586 J9 NEOPLASIA JI Neoplasia PD DEC PY 2013 VL 15 IS 12 BP 1371 EP + DI 10.1593/neo.131400 PG 10 WC Oncology SC Oncology GA 295PO UT WOS:000330128200006 PM 24403859 ER PT J AU McDermott, S Thayer, SP Fernandez-Del Castillo, C Mino-Kenudson, M Weissleder, R Harisinghani, MG AF McDermott, Shaunagh Thayer, Sarah P. Fernandez-Del Castillo, Carlos Mino-Kenudson, Mari Weissleder, Ralph Harisinghani, Mukesh G. TI Accurate Prediction of Nodal Status in Preoperative Patients with Pancreatic Ductal Adenocarcinoma Using Next-Gen Nanoparticle SO TRANSLATIONAL ONCOLOGY LA English DT Article ID PROGNOSTIC-SIGNIFICANCE; CANCER; METASTASES; DIAGNOSIS; SURVIVAL; IMPACT; CHEMOTHERAPY; RADIOTHERAPY; THERAPY; UTILITY AB OBJECTIVE: The objective of this study is to assess lymphotropic nanoparticle-enhanced magnetic resonance imaging (LNMRI) in identifying malignant nodal involvement in patients with pancreatic ductal adenocarcinoma. METHODS: Magnetic resonance imaging was performed in 13 patients with known or high index of suspicion of pancreatic cancer and who were scheduled for surgical resection. Protocols included T2*-weighted imaging before and after administration of Ferumoxytol (Feraheme) for the evaluation of lymph node involvement. Eleven of the 13 patients underwent a Whipple procedure and lymph node dissection. Nodes that lacked contrast uptake were deemed malignant, and those that demonstrated homogeneous uptake were deemed benign. RESULTS: A total of 264 lymph nodes were resection, of which 17 were malignant. The sensitivity and specificity of LNMRI was 76.5% and 98.4% at a nodal level and 83.3% and 80% at a patient level. CONCLUSION: LNMRI demonstrated high sensitivity and specificity in patients with pancreatic ductal adenocarcinoma. C1 [McDermott, Shaunagh; Weissleder, Ralph; Harisinghani, Mukesh G.] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. [McDermott, Shaunagh; Weissleder, Ralph; Harisinghani, Mukesh G.] Massachusetts Gen Hosp, Ctr Syst Biol, Boston, MA 02114 USA. [Thayer, Sarah P.; Fernandez-Del Castillo, Carlos] Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. [Mino-Kenudson, Mari] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. RP McDermott, S (reprint author), Massachusetts Gen Hosp, 55 Fruit St, Boston, MA 02114 USA. EM smcdermott1@partners.org FU GI Spore FX We thank GI Spore for financial support. NR 37 TC 12 Z9 12 U1 1 U2 7 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1944-7124 EI 1936-5233 J9 TRANSL ONCOL JI Transl. Oncol. PD DEC PY 2013 VL 6 IS 6 BP 670 EP 675 DI 10.1593/tlo.13400 PG 6 WC Oncology SC Oncology GA 298RP UT WOS:000330342400008 PM 24466369 ER PT J AU Brennan, MA Gallun, FJ Souza, PE Stecker, GC AF Brennan, Marc A. Gallun, Frederick J. Souza, Pamela E. Stecker, G. Christopher TI Temporal Resolution With a Prescriptive Fitting Formula SO AMERICAN JOURNAL OF AUDIOLOGY LA English DT Article DE amplification or hearing aids; psychoacoustics; adults with hearing loss ID FAST-ACTING COMPRESSION; SPEECH RECOGNITION; HEARING; AMPLIFICATION; LISTENERS; LOUDNESS AB Purpose: Authors of previous work using laboratory-based paradigms documented that wide dynamic range compression (WDRC) may improve gap detection compared to linear amplification. The purpose of this study was to measure temporal resolution using WDRC fit with compression ratios set for each listener's hearing loss. Method: Nineteen adults with mild-to-moderate hearing loss fitted with WDRC or linear amplification set to a prescriptive fitting method participated in this study. Subjects detected amplitude modulations and gaps. Two types of noise carrier were used: narrowband (1995-2005 Hz) and broadband (100-8000 Hz). Results: Small differences between WDRC and linear amplification were observed in the measures of temporal resolution. Modulation detection thresholds worsened by a mean of 0.7 dB with WDRC compared to linear amplification. This reduction was observed for both carrier types. Gap detection thresholds did not differ between the 2 amplification conditions. Conclusions: WDRC set using a prescriptive fitting method with individualized compression ratios had a small but statistically significant effect on measures of modulation thresholds. Differences were not observed between the two amplification conditions for the measures of gap detection. These findings contrast with previous work using fixed compression ratios, suggesting that the effect of the fitting method on the compression ratio should be considered when attempting to generalize the effect of WDRC on temporal resolution to the clinical setting. C1 [Brennan, Marc A.; Stecker, G. Christopher] Univ Washington, Seattle, WA 98195 USA. [Gallun, Frederick J.] Portland VA Med Ctr, Natl Ctr Rehabilitat Auditory Res, Portland, OR USA. [Souza, Pamela E.] Northwestern Univ, Evanston, IL USA. RP Brennan, MA (reprint author), Univ Washington, Seattle, WA 98195 USA. EM Marc.Brennan@boystown.org FU National Institutes of Health [F31 DC010978-01, P30 DC 04661, T32 DC000033, R01 DC011548, R01 DC006014, I01 RX000536, VA-RRD CD2 C4963W] FX The authors wish to thank Ryan McCreery for assistance with the statistical analysis. This work was supported by National Institutes of Health Grants F31 DC010978-01, P30 DC 04661, T32 DC000033, R01 DC011548, R01 DC006014, I01 RX000536, and VA-RR&D CD2 C4963W. A portion of these data were presented at the 2010 American Auditory Society Annual Meeting and at the 2010 International Hearing Aid Research Conference. NR 35 TC 3 Z9 3 U1 0 U2 3 PU AMER SPEECH-LANGUAGE-HEARING ASSOC PI ROCKVILLE PA 10801 ROCKVILLE PIKE, ROCKVILLE, MD 20852-3279 USA SN 1059-0889 EI 1558-9137 J9 AM J AUDIOL JI Am. J. Audiol. PD DEC PY 2013 VL 22 IS 2 BP 216 EP 225 DI 10.1044/1059-0889(2013/13-0001) PG 10 WC Audiology & Speech-Language Pathology; Otorhinolaryngology SC Audiology & Speech-Language Pathology; Otorhinolaryngology GA 294EF UT WOS:000330024500003 PM 23824436 ER PT J AU John, J Thannickal, TC McGregor, R Ramanathan, L Ohtsu, H Nishino, S Sakai, N Yamanaka, A Stone, C Cornford, M Siegel, JM AF John, Joshi Thannickal, Thomas C. McGregor, Ronald Ramanathan, Lalini Ohtsu, Hiroshi Nishino, Seiji Sakai, Noriaki Yamanaka, Akhiro Stone, Carly Cornford, Marcia Siegel, Jerome M. TI Greatly Increased Numbers of Histamine Cells in Human Narcolepsy with Cataplexy SO ANNALS OF NEUROLOGY LA English DT Article ID CEREBROSPINAL-FLUID HISTAMINE; HYPOCRETIN OREXIN; PARKINSONS-DISEASE; TUBEROMAMMILLARY NUCLEUS; HISTIDINE-DECARBOXYLASE; NEURONS; SYSTEM; RECEPTOR; MICE; SLEEP AB ObjectiveTo determine whether histamine cells are altered in human narcolepsy with cataplexy and in animal models of this disease. MethodsImmunohistochemistry for histidine decarboxylase (HDC) and quantitative microscopy were used to detect histamine cells in human narcoleptics, hypocretin (Hcrt) receptor-2 mutant dogs, and 3 mouse narcolepsy models: Hcrt (orexin) knockouts, ataxin-3-orexin, and doxycycline-controlled-diphtheria-toxin-A-orexin. ResultsWe found an average 64% increase in the number of histamine neurons in human narcolepsy with cataplexy, with no overlap between narcoleptics and controls. However, we did not see altered numbers of HDC cells in any of the animal models of narcolepsy. InterpretationChanges in histamine cell numbers are not required for the major symptoms of narcolepsy, because all animal models have these symptoms. The histamine cell changes we saw in humans did not occur in the 4 animal models of Hcrt dysfunction we examined. Therefore, the loss of Hcrt receptor-2, of the Hcrt peptide, or of Hcrt cells is not sufficient to produce these changes. We speculate that the increased histamine cell numbers we see in human narcolepsy may instead be related to the process causing the human disorder. Although research has focused on possible antigens within the Hcrt cells that might trigger their autoimmune destruction, the present findings suggest that the triggering events of human narcolepsy may involve a proliferation of histamine-containing cells. We discuss this and other explanations of the difference between human narcoleptics and animal models of narcolepsy, including therapeutic drug use and species differences. Ann Neurol 2013;74:786-793 C1 [John, Joshi; Thannickal, Thomas C.; McGregor, Ronald; Ramanathan, Lalini; Stone, Carly; Siegel, Jerome M.] Univ Calif Los Angeles, Inst Neuropsychiat, Vet Adm Greater Los Angeles Healthcare Syst, Los Angeles, CA 90024 USA. [John, Joshi; Thannickal, Thomas C.; McGregor, Ronald; Ramanathan, Lalini; Stone, Carly; Siegel, Jerome M.] Univ Calif Los Angeles, Brain Res Inst, Los Angeles, CA 90024 USA. [Ohtsu, Hiroshi] Tohoku Univ, Grad Sch Engn, Sendai, Miyagi 980, Japan. [Nishino, Seiji; Sakai, Noriaki] Stanford Univ, Sch Med, Stanford Sleep Res Ctr, Palo Alto, CA 94304 USA. [Yamanaka, Akhiro] Nagoya Univ, Environm Med Res Inst, Dept Neurosci 2, Nagoya, Aichi 464, Japan. [Cornford, Marcia] Harbor Univ Calif, Los Angeles Med Ctr, Dept Pathol, Torrance, CA USA. RP John, J (reprint author), Univ Calif Los Angeles, VA GLAHS, 16111 Plummer St, North Hills, CA 91343 USA. EM jjohn@ucla.edu; thomastc@ucla.edu; JSiegel@ucla.edu FU Medical Research Service of the Department of Veterans Affairs; NIH [NS14610, MH064109] FX This study was supported by the Medical Research Service of the Department of Veterans Affairs and NIH grants NS14610 and MH064109 to J.M.S. NR 47 TC 31 Z9 31 U1 1 U2 11 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 DEC PY 2013 VL 74 IS 6 BP 786 EP 793 DI 10.1002/ana.23968 PG 8 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 292GV UT WOS:000329891100009 PM 23821583 ER PT J AU Cruzat, A Shukla, A Dohlman, CH Colby, K AF Cruzat, Andrea Shukla, Anita Dohlman, Claes H. Colby, Kathryn TI Wound Anatomy After Type 1 Boston KPro Using Oversized Back Plates SO CORNEA LA English DT Article DE keratoprosthesis; retroprosthetic membrane; corneal wound anatomy ID OPTICAL COHERENCE TOMOGRAPHY; RETROPROSTHETIC MEMBRANES; ENDOTHELIAL KERATOPLASTY; RISK-FACTORS; KERATOPROSTHESIS; PACHYMETRY; OUTCOMES; CORNEA; DOMAIN AB Purpose:To compare the anatomy of the graft-host junction and anterior chamber angle after Boston Keratoprosthesis (KPro) placement using oversized (9.5-mm) and standard (8.5-mm) back plates.Methods:Six patients with 9.5-mm titanium back plates and 10 patients with 8.5-mm titanium back plates were imaged by anterior segment optical coherence tomography 6 to 12 months after KPro placement. The location of the graft-host junction in relation to the back plate, the corneal thickness at the graft-host junction, and the anterior chamber angle were assessed. The clinical outcomes and incidence of retroprosthetic membrane (RPM) formation in this cohort were retrospectively evaluated.Results:The oversized back plates completely covered the graft-host junction in all quadrants, allowing the complete apposition of the posterior surface of the carrier graft with the host cornea, with decreased graft-host junction wound thickness. The standard back plates covered the posterior aspect of the carrier graft but not the graft-host junction or the host cornea, resulting in a significantly thicker graft-host junction. None of the patients with larger back plates developed a significant RPM during a 12-month follow-up period. One patient with a larger back plate developed a corneal melt at the KPro stem as a result of chronic exposure.Conclusions:Oversized KPro back plates effectively cover the graft-host junction without any adverse effects on angle anatomy or wound healing. This may be a strategy to provide better wound apposition, reduce RPM formation, and reduce angle closure from iris synechiae to the wound. C1 Massachusetts Eye & Ear Infirm, Cornea & Refract Surg Serv, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Ophthalmol, Boston, MA USA. RP Colby, K (reprint author), Massachusetts Eye & Ear Infirm, 243 Charles St, Boston, MA 02114 USA. EM kacolby@meei.harvard.edu OI Cruzat, Andrea/0000-0002-3724-7037 FU Boston Keratoprosthesis Research Fund, Massachusetts Eye and Ear Infirmary FX Supported by the Boston Keratoprosthesis Research Fund, Massachusetts Eye and Ear Infirmary. NR 33 TC 7 Z9 7 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0277-3740 EI 1536-4798 J9 CORNEA JI Cornea PD DEC PY 2013 VL 32 IS 12 BP 1531 EP 1536 DI 10.1097/ICO.0b013e3182a854ac PG 6 WC Ophthalmology SC Ophthalmology GA 292SX UT WOS:000329923800007 PM 24097186 ER PT J AU Carchman, EH Whelan, S Loughran, P Mollen, K Stratamirovic, S Shiva, S Rosengart, MR Zuckerbraun, BS AF Carchman, Evie H. Whelan, Sean Loughran, Patricia Mollen, Kevin Stratamirovic, Sladjana Shiva, Sruti Rosengart, Matthew R. Zuckerbraun, Brian S. TI Experimental sepsis-induced mitochondrial biogenesis is dependent on autophagy, TLR4, and TLR9 signaling in liver SO FASEB JOURNAL LA English DT Article DE lipopolysaccharide; Toll-like receptor 4; VPS34; peroxisome proliferator-activated receptor-gamma coactivator; PGC-1 alpha ID NITRIC-OXIDE; IN-VITRO; INFLAMMATORY RESPONSES; ADAPTIVE IMMUNITY; INNATE; DNA; FAILURE; MICE; HEPATOCYTES; ACTIVATION AB Organ injury in sepsis is initially characterized by dysfunction without cell death and structural damage, and thus with the ability to recover organ function. Adaptive metabolic responses to sepsis can prevent bioenergetic failure and death. These studies were aimed at investigating the influence of sepsis on mitochondrial homeostasis, focusing on removal of dysfunctional mitochondria and restitution of a healthy mitochondrial population. These data demonstrate decreased hepatic oxidative phosphorylation by 31 +/- 11% following murine cecal ligation and puncture (CLP) at 8 h and 34 +/- 9% following LPS treatment in vitro at 12 h (P<0.05). In addition, there was a loss of mitochondrial membrane potential. Mitochondrial density and number initially decreased (relative area per micrograph of 64 +/- 10% at baseline vs. 39 +/- 13% at 8 h following LPS; P<0.05) and was associated with an increase in autophagy and mitophagy. CLP-induced markers of mitochondrial biogenesis and mitochondrial number and density recovered over time. Furthermore, these data suggest that mitochondrial biogenesis was dependent on an autophagy and mitochondrial DNA/Toll-like receptor 9 (TLR9) signaling pathway. These results suggest that hepatocyte survival and maintenance of function in sepsis is dependent on a mitochondrial homeostasis pathway marked by mitophagy and biogenesis. C1 [Carchman, Evie H.; Whelan, Sean; Loughran, Patricia; Mollen, Kevin; Stratamirovic, Sladjana; Rosengart, Matthew R.; Zuckerbraun, Brian S.] Univ Pittsburgh, Dept Surg, Pittsburgh, PA USA. [Shiva, Sruti] Univ Pittsburgh, Dept Pharmacol, Pittsburgh, PA 15261 USA. [Shiva, Sruti; Zuckerbraun, Brian S.] Univ Pittsburgh, Vasc Med Inst, Pittsburgh, PA USA. [Carchman, Evie H.; Loughran, Patricia; Stratamirovic, Sladjana; Zuckerbraun, Brian S.] Vet Affairs Pittsburgh Healthcare Syst, Pittsburgh, PA USA. RP Zuckerbraun, BS (reprint author), F1200PUH,200 Lothrop St, Pittsburgh, PA 15213 USA. EM zuckerbraunbs@upmc.edu FU U.S. National Institutes of Health [R01 GM082830, GM082852]; U.S. Veterans Affairs Merit Award [1I01BX000566]; U.S. Department of Defense grant [DM102439] FX This work is supported by U.S. National Institutes of Health grants R01 GM082830 (B.S.Z.) and GM082852 (M. R. R.), U.S. Veterans Affairs Merit Award 1I01BX000566 (B.S.Z.), and U.S. Department of Defense grant DM102439 (B.S.Z.). Author contributions: E. H. C. and B.S.Z., study concept and design; E. H. C., S. P. W., and P. L., acquisition of data; E. H. C., M. R. R., S.Sh., K. P. M., and B.S.Z., analysis and interpretation of data; E. H. C., S. P. M., and B.S.Z., drafting of the manuscript; E. H. C. and B.S.Z., critical revision of the manuscript for important intellectual content and statistical analysis; B.S.Z., acquisition of funding; S.St., technical support. The authors declare no conflicts of interest. NR 36 TC 23 Z9 29 U1 0 U2 17 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 EI 1530-6860 J9 FASEB J JI Faseb J. PD DEC PY 2013 VL 27 IS 12 BP 4703 EP 4711 DI 10.1096/fj.13-229476 PG 9 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 293UK UT WOS:000329999000006 PM 23982147 ER PT J AU Lee, RJ Chen, B Doghramji, L Adappa, ND Palmer, JN Kennedy, DW Cohen, NA AF Lee, Robert J. Chen, Bei Doghramji, Laurel Adappa, Nithin D. Palmer, James N. Kennedy, David W. Cohen, Noam A. TI Vasoactive intestinal peptide regulates sinonasal mucociliary clearance and synergizes with histamine in stimulating sinonasal fluid secretion SO FASEB JOURNAL LA English DT Article DE allergic rhinitis; chronic rhinosinusitis; ciliary beat frequency; cystic fibrosis transmembrane conductance regulator; CFTR ID CILIARY BEAT FREQUENCY; HUMAN NASAL-MUCOSA; PERENNIAL ALLERGIC RHINITIS; SEROUS ACINAR-CELLS; CHRONIC RHINOSINUSITIS; CYSTIC-FIBROSIS; NITRIC-OXIDE; RECEPTOR PHARMACOLOGY; NEUTRAL ENDOPEPTIDASE; MESSENGER-RNA AB Mucociliary clearance (MCC) is the primary physical airway defense against inhaled pathogens and particulates. MCC depends on both proper fluid/mucus homeostasis and epithelial ciliary beating. Vasoactive intestinal peptide (VIP) is a neurotransmitter expressed in the sinonasal epithelium that is up-regulated in allergy. However, the effects of VIP on human sinonasal physiology are unknown, as are VIP's interactions with histamine, a major regulator of allergic disease. We imaged ciliary beat frequency, mucociliary transport, apical Cl- permeability, and airway surface liquid (ASL) height in primary human sinonasal air-liquid-interface cultures to investigate the effects of VIP and histamine. VIP stimulated an increase in ciliary beat frequency (EC50 0.5 mu M; maximal increase similar to 40% compared with control) and cystic fibrosis transmembrane conductance regulator (CFTR)-dependent and Na(+)K(+)2Cl(-) cotransporter-dependent fluid secretion, all requiring cAMP/PKA signaling. Histamine activated Ca2+ signaling that increased ASL height but not ciliary beating. Low concentrations of VIP and histamine had synergistic effects on CFTR-dependent fluid secretion, revealed by increased ASL heights. An up-regulation of VIP in histamine-driven allergic rhinitis would likely enhance mucosal fluid secretion and contribute to allergic rhinorrhea. Conversely, a loss of VIP-activated secretion in patients with CF may impair mucociliary transport, contributing to increased incidences of sinonasal infections and rhinosinusitis. C1 [Lee, Robert J.; Chen, Bei; Doghramji, Laurel; Adappa, Nithin D.; Palmer, James N.; Kennedy, David W.; Cohen, Noam A.] Univ Penn, Dept Otorhinolaryngol Head & Neck Surg, Philadelphia, PA 19104 USA. [Cohen, Noam A.] Philadelphia Vet Affairs Med Ctr, Surg Serv, Philadelphia, PA USA. RP Cohen, NA (reprint author), Hosp Univ Penn, Dept Otorhinolaryngol Head & Neck Surg, Ravdin Bldg,5th Floor,3400 Spruce St, Philadelphia, PA 19104 USA. EM cohenn@uphs.upenn.edu OI Cohen, Noam/0000-0002-9462-3932; Lee, Robert/0000-0001-5826-6686 FU Flight Attendants Medical Research Institute FX This work was supported by a grant from The Flight Attendants Medical Research Institute and a philanthropic contribution from the RLG Foundation, Inc. (to N.A.C.). NR 69 TC 18 Z9 18 U1 0 U2 3 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 EI 1530-6860 J9 FASEB J JI Faseb J. PD DEC PY 2013 VL 27 IS 12 BP 5094 EP 5103 DI 10.1096/fj.13-234476 PG 10 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 293UK UT WOS:000329999000041 PM 23934280 ER PT J AU Bever, GJ Jakobiec, FA Mendoza, PR Hatton, MP AF Bever, Gregory J. Jakobiec, Frederick A. Mendoza, Pia R. Hatton, Mark P. TI Congenital Megacaruncle: A Unique and Innocent Ocular Adnexal Anomaly SO JAMA OPHTHALMOLOGY LA English DT Letter ID CARUNCLE C1 [Bever, Gregory J.] Boston Univ, Sch Med, Boston, MA 02118 USA. [Jakobiec, Frederick A.; Mendoza, Pia R.] Massachusetts Eye & Ear Infirm, David G Cogan Lab Ophthalm Pathol, Boston, MA 02114 USA. [Jakobiec, Frederick A.; Mendoza, Pia R.; Hatton, Mark P.] Harvard Univ, Sch Med, Dept Ophthalmol, Boston, MA 02115 USA. [Hatton, Mark P.] Ophthalm Consultants Boston, Boston, MA USA. RP Jakobiec, FA (reprint author), Massachusetts Eye & Ear Infirm, David G Cogan Lab Ophthalm Pathol, 243 Charles St,Ste 328, Boston, MA 02114 USA. EM fred_jakobiec@meei.harvard.edu NR 8 TC 1 Z9 1 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60654-0946 USA SN 2168-6165 EI 2168-6173 J9 JAMA OPHTHALMOL JI JAMA Ophthalmol. PD DEC PY 2013 VL 131 IS 12 BP 1641 EP 1643 DI 10.1001/jamaophthalmo1.2013.4401 PG 3 WC Ophthalmology SC Ophthalmology GA 291SU UT WOS:000329850600025 PM 24113762 ER PT J AU Miller, FG Joffe, S AF Miller, Franklin G. Joffe, Steven TI Phase 1 oncology trials and informed consent SO JOURNAL OF MEDICAL ETHICS LA English DT Article DE Informed Consent ID I CANCER TRIALS; THERAPEUTIC MISCONCEPTION; CLINICAL-TRIALS; BENEFIT; COMMUNICATION; PERCEPTIONS; PHYSICIANS AB Ethical concerns have been raised about the quality of informed consent by participants in phase 1 oncology trials. Interview surveys indicate that substantial proportions of trial participants do not understand the purpose of these trialsevaluating toxicity and dosing for subsequent efficacy studiesand overestimate the prospect of therapeutic benefit that they offer. In this article we argue that although these data suggest the desirability of enhancing the process of information disclosure and assessment of comprehension of the implications of study participation, they do not necessarily invalidate consent by phase 1 trial participants. C1 [Miller, Franklin G.] NIH, Dept Bioeth, Bethesda, MD 20892 USA. [Joffe, Steven] Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. RP Miller, FG (reprint author), NIH, Warren G Magnuson Clin Ctr, Bldg 10,Room 1C118, Bethesda, MD 20892 USA. EM fmiller@nih.gov OI Joffe, Steven/0000-0002-0667-7384 NR 25 TC 7 Z9 7 U1 0 U2 4 PU BMJ PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0306-6800 EI 1473-4257 J9 J MED ETHICS JI J. Med. Ethics PD DEC PY 2013 VL 39 IS 12 BP 761 EP 764 DI 10.1136/medethics-2012-100832 PG 4 WC Ethics; Medical Ethics; Social Issues; Social Sciences, Biomedical SC Social Sciences - Other Topics; Medical Ethics; Social Issues; Biomedical Social Sciences GA 291EG UT WOS:000329809900011 PM 23161617 ER PT J AU McDuff, SGR Taich, ZJ Lawson, JD Sanghvi, P Wong, ET Barker, FG Hochberg, FH Loeffler, JS Warnke, PC Murphy, KT Mundt, AJ Carter, BS McDonald, CR Chen, CC AF McDuff, Susan G. R. Taich, Zachary J. Lawson, Joshua D. Sanghvi, Parag Wong, Eric T. Barker, Fred G., II Hochberg, Fred H. Loeffler, Jay S. Warnke, Peter C. Murphy, Kevin T. Mundt, Arno J. Carter, Bob S. McDonald, Carrie R. Chen, Clark C. TI Neurocognitive assessment following whole brain radiation therapy and radiosurgery for patients with cerebral metastases SO JOURNAL OF NEUROLOGY NEUROSURGERY AND PSYCHIATRY LA English DT Review ID PROPHYLACTIC CRANIAL IRRADIATION; CELL LUNG-CANCER; CENTRAL-NERVOUS-SYSTEM; VERBAL-LEARNING TEST; PARTITIONING ANALYSIS RPA; MENTAL-STATE-EXAMINATION; DNA-REPAIR GENES; QUALITY-OF-LIFE; PHASE-III TRIAL; BREAST-CANCER AB The treatment of metastatic brain lesions remains a central challenge in oncology. Because most chemotherapeutic agents do not effectively cross the blood-brain barrier, it is widely accepted that radiation remains the primary modality of treatment. The mode by which radiation should be delivered has, however, become a source of intense controversy in recent years. The controversy involves whether patients with a limited number of brain metastases should undergo whole brain radiation therapy (WBRT) or stereotactic radiosurgery (SRS) delivered only to the radiographically visible tumours. Survival is comparable for patients treated with either modality. Instead, the controversy involves the neurocognitive function (NCF) of radiating cerebrum that appeared radiographically normal relative to effects of the growth from micro-metastatic foci. A fundamental question in this debate involves quantifying the effect of WBRT in patients with cerebral metastasis. To disentangle the effects of WBRT on neurocognition from the effects inherent to the underlying disease, we analysed the results from randomised controlled studies of prophylactic cranial irradiation in oncology patients as well as studies where patients with limited cerebral metastasis were randomised to SRS versus SRS+WBRT. In aggregate, these results suggest deleterious effects of WBRT in select neurocognitive domains. However, there are insufficient data to resolve the controversy of upfront WBRT versus SRS in the management of patients with limited cerebral metastases. C1 [McDuff, Susan G. R.; Taich, Zachary J.; Carter, Bob S.; Chen, Clark C.] Univ Calif San Diego, Ctr Theoret & Appl Neurooncol, La Jolla, CA 92093 USA. [Lawson, Joshua D.; Sanghvi, Parag; Murphy, Kevin T.; Mundt, Arno J.] Univ Calif San Diego, Dept Radiat Med & Appl Sci, La Jolla, CA 92093 USA. [Wong, Eric T.] Beth Israel Deaconess Med Ctr, Dept Neurol, Boston, MA 02215 USA. [Barker, Fred G., II; Hochberg, Fred H.] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. [Loeffler, Jay S.] Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. [Warnke, Peter C.] Univ Chicago, Med Ctr, Div Neurosurg, Chicago, IL 60637 USA. [Carter, Bob S.; Chen, Clark C.] Univ Calif San Diego, Div Neurosurg, La Jolla, CA 92093 USA. [McDonald, Carrie R.] Univ Calif San Diego, Dept Psychiat, La Jolla, CA 92093 USA. [McDonald, Carrie R.] Univ Calif San Diego, Multimodal Imaging Lab, La Jolla, CA 92093 USA. RP Chen, CC (reprint author), Univ Calif San Diego, Div Neurosurg, Director Stereotact & Radiosurg, 3855 Hlth Sci Dr 0987, La Jolla, CA 92093 USA. EM clarkchen@ucsd.edu OI Taich, Zachary/0000-0002-2533-0888 FU San Diego Gamma Knife Center; Doris Duke Charitable Foundation; Sontag Foundation; Burroughs Wellcome Fund; Forbeck Foundation; Kimmel Foundation FX ZT is supported by an educational grant from the San Diego Gamma Knife Center. CCC is supported by the Doris Duke Charitable Foundation, Sontag Foundation, Burroughs Wellcome Fund, Forbeck Foundation, and Kimmel Foundation. NR 89 TC 27 Z9 28 U1 0 U2 5 PU BMJ PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0022-3050 EI 1468-330X J9 J NEUROL NEUROSUR PS JI J. Neurol. Neurosurg. Psychiatry PD DEC PY 2013 VL 84 IS 12 BP 1384 EP 1391 DI 10.1136/jnnp-2013-305166 PG 8 WC Clinical Neurology; Psychiatry; Surgery SC Neurosciences & Neurology; Psychiatry; Surgery GA 292QB UT WOS:000329916000019 PM 23715918 ER PT J AU Belkind-Gerson, J Surjanhata, B Kuo, B Goldstein, AM AF Belkind-Gerson, Jaime Surjanhata, Brian Kuo, Braden Goldstein, Allan M. TI Bear-Down Maneuver Is a Useful Adjunct in the Evaluation of Children With Chronic Constipation SO JOURNAL OF PEDIATRIC GASTROENTEROLOGY AND NUTRITION LA English DT Article DE anorectal manometry; balloon expulsion test; bear-down maneuver; constipation; dyssynergic defecation ID DYSFUNCTIONAL ELIMINATION SYNDROME; DYSSYNERGIC DEFECATION; ANORECTAL MANOMETRY; CHILDHOOD CONSTIPATION; BIOFEEDBACK THERAPY; ENCOPRESIS; EFFICACY; UTILITY; TESTS AB Background and Objectives:Chronic constipation is a common problem in pediatrics and often the result of obstructed defecation. The aim of this study was to determine the use of the bear-down maneuver (BDM) in the evaluation of children with chronic constipation and to establish optimal conditions for its performance.Methods:This retrospective study compares BDM with balloon expulsion testing (BET) during anorectal manometry in 38 children with chronic constipation. BDM was performed with 0-, 20-, 40-, and 60-mL balloon inflation. BET, performed with a 60-mL balloon, was considered normal if the balloon was expelled within 1 minute.Results:Rectal pressure during BDM was 48% higher in patients able to expel the balloon during BET compared with those who could not (P<0.05). Anal canal pressure was 46% lower in patients able to expel the balloon (P<0.05). A rectoanal pressure differential greater than zero during BDM was 90% predictive that the subject would be able to expel the balloon. The optimal balloon inflation volume was 60 mL.Conclusions:BDM using an inflated balloon provides valuable mechanistic information in the evaluation of children with dyssynergic defecation. We found that patients often had either an insufficient rectal pressure during bear-down or an abnormally high anal canal pressure. This information may be useful in planning further treatment for these children. C1 [Belkind-Gerson, Jaime; Goldstein, Allan M.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Neurogastroenterol Program, Boston, MA 02114 USA. [Belkind-Gerson, Jaime] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Pediat Gastroenterol, Boston, MA 02114 USA. [Surjanhata, Brian; Kuo, Braden] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Gastrointestinal Unit, Boston, MA 02114 USA. [Goldstein, Allan M.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Pediat Surg, Boston, MA 02114 USA. RP Belkind-Gerson, J (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp Children, Neurogastroenterol Program, 175 Cambridge St,575, Boston, MA 02114 USA. EM jbelkindgerson@partners.org FU International Foundation for Functional Gastrointestinal Disorders FX Partial financial support was provided as a grant from the International Foundation for Functional Gastrointestinal Disorders. NR 23 TC 0 Z9 0 U1 1 U2 4 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 DEC PY 2013 VL 57 IS 6 BP 775 EP 779 DI 10.1097/MPG.0b013e3182a698df PG 5 WC Gastroenterology & Hepatology; Nutrition & Dietetics; Pediatrics SC Gastroenterology & Hepatology; Nutrition & Dietetics; Pediatrics GA 293AC UT WOS:000329942800018 PM 23945314 ER PT J AU Wang, J Tang, C Ferruzzi, MG Gong, B Song, BJ Janle, EM Chen, TY Cooper, B Varghese, M Cheng, A Freire, D Bilski, A Roman, J Nguyen, T Ho, L Talcott, ST Simon, JE Wu, QL Pasinetti, GM AF Wang, Jun Tang, Cheuk Ferruzzi, Mario G. Gong, Bing Song, Brian J. Janle, Elsa M. Chen, Tzu-Ying Cooper, Bruce Varghese, Merina Cheng, Alice Freire, Daniel Bilski, Amanda Roman, Jessica Tuyen Nguyen Ho, Lap Talcott, Stephen T. Simon, James E. Wu, Qingli Pasinetti, Giulio M. TI Role of standardized grape polyphenol preparation as a novel treatment to improve synaptic plasticity through attenuation of features of metabolic syndrome in a mouse model SO MOLECULAR NUTRITION & FOOD RESEARCH LA English DT Article DE Metabolic syndrome; Polyphenols; Standardized grape polyphenol preparation; Synaptic plasticity ID INDEPENDENT COMPONENT ANALYSIS; LONG-TERM POTENTIATION; ALZHEIMERS-DISEASE; COGNITIVE DETERIORATION; DIETARY POLYPHENOLS; RATS; RESVERATROL; NEUROPATHOLOGY; MEMORY; SUPPLEMENTATION AB ScopeMetabolic syndrome has become an epidemic and poses tremendous burden on the health system. People with metabolic syndrome are more likely to experience cognitive decline. As obesity and sedentary lifestyles become more common, the development of early prevention strategies is critical. In this study, we explore the potential beneficial effects of a combinatory polyphenol preparation composed of grape seed extract, Concord purple grape juice extract, and resveratrol, referred to as standardized grape polyphenol preparation (SGP), on peripheral as well as brain dysfunction induced by metabolic syndrome. Methods and resultsWe found dietary fat content had minimal effect on absorption of metabolites of major polyphenols derived from SGP. Using a diet-induced animal model of metabolic syndrome (DIM), we found that brain functional connectivity and synaptic plasticity are compromised in the DIM mice. Treatment with SGP not only prevented peripheral metabolic abnormality but also improved brain synaptic plasticity. ConclusionOur study demonstrated that SGP, comprised of multiple bioavailable and bioactive components targeting a wide range of metabolic syndrome related pathological features, provides greater global protection against peripheral and central nervous system dysfunctions and can be potentially developed as a novel prevention/treatment for improving brain connectivity and synaptic plasticity important for learning and memory. C1 [Wang, Jun; Gong, Bing; Varghese, Merina; Cheng, Alice; Freire, Daniel; Bilski, Amanda; Ho, Lap; Pasinetti, Giulio M.] Icahn Sch Med Mt Sinai, Dept Neurol, New York, NY 10029 USA. [Tang, Cheuk; Roman, Jessica; Tuyen Nguyen] Icahn Sch Med Mt Sinai, Dept Radiol, New York, NY 10029 USA. [Ferruzzi, Mario G.; Song, Brian J.; Janle, Elsa M.; Chen, Tzu-Ying; Cooper, Bruce] Purdue Univ, Dept Food Sci, W Lafayette, IN 47907 USA. [Talcott, Stephen T.] Purdue Univ, Dept Foods & Nutr, W Lafayette, IN 47907 USA. [Talcott, Stephen T.] Texas A&M Univ, Dept Nutr & Food Sci, College Stn, TX USA. [Wang, Jun; Simon, James E.; Wu, Qingli] Rutgers State Univ, Dept Plant Biol & Pathol, New Use Agr & Nat Plant Prod Program, New Brunswick, NJ 08903 USA. [Ho, Lap; Pasinetti, Giulio M.] James J Peters Vet Affairs Med Ctr, Geriatr Res Educ & Clin Ctr, Bronx, NY USA. RP Pasinetti, GM (reprint author), Icahn Sch Med Mt Sinai, Dept Neurol, 1 Gustave L Levy Pl,Box 1137, New York, NY 10029 USA. EM giulio.pasinetti@mssm.edu OI Varghese, Merina/0000-0002-1517-3903 FU NIH [AT004511] FX This study was supported by NIH grant AT004511. NR 48 TC 10 Z9 10 U1 0 U2 9 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1613-4125 EI 1613-4133 J9 MOL NUTR FOOD RES JI Mol. Nutr. Food Res. PD DEC PY 2013 VL 57 IS 12 BP 2091 EP 2102 DI 10.1002/mnfr.201300230 PG 12 WC Food Science & Technology SC Food Science & Technology GA 293AZ UT WOS:000329945100001 PM 23963661 ER PT J AU Walker, RH Fink, JK AF Walker, Ruth H. Fink, John K. TI Morphea and Parry-Romberg syndrome associated with a mixed movement disorder SO PARKINSONISM & RELATED DISORDERS LA English DT Letter DE Parry-Romberg; Morphea; Scleroderma; Dystonia; Hemiparkinsonism ID LOCALIZED SCLERODERMA; FOCAL DYSTONIA C1 [Walker, Ruth H.] James J Peters Vet Affairs Med Ctr, Dept Neurol, Bronx, NY 10468 USA. [Walker, Ruth H.] Mt Sinai Sch Med, New York, NY USA. [Fink, John K.] Univ Michigan, Dept Neurol, Ann Arbor, MI USA. [Fink, John K.] Ann Arbor Vet Med Ctr, Geriatr Res Educ & Clin Ctr, Ann Arbor, MI USA. RP Walker, RH (reprint author), James J Peters Vet Affairs Med Ctr, Dept Neurol, 130 W Kingsbridge Rd, Bronx, NY 10468 USA. EM ruth.walker@mssm.edu FU NINDS NIH HHS [R01 NS069700, R01NS069700] NR 5 TC 1 Z9 2 U1 0 U2 0 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 DEC PY 2013 VL 19 IS 12 BP 1169 EP 1170 DI 10.1016/j.parkreldis.2013.07.025 PG 2 WC Clinical Neurology SC Neurosciences & Neurology GA 295AV UT WOS:000330089900021 PM 23968650 ER PT J AU Wei, JX Mialki, RK Dong, S Khoo, A Mallampalli, RK Zhao, YT Zhao, J AF Wei, Jianxin Mialki, Rachel K. Dong, Su Khoo, Andrew Mallampalli, Rama K. Zhao, Yutong Zhao, Jing TI A new mechanism of RhoA ubiquitination and degradation: Roles of SCFFBXL19 E3 ligase and Erk2 SO BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR CELL RESEARCH LA English DT Article DE Small GTPase protein; Protein stability; Ubiquitin-proteasome system; Phosphorylation; Cell proliferation; Stress fiber ID SIGNAL-INDUCED UBIQUITINATION; KAPPA-B-ALPHA; F-BOX; DEPENDENT PROTEOLYSIS; ACTIN CYTOSKELETON; CELL-CYCLE; PROTEASOME PATHWAY; C-MYC; PROTEIN; PHOSPHORYLATION AB RhoA is a small GTPase multifunctional protein that regulates cell proliferation and cytoskeletal reorganization. Regulation of its protein stability plays an important role in its biological functions. We have shown that a Skp1-Cul1-F-box (SCF) FBXL19 E3 ubiquitin ligase targets Rac1, a related member of the Rho family for ubiquitination and degradation. Here, SCFFBXL19:19 mediates RhoA ubiquitination and proteasomal degradation in lung epithelial cells. Ectopically expressed FBXL19 decreased RhoA wild type, active, and inactive forms. Cellular depletion of FBXL19 increased RhoA protein levels and extended its half-life. FBXL19 bound the small GTPase in the cytoplasm leading to RhoA ubiquitination at Lys(135). A RhoA(K135R) mutant protein was resistant to SCFFBXL19-mediated ubiquitination and degradation and exhibited a longer lifespan. Protein kinase Erk2-mediated phosphorylation of RhoA was both sufficient and required for SCFFBXL19-mediated RhoA ubiquitination and degradation. Thus, SCFFBXL19 targets RhoA for its disposal, a process regulated by Erk2. Ectopically expressed FBXL19 reduced phosphorylation of p27 and cell proliferation, a process mediated by RhoA. Further, FBXL19 cellular expression diminished lysophosphatidic acid (LPA)-induced phosphorylation of myosin light chain (MLC) and stress fiber formation. Hence, SCFFBXL19 functions as a RhoA antagonist during cell proliferation and cytoskeleton rearrangement These results provide the first evidence of an F-box protein targeting RhoA thereby modulating its cellular lifespan that impacts cell proliferation and cytoskeleton rearrangement. (c) 2013 Elsevier B.V. All rights reserved. C1 [Wei, Jianxin; Mialki, Rachel K.; Dong, Su; Khoo, Andrew; Mallampalli, Rama K.; Zhao, Yutong; Zhao, Jing] Univ Pittsburgh, Sch Med, Dept Med, Pittsburgh, PA 15213 USA. [Wei, Jianxin; Mialki, Rachel K.; Dong, Su; Khoo, Andrew; Mallampalli, Rama K.; Zhao, Yutong; Zhao, Jing] Univ Pittsburgh, Sch Med, Acute Lung Injury Ctr Excellence, Pittsburgh, PA 15213 USA. [Mallampalli, Rama K.] Univ Pittsburgh, Sch Med, Dept Cell Biol & Physiol, Pittsburgh, PA 15213 USA. [Mallampalli, Rama K.] Vet Affairs Pittsburgh Healthcare Syst, Med Specialty Serv Line, Pittsburgh, PA USA. [Dong, Su] Jilin Univ, Hosp 1, Dept Anesthesia, Changchun 130023, Jilin, Peoples R China. RP Zhao, J (reprint author), Univ Pittsburgh, Sch Med, Dept Med, 3459 5th Ave NW,628 MUH, Pittsburgh, PA 15213 USA. EM zhaoj@upmc.edu RI Wei, Jianxin/P-5431-2016 FU US National Institutes of Health [RO1 HL01916, HL112791, HL096376, HL097376, HL098174]; American Heart Association [12SDG9050005]; US Department of Veterans Affairs FX This study was supported by the US National Institutes of Health RO1 HL01916 and HL112791 (to Y.Z.), HL096376, HL097376 and HL098174 (to R.K.M.), American Heart Association awards 12SDG9050005 (J.Z.), and a Merit Review Award from the US Department of Veterans Affairs (to R.K.M.). NR 43 TC 13 Z9 14 U1 1 U2 6 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0167-4889 EI 0006-3002 J9 BBA-MOL CELL RES JI Biochim. Biophys. Acta-Mol. Cell Res. PD DEC PY 2013 VL 1833 IS 12 BP 2757 EP 2764 DI 10.1016/j.bbamcr2013.07.005 PG 8 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 288FA UT WOS:000329596200019 PM 23871831 ER PT J AU Nunn, ME Fish, MD Garcia, RI Kaye, EK Figueroa, R Gohel, A Ito, M Lee, HJ Williams, DE Miyamoto, T AF Nunn, M. E. Fish, M. D. Garcia, R. I. Kaye, E. K. Figueroa, R. Gohel, A. Ito, M. Lee, H. J. Williams, D. E. Miyamoto, T. TI Retained Asymptomatic Third Molars and Risk for Second Molar Pathology SO JOURNAL OF DENTAL RESEARCH LA English DT Article DE caries; periodontal disease; cohort study; alveolar bone loss; longitudinal study ID PERIODONTAL PATHOLOGY; YOUNG-ADULTS; HEALTH; DISEASE; TIME AB Prophylactic extraction of unerupted asymptomatic third molars is the most common oral surgery procedure in the United States. However, limited evidence exists to justify its costs and associated morbidity. We analyzed data collected over 25 years from 416 adult men enrolled in the Veterans Affairs Dental Longitudinal Study to evaluate the association of retained asymptomatic third molars with risk of adjacent second molar pathology (caries and/or periodontitis), based on third molar status (i.e., absent, erupted, or unerupted). Unerupted molars were further categorized as either soft tissue or bony impacted. We found that the lowest prevalence and incidence of second molar pathology occurred when the adjacent third molar was absent. The presence of a third molar that was soft tissue impacted increased the risk of incident second molar pathology 4.88-fold (95% confidence interval: 2.62, 9.08). Having an erupted or bony impacted third molar increased the risk of incident second molar pathology by 1.74 (95% confidence interval: 1.34, 2.25) and 2.16 (95% confidence interval: 1.56, 2.99), respectively. The retention of third molars is associated with increased risk of second molar pathology in middle-aged and older adult men. C1 [Nunn, M. E.; Miyamoto, T.] Creighton Univ, Sch Dent, Dept Periodontol, Omaha, NE 68178 USA. [Fish, M. D.; Garcia, R. I.; Kaye, E. K.] Boston Univ, Henry M Goldman Sch Dent Med, Dept Hlth Policy & Hlth Serv Res, Boston, MA 02215 USA. [Garcia, R. I.] VA Boston Healthcare Syst, Boston, MA USA. [Figueroa, R.] Boston Univ, Henry M Goldman Sch Dent Med, Dept Oral & Maxillofacial Surg, Boston, MA 02215 USA. [Gohel, A.] Boston Univ, Henry M Goldman Sch Dent Med, Dept Oral & Maxillofacial Radiol, Boston, MA 02215 USA. [Ito, M.] Nihon Univ, Sch Dent Matsudo, Dept Removable Prosthodont, Chiba, Japan. [Lee, H. J.] Seoul Natl Univ, Bundang Hosp, Dept Periodontol, Songnam, South Korea. [Williams, D. E.] Creighton Univ, Sch Dent, Dept Oral & Maxillofacial Surg, Omaha, NE 68178 USA. RP Nunn, ME (reprint author), Creighton Univ, Sch Dent, Dept Periodontol, Omaha, NE 68178 USA. EM nunn@creighton.edu FU U.S. Department of Veterans Affairs Cooperative Studies Program; National Institute of Dental and Craniofacial Research [K24 DE000419, R01 DE019656]; Veterans Affairs Health Services Research and Development Service FX The Veterans Affairs Dental Longitudinal Study and Normative Aging Study are components of the Massachusetts Veterans Epidemiology Research and Information Center, supported by the U.S. Department of Veterans Affairs Cooperative Studies Program. Dr. Garcia was a recipient of a Veterans Affairs Career Development Award in Health Services Research from the Veterans Affairs Health Services Research and Development Service. This work was also supported by the National Institute of Dental and Craniofacial Research (K24 DE000419 and R01 DE019656). Views expressed in this article are solely those of the authors and do not necessarily represent the views of the U.S. Department of Veterans Affairs. The authors declare no potential conflicts of interest with respect to the authorship and/or publication of this article. NR 21 TC 18 Z9 18 U1 1 U2 3 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0022-0345 EI 1544-0591 J9 J DENT RES JI J. Dent. Res. PD DEC PY 2013 VL 92 IS 12 BP 1095 EP 1099 DI 10.1177/0022034513509281 PG 5 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 286SZ UT WOS:000329490300008 PM 24132082 ER PT J AU Pugach, MK Suggs, C Li, Y Wright, JT Kulkarni, AB Bartlett, JD Gibson, CW AF Pugach, M. K. Suggs, C. Li, Y. Wright, J. T. Kulkarni, A. B. Bartlett, J. D. Gibson, C. W. TI M180 Amelogenin Processed by MMP20 is Sufficient for Decussating Murine Enamel SO JOURNAL OF DENTAL RESEARCH LA English DT Article DE matrix metalloproteinase-20; knockout mouse; transgenic mouse; amelogenesis; imperfecta; ameloblasts; tooth calcification ID NULL MOUSE ENAMEL; DENTAL ENAMEL; IMPERFECTA PHENOTYPE; MICE DISPLAY; MMP-20; MATRIX; EXPRESSION; PROTEINS; CLEAVAGE; RESCUE AB Amelogenin (AMELX) and matrix metalloproteinase-20 (MMP20) are essential for proper enamel development. Amelx and Mmp20 mutations cause amelogenesis imperfecta. MMP20, a protease secreted by ameloblasts, is responsible for processing enamel proteins, including AMELX, during the secretory stage of enamel formation. Of at least 16 different amelogenin splice products, the most abundant isoform found in murine ameloblasts and developing enamel is the M180 protein. To understand the role of MMP20 processing of M180 AMELX, we generated AmelxKO/Mmp20KO (DKO) mice with an amelogenin (M180Tg) transgene. We analyzed the enamel phenotype by SEM to determine enamel structure and thickness, mu CT, and by nanoindentation to quantify enamel mechanical properties. M180Tg/DKO mouse enamel had 37% of the hardness of M180Tg/AmelxKO teeth and demonstrated a complete lack of normal prismatic architecture. Although molar enamel of M180Tg/AmelxKO mice was thinner than WT, it had similar mechanical properties and decussating enamel prisms, which were abolished by the loss of MMP20 in the M180Tg/DKO mice. Retention of the C-terminus or complete lack of this domain is unable to rescue amelogenin null enamel. We conclude that among amelogenins, M180 alone is sufficient for normal enamel mechanical properties and prism patterns, but that additional amelogenin splice products are required to restore enamel thickness. C1 [Pugach, M. K.; Li, Y.; Gibson, C. W.] Univ Penn, Sch Dent Med, Dept Anat & Cell Biol, Philadelphia, PA 19104 USA. [Suggs, C.; Wright, J. T.] Univ N Carolina, Sch Dent, Chapel Hill, NC 27599 USA. [Kulkarni, A. B.] Natl Inst Dent & Craniofacial Res, Funct Genom Sect, Lab Cell & Dev Biol, NIH, Bethesda, MD 20892 USA. [Pugach, M. K.; Bartlett, J. D.] Harvard Univ, Sch Dent Med, Dept Mineralized Tissue Biol, Forsyth Inst, Cambridge, MA 02142 USA. [Pugach, M. K.; Bartlett, J. D.] Harvard Univ, Sch Dent Med, Dept Dev Biol, Cambridge, MA 02142 USA. RP Pugach, MK (reprint author), Univ Penn, Sch Dent Med, Dept Anat & Cell Biol, 240 S 40th St, Philadelphia, PA 19104 USA. EM mpugach@forsyth.org FU National Institutes of Health (NIDCR) [DE019968, DE011089, DE016276, DE022624] FX The authors thank Hui Xue from the University of Pennsylvania for assistance with protein analysis and Zhorro Nikolov from the Centralized Research Facilities at Drexel University for assistance with nanoindentation. This research was supported by the National Institutes of Health (NIDCR grants DE019968, DE011089, DE016276, DE022624). The authors declare no potential conflicts of interest with respect to the authorship and/or publication of this article. NR 32 TC 4 Z9 5 U1 2 U2 6 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0022-0345 EI 1544-0591 J9 J DENT RES JI J. Dent. Res. PD DEC PY 2013 VL 92 IS 12 BP 1118 EP 1122 DI 10.1177/0022034513506444 PG 5 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 286SZ UT WOS:000329490300012 PM 24072097 ER PT J AU Guan, X Bartlett, JD AF Guan, X. Bartlett, J. D. TI MMP20 Modulates Cadherin Expression in Ameloblasts as Enamel Develops SO JOURNAL OF DENTAL RESEARCH LA English DT Article DE enamel biomineralization; formation; matrix metalloproteinases (MMPs); gene expression; cadherins; ameloblast; junctional complexes ID HYPOMATURATION AMELOGENESIS IMPERFECTA; N-CADHERIN; CELLS; PHENOTYPE; ADHESION; MUTATIONS; PROMOTES; TRIGGERS; JUNCTION; TIGHT AB Matrix metalloproteinase-20 (enamelysin, MMP20) is essential for dental enamel development. Seven different MMP20 mutations in humans cause non-syndromic enamel malformations, termed amelogenesis imperfecta, and ablation of Mmp20 in mice results in thin brittle enamel with a dysplastic rod pattern. Healthy enamel formation requires the sliding movement of ameloblasts in rows during the secretory stage of development. This is essential for formation of the characteristic decussating enamel rod pattern observed in rodents, and this is also when MMP20 is secreted into the enamel matrix. Therefore, we propose that MMP20 facilitates ameloblast movement by cleaving ameloblast cell-cell contacts. Here we show that MMP20 cleaves the extracellular domains of the E- and N-cadherin adherens junction proteins, that both E- and N-cadherin transcripts are expressed at significantly higher levels in Mmp20 null vs. wild-type (WT) mice, and that in Mmp20 ablated mice, high-level ameloblast N-cadherin expression persists during the maturation stage of development. Furthermore, we show that E-cadherin gene expression is down-regulated from the pre-secretory to the secretory stage, while N-cadherin levels are up-regulated. This E- to N-cadherin switch supports epithelial migration in other tissues and may be an important event necessary for the ameloblasts to start moving in rows that slide by one another. C1 [Bartlett, J. D.] Dept Mineralized Tissue Biol, Cambridge, MA 02142 USA. Harvard Univ, Sch Dent Med, Forsyth Inst, Cambridge, MA 02142 USA. RP Bartlett, JD (reprint author), Dept Mineralized Tissue Biol, 245 1st St, Cambridge, MA 02142 USA. EM jbartlett@forsyth.org FU National Institute of Dental and Craniofacial Research of the National Institutes of Health [RO1DE016276] FX We thank Dr. Toshihiro Sugiyama for his generous gift of ALC cells and Justine Dobeck for providing mouse incisor sections and thoughtful discussions. Research reported in this publication was supported by the National Institute of Dental and Craniofacial Research of the National Institutes of Health (grant RO1DE016276). The authors declare no potential conflicts of interest with respect to the authorship and/or publication of this article. NR 30 TC 7 Z9 7 U1 0 U2 0 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0022-0345 EI 1544-0591 J9 J DENT RES JI J. Dent. Res. PD DEC PY 2013 VL 92 IS 12 BP 1123 EP 1128 DI 10.1177/0022034513506581 PG 6 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 286SZ UT WOS:000329490300013 PM 24067343 ER PT J AU Bredella, MA Gill, CM Keating, LK Torriani, M Anderson, EJ Punyanitya, M Wilson, KE Kelly, TL Miller, KK AF Bredella, Miriam A. Gill, Corey M. Keating, Leigh K. Torriani, Martin Anderson, Ellen J. Punyanitya, Mark Wilson, Kevin E. Kelly, Thomas L. Miller, Karen K. TI Assessment of Abdominal Fat Compartments Using DXA in Premenopausal Women From Anorexia Nervosa to Morbid Obesity SO OBESITY LA English DT Article ID X-RAY ABSORPTIOMETRY; ADIPOSE-TISSUE; VISCERAL FAT; COMPUTED-TOMOGRAPHY; RESONANCE SPECTROSCOPY; METABOLIC SYNDROME; BODY-COMPOSITION; RISK-FACTORS; CT; QUANTIFICATION AB Objective: To test a newly developed dual energy X-ray absorptiometry (DXA) method for abdominal fat depot quantification in subjects with anorexia nervosa (AN), normal weight, and obesity using CT as a gold standard. Design and Methods: 135 premenopausal women (overweight/obese: n = 89, normal-weight: n = 27, AN: n = 19); abdominal visceral adipose tissue (VAT), subcutaneous adipose tissue (SAT), and total adipose tissue (TAT) areas determined on CT and DXA. Results: There were strong correlations between DXA and CT measurements of abdominal fat compartments in all groups with the strongest correlation coefficients in the normal-weight and overweight/obese groups. Correlations of DXA and CT VAT measurements were strongest in the obese group and weakest in the AN group. DXA abdominal fat depots were higher in all groups compared to CT, with the largest % mean difference in the AN group and smallest in the obese group. Conclusion: A new DXA technique is able to assess abdominal fat compartments including VAT in premenopausal women across a large weight spectrum. However, DXA measurements of abdominal fat were higher than CT, and this percent bias was most pronounced in the AN subjects and decreased with increasing weight, suggesting that this technique may be more useful in obese individuals. C1 [Bredella, Miriam A.; Gill, Corey M.; Torriani, Martin] Dept Radiol, Boston, MA USA. [Keating, Leigh K.; Anderson, Ellen J.] CTSA Metab & Nutr, Boston, MA USA. [Punyanitya, Mark] Columbia Univ, St Lukes Roosevelt Hosp, Dept Med, Obes Res Ctr, New York, NY USA. [Wilson, Kevin E.; Kelly, Thomas L.] Hologic Inc, Res & Dev, Bedford, MA USA. [Miller, Karen K.] Massachusetts Gen Hosp, Neuroendocrine Unit, Boston, MA 02114 USA. [Miller, Karen K.] Harvard Univ, Sch Med, Boston, MA USA. RP Bredella, MA (reprint author), Dept Radiol, Boston, MA USA. EM mbredella@partners.org OI Punyanitya, Mark/0000-0003-3678-2262 FU [R01 HL-077674]; [UL1 RR025758]; [R01 MH083657]; [K23 RR-23090] FX This work was supported in part by the following grants: R01 HL-077674, UL1 RR025758, R01 MH083657 and K23 RR-23090. NR 34 TC 11 Z9 11 U1 0 U2 3 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1930-7381 EI 1930-739X J9 OBESITY JI Obesity PD DEC PY 2013 VL 21 IS 12 BP 2458 EP 2464 DI 10.1002/oby.20424 PG 7 WC Endocrinology & Metabolism; Nutrition & Dietetics SC Endocrinology & Metabolism; Nutrition & Dietetics GA 288LT UT WOS:000329614200043 PM 23512706 ER PT J AU Foo, JP Aronis, KN Chamberland, JP Thakkar, B Hamnvik, OP Brinkoetter, M Zaichenko, L Mantzoros, CS AF Foo, Joo-Pin Aronis, Konstantinos N. Chamberland, John P. Thakkar, Bindiya Hamnvik, Ole-Petter Brinkoetter, Mary Zaichenko, Lesya Mantzoros, Christos S. TI Gender Dimorphism and Lack of Day/Night Variation or Effects of Energy Deprivation on Undercarboxylated Osteocalcin Levels in Humans SO OBESITY LA English DT Article ID METHIONYL HUMAN LEPTIN; POSTMENOPAUSAL WOMEN; BONE-DENSITY; WEIGHT-LOSS; HIP FRACTURE; HEALTHY-MEN; VITAMIN-K; FAT MASS; GLUCOSE; AGE AB Objective Undercarboxylated osteocalcin (ucOC) is a bone marker with potent metabolic effects. Leptin regulates Esp gene expression and osteocalcin carboxylation in animal models. We aim to elucidate day/night patterns of ucOC levels, whether short-term and/or chronic energy deprivation alters ucOC levels, and whether leptin may mediate these changes in humans. Design and Methods Twelve healthy males and females were studied for 72 h in the fed state to study day/night pattern of ucOC. The six female subjects were also studied in a crossover interventional study in the fasting state for 72 h with administration of either placebo or metreleptin in physiological doses. Blood samples were obtained hourly from 0800 a.m. on day 3 until 0800 a.m. on day 4. In a separate study, eleven obese subjects who underwent bariatric surgery were followed for 24 weeks to examine the effects of postsurgery weight loss on ucOC levels. Results Males have higher ucOC levels compared to females. There is no day/night variation pattern of circulating ucOC in humans. Short-term and chronic energy deprivation or leptin administrations do not alter ucOC levels. Conclusions The hypothesis that ucOC plays a role in energy homeostasis or of leptin in regulating ucOC in humans is not supported. C1 [Foo, Joo-Pin; Aronis, Konstantinos N.; Chamberland, John P.; Thakkar, Bindiya; Brinkoetter, Mary; Zaichenko, Lesya; Mantzoros, Christos S.] Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Div Endocrinol Diabet & Metab, Boston, MA 02215 USA. [Aronis, Konstantinos N.; Chamberland, John P.; Thakkar, Bindiya; Hamnvik, Ole-Petter; Mantzoros, Christos S.] Harvard Univ, Sch Med, Boston VA Healthcare Syst, Endocrinol Sect, Boston, MA 02215 USA. [Hamnvik, Ole-Petter] Harvard Univ, Brigham & Womens Hosp, Sch Med, Div Endocrinol Diabet & Hypertens, Boston, MA 02115 USA. RP Mantzoros, CS (reprint author), Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Div Endocrinol Diabet & Metab, Boston, MA 02215 USA. EM cmantzor@bidmc.harvard.edu RI Aronis, Konstantinos/F-3586-2012; Hamnvik, Ole-Petter/D-1719-2011; OI Aronis, Konstantinos/0000-0001-7189-8434; Chamberland, John/0000-0002-7862-1371; Zaichenko, Lesya/0000-0001-8489-3886 FU National Institute of Diabetes and Digestive and Kidney Diseases [58785, 79929, 81913]; Clinical Science Research and Development Service of the VA Office of Research and Development [1I01CX000422-01A1]; Harvard Clinical and Translational Science Center, from the National Center for Research Resources [UL1 RR025758-] FX The Mantzoros Laboratory is supported by the National Institute of Diabetes and Digestive and Kidney Diseases grants 58785, 79929 and 81913. The Mantzoros Laboratory is also supported by Award Number 1I01CX000422-01A1 from the Clinical Science Research and Development Service of the VA Office of Research and Development. Amylin Pharmaceuticals, Inc. supplied metreleptin for this study and approved the design of the study but had no role in the study design; conduct of the study; collection, management, analysis, and interpretation of the data; or the preparation, review, or approval of the manuscript. The project described was also supported by Grant Number UL1 RR025758- Harvard Clinical and Translational Science Center, from the National Center for Research Resources. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Center for Research Resources or the National Institutes of Health. NR 35 TC 0 Z9 0 U1 0 U2 4 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1930-7381 EI 1930-739X J9 OBESITY JI Obesity PD DEC PY 2013 VL 21 IS 12 BP E527 EP E532 DI 10.1002/oby.20453 PG 6 WC Endocrinology & Metabolism; Nutrition & Dietetics SC Endocrinology & Metabolism; Nutrition & Dietetics GA 288LT UT WOS:000329614200001 PM 23512912 ER PT J AU Bi, WL Chiocca, EA AF Bi, Wenya Linda Chiocca, E. Antonio TI Adult Cerebellar Glioblastomas: A Distinct Entity or Parcel of the Whole? SO WORLD NEUROSURGERY LA English DT Editorial Material DE Cerebellar; Cerebellum; Glioblastoma; Glioma; SEER; Survival ID PROGNOSTIC-FACTORS; MALIGNANT GLIOMAS; RESECTION; SURVIVAL; EXTENT; MULTIFORME; SURGERY; IMPACT C1 [Bi, Wenya Linda; Chiocca, E. Antonio] Harvard Univ, Sch Med, Dept Neurosurg, Boston, MA 02114 USA. [Chiocca, E. Antonio] Brigham & Womens Faulkner Hosp, Inst Neurosci, Boston, MA USA. [Chiocca, E. Antonio] Dana Farber Canc Inst, Ctr Neurooncol, Boston, MA 02115 USA. RP Chiocca, EA (reprint author), Harvard Univ, Sch Med, Dept Neurosurg, Boston, MA 02114 USA. EM eachiocca@partners.org NR 24 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 1878-8750 EI 1878-8769 J9 WORLD NEUROSURG JI World Neurosurg. PD DEC PY 2013 VL 80 IS 6 BP E181 EP E183 DI 10.1016/j.wneu.2013.03.040 PG 3 WC Clinical Neurology; Surgery SC Neurosciences & Neurology; Surgery GA 290DL UT WOS:000329733300004 PM 23792905 ER PT J AU Rho, J Chung, J Im, H Liong, M Shao, HL Castro, CM Weissleder, R Lee, H AF Rho, Junsung Chung, Jaehoon Im, Hyungsoon Liong, Monty Shao, Huilin Castro, Cesar M. Weissleder, Ralph Lee, Hakho TI Magnetic Nanosensor for Detection and Profiling of Erythrocyte-Derived Microvesicles SO ACS NANO LA English DT Article DE nanotechnology; biosensor; microvesicles; microfluidics; blood; transfusion ID RED-BLOOD-CELLS; INDEPENDENT RISK-FACTOR; MULTIPLE ORGAN FAILURE; NITRIC-OXIDE; STORAGE LESION; IN-VITRO; TRANSFUSION; MICROPARTICLES; MECHANISM; NANOPARTICLES AB During the course of their lifespan, erythrocytes actively shed phospholipid-bound microvesicles (MVs). In stored blood, the number of these erythrocyte-derived MVs has been observed to increase over time, suggesting their potential value as a quality metric for blood products. The lack of sensitive, standardized MV assays, however, poses a significant barrier to implementing MV analyses into clinical settings. Here, we report on a new nanotechnology platform capable of rapid and sensitive MV detection in packed red blood cell (pRBC) units. A filter-assisted microfluidic device was designed to enrich MVs directly from pRBC units, and label them with target-specific magnetic nanoparticles. Subsequent detection using a miniaturized nuclear magnetic resonance system enabled accurate MV quantification as well as the detection of key molecular markers (CD44, 047, CD55). When the developed platform was applied, MVs in stored blood units could also be monitored longitudinally. Our results showed that MV counts increase over time and, thus, could serve as an effective metric of blood aging. Furthermore, our studies found that MVs have the capacity to generate oxidative stress and consume nitric oxide. By advancing our understanding of MV biology, we expect that the developed platform will lead to improved blood product quality and transfusion safety. C1 [Rho, Junsung; Chung, Jaehoon; Im, Hyungsoon; Liong, Monty; Shao, Huilin; Castro, Cesar M.; Weissleder, Ralph; Lee, Hakho] Massachusetts Gen Hosp, Ctr Syst Biol, Boston, MA 02114 USA. [Castro, Cesar M.] Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA. [Weissleder, Ralph] Harvard Univ, Sch Med, Dept Syst Biol, Boston, MA 02115 USA. RP Lee, H (reprint author), Massachusetts Gen Hosp, Ctr Syst Biol, 185 Cambridge St,CPZN 5206, Boston, MA 02114 USA. EM hlee@mgh.harvard.edu RI Im, Hyungsoon/A-3178-2009 OI Im, Hyungsoon/0000-0002-0626-1346 FU HHMI; National Institute of Health [R01-HL113156, R01-EB010011, R01-EB00462605A1]; NHLBI [HHSN268201000044C] FX The authors thank Y. Fisher-Jeffes for review of the manuscript; N. Sergeyev for synthesis of MNPs; H. Chung, and J. Higgins for many helpful discussions; X. Breakefield and L. Balaj for the use of NTA. This work was supported in part by an HHMI Medical Research Fellows Program grant (J.R.), and by the following National Institute of Health Grants: R01-HL113156 (H.L.), R01-EB010011 (R.W.), R01-EB00462605A1 (R.W.) and NHLBI contract HHSN268201000044C (R.W.). NR 32 TC 23 Z9 23 U1 6 U2 69 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 DEC PY 2013 VL 7 IS 12 BP 11227 EP 11233 DI 10.1021/nn405016y PG 7 WC Chemistry, Multidisciplinary; Chemistry, Physical; Nanoscience & Nanotechnology; Materials Science, Multidisciplinary SC Chemistry; Science & Technology - Other Topics; Materials Science GA 281YO UT WOS:000329137100086 PM 24295203 ER PT J AU Stitziel, NO Fouchier, SW Sjouke, B Peloso, GM Moscoso, AM Auer, PL Goel, A Gigante, B Barnes, TA Melander, O Orho-Melander, M Duga, S Sivapalaratnam, S Nikpay, M Martinelli, N Girelli, D Jackson, RD Kooperberg, C Lange, LA Ardissino, D McPherson, R Farrall, M Watkins, H Reilly, MP Rader, DJ de Faire, U Schunkert, H Erdmann, J Samani, NJ Charnas, L Altshuler, D Gabriel, S Kastelein, JJP Defesche, JC Nederveen, AJ Kathiresan, S Hovingh, GK AF Stitziel, Nathan O. Fouchier, Sigrid W. Sjouke, Barbara Peloso, Gina M. Moscoso, Alessa M. Auer, Paul L. Goel, Anuj Gigante, Bruna Barnes, Timothy A. Melander, Olle Orho-Melander, Marju Duga, Stefano Sivapalaratnam, Suthesh Nikpay, Majid Martinelli, Nicola Girelli, Domenico Jackson, Rebecca D. Kooperberg, Charles Lange, Leslie A. Ardissino, Diego McPherson, Ruth Farrall, Martin Watkins, Hugh Reilly, Muredach P. Rader, Daniel J. de Faire, Ulf Schunkert, Heribert Erdmann, Jeanette Samani, Nilesh J. Charnas, Lawrence Altshuler, David Gabriel, Stacey Kastelein, John J. P. Defesche, Joep C. Nederveen, Aart J. Kathiresan, Sekar Hovingh, G. Kees CA Natl Heart Lung Blood Inst GO TI Exome Sequencing and Directed Clinical Phenotyping Diagnose Cholesterol Ester Storage Disease Presenting as Autosomal Recessive Hypercholesterolemia SO ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY LA English DT Article DE genetics; hypercholesterolemia; myocardial infarction ID LYSOSOMAL ACID LIPASE; E8SJM MUTATION; HETEROZYGOSITY; IDENTIFICATION; WOLMAN AB Objective Autosomal recessive hypercholesterolemia is a rare inherited disorder, characterized by extremely high total and low-density lipoprotein cholesterol levels, that has been previously linked to mutations in LDLRAP1. We identified a family with autosomal recessive hypercholesterolemia not explained by mutations in LDLRAP1 or other genes known to cause monogenic hypercholesterolemia. The aim of this study was to identify the molecular pathogenesis of autosomal recessive hypercholesterolemia in this family. Approach and Results We used exome sequencing to assess all protein-coding regions of the genome in 3 family members and identified a homozygous exon 8 splice junction mutation (c.894G>A, also known as E8SJM) in LIPA that segregated with the diagnosis of hypercholesterolemia. Because homozygosity for mutations in LIPA is known to cause cholesterol ester storage disease, we performed directed follow-up phenotyping by noninvasively measuring hepatic cholesterol content. We observed abnormal hepatic accumulation of cholesterol in the homozygote individuals, supporting the diagnosis of cholesterol ester storage disease. Given previous suggestions of cardiovascular disease risk in heterozygous LIPA mutation carriers, we genotyped E8SJM in >27 000 individuals and found no association with plasma lipid levels or risk of myocardial infarction, confirming a true recessive mode of inheritance. Conclusions By integrating observations from Mendelian and population genetics along with directed clinical phenotyping, we diagnosed clinically unapparent cholesterol ester storage disease in the affected individuals from this kindred and addressed an outstanding question about risk of cardiovascular disease in LIPA E8SJM heterozygous carriers. C1 [Stitziel, Nathan O.] Washington Univ Sch Med, Cardiovasc Div, Dept Med, St Louis, MO USA. [Stitziel, Nathan O.] Washington Univ Sch Med, Div Stat Genom, St Louis, MO USA. [Sjouke, Barbara; Sivapalaratnam, Suthesh; Kastelein, John J. P.; Hovingh, G. Kees] Univ Amsterdam, Acad Med Ctr, Dept Vasc Med, NL-1105 AZ Amsterdam, Netherlands. [Fouchier, Sigrid W.; Defesche, Joep C.] Univ Amsterdam, Acad Med Ctr, Dept Expt Vasc Med, NL-1105 AZ Amsterdam, Netherlands. [Nederveen, Aart J.] Univ Amsterdam, Acad Med Ctr, NL-1105 AZ Amsterdam, Netherlands. [Peloso, Gina M.; Moscoso, Alessa M.; Ardissino, Diego; Kathiresan, Sekar] Ctr Human Genet Res, Boston, MA USA. [Peloso, Gina M.; Moscoso, Alessa M.; Ardissino, Diego; Kathiresan, Sekar] Broad Inst, Program Med & Populat Genet, Cambridge, MA USA. [Auer, Paul L.; Kooperberg, Charles] Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA. [Goel, Anuj; Farrall, Martin; Watkins, Hugh] Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford, England. [Goel, Anuj; Farrall, Martin; Watkins, Hugh] Univ Oxford, Radcliffe Dept Med, Oxford, England. [Gigante, Bruna; de Faire, Ulf] Karolinska Inst, Inst Environm Med, Div Cardiovasc Epidemiol, S-10401 Stockholm, Sweden. [Barnes, Timothy A.; Samani, Nilesh J.] Univ Leicester, Dept Cardiovasc Sci, Leicester, Leics, England. [Barnes, Timothy A.; Samani, Nilesh J.] Glenfield Hosp, Leicester NIHR Biomed Res Unit Cardiovasc Dis, Leicester, Leics, England. [Melander, Olle] Lund Univ, Dept Clin Sci Hypertens & Cardiovasc Dis, Skania Univ Hosp, Malmo, Sweden. [Orho-Melander, Marju] Lund Univ, Skania Univ Hosp, Malmo, Sweden. [Duga, Stefano] Univ Milan, Dipartimento Biotecnol Med & Med Traslaz, Milan, Italy. [Nikpay, Majid] Univ Ottawa Heart Inst, Atherogen Lab, Ottawa, ON, Canada. [Martinelli, Nicola; Girelli, Domenico] Univ Verona, Dept Med, I-37100 Verona, Italy. [Jackson, Rebecca D.] Ohio State Univ, Div Endocrinol Diabet & Metab, Columbus, OH 43210 USA. [Lange, Leslie A.] Univ N Carolina, Dept Epidemiol, Chapel Hill, NC USA. [Lange, Leslie A.] Univ N Carolina, Dept Genet & Biostat, Chapel Hill, NC USA. [Lange, Leslie A.] Univ N Carolina, Dept Bioinformat, Chapel Hill, NC USA. [Lange, Leslie A.] Univ N Carolina, Dept Computat Biol, Chapel Hill, NC USA. [Ardissino, Diego] Azienda Osped Univ Parma, Div Cardiol, Parma, Italy. [McPherson, Ruth] Univ Ottawa Heart Inst, John & Jennifer Ruddy Canadian Cardiovasc Genet C, Ottawa, ON, Canada. [Reilly, Muredach P.; Rader, Daniel J.] Univ Penn, Inst Translat Med & Therapeut, Philadelphia, PA 19104 USA. [Reilly, Muredach P.; Rader, Daniel J.] Univ Penn, Cardiovasc Inst, Perelman Sch Med, Philadelphia, PA 19104 USA. [Schunkert, Heribert] Deutsch Herzzentrum Munich, Munich, Germany. [Schunkert, Heribert] Tech Univ Munich, D-80290 Munich, Germany. [Schunkert, Heribert] DZHK German Res Ctr Cardiovasc Res, Munich, Germany. [Erdmann, Jeanette] Med Univ Lubeck, Inst Integrat & Expt Genom, D-23538 Lubeck, Germany. [Erdmann, Jeanette] DZHK German Res Ctr Cardiovasc Res, Lubeck, Germany. [Charnas, Lawrence] Shire HGT, Discovery Med, Lexington, MA USA. [Altshuler, David] Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. [Kathiresan, Sekar] Massachusetts Gen Hosp, Cardiovasc Res Ctr, Boston, MA 02114 USA. [Altshuler, David] Harvard Univ, Sch Med, Dept Genet, Boston, MA USA. [Kathiresan, Sekar] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. RP Kathiresan, S (reprint author), Massachusetts Gen Hosp, Ctr Human Genet Res, 185 Cambridge St,CPZN 5-252, Boston, MA 02114 USA. EM skathiresan@partners.org; g.k.hovingh@amc.uva.nl RI Altshuler, David/A-4476-2009; Duga, Stefano/F-8173-2014; Martinelli, Nicola/J-5622-2016; Erdmann, Jeanette/P-7513-2014; OI Altshuler, David/0000-0002-7250-4107; Martinelli, Nicola/0000-0001-6465-5119; Erdmann, Jeanette/0000-0002-4486-6231; Stitziel, Nathan/0000-0002-4963-8211; Gigante, Bruna/0000-0003-4508-7990; Duga, Stefano/0000-0003-3457-1410; Watkins, Hugh/0000-0002-5287-9016 FU National Institutes of Health, Shire Human Genetic Therapies; National Institutes of Health (NIH)/National Heart, Lung, and Blood Institute (NHLBI) [K08-HL114642]; British Heart Foundation; National Institute for Health Research Senior Investigator; Lifetime Achievement Award of the Dutch Heart Foundation [2010T082]; NIH [R01 HL107816]; Veni grant from the Netherlands Organisation for Scientific Research (NWO) [91612122]; Netherlands CardioVascular Research Initiative [CVON2011-19]; European Union [TransCard: FP7-603091-2]; Fondation LeDucq FX This study was funded by National Institutes of Health, Shire Human Genetic Therapies. N.O. Stitziel is supported, in part, by a career development award from the National Institutes of Health (NIH)/National Heart, Lung, and Blood Institute (NHLBI) (K08-HL114642). N.J. Samani is funded by the British Heart Foundation and is a National Institute for Health Research Senior Investigator. J.J.P. Kastelein is a recipient of the Lifetime Achievement Award of the Dutch Heart Foundation (2010T082). S. Kathiresan is funded by NIH R01 HL107816. G.K. Hovingh is a recipient of a Veni grant (project number 91612122) from the Netherlands Organisation for Scientific Research (NWO) and grants from the Netherlands CardioVascular Research Initiative (CVON2011-19; Genius), the European Union (TransCard: FP7-603091-2) and Fondation LeDucq (2009-2014). NR 21 TC 34 Z9 34 U1 1 U2 13 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1079-5642 EI 1524-4636 J9 ARTERIOSCL THROM VAS JI Arterioscler. Thromb. Vasc. Biol. PD DEC PY 2013 VL 33 IS 12 BP 2909 EP 2914 DI 10.1161/ATVBAHA.113.302426 PG 6 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA 283YW UT WOS:000329283900028 PM 24072694 ER PT J AU Merenbakh-Lamin, K Ben-Baruch, N Yeheskel, A Dvir, A Soussan-Gutman, L Jeselsohn, R Yelensky, R Brown, M Miller, VA Sarid, D Rizel, S Klein, B Rubinek, T Wolf, I AF Merenbakh-Lamin, Keren Ben-Baruch, Noa Yeheskel, Adva Dvir, Addie Soussan-Gutman, Lior Jeselsohn, Rinath Yelensky, Roman Brown, Myles Miller, Vincent A. Sarid, David Rizel, Shulamith Klein, Baruch Rubinek, Tami Wolf, Ido TI D538G Mutation in Estrogen Receptor-alpha: A Novel Mechanism for Acquired Endocrine Resistance in Breast Cancer SO CANCER RESEARCH LA English DT Article ID TAMOXIFEN; FULVESTRANT; METASTASIS; RESOLUTION; MODULATOR; COMPLEX; CELLS; TRIAL AB Resistance to endocrine therapy occurs in virtually all patients with estrogen receptor alpha (ER alpha)-positive metastatic breast cancer, and is attributed to various mechanisms including loss of ER alpha expression, altered activity of coregulators, and cross-talk between the ER alpha and growth factor signaling pathways. To our knowledge, acquired mutations of the ER alpha have not been described as mediating endocrine resistance. Samples of 13 patients with metastatic breast cancer were analyzed for mutations in cancer-related genes. In five patients who developed resistance to hormonal therapy, a mutation of A to G at position 1,613 of ER alpha, resulting in a substitution of aspartic acid at position 538 to glycine (D538G), was identified in liver metastases. Importantly, the mutation was not detected in the primary tumors obtained prior to endocrine treatment. Structural modeling indicated that D538G substitution leads to a conformational change in the ligand-binding domain, which mimics the conformation of activated ligand-bound receptor and alters binding of tamoxifen. Indeed, experiments in breast cancer cells indicated constitutive, ligand-independent transcriptional activity of the D538G receptor, and overexpression of it enhanced proliferation and conferred resistance to tamoxifen. These data indicate a novel mechanism of acquired endocrine resistance in breast cancer. Further studies are needed to assess the frequency of D538G-ER alpha among patients with breast cancer and explore ways to inhibit its activity and restore endocrine sensitivity. (C)2013 AACR. C1 [Merenbakh-Lamin, Keren; Sarid, David; Rubinek, Tami; Wolf, Ido] Tel Aviv Sourasky Med Ctr, Dept Oncol, IL-64239 Tel Aviv, Israel. [Merenbakh-Lamin, Keren; Wolf, Ido] Tel Aviv Univ, Sackler Fac Med, IL-69978 Tel Aviv, Israel. [Yeheskel, Adva] Tel Aviv Univ, George S Wise Fac Life Sci, Bioinformat Unit, IL-69978 Tel Aviv, Israel. [Klein, Baruch] Assuta Med Ctr, Tel Aviv, Israel. [Ben-Baruch, Noa] Kaplan Med Ctr, Rehovot, Israel. [Dvir, Addie; Soussan-Gutman, Lior] Oncotest Teva Pharmaceut Ind, Petah Tiqwa, Israel. [Rizel, Shulamith] Rabin Med Ctr, Davidoff Ctr, Inst Oncol, Petah Tiqwa, Israel. [Jeselsohn, Rinath; Brown, Myles] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Med Oncol,Dana Farber Canc Inst, Boston, MA 02115 USA. [Jeselsohn, Rinath; Brown, Myles] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Med, Boston, MA 02115 USA. [Yelensky, Roman; Miller, Vincent A.] Fdn Med, Cambridge, MA USA. RP Wolf, I (reprint author), Tel Aviv Sourasky Med Ctr, Dept Oncol, 6 Weizmann St, IL-64239 Tel Aviv, Israel. EM wolf-i@inter.net.il OI Brown, Myles/0000-0002-8213-1658 FU Israel Cancer Association; Margaret Stultz foundation, the Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel; Israel Science Foundation [1112/09]; TASMC excellence fund FX This work was financially supported by the Israel Cancer Association; The Margaret Stultz foundation, the Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel; the Israel Science Foundation (grant no. 1112/09); and TASMC excellence fund. NR 28 TC 90 Z9 90 U1 1 U2 13 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD DEC 1 PY 2013 VL 73 IS 23 BP 6856 EP 6864 DI 10.1158/0008-5472.CAN-13-1197 PG 9 WC Oncology SC Oncology GA 279DS UT WOS:000328941200003 PM 24217577 ER PT J AU Heidari, P Wehrenberg-Klee, E Habibollahi, P Yokell, D Kulke, M Mahmood, U AF Heidari, Pedram Wehrenberg-Klee, Eric Habibollahi, Peiman Yokell, Daniel Kulke, Matthew Mahmood, Umar TI Free Somatostatin Receptor Fraction Predicts the Antiproliferative Effect of Octreotide in a Neuroendocrine Tumor Model: Implications for Dose Optimization SO CANCER RESEARCH LA English DT Article ID BRAIN TRANSFER CONSTANTS; TIME UPTAKE DATA; GRAPHICAL EVALUATION; IN-VIVO; PET/CT; GUIDELINES; GA-68-DOTATATE; OCTREOSCAN; PEPTIDES AB Somatostatin receptors (SSTR) are highly expressed in well-differentiated neuroendocrine tumors (NET). Octreotide, an SSTR agonist, has been used to suppress the production of vasoactive hormones and relieve symptoms of hormone hypersecretion with functional NETs. In a clinical trial, an empiric dose of octreotide treatment prolonged time to tumor progression in patients with small bowel neuroendocrine (carcinoid) tumors, irrespective of symptom status. However, there has yet to be a dose optimization study across the patient population, and methods are currently lacking to optimize dosing of octreotide therapy on an individual basis. Multiple factors such as total tumor burden, receptor expression levels, and nontarget organ metabolism/excretion may contribute to a variation in SSTR octreotide occupancy with a given dose among different patients. In this study, we report the development of an imaging method to measure surface SSTR expression and occupancy level using the PET radiotracer Ga-68-DOTATOC. In an animal model, SSTR occupancy by octreotide was assessed quantitatively with Ga-68-DOTATOC PET, with the finding that increased occupancy resulted in decreased tumor proliferation rate. The results suggested that quantitative SSTR imaging during octreotide therapy has the potential to determine the fractional receptor occupancy in NETs, thereby allowing octreotide dosing to be optimized readily in individual patients. Clinical trials validating this approach are warranted. (C)2013 AACR. C1 [Heidari, Pedram; Wehrenberg-Klee, Eric; Habibollahi, Peiman; Yokell, Daniel; Mahmood, Umar] Harvard Univ, Sch Med, Dept Radiol, Massachusetts Gen Hosp,Div Nucl Med & Mol Imaging, Boston, MA 02115 USA. [Kulke, Matthew] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. RP Mahmood, U (reprint author), Massachusetts Gen Hosp, Dept Radiol, Div Nucl Med & Mol Imaging, Boston, MA 02114 USA. EM umahmood@mgh.harvard.edu FU NIH [R01CA166582, U01CA143056, U01CA084301, P50CA127003] FX This research was supported in part by NIH grants R01CA166582, U01CA143056, U01CA084301, and P50CA127003. NR 26 TC 9 Z9 9 U1 1 U2 4 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD DEC 1 PY 2013 VL 73 IS 23 BP 6865 EP 6873 DI 10.1158/0008-5472.CAN-13-1199 PG 9 WC Oncology SC Oncology GA 279DS UT WOS:000328941200004 PM 24080280 ER PT J AU Duraiswamy, J Freeman, GJ Coukos, G AF Duraiswamy, Jaikumar Freeman, Gordon J. Coukos, George TI Therapeutic PD-1 Pathway Blockade Augments with Other Modalities of Immunotherapy T-Cell Function to Prevent Immune Decline in Ovarian Cancer SO CANCER RESEARCH LA English DT Article ID CHRONIC VIRAL-INFECTION; DENDRITIC CELLS; REGULATORY T; IN-VIVO; GM-CSF; SUPPRESSOR-CELLS; TUMOR-IMMUNITY; MYELOID CELLS; ACTIVATION; TOLERANCE AB The tumor microenvironment mediates induction of the immunosuppressive programmed cell death-1 (PD-1) pathway, and targeted interventions against this pathway can help restore antitumor immunity. To gain insight into these responses, we studied the interaction between PD-1 expressed on T cells and its ligands (PD-1:PD-L1, PD-1:PD-L2, and PD-L1:B7.1), expressed on other cells in the tumor microenvironment, using a syngeneic orthotopic mouse model of epithelial ovarian cancer (ID8). Exhaustion of tumor-infiltrating lymphocytes (TIL) correlated with expression of PD-1 ligands by tumor cells and tumor-derived myeloid cells, including tumor-associated macrophages (TAM), dendritic cells, and myeloid-derived suppressor cells (MDSC). When combined with GVAX or FVAX vaccination (consisting of irradiated ID8 cells expressing granulocyte macrophage colony-stimulating factor or FLT3 ligand) and costimulation by agonistic alpha-4-1BB or TLR 9 ligand, antibody-mediated blockade of PD-1 or PD-L1 triggered rejection of ID8 tumors in 75% of tumor-bearing mice. This therapeutic effect was associated with increased proliferation and function of tumor antigen-specific effector CD8(+) T cells, inhibition of suppressive regulatory T cells (Treg) and MDSC, upregulation of effector T-cell signaling molecules, and generation of T memory precursor cells. Overall, PD-1/PD-L1 blockade enhanced the amplitude of tumor immunity by reprogramming suppressive and stimulatory signals that yielded more powerful cancer control. (C)2013 AACR. C1 [Duraiswamy, Jaikumar; Coukos, George] Univ Penn, Perelman Sch Med, Ovarian Canc Res Ctr, Philadelphia, PA 19104 USA. [Freeman, Gordon J.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Coukos, George] Univ Lausanne Hosp, Dept Oncol, Lausanne, Switzerland. [Coukos, George] Univ Lausanne Hosp, Ludwig Ctr Canc Res, Lausanne, Switzerland. RP Coukos, G (reprint author), Ludwig Inst Canc Res, Ch Boveresses 155, CH-1066 Epalinges, Switzerland. EM george.coukos@chuv.ch FU NIH [CA083638]; [NIH-P01 AI056299] FX This work was financially supported by NIH CA083638 (G. Coukos), Pilot (J. Duraiswamy), and NIH-P01 AI056299 (G. J. Freeman) grants. NR 53 TC 81 Z9 87 U1 10 U2 27 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD DEC 1 PY 2013 VL 73 IS 23 BP 6900 EP 6912 DI 10.1158/0008-5472.CAN-13-1550 PG 13 WC Oncology SC Oncology GA 279DS UT WOS:000328941200007 PM 23975756 ER PT J AU Kulkarni, AA Roy, B Rao, PS Wyant, GA Mahmoud, A Ramachandran, M Sengupta, P Goldman, A Kotamraju, VR Basu, S Mashelkar, RA Ruoslahti, E Dinulescu, DM Sengupta, S AF Kulkarni, Ashish A. Roy, Bhaskar Rao, Poornima S. Wyant, Gregory A. Mahmoud, Ayaat Ramachandran, Madhumitha Sengupta, Poulomi Goldman, Aaron Kotamraju, Venkata Ramana Basu, Sudipta Mashelkar, Raghunath A. Ruoslahti, Erkki Dinulescu, Daniela M. Sengupta, Shiladitya TI Supramolecular Nanoparticles That Target Phosphoinositide-3-Kinase Overcome Insulin Resistance and Exert Pronounced Antitumor Efficacy SO CANCER RESEARCH LA English DT Article ID CANCER; INHIBITORS; DELIVERY; PATHWAY; TUMORS; NANOTECHNOLOGY; OPPORTUNITIES; METABOLISM; CHALLENGES; 3-KINASES AB The centrality of phosphoinositide-3-kinase (PI3K) in cancer etiology is well established, but clinical translation of PI3K inhibitors has been limited by feedback signaling, suboptimal intratumoral concentration, and an insulin resistance "class effect." This study was designed to explore the use of supramolecular nanochemistry for targeting PI3K to enhance antitumor efficacy and potentially overcome these limitations. PI3K inhibitor structures were rationally modified using a cholesterol-based derivative, facilitating supramolecular nanoassembly with L-alpha-phosphatidylcholine and DSPE-PEG [1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[amino(polythylene glycol)]. The supramolecular nanoparticles (SNP) that were assembled were physicochemically characterized and functionally evaluated in vitro. Antitumor efficacy was quantified in vivo using 4T1 breast cancer and K-Ras(LSL/+)/Pten(fl/fl) ovarian cancer models, with effects on glucose homeostasis evaluated using an insulin sensitivity test. The use of PI103 and PI828 as surrogate molecules to engineer the SNPs highlighted the need to keep design principles in perspective; specifically, potency of the active molecule and the linker chemistry were critical principles for efficacy, similar to antibody-drug conjugates. We found that the SNPs exerted a temporally sustained inhibition of phosphorylation of Akt, mTOR, S6K, and 4EBP in vivo. These effects were associated with increased antitumor efficacy and survival as compared with PI103 and PI828. Efficacy was further increased by decorating the nanoparticle surface with tumor-homing peptides. Notably, the use of SNPs abrogated the insulin resistance that has been associated widely with other PI3K inhibitors. This study provides a preclinical foundation for the use of supramolecular nanochemistry to overcome current challenges associated with PI3K inhibitors, offering a paradigm for extension to other molecularly targeted therapeutics being explored for cancer treatment. (C)2013 AACR. C1 [Kulkarni, Ashish A.; Roy, Bhaskar; Rao, Poornima S.; Mahmoud, Ayaat; Ramachandran, Madhumitha; Sengupta, Poulomi; Goldman, Aaron; Basu, Sudipta; Mashelkar, Raghunath A.; Sengupta, Shiladitya] Brigham & Womens Hosp, Div Biomed Engn, Lab Nanomed, Dept Med, Cambridge, MA 02139 USA. [Kulkarni, Ashish A.; Goldman, Aaron; Sengupta, Shiladitya] MIT, Harvard Mit Div Hlth Sci & Technol, Cambridge, MA 02139 USA. [Kulkarni, Ashish A.; Basu, Sudipta; Sengupta, Shiladitya] Indo US Joint Ctr Nanobiotechnol, Cambridge, MA 02139 USA. [Wyant, Gregory A.; Dinulescu, Daniela M.] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. [Kulkarni, Ashish A.; Goldman, Aaron; Dinulescu, Daniela M.; Sengupta, Shiladitya] Harvard Univ, Sch Med, Boston, MA USA. [Sengupta, Shiladitya] Dana Farber Canc Inst, Brookline, MA USA. [Kotamraju, Venkata Ramana; Ruoslahti, Erkki] Sanford Burnham Med Res Inst, Canc Res Ctr, San Diego, CA USA. [Kotamraju, Venkata Ramana; Ruoslahti, Erkki] Univ Calif Santa Barbara, Ctr Nanomed, Dept Cell Mol & Dev Biol, Santa Barbara, CA 93106 USA. [Basu, Sudipta] IISER, Pune 411021, Maharashtra, India. [Sengupta, Poulomi; Mashelkar, Raghunath A.] Natl Chem Labs, Pune, Maharashtra, India. RP Sengupta, S (reprint author), Brigham & Womens Hosp, 65 Landsdowne St,Room 317, Cambridge, MA 02139 USA. EM akulkarni@research.bwh.harvard.edu; sudipta.basu@iiserpune.ac.in; shiladit@mit.edu FU U.S. Department of Defense (DOD) Breast Cancer Research Program (BCRP) Era of Hope Scholar Award [W81XWH-07-1-0482]; DOD Collaborative Innovator Grant [W81XWH-09-0698/700]; NIH [R01 1R01CA135242-01A2]; American Lung Association Discovery Award [LCD-259932-N]; Department of Defense Ovarian Cancer Research Program [W81XWH-10-1-0263]; V Foundation Scholar Award; Ovarian Cancer Research Fund Liz Tilberis Award; Mildred Moorman Ovarian Cancer Research Fund; Burroughs Wellcome Foundation; Mary Kay Ash Foundation; Rivkin Foundation FX This work was supported by U.S. Department of Defense (DOD) Breast Cancer Research Program (BCRP) Era of Hope Scholar Award W81XWH-07-1-0482, a DOD Collaborative Innovator Grant W81XWH-09-0698/700, NIH grant R01 1R01CA135242-01A2, and an American Lung Association Discovery Award (LCD-259932-N; S. Sengupta), Department of Defense Ovarian Cancer Research Program Award W81XWH-10-1-0263, a V Foundation Scholar Award, an Ovarian Cancer Research Fund Liz Tilberis Award, by the Burroughs Wellcome, Mary Kay Ash, and Rivkin Foundations, and by a generous contribution from the Mildred Moorman Ovarian Cancer Research Fund (D.M. Dinulescu). NR 33 TC 12 Z9 13 U1 2 U2 26 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD DEC 1 PY 2013 VL 73 IS 23 BP 6987 EP 6997 DI 10.1158/0008-5472.CAN-12-4477 PG 11 WC Oncology SC Oncology GA 279DS UT WOS:000328941200014 PM 24121488 ER PT J AU Huang, YH Stylianopoulos, T Duda, DG Fukumura, D Jain, RK AF Huang, Yuhui Stylianopoulos, Triantafyllos Duda, Dan G. Fukumura, Dai Jain, Rakesh K. TI Benefits of Vascular Normalization Are Dose and Time Dependent-Letter SO CANCER RESEARCH LA English DT Letter ID TUMOR MICROENVIRONMENT; BLOOD-VESSELS C1 [Huang, Yuhui; Stylianopoulos, Triantafyllos; Duda, Dan G.; Fukumura, Dai; Jain, Rakesh K.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Steele Lab Tumor Biol,Dept Radiat Oncol, Boston, MA 02114 USA. RP Jain, RK (reprint author), Harvard Univ, Sch Med, 100 Blossom St,Cox 734, Boston, MA 02114 USA. EM jain@steele.mgh.harvard.edu OI Huang, Yuhui/0000-0003-1985-3575; Stylianopoulos, Triantafyllos/0000-0002-3093-1696 FU NCI NIH HHS [R01 CA126642, P01 CA080124] NR 5 TC 21 Z9 21 U1 0 U2 11 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD DEC 1 PY 2013 VL 73 IS 23 BP 7144 EP 7146 DI 10.1158/0008-5472.CAN-13-1989 PG 3 WC Oncology SC Oncology GA 279DS UT WOS:000328941200028 PM 24265277 ER PT J AU Deng, XY Eskandar, EN Eden, UT AF Deng, Xinyi Eskandar, Emad N. Eden, Uri T. TI A point process approach to identifying and tracking transitions in neural spiking dynamics in the subthalamic nucleus of Parkinson's patients SO CHAOS LA English DT Article ID TRAIN DATA-ANALYSIS; ALZHEIMERS-DISEASE; REFRACTORY PERIOD; WORKING-MEMORY; POWER SPECTRUM; PHASE-LOCKING; OSCILLATIONS; SCHIZOPHRENIA; EEG; SYNCHRONY AB Understanding the role of rhythmic dynamics in normal and diseased brain function is an important area of research in neural electrophysiology. Identifying and tracking changes in rhythms associated with spike trains present an additional challenge, because standard approaches for continuous-valued neural recordings-such as local field potential, magnetoencephalography, and electroencephalography data-require assumptions that do not typically hold for point process data. Additionally, subtle changes in the history dependent structure of a spike train have been shown to lead to robust changes in rhythmic firing patterns. Here, we propose a point process modeling framework to characterize the rhythmic spiking dynamics in spike trains, test for statistically significant changes to those dynamics, and track the temporal evolution of such changes. We first construct a two-state point process model incorporating spiking history and develop a likelihood ratio test to detect changes in the firing structure. We then apply adaptive state-space filters and smoothers to track these changes through time. We illustrate our approach with a simulation study as well as with experimental data recorded in the subthalamic nucleus of Parkinson's patients performing an arm movement task. Our analyses show that during the arm movement task, neurons underwent a complex pattern of modulation of spiking intensity characterized initially by a release of inhibitory control at 20-40 ms after a spike, followed by a decrease in excitatory influence at 40-60 ms after a spike. (C) 2013 AIP Publishing LLC. C1 [Deng, Xinyi; Eden, Uri T.] Boston Univ, Dept Math & Stat, Boston, MA 02215 USA. [Eskandar, Emad N.] Massachusetts Gen Hosp, Dept Neurosurg, Boston, MA 02114 USA. [Eskandar, Emad N.] Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Deng, XY (reprint author), Boston Univ, Dept Math & Stat, Boston, MA 02215 USA. EM xinyi@math.bu.edu FU National Science Foundation [IIS-0643995]; National Institute of Neurological Disorders and Stroke [R01 NS073118] FX This work was supported by grants from the National Science Foundation [IIS-0643995] and the National Institute of Neurological Disorders and Stroke [R01 NS073118]. NR 43 TC 2 Z9 2 U1 0 U2 2 PU AMER INST PHYSICS PI MELVILLE PA CIRCULATION & FULFILLMENT DIV, 2 HUNTINGTON QUADRANGLE, STE 1 N O 1, MELVILLE, NY 11747-4501 USA SN 1054-1500 EI 1089-7682 J9 CHAOS JI Chaos PD DEC PY 2013 VL 23 IS 4 AR 046102 DI 10.1063/1.4818546 PG 14 WC Mathematics, Applied; Physics, Mathematical SC Mathematics; Physics GA 282LK UT WOS:000329172700043 PM 24387581 ER PT J AU Channick, R Preston, I Klinger, JR AF Channick, Richard Preston, Iona Klinger, James R. TI Oral Therapies for Pulmonary Arterial Hypertension Endothelin Receptor Antagonists and Phosphodiesterase-5 Inhibitors SO CLINICS IN CHEST MEDICINE LA English DT Article DE Pulmonary arterial hypertension; Oral therapy; Endothelin receptor antagonists; Phosphodiesterase-5 inhibitors ID SMOOTH-MUSCLE-CELLS; ISCHEMIC OPTIC NEUROPATHY; INHALED NITRIC-OXIDE; RANDOMIZED CONTROLLED-TRIAL; BRAIN NATRIURETIC PEPTIDE; DOUBLE-BLIND; ERECTILE DYSFUNCTION; EISENMENGER-SYNDROME; BOSENTAN THERAPY; VASCULAR-TONE AB The development of orally active pulmonary vasodilators has been a major breakthrough in the treatment of pulmonary arterial hypertension (PAH). Orally active medications greatly enhanced patient access to PAH treatment and increased an interest in the diagnosis and treatment of this disease that still continues. Four different orally active drugs are currently available for the treatment of PAH and several more are undergoing evaluation. This article discusses the mechanisms by which endothelin receptor antagonists and phosphodiesterase-5 inhibitors mitigate pulmonary hypertensive responses, and reviews the most recent data concerning their efficacy and limitations in the treatment of PAH. C1 [Channick, Richard] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Pulm & Crit Care Med, Boston, MA 02114 USA. [Preston, Iona] Tufts Univ, New England Med Ctr, Div Pulm & Crit Care Med, Boston, MA 02111 USA. [Klinger, James R.] Brown Univ, Rhode Isl Hosp, Alpert Med Sch, Div Pulm Sleep & Crit Care Med, Providence, RI 02903 USA. RP Channick, R (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Pulm & Crit Care Med, Boston, MA 02114 USA. EM rchannick@partners.org FU Actelion; Bayer; Gilead; Ikaria; United Therapeutics; Aires; GeNO FX Klinger: Grant Support: Actelion, Bayer, Gilead, Ikaria, United Therapeutics. Consultant: Bayer, United Therapeutics. Steering Committee: Bayer; Channick: Grant Support: Actelion, Bayer, United Therapeutics. Consultant: Actelion, Bayer, United Therapeutics. Steering Committee: Bayer, Actelion; Preston: Grant Support: Actelion, Aires, GeNO, Gilead, United Therapeutics. Consultant: Actelion, Bayer, Gilead, United Therapeutics. NR 85 TC 4 Z9 4 U1 0 U2 1 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0272-5231 EI 1557-8216 J9 CLIN CHEST MED JI Clin. Chest Med. PD DEC PY 2013 VL 34 IS 4 BP 811 EP + DI 10.1016/j.ccm.2013.09.005 PG 15 WC Respiratory System SC Respiratory System GA 281GB UT WOS:000329086900014 PM 24267306 ER PT J AU Lin, HZ Ketcham, JD Rosenquist, JN Simon, KI AF Lin, Haizhen Ketcham, Jonathan D. Rosenquist, James N. Simon, Kosali I. TI Financial distress and use of mental health care: Evidence from antidepressant prescription claims SO ECONOMICS LETTERS LA English DT Article DE Financial distress; Housing crisis; Mental health; Prescription ID HOUSING WEALTH AB Using nationwide county-level longitudinal data, we show that recent declines in housing prices are associated with an increased utilization of antidepressant prescriptions among the near elderly. Our results persist in difference-in-difference models using either all non-antidepressant drugs or statins as controls. (C) 2013 Elsevier B.V. All rights reserved. C1 [Lin, Haizhen] Indiana Univ, Kelley Sch Business, Dept Business Econ & Publ Policy, Bloomington, IN 47401 USA. [Ketcham, Jonathan D.] Arizona State Univ, WP Carey Sch Business, Dept Mkt, Tempe, AZ 85287 USA. [Rosenquist, James N.] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. [Rosenquist, James N.] Harvard Univ, Sch Med, Cambridge, MA 02138 USA. [Simon, Kosali I.] Indiana Univ, SPEA, Bloomington, IN 47401 USA. [Simon, Kosali I.] NBER, Cambridge, MA 02138 USA. RP Lin, HZ (reprint author), Indiana Univ, Kelley Sch Business, 1309 E 10th St, Bloomington, IN 47401 USA. EM hzlin@indiana.edu NR 17 TC 4 Z9 4 U1 0 U2 7 PU ELSEVIER SCIENCE SA PI LAUSANNE PA PO BOX 564, 1001 LAUSANNE, SWITZERLAND SN 0165-1765 EI 1873-7374 J9 ECON LETT JI Econ. Lett. PD DEC PY 2013 VL 121 IS 3 BP 449 EP 453 DI 10.1016/j.econlet.2013.09.004 PG 5 WC Economics SC Business & Economics GA 282BP UT WOS:000329145500023 ER PT J AU Moon, HS Mantzoros, CS AF Moon, Hyun-Seuk Mantzoros, Christos S. TI Adiponectin and metformin additively attenuate IL1 beta-induced malignant potential of colon cancer SO ENDOCRINE-RELATED CANCER LA English DT Article DE adiponectin; metformin; interleukin 1 beta; colon cancer; malignant potential; LKB1 ID ACTIVATED PROTEIN-KINASE; BREAST-CANCER; IN-VITRO; OVARIAN-CANCER; COLORECTAL-CANCER; RISK; GROWTH; CELLS; VIVO; MECHANISMS AB Both adiponectin (AD) and metformin (Met) have been proposed to downregulate cell proliferation of colon cancer cells, but whether their effect might be additive has not been studied to date. Genetic studies in humans have suggested an important role for interleukin 1 beta (IL1 beta) in cancer pathogenesis. Direct evidence that IL1 beta contributes to the development of colon cancer has not yet been fully confirmed and no previous studies have evaluated how IL1 beta may interact with AD and/or Met to regulate malignant potential and intracellular signaling pathways in human and mouse colon cancer cells. We conducted in vitro studies using human (LoVo) and mouse (MCA38) colon cancer cell lines to evaluate whether AD and Met alone or in combination may antagonize IL1 beta-regulated malignant potential in human and mouse colon cancer cell lines. IL1 beta increased malignant potential and regulated the expression of tumor suppressor (p53) and cell cycle regulatory genes (p21, p27, and cyclin E2) in human and mouse colon cancer cell lines. These effects were reversed by co-administration of AD and/or Met and were additively altered by AD and Met in combination in a STAT3-and AMPK/LKB1-dependent manner. We also observed using fluorescence activated cell sorter analysis that IL1 beta-regulated cell cycle progression is altered by AD and Met alone or in combination. Our novel mechanistic studies provide evidence for an important role for IL1 beta in colon cancer and suggest that AD and/or Met might be useful agents in the management or chemoprevention of IL1b-induced colon carcinogenesis. C1 [Moon, Hyun-Seuk; Mantzoros, Christos S.] Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Div Endocrinol Diabet & Metab, Boston, MA 02215 USA. [Mantzoros, Christos S.] Harvard Univ, Sch Med, Boston VA Healthcare Syst, Endocrinol Sect, Boston, MA 02130 USA. RP Mantzoros, CS (reprint author), Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Div Endocrinol Diabet & Metab, Boston, MA 02215 USA. EM cmantzor@bidmc.harvard.edu RI Moon, Hyun-Seuk/G-8576-2015 OI Moon, Hyun-Seuk/0000-0002-5216-2090 FU National Institute of Diabetes and Digestive and Kidney Diseases [58785, 79929, 81913]; Clinical Science Research and Development Service of the VA Office of Research and Development [1I01CX000422-01A1] FX This work was supported by the National Institute of Diabetes and Digestive and Kidney Diseases grant numbers 58785, 79929, and 81913 and by Award Number 1I01CX000422-01A1 from the Clinical Science Research and Development Service of the VA Office of Research and Development. NR 32 TC 4 Z9 5 U1 0 U2 3 PU BIOSCIENTIFICA LTD PI BRISTOL PA EURO HOUSE, 22 APEX COURT WOODLANDS, BRADLEY STOKE, BRISTOL BS32 4JT, ENGLAND SN 1351-0088 EI 1479-6821 J9 ENDOCR-RELAT CANCER JI Endocr.-Relat. Cancer PD DEC PY 2013 VL 20 IS 6 BP 849 EP 859 DI 10.1530/ERC-13-0240 PG 11 WC Oncology; Endocrinology & Metabolism SC Oncology; Endocrinology & Metabolism GA 282WZ UT WOS:000329206500014 PM 24157941 ER PT J AU Fuchsluger, TA Mueller, C Dana, R AF Fuchsluger, T. A. Mueller, C. Dana, R. TI Adeno-Associated Viral vector serotypes for gene transfer to corneal endothelial cells: a comparison of serotypres SO HUMAN GENE THERAPY LA English DT Meeting Abstract CT Collaborative Congress of the European-Society-for-Gene-and-Cell-Therapy and the Spanish-Society-for-Gene-and-Cell-Therapy CY OCT 25-28, 2013 CL Madrid, SPAIN SP European Soc Gene & Cell Therapy, Spanish Soc Gene & Cell Therapy C1 [Fuchsluger, T. A.] Univ Dusseldorf, Dept Ophthalmol, Dusseldorf, Germany. [Mueller, C.] Univ Massachusetts, Pediat & Gene Therapy Ctr, Sch Med, Worcester, MA 01605 USA. [Mueller, C.] Univ Massachusetts, Sch Med, Dept Pediat, Worcester, MA USA. [Fuchsluger, T. A.; Dana, R.] Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Schepens Eye Res Inst,Dept Ophthalmol, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MARY ANN LIEBERT, INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1043-0342 EI 1557-7422 J9 HUM GENE THER JI Hum. Gene Ther. PD DEC 1 PY 2013 VL 24 IS 12 BP A140 EP A140 PG 1 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA 271UU UT WOS:000328417900424 ER PT J AU Guda, S Devine, A Schambach, A Moritz, T Schlaeger, T Williams, D AF Guda, S. Devine, A. Schambach, A. Moritz, T. Schlaeger, T. Williams, D. TI Approaches to the study of reprogramming-induced genomic instability in Fanconi anemia (FA) cells and the role of the FA pathway in early hematopoietic commitment SO HUMAN GENE THERAPY LA English DT Meeting Abstract CT Collaborative Congress of the European-Society-for-Gene-and-Cell-Therapy and the Spanish-Society-for-Gene-and-Cell-Therapy CY OCT 25-28, 2013 CL Madrid, SPAIN SP European Soc Gene & Cell Therapy, Spanish Soc Gene & Cell Therapy C1 Harvard Univ, Sch Med, Boston Childrens Hosp, Boston, MA USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Stem Cell Inst, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU MARY ANN LIEBERT, INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1043-0342 EI 1557-7422 J9 HUM GENE THER JI Hum. Gene Ther. PD DEC 1 PY 2013 VL 24 IS 12 BP A19 EP A20 PG 2 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA 271UU UT WOS:000328417900058 ER PT J AU Kahraman, S Dirice, E Altunbas, HA Sanlioglu, AD AF Kahraman, S. Dirice, E. Altunbas, H. A. Sanlioglu, A. D. TI sTRAIL treatment induces beta cell proliferation SO HUMAN GENE THERAPY LA English DT Meeting Abstract CT Collaborative Congress of the European-Society-for-Gene-and-Cell-Therapy and the Spanish-Society-for-Gene-and-Cell-Therapy CY OCT 25-28, 2013 CL Madrid, SPAIN SP European Soc Gene & Cell Therapy, Spanish Soc Gene & Cell Therapy C1 [Kahraman, S.; Sanlioglu, A. D.] Akdeniz Univ, Gene & Cell Therapy Ctr, TR-07058 Antalya, Turkey. [Dirice, E.] Harvard Univ, Sch Med, Joslin Diabet Ctr, Boston, MA 02115 USA. [Altunbas, H. A.] Akdeniz Univ, Fac Med, Div Endocrinol & Metab Dis, TR-07058 Antalya, Turkey. RI Altunbas, Hasan/C-4199-2016 NR 0 TC 0 Z9 0 U1 0 U2 0 PU MARY ANN LIEBERT, INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1043-0342 EI 1557-7422 J9 HUM GENE THER JI Hum. Gene Ther. PD DEC 1 PY 2013 VL 24 IS 12 BP A145 EP A145 PG 1 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA 271UU UT WOS:000328417900438 ER PT J AU Kaufmann, KB Brendel, C de Mos, J Grez, M AF Kaufmann, K. B. Brendel, C. de Mos, J. Grez, M. TI Enhancing myeloid specific gene expression by improving transcription factor binding to the miR-223 promoter SO HUMAN GENE THERAPY LA English DT Meeting Abstract CT Collaborative Congress of the European-Society-for-Gene-and-Cell-Therapy and the Spanish-Society-for-Gene-and-Cell-Therapy CY OCT 25-28, 2013 CL Madrid, SPAIN SP European Soc Gene & Cell Therapy, Spanish Soc Gene & Cell Therapy C1 [Kaufmann, K. B.; de Mos, J.; Grez, M.] Biomed Res Inst, Frankfurt, Germany. [Brendel, C.] Harvard Univ, Sch Med, Childrens Hosp Boston, Div Hematol Oncol, Boston, MA USA. [Brendel, C.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MARY ANN LIEBERT, INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1043-0342 EI 1557-7422 J9 HUM GENE THER JI Hum. Gene Ther. PD DEC 1 PY 2013 VL 24 IS 12 BP A76 EP A76 PG 1 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA 271UU UT WOS:000328417900228 ER PT J AU Lobo, R Kiernan, TJ Jaff, MR AF Lobo, R. Kiernan, T. J. Jaff, M. R. TI Medical therapy for critical limb ischemia and the diabetic foot: an update SO JOURNAL OF CARDIOVASCULAR SURGERY LA English DT Review DE Peripheral arterial disease; Gangrene; Diabetes mellitus ID PERIPHERAL ARTERIAL-DISEASE; RANDOMIZED CONTROLLED-TRIALS; AMERICAN-HEART-ASSOCIATION; PLACEBO-CONTROLLED TRIAL; INTERMITTENT CLAUDICATION; CARDIOVASCULAR-DISEASE; VASCULAR-DISEASE; SMOKING-CESSATION; MYOCARDIAL-INFARCTION; PHYSICAL-ACTIVITY AB Critical limb ischemia is the most severe manifestation of chronic peripheral artery disease (PAD). The goal of medical care is to provide symptomatic relief in patients who are unsuitable for percutaneous or surgical revascularization and to reduce systemic cardiovascular risk. PAD is a common manifestation of systemic atherosclerosis and is associated with significant morbidity and mortality. PAD represents a marker for premature cardiovascular events. Patients with PAD, even in the absence of a history of myocardial infarction or ischemic stroke, have approximately the same relative risk of death from cardiovascular causes as do patients with a history of coronary or cerebrovascular disease alone. The PARTNERS study demonstrated that patients with PAD were less likely to receive appropriate treatment for their atherosclerotic risk factors than those who were being treated for coronary artery disease. The long term prognosis of patients with PAD is significantly worse than for patients with coronary artery disease alone. Newer therapies are being investigated to treat patients with critical limb ischemia who are unsuitable candidates for revascularization, and these will be discussed briefly. C1 [Lobo, R.; Kiernan, T. J.] Univ Limerick, Univ Hosp Limerick, Grad Entry Med Sch, Dept Cardiol, Limerick, Ireland. [Jaff, M. R.] Massachusetts Gen Hosp, Inst Heart Vasc & Stroke Care, Boston, MA 02114 USA. RP Lobo, R (reprint author), Univ Limerick, Univ Hosp Limerick, Grad Entry Med Sch, Dept Cardiol, Limerick, Ireland. NR 71 TC 0 Z9 0 U1 1 U2 9 PU EDIZIONI MINERVA MEDICA PI TURIN PA CORSO BRAMANTE 83-85 INT JOURNALS DEPT., 10126 TURIN, ITALY SN 0021-9509 EI 1827-191X J9 J CARDIOVASC SURG JI J. Cardiovasc. Surg. PD DEC PY 2013 VL 54 IS 6 BP 671 EP 678 PG 8 WC Cardiac & Cardiovascular Systems; Surgery; Peripheral Vascular Disease SC Cardiovascular System & Cardiology; Surgery GA 283SR UT WOS:000329267800002 PM 24126505 ER PT J AU Legro, RS Arslanian, SA Ehrmann, DA Hoeger, KM Murad, MH Pasquali, R Welt, CK AF Legro, Richard S. Arslanian, Silva A. Ehrmann, David A. Hoeger, Kathleen M. Murad, M. Hassan Pasquali, Renato Welt, Corrine K. TI Diagnosis and Treatment of Polycystic Ovary Syndrome: An Endocrine Society Clinical Practice Guideline SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID IMPAIRED GLUCOSE-TOLERANCE; FATTY LIVER-DISEASE; ESTRADIOL-CYPROTERONE ACETATE; DEPENDENT DIABETES-MELLITUS; LIFE-STYLE MODIFICATION; ANTI-MULLERIAN HORMONE; ENDOMETRIAL THICKNESS MEASUREMENT; CONGENITAL ADRENAL-HYPERPLASIA; COMBINED ORAL-CONTRACEPTIVES; REGULAR MENSTRUAL CYCLES AB Objective: The aim was to formulate practice guidelines for the diagnosis and treatment of polycystic ovary syndrome (PCOS). Participants: An Endocrine Society-appointed Task Force of experts, a methodologist, and a medical writer developed the guideline. Evidence: This evidence-based guideline was developed using the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) system to describe both the strength of recommendations and the quality of evidence. Consensus Process: One group meeting, several conference calls, and e-mail communications enabled consensus. Committees and members of The Endocrine Society and the European Society of Endocrinology reviewed and commented on preliminary drafts of these guidelines. Two systematic reviews were conducted to summarize supporting evidence. Conclusions: We suggest using the Rotterdam criteria for diagnosing PCOS (presence of two of the following criteria: androgen excess, ovulatory dysfunction, or polycystic ovaries). Establishing a diagnosis of PCOS is problematic in adolescents and menopausal women. Hyperandrogenism is central to the presentation in adolescents, whereas there is no consistent phenotype in postmenopausal women. Evaluation of women with PCOS should exclude alternate androgen-excess disorders and risk factors for endometrial cancer, mood disorders, obstructive sleep apnea, diabetes, and cardiovascular disease. Hormonal contraceptives are the first-line management for menstrual abnormalities and hirsutism/acne in PCOS. Clomiphene is currently the first-line therapy for infertility; metformin is beneficial for metabolic/glycemic abnormalities and for improving menstrual irregularities, but it has limited or no benefit in treating hirsutism, acne, or infertility. Hormonal contraceptives and metformin are the treatment options in adolescents with PCOS. The role of weight loss in improving PCOS status per se is uncertain, but lifestyle intervention is beneficial in over-weight/obese patients for other health benefits. Thiazolidinediones have an unfavorable risk-benefit ratio overall, and statins require further study. C1 [Legro, Richard S.] Penn State Univ, Coll Med, Hershey, PA 17033 USA. [Arslanian, Silva A.] Univ Pittsburgh, Med Ctr, Childrens Hosp Pittsburgh, Pittsburgh, PA 15224 USA. [Ehrmann, David A.] Univ Chicago, Chicago, IL 60637 USA. [Hoeger, Kathleen M.] Univ Rochester, Med Ctr, Rochester, NY 14627 USA. [Murad, M. Hassan] Mayo Clin, Rochester, MN 55905 USA. [Pasquali, Renato] Univ Alma Mater Studiorum, Orsola Malpighi Hosp, I-40126 Bologna, Italy. [Welt, Corrine K.] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Legro, RS (reprint author), Endocrine Soc, 8401 Connecticut Ave,Suite 900, Chevy Chase, MD 20815 USA. EM govt-prof@endocrine.org OI Welt, Corrine/0000-0002-8219-5504; Murad, Mohammad Hassan/0000-0001-5502-5975 FU NICHD NIH HHS [R01 HD065029]; NIDDK NIH HHS [P30 DK020595, P60 DK020595] NR 297 TC 256 Z9 284 U1 15 U2 82 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0021-972X EI 1945-7197 J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD DEC PY 2013 VL 98 IS 12 BP 4565 EP 4592 DI 10.1210/jc.2013-2350 PG 28 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 272RF UT WOS:000328477200023 PM 24151290 ER PT J AU Welt, CK Carmina, E AF Welt, Corrine K. Carmina, Enrico TI Lifecycle of Polycystic Ovary Syndrome (PCOS): From In Utero to Menopause SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Review ID ANTI-MULLERIAN HORMONE; TERM-FOLLOW-UP; REGULAR MENSTRUAL CYCLES; ANTRAL FOLLICLE COUNTS; CARDIOVASCULAR-DISEASE; SERUM CONCENTRATIONS; RISK-FACTORS; YOUNG-WOMEN; POSTMENOPAUSAL WOMEN; PRECOCIOUS PUBARCHE AB Context: Polycystic ovary syndrome (PCOS) is diagnosed during the reproductive years when women present with 2 of 3 of the following criteria: 1) irregular menstrual cycles or anovulation, 2) hyperandrogenism, and 3) PCO morphology. However, there is evidence that PCOS can be identified from early infancy to puberty based on predisposing environmental influences. There is also increasing information about the PCOS phenotype after menopause. The goal of this review is to summarize current knowledge about the appearance of PCOS at different life stages and the influence of reproductive maturation and senescence on the PCOS phenotype. Evidence: PubMed, the bibliography from the Evidence-Based PCOS Workshop, and the reference lists from identified manuscripts were reviewed. Evidence Synthesis: The current data suggest that daughters of women with PCOS have a greater follicle complement and mild metabolic abnormalities from infancy. PCOS is often diagnosed in puberty with the onset of hyperandrogenism and may be preceded by premature pubarche. During the reproductive years, there is a gradual decrease in the severity of the cardinal features of PCOS. Menopausal data suggest that the majority of women who had PCOS during their reproductive years continue to manifest cardiovascular risk factors. However, the majority do not present an increased risk for cardiovascular morbidity and mortality, perhaps because women with no history of PCOS may catch up after menopause. Conclusion: The current data provide a comprehensive starting point to understand the phenotype of PCOS across the lifespan. However, limitations such as a bias of ascertainment in childhood, age-based changes during reproductive life, and the small numbers studied during menopause point to the need for additional longitudinal studies to expand the current knowledge. C1 [Welt, Corrine K.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Carmina, Enrico] Univ Palermo, Endocrinol & Metab Unit, I-90139 Palermo, Italy. RP Welt, CK (reprint author), Massachusetts Gen Hosp, BHX 511,55 Fruit St, Boston, MA 02114 USA. EM cwelt@partners.org OI Welt, Corrine/0000-0002-8219-5504 FU National Institutes of Health [1R01HD065029]; ADA [1-10-CT-57]; [1 UL1 RR025758] FX This work was supported by the National Institutes of Health 1R01HD065029 (to C. K. W.), ADA 1-10-CT-57 (to C. K. W.), and 1 UL1 RR025758 to Harvard Clinical and Translational Science Center. NR 84 TC 28 Z9 29 U1 4 U2 17 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0021-972X EI 1945-7197 J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD DEC PY 2013 VL 98 IS 12 BP 4629 EP 4638 DI 10.1210/jc.2013-2375 PG 10 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 272RF UT WOS:000328477200030 PM 24064685 ER PT J AU Domecq, JP Prutsky, G Mullan, RJ Sundaresh, V Wang, AT Erwin, PJ Welt, C Ehrmann, D Montori, VM Murad, MH AF Domecq, Juan Pablo Prutsky, Gabriela Mullan, Rebecca J. Sundaresh, Vishnu Wang, Amy T. Erwin, Patricia J. Welt, Corrine Ehrmann, David Montori, Victor M. Murad, Mohammad Hassan TI Adverse Effects of the Common Treatments for Polycystic Ovary Syndrome: A Systematic Review and Meta-Analysis SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Review ID LIFE-STYLE MODIFICATION; PRACTITIONERS ORAL-CONTRACEPTION; LOW-DOSE FLUTAMIDE; OBESE WOMEN; INSULIN-RESISTANCE; LONG-TERM; METFORMIN THERAPY; NONOBESE WOMEN; YOUNG-WOMEN; METABOLIC SYNDROME AB Context: Polycystic ovary syndrome (PCOS) is common among women of childbearing age and the available pharmacological therapies have different side-effect profiles. Objective: We summarized the evidence about the side effects of oral contraceptive pills, metformin, and anti-androgens in women with PCOS. Data Source: Sources included Ovid Medline, OVID EMBASE, OVID Cochrane Library, Web of Science, Scopus, PsycInfo, and CINAHL from inception through April 2011. Study Selection: We included comparative observational studies enrolling women with PCOS who received the agents of choice for at least 6 months and reported adverse effects. Data Extraction: Using a standardized, piloted, and Web-based data extraction form and working in duplicate, we abstracted data from each study and performed meta-analysis when possible. Data Synthesis: We found 22 eligible studies of which 20 were randomized. No study reported severe side effects (eg, lactic acidosis, thromboembolic episodes, liver toxicity, cancer incidence, or pregnancy loss). Meta-analysis demonstrated no significant change in weight in oral contraceptive pills or flutamide users. Indirect evidence from populations without PCOS demonstrated no increased risk of lactic acidosis with metformin, only case reports of liver toxicity with flutamide (no comparative evidence), and increased relative risk difference of venous thromboembolism with oral contraceptive pills but very low absolute risk. Evidence on mortality, cardiovascular mortality, and cancer was inconclusive. Conclusions: Drugs commonly used to treat PCOS appear to be associated with very low risk of severe adverse effects although data are extrapolated from other populations. C1 [Domecq, Juan Pablo; Prutsky, Gabriela; Mullan, Rebecca J.; Sundaresh, Vishnu; Wang, Amy T.; Erwin, Patricia J.; Montori, Victor M.; Murad, Mohammad Hassan] Mayo Clin, Knowledge & Evaluat Res Unit, Rochester, MN 55905 USA. [Domecq, Juan Pablo; Prutsky, Gabriela; Montori, Victor M.] Unidad Conocimiento & Evidencia, Lima, Peru. [Mullan, Rebecca J.] Univ Minnesota, Sch Med, Minneapolis, MN 55455 USA. [Welt, Corrine] Massachusetts Gen Hosp, Reprod Endocrine Unit, Boston, MA 02114 USA. [Ehrmann, David] Univ Chicago, Endocrinol Sect, Chicago, IL 60637 USA. [Montori, Victor M.] Mayo Clin, Div Endocrinol, Rochester, MN 55905 USA. [Murad, Mohammad Hassan] Mayo Clin, Div Prevent Occupat & Aerosp Med, Rochester, MN 55905 USA. [Domecq, Juan Pablo] Henry Ford Hosp, Dept Internal Med, Detroit, MI 48202 USA. [Prutsky, Gabriela] Wayne State Univ, Childrens Hosp Michigan, Dept Pediat, Sch Med,Detroit Med Ctr, Detroit, MI 48201 USA. [Sundaresh, Vishnu] Louisiana State Univ, Hlth Sci Ctr, Div Endocrinol & Metab, Shreveport, LA 33932 USA. RP Murad, MH (reprint author), Mayo Clin, Knowledge & Evaluat Res Unit, 200 1st St SW, Rochester, MN 55905 USA. EM Murad.mohammad@mayo.edu RI amy.tu.wang, amy.tu.wang/F-8331-2014; OI amy.tu.wang, amy.tu.wang/0000-0002-0929-1399; Welt, Corrine/0000-0002-8219-5504; Murad, Mohammad Hassan/0000-0001-5502-5975; Montori, Victor/0000-0003-0595-2898 FU NICHD NIH HHS [R01 HD065029] NR 63 TC 28 Z9 29 U1 0 U2 7 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0021-972X EI 1945-7197 J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD DEC PY 2013 VL 98 IS 12 BP 4646 EP 4654 DI 10.1210/jc.2013-2374 PG 9 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 272RF UT WOS:000328477200032 PM 24092830 ER PT J AU Ross, DS AF Ross, Douglas S. TI Predicting Outcome in Patients with Thyroid Cancer SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Editorial Material ID ASSOCIATION; RECURRENCE; CARCINOMA; THERAPY; SYSTEM C1 [Ross, Douglas S.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Ross, Douglas S.] Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Ross, DS (reprint author), Massachusetts Gen Hosp, Thyroid Unit ACC 730 S, 32 Fruit St, Boston, MA 02114 USA. EM dross@partners.org NR 16 TC 1 Z9 2 U1 0 U2 0 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0021-972X EI 1945-7197 J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD DEC PY 2013 VL 98 IS 12 BP 4673 EP 4675 DI 10.1210/jc.2013-3989 PG 3 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 272RF UT WOS:000328477200037 PM 24311794 ER PT J AU Park, KH Zaichenko, L Brinkoetter, M Thakkar, B Sahin-Efe, A Joung, KE Tsoukas, MA Geladari, EV Huh, JY Dincer, F Davis, CR Crowell, JA Mantzoros, CS AF Park, Kyung Hee Zaichenko, Lesya Brinkoetter, Mary Thakkar, Bindiya Sahin-Efe, Ayse Joung, Kyoung Eun Tsoukas, Michael A. Geladari, Eleni V. Huh, Joo Young Dincer, Fadime Davis, Cynthia R. Crowell, Judith A. Mantzoros, Christos S. TI Circulating Irisin in Relation to Insulin Resistance and the Metabolic Syndrome SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID MESSENGER-RNA EXPRESSION; BROWN ADIPOSE-TISSUE; SKELETAL-MUSCLE; CARDIOVASCULAR-DISEASE; PRECURSOR FNDC5; EXERCISE; OBESITY; FAT; HOMEOSTASIS; INCREASE AB Context: Irisin, a recently identified hormone, has been proposed to regulate energy homeostasis and obesity in mice. Whether irisin levels are associated with risk of the metabolic syndrome (MetS), cardiometabolic variables, and cardiovascular disease (CVD) risk in humans remains unknown. Objective: Our objective was to assess the associations between baseline serum irisin levels and MetS, cardiometabolic variables, and CVD risk. Design, Setting, and Subjects: We conducted a comparative cross-sectional evaluation of baseline circulating levels of the novel hormone irisin and the established adipokine adiponectin with MetS, cardiometabolic variables, and CVD risk in a sample of 151 subjects. Results: Baseline irisin levels were significantly higher in subjects with MetS than in subjects without MetS. Irisin was associated negatively with adiponectin (r = -0.4, P < .001) and positively with body mass index (r = 0.22, P = .008), systolic (r = 0.17, P = .04) and diastolic (r = 0.27, P = .001) blood pressure, fasting glucose (r = 0.25, P = .002), triglycerides (r = 0.25, P = .003), and homeostasis model assessment for insulin resistance (r = 0.33, P < .001). After adjustment for potential confounders, including body mass index, subjects in the highest tertile of irisin levels were more likely to have MetS (odds ratio [OR] = 9.44, 95% confidence interval [CI] = 2.66-33.44), elevated fasting blood glucose (OR = 5.80, 95% CI = 1.72-19.60), high triglycerides (OR = 3.89, 95% CI = 1.16-13.03), and low high-density lipoprotein cholesterol (OR = 3.30, 95% CI = 1.18-9.20). Irisin was independently associated with homeostasis model assessment for insulin resistance and general Framingham risk profile in multiple linear regression analyses after adjustment for confounders. Adiponectin demonstrated the expected associations with outcomes. Conclusions: Irisin is associated with increased risk of MetS, cardiometabolic variables, and CVD in humans, indicating either increased secretion by adipose/muscle tissue and/or a compensatory increase of irisin to overcome an underlying irisin resistance in these subjects. C1 [Park, Kyung Hee; Zaichenko, Lesya; Brinkoetter, Mary; Thakkar, Bindiya; Sahin-Efe, Ayse; Geladari, Eleni V.; Huh, Joo Young; Dincer, Fadime; Mantzoros, Christos S.] Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Div Endocrinol Diabet & Metab, Boston, MA 02215 USA. [Park, Kyung Hee] Hallym Univ, Sacred Heart Hosp, Dept Family Med, Gyeonggi Do 431070, South Korea. [Tsoukas, Michael A.] McGill Univ, Ctr Hlth, Div Endocrinol & Metab, Montreal, PQ H3A 1A1, Canada. [Joung, Kyoung Eun] Boston Childrens Hosp, Div Newborn Med, Boston, MA 02115 USA. [Sahin-Efe, Ayse; Mantzoros, Christos S.] Harvard Univ, Sch Med, Boston VA Healthcare Syst, Endocrinol Sect, Boston, MA 02130 USA. [Davis, Cynthia R.; Crowell, Judith A.] Judge Baker Childrens Ctr, Boston, MA 02120 USA. [Crowell, Judith A.] SUNY Stony Brook, Sch Med, Dept Psychiat & Behav Sci, Stony Brook, NY 11794 USA. RP Mantzoros, CS (reprint author), Harvard Univ, Sch Med, JP9B52A, Boston, MA 02130 USA. EM cmantzor@bidmc.harvard.edu OI Zaichenko, Lesya/0000-0001-8489-3886; Park, Kyung Hee/0000-0001-9806-0076 FU National Institute on Aging [R01 AG032030]; National Institute of Diabetes and Digestive and Kidney Diseases [81913]; National Center for Research Resources [UL1 RR025758] FX This study was supported by National Institute on Aging Grant R01 AG032030 and National Institute of Diabetes and Digestive and Kidney Diseases Grant 81913. The project described was supported by Grant UL1 RR025758 to the Harvard Clinical and Translational Science Center, from the National Center for Research Resources. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Center for Research Resources or the National Institutes of Health. NR 37 TC 109 Z9 119 U1 3 U2 28 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0021-972X EI 1945-7197 J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD DEC PY 2013 VL 98 IS 12 BP 4899 EP 4907 DI 10.1210/jc.2013-2373 PG 9 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 272RF UT WOS:000328477200064 PM 24057291 ER PT J AU Iwama, S Welt, CK Romero, CJ Radovick, S Caturegli, P AF Iwama, Shintaro Welt, Corrine K. Romero, Christopher J. Radovick, Sally Caturegli, Patrizio TI Clinical Case Seminar: Isolated Prolactin Deficiency Associated With Serum Autoantibodies Against Prolactin-Secreting Cells (vol 98, pg 3920, 2013) SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Correction C1 [Welt, Corrine K.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Reprod Endocrine Unit,Dept Med, Boston, MA 02114 USA. NR 1 TC 0 Z9 0 U1 0 U2 0 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0021-972X EI 1945-7197 J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD DEC PY 2013 VL 98 IS 12 BP 4992 EP 4992 DI 10.1210/jc.2013-3904 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 272RF UT WOS:000328477200073 ER PT J AU Su, HI Maas, K Sluss, PM Chang, RJ Hall, JE Joffe, H AF Su, H. Irene Maas, Kevin Sluss, Patrick M. Chang, R. Jeffrey Hall, Janet E. Joffe, Hadine TI The Impact of Depot GnRH Agonist on AMH Levels in Healthy Reproductive-Aged Women SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID ANTI-MULLERIAN HORMONE; ANTIMULLERIAN HORMONE; MENSTRUAL-CYCLE; PREMENOPAUSAL WOMEN; OVARIAN RESERVE; BREAST-CANCER; CHEMOTHERAPY; EXPRESSION; PREDICTOR; MENOPAUSE AB Context: GnRH agonists (GnR Ha) are being used experimentally in an attempt to preserve fertility in young female cancer patients undergoing chemotherapy. Anti-Mullerian hormone (AMH) produced by ovarian granulosa cells may serve as a marker of ovarian reserve, but it is not clear whether this marker is useful during GnRHa treatment. Objective: The purpose of this study was to determine the effect of a depot GnRHa on AMH levels. Design: Depot leuprolide (3.75 mg) was administered in the midluteal phase (MLP) in healthy women. Assessments of AM H, FSH, LH, estradiol, and progesterone were performed in the early follicular phase (EFP) and MLP before GnRHa treatment and approximately 7, 14, and 30 days after GnRHa administration. Setting: The study was conducted in a university research center. Patients: Participants were 33 healthy, premenopausal women aged 18 to 45 years old with regular menses. Results: EFP and MLP AMH levels were similar before GnRHa administration. Relative to MLP AMH levels, AM H decreased 7 days after GnRHa administration by a median of 24% (P<.001) and then increased above pretreatment levels 14 and 30 days after GnRHa by 13% and 32%, respectively (P<.001). Changes in AMH levels did not correlate with changes in gonadotropins, estradiol, or progesterone. Conclusions: Significant changes in AM H levels occur in the first 4 weeks after depot leuprolide administration, suggesting that AMH may not be a reliable marker of ovarian reserve during this interval. Changes in AMH occurred independent of gonadotropin levels, supporting a direct effect of GnRHa on granulosa cell expression of AM H or an indirect effect of GnRHa on the development and/or dynamics of the follicle pool. C1 [Su, H. Irene; Maas, Kevin; Chang, R. Jeffrey] Univ Calif San Diego, Moores Canc Ctr, San Diego, CA 92093 USA. [Sluss, Patrick M.; Hall, Janet E.; Joffe, Hadine] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. RP Joffe, H (reprint author), Massachusetts Gen Hosp, Dept Psychiat, Simches Res Bldg,185 Cambridge St,Suite 2000, Boston, MA 02114 USA. EM hjoffe@partners.org OI Hall, Janet/0000-0003-4644-3061 FU National Institutes of Health [HD058799, 5R01MH082922]; American Cancer Society [MRSG-08-110-01-CCE]; Cephalon/Teva FX This work was supported by the National Institutes of Health (grants HD058799 to H.I.S. and 5R01MH082922 to H.J.) and American Cancer Society (grant MRSG-08-110-01-CCE to H.I.S.).; H.J. has received grant funding from Cephalon/Teva, serves on the advisory board for Noven Pharmaceuticals and is an unpaid consultant to Sunovion. H.I.S. has served on the advisory board for Ferring Pharmaceuticals. the other authors have nothing to disclose. NR 21 TC 17 Z9 19 U1 1 U2 6 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0021-972X EI 1945-7197 J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD DEC PY 2013 VL 98 IS 12 BP E1961 EP E1966 DI 10.1210/jc.2013-2410 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 272RF UT WOS:000328477200013 PM 24081742 ER PT J AU Tai, B Saxon, AJ Ling, W AF Tai, Betty Saxon, Andrew J. Ling, Walter TI Medication-assisted therapy for opioid addiction SO JOURNAL OF FOOD AND DRUG ANALYSIS LA English DT Article; Proceedings Paper CT International Conference on Global Health (ICGH) CY APR 17-19, 2013 CL Taipei, TAIWAN DE Buprenorphine; Chronic care model; Methadone; Opioid addiction ID BUPRENORPHINE-NALOXONE; CARE AB The "Medication-Assisted Therapy for Opioid Addiction" session was chaired by Dr Betty Tai and had three presenters. The presenters (and their topics) were: Dr Andrew J. Saxon (methadone and buprenorphine for treatment of opioid addiction and human immunodeficiency virus risk reduction); Dr Walter Ling (opioid antagonist treatment for opioid addiction); and Dr Betty Tai (chronic care model for substance use disorder). Copyright (C) 2013, Food and Drug Administration, Taiwan. Published by Elsevier Taiwan LLC. All rights reserved. C1 [Tai, Betty] Natl Inst Drug Abuse, Ctr Clin Trials Network, Bethesda, MD 20892 USA. [Saxon, Andrew J.] VA Puget Sound Hlth Care Syst, Ctr Excellence Subst Abuse Treatment & Educ, Seattle, WA USA. [Saxon, Andrew J.] Univ Washington, Dept Psychiat & Behav Sci, Seattle, WA 98195 USA. [Ling, Walter] Univ Calif Los Angeles, David Geffen Sch Med, Integrated Subst Abuse Programs, Los Angeles, CA 90095 USA. RP Tai, B (reprint author), Natl Inst Drug Abuse, Ctr Clin Trials Network, 6001 Execut Blvd, Bethesda, MD 20892 USA. EM btai@nida.nih.gov FU NIDA NIH HHS [R13 DA035084, P30 DA016383] NR 11 TC 4 Z9 4 U1 0 U2 4 PU FOOD & DRUG ADMINSTRATION PI TAIPEI PA 161-2 KUNYANG STREET, NANGANG, TAIPEI, 00000, TAIWAN SN 1021-9498 J9 J FOOD DRUG ANAL JI J. Food Drug Anal. PD DEC PY 2013 VL 21 SU 4 BP S13 EP S15 DI 10.1016/j.jfda.2013.09.023 PG 3 WC Food Science & Technology; Pharmacology & Pharmacy SC Food Science & Technology; Pharmacology & Pharmacy GA 285VJ UT WOS:000329422800007 PM 25264415 ER PT J AU Fachko, MJ Xiao, CH Bowles, KH Robinson, KM Libonati, JR AF Fachko, Michael J. Xiao, Canhau Bowles, Kathryn H. Robinson, Keith M. Libonati, Joseph R. TI Cardiovascular Effects and Enjoyment of Exercise Gaming in Older Adults SO JOURNAL OF GERONTOLOGICAL NURSING LA English DT Article ID HEART-RATE RECOVERY; ACTIVE VIDEO GAMES; SUDDEN CARDIAC DEATH; PHYSICAL-ACTIVITY; VIRTUAL-REALITY; ENERGY-EXPENDITURE; BARRIERS; CHILDREN; REHABILITATION; TECHNOLOGY AB The purpose of this study was to quantify the cardiovascular responses and enjoyment of one trial of electronic exercise gaming (EG) (Nintendo (R) Wii (TM) Tennis) in healthy, older adults (mean age = 81 [SD = 4 years]). Findings indicate that 15 minutes of EG moderately increased heart rate (p < 0.001), blood pressure (p < 0001), and perceived exertion (p < 00001) compared to resting levels. This corresponded to achieving 64% of age-predicted maximum heart rate. No differences were observed for the cardiovascular responses to EG between genders, but participants taking beta-blocker drugs showed an attenuated response (p < 0.05). All participants completed EG tennis without excessive fatigue, with 86% of participants enjoying the experience. There were only a few cases of EG-related arrhythmias (n = 2) and post-exercise muscle soreness (n = 3). These results suggest that Nintendo Wii Tennis EG technology represents an enjoyable, moderate intensity physical activity for healthy, older adults. C1 [Fachko, Michael J.] Univ Penn, Perelman Sch Med, Ctr Sleep & Circadian Neurobiol, Philadelphia, PA 19104 USA. [Bowles, Kathryn H.] Univ Penn, Sch Nursing, Ctr Integrat Sci Aging, Philadelphia, PA 19104 USA. [Robinson, Keith M.] Univ Penn, Philadelphia VA Med Ctr, Philadelphia, PA 19104 USA. [Robinson, Keith M.] Univ Penn, Perelman Sch Med, Dept Phys Med & Rehabil, Philadelphia, PA 19104 USA. [Libonati, Joseph R.] Univ Penn, Sch Nursing, Lab Innovat & Translat Nursing Res, Philadelphia, PA 19104 USA. [Xiao, Canhau] Emory Univ, Nell Hodgson Woodruff Sch Nursing, Atlanta, GA 30322 USA. RP Libonati, JR (reprint author), Univ Penn, Sch Nursing, Lab Innovat & Translat Nursing Res, 135 Claire M Fagin Hall,418 Curie Blvd, Philadelphia, PA 19104 USA. EM jlibonat@nursing.upenn.edu NR 57 TC 4 Z9 4 U1 2 U2 14 PU SLACK INC PI THOROFARE PA 6900 GROVE RD, THOROFARE, NJ 08086 USA SN 0098-9134 EI 1938-243X J9 J GERONTOL NURS JI J. Gerontol. Nurs. PD DEC PY 2013 VL 39 IS 12 BP 43 EP 54 PG 12 WC Geriatrics & Gerontology; Gerontology; Nursing SC Geriatrics & Gerontology; Nursing GA 282RG UT WOS:000329189600007 PM 23855328 ER PT J AU Newhouse, JP McWilliams, JM Price, M Huang, J Fireman, B Hsu, J AF Newhouse, Joseph P. McWilliams, J. Michael Price, Mary Huang, Jie Fireman, Bruce Hsu, John TI Do Medicare Advantage plans select enrollees in higher margin clinical categories? SO JOURNAL OF HEALTH ECONOMICS LA English DT Article DE Selection; Risk adjustment; Medicare ID PREVIOUSLY UNINSURED ADULTS; MANAGED HEALTH-CARE; RISK-ADJUSTMENT; ADVERSE SELECTION; MARKETS; MODEL AB The CMS-HCC risk adjustment system for Medicare Advantage (MA) plans calculates weights, which are effectively relative prices, for beneficiaries with different observable characteristics. To do so it uses the relative amounts spent per beneficiary with those characteristics in Traditional Medicare (TM). For multiple reasons one might expect relative amounts in MA to differ from TM, thereby making some beneficiaries more profitable to treat than others. Much of the difference comes from differences in how TM and MA treat different diseases or diagnoses. Using data on actual medical spending from two MAHMO plans, we show that the weights calculated from MA costs do indeed differ from those calculated using TM spending. One of the two plans (Plan 1) is more typical of MA-HMO plans in that it contracts with independent community providers, while the other (Plan 2) is vertically integrated with care delivery. We calculate margins, or average revenue/average cost, for Medicare beneficiaries in the two plans who have one of 48 different combinations of medical conditions. The two plans' margins for these 48 conditions are correlated (r= 0.39, p <0.01). Both plans have margins that are more positive for persons with conditions that are managed by primary care physicians and where medical management can be effective. Conversely they have lower margins for persons with conditions that tend to be treated by specialists with greater market power than primary care physicians and for acute conditions where little medical management is possible. The two plan's margins among beneficiaries with different observable characteristics vary over a range of 160 and 98 percentage points, respectively, and thus would appear to offer substantial incentive for selection by HCC. Nonetheless, we find no evidence of overrepresentation of beneficiaries in high margin HCC's in either plan. Nor, using the margins from Plan 1, the more typical plan, do we find evidence of overrepresentation of high margin HCC's in Medicare more generally. These results do not permit a conclusion on overall social efficiency, but we note that selection according to margin could be socially efficient. In addition, our findings suggest there are omitted interaction terms in the risk adjustment model that Medicare currently uses. (C) 2013 Elsevier B.V. All rights reserved. C1 [Newhouse, Joseph P.] Harvard Univ, Kennedy Sch, Boston, MA 02115 USA. [Newhouse, Joseph P.; McWilliams, J. Michael; Hsu, John] Harvard Univ, Sch Med, Dept Hlth Care Policy, Boston, MA 02115 USA. [Newhouse, Joseph P.] Harvard Univ, Sch Publ Hlth, Dept Hlth Policy & Management, Boston, MA 02115 USA. [McWilliams, J. Michael] Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. [Price, Mary; Huang, Jie; Fireman, Bruce] Kaiser Permanente No Calif, Div Res, Pasadena, CA USA. [Hsu, John] Massachusetts Gen Hosp, Mongan Inst Hlth Policy, Boston, MA 02114 USA. [Hsu, John] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. RP Newhouse, JP (reprint author), Harvard Univ, 180 Longwood Ave, Boston, MA 02115 USA. EM joseph_newhouse@harvard.edu FU National Institute of Aging [P01-032952]; Beeson Career Development Award Program (National Institute on Aging) [K08 AG038354]; the Beeson Career Development Award Program (American Federation for Aging Research) FX The authors would like to acknowledge support from the National Institute of Aging, Grant P01-032952, and from the Beeson Career Development Award Program (National Institute on Aging K08 AG038354 and the American Federation for Aging Research). Newhouse wishes to disclose that he is a director of and holds equity in Aetna, which sells Medicare Advantage plans. The authors thank Tom McGuire for comments on an earlier draft. NR 24 TC 10 Z9 10 U1 0 U2 11 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 DEC PY 2013 VL 32 IS 6 BP 1278 EP 1288 DI 10.1016/j.jhealeco.2013.09.003 PG 11 WC Economics; Health Care Sciences & Services; Health Policy & Services SC Business & Economics; Health Care Sciences & Services GA 283VM UT WOS:000329275100024 PM 24308879 ER PT J AU Cacciatore, S Tenori, L AF Cacciatore, Stefano Tenori, Leonardo TI Brain cholesterol homeostasis in Wilson disease SO MEDICAL HYPOTHESES LA English DT Article ID CENTRAL-NERVOUS-SYSTEM; GENE KNOCKOUT MICE; ALZHEIMERS-DISEASE; COPPER ACCUMULATION; PROTEIN OXIDATION; IN-VITRO; TURNOVER; METABOLISM; 24S-HYDROXYCHOLESTEROL; MECHANISM AB Wilson disease (WD) is an autosomal recessive inherited disorder of copper (Cu) metabolism, resulting in pathological accumulation of Cu in many organs and tissues, predominantly in the liver and brain. There clearly is a close and complex relationship between Cu and the cholesterol's metabolic pathway; therefore any theory about the cholesterol metabolism in the brain of patients with WD must take it into account. The hypothesis presented in this paper is that the imbalance in cerebral copper homeostasis caused by WD may plays a key role in the derangement of the cholesterol homeostasis in the brain, and thus promoting the observed WD related neurological disorders. Crown Copyright (C) 2013 Published by Elsevier Ltd. All rights reserved. C1 [Cacciatore, Stefano] Harvard Univ, Sch Med, Dept Med Oncol, Dana Farber Canc Inst, Boston, MA 02115 USA. [Cacciatore, Stefano] Univ Rovira & Virgili, Spanish Biomed Res Ctr Diabet & Associated Metab, E-43007 Tarragona, Spain. [Tenori, Leonardo] FiorGen Fdn, I-50019 Sesto Fiorentino, Italy. RP Cacciatore, S (reprint author), Harvard Univ, Sch Med, Dept Med Oncol, Dana Farber Canc Inst, Boston, MA 02115 USA. EM stefano_cacciatore@dfci.harvard.edu RI Tenori, Leonardo/J-9258-2016; OI Tenori, Leonardo/0000-0001-6438-059X; Cacciatore, Stefano/0000-0001-7052-7156 FU FIRC (Fondazione Italiana per la Ricerca sul Cancro); Associazione Italiana per la Ricerca sul Cancro FX S.C. was supported by a fellowship from FIRC (Fondazione Italiana per la Ricerca sul Cancro). NR 35 TC 3 Z9 3 U1 0 U2 1 PU CHURCHILL LIVINGSTONE PI EDINBURGH PA JOURNAL PRODUCTION DEPT, ROBERT STEVENSON HOUSE, 1-3 BAXTERS PLACE, LEITH WALK, EDINBURGH EH1 3AF, MIDLOTHIAN, SCOTLAND SN 0306-9877 EI 1532-2777 J9 MED HYPOTHESES JI Med. Hypotheses PD DEC PY 2013 VL 81 IS 6 BP 1127 EP 1129 DI 10.1016/j.mehy.2013.10.018 PG 3 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 284QJ UT WOS:000329334800036 PM 24176139 ER PT J AU Kim, S Jabori, S O'Connell, J Freeman, S Fung, CC Ekram, S Unawame, A Van Norman, G AF Kim, Sara Jabori, Sinan O'Connell, Jessica Freeman, Shanna Fung, Cha Chi Ekram, Sahrish Unawame, Amruta Van Norman, Gail TI Research methodologies in informed consent studies involving surgical and invasive procedures: Time to re-examine? SO PATIENT EDUCATION AND COUNSELING LA English DT Review DE Informed consent; Patient perspectives; Ethics; Research design ID ENDOSCOPIC SINUS SURGERY; IV-CONTRAST MATERIAL; CARDIAC-SURGERY; GASTROINTESTINAL ENDOSCOPY; WRITTEN INFORMATION; PATIENTS RECALL; PATIENTS WANT; PATIENT COMPREHENSION; QUESTIONNAIRE SURVEY; MEDICAL-EDUCATION AB Objective: We conducted a review of informed consent studies involving surgical and invasive procedures and report the degree to which current research targets a broader scope cif patient outcomes beyond comprehension. Methods: Using PubMed, Cumulative Index to Nursing and Allied Health Literature, and Excerpta Medical Database, we identified 97 articles for review. Six members coded articles and generated scores of study design quality. Results: The mean quality score (10.7 out of a total score of 20) was low. Most studies were single institution-based, relying on one-time data collections. Randomly assigning subjects to study conditions, using power analysis to determine subject numbers, and reporting psychometric evidence, such as reliability and validity, were not widely reported. Most frequently targeted patient outcomes were knowledge, understanding and satisfaction. Core informed consent outcomes (e.g. capacity, voluntariness, decision making) and emotional factors (e.g. anxiety) were not extensively addressed. Conclusion: Informed consent research may benefit from applying qualitative methods to more directly tap into patients' beliefs and decisions by eliciting in patients' own words their emotions and reasoning around processing informed consent content. Practice implications: Research that addresses patient perspectives toward surgical interventions should tap into underexplored ethical and emotional factors that shape decision making. (C) 2013 Elsevier Ireland Ltd. All rights reserved. C1 [Kim, Sara; Ekram, Sahrish] Univ Washington, Sch Med, Dept Surg, ISIS, Seattle, WA 98195 USA. [Jabori, Sinan; O'Connell, Jessica] Univ Calif Los Angeles, David Geffen Sch Med, UCLA Gonda Goldschmied Vasc Ctr, Div Vasc Surg, Los Angeles, CA 90095 USA. [O'Connell, Jessica; Freeman, Shanna] VA Greater Los Angeles Healthcare Syst, Vasc Surg Serv, Los Angeles, CA USA. [Fung, Cha Chi] Univ So Calif, Keck Sch Med, Dept Med Educ, Los Angeles, CA 90033 USA. [Unawame, Amruta] Massachusetts Gen Hosp, PDY2, Boston, MA 02114 USA. [Van Norman, Gail] Univ Washington, Sch Med, Dept Anesthesiol & Pain Med, Seattle, WA 98195 USA. [Van Norman, Gail] Univ Washington, Sch Med, Dept Bioeth & Humanities, Seattle, WA 98195 USA. RP Kim, S (reprint author), Univ Washington, Sch Med, Dept Surg, Box 356410,1959 NE Pacific,Room SP-1120, Seattle, WA 98195 USA. EM sarakim@uw.edu NR 116 TC 1 Z9 1 U1 1 U2 8 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0738-3991 J9 PATIENT EDUC COUNS JI Patient Educ. Couns. PD DEC PY 2013 VL 93 IS 3 BP 559 EP 566 DI 10.1016/j.pec.2013.08.018 PG 8 WC Public, Environmental & Occupational Health; Social Sciences, Interdisciplinary SC Public, Environmental & Occupational Health; Social Sciences - Other Topics GA 283SM UT WOS:000329267300030 PM 24021416 ER PT J AU Feudtner, C Womer, J Augustin, R Remke, S Wolfe, J Friebert, S Weissman, D AF Feudtner, Chris Womer, James Augustin, Rachel Remke, Stacy Wolfe, Joanne Friebert, Sarah Weissman, David TI Pediatric Palliative Care Programs in Children's Hospitals: A Cross-Sectional National Survey SO PEDIATRICS LA English DT Article DE pediatric; palliative care; hospice care; hospital care; survey ID COMPLEX CHRONIC CONDITIONS; MEDICAL COMPLEXITY; WASHINGTON-STATE; UNITED-STATES; CANCER; SERVICE; AVAILABILITY; LIFE; END; IMPLEMENTATION AB BACKGROUND: Pediatric palliative care (PPC) programs facilitate the provision of comprehensive care to seriously ill children. Over the past 10 years many such programs have been initiated by children's hospitals, but little is known about their number, staff composition, services offered, sources of support, or national distribution. METHODS: In the summer of 2012, we surveyed 226 hospitals as identified by the National Association of Children's Hospitals and Related Institutions. The survey instrument gathered data about whether their institution had a PPC program, and for hospitals with programs, it asked for a wide range of information including staffing, patient age range, services provided, and financial support. RESULTS: Of the 162 hospitals that provided data (71.7% response rate), 69% reported having a PPC program. The rate of new program creation peaked in 2008, with 12 new programs created that year, and 10 new programs in 2011. Most programs offer only inpatient services, and most only during the work week. The number of consults per year varied substantially across programs, and was positively associated with hospital bed size and number of funded staff members. PPC programs report a high level of dependence on hospital funding. CONCLUSIONS: PPC programs are becoming common in children's hospitals throughout the United States yet with marked variation in how these programs are staffed, the level of funding for staff effort to provide PPC, and the number of consultations performed annually. Guidelines for PPC team composition, funding, and consultation standards may be warranted to ensure the highest quality of PPC. C1 [Feudtner, Chris; Womer, James] Childrens Hosp Philadelphia, Philadelphia, PA 19104 USA. [Womer, James] Temple Univ, Sch Med, Philadelphia, PA 19122 USA. [Augustin, Rachel; Weissman, David] Ctr Adv Palliat Care, New York, NY USA. [Remke, Stacy] Univ Minnesota, Sch Social Work, Minneapolis, MN 55455 USA. [Wolfe, Joanne] Boston Childrens Hosp, Dana Farber Canc Inst, Div Pediat Palliat Care, Boston, MA USA. [Wolfe, Joanne] Boston Childrens Hosp, Dept Med, Boston, MA USA. [Friebert, Sarah] Akron Childrens Hosp, Haslinger Family Pediat Palliat Care Div, Akron, OH USA. RP Feudtner, C (reprint author), Childrens Hosp Philadelphia, Room 1523,34th & Civ Ctr Blvd, Philadelphia, PA 19104 USA. EM feudtner@email.chop.edu FU Cameron and Hayden Lord Foundation (New York, NY) FX Supported by a grant from the Cameron and Hayden Lord Foundation (New York, NY). NR 44 TC 38 Z9 38 U1 2 U2 13 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 DEC PY 2013 VL 132 IS 6 BP 1063 EP 1070 DI 10.1542/peds.2013-1286 PG 8 WC Pediatrics SC Pediatrics GA 282IG UT WOS:000329163900047 PM 24190689 ER PT J AU Shaw, SY Tran, K Castoreno, AB Peloquin, JM Lassen, KG Khor, B Aldrich, LN Tan, PH Graham, DB Kuballa, P Goel, G Daly, MJ Shamji, AF Schreiber, SL Xavier, RJ AF Shaw, Stanley Y. Khoa Tran Castoreno, Adam B. Peloquin, Joanna M. Lassen, Kara G. Khor, Bernard Aldrich, Leslie N. Tan, Pauline H. Graham, Daniel B. Kuballa, Petric Goel, Gautam Daly, Mark J. Shamji, Alykhan F. Schreiber, Stuart L. Xavier, Ramnik J. TI Selective Modulation of Autophagy, Innate Immunity, and Adaptive Immunity by Small Molecules SO ACS CHEMICAL BIOLOGY LA English DT Article ID INFLAMMATORY-BOWEL-DISEASE; MYCOBACTERIUM-TUBERCULOSIS; CHEMICAL MODULATORS; SCREEN; CELLS; PATHOGENESIS; SUSCEPTIBILITY; INTERLEUKIN-1; MECHANISM; INDUCERS AB Autophagy is an evolutionarily conserved catabolic process that directs cytoplasmic proteins, organelles and microbes to lysosomes for degradation. Autophagy acts at the intersection of pathways involved in cellular stress, host defense, and modulation of inflammatory and immune responses; however, the details of how the autophagy network intersects with these processes remain largely undefined. Given the role of autophagy in several human diseases, it is important to determine the extent to which modulators of autophagy also modify inflammatory or immune pathways and whether it is possible to modulate a subset of these pathways selectively. Here, we identify small-molecule inducers of basal autophagy (including several FDA-approved drugs) and characterize their effects on IL-1 beta production, autophagic engulfment and killing of intracellular bacteria, and development of T-reg, T(H)17, and T(H)1 subsets from naive T cells. Autophagy inducers with distinct, selective activity profiles were identified that reveal the functional architecture of connections between autophagy, and innate and adaptive immunity. In macrophages from mice bearing a conditional deletion of the essential autophagy gene Atg16L1, the small molecules inhibit IL-1 beta production to varying degrees suggesting that individual compounds may possess both autophagy-dependent and autophagy-independent activity on immune pathways. The small molecule autophagy inducers constitute useful probes to test the contributions of autophagy-related pathways in diseases marked by impaired autophagy or elevated IL-1 beta and to test novel therapeutic hypotheses. C1 [Shaw, Stanley Y.; Khoa Tran; Tan, Pauline H.] Massachusetts Gen Hosp, Ctr Syst Biol, Boston, MA 02114 USA. [Peloquin, Joanna M.; Khor, Bernard; Kuballa, Petric; Goel, Gautam; Xavier, Ramnik J.] Massachusetts Gen Hosp, Ctr Computat & Integrat Biol, Boston, MA 02114 USA. [Shaw, Stanley Y.; Castoreno, Adam B.; Lassen, Kara G.; Aldrich, Leslie N.; Daly, Mark J.; Shamji, Alykhan F.; Schreiber, Stuart L.; Xavier, Ramnik J.] Broad Inst Harvard & MIT, Cambridge, MA 02142 USA. [Aldrich, Leslie N.; Graham, Daniel B.; Schreiber, Stuart L.] Harvard Univ, Dept Chem & Chem Biol, Cambridge, MA 02138 USA. [Daly, Mark J.] Massachusetts Gen Hosp, Analyt & Translat Genet Unit, Boston, MA 02114 USA. [Schreiber, Stuart L.] Harvard Univ, Howard Hughes Med Inst, Cambridge, MA 02138 USA. RP Shaw, SY (reprint author), Massachusetts Gen Hosp, Ctr Syst Biol, Boston, MA 02114 USA. EM shaw.stanley@mgh.harvard.edu; xavier@molbio.mgh.harvard.edu OI Khor, Bernard/0000-0003-4689-5092 FU National Institutes of Health (NIH) [DK 043351, DK 097485, DK092405, HHSN268201000044C]; MGH Center for the Study of Inflammatory Bowel Disease [DK 043351]; Helmsley Trust FX This work was supported with funds from National Institutes of Health (NIH) grants DK 043351, DK 097485, and DK092405 (R.J.X.), HHSN268201000044C (S.Y.S.), a PFS grant from the MGH Center for the Study of Inflammatory Bowel Disease (DK 043351) (S.Y.S.), and the Helmsley Trust (R.J.X. and S.L.S.). The authors declare that they have no competing interests. NR 39 TC 27 Z9 27 U1 3 U2 19 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 1554-8929 EI 1554-8937 J9 ACS CHEM BIOL JI ACS Chem. Biol. PD DEC PY 2013 VL 8 IS 12 BP 2724 EP 2733 DI 10.1021/cb400352d PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 281CW UT WOS:000329078100016 PM 24168452 ER PT J AU Casagrande, L Dalpian, DM Ardenghi, TM Zanatta, FB Balbinot, CEA Garcia-Godoy, F de Araujo, FB AF Casagrande, Luciano Dalpian, Debora Martini Ardenghi, Thiago Machado Zanatta, Fabricio Batistin Agostini Balbinot, Carlos Eduardo Garcia-Godoy, Franklin de Araujo, Fernando Borba TI Randomized clinical trial of adhesive restorations in primary molars. 18-month results SO AMERICAN JOURNAL OF DENTISTRY LA English DT Article ID INDIRECT PULP TREATMENT; PRIMARY TEETH; POSTERIOR PRIMARY; LONGEVITY; AMALGAM AB Purpose: To evaluate the clinical performance of adhesive restorations of resin composite and resin-modified glass-ionomer cements in primary molars. Methods: This randomized clinical trial included subjects (5-9 year-old children) selected at two university centers (UFRGS and UNIFRA). The sample consisted of 132 primary molars presenting active cavitated carious lesions (with radiographic involvement of the inner half of the dentin), located on the occlusal and occlusal-proximal surface. The sample was randomly divided into three groups, according to the restorative material: (G1) universal restorative system (Adper Single Bond 2 system and Filtek Z350); (G2): Resin-modified glass-ionomer cement (Vitremer); and (G3): Low shrink restorative system (Filtek P90). The restorations were clinically and radiographically followed every 6 months for up to 18 months using the USPHS modified criteria for clinical evaluation. Survival estimates for restoration longevity were evaluated using the Kaplan-Meier method. Log-rank test (P< 0.05) was used to compare the differences in the success rate according to the type of the restorative material. Results: The type of restorative material used did not influence the longevity of the restorations. After clinical follow-up, there was no statistical difference in the rates of success for the three materials used to restore active cavitated carious lesions in primary molars. The survival rates for the follow-up were similar regarding the number of restored surfaces and the caries removal technique (partial or complete). Mean estimated time of survival was 17.2 months (95% CI: 16.7-17.7). Estimated survival rates of the restorations were 100%, 98%, 88% and 65% at 1, 6, 12 and 18 months of clinical evaluations, respectively. C1 [Casagrande, Luciano; de Araujo, Fernando Borba] Univ Fed Rio Grande do Sul, Sch Dent, Dept Pediat Dent, BR-90035003 Porto Alegre, RS, Brazil. [Dalpian, Debora Martini; Agostini Balbinot, Carlos Eduardo] Franciscan Univ Ctr, Sch Dent, Santa Maria, RS, Brazil. [Ardenghi, Thiago Machado; Zanatta, Fabricio Batistin] Univ Fed Santa Maria, Postgrad Program Dent, Santa Maria, RS, Brazil. [Garcia-Godoy, Franklin] Univ Tennessee, Hlth Sci Ctr, Memphis, TN USA. [Garcia-Godoy, Franklin] Forsyth Ctr, Cambridge, MA USA. RP Casagrande, L (reprint author), Univ Fed Rio Grande do Sul, Sch Dent, Dept Pediat Dent, Ramiro Barcelos 2492, BR-90035003 Porto Alegre, RS, Brazil. EM luciano.casagrande@ufrgs.br OI Araujo, Fernando/0000-0001-6471-5564 FU FAPERGS (Fundacao de Amparo a Pesquisa do Estado do Rio Grande do Sul) [1010205-0] FX The authors declared no conflict of interest. The study was funded by FAPERGS (Fundacao de Amparo a Pesquisa do Estado do Rio Grande do Sul) (process n.1010205-0). NR 19 TC 10 Z9 12 U1 0 U2 10 PU MOSHER & LINDER, INC PI WESTON PA 318 INDIAN TRACE SUITE 500, WESTON, FL 33326 USA SN 0894-8275 J9 AM J DENT JI Am. J. Dent. PD DEC PY 2013 VL 26 IS 6 BP 351 EP 355 PG 5 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 278XN UT WOS:000328923300010 PM 24640441 ER PT J AU Paunescu, TG Lu, HAJ Russo, LM Pastor-Soler, NM McKee, M McLaughlin, MM Bartlett, BE Breton, S Brown, D AF Paunescu, Teodor G. Lu, Hua A. J. Russo, Leileata M. Pastor-Soler, Nuria M. McKee, Mary McLaughlin, Margaret M. Bartlett, Bianca E. Breton, Sylvie Brown, Dennis TI Vasopressin induces apical expression of caveolin in rat kidney collecting duct principal cells SO AMERICAN JOURNAL OF PHYSIOLOGY-RENAL PHYSIOLOGY LA English DT Article DE renal epithelia; caveolae; Brattleboro rats; aquaporin-2 trafficking; immunofluorescence; water transport ID TRANS-GOLGI-NETWORK; B2 SUBUNIT ISOFORM; PLASMA-MEMBRANE; V-ATPASE; INTERCALATED CELLS; EPITHELIAL-CELLS; MDCK CELLS; BINDING PROTEIN; WATER CHANNEL; GENE FAMILY AB Caveolin (Cav)1 is expressed in the basolateral membrane domain of renal collecting duct (CD) principal cells (PCs), where it is associated with caveolae. To reveal any potential involvement of Cav1 in vasopressin signaling, we used specific monoclonal and polyclonal antibodies to examine its localization in CD PCs of Brattleboro (BB) rats treated with vasopressin (DDAVP). Compared with controls, immunofluorescence revealed a time-dependent increase in Cav1 expression in the apical membrane domain of PCs, where it overlapped with aquaporin-2 (AQP2). After 24 h of DDAVP treatment, Cav1 was visible as an increased number of small apical spots. The staining gradually became more extensive, and, after 2 wk of DDAVP, it occupied the majority of the apical membrane domain of many PCs. Cav1 also assumed an apical localization in PCs of DDAVP-treated Sprague-Dawley and Long-Evans rats. Similarly, Cav2 appeared at the apical pole of PCs after DDAVP treatment of BB, Sprague-Dawley, and Long-Evans rats. Immunogold electron microscopy confirmed bipolar Cav1 membrane expression in DDAVP-treated BB rats, whereas caveolae were only detected on the basolateral membrane. Immunoblot analysis of BB rat whole kidney homogenates revealed no significant increase in Cav1 levels in DDAVP-treated rats, suggesting that DDAVP induces Cav1 relocalization or modifies its targeting. We conclude that Cav1 and Cav2 trafficking and membrane localization are dramatically altered by the action of DDAVP. Importantly, the absence of apical caveolae indicates that while Cavs may have an as yet undetermined role in vasopressin-regulated signaling processes, this is probably unrelated to AQP2 internalization by caveolae. C1 [Paunescu, Teodor G.; Lu, Hua A. J.; Russo, Leileata M.; McKee, Mary; McLaughlin, Margaret M.; Bartlett, Bianca E.; Breton, Sylvie; Brown, Dennis] Massachusetts Gen Hosp, MGH Ctr Syst Biol, Program Membrane Biol, Boston, MA 02114 USA. [Paunescu, Teodor G.; Lu, Hua A. J.; Russo, Leileata M.; McKee, Mary; McLaughlin, Margaret M.; Bartlett, Bianca E.; Breton, Sylvie; Brown, Dennis] Massachusetts Gen Hosp, Div Nephrol, Boston, MA 02114 USA. [Paunescu, Teodor G.; Lu, Hua A. J.; Russo, Leileata M.; Breton, Sylvie; Brown, Dennis] Harvard Univ, Sch Med, Boston, MA USA. [Pastor-Soler, Nuria M.] Univ Pittsburgh, Sch Med, Dept Med, Renal Electrolyte Div, Pittsburgh, PA 15213 USA. [Pastor-Soler, Nuria M.] Univ Pittsburgh, Sch Med, Dept Cell Biol, Pittsburgh, PA USA. RP Paunescu, TG (reprint author), Massachusetts Gen Hosp, Simches Res Ctr, Div Nephrol, Program Membrane Biol, 185 Cambridge St,CPZN8150, Boston, MA 02114 USA. EM Paunescu.Teodor@mgh.harvard.edu FU National Institutes of Health (NIH) [DK-73266, DK-075940, HD-045524, DK-38452, DK-96586]; Boston Area Diabetes and Endocrinology Research Center (NIH) [DK-57521]; MGH Center for the Study of Inflammatory Bowel Disease (NIH) [DK-43351] FX This work was supported by National Institutes of Health (NIH) Grants DK-73266 (to T. G. Paunescu), DK-075940 (to H. A. J. Lu), HD-045524 (to N. M. Pastor-Soler), DK-38452 (to D. Brown and S. Breton), and DK-96586 (to D. Brown). Additional support for the Program in Membrane Biology Microscopy Core comes from the Boston Area Diabetes and Endocrinology Research Center (NIH Grant DK-57521) and the MGH Center for the Study of Inflammatory Bowel Disease (NIH Grant DK-43351). NR 76 TC 5 Z9 5 U1 0 U2 1 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 1931-857X EI 1522-1466 J9 AM J PHYSIOL-RENAL JI Am. J. Physiol.-Renal Physiol. PD DEC PY 2013 VL 305 IS 12 BP F1783 EP F1795 DI 10.1152/ajprenal.00622.2012 PG 13 WC Physiology; Urology & Nephrology SC Physiology; Urology & Nephrology GA 278IP UT WOS:000328883300017 PM 24133120 ER PT J AU Peloquin, JM Nguyen, DD AF Peloquin, Joanna M. Nguyen, Deanna D. TI The microbiota and inflammatory bowel disease: Insights from animal models SO ANAEROBE LA English DT Article; Proceedings Paper CT 11th Biennial Congress of the Anaerobe-Society-of-the-Americas CY JUN 27-JUL 01, 2012 CL San Francisco, CA SP Anaerobe Soc Amer DE Colitis; Inflammatory bowel disease; Microbiota; Animal models ID SEGMENTED FILAMENTOUS BACTERIA; MUCOSAL IMMUNE-SYSTEM; T-HELPER-CELLS; HELICOBACTER-HEPATICUS; COLON-CANCER; INTERLEUKIN-10-DEFICIENT MICE; COLITIS; INFECTION; DIFFERENTIATION; ENTEROCOLITIS AB Inflammatory bowel disease (IBD) is thought to result from a dysregulated immune response to intestinal microbial flora in individuals with genetic predisposition(s). Genome-wide association studies (GWAS) in human IBD have identified more than 150 associated loci, some of which are key players in innate immunity and bacterial handling, reflecting the importance of the microbiota in disease pathogenesis. In fact, the presence of a microbial flora is not only crucial to the development of a normal murine immune system but also critical for the development of disease in the majority of animal models of IBD. Although animal models do not perfectly recapitulate human IBD, they have led to the discovery of important concepts in IBD pathogenesis, such as the central role of microbiota in disease development and perpetuation. Many genetically susceptible models do not develop colitis when raised in a germ-free or Helicobacter-free environment. In fact, disease in most models can be attenuated or completely abolished with antibiotic treatment. Moreover, an interplay between intestinal microbiota and mucosal immune activation is suggested by the presence of serum antibodies against the Cbir1 flagellin, an immunodominant antigen that activates TLR5, in certain models of spontaneous colitis as well as in human patients. Furthermore, T cells reactive to Cbir1 are able to induce disease in recipient mice upon adoptive cell transfer, demonstrating the pro-inflammatory properties of certain bacterial products. In fact, it has been shown that transfer of certain intestinal bacteria from a specific genetically altered mouse model with spontaneous colitis can induce disease in wild-type mice upon co-housing or direct feeding. These observations demonstrate the pathogenic potential of intestinal microbiota in IBD. However, intestinal bacteria are not always maladaptive in mucosal homeostasis. Both Bacteroides fragilis and Clostridium species promote the number and function of a certain regulatory T cell subset in the colon leading to protection against murine colitis. In fact, normal development of regulatory cells and epithelial cell integrity are abolished in the absence of an intestinal flora, suggestive of the need for certain microbial components to induce beneficial anti-inflammatory mechanisms. All in all, altered immune responses to microbes play a crucial role in IBD pathogenesis. However, certain components of the microbiota are also likely critical for normal development of regulatory mechanisms that contribute to mucosal homeostasis. Findings in animal models highlight the concept that IBD is a disease that results from the interplay of genetics and microbial/environmental factors. (C) 2013 Elsevier Ltd. All rights reserved. C1 [Peloquin, Joanna M.; Nguyen, Deanna D.] Massachusetts Gen Hosp, Gastrointestinal Unit, Boston, MA 02114 USA. [Peloquin, Joanna M.; Nguyen, Deanna D.] Massachusetts Gen Hosp, Ctr Study Inflammatory Bowel Dis, Boston, MA 02114 USA. [Peloquin, Joanna M.; Nguyen, Deanna D.] Harvard Univ, Sch Med, Boston, MA USA. RP Nguyen, DD (reprint author), Massachusetts Gen Hosp, Gastrointestinal Unit, 55 Fruit St Jackson 8th Floor, Boston, MA 02114 USA. EM dnguyen3@partners.org FU NIDDK NIH HHS [K08DK083430, K08 DK083430] NR 44 TC 13 Z9 14 U1 5 U2 22 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 1075-9964 EI 1095-8274 J9 ANAEROBE JI Anaerobe PD DEC PY 2013 VL 24 BP 102 EP 106 DI 10.1016/j.anaerobe.2013.04.006 PG 5 WC Microbiology SC Microbiology GA 278TJ UT WOS:000328912400021 PM 23603043 ER PT J AU Selvi, F Dodson, TB Nattestad, A Robertson, K Tolstunov, L AF Selvi, Firat Dodson, Thomas B. Nattestad, Anders Robertson, Kevin Tolstunov, Len TI Factors that are associated with injury to the inferior alveolar nerve in high-risk patients after removal of third molars SO BRITISH JOURNAL OF ORAL & MAXILLOFACIAL SURGERY LA English DT Article DE Inferior alveolar nerve (IAN); Nerve injury; Mandibular third molar; Computed tomography (CT); Cone-beam computed tomography (CBCT); Panoramic radiography ID CONVENTIONAL PANORAMIC RADIOGRAPHY; BEAM COMPUTED-TOMOGRAPHY; TOPOGRAPHIC RELATIONSHIP; NEUROSENSORY DEFICITS; SURGERY; EXTRACTION; RELIABILITY; MANAGEMENT; PROXIMITY; ACCURACY AB Our aim was to answer the question: "Among patients at high risk of injury to the inferior alveolar nerve (IAN) after removal of 3rd molars, what factors are associated with postoperative neurosensory deficits?" We organized a retrospective, two-center study and enrolled a group of subjects who were at increased risk of injury to the IAN after removal of 3rd molars because radiographic findings indicated a risk on panoramic radiography that was high enough to warrant preoperative computed tomography (CT). The primary outcome variable was postoperative injury to the IAN. We used descriptive, bivariate, and multivariate analyses to assess the significance of differences, and probabilities of less than 0.05 were accepted as significant. We studied 149 subjects who had 235 3rd molars removed. Their mean (SD) age was 31 (11) years and 25/235 (11%) of 3rd molars were associated with injury to the IAN. In the multiple logistic regression model, increasing age (odds ratio (OR) 1.05, 95% CI 1.01-1.1, p = 0.04), female sex (OR 5.3, 95% CI 1.6-16.9,p = 0.005), and the size (mm) of the cortical perforation in the inferior alveolar canal (IAC) viewed on the coronal CT cut (OR 1.3; 95% CI 1.0-1.6, p = 0.03) were associated with an increased risk of postoperative injury to the IAN. Age, sex, and the size of the perforation in the IAC on the coronal CT were associated with an increased risk of injury to the IAN. These findings may help to guide recommendations for treatment of patients at high risk of injury to the IAN during removal of 3rd molars. (C) 2013 The British Association of Oral and Maxillofacial Surgeons. Published by Elsevier Ltd. All rights reserved. C1 [Selvi, Firat] Istanbul Univ, Fac Dent, Dept Oral & Maxillofacial Surg, Istanbul, Turkey. [Dodson, Thomas B.] Harvard Univ, Sch Dent Med, Massachusetts Gen Hosp, Ctr Appl Clin Invest,Dept Oral & Maxillofacial Su, Boston, MA 02115 USA. [Nattestad, Anders; Tolstunov, Len] Univ Pacific, Arthur A Dugoni Sch Dent, Dept Oral & Maxillofacial Surg, San Francisco, CA USA. [Robertson, Kevin] Univ Pacific, Arthur A Dugoni Sch Dent, San Francisco, CA USA. [Tolstunov, Len] Univ Calif San Francisco, San Francisco, CA 94143 USA. RP Selvi, F (reprint author), Istanbul Univ, Fac Dent, Dept Oral & Maxillofacial Surg, Istanbul, Turkey. EM firatselvi@gmail.com FU International Postdoctoral Research Fellowship Program of the Scientific and Technological Research Council of Turkey (TUBITAK); Bilim Insani Destekleme Daire Baskanligi (BIDEB), Ankara, Turkey; Center for Applied Clinical Investigation, Department of Oral and Maxillofacial Surgery, Massachusetts General Hospital, Boston, MA FX This study was supported and funded in part by International Postdoctoral Research Fellowship Program of the Scientific and Technological Research Council of Turkey (TUBITAK), Bilim Insani Destekleme Daire Baskanligi (BIDEB), Ankara, Turkey, and the Center for Applied Clinical Investigation, Department of Oral and Maxillofacial Surgery, Massachusetts General Hospital, Boston, MA. The authors would like to thank Fatima Saleem, BA and Brad Tricomi, BS, MS, for helping create and reformat the figures. NR 23 TC 4 Z9 6 U1 1 U2 10 PU CHURCHILL LIVINGSTONE PI EDINBURGH PA JOURNAL PRODUCTION DEPT, ROBERT STEVENSON HOUSE, 1-3 BAXTERS PLACE, LEITH WALK, EDINBURGH EH1 3AF, MIDLOTHIAN, SCOTLAND SN 0266-4356 J9 BRIT J ORAL MAX SURG JI Br. J. Oral Maxillofac. Surg. PD DEC PY 2013 VL 51 IS 8 BP 868 EP 873 DI 10.1016/j.bjoms.2013.08.007 PG 6 WC Dentistry, Oral Surgery & Medicine; Surgery SC Dentistry, Oral Surgery & Medicine; Surgery GA 280DY UT WOS:000329010100038 PM 24012054 ER PT J AU Brooks-Worrell, B Palmer, JP AF Brooks-Worrell, Barbara Palmer, Jerry P. TI Prevention versus intervention of type 1 diabetes SO CLINICAL IMMUNOLOGY LA English DT Review DE Type 1 diabetes; Type 2 diabetes; Islet autoimmunity; Prediction; Intervention; Prevention ID STEM-CELL TRANSPLANTATION; PLACEBO-CONTROLLED TRIAL; RECENT-ONSET; DOUBLE-BLIND; DIETARY INTERVENTION; CD3-ANTIBODY THERAPY; NATURAL-HISTORY; MELLITUS; INSULIN; AUTOIMMUNITY AB Type 1 diabetes (T1D) is a cell-mediated autoimmune disease. New cases of T1D are on the increase and exogenous insulin therapy is the only intervention regularly initiated for T1D patients. Though tremendous strides have been made in prediction of T1D, prevention and intervention strategies have not experienced the same success. In this review, we will discuss some possible reasons why new intervention therapies for T1D have not been implemented into the mainstream treatment regimen for T1D patients. We will also discuss potential caveats for why prevention and intervention trials in T1D may not have experienced the same success as prediction trials. (C) 2013 Elsevier Inc. All rights reserved. C1 [Brooks-Worrell, Barbara] Univ Washington, Dept Med, Seattle, WA 98108 USA. VA Puget Sound Hlth Care Syst, Dept Med, Seattle, WA 98108 USA. RP Brooks-Worrell, B (reprint author), VA Puget Sound Hlth Care Syst, 1660 S Columbian Way, Seattle, WA 98108 USA. EM bbrooks@u.washington.edu NR 53 TC 5 Z9 5 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 1521-6616 EI 1521-7035 J9 CLIN IMMUNOL JI Clin. Immunol. PD DEC PY 2013 VL 149 IS 3 SI SI BP 332 EP 338 DI 10.1016/j.clim.2013.05.018 PN A PG 7 WC Immunology SC Immunology GA 278FN UT WOS:000328874700009 PM 23803322 ER PT J AU DeFife, JA Malone, JC DiLallo, J Westen, D AF DeFife, Jared A. Malone, Johanna C. DiLallo, John Westen, Drew TI Assessing Adolescent Personality Disorders With the Shedler-Westen Assessment Procedure for Adolescents SO CLINICAL PSYCHOLOGY-SCIENCE AND PRACTICE LA English DT Article DE adolescent personality disorders; diagnosis and classification; dimensional diagnosis; personality pathology; Shedler-Westen Assessment ProcedureAdolescent version ID ASSESSMENT PROCEDURE SWAP; AXIS-II DISORDERS; MMPI T-SCORES; 5-FACTOR MODEL; DSM-III; INTERNAL CONSISTENCY; ATTACHMENT PATTERNS; CLINICAL-ASSESSMENT; INFORMANT-REPORTS; SELF-REPORTS AB This two-part study describes the development and validation of a method for quantifying adolescent personality pathology using the latest edition of the Shedler-Westen Assessment Procedure for Adolescents (SWAP-II-A), an instrument designed to be used by clinically experienced observers. In Study 1, experienced psychologists and psychiatrists described a normative clinical sample of 950 North American patients. Study 2 applied the SWAP-II-A in a day treatment setting. Results indicated that SWAP-II-A personality disorder (PD) scales evidenced high internal consistency, construct validity with Diagnostic and Statistical Manual of Mental Disorders (5th ed.) symptoms and diagnoses, and concurrent validity with Child Behavior Checklist (CBCL) ratings. Independent observers saw patients similarly, and PD assessments were significantly associated with CBCL scale scores and ward behavior. C1 [DeFife, Jared A.] Emory Univ, Sch Med, Dept Psychiat & Behav Sci, Atlanta, GA 30322 USA. [Malone, Johanna C.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Psychiat, Cambridge, MA 02138 USA. [DiLallo, John] NYU, Sch Med, New York City Adm Childrens Serv, New York, NY 10003 USA. [Westen, Drew] Emory Univ, Dept Psychol, Atlanta, GA 30322 USA. [Westen, Drew] Emory Univ, Dept Psychiat, Atlanta, GA 30322 USA. RP DeFife, JA (reprint author), Emory Univ, Sch Med, Dept Psychiat & Behav Sci, 1365 Clifton Rd NE,Bldg B,Suite B6117, Atlanta, GA 30322 USA. EM jdefife@emory.edu NR 90 TC 3 Z9 3 U1 3 U2 4 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0969-5893 EI 1468-2850 J9 CLIN PSYCHOL-SCI PR JI Clin. Psychol.-Sci. Pract. PD DEC PY 2013 VL 20 IS 4 BP 393 EP 407 DI 10.1111/cpsp.12049 PG 15 WC Psychology, Clinical SC Psychology GA 264RB UT WOS:000327896800004 ER PT J AU Nicolay, BN Dyson, NJ AF Nicolay, Brandon N. Dyson, Nicholas J. TI The multiple connections between pRB and cell metabolism SO CURRENT OPINION IN CELL BIOLOGY LA English DT Article ID RETINOBLASTOMA TUMOR-SUPPRESSOR; KINASE GENE PROMOTER; S-PHASE; ADIPOCYTE DIFFERENTIATION; MITOCHONDRIAL BIOGENESIS; PROTEIN; RB; E2F; ACTIVATION; SENESCENCE AB The pRB tumor suppressor is traditionally seen as an important regulator of the cell cycle. pRB represses the transcriptional activation of a diverse set of genes by the E2F transcription factors and prevents inappropriate S-phase entry. Advances in our understanding of pRB have documented roles that extend beyond the cell cycle and this review summarizes recent studies that link pRB to the control of cell metabolism. pRB has been shown to regulate glucose tolerance, mitogenesis, glutathione synthesis, and the expression of genes involved in central carbon metabolism. Several studies have demonstrated that pRB directly targets a set of genes that are crucial for nucleotide metabolism, and this seems likely to represent one of the ways by which pRB influences the G1/S-phase transition and S-phase progression. C1 [Nicolay, Brandon N.; Dyson, Nicholas J.] Massachusetts Gen Hosp, Ctr Canc, Mol Oncol Lab, Charlestown, MA 02129 USA. RP Nicolay, BN (reprint author), Massachusetts Gen Hosp, Ctr Canc, Mol Oncol Lab, Bldg 149,13th St, Charlestown, MA 02129 USA. EM bnicolay@partners.org; dyson@helix.mgh.harvard.edu FU NIH NRSA fellowship [F32CA165856]; MGH Federal Share of Program Income [C06 CA059267] FX We apologize to our colleagues whose work we failed to include due to space limitations. BNN is supported by the NIH NRSA fellowship F32CA165856. N.J.D. is the James and Shirley Curvey MGH Research Scholar. This work was supported by the MGH Federal Share of Program Income under C06 CA059267. NR 47 TC 17 Z9 17 U1 0 U2 1 PU CURRENT BIOLOGY LTD PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0955-0674 EI 1879-0410 J9 CURR OPIN CELL BIOL JI Curr. Opin. Cell Biol. PD DEC PY 2013 VL 25 IS 6 BP 735 EP 740 DI 10.1016/j.ceb.2013.07.012 PG 6 WC Cell Biology SC Cell Biology GA 277CO UT WOS:000328796200010 PM 23916769 ER PT J AU Sunyaev, SR Roth, FP AF Sunyaev, Shamil R. Roth, Frederick P. TI Systems biology and the analysis of genetic variation SO CURRENT OPINION IN GENETICS & DEVELOPMENT LA English DT Editorial Material C1 [Sunyaev, Shamil R.] Harvard Univ, Sch Med, Div Genet, Brigham & Womens Hosp,Dept Med, Boston, MA 02115 USA. [Roth, Frederick P.] Univ Toronto, Donnelly Ctr, Toronto, ON M5S 3E1, Canada. [Roth, Frederick P.] Univ Toronto, Dept Mol Genet, Toronto, ON M5S 3E1, Canada. [Roth, Frederick P.] Univ Toronto, Dept Comp Sci, Toronto, ON M5S 3E1, Canada. [Roth, Frederick P.] Mt Sinai Hosp, Lunenfeld Tanenbaum Res Inst, Toronto, ON M5G 1X5, Canada. [Roth, Frederick P.] Dana Farber Canc Inst, Ctr Canc Syst Biol, Boston, MA 02115 USA. RP Sunyaev, SR (reprint author), Harvard Univ, Sch Med, Div Genet, Brigham & Womens Hosp,Dept Med, 77 Ave Louis Pasteur, Boston, MA 02115 USA. EM ssunyaev@rics.bwh.harvard.edu; fritz.roth@utoronto.ca RI Roth, Frederick/H-6308-2011; OI Roth, Frederick/0000-0002-6628-649X FU NCI NIH HHS [U54 CA143874]; NHGRI NIH HHS [HG001715, HG004233, P50 HG004233, R01 HG001715, U01 HG001715, U01 HG006500, U41 HG001715]; NHLBI NIH HHS [HL107440, U01 HL107440]; NIDDK NIH HHS [R01 DK095721]; NIGMS NIH HHS [R01 GM078598]; NIMH NIH HHS [R01 MH101244] NR 0 TC 1 Z9 1 U1 1 U2 8 PU CURRENT BIOLOGY LTD PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0959-437X EI 1879-0380 J9 CURR OPIN GENET DEV JI Curr. Opin. Genet. Dev. PD DEC PY 2013 VL 23 IS 6 BP 599 EP 601 DI 10.1016/j.gde.2013.11.010 PG 3 WC Cell Biology; Genetics & Heredity SC Cell Biology; Genetics & Heredity GA 280CO UT WOS:000329006500001 PM 24291212 ER PT J AU Savova, V Vigneau, S Gimelbrant, AA AF Savova, Virginia Vigneau, Sebastien Gimelbrant, Alexander A. TI Autosomal monoallelic expression: genetics of epigenetic diversity? SO CURRENT OPINION IN GENETICS & DEVELOPMENT LA English DT Article ID X-CHROMOSOME INACTIVATION; ASYNCHRONOUS REPLICATION; ALLELIC INACTIVATION; RECEPTOR GENES; RETT-SYNDROME; LINKED GENE; MOUSE; CHOICE; METHYLATION; CANCER AB In mammals, relative expression of the two parental alleles of many genes is controlled by one of three major epigenetic phenomena: X chromosome inactivation, imprinting, and mitotically stable autosomal monoallelic expression (MAE). MAE affects a large fraction of human autosomal genes and introduces enormous epigenetic heterogeneity in otherwise similar cell populations. Despite its prevalence, many functional and mechanistic aspects of MAE biology remain unknown. Several lines of evidence imply that MAE establishment and maintenance are controlled by a variety of genetic elements. Based on known genomic features regulating X-inactivation and imprinting, we outline likely features of MAE-controlling elements. We also assess implications of MAE for genotype-phenotype relationship, with a focus on haploinsufficiency. C1 [Savova, Virginia; Gimelbrant, Alexander A.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Canc Biol,Dept Genet, Boston, MA 02215 USA. [Vigneau, Sebastien] Univ Penn, Dept Cell & Dev Biol, Perelman Sch Med, Philadelphia, PA 19104 USA. RP Gimelbrant, AA (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Canc Biol,Dept Genet, 450 Brookline Ave, Boston, MA 02215 USA. EM gimelbrant@mail.dfci.harvard.edu OI Vigneau, Sebastien/0000-0002-9091-2067 FU Susan Smith Women's Cancers Program FX We thank Marisa Bartolomei, Suzanne Gaudet, and Mitzi Kuroda for commenting on the manuscript, and members of the Gimelbrant lab for stimulating discussions. VS is supported by Susan Smith Women's Cancers Program; SV is a fellow of the American Heart Association; AG is a Pew scholar. NR 58 TC 10 Z9 10 U1 0 U2 7 PU CURRENT BIOLOGY LTD PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0959-437X EI 1879-0380 J9 CURR OPIN GENET DEV JI Curr. Opin. Genet. Dev. PD DEC PY 2013 VL 23 IS 6 BP 642 EP 648 DI 10.1016/j.gde.2013.09.001 PG 7 WC Cell Biology; Genetics & Heredity SC Cell Biology; Genetics & Heredity GA 280CO UT WOS:000329006500007 PM 24075575 ER PT J AU Sahni, N Yi, S Zhong, Q Jailkhani, N Charloteaux, B Cusick, ME Vidal, M AF Sahni, Nidhi Yi, Song Zhong, Quan Jailkhani, Noor Charloteaux, Benoit Cusick, Michael E. Vidal, Marc TI Edgotype: a fundamental link between genotype and phenotype SO CURRENT OPINION IN GENETICS & DEVELOPMENT LA English DT Article ID PROTEIN-PROTEIN INTERACTIONS; HIPPEL-LINDAU-DISEASE; INTERACTOME NETWORK; INTERACTION MAP; EDGETIC PERTURBATION; MONOGENIC DISEASE; REVERSE 2-HYBRID; COMPLEX DISEASE; C-ELEGANS; MUTATION AB Classical 'one-gene/one-disease' models cannot fully reconcile with the increasingly appreciated prevalence of complicated genotype-to-phenotype associations in human disease. Genes and gene products function not in isolation but as components of intricate networks of macromolecules (DNA, RNA, or proteins) and metabolites linked through biochemical or physical interactions, represented in 'interactome' network models as 'nodes' and 'edges', respectively. Accordingly, mechanistic understanding of human disease will require understanding of how disease-causing mutations affect systems or interactome properties. The study of 'edgetics' uncovers specific loss or gain of interactions (edges) to interpret genotype-to-phenotype relationships. We review how distinct genetic variants, the genotype, lead to distinct phenotypic outcomes, the phenotype, through edgetic perturbations in interactome networks altogether representing the 'edgotype'. C1 [Sahni, Nidhi; Yi, Song; Zhong, Quan; Jailkhani, Noor; Charloteaux, Benoit; Cusick, Michael E.; Vidal, Marc] Dana Farber Canc Inst, Ctr Canc Syst Biol, Boston, MA 02215 USA. [Sahni, Nidhi; Yi, Song; Zhong, Quan; Jailkhani, Noor; Charloteaux, Benoit; Cusick, Michael E.; Vidal, Marc] Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02215 USA. [Sahni, Nidhi; Yi, Song; Zhong, Quan; Jailkhani, Noor; Charloteaux, Benoit; Cusick, Michael E.; Vidal, Marc] Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA. RP Vidal, M (reprint author), Dana Farber Canc Inst, Ctr Canc Syst Biol, Boston, MA 02215 USA. EM marc_vidal@dfci.harvard.edu FU NHGRI NIH HHS [R01 HG001715, P50 HG004233, RC4 HG006066] NR 98 TC 34 Z9 34 U1 2 U2 17 PU CURRENT BIOLOGY LTD PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0959-437X EI 1879-0380 J9 CURR OPIN GENET DEV JI Curr. Opin. Genet. Dev. PD DEC PY 2013 VL 23 IS 6 BP 649 EP 657 DI 10.1016/j.gde.2013.11.002 PG 9 WC Cell Biology; Genetics & Heredity SC Cell Biology; Genetics & Heredity GA 280CO UT WOS:000329006500008 PM 24287335 ER PT J AU Liu, CC Galougahi, KK Weisbrod, RM Hansen, T Ravaie, R Nunez, A Liu, YB Fry, N Garcia, A Hamilton, EJ Sweadner, KJ Cohen, RA Figtree, GA AF Liu, Chia-Chi Galougahi, Keyvan Karimi Weisbrod, Robert M. Hansen, Thomas Ravaie, Ramtin Nunez, Andrea Liu, Yi B. Fry, Natasha Garcia, Alvaro Hamilton, Elisha J. Sweadner, Kathleen J. Cohen, Richard A. Figtree, Gemma A. TI Oxidative inhibition of the vascular Na+-K+ pump via NADPH oxidase-dependent pi-subunit glutathionylation: Implications for angiotensin beta(1)-induced vascular dysfunction SO FREE RADICAL BIOLOGY AND MEDICINE LA English DT Article DE Na+-K+ pump; Glutathionylation; Angiotensin II; NADPH oxidase; Vascular tone regulation; Oxidative signaling ID SMOOTH-MUSCLE-CELLS; SODIUM-POTASSIUM PUMP; HIGH-RISK PATIENTS; NITRIC-OXIDE; REACTIVE OXYGEN; NAD(P)H OXIDASE; BLOOD-PRESSURE; FXYD PROTEINS; CARDIOVASCULAR-DISEASE; INDUCED HYPERTENSION AB Glutathionylation of the Na+-K+ pump's beta(1)-subunit is a key molecular mechanism of physiological and pathophysiological pump inhibition in cardiac myocytes. Its contribution to Na+-K+ pump regulation in other tissues is unknown, and cannot be assumed given the dependence on specific beta-subunit isoform expression and receptor-coupled pathways. As Na+-K+ pump activity is an important determinant of vascular tone through effects on [Ca2+](i), we have examined the role of oxidative regulation of the Na+-K+ pump in mediating angiotensin II (Ang II)-induced increases in vascular reactivity. beta(1)-subunit glutathione adducts were present at baseline and increased by exposure to Ang II in rabbit aortic rings, primary rabbit aortic vascular smooth muscle cells (VSMCs), and human arterial segments. In VSMCs, Ang II-induced glutathionylation was associated with marked reduction in Na+-K+ ATPase activity, an effect that was abolished by the NADPH oxidase inhibitory peptide, tat-gp91 ds. In aortic segments, Ang II-induced glutathionylation was associated with decreased K+-induced vasorelaxation, a validated index of pump activity. Ang II-induced oxidative inhibition of Na+-K+ ATPase and decrease in K+-induced relaxation were reversed by preincubation of VSMCs and rings with recombinant FXYD3 protein that is known to facilitate deglutathionylation of beta(1)-subunit. Knock-out of FXYD1 dramatically decreased K+-induced relaxation in a mouse model. Attenuation of Ang II signaling in vivo by captopril (8 mg/kg/day for 7 days) decreased superoxide-sensitive DHE levels in the media of rabbit aorta, decreased (beta(1)-subunit glutathionylation, and enhanced K+-induced vasorelaxation. Ang II inhibits the Na+-K+ pump in VSMCs via NADPH oxidase-dependent glutathionylation of the pump's beta(1)-subunit, and this newly identified signaling pathway may contribute to altered vascular tone. FXYD proteins reduce oxidative inhibition of the Na+-K+ pump and may have an important protective role in the vasculature under conditions of oxidative stress. (C) 2013 Elsevier Inc. All rights reserved. C1 [Liu, Chia-Chi; Galougahi, Keyvan Karimi; Hansen, Thomas; Ravaie, Ramtin; Nunez, Andrea; Fry, Natasha; Garcia, Alvaro; Hamilton, Elisha J.; Figtree, Gemma A.] Univ Sydney, North Shore Heart Res Grp, Kolling Inst Med Res, St Leonards, NSW 2065, Australia. [Galougahi, Keyvan Karimi; Figtree, Gemma A.] Royal N Shore Hosp, Dept Cardiol, Sydney, NSW, Australia. [Weisbrod, Robert M.; Cohen, Richard A.] Boston Univ, Sch Med, Whitaker Cardiovasc Inst, Vasc Biol Sect,Dept Med, Boston, MA 02118 USA. [Liu, Yi B.; Sweadner, Kathleen J.] Massachusetts Gen Hosp, Lab Membrane Biol, Boston, MA 02114 USA. RP Figtree, GA (reprint author), Univ Sydney, Royal N Shore Hosp, Kolling Inst Med Res, North Shore Heart Res Grp, St Leonards, NSW 2065, Australia. EM gemma.figtree@sydney.edu.au RI Hamilton, Elisha/F-8187-2010; Garcia, Alvaro/E-6573-2015 OI Hamilton, Elisha/0000-0002-1892-352X; FU Heart Research Australia; National Health & Medical Research Council [633252]; National Heart Foundation of Australia [PF 12S 6924]; NHLBI [RO1 HL031607, R37 HL104017]; University of Sydney Medical Foundation; Sylvia and Charles Viertel Charitable Foundation FX Dr. Ramtin Ravaie was tragically killed in an accident in July 2012, and is included as a co-author due to his contribution to the design, performance, and analysis of organ bath experiments. We thank Professor Amy Tucker for the generous provision of FXYD-/- mice. The work was supported by grants from the Heart Research Australia (former North Shore Heart Research Foundation) and the National Health & Medical Research Council (Project Grant 633252). C.C.L. was supported by a Fellowship (PF 12S 6924) from the National Heart Foundation of Australia. RAC is supported by NHLBI grants RO1 HL031607 and R37 HL104017. G.F. was supported by the University of Sydney Medical Foundation and the Sylvia and Charles Viertel Charitable Foundation. The authors declare that they have no conflict of interests. NR 82 TC 13 Z9 14 U1 0 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0891-5849 EI 1873-4596 J9 FREE RADICAL BIO MED JI Free Radic. Biol. Med. PD DEC PY 2013 VL 65 BP 563 EP 572 DI 10.1016/j.freeradbiomed.2013.06.040 PG 10 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA 278DI UT WOS:000328868900054 PM 23816524 ER PT J AU St Denis, TG Vecchio, D Zadlo, A Rineh, A Sadasivam, M Avci, P Huang, L Kozinska, A Chandran, R Sarna, T Hamblin, MR AF St Denis, Tyler G. Vecchio, Daniela Zadlo, Andrzej Rineh, Ardeshir Sadasivam, Magesh Avci, Pinar Huang, Liyi Kozinska, Anna Chandran, Rakkiyappan Sarna, Tadeusz Hamblin, Michael R. TI Thiocyanate potentiates antimicrobial photodynamic therapy: In situ generation of the sulfur trioxide radical anion by singlet oxygen SO FREE RADICAL BIOLOGY AND MEDICINE LA English DT Article DE Thiocyanate; Antimicrobial photodynamic inactivation; Sulfite; Cyanide; ESR spin trapping; Gram-positive bacteria; Gram-negative bacteria ID PEROXIDASE-CATALYZED OXIDATION; HYDROGEN-PEROXIDE; HORSERADISH-PEROXIDASE; METHYLENE-BLUE; INACTIVATION; MECHANISMS; PHOTOLYSIS; BACTERIA; PERSULFOXIDE; RESISTANCE AB Antimicrobial photodynamic therapy (PDT) is used for the eradication of pathogenic microbial cells and involves the light excitation of dyes in the presence of O-2, yielding reactive oxygen species including the hydroxyl radical ((OH)-O-center dot) and singlet oxygen (O-1(2)). In order to chemically enhance PDT by the formation of longer-lived radical species, we asked whether thiocyanate (SCN-) could potentiate the methylene blue (MB) and light-mediated killing of the gram-positive Staphylococcus aureus and the gram-negative Escherichia coli. SCN- enhanced PDT (10 mu M MB, 5J/cm(2) 660 nm by) killing in a concentration-dependent manner of S. aureus by 2.5 log(10) to a maximum of 4.2 log(10) at 10 mM (P<0.001) and increased killing of E. coli by 3.6 log(10) to a maximum of 5.0 log(10) at 10 mM (P<0.01). We determined that sCN(-) rapidly depleted O-2 from an irradiated MB system, reacting exclusively with O-1(2), without quenching the MB excited triplet state. SCN- reacted with O-1(2), producing a sulfur trioxide radical anion (a sulfur-centered radical demonstrated by EPR spin trapping). We found that MB-PDT of SCN- in solution produced both sulfite and cyanide anions, and that addition of each of these salts separately enhanced MB-PDT killing of bacteria. We were unable to detect EPR signals of (OH)-O-center dot, which, together with kinetic data, strongly suggests that MB, known to produce (OH)-O-center dot and O-1(2), may, under the conditions used, preferentially form O-1(2). (C) 2013 Elsevier Inc. All rights reserved. C1 [St Denis, Tyler G.] Columbia Univ, Dept Chem, New York, NY 10027 USA. [St Denis, Tyler G.; Vecchio, Daniela; Rineh, Ardeshir; Sadasivam, Magesh; Avci, Pinar; Huang, Liyi; Chandran, Rakkiyappan; Hamblin, Michael R.] Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA. [Vecchio, Daniela; Avci, Pinar; Huang, Liyi; Hamblin, Michael R.] Semmelweis Univ, Sch Med, Dept Dermatol Dermatooncol & Venerol, H-1085 Budapest, Hungary. [Zadlo, Andrzej; Kozinska, Anna; Sarna, Tadeusz] Jagiellonian Univ, Fac Biochem Biophys & Biotechnol, PL-31007 Krakow, Poland. [Rineh, Ardeshir] Univ Wollongong, Sch Chem, N5W2522, Wollongong, NSW 2522, Australia. [Avci, Pinar] Semmelweis Univ, Sch Med, Dept Dermatol, H-1085 Budapest, Hungary. [Huang, Liyi] Guangxi Med Univ, Affiliated Coll & Hosp 1, Dept Infect Dis, Nanning, Peoples R China. [Kozinska, Anna] Jagiellonian Univ, Fac Phys Astron & Appl Comp Sci, PL-31007 Krakow, Poland. [Hamblin, Michael R.] Harvard MIT, Div Hlth Sci & Technol, Cambridge, MA USA. RP Hamblin, MR (reprint author), Massachusetts Gen Hosp, Wellman Ctr Photomed, BAR414, 40 Blossom St, Boston, MA 02114 USA. EM hamblin@helix.mgh.harvard.edu OI Hamblin, Michael/0000-0001-6431-4605 FU Columbia University I. I. Rabi Science Research Fellowship; National Science Centre [2011/03/B/NZ1/00007]; NIH [R01A1050875] FX We thank Michael Davies of the Heart Research Institute in Australia and Nicholas J. Turro of Columbia University in New York for invaluable discussion on the mechanism of SO3center dot- formation. Research conducted by Tyler G. St. Denis is supported by the Columbia University I. I. Rabi Science Research Fellowship. Research conducted by the Tadeusz Sarna Laboratory in Poland is supported by National Science Centre (2011/03/B/NZ1/00007). Research conducted in the Hamblin Laboratory is supported by NIH (R01A1050875). NR 50 TC 3 Z9 3 U1 3 U2 36 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0891-5849 EI 1873-4596 J9 FREE RADICAL BIO MED JI Free Radic. Biol. Med. PD DEC PY 2013 VL 65 BP 800 EP 810 DI 10.1016/j.freeradbiomed.2013.08.162 PG 11 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA 278DI UT WOS:000328868900075 PM 23969112 ER PT J AU Benavides, GA Liang, QL Dodson, M Darley-Usmar, V Zhang, JH AF Benavides, Gloria A. Liang, Qiuli Dodson, Matthew Darley-Usmar, Victor Zhang, Jianhua TI Inhibition of autophagy and glycolysis by nitric oxide during hypoxia-reoxygenation impairs cellular bioenergetics and promotes cell death in primary neurons SO FREE RADICAL BIOLOGY AND MEDICINE LA English DT Article DE DetaNONOate; LC3; 3-MA; Mitochondria; Glucose; 2-DG; Free radicals ID ISCHEMIC BRAIN-INJURY; CYTOCHROME-C-OXIDASE; OXIDATIVE STRESS; MITOCHONDRIAL DYSFUNCTION; NEUROTRANSMITTER RELEASE; LIPID-PEROXIDATION; ENDOTHELIAL-CELLS; SYNTHASE GENE; PEROXYNITRITE; PATHWAY AB Excessive nitric oxide (NO) production is known to damage mitochondrial proteins and the autophagy repair pathway and so can potentially contribute to neurotoxicity. Accordingly, we hypothesized that protection against protein damage from reactive oxygen and nitrogen species under conditions of low oxygen by the autophagy pathway in neurons would be impaired by NO and enhance bioenergetic dysfunction. Rat primary cortical neurons had the same basal cellular respiration in hypoxia as in normoxia, whereas NO-exposed cells exhibited a gradual decrease in mitochondrial respiration in hypoxia. Upon reoxygenation, the respiration in NO-treated cells did not recover to prehypoxic levels. Hypoxia-reoxygenation in the presence of NO was associated with inhibition of autophagy, and the inability to recover during reoxygenation was exacerbated by an inhibitor of autophagy, 3-methyladenine. The effects of hypoxia could be recapitulated by inhibiting glycolytic flux under normoxic conditions. Under both normoxic and hypoxic conditions NO exposure induced immediate stimulation of glycolysis, but prolonged NO exposure, associated with irreversible inhibition of mitochondrial respiration in hypoxia, inhibited glycolysis. Importantly, we found that NO inhibited basal respiration under normoxic conditions only when glucose was absent from the medium or glycolysis was inhibited by 2-deoxy-oglucose, revealing a novel NO-dependent mechanism for the inhibition of mitochondrial respiration that is modulated by glycolysis. Taken together these data suggest an oxygen-dependent interaction between mitochondrial respiration, glycolysis, and autophagy in protecting neuronal cells exposed to NO. Importantly, they indicate that mitochondrial dysfunction is intimately linked to a failure of glycolytic flux induced by exposure to NO. In addition, these studies provide new insights into the understanding of how autophagy and NO may play interactive roles in neuroinflammation-induced cellular damage, which is pertinent to our understanding of the pathology of neurodegenerative diseases in which excessive NO is generated. (C) 2013 Elsevier Inc. All rights reserved. C1 [Benavides, Gloria A.; Liang, Qiuli; Dodson, Matthew; Darley-Usmar, Victor; Zhang, Jianhua] Univ Alabama Birmingham, Ctr Free Rad Biol, Birmingham, AL 35294 USA. [Benavides, Gloria A.; Liang, Qiuli; Dodson, Matthew; Darley-Usmar, Victor; Zhang, Jianhua] Univ Alabama Birmingham, Dept Pathol, Birmingham, AL 35294 USA. [Zhang, Jianhua] Birmingham VA Med Ctr, Dept Vet Affairs, Birmingham, AL 35233 USA. RP Zhang, JH (reprint author), Univ Alabama Birmingham, Dept Pathol, Birmingham, AL 35294 USA. EM zhanja@uab.edu FU VA merit award; [NIHR01-NS064090] FX We thank IDDEC Core B for primary neuron cultures and members of the Dr. Zhang and Dr. Darley-Usmar laboratories for technical help and discussions. This work was supported by NIHR01-NS064090 and a VA merit award (to J.Z.). V.D.U. is a member of the Seahorse Biosciences Scientific Advisory Board. NR 56 TC 19 Z9 21 U1 5 U2 18 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0891-5849 EI 1873-4596 J9 FREE RADICAL BIO MED JI Free Radic. Biol. Med. PD DEC PY 2013 VL 65 BP 1215 EP 1228 DI 10.1016/j.freeradbiomed.2013.09.006 PG 14 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA 278DI UT WOS:000328868900115 PM 24056030 ER PT J AU Ishikado, A Sono, Y Matsumoto, M Robida-Stubbs, S Okuno, A Goto, M King, GL Blackwell, TK Makin, T AF Ishikado, Atsushi Sono, Yoko Matsumoto, Motonobu Robida-Stubbs, Stacey Okuno, Aya Goto, Masashi King, George L. Blackwell, T. Keith Makin, Taketoshi TI Willow bark extract increases antioxidant enzymes and reduces oxidative stress through activation of Nrf2 in vascular endothelial cells and Caenorhabditis elegans SO FREE RADICAL BIOLOGY AND MEDICINE LA English DT Article DE Willow bark extract; Nrf2; Antioxidant enzyme; HUVEC; Caenorhabditis elegans; Oxidative stress; Free radicals ID TRANSCRIPTION FACTOR NRF2; NF-E2-RELATED FACTOR-2; HEME OXYGENASE-1; GENE-EXPRESSION; HUMAN-DISEASES; FACTOR SKN-1; C. ELEGANS; PATHWAY; GLUTATHIONE; LONGEVITY AB Willow bark extract (WBE) is listed in the European Pharmacopoeia and has been traditionally used for treating fever, pain, and inflammation. Recent studies have demonstrated its clinical usefulness. This study investigated the antioxidative effects of WBE in human umbilical vein endothelial cells (HUVECs) and Caenorhabditis elegans. WBE prevented oxidative-stress-induced cytotoxicity of HUVECs and death of C. elegans. WBE dose-dependently increased mRNA and protein expression levels of the nuclear factor erythroid 2-related factor 2 (Nrf2) target genes heme oxygenase-1, gamma-glutamylcysteine ligase modifier and catalytic subunits, and p62 and intracellular glutathione (GSH) in HUVECs. In the nematode C elegans, WBE increased the expression of the gcs-1::green fluorescent protein reporter, a well-characterized target of the Nrf2 ortholog SKN-1, in a manner that was SKN-1-dependent. WBE increased intranuclear expression and DNA binding of Nrf2 and the activity of an antioxidant response element (ARE) reporter plasmid in HUVECs. WBE-induced expression of Nrf2-regulated genes and increased GSH levels in HUVECs were reduced by Nrf2 and p38 small interfering (si) RNAs and by the p38-specific inhibitor SB203580. Nrf2 siRNA reduced the cytoprotective effect of WBE against oxidative stress in HUVECs. Salicin, a major anti-inflammatory ingredient of WBE, failed to activate ARE-luciferase activity, whereas a salicin-free WBE fraction showed intensive activity. WBE induced antioxidant enzymes and prevented oxidative stress through activation of Nrf2 independent of salicin, providing a new potential explanation for the clinical usefulness of WBE. (C) 2012 Elsevier Inc. All rights reserved. C1 [Ishikado, Atsushi; Sono, Yoko; Matsumoto, Motonobu; Okuno, Aya; Goto, Masashi; Makin, Taketoshi] Sunstar Inc, R&D Dept, Osaka 5691195, Japan. [Blackwell, T. Keith] Harvard Univ, Sch Med, Joslin Diabet Ctr, Res Div,Sect Islet Cell & Regenerat Biol, Boston, MA 02215 USA. [King, George L.] Harvard Univ, Sch Med, Joslin Diabet Ctr, Res Div,Sect Vasc Cell Biol, Boston, MA 02215 USA. RP Blackwell, TK (reprint author), Harvard Univ, Sch Med, Joslin Diabet Ctr, Res Div,Sect Islet Cell & Regenerat Biol, Boston, MA 02215 USA. EM Keith.Blacicwell@joslin.harvard.edu; taketoshi.makino@jp.sunstar.com FU NIH [GM62891] FX We thank Minori Miyata for helpful support in the analysis of WBE by HPLC. This work was supported in part by a grant from the NIH (GM62891). NR 49 TC 7 Z9 10 U1 2 U2 17 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0891-5849 EI 1873-4596 J9 FREE RADICAL BIO MED JI Free Radic. Biol. Med. PD DEC PY 2013 VL 65 BP 1506 EP 1515 DI 10.1016/j.freeradbiomed.2012.12.006 PG 10 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA 278DI UT WOS:000328868900145 PM 23277146 ER PT J AU Cushing, T Paterson, R Haukoos, J Harris, NS AF Cushing, Tracy Paterson, Ryan Haukoos, Jason Harris, N. Stuart TI Intraocular Pressure Is Not Associated with Acute Mountain Sickness SO HIGH ALTITUDE MEDICINE & BIOLOGY LA English DT Article DE acetazolamide; acute mountain sickness; arterial oxygen saturation; Diamox; ocular conditions ID CENTRAL CORNEAL THICKNESS; GOLDMANN APPLANATION TONOMETRY; HIGH-ALTITUDE CLIMB; INTRACRANIAL-PRESSURE; POPULATION; GLAUCOMA; AGREEMENT; EXERCISE; MODERATE; AGE AB Cushing, Tracy, Ryan Paterson, Jason Haukoos, and N. Stuart Harris. Intraocular pressure is not associated with acute mountain sickness. High Alt Med Biol 14:342-345, 2013.Objective: Acute mountain sickness (AMS) is common at high altitude and may lead to high altitude cerebral edema (HACE) if not properly recognized. Previous studies have suggested that AMS is associated with increases in intracranial pressure (ICP). Increased ICP has been associated with increased intra-ocular pressure (IOP). This study was designed to determine the association between IOP and AMS. Methods: Subjects were recruited from a convenience sample of travelers in the Khumbu region of Nepal, elevation 14,410ft (4392m). Study participation involved completion of a questionnaire to assess for AMS by the Lake Louise Score (LLS), followed by three IOP measurements in each eye. Investigators were blinded to the LLS. Subjects with a history of ocular surgery were excluded. Three IOP measurements per eye were made using an applanation tonometer (Tono-Pen XL (R), Reichart Technologies) and averaged across both eyes. Multivariable logistic regression analysis was used to estimate the association between IOP and AMS while adjusting for age, ascent or descent, and use of acetazolamide. IOP and blood O-2 saturation were compared using a Spearman correlation coefficient. Results: 161 subjects were enrolled with a median age of 36 (IQR: 29-45) years; 60% were male, 75% were ascending, and 64% were taking acetazolamide; additionally, 38%, (95% CI: 31%-47%) were diagnosed with AMS (LLS 3). The median IOP was 21 (IQR 18-24) mmHg. The logistic regression model demonstrated no association between IOP and AMS as measured by LLS (odds ratio [OR] 1.0, 95% CI: 0.9-1.1),age (OR 1.0, 95% CI: 0.9-1.0) or with use of acetazolamide (OR 1.4, 95% CI: 0.6-2.6). Ascent (OR 0.4, 95% CI: 0.2-0.9) was negatively associated with IOP but not significantly so. IOP and O-2 saturation were not correlated (p=0.93). Conclusions: IOP measured at high altitude is not associated with the diagnosis of AMS. Other approaches to diagnose AMS easily and accurately are needed. C1 [Cushing, Tracy; Paterson, Ryan; Haukoos, Jason] Denver Hlth Med Ctr, Dept Emergency Med, Denver, CO 80204 USA. [Harris, N. Stuart] Massachusetts Gen Hosp, Dept Emergency Med, Boston, MA 02114 USA. RP Cushing, T (reprint author), Denver Hlth Med Ctr, Dept Emergency Med, 660 Bannock St, Denver, CO 80204 USA. EM tracycushing@gmail.com NR 34 TC 1 Z9 1 U1 0 U2 4 PU MARY ANN LIEBERT, INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1527-0297 EI 1557-8682 J9 HIGH ALT MED BIOL JI High Alt. Med. Biol. PD DEC 1 PY 2013 VL 14 IS 4 BP 342 EP 345 DI 10.1089/ham.2013.1024 PG 4 WC Biophysics; Public, Environmental & Occupational Health; Sport Sciences SC Biophysics; Public, Environmental & Occupational Health; Sport Sciences GA 282HX UT WOS:000329162900009 PM 24377341 ER PT J AU Stengel, A Tache, Y AF Stengel, A. Tache, Y. TI Role of NUCB2/Nesfatin-1 in the Hypothalamic Control of Energy Homeostasis SO HORMONE AND METABOLIC RESEARCH LA English DT Review DE body weight; food intake; hypothalamus; NUCB2; nesfatin-1; obesity; satiation ID INTER-MEAL INTERVALS; BODY-MASS INDEX; FOOD-INTAKE; NESFATIN-1 INFLUENCES; ARCUATE NUCLEUS; RAT-BRAIN; NEURONS; MICE; IMMUNOREACTIVITY; NEUROPEPTIDE AB Hunger and satiety are regulated in a complex fashion by a few food intake stimulatory (orexigenic) and a multitude of inhibitory (anorexigenic) factors produced in the periphery (mainly in the gastrointestinal tract) or directly in the brain. Within the brain, the hypothalamus plays a pivotal role as a production site of food intake regulatory factors. Importantly, this site integrates peripheral and central signaling factors to orchestrate food intake and in the long term body weight. Our knowledge on these regulatory pathways is not static but rather rapidly changing as new factors as well as up- and downstream signaling pathways of already known transmitters are uncovered. Hypothalamic nucleobindin2 (NUCB2), the precursor of nesfatin-1, was first described in 2006 and nesfatin-1 found to be a novel anorexigenic modulator of food intake and body weight. The initial report stimulated several groups to investigate the biological actions of nesfatin-1 and subsequent studies delineated the underlying brain mechanisms involved in its food reducing effect. Of interest was the demonstration that NUCB2 also exerts its anorexigenic action in the paraventricular nucleus of the hypothalamus and is regulated at this site by changes in metabolic status with a diurnal rhythm inversely related to that of feeding in rats. The present review describes the current state-of-knowledge on central nesfatin-1's effects on food intake and body weight and highlights important missing links regarding cellular signaling mechanisms involved in nesfatin-1's action. C1 [Stengel, A.] Charite, Charite Ctr Internal Med & Dermatol, Div Gen Internal & Psychosomat Med, D-13353 Berlin, Germany. [Tache, Y.] Univ Calif Los Angeles, Dept Med, CURE Digest Dis Res Ctr, Los Angeles, CA 90024 USA. [Tache, Y.] Univ Calif Los Angeles, Div Digest Dis, Ctr Neurobiol Stress, Los Angeles, CA USA. [Tache, Y.] VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. RP Tache, Y (reprint author), VA GLA Healthcare Syst, Ctr Neurobiol Stress, CURE Bldg 115,Room 117,11301 Wilshire Blvd, Los Angeles, CA 90073 USA. EM ytache@mednet.ucla.edu FU German Research Foundation [STE 1765/3-1]; Charite University [UFF 89-441-176]; NIH [R01 DK-33061]; NIH Center Grant [DK-41301]; VA Research Career Scientist FX This work was supported by German Research Foundation STE 1765/3-1 (A. S.) and Charite University Funding UFF 89-441-176 (A. S.), NIH R01 DK-33061, NIH Center Grant DK-41301 (Animal Core), and VA Research Career Scientist (Y.T.). NR 51 TC 9 Z9 9 U1 0 U2 11 PU GEORG THIEME VERLAG KG PI STUTTGART PA RUDIGERSTR 14, D-70469 STUTTGART, GERMANY SN 0018-5043 EI 1439-4286 J9 HORM METAB RES JI Horm. Metab. Res. PD DEC PY 2013 VL 45 IS 13 BP 975 EP 979 DI 10.1055/s-0033-1351324 PG 5 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 269KW UT WOS:000328241200009 PM 24048879 ER PT J AU Gordon, MS Rodbell, KP Tang, HHK Yashchin, E Cascio, EW McNally, BD AF Gordon, Michael S. Rodbell, Kenneth P. Tang, Henry H. K. Yashchin, Emmanuel Cascio, Ethan W. McNally, Brendan D. TI Selected Topics in Ultra-Low Emissivity Alpha-Particle Detection SO IEEE TRANSACTIONS ON NUCLEAR SCIENCE LA English DT Article; Proceedings Paper CT 50th annual IEEE Nuclear and Space Radiation Effects Conference (NSREC) CY JUL 08-12, 2013 CL San Francisco, CA DE Alpha particles; ionization detectors; low-background; Poisson statistics; protons; terrestrial neutrons ID COUNTER AB In an effort to better understand the contribution of terrestrial protons to the counter background, we have developed a model to examine the production of protons, within an ionization counter from the interaction of incident neutrons on the counter material. Results of high energy proton irradiation on an UltraLo-1800 XIA alpha-particle counter are shown which indicate that the active signal discrimination is very effective at rejecting most of the detected events. A Poisson model is described which gives guidance on making appropriate measurement times and acceptance criteria for detectors with a range of backgrounds. C1 [Gordon, Michael S.; Rodbell, Kenneth P.; Tang, Henry H. K.; Yashchin, Emmanuel] IBM TJ Watson Res Ctr, Yorktown Hts, NY 10598 USA. [Cascio, Ethan W.] Massachusetts Gen Hosp, Francis H Burr Proton Therapy Ctr, Boston, MA 02114 USA. [McNally, Brendan D.] XIA LLC, Hayward, CA 94544 USA. RP Gordon, MS (reprint author), IBM TJ Watson Res Ctr, Yorktown Hts, NY 10598 USA. EM gor-donm@us.ibm.com; ecascio@partners.org; brendan@xia.com OI McNally, Brendan/0000-0002-2532-666X NR 23 TC 4 Z9 4 U1 0 U2 6 PU IEEE-INST ELECTRICAL ELECTRONICS ENGINEERS INC PI PISCATAWAY PA 445 HOES LANE, PISCATAWAY, NJ 08855-4141 USA SN 0018-9499 EI 1558-1578 J9 IEEE T NUCL SCI JI IEEE Trans. Nucl. Sci. PD DEC PY 2013 VL 60 IS 6 BP 4265 EP 4274 DI 10.1109/TNS.2013.2287459 PN 1 PG 10 WC Engineering, Electrical & Electronic; Nuclear Science & Technology SC Engineering; Nuclear Science & Technology GA 279NY UT WOS:000328967900032 ER PT J AU Lane, HY Lin, CH Green, MF Hellemann, G Huang, CC Chen, PW Tun, R Chang, YC Tsai, GCE AF Lane, Hsien-Yuan Lin, Ching-Hua Green, Michael F. Hellemann, Gerhard Huang, Chih-Chia Chen, Po-Wei Tun, Rene Chang, Yue-Cung Tsai, Guochuan E. TI Add-on Treatment of Benzoate for Schizophrenia A Randomized, Double-blind, Placebo-Controlled Trial of D-Amino Acid Oxidase Inhibitor SO JAMA PSYCHIATRY LA English DT Article ID CONSENSUS COGNITIVE BATTERY; SARCOSINE N-METHYLGLYCINE; TRANSPORTER-I INHIBITOR; D-SERINE; EMOTIONAL INTELLIGENCE; ANTIPSYCHOTIC-DRUGS; NEGATIVE SYMPTOMS; EFFICACY; DEFICITS; SCALE AB IMPORTANCE In addition to dopaminergic hyperactivity, hypofunction of the N-methyl-D-aspartate receptor (NMDAR) has an important role in the pathophysiology of schizophrenia. Enhancing NMDAR-mediated neurotransmission is considered a novel treatment approach. To date, several trials on adjuvant NMDA-enhancing agents have revealed beneficial, but limited, efficacy for positive and negative symptoms and cognition. Another method to enhance NMDA function is to raise the levels of D-amino acids by blocking their metabolism. Sodium benzoate is a D-amino acid oxidase inhibitor. OBJECTIVE To examine the clinical and cognitive efficacy and safety of add-on treatment of sodium benzoate for schizophrenia. DESIGN, SETTING, AND PARTICIPANTS A randomized, double-blind, placebo-controlled trial in 2 major medical centers in Taiwan composed of 52 patients with chronic schizophrenia who had been stabilized with antipsychotic medications for 3 months or longer. INTERVENTIONS Six weeks of add-on treatment of 1 g/d of sodium benzoate or placebo. MAIN OUTCOMES AND MEASURES The primary outcome measure was the Positive and Negative Syndrome Scale (PANSS) total score. Clinical efficacy and adverse effects were assessed biweekly. Cognitive functions were measured before and after the add-on treatment. RESULTS Benzoate produced a 21% improvement in PANSS total score and large effect sizes (range, 1.16-1.69) in the PANSS total and subscales, Scales for the Assessment of Negative Symptoms-20 items, Global Assessment of Function, Quality of Life Scale and Clinical Global Impression and improvement in the neurocognition subtests as recommended by the National Institute of Mental Health's Measurement and Treatment Research to Improve Cognition in Schizophrenia initiative, including the domains of processing speed and visual learning. Benzoate was well tolerated without significant adverse effects. CONCLUSIONS AND RELEVANCE Benzoate adjunctive therapy significantly improved a variety of symptom domains and neurocognition in patients with chronic schizophrenia. The preliminary results show promise for D-amino acid oxidase inhibition as a novel approach for new drug development for schizophrenia. C1 [Lane, Hsien-Yuan; Huang, Chih-Chia] China Med Univ Hosp, Dept Psychiat, Taichung, Taiwan. [Lane, Hsien-Yuan; Huang, Chih-Chia] China Med Univ, Inst Clin Med Sci, Taichung, Taiwan. [Lin, Ching-Hua] Kaohsiung Municipal Kai Syuan Psychiat Hosp, Dept Adult Psychiat, Kaohsiung, Taiwan. [Green, Michael F.; Hellemann, Gerhard] Univ Calif Los Angeles, Semel Inst Neurosci & Human Behav, Los Angeles, CA 90024 USA. [Green, Michael F.] Vet Affairs Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. [Chen, Po-Wei] Taichung Chin Ho Hosp, Dept Psychiat, Taichung, Taiwan. [Tun, Rene; Tsai, Guochuan E.] Harbor UCLA Med Ctr, Dept Psychiat, Torrance, CA 90509 USA. [Chang, Yue-Cung] Tamkang Univ, Dept Math, Taipei, Taiwan. RP Tsai, GCE (reprint author), Harbor UCLA Med Ctr, Dept Psychiat, 1000 W Carson St, Torrance, CA 90509 USA. EM etsai@labiomed.org FU National Science Council of Taiwan [NSC-97-2314-B-039-006-MY3, NSC-99-2314-B-280-001-MY3, NSC-99-2811-B-039-005, NSC-100-2627-B-039-001, NSC-101-2314-B-039-030-MY3, NSC-101-2627-B-039-001]; National Health Research Institutes of Taiwan [NHRI-EX-101-9904NI]; Taiwan Department of Health Clinical Trial and Research Center of Excellence [DOH102-TD-B-111-004]; China Medical University Hospital [CMU 101-AWARD-13, DMR-99-153, DMR-99-117] FX This work was supported in part by grants NSC-97-2314-B-039-006-MY3, NSC-99-2314-B-280-001-MY3, NSC-99-2811-B-039-005, NSC-100-2627-B-039-001, NSC-101-2314-B-039-030-MY3, and NSC-101-2627-B-039-001 from the National Science Council of Taiwan, grant NHRI-EX-101-9904NI from the National Health Research Institutes of Taiwan, grant DOH102-TD-B-111-004 from the Taiwan Department of Health Clinical Trial and Research Center of Excellence, and grants CMU 101-AWARD-13, DMR-99-153, and DMR-99-117 from the China Medical University Hospital. NR 72 TC 41 Z9 44 U1 1 U2 10 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60654-0946 USA SN 2168-622X EI 2168-6238 J9 JAMA PSYCHIAT JI JAMA Psychiatry PD DEC PY 2013 VL 70 IS 12 BP 1267 EP 1275 DI 10.1001/jamapsychiatry.2013.2159 PG 9 WC Psychiatry SC Psychiatry GA 279HK UT WOS:000328950800005 PM 24089054 ER PT J AU Iltis, AS Misra, S Dunn, LB Brown, GK Campbell, A Earll, SA Glowinski, A Hadley, WB Pies, R DuBois, JM AF Iltis, Ana S. Misra, Sahana Dunn, Laura B. Brown, Gregory K. Campbell, Amy Earll, Sarah A. Glowinski, Anne Hadley, Whitney B. Pies, Ronald DuBois, James M. TI Addressing Risks to Advance Mental Health Research SO JAMA PSYCHIATRY LA English DT Article ID RANDOMIZED CONTROLLED-TRIAL; INTERVENTION EFFECTIVENESS CATIE; SCHIZOPHRENIA RESEARCH PROTOCOLS; CLINICAL ANTIPSYCHOTIC TRIALS; ASSESSING DECISIONAL CAPACITY; INFORMED-CONSENT; BIPOLAR DISORDER; RESEARCH ETHICS; RESEARCH PARTICIPANTS; PEDIATRIC RESEARCH AB IMPORTANCE Risk communication and management are essential to the ethical conduct of research, yet addressing risks may be time consuming for investigators and institutional review boards may reject study designs that seem too risky. This can discourage needed research, particularly in higher-risk protocols or those enrolling potentially vulnerable individuals, such as those with some level of suicidality. Improved mechanisms for addressing research risks may facilitate much needed psychiatric research. OBJECTIVE To provide mental health researchers with practical approaches to (1) identify and define various intrinsic research risks, (2) communicate these risks to others (eg, potential participants, regulatory bodies, and society), (3) manage these risks during the course of a study, and (4) justify the risks. EVIDENCE REVIEW As part of a National Institute of Mental Health-funded scientific meeting series, a public conference and a closed-session expert panel meeting were held on managing and disclosing risks in mental health clinical trials. The expert panel reviewed the literature with a focus on empirical studies and developed recommendations for best practices and further research on managing and disclosing risks in mental health clinical trials. No institutional review board-review was required because there were no human subjects. FINDINGS Challenges, current data, practical strategies, and topics for future research are addressed for each of 4 key areas pertaining to management and disclosure of risks in clinical trials: identifying and defining risks, communicating risks, managing risks during studies, and justifying research risks. CONCLUSIONS AND RELEVANCE Empirical data on risk communication, managing risks, and the benefits of research can support the ethical conduct of mental health research and may help investigators better conceptualize and confront risks and to gain institutional review board-approval. C1 [Iltis, Ana S.] Wake Forest Univ, Ctr Bioeth Hlth & Soc, Winston Salem, NC 27109 USA. [Iltis, Ana S.] Wake Forest Univ, Dept Philosophy, Winston Salem, NC 27109 USA. [Misra, Sahana] Portland VA Med Ctr, Mental Hlth & Clin Neurosci Div, Portland, OR USA. [Misra, Sahana] Oregon Hlth & Sci Univ, Dept Psychiat, Portland, OR 97201 USA. [Dunn, Laura B.] Univ Calif San Francisco, Dept Psychiat, UCSF Helen Diller Family Comprehens Canc Ctr, San Francisco, CA USA. [Dunn, Laura B.] Univ Calif San Francisco, Dept Psychooncol, UCSF Helen Diller Family Comprehens Canc Ctr, San Francisco, CA 94143 USA. [Brown, Gregory K.] Univ Penn, Perelman Sch Med, Philadelphia, PA 19104 USA. [Campbell, Amy] SUNY Upstate Med Univ, Ctr Bioeth & Humanities, Syracuse, NY 13210 USA. [Earll, Sarah A.] St Louis Empowerment, St Louis, MO USA. [Glowinski, Anne] Washington Univ, Sch Med, Dept Psychiat Child, St Louis, MO USA. [Hadley, Whitney B.] Syracuse Univ, Falk Coll Sports & Human Dynam, Syracuse, NY USA. [Pies, Ronald] SUNY Upstate Med Univ, Dept Psychiat, Syracuse, NY 13210 USA. [DuBois, James M.] Washington Univ, Sch Med, Dept Med, St Louis, MO 63110 USA. [DuBois, James M.] St Louis Univ, Ctr Hlth Care Eth, St Louis, MO 63104 USA. RP DuBois, JM (reprint author), St Louis Univ, Albert Gnaegi Ctr Hlth Care Eth, Salus Ctr, 3545 Lafayette,5th Floor, St Louis, MO 63104 USA. EM jdubois@wustl.edu FU National Institute of Mental Health [1R13MH079690]; National Center for Advancing Translational Science, National Institutes of Health [UL1 TR000448] FX This work was supported by the National Institute of Mental Health (grant 1R13MH079690) and the National Center for Advancing Translational Science (grant UL1 TR000448), National Institutes of Health. NR 101 TC 6 Z9 6 U1 3 U2 11 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60654-0946 USA SN 2168-622X EI 2168-6238 J9 JAMA PSYCHIAT JI JAMA Psychiatry PD DEC PY 2013 VL 70 IS 12 BP 1363 EP 1371 DI 10.1001/jamapsychiatry.2013.2105 PG 9 WC Psychiatry SC Psychiatry GA 279HK UT WOS:000328950800016 PM 24173618 ER PT J AU Nan, H Morikawa, T Suuriniemi, M Imamura, Y Werner, L Kuchiba, A Yamauchi, M Hunter, DJ Kraft, P Giovannucci, EL Fuchs, CS Ogino, S Freedman, ML Chan, AT AF Nan, Hongmei Morikawa, Teppei Suuriniemi, Miia Imamura, Yu Werner, Lillian Kuchiba, Aya Yamauchi, Mai Hunter, David J. Kraft, Peter Giovannucci, Edward L. Fuchs, Charles S. Ogino, Shuji Freedman, Matthew L. Chan, Andrew T. TI Aspirin Use, 8q24 Single Nucleotide Polymorphism rs6983267, and Colorectal Cancer According to CTNNB1 Alterations SO JNCI-JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Article ID NONSTEROIDAL ANTIINFLAMMATORY DRUGS; WIDE ASSOCIATION SCAN; FAMILIAL ADENOMATOUS POLYPOSIS; CORONARY-HEART-DISEASE; NUCLEAR BETA-CATENIN; BODY-MASS INDEX; COLON-CANCER; RANDOMIZED-TRIAL; SUSCEPTIBILITY LOCUS; PHYSICAL-ACTIVITY AB Regular aspirin use reduces the risk for colorectal cancer (CRC), possibly through inhibition of WNT/cadherin-associated protein 1 (CTNNB1 or -catenin) signaling. The single nucleotide polymorphism (SNP) rs6983267 on chromosome 8q24 is a CRC susceptibility locus that affects binding activity of transcription factor 7 like-2 (TCF7L2) to CTNNB1, thereby altering expression of target oncogenes, including MYC. We evaluated regular aspirin use and CRC risk according to genotypes of SNP rs6983267 and CTNNB1 expression status in two prospective casecontrol studies (840 CRC case patients and 1686 age- and race-matched control subjects) nested within the Nurses Health Study and the Health Professionals Follow-up Study. We estimated odds ratios (ORs) and 95% confidence intervals (CIs) using unconditional logistic regression models. All statistical tests were two-sided. A lower risk of CRC was associated with regular aspirin use and the T allele of rs6983267. The effect of aspirin was confined to individuals with protective T allele of rs6983267 (additive matching factorsadjusted OR for T allele 0.83; 95% CI 0.74 to 0.94; P-trend .002; P-interaction .01). Additionally, the T allele of rs6983267 was associated with a reduced expression of MYC oncogene (P-trend .03). Moreover, among individuals with protective T allele, the effect of regular aspirin use was limited to those with positive nuclear CTNNB1 expression. In a functional analysis, in vitro treatment of LS174T cells (a cell line heterozygous for rs6983267) with aspirin was statistically significantly associated with higher G/T allelic ratio of TCF7L2 immunoprecipitated DNA (P .03). Our results support an influence of aspirin on WNT/CTNNB1 signaling and suggest that aspirin chemoprevention may be tailored according to rs6983267 genotype. C1 [Nan, Hongmei] Univ Maryland, Sch Med, Dept Epidemiol & Publ Hlth, Div Canc Epidemiol, Baltimore, MD 21201 USA. [Nan, Hongmei; Hunter, David J.; Giovannucci, Edward L.; Fuchs, Charles S.; Chan, Andrew T.] Brigham & Womens Hosp, Dept Med, Channing Div Network Med, Boston, MA 02115 USA. [Hunter, David J.; Kraft, Peter; Giovannucci, Edward L.; Ogino, Shuji] Brigham & Womens Hosp, Dept Epidemiol, Boston, MA 02115 USA. [Chan, Andrew T.] Harvard Univ, Sch Med, Boston, MA USA. [Morikawa, Teppei; Imamura, Yu; Kuchiba, Aya; Yamauchi, Mai; Ogino, Shuji] Dana Farber Canc Inst, Ctr Mol Oncol Pathol, Boston, MA 02115 USA. [Morikawa, Teppei; Suuriniemi, Miia; Imamura, Yu; Kuchiba, Aya; Yamauchi, Mai; Fuchs, Charles S.; Ogino, Shuji; Freedman, Matthew L.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Werner, Lillian] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA. [Hunter, David J.; Giovannucci, Edward L.; Ogino, Shuji] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. [Hunter, David J.; Giovannucci, Edward L.] Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA. [Freedman, Matthew L.] Broad Inst, Program Med & Populat Genet, Cambridge, MA USA. [Chan, Andrew T.] Massachusetts Gen Hosp, Div Gastroenterol, Boston, MA 02114 USA. RP Chan, AT (reprint author), Massachusetts Gen Hosp, Div Gastroenterol, GRJ 825C, Boston, MA 02114 USA. EM achan@partners.org FU U.S. National Institute of Health [P01 CA87969, P50 CA127003, R01 CA151993, R01 CA137178, K24 DK098311] FX This work was supported by U.S. National Institute of Health grants (P01 CA87969 to ELG; P50 CA127003 to CSF; R01 CA151993 to SO; R01 CA137178 to ATC; and K24 DK098311 to ATC). ATC is a Damon Runyon Clinical Investigator. NR 51 TC 20 Z9 22 U1 1 U2 10 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0027-8874 EI 1460-2105 J9 JNCI-J NATL CANCER I JI JNCI-. Natl. Cancer Inst. PD DEC PY 2013 VL 105 IS 24 BP 1852 EP 1861 DI 10.1093/jnci/djt331 PG 10 WC Oncology SC Oncology GA 280UU UT WOS:000329057100006 PM 24317174 ER PT J AU Pettersson, A Lis, RT Meisner, A Flavin, R Stack, EC Fiorentino, M Finn, S Graff, RE Penney, KL Rider, JR Nuttall, EJ Martin, NE Sesso, HD Pollak, M Stampfer, MJ Kantoff, PW Giovannucci, EL Loda, M Mucci, LA AF Pettersson, Andreas Lis, Rosina T. Meisner, Allison Flavin, Richard Stack, Edward C. Fiorentino, Michelangelo Finn, Stephen Graff, Rebecca E. Penney, Kathryn L. Rider, Jennifer R. Nuttall, Elizabeth J. Martin, Neil E. Sesso, Howard D. Pollak, Michael Stampfer, Meir J. Kantoff, Philip W. Giovannucci, Edward L. Loda, Massimo Mucci, Lorelei A. TI Modification of the Association Between Obesity and Lethal Prostate Cancer by TMPRSS2:ERG SO JNCI-JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Article ID FATTY-ACID SYNTHASE; BODY-MASS INDEX; ERG EXPRESSION; EWING SARCOMA; PROGRESSION; SURVIVAL; FUSION; COHORT; RISK; PATHOGENESIS AB TMPRSS2:ERG is a hormonally regulated gene fusion present in about half of prostate tumors. We investigated whether obesity, which deregulates several hormonal pathways, interacts with TMPRSS2:ERG to impact prostate cancer outcomes. The study included 1243 participants in the prospective Physicians Health Study and Health Professionals Follow-Up Study diagnosed with prostate cancer between 1982 and 2005. ERG overexpression (a TMPRSS2:ERG marker) was assessed by immunohistochemistry of tumor tissue from radical prostatectomy or transurethral resection of the prostate. Body mass index (BMI) and waist circumference, measured on average 1.3 years and 5.3 years before diagnosis, respectively, were available from questionnaires. Data on BMI at baseline was also available. We used Cox regression to calculate hazard ratios and 95% confidence intervals (CIs). All statistical tests were two-sided. During a mean follow-up of 12.8 years, 119 men developed lethal disease (distant metastases or prostate cancer death). Among men with ERG-positive tumors, the multivariable hazard ratio for lethal prostate cancer was 1.48 (95% CI 0.98 to 2.23) per 5-unit increase in BMI before diagnosis, 2.51 (95% CI 1.26 to 4.99) per 8-inch increase in waist circumference before diagnosis, and 2.22 (95% CI 1.35 to 3.63) per 5-unit increase in BMI at baseline. The corresponding hazard ratios among men with ERG-negative tumors were 1.10 (95% CI 0.76 to1.59; P-interaction .24), 1.14 (95% CI 0.62 to 2.10; P-interaction .09), and 0.78 (95% CI 0.52 to 1.19; P-interaction .001). These results suggest that obesity is linked with poorer prostate cancer prognosis primarily in men with tumors harboring the gene fusion TMPRSS2:ERG. C1 [Pettersson, Andreas; Meisner, Allison; Fiorentino, Michelangelo; Graff, Rebecca E.; Penney, Kathryn L.; Rider, Jennifer R.; Nuttall, Elizabeth J.; Stampfer, Meir J.; Giovannucci, Edward L.; Mucci, Lorelei A.] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. [Stampfer, Meir J.; Giovannucci, Edward L.] Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA. [Pettersson, Andreas; Penney, Kathryn L.; Rider, Jennifer R.; Stampfer, Meir J.; Giovannucci, Edward L.; Mucci, Lorelei A.] Brigham & Womens Hosp, Dept Med, Channing Div Network Med, Boston, MA 02115 USA. [Sesso, Howard D.] Brigham & Womens Hosp, Dept Med, Div Prevent Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. [Lis, Rosina T.; Stack, Edward C.; Loda, Massimo] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. [Lis, Rosina T.; Flavin, Richard; Stack, Edward C.; Fiorentino, Michelangelo; Finn, Stephen; Martin, Neil E.; Loda, Massimo] Dana Farber Canc Inst, Ctr Mol Oncol Pathol, Boston, MA 02115 USA. [Martin, Neil E.] Dana Farber Canc Inst, Dept Radiat Oncol, Boston, MA 02115 USA. [Kantoff, Philip W.] Dana Farber Canc Inst, Lank Ctr Genitourinary Oncol, Boston, MA 02115 USA. [Flavin, Richard; Finn, Stephen] Univ Dublin Trinity Coll, Dublin 2, Ireland. [Fiorentino, Michelangelo] St Orsola Marcello Malpighi Hosp, Pathol Unit, Addarii Inst, Bologna, Italy. [Pollak, Michael] McGill Univ, Dept Med, Montreal, PQ, Canada. RP Mucci, LA (reprint author), Harvard Univ, Sch Publ Hlth, 677 Huntington Ave, Boston, MA 02115 USA. EM lmucci@hsph.harvard.edu RI Martin, Neil/E-2193-2014; OI Martin, Neil/0000-0002-8164-8516; Rider, Jennifer/0000-0002-2637-6036; Finn, Stephen/0000-0002-8628-5814 FU Dana-Farber/Harvard Cancer Center Specialized Programs of Research Excellence program in prostate cancer [5P50CA090381-08]; National Cancer Institute [T32 CA009001, R25 CA098566, CA55075, CA141298, CA13389, CA-34944, CA-40360, CA-097193, EDRN U01 CA113913, PO1 CA055075]; National Heart, Lung, and Blood Institute [HL-26490, HL-34595]; Prostate Cancer Foundation; Swedish Research Council [2009-7309]; Royal Physiographic Society in Lund FX This work was supported by the Dana-Farber/Harvard Cancer Center Specialized Programs of Research Excellence program in prostate cancer (5P50CA090381-08); the National Cancer Institute (T32 CA009001 to KLP; R25 CA098566 to REG; CA55075, CA141298, CA13389, CA-34944, CA-40360, CA-097193, EDRN U01 CA113913, and PO1 CA055075); the National Heart, Lung, and Blood Institute (HL-26490 and HL-34595); the Prostate Cancer Foundation (to LAM, KLP, and NEM); the Swedish Research Council (Reg. No. 2009-7309 to AP), and the Royal Physiographic Society in Lund (to AP). NR 30 TC 22 Z9 22 U1 0 U2 4 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0027-8874 EI 1460-2105 J9 JNCI-J NATL CANCER I JI JNCI-. Natl. Cancer Inst. PD DEC PY 2013 VL 105 IS 24 BP 1881 EP 1890 DI 10.1093/jnci/djt332 PG 10 WC Oncology SC Oncology GA 280UU UT WOS:000329057100009 PM 24292212 ER PT J AU Fuchs, CS Ogino, S AF Fuchs, Charles S. Ogino, Shuji TI Aspirin Therapy for Colorectal Cancer With PIK3CA Mutation: Simply Complex! SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID NF-KAPPA-B; NONSTEROIDAL ANTIINFLAMMATORY DRUGS; RANDOMIZED-TRIAL; BETA-CATENIN; COLON-CANCER; ADENOMAS; PATHWAY; PREVENTION; ACTIVATION; EXPRESSION C1 [Fuchs, Charles S.; Ogino, Shuji] Dana Farber Canc Inst, Boston, MA 02115 USA. RP Fuchs, CS (reprint author), Dana Farber Canc Inst, Boston, MA 02115 USA. NR 49 TC 11 Z9 11 U1 0 U2 13 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 DEC 1 PY 2013 VL 31 IS 34 BP 4358 EP 4361 DI 10.1200/JCO.2013.52.0080 PG 4 WC Oncology SC Oncology GA 277KD UT WOS:000328816600013 PM 24166520 ER PT J AU Winges, KM Werner, JS Harvey, DJ Cello, KE Durbin, MK Balcer, LJ Calabresi, PA Keltner, JL AF Winges, Kimberly M. Werner, John S. Harvey, Danielle J. Cello, Kimberly E. Durbin, Mary K. Balcer, Laura J. Calabresi, Peter A. Keltner, John L. TI Baseline Retinal Nerve Fiber Layer Thickness and Macular Volume Quantified by OCT in the North American Phase 3 Fingolimod Trial for Relapsing-Remitting Multiple Sclerosis SO JOURNAL OF NEURO-OPHTHALMOLOGY LA English DT Article ID OPTICAL COHERENCE TOMOGRAPHY; ORAL FINGOLIMOD; AXONAL LOSS; ATROPHY; PATHOLOGY; NEURITIS; NEUROPATHIES; DISABILITY; VISION AB Background:Patients with multiple sclerosis (MS) demonstrate thinning of peripapillary retinal nerve fiber layer (RNFL) and decreased macular volume as measured by optical coherence tomography (OCT). To our knowledge, there are no previous reports from a large MS OCT database with strict quality control measures that quantitate RNFL and macula in patients with relapsing-remitting multiple sclerosis.Methods:The University of California Davis OCT Reading Center gathered OCT data at baseline as part of the North American phase 3 trial of fingolimod (Gilenya). Average RNFL thickness (RNFLT) and macular volume (TMV) were measured using time domain OCT (TD-OCT). RNFL quadrants, clock hours, and macular subfields were included. With strict quality control and accounting for signal strength differences, scans were categorized as reduced or not reduced for each field, based on being less than 5th percentile for age-matched controls derived from the normative database in the scanner software. Patients were deemed abnormal if at least 1 eye had reduced values for a given parameter. Patients with abnormalities in corresponding RNFL and macular subfields were compared by cross-tabulation.Results:The TD-OCT data were prospectively collected from 939 of the 1,083 trial patients, 712 of whom met all final quality and data inclusion criteria. Of the final cohort, 242 (34.0%) demonstrated reduced (less than 5th percentile) average RNFLT in at least 1 eye. One hundred seventy-eight (25.0%) patients had reduced TMV. One hundred twenty-eight (18.0%) demonstrated both reduced TMV and RNFLT in the same eye, whereas 42 (5.8%) had reduced TMV and RNFLT in both eyes. Of the 242 patients with reduced average RNFL thickness, 128 (52.9%) also had reduced TMV. Fifty patients had reduced TMV in the absence of reduced RNFLT in at least 1 eye, a cohort prevalence of 7.0%. Quadrant and subfield analysis showed a predominance of temporal and inferior RNFL thinning, with inferior macular thinning corresponding best to RNFL thinning.Conclusion:RNFL and macular thinning/volume loss is common at baseline in relapsing-remitting multiple sclerosis, as measured by TD-OCT. When the RNFL is thin, the macular volume is reduced in more than half of the patients. There is a population of reduced TMV without any reduction in RNFLT. Documenting the prevalence and distribution of these structural abnormalities supports recent reports and suggests new retinal areas to probe for functional vision changes in MS. C1 [Winges, Kimberly M.] Vet Adm Med Ctr, Dept Ophthalmol, Portland, OR USA. [Winges, Kimberly M.; Werner, John S.; Cello, Kimberly E.; Keltner, John L.] Univ Calif Davis, Sch Med, Dept Ophthalmol & Vis Sci, Davis, CA 95616 USA. [Harvey, Danielle J.] Univ Calif Davis, Sch Med, Div Biostat, Davis, CA 95616 USA. Univ Calif Davis, Sch Med, Dept Publ Hlth Sci, Davis, CA 95616 USA. [Keltner, John L.] Univ Calif Davis, Sch Med, Dept Neurol, Davis, CA 95616 USA. [Keltner, John L.] Univ Calif Davis, Sch Med, Dept Neurosurg, Davis, CA 95616 USA. [Durbin, Mary K.] Carl Zeiss Meditec Inc, Dublin, CA USA. [Balcer, Laura J.] NYU, Dept Neurol, Langone Med Ctr, New York, NY 10016 USA. [Calabresi, Peter A.] Johns Hopkins Univ, Sch Med, Dept Neurol, Baltimore, MD 21205 USA. RP Winges, KM (reprint author), Portland VA Med Ctr, Dept Ophthalmol, Mail Code P3EYE,3710 SW US Vet Hosp Rd, Portland, OR 97239 USA. EM kim.winges@gmail.com FU Novartis Pharmaceuticals Corporation; Research to Prevent Blindness; Department of Veterans Affairs FX Novartis Pharmaceuticals Corporation funded OCT data collection as part of the fingolimod phase 3 clinical trial NCT00355134. Partial support was also provided by an unrestricted grant from Research to Prevent Blindness to University of California Davis, CA. KMW received support from the Department of Veterans Affairs. NR 32 TC 1 Z9 1 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1070-8022 EI 1536-5166 J9 J NEURO-OPHTHALMOL JI J. Neuro-Ophthal. PD DEC PY 2013 VL 33 IS 4 BP 341 EP 348 DI 10.1097/WNO.0b013e31829c51f7 PG 8 WC Clinical Neurology; Ophthalmology SC Neurosciences & Neurology; Ophthalmology GA 277KW UT WOS:000328819100009 ER PT J AU Patel, MM Stacy, RC AF Patel, Mrinali M. Stacy, Rebecca C. TI Paraneoplastic Dermatomyositis Related to a Chondrosarcoma Involving the Cavernous Sinus SO JOURNAL OF NEURO-OPHTHALMOLOGY LA English DT Editorial Material ID POLYMYOSITIS; MYOPATHY; CANCER; RISK AB Approximately one third of all cases of dermatomyositis may be associated with malignancy. We describe a patient with unexplained rash, joint pain, and muscle weakness, who subsequently developed a cavernous sinus syndrome due to a central nervous system chondrosarcoma. Discovery of this tumor and further dermatologic evaluation, including skin biopsy, resulted in diagnosis of paraneoplastic dermatomyositis due to cavernous sinus chondrosarcoma. C1 [Patel, Mrinali M.; Stacy, Rebecca C.] Harvard Univ, Sch Med, Dept Ophthalmol, Massachusetts Eye & Ear Infirm, Boston, MA USA. RP Stacy, RC (reprint author), Massachusetts Eye & Ear Infirm, Dept Ophthalmol, 243 Charles St, Boston, MA 02114 USA. EM rebecca_stacy@meei.harvard.edu NR 7 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 1070-8022 EI 1536-5166 J9 J NEURO-OPHTHALMOL JI J. Neuro-Ophthal. PD DEC PY 2013 VL 33 IS 4 BP 363 EP 366 DI 10.1097/WNO.0b013e3182a30480 PG 4 WC Clinical Neurology; Ophthalmology SC Neurosciences & Neurology; Ophthalmology GA 277KW UT WOS:000328819100013 PM 24051424 ER PT J AU Rizzo, JF AF Rizzo, Joseph F., III TI Festschrift for Simmons Lessell, MD SO JOURNAL OF NEURO-OPHTHALMOLOGY LA English DT News Item C1 Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Ophthalmol, Boston, MA 02115 USA. RP Rizzo, JF (reprint author), Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Ophthalmol, Boston, MA 02115 USA. NR 0 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 1070-8022 EI 1536-5166 J9 J NEURO-OPHTHALMOL JI J. Neuro-Ophthal. PD DEC PY 2013 VL 33 IS 4 BP E25 EP E26 DI 10.1097/WNO.0000000000000056 PG 2 WC Clinical Neurology; Ophthalmology SC Neurosciences & Neurology; Ophthalmology GA 277KW UT WOS:000328819100003 ER PT J AU Chaudhuri, SE Karmali, F Merfeld, DM AF Chaudhuri, Shomesh E. Karmali, Faisal Merfeld, Daniel M. TI Whole body motion-detection tasks can yield much lower thresholds than direction-recognition tasks: implications for the role of vibration SO JOURNAL OF NEUROPHYSIOLOGY LA English DT Article DE signal detection theory; perception; psychophysics; discrimination; human ID ANGULAR ACCELERATION; PSYCHOMETRIC FUNCTIONS; HUMAN DISCRIMINATION; VERTICAL AXIS; PERCEPTION; NOISE; TILT; SENSITIVITY; FREQUENCY; MOVEMENT AB Earlier spatial orientation studies used both motion-detection (e. g., did I move?) and direction-recognition (e.g., did I move left/right?) paradigms. The purpose of our study was to compare thresholds measured with motion-detection and direction-recognition tasks on a standard Moog motion platform to see whether a substantial fraction of the reported threshold variation might be explained by the use of different discrimination tasks in the presence of vibrations that vary with motion. Thresholds for the perception of yaw rotation about an earth-vertical axis and for interaural translation in an earth-horizontal plane were determined for four healthy subjects with standard detection and recognition paradigms. For yaw rotation two-interval detection thresholds were, on average, 56 times smaller than two-interval recognition thresholds, and for interaural translation two-interval detection thresholds were, on average, 31 times smaller than two-interval recognition thresholds. This substantive difference between recognition thresholds and detection thresholds is one of our primary findings. For motions near our measured detection threshold, we measured vibrations that matched previously established vibration thresholds. This suggests that vibrations contribute to whole body motion detection. We also recorded yaw rotation thresholds on a second motion device with lower vibration and found direction-recognition and motion-detection thresholds that were not significantly different from one another or from the direction-recognition thresholds recorded on our Moog platform. Taken together, these various findings show that yaw rotation recognition thresholds are relatively unaffected by vibration when moderate (up to similar to 0.08 m/s(2)) vibration cues are present. C1 [Chaudhuri, Shomesh E.; Karmali, Faisal; Merfeld, Daniel M.] Massachusetts Eye & Ear Infirm, Jenks Vestibular Physiol Lab, Boston, MA 02114 USA. [Karmali, Faisal; Merfeld, Daniel M.] Harvard Univ, Sch Med, Dept Otol & Laryngol, Boston, MA 02115 USA. RP Merfeld, DM (reprint author), Jenks Vestibular Physiol Lab, 243 Charles St,Rm 421, Boston, MA 02114 USA. EM dan_merfeld@meei.harvard.edu OI Karmali, Faisal/0000-0002-1140-4954 FU National Institute on Deafness and Other Communication Disorders [DC-04158] FX This research was supported by National Institute on Deafness and Other Communication Disorders Grant DC-04158. NR 55 TC 9 Z9 9 U1 0 U2 4 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-3077 EI 1522-1598 J9 J NEUROPHYSIOL JI J. Neurophysiol. PD DEC PY 2013 VL 110 IS 12 BP 2764 EP 2772 DI 10.1152/jn.00091.2013 PG 9 WC Neurosciences; Physiology SC Neurosciences & Neurology; Physiology GA 278KR UT WOS:000328889700008 PM 24068754 ER PT J AU da Silva, MC Conti, CL Klauss, J Alves, LG Cavalcante, HMD Fregni, F Nitsche, MA Nakamura-Palacios, EM AF da Silva, Morgana Croce Conti, Catarine Lima Klauss, Jaisa Alves, Luana Gaburro do Nascimento Cavalcante, Henrique Mineiro Fregni, Felipe Nitsche, Michael A. Nakamura-Palacios, Ester Miyuki TI Behavioral effects of transcranial Direct Current Stimulation (tDCS) induced dorsolateral prefrontal cortex plasticity in alcohol dependence SO JOURNAL OF PHYSIOLOGY-PARIS LA English DT Article DE Anodal tDCS; Alcoholics; Prefrontal cortex; EEG; Event-related potential; LORETA ID ELECTROMAGNETIC TOMOGRAPHY LORETA; FRONTAL ASSESSMENT BATTERY; COMPULSIVE DRINKING SCALE; IMPROVING WORKING-MEMORY; HUMAN MOTOR CORTEX; DOUBLE-BLIND; CORTICAL EXCITABILITY; MAJOR DEPRESSION; DC STIMULATION; BRAIN-STIMULATION AB Transcranial Direct Current Stimulation (tDCS) has been shown to reduce acute substance craving in drug addicts, and improve cognition in neuropsychiatric patients. Here we aimed to explore further tDCS induced behavioral and neurophysiological modulation including assessment of relapse rate over a prolonged time course in alcoholism. We examined the effects of repeated anodal tDCS (2 mA, 35 cm(2), 20 min) over the left dorsolateral prefrontal cortex (DLPFC) on relapse to the use of alcohol in alcoholics from outpatient services, who received additional routine clinical treatment. Furthermore, event related potentials (ERPs), cognitive and frontal executive processes, craving, depressive and anxiety symptoms were obtained before and after treatment. From thirteen alcoholic subjects, seven were randomized to sham-tDCS and six to real tDCS treatment (once a week for five consecutive weeks). Depressive symptoms and craving were reduced to a larger extent in the tDCS group compared to the sham group (p = 0.005 and p = 0.015, respectively). On the other hand, active tDCS was able to block the increase in neural activation triggered by alcohol related and neutral cues in prefrontal cortex (PFC) as indexed by ERP as seen in the sham-tDCS group. Finally, there was a trend for increased change in executive function in the tDCS group compared to the sham-tDCS group (p = 0.082), and, similarly, a trend for more relapses in the tDCS group compared to sham tDCS (four alcoholic subjects (66.7%) vs. one (14.3%), p = 0.053). These results confirm the previous findings of tDCS effects on craving in alcoholism and also extend these findings as we showed also tDCS-related mood improvement. However, potential increase in relapse is possible; thus the clinical value of an increase in craving and improvement in depression and executive function needs to be carefully assessed in further studies; including investigation of optimal parameters of stimulation. (C) 2013 Elsevier Ltd. All rights reserved. C1 [da Silva, Morgana Croce; Conti, Catarine Lima; Klauss, Jaisa; Alves, Luana Gaburro; do Nascimento Cavalcante, Henrique Mineiro; Nakamura-Palacios, Ester Miyuki] Univ Fed Espirito Santo, Program Postgrad Physiol Sci, Lab Cognit Sci & Neuropsychopharmacol, BR-29047105 Vitoria, ES, Brazil. [da Silva, Morgana Croce; Conti, Catarine Lima; Klauss, Jaisa; Alves, Luana Gaburro; do Nascimento Cavalcante, Henrique Mineiro; Nakamura-Palacios, Ester Miyuki] Harvard Univ, Sch Med, Dept Phys Med & Rehabil, Lab Neuromodulat, Boston, MA USA. [Fregni, Felipe] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. [Fregni, Felipe] Harvard Univ, Beth Israel Deaconess Med Ctr, Dept Neurol, Berenson Allen Ctr Noninvas Brain Stimulat,Med Sc, Boston, MA 02215 USA. [Nitsche, Michael A.] Univ Gottingen, Dept Clin Neurophysiol, Univ Med Ctr, Lab Neuroplast, D-37073 Gottingen, Germany. RP Nakamura-Palacios, EM (reprint author), Univ Fed Espirito Santo, Ctr Ciencias Saude, Programa Posgrad Ciencias Fisiol, Av Marechal Campos 1468, BR-29047105 Vitoria, ES, Brazil. EM emnpalacios@gmail.com FU CNPq; CAPES FX We want to thank patients and families who agreed to participate in this study, Dr. Maria da Penha Zago-Gomes and Dr. Janine Andrade Moscon for recruiting and referring alcoholic patients, Dr. Roney Welinton Dias de Oliveira for clinical examination of alcoholic patients and graduating students who helped to collect part of the data. MCS, JAM and CLC were recipients of governmental (CNPq or CAPES) student fellowships. NR 92 TC 26 Z9 26 U1 4 U2 21 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0928-4257 EI 1769-7115 J9 J PHYSIOL-PARIS JI J. Physiol.-Paris PD DEC PY 2013 VL 107 IS 6 SI SI BP 493 EP 502 DI 10.1016/j.jphysparis.2013.07.003 PG 10 WC Neurosciences; Physiology SC Neurosciences & Neurology; Physiology GA 278UQ UT WOS:000328915800009 PM 23891741 ER PT J AU Gorfine, M Hsu, L Parmigiani, G AF Gorfine, Malka Hsu, Li Parmigiani, Giovanni TI Frailty Models for Familial Risk With Application to Breast Cancer SO JOURNAL OF THE AMERICAN STATISTICAL ASSOCIATION LA English DT Article DE Familial risk prediction; Multivariate survival; Risk index; ROC analysis ID FULL LIKELIHOOD APPROACH; BRCA2 MUTATIONS; CARRIER PROBABILITIES; SUSCEPTIBILITY GENES; REGRESSION-MODELS; SURVIVAL ANALYSIS; PREDICTING BRCA1; ASHKENAZI JEWS; HISTORY; DESIGNS AB In evaluating familial risk for disease we have two main statistical tasks: assessing the probability of carrying an inherited genetic mutation conferring higher risk, and predicting the absolute risk of developing diseases over time for those individuals whose mutation status is known. Despite substantial progress, much remains unknown about the role of genetic and environmental risk factors, about the sources of variation in risk among families that carry high-risk mutations, and about the sources of familial aggregation beyond major Mendelian effects. These sources of heterogeneity contribute substantial variation in risk across families. In this article we present simple and efficient methods for accounting for this variation in familial risk assessment. Our methods are based on frailty models. We implemented them in the context of generalizing Mendelian models of cancer risk, and compared our approaches to others that do not consider heterogeneity across families. Our extensive simulation study demonstrates that when predicting the risk of developing a disease over time conditional on carrier status, accounting for heterogeneity results in a substantial improvement in the area under the curve of the receiver operating characteristic. On the other hand, the improvement for carriership probability estimation is more limited. We illustrate the utility of the proposed approach through the analysis of BRCA1 and BRCA2 mutation carriers in the Washington Ashkenazi Kin-Cohort Study of Breast Cancer. Supplementary materials for this article are available online. C1 [Gorfine, Malka] Technion Israel Inst Technol, Fac Ind Engn & Management, IL-32000 Haifa, Israel. [Hsu, Li] Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, Seattle, WA 98109 USA. [Parmigiani, Giovanni] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02215 USA. [Parmigiani, Giovanni] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. RP Gorfine, M (reprint author), Technion Israel Inst Technol, Fac Ind Engn & Management, IL-32000 Haifa, Israel. EM gorfinm@ie.technion.ac.il; lih@fhcrc.org; gp@jimmy.harvard.edu FU Susan G Komen Breast Cancer Foundation [KG081303]; NIH [P01CA53996, R01AG014358, P50CA138293]; Israel Science Foundation (ISF) [2012898]; [NIH/NCI 5P30 CA006516-46]; [1R21CA177233-01] FX The authors thank Dr. Nilanjan Chatterjee for faciliating the access of the Washington Ashkenazi Jewish data. Work of Giovanni Parmigiani is supported by grant KG081303 from the Susan G Komen Breast Cancer Foundation and grants NIH/NCI 5P30 CA006516-46 and 1R21CA177233-01. Work of Li Hsu is supported by NIH grants P01CA53996, R01AG014358, and P50CA138293. Work of Malka Gorfine is supported by the Israel Science Foundation (ISF) grant 2012898. The R code for running our methods can be provided upon request by the first author. NR 39 TC 2 Z9 2 U1 1 U2 7 PU AMER STATISTICAL ASSOC PI ALEXANDRIA PA 732 N WASHINGTON ST, ALEXANDRIA, VA 22314-1943 USA SN 0162-1459 EI 1537-274X J9 J AM STAT ASSOC JI J. Am. Stat. Assoc. PD DEC PY 2013 VL 108 IS 504 BP 1205 EP 1215 DI 10.1080/01621459.2013.818001 PG 11 WC Statistics & Probability SC Mathematics GA 278RZ UT WOS:000328908700007 PM 24678132 ER PT J AU Yu, JB Efstathiou, JA Bekelman, JE AF Yu, James B. Efstathiou, Jason A. Bekelman, Justin E. TI Proton Radiotherapy for Prostate Cancer: How Did We Get Here, and Where Do We Go From Here? SO ONCOLOGY-NEW YORK LA English DT Editorial Material ID INTENSITY-MODULATED RADIOTHERAPY; RADIATION-THERAPY; BEAM THERAPY; ONCOLOGY; TECHNOLOGY; TOXICITY; PATTERNS; OUTCOMES; CARE C1 [Yu, James B.] Yale Univ, Sch Med, Dept Therapeut Radiol, New Haven, CT 06510 USA. [Efstathiou, Jason A.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiat Oncol, Boston, MA USA. [Bekelman, Justin E.] Univ Penn, Perelman Sch Med, Abramson Canc Ctr, Dept Radiat Oncol, Philadelphia, PA 19104 USA. RP Yu, JB (reprint author), Yale Univ, Sch Med, Dept Therapeut Radiol, New Haven, CT 06510 USA. NR 26 TC 0 Z9 0 U1 1 U2 5 PU UBM MEDICA PI NORWALK PA 535 CONNECTICUT AVE, STE 300, NORWALK, CT 06854 USA SN 0890-9091 J9 ONCOLOGY-NY JI Oncology-NY PD DEC PY 2013 VL 27 IS 12 BP 1293 EP 1294 PG 2 WC Oncology SC Oncology GA 280EV UT WOS:000329012400014 PM 24624550 ER PT J AU Dow, SJ Kelly, JF AF Dow, Sarah J. Kelly, John F. TI Listening to Youth: Adolescents' Reasons for Substance Use as a Unique Predictor of Treatment Response and Outcome SO PSYCHOLOGY OF ADDICTIVE BEHAVIORS LA English DT Article DE adolescents; addiction treatment; substance use disorder; phenotype; reasons for substance use ID ALCOHOL-USE DISORDERS; DRUG-USE; ABUSE TREATMENT; MARIJUANA USE; FORM 90; RELAPSE; DRINKING; MODEL; VULNERABILITY; RELIABILITY AB National efforts have focused on improving adolescent substance use disorder (SUD) treatment outcomes, yet improvements remain modest. Because adolescents are noteworthy for heterogeneity in their clinical profiles, treatment might be enhanced by the identification of clinical subgroups for which interventions could be more effectively tailored. Some of these subgroups, such as those based on abstinence motivation, substance involvement, and psychiatric status are promising candidates. This study examined the unique predictive utility of adolescents' primary reason for alcohol and other drug use. Adolescent outpatients (N = 109; 27% female, aged 14-19) were assessed at treatment intake on their reason for substance use, as well as demographic, substance use, and clinical variables, and reassessed at 3, 6, and 12 months. Reason for use fell into two broad domains: using to enhance a positive state (positive reinforcement [PR]; 47% of youth) and using to cope with a negative state (negative reinforcement [NR]; 53% of youth). Compared with PR patients, NR patients were significantly more substance involved, reported more psychological distress, and had a more extensive treatment history. It is important to note that NR patients showed a significant treatment response, whereas PR patients showed no improvement. PR-NR status also uniquely predicted treatment response and outcome independent of a variety of other predictors, including abstinence motivation, self-efficacy, coping, and prior treatment. Adolescents' primary reason for substance use may provide unique clinical information that could inform treatment planning and patient-treatment matching. C1 [Dow, Sarah J.; Kelly, John F.] Massachusetts Gen Hosp, Harvard Ctr Addict Med, Dept Psychiat, Boston, MA 02114 USA. RP Kelly, JF (reprint author), Massachusetts Gen Hosp, Harvard Ctr Addict Med, 60 Staniford St, Boston, MA 02114 USA. EM jkelly11@partners.org FU NIAAA NIH HHS [R01 AA015526] NR 50 TC 8 Z9 8 U1 6 U2 22 PU EDUCATIONAL PUBLISHING FOUNDATION-AMERICAN PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST, NE, WASHINGTON, DC 20002-4242 USA SN 0893-164X EI 1939-1501 J9 PSYCHOL ADDICT BEHAV JI Psychol. Addict. Behav. PD DEC PY 2013 VL 27 IS 4 BP 1122 EP 1131 DI 10.1037/a0031065 PG 10 WC Substance Abuse; Psychology, Multidisciplinary SC Substance Abuse; Psychology GA 280PZ UT WOS:000329044500023 PM 23276316 ER PT J AU Lund, TC Hume, H Allain, JP McCullough, J Dzik, W AF Lund, Troy C. Hume, Heather Allain, Jean P. McCullough, Jeffrey Dzik, Walter TI The blood supply in Sub-Saharan Africa: Needs, challenges, and solutions SO TRANSFUSION AND APHERESIS SCIENCE LA English DT Article DE Sub Saharan Africa; Transfusion; Blood Supply; Global ID ACUTE CHEST SYNDROME; SICKLE-CELL-DISEASE; FALCIPARUM-MALARIA; REPLACEMENT DONORS; MATERNAL MORTALITY; 1ST-TIME VOLUNTEER; RELATIVE SAFETY; GLOBAL HEALTH; SEVERE ANEMIA; CHILDREN AB Sub-Saharan Africa (SSA) is burdened with a growing population and poor health care resources. Transfusion medicine is uniquely affected for SSA as a result of a combination of factors which put tremendous pressure on the blood supply. In this review, we consider these factors including: malaria, sickle cell anemia, transfusion medicine infrastructure, and past transfusion medicine policies including those which are tied to foreign aid, such as a VNRD-only practice. We also consider how SSA can overcome some of these hurdles to achieve a safe and adequate blood supply for its people through the advent of new vaccines, medications, infrastructure development, policy changes, and education. (C) 2013 Elsevier Ltd. All rights reserved. C1 [Lund, Troy C.] Univ Minnesota, Dept Pediat Blood & Marrow Transplant, Minneapolis, MN 55455 USA. [Hume, Heather] Univ Montreal, CHU St Justine, Serv Hematol Oncol, Dept Pediat, Montreal, PQ H3T 1C5, Canada. [Allain, Jean P.] Univ Cambridge, Dept Haematol, Div Transfus Med, Cambridge, England. [McCullough, Jeffrey] Univ Minnesota, Dept Lab Med & Pathol, Minneapolis, MN 55455 USA. [Dzik, Walter] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. RP Lund, TC (reprint author), Univ Minnesota, MCRB, Room 460G,425 East River Rd, Minneapolis, MN 55455 USA. EM lundx072@umn.edu; heather.hume@umontreal.ca; jpa1000@cam.ac.uk; mccul001@umn.edu; SDZIK@PARTNERS.ORG NR 38 TC 12 Z9 12 U1 0 U2 3 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 1473-0502 J9 TRANSFUS APHER SCI JI Transfus. Apher. Sci. PD DEC PY 2013 VL 49 IS 3 BP 416 EP 421 DI 10.1016/j.transci.2013.06.014 PG 6 WC Hematology SC Hematology GA 280EW UT WOS:000329012500010 PM 23871466 ER PT J AU Wamala, I Matar, AJ Farkash, E Wang, ZR Huang, CA Sachs, DH AF Wamala, Isaac Matar, Abraham J. Farkash, Evan Wang, Zhirui Huang, Christene A. Sachs, David H. TI Recombinant anti-monkey CD3 immunotoxin depletes peripheral lymph node T lymphocytes more effectively than rabbit anti-thymocyte globulin in naive baboons SO TRANSPLANT IMMUNOLOGY LA English DT Article DE T-cell; ATG; Immunotoxin; Depletion; Lymph node ID RENAL-ALLOGRAFT SURVIVAL; TOXIN-BASED IMMUNOTOXIN; CELL DEPLETION; MONOCLONAL-ANTIBODY; INDUCTION THERAPY; KIDNEY ALLOGRAFT; MIXED CHIMERISM; RHESUS-MONKEYS; BONE-MARROW; TOLERANCE AB T cell depletion is an important procedure for both experimental and therapeutic immune modulation. Rabbit anti-thymocyte globulin (ATG), which is a commonly used T cell depletion antibody in clinical organ and cell transplantation protocols, is effective in temporarily depleting peripheral blood T lymphocytes but only moderately effective in depleting peripheral lymph node T cells which comprise the majority of T lymphocytes. A recombinant anti-CD3 immunotoxin, A-dmDT390-scfbDb (007), has been developed and shown in an initial study to retain the lymph node depleting properties of conjugated CD3 immunotoxin. This agent could potentially be used synergistically with or as a replacement for rabbit ATG in preclinical primate models of transplantation. We directly compared the peripheral blood and lymph node depleting abilities of this recombinant anti-CD3 immunotoxin and rabbit ATG in naive animals at clinically tolerated doses. Baboons were treated with a full course of either rabbit ATG (n = 2) or CD3 immunotoxin (n = 3). Peripheral blood and lymph node T lymphocytes were measured before and following treatment. Peripheral blood CD3 + cells fell below 100 cells/mu L in every animal. In the two animals receiving ATG, CD3 + cells represented 53% and 68% of lymph node cells two days following a full course of rabbit ATG. In contrast, CD3 + cells represented 3%, 5%, and 38% in lymph nodes following a full course of CD3-IT. Thus, recombinant anti-monkey CD3 immunotoxin showed improved peripheral lymph node T lymphocyte depletion to rabbit ATG and spared other immune cells. (C) 2013 Published by Elsevier B.V. C1 [Wamala, Isaac; Matar, Abraham J.; Wang, Zhirui; Huang, Christene A.; Sachs, David H.] Massachusetts Gen Hosp, Transplantat Biol Res Ctr, Boston, MA 02114 USA. [Farkash, Evan] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Wamala, Isaac] Cleveland Clin, Dept Surg, Cleveland, OH USA. [Matar, Abraham J.] Univ Cent Florida, Coll Med, Orlando, FL 32816 USA. RP Sachs, DH (reprint author), Transplantat Biol Res Ctr, MGH East,149 13th St Suite 9019, Boston, MA 02129 USA. EM david.sachs@tbrc.mgh.harvard.edu OI Huang, Christene/0000-0001-9824-5716 FU NIH [5P01AI45897, U19AI051731] FX The authors would like to thank Drs. Radbeh Torabi and Vimukthi Pathiraja for assistance with surgical procedures in this study and Rebecca Brophy for editorial work on the manuscript. This work was supported by NIH 5P01AI45897 and U19AI051731. NR 27 TC 3 Z9 3 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0966-3274 EI 2210-3384 J9 TRANSPL IMMUNOL JI Transpl. Immunol. PD DEC PY 2013 VL 29 IS 1-4 BP 60 EP 63 DI 10.1016/j.trim.2013.10.004 PG 4 WC Immunology; Transplantation SC Immunology; Transplantation GA 282BQ UT WOS:000329145600011 PM 24157659 ER PT J AU Kahle, KT Deeb, TZ Puskarjov, M Silayeva, L Liang, B Kaila, K Moss, SJ AF Kahle, Kristopher T. Deeb, Tarek Z. Puskarjov, Martin Silayeva, Liliya Liang, Bo Kaila, Kai Moss, Stephen J. TI Modulation of neuronal activity by phosphorylation of the K-CI cotransporter KCC2 SO TRENDS IN NEUROSCIENCES LA English DT Review ID CATION-CHLORIDE COTRANSPORTERS; TEMPORAL-LOBE EPILEPSY; CL-COTRANSPORTER; GABA(A) RECEPTORS; INHIBITORY NEUROTRANSMISSION; SYNAPTIC INHIBITION; STATUS EPILEPTICUS; HIPPOCAMPAL INTERNEURONS; PYRAMIDAL NEURONS; PROTEIN-KINASES AB The K-CI cotransporter KCC2 establishes the low intraneuronal Cl- levels required for the hyperpolarizing inhibitory postsynaptic potentials mediated by ionotropic gamma-aminobutyric acid receptors (GABA(A)Rs) and glycine receptors (GlyRs). Decreased KCC2-mediated Cl- extrusion and impaired hyperpolarizing GABA(A)R- and/or GlyR-mediated currents have been implicated in epilepsy, neuropathic pain, and spasticity. Recent evidence suggests that the intrinsic ion transport rate, cell surface stability, and plasmalemmal trafficking of KCC2 are rapidly and reversibly modulated by the (de)phosphorylation of critical serine, threonine, and tyrosine residues in the C terminus of this protein. Alterations in KCC2 phosphorylation have been associated with impaired KCC2 function in several neurological diseases. Targeting KCC2 phosphorylation directly or indirectly via upstream regulatory kinases might be a novel strategy to modulate GABA- and/or glycinergic signaling for therapeutic benefit. C1 [Kahle, Kristopher T.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Neurosurg, Boston, MA 02114 USA. [Kahle, Kristopher T.] Boston Childrens Hosp, Howard Hughes Med Inst, Dept Cardiol, Manton Ctr Orphan Dis Res, Boston, MA 02115 USA. [Deeb, Tarek Z.; Silayeva, Liliya; Moss, Stephen J.] Tufts Univ, Sch Med, Dept Neurosci, Boston, MA 02111 USA. [Puskarjov, Martin; Kaila, Kai] Univ Helsinki, Dept Biosci, FI-00014 Helsinki, Finland. [Puskarjov, Martin; Kaila, Kai] Univ Helsinki, Ctr Neurosci, FI-00014 Helsinki, Finland. [Liang, Bo] Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA. [Moss, Stephen J.] UCL, Dept Neurosci Physiol & Pharmacol, London WC1E 6BT, England. RP Kahle, KT (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Neurosurg, Boston, MA 02114 USA. EM kkahle@enders.tch.harvard.edu RI Kaila, Kai/R-8528-2016 OI Kaila, Kai/0000-0003-0668-5955 FU Letten Foundation; Academy of Finland; Sigrid Juselius Foundation; Jane and Aatos Erkko Foundation; National Institutes of Health; Simons Foundation Autism Research Initiative; Manton Center for Orphan Disease Research; Congress of Neurological Surgeons FX The authors would like to thank Mingfeng Li and Nenad Sestan for providing the data in Figure 5. The authors' original research work was supported by grants from the Letten Foundation, the Academy of Finland, the Sigrid Juselius Foundation, the Jane and Aatos Erkko Foundation (KK); the National Institutes of Health (K.T.K.); Simons Foundation Autism Research Initiative (S.J.M.); the Manton Center for Orphan Disease Research (KT.K);. and the Congress of Neurological Surgeons (KT.K.). NR 105 TC 58 Z9 58 U1 3 U2 18 PU ELSEVIER SCIENCE LONDON PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0166-2236 J9 TRENDS NEUROSCI JI Trends Neurosci. PD DEC PY 2013 VL 36 IS 12 BP 726 EP 737 DI 10.1016/i.tins.2013.08.006 PG 12 WC Neurosciences SC Neurosciences & Neurology GA 281CQ UT WOS:000329077500005 PM 24139641 ER PT J AU Nawaz, H Mounzer, R Yadav, D Yabes, JG Slivka, A Whitcomb, DC Papachristou, GI AF Nawaz, Haq Mounzer, Rawad Yadav, Dhiraj Yabes, Jonathan G. Slivka, Adam Whitcomb, David C. Papachristou, Georgios I. TI Revised Atlanta and Determinant-Based Classification: Application in a Prospective Cohort of Acute Pancreatitis Patients SO AMERICAN JOURNAL OF GASTROENTEROLOGY LA English DT Article ID PERSISTENT ORGAN FAILURE; PROSPECTIVE-VALIDATION; SEVERITY; SCORE; MORTALITY; DISEASE AB OBJECTIVES: Atlanta classification (Atlanta 1992) of acute pancreatitis (AP) has several limitations. Two new classification systems were recently proposed: the Atlanta reclassification (Atlanta 2012) and the determinant-based classification (DBC). The aim of our study was to: (i) determine the association between different severity categories and clinical outcomes and (ii) perform a head-to-head comparison between Atlanta 1992, Atlanta 2012, and DBC in predicting these clinical outcomes. METHODS: A total of 256 prospectively enrolled patients were assigned a severity category for all three classifications. Five clinical outcomes were evaluated: mortality, intensive care unit (ICU) admission and length of stay (LOS), need for interventions, and hospital LOS. Pairwise testing between severity grades within a classification system was performed using Fisher's exact and Kruskal-Wallis tests. Predictive accuracies were evaluated using area under the ROC curve (AUC) and Somer's D co-efficient. RESULTS: Overall, higher grades of severity were associated with worse clinical outcomes for all three classification systems. Atlanta 2012 and DBC performed better than Atlanta 1992 and were comparable in predicting mortality (AUC 0.89 for both vs. 0.76, P < 0.001), ICU admission (AUC 0.91 for both vs. 0.80, P < 0.001), and ICU LOS (Somer's D 0.21 and 0.28 vs. 0.07, P < 0.05). DBC performed better in predicting need for interventions (AUC 0.93 vs. 0.85, P < 0.001), whereas Atlanta 2012 performed better in predicting hospital LOS (Somer's D 0.43 vs. 0.37, P = 0.04). CONCLUSIONS: Atlanta 2012 and DBC severity categories accurately reflected clinical outcomes in our cohort and were superior to Atlanta 1992. These novel classification systems can guide the selection of homogeneous patient populations for clinical research and provide an accurate spectrum of disease severity categories in the clinical setting. C1 [Nawaz, Haq; Mounzer, Rawad; Yadav, Dhiraj; Slivka, Adam; Whitcomb, David C.; Papachristou, Georgios I.] Univ Pittsburgh, Med Ctr, Dept Med, Div Gastroenterol Hepatol & Nutr, Pittsburgh, PA 15213 USA. [Yabes, Jonathan G.] Univ Pittsburgh, Sch Med, Hlth Care Data Ctr, Res Ctr, Pittsburgh, PA USA. [Papachristou, Georgios I.] Vet Affairs Pittsburgh Hlth Syst, Dept Med, Div Gastroenterol, Pittsburgh, PA USA. RP Papachristou, GI (reprint author), Univ Pittsburgh, Med Ctr, Dept Med, Div Gastroenterol Hepatol & Nutr, Pittsburgh, PA 15213 USA. EM papachri@pitt.edu FU Veterans Affairs VA Merit Review [PR000000496] FX Veterans Affairs VA Merit Review (PR000000496). NR 24 TC 40 Z9 43 U1 1 U2 8 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 DEC PY 2013 VL 108 IS 12 BP 1911 EP 1917 DI 10.1038/ajg.2013.348 PG 7 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 272KM UT WOS:000328459300013 PM 24126632 ER PT J AU Welzel, TM Graubard, BI Quraishi, S Zeuzem, S Davila, JA El-Serag, HB McGlynn, KA AF Welzel, Tania M. Graubard, Barry I. Quraishi, Sabah Zeuzem, Stefan Davila, Jessica A. El-Serag, Hashem B. McGlynn, Katherine A. TI Hepatocellular Carcinoma and Smoking: Oblivion or Contempt? Response SO AMERICAN JOURNAL OF GASTROENTEROLOGY LA English DT Letter C1 [Welzel, Tania M.; Zeuzem, Stefan] Johann Wolfgang Goethe Univ Hosp, Frankfurt, Germany. [Graubard, Barry I.; Quraishi, Sabah; McGlynn, Katherine A.] NCI, Div Canc Epidemiol & Genet, NIH, DHHS, Bethesda, MD 20892 USA. [Davila, Jessica A.; El-Serag, Hashem B.] Houston Vet Affairs Med Ctr, Houston, TX USA. [Davila, Jessica A.; El-Serag, Hashem B.] Baylor Coll Med, Houston, TX 77030 USA. RP McGlynn, KA (reprint author), NCI, DCEG, EPS 5022 6120 Execut Blvd, Rockville, MD 20852 USA. EM mcglynnk@mail.nih.gov NR 5 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0002-9270 EI 1572-0241 J9 AM J GASTROENTEROL JI Am. J. Gastroenterol. PD DEC PY 2013 VL 108 IS 12 BP 1931 EP 1931 DI 10.1038/ajg.2013.342 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 272KM UT WOS:000328459300020 PM 24300871 ER PT J AU Wang, JM Isenberg, JS Billiar, TR Chen, AF AF Wang, Jie-Mei Isenberg, Jeffery S. Billiar, Timothy R. Chen, Alex F. TI Thrombospondin-1/CD36 pathway contributes to bone marrow-derived angiogenic cell dysfunction in type 1 diabetes via Sonic hedgehog pathway suppression SO AMERICAN JOURNAL OF PHYSIOLOGY-ENDOCRINOLOGY AND METABOLISM LA English DT Article DE bone marrow-derived angiogenic cells; Sonic hedgehog; thrombospondin-1; type 1 diabetes ID ENDOTHELIAL PROGENITOR CELLS; NITRIC-OXIDE; GENE-THERAPY; PROTEIN THROMBOSPONDIN-1; OXIDATIVE STRESS; TISSUE SURVIVAL; CD36; EXPRESSION; ACTIVATION; CD47 AB Refractory wounds in diabetic patients present a significant clinical problem. Sonic hedgehog (SHH), a morphogenic protein central to wound repair, is deficient in diabetes. Regulation of SHH in wound healing is poorly understood. We hypothesize that thrombospondin-1 (TSP-1), through its receptor CD36, contributes to the SHH signaling defect in bone marrow-derived angiogenic cells (BMACs) in type 1 diabetic mice. Isolated BMACs from TSP-1-knockout mice demonstrated improved tube formation, migration, and adhesion in parallel with active SHH signaling. BMACs from STZ-induced type 1 diabetic mice showed significantly impaired Matrigel tube formation (n = 5; P < 0.05 vs. control), which was rescued by TSP-1 depletion (n = 5; P < 0.05 STZ-TSP-1(-/-) vs. STZ-WT) or exogenous SHH (20 mg/l, 24 h, n = 4; P < 0.05 vs. STZ-control). The expression of CD36 was elevated in BMACs from STZ mice (n = 4; P < 0.05). SHH signaling was significantly higher in BMACs from TSP-1(-/-) mice and TSP-1 receptor CD36-knockout mice (n = 6; P < 0.05 vs. WT) but not CD47-knockout mice (n = 3; P > 0.05 vs. WT). The impairment of recombinant human TSP-1 (2.2 nM, 24 h) on BMAC Matrigel tube formation was delayed significantly by CD36 deletion (n = 5; P < 0.05). CD36(-/-) BMACs demonstrated better tube formation under both normal and diabetic conditions with active SHH signaling (n = 4; P < 0.05 vs. WT BMACs). In conclusion, The TSP-1/CD36 pathway contributes to the SHH signaling defect, resulting in BMAC dysfunction in type 1 diabetic mice. C1 [Wang, Jie-Mei; Billiar, Timothy R.; Chen, Alex F.] Univ Pittsburgh, Sch Med, Dept Surg, Pittsburgh, PA USA. [Wang, Jie-Mei; Chen, Alex F.] Vet Affairs Pittsburgh Healthcare Syst, Vasc Surg Res, Pittsburgh, PA USA. [Wang, Jie-Mei; Chen, Alex F.] Cent S Univ, Dept Cardiol, Changsha 410013, Hunan, Peoples R China. [Wang, Jie-Mei; Chen, Alex F.] Cent S Univ, Ctr Clin Pharmacol, Xiangya Hosp 3, Changsha 410013, Hunan, Peoples R China. [Isenberg, Jeffery S.] Univ Pittsburgh, Sch Med, Div Pulm Allergy & Crit Care Med, Pittsburgh, PA USA. RP Chen, AF (reprint author), Cent S Univ, Xiangya Hosp 3, 138 Tong Zi Bo Rd, Changsha 410013, Hunan, Peoples R China. EM afychen@yahoo.com OI WANG, JIEMEI/0000-0002-8723-4410 FU National Institute of General Medical Sciences [R01-GM-077352]; Veterans Affairs Rehabilitation Research & Development Merit Awards [I01RX000244, 1I01RX000652]; American Diabetes Association Research Award; National Science Foundation of China (NSFC) [81130004]; NSFC for Distinguished Young Scholars of China Award [81300240]; American Heart Association Scientist Development Grant [13SDG16930098] FX This work was supported in part by National Institute of General Medical Sciences Grant R01-GM-077352 (to A. F. Chen), Veterans Affairs Rehabilitation Research & Development Merit Awards I01RX000244 and 1I01RX000652 (to A. F. Chen), American Diabetes Association Research Award 7-11-BS-23 (to A. F. Chen), National Science Foundation of China (NSFC) Key Research Project no. 81130004 (to A. F. Chen), NSFC for Distinguished Young Scholars of China Award no. 81300240 (to J. M. Wang), and American Heart Association Scientist Development Grant 13SDG16930098 (to J. M. Wang). NR 48 TC 7 Z9 7 U1 0 U2 5 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0193-1849 EI 1522-1555 J9 AM J PHYSIOL-ENDOC M JI Am. J. Physiol.-Endocrinol. Metab. PD DEC PY 2013 VL 305 IS 12 BP E1464 EP E1472 DI 10.1152/ajpendo.00516.2013 PG 9 WC Endocrinology & Metabolism; Physiology SC Endocrinology & Metabolism; Physiology GA 276LR UT WOS:000328752300005 PM 24148348 ER PT J AU Dodson, M Liang, QL Johnson, MS Redmann, M Fineberg, N Darley-Usmar, VM Zhang, JH AF Dodson, Matthew Liang, Qiuli Johnson, Michelle S. Redmann, Matthew Fineberg, Naomi Darley-Usmar, Victor M. Zhang, Jianhua TI Inhibition of glycolysis attenuates 4-hydroxynonenal-dependent autophagy and exacerbates apoptosis in differentiated SH-SY5Y neuroblastoma cells SO AUTOPHAGY LA English DT Article DE autophagy; oxidative stress; 4-hydroxynonenal; glycolysis; apoptosis; ATP; glutathione; Z-VAD; 3-MA ID CEREBRAL GLUCOSE-METABOLISM; AMYLOID BETA-PEPTIDE; LIPID-PEROXIDATION; OXIDATIVE STRESS; NEURODEGENERATIVE DISEASES; PARKINSONS-DISEASE; ALZHEIMERS-DISEASE; PROTEIN OXIDATION; REDOX PROTEOMICS; STROKE PATIENTS AB How cellular metabolic activities regulate autophagy and determine the susceptibility to oxidative stress and ultimately cell death in neuronal cells is not well understood. An important example of oxidative stress is 4-hydroxynonenal (HNE), which is a lipid peroxidation product that is formed during oxidative stress, and accumulates in neurodegenerative diseases causing damage. The accumulation of toxic oxidation products such as HNE, is a prevalent feature of neurodegenerative diseases, and can promote organelle and protein damage leading to induction of autophagy. In this study, we used differentiated SH-SY5Y neuroblastoma cells to investigate the mechanisms and regulation of cellular susceptibility to HNE toxicity and the relationship to cellular metabolism. We found that autophagy is immediately stimulated by HNE at a sublethal concentration. Within the same time frame, HNE induces concentration dependent CASP3/caspase 3 activation and cell death. Interestingly, both basal and HNE-activated autophagy, were regulated by glucose metabolism. Inhibition of glucose metabolism by 2-deoxyglucose (2DG), at a concentration that inhibited autophagic flux, further exacerbated CASP3 activation and cell death in response to HNE. Cell death was attenuated by the pan-caspase inhibitor Z-VAD-FMK. Specific inhibition of glycolysis using koningic acid, a GAPDH inhibitor, inhibited autophagic flux and exacerbated HNE-induced cell death similarly to 2DG. The effects of 2DG on autophagy and HNE-induced cell death could not be reversed by addition of mannose, suggesting an ER stress-independent mechanism. 2DG decreased LAMP1 and increased BCL2 levels suggesting that its effects on autophagy may be mediated by more than one mechanism. Furthermore, 2DG decreased cellular ATP, and 2DG and HNE combined treatment decreased mitochondrial membrane potential. We conclude that glucose-dependent autophagy serves as a protective mechanism in response to HNE. C1 [Dodson, Matthew; Liang, Qiuli; Johnson, Michelle S.; Redmann, Matthew; Darley-Usmar, Victor M.; Zhang, Jianhua] Univ Alabama Birmingham, Dept Pathol, Ctr Free Rad Biol, Birmingham, AL 35294 USA. [Liang, Qiuli; Zhang, Jianhua] Birmingham VA Med Ctr, Dept Vet Affairs, Birmingham, AL USA. [Fineberg, Naomi] Univ Alabama Birmingham, Sch Publ Hlth, Dept Biostat, Birmingham, AL 35294 USA. RP Zhang, JH (reprint author), Univ Alabama Birmingham, Dept Pathol, Ctr Free Rad Biol, Birmingham, AL 35294 USA. EM zhanja@uab.edu OI Zhang, Jianhua/0000-0002-2128-9574 FU VA merit award; [NIHR01-NS064090] FX We thank members of the laboratories of Dr Zhang and Dr Darley-Usmar for technical help and discussions. This work was supported by NIHR01-NS064090 and a VA merit award (to JZ). NR 57 TC 18 Z9 19 U1 2 U2 12 PU LANDES BIOSCIENCE PI AUSTIN PA 1806 RIO GRANDE ST, AUSTIN, TX 78702 USA SN 1554-8627 EI 1554-8635 J9 AUTOPHAGY JI Autophagy PD DEC 1 PY 2013 VL 9 IS 12 BP 1996 EP 2008 DI 10.4161/auto.26094 PG 13 WC Cell Biology SC Cell Biology GA 270DT UT WOS:000328299800007 PM 24145463 ER PT J AU Gutner, CA Casement, MD Gilbert, KS Resick, PA AF Gutner, Cassidy A. Casement, Melynda D. Gilbert, Karina Stavitsky Resick, Patricia A. TI Change in sleep symptoms across Cognitive Processing Therapy and Prolonged Exposure: A longitudinal perspective SO BEHAVIOUR RESEARCH AND THERAPY LA English DT Article DE Posttraumatic stress disorder; Trauma; Sleep; Follow-up ID POSTTRAUMATIC-STRESS-DISORDER; ADMINISTERED PTSD SCALE; FEMALE RAPE VICTIMS; DEPRESSIVE SYMPTOMS; BEHAVIORAL THERAPY; INSOMNIA; DISTURBANCE; EXTINCTION; PREDICTORS; MECHANISMS AB Sleep disturbance is a core component in posttraumatic stress disorder (PTSD). Although cognitive-behavioral treatments for PTSD reduce the severity of sleep symptoms, they do not lead to complete remission. The present study examines the impact of Cognitive Processing Therapy (CPT) and Prolonged Exposure (PE) on subjective measures of sleep disturbance from treatment randomization through long-term follow-up (LTFU). Participants were 171 female rape victims with PTSD who were randomly assigned to CPT, PE, or Minimal Attention (MA). After 6-weeks, the MA group was randomized to CPT or PE. Sleep symptoms were assessed at baseline, post-MA, post-treatment, 3-months, 9-months and LTFU using the Pittsburgh Sleep Quality Index (PSQI) and nightmare and insomnia items from the Clinician Administered PTSD Scale. Change in sleep during MA, from pre- to post-treatment for CPT and PE, and from post-treatment through LTFU was assessed using piecewise hierarchical linear modeling with the intent-to-treat sample. Controlling for medication, sleep improved during CPT and PE compared to MA, and treatment gains were maintained through LTFU. CPT and PE were equally efficacious and improvements persist over LTFU, yet, neither produced remission of sleep disturbance. Overall, sleep symptoms do not remit and may warrant sleep-specific treatments. Published by Elsevier Ltd. C1 [Gutner, Cassidy A.; Casement, Melynda D.; Resick, Patricia A.] VA Boston Healthcare Syst, Natl Ctr Posttraumat Stress Disorder, Boston, MA USA. [Gutner, Cassidy A.; Casement, Melynda D.; Resick, Patricia A.] Boston Univ, Sch Med, Boston, MA 02118 USA. [Gilbert, Karina Stavitsky] VA Boston Healthcare Syst, Boston, MA USA. RP Gutner, CA (reprint author), VA Boston Healthcare Syst, Natl Ctr Posttraumat Stress Disorder, 150 South Huntington Ave 116B-3, Boston, MA USA. EM cassidy.gutner@va.gov OI Gutner, Cassidy A./0000-0002-9406-6638; Casement, Melynda/0000-0002-5906-0994 FU NIMH NIH HHS [R01 MH051509, T32 MH019836, 1R01 MH51509, T32 MH019836-15A2] NR 47 TC 12 Z9 12 U1 1 U2 8 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0005-7967 EI 1873-622X J9 BEHAV RES THER JI Behav. Res. Ther. PD DEC PY 2013 VL 51 IS 12 BP 817 EP 822 DI 10.1016/j.brat.2013.09.008 PG 6 WC Psychology, Clinical SC Psychology GA 276AB UT WOS:000328719400005 PM 24184428 ER PT J AU Jang, HS Han, SJ Kim, JI Lee, S Lipschutz, JH Park, KM AF Jang, Hee-Seong Han, Sang Jun Kim, Jee In Lee, Sanggyu Lipschutz, Joshua H. Park, Kwon Moo TI Activation of ERK accelerates repair of renal tubular epithelial cells, whereas it inhibits progression of fibrosis following ischemia/reperfusion injury SO BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE LA English DT Article DE Ischemia; Mitogen-activated protein kinase; Regeneration; Proliferation; Primary cilium; Exocyst ID ACUTE KIDNEY INJURY; INDUCED FUNCTIONAL INJURY; MAPK KINASE ACTIVATION; MARROW-DERIVED CELLS; OXIDATIVE STRESS; TUBULOINTERSTITIAL FIBROSIS; MESENCHYMAL TRANSITION; PRIMARY CILIOGENESIS; REPERFUSION INJURY; PROXIMAL TUBULE AB Extracellular signal-regulated kinase (ERR) signals play important roles in cell death and survival. However, the role of ERR in the repair process after injury remains to be defined in the kidney. Here, we investigated the role of ERR in proliferation and differentiation of tubular epithelial cells, and proliferation of interstitial cells following ischemia/reperfusion (I/R) injury in the mouse kidney. Mice were subjected to 30 min of renal ischemia. Some mice were administered with U0126, a specific upstream inhibitor of ERK, daily during the recovery phase, beginning at I day after ischemia until sacrifice. I/R caused severe tubular cell damage and functional loss in the kidney. Nine days after ischemia, the kidney was restored functionally with a partial restoration of damaged tubules and expansion of fibrotic lesions. ERR was activated by I/R and the activated ERK was sustained for 9 days. U0126 inhibited the proliferation, basolateral relocalization of Na,K-ATPase and lengthening of primary cilia in tubular epithelial cells, whereas it enhanced the proliferation of interstitial cells and accumulation of extracellular matrix. Furthermore, U0126 elevated the expression of cell cycle arrest-related proteins, p21 and phospholylated-chk2 in the post-ischemic kidney. U0126 mitigated the post-I/R increase of Sec10 which is a crucial component of exocyst complex and an important factor in ciliogenesis and tubulogenesis. U0126 also enhanced the expression of fibrosis-related proteins, TGF-beta 1 and phosphorylated NF-kappa B after ischemia. Our findings demonstrate that activation of ERK is required for both the restoration of damaged tubular epithelial cells and the inhibition of fibrosis progression following injury. (C) 2013 Elsevier B.V. All rights reserved. C1 [Jang, Hee-Seong; Han, Sang Jun; Kim, Jee In; Park, Kwon Moo] Kyungpook Natl Univ, Sch Med, Dept Anat, Taegu 700422, South Korea. [Jang, Hee-Seong; Kim, Jee In; Park, Kwon Moo] Kyungpook Natl Univ, Sch Med, Cardiovasc Res Inst, Taegu 700422, South Korea. [Lee, Sanggyu] Kyungpook Natl Univ, Sch Life Sci & Biotechnol, Taegu 702701, South Korea. [Lipschutz, Joshua H.] Philadelphia Vet Affairs Med Ctr, Dept Med, Philadelphia, PA USA. [Lipschutz, Joshua H.] Univ Penn, Philadelphia, PA 19104 USA. RP Park, KM (reprint author), Kyungpook Natl Univ, Sch Med, Dept Anat, 101 Dongindong, Taegu 700422, South Korea. EM kmpark@knu.ac.kr OI Jang, Hee-Seong/0000-0002-9620-351X FU Korea Health Technology RD Project; Ministry of Health & Welfare, Republic of Korea [A111366]; National Research Foundation; Korean Government [NRF-2011-220-E00001] FX This study was supported by a grant of the Korea Health Technology R&D Project, the Ministry of Health & Welfare, Republic of Korea (A111366 to KMP) and by the National Research Foundation Grant funded by the Korean Government (NRF-2011-220-E00001 to KMP). NR 57 TC 26 Z9 26 U1 0 U2 7 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0925-4439 EI 0006-3002 J9 BBA-MOL BASIS DIS JI Biochim. Biophys. Acta-Mol. Basis Dis. PD DEC PY 2013 VL 1832 IS 12 BP 1998 EP 2008 DI 10.1016/j.bbadis.2013.07.001 PG 11 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA 260AO UT WOS:000327567600010 PM 23851027 ER PT J AU Gaggin, HK Januzzi, JL AF Gaggin, Hanna K. Januzzi, James L., Jr. TI Biomarkers and diagnostics in heart failure SO BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE LA English DT Review DE Heart failure; Biomarker; Diagnosis; Prognosis; Management ID BRAIN NATRIURETIC PEPTIDE; GROWTH-DIFFERENTIATION FACTOR-15; EMERGENCY-DEPARTMENT PRIDE; VENTRICULAR SYSTOLIC DYSFUNCTION; RECEPTOR FAMILY-MEMBER; LONG-TERM MORTALITY; PROGNOSTIC VALUE; MYOCARDIAL-INFARCTION; ACUTE DYSPNEA; TROPONIN-T AB Heart failure (HF) biomarkers have dramatically impacted the way HF patients are evaluated and managed. B-type natriuretic peptide (BNP) and N-terminal proBNP (NT-proBNP) are the gold standard biomarkers in determining the diagnosis and prognosis of HF, and studies on natriuretic peptide-guided HF management look promising. An array of additional biomarkers has emerged, each reflecting different pathophysiological processes in the development and progression of HF: myocardial insult, inflammation and remodeling. Novel biomarkers, such as mid-regional pro atrial natriuretic peptide (MR-proANP), mid-regional pro adrenomedullin (MR-proADM), highly sensitive troponins, soluble ST2 (sST2), growth differentiation factor (GDF)-15 and Galectin-3, show potential in determining prognosis beyond the established natriuretic peptides, but their role in the clinical care of the patient is still partially defined and more studies are needed. This article is part of a Special Issue entitled: Heart failure pathogenesis and emerging diagnostic and therapeutic interventions. (C) 2013 Elsevier B.V. All rights reserved. C1 [Gaggin, Hanna K.; Januzzi, James L., Jr.] Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. RP Januzzi, JL (reprint author), 55 Fruit St,Yawkey 5984, Boston, MA 02114 USA. EM hgaggin@partners.org; jjanuzzi@partners.org NR 97 TC 66 Z9 73 U1 2 U2 27 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0925-4439 EI 0006-3002 J9 BBA-MOL BASIS DIS JI Biochim. Biophys. Acta-Mol. Basis Dis. PD DEC PY 2013 VL 1832 IS 12 BP 2442 EP 2450 DI 10.1016/j.bbadis.2012.12.014 PG 9 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA 260AO UT WOS:000327567600055 PM 23313577 ER PT J AU Vriend, LEM Hamer, PCD Van Noorden, CJF Wurdinger, T AF Vriend, Lianne E. M. Hamer, Philip C. De Witt Van Noorden, Cornelis J. F. Wuerdinger, Thomas TI WEE1 inhibition and genomic instability in cancer SO BIOCHIMICA ET BIOPHYSICA ACTA-REVIEWS ON CANCER LA English DT Review DE WEE1 kinase; Cancer; Genomic instability; Chromosomal instability; p53; Cell cycle checkpoint ID CHECKPOINT KINASE WEE1; DNA-DAMAGING AGENTS; CHROMOSOMAL INSTABILITY; CELL-CYCLE; TYROSINE KINASE; GENE-EXPRESSION; IONIZING-RADIATION; SPINDLE CHECKPOINT; ANTITUMOR-ACTIVITY; BUDDING YEAST AB One of the hallmarks of cancer is genomic instability controlled by cell cycle checkpoints. The G(1) and G(2) checkpoints allow DNA damage responses, whereas the mitotic checkpoint enables correct seggregation of the sister chromosomes to prevent aneuploidy. Cancer cells often lack a functional G(1) arrest and rely on G(2) arrest for DNA damage responses. WEE1 kinase is an important regulator of the G(2) checkpoint and is overexpressed in various cancer types. Inhibition of WEE1 is a promising strategy in cancer therapy in combination with DNA-damaging agents, especially when cancer cells harbor p53 mutations, as it causes mitotic catastrophy when DNA is not repaired during G(2) arrest. Cancer cell response to WEE1 inhibition monotherapy has also been demonstrated in various types of cancer, including p53 wild-type cancers. We postulate that chromosomal instability can explain tumor response to WEE1 monotherapy. Therefore, chromosomal instability may need to be taken into account when determining the most effective strategy for the use of WEE1 inhibitors in cancer therapy. (C) 2013 Elsevier B.V. All rights reserved. C1 [Vriend, Lianne E. M.; Hamer, Philip C. De Witt; Wuerdinger, Thomas] Vrije Univ Amsterdam, Med Ctr, Neurosurg Ctr Amsterdam, Amsterdam, Netherlands. [Vriend, Lianne E. M.; Hamer, Philip C. De Witt; Wuerdinger, Thomas] Vrije Univ Amsterdam, Med Ctr, Neurooncol Res Grp, Canc Ctr Amsterdam, Amsterdam, Netherlands. [Vriend, Lianne E. M.; Van Noorden, Cornelis J. F.] Univ Amsterdam, Acad Med Ctr, Dept Cell Biol & Histol, NL-1105 AZ Amsterdam, Netherlands. [Wuerdinger, Thomas] Massachusetts Gen Hosp, Dept Neurol, Mol Neurogenet Unit, Charlestown, MA USA. [Wuerdinger, Thomas] Harvard Univ, Sch Med, Charlestown, MA USA. RP Wurdinger, T (reprint author), Vrije Univ Amsterdam Med Ctr, CCA Room 3-34,De Boelelaan 1117, NL-1081 HV Amsterdam, Netherlands. EM t.wurdinger@vumc.nl RI De Witt Hamer, Philip/E-7630-2013 OI De Witt Hamer, Philip/0000-0003-2988-8544 NR 84 TC 20 Z9 20 U1 0 U2 14 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0304-419X EI 0006-3002 J9 BBA-REV CANCER JI Biochim. Biophys. Acta-Rev. Cancer PD DEC PY 2013 VL 1836 IS 2 BP 227 EP 235 DI 10.1016/j.bbcan.2013.05.002 PG 9 WC Biochemistry & Molecular Biology; Biophysics; Oncology SC Biochemistry & Molecular Biology; Biophysics; Oncology GA 280DT UT WOS:000329009600004 PM 23727417 ER PT J AU Smith, MW Giardina, TD Murphy, DR Laxmisan, A Singh, H AF Smith, Michael W. Giardina, Traber Davis Murphy, Daniel R. Laxmisan, Archana Singh, Hardeep TI Resilient actions in the diagnostic process and system performance SO BMJ QUALITY & SAFETY LA English DT Article DE Patient safety; Diagnostic errors; Medical error; measurement; epidemiology; Primary care; Quality measurement ID HEALTH-CARE; PATIENT SAFETY; CANCER-DIAGNOSIS; MISSED OPPORTUNITIES; COLORECTAL-CANCER; ADVERSE EVENTS; FOLLOW-UP; ERRORS; QUALITY; FRAMEWORK AB Objectives Systemic issues can adversely affect the diagnostic process. Many system-related barriers can be masked by resilient' actions of frontline providers (ie, actions supporting the safe delivery of care in the presence of pressures that the system cannot readily adapt to). We explored system barriers and resilient actions of primary care providers (PCPs) in the diagnostic evaluation of cancer. Methods We conducted a secondary data analysis of interviews of PCPs involved in diagnostic evaluation of 29 lung and colorectal cancer cases. Cases covered a range of diagnostic timeliness and were analysed to identify barriers for rapid diagnostic evaluation, and PCPs' actions involving elements of resilience addressing those barriers. We rated these actions according to whether they were usual or extraordinary for typical PCP work. Results Resilient actions and associated barriers were found in 59% of the cases, in all ranges of timeliness, with 40% involving actions rated as beyond typical. Most of the barriers were related to access to specialty services and coordination with patients. Many of the resilient actions involved using additional communication channels to solicit cooperation from other participants in the diagnostic process. Discussion Diagnostic evaluation of cancer involves several resilient actions by PCPs targeted at system deficiencies. PCPs' actions can sometimes mitigate system barriers to diagnosis, and thereby impact the sensitivity of downstream' measures (eg, delays) in detecting barriers. While resilient actions might enable providers to mitigate system deficiencies in the short run, they can be resource intensive and potentially unsustainable. They complement, rather than substitute for, structural remedies to improve system performance. Measures to detect and fix system performance issues targeted by these resilient actions could facilitate diagnostic safety. C1 [Smith, Michael W.; Giardina, Traber Davis; Murphy, Daniel R.; Laxmisan, Archana; Singh, Hardeep] Houston VA HSR&D Ctr Excellence, Houston, TX USA. [Smith, Michael W.; Giardina, Traber Davis; Murphy, Daniel R.; Laxmisan, Archana; Singh, Hardeep] Ctr Inquiry Improve Outpatient Safety Effect Elec, Houston, TX USA. [Smith, Michael W.; Giardina, Traber Davis; Murphy, Daniel R.; Laxmisan, Archana; Singh, Hardeep] Baylor Coll Med, Michael E DeBakey Vet Affairs Med Ctr, Dept Med, Houston, TX 77030 USA. [Smith, Michael W.; Giardina, Traber Davis; Murphy, Daniel R.; Laxmisan, Archana; Singh, Hardeep] Sect Hlth Serv Res, Houston, TX USA. RP Smith, MW (reprint author), Houston VA Med Ctr 152, 2002 Holcombe Blvd, Houston, TX 77030 USA. EM ms6@bcm.edu RI McLean, Laurence /C-7367-2014; OI Davis Giardina, Traber/0000-0002-9184-6524 FU Federal Funding Agency FX This paper was funded by the Federal Funding Agency, sponsor of K23 award. NR 61 TC 5 Z9 5 U1 4 U2 13 PU BMJ PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 2044-5415 EI 2044-5423 J9 BMJ QUAL SAF JI BMJ Qual. Saf. PD DEC PY 2013 VL 22 IS 12 BP 1006 EP 1013 DI 10.1136/bmjqs-2012-001661 PG 8 WC Health Care Sciences & Services; Health Policy & Services SC Health Care Sciences & Services GA 269NA UT WOS:000328246800009 PM 23813210 ER PT J AU Seigers, R Schagen, SB Van Tellingen, O Dietrich, J AF Seigers, R. Schagen, S. B. Van Tellingen, O. Dietrich, J. TI Chemotherapy-related cognitive dysfunction: current animal studies and future directions SO BRAIN IMAGING AND BEHAVIOR LA English DT Article DE Review; Animal; Chemotherapy; Cognition; Impairment; Cytostatic ID HIPPOCAMPAL CELL-PROLIFERATION; INDUCED OXIDATIVE STRESS; CENTRAL-NERVOUS-SYSTEM; BREAST-CANCER; MEMORY DEFICITS; IN-VIVO; INTRATHECAL METHOTREXATE; PROPHYLACTIC ACTION; ADULT NEUROGENESIS; DRUG ADRIAMYCIN AB Cognitive impairment is a potential long-term side effect of adjuvant chemotherapy that can have a major impact on the quality of life of cancer survivors. There is a growing number of preclinical studies addressing this issue, thereby extending our knowledge of the mechanisms underlying chemotherapy-induced neurotoxicity. In this review, we will summarize the recent advances and important findings presented in these studies. Emerging challenges, such as the development of neuroprotective strategies, and the role of the blood-brain barrier on cognitive impairment will be described and future directions in this field of investigation will be outlined. C1 [Seigers, R.; Schagen, S. B.] Netherlands Canc Inst, Dept Psychosocial Res & Epidemiol, Amsterdam, Netherlands. [Van Tellingen, O.] Netherlands Canc Inst, Div Mol Biol, Amsterdam, Netherlands. [Dietrich, J.] Harvard Univ, Sch Med, Dept Neurol, Massachusetts Gen Hosp,Canc Ctr,Div Neurooncol, Boston, MA 02115 USA. RP Seigers, R (reprint author), Netherlands Canc Inst, Dept Psychosocial Res & Epidemiol, Amsterdam, Netherlands. EM R.seigers@nki.nl NR 82 TC 31 Z9 32 U1 1 U2 28 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1931-7557 EI 1931-7565 J9 BRAIN IMAGING BEHAV JI Brain Imaging Behav. PD DEC PY 2013 VL 7 IS 4 SI SI BP 453 EP 459 DI 10.1007/s11682-013-9250-3 PG 7 WC Neuroimaging SC Neurosciences & Neurology GA 277XY UT WOS:000328853800006 PM 23949877 ER PT J AU Pomykala, KL Ganz, PA Bower, JE Kwan, L Castellon, SA Mallam, S Cheng, I Ahn, R Breen, EC Irwin, MR Silverman, DHS AF Pomykala, K. L. Ganz, P. A. Bower, J. E. Kwan, L. Castellon, S. A. Mallam, S. Cheng, I. Ahn, R. Breen, E. C. Irwin, M. R. Silverman, D. H. S. TI The association between pro-inflammatory cytokines, regional cerebral metabolism, and cognitive complaints following adjuvant chemotherapy for breast cancer SO BRAIN IMAGING AND BEHAVIOR LA English DT Article DE Positron emission tomography; Brain imaging; Breast cancer; Cognitive complaints; Chemotherapy; Pro-inflammatory cytokines ID LONGITUDINAL ASSESSMENT; CHEMORADIATION THERAPY; SYSTEMIC CHEMOTHERAPY; SURVIVORS; FATIGUE; DYSFUNCTION; WOMEN; DEPRESSION; SYMPTOMS; PERFORMANCE AB To examine relationships following adjuvant chemotherapy between circulating pro-inflammatory cytokines, regional cerebral metabolism, and cognitive complaints in early stage breast cancer patients. 33 breast cancer patients who had completed initial treatment (surgery, +/- radiation, 23 chemotherapy, 10 no chemotherapy) obtained resting (18)F-FDG PET/CT brain imaging at baseline and 1 year later. Pro-inflammatory cytokine markers (IL-1ra, sTNF-RII, CRP, and IL-6) and cognitive complaints were also assessed at both time points. At baseline, consistent correlations were seen between the left medial frontal and right inferior lateral anterior temporal cortices and inflammatory markers within the chemotherapy group, and not in the no chemotherapy group. After 1 year, correlations persisted in the medial frontal cortex and the temporal cortex, the latter shifting superiorly. Both of these regional correlations demonstrated the highest levels of significance when looking across the 1 year time frame (IL-1ra: peak voxel p < 0.0005; cluster size p < 0.0005, p = 0.001 after correction (medial prefrontal), p < 0.0005; cluster size p = 0.001, p = 0.029 corr. (anterior temporal), sTNF-RII: p < 0.0005; cluster size p = 0.001, p = 0.040 corr. (medial prefrontal)). Positive correlations were also seen within the chemotherapy group between baseline memory complaints and the medial frontal (p < 0.0005; cluster size p < 0.0005, p < 0.0005 corr.) and anterior temporal (p < 0.0005; cluster size p < 0.0005, p = 0.002 corr.) cortices at baseline and 1 year later. Metabolism in the medial prefrontal cortex and anterior temporal cortex was found to correlate with both memory complaints and cytokine marker levels in chemotherapy patients. C1 [Pomykala, K. L.; Mallam, S.; Cheng, I.; Ahn, R.; Silverman, D. H. S.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Mol & Med Pharmacol, Los Angeles, CA 90095 USA. [Ganz, P. A.] UCLA Fielding Sch Publ Hlth, Dept Hlth Policy & Management, Los Angeles, CA USA. [Ganz, P. A.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Med, Los Angeles, CA 90095 USA. [Ganz, P. A.; Bower, J. E.; Kwan, L.] Univ Calif Los Angeles, Jonsson Comprehens Canc Ctr, Div Canc Prevent & Control Res, Los Angeles, CA 90024 USA. [Bower, J. E.; Irwin, M. R.] Univ Calif Los Angeles, Dept Psychol, Los Angeles, CA 90024 USA. [Bower, J. E.; Breen, E. C.; Irwin, M. R.] Semel Inst Neurosci, Cousins Ctr Psychoneuroimmunol, Los Angeles, CA USA. [Castellon, S. A.] VA Greater Los Angeles Hlth Care Syst, Los Angeles, CA USA. [Castellon, S. A.; Breen, E. C.; Irwin, M. R.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Psychiat & Biobehav Sci, Los Angeles, CA 90095 USA. RP Silverman, DHS (reprint author), Univ Calif Los Angeles, David Geffen Sch Med, Dept Mol & Med Pharmacol, 200 Med Plaza,Suite B114,Mail Code 737024, Los Angeles, CA 90095 USA. EM dsilver@ucla.edu RI Irwin, Michael/H-4870-2013 OI Irwin, Michael/0000-0002-1502-8431 FU NIH/NCI [R01 CA 109650]; Breast Cancer Research Foundation [R01-AG034588, R01-AG026364, R01CA160245-01, R01-CA119159, R01HL095799, R01 DA032922-01, P30-AG028748]; UCLA CTSI [UL1TR000124]; Cousins Center for Psychoneuroimmunology FX Supported by grant NIH/NCI R01 CA 109650 and the Breast Cancer Research Foundation (PAG); R01-AG034588; R01-AG026364; R01CA160245-01; R01-CA119159; R01HL095799; R01 DA032922-01; P30-AG028748 to MRI; and UCLA CTSI UL1TR000124, the Cousins Center for Psychoneuroimmunology (MRI). NR 56 TC 23 Z9 24 U1 1 U2 11 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1931-7557 EI 1931-7565 J9 BRAIN IMAGING BEHAV JI Brain Imaging Behav. PD DEC PY 2013 VL 7 IS 4 SI SI BP 511 EP 523 DI 10.1007/s11682-013-9243-2 PG 13 WC Neuroimaging SC Neurosciences & Neurology GA 277XY UT WOS:000328853800011 PM 23835929 ER PT J AU Ercoli, LM Castellon, SA Hunter, AM Kwan, L Kahn-Mills, BA Cernin, PA Leuchter, AF Ganz, PA AF Ercoli, Linda M. Castellon, Steven A. Hunter, Aimee M. Kwan, Lorna Kahn-Mills, Barbara A. Cernin, Paul A. Leuchter, Andrew F. Ganz, Patricia A. TI Assessment of the feasibility of a rehabilitation intervention program for breast cancer survivors with cognitive complaints SO BRAIN IMAGING AND BEHAVIOR LA English DT Article DE Breast cancer; Chemotherapy; Cognitive; qEEG; Rehabilitation; Intervention ID ADJUVANT CHEMOTHERAPY; DOSE CHEMOTHERAPY; MEMORY; DYSFUNCTION; PERFORMANCE; TRIAL; MANAGEMENT; TAMOXIFEN; WORKSHOP; WOMEN AB To assess the feasibility of a cognitive rehabilitation program in breast cancer survivors (BCS) with persistent post-treatment cognitive complaints. BCS with cognitive complaints, 18-months to 5-years post-treatment, were recruited for a once-weekly, five-week, group cognitive training intervention. Outcome measures included self-reported mood and cognitive function, and neurocognitive tests administered at pre-intervention, immediate-, two-month and four-month post-intervention. A sub-study in eight participants evaluated resting state quantitative electroencephalography (qEEG) changes from pre- to immediate post-intervention in relationship to post-intervention changes in cognitive complaints. Twenty-seven BCS completed the protocol and tolerated the intervention well. We observed significant reductions in total and memory-specific cognitive complaints from pre-intervention to immediate post-intervention (p = 0.031 and p = 0.009, respectively) and at four-months post-intervention (p < 0.0001 and p < 0.001, respectively). Significant improvement in neurocognitive tests were found for Symbol Digit, Stroop, and Trails A tests (df = 26, all p's < 0.05). Effect sizes for changes from pre-intervention to immediate and to four-month post intervention ranged from 0.429 to 0.607, and from 0.439 to 0.741, respectively. Increase in qEEG absolute alpha power over the course of the intervention was associated with reduced complaints at immediate post-intervention (r = -0.78, p = 0.021), two-months (r range = -0.76 to -0.82, p-value range 0.004 to 0.03), and four-months (r = -0.71, p = 0.048). A five-week group cognitive training intervention is feasible and well tolerated. Cognitive complaints and neurocognitive test performances showed positive changes. qEEG may serve as a potential biomarker for improvement in self-reported complaints. A randomized clinical trial is underway to test the efficacy of the intervention. C1 [Ercoli, Linda M.; Hunter, Aimee M.; Cernin, Paul A.; Leuchter, Andrew F.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Psychiat & Biobehav Sci, Los Angeles, CA 90095 USA. [Ercoli, Linda M.; Hunter, Aimee M.; Cernin, Paul A.; Leuchter, Andrew F.] Univ Calif Los Angeles, David Geffen Sch Med, Semel Inst Neurosci & Human Behav, Los Angeles, CA 90095 USA. [Castellon, Steven A.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Psychol, Los Angeles, CA 90095 USA. [Castellon, Steven A.] VA Greater Los Angeles Hlth Care Syst, Dept Psychiat & Mental Hlth, Los Angeles, CA USA. [Hunter, Aimee M.; Leuchter, Andrew F.] Univ Calif Los Angeles, Semel Inst Neurosci & Human Behav, Lab Brain Behav & Pharmacol, Los Angeles, CA 90024 USA. [Hunter, Aimee M.; Leuchter, Andrew F.] Univ Calif Los Angeles, Semel Inst Neurosci & Human Behav, Depress Res & Clin Program, Los Angeles, CA 90024 USA. [Kwan, Lorna; Kahn-Mills, Barbara A.; Ganz, Patricia A.] Univ Calif Los Angeles, Jonsson Comprehens Canc Ctr, Los Angeles, CA 90024 USA. [Ganz, Patricia A.] Univ Calif Los Angeles, Sch Med, Los Angeles, CA USA. [Ganz, Patricia A.] Univ Calif Los Angeles, Sch Publ Hlth, Los Angeles, CA 90024 USA. RP Ercoli, LM (reprint author), Univ Calif Los Angeles, David Geffen Sch Med, Dept Psychiat & Biobehav Sci, Los Angeles, CA 90095 USA. EM lercoli@mednet.ucla.edu FU Breast Cancer Research Foundation; Jonsson Cancer Center Foundation FX Funding for this research was provided by the Breast Cancer Research Foundation and the Jonsson Cancer Center Foundation. We thank the participants for their contribution to this research. NR 55 TC 19 Z9 19 U1 3 U2 11 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1931-7557 EI 1931-7565 J9 BRAIN IMAGING BEHAV JI Brain Imaging Behav. PD DEC PY 2013 VL 7 IS 4 SI SI BP 543 EP 553 DI 10.1007/s11682-013-9237-0 PG 11 WC Neuroimaging SC Neurosciences & Neurology GA 277XY UT WOS:000328853800014 PM 23955490 ER PT J AU Sammon, JD Kaczmarek, BF Ravi, P Sun, M Roghmann, F Sukumar, S Ghani, K Sharma, P Karakiewicz, PI Peabody, JO Elder, JS Menon, M Trinh, QD AF Sammon, Jesse D. Kaczmarek, Bartosz F. Ravi, Praful Sun, Maxine Roghmann, Florian Sukumar, Shyam Ghani, Khurshid Sharma, Pranav Karakiewicz, Pierre I. Peabody, James O. Elder, Jack S. Menon, Mani Quoc-Dien Trinh TI Effect of metastatic site on emergency department disposition in men with metastatic prostate cancer SO CANADIAN JOURNAL OF UROLOGY LA English DT Article DE prostate cancer; metastasis; emergency department; admission disposition ID IMPROVING PRIMARY-CARE; UNITED-STATES; RADICAL PROSTATECTOMY; BONE METASTASES; CHRONIC ILLNESS; SURVIVAL RATES; RISK; PATTERNS; TRENDS; STATISTICS AB Introduction: Though the prevalence of metastatic prostate cancer is decreasing, the rate of admission from the emergency department (ED) is increasing. Little is known about the implications of metastatic site on a patient's ED course and admission. Materials and methods: A weighted estimate of 15,367 patients with metastatic prostate cancer who presented to the ED between January 1, 2006 and December 31, 2009 was abstracted from the United States Nationwide Emergency Department Sample (NEDS). Descriptive statistics were used to elaborate patient and hospital characteristics of the metastatic prostate cancer population and logistic regression models were fitted to identify predictors of admission. Results: The most common site of metastasis in patients with metastatic prostate cancer presenting to the ED was bone (80.6%), followed by liver (13.2%), lung (9.3) and other genitourinary sites (8.1%). Over the study period, there was an increase in prevalence of the four commonest metastatic sites, and admission rates varied between metastatic sites (83.2% for bone to 95.2% for nodal metastasis). Substantial variability in the rate of inpatient mortality was noted. Increasing age, Northeast region, increased comorbidity burden, and the presence of nodal metastases and other urinary metastases were shown to be independent predictors of hospital admission. Conclusions: The commonest metastatic site in patients presenting to United States EDs with metastatic prostate cancer between 2006 and 2009 was bone. Patients presenting with nodal metastases were most likely to be admitted. Independent predictors of hospitalization included age, Northeast region, increased comorbidities, nodal metastases and other urinary metastases. C1 [Sammon, Jesse D.; Kaczmarek, Bartosz F.; Ravi, Praful; Sukumar, Shyam; Ghani, Khurshid; Sharma, Pranav; Peabody, James O.; Elder, Jack S.; Menon, Mani; Quoc-Dien Trinh] Henry Ford Hlth Syst, Vattikuti Urol Inst, Detroit, MI 48202 USA. [Sammon, Jesse D.; Kaczmarek, Bartosz F.; Sukumar, Shyam; Ghani, Khurshid; Sharma, Pranav; Quoc-Dien Trinh] Henry Ford Hlth Syst, VUI Ctr Outcomes Res Analyt & Evaluat, Detroit, MI 48202 USA. [Sun, Maxine; Roghmann, Florian; Karakiewicz, Pierre I.] Univ Montreal, Ctr Hlth, Canc Prognost & Hlth Outcomes Unit, Montreal, PQ, Canada. [Quoc-Dien Trinh] Harvard Univ, Sch Med, Dana Farber Canc Inst, Brigham & Womens Hosp,Div Urol Surg, Boston, MA 02115 USA. [Quoc-Dien Trinh] Harvard Univ, Sch Med, Dana Farber Canc Inst, Brigham & Womens Hosp,Ctr Surg & Publ Hlth, Boston, MA 02115 USA. RP Sammon, JD (reprint author), Henry Ford Hlth Syst, Vattikuti Urol Inst, 2799 W Grand Blvd, Detroit, MI 48202 USA. NR 22 TC 3 Z9 3 U1 1 U2 4 PU CANADIAN J UROLOGY PI ST LAURENT PA 2330 WARD ST, STE 604, ST LAURENT, QUEBEC H4M 2V6, CANADA SN 1195-9479 J9 CAN J UROL JI Can. J. Urol. PD DEC PY 2013 VL 20 IS 6 BP 7008 EP 7014 PG 7 WC Urology & Nephrology SC Urology & Nephrology GA 275ZG UT WOS:000328717300003 PM 24331341 ER PT J AU Leung, CP Klausner, AP Habibi, JR King, AB Feldman, AS AF Leung, Cynthia P. Klausner, Adam P. Habibi, Joseph R. King, Ashley B. Feldman, Adam S. TI Audience response system: a new learning tool for urologic conferences SO CANADIAN JOURNAL OF UROLOGY LA English DT Article DE urology; audience research; medical education; conferences ID ATTITUDES; RESIDENTS; EDUCATION AB Introduction: Audience response systems (ARS) have not been used to gauge knowledge transfer and retention in the setting of large medical conferences. In this study, we explore the utility of an ARS as an educational tool in the setting of a large urology conference. Materials and methods: At the 2011 joint meeting of the Mid-Atlantic and New England sections of the American Urological Association, conference attendees were able to use a web-based and cell-phone accessed ARS. At the meeting, six ARS questions were asked during five point-counterpoint debate topics covering areas of prostate cancer, incontinence, pediatrics, stone disease, and renal cancer. Questions were presented by expert representatives from each of the sections; questions were structured as management options for predefined cases. At the beginning and end of each 15-minute session, attendees were asked to use the ARS to select the best management option. Results: In five out of the six questions (83%) more than 10% of responses were changed following the presentation of the point-counterpoint session and a > 25% change in response was noted in two out of the six questions (33%). A statistically significant change was noted for one question relating to management of urolithiasis in pregnancy (p = 0.037). Conclusions: This is the first study which demonstrates the potential utility of an ARS in a large urology conference. With fitrther research it may be possible to use this technology to identify high-yield topics for medical education and improve outcomes during lecture-based educational activities. C1 [Leung, Cynthia P.; Klausner, Adam P.; Habibi, Joseph R.; King, Ashley B.] Virginia Commonwealth Univ, Sch Med, Dept Surg, Div Urol, Richmond, VA 23298 USA. [Feldman, Adam S.] Massachusetts Gen Hosp, Dept Urol, Boston, MA 02114 USA. RP Klausner, AP (reprint author), Virginia Commonwealth Univ, Sch Med, Dept Surg, Div Urol, POB 980118, Richmond, VA 23298 USA. NR 11 TC 2 Z9 2 U1 0 U2 3 PU CANADIAN J UROLOGY PI ST LAURENT PA 2330 WARD ST, STE 604, ST LAURENT, QUEBEC H4M 2V6, CANADA SN 1195-9479 J9 CAN J UROL JI Can. J. Urol. PD DEC PY 2013 VL 20 IS 6 BP 7042 EP 7045 PG 4 WC Urology & Nephrology SC Urology & Nephrology GA 275ZG UT WOS:000328717300008 PM 24331346 ER PT J AU Wiener, RS Slatore, CG AF Wiener, Renda Soylemez Slatore, Christopher G. TI Framing Discussions About CT Scan Screening for Lung Cancer So That Patients See the Whole Picture SO CHEST LA English DT Editorial Material ID WORKS C1 [Wiener, Renda Soylemez] Boston Univ, Sch Med, Ctr Pulm, Boston, MA 02118 USA. [Wiener, Renda Soylemez] Edith Nourse Rogers Mem Vet Hosp, Ctr Healthcare Org & Implementat Res, Bedford, MA USA. [Wiener, Renda Soylemez] Dartmouth Inst Hlth Policy & Clin Practice, Hanover, NH USA. [Slatore, Christopher G.] Portland VA Med Ctr, Portland, OR USA. [Slatore, Christopher G.] Portland VA Med Ctr, Sect Pulm & Crit Care Med, Portland, OR USA. [Slatore, Christopher G.] Oregon Hlth & Sci Univ, Dept Med, Div Pulm & Crit Care Med, Portland, OR 97201 USA. RP Wiener, RS (reprint author), Boston Univ, Sch Med, Ctr Pulm, 72 E Concord St,R-304, Boston, MA 02118 USA. EM rwiener@bu.edu OI Wiener, Renda/0000-0001-7712-2135; Slatore, Christopher/0000-0003-0958-8122 FU NCI NIH HHS [K07 CA138772] NR 12 TC 1 Z9 1 U1 0 U2 1 PU AMER COLL CHEST PHYSICIANS PI NORTHBROOK PA 3300 DUNDEE ROAD, NORTHBROOK, IL 60062-2348 USA SN 0012-3692 J9 CHEST JI Chest PD DEC PY 2013 VL 144 IS 6 BP 1749 EP 1750 DI 10.1378/chest.13-1521 PG 3 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 272IU UT WOS:000328454500004 PM 24297116 ER PT J AU Almeida, FA Casal, RF Jimenez, CA Eapen, GA Uzbeck, M Sarkiss, M Rice, D Morice, RC Ost, DE AF Almeida, Francisco A. Casal, Roberto F. Jimenez, Carlos A. Eapen, George A. Uzbeck, Mateen Sarkiss, Mona Rice, David Morice, Rodolfo C. Ost, David E. TI Quality Gaps and Comparative Effectiveness in Lung Cancer Staging The Impact of Test Sequencing on Outcomes SO CHEST LA English DT Article ID TRANSBRONCHIAL NEEDLE ASPIRATION; POSITRON-EMISSION-TOMOGRAPHY; CLINICAL-PRACTICE GUIDELINES; SOLITARY PULMONARY NODULE; ENDOSCOPIC ULTRASOUND; CONTROLLED-TRIAL; MEDIASTINOSCOPY; BRONCHOSCOPY; DIAGNOSIS; REGISTRY AB Background: Evidence-based guidelines recommend mediastinal sampling as the first invasive test in patients with suspected lung cancer and mediastinal adenopathy. The goal of this study was to assess practice patterns and outcomes of diagnostic strategies in this patient population. Methods: We conducted a retrospective analysis of all patients in 2009 who had mediastinal adenopathy without distant metastatic disease to determine whether guideline-consistent care was delivered. Guideline-consistent care was defined as mediastinal lymph node sampling being performed as part of the first invasive procedure. Results: One hundred thirty-seven patients were included. Guideline-consistent care was provided in 30 cases (22%). Patients receiving guideline-consistent care had fewer invasive tests than patients with guideline-inconsistent care (1.3 +/- 0.5 tests/patient vs 2.3 +/- 0.5 tests/patient, respectively; P<.0001) and fewer complications (0 of 30, 0% vs 18 of 108, 17%; P=.01). Most of the complications (16 of 18) were related to CT image-guided needle biopsy. Endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) was sufficient to guide treatment decisions without any other invasive tests in 88 patients (64%). Although not all the complications and costs due to CT image-guided biopsies could have been avoided, roughly two-thirds could have been eliminated by just changing the testing sequence. Conclusion: Quality gaps in lung cancer staging in patients with mediastinal adenopathy are common and lead to unnecessary testing and increased complications. In patients with suspected lung cancer without distant metastatic disease with mediastinal adenopathy, EBUS-TBNA should be the first test. C1 [Almeida, Francisco A.] Cleveland Clin, Dept Pulm Allergy & Crit Care Med, Cleveland, OH 44106 USA. [Casal, Roberto F.] Baylor Coll Med, Michael E DeBakey Vet Affairs Med Ctr, Dept Pulm & Crit Care Med, Houston, TX 77030 USA. [Jimenez, Carlos A.; Eapen, George A.; Morice, Rodolfo C.; Ost, David E.] Univ Texas MD Anderson Canc Ctr, Dept Pulm Med, Houston, TX 77030 USA. [Sarkiss, Mona] Univ Texas MD Anderson Canc Ctr, Dept Anesthesia, Houston, TX 77030 USA. [Rice, David] Univ Texas MD Anderson Canc Ctr, Dept Thorac Surg, Houston, TX 77030 USA. [Uzbeck, Mateen] Our Lady Lourdes & Beaumont Hosp, Dept Pulm Med, Dublin, Ireland. RP Ost, DE (reprint author), Univ Texas MD Anderson Canc Ctr, Dept Pulm Med, Unit 1462,1515 Holcombe Blvd, Houston, TX 77030 USA. EM dost@mdanderson.org OI Ost, David/0000-0001-6351-5552 FU Olympus Corporation FX The authors have reported to CHEST the following conflicts of interest: In the last 3 years, Dr Eapen has received unrestricted educational grants from the Olympus Corporation and has provided consulting services to the Pentax Ricoch Imaging Co, Ltd. Dr Rice is a consultant to Olympus Corporation and teaches courses on EBUS. Drs Almeida, Casal, Jimenez, Uzbeck, Sarkiss, Morice, and Ost have reported that no potential conflicts of interest exist with any companies/organizations whose products or services may be discussed in this article. NR 34 TC 17 Z9 17 U1 0 U2 13 PU AMER COLL CHEST PHYSICIANS PI NORTHBROOK PA 3300 DUNDEE ROAD, NORTHBROOK, IL 60062-2348 USA SN 0012-3692 J9 CHEST JI Chest PD DEC PY 2013 VL 144 IS 6 BP 1776 EP 1782 DI 10.1378/chest.12-3046 PG 7 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 272IU UT WOS:000328454500011 PM 23703671 ER PT J AU Tanner, NT Egede, LE Shamblin, C Gebregziabher, M Silvestri, GA AF Tanner, Nichole T. Egede, Leonard E. Shamblin, Clayton Gebregziabher, Mulugeta Silvestri, Gerard A. TI Attitudes and Beliefs Toward Lung Cancer Screening Among US Veterans SO CHEST LA English DT Article ID SMOKERS; SYSTEM; TRIAL AB Background: Lung cancer (LC) is the leading cause of cancer-related death for veterans cared for by the US Veterans Health Administration. The LC burden among veterans is almost double that of the general population. Before implementation of an LC screening program, we set out to assess the role of beliefs and attitudes toward LC screening among veterans. Methods: Veterans presenting to the Ralph H. Johnson VA Medical Center were invited to complete a self-administered survey. The survey comprised questions about demographics, smoking status, health status, and knowledge about LC and willingness to be screened. Responses from veteran ever and never smokers were compared. Results: A total of 209 veterans completed the survey. Smokers were significantly (P<.05) more likely than never smokers to be less educated, have a lower income, and report poorer health. Smokers were more likely than never smokers to have two or more comorbidities, which trended toward significance (P=.062). Smokers were more likely to have been told by a physician that they were at high risk for LC and to believe that they were at risk. Nearly all veterans surveyed (92.8%) would have a CT scan for LC screening, and 92.4% would have surgery for a screen-detected LC. Conclusions: Veterans are overwhelmingly willing to undergo screening for LC, and it seems that participation will not be a barrier to implementation of an LC screening program. The mortality benefit of LC screening, however, may not be generalizable to the veteran population because of a higher number of comorbid conditions. C1 [Tanner, Nichole T.; Shamblin, Clayton; Silvestri, Gerard A.] Med Univ S Carolina, Div Pulm & Crit Care Allergy & Sleep Med, Charleston, SC 29425 USA. [Egede, Leonard E.] Med Univ S Carolina, Dept Internal Med, Div Internal Med & Geriatr, Charleston, SC 29425 USA. [Egede, Leonard E.] Med Univ S Carolina, Ctr Hlth Dispar Res, Charleston, SC 29425 USA. [Gebregziabher, Mulugeta] Med Univ S Carolina, Dept Biostat Bioinformat & Epidemiol, Charleston, SC 29425 USA. [Tanner, Nichole T.; Egede, Leonard E.] Ralph H Johnson VA Med Ctr, Charleston VA Res Enhancement Award Program, Ctr Dis Prevent & Hlth Intervent Diverse Populat, Charleston, SC USA. RP Tanner, NT (reprint author), Med Univ S Carolina, Div Pulm & Crit Care Allergy & Sleep Med, 96 Jonathan Lucas St,Ste 812 CSB, Charleston, SC 29425 USA. EM tripici@musc.edu OI Gebregziabher, Mulugeta/0000-0002-4826-481X FU National Institutes of Health (NIH) [1K24CA12049-01A1]; South Carolina Clinical and Translational Research Institute Bio-medical Informatics Services [NIH 1UL1RR029882] FX This study was supported by grants from the National Institutes of Health (NIH) [1K24CA12049-01A1] and South Carolina Clinical and Translational Research Institute Bio-medical Informatics Services [NIH 1UL1RR029882]. NR 17 TC 10 Z9 10 U1 0 U2 6 PU AMER COLL CHEST PHYSICIANS PI NORTHBROOK PA 3300 DUNDEE ROAD, NORTHBROOK, IL 60062-2348 USA SN 0012-3692 J9 CHEST JI Chest PD DEC PY 2013 VL 144 IS 6 BP 1783 EP 1787 DI 10.1378/chest.13-0056 PG 5 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 272IU UT WOS:000328454500012 PM 23764896 ER PT J AU Chan, MM Chan, MM Mengshol, JA Fish, DN Chan, ED AF Chan, Mallory M. Chan, Michael M. Mengshol, John Andrew Fish, Douglas N. Chan, Edward D. TI Octreotide A Drug Often Used in the Critical Care Setting but Not Well Understood SO CHEST LA English DT Review ID TYPE-1 HEPATORENAL-SYNDROME; SULFONYLUREA-INDUCED HYPOGLYCEMIA; PLACEBO-CONTROLLED TRIAL; CIRRHOTIC-PATIENTS; SOMATOSTATIN RECEPTORS; NEUROENDOCRINE TUMORS; VARICEAL HEMORRHAGE; DOUBLE-BLIND; POSTOPERATIVE CHYLOTHORAX; ENDOSCOPIC TREATMENT AB While the canonical function of somatostatin (SST) is to inhibit the secretion of growth hormone, it has a number of other physiologic effects that are less widely appreciated. Octreotide, an analog of SST, is not uncommonly used in the critical care setting, particularly for the treatment of variceal hemorrhage. Herein, we discuss the biology and pharmacology of SST, octreotide, and other SST analogs. We also review the evidence behind their use in esophageal variceal bleeds, hepatorenal syndrome, hypoglycemia due to sulfonylurea poisoning, and chylous pleural effusions. C1 Univ Colorado, Sch Med, Denver, CO USA. [Fish, Douglas N.] Univ Colorado, Skaggs Sch Pharm & Pharmaceut Sci, Aurora, CO USA. [Mengshol, John Andrew] Univ Colorado Anschutz Med Campus, Div Gastroenterol, Aurora, CO USA. Univ Colorado Anschutz Med Campus, Div Pulm Sci & Crit Care Med, Aurora, CO USA. [Mengshol, John Andrew] Denver Vet Affairs Med Ctr, Dept Med, Denver, CO USA. Natl Jewish Hlth, Dept Med, Denver, CO 80206 USA. Natl Jewish Hlth, Dept Acad Affairs, Denver, CO 80206 USA. RP Chan, ED (reprint author), Natl Jewish Hlth, D509 Neustadt Bldg,1400 Jackson St, Denver, CO 80206 USA. EM chane@njhealth.org NR 75 TC 3 Z9 4 U1 1 U2 5 PU AMER COLL CHEST PHYSICIANS PI GLENVIEW PA 2595 PATRIOT BLVD, GLENVIEW, IL 60026 USA SN 0012-3692 J9 CHEST JI Chest PD DEC PY 2013 VL 144 IS 6 BP 1937 EP 1945 DI 10.1378/chest.13-0382 PG 9 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 272IU UT WOS:000328454500032 PM 24297127 ER PT J AU Balboni, MJ AF Balboni, Michael J. TI A Theological Assessment of Spiritual Assessments SO CHRISTIAN BIOETHICS LA English DT Article DE medicine; pluralism; religion; spiritual assessment; spiritual care; spirituality ID QUALITY-OF-LIFE; ADVANCED CANCER-PATIENTS; MEDICAL-CARE; END; ASSOCIATIONS; RELIGION; SUPPORT; NEEDS; PHYSICIANS; PROVISION AB Spiritual care within secular, pluralistic health care settings cannot be separated from particular theological claims. This claim is based on four arguments: (1) Practical-clinical questions concerning the role of spirituality and religion in healthcare are laden theological debates. (2) All spiritual assessments, including narrative-based methods and functional assessment tools, have embedded theological norms that fail to solve pluralism. (3) Future models of spiritual assessment and care can be constructively developed based on a correlation between contemporary health care settings and substantive Christian approaches. (4) Questions about how to practically provide spiritual care must also include theological evaluation of secular medicine. Consequently, spiritual assessment requires particular, tradition-mediated understandings. Future spiritual care models must simultaneously balance the irreducible pluralism of health care, the inescapable particularity of the theological traditions guiding our institutions and social systems, and the overwhelming spiritual needs experienced by patients facing life-threatening illness. C1 [Balboni, Michael J.] Harvard Univ, Sch Med, Boston, MA USA. RP Balboni, MJ (reprint author), Dana Farber Canc Inst, Dept Psychosocial Oncol & Palliat Care, 450 Brookline Ave,Dana 1101, Boston, MA 02215 USA. EM Michael_Balboni@dfci.harvard.edu NR 44 TC 2 Z9 2 U1 2 U2 5 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1380-3603 EI 1744-4195 J9 CHRIST BIOET JI Christ. Bioet. PD DEC PY 2013 VL 19 IS 3 BP 313 EP 331 DI 10.1093/cb/cbt023 PG 19 WC Philosophy; Religion SC Philosophy; Religion GA 271DM UT WOS:000328371200006 ER PT J AU Acha, MR Milan, D AF Acha, Moshe Rav Milan, David TI Who Should Receive the Subcutaneous Implanted Defibrillator? Timing Is Not Right to Replace the Transvenous Implantable Cardioverter Defibrillator SO CIRCULATION-ARRHYTHMIA AND ELECTROPHYSIOLOGY LA English DT Article DE defibrillators; implantable ID VENTRICULAR ELECTROGRAM AMPLITUDE; RX-II TRIAL; HEART-FAILURE; CARDIAC-RESYNCHRONIZATION; PRIMARY PREVENTION; RISK-FACTORS; ICD; MORTALITY; THERAPY; INTERVENTIONS C1 [Acha, Moshe Rav; Milan, David] Massachusetts Gen Hosp, Cardiac Arrhythmia Serv, Charlestown, MA 02129 USA. RP Milan, D (reprint author), Massachusetts Gen Hosp, Cardiac Arrhythmia Serv, 149 13th St,CVRC 4th Floor, Charlestown, MA 02129 USA. EM dmilan@partners.org NR 28 TC 4 Z9 4 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1941-3149 EI 1941-3084 J9 CIRC-ARRHYTHMIA ELEC JI Circ.-Arrhythmia Electrophysiol. PD DEC PY 2013 VL 6 IS 6 BP 1246 EP 1251 DI 10.1161/CIRCEP.113.000445 PG 6 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 273HN UT WOS:000328526000039 ER PT J AU Anderson, CD Rosand, J AF Anderson, Christopher D. Rosand, Jonathan TI Genome-Wide Linkage Approach Yields Novel Early Onset Myocardial Infarction Locus in East Asians SO CIRCULATION-CARDIOVASCULAR GENETICS LA English DT Editorial Material DE Editorials; genetic linkage; genetics; humans; myocardial infarction ID CORONARY-ARTERY-DISEASE; COMPLEX DISEASES; HERITABILITY; ASSOCIATION; VARIANTS; MUTATION; GENETICS; STROKE; MEF2A; RISK C1 Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA. Massachusetts Gen Hosp, Div Neurocrit Care & Emergency Neurol, Boston, MA 02114 USA. RP Anderson, CD (reprint author), Ctr Human Genet Res, 185 Cambridge St,CZPN 6818, Boston, MA 02114 USA. EM cdanderson@partners.org OI Anderson, Christopher/0000-0002-0053-2002 NR 16 TC 1 Z9 1 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1942-3268 J9 CIRC-CARDIOVASC GENE JI Circ.-Cardiovasc. Genet. PD DEC PY 2013 VL 6 IS 6 BP 531 EP 532 DI 10.1161/CIRCGENETICS.113.000378 PG 2 WC Cardiac & Cardiovascular Systems; Genetics & Heredity SC Cardiovascular System & Cardiology; Genetics & Heredity GA 274TR UT WOS:000328629600003 PM 24347618 ER PT J AU Elmariah, S Palacios, IF McAndrew, T Hueter, I Inglessis, I Baker, JN Kodali, S Leon, MB Svensson, L Pibarot, P Douglas, PS Fearon, WF Kirtane, AJ Maniar, HS Passeri, JJ AF Elmariah, Sammy Palacios, Igor F. McAndrew, Thomas Hueter, Irene Inglessis, Ignacio Baker, Joshua N. Kodali, Susheel Leon, Martin B. Svensson, Lars Pibarot, Philippe Douglas, Pamela S. Fearon, William F. Kirtane, Ajay J. Maniar, Hersh S. Passeri, Jonathan J. CA PARTNER Investigators TI Outcomes of Transcatheter and Surgical Aortic Valve Replacement in High-Risk Patients With Aortic Stenosis and Left Ventricular Dysfunction Results From the Placement of Aortic Transcatheter Valves (PARTNER) Trial (Cohort A) SO CIRCULATION-CARDIOVASCULAR INTERVENTIONS LA English DT Article DE aortic valve replacement; heart failure; surgery; transcatheter aortic valve implantation; ventricular dysfunction; left ID EJECTION FRACTION; SYSTOLIC FUNCTION; CARDIAC-SURGERY; HEART-FAILURE; LOW-GRADIENT; IMPLANTATION; ECHOCARDIOGRAPHY; RECOMMENDATIONS; MORTALITY; SURVIVAL AB Background The Placement of Aortic Transcatheter Valves (PARTNER) trial demonstrated similar survival after transcatheter and surgical aortic valve replacement (TAVR and SAVR, respectively) in high-risk patients with symptomatic, severe aortic stenosis. The aim of this study was to evaluate the effect of left ventricular (LV) dysfunction on clinical outcomes after TAVR and SAVR and the impact of aortic valve replacement technique on LV function. Methods and Results The PARTNER trial randomized high-risk patients with severe aortic stenosis to TAVR or SAVR. Patients were stratified by the presence of LV ejection fraction (LVEF) <50%. All-cause mortality was similar for TAVR and SAVR at 30-days and 1 year regardless of baseline LV function and valve replacement technique. In patients with LV dysfunction, mean LVEF increased from 35.78.5% to 48.611.3% (P<0.0001) 1 year after TAVR and from 38.0 +/- 8.0% to 50.1 +/- 10.8% after SAVR (P<0.0001). Higher baseline LVEF (odds ratio, 0.90 [95% confidence interval, 0.86, 0.95]; P<0.0001) and previous permanent pacemaker (odds ratio, 0.34 [95% confidence interval, 0.15, 0.81]) were independently associated with reduced likelihood of 10% absolute LVEF improvement by 30 days; higher mean aortic valve gradient was associated with increased odds of LVEF improvement (odds ratio, 1.04 per 1 mmHg [95% confidence interval, 1.01, 1.08]). Failure to improve LVEF by 30 days was associated with adverse 1-year outcomes after TAVR but not SAVR. Conclusions In high-risk patients with severe aortic stenosis and LV dysfunction, mortality rates and LV functional recovery were comparable between valve replacement techniques. TAVR is a feasible alternative for patients with symptomatic severe aortic stenosis and LV dysfunction who are at high risk for SAVR. Clinical Trial Registration URL: http://www.clinicaltrials.gov. Unique identifier: NCT00530894. C1 [Elmariah, Sammy; Palacios, Igor F.; Inglessis, Ignacio; Baker, Joshua N.; Passeri, Jonathan J.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Cardiol,Dept Med, Boston, MA USA. [Elmariah, Sammy] Harvard Clin Res Inst, Boston, MA USA. [McAndrew, Thomas; Hueter, Irene; Kodali, Susheel; Leon, Martin B.; Kirtane, Ajay J.] Columbia Univ, Med Ctr, New York Presbyterian Hosp, New York, NY 10027 USA. [Svensson, Lars] Cleveland Clin, Dept Cardiovasc Med, Cleveland, OH USA. [Pibarot, Philippe] Univ Laval, Quebec Heart & Lung Inst, Quebec City, PQ, Canada. [Douglas, Pamela S.] Duke Univ, Med Ctr, Duke Clin Res Inst, Durham, NC USA. [Fearon, William F.] Stanford Univ, Sch Med, Div Cardiovasc Med, Stanford, CA 94305 USA. [Maniar, Hersh S.] Washington Univ, Div Cardiothorac Surg, St Louis, MO USA. RP Elmariah, S (reprint author), Massachusetts Gen Hosp, 55 Fruit St,YAW 5D, Boston, MA 02114 USA. EM elmariah@gmail.com; jpasseri@partners.org FU Edwards Lifesciences, Inc. FX The Placement of Aortic Transcatheter Valves (PARTNER) trial was supported by Edwards Lifesciences, Inc. NR 26 TC 31 Z9 32 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1941-7640 EI 1941-7632 J9 CIRC-CARDIOVASC INTE JI Circ.-Cardiovasc. Interv. PD DEC PY 2013 VL 6 IS 6 BP 604 EP 614 DI 10.1161/CIRCINTERVENTIONS.113.000650 PG 11 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 273CM UT WOS:000328511300007 PM 24221391 ER PT J AU Miceli, T Lilleby, K Noonan, K Kurtin, S Faiman, B Mangan, PA AF Miceli, Teresa Lilleby, Kathryn Noonan, Kimberly Kurtin, Sandra Faiman, Beth Mangan, Patricia A. TI Autologous Hematopoietic Stem Cell Transplantation for Patients With Multiple Myeloma: An Overview for Nurses in Community Practice SO CLINICAL JOURNAL OF ONCOLOGY NURSING LA English DT Article ID SURVIVORSHIP CARE PLAN; QUALITY-OF-LIFE; BONE-MARROW-TRANSPLANTATION; LEADERSHIP BOARD; CONSENSUS STATEMENTS; GUIDELINES; THERAPY; LENALIDOMIDE; MAINTENANCE; RECIPIENTS AB Autologous hematopoietic stem cell transplantation (AHSCT) is approved for the treatment of select solid tumors, autoimmune disorders, and most hematologic malignancies. Multiple myeloma (MM) is the most common indication for AHSCT. Despite improvement in response and survival rates in the era of novel agents, AHSCT remains an important treatment option for patients with MM who are eligible. Clinical management of patients with MM requires a multidisciplinary approach that incorporates healthcare professionals in a number of clinical settings as well as caregivers and the patient. Patients about to undergo AHSCT are generally referred to tertiary care centers that specialize in ASCT. Pre- and post-transplantation treatments and long-term follow-up often are managed by a community-based referring oncologist in collaboration with the transplantation team. Oncology nurses play an integral role in the care of patients with MM in each clinical setting. This article aims to provide non-transplantation oncology nurses with guidelines for education, clinical management, and support of patients with MM undergoing AHSCT with a primary focus on the pre- and post-transplantation period. C1 [Miceli, Teresa] Mayo Clin, William von Liebig Transplant Ctr, Coll Med, Rochester, MN USA. [Lilleby, Kathryn] Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA. [Noonan, Kimberly] Dana Farber Canc Inst, Boston, MA 02115 USA. [Kurtin, Sandra] Univ Arizona, Ctr Canc, Div Hematol Oncol, Tucson, AZ USA. [Faiman, Beth] Cleveland Clin, Taussig Canc Ctr, Cleveland, OH USA. [Mangan, Patricia A.] Univ Penn, Abramson Canc Ctr, Dept Hematol Malignancies, Philadelphia, PA 19104 USA. [Mangan, Patricia A.] Univ Penn, Abramson Canc Ctr, Bone Marrow & Stem Cell Transplant Programs, Philadelphia, PA 19104 USA. RP Miceli, T (reprint author), Mayo Clin, William von Liebig Transplant Ctr, Coll Med, Rochester, MN USA. EM miceli.teresa@mayo.edu FU Sanofi Oncology FX Teresa Miceli, RN, BSN, OCN (R), is a bone marrow transplantation nurse coordinator and assistant professor of nursing in the College of Medicine in the William von Liebig Transplant Center at the Mayo Clinic in Rochester, MN; Kathryn Lilleby, RN, is a clinical research nurse at the Fred Hutchinson Cancer Research Center in Seattle, WA; Kimberly Noonan, RN, ANP-BC, is an adult nurse practitioner at the Dana-Farber Cancer Institute in Boston, MA; Sandra Kurtin, RN, MS, AOCN (R), ANP-C, is a nurse practitioner and clinical assistant professor of medicine in the Hematology/Oncology Division of the University of Arizona Cancer Center in Tucson; Beth Faiman, MSN, APRN-BC, AOCN, is a nurse practitioner in the Taussig Cancer Center at the Cleveland Clinic in Ohio; and Patricia A. Mangan, MSN, APRN-BC is a nurse lead in the Department of Hematologic Malignancies and Bone Marrow and Stem Cell Transplant Programs in the Abramson Cancer Center at the University of Pennsylvania in Philadelphia. The authors received editorial support from Alita Anderson, MD, with Eubio Medical Communications, and Joyce Divine, PhD, with ScienceFirst LLC, in preparation of this article supported by Sanofi Oncology. The authors are fully responsible for content and editorial decisions about this article. Kurtin is a consultant for Celgene Corporation, Novartis Pharmaceuticals, Millennium: The Takeda Oncology Company, and Onyx Pharmaceuticals. Mangan has received honoraria from Celgene Corporation, Millennium:The Takeda Oncology Company, Onyx Pharmaceuticals, and Sanofi-Aventis. Miceli, Lilleby, Noonan, and Faiman have no financial relationships to disclose. The content of this article has been reviewed by independent peer reviewers to ensure that it is balanced, objective, and free from commercial bias. No financial relationships relevant to the content of this article have been disclosed by the independent peer reviewers or editorial staff. Miceli can be reached at miceli.teresa@mayo.edu, with copy to editor at CJONEditor@ons.org. (Submitted July 2013. Revision submitted September 2013. Accepted for publication September 8, 2013.) NR 73 TC 3 Z9 3 U1 1 U2 5 PU ONCOLOGY NURSING SOC PI PITTSBURGH PA 125 ENTERPRISE DR, PITTSBURGH, PA 15275 USA SN 1092-1095 EI 1538-067X J9 CLIN J ONCOL NURS JI Clin. J. Oncol. Nurs. PD DEC PY 2013 VL 17 IS 6 SU S BP 13 EP 24 DI 10.1188/13.CJON.S2.13-24 PG 12 WC Oncology; Nursing SC Oncology; Nursing GA 277DR UT WOS:000328799600002 PM 24280455 ER PT J AU Faiman, B Miceli, T Noonan, K Lilleby, K AF Faiman, Beth Miceli, Teresa Noonan, Kimberly Lilleby, Kathryn TI Clinical Updates in Blood and Marrow Transplantation in Multiple Myeloma SO CLINICAL JOURNAL OF ONCOLOGY NURSING LA English DT Article ID STEM-CELL TRANSPLANTATION; VERSUS-HOST-DISEASE; HIGH-DOSE MELPHALAN; PLUS G-CSF; CONSENSUS STATEMENT; MOBILIZATION; PLERIXAFOR; THERAPY; BORTEZOMIB; LYMPHOMA AB The process of hematopoietic stem cell transplantation (HSCT) is well defined, yet debate remains surrounding the role and timing of HSCT in patients with multiple myeloma (MM). Since the 1980s, survival advances have been made with the use of newer agents by recognizing the role of transplantation, identifying the anticipated side effects at each phase, and improving supportive care strategies. Data support transplantation as part of the treatment strategy, but the optimal induction regimen and timing of transplantation have yet to be defined. The general consensus is that eligible patients should undergo autologous HSCT at some point in the treatment spectrum, preferably earlier rather than later in the disease. Allogeneic transplantation is only recommended in the context of a clinical trial and in patients with high-risk disease. The transplantation process can be overwhelming for patients and caregivers. Nurses play a key role in improving outcomes by caring for patients and families throughout the transplantation experience and, therefore, need to be knowledgeable about the process. This article is intended to expand discussion on the role of nurses in assisting patients and families undergoing transplantation to include an overview of the acute care phase of the transplantation process. C1 [Faiman, Beth] Cleveland Clin, Taussig Canc Ctr, Cleveland, OH USA. [Miceli, Teresa] Mayo Clin, William von Liebig Transplant Ctr, Coll Med, Rochester, MN USA. [Noonan, Kimberly] Dana Farber Canc Inst, Boston, MA 02115 USA. [Lilleby, Kathryn] Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA. RP Faiman, B (reprint author), Cleveland Clin, Taussig Canc Ctr, Cleveland, OH USA. EM faimanb@ccf.org FU Sanofi Oncology FX The authors received editorial support from Alita Anderson, MD, with Eubio Medical Communications, in preparation of this article supported by Sanofi Oncology. NR 58 TC 2 Z9 2 U1 0 U2 1 PU ONCOLOGY NURSING SOC PI PITTSBURGH PA 125 ENTERPRISE DR, PITTSBURGH, PA 15275 USA SN 1092-1095 EI 1538-067X J9 CLIN J ONCOL NURS JI Clin. J. Oncol. Nurs. PD DEC PY 2013 VL 17 IS 6 SU S BP 33 EP 41 DI 10.1188/13.CJON.S2.33-41 PG 9 WC Oncology; Nursing SC Oncology; Nursing GA 277DR UT WOS:000328799600004 PM 24280457 ER PT J AU Abramovitch, A Abramowitz, JS Mittelman, A AF Abramovitch, Amitai Abramowitz, Jonathan S. Mittelman, Andrew TI The neuropsychology of adult obsessive-compulsive disorder: A meta-analysis SO CLINICAL PSYCHOLOGY REVIEW LA English DT Article DE Executive functions; Memory; Neuropsychological; Obsessive-compulsive disorder; OCD; Meta-analyses ID COGNITIVE DEFICITS; SYMPTOM DIMENSIONS; EXECUTIVE FUNCTION; NEUROCOGNITIVE ENDOPHENOTYPES; MEMORY IMPAIRMENT; BRAIN ACTIVATION; NONVERBAL MEMORY; TEST-PERFORMANCE; PANIC DISORDER; OCD AB A vast and heterogeneous body of literature on the neuropsychology of obsessive-compulsive disorder (OCD) has accumulated in recent decades, yielding inconsistent results. In an attempt to quantitatively summarize the literature, we conducted a meta-analysis of 115 studies (including 3452 patients), comparing adult OCD patients with healthy controls on tests of 10 neuropsychological domains. Across studies, medium mean effect sizes were found for all executive function subdomains, processing speed, and sustained attention. Small effect sizes were found for visuospatial abilities and working memory. A large effect size was found for non-verbal memory whereas a small effect size was found for verbal memory, where only the former was found to be associated with impairments in executive functions. Moderators of effect sizes were also investigated. Results are discussed in terms of their clinical significance as well as their implications for current neurobiological models of OCD and methodological caveats. (C) 2013 Elsevier Ltd. All rights reserved. C1 [Abramovitch, Amitai] Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA. [Abramovitch, Amitai; Mittelman, Andrew] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. [Abramowitz, Jonathan S.] Univ N Carolina, Dept Psychol, Chapel Hill, NC USA. RP Abramovitch, A (reprint author), Massachusetts Gen Hosp, Dept Psychiat, 185 Cambridge St,Suite 2000, Boston, MA 02114 USA. EM aabramovitch@partners.org RI Abramovitch, Amitai/I-3333-2012 OI Abramovitch, Amitai/0000-0001-9640-0970 NR 71 TC 66 Z9 67 U1 6 U2 42 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0272-7358 EI 1873-7811 J9 CLIN PSYCHOL REV JI Clin. Psychol. Rev. PD DEC PY 2013 VL 33 IS 8 BP 1163 EP 1171 DI 10.1016/j.cpr.2013.09.004 PG 9 WC Psychology, Clinical SC Psychology GA 272DH UT WOS:000328440000019 PM 24128603 ER PT J AU Barry, MJ Andriole, GL Culkin, DJ Fox, SH Jones, KM Carlyle, MH Wilt, TJ AF Barry, Michael J. Andriole, Gerald L. Culkin, Daniel J. Fox, Steven H. Jones, Karen M. Carlyle, Maureen H. Wilt, Timothy J. TI Ascertaining cause of death among men in the Prostate Cancer Intervention Versus Observation Trial SO CLINICAL TRIALS LA English DT Article ID COMPARING RADICAL PROSTATECTOMY; FOLLOW-UP; MORTALITY AB Background The Prostate Cancer Intervention Versus Observation Trial (PIVOT) randomized 731 men with localized prostate cancer to radical prostatectomy or observation. Purpose We describe the methods and results for cause-of-death assignments in PIVOT, and compare them to alternative strategies for ascertaining prostate cancer-specific mortality, as well as to the methods and results in the similar Scandinavian Prostate Cancer Group Study 4 (SPCG-4) trial. Methods Three PIVOT Endpoints Committee members, blinded to randomized treatment assignments, reviewed medical records and death certificates when available to assign a cause of death using a primary and a secondary adjudication question. Initial disagreements were resolved through discussion. The level of initial agreement among committee members was examined, as well as guesses at randomized treatment assignments for a convenience sample of cases. Final cause of death determinations were compared to death certificates. Results Complete agreement on cause of death by all three committee members before any discussion was achieved in 200/354 (56%) cases on the primary and 209/354 (59%) cases on the secondary. However, complete agreement on the primary rose to 306/354 (86%) when definite' and probably' categories were collapsed, as planned a priori. The three committee members' proportions of correct guesses of randomized treatment assignment were 82/121 (68%), 113/148 (76%), and 99/134 (74%). Using the committee's final adjudications as a gold standard, death certificates had suboptimal sensitivities, specificities, or predictive values depending on how they were used to determine cause of death. Limitations There was no separate gold standard' by which to judge the accuracy of the final endpoints committee adjudications, and useful death certificates could not be obtained on about a third of PIVOT participants who died. Conclusions The low level of initial agreement on cause of death among endpoint committee members and the potential for biased determinations due to partial unblinding to treatment assignment raise methodologic concerns about using prostate cancer mortality as an endpoint in clinical trials like PIVOT. C1 [Barry, Michael J.] Massachusetts Gen Hosp, Div Gen Med, Boston, MA 02114 USA. [Andriole, Gerald L.] Washington Univ, Sch Med, Div Urol Surg, St Louis, MO 63110 USA. [Culkin, Daniel J.] Univ Oklahoma, Hlth Sci Ctr, Dept Urol, Oklahoma City, OK USA. [Fox, Steven H.] Agcy Healthcare Res & Qual, Rockville, MD USA. [Jones, Karen M.] Cooperat Studies Coordinating Ctr, Dept Vet Affairs Med Ctr, Perry Point, MD USA. [Carlyle, Maureen H.; Wilt, Timothy J.] Minneapolis VA Ctr Chron Dis Outcomes Res, Minneapolis, MN USA. RP Barry, MJ (reprint author), Massachusetts Gen Hosp, Div Gen Med, 50 Staniford St,9th Floor, Boston, MA 02114 USA. EM mbarry@partners.org FU Department of Veterans Affairs Cooperative Studies Program [CSP-407]; Agency for Healthcare Research and Quality FX This work was supported by the Department of Veterans Affairs Cooperative Studies Program (CSP-407), with participation from the National Cancer Institute (Protocol number NCI-T94-0131O), and the Agency for Healthcare Research and Quality. Supplemental funding specifically for the analyses in this article was provided by the Agency for Healthcare Research and Quality. NR 15 TC 8 Z9 8 U1 0 U2 2 PU SAGE PUBLICATIONS LTD PI LONDON PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND SN 1740-7745 EI 1740-7753 J9 CLIN TRIALS JI Clin. Trials PD DEC PY 2013 VL 10 IS 6 BP 907 EP 914 DI 10.1177/1740774513498008 PG 8 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 275LB UT WOS:000328676700009 PM 23988464 ER PT J AU Moore, JG Ross, SM Williams, BA AF Moore, Jeffrey G. Ross, Scott M. Williams, Brian A. TI Regional anesthesia and ambulatory surgery SO CURRENT OPINION IN ANESTHESIOLOGY LA English DT Article DE ambulatory anesthesia; healthcare economics; nerve block; postoperative nausea and vomiting; regional anesthesia ID PERIPHERAL-NERVE BLOCKS; RANDOMIZED CONTROLLED-TRIAL; ABDOMINIS PLANE BLOCK; OUTPATIENT KNEE ARTHROSCOPY; ELIMINATING POSTOPERATIVE NAUSEA; CRUCIATE LIGAMENT RECONSTRUCTION; THORACIC PARAVERTEBRAL BLOCK; MINIDOSE LIDOCAINE-FENTANYL; OFF-PATENT ANTIEMETICS; RECTUS SHEATH BLOCK AB Purpose of reviewAdvances in surgery and anesthesia have allowed for more surgeries to be done on an outpatient basis. A recent important advance entails availability of suitable recovery criteria to capitalize on the benefits of regional anesthesia for ambulatory surgery. With ever-escalating healthcare costs and expectations for faster recovery, anesthesiologists are now challenged to design anesthesia plans focused on Phase I postanesthesia care unit bypass and early facility discharge. Satisfying the recently published WAKE Score criteria upon operating room exit is associated with hospital cost reductions. This review highlights regional anesthesia techniques with focus on outpatient orthopedics. We also discuss multimodalities' addressing postoperative nausea and vomiting prophylaxis, perioperative analgesia (including perineural analgesia), and sedation-hypnosis, which are all central to timely recovery using now-available suitable recovery criteria.Recent findingsUltrasound-guided regional anesthesia has increased the comfort level for many anesthesiologists performing blocks. Other advances include better monitoring of anesthetic depth for titration of sedatives, en route to avoiding emetogenic and hyperalgesic volatile anesthetics.SummaryRoutine regional anesthesia use, multimodal postoperative nausea and vomiting prophylaxis, multimodal sedation-hypnosis, and multimodal analgesia, along with avoiding volatile agents and short-duration opioids, can lead to both routine Phase 1 postanesthesia care unit bypass and expedited same-day discharge, when using suitable recovery criteria. C1 [Moore, Jeffrey G.; Ross, Scott M.; Williams, Brian A.] Univ Pittsburgh, Sch Med, Dept Anesthesiol, Pittsburgh, PA 15240 USA. RP Williams, BA (reprint author), Univ Pittsburgh, Sch Med, Dept Anesthesiol, VA Pittsburgh Hlth Syst, Pittsburgh, PA 15240 USA. EM williamsba@anes.upmc.edu FU National Institutes of Health [K01DA025146]; Department of Defense [PRORP OR090012] FX Departmental resources were used for the underwriting of professional effort in the preparation of this article. Drs. J.G.M. and S.M.R. have no potential conflicts of interest to disclose. Dr B.A.W. was funded by the National Institutes of Health (2008-2010 K01DA025146, 'Peripheral Nerve Blocks with Multimodal Analgesics'). At the time of article submission, Dr B.A.W. was funded by the Department of Defense (2010-2013 PRORP OR090012, 'Enhancing Post-Traumatic Pain Relief with Alternative Perineural Drugs'). NR 86 TC 4 Z9 5 U1 0 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0952-7907 EI 1473-6500 J9 CURR OPIN ANESTHESIO JI Curr. Opin. Anesthesiol. PD DEC PY 2013 VL 26 IS 6 BP 652 EP 660 DI 10.1097/ACO.0000000000000011 PG 9 WC Anesthesiology SC Anesthesiology GA 268EW UT WOS:000328153000003 PM 24113264 ER PT J AU Dohlman, LE AF Dohlman, Lena E. TI Anesthesia education across borders SO CURRENT OPINION IN ANESTHESIOLOGY LA English DT Article DE anesthesia education; anesthesia safety; developing world; global health programs ID GLOBAL HEALTH; WORLD; CARE; INFRASTRUCTURE; EXPERIENCES; ROTATIONS; TRAINEES; SYSTEMS; NEEDS AB Purpose of reviewChanging attitudes toward global health are affecting medical education programs at all levels in the sUSA and abroad. This review describes some of these changes, and how these affect the educational aspects of US global health programs and anesthesia training in developing countries.Recent findingsInterest in global health has surged in the past decade, and support for programs has increased in medical schools, university hospitals and from the US government. Recognition of the surgical burden of disease as a global public health problem has been slow but is also increasing. Anesthesia involvement in building healthcare education infrastructure and workforce in low-resource countries is needed and important, and benefits can be had on both sides of the border.SummaryThe past 5 years have brought a new global focus on workforce development and education in anesthesia. Programs need to be supported by all stakeholders and monitored for safety, quality and outcomes. C1 [Dohlman, Lena E.] Harvard Univ, Sch Med, Dept Anesthesia, Massachusetts Gen Hosp, Boston, MA 02115 USA. RP Dohlman, LE (reprint author), MGH, Dept Anesthesia Crit Care & Pain Management, 55 Fruit St, Boston, MA 02114 USA. EM Ldohlman@partners.org NR 31 TC 0 Z9 0 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0952-7907 EI 1473-6500 J9 CURR OPIN ANESTHESIO JI Curr. Opin. Anesthesiol. PD DEC PY 2013 VL 26 IS 6 BP 732 EP 736 DI 10.1097/ACO.0000000000000013 PG 5 WC Anesthesiology SC Anesthesiology GA 268EW UT WOS:000328153000015 PM 24113269 ER PT J AU Kline, JA Hernandez, J Hogg, MM Jones, AE Courtney, DM Kabrhel, C Nordenholz, KE Diercks, DB Rondina, MT Klinger, JR AF Kline, Jeffrey A. Hernandez, Jackeline Hogg, Melanie M. Jones, Alan E. Courtney, D. Mark Kabrhel, Christopher Nordenholz, Kristen E. Diercks, Deborah B. Rondina, Matthew T. Klinger, James R. TI Rationale and methodology for a multicentre randomised trial of fibrinolysis for pulmonary embolism that includes quality of life outcomes SO EMERGENCY MEDICINE AUSTRALASIA LA English DT Article DE controlled trial; fibrinolysis; indemnification; methodology; thrombolysis; venous thromboembolism ID 6-MINUTE WALK TEST; ACUTE MYOCARDIAL-INFARCTION; RIGHT-VENTRICULAR DYSFUNCTION; DEEP VENOUS THROMBOSIS; THROMBOLYTIC THERAPY; BOLUS TENECTEPLASE; NORMOTENSIVE PATIENTS; EMERGENCY-DEPARTMENT; QUESTIONNAIRE; MANAGEMENT AB BackgroundSubmassive pulmonary embolism (PE) has a low mortality rate but can degrade functional capacity. ObjectiveThe present study aims to provide rationale, methodology, and initial findings of a multicentre, randomised trial of fibrinolysis for PE that used a composite end-point, including quality of life measures. MethodsThis investigator-initiated study was funded by a contract between a corporate partner and the investigator's hospital (the prime site). The investigator was the Food and Drug Administration (FDA) sponsor. The prime site subcontracted, indemnified, and trained consortia members. Consenting, normotensive patients with PE and right ventricular strain (by echocardiography or biomarkers) received low-molecular-weight heparin and random assignment to a single bolus of tenecteplase or placebo in double-blinded fashion. The outcomes were: (i) in-hospital rate of intubation, vasopressor support, and major haemorrhage, or (ii) at 90 days, death, recurrent PE, or composite that defined poor quality of life (echocardiography, 6min walk test and surveys). The planned sample size was n = 200. ResultsEight sites enrolled 87 patients over 5 years. The ratio of patients screened for each enrolled was 7.4 to 1, equating to 11h screening time per patient enrolled. Primary barrier to enrolment was the cost of screening. Two patients died (2.5%, 95%CI [0-8%]), one developed shock, but 18 (22%, 95%CI: [13-30%]) had a poor quality of life. ConclusionsAn investigator-initiated, FDA-regulated, multicentre trial of fibrinolysis for submassive PE was conducted, but was limited by screening costs and a low mortality rate. Quality of life measurements might represent a more important patient-centred end-point. C1 [Kline, Jeffrey A.] Indiana Univ Sch Med, Dept Emergency Med, Indianapolis, IN 46202 USA. [Kline, Jeffrey A.] Indiana Univ Sch Med, Dept Cellular & Integrat Physiol, Indianapolis, IN 46202 USA. [Hernandez, Jackeline; Hogg, Melanie M.] Carolinas Med Ctr, Dept Emergency Med, Charlotte, NC 28203 USA. [Jones, Alan E.] Univ Mississippi, Med Ctr, Dept Emergency Med, Jackson, MS 39216 USA. [Courtney, D. Mark] Northwestern Univ, Dept Emergency Med, Feinberg Sch Med, Chicago, IL 60611 USA. [Kabrhel, Christopher] Massachusetts Gen Hosp, Dept Emergency Med, Boston, MA 02114 USA. [Nordenholz, Kristen E.] Univ Colorado, Dept Emergency Med, Sch Med Aurora, Boulder, CO 80309 USA. [Diercks, Deborah B.] Univ Calif Davis, Dept Emergency Med, Sacramento, CA 95817 USA. [Rondina, Matthew T.] Univ Utah, Dept Internal Med, Salt Lake City, UT 84112 USA. [Klinger, James R.] Brown Univ, Sch Med, Dept Internal Med, Providence, RI 02912 USA. RP Kline, JA (reprint author), Indiana Univ Sch Med, Dept Emergency Med, Regenstrief R2200,1050 Wishard Blvd, Indianapolis, IN 46202 USA. EM jefkline@iupui.edu OI Kabrhel, Christopher/0000-0002-8699-7176 FU Genentech, Inc. FX The present study was funded by an investigator-initiated grant from Genentech, Inc. NR 51 TC 5 Z9 5 U1 1 U2 8 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1742-6731 EI 1742-6723 J9 EMERG MED AUSTRALAS JI Emerg. Med. Australas. PD DEC PY 2013 VL 25 IS 6 BP 515 EP 526 DI 10.1111/1742-6723.12159 PG 12 WC Emergency Medicine SC Emergency Medicine GA 266CN UT WOS:000328000000006 PM 24224521 ER PT J AU Fehling, M Nelson, BD Venkatapuram, S AF Fehling, Maya Nelson, Brett D. Venkatapuram, Sridhar TI Limitations of the Millennium Development Goals: a literature review SO GLOBAL PUBLIC HEALTH LA English DT Article DE Millennium Development Goals (MDG); post-2015; public health policy; development ID SUB-SAHARAN AFRICA; REPRODUCTIVE HEALTH; POVERTY REDUCTION; HUMAN-RIGHTS; FASTER PROGRESS; EDUCATION; MDGS; AGENDA; POST-2015; TARGETS AB With the Millennium Development Goals (MDGs) showing uneven progress, this review identifies possible limitations arising from the MDG framework itself rather than extrinsic issues. A multidisciplinary literature review was conducted with a focus on limitations in the formulation of the MDGs, their structure, content and implementation. Of 1837 MDG-related articles, 90 met criteria for analysis. Articles describe MDGs as being created by only a few stakeholders without adequate involvement by developing countries and overlooking development objectives previously agreed upon. Others claim MDGs are unachievable and simplistic, not adapted to national needs, do not specify accountable parties and reinforce vertical interventions. While MDGs have promoted increased health and well-being in many countries by recognising and deliberating on the possible constraints of the MDG framework, the post-2015 agenda may have even greater impact. C1 [Fehling, Maya] Univ Med Berlin, Charite, Inst Trop Med & Int Hlth, Berlin, Germany. [Nelson, Brett D.] Massachusetts Gen Hosp, Dept Pediat, Boston, MA 02114 USA. [Nelson, Brett D.] Massachusetts Gen Hosp, Dept Emergency Med, Boston, MA 02114 USA. [Nelson, Brett D.] Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. [Venkatapuram, Sridhar] Kings Coll London, Dept Social Sci Hlth & Med, London WC2R 2LS, England. [Venkatapuram, Sridhar] Univ Cambridge, Dept Sociol, Cambridge, England. RP Fehling, M (reprint author), Univ Med Berlin, Charite, Inst Trop Med & Int Hlth, Berlin, Germany. EM maya.fehling@gmail.com OI Nelson, Brett/0000-0002-5049-1798; Venkatapuram, Sridhar/0000-0003-3076-0783 FU Wellcome Trust NR 67 TC 25 Z9 25 U1 4 U2 32 PU ROUTLEDGE JOURNALS, TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXFORDSHIRE, ENGLAND SN 1744-1692 EI 1744-1706 J9 GLOB PUBLIC HEALTH JI Glob. Public Health PD DEC 1 PY 2013 VL 8 IS 10 BP 1109 EP 1122 DI 10.1080/17441692.2013.845676 PG 14 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 269LS UT WOS:000328243400002 PM 24266508 ER PT J AU Ganmaa, D Rich-Edwards, JW Frazier, LA Davaalkham, D Oyunbileg, G Janes, C Potischman, N Hoover, R Troisi, R AF Ganmaa, Davaasambuu Rich-Edwards, Janet W. Frazier, Lindsay A. Davaalkham, Dambadarjaa Oyunbileg, Gankhuyag Janes, Craig Potischman, Nancy Hoover, Robert Troisi, Rebecca TI A comparison of migrants to, and women born in, urban Mongolia: demographic, reproductive, anthropometric and lifestyle characteristics SO INTERNATIONAL HEALTH LA English DT Article DE Lifestyle; Reproductive factors; Diet; Non-communicable diseases; Mongolia; Asia ID CONSUMPTION; POPULATION; DISEASES; CHINA; RISK; DIET AB Mongolia has experienced vast migration from rural to urban areas since the 1950s. We hypothesized that women migrating to Ulaanbaatar, the capital, would differ in factors related to future chronic disease risk compared with women who were born in Ulaanbaatar. Premenopausal mothers (aged 44 years) of children attending two schools (one in the city centre and one in the outskirts) in Ulaanbaatar were recruited for the study. During April and May 2009, 420 women were interviewed about migration, reproductive history and lifestyle factors and anthropometric measurements were taken. Women born in (n178) and outside (n242) Ulaanbaatar were similar in education and marital status, but the latter appeared to have a more traditional lifestyle including being more likely to have lived as a nomadic herder (22.3 vs 5.6; p0.001) and to currently live in a traditional yurt or ger (40.1 vs 29.2). Ever-use of hormonal contraception was more common in women born outside Ulaanbaatar (52.1 vs 38.2; p0.005) and their age at first live birth was older (26.0 vs 20.8 for 25 vs 25 years). Although the number of pregnancies was similar, the number of live births was greater for those born outside Ulaanbaatar (p0.002). Women born in Ulaanbaatar were more likely to have smoked cigarettes (24.7 vs 11.2; p0.001). Women born outside Ulaanbaatar were more likely to consume the traditional meat and dairy diet. Rural migrants to Mongolias capital have retained a traditional lifestyle in some, but not all, respects. Internal migrant populations may provide the opportunity to assess the effect of changes in isolated risk factors for subsequent chronic disease. C1 [Ganmaa, Davaasambuu] Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA. [Ganmaa, Davaasambuu; Rich-Edwards, Janet W.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Connors Ctr Womens Hlth & Gender Biol, Boston, MA 02115 USA. [Ganmaa, Davaasambuu; Rich-Edwards, Janet W.; Frazier, Lindsay A.] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. [Frazier, Lindsay A.] Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. [Frazier, Lindsay A.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Channing Lab,Dept Med, Boston, MA 02115 USA. [Davaalkham, Dambadarjaa; Oyunbileg, Gankhuyag] Univ Mongolia, Ulaanbaatar, Mongol Peo Rep. [Janes, Craig] Simon Fraser Univ, Fac Hlth Sci, Burnaby, BC V5A 1S6, Canada. [Potischman, Nancy] NCI, Div Canc Control & Populat Sci, US Dept HHS, Bethesda, MD 20892 USA. [Hoover, Robert; Troisi, Rebecca] NCI, Div Canc Epidemiol & Genet, US Dept HHS, Bethesda, MD 20892 USA. RP Ganmaa, D (reprint author), Harvard Univ, Sch Publ Hlth, Dept Nutr, 665 Huntington Ave,Bldg 2,Room 341B, Boston, MA 02115 USA. EM gdavaasa@hsph.harvard.edu FU National Cancer Institute, National Institutes of Health, Bethesda, MD, USA FX This work was supported by a contract from the National Cancer Institute, National Institutes of Health, Bethesda, MD, USA. NR 17 TC 3 Z9 3 U1 2 U2 10 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1876-3413 EI 1876-3405 J9 INT HEALTH JI Int. Health PD DEC PY 2013 VL 5 IS 4 BP 244 EP 250 DI 10.1093/inthealth/iht020 PG 7 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 271BH UT WOS:000328364800002 PM 24021762 ER PT J AU Singh, AK Prasad, KN Prasad, A Tripathi, M Gupta, RK Husain, N AF Singh, Aloukick K. Prasad, Kashi N. Prasad, Amit Tripathi, Mukesh Gupta, Rakesh K. Husain, Nuzhat TI Immune responses to viable and degenerative metacestodes of Taenia solium in naturally infected swine SO INTERNATIONAL JOURNAL FOR PARASITOLOGY LA English DT Article DE Neurocysticercosis; Immune response; Taenia solium cyst ID PORCINE CYSTICERCOSIS; MURINE CYSTICERCOSIS; TRYPANOSOMA-CRUZI; TH2 PROFILE; NORTH-INDIA; NEUROCYSTICERCOSIS; IDENTIFICATION; CYTOKINE; HISTOPATHOLOGY; HETEROGENEITY AB Neurocysticercosis, caused by the larvae of the pork tapeworm Taenia solium, is the most common helminth infection of the CNS in humans worldwide. There is no existing animal model of neurocysticercosis that resembles human infection. To overcome this limitation, swine (the natural intermediate host of the parasite) may be a suitable model. The immune response associated with different stages of the parasite larva (metacestode) has not yet been explored. Therefore, we investigated the immune response to various stages of the metacestode (cyst) in the brain and muscles of naturally infected swine. Swine with neurocysticercosis (n = 10) and healthy controls (n = 10), as confirmed by magnetic resonance imaging, were included in this study. The animals were sacrificed, and the tissues containing viable or degenerative metacestods in the brain and infected muscles were collected and subjected to reverse transcriptase-PCR and ELISA to determine the expression of different cytokines (IFN-gamma, TNF-alpha, IL-1 beta, IL-2, IL-4 IL-6, IL-8 and IL-10). Higher expression of IL-10 was found to be associated with viable cysts. Degenerating cysts displayed significantly increased levels of IFN-gamma, TNF-alpha, IL-1 beta, IL-2, IL-6 and IL-8, whereas calcified cysts had elevated levels of IL-4, IL-10, TNF-alpha and IL-6. The present study indicated a strong regulatory (IL-10) and Th1 cytokine response in viable and degenerating cysts, respectively, whereas calcified cysts had a mixed anti-inflammatory (IL-4), regulatory (IL-10) and pro-inflammatory (TNF-alpha and IL-6) response. Thus, Th1 and Th2 immune response operate in the vicinity of metacestodes and the type of immune response may be responsible for disease severity. (C) 2013 Australian Society for Parasitology Inc. Published by Elsevier Ltd. All rights reserved. C1 [Singh, Aloukick K.; Prasad, Kashi N.; Prasad, Amit] Sanjay Gandhi Postgrad Inst Med Sci, Dept Microbiol, Lucknow 226014, Uttar Pradesh, India. [Tripathi, Mukesh] Sanjay Gandhi Postgrad Inst Med Sci, Dept Anaesthesiol, Lucknow 226014, Uttar Pradesh, India. [Gupta, Rakesh K.] Sanjay Gandhi Postgrad Inst Med Sci, Dept Radiodiag, Lucknow 226014, Uttar Pradesh, India. [Husain, Nuzhat] Dr Ram Manohar Lohia Inst Med Sci, Dept Pathol, Lucknow 226010, Uttar Pradesh, India. [Prasad, Amit] Massachusetts Gen Hosp, Ctr Immunol & Inflammatory Dis, Div Rheumatol Allergy & Immunol, Charlestown, MA 02129 USA. [Prasad, Amit] Harvard Univ, Sch Med, Charlestown, MA 02129 USA. RP Prasad, KN (reprint author), Sanjay Gandhi Postgrad Inst Med Sci, Dept Microbiol, Lucknow 226014, Uttar Pradesh, India. EM knprasad@sgpgi.ac.in FU Department of Science and Technology, Government of India, New Delhi [SR/SO/HS-21/2008] FX The study was supported by Grant SR/SO/HS-21/2008 from the Department of Science and Technology, Government of India, New Delhi. NR 48 TC 7 Z9 8 U1 0 U2 17 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0020-7519 EI 1879-0135 J9 INT J PARASITOL JI Int. J. Parasit. PD DEC PY 2013 VL 43 IS 14 BP 1101 EP 1107 DI 10.1016/j.ijpara.2013.07.009 PG 7 WC Parasitology SC Parasitology GA 278YB UT WOS:000328924700002 PM 24184156 ER PT J AU McCaffery, JM Papandonatos, GD Huggins, GS Peter, I Kahn, SE Knowler, WC Hudnall, GE Lipkin, EW Kitabchi, AE Wagenknecht, LE Wing, RR AF McCaffery, J. M. Papandonatos, G. D. Huggins, G. S. Peter, I. Kahn, S. E. Knowler, W. C. Hudnall, G. E. Lipkin, E. W. Kitabchi, A. E. Wagenknecht, L. E. Wing, R. R. CA Genetic Subgrp Look AHEAD Look AHEAD Res Grp TI FTO predicts weight regain in the Look AHEAD clinical trial SO INTERNATIONAL JOURNAL OF OBESITY LA English DT Article DE type 2 diabetes; weight loss; diet; genetics ID GENOME-WIDE ASSOCIATION; DIABETES PREVENTION PROGRAM; LIFE-STYLE INTERVENTION; OBESITY-RELATED TRAITS; REDUCES ENERGY-INTAKE; BODY-MASS INDEX; NEUROTROPHIC FACTOR; ADULT OBESITY; CHILDHOOD OBESITY; RISK-FACTORS AB BACKGROUND: Genome-wide association studies have provided new insights into the genetic factors that contribute to the development of obesity. We hypothesized that these genetic markers would also predict magnitude of weight loss and weight regain after initial weight loss. METHODS: Established obesity risk alleles available on the Illumina CARe iSelect (IBC) chip were characterized in 3899 overweight or obese participants with type 2 diabetes from the Look AHEAD (Action for Health in Diabetes), a randomized trial to determine the effects of intensive lifestyle intervention (ILI) and diabetes support and education (DSE) on cardiovascular morbidity and mortality. Primary analyses examined the interaction between 13 obesity risk polymorphisms in eight genes and randomized treatment arm in predicting weight change at year 1, and weight regain at year 4 among individuals who lost 3% or more of their baseline weight by year 1. RESULTS: No single-nucleotide polymorphisms (SNPs) were significantly associated with magnitude of weight loss or interacted with treatment arm at year 1. However, fat mass and obesity associated gene (FTO) rs3751812 predicted weight regain within DSE (1.56 kg per risk allele, P = 0.005), but not ILI (P = 0.761), resulting in SNP x treatment arm interaction (P = 0.009). In a partial replication of prior research, the obesity risk (G) allele at BDNF rs6265 was associated with greater weight regain across treatment arms (0.773 kg per risk allele), although results were of borderline statistical significance (P = 0.051). CONCLUSIONS: Variations in the FTO and BDNF loci may contribute risk of weight regain after weight loss. C1 [McCaffery, J. M.; Wing, R. R.] Miriam Hosp, Dept Psychiat & Human Behav, Weight Control & Diabet Res Ctr, Providence, RI 02903 USA. [McCaffery, J. M.; Wing, R. R.] Brown Med Sch, Providence, RI USA. [Papandonatos, G. D.] Brown Univ, Ctr Stat Sci, Providence, RI 02912 USA. [Huggins, G. S.] Tufts Med Ctr, Mol Cardiol Res Inst, MCRI Ctr Translat Genom, Boston, MA USA. [Peter, I.] Mt Sinai Sch Med, Dept Genet & Genom Sci, New York, NY USA. [Kahn, S. E.; Kitabchi, A. E.] Univ Washington, Dept Med, Div Metab Endocrinol & Nutr, VA Puget Sound Hlth Care Syst, Seattle, WA 98195 USA. [Knowler, W. C.] Natl Inst Diabet & Digest & Kidney Dis, Phoenix, AZ USA. [Hudnall, G. E.] Baylor Coll Med, Houston, TX 77030 USA. [Hudnall, G. E.] Michael E DeBakey VA Med Ctr, Houston, TX USA. [Lipkin, E. W.] Univ Tennessee, Ctr Hlth Sci, Div Endocrinol Diabet & Metab, Memphis, TN 38163 USA. [Wagenknecht, L. E.] Wake Forest Univ, Bowman Gray Sch Med, Dept Publ Hlth Sci, Winston Salem, NC 27103 USA. RP McCaffery, JM (reprint author), Miriam Hosp, Dept Psychiat & Human Behav, Weight Control & Diabet Res Ctr, 196 Richmond St, Providence, RI 02903 USA. EM jeanne_mccaffery@brown.edu RI Papandonatos, George/J-2328-2014; OI Papandonatos, George/0000-0001-6770-932X; Kahn, Steven/0000-0001-7307-9002 FU Department of Health and Human Services through National Institutes of Health [DK57136, DK57149, DK56990, DK57177, DK57171, DK57151, DK57182, DK57131, DK57002, DK57078, DK57154, DK57178, DK57219, DK57008, DK57135, DK56992]; National Institute of Diabetes and Digestive and Kidney Diseases; National Heart, Lung and Blood Institute; National Institute of Nursing Research; National Center on Minority Health and Health Disparities; Office of Research on Women's Health; Centers for Disease Control and Prevention; Johns Hopkins Medical Institutions Bayview General Clinical Research Center [M01RR02719]; Massachusetts General Hospital Mallinckrodt General Clinical Research Center [M01RR01066]; University of Colorado Health Sciences Center General Clinical Research Center [M01RR00051]; Clinical and Nutrition Research Unit [P30 DK48520]; University of Tennessee at Memphis General Clinical Research Center [M01RR0021140]; University of Pittsburgh General Clinical Research Center [M01RR000056 44]; NIH [DK 046204, DK072497]; VA Puget Sound Health Care System and Department of Veterans Affairs; Frederic C Bartter General Clinical Research Center [M01RR01346]; Training Program in Cardiovascular Research (NIH) [5T32HL069770] FX We acknowledge the Look AHEAD sites that participated in this ancillary study. This study is supported by the Department of Health and Human Services through the following cooperative agreements from the National Institutes of Health: DK57136, DK57149, DK56990, DK57177, DK57171, DK57151, DK57182, DK57131, DK57002, DK57078, DK57154, DK57178, DK57219, DK57008, DK57135 and DK56992. The following federal agencies have contributed support: National Institute of Diabetes and Digestive and Kidney Diseases; National Heart, Lung and Blood Institute; National Institute of Nursing Research; National Center on Minority Health and Health Disparities; Office of Research on Women's Health; and the Centers for Disease Control and Prevention. Additional support was received from The Johns Hopkins Medical Institutions Bayview General Clinical Research Center (M01RR02719); the Massachusetts General Hospital Mallinckrodt General Clinical Research Center (M01RR01066); the University of Colorado Health Sciences Center General Clinical Research Center (M01RR00051) Clinical and Nutrition Research Unit (P30 DK48520); the University of Tennessee at Memphis General Clinical Research Center (M01RR0021140); the University of Pittsburgh General Clinical Research Center (M01RR000056 44) and NIH grants (DK 046204 and DK072497); and VA Puget Sound Health Care System and Department of Veterans Affairs; Frederic C Bartter General Clinical Research Center (M01RR01346). AKH was supported by the Training Program in Cardiovascular Research (NIH, 5T32HL069770). The following organizations have committed to make major contributions to Look AHEAD: Federal Express; Health Management Resources; Johnson & Johnson, LifeScan Inc.; Optifast-Novartis Nutrition; Roche Pharmaceuticals; Ross Product Division of Abbott Laboratories; Slim-Fast Foods Company; and Unilever. NR 38 TC 12 Z9 12 U1 0 U2 14 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0307-0565 EI 1476-5497 J9 INT J OBESITY JI Int. J. Obes. PD DEC PY 2013 VL 37 IS 12 BP 1545 EP 1552 DI 10.1038/ijo.2013.54 PG 8 WC Endocrinology & Metabolism; Nutrition & Dietetics SC Endocrinology & Metabolism; Nutrition & Dietetics GA 272JJ UT WOS:000328456200005 PM 23628854 ER PT J AU Ahmad, NN Pfalzer, A Kaplan, LM AF Ahmad, N. N. Pfalzer, A. Kaplan, L. M. TI Roux-en-Y gastric bypass normalizes the blunted postprandial bile acid excursion associated with obesity SO INTERNATIONAL JOURNAL OF OBESITY LA English DT Article DE bariatric surgery; energy expenditure; metabolomics; postprandial bile acids; TGR5; FXR ID GLUCAGON-LIKE PEPTIDE-1; BROWN ADIPOSE-TISSUE; ENERGY-EXPENDITURE; WEIGHT-LOSS; NUCLEAR RECEPTOR; BARIATRIC SURGERY; GLUCOSE-TOLERANCE; HUMANS; SERUM; IDENTIFICATION AB BACKGROUND: Bile acids (BAs) are nutrient-responsive hormones that modulate energy balance through cell surface and nuclear receptors. Postprandial plasma BAs have been found to be decreased in obesity. OBJECTIVE: We aimed to determine whether meal-stimulated circulating BA levels are altered by Roux-en-Y gastric bypass (RYGB), an operation that modifies the neurohumoral determinants of food intake and energy expenditure to cause significant and durable weight loss. DESIGN: Longitudinal study measuring fasting and postprandial plasma BAs before and after RYGB. SUBJECTS: Five obese surgical patients and eight lean controls underwent frequent blood sampling after a standard liquid meal. Obese subjects were also tested at 1, 4 and 40 weeks after RYGB. Primary and secondary circulating BAs, as well as their glycine and taurine conjugates, were measured via reverse-phase high-performance liquid chromatography/mass spectroscopy. RESULTS: We found that postprandial excursion of conjugated BAs was 52.4% lower in obese than in lean individuals by area-under-the-curve (AUC) analysis (378 vs 793 mu mol min l(-1), respectively, P<0.05). By 40 weeks after RYGB, the meal-induced rise in conjugated BAs increased by 55.5% to the level of healthy lean controls (378 pre-op vs 850 mu mol min l(-) post-op by AUC analyses, P<0.05). In contrast, postprandial concentrations of unconjugated BAs were similar in lean and obese individuals and were not affected by surgery. CONCLUSION: In light of the growing evidence that BAs have key roles in glucose, lipid and energy homeostasis, the observation that RYGB normalizes the blunted postprandial circulating BA response in obesity suggests that BAs may contribute to the improvement in meal-related physiology seen after RYGB. Further studies are warranted to examine this hypothesis and to determine the degree to which an augmented BA response to nutrient ingestion may mediate the increased incretin response, brown adipose tissue activation and thermic effect of feeding that has been observed after this operation. C1 [Ahmad, N. N.; Pfalzer, A.; Kaplan, L. M.] Massachusetts Gen Hosp, Obes Metab & Nutr Inst, Gastrointestinal Unit, Charlestown, MA 02129 USA. [Ahmad, N. N.; Pfalzer, A.; Kaplan, L. M.] Massachusetts Gen Hosp, MGH Weight Ctr, Charlestown, MA 02129 USA. [Ahmad, N. N.; Pfalzer, A.; Kaplan, L. M.] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. RP Kaplan, LM (reprint author), Massachusetts Gen Hosp, Obes Metab & Nutr Inst, 149 13th St,Room 8219, Charlestown, MA 02129 USA. EM LMKaplan@partners.org FU National Institutes of Health [DK083230, KL2 RR025757, DK08866, DK090956, UL1 RR025758]; Ethicon Endo-Surgery FX This study was supported by grants DK083230, KL2 RR025757, DK08866, DK090956 and UL1 RR025758 from the National Institutes of Health and a research grant from Ethicon Endo-Surgery. NR 56 TC 50 Z9 50 U1 0 U2 7 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0307-0565 EI 1476-5497 J9 INT J OBESITY JI Int. J. Obes. PD DEC PY 2013 VL 37 IS 12 BP 1553 EP 1559 DI 10.1038/ijo.2013.38 PG 7 WC Endocrinology & Metabolism; Nutrition & Dietetics SC Endocrinology & Metabolism; Nutrition & Dietetics GA 272JJ UT WOS:000328456200006 PM 23567924 ER PT J AU Figueroa, AL Abdelbaky, A Truong, QA Corsini, E MacNabb, MH Lavender, ZR Lawler, MA Grinspoon, SK Brady, TJ Nasir, K Hoffmann, U Tawakol, A AF Figueroa, Amparo L. Abdelbaky, Amr Truong, Quynh A. Corsini, Erin MacNabb, Megan H. Lavender, Zachary R. Lawler, Meredith A. Grinspoon, Steven K. Brady, Thomas J. Nasir, Khurram Hoffmann, Udo Tawakol, Ahmed TI Measurement of Arterial Activity on Routine FDG PET/CT Images Improves Prediction of Risk of Future CV Events SO JACC-CARDIOVASCULAR IMAGING LA English DT Article DE cardiovascular events; FDG-PET; inflammation; risk factors ID POSITRON-EMISSION-TOMOGRAPHY; ATHEROSCLEROTIC PLAQUE INFLAMMATION; CARDIOVASCULAR EVENTS; REACTIVE PROTEIN; DISEASE; FLUORODEOXYGLUCOSE; CANCER; MACROPHAGES; FEASIBILITY; BIOMARKERS AB OBJECTIVES This study sought to determine whether arterial inflammation measured by F-18-fluoro-deoxyglucose positron emission tomography (F-18-FDG-PET) improves prediction of cardiovascular disease (CVD) beyond traditional risk factors. BACKGROUND It is unknown whether arterial F-18-FDG uptake measured with routine PET imaging provides incremental value for predicting CVD events beyond Framingham risk score (FRS). METHODS We consecutively identified 513 individuals from 6,088 patients who underwent F-18-FDG-PET and computed tomography (CT) imaging at Massachusetts General Hospital between 2005 and 2008 and who met additional inclusion criteria: >= 30 years of age, no prior CVD, and free of cancer. CVD events were independently adjudicated, while blinded to clinical data, using medical records to determine incident stroke, transient ischemic attack, acute coronary syndrome, revascularization, new-onset angina, peripheral arterial disease, heart failure, or CVD death. FDG uptake was measured in the ascending aorta (as target-to-background-ratio [TBR]), while blinded to clinical data. RESULTS During follow-up (median 4.2 years), 44 participants developed CVD (2 per 100 personyears at risk). TBR strongly predicted subsequent CVD independent of traditional risk factors (hazard ratio: 4.71; 95% confidence interval [Cl]: 1.98 to 11.2; p < 0.001) and (hazard ratio: 4.13; 95% Cl: 1.59 to 10.76; p = 0.004) after further adjustment for coronary calcium score. Addition of arterial PET measurement to FRS scores improved the C-statistic (mean standard error 0.62 +/- 0.03 vs. 0.66 +/- 0.03). Further, incorporation of TBR into a model with FRS variables resulted in an integrated discrimination of 5% (95% Cl: 0.36 to 9.87). Net reclassification improvements were 27.48% (95% Cl: 16.27 to 39.92) and 22.3% (95% Cl: 11.54 to 35.42) for the 10% and 6% intermediate-risk cut points, respectively. Moreover, TBR was inversely associated with the timing of CVD (beta -0.096; p < 0.0001). CONCLUSIONS Arterial FDG uptake, measured from routinely obtained PET/CT images, substantially improved incident CVD prediction beyond FRS among individuals undergoing cancer surveillance and provided information on the potential timing of such events. (C) 2013 by the American College of Cardiology Foundation C1 [Figueroa, Amparo L.; Abdelbaky, Amr; Truong, Quynh A.; Corsini, Erin; MacNabb, Megan H.; Lavender, Zachary R.; Lawler, Meredith A.; Brady, Thomas J.; Hoffmann, Udo; Tawakol, Ahmed] Massachusetts Gen Hosp, Dept Imaging, Cardiac MR PET CT Program, Boston, MA 02114 USA. [Figueroa, Amparo L.; Abdelbaky, Amr; Truong, Quynh A.; Corsini, Erin; MacNabb, Megan H.; Lavender, Zachary R.; Lawler, Meredith A.; Brady, Thomas J.; Hoffmann, Udo; Tawakol, Ahmed] Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. [Figueroa, Amparo L.; Abdelbaky, Amr; Truong, Quynh A.; Corsini, Erin; MacNabb, Megan H.; Lavender, Zachary R.; Lawler, Meredith A.; Grinspoon, Steven K.; Brady, Thomas J.; Hoffmann, Udo; Tawakol, Ahmed] Harvard Univ, Sch Med, Boston, MA USA. [Truong, Quynh A.; Tawakol, Ahmed] Massachusetts Gen Hosp, Dept Med, Div Cardiol, Boston, MA 02114 USA. [Grinspoon, Steven K.] Massachusetts Gen Hosp, Program Nutr Metab, Boston, MA 02114 USA. [Nasir, Khurram] Florida Int Univ, Robert Stempel Coll Publ Hlth,Herbert Wertheim Co, Dept Med,Dept Epidemiol, Ctr Prevent & Wellness Res,Baptist Hlth South Flo, Miami, FL 33199 USA. [Nasir, Khurram] Johns Hopkins Univ, Ciccarone Ctr Prevent Cardiol, Baltimore, MD USA. RP Tawakol, A (reprint author), Massachusetts Gen Hosp, 165 Cambridge St,Suite 400, Boston, MA 02114 USA. EM atawakol@partners.org NR 40 TC 61 Z9 61 U1 1 U2 7 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1936-878X EI 1876-7591 J9 JACC-CARDIOVASC IMAG JI JACC-Cardiovasc. Imag. PD DEC PY 2013 VL 6 IS 12 BP 1250 EP 1259 DI 10.1016/j.jcmg.2013.08.006 PG 10 WC Cardiac & Cardiovascular Systems; Radiology, Nuclear Medicine & Medical Imaging SC Cardiovascular System & Cardiology; Radiology, Nuclear Medicine & Medical Imaging GA 275DY UT WOS:000328657700003 PM 24269261 ER PT J AU Kallenbach, K Sundt, TM Marwick, TH AF Kallenbach, Klaus Sundt, Thoralf M. Marwick, Thomas H. TI Aortic Surgery for Ascending Aortic Aneurysms Under 5.0 cm in Diameter in the Presence of Bicuspid Aortic Valve SO JACC-CARDIOVASCULAR IMAGING LA English DT Editorial Material DE aortic aneurysm; bicuspid aortic valve; surgery ID SINGLE-CENTER EXPERIENCE; INTERNATIONAL REGISTRY; DISSECTION IRAD; REPLACEMENT; AORTOPATHY; DILATATION; MORTALITY; OPERATION; DISEASE; SIZE C1 [Kallenbach, Klaus] Univ Heidelberg Hosp, Dept Cardiac Surg, Heidelberg, Germany. [Sundt, Thoralf M.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Cardiac Surg, Boston, MA USA. [Marwick, Thomas H.] Menzies Res Inst Tasmania, Hobart, Tas, Australia. RP Kallenbach, K (reprint author), Heidelberg Univ, INF 110, D-69120 Heidelberg, Germany. EM klaus.kallenbach@med.uni-heidelberg.de; tsundt@partners.org; Tom.Marwick@utas.edu.au NR 39 TC 6 Z9 6 U1 0 U2 4 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1936-878X EI 1876-7591 J9 JACC-CARDIOVASC IMAG JI JACC-Cardiovasc. Imag. PD DEC PY 2013 VL 6 IS 12 BP 1321 EP 1326 DI 10.1016/j.jcmg.2013.08.009 PG 6 WC Cardiac & Cardiovascular Systems; Radiology, Nuclear Medicine & Medical Imaging SC Cardiovascular System & Cardiology; Radiology, Nuclear Medicine & Medical Imaging GA 275DY UT WOS:000328657700013 PM 24332284 ER PT J AU Osborn, EA Jaffer, FA AF Osborn, Eric A. Jaffer, Farouc A. TI The Advancing Clinical Impact of Molecular Imaging in CVD SO JACC-CARDIOVASCULAR IMAGING LA English DT Article DE aneurysm; atherosclerosis; heart failure; molecular imaging; myocardial infarction; thrombosis; valvular disease; vascular injury ID POSITRON-EMISSION-TOMOGRAPHY; NEAR-INFRARED FLUORESCENCE; VESSEL WALL INFLAMMATION; FDG-PET-CT; IN-VIVO; ATHEROSCLEROTIC PLAQUE; F-18-FDG PET; CAROTID ATHEROSCLEROSIS; VASCULAR INFLAMMATION; AORTIC-STENOSIS AB Molecular imaging seeks to unravel critical molecular and cellular events in living subjects by providing complementary biological information to current structural clinical imaging modalities. In recent years, molecular imaging efforts have marched forward into the clinical cardiovascular arena, and are now actively illuminating new biology in a broad range of conditions, including atherosclerosis, myocardial infarction, thrombosis, vasculitis, aneurysm, cardiomyopathy, and valvular disease. Development of novel molecular imaging reporters is occurring for many clinical cardiovascular imaging modalities (positron emission tomography, single-photon emission computed,tomography, magnetic resonance imaging), as well as in translational platforms such as intravascular fluorescence imaging. The ability to image, track, and quantify molecular biomarkers in organs not routinely amenable to biopsy (e.g., the heart and vasculature) open new clinical opportunities to tailor therapeutics based on a cardiovascular disease molecular profile. In addition, molecular imaging is playing an increasing role in atherosclerosis drug development in phase II clinical trials. Here, we present state-of-the-art clinical cardiovascular molecular imaging strategies, and explore promising translational approaches positioned for clinical testing in the near term.(C) 2013 by the American College of Cardiology Foundation C1 [Osborn, Eric A.] Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Div Cardiol, Boston, MA 02215 USA. [Osborn, Eric A.; Jaffer, Farouc A.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Cardiol,Cardiovasc Res Ctr, Boston, MA USA. [Jaffer, Farouc A.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Mol Imaging Res, Boston, MA USA. [Jaffer, Farouc A.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Wellman Ctr Photomed, Boston, MA USA. RP Jaffer, FA (reprint author), Massachusetts Gen Hosp, Cardiovasc Res Ctr, Simches Res Bldg 3206,185 Cambridge St, Boston, MA 02114 USA. EM fjaffer@mgh.harvard.edu FU National Institutes of Health [R01 HL108229]; American Heart Association Scientist Development [0830352N]; NIH [T32 HL007374]; Abbott Vascular, Merck Co.; Kowa Company, Ltd.; [13GRNT1760040] FX Funded by a National Institutes of Health grant R01 HL108229, American Heart Association Scientist Development Grant #0830352N and Grant-in-Aid #13GRNT1760040, and NIH T32 HL007374 support for Dr. Osborn. Dr. Jaffer has received research funding from Abbott Vascular, Merck & Co., and Kowa Company, Ltd. NR 39 TC 27 Z9 27 U1 2 U2 15 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1936-878X EI 1876-7591 J9 JACC-CARDIOVASC IMAG JI JACC-Cardiovasc. Imag. PD DEC PY 2013 VL 6 IS 12 BP 1327 EP 1341 DI 10.1016/j.jcmg.2013.09.014 PG 15 WC Cardiac & Cardiovascular Systems; Radiology, Nuclear Medicine & Medical Imaging SC Cardiovascular System & Cardiology; Radiology, Nuclear Medicine & Medical Imaging GA 275DY UT WOS:000328657700014 PM 24332285 ER PT J AU Naganuma, T Chieffo, A Meliga, E Capodanno, D Park, SJ Onuma, Y Valgimigli, M Jegere, S Makkar, RR Palacios, IF Costopoulos, C Kim, YH Buszman, PP Chakravarty, T Sheiban, I Mehran, R Naber, C Margey, R Agnihotri, A Marra, S Capranzano, P Leon, MB Moses, JW Fajadet, J Lefevre, T Morice, MC Erglis, A Tamburino, C Alfieri, O Serruys, PW Colombo, A AF Naganuma, Toru Chieffo, Alaide Meliga, Emanuele Capodanno, Davide Park, Seung-Jung Onuma, Yoshinobu Valgimigli, Marco Jegere, Sanda Makkar, Raj R. Palacios, Igor F. Costopoulos, Charis Kim, Young-Hak Buszman, Piotr P. Chakravarty, Tarun Sheiban, Imad Mehran, Roxana Naber, Christoph Margey, Ronan Agnihotri, Arvind Marra, Sebastiano Capranzano, Piera Leon, Martin B. Moses, Jeffrey W. Fajadet, Jean Lefevre, Thierry Morice, Marie-Claude Erglis, Andrejs Tamburino, Corrado Alfieri, Ottavio Serruys, Patrick W. Colombo, Antonio TI Long-Term Clinical Outcomes After Percutaneous Coronary Intervention for Ostial/Mid-Shaft Lesions Versus Distal Bifurcation Lesions in Unprotected Left Main Coronary Artery The DELTA Registry (Drug-Eluting Stent for Left Main Coronary Artery Disease): A Multicenter Registry Evaluating Percutaneous Coronary Intervention Versus Coronary Artery Bypass Grafting for Left Main Treatment SO JACC-CARDIOVASCULAR INTERVENTIONS LA English DT Article DE distal bifurcation lesion; drug-eluting stent(s); ostial/mid-shaft lesion; unprotected left main coronary artery ID BARE-METAL STENTS; SURGICAL REVASCULARIZATION; ANGIOGRAPHIC OUTCOMES; FOLLOW-UP; IMPLANTATION; STENOSIS; CARDIOLOGY; SOCIETY; TAXUS AB Objectives The aim of this study was to compare, in a large all-comer registry, the long-term clinical outcomes after percutaneous coronary intervention (PCI) with drug-eluting stents (DES) for ostial/mid-shaft lesions versus distal bifurcation lesions in unprotected left main coronary artery (ULMCA) stenosis. Background Limited data are available regarding clinical outcomes following DES implantation at the different ULMCA sites. Methods Patients with ULMCA stenosis treated by PCI with DES were analyzed in this multinational registry. Results A total of 1,612 patients were included: 482 were treated for ostial/mid-shaft lesions versus 1,130 for distal bifurcation lesions. At a median follow-up period of 1,250 (interquartile range: 987 to 1,564) days, PCI for distal bifurcation lesions was associated with a higher incidence of major adverse cardiac events (propensity-score adjusted hazard ratio [HR]: 1.48, 95% confidence interval [CI]: 1.16 to 1.89; p = 0.001), largely because of the higher target vessel revascularization rate observed in this group as compared to the ostial/mid-shaft lesions group (propensity-score adjusted HR: 1.68, 95% CI: 1.19 to 2.38; p = 0.003). These results were sustained following propensity-score matched analysis. With regard to all-cause death and the composite endpoint of all-cause death and myocardial infarction, propensity-score adjusted analysis suggested a trend toward higher rates of these in the distal ULMCA PCI group, although this was not observed in the propensity-score matched analysis. Conclusions This study demonstrates that PCI for ostial/mid-shaft lesions is associated with better clinical outcomes than are distal bifurcation lesions in ULMCA, largely because there is a lower need for repeat revascularization in ostial/mid-shaft lesions. (C) 2013 by the American College of Cardiology Foundation C1 [Naganuma, Toru; Chieffo, Alaide; Costopoulos, Charis; Alfieri, Ottavio; Colombo, Antonio] Ist Sci San Raffaele, Dept Cardiothorac & Vasc Dis, I-20132 Milan, Italy. [Meliga, Emanuele] AO Ordine Mauriziano Umberto I, Intervent Cardiol Unit, Turin, Italy. [Capodanno, Davide; Capranzano, Piera; Tamburino, Corrado] Univ Catania, Ferrarotto Hosp, Cardiovasc Dept, Catania, Italy. [Park, Seung-Jung; Kim, Young-Hak] Univ Ulsan, Coll Med, Asan Med Ctr, Dept Cardiol,Ctr Med Res & Informat, Seoul, South Korea. [Onuma, Yoshinobu; Serruys, Patrick W.] Erasmus MC, Thoraxctr, Rotterdam, Netherlands. [Valgimigli, Marco] Univ Ferrara, S Anna Hosp, Cardiovasc Inst, I-44100 Ferrara, Italy. [Jegere, Sanda; Erglis, Andrejs] Pauls Stradins Clin Univ Hosp, Latvian Ctr Cardiol, Riga, Latvia. [Jegere, Sanda; Erglis, Andrejs] Latvian State Univ, Inst Cardiol, LV-1063 Riga, Latvia. [Makkar, Raj R.; Chakravarty, Tarun] Cedars Sinai Med Ctr, Cedars Sinai Heart Inst, Los Angeles, CA 90048 USA. [Palacios, Igor F.; Margey, Ronan; Agnihotri, Arvind] Massachusetts Gen Hosp, Cardiac Catheterizat Lab, Boston, MA 02114 USA. [Palacios, Igor F.; Margey, Ronan; Agnihotri, Arvind] Harvard Univ, Sch Med, Boston, MA USA. [Buszman, Piotr P.] Ctr Cardiovasc Res & Dev Amer Heart Poland, Katowice, Poland. [Sheiban, Imad; Marra, Sebastiano] Univ Turin, S Giovanni Battista Molinette Hosp, Div Cardiol, Turin, Italy. [Mehran, Roxana] Mt Sinai Med Ctr, New York, NY 10029 USA. [Leon, Martin B.; Moses, Jeffrey W.] Columbia Univ, Med Ctr, New York, NY USA. [Leon, Martin B.; Moses, Jeffrey W.] Cardiovasc Res Fdn, New York, NY USA. [Naber, Christoph; Fajadet, Jean] Clin Pasteur, Toulouse, France. [Lefevre, Thierry; Morice, Marie-Claude] Inst Hosp Jacques Cartier, Massy, France. RP Colombo, A (reprint author), Ist Sci San Raffaele, Dept Cardiothorac & Vasc Dis, Via Olgettina 60, I-20132 Milan, Italy. EM colombo.antonio@hsr.it FU Lilly; Medtronic; Edwards Lifesciences; Abbott Vascular; Capricor; St. Jude Medical; Bristol-Myers Squibb/Sanofi; Medicines Company; Lily/Daiichi Sankyo; Biotronik; Direct Flow; Sadra Medical; Stentys; Icon; Boston Scientific FX Dr. Capodanno has received speaker's honoraria from Eli-Lilly and AstraZeneca. Dr. Makkar is a consultant to Medtronic and Abiomed; is a proctor for Edwards Lifesciences; has received speaker's fees from Lilly and Medtronic; has received equity from Entourage Medical Technologies; and has received research grants from Edwards Lifesciences, Medtronic, Abbott Vascular, Capricor, and St. Jude Medical. Dr. Mehran is a consultant to Abbott Vascular, AstraZeneca, Boston Scientific, Covidien, The Medicines Company, Janssen (Johnson and Johnson), Regado Biosciences, Maya Medical, and Merck; and has received research grant support from Bristol-Myers Squibb/Sanofi, The Medicines Company, and Lily/Daiichi Sankyo. Dr. Naber is a speaker for Abbott Vascular, Cordis, Biotronik, Biosensors, Cirdus, Medtronic, Stentys, Daiichi Sankyo, The Medicines Company, Edwards Lifesciences, Boston Scientific, and St. Jude Medical; has received research support from Abbott Vascular, Biotronik, Direct Flow, St. Jude Medical, Sadra Medical, Stentys, and Icon; and is on the advisory board of Biotronik and Abbott Vascular. Dr. Margey is a proctor for Edwards Lifesciences. Dr. Agnihotri is a consultant for Edwards Lifesciences. Dr. Moses is a consultant for Cordis and Boston Scientific. Dr. Erglis is a consultant for and is on the speakers' bureaus of Medtronic, Boston Scientific, Cordis (Johnson and Johnson), Biosensors, and Abbott Vascular; and has received research contracts from Abbott Vascular and Boston Scientific. Dr. Tamburino has received honoraria from Celonova, Medtronic, Cardiokinetix, and Abbott Vascular. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose. NR 20 TC 17 Z9 18 U1 0 U2 7 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1936-8798 EI 1876-7605 J9 JACC-CARDIOVASC INTE JI JACC-Cardiovasc. Interv. PD DEC PY 2013 VL 6 IS 12 BP 1242 EP 1249 DI 10.1016/j.jcin.2013.08.005 PG 8 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 272KI UT WOS:000328458800004 PM 24355114 ER PT J AU Ojeifo, O Wiviott, SD Antman, EM Murphy, SA Udell, JA Bates, ER Mega, JL Sabatine, MS O'Donoghue, ML AF Ojeifo, Oluseyi Wiviott, Stephen D. Antman, Elliott M. Murphy, Sabina A. Udell, Jacob A. Bates, Eric R. Mega, Jessica L. Sabatine, Marc S. O'Donoghue, Michelle L. TI Concomitant Administration of Clopidogrel With Statins or Calcium-Channel Blockers Insights From the TRITON-TIMI 38 (Trial to Assess Improvement in Therapeutic Outcomes by Optimizing Platelet Inhibition With Prasugrel-Thrombolysis In Myocardial Infarction 38) SO JACC-CARDIOVASCULAR INTERVENTIONS LA English DT Article DE clopidogrel; clopidogrel response variability; drug-drug interactions; drug metabolism; prasugrel ID ACUTE CORONARY SYNDROMES; ATORVASTATIN AB Objectives This study sought to evaluate the clinical relevance of potential clopidogrel drug-drug interactions. Background Some studies have demonstrated that statins and calcium-channel blockers (CCBs) may attenuate the pharmacodynamic effects of clopidogrel. Methods The TRITON-TIMI 38 (Trial to Assess Improvement in Therapeutic Outcomes by Optimizing Platelet Inhibition With Prasugrel-Thrombolysis in Myocardial Infarction 38) enrolled 13,608 patients with an acute coronary syndrome (ACS) and planned percutaneous coronary intervention (PCI), and randomized them to clopidogrel or prasugrel. Use of a statin or CCB was left to the discretion of the treating physician. A multivariable Cox model with propensity score was employed to evaluate the association between statin or CCB use and clinical outcomes. Results Of the 6,795 subjects assigned to clopidogrel, 4,794 (70.6%) were on a CYP3A4-metabolized statin, and 966 (14.2%) were on a CCB at randomization. The risk of cardiovascular (CV) death, myocardial infarction (MI), or stroke was similar regardless of baseline use of statins (adjusted hazard ratio [HR]: 1.02, 95% confidence interval [CI]: 0.85 to 1.22) or CCBs (adjusted HR: 1.16; 95% CI: 0.94 to 1.43) in clopidogrel-treated patients. Further, the combined use of a CCB and atorvastatin 80 mg daily (adjusted HR: 0.82; 95% CI: 0.37 to 1.84), or a CCB, statin, and proton pump inhibitor (adjusted HR: 1.04; 95% CI: 0.70 to 1.54) were not associated with an increased risk of CV death, MI, or stroke. The use of statins or CCBs did not modify the relative efficacy of prasugrel versus clopidogrel for the primary endpoint (p for interaction = 0.43, 0.55, respectively). Conclusions In patients with ACS undergoing PCI, the use of statins or CCBs was not associated with an increased risk of CV events in clopidogrel-treated patients. Consistent results were observed when the drugs were administered alone, together, or in combination with proton pump inhibitors. (C) 2013 by the American College of Cardiology Foundation C1 [Ojeifo, Oluseyi] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. [Wiviott, Stephen D.; Antman, Elliott M.; Murphy, Sabina A.; Mega, Jessica L.; Sabatine, Marc S.; O'Donoghue, Michelle L.] Brigham & Womens Hosp, Div Cardiovasc, TIMI Study Grp, Boston, MA 02115 USA. [Udell, Jacob A.] Univ Toronto, Womens Coll Hosp, Div Cardiol, Toronto, ON, Canada. [Bates, Eric R.] Univ Michigan, Dept Internal Med, Ann Arbor, MI 48109 USA. RP O'Donoghue, ML (reprint author), Brigham & Womens Hosp, Div Cardiovasc, TIMI Study Grp, 350 Longwood Ave,1st Floor, Boston, MA 02115 USA. EM modonoghue@partners.org FU Merck Co.; Eisai; AstraZeneca; Eli Lilly and Company/Daichi Sankyo; Eli Lilly and Company; Daiichi Sankyo; Jannsen Pharmaceuticals; Bayer HealthCare; Bristol-Myers Squibb; Sanofi-aventis; Brigham and Women's Hospital from Abbott Laboratories; Amgen; AstraZeneca/Bristol-Myers Squibb Alliance; Critical Diagnostics; Daiichi-Sankyo; Genzyme; GlaxoSmithKline; Intarcia; Merck; Roche Diagnostics; Takeda FX Dr. Wiviott is a consultant for Angelmed, Eisai, Aegerion, Janssen Pharmaceuticals, St. Jude Medical, and Xoma; and has received research funding from Merck & Co., Eisai, AstraZeneca, and Eli Lilly and Company/Daichi Sankyo. Dr. Antman has received research funding from Eli Lilly and Company and Daiichi Sankyo. Ms. Murphy has received research funding from Eli Lilly and Company. Dr. Bates is on the advisory boards of Daichi Sankyo, AstraZeneca, Eli Lilly and Company, and Sanofi-aventis. Dr. Mega has received research funding from Jannsen Pharmaceuticals, Bayer HealthCare, AstraZeneca, Eli Lilly and Company, Daiichi Sankyo, Bristol-Myers Squibb, and Sanofi-aventis; and is a consultant for Boehringer Ingelheim and Janssen Pharmaceuticals. Dr. Sabatine has received research funding through Brigham and Women's Hospital from Abbott Laboratories, Amgen, AstraZeneca, AstraZeneca/Bristol-Myers Squibb Alliance, Critical Diagnostics, Daiichi-Sankyo, Eisai, Genzyme, GlaxoSmithKline, Intarcia, Merck, Roche Diagnostics, Sanofi-aventis, and Takeda; and is a consultant for Aegerion, Amgen, AstraZeneca/Bristol-Myers Squibb Alliance, Intarcia, Pfizer, Sanofi-aventis, and Vertex. Dr. O'Donoghue has received research funding from GlaxoSmithKline and AstraZeneca and is a consultant for Aegerion. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose. The TRITON-TIMI 38 trial was sponsored by Daiichi Sankyo and Eli Lilly and Company. The current analysis received no sources of external funding. The TIMI Study Group has an independent copy of the trial database and conducted the current analysis. NR 26 TC 14 Z9 17 U1 0 U2 4 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1936-8798 EI 1876-7605 J9 JACC-CARDIOVASC INTE JI JACC-Cardiovasc. Interv. PD DEC PY 2013 VL 6 IS 12 BP 1275 EP 1281 DI 10.1016/j.jcin.2013.06.014 PG 7 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 272KI UT WOS:000328458800009 PM 24239201 ER PT J AU Krop, IE Burstein, HJ AF Krop, Ian E. Burstein, Harold J. TI Trastuzumab: Qui Bono? SO JNCI-JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Editorial Material ID METASTATIC BREAST-CANCER; PERTUZUMAB PLUS TRASTUZUMAB; ADJUVANT TRASTUZUMAB; PHASE-II; OPEN-LABEL; TRIAL; CHEMOTHERAPY; BENEFIT; N9831; HER2 C1 [Krop, Ian E.; Burstein, Harold J.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. RP Burstein, HJ (reprint author), Dana Farber Canc Inst, 450 Brookline Ave, Boston, MA 02215 USA. EM hburstein@partners.org NR 26 TC 3 Z9 3 U1 0 U2 2 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0027-8874 EI 1460-2105 J9 JNCI-J NATL CANCER I JI JNCI-. Natl. Cancer Inst. PD DEC PY 2013 VL 105 IS 23 BP 1772 EP 1775 DI 10.1093/jnci/djt336 PG 4 WC Oncology SC Oncology GA 271DE UT WOS:000328370000004 PM 24262439 ER PT J AU Ogino, S Liao, XY Imamura, Y Yamauchi, M McCleary, NJ Ng, K Niedzwiecki, D Saltz, LB Mayer, RJ Whittom, R Hantel, A Benson, AB Mowat, RB Spiegelman, D Goldberg, RM Bertagnolli, MM Meyerhardt, JA Fuchs, CS AF Ogino, Shuji Liao, Xiaoyun Imamura, Yu Yamauchi, Mai McCleary, Nadine J. Ng, Kimmie Niedzwiecki, Donna Saltz, Leonard B. Mayer, Robert J. Whittom, Renaud Hantel, Alexander Benson, Al B., III Mowat, Rex B. Spiegelman, Donna Goldberg, Richard M. Bertagnolli, Monica M. Meyerhardt, Jeffrey A. Fuchs, Charles S. CA Alliance Clin Trials Oncology TI Predictive and Prognostic Analysis of PIK3CA Mutation in Stage III Colon Cancer Intergroup Trial SO JNCI-JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Article ID METASTATIC COLORECTAL-CANCER; ISLAND METHYLATOR PHENOTYPE; MOLECULAR PATHOLOGICAL EPIDEMIOLOGY; MICROSATELLITE INSTABILITY; BRAF MUTATION; KRAS MUTATION; CORRESPONDING METASTASES; PERSONALIZED MEDICINE; ADJUVANT THERAPY; POOR-PROGNOSIS AB Somatic mutations in PIK3CA (phosphatidylinositol-4,5-bisphosphonate 3-kinase [PI3K], catalytic subunit alpha gene) activate the PI3K-AKT signaling pathway and contribute to pathogenesis of various malignancies, including colorectal cancer. We examined associations of PIK3CA oncogene mutation with relapse, survival, and treatment efficacy in 627 stage III colon carcinoma case subjects within a randomized adjuvant chemotherapy trial (5-fluorouracil and leucovorin [FU/LV] vs irinotecan [CPT11], fluorouracil and leucovorin [IFL]; Cancer and Leukemia Group B 89803 [Alliance]). We detected PIK3CA mutation in exons 9 and 20 by polymerase chain reaction and pyrosequencing. Cox proportional hazards model was used to assess prognostic and predictive role of PIK3CA mutation, adjusting for clinical features and status of routine standard molecular pathology features, including KRAS and BRAF mutations and microsatellite instability (mismatch repair deficiency). All statistical tests were two-sided. Compared with PIK3CA wild-type cases, overall status of PIK3CA mutation positivity or the presence of PIK3CA mutation in either exon 9 or 20 alone was not statistically significantly associated with recurrence-free, disease-free, or overall survival (log-rank P > .70; P > .40 in multivariable regression models). There was no statistically significant interaction between PIK3CA and KRAS (or BRAF) mutation status in survival analysis (P-interaction > .18). PIK3CA mutation status did not appear to predict better or worse response to IFL therapy compared with FU/LV therapy (P-interaction > .16). Overall tumor PIK3CA mutation status is not associated with stage III colon cancer prognosis. PIK3CA mutation does not appear to serve as a predictive tumor molecular biomarker for response to irinotecan-based adjuvant chemotherapy. C1 [Ogino, Shuji; Liao, Xiaoyun; Imamura, Yu; Yamauchi, Mai; McCleary, Nadine J.; Ng, Kimmie; Mayer, Robert J.; Meyerhardt, Jeffrey A.; Fuchs, Charles S.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Ogino, Shuji; Liao, Xiaoyun; Imamura, Yu; Yamauchi, Mai; McCleary, Nadine J.; Ng, Kimmie; Mayer, Robert J.; Meyerhardt, Jeffrey A.; Fuchs, Charles S.] Harvard Univ, Sch Med, Boston, MA 02215 USA. [Ogino, Shuji] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. [Spiegelman, Donna; Fuchs, Charles S.] Brigham & Womens Hosp, Dept Med, Channing Div Network Med, Boston, MA 02115 USA. [Bertagnolli, Monica M.] Brigham & Womens Hosp, Dept Surg, Boston, MA 02115 USA. [Ogino, Shuji; Spiegelman, Donna] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. [Spiegelman, Donna] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. [Niedzwiecki, Donna] Duke Univ, Med Ctr, Alliance Stat & Data Ctr, Durham, NC USA. [Saltz, Leonard B.] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. [Whittom, Renaud] Hop Sacre Coeur, Montreal, PQ H4J 1C5, Canada. [Hantel, Alexander] Loyola Univ, Stritch Sch Med, Maywood, IL 60153 USA. [Benson, Al B., III] Northwestern Univ, Chicago, IL 60611 USA. [Mowat, Rex B.] Toledo Community Hosp Oncol Program, Toledo, OH USA. [Goldberg, Richard M.] Ohio State Univ, Ctr Comprehens Canc, Div Med Oncol, Columbus, OH 43210 USA. RP Ogino, S (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, 450 Brookline Ave,Rm M422, Boston, MA 02215 USA. EM shuji_ogino@dfci.harvard.edu RI Goldberg , Richard/M-1311-2013 FU National Institute of Health [CA031946, CA33601, R01 CA151993, K07 CA148894, R01 CA149222, R01 CA118553, P50 CA127003]; Pfizer Oncology; [CA77651]; [CO15]; [CA32102]; [CA46282]; [CA17145]; [CA21115]; [CA35415]; [CA077658] FX The research for CALGB 89803 (Alliance) (ClinicalTrials.gov Identifier: NCT00003835) was supported, in part, by grants from the National Institute of Health (CA031946) to Alliance for Clinical Trials in Oncology (Monica M. Bertagnolli, MD, Chairperson) and to the Alliance Statistics and Data Center (Daniel J. Sargent, PhD, CA33601), as well as support from Pharmacia & Upjohn Company, now Pfizer Oncology. S.O., K.N., D. S., J. A. M. and C. S. F. were supported in part by grants from the National Institute of Health (grant numbers R01 CA151993 [to SO], K07 CA148894 [to KN], R01 CA149222 [to JAM], R01 CA118553 [to CSF], P50 CA127003 [to CSF]). Other authors were supported in part by the following grants: CA33601 (DN); CA77651 (LBS); CO15 (RW); CA32102 (AH); CA46282 (AH); CA17145 (ABB); CA21115 (ABB); CA35415 (RBM); CA077658 (RMG); and CA031946 (MMB). NR 77 TC 18 Z9 19 U1 0 U2 4 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0027-8874 EI 1460-2105 J9 JNCI-J NATL CANCER I JI JNCI-. Natl. Cancer Inst. PD DEC PY 2013 VL 105 IS 23 BP 1789 EP 1798 DI 10.1093/jnci/djt298 PG 10 WC Oncology SC Oncology GA 271DE UT WOS:000328370000008 PM 24231454 ER PT J AU Rutter, CM Johnson, EA Feuer, EJ Knudsen, AB Kuntz, KM Schrag, D AF Rutter, Carolyn M. Johnson, Eric A. Feuer, Eric J. Knudsen, Amy B. Kuntz, Karen M. Schrag, Deborah TI Secular Trends in Colon and Rectal Cancer Relative Survival SO JNCI-JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Article ID METASTATIC COLORECTAL-CANCER; FECAL-OCCULT-BLOOD; RANDOMIZED CONTROLLED-TRIAL; ADJUVANT THERAPY; UNITED-STATES; MORTALITY; METAANALYSIS; FLUOROURACIL; CHEMOTHERAPY; POPULATIONS AB Treatment options for colorectal cancer (CRC) have improved substantially over the past 25 years. Measuring the impact of these improvements on survival outcomes is challenging, however, against the background of overall survival gains from advancements in the prevention, screening, and treatment of other conditions. Relative survival is a metric that accounts for these concurrent changes, allowing assessment of changes in CRC survival. We describe stage- and location-specific trends in relative survival after CRC diagnosis. We analyzed survival outcomes for 233965 people in the Surveillance Epidemiology and End Results (SEER) program who were diagnosed with CRC between January 1, 1975, and December 31, 2003. All models were adjusted for sex, race (black vs white), age at diagnosis, time since diagnosis, and diagnosis year. We estimated the proportional difference in survival for CRC patients compared with overall survival for age-, sex-, race-, and period-matched controls to account for concurrent changes in overall survival using two-sided Wald tests. We found statistically significant reductions in excess hazard of mortality from CRC in 2003 relative to 1975, with excess hazard ratios ranging from 0.75 (stage IV colon cancer; P < .001) to 0.32 (stage I rectal cancer; P < .001), indicating improvements in relative survival for all stages and cancer locations. These improvements occurred in earlier years for patients diagnosed with stage I cancers, with smaller but continuing improvements for later-stage cancers. Our results demonstrate a steady trend toward improved relative survival for CRC, indicating that treatment and surveillance improvements have had an impact at the population level. C1 [Rutter, Carolyn M.; Johnson, Eric A.] Grp Hlth Res Inst, Seattle, WA 98101 USA. [Feuer, Eric J.] NCI, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA. [Knudsen, Amy B.] Massachusetts Gen Hosp, Inst Technol Assessment, Dept Radiol, Boston, MA 02114 USA. [Kuntz, Karen M.] Univ Minnesota, Sch Publ Hlth, Div Hlth Policy & Management, Minneapolis, MN USA. [Schrag, Deborah] Harvard Univ, Sch Med, Dana Farber Canc Inst, Div Med Oncol, Boston, MA 02115 USA. RP Rutter, CM (reprint author), Grp Hlth Res Inst, 1730 Minor Ave,Ste 1600, Seattle, WA 98101 USA. EM rutter.c@ghc.org FU National Cancer Institute of the National Institutes of Health [U01CA52959] FX Research reported in this publication was supported by the National Cancer Institute of the National Institutes of Health under award No. U01CA52959. NR 44 TC 17 Z9 17 U1 0 U2 2 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0027-8874 EI 1460-2105 J9 JNCI-J NATL CANCER I JI JNCI-. Natl. Cancer Inst. PD DEC PY 2013 VL 105 IS 23 BP 1806 EP 1813 DI 10.1093/jnci/djt299 PG 8 WC Oncology SC Oncology GA 271DE UT WOS:000328370000010 PM 24174654 ER PT J AU Daughters, SB Gorka, SM Magidson, JF MacPherson, L Seitz-Brown, CJ AF Daughters, Stacey B. Gorka, Stephanie M. Magidson, Jessica F. MacPherson, Laura Seitz-Brown, C. J. TI The role of gender and race in the relation between adolescent distress tolerance and externalizing and internalizing psychopathology SO JOURNAL OF ADOLESCENCE LA English DT Article DE Adolescence; Distress tolerance; Externalizing; Internalizing; Psychopathology ID BORDERLINE PERSONALITY-DISORDER; CHILDRENS DEPRESSIVE SYMPTOMS; AFRICAN-AMERICAN ADOLESCENTS; RACIAL-DIFFERENCES; SENSATION SEEKING; TASK PERSISTENCE; SEX-DIFFERENCES; ALCOHOL-USE; RACIAL/ETHNIC DIFFERENCES; PSYCHIATRIC-DISORDERS AB Distress tolerance (DT) is an established construct contributing to the onset and maintenance of psychopathology in adulthood; however, few studies have examined the role of DT in older adolescent psychopathology. Emerging data suggest that gender and race may influence this relation. Therefore, the current study examined the relation between gender, race, and DT on parent-reported internalizing and externalizing DSM-oriented symptoms among a community sample of 128, 14-18 year old adolescents. Results indicated a moderating effect of gender on affective problems, such that females with low DT, but not males, displayed significantly greater affective problems. Findings also indicated a significant moderating effect of race, such that Caucasians with low DT, but not African Americans, displayed significantly higher somatic, oppositional defiant, and conduct problems. These findings suggest that DT is an important clinical variable in older adolescence, particularly among Caucasians and females. (C) 2013 The Foundation for Professionals in Services for Adolescents. Published by Elsevier Ltd. All rights reserved. C1 [Daughters, Stacey B.] Univ N Carolina, Dept Psychol, Chapel Hill, NC 27599 USA. [Gorka, Stephanie M.] Univ Illinois, Dept Psychol, Chicago, IL 60680 USA. [Magidson, Jessica F.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Cambridge, MA 02138 USA. [MacPherson, Laura; Seitz-Brown, C. J.] Univ Maryland, Dept Psychol, College Pk, MD 20742 USA. RP Daughters, SB (reprint author), Univ N Carolina, Dept Psychol, 247 Davie Hall, Chapel Hill, NC 27599 USA. EM daughter@unc.edu FU NIDA NIH HHS [R21 DA022741, R21DA022741] NR 105 TC 5 Z9 5 U1 4 U2 15 PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 0140-1971 EI 1095-9254 J9 J ADOLESCENCE JI J. Adolesc. PD DEC PY 2013 VL 36 IS 6 BP 1053 EP 1065 DI 10.1016/j.adolescence.2013.08.008 PG 13 WC Psychology, Developmental SC Psychology GA 275XX UT WOS:000328713800006 PM 24215952 ER PT J AU Morshed, SA Ma, R Latif, R Davies, TE AF Morshed, Syed A. Ma, Risheng Latif, Rauf Davies, Terry E. TI How one TSH receptor antibody induces thyrocyte proliferation while another induces apoptosis SO JOURNAL OF AUTOIMMUNITY LA English DT Article DE Thyrocyte; TSH receptor; Antibodies; ROS-signaling; Apoptosis; Proliferation ID HUMAN THYROTROPIN RECEPTOR; GRAVES-DISEASE; SYNTHETIC PEPTIDES; SIGNALING CASCADES; OXIDATIVE STRESS; GENE-EXPRESSION; MITOCHONDRIA; CREB; IDENTIFICATION; RESPONSES AB Thyroid stimulating hormone (TSH) activates two major G-protein arms, Gs alpha and Gq leading to initiation of down-stream signaling cascades for survival, proliferation and production of thyroid hormones. Antibodies to the TSH receptor (TSHR-Abs), found in patients with Graves' disease, may have stimulating, blocking, or neutral actions on the thyroid cell. We have shown previously that such TSHR-Abs are distinct signaling imprints after binding to the TSHR and that such events can have variable functional consequences for the cell. In particular, there is a great contrast between stimulating (S) TSHR-Abs, which induce thyroid hormone synthesis and secretion as well as thyroid cell proliferation, compared to so called "neutral" (N) TSHR-Abs which may induce thyroid cell apoptosis via reactive oxygen species (ROS) generation. In the present study, using a rat thyrocyte (FRTL-5) ex vivo model system, our hypothesis was that while N-TSHR-Abs can induce apoptosis via activation of mitochondrial ROS (mR0S), the S-TSHR-Abs are able to stimulate cell survival and avoid apoptosis by actively suppressing mR0S. Using fluorescent microscopy, fluorometry, live cell imaging, immunohistochemistry and immunoblot assays, we have observed that S-TSHR-Abs do indeed suppress mROS and cellular stress and this suppression is exerted via activation of the PKA/CREB and AKT/mTOR/S6K signaling cascades. Activation of these signaling cascades, with the suppression of mR0S, initiated cell proliferation. In sharp contrast, a failure to activate these signaling cascades with increased activation of mROS induced by N-TSHR-Abs resulted in thyroid cell apoptosis. Our current findings indicated that signaling diversity induced by different TSHR-Abs regulated thyroid cell fate. While S-TSHR-Abs may rescue cells from apoptosis and induce thyrocyte proliferation, N-TSHR-Abs aggravate the local inflammatory infiltrate within the thyroid gland, or in the retro-orbit, by inducing cellular apoptosis; a phenomenon known to activate innate and by-stander immune-reactivity via DNA release from the apoptotic cells. Published by Elsevier Ltd. C1 [Morshed, Syed A.] Icahn Sch Med Mt Sinai, Thyroid Res Unit, New York, NY USA. James J Peters VA Med Ctr, New York, NY USA. RP Morshed, SA (reprint author), Vet Adm Med Ctr, Room 2F-26,130 West Kingsbridge Rd, Bronx, NY 10468 USA. EM syed.morshed@mssm.edu FU NIH [DK069713, DK052464]; VA Merit Award Program FX Supported in part by NIH grants DK069713, DK052464 and the VA Merit Award Program. NR 34 TC 11 Z9 11 U1 1 U2 5 PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 0896-8411 EI 1095-9157 J9 J AUTOIMMUN JI J. Autoimmun. PD DEC PY 2013 VL 47 BP 17 EP 24 DI 10.1016/j.jaut.2013.07.009 PG 8 WC Immunology SC Immunology GA 273HY UT WOS:000328527100002 PM 23958398 ER PT J AU Fitzsimons, MG Ishizawa, Y Baker, KH AF Fitzsimons, Michael G. Ishizawa, Yumiko Baker, Keith H. TI Drug testing physicians for substances of abuse: case report of a false-positive result SO JOURNAL OF CLINICAL ANESTHESIA LA English DT Article DE Anesthesiologists; Drug testing; Ketamine; Substance abuse ID KETAMINE; PHENCYCLIDINE; URINE; ANESTHETICS; EXPERIENCE AB The risk of a false-positive urine drug screen is one of the major impediments to widespread implementation of drug testing programs in anesthesiology. A case of a false-positive urine screen for ketamine in an anesthesia provider is presented, with recommendations for methods of managing such an event. (C) 2013 Elsevier Inc. All rights reserved. C1 [Fitzsimons, Michael G.; Ishizawa, Yumiko; Baker, Keith H.] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Fitzsimons, Michael G.; Ishizawa, Yumiko; Baker, Keith H.] Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, Boston, MA 02114 USA. RP Fitzsimons, MG (reprint author), Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, 55 Fruit St, Boston, MA 02114 USA. EM mfitzsimons@partners.org NR 17 TC 3 Z9 3 U1 0 U2 4 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0952-8180 EI 1873-4529 J9 J CLIN ANESTH JI J. Clin. Anesth. PD DEC PY 2013 VL 25 IS 8 BP 669 EP 671 DI 10.1016/j.jclinane.2013.05.009 PG 3 WC Anesthesiology SC Anesthesiology GA 280FC UT WOS:000329013100013 PM 23988805 ER PT J AU Simon, M AF Simon, Mirela TI Untitled SO JOURNAL OF CLINICAL NEUROPHYSIOLOGY LA English DT Editorial Material C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Simon, M (reprint author), Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0736-0258 EI 1537-1603 J9 J CLIN NEUROPHYSIOL JI J. Clin. Neurophysiol. PD DEC PY 2013 VL 30 IS 6 BP 553 EP 553 DI 10.1097/01.wnp.0000436889.10843.f4 PG 1 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 277KT UT WOS:000328818800001 PM 24300980 ER PT J AU Simon, MV AF Simon, Mirela V. TI Intraoperative Neurophysiologic Sensorimotor Mapping and Monitoring in Supratentorial Surgery SO JOURNAL OF CLINICAL NEUROPHYSIOLOGY LA English DT Review DE Central sulcus localization; SSEPs phase reversal technique; Cortical motor mapping; Subcortical motor mapping; After discharges ID MOTOR-EVOKED-POTENTIALS; LOW-GRADE GLIOMAS; CENTRAL-NERVOUS-SYSTEM; BRAIN-TUMORS; ELECTRICAL-STIMULATION; SURGICAL RESECTION; PROGNOSTIC-FACTORS; EPILEPSY SURGERY; FUNCTIONAL NEURONAVIGATION; PREOPERATIVE LOCALIZATION AB It has been shown that aggressive removal of gliomas improves survival and the quality of life in both adults and children. Conversely, there is a strong correlation between incomplete resection of an epileptic focus and poor seizure control outcome in epilepsy surgery. Thus, it is no surprise that maximal resection of supratentorial lesions remains a priority in neurologic surgery. In many circumstances, this is difficult to achieve because of the close proximity of functionally eloquent regions. As a consequence, accurate identification of the latter is imperative to reliably identify safe boundaries for resection and to expand them as much as possible, while preserving neurologic function. Along these lines, preservation of sensorimotor function, with significant impact on postoperative outcome and quality of life, remains essential as achieving maximal resection. Although there is a wide range of methods that could be used for functional sensorimotor mapping, intraoperative neurophysiologic techniques are still considered by many to be the gold standard. This article provides a detailed overview of these techniques, their principles, and several alternative methodologies. Although the overview directly reflects the current practice at our institution, it also shows the temporal evolution of the major motor mapping methods, relating them to all significant contributions made over the years by different experts in the field. I have tried to exemplify the relevant points of these techniques by using as many pictures and clinical examples as possible. C1 [Simon, Mirela V.] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. [Simon, Mirela V.] Harvard Univ, Sch Med, Boston, MA USA. RP Simon, MV (reprint author), Massachusetts Gen Hosp, Dept Neurol, WACC 739 G,55 Fruit St, Boston, MA 02114 USA. EM mvsimon@partners.org NR 97 TC 2 Z9 2 U1 1 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0736-0258 EI 1537-1603 J9 J CLIN NEUROPHYSIOL JI J. Clin. Neurophysiol. PD DEC PY 2013 VL 30 IS 6 BP 571 EP 590 DI 10.1097/01.wnp.0000436897.02502.78 PG 20 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 277KT UT WOS:000328818800003 PM 24300982 ER PT J AU Kilbride, RD AF Kilbride, Ronan D. TI Intraoperative Functional Cortical Mapping of Language SO JOURNAL OF CLINICAL NEUROPHYSIOLOGY LA English DT Review DE Functional cortical mapping; Neurosurgery; Epilepsy; Intraoperative neurophysiology ID ELECTRICAL-STIMULATION; CORTEX; LOCALIZATION; AREA; MRI AB Intraoperative neurophysiologic monitoring endeavors to preserve the integrity of the nervous system at a time of potential risk. The examination of language function in the operative setting is a unique task that requires a detailed and systematic approach to be carried out efficiently and reliably in this dynamic environment. In this review, we detail the technique used to identify eloquent language cortex during awake craniotomy. This technique requires a coordinated effort to testing, which is reliant on preoperative assessment and structured approach to functional cortical mapping by the surgical, anesthetic, and neurophysiology teams. Despite the intricate nature of this modality of testing, the accurate identification of language areas facilitates neurosurgeries for tumor and focal epilepsy syndromes in the dominant cerebral hemisphere, which depend on maximal margins of resection for best outcomes. C1 [Kilbride, Ronan D.] Massachusetts Gen Hosp, Div Intraoperat Neurophysiol, Boston, MA 02114 USA. RP Kilbride, RD (reprint author), Beaumont Hosp, Dept Clin Neurophysiol, Beaumont Rd, Dublin 9, Ireland. EM ronankilbride@beaumont.ie NR 14 TC 1 Z9 1 U1 1 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0736-0258 EI 1537-1603 J9 J CLIN NEUROPHYSIOL JI J. Clin. Neurophysiol. PD DEC PY 2013 VL 30 IS 6 BP 591 EP 596 DI 10.1097/01.wnp.0000436900.48243.9f PG 6 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 277KT UT WOS:000328818800004 PM 24300983 ER PT J AU Nair, DG AF Nair, Dinesh G. TI Intraoperative Mapping of Roots, Plexuses, and Nerves SO JOURNAL OF CLINICAL NEUROPHYSIOLOGY LA English DT Review DE Intraoperative mapping; Nerve roots; Plexus; Peripheral nerves; Triggered EMG; Nerve to nerve; MEP; SSEP ID PEDICLE SCREW PLACEMENT; SOMATOSENSORY-EVOKED POTENTIALS; ELECTRICAL-STIMULATION; CLINICAL CORRELATION; H-REFLEX; SURGERY; ELECTROMYOGRAPHY; INJURY; CORD; EMG AB The use of intraoperative mapping of neural structures has come to be an indispensable technique to prevent or minimize postoperative morbidity. In this article, I briefly mention its use in mapping nerve roots, plexuses, and peripheral nerves. The reader may find some mention of monitoring techniques, too, as monitoring and mapping are seldom done separately. I include the technical details of different mapping modalities, relevant anatomy, and clinical applications, as appropriate. C1 [Nair, Dinesh G.] Harvard Univ, Sch Med, Dept Neurol, Massachusetts Gen Hosp, Boston, MA 02115 USA. RP Nair, DG (reprint author), Massachusetts Gen Hosp, Dept Neurol, 55 Fruit St, Boston, MA 02114 USA. EM dnair@mgh.harvard.edu NR 61 TC 2 Z9 2 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0736-0258 EI 1537-1603 J9 J CLIN NEUROPHYSIOL JI J. Clin. Neurophysiol. PD DEC PY 2013 VL 30 IS 6 BP 613 EP 619 DI 10.1097/01.wnp.0000436893.23587.35 PG 7 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 277KT UT WOS:000328818800007 PM 24300986 ER PT J AU Shoup, TM Yokell, DL Rice, PA Jackson, RN Livni, E Johnson, KA Brady, TJ Vasdev, N AF Shoup, Timothy M. Yokell, Daniel L. Rice, Peter A. Jackson, Raul N. Livni, Eli Johnson, Keith A. Brady, Thomas J. Vasdev, Neil TI A concise radiosynthesis of the tau radiopharmaceutical, [F-18]T807 SO JOURNAL OF LABELLED COMPOUNDS & RADIOPHARMACEUTICALS LA English DT Article DE T807; tau; PET; fluorine-18 ID ALZHEIMERS-DISEASE; PET; DERIVATIVES; PATHOLOGY AB Fluorine-18 labeled 7-(6-fluoropyridin-3-yl)-5H-pyrido[4,3-b]indole ([F-18]T807) is a potent and selective agent for imaging paired helical filaments of tau and is among the most promising PET radiopharmaceuticals for this target in early clinical trials. The present study reports a simplified one-step method for the synthesis of [F-18]T807 that is broadly applicable for routine clinical production using a GE TRACERlab FXFN radiosynthesis module. Key facets of our optimized radiosynthesis include development and use of a more soluble protected precursor, tert-butyl 7-(6-nitropyridin-3-yl)-5H-pyrido[4,3-b]indole-5-carboxylate, as well as new HPLC separation conditions that enable a facile one-step synthesis. During the nucleophilic fluorinating reaction with potassium cryptand [F-18]fluoride (K[F-18]/K-222) in DMSO at 130 degrees C over 10min the precursor is concurrently deprotected. Formulated [F-18]T807 was prepared in an uncorrected radiochemical yield of 14 +/- 3%, with a specific activity of 216 +/- 60GBq/mu mol (5837 +/- 1621mCi/mu mol) at the end of synthesis (60min; n=3) and validated for human use. This methodology offers the advantage of faster synthesis in fewer steps, with simpler automation that we anticipate will facilitate widespread clinical use of [F-18]T807. Copyright (c) 2013 John Wiley & Sons, Ltd. C1 [Shoup, Timothy M.; Yokell, Daniel L.; Rice, Peter A.; Jackson, Raul N.; Livni, Eli; Johnson, Keith A.; Brady, Thomas J.; Vasdev, Neil] Massachusetts Gen Hosp, Div Nucl Med & Mol Imaging, Boston, MA 02114 USA. [Shoup, Timothy M.; Livni, Eli; Johnson, Keith A.; Brady, Thomas J.; Vasdev, Neil] Harvard Univ, Sch Med, Dept Radiol, Boston, MA 02114 USA. RP Vasdev, N (reprint author), Massachusetts Gen Hosp, 55 Fruit St,White 427, Boston, MA 02114 USA. EM vasdev.neil@mgh.harvard.edu FU NIA NIH HHS [P01 AG036694] NR 14 TC 22 Z9 22 U1 0 U2 7 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0362-4803 EI 1099-1344 J9 J LABELLED COMPD RAD JI J. Label. Compd. Radiopharm. PD DEC PY 2013 VL 56 IS 14 BP 736 EP 740 DI 10.1002/jlcr.3098 PG 5 WC Biochemical Research Methods; Chemistry, Medicinal; Chemistry, Analytical SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy; Chemistry GA 273RL UT WOS:000328553900009 PM 24339014 ER PT J AU Rabow, M Kvale, E Barbour, L Cassel, JB Cohen, S Jackson, V Luhrs, C Nguyen, V Rinaldi, S Stevens, D Spragens, L Weissman, D AF Rabow, Michael Kvale, Elizabeth Barbour, Lisa Cassel, J. Brian Cohen, Susan Jackson, Vicki Luhrs, Carol Vincent Nguyen Rinaldi, Simone Stevens, Donna Spragens, Lynn Weissman, David TI Moving Upstream: A Review of the Evidence of the Impact of Outpatient Palliative Care SO JOURNAL OF PALLIATIVE MEDICINE LA English DT Article ID QUALITY-OF-LIFE; MULTIDISCIPLINARY SYMPTOM CONTROL; RANDOMIZED CONTROLLED-TRIAL; CELL LUNG-CANCER; CLINICAL ONCOLOGY; AMERICAN SOCIETY; IMPROVE OUTCOMES; HEART-FAILURE; SHORT-TERM; DEATH AB Background: There is good evidence for the efficacy of inpatient palliative care in improving clinical care, patient and provider satisfaction, quality of life, and health care utilization. However, the evidence for the efficacy of nonhospice outpatient palliative care is less well known and has not been comprehensively reviewed. Objective: To review and assess the evidence of the impact of outpatient palliative care. Methods: Our study was a review of published, peer-reviewed outcomes research, including both observational studies and controlled trials of nonhospice outpatient palliative care services. We assessed patient, family caregiver, and clinician satisfaction; clinical outcomes including symptom management, quality of life, and mortality; and heath care utilization outcomes including readmission rates, hospice use, and cost. Results: Four well-designed randomized interventions as well as a growing body of nonrandomized studies indicate that outpatient palliative care services can: 1) improve patient satisfaction, 2) improve symptom control and quality of life, 3) reduce health care utilization, and 4) lengthen survival in a population of lung cancer patients. Conclusions: The available evidence supports the ongoing expansion of innovative outpatient palliative care service models throughout the care continuum to all patients with serious illness. C1 [Rabow, Michael] Univ Calif San Francisco, Dept Internal Med, San Francisco, CA 94143 USA. [Rabow, Michael; Kvale, Elizabeth; Barbour, Lisa; Cassel, J. Brian; Cohen, Susan; Jackson, Vicki; Luhrs, Carol; Vincent Nguyen; Rinaldi, Simone; Stevens, Donna; Spragens, Lynn; Weissman, David] Ctr Adv Palliat Care, Improving Outpatient Palliat Care IPAL OP, New York, NY USA. [Kvale, Elizabeth] Univ Alabama Birmingham, Ctr Palliat & Support Care, Birmingham, AL USA. [Barbour, Lisa] Kaiser Permanente, Dept Internal Med, Denver, CO USA. [Cassel, J. Brian] Virginia Commonwealth Univ, Massey Canc Ctr, Richmond, VA USA. [Cohen, Susan] NYU, Sch Med, Dept Gen Internal Med, New York, NY USA. [Jackson, Vicki; Rinaldi, Simone] Massachusetts Gen Hosp, Dept Palliat Med, Boston, MA 02114 USA. [Luhrs, Carol] Suny Downstate Med Ctr, Dept Med Oncol, Brooklyn, NY 11203 USA. [Vincent Nguyen] Hoag Med Ctr, Dept Palliat Care, Newport Beach, CA USA. [Stevens, Donna] Lehigh Valley Hlth Network, Allentown, PA USA. [Spragens, Lynn] Spragens & Associates LLC, Durham, NC USA. [Weissman, David] Med Coll Wisconsin, Dept Neoplast Dis, Milwaukee, WI 53226 USA. RP Rabow, M (reprint author), UCSF Mt Zion, 1545 Divisadero St,313, San Francisco, CA 94143 USA. EM mrabow@medicine.ucsf.edu NR 74 TC 47 Z9 47 U1 3 U2 18 PU MARY ANN LIEBERT, INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1096-6218 EI 1557-7740 J9 J PALLIAT MED JI J. Palliat. Med. PD DEC 1 PY 2013 VL 16 IS 12 BP 1540 EP 1549 DI 10.1089/jpm.2013.0153 PG 10 WC Health Care Sciences & Services SC Health Care Sciences & Services GA 269DD UT WOS:000328220000010 PM 24225013 ER PT J AU Dachman, AH Yee, J AF Dachman, Abraham H. Yee, Judy TI The Challenges of CT Colonography Reimbursement SO JOURNAL OF THE AMERICAN COLLEGE OF RADIOLOGY LA English DT Article DE CT colonography; colorectal cancer; technology adoption ID COMPUTED TOMOGRAPHIC COLONOGRAPHY; EXTRACOLONIC FINDINGS; COLORECTAL-CANCER; VIRTUAL COLONOSCOPY; ASYMPTOMATIC ADULTS; SCREENING POPULATION; ADENOMATOUS POLYPS; ECONOMIC-IMPACT; TASK-FORCE; ACCURACY AB CT colonography has been shown to be an effective method to screen for colorectal cancer. However, at present, full endorsement and reimbursement for screening CT colonography, particularly by the US Preventive Services Task Force and CMS, respectively, are absent, so this screening option is infrequently used, and optical colonoscopy remains the de facto standard screening option. The authors summarize the past accomplishments that led to the current state of reimbursement and outline the remaining challenges and road to full acceptance and reimbursement of screening CT colonography nationally. C1 [Dachman, Abraham H.] Univ Chicago, Med Ctr, Chicago, IL 60637 USA. [Yee, Judy] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Yee, Judy] San Francisco VA Med Ctr, San Francisco, CA USA. RP Dachman, AH (reprint author), Univ Chicago, Med Ctr, 5841 S Maryland Ave,MC 2026, Chicago, IL 60637 USA. EM andachma@uchicago.edu FU Hologic (Bedford, Massachusetts); UC Tech (Chicago, Illinois); Bracco (Milan, Italy); EchoPixel (Sunnyvale, California) FX Dr Dachman is an instructor of virtual colonoscopy courses for GE Healthcare (Milwaukee, Wisconsin) and receives royalties from Hologic (Bedford, Massachusetts) and UC Tech (Chicago, Illinois). Dr Yee has received research grants from Bracco (Milan, Italy) and EchoPixel (Sunnyvale, California) and is chair of the Colon Cancer Committee for the ACR (Reston, Virginia). NR 57 TC 5 Z9 6 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1546-1440 J9 J AM COLL RADIOL JI J. Am. Coll. Radiol. PD DEC PY 2013 VL 10 IS 12 BP 937 EP 942 DI 10.1016/j.jacr.2013.09.014 PG 6 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 277DX UT WOS:000328800300016 PM 24295944 ER PT J AU Dill, KE George, E Abbara, S Cummings, K Francois, CJ Gerhard-Herman, MD Gornik, HL Hanley, M Kalva, SP Kirsch, J Kramer, CM Majdalany, BS Moriarty, JM Oliva, IB Schenker, MP Strax, R Rybicki, FJ AF Dill, Karin E. George, Elizabeth Abbara, Suhny Cummings, Kristopher Francois, Christopher J. Gerhard-Herman, Marie D. Gornik, Heather L. Hanley, Michael Kalva, Sanjeeva P. Kirsch, Jacobo Kramer, Christopher M. Majdalany, Bill S. Moriarty, John M. Oliva, Isabel B. Schenker, Matthew P. Strax, Richard Rybicki, Frank J. TI ACR Appropriateness Criteria Imaging for Transcatheter Aortic Valve Replacement SO JOURNAL OF THE AMERICAN COLLEGE OF RADIOLOGY LA English DT Article DE Appropriateness criteria; transcatheter aortic valve replacement; aortic valve stenosis; magnetic resonance angiography; computed tomographic angiography; echocardiography ID MULTIDETECTOR COMPUTED-TOMOGRAPHY; VALVULAR HEART-DISEASE; CARDIOVASCULAR MAGNETIC-RESONANCE; COREVALVE REVALVING SYSTEM; LANDING ZONE CALCIFICATION; CORONARY CT ANGIOGRAPHY; INTRAVASCULAR ULTRASOUND; EAE/ASE RECOMMENDATIONS; ANNULUS DIMENSIONS; ROOT ANATOMY AB Although aortic valve replacement is the definitive therapy for severe aortic stenosis, almost half of patients with severe aortic stenosis are unable to undergo conventional aortic valve replacement because of advanced age, comorbidities, or prohibitive surgical risk. Treatment options have been recently expanded with the introduction of catheter-based implantation of a bioprosthetic aortic valve, referred to as transcatheter aortic valve replacement. Because this procedure is characterized by lack of exposure of the operative field, image guidance plays a critical role in preprocedural planning. This guideline document evaluates several preintervention imaging examinations that focus on both imaging at the aortic valve plane and planning in the supravalvular aorta and iliofemoral system. The ACR Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed every 2 years by a multidisciplinary expert panel. The guideline development and review include an extensive analysis of current medical literature from peer-reviewed journals and the application of a well-established consensus methodology (modified Delphi) to rate the appropriateness of imaging and treatment procedures by the panel. In those instances in which evidence is lacking or not definitive, expert opinion may be used to recommend imaging or treatment. C1 [Dill, Karin E.] Univ Chicago, Chicago, IL 60637 USA. [George, Elizabeth; Rybicki, Frank J.] Brigham & Womens Hosp, Appl Imaging Sci Lab, Boston, MA 02115 USA. [George, Elizabeth; Rybicki, Frank J.] Harvard Univ, Sch Med, Boston, MA USA. [Abbara, Suhny] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Cummings, Kristopher] Washington Univ, Sch Med, Mallinckrodt Inst Radiol, St Louis, MO USA. [Francois, Christopher J.] Univ Wisconsin, Madison, WI USA. [Gerhard-Herman, Marie D.; Schenker, Matthew P.] Brigham & Womens Hosp, Boston, MA 02115 USA. [Gerhard-Herman, Marie D.; Gornik, Heather L.; Kramer, Christopher M.] Amer Coll Cardiol, Washington, DC USA. [Gornik, Heather L.] Cleveland Clin, Cleveland, OH 44106 USA. [Hanley, Michael; Kramer, Christopher M.] Univ Virginia Hlth Syst, Charlottesville, VA USA. [Kalva, Sanjeeva P.] UT Southwestern Med Ctr, Dallas, TX USA. [Kirsch, Jacobo] Cleveland Clin, Weston, FL USA. [Majdalany, Bill S.] Ohio State Univ Hosp, Columbus, OH 43210 USA. [Moriarty, John M.] Univ Calif Los Angeles, Los Angeles, CA USA. [Oliva, Isabel B.] Univ Arizona, Coll Med, Tucson, AZ USA. [Strax, Richard] Greater Houston Radiol, Houston, TX USA. RP Rybicki, FJ (reprint author), Amer Coll Radiol, 1891 Preston White Dr, Reston, VA 20191 USA. EM FRYBICKI@PARTNERS.ORG NR 77 TC 7 Z9 7 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1546-1440 J9 J AM COLL RADIOL JI J. Am. Coll. Radiol. PD DEC PY 2013 VL 10 IS 12 BP 957 EP 965 DI 10.1016/j.jacr.2013.09.002 PG 9 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 277DX UT WOS:000328800300020 PM 24183748 ER PT J AU Dimopoulos, G Koulenti, D Blot, S Sakr, Y Anzueto, A Spies, C Violan, JS Kett, D Armaganidis, A Martin, C Vincent, JL AF Dimopoulos, George Koulenti, Despoina Blot, Stijn Sakr, Yasser Anzueto, Antonio Spies, Claudia Sole Violan, Jordi Kett, Daniel Armaganidis, Apostolos Martin, Claude Vincent, Jean Louis CA Extended Prevalence Infection TI Critically Ill Elderly Adults with Infection: Analysis of the Extended Prevalence of Infection in Intensive Care Study SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Article DE critically ill; age; infections ID REQUIRING VENTILATORY SUPPORT; BLOOD-STREAM INFECTIONS; MECHANICAL VENTILATION; NOSOCOMIAL INFECTIONS; RISK-FACTORS; OLD PATIENTS; UNIT; MORTALITY; AGE; EPIDEMIOLOGY AB ObjectivesTo determine the effect of age on patterns of infection and on outcomes in individuals with infection. DesignAnalysis of data from an international, observational, point-prevalence study: Extended Prevalence of Infection in Intensive Care (EPIC II). SettingIntensive care units (ICUs; N=1,265) in 75 countries. ParticipantsAll adults present in a participating ICU on May 8, 2007. Individuals with an infection were included and classified according to age (18-44, 45-64, 65-74, 75-84, 85). MeasurementsDemographic, physiological, bacteriological, and therapeutic data were collected on the day of the study. Outcome data were collected until hospital discharge or for 60days. ResultsOf the 13,796 adults enrolled in EPIC II, 7,087 (51.4%) had an infection. Of these, 330 (4.7%) were aged 85 and older, 1,405 (19.8%) were 75 to 84, 1,713 (24.2%) were 65 to 74, 2,358 (33.3%) were 45 to 64, and 1,281 (18.1%) were 18 to 44. Severity of illness did not differ between groups. Those aged 85 and older had fewer bloodstream infections than those younger than 75, fewer central nervous system infections than those who were younger than 65, and more abdominal infections than those who were younger than 45. A microbiological diagnosis was established less frequently in participants aged 85 and older than in younger participants. Gram-negative microorganisms were more frequently isolated in those aged 85 and older than in other groups. ICU and hospital mortality were significantly higher in participants aged 85 and older than in those who were younger than 65. ConclusionA large proportion of individuals in the ICU with infection are aged 65 and older. Patterns of infection, including site and type of microorganism, vary according to age. Being aged 85 and older was an independent risk factor for mortality in individuals in the ICU with infection. C1 [Dimopoulos, George; Koulenti, Despoina; Armaganidis, Apostolos] Attikon Univ Hosp, Dept Crit Care Med, Athens, Greece. [Blot, Stijn] Ghent Univ Hosp, Dept Internal Med, Ghent, Belgium. [Sakr, Yasser] Univ Jena, Dept Anesthesiol & Intens Care, Jena, Germany. [Anzueto, Antonio] Univ Texas Hlth Sci Ctr San Antonio, Dept Pulm & Crit Care, San Antonio, TX 78229 USA. [Anzueto, Antonio] Univ Texas Hlth Sci Ctr San Antonio, South Texas Vet Hlth Care Syst, San Antonio, TX 78229 USA. [Spies, Claudia] Charite, Campus Virchow Klinikum, Dept Anesthesiol & Intens Care, D-13353 Berlin, Germany. [Spies, Claudia] Charite, Campus Charite Mitte, D-13353 Berlin, Germany. [Sole Violan, Jordi] Hosp Dr Negrin, Intens Care Unit, Las Palmas Gran Canaria, Spain. [Kett, Daniel] Univ Miami, Miller Sch Med, Dept Med, Div Pulm & Crit Care, Miami, FL 33136 USA. [Kett, Daniel] Jackson Mem Hosp, Miami, FL 33136 USA. [Martin, Claude] Hosp Nord, Dept Anesthesiol & Intens Care, Marseille, France. [Vincent, Jean Louis] Univ Libre Brussels, Erasme Hosp, Dept Intens Care, Brussels, Belgium. RP Dimopoulos, G (reprint author), Univ Athens, Sch Med, Univ Hosp Attikon, Dept Crit Care, 1 Rimini Str, Athens 12462, Greece. EM gdimop@med.uoa.gr RI Sakr, Yasser/D-9802-2013; Koulenti, Despoina/D-4851-2010 OI Koulenti, Despoina/0000-0003-4364-2612 NR 35 TC 6 Z9 8 U1 0 U2 4 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 DEC PY 2013 VL 61 IS 12 BP 2065 EP 2071 DI 10.1111/jgs.12544 PG 7 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 271UB UT WOS:000328416000001 PM 24479140 ER PT J AU Shega, JW Andrew, M Kotwal, A Lau, DT Herr, K Ersek, M Weiner, DK Chin, MH Dale, W AF Shega, Joseph W. Andrew, Melissa Kotwal, Ashwin Lau, Denys T. Herr, Keela Ersek, Mary Weiner, Debra K. Chin, Marshall H. Dale, William TI Relationship Between Persistent Pain and 5-Year Mortality: A Population-Based Prospective Cohort Study SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Article DE pain; mortality; older adult ID DWELLING OLDER-ADULTS; LOW-BACK-PAIN; HEALTH-CARE UTILIZATION; COGNITIVE IMPAIRMENT; PHYSICAL FUNCTION; MANAGEMENT; PREVALENCE; FRAILTY; PEOPLE; OSTEOARTHRITIS AB ObjectivesTo assess the association between self-reported noncancer pain and 5-year mortality. DesignCohort. SettingCommunity-dwelling older adults. ParticipantsCanadian Study of Health and Aging 1996 wave. MeasurementsRegistrar of Vital Statistics-established 5-year mortality. Noncancer pain was assessed using the 5-point verbal descriptor scale, dichotomized into no or very mild versus moderate, severe, or very severe pain. Frailty was the accumulation of health deficits. Cognitive status (Modified Mini-Mental State Examination) and depressed mood (five-item mental health screening questionnaire) were also assessed. Multivariable logistic regression and Cox proportional hazards were used to analyze the relationship between pain and 5-year mortality. ResultsOf 5,703 participants, 4,694 (82.3%) had complete data for analysis; 1,663 of these (35.4%) reported moderate, severe, or very severe pain, and 1,343 (28.6%) had died at 5-year follow-up. Four hundred ninety-six of those who died (29.8%) reported moderate, severe, or very severe pain and 847 (27.9%) no or very mild pain. Multivariate logistic analysis found that individuals with moderate, severe, or very severe pain had lower odds of 5-year mortality than those with no or very mild pain (odds ratio=0.78, 95% confidence interval (CI)=0.66-0.92; P<.001). The risk of death was lower in persons reporting moderate or greater pain than in those with no or very mild pain (HR=0.85, 95% CI=0.75-0.96; P=.01). An interaction between pain and sex explained this effect. Men with pain were not significantly more likely than men without pain to die (HR=1.00, 95% CI=0.84-1.19; P=.99), whereas women without pain (HR=0.54, 95% CI=0.47-0.63; P<0.01) and women with pain (HR=0.40; CI=0.33-0.47; P<.01) had less risk of death than men without and with pain, respectively. ConclusionOlder women with pain were less likely to die within 5years than older women without pain, men in pain, or men without pain. C1 [Shega, Joseph W.; Kotwal, Ashwin; Dale, William] Univ Chicago, Sect Geriatr & Palliat Med, Chicago, IL 60637 USA. [Andrew, Melissa] Dalhousie Univ, Div Geriatr Med, Halifax, NS, Canada. [Lau, Denys T.] Ctr Dis Control & Prevent, Div Hlth Care Stat, Natl Ctr Hlth Stat, Atlanta, GA USA. [Lau, Denys T.] Univ Illinois, Coll Pharm, Dept Pharm Adm, Chicago, IL USA. [Herr, Keela] Univ Iowa, Coll Nursing, Iowa City, IA 52242 USA. [Ersek, Mary] Univ Penn, Sch Nursing, Philadelphia, PA 19104 USA. [Weiner, Debra K.] Univ Pittsburgh, Vet Affairs Pittsburgh Healthcare Syst, Geriatr Res Educ & Clin Ctr, Pittsburgh, PA USA. [Weiner, Debra K.] Univ Pittsburgh, Dept Med, Pittsburgh, PA USA. [Weiner, Debra K.] Univ Pittsburgh, Dept Psychiat, Pittsburgh, PA USA. [Weiner, Debra K.] Univ Pittsburgh, Dept Anesthesiol, Pittsburgh, PA USA. [Chin, Marshall H.] Univ Chicago, Gen Internal Med Sect, Chicago, IL 60637 USA. [Dale, William] Univ Chicago, Sect Hematol & Oncol, Chicago, IL 60637 USA. RP Shega, JW (reprint author), Univ Chicago, Sect Geriatr & Palliat Med, MC 6098,5841 S Maryland Ave, Chicago, IL 60637 USA. EM jshega@gmail.com FU National Health Research Development Program [6606-3954-MC(S)]; National Institute on Aging [K23AG029815]; Canadian Institutes of Health Research [MOP-62823]; National Institute of Diabetes and Digestive and Kidney Diseases Midcareer Investigator Award in Patient-Oriented Research [K24 DK071933]; Chicago Center for Diabetes Translation Research [P30 DK092949] FX All the data reported here were gathered using public funding from the National Health Research Development Program, which administrated a grant from the Seniors' Independence Research program (6606-3954-MC(S)). Funding for these analyses came from a career development award from the National Institute on Aging (K23AG029815) and from the Canadian Institutes of Health Research through an operating grant (MOP-62823). Dr. Chin was supported by a National Institute of Diabetes and Digestive and Kidney Diseases Midcareer Investigator Award in Patient-Oriented Research (K24 DK071933) and the Chicago Center for Diabetes Translation Research (P30 DK092949). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health, the National Institute on Aging, the Centers for Disease Control and Prevention, or the National Center for Health Statistics. NR 41 TC 4 Z9 4 U1 2 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 DEC PY 2013 VL 61 IS 12 BP 2135 EP 2141 DI 10.1111/jgs.12554 PG 7 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 271UB UT WOS:000328416000010 PM 24320761 ER PT J AU Reuben, DB Evertson, LC Wenger, NS Serrano, K Chodosh, J Ercoli, L Tan, ZS AF Reuben, David B. Evertson, Leslie C. Wenger, Neil S. Serrano, Katherine Chodosh, Joshua Ercoli, Linda Tan, Zaldy S. TI The University of California at Los Angeles Alzheimer's and Dementia Care Program for Comprehensive, Coordinated, Patient-Centered Care: Preliminary Data SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Article DE Alzheimer's disease; dementia; care coordination; caregiver support ID MANAGEMENT INTERVENTION; COGNITIVE IMPAIRMENT; CONTROLLED-TRIAL; OLDER-ADULTS; QUALITY; DISEASE; DEPRESSION; COMMUNITY; IMPROVE; MODELS AB Dementia is a chronic disease that requires medical and social services to provide high-quality care and prevent complications. As a result of time constraints in practice, lack of systems-based approaches, and poor integration of community-based organizations (CBOs), the quality of care for dementia is poorer than that for other diseases that affect older persons. The University of California at Los Angeles (UCLA) Alzheimer's and Dementia Care (UCLA ADC) program partners with CBOs to provide comprehensive, coordinated, patient-centered care for individuals with Alzheimer's disease and other dementias. The goals of the program are to maximize function, independence, and dignity; minimize caregiver strain and burnout; and reduce unnecessary costs. The UCLA ADC program consists of five core components: recruitment and a dementia registry, structured needs assessments of individuals in the registry and their caregivers, creation and implementation of individualized dementia care plans based on needs assessments and input from the primary care physicians, monitoring and revising care plans as needed, and around-the-clock access for assistance and advice. The program uses a comanagement model with a nurse practitioner Dementia Care Manager working with primary care physicians and CBOs. Based on the first 150 individuals served, the most common recommendations in the initial care plans were referrals to support groups (73%) and Alzheimer's Association Safe Return (73%), caregiver training (45%), and medication adjustment (41%). The program will be evaluated on its ability to achieve the triple aim of better care for individuals, better health for populations, and lower costs. C1 [Reuben, David B.; Evertson, Leslie C.; Serrano, Katherine; Tan, Zaldy S.] Univ Calif Los Angeles, David Geffen Sch Med, Multicampus Program Geriatr Med & Gerontol, Los Angeles, CA 90095 USA. [Wenger, Neil S.] Univ Calif Los Angeles, David Geffen Sch Med, Div Gen Internal Med & Hlth Serv Res, Los Angeles, CA 90095 USA. [Chodosh, Joshua] Vet Affairs Greater Los Angeles Healthcare Syst, Geriatr Res Educ & Clin Ctr, Los Angeles, CA USA. [Ercoli, Linda] Univ Calif Los Angeles, David Geffen Sch Med, Dept Psychiat, Div Geriatr Psychol, Los Angeles, CA 90095 USA. RP Reuben, DB (reprint author), Univ Calif Los Angeles, David Geffen Sch Med, 10945 Le Conte Ave,Suite 2339, Los Angeles, CA 90095 USA. EM dreuben@mednet.ucla.edu OI Chodosh, Joshua/0000-0001-7784-4306 FU Centers for Medicare and Medicaid Services [CMS-1C1-12-0001]; Centers for Medicare and Medicaid Innovation [1C1CMS330982-01-00]; UCLA Claude Pepper Older Americans Independence Center; National Institute on Aging [5P30AG028748] FX The project described was supported by Funding Opportunity CMS-1C1-12-0001 from Centers for Medicare and Medicaid Services (1C1CMS330982-01-00) Centers for Medicare and Medicaid Innovation and by the UCLA Claude Pepper Older Americans Independence Center, funded by the National Institute on Aging (5P30AG028748). The contents are solely the responsibility of the authors and do not necessarily represent the official views of HHS or any of its agencies. NR 20 TC 14 Z9 14 U1 5 U2 19 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 DEC PY 2013 VL 61 IS 12 BP 2214 EP 2218 DI 10.1111/jgs.12562 PG 5 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 271UB UT WOS:000328416000021 PM 24329821 ER PT J AU Mohler, JL Kantoff, PW Armstrong, AJ Bahnson, RR Cohen, M D'Amico, AV Eastham, JA Enke, CA Farrington, TA Higano, CS Horwitz, EM Kawachi, MH Kuettel, M Lee, RJ MacVicar, GR Malcolm, AW Miller, D Plimack, ER Pow-Sang, JM Richey, S Roach, M Rohren, E Rosenfeld, S Small, EJ Srinivas, S Stein, C Strope, SA Tward, J Walsh, PC Shead, DA Ho, M AF Mohler, James L. Kantoff, Philip W. Armstrong, Andrew J. Bahnson, Robert R. Cohen, Michael D'Amico, Anthony Victor Eastham, James A. Enke, Charles A. Farrington, Thomas A. Higano, Celestia S. Horwitz, Eric Mark Kawachi, Mark H. Kuettel, Michael Lee, Richard J. MacVicar, Gary R. Malcolm, Arnold W. Miller, David Plimack, Elizabeth R. Pow-Sang, Julio M. Richey, Sylvia Roach, Mack, III Rohren, Eric Rosenfeld, Stan Small, Eric J. Srinivas, Sandy Stein, Cy Strope, Seth A. Tward, Jonathan Walsh, Patrick C. Shead, Dorothy A. Ho, Maria TI Prostate Cancer, Version 1.2014 Featured Updates to the NCCN Guidelines SO JOURNAL OF THE NATIONAL COMPREHENSIVE CANCER NETWORK LA English DT Article ID CONTINUOUS ANDROGEN DEPRIVATION; RANDOMIZED-TRIALS; EMITTING RA-223; BONE METASTASIS; INTERMITTENT; THERAPY; FINNPROSTATE; SUPPRESSION; MANAGEMENT; ONCOLOGY AB The NCCN Guidelines for Prostate Cancer provide multidisciplinary recommendations on the clinical management of patients with prostate cancer. This report highlights notable recent updates. Radium-223 dichloride is a first-in-class radiopharmaceutical that recently received approval for the treatment of patients with symptomatic bone metastases and no known visceral disease. It received a category 1 recommendation as both a first-line and second-line option. The NCCN Prostate Cancer Panel also revised recommendations on the choice of intermittent or continuous androgen deprivation therapy based on recent phase III clinical data comparing the 2 strategies in the nonmetastatic and metastatic settings. C1 [Mohler, James L.; Kuettel, Michael] Roswell Pk Canc Inst, Buffalo, NY USA. [Bahnson, Robert R.] Ohio State Univ, Ctr Comprehens Canc, James Canc Hosp, Columbus, OH 43210 USA. [Bahnson, Robert R.] Solove Res Inst, Columbus, OH USA. [Cohen, Michael; Tward, Jonathan] Univ Utah, Huntsman Canc Inst, Salt Lake City, UT 84112 USA. [Eastham, James A.] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. [Higano, Celestia S.] Univ Washington, Seattle Canc Care Alliance, Seattle, WA 98195 USA. [Horwitz, Eric Mark; Plimack, Elizabeth R.] Fox Chase Canc Ctr, Philadelphia, PA 19111 USA. [Lee, Richard J.] Massachusetts Gen Hosp Canc Ctr, Boston, MA 02114 USA. [MacVicar, Gary R.] Northwestern Univ, Robert H Lurie Comprehens Canc Ctr, Evanston, IL 60208 USA. [Miller, David] Univ Michigan, Comprehens Canc Ctr, Ann Arbor, MI 48109 USA. [Richey, Sylvia] Univ Tennessee, Hlth Sci Ctr, St Jude Childrens Res Hosp, Knoxville, TN 37996 USA. [Rohren, Eric] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. [Srinivas, Sandy] Stanford Canc Inst, Stanford, CA USA. [Strope, Seth A.] Washington Univ, Sch Med, St Louis, MO 63130 USA. [Walsh, Patrick C.] Sidney Kimmel Comprehens Canc Ctr Johns Hopkins, Sidney, BC, Canada. RP Mohler, JL (reprint author), Roswell Pk Canc Inst, Buffalo, NY USA. OI Strope, Seth/0000-0002-5176-1550 FU Site PI for Active Biotech AB; Bristol-Myers Squibb Company; Dendreon Corporation; ImClone Systems Incorporated; Johnson & Johnson Services, Inc.; Medivation, Inc.; Pfizer Inc.; sanofi-aventis U. S. LLC; Exelixis Inc.; Millennium Pharmaceuticals, Inc. FX The following authors have disclosed the following relevant financial relationships: Dr. Armstrong: Site PI for Active Biotech AB; Bristol-Myers Squibb Company; Dendreon Corporation; ImClone Systems Incorporated; Johnson & Johnson Services, Inc.; Medivation, Inc.; Pfizer Inc.; and sanofi-aventis U. S. LLC. Steering committee member for Active Biotech AB; Bristol-Myers Squibb Company; Dendreon Corporation; and Medivation, Inc. Consultant for Active Biotech AB; Bristol-Myers Squibb Company; Dendreon Corporation; Ipsen; and sanofi-aventis U. S. LLC. Advisory board member for Amgen Inc.; Bayer HealthCare; Bristol-Myers Squibb Company. Site subinvestigator for Johnson & Johnson Services, Inc. and Pfizer Inc. Research collaborator for Johnson & Johnson Services, Inc. PI for Novartis Pharmaceuticals Corporation and KangLaiTe U. S. A. Inc. Speakers bureau member for Dendreon Corporation; Johnson & Johnson Services, Inc.; and sanofi-aventis U. S. LLC. Dr. Bahnson: PI for AVEO Pharmaceuticals, Inc. Advisory board member for AVEO Pharmaceuticals, Inc. Expert witness for Young, Ricchiuti, Caldwell, and Heller, LLC.; Dr. Higano: Site PI for Bayer HealthCare; Genentech, Inc.; and Aragon Pharmaceuticals Inc. Research support from Exelixis Inc.; Millennium Pharmaceuticals, Inc.; and Medivation, Inc. Data Safety Monitoring Board member for Millennium Pharmaceuticals, Inc. PI for Teva Pharmaceutical Industries Ltd. Advisory board member for Abbott Laboratories; Bayer HealthCare; Genentech, Inc.; Johnson & Johnson Services, Inc.; Millennium Pharmaceuticals, Inc.; Ferring Pharmaceuticals; Medivation, Inc.; and Pfizer Inc. Steering committee member for Dendreon Corporation and Veridex, LLC. NR 27 TC 46 Z9 50 U1 0 U2 7 PU HARBORSIDE PRESS PI COLD SPRING HARBOR PA 37 MAIN ST, COLD SPRING HARBOR, NY 11724 USA SN 1540-1405 EI 1540-1413 J9 J NATL COMPR CANC NE JI J. Natl. Compr. Cancer Netw. PD DEC PY 2013 VL 11 IS 12 BP 1471 EP 1479 PG 9 WC Oncology SC Oncology GA 274XH UT WOS:000328639000005 PM 24335682 ER PT J AU Darbousset, R Thomas, G Mezouar, S Renne, T Mackman, N Dignat-George, F Panicot-Dubois, L Dubois, C AF Darbousset, R. Thomas, G. Mezouar, S. Renne, T. Mackman, N. Dignat-George, F. Panicot-Dubois, L. Dubois, C. TI Tissue factor expressing neutrophils initiate coagulation on injured vessel walls SO JOURNAL OF THROMBOSIS AND HAEMOSTASIS LA English DT Meeting Abstract DE intravital microscopy; Neutrophils; thrombus formation; Tissue factor C1 [Darbousset, R.; Mezouar, S.; Dignat-George, F.; Panicot-Dubois, L.; Dubois, C.] Aix Marseille Univ, Inserm UMR S1076, Marseille, France. [Thomas, G.] Harvard Univ, Sch Med, Immune Dis Inst, Boston, MA USA. [Renne, T.] Karolinska Inst, Dept Mol Med & Surg, Stockholm, Sweden. [Renne, T.] Karolinska Inst, Ctr Mol Med, Stockholm, Sweden. [Renne, T.] St Gorans Univ Hosp, S-11281 Stockholm, Sweden. [Mackman, N.] Univ N Carolina, Dept Med, Chapel Hill, NC USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1538-7933 EI 1538-7836 J9 J THROMB HAEMOST JI J. Thromb. Haemost. PD DEC PY 2013 VL 11 SU 3 SI SI BP 3 EP 3 PG 1 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA 265BL UT WOS:000327924600008 ER PT J AU Zwicker, J Liebman, HA Bauer, KA Caughey, T Rosovsky, R Mantha, S Kessler, CM Eneman, J Raghavan, V Lenz, HJ Bullock, A Buchbinder, E Campigotto, F Neuberg, D Furie, B AF Zwicker, J. Liebman, H. A. Bauer, K. A. Caughey, T. Rosovsky, R. Mantha, S. Kessler, C. M. Eneman, J. Raghavan, V Lenz, H. J. Bullock, A. Buchbinder, E. Campigotto, F. Neuberg, D. Furie, B. TI A randomized-controlled phase II trial of primary thromboprophylaxis with enoxaparin in cancer patients with elevated tissue factor bearing microparticles (the microtec study) SO JOURNAL OF THROMBOSIS AND HAEMOSTASIS LA English DT Meeting Abstract DE cancer thrombosis; lmwh; tissue factor bearing microparticles C1 [Zwicker, J.; Bauer, K. A.; Furie, B.] Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Div Hemostasis Thrombosis, Boston, MA 02215 USA. [Liebman, H. A.] Univ So Calif, Los Angeles, CA USA. [Caughey, T.] Mt Auburn Hosp, Cambridge, England. [Rosovsky, R.] Harvard Univ, Sch Med, Div Hematol Oncol, MGH, Boston, MA USA. [Mantha, S.] Lahey Clin Fdn, Div Hematol Oncol, Burlington, MA USA. [Kessler, C. M.] Georgetown Univ, Med Ctr, Lombardi Comprehens Canc Ctr, Washington, DC 20007 USA. [Eneman, J.] York Hosp, York, N Yorkshire, England. [Raghavan, V] Harvard Univ, Sch Med, Mt Auburn Hosp, Cambridge, MA 02138 USA. [Lenz, H. J.] Univ So Calif, Keck Sch Med, Los Angeles, CA 90033 USA. [Buchbinder, E.] Harvard Univ, Sch Med, Div Hematol Oncol, Beth Israel Deaconess Med Ctr, Cambridge, MA 02138 USA. [Campigotto, F.; Neuberg, D.] Dana Farber Harvard Canc Ctr, Dept Biostat & Computat Biol, Boston, MA USA. NR 0 TC 1 Z9 1 U1 1 U2 1 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 DEC PY 2013 VL 11 SU 3 SI SI BP 6 EP 6 PG 1 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA 265BL UT WOS:000327924600014 ER PT J AU Vogt, D Smith, BN King, LA King, DW Knight, J Vasterling, JJ AF Vogt, Dawne Smith, Brian N. King, Lynda A. King, Daniel W. Knight, Jeffrey Vasterling, Jennifer J. TI Deployment Risk and Resilience Inventory-2 (DRRI-2): An Updated Tool for Assessing Psychosocial Risk and Resilience Factors Among Service Members and Veterans SO JOURNAL OF TRAUMATIC STRESS LA English DT Article ID PSYCHOLOGICAL-ASSESSMENT; CONTENT VALIDITY; STRESS; EXPERIENCES; MILITARY; FEMALE; SCALE AB The Deployment Risk and Resilience Inventory (DRRI) is a widely used instrument for assessing deployment-related risk and resilience factors among war veterans. A revision of this instrument was recently undertaken to enhance the DRRI's applicability across a variety of deployment-related circumstances and military subgroups. The resulting suite of 17 distinct DRRI-2 scales is the product of a multiyear psychometric endeavor that involved (a) focus groups with Operation Enduring Freedom/Operation Iraqi Freedom (OEF/OIF) veterans to inform an assessment of the content validity of original DRRI measures, (b) examination of item and scale characteristics of revised scales in a national sample of 469 OEF/OIF veterans, and (c) administration of refined scales to a second national sample of 1,046 OEF/OIF veterans to confirm their psychometric quality. Both classical test theory and item response theory analytical strategies were applied to inform major revisions, which included updating the coverage of warfare-related stressors, expanding the assessment of family factors throughout the deployment cycle, and shortening scales. Finalized DRRI-2 scales demonstrated strong internal consistency reliability and criterion-related validity. The DRRI-2 can be applied to examine the role that psychosocial factors play in postdeployment health and inform interventions aimed at reducing risk and enhancing resilience among war veterans. C1 [Vogt, Dawne; Smith, Brian N.; King, Lynda A.] VA Boston Healthcare Syst, Natl Ctr PTSD, Womens Hlth Sci Div, Boston, MA 02130 USA. [Vogt, Dawne; Smith, Brian N.; King, Lynda A.; King, Daniel W.; Knight, Jeffrey; Vasterling, Jennifer J.] Boston Univ, Sch Med, Dept Psychiat, Boston, MA 02118 USA. [King, Lynda A.; King, Daniel W.] Boston Univ, Sch Med, Dept Psychol, Boston, MA 02118 USA. [King, Daniel W.; Knight, Jeffrey; Vasterling, Jennifer J.] VA Boston Healthcare Syst, Natl Ctr PTSD, Behav Sci Div, Boston, MA 02130 USA. [Vasterling, Jennifer J.] VA Boston Healthcare Syst, Psychol Serv, Boston, MA 02130 USA. RP Vogt, D (reprint author), VA Boston Healthcare Syst, Natl Ctr PTSD 116B 3, 150 South Huntington Ave, Boston, MA 02130 USA. EM Dawne.Vogt@va.gov NR 23 TC 29 Z9 29 U1 5 U2 26 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0894-9867 EI 1573-6598 J9 J TRAUMA STRESS JI J. Trauma Stress PD DEC PY 2013 VL 26 IS 6 BP 710 EP 717 DI 10.1002/jts.21868 PG 8 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA 273WL UT WOS:000328566900009 PM 24490250 ER PT J AU Miller, MW Wolf, EJ Hein, C Prince, L Reardon, AF AF Miller, Mark W. Wolf, Erika J. Hein, Christina Prince, Lauren Reardon, Annemarie F. TI Psychological Effects of the Marathon Bombing on Boston-Area Veterans With Posttraumatic Stress Disorder SO JOURNAL OF TRAUMATIC STRESS LA English DT Article AB This study examined the psychological impact of the Boston Marathon bombing using data from an ongoing longitudinal study of Boston-area veterans with posttraumatic stress disorder (PTSD; N = 71). Participants were assessed by telephone within 1 week of the end of the event; 42.3% of participants reported being personally affected by the bombings and/or the manhunt that followed. The majority of them reported that the bombing reminded them of their own traumas and/or caused other emotional distress. Examination of change in posttraumatic stress disorder (PTSD) symptoms from a prebombing assessment an average of 2months earlier to 1 week after the event revealed no significant change in symptoms across the sample as a whole. However, examination of patterns of change at the individual level revealed significant correlations (r = .33; p = .005) between distress at the time of the event and change in total PTSD symptom severity, with this effect accounted for primarily by increases in intrusion and avoidance symptoms (rs = .35 and .31, ps = .002 and .008, respectively). Findings of this study should raise awareness of the potential impact of terror attacks, mass shootings, and other events of this type on the well-being of individuals with histories of trauma and/or pre-existing PTSD. C1 [Miller, Mark W.; Wolf, Erika J.; Hein, Christina; Prince, Lauren; Reardon, Annemarie F.] VA Boston Healthcare Syst, Natl Ctr PTSD, Boston, MA 02130 USA. [Miller, Mark W.; Wolf, Erika J.] Boston Univ, Sch Med, Dept Psychiat, Boston, MA 02118 USA. RP Miller, MW (reprint author), VA Boston Healthcare Syst, Natl Ctr PTSD 116B 2, 150 South Huntington Ave, Boston, MA 02130 USA. EM mark.miller5@va.gov RI Miller, Mark/G-7322-2011; OI Miller, Mark/0000-0001-6393-8563; Wolf, Erika/0000-0003-2666-2435 FU CSRD VA [I01 CX000431] NR 8 TC 5 Z9 6 U1 1 U2 8 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0894-9867 EI 1573-6598 J9 J TRAUMA STRESS JI J. Trauma Stress PD DEC PY 2013 VL 26 IS 6 BP 762 EP 766 DI 10.1002/jts.21865 PG 5 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA 273WL UT WOS:000328566900015 PM 24343753 ER PT J AU Iverson, KM Mercado, R Carpenter, SL Street, AE AF Iverson, Katherine M. Mercado, Rowena Carpenter, Sarah L. Street, Amy E. TI Intimate Partner Violence Among Women Veterans: Previous Interpersonal Violence as a Risk Factor SO JOURNAL OF TRAUMATIC STRESS LA English DT Article ID SEXUAL-ABUSE; HEALTH; TRAUMA; REVICTIMIZATION; VALIDATION; HISTORY AB Experiences of abuse during childhood or military service may increase women veterans' risk for intimate partner violence (IPV) victimization. This study examined the relative impact of 3 forms of interpersonal violence exposure (childhood physical abuse [CPA], childhood sexual abuse [CSA], and unwanted sexual experiences during military service) and demographic and military characteristics on past-year IPV among women veterans. Participants were 160 female veteran patients at Veterans Afffairs hospitals in New England who completed a paper-and-pencil mail survey that included validated assessments of past-year IPV and previous interpersonal violence exposures. Women who reported CSA were 3.06 times, 95% confidence interval (CI) [1.14, 8.23], more likely to report past-year IPV relative to women who did not experience CSA. Similarly, women who reported unwanted sexual experiences during military service were 2.33 times, 95% CI [1.02, 5.35], more likely to report past-year IPV compared to women who did not report such experiences. CPA was not associated with IPV risk. Having less education and having served in the Army (vs. other branches) were also associated with greater risk of experiencing IPV in the past year. Findings have implications for assisting at risk women veterans in reducing their risk for IPV through detection and intervention efforts. C1 [Iverson, Katherine M.; Street, Amy E.] VA Boston Healthcare Syst, Natl Ctr PTSD, Boston, MA 02130 USA. [Iverson, Katherine M.; Street, Amy E.] Boston Univ, Sch Med, Dept Psychiat, Boston, MA 02118 USA. [Mercado, Rowena] VA Boston Healthcare Syst, Harvard South Shore Psychiat Residency Program, Boston, MA 02130 USA. [Mercado, Rowena] Harvard Univ, Sch Med, Boston, MA USA. [Carpenter, Sarah L.] Suffolk Univ, Dept Psychol, Boston, MA 02114 USA. RP Iverson, KM (reprint author), VA Boston Healthcare Syst, 150 S Huntington Ave 116B-3, Boston, MA 02130 USA. EM katherine.iverson@va.gov NR 18 TC 7 Z9 7 U1 0 U2 14 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0894-9867 EI 1573-6598 J9 J TRAUMA STRESS JI J. Trauma Stress PD DEC PY 2013 VL 26 IS 6 BP 767 EP 771 DI 10.1002/jts.21867 PG 5 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA 273WL UT WOS:000328566900016 PM 24243652 ER PT J AU Lehavot, K Der-Martirosian, C Simpson, TL Shipherd, JC Washington, DL AF Lehavot, Keren Der-Martirosian, Claudia Simpson, Tracy L. Shipherd, Jillian C. Washington, Donna L. TI The Role of Military Social Support in Understanding the Relationship Between PTSD, Physical Health, and Healthcare Utilization in Women Veterans SO JOURNAL OF TRAUMATIC STRESS LA English DT Article ID STRESS; VA; SYMPTOMATOLOGY; SYMPTOMS; SERVICES; TRAUMA; RISK AB Posttraumatic stress disorder (PTSD) is a significant predictor of both poorer physical health and increased health care utilization, whereas adequate social support is associated with better physical health and less health care utilization. However, research has not previously examined the simultaneous effects of PTSD and social support on health and health care utilization. This study examined both the independent and interactive effects of PTSD and a particular type of social support (postactive-duty social support from military friends) on self-reported physical health and number of Veterans Health Administration (VHA) visits in the last year. These relationships were examined in a representative, national sample of 3,524 women veterans who completed telephone interviews as part of the National Survey of Women Veterans in 2008-2009. Regression analyses were conducted using these cross-sectional data to examine main effects of PTSD and military social support on physical health and VHA utilization and their interaction. Screening positive for PTSD was associated with poorer health (B= -3.19, SE= 1.47) and increased VHA utilization (B= 0.98, SE= 0.16), whereas greater military social support was associated with better health (B= 0.97, SE= 0.44) and less frequent VHA utilization (B= -0.15, SE= 0.05). Neither moderation model was significant, such that military social support behaved in a similar way regardless of PTSD status. C1 [Lehavot, Keren; Simpson, Tracy L.] VA Puget Sound Hlth Care Syst, Seattle, WA USA. [Lehavot, Keren; Simpson, Tracy L.] Univ Washington, Dept Psychiat & Behav Sci, Seattle, WA 98195 USA. [Der-Martirosian, Claudia] VEMEC, Dept Vet Affairs, North Hills, CA USA. [Shipherd, Jillian C.] Natl Ctr PTSD, Womens Hlth Sci Div, Boston, MA USA. [Shipherd, Jillian C.] VA Boston Healthcare Syst, Boston, MA USA. [Shipherd, Jillian C.] Boston Univ, Sch Med, Boston, MA 02118 USA. [Shipherd, Jillian C.] VA Patient Care Serv LGBT Program, Washington, DC USA. [Washington, Donna L.] CSHIIP, VA Greater Los Angeles Hlth Serv Res & Dev HSR&D, Sepulveda, CA USA. [Washington, Donna L.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Med, Los Angeles, CA 90095 USA. RP Lehavot, K (reprint author), 1660 S Columbian Way S-116 POC, Seattle, WA 98108 USA. EM klehavot@uw.edu NR 21 TC 6 Z9 6 U1 3 U2 12 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0894-9867 EI 1573-6598 J9 J TRAUMA STRESS JI J. Trauma Stress PD DEC PY 2013 VL 26 IS 6 BP 772 EP 775 DI 10.1002/jts.21859 PG 4 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA 273WL UT WOS:000328566900017 PM 24203114 ER PT J AU Sloan, DM Lee, DJ Litwack, SD Sawyer, AT Marx, BP AF Sloan, Denise M. Lee, Daniel J. Litwack, Scott D. Sawyer, Alice T. Marx, Brian P. TI Written Exposure Therapy for Veterans Diagnosed with PTSD: A Pilot Study SO JOURNAL OF TRAUMATIC STRESS LA English DT Article ID POSTTRAUMATIC-STRESS-DISORDER; COGNITIVE PROCESSING THERAPY; RANDOMIZED CLINICAL-TRIAL; DISCLOSURE; VICTIMS AB There is a need to identify alternative treatment options for posttraumatic stress disorder (PTSD), especially among veterans where PTSD tends to be more difficult to treat and dropout rates are especially high. One potential alternative is written exposure therapy, a brief intervention shown to treat PTSD among civilians effectively. This study investigated the feasibility and tolerability of written exposure therapy in an uncontrolled trial with a sample of 7 male veterans diagnosed with PTSD. Findings indicated that written exposure therapy was well tolerated and well received. Only 1 of the 7 veterans dropped out of treatment, no adverse events occurred during the course of treatment, and veterans provided high treatment satisfaction ratings. Clinically significant improvements in PTSD symptom severity were observed for 4 veterans at posttreatment and 6 veterans at the 3-month follow up. Moreover, 5 of the 7 veterans no longer met diagnostic criteria for PTSD 3 months following treatment. These findings suggest that written exposure therapy holds promise as a brief, well tolerated treatment for veterans with PTSD. However, additional research using randomized controlled trial methodology is needed to confirm its efficacy. C1 [Sloan, Denise M.; Marx, Brian P.] VA Natl Ctr PTSD, Boston, MA USA. [Sloan, Denise M.; Lee, Daniel J.; Litwack, Scott D.; Sawyer, Alice T.; Marx, Brian P.] VA Boston Healthcare Syst, Boston, MA 02130 USA. [Sloan, Denise M.; Lee, Daniel J.; Sawyer, Alice T.; Marx, Brian P.] Boston Univ, Sch Med, Dept Psychiat, Boston, MA 02118 USA. RP Sloan, DM (reprint author), VA Boston Healthcare Syst, Natl Ctr PTSD 116B 2, 150 S Huntington Ave, Boston, MA 02130 USA. EM Denise.Sloan@va.gov FU NIMH NIH HHS [R34 MH077658, R34MH077658-02] NR 24 TC 1 Z9 1 U1 1 U2 13 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0894-9867 EI 1573-6598 J9 J TRAUMA STRESS JI J. Trauma Stress PD DEC PY 2013 VL 26 IS 6 BP 776 EP 779 DI 10.1002/jts.21858 PG 4 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA 273WL UT WOS:000328566900018 PM 24203914 ER PT J AU Frigerio, A Bhama, PK Tan, OT AF Frigerio, Alice Bhama, Prabhat K. Tan, Oon T. TI Quantitative Three-Dimensional Assessment of Port-Wine Stain Clearance After Laser Treatments SO LASERS IN SURGERY AND MEDICINE LA English DT Article DE port-wine stain; laser photocoagulation; 3dMD ID PULSED DYE-LASER; STURGE-WEBER SYNDROME; PHOTOTHERMOLYSIS AB Background and Objectives: Outcomes analysis of laser treatment for port-wine stains (PWS) has been hampered by the lack of an objective measure of surface area and volume; moreover, treatment success is often gauged by clinician subjective assessment. Three-dimensional (3D) surface imaging has been applied in several medical disciplines to quantify surface changes, with promising results. We hypothesized that 3D surface imaging could be used to objectively measure changes in area and volume of PWS following laser treatment. Study Design/Materials and Methods: We performed a retrospective review of consecutive patients with PWS treated over a 20-month time period. Area and volume of the lesions were measured using 3dMD photogrammetric software (3dMD; Atlanta, GA) before and after a series of sequential pulsed dye laser and/or alexandrite laser treatments. Results: Fifty-five patients with 59 PWS were included in the study. The initial average measured area was 45.6cm(2); final average measured area decreased to 34.6cm(2) (P < 0.001). The average volume change was 1.20ml for all PWS included in the study and 1.90ml for lesions that received at least five laser treatments within the study period. Conclusion: Three-dimensional photography demonstrated area and volume changes in patients with PWS after laser treatments. Future studies to determine if statistically significant changes correlate with clinically appreciable changes are warranted. Lasers Surg. Med. 45:633-638, 2013. (c) 2013 Wiley Periodicals, Inc. C1 [Frigerio, Alice; Tan, Oon T.] Harvard Univ, Massachusetts Eye & Ear Infirm, Carolyn & Peter Lynch Ctr Laser & Reconstruct Sur, Sch Med, Boston, MA 02114 USA. [Bhama, Prabhat K.] Harvard Univ, Massachusetts Eye & Ear Infirm, Div Facial Plast & Reconstruct Surg, Med Sch,Dept Otol & Laryngol, Boston, MA 02114 USA. RP Frigerio, A (reprint author), Harvard Univ, Massachusetts Eye & Ear Infirm, Carolyn & Peter Lynch Ctr Laser & Reconstruct Sur, Sch Med, 243 Charles St, Boston, MA 02114 USA. EM alice_frigerio@meei.harvard.edu OI Frigerio, Alice/0000-0001-9202-9553 NR 17 TC 0 Z9 1 U1 1 U2 4 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 DEC PY 2013 VL 45 IS 10 BP 633 EP 638 DI 10.1002/lsm.22176 PG 6 WC Dermatology; Surgery SC Dermatology; Surgery GA 270VX UT WOS:000328348400003 PM 24339253 ER PT J AU Cirstea, D Hideshima, T Santo, L Eda, H Mishima, Y Nemani, N Hu, Y Mimura, N Cottini, F Gorgun, G Ohguchi, H Suzuki, R Loferer, H Munshi, NC Anderson, KC Raje, N AF Cirstea, D. Hideshima, T. Santo, L. Eda, H. Mishima, Y. Nemani, N. Hu, Y. Mimura, N. Cottini, F. Gorgun, G. Ohguchi, H. Suzuki, R. Loferer, H. Munshi, N. C. Anderson, K. C. Raje, N. TI Small-molecule multi-targeted kinase inhibitor RGB-286638 triggers P53-dependent and -independent anti-multiple myeloma activity through inhibition of transcriptional CDKs SO LEUKEMIA LA English DT Article DE myeloma; p53; transcription; CDKs; apoptosis ID RNA-POLYMERASE-II; CYCLIN-DEPENDENT KINASES; TERMINAL DOMAIN; P53; EXPRESSION; MDM2; PATHWAY; PATHOGENESIS; ROSCOVITINE; ACTIVATION AB Small-molecule multi-targeted cyclin-dependent kinase (CDK) inhibitors (CDKIs) are of particular interest due to their potent antitumor activity independent of p53 gene alterations. P53 deletion is associated with a very poor prognosis in multiple myeloma (MM). In this regard, we tested the anti-MM activity of RGB-286638, an indenopyrazole-derived CDKI with Ki-nanomolar activity against transcriptional CDKs. We examined RGB-286638' s mode-of-action in MM cell lines with wild-type (wt)-p53 and those expressing mutant p53. RGB-286638 treatment resulted in MM cytotoxicity in vitro associated with inhibition of MM tumor growth and prolonged survival in vivo. RGB-286638 displayed caspase-dependent apoptosis in both wt-p53 and mutant-p53 cells that was closely associated with the downregulation of RNA polymerase II phosphorylation and inhibition of transcription. RGB-286638 triggered p53 accumulation via nucleolar stress and loss of Mdm2, accompanied by induction of p53 DNA-binding activity. In addition, RGB-286638 mediated p53-independent activity, which was confirmed by cytotoxicity in p53-knockdown and p53-mutant cells. We also demonstrated downregulation of oncogenic miR-19, miR-92a-1 and miR-21. Our data provide the rationale for the development of transcriptional CDKIs as therapeutic agents, which activate p53 in competent cells, while circumventing p53 deficiency through alternative p53-independent cell death mechanisms in p53-mutant/ deleted cells. C1 [Cirstea, D.; Santo, L.; Eda, H.; Mishima, Y.; Nemani, N.; Raje, N.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, MGH Canc Ctr, Boston, MA 02114 USA. [Cirstea, D.; Hideshima, T.; Hu, Y.; Mimura, N.; Cottini, F.; Gorgun, G.; Ohguchi, H.; Suzuki, R.; Munshi, N. C.; Anderson, K. C.; Raje, N.] Dana Farber Canc Inst, Leebow Inst Myeloma Therapeut, Boston, MA 02115 USA. [Cirstea, D.; Hideshima, T.; Hu, Y.; Mimura, N.; Cottini, F.; Gorgun, G.; Ohguchi, H.; Suzuki, R.; Munshi, N. C.; Anderson, K. C.; Raje, N.] Dana Farber Canc Inst, Jerome Lipper Multiple Myeloma Dis Ctr, Boston, MA 02115 USA. RP Raje, N (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, MGH Canc Ctr, POB 216,55 Fruit St, Boston, MA 02114 USA. EM nraje@partners.org FU Grant CDA SPORE; NIH/NCI [P50 CA100707] FX This study was supported by Grant CDA SPORE and NIH/NCI Grant no. P50 CA100707. RGB-286638 compound was provided by Agennix USA Inc. NR 41 TC 17 Z9 17 U1 0 U2 8 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 DEC PY 2013 VL 27 IS 12 BP 2366 EP 2375 DI 10.1038/leu.2013.194 PG 10 WC Oncology; Hematology SC Oncology; Hematology GA 272KX UT WOS:000328460600012 PM 23807770 ER PT J AU Shampo, MA Kyle, RA Steensma, DP AF Shampo, Marc A. Kyle, Robert A. Steensma, David P. TI Alois Alzheimer-Alzheimer Disease SO MAYO CLINIC PROCEEDINGS LA English DT Editorial Material C1 [Shampo, Marc A.; Kyle, Robert A.] Mayo Clin, Rochester, MN 55905 USA. [Steensma, David P.] Dana Farber Canc Inst, Boston, MA 02115 USA. RP Shampo, MA (reprint author), Mayo Clin, Rochester, MN 55905 USA. NR 0 TC 1 Z9 1 U1 3 U2 7 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0025-6196 EI 1942-5546 J9 MAYO CLIN PROC JI Mayo Clin. Proc. PD DEC PY 2013 VL 88 IS 12 BP E155 EP E155 DI 10.1016/j.mayocp.2013.01.031 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA 258TG UT WOS:000327481000004 PM 24290132 ER PT J AU Mistry, H Hsieh, G Buhrlage, SJ Huang, M Park, E Cuny, GD Galinsky, I Stone, RM Gray, NS D'Andrea, AD Parmar, K AF Mistry, Helena Hsieh, Grace Buhrlage, Sara J. Huang, Min Park, Eunmi Cuny, Gregory D. Galinsky, Ilene Stone, Richard M. Gray, Nathanael S. D'Andrea, Alan D. Parmar, Kalindi TI Small-Molecule Inhibitors of USP1 Target ID1 Degradation in Leukemic Cells SO MOLECULAR CANCER THERAPEUTICS LA English DT Article ID FANCONI-ANEMIA PATHWAY; LOOP-HELIX PROTEINS; CROSS-LINK REPAIR; DEUBIQUITINATING ENZYME; CANCER CELLS; TRANSCRIPTIONAL REGULATOR; INDUCED APOPTOSIS; ID-1 PROTEIN; IN-VIVO; COMPLEX AB Inhibitor of DNA binding 1 (ID1) transcription factor is essential for the proliferation and progression of many cancer types, including leukemia. However, the ID1 protein has not yet been therapeutically targeted in leukemia. ID1 is normally polyubiquitinated and degraded by the proteasome. Recently, it has been shown that USP1, a ubiquitin-specific protease, deubiquitinates ID1 and rescues it from proteasome degradation. Inhibition of USP1 therefore offers a new avenue to target ID1 in cancer. Here, using a ubiquitin- rhodamine- based high-throughput screening, we identified small-molecule inhibitors of USP1 and investigated their therapeutic potential for leukemia. These inhibitors blocked the deubiquitinating enzyme activity of USP1 in vitro in a dose-dependent manner with an IC50 in the high nanomolar range. USP1 inhibitors promoted the degradation of ID1 and, concurrently, inhibited the growth of leukemic cell lines in a dose-dependent manner. A known USP1 inhibitor, pimozide, also promoted ID1 degradation and inhibited growth of leukemic cells. In addition, the growth of primary acute myelogenous leukemia (AML) patient-derived leukemic cells was inhibited by a USP1 inhibitor. Collectively, these results indicate that the novel small-molecule inhibitors of USP1 promote ID1 degradation and are cytotoxic to leukemic cells. The identification of USP1 inhibitors therefore opens up a new approach for leukemia therapy. (C)2013 AACR. C1 [Mistry, Helena; Hsieh, Grace; Huang, Min; Park, Eunmi; D'Andrea, Alan D.; Parmar, Kalindi] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Radiat Oncol, Boston, MA 02215 USA. [Buhrlage, Sara J.; Gray, Nathanael S.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02215 USA. [Galinsky, Ilene; Stone, Richard M.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02215 USA. [Cuny, Gregory D.] Brigham & Womens Hosp, Harvard Ctr Neurodegenerat & Repair, Lab Drug Discovery Neurodegenerat, Cambridge, MA USA. [Cuny, Gregory D.] Harvard Univ, Sch Med, Cambridge, MA 02138 USA. RP Parmar, K (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Div Genom Stabil & DNA Repair,Dept Radiat Oncol, 450 Brookline Ave, Boston, MA 02215 USA. EM alan_dandrea@dfci.harvard.edu; Kalindi_Parmar@dfci.harvard.edu OI huang, min/0000-0001-6735-1612 FU Leukemia & Lymphoma Society [6237-13]; NIH [1RC4 DK090913-01, 2P01HL048546, 2RO1 DK43889, 5R37HL52725-18] FX This research was supported by a Translational Research Grant from the Leukemia & Lymphoma Society (6237-13) and the NIH grants (1RC4 DK090913-01, 2P01HL048546, 2RO1 DK43889, and 5R37HL52725-18; to A. D. D'Andrea). NR 50 TC 29 Z9 29 U1 1 U2 8 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 DEC PY 2013 VL 12 IS 12 BP 2651 EP 2662 DI 10.1158/1535-7163.MCT-13-0103-T PG 12 WC Oncology SC Oncology GA 272UK UT WOS:000328486600004 PM 24130053 ER PT J AU Janzen, DM Paik, DY Rosales, MA Yep, B Cheng, DH Witte, ON Kayadibi, H Ryan, CM Jung, ME Faull, K Memarzadeh, S AF Janzen, Deanna M. Paik, Daniel Y. Rosales, Miguel A. Yep, Brian Cheng, Donghui Witte, Owen N. Kayadibi, Huseyin Ryan, Christopher M. Jung, Michael E. Faull, Kym Memarzadeh, Sanaz TI Low Levels of Circulating Estrogen Sensitize PTEN-Null Endometrial Tumors to PARP Inhibition In Vivo SO MOLECULAR CANCER THERAPEUTICS LA English DT Article ID BREAST-CANCER CELLS; POLY(ADP-RIBOSE) POLYMERASE; PHASE-I; HOMOLOGOUS RECOMBINATION; MUTANT-CELLS; CARCINOMA; RECURRENT; OLAPARIB; EXPRESSION; AROMATASE AB Earlier in vitro work demonstrated that PARP inhibition induces cell death in PTEN-null endometrial cancer cell lines, but the in vivo therapeutic efficacy of these agents against endometrial cancer remains unknown. Here, we test the efficacy of AZD2281 (olaparib), an oral PARP inhibitor, in the therapy of PTEN-null endometrial tumors in a preclinical endometrial cancer mouse model. Primary endometrial tumors were generated by epithelial loss of PTEN using an in vivo model. This model recapitulates epithelial-specific loss of PTEN seen in human tumors, and histologically resembles endometrioid carcinomas, the predominant subtype of human endometrial cancers. Olaparib was administered orally to tumor-bearing mice in two hormonal extremes: high or low estrogen. Olaparib treatment achieved a significant reduction in tumor size in a low estrogenic milieu. In striking contrast, no response to olaparib was seen in tumors exposed to high levels of estrogen. Two key observations were made when estrogen levels were dropped: (i) the serum concentration of olaparib was significantly increased, resulting in sustained PARP inhibition at the tumor bed; and (ii) the homologous recombination pathway was compromised, as evidenced by decreased Rad51 protein expression and function. These two mechanisms may account for the sensitization of PTEN-null tumors to olaparib with estrogen deprivation. Results of this preclinical trial suggest that orally administered PARP inhibitors in a low estrogenic hormonal milieu can effectively target PTEN-null endometrial tumors. Extension of this work to clinical trials could personalize the therapy of women afflicted with advanced endometrial cancer using well-tolerated orally administered therapeutic agents. (C)2013 AACR. C1 [Janzen, Deanna M.; Paik, Daniel Y.; Rosales, Miguel A.; Yep, Brian; Memarzadeh, Sanaz] Univ Calif Los Angeles, David Geffen Sch Med, Dept Obstet & Gynecol, Los Angeles, CA 90095 USA. [Witte, Owen N.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Mol & Med Pharmacol, Los Angeles, CA 90095 USA. [Kayadibi, Huseyin; Ryan, Christopher M.; Faull, Kym] Univ Calif Los Angeles, David Geffen Sch Med, Dept Psychiat & Biobehav Sci, Los Angeles, CA 90095 USA. [Witte, Owen N.] Univ Calif Los Angeles, Dept Microbiol Immunol & Mol Genet, Los Angeles, CA 90095 USA. [Jung, Michael E.] Univ Calif Los Angeles, Dept Chem & Biochem, Los Angeles, CA 90095 USA. [Memarzadeh, Sanaz] VA Greater Los Angeles Hlth Care Syst, Los Angeles, CA USA. [Witte, Owen N.; Memarzadeh, Sanaz] Univ Calif Los Angeles, Eli & Edythe Broad Ctr Regenerat Med & Stem Cell, Los Angeles, CA 90095 USA. [Cheng, Donghui; Witte, Owen N.] Univ Calif Los Angeles, Howard Hughes Med Inst, Los Angeles, CA 90095 USA. RP Memarzadeh, S (reprint author), Univ Calif Los Angeles, 555 Westwood Plaza,Level B,Box 957243,1015 Terasa, Los Angeles, CA 90095 USA. EM smemarzadeh@mednet.ucla.edu FU Concern foundation; CDU/UCLA NIH/NCI [U54-CA-143931]; VA CDA-2 Award; Scholars in Translational Medicine Program; Mary Kay Foundation Award; STOP Cancer Award; Broad Stem Cell Research Center Research Award; Sidney Kimmel Foundation award; National Center for Research Resources Grant [UL1TR000124]; University of California Cancer Research Coordinating Committee FX This work was financially supported by the Concern foundation, CDU/UCLA NIH/NCI Grant #U54-CA-143931, VA CDA-2 Award, Scholars in Translational Medicine Program, Mary Kay Foundation Award, STOP Cancer Award, Broad Stem Cell Research Center Research Award, Sidney Kimmel Foundation award, National Center for Research Resources Grant UL1TR000124, and the University of California Cancer Research Coordinating Committee grant to S. Memarzadeh. O.N. Witte is an Investigator of the Howard Hughes Medical Institute. NR 50 TC 9 Z9 10 U1 0 U2 4 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 DEC PY 2013 VL 12 IS 12 BP 2917 EP 2928 DI 10.1158/1535-7163.MCT-13-0572 PG 12 WC Oncology SC Oncology GA 272UK UT WOS:000328486600028 PM 24222661 ER PT J AU Okun, MS Weintraub, D AF Okun, Michael S. Weintraub, Daniel TI Should Impulse Control Disorders and Dopamine Dysregulation Syndrome Be Indications for Deep Brain Stimulation and Intestinal Levodopa? SO MOVEMENT DISORDERS LA English DT Article ID PARKINSONS-DISEASE; SUBTHALAMIC STIMULATION; COMPULSIVE BEHAVIORS; NUCLEUS-ACCUMBENS; MANAGEMENT; ADDICTION; MEDICATION; MECHANISMS; AMANTADINE; RELEASE C1 [Okun, Michael S.] Univ Florida, Ctr Movement Disorders & Neurorestorat, Dept Neurol, Gainesville, FL 32610 USA. [Okun, Michael S.] Univ Florida, Ctr Movement Disorders & Neurorestorat, Dept Neurosurg, Gainesville, FL 32610 USA. [Weintraub, Daniel] Univ Penn, Dept Psychiat, Perelman Sch Med, Philadelphia, PA 19104 USA. [Weintraub, Daniel] Philadelphia Vet Affairs Med Ctr, Parkinsons Dis Res Educ & Clin Ctr, Philadelphia, PA USA. RP Okun, MS (reprint author), Univ Florida, J Hillis Miller Hlth Ctr, Dept Neurol, 100 S Newell Dr,Room L3-101, Gainesville, FL 32610 USA. EM okun@neurology.ufl.edu OI Okun, Michael/0000-0002-6247-9358 FU NINDS NIH HHS [K23 NS044997] NR 49 TC 7 Z9 7 U1 0 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 DEC PY 2013 VL 28 IS 14 BP 1915 EP 1919 DI 10.1002/mds.25735 PG 5 WC Clinical Neurology SC Neurosciences & Neurology GA 264TB UT WOS:000327902400003 PM 24243803 ER PT J AU DeMuth, PC Li, AV Abbink, P Liu, JY Li, HL Stanley, KA Smith, KM Lavine, CL Seaman, MS Kramer, JA Miller, AD Abraham, W Suh, H Elkhader, J Hammond, PT Barouch, DH Irvine, DJ AF DeMuth, Peter C. Li, Adrienne V. Abbink, Peter Liu, Jinyan Li, Hualin Stanley, Kelly A. Smith, Kaitlin M. Lavine, Christy L. Seaman, Michael S. Kramer, Joshua A. Miller, Andrew D. Abraham, Wuhbet Suh, Heikyung Elkhader, Jamal Hammond, Paula T. Barouch, Dan H. Irvine, Darrell J. TI Vaccine delivery with microneedle skin patches in nonhuman primates SO NATURE BIOTECHNOLOGY LA English DT Letter ID HUMANS; MODELS; DRUG C1 [DeMuth, Peter C.; Li, Adrienne V.; Abraham, Wuhbet; Suh, Heikyung; Elkhader, Jamal; Irvine, Darrell J.] MIT, Dept Biol Engn, Cambridge, MA 02139 USA. [DeMuth, Peter C.; Abraham, Wuhbet; Suh, Heikyung; Hammond, Paula T.; Irvine, Darrell J.] MIT, Koch Inst Integrat Canc Res, Cambridge, MA 02139 USA. [Abbink, Peter; Liu, Jinyan; Li, Hualin; Stanley, Kelly A.; Smith, Kaitlin M.; Lavine, Christy L.; Seaman, Michael S.; Barouch, Dan H.] Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Ctr Virol & Vaccine Res, Boston, MA 02215 USA. [Kramer, Joshua A.; Miller, Andrew D.] Harvard Univ, Sch Med, New England Primate Res Ctr, Southborough, MA 01772 USA. [Abraham, Wuhbet; Suh, Heikyung] MIT, Dept Mat Sci & Engn, Cambridge, MA 02139 USA. [Hammond, Paula T.] MIT, Dept Chem Engn, Cambridge, MA 02139 USA. [Hammond, Paula T.; Irvine, Darrell J.] MIT, Inst Soldier Nanotechnol, Cambridge, MA 02139 USA. [Barouch, Dan H.; Irvine, Darrell J.] Ragon Inst Massachusetts Gen Hosp MIT & Harvard, Charlestown, MA USA. [Irvine, Darrell J.] Howard Hughes Med Inst, Chevy Chase, MD USA. RP DeMuth, PC (reprint author), MIT, Dept Biol Engn, 77 Massachusetts Ave, Cambridge, MA 02139 USA. EM hammond@mit.edu; dbarouch@bidmc.harvard.edu; djirvine@mit.edu FU Howard Hughes Medical Institute; NCI NIH HHS [P30 CA014051]; NIAID NIH HHS [AI095109, AI060354, AI078526, AI095985, AI096040, P30 AI060354, R01 AI095109, U19 AI078526, U19 AI095985, U19 AI096040] NR 12 TC 16 Z9 16 U1 5 U2 41 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1087-0156 EI 1546-1696 J9 NAT BIOTECHNOL JI Nat. Biotechnol. PD DEC PY 2013 VL 31 IS 12 BP 1082 EP 1085 DI 10.1038/nbt.2759 PG 5 WC Biotechnology & Applied Microbiology SC Biotechnology & Applied Microbiology GA 269OW UT WOS:000328251900018 PM 24316643 ER PT J AU Mendenhall, EM Williamson, KE Reyon, D Zou, JY Ram, O Joung, JK Bernstein, BE AF Mendenhall, Eric M. Williamson, Kaylyn E. Reyon, Deepak Zou, James Y. Ram, Oren Joung, J. Keith Bernstein, Bradley E. TI Locus-specific editing of histone modifications at endogenous enhancers SO NATURE BIOTECHNOLOGY LA English DT Article ID GENE-EXPRESSION; TAL EFFECTORS; GENOME; DNA; CHROMATIN; TRANSCRIPTION; DEMETHYLATION; ELEMENTS; REGIONS; CELLS AB Mammalian gene regulation is dependent on tissue-specific enhancers that can act across large distances to influence transcriptional activity(1-3). Mapping experiments have identified hundreds of thousands of putative enhancers whose functionality is supported by cell type-specific chromatin signatures and striking enrichments for disease-associated sequence variants(4-11). However, these studies did not address the in vivo functions of the putative elements or their chromatin states and did not determine which genes, if any, a given enhancer regulates. Here we present a strategy to investigate endogenous regulatory elements by selectively altering their chromatin state using programmable reagents. Transcription activator-like (TAL) effector repeat domains fused to the LSD1 histone demethylase efficiently remove enhancer-associated chromatin modifications from target loci, without affecting control regions. We find that inactivation of enhancer chromatin by these fusion proteins frequently causes downregulation of proximal genes, revealing enhancer target genes. Our study demonstrates the potential of epigenome editing tools to characterize an important class of functional genomic elements. C1 [Mendenhall, Eric M.; Williamson, Kaylyn E.; Zou, James Y.; Ram, Oren; Bernstein, Bradley E.] Howard Hughes Med Inst, Chevy Chase, MD USA. [Mendenhall, Eric M.; Williamson, Kaylyn E.; Reyon, Deepak; Zou, James Y.; Ram, Oren; Joung, J. Keith; Bernstein, Bradley E.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Mendenhall, Eric M.; Williamson, Kaylyn E.; Reyon, Deepak; Zou, James Y.; Ram, Oren; Joung, J. Keith; Bernstein, Bradley E.] Massachusetts Gen Hosp, Ctr Canc Res, Boston, MA 02114 USA. [Mendenhall, Eric M.; Williamson, Kaylyn E.; Reyon, Deepak; Zou, James Y.; Ram, Oren; Joung, J. Keith; Bernstein, Bradley E.] Harvard Univ, Sch Med, Boston, MA USA. [Mendenhall, Eric M.; Williamson, Kaylyn E.; Zou, James Y.; Ram, Oren; Bernstein, Bradley E.] Broad Inst Harvard & MIT, Cambridge, MA USA. [Mendenhall, Eric M.; Williamson, Kaylyn E.; Ram, Oren; Bernstein, Bradley E.] Massachusetts Gen Hosp, Ctr Syst Biol, Boston, MA 02114 USA. [Zou, James Y.] Harvard Univ, Sch Engn & Appl Sci, Cambridge, MA 02138 USA. RP Bernstein, BE (reprint author), Howard Hughes Med Inst, Chevy Chase, MD USA. EM bernstein.bradley@mgh.harvard.edu OI Mendenhall, Eric/0000-0002-7395-6295 FU Howard Hughes Medical Institute; National Human Genome Research Institute's ENCODE Project [U54 HG004570, U54 HG006991]; US National Institutes of Health Common Fund for Epigenomics [U01 ES017155]; NIH [DP1 GM105378, P50 HG005550]; Jim and Ann Orr MGH Research Scholar Award FX We thank members of the Bernstein laboratory and the Broad Institute's Epigenomics Program and for constructive comments and criticisms. We thank N. Shoresh, S. Kadri, M. Guttman and M. Garber for assistance with analysis. This research was supported by the Howard Hughes Medical Institute (to B.E.B.), the National Human Genome Research Institute's ENCODE Project U54 HG004570, U54 HG006991 (to B.E.B.), US National Institutes of Health Common Fund for Epigenomics U01 ES017155 (to B. E.B.), NIH Director's Pioneer Award DP1 GM105378 (to J.K.J.), NIH P50 HG005550 (to J.K.J.), and the Jim and Ann Orr MGH Research Scholar Award (to J.K.J.). NR 31 TC 155 Z9 160 U1 6 U2 51 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1087-0156 EI 1546-1696 J9 NAT BIOTECHNOL JI Nat. Biotechnol. PD DEC PY 2013 VL 31 IS 12 BP 1133 EP + DI 10.1038/nbt.2701 PG 5 WC Biotechnology & Applied Microbiology SC Biotechnology & Applied Microbiology GA 269OW UT WOS:000328251900027 PM 24013198 ER PT J AU Maeder, ML Angstman, JF Richardson, ME Linder, SJ Cascio, VM Tsai, SQ Ho, QH Sander, JD Reyon, D Bernstein, BE Costello, JF Wilkinson, MF Joung, JK AF Maeder, Morgan L. Angstman, James F. Richardson, Marcy E. Linder, Samantha J. Cascio, Vincent M. Tsai, Shengdar Q. Ho, Quan H. Sander, Jeffry D. Reyon, Deepak Bernstein, Bradley E. Costello, Joseph F. Wilkinson, Miles F. Joung, J. Keith TI Targeted DNA demethylation and activation of endogenous genes using programmable TALE-TET1 fusion proteins SO NATURE BIOTECHNOLOGY LA English DT Article ID IN-VIVO; MAMMALIAN DEVELOPMENT; CYTOSINE METHYLATION; TET PROTEINS; CELLS; 5-CARBOXYLCYTOSINE; 5-METHYLCYTOSINE; SEQUENCES; METHYLTRANSFERASES; 5-FORMYLCYTOSINE AB Genome-wide studies have defined cell type-specific patterns of DNA methylation(1) that are important for regulating gene expression in both normal development(2) and disease(3). However, determining the functional significance of specific methylation events remains challenging, owing to the lack of methods for removing such modifications in a targeted manner. Here we describe an approach for efficient targeted demethylation of specific CpGs in human cells using fusions of engineered transcription activator-like effector (TALE) repeat arrays and the TET1 hydroxylase catalytic domain. Using these TALE-TET1 fusions, we demonstrate that modification of critical methylated promoter CpG positions can lead to substantial increases in the expression of endogenous human genes. Our results delineate a strategy for understanding the functional significance of specific CpG methylation marks in the context of endogenous gene loci and validate programmable DNA demethylation reagents with potential utility for research and therapeutic applications. C1 [Maeder, Morgan L.; Angstman, James F.; Linder, Samantha J.; Cascio, Vincent M.; Tsai, Shengdar Q.; Ho, Quan H.; Sander, Jeffry D.; Reyon, Deepak; Bernstein, Bradley E.; Joung, J. Keith] Massachusetts Gen Hosp, Dept Pathol, Charlestown, MA USA. [Maeder, Morgan L.; Angstman, James F.; Linder, Samantha J.; Cascio, Vincent M.; Tsai, Shengdar Q.; Ho, Quan H.; Sander, Jeffry D.; Reyon, Deepak; Bernstein, Bradley E.; Joung, J. Keith] Massachusetts Gen Hosp, Ctr Canc Res, Charlestown, MA USA. [Maeder, Morgan L.; Angstman, James F.; Linder, Samantha J.; Cascio, Vincent M.; Tsai, Shengdar Q.; Sander, Jeffry D.; Reyon, Deepak; Joung, J. Keith] Massachusetts Gen Hosp, Ctr Computat & Integrat Biol, Charlestown, MA USA. [Maeder, Morgan L.; Joung, J. Keith] Harvard Univ, Sch Med, Program Biol & Biomed Sci, Boston, MA USA. [Angstman, James F.] Harvard Univ, Dept Mol & Cellular Biol, Grad Program Mol Cells & Organisms, Cambridge, MA 02138 USA. [Richardson, Marcy E.; Wilkinson, Miles F.] Univ Calif San Diego, Sch Med, Dept Reprod Med, San Diego, CA 92103 USA. [Tsai, Shengdar Q.; Sander, Jeffry D.; Reyon, Deepak; Bernstein, Bradley E.; Joung, J. Keith] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. [Bernstein, Bradley E.] Howard Hughes Med Inst, Chevy Chase, MD USA. [Bernstein, Bradley E.] Broad Inst Harvard & MIT, Cambridge, MA USA. [Costello, Joseph F.] Univ Calif San Francisco, Dept Neurol Surg, San Francisco, CA USA. [Wilkinson, Miles F.] Univ Calif San Diego, Inst Genom Med, San Diego, CA 92103 USA. RP Joung, JK (reprint author), Massachusetts Gen Hosp, Dept Pathol, Charlestown, MA USA. EM jjoung@partners.org FU National Institutes of Health (NIH) [DP1 GM105378, P50 HG005550, R01 HD053808, R01 HD045595, R01 CA169316, F32 GM105189, P30 NS45776]; Defense Advanced Research Projects Agency (DARPA) [W911NF-11-2-0056]; Karen Osney Brownstein Endowed Chair; Jim and Ann Orr Massachusetts General Hospital (MGH) Research Scholar Award; US National Science Foundation Graduate Research Fellowship FX This work was supported by a National Institutes of Health (NIH) Director's Pioneer Award DP1 GM105378 (to J.K.J.), NIH P50 HG005550 (to J.K.J.), NIH R01 HD053808 (to M.F.W.), NIH R01 HD045595 (to M.F.W.), NIH R01 CA169316 (to J.F.C.), NIH F32 GM105189 (to S.Q.T.), Defense Advanced Research Projects Agency (DARPA) W911NF-11-2-0056 (to J.K.J.), the Karen Osney Brownstein Endowed Chair (to J.F.C.), the Jim and Ann Orr Massachusetts General Hospital (MGH) Research Scholar Award (to J.K.J.) and a US National Science Foundation Graduate Research Fellowship (to M. L. M.). We thank the MGH Nucleic Acid Quantitation Core (supported by NIH P30 NS45776) for use of their real-time PCR machine. NR 32 TC 158 Z9 164 U1 5 U2 31 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1087-0156 EI 1546-1696 J9 NAT BIOTECHNOL JI Nat. Biotechnol. PD DEC PY 2013 VL 31 IS 12 BP 1137 EP + DI 10.1038/nbt.2726 PG 8 WC Biotechnology & Applied Microbiology SC Biotechnology & Applied Microbiology GA 269OW UT WOS:000328251900028 PM 24108092 ER PT J AU Weimer, MB Macey, TA Nicolaidis, C Dobscha, SK Duckart, JP Morasco, BJ AF Weimer, Melissa B. Macey, Tara A. Nicolaidis, Christina Dobscha, Steven K. Duckart, Jonathan P. Morasco, Benjamin J. TI Sex Differences in the Medical Care of VA Patients with Chronic Non-Cancer Pain SO PAIN MEDICINE LA English DT Article DE Chronic Pain; Veteran Women; Sex Differences; Chronic Opioid Therapy ID HEALTH-CARE; MUSCULOSKELETAL PAIN; OPIOID THERAPY; WOMEN VETERANS; PREVALENCE; GENDER; POPULATION; FIBROMYALGIA; MANAGEMENT; MEN AB ObjectiveDespite a growing number of women seeking medical care in the veterans affairs (VA) system, little is known about the characteristics of their chronic pain or the pain care they receive. This study sought to determine if sex differences are present in the medical care veterans received for chronic pain. DesignRetrospective cohort study using VA administrative data. SubjectsThe subjects were 17,583 veteran patients with moderate to severe chronic non-cancer pain treated in the Pacific Northwest during 2008. MethodsMultivariate logistic regression assessed for sex differences in primary care utilization, prescription of chronic opioid therapy, visits to emergency departments for a pain-related diagnosis, and physical therapy referral. ResultsCompared with male veterans, female veterans were more often diagnosed with two or more pain conditions, and had more of the following pain-related diagnoses: fibromyalgia, low back pain, inflammatory bowel disease, migraine headache, neck or joint pain, and arthritis. After adjustment for demographic characteristics, pain diagnoses, mental health diagnoses, substance use disorders, and medical comorbidity, women had lower odds of being prescribed chronic opioid therapy (adjusted OR [AOR] 0.67, 95% CI 0.58-0.78), greater odds of visiting an emergency department for a pain-related complaint (AOR 1.40, 95% CI 1.18-1.65), and greater odds of receiving physical therapy (AOR 1.19, 95% CI 1.05-1.33). Primary care utilization was not significantly different between sexes. ConclusionsSex differences are present in the care female veterans receive for chronic pain. Further research is necessary to understand the etiology of the observed differences and their associations with clinical outcomes. C1 [Weimer, Melissa B.; Nicolaidis, Christina] Oregon Hlth & Sci Univ, Dept Med, Portland, OR 97239 USA. [Macey, Tara A.; Dobscha, Steven K.; Morasco, Benjamin J.] Oregon Hlth & Sci Univ, Dept Psychiat, Portland, OR 97239 USA. [Nicolaidis, Christina] Oregon Hlth & Sci Univ, Dept Publ Hlth & Prevent Med, Portland, OR 97239 USA. [Dobscha, Steven K.; Morasco, Benjamin J.] Portland VA Med Ctr, Mental Hlth & Clin Neurosci Div, Portland, OR USA. [Dobscha, Steven K.; Duckart, Jonathan P.; Morasco, Benjamin J.] Portland VA Med Ctr, Portland Ctr Study Chron Comorbid Mental & Phys D, Portland, OR USA. RP Weimer, MB (reprint author), Oregon Hlth & Sci Univ, 3181 SW Sam Jackson Pk Rd,L-475, Portland, OR 97239 USA. EM weimerm@ohsu.edu FU National Institute of Drug Abuse [K23DA023467]; Oregon Clinical and Translational Research Institute (OCTRI) from the National Center for Advancing Translational Sciences (NCATS), a component of the National Institutes of Health (NIH) [UL1 RR024140] FX The authors wish to thank Michael R. Lasarev, MS, for help with statistical consultation. This study was supported in part by award K23DA023467 from the National Institute of Drug Abuse to Dr. Morasco. This publication was made possible with support from the Oregon Clinical and Translational Research Institute (OCTRI), grant number UL1 RR024140 from the National Center for Advancing Translational Sciences (NCATS), a component of the National Institutes of Health (NIH). Dr. Weimer's time was supported by the Samuel F. Wise Trust. The content of this manuscript is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health, National Institute on Drug Abuse, or the Department of Veterans Affairs. NR 33 TC 8 Z9 8 U1 1 U2 4 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1526-2375 EI 1526-4637 J9 PAIN MED JI Pain Med. PD DEC PY 2013 VL 14 IS 12 BP 1839 EP 1847 DI 10.1111/pme.12177 PG 9 WC Medicine, General & Internal SC General & Internal Medicine GA 270WH UT WOS:000328349400008 PM 23802846 ER PT J AU Edelman, EJ Gordon, KS Lo Re, V Skanderson, M Fiellin, DA Justice, AC AF Edelman, E. Jennifer Gordon, Kirsha S. Lo Re, Vincent, III Skanderson, Melissa Fiellin, David A. Justice, Amy C. CA VACS Project Team TI Acetaminophen receipt among HIV-infected patients with advanced hepatic fibrosis SO PHARMACOEPIDEMIOLOGY AND DRUG SAFETY LA English DT Article DE acetaminophen; HIV; hepatitis C; Veterans; medication; pharmacoepidemiology ID PRESCRIPTION PATTERNS; LIVER-DISEASE; OVERDOSE; COHORT; PAIN AB PurposeHIV-infected patients may be at particular risk for acetaminophen-induced hepatotoxicity, but acetaminophen use in the context of liver injury has been incompletely examined among HIV-infected patients. Among a sample of HIV-infected patients, we aimed to determine acetaminophen exposure, assess the cross-sectional association between acetaminophen exposure and advanced hepatic fibrosis, and determine whether factors associated with acetaminophen exposure varied by HCV status. MethodsWe conducted a cross-sectional analysis of the Veterans Aging Cohort Study. Advanced hepatic fibrosis was defined as a FIB-4>3.25, a composite score calculated based on age, alanine aminotransferase, aspartate aminotransferase, and platelet count. Multivariable ordered polytomous logistic regression was used to determine the association between FIB-4 status and acetaminophen exposure stratified by HCV status. ResultsAmong HIV-infected patients (n=14885), 31% received at least one acetaminophen prescription. Among those receiving acetaminophen, acetaminophen overuse was common among both HIV-monoinfected and HIV/HCV-coinfected patients (846 [31%] vs 596[32%], p=0.79). After stratifying by HCV status, those with evidence of advanced liver fibrosis were equally likely to be exposed to acetaminophen. Furthermore, HIV-monoinfected patients with an alcohol use disorder were more likely to have acetaminophen overuse (OR [95%CI]=1.56 [1.21-2.02]). ConclusionsStrategies to minimize acetaminophen exposure, especially for HIV-monoinfected patients, are warranted. Copyright (c) 2013 John Wiley & Sons, Ltd. C1 [Edelman, E. Jennifer; Fiellin, David A.; Justice, Amy C.] Yale Univ, Sch Med, Dept Med, New Haven, CT 06520 USA. [Edelman, E. Jennifer; Fiellin, David A.; Justice, Amy C.] Yale Univ, Sch Publ Hlth, Ctr Interdisciplinary Res AIDS, New Haven, CT 06520 USA. [Gordon, Kirsha S.; Skanderson, Melissa; Justice, Amy C.] VA Connecticut Healthcare Syst, West Haven, CT USA. [Lo Re, Vincent, III] Univ Penn, Dept Med, Div Infect Dis, Perelman Sch Med, Philadelphia, PA 19104 USA. [Lo Re, Vincent, III] Univ Penn, Perelman Sch Med, Ctr Clin Epidemiol & Biostat, Philadelphia, PA 19104 USA. [Skanderson, Melissa] VA Pittsburgh Healthcare Syst, Pittsburgh, PA USA. RP Edelman, EJ (reprint author), Yale Univ, Sch Med, POB 208093, New Haven, CT 06520 USA. EM ejennifer.edelman@yale.edu RI Lo Re, Vincent/N-7817-2015; OI Fiellin, David/0000-0002-4006-010X FU Society of General Internal Medicine's Lawrence Linn Award; Robert Wood Johnson Foundation Clinical Scholars Program; Department of Veterans Affairs; Veterans Aging Cohort study; National Institute on Alcohol Abuse and Alcoholism [U10 AA 13566] FX This work was generously supported by the Society of General Internal Medicine's Lawrence Linn Award, the Robert Wood Johnson Foundation Clinical Scholars Program, the Department of Veterans Affairs, and the Veterans Aging Cohort study, funded by the National Institute on Alcohol Abuse and Alcoholism (U10 AA 13566). NR 19 TC 3 Z9 4 U1 1 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 DEC PY 2013 VL 22 IS 12 BP 1352 EP 1356 DI 10.1002/pds.3517 PG 5 WC Public, Environmental & Occupational Health; Pharmacology & Pharmacy SC Public, Environmental & Occupational Health; Pharmacology & Pharmacy GA 258GG UT WOS:000327446700014 PM 24285468 ER PT J AU de Melo, WDMA Lee, AN Perussi, JR Hamblin, MR AF Martins Antunes de Melo, Wanessa de Cassia Lee, Alexander N. Perussi, Janice Rodrigues Hamblin, Michael R. TI Electroporation enhances antimicrobial photodynamic therapy mediated by the hydrophobic photosensitizer, hypericin SO PHOTODIAGNOSIS AND PHOTODYNAMIC THERAPY LA English DT Article DE Antimicrobial photodynamic therapy; Hypericin; Electroporation; E. coli; S. aureus ID IN-VITRO; INFECTIONS AB The effective transport of photosensitizers (PS) across the membrane and the intracellular accumulation of PS are the most crucial elements in antimicrobial photodynamic therapy (aPDT). However, due to the morphological complexity of Gram-negative bacteria the penetration of PS is limited, especially hydrophobic PS. Electroporation (EP) could increase the effectiveness of aPDT, by promoting the formation of transient pores that enhance the permeability of the bacterial membrane to PS. In this study we evaluated the combination of aPDT mediated by the hydrophobic PS, hypericin and EP (aPDT/EP) against Gram-positive Staphylococcus aureus and Gram-negative Escherichia coli. These bacteria were exposed to light (590 nm) in the presence of hypericin (4 mu M), following electroporation. The results showed that aPDT/EP inactivated 3.67 logs more E. coli and 2.65 logs more S. aureus than aPDT alone. Based on these results we suggest that EP can potentiate the aPDT effect. (C) 2013 Elsevier B.V. All rights reserved. C1 [Martins Antunes de Melo, Wanessa de Cassia; Perussi, Janice Rodrigues] Univ Sao Paulo, EESC FMRP IQSC, Programa Posgrad Interunidades Bioengn, Sao Carlos, SP, Brazil. [Martins Antunes de Melo, Wanessa de Cassia; Lee, Alexander N.; Hamblin, Michael R.] Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA. [Martins Antunes de Melo, Wanessa de Cassia; Hamblin, Michael R.] Harvard Univ, Sch Med, Dept Dermatol, Boston, MA 02115 USA. [Lee, Alexander N.] John Jay High Sch, Cross River, NY USA. [Perussi, Janice Rodrigues] Univ Sao Paulo, Inst Quim Sao Carlos, Sao Carlos, SP, Brazil. [Hamblin, Michael R.] Harvard MIT Div Hlth Sci & Technol, Cambridge, MA USA. RP Hamblin, MR (reprint author), Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA. EM hamblin@helix.mgh.harvard.edu OI Hamblin, Michael/0000-0001-6431-4605 FU Coordenacao de Aperfeicoamento de Pessoal de Nivel Superior (CAPES); US NIH [R01AI050875] FX Wanessa Melo expresses sincere thanks for the financial support from Coordenacao de Aperfeicoamento de Pessoal de Nivel Superior (CAPES). Research in the Hamblin laboratory was supported by US NIH grant R01AI050875. NR 18 TC 9 Z9 9 U1 2 U2 12 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1572-1000 EI 1873-1597 J9 PHOTODIAGN PHOTODYN JI Photodiagnosis Photodyn. Ther. PD DEC PY 2013 VL 10 IS 4 BP 647 EP 650 DI 10.1016/j.pdpdt.2013.08.001 PG 4 WC Oncology SC Oncology GA 275HM UT WOS:000328666900042 ER PT J AU Maruvka, YE Shnerb, NM AF Maruvka, Yosef E. Shnerb, Nadav M. TI First principles theories for last name dynamics Comment SO PHYSICS OF LIFE REVIEWS LA English DT Editorial Material C1 [Maruvka, Yosef E.] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA. [Maruvka, Yosef E.] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. [Shnerb, Nadav M.] Bar Ilan Univ, Dept Phys, IL-52900 Ramat Gan, Israel. RP Maruvka, YE (reprint author), Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA. EM ymaruvka@jimmy.harvard.edu NR 9 TC 0 Z9 0 U1 0 U2 4 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1571-0645 EI 1873-1457 J9 PHYS LIFE REV JI Phys. Life Rev. PD DEC PY 2013 VL 10 IS 4 BP 422 EP 423 DI 10.1016/j.plrev.2013.07.024 PG 2 WC Biology; Biophysics SC Life Sciences & Biomedicine - Other Topics; Biophysics GA 275FK UT WOS:000328661500005 PM 23973008 ER PT J AU Miller, LS Sandel, ME AF Miller, Lawrence S. Sandel, M. Elizabeth TI Dr. Rene Cailliet: Advancing the Field of Musculoskeletal Medicine by Making the Complicated Understandable SO PM&R LA English DT Editorial Material C1 [Miller, Lawrence S.] Univ Calif Los Angeles, Los Angeles, CA USA. [Miller, Lawrence S.] Vet Adm Greater Los Angeles Healthcare Syst, Vet Adm GLAHS UCLA PM&R Residency & Fellowship Pr, Los Angeles, CA USA. [Sandel, M. Elizabeth] Univ Calif Hlth Syst, Sacramento, CA USA. RP Miller, LS (reprint author), 1158 26th St,Suite 458, Santa Monica, CA USA. EM lsmillermd@gmail.com 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 1934-1482 EI 1934-1563 J9 PM&R JI PM&R PD DEC PY 2013 VL 5 IS 12 BP 991 EP 995 DI 10.1016/j.pmrj.2013.10.008 PG 5 WC Rehabilitation; Sport Sciences SC Rehabilitation; Sport Sciences GA 277CJ UT WOS:000328795700001 PM 24332228 ER PT J AU Turner, AP Chapko, MK Yanez, D Leipertz, SL Sloan, AP Whitham, RH Haselkorn, JK AF Turner, Aaron P. Chapko, Michael K. Yanez, David Leipertz, Steve L. Sloan, Alicia P. Whitham, Ruth H. Haselkorn, Jodie K. TI Access to Multiple Sclerosis Specialty Care SO PM&R LA English DT Article ID QUALITY-OF-LIFE; HEALTH-CARE; REHABILITATION SERVICES; DISABLING CONDITIONS; MENTAL-HEALTH; PEOPLE; VETERANS; DISABILITIES; PATTERNS; REGISTRY AB Background: Health care providers recommend an annual visit to a multiple sclerosis specialty care provider. Objective: To examine potential barriers to the implementation of this recommendation in the Veterans Health Administration. Design: Observational cohort study. Setting: Veterans Health Administration. Participants: Participants were drawn from the Veterans Affairs Multiple Sclerosis National Data Repository and were included if they had an outpatient visit in 2007 and were alive in 2008 (N = 14,723). Main Outcome Measurements: Specialty care visit, receipt of medical services. Results: A total of 9643 (65.5%) participants had a specialty care visit in 2007. Veterans who were service connected, had greater medical comorbidity, and who lived in urban settings were more likely to have received a specialty care visit. Veterans who were older and had to travel greater distances to a center were less likely to have a specialty care visit. Conclusions: Access to care in rural areas and areas at a greater distance from a major medical center represent notable barriers to rehabilitation and other multiple sclerosis-related care. C1 [Turner, Aaron P.] Vet Affairs Puget Sound Hlth Care Syst, Dept Rehabil Med, Seattle, WA 98108 USA. [Turner, Aaron P.; Leipertz, Steve L.; Sloan, Alicia P.; Haselkorn, Jodie K.] Vet Affairs, Multiple Sclerosis Ctr Excellence West, Seattle, WA USA. [Turner, Aaron P.; Haselkorn, Jodie K.] Univ Washington, Dept Phys Med & Rehabil, Seattle, WA 98195 USA. [Chapko, Michael K.; Yanez, David; Haselkorn, Jodie K.] Vet Affairs Puget Sound Hlth Care Syst, Seattle, WA 98108 USA. [Yanez, David] Univ Washington, Dept Biostat, Seattle, WA 98195 USA. [Whitham, Ruth H.] Portland VA Med Ctr, Multiple Sclerosis Ctr Excellence West, Portland, OR USA. [Whitham, Ruth H.] Oregon Hlth & Sci Univ, Dept Neurol, Portland, OR 97201 USA. [Haselkorn, Jodie K.] Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA. RP Turner, AP (reprint author), Vet Affairs Puget Sound Hlth Care Syst, Dept Rehabil Med, S-117-RCS,1660 S Columbian Way, Seattle, WA 98108 USA. EM Aaron.Turner@va.gov OI sloan, alicia/0000-0003-4891-3266; Turner, Aaron/0000-0001-6897-8003 FU U.S. Department of Veterans Affairs, Office of Research and Development Rehabilitation R&D Program, Health Services R&D Program Quality Enhancement Research Initiative QUERI Project [RRP 07-344]; Research and Development Rehabilitation R&D Program Career Development Award [B4927W]; Veterans Affairs Multiple Sclerosis Center of Excellence West FX This material is based upon work supported by the U.S. Department of Veterans Affairs, Office of Research and Development Rehabilitation R&D Program, Health Services R&D Program Quality Enhancement Research Initiative QUERI Project RRP 07-344 (Haselkom PI), Research and Development Rehabilitation R&D Program Career Development Award B4927W (Turner PI) and the Veterans Affairs Multiple Sclerosis Center of Excellence West. NR 20 TC 4 Z9 4 U1 0 U2 4 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1934-1482 EI 1934-1563 J9 PM&R JI PM&R PD DEC PY 2013 VL 5 IS 12 BP 1044 EP 1050 DI 10.1016/j.pmrj.2013.07.009 PG 7 WC Rehabilitation; Sport Sciences SC Rehabilitation; Sport Sciences GA 277CJ UT WOS:000328795700007 PM 23920332 ER PT J AU Nyer, M Doorley, J Durham, K Yeung, AS Freeman, MP Mischoulon, D AF Nyer, Maren Doorley, James Durham, Kelley Yeung, Albert S. Freeman, Marlene P. Mischoulon, David TI What is the Role of Alternative Treatments in Late-life Depression? SO PSYCHIATRIC CLINICS OF NORTH AMERICA LA English DT Article DE Late-life depression; Natural remedies; Exercise; Yoga; Tai chi; Massage therapy; Music therapy; Spirituality ID QUALITY-OF-LIFE; RANDOMIZED-CONTROLLED-TRIAL; ADENOSYL-L-METHIONINE; TAI-CHI-CHUAN; SEROTONIN REUPTAKE INHIBITORS; OLDER-ADULTS; PHYSICAL-ACTIVITY; CLINICAL-TRIAL; MAJOR DEPRESSION; HEALTH-BENEFITS AB Late-life depression remains challenging to treat. One major limitation to treatment is the concern over medication-related side effects to which the elderly are especially vulnerable. Also, because many elderly people are already taking multiple medications for medical conditions, there is the concern over drug-drug interactions. This article reviews various complementary and alternative medicine interventions for late-life depression, including natural remedies, exercise, yoga, tai chi, massage therapy, music therapy, and religion and spirituality. C1 [Nyer, Maren; Doorley, James; Durham, Kelley; Yeung, Albert S.; Mischoulon, David] Harvard Univ, Depress Clin & Res Program, Dept Psychiat, Massachusetts Gen Hosp,Med Sch, Boston, MA 02114 USA. [Freeman, Marlene P.] Harvard Univ, Perinatal & Reprod Psychiat Program, Dept Psychiat, Massachusetts Gen Hosp,Med Sch, Boston, MA 02114 USA. RP Nyer, M (reprint author), Harvard Univ, Depress Clin & Res Program, Dept Psychiat, Massachusetts Gen Hosp,Med Sch, 1 Bowdoin Sq,6th Floor, Boston, MA 02114 USA. EM mnyer@partners.org NR 140 TC 3 Z9 3 U1 6 U2 36 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0193-953X EI 1558-3147 J9 PSYCHIAT CLIN N AM JI Psychiatr. Clin. North Amer. PD DEC PY 2013 VL 36 IS 4 BP 577 EP + DI 10.1016/j.psc.2013.08.012 PG 22 WC Psychiatry SC Psychiatry GA 278VM UT WOS:000328918000010 PM 24229658 ER PT J AU Oto, J Chenelle, CT Marchese, AD Kacmarek, RM AF Oto, Jun Chenelle, Christopher T. Marchese, Andrew D. Kacmarek, Robert M. TI A Comparison of Leak Compensation in Acute Care Ventilators During Noninvasive and Invasive Ventilation: A Lung Model Study SO RESPIRATORY CARE LA English DT Article DE leak compensation; mechanical ventilation; acute care ventilator ID PRESSURE SUPPORT VENTILATION; MECHANICAL VENTILATION; ENDOTRACHEAL INTUBATION; ICU VENTILATORS; ASYNCHRONY; COMPLICATIONS; PERFORMANCE; TRIGGER; BENCH AB BACKGROUND: Although leak compensation has been widely introduced to acute care ventilators to improve patient-ventilator synchronization in the presence of system leaks, there are no data on these ventilators' ability to prevent triggering and cycling asynchrony. The goal of this study was to evaluate the ability of leak compensation in acute care ventilators during invasive and noninvasive ventilation (NW). METHODS: Using a lung simulator, the impact of system leaks was compared on 7 ICU ventilators and 1 dedicated NW ventilator during triggering and cycling at 2 respiratory mechanics (COPD and ARDS models) settings, various modes of ventilation (NW mode [pressure support ventilation], and invasive mode [pressure support and continuous mandatory ventilation]), and 2 PEEP levels (5 and 10 cm H2O). Leak levels used were up to 35-36 L/min in NW mode and 26-27 L/min in invasive mode. RESULTS: Although all of the ventilators were able to synchronize with the simulator at baseline, only 4 of the 8 ventilators synchronized to all leaks in NW mode, and 2 of the 8 ventilators in invasive mode. The number of breaths to synchronization was higher during increasing than during decreasing leak. In the COPD model, miss-triggering occurred more frequently and required a longer time to stabilize tidal volume than in the ARDS model. The PB840 required fewer breaths to synchronize in both invasive and noninvasive modes, compared with the other ventilators (P < .001). CONCLUSIONS: Leak compensation in invasive and noninvasive modes has wide variations between ventilators. The PB840 and the V60 were the only ventilators to acclimate to all leaks, but there were differences in performance between these 2 ventilators. It is not clear if these differences have clinical importance. (C) 2013 Daedalus Enterprises C1 [Oto, Jun; Chenelle, Christopher T.; Marchese, Andrew D.; Kacmarek, Robert M.] Massachusetts Gen Hosp, Resp Care Serv, Boston, MA 02114 USA. RP Kacmarek, RM (reprint author), Massachusetts Gen Hosp, Resp Care Serv, 55 Fruit St, Boston, MA 02114 USA. EM rkacmarek@partners.org OI Chenelle, Christopher/0000-0002-1499-9973 FU Covidien FX This research was partly supported by Covidien. Dr Kacmarek has disclosed relationships with Magnet and Covidien. The other authors have disclosed no other conflicts of interest. NR 21 TC 13 Z9 14 U1 0 U2 2 PU DAEDALUS ENTERPRISES INC PI IRVING PA 9425 N MAC ARTHUR BLVD, STE 100, IRVING, TX 75063-4706 USA SN 0020-1324 EI 1943-3654 J9 RESP CARE JI Respir. Care PD DEC PY 2013 VL 58 IS 12 BP 2027 EP 2037 DI 10.4187/respcare.02466 PG 11 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 275HK UT WOS:000328666700002 PM 23696688 ER PT J AU Strickland, SL Rubin, BK Drescher, GS Haas, CF O'Malley, CA Volsko, TA Branson, RD Hess, DR AF Strickland, Shawna L. Rubin, Bruce K. Drescher, Gail S. Haas, Carl F. O'Malley, Catherine A. Volsko, Teresa A. Branson, Richard D. Hess, Dean R. TI AARC Clinical Practice Guideline: Effectiveness of Nonpharmacologic Airway Clearance Therapies in Hospitalized Patients SO RESPIRATORY CARE LA English DT Article DE airway clearance therapy; ACT; chest physiotherapy; CPT; atelectasis; secretion clearance; percussion ID POSTOPERATIVE PULMONARY COMPLICATIONS; INTRAPULMONARY PERCUSSIVE VENTILATION; AMYOTROPHIC-LATERAL-SCLEROSIS; DUCHENNE MUSCULAR-DYSTROPHY; RANDOMIZED CONTROLLED-TRIAL; TIDAL-VOLUME VENTILATION; MAJOR ABDOMINAL-SURGERY; CHEST-WALL OSCILLATION; MOTOR-NEURON DISEASE; INCENTIVE SPIROMETRY AB Airway clearance therapy (ACT) is used in a variety of settings for a variety of ailments. These guidelines were developed from a systematic review with the purpose of determining whether the use of nonpharmacologic ACT improves oxygenation, reduces length of time on the ventilator, reduces stay in the ICU, resolves atelectasis/consolidation, and/or improves respiratory mechanics, versus usual care in 3 populations. For hospitalized, adult and pediatric patients without cystic fibrosis, 1) chest physiotherapy (CPT) is not recommended for the routine treatment of uncomplicated pneumonia; 2) ACT is not recommended for routine use in patients with COPD; 3) ACT may be considered in patients with COPD with symptomatic secretion retention, guided by patient preference, toleration, and effectiveness of therapy; 4) ACT is not recommended if the patient is able to mobilize secretions with cough, but instruction in effective cough technique may be useful. For adult and pediatric patients with neuromuscular disease, respiratory muscle weakness, or impaired cough, 1) cough assist techniques should be used in patients with neuromuscular disease, particularly when peak cough flow is < 270 L/min; CPT, positive expiratory pressure, intrapulmonary percussive ventilation, and high-frequency chest wall compression cannot be recommended, due to insufficient evidence. For postoperative adult and pediatric patients, 1) incentive spirometry is not recommended for routine, prophylactic use in postoperative patients, 2) early mobility and ambulation is recommended to reduce postoperative complications and promote airway clearance, 3) ACT is not recommended for routine postoperative care. The lack of available high-level evidence related to ACT should prompt the design and completion of properly designed studies to determine the appropriate role for these therapies. (C) 2013 Daedalus Enterprises C1 [Strickland, Shawna L.] Amer Assoc Resp Care, Irving, TX 75063 USA. [Rubin, Bruce K.] Virginia Commonwealth Univ, Childrens Hosp Richmond, Richmond, VA USA. [Drescher, Gail S.] Washington Hosp Ctr, Washington, DC 20010 USA. [Haas, Carl F.] Univ Michigan Hlth Syst, Ann Arbor, MI USA. [O'Malley, Catherine A.] Ann & Robert H Lurie Childrens Hosp Chicago, Chicago, IL USA. [Volsko, Teresa A.] Akron Childrens Hosp, Akron, OH USA. [Branson, Richard D.] Univ Cincinnati, Coll Med, Cincinnati, OH USA. [Hess, Dean R.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. RP Strickland, SL (reprint author), Amer Assoc Resp Care, 9425 N MacArthur Blvd,Suite 100, Irving, TX 75063 USA. EM shawna.strickland@aarc.org OI Volsko, Teresa/0000-0001-5111-898X NR 58 TC 21 Z9 28 U1 5 U2 23 PU DAEDALUS ENTERPRISES INC PI IRVING PA 9425 N MAC ARTHUR BLVD, STE 100, IRVING, TX 75063-4706 USA SN 0020-1324 EI 1943-3654 J9 RESP CARE JI Respir. Care PD DEC PY 2013 VL 58 IS 12 BP 2187 EP 2193 DI 10.4187/respcare.02925 PG 7 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 275HK UT WOS:000328666700020 PM 24222709 ER PT J AU Elsaman, AM Radwan, AR Akmatov, MK Della Beffa, C Walker, A Mayer, CT Dai, L Nativ, S Rygg, M Atsali, E Saijo, K Ogdie, AR Srinivasulu, N Fathi, N Schumacher, HR Pessler, F AF Elsaman, Ahmed M. Radwan, Ahmed R. Akmatov, Manas K. Della Beffa, Cristina Walker, Alisha Mayer, Christian T. Dai, Lie Nativ, Simona Rygg, Marite Atsali, Erato Saijo, Kaoru Ogdie, Alexis R. Srinivasulu, Nagaraj Fathi, Nihal Schumacher, H. Ralph Pessler, Frank TI Amyloid arthropathy associated with multiple myeloma: A systematic analysis of 101 reported cases SO SEMINARS IN ARTHRITIS AND RHEUMATISM LA English DT Review DE Amyloid; Amyloid; Arthritis; Arthropathy; Multiple myeloma ID SIMULATING RHEUMATOID DISEASE; ARTHRITIS; DIAGNOSIS AB Objective: Amyloid deposition in multiple myeloma (MM) may lead to an arthropathy resembling rheumatoid arthritis (RA). Since a systematic description of its natural history is lacking, we have performed a systematic analysis of all published cases. Methods: Literature review featuring backward and forward database searches and direct inspection of reference lists. Inclusion criteria were as follows: publication between 1931 and 2012, diagnosis of multiple myeloma, and demonstration of light chain amyloid (AL) in any organ or in synovial fluid, arthritis, or synovitis. Results: Overall, 101 cases were identified. Median age was 59 years and the male-to-female ratio was 1:1. A systemic manifestation of MM was reported in 88 cases. In 53 of these, characteristic physical findings (carpal tunnel syndrome, macroglossia, shoulder pad, and soft tissue swelling/masses) were present. Arthritis manifested before the diagnosis of MM in 63 cases, with 33 cases initially misdiagnosed as RA. There were 72 cases of poly-, 17 of oligo-, and three of monoarthritis. The shoulder joint was most commonly affected, followed by knees and small hand joints. Median synovial fluid leukocyte count was 2460 cells/mm(3), and was normal in seven cases. Synovial histopathology often featured mild synovitis without plasma cell infiltration. Imaging revealed articular or periarticular inflammation in many cases and bone lesions near 22% of affected joints. Treatments varied but led to some improvement in the majority of cases. Conclusions: These results solidify previous experience that MM arthropathy tends to feature a symmetric RF-negative nonerosive polyarthritis. However, the results also highlight the diversity of its presentations and stress the importance of arthropathy as a potentially under-recognized presenting manifestation of MM. (C) 2013 Elsevier Inc. All rights reserved. C1 [Elsaman, Ahmed M.; Radwan, Ahmed R.] Sohag Univ, Dept Rheumatol & Rehabil, Sohag, Egypt. [Akmatov, Manas K.; Della Beffa, Cristina; Walker, Alisha] Helmholtz Ctr Infect Res, Dept Epidemiol, Braunschweig, Germany. [Dai, Lie] Sun Yat Sen Univ, Sun Yat Sen Mem Hosp, Dept Rheumatol, Guangzhou 510275, Guangdong, Peoples R China. [Nativ, Simona] Columbia Presbyterian Med Ctr, Div Rheumatol, New York, NY USA. [Rygg, Marite] Norwegian Univ Sci & Technol, Childrens & Womens Hlth, Dept Lab Med, N-7034 Trondheim, Norway. [Rygg, Marite] St Olavs Hosp, Dept Pediat, Trondheim, Norway. [Atsali, Erato] Attikon Univ Hosp, Rheumatol & Bone Metab Dept, Haidari, Greece. [Saijo, Kaoru] Univ Calif San Diego, Sch Med, Dept Cellular & Mol Med, La Jolla, CA 92093 USA. [Ogdie, Alexis R.; Schumacher, H. Ralph] Univ Penn, Div Rheumatol, Philadelphia, PA 19104 USA. [Srinivasulu, Nagaraj] PD Hinduja Natl Hosp, Dept Rheumatol, Bombay, Maharashtra, India. [Srinivasulu, Nagaraj] MRC, Bombay, Maharashtra, India. [Srinivasulu, Nagaraj] SPARSH Hosp, Bangalore, Karnataka, India. [Fathi, Nihal] Assiut Univ, Dept Rheumatol & Rehabil, Assiut, Egypt. [Schumacher, H. Ralph] Philadelphia VA Med Ctr, Div Rheumatol, Philadelphia, PA USA. [Della Beffa, Cristina; Pessler, Frank] TWINCORE Ctr Expt & Clin Infect Res, D-30625 Hannover, Germany. RP Pessler, F (reprint author), TWINCORE Ctr Expt & Clin Infect Res, Feodor Lynen Str 7-9, D-30625 Hannover, Germany. EM frank.pessler@twincore.de OI Ogdie, Alexis/0000-0002-4639-0775 FU German Academic Exchange Service (DAAD) [51309219]; Ministry of Higher Education and Scientific Research of the Arab Republic of Egypt; Helmholtz Association FX We thank Dr. Stefanie Castell (Helmholtz Centre for Infection Research) for helpful discussion and critical reading of the manuscript. The study was supported by the German-Egyptian Scientific Project (GESP) Grant no. 51309219 from the German Academic Exchange Service (DAAD) and the Ministry of Higher Education and Scientific Research of the Arab Republic of Egypt, and with intramural funds from the Helmholtz Association (program Infection and Immunity). NR 24 TC 6 Z9 6 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 0049-0172 EI 1532-866X J9 SEMIN ARTHRITIS RHEU JI Semin. Arthritis Rheum. PD DEC PY 2013 VL 43 IS 3 BP 405 EP 412 DI 10.1016/j.semarthrit.2013.07.004 PG 8 WC Rheumatology SC Rheumatology GA 277DV UT WOS:000328800000014 PM 23992800 ER PT J AU McCabe, MS Partridge, AH Grunfeld, E Hudson, MM AF McCabe, Mary S. Partridge, Ann H. Grunfeld, Eva Hudson, Melissa M. TI Risk-Based Health Care, the Cancer Survivor, the Oncologist, and the Primary Care Physician SO SEMINARS IN ONCOLOGY LA English DT Review ID RANDOMIZED CONTROLLED-TRIAL; ROUTINE FOLLOW-UP; QUALITY-OF-CARE; BREAST-CANCER; NURSE; PRACTITIONERS; PATIENT; MODELS; COHORT AB Cancer survivors face substantial risks for morbidity, reduced quality of life, and premature mortality related to the cancer itself and/or the interventions undertaken to control cancer. Risk-based care that involves a personalized systematic plan of periodic screening, surveillance, and prevention relevant to the cancer experience is recommended to address the comprehensive health needs of the growing population of cancer survivors. Risk-based care and coordination between oncology and primary care providers have been identified as important metrics of quality cancer survivorship care. Various models of survivorship care, treatment summaries, and survivorship care plans have been promoted as methods to facilitate communication among providers across care transitions and improve survivor access to quality survivorship care. However, research supporting the feasibility of implementing these practices and their effectiveness in enhancing health outcomes is limited. This article reviews key concepts underpinning clinical and research initiatives endeavoring to improve access to quality care among long-term survivors and summarizes results of intervention studies implementing these elements in transitioning survivors from oncology to primary care providers for long-term follow-up care. (C) 2013 Elsevier Inc. All rights reserved. C1 [McCabe, Mary S.] Mem Sloan Kettering Canc Ctr, Survivorship Program, New York, NY 10021 USA. [Partridge, Ann H.] Dana Farber Canc Inst, Adult Survivorship Program, Boston, MA 02115 USA. [Partridge, Ann H.] Brigham & Womens Hosp, Boston, MA 02115 USA. [Grunfeld, Eva] Univ Toronto, Ontario Inst Canc Res, Toronto, ON M5S 1A1, Canada. [Grunfeld, Eva] Univ Toronto, Dept Family & Community Med, Toronto, ON M5S 1A1, Canada. [Hudson, Melissa M.] St Jude Childrens Res Hosp, Canc Survivorship Div, Memphis, TN 38105 USA. RP Hudson, MM (reprint author), St Jude Childrens Res Hosp, Dept Oncol, Canc Survivorship Div, 262 Danny Thomas Pl,Mailstop 735, Memphis, TN 38105 USA. EM melissa.hudson@stjude.org FU Cancer Center Support (CORE) [CA 21765]; Ontario Institute for Cancer Research (OICR); Ontario Ministry of Research and Innovation (MRI); ALSAC FX Dr Hudson is supported in part by the Cancer Center Support (CORE) Grant No. CA 21765 (R. Gilbertson, Principal Investigator) from the National Cancer Institute and by the ALSAC. Dr Grunfeld is support by a clinician scientist award from the Ontario Institute for Cancer Research (OICR) with funds from the Ontario Ministry of Research and Innovation (MRI). The opinions, results, and conclusions reported are those of the authors and are independent from the funding sources and no endorsement by OICR or MRI is intended or should be inferred. NR 55 TC 22 Z9 22 U1 2 U2 10 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0093-7754 EI 1532-8708 J9 SEMIN ONCOL JI Semin. Oncol. PD DEC PY 2013 VL 40 IS 6 BP 804 EP 812 DI 10.1053/j.seminoncol.2013.09.004 PG 9 WC Oncology SC Oncology GA 277DS UT WOS:000328799700013 PM 24331199 ER PT J AU Szymusiak, RS AF Szymusiak, Ronald S. TI New Insights into Melanin Concentrating Hormone and Sleep: A Critical Topics Forum INTRODUCTION SO SLEEP LA English DT Editorial Material ID PARADOXICAL SLEEP; NEURONS; OREXIN C1 [Szymusiak, Ronald S.] Univ Calif Los Angeles, VA Greater Los Angeles Healthcare Syst, Res Serv, Los Angeles, CA USA. [Szymusiak, Ronald S.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Med, Los Angeles, CA 90095 USA. [Szymusiak, Ronald S.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Neurobiol, Los Angeles, CA 90095 USA. RP Szymusiak, RS (reprint author), UCLA VA Greater Los Angeles Healthcare Syst, Dept Med, David Geffen Sch Med, Sepulveda, CA 91343 USA. EM rszym@ucla.edu NR 20 TC 3 Z9 3 U1 0 U2 4 PU AMER ACAD SLEEP MEDICINE PI WESTCHESTER PA ONE WESTBROOK CORPORATE CTR, STE 920, WESTCHESTER, IL 60154 USA SN 0161-8105 EI 1550-9109 J9 SLEEP JI Sleep PD DEC 1 PY 2013 VL 36 IS 12 BP 1765 EP 1766 DI 10.5665/sleep.3184 PG 2 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 262YH UT WOS:000327773300001 ER PT J AU McGinty, D Alam, N AF McGinty, Dennis Alam, Noor TI MCH Neurons: The End of the Beginning SO SLEEP LA English DT Editorial Material ID SLEEP; HYPOCRETIN; GABA C1 [McGinty, Dennis; Alam, Noor] Vet Affairs Greater Los Angeles Healthcare Syst, Res Serv, Sepulveda, CA USA. [McGinty, Dennis] Univ Calif Los Angeles, Dept Psychol, Los Angeles, CA 90024 USA. [Alam, Noor] Univ Calif Los Angeles, Dept Med, Los Angeles, CA 90024 USA. RP McGinty, D (reprint author), VAGLAHS, Res Serv 151A3, 16111 Plummer St, North Hills, CA 91343 USA. EM dmcginty@ucla.edu NR 12 TC 5 Z9 5 U1 0 U2 5 PU AMER ACAD SLEEP MEDICINE PI WESTCHESTER PA ONE WESTBROOK CORPORATE CTR, STE 920, WESTCHESTER, IL 60154 USA SN 0161-8105 EI 1550-9109 J9 SLEEP JI Sleep PD DEC 1 PY 2013 VL 36 IS 12 BP 1773 EP 1774 DI 10.5665/sleep.3190 PG 2 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 262YH UT WOS:000327773300004 PM 24293747 ER PT J AU Blouin, AM Siegel, JM AF Blouin, Ashley M. Siegel, Jerome M. TI Relation of Melanin Concentrating Hormone Levels to Sleep, Emotion and Hypocretin Levels SO SLEEP LA English DT Editorial Material ID OREXIN; NEURONS; RELEASE C1 [Blouin, Ashley M.] Scripps Res Inst, Dept Metab & Aging, Jupiter, FL USA. [Blouin, Ashley M.] Scripps Res Inst, Dept Neurosci, Jupiter, FL USA. [Siegel, Jerome M.] Univ Calif Los Angeles, Neuropsychiat Inst, VA Greater Los Angeles Healthcare Syst, North Hills, CA 91343 USA. [Siegel, Jerome M.] Univ Calif Los Angeles, Brain Res Inst, North Hills, CA 91343 USA. RP Siegel, JM (reprint author), Univ Calif Los Angeles, Neuropsychiat Inst, VA Greater Los Angeles Healthcare Syst, 16111 Plummer St, North Hills, CA 91343 USA. NR 14 TC 3 Z9 3 U1 0 U2 4 PU AMER ACAD SLEEP MEDICINE PI WESTCHESTER PA ONE WESTBROOK CORPORATE CTR, STE 920, WESTCHESTER, IL 60154 USA SN 0161-8105 EI 1550-9109 J9 SLEEP JI Sleep PD DEC 1 PY 2013 VL 36 IS 12 BP 1777 EP 1777 DI 10.5665/sleep.3194 PG 1 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 262YH UT WOS:000327773300006 PM 24293749 ER PT J AU Pelluru, D Konadhode, R Shiromani, PJ AF Pelluru, Dheeraj Konadhode, RodaRani Shiromani, Priyattam J. TI MCH Neurons Are the Primary Sleep-Promoting Group SO SLEEP LA English DT Editorial Material ID MELANIN-CONCENTRATING HORMONE; REPORTER GENE; HYPOCRETIN; HYPOTHALAMUS; STIMULATION; ACTIVATION; EXPRESSION; NUCLEUS C1 [Shiromani, Priyattam J.] Ralph H Johnson VA, Charleston, SC 29425 USA. [Shiromani, Priyattam J.] Med Univ S Carolina, Charleston, SC 29425 USA. RP Shiromani, PJ (reprint author), Ralph H Johnson VA, Charleston, SC 29425 USA. EM shiroman@musc.edu FU NIMH NIH HHS [R01 MH055772]; NINDS NIH HHS [R21 NS079940, R21 NS084477] NR 21 TC 10 Z9 10 U1 0 U2 3 PU AMER ACAD SLEEP MEDICINE PI WESTCHESTER PA ONE WESTBROOK CORPORATE CTR, STE 920, WESTCHESTER, IL 60154 USA SN 0161-8105 EI 1550-9109 J9 SLEEP JI Sleep PD DEC 1 PY 2013 VL 36 IS 12 BP 1779 EP 1781 DI 10.5665/sleep.3196 PG 3 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 262YH UT WOS:000327773300007 PM 24293750 ER PT J AU Bjornsdottir, E Janson, C Sigurdsson, JF Gehrman, P Perlis, M Juliusson, S Arnardottir, ES Kuna, ST Pack, AI Gislason, T Benediktsdottir, B AF Bjornsdottir, Erla Janson, Christer Sigurdsson, Jon F. Gehrman, Philip Perlis, Michael Juliusson, Sigurdur Arnardottir, Erna S. Kuna, Samuel T. Pack, Allan I. Gislason, Thorarinn Benediktsdottir, Bryndis TI Symptoms of Insomnia among Patients with Obstructive Sleep Apnea Before and After Two Years of Positive Airway Pressure Treatment SO SLEEP LA English DT Article DE Adherence; CPAP; insomnia; obstructive sleep apnea ID BREATHING DISORDERS; COMORBID INSOMNIA; RELIABILITY AB Study Objectives: To assess the changes of insomnia symptoms among patients with obstructive sleep apnea (OSA) from starting treatment with positive airway pressure (PAP) to a 2-y follow-up. Design: Longitudinal cohort study. Setting: Landspitali-The National University Hospital of Iceland. Participants: There were 705 adults with OSA who were assessed prior to and 2 y after starting PAP treatment. Intervention: PAP treatment for OSA. Measurements and Results: All patients underwent a medical examination along with a type 3 sleep study and answered questionnaires on health and sleep before and 2 y after starting PAP treatment. The change in prevalence of insomnia symptoms by subtype was assessed by questionnaire and compared between individuals who were using or not using PAP at follow-up. Symptoms of middle insomnia were most common at baseline and improved significantly among patients using PAP (from 59.4% to 30.7%, P < 0.001). Symptoms of initial insomnia tended to persist regardless of PAP treatment, and symptoms of late insomnia were more likely to improve among patients not using PAP. Patients with symptoms of initial and late insomnia at baseline were less likely to adhere to PAP (odds ratio [OR] 0.56, P = 0.007, and OR 0.53, P < 0.001, respectively). Conclusion: Positive airway pressure treatment significantly reduced symptoms of middle insomnia. Symptoms of initial and late insomnia, however, tended to persist regardless of positive airway pressure treatment and had a negative effect on adherence. Targeted treatment for insomnia may be beneficial for patients with obstructive sleep apnea comorbid with insomnia and has the potential to positively affect adherence to positive airway pressure. C1 [Bjornsdottir, Erla; Sigurdsson, Jon F.; Arnardottir, Erna S.; Gislason, Thorarinn; Benediktsdottir, Bryndis] Univ Iceland, Fac Med, Reykjavik, Iceland. [Janson, Christer] Uppsala Univ, Dept Med Sci Resp Med & Allergol, S-75105 Uppsala, Sweden. [Bjornsdottir, Erla; Arnardottir, Erna S.; Gislason, Thorarinn; Benediktsdottir, Bryndis] Landspitali Natl Univ Hosp Iceland, Dept Resp Med & Sleep, Reykjavik, Iceland. [Gehrman, Philip; Perlis, Michael; Kuna, Samuel T.; Pack, Allan I.] Univ Penn, Ctr Sleep & Circadian Neurobiol, Philadelphia, PA 19104 USA. [Gehrman, Philip; Perlis, Michael; Kuna, Samuel T.; Pack, Allan I.] Univ Penn, Dept Med, Div Sleep Med, Perelman Sch Med, Philadelphia, PA 19104 USA. [Gehrman, Philip; Perlis, Michael] Univ Penn, Sch Med, Dept Psychiat, Philadelphia, PA 19104 USA. [Sigurdsson, Jon F.] Landspitali Natl Univ Hosp Iceland, Mental Hlth Serv, Reykjavik, Iceland. [Juliusson, Sigurdur] Landspitali Natl Univ Hosp Iceland, Dept Otolaryngol, Reykjavik, Iceland. [Kuna, Samuel T.] Philadelphia Vet Affairs Med Ctr, Philadelphia, PA USA. RP Bjornsdottir, E (reprint author), Landspitali Univ Hosp Fossvogi, Dept Resp Med & Sleep E7, IS-108 Reykjavik, Iceland. EM erlabjo@gmail.com RI Sigurdsson, Jon Fridrik/M-1844-2015 OI Sigurdsson, Jon Fridrik/0000-0001-6873-8157 FU NIH [HL72067, HL94307]; Eimskip Fund of the University of Iceland; Landspitali University Hospital Research Fund; Philips Respironics FX This was not an industry supported study. Support for this study was provided by NIH grant HL72067 for "A Family Linkage Study of Obstructive Sleep Apnoea" and HL94307 for "Endophenotypes of Sleep Apnea and Role of Obesity," the Eimskip Fund of the University of Iceland and the Landspitali University Hospital Research Fund. Dr. Kuna has received grant support from Philips Respironics. Dr. Arnardottir is a consultant for Nox Medical and has received honorarium from ResMed and Pfizer, Iceland. Dr. Gehrman is a consultant for Design Interactive, Inc. The other authors have indicated no financial conflicts of interest. NR 24 TC 18 Z9 18 U1 0 U2 6 PU AMER ACAD SLEEP MEDICINE PI WESTCHESTER PA ONE WESTBROOK CORPORATE CTR, STE 920, WESTCHESTER, IL 60154 USA SN 0161-8105 EI 1550-9109 J9 SLEEP JI Sleep PD DEC 1 PY 2013 VL 36 IS 12 BP 1901 EP 1909 DI 10.5665/sleep.3226 PG 9 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 262YH UT WOS:000327773300022 PM 24293765 ER PT J AU Joffe, H Crawford, S Economou, N Kim, S Regan, S Hall, JE White, D AF Joffe, Hadine Crawford, Sybil Economou, Nicole Kim, Semmie Regan, Susan Hall, Janet E. White, David TI A Gonadotropin-Releasing Hormone Agonist Model Demonstrates That Nocturnal Hot Flashes Interrupt Objective Sleep SO SLEEP LA English DT Article DE Menopause; hot flashes; awakenings; wake time after sleep onset; polysomnography ID CORE BODY-TEMPERATURE; BREAST-CANCER SURVIVORS; MENOPAUSAL TRANSITION; VASOMOTOR SYMPTOMS; PREMENSTRUAL-SYNDROME; POSTMENOPAUSAL WOMEN; MASS-SPECTROMETRY; DEPRESSION SCALE; SELF-REPORT; DISTURBANCE AB Objectives: Sleep interruption is often reported by women with hot flashes and night sweats (or vasomotor symptoms, VMS). Although women report that VMS awaken them, polysomnography (PSG) studies have not consistently supported this contention. Design: We mimicked menopause using a gonadotropin-releasing hormone agonist (GnRHa) to investigate whether VMS increase awakenings and wake after sleep onset (WASO). VMS, serum estradiol, and at-home PSGs (two pretreatment, two posttreatment) were measured before and after 4 weeks on GnRHa. Regression models were used to determine the effect of increasing VMS frequency on awakenings and WASO, as measured objectively and subjectively. Participants: Twenty-nine healthy women (mean 27.3 y). Setting: Academic medical center. Interventions: Depot GnRHa (leuprolide 3.75-mg). Results: Serum estradiol was rapidly and uniformly suppressed on GnRHa. Persistent VMS were reported by 69% of women. The number of nighttime VMS correlated directly with the degree of sleep disturbance. Each additional reported nighttime VMS was associated with a 62% increase from baseline in PSG-measured WASO (P = 0.007), a 3% increase in awakenings (P = 0.05), and 6% increase in %N1 sleep (P = 0.02). Nighttime VMS were also associated with increased perceived WASO (312%; P = 0.02), awakenings (16%; P = 0.007), Insomnia Severity Index (P = 0.03), and Pittsburgh Sleep Quality Index (P = 0.03) scores, and decreased perceived sleep efficiency (P = 0.01). Objectively recorded nighttime VMS correlated with PSG-measured WASO (r(s) = 0.45, P = 0.02). Conclusions: This menopause model demonstrates that nighttime vasomotor symptoms correlate with increased sleep fragmentation. These findings are consistent with a specific contribution of vasomotor symptoms to polysomnography-measured sleep interruption suggesting that nighttime vasomotor symptoms interrupt sleep in the setting of menopause. C1 [Joffe, Hadine; Kim, Semmie] Harvard Univ, Brigham & Womens Hosp, Sch Med, Womens Hormones & Aging Res Program,Dept Psychiat, Boston, MA 02115 USA. [Joffe, Hadine] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Psychosocial Oncol & Palliat Care Med, Boston, MA 02115 USA. [Joffe, Hadine; Economou, Nicole; Kim, Semmie] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Womens Mental Hlth,Dept Psychiat, Boston, MA USA. [Crawford, Sybil] Univ Massachusetts, Sch Med, Dept Med, Div Prevent & Behav Med, Boston, MA 02125 USA. [Regan, Susan] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Gen Med Div,Dept Med, Boston, MA USA. [Hall, Janet E.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Reprod Endocrinol,Dept Med, Boston, MA USA. [White, David] Harvard Univ, Brigham & Womens Hosp, Sch Med, Div Sleep Med,Dept Med, Boston, MA 02115 USA. RP Joffe, H (reprint author), Brigham & Womens Hosp, Dept Psychiat, Womens Hormones & Aging Res Program, 75 Francis St, Boston, MA 02115 USA. EM hjoffe@partners.org OI Hall, Janet/0000-0003-4644-3061 FU [5R01MH082922] FX Drs. Hall and White contributed equally as senior authors. The authors acknowledge Judith Boucher, RPSGT, and Susan Dougherty, RPSGT, for assistance conducting the ambulatory PSG studies, and Daniel Aeschbach, PhD, and Brandon Lockyer, RPSGT, in the Sleep & EEG Core of the Harvard Medical School Division of Sleep Medicine for assistance with sleep stage scoring. The work was performed at Massachusetts General Hospital. Funding source was 5R01MH082922 (to Dr. Joffe). ClinicalTrials.govIdentifier: NCT01116401. NR 49 TC 16 Z9 16 U1 0 U2 1 PU AMER ACAD SLEEP MEDICINE PI WESTCHESTER PA ONE WESTBROOK CORPORATE CTR, STE 920, WESTCHESTER, IL 60154 USA SN 0161-8105 EI 1550-9109 J9 SLEEP JI Sleep PD DEC 1 PY 2013 VL 36 IS 12 BP 1977 EP 1985 DI 10.5665/sleep.3244 PG 9 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 262YH UT WOS:000327773300031 PM 24293774 ER PT J AU Dazley, JM Cha, TD Harris, MB Bono, CM AF Dazley, Justin M. Cha, Thomas D. Harris, Mitchel B. Bono, Christopher M. TI Closing the loop between evidence-based medicine and care delivery: a possible role for clinical audits in spinal surgery SO SPINE JOURNAL LA English DT Review DE Clinical audit; Evidence-based medicine; Re-audit ID LUMBAR-DISK HERNIATION; RESEARCH TRIAL SPORT; LOW-BACK-PAIN; RANDOMIZED-TRIAL; NONOPERATIVE TREATMENT; FUSION; VERTEBROPLASTY; FRACTURES AB BACKGROUND CONTEXT: Evidence-based medicine (EBM) should be the ultimate force driving change in clinical practice. This process generally occurs through a trickle-down phenomenon by which practice recommendations are revised, modified, and/or changed based on the best published data. Recommendations are subsequently incorporated by individual physicians. The fundamental assumption that drives this paradigm is that adopting evidence-based recommendations and/or treatment guidelines will result in improved outcomes. Unfortunately, to date, the paradigm does not have an effective feedback loop that would then evaluate whether the changes did, in fact, improve outcomes. PURPOSE: To explore the process of clinical audits as a mechanism by which to provide a feedback loop to evaluate the results of spinal surgery on an individual basis and whether those results can be improved. STUDY DESIGN: Review article, discussion. METHODS: A literature review of the current data regarding clinical audits was performed, and a discussion of how they may apply to spinal surgery is offered. RESULTS: Clinical audits have been used outside the United States, particularly in the United Kingdom, to fulfill this function. A clinical audit would allow a practicing spinal surgeon to examine his or her individual experience and determine if it is achieving the expected outcome based on published results. In the most important feature of a clinical audit, the reaudit, if an individual's results are found to be inconsistent with published results, it presents an opportunity to identify if there are reconcilable differences from which potential improvements can be made. Effectively, this "closes the loop'' between EBM and actual clinical practice. CONCLUSIONS: Documenting improved outcomes through the audit process can impact spinal care in several ways. Patients would receive a clear message that their doctors are interested in improving care. Hospitals will use the information to optimize treatment algorithms. Finally, insurers might make the audit process more tenable or attractive by indicating a physician's voluntary participation as a criterion to be a preferred provider. (C) 2013 Elsevier Inc. All rights reserved. C1 Massachusetts Gen Hosp, Brigham & Womens Hosp, Dept Orthopaed Surg, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Bono, CM (reprint author), Brigham & Womens Hosp, Dept Orthopaed Surg, Orthopaed Spine Serv, 75 Francis St, Boston, MA 02115 USA. EM bonocm@me.com FU Globus; AOSpine; OREF FX JMD: Fellowship Support: Globus (none, Paid directly to institution/employer), AOSpine (none, Paid directly to institution/employer), OREF (none, Paid directly to institution/employer). TDC: Fellowship Support: AOSpine (E, Paid directly to institution/employer), Globus (E, Paid directly to institution/employer), OREF (D, Paid directly to institution/employer). MBH: Consulting: Harvard Consulting Research Institute (B); Board of Directors: NASS (none). CMB: Royalties: Wolters Kluwer (A), Informa Healthcare (A); Consulting: Harvard Clinical Research Institute (B), Intrinsic Therapeutics (B); Fellowship Support: OREF (D, Paid directly to institution/employer). NR 23 TC 0 Z9 0 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1529-9430 EI 1878-1632 J9 SPINE J JI Spine Journal PD DEC PY 2013 VL 13 IS 12 BP 1951 EP 1957 DI 10.1016/j.spinee.2013.03.055 PG 7 WC Clinical Neurology; Orthopedics SC Neurosciences & Neurology; Orthopedics GA 272XG UT WOS:000328495800038 PM 23830825 ER PT J AU Boyaci, B Hornicek, FJ Nielsen, GP DeLaney, TF Pedlow, FX Mansfield, FL Carrier, CS Harms, J Schwab, JH AF Boyaci, Bilal Hornicek, Francis J. Nielsen, G. Petur DeLaney, Thomas F. Pedlow, Frank X., Jr. Mansfield, Frederick L. Carrier, Charles S. Harms, Jurgen Schwab, Joseph H. TI Epithelioid hemangioma of the spine: a case series of six patients and review of the literature SO SPINE JOURNAL LA English DT Review DE Epithelioid hemangioma; Benign vascular tumor; Spine; Case study; Spinal cord compression ID ANGIOLYMPHOID HYPERPLASIA; HISTIOCYTOID HEMANGIOMA; BONE; ANGIOSARCOMA; HEMANGIOENDOTHELIOMA; EOSINOPHILIA; SKIN; LESION; GRADE; TUMOR AB BACKGROUND CONTEXT: Epithelioid hemangioma (EH) of bone is a benign vascular tumor that can be locally aggressive. It rarely arises in the spine, and the optimum management of EH of the vertebrae is not well delineated. PURPOSE: The report describes our experience treating six patients with EH of the spine in an effort to document the treatment of the rare spinal presentation. STUDY DESIGN: This study is designed as a retrospective cohort study. PATIENT SAMPLE: A continuous series of patients with the diagnosis of EH of the spine who presented at our institution. OUTCOME MEASURES: The clinical and radiographic follow-up of the patient population is documented. METHODS: The Bone Sarcoma Registry at our institution was used to obtain a list of all patients diagnosed with EH of the spine. Medical records, radiographs, and pathology reports were retrospectively reviewed in all cases. Only biopsy-proven cases were included. RESULTS: The six patients included five men and one woman who ranged in age from 20 to 58 years (with an average age of 40 years). The follow-up available for all six patients ranged from 6 to 115 (average 46.8) months. All patients presented with lytic vertebral body lesions. Five patients presented with pain secondary to their tumor, and the tumor in the sixth patient was found incidentally during the workup for a herniated disc. Three patients required surgical management for instability secondary to the destructive nature of their tumors, and two other patients required emergent decompression secondary to spinal cord compression by the tumor. The sixth patient was treated expectantly after biopsy confirmation. Three patients received postoperative radiation therapy as gross tumor remained after surgery. Three patients had gross total resections and did not receive postoperative radiation. Preoperative embolization was used in four patients. One patient continued to have back pain after surgery and radiation and another continued to have ataxia after surgery and radiation. No tumor locally recurred or progressed. CONCLUSIONS: Our data suggest that EH of the spine can be locally aggressive and lead to instability and cord compression. Surgery is required in such instances; however, observation should be considered in patients without instability or cord compression. (C) 2013 Elsevier Inc. All rights reserved. C1 [Boyaci, Bilal; Harms, Jurgen] Klinikum Langensteinbach, Dept Orthopaed Surg, Langensteinbach, Germany. [Hornicek, Francis J.; Pedlow, Frank X., Jr.; Mansfield, Frederick L.; Carrier, Charles S.; Schwab, Joseph H.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Orthoped Surg, Boston, MA 02114 USA. [Nielsen, G. Petur] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Nielsen, G. Petur] Harvard Univ, Sch Med, Massachusetts Gen Hosp, James Homer Wright Pathol Labs, Boston, MA 02114 USA. [DeLaney, Thomas F.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. RP Schwab, JH (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Orthoped Surg, 55 Fruit St,Yawkey 3, Boston, MA 02114 USA. EM jhschwab@partners.org NR 20 TC 4 Z9 4 U1 0 U2 8 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1529-9430 EI 1878-1632 J9 SPINE J JI Spine Journal PD DEC PY 2013 VL 13 IS 12 BP E7 EP E13 DI 10.1016/j.spinee.2013.06.070 PG 7 WC Clinical Neurology; Orthopedics SC Neurosciences & Neurology; Orthopedics GA 272XG UT WOS:000328495800002 PM 24045160 ER PT J AU Duailibi, SE Duailibi, MT Ferreira, LM Salmazi, KILC Salvadori, MC Teixeira, FD Pasquarelli, A Vacanti, JP Yelick, PC AF Duailibi, Silvio Eduardo Duailibi, Monica Talarico Ferreira, Lydia Masako Ladislau Carvalho Salmazi, Karina Inacio Salvadori, Maria Cecilia Teixeira, Fernanda de Sa Pasquarelli, Alberto Vacanti, Joseph Phillip Yelick, Pamela Crotty TI Tooth Tissue Engineering: The Influence of Hydrophilic Surface on Nanocrystalline Diamond Films for Human Dental Stem Cells SO TISSUE ENGINEERING PART A LA English DT Article ID BIOENGINEERED TEETH; MORPHOGENESIS; REGENERATION AB New techniques for tissue engineering (TE) are rapidly emerging. The basic concept of autologous TE is to isolate cells from small biopsy specimens, and to expand these cells in culture for subsequent seeding onto biodegradable scaffolds. Nanocrystalline diamond films have attracted the attention of researchers from a variety of different areas in recent years, due to their unique and exceptional properties. In this approach, human dental stem cells (hDSCs) were characterized by flow cytometry and grown on diamond films with hydrogen (H)-terminated and oxygen (O)-terminated surfaces for 28 days, and then removed by lysis and washing with distilled water. Energy dispersive spectroscopy analysis was performed, showing that the regions with O-terminated surfaces contained much higher levels of deposited calcium, oxygen, and phosphorus. These results suggest that the extracellular matrix was considerably more developed in the O-terminated regions, as compared with the H-terminated regions. In addition, optical microscopy of hDSCs cultured on the diamond substrate with H- and O-terminated surfaces, before washing with distilled water, showed preferential directions of the cells arrangement, where orthogonal lines suggest that the cells appeared to be following the O-terminated regions or hydrophilic surface. These findings suggest that O-terminated diamond surfaces prepared on biodegradable scaffolds can be useful for mineralized dental tissue formation. C1 [Duailibi, Silvio Eduardo; Duailibi, Monica Talarico; Ferreira, Lydia Masako] Univ Fed Sao Paulo, CTCMol, UNIFESP, Dept Med,Div Plast Surg,Ctr Cellular & Mol Therap, BR-04044010 Sao Paulo, Brazil. [Duailibi, Silvio Eduardo] Univ Fed Sao Paulo, UNIFESP, Inst Sci & Technol, Sao Jose Dos Campos, SP, Brazil. [Duailibi, Silvio Eduardo; Duailibi, Monica Talarico] INCT Biofabris, Nacl Inst Sci & Technol, Biofabricat Inst, Sao Paulo, Brazil. [Ladislau Carvalho Salmazi, Karina Inacio] Univ Sao Paulo, Dept Med, Div Clin Immunol & Allergy, Sao Paulo, Brazil. [Salvadori, Maria Cecilia; Teixeira, Fernanda de Sa] Univ Sao Paulo, Inst Phys, Sao Paulo, Brazil. [Pasquarelli, Alberto] Univ Ulm, Dept Electron Devices & Circuits, D-89069 Ulm, Germany. [Vacanti, Joseph Phillip] Massachusetts Gen Hosp, Lab Tissue Engn & Organ Fabricat, Boston, MA 02114 USA. [Vacanti, Joseph Phillip] Harvard Univ, Sch Med, Dept Surg, Boston, MA 02115 USA. [Yelick, Pamela Crotty] Tufts Univ, Dept Oral & Maxillofacial Pathol, Boston, MA 02111 USA. RP Duailibi, MT (reprint author), Univ Fed Sao Paulo, CTCMol, Rua Mirassol 207, BR-04044010 Sao Paulo, Brazil. EM monica@duailibiodonto.com.br RI Teixeira, Fernanda/A-9395-2013; Salvadori, Maria Cecilia/A-9379-2013 FU UNIFESP; Plastic Surgery Department; FAPESP; CNPq; Instituto Nacional de Ciencia e Tecnologia (INCT)-Biofabrication [CNPq 5736661/2008-1, FAPESP 08/57860-3]; Rede Biofab, Ibero-American Network of Biofabrication-BIOFAB-CYTED [208RT0340]; NIH/NIDCR/NIBIB [DE016132, TW007665]; CNPq [310048/2011-7 e 310049/2011-3] FX We would like to thank Dr. Esper Georges Kallas for providing technical support of the LIM 60, Medical Investigation Laboratories (Kallas Lab), University of Sao Paulo. We thank the Brazilian sponsors UNIFESP, Plastic Surgery Department, FAPESP, CNPq, Instituto Nacional de Ciencia e Tecnologia (INCT)-Biofabrication (CNPq 5736661/2008-1 and FAPESP 08/57860-3), the Rede Biofab, Ibero-American Network of Biofabrication-BIOFAB-CYTED (208RT0340), and NIH/NIDCR/NIBIB for their continued support (DE016132, TW007665 [P.C.Y.]). We also thank CNPq for scholarship productivity of S.E.D. and M.T.D. (310048/2011-7 e 310049/2011-3). NR 24 TC 4 Z9 4 U1 1 U2 8 PU MARY ANN LIEBERT, INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1937-3341 EI 1937-335X J9 TISSUE ENG PT A JI Tissue Eng. Part A PD DEC 1 PY 2013 VL 19 IS 23-24 BP 2537 EP 2543 DI 10.1089/ten.tea.2012.0628 PG 7 WC Cell & Tissue Engineering; Biotechnology & Applied Microbiology; Cell Biology SC Cell Biology; Biotechnology & Applied Microbiology GA 270QO UT WOS:000328333700001 PM 23863195 ER PT J AU Buckner, RL Krienen, FM AF Buckner, Randy L. Krienen, Fenna M. TI The evolution of distributed association networks in the human brain SO TRENDS IN COGNITIVE SCIENCES LA English DT Review ID INTRINSIC FUNCTIONAL CONNECTIVITY; PRIMATE CEREBRAL-CORTEX; HUMAN CORTICAL DEVELOPMENT; POSTERIOR PARIETAL CORTEX; VISUAL AREA MT; RHESUS-MONKEY; MACAQUE MONKEY; PREFRONTAL CORTEX; FRONTAL-LOBE; CORTICOCORTICAL CONNECTIONS AB The human cerebral cortex is vastly expanded relative to other primates and disproportionately occupied by distributed association regions. Here we offer a hypothesis about how association networks evolved their prominence and came to possess circuit properties vital to human cognition. The rapid expansion of the cortical mantle may have untethered large portions of the cortex from strong constraints of molecular gradients and early activity cascades that lead to sensory hierarchies. What fill the gaps between these hierarchies are densely interconnected networks that widely span the cortex and mature late into development. Limitations of the tethering hypothesis are discussed as well as its broad implications for understanding critical features of the human brain as a byproduct of size scaling. C1 [Buckner, Randy L.; Krienen, Fenna M.] Harvard Univ, Dept Psychol, Ctr Brain Sci, Cambridge, MA 02138 USA. [Buckner, Randy L.; Krienen, Fenna M.] Massachusetts Gen Hosp, Dept Radiol, Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA USA. [Buckner, Randy L.] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. RP Buckner, RL (reprint author), Harvard Univ, Dept Psychol, Ctr Brain Sci, 33 Kirkland St, Cambridge, MA 02138 USA. EM randy_buckner@harvard.edu NR 177 TC 74 Z9 74 U1 6 U2 57 PU ELSEVIER SCIENCE LONDON PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 1364-6613 J9 TRENDS COGN SCI JI TRENDS COGN. SCI. PD DEC PY 2013 VL 17 IS 12 BP 648 EP 665 DI 10.1016/j.tics.2013.09.017 PG 18 WC Behavioral Sciences; Neurosciences; Psychology, Experimental SC Behavioral Sciences; Neurosciences & Neurology; Psychology GA 276AD UT WOS:000328719600010 PM 24210963 ER PT J AU Liu, S Ren, JA Xia, QY Wu, XW Han, G Ren, HJ Yan, DS Wang, GF Gu, GS Li, JS AF Liu, Song Ren, Jianan Xia, Qiuyuan Wu, Xiuwen Han, Gang Ren, Huajian Yan, Dongsheng Wang, Gefei Gu, Guosheng Li, Jieshou TI Preliminary Case-control Study to Evaluate Diagnostic Values of C-Reactive Protein and Erythrocyte Sedimentation Rate in Differentiating Active Crohn's Disease From Intestinal Lymphoma, Intestinal Tuberculosis and Behcet's Syndrome SO AMERICAN JOURNAL OF THE MEDICAL SCIENCES LA English DT Article DE Crohn's disease; CRP; ESR; Biomarker; Differentiation ID INFLAMMATORY-BOWEL-DISEASE; ULCERATIVE-COLITIS; SEROLOGICAL MARKERS; MESENTERIC FAT; BIOMARKERS; DISORDERS; AID; IBD AB Background:There are few evidences of C-reactive protein (CRP), erythrocyte sedimentation rate (ESR) and white blood cell (WBC) in differentiating active Crohn's disease (CD) from intestinal lymphoma (IL), intestinal tuberculosis (ITB) and Behcet's syndrome (BD). This study is designed to investigate potential differential capacity of the 3 biomarkers between these disorders.Methods:A hospital-based case-control study was performed. A total of 29 active CD, 25 IL, 30 ITB and 17 BD patients were collected. Laboratory parameters were drawn from the first blood test results on admission.Results:In active CD group, the level of CRP was 20.2 4.26 mg/dL, which was statistically lower than IL (59.9 +/- 10.8 mg/dL, P < 0.0001). Similarly, the level of ESR reached its lowest point in active CD group (23.8 +/- 3.18 mm/hr), compared with 46.6 +/- 6.46 mm/hr in IL group (P = 0.0002). CRP showed a possible diagnostic value in differentiation of IL from active CD (odds ratio = 1.028, P = 0.046). CRP also exhibited a superior ability (area under curve [AUC] = 0.821) than ESR (AUC = 0.797) and CRP+ESR (AUC = 0.800) in distinguishing active CD from IL. The optimal cutoff value was 19.7 mg/dL, and the sensitivity and specificity were 62.1% and 96.0%, respectively.Conclusions:A significant decreased level of CRP and ESR was confirmed in active CD compared with IL. Current study demonstrated a possible differential value of CRP between active CD and IL. Further studies would be performed to validate their clinical significances. C1 [Liu, Song; Ren, Jianan; Wu, Xiuwen; Ren, Huajian; Yan, Dongsheng; Wang, Gefei; Gu, Guosheng; Li, Jieshou] Nanjing Univ, Sch Med, Dept Gen Surg, Jinling Hosp, Nanjing 210008, Jiangsu, Peoples R China. [Xia, Qiuyuan] Nanjing Univ, Sch Med, Dept Pathol, Jinling Hosp, Nanjing 210008, Jiangsu, Peoples R China. [Han, Gang] Jilin Univ, Affiliated Hosp 2, Dept Gen Surg, Gen Surg Ctr, Changchun, Jilin, Peoples R China. [Liu, Song] Massachusetts Gen Hosp, Ctr Study Inflammatory Bowel Dis, Boston, MA 02114 USA. [Liu, Song] Harvard Univ, Sch Med, Boston, MA USA. RP Ren, JA (reprint author), Jinling Hosp, Dept Gen Surg, 305 East Zhongshan Rd, Nanjing 210002, Jiangsu, Peoples R China. EM jiananr@gmail.com OI LIU, SONG/0000-0002-4780-9697; Ren, Jianan/0000-0002-7978-8093 FU National Nature Science Foundation of China [81270478/H0312]; Climb Program in Natural Science Foundation of Jiangsu Province for Distinguished Scholars [BK2010017] FX This work was supported by from the National Nature Science Foundation of China Grant 81270478/H0312 and the Climb Program in Natural Science Foundation of Jiangsu Province for Distinguished Scholars Grant BK2010017. NR 30 TC 13 Z9 15 U1 2 U2 10 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0002-9629 EI 1538-2990 J9 AM J MED SCI JI Am. J. Med. Sci. PD DEC PY 2013 VL 346 IS 6 BP 467 EP 472 DI 10.1097/MAJ.0b013e3182959a18 PG 6 WC Medicine, General & Internal SC General & Internal Medicine GA 266CS UT WOS:000328000500006 PM 23689052 ER PT J AU Guermazi, A Hayashi, D Smith, SE Palmer, W Katz, JN AF Guermazi, Ali Hayashi, Daichi Smith, Stacy E. Palmer, William Katz, Jeffrey N. TI Imaging of Blast Injuries to the Lower Extremities Sustained in the Boston Marathon Bombing SO ARTHRITIS CARE & RESEARCH LA English DT Article ID LONDON ATTACKS; LEAD ARTHROPATHY; AMPUTATIONS C1 [Guermazi, Ali; Hayashi, Daichi] Boston Univ, Sch Med, Boston Med Ctr, Boston, MA 02118 USA. [Smith, Stacy E.; Katz, Jeffrey N.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Boston, MA 02115 USA. [Palmer, William] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. RP Guermazi, A (reprint author), Boston Univ, Sch Med, 820 Harrison Ave,FGH Bldg,3rd Floor, Boston, MA 02118 USA. EM guermazi@bu.edu NR 20 TC 5 Z9 6 U1 0 U2 4 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 2151-464X EI 2151-4658 J9 ARTHRIT CARE RES JI Arthritis Care Res. PD DEC PY 2013 VL 65 IS 12 BP 1893 EP 1898 DI 10.1002/acr.22113 PG 6 WC Rheumatology SC Rheumatology GA 262PT UT WOS:000327750800001 PM 24039123 ER PT J AU Liao, KP Cai, TX Gainer, VS Cagan, A Murphy, SN Liu, CC Churchill, S Shaw, SY Kohane, I Solomon, DH Plenge, RM Karlson, EW AF Liao, Katherine P. Cai, Tianxi Gainer, Vivian S. Cagan, Andrew Murphy, Shawn N. Liu, Chihchin Churchill, Susanne Shaw, Stanley Y. Kohane, Isaac Solomon, Daniel H. Plenge, Robert M. Karlson, Elizabeth W. TI Lipid and Lipoprotein Levels and Trend in Rheumatoid Arthritis Compared to the General Population SO ARTHRITIS CARE & RESEARCH LA English DT Article ID CARDIOVASCULAR RISK-FACTORS; MORTALITY; RECORDS AB ObjectiveDifferences in lipid levels associated with cardiovascular (CV) risk between rheumatoid arthritis (RA) patients and the general population remain unclear. Determining these differences is important in understanding the role of lipids in CV risk in RA. MethodsWe studied 2,005 RA subjects from 2 large academic medical centers. We extracted electronic medical record data on the first low-density lipoprotein (LDL) measurement, and total cholesterol and high-density lipoprotein (HDL) measurements within 1 year of the LDL measurement. Subjects with an electronic statin prescription prior to the first LDL measurement were excluded. We compared lipid levels in RA patients to recently published levels from the general US population using the t-test and stratifying by published parameters, i.e., 2007-2010, and women. We determined lipid trends using separate linear regression models for total cholesterol, LDL cholesterol, and HDL cholesterol, testing the association between year of measurement (1989-2010) and lipid level, adjusted by age and sex. Lipid trends in RA were qualitatively compared to the published general population trends. ResultsWomen with RA had a significantly lower total cholesterol (186 versus 200 mg/dl; P = 0.002) and LDL cholesterol (105 versus 118 mg/dl; P = 0.001) compared to the general population (2007-2010). HDL cholesterol was not significantly different in the 2 groups. In the RA cohort, total cholesterol and LDL cholesterol significantly decreased each year, while HDL cholesterol increased (all with P < 0.0001), consistent with overall trends observed in a previous study. ConclusionRA patients appear to have an overall lower total cholesterol and LDL cholesterol than the general population despite the general overall risk of CV disease in RA from observational studies. C1 [Liao, Katherine P.; Liu, Chihchin; Solomon, Daniel H.; Plenge, Robert M.; Karlson, Elizabeth W.] Brigham & Womens Hosp, Boston, MA 02115 USA. [Cai, Tianxi; Kohane, Isaac] Harvard Univ, Boston, MA 02115 USA. [Gainer, Vivian S.; Cagan, Andrew; Murphy, Shawn N.; Churchill, Susanne] Partners Healthcare, Charlestown, MA USA. [Murphy, Shawn N.; Shaw, Stanley Y.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Plenge, Robert M.] Broad Inst, Cambridge, MA USA. RP Liao, KP (reprint author), Brigham & Womens Hosp, Div Rheumatol Immunol & Allergy, 75 Francis St,PBB B3, Boston, MA 02115 USA. EM kliao@partners.org FU Informatics for Integrating Biology and the Bedside (i2b2) project/NIH [U54-LM-008748]; NIH [K08-AR-060257, K24-AR-055989, R01-AR-057108, R01-AR-056768, U01-GM-092691, R01-AR-059648, K24-AR-052501]; Harold and Duval Bowen Fund; Burroughs Wellcome Fund FX Supported by the Informatics for Integrating Biology and the Bedside (i2b2) project/NIH (grant U54-LM-008748). Dr. Liao's work was supported by the NIH (grant K08-AR-060257) and the Harold and Duval Bowen Fund. Dr. Solomon's work was supported by the NIH (grant K24-AR-055989). Dr. Plenge's work was supported by the NIH (grants R01-AR-057108, R01-AR-056768, U01-GM-092691, and R01-AR-059648) and he holds a Career Award for Medical Scientists from the Burroughs Wellcome Fund. Dr. Karlson's work was supported by the NIH (grant K24-AR-052501). NR 15 TC 21 Z9 22 U1 0 U2 2 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 2151-464X EI 2151-4658 J9 ARTHRIT CARE RES JI Arthritis Care Res. PD DEC PY 2013 VL 65 IS 12 BP 2046 EP 2050 DI 10.1002/acr.22091 PG 5 WC Rheumatology SC Rheumatology GA 262PT UT WOS:000327750800020 PM 23925980 ER PT J AU Cai, S Hong, TS Goldberg, SI Fernandez-del Castillo, C Thayer, SP Ferrone, CR Ryan, DP Blaszkowsky, LS Kwak, EL Willett, CG Lillemoe, KD Warshaw, AL Wo, JY AF Cai, Sophie Hong, Theodore S. Goldberg, Saveli I. Fernandez-del Castillo, Carlos Thayer, Sarah P. Ferrone, Cristina R. Ryan, David P. Blaszkowsky, Lawrence S. Kwak, Eunice L. Willett, Christopher G. Lillemoe, Keith D. Warshaw, Andrew L. Wo, Jennifer Y. TI Updated Long-Term Outcomes and Prognostic Factors for Patients With Unresectable Locally Advanced Pancreatic Cancer Treated With Intraoperative Radiotherapy at the Massachusetts General Hospital, 1978 to 2010 SO CANCER LA English DT Article DE pancreatic cancer; locally advanced; radiotherapy; chemotherapy; survival ID PHASE-III TRIAL; COMORBIDITY INDEX; RADIATION-THERAPY; GEMCITABINE; CARCINOMA; SURVIVAL; AGE; CHEMOTHERAPY; CHEMORADIATION; ADENOCARCINOMA AB BACKGROUNDIn the current study, the authors evaluated long-term outcomes, intraoperative radiotherapy (IORT)-related toxicity, and prognostic factors for overall survival (OS) among patients with unresectable locally advanced pancreatic cancer (LAPC) who received IORT as part of their treatment at the Massachusetts General Hospital (MGH). METHODSMedical records were reviewed for 194 consecutive patients with unresectable LAPC who were treated with IORT at MGH between 1978 and 2010. OS was calculated using the Kaplan-Meier method. Prognostic factors were evaluated at the univariate level by the log-rank test and at the multivariate level by the Cox proportional hazards model. Rates of disease progression and treatment toxicity were calculated. RESULTSThe 1-year, 2-year, and 3-year survival rates were 49%, 16%, and 6%, respectively. Six patients (3%) survived for >5 years. The median OS was 12.0 months. Among 183 patients with known post-IORT disease status, the 2-year local progression-free survival and distant metastasis-free survival rates were 41% and 28%, respectively. On multivariate analysis, an IORT applicator diameter 8 cm (hazards ratio [HR], 0.51; 95% confidence interval [95% CI], 0.30-0.84 [P=.009]), a Charlson age-comorbidity index 3 (HR, 0.47; 95% CI, 0.31-0.73 [P=.001]), and receipt of chemotherapy (HR, 0.46; 95% CI, 0.33-0.66 [P<.001]) predicted improved OS. The median OS for patients with all 3 positive prognostic factors was 21.2 months. CONCLUSIONSWell-selected patients with LAPC with small tumors and low Charlson age-comorbidity indices can achieve good long-term survival outcomes with a treatment regimen that incorporates chemotherapy and IORT. Cancer 2013;119:4196-4204. (c) 2013 American Cancer Society. Among 194 patients with unresectable locally advanced pancreatic cancer who received intraoperative radiotherapy as part of their treatment, the 1-year, 2-year, 3-year, and 5-year overall survival rates were 49%, 16%, 6%, and 3%, respectively. Small tumor diameter, low Charlson age-comorbidity index, and receipt of chemotherapy were found to be independently predictive of improved survival, with a median overall survival of 21.2 months for patients with all 3 favorable prognostic factors. C1 [Cai, Sophie] Harvard Univ, Sch Med, Boston, MA USA. [Hong, Theodore S.; Goldberg, Saveli I.; Wo, Jennifer Y.] Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. [Fernandez-del Castillo, Carlos; Thayer, Sarah P.; Ferrone, Cristina R.; Lillemoe, Keith D.; Warshaw, Andrew L.] Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. [Ryan, David P.; Blaszkowsky, Lawrence S.; Kwak, Eunice L.] Massachusetts Gen Hosp, Dept Med Oncol, Boston, MA 02114 USA. [Willett, Christopher G.] Duke Univ, Med Ctr, Dept Radiat Oncol, Durham, NC USA. RP Wo, JY (reprint author), Massachusetts Gen Hosp, Dept Radiat Oncol, 100 Blossom St,Cox 3, Boston, MA 02114 USA. EM jwo@partners.org FU NCI NIH HHS [P01 CA117969, R01 CA169086] NR 28 TC 15 Z9 15 U1 0 U2 6 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0008-543X EI 1097-0142 J9 CANCER-AM CANCER SOC JI Cancer PD DEC 1 PY 2013 VL 119 IS 23 BP 4196 EP 4204 DI 10.1002/cncr.28329 PG 9 WC Oncology SC Oncology GA 263UF UT WOS:000327832800020 PM 24006012 ER PT J AU Yang, FC Tan, T Huang, TW Christianson, J Samad, OA Liu, Y Roberson, D Davis, BM Ma, QF AF Yang, Fu-Chia Tan, Taralyn Huang, Tianwen Christianson, Julie Samad, Omar A. Liu, Yang Roberson, David Davis, Brian M. Ma, Qiufu TI Genetic Control of the Segregation of Pain-Related Sensory Neurons Innervating the Cutaneous versus Deep Tissues SO CELL REPORTS LA English DT Article ID NEUROPATHIC PAIN; VISCERAL PAIN; MOLECULAR-MECHANISMS; TRANSCRIPTION FACTOR; NOCICEPTIVE NEURONS; MUSCLE AFFERENTS; CELLULAR BASIS; MOUSE; COLD; EXPRESSION AB Mammalian pain-related sensory neurons are derived from TrkA lineage neurons located in the dorsal root ganglion. These neurons project to peripheral targets throughout the body, which can be divided into superficial and deep tissues. Here, we find that the transcription factor Runx1 is required for the development of many epidermis-projecting TrkA lineage neurons. Accordingly, knockout of Runx1 leads to the selective loss of sensory innervation to the epidermis, whereas deep tissue innervation and two types of deep tissue pain are unaffected. Within these cutaneous neurons, Runx1 suppresses a large molecular program normally associated with sensory neurons that innervate deep tissues, such as muscle and visceral organs. Ectopic expression of Runx1 in these deep sensory neurons causes a loss of this molecular program and marked deficits in deep tissue pain. Thus, this study provides insight into a genetic program controlling the segregation of cutaneous versus deep tissue pain pathways. C1 [Yang, Fu-Chia; Huang, Tianwen; Samad, Omar A.; Liu, Yang; Ma, Qiufu] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. [Yang, Fu-Chia; Tan, Taralyn; Huang, Tianwen; Samad, Omar A.; Liu, Yang; Roberson, David; Ma, Qiufu] Harvard Univ, Sch Med, Dept Neurobiol, Boston, MA 02115 USA. [Christianson, Julie; Davis, Brian M.] Univ Pittsburgh, Med Ctr, Dept Med, Pittsburgh, PA 15261 USA. RP Ma, QF (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, 450 Brookline Ave, Boston, MA 02115 USA. EM qiufu_ma@dfci.harvard.edu OI Christianson, Julie/0000-0003-4117-5192; Davis, Brian/0000-0002-4646-0569 FU NIDCR, NIH [R01 DE018025]; NINDS, NIH [P01 NS047572, R01 NS050758] FX We thank Dr. Nancy Speck and Dr. Gary Gilliland for the floxed Runx1 mice, Dr. Rohini Kuner for the Nav1.8Cre/+ mice, Dr. David Rowitch for the Wnt1Cre/+ mice, Dr. Sylvia Arber for the TauLSL-mEGFP and the TauLSL-Runx1 mice, Dr. Mark Zylka for the MrgprdGFP/+ mice, Dr. Bradford Lowell for the VGLUT3Cre/+ mice, and Dr. Tsukasa Okuda for the Delta-446 mice. We also thank the Allen Brain Institute and the Jackson Laboratory for the Rosa26LSL-tdTomato mice and GENSAT and the MMRRC at University of California, Davis for the Prokr2Cre/+ mice. We thank Dr. Clifford Woolf for helpful discussions and comments. This work was supported by the NIH grants from NIDCR (R01 DE018025 for the Ma lab) and NINDS (P01 NS047572 for the Ma lab and R01 NS050758 for the Davis lab). NR 59 TC 13 Z9 13 U1 0 U2 3 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 2211-1247 J9 CELL REP JI Cell Reports PD DEC PY 2013 VL 5 IS 5 BP 1353 EP 1364 DI 10.1016/j.celrep.2013.11.005 PG 12 WC Cell Biology SC Cell Biology GA 269UB UT WOS:000328266400018 PM 24316076 ER PT J AU Spitler, R Schwappacher, R Wu, T Kong, XD Yokomori, K Pilz, RB Boss, GR Berns, MW AF Spitler, Ryan Schwappacher, Raphaela Wu, Tao Kong, Xiangduo Yokomori, Kyoko Pilz, Renate B. Boss, Gerry R. Berns, Michael W. TI Nitrosyl-cobinamide (NO-Cbi), a new nitric oxide donor, improves wound healing through cGMP/cGMP-dependent protein kinase SO CELLULAR SIGNALLING LA English DT Article DE Nitric oxide; Wound healing; Cell migration; PKG; ERK; Src ID COBALAMIN PRECURSOR COBINAMIDE; CANCER CELL-MIGRATION; BREAST-CANCER; SMOOTH-MUSCLE; CYCLIC-GMP; GUANYLATE-CYCLASE; SYNTHASE ACTIVITY; IN-VIVO; CGMP; ACTIVATION AB Nitric oxide (NO) donors have been shown to improve wound healing, but the mechanism is not well defined. Here we show that the novel NO donor nitrosyl-cobinamide (NO-Cbi) improved in vitro wound healing in several cell types, including an established line of lung epithelial cells and primary human lung fibroblasts. On a molar basis, NO-Cbi was more effective than two other NO donors, with the effective NO-Cbi concentration ranging from 3 to 10 mu M, depending on the cell type. Improved wound healing was secondary to increased cell migration and not cell proliferation. The wound healing effect of NO-Cbi was mediated by cGMP, mainly through cGMP-dependent protein kinase type I (PKGI), as determined using pharmacological inhibitors and activators, and siRNAs targeting PKG type I and II. Moreover, we found that Src and ERR were two downstream mediators of NO-Cbi's effect. We conclude that NO-Cbi is a potent inducer of cell migration and wound closure, acting via cGMP, PKG, Src, and extracellular signal regulated kinase (ERK). (C) 2013 Elsevier Inc. All rights reserved. C1 [Spitler, Ryan; Kong, Xiangduo; Yokomori, Kyoko; Berns, Michael W.] Univ Calif Irvine, Irvine, CA 92612 USA. [Schwappacher, Raphaela; Pilz, Renate B.; Boss, Gerry R.; Berns, Michael W.] Univ Calif San Diego, La Jolla, CA 92093 USA. [Wu, Tao] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. RP Spitler, R (reprint author), Univ Calif Irvine, Beckman Laser Inst, Dept Dev & Cell Biol, 1002 Hlth Sci Rd, Irvine, CA 92612 USA. EM rspitler@uci.edu FU Military Photomedicine Program, AFSOR [FA9550-08-1-0384]; CounterACT Program, Office of the Director, National Institutes of Health; National Institute of Neurological Disorders and Stroke [U01NS058030] FX Military Photomedicine Program, AFOSR Grant # FA9550-08-1-0384; CounterACT Program, Office of the Director, National Institutes of Health and the National Institute of Neurological Disorders and Stroke, Grant # U01NS058030. NR 60 TC 8 Z9 8 U1 2 U2 16 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0898-6568 EI 1873-3913 J9 CELL SIGNAL JI Cell. Signal. PD DEC PY 2013 VL 25 IS 12 BP 2374 EP 2382 DI 10.1016/j.cellsig.2013.07.029 PG 9 WC Cell Biology SC Cell Biology GA 268OG UT WOS:000328179800004 PM 23920342 ER PT J AU Bera, A Ghosh-Choudhury, N Dey, N Das, F Kasinath, BS Abboud, HE Choudhury, GG AF Bera, Amit Ghosh-Choudhury, Nandini Dey, Nirmalya Das, Falguni Kasinath, Balakuntalam S. Abboud, Hanna E. Choudhury, Goutam Ghosh TI NF kappa B-mediated cyclin D1 expression by microRNA-21 influences renal cancer cell proliferation SO CELLULAR SIGNALLING LA English DT Article DE MicroRNA; Renal cancer; PTEN; NF kappa B ID TUMOR-SUPPRESSOR; MAMMALIAN TARGET; RETINOBLASTOMA PROTEIN; TRANSGENIC MICE; KIDNEY CANCER; PI3K PATHWAY; PTEN; CARCINOMA; MUTATION; GENE AB MicroRNAs regulate post-transcriptomic landscape in many tumors including renal cell carcinoma. We have recently shown significantly increased expression of miR-21 in renal tumors and that this miRNA contributes to the proliferation of renal cancer cells in culture. However, the mechanism by which nniR-21 regulates renal cancer cell proliferation is poorly understood. Addiction to constitutive NF kappa B activity is hallmark of many cancers including renal cancer. Using miR-21 Sponge in renal cancer cells to block endogenous function of miR-21, we show inhibition of phosphorylation of p65 subunit of NF kappa B, IKK beta and I kappa B, which results in attenuation of NF kappa B transcriptional activity. Subtle reduction in the tumor suppressor PTEN has been linked to various malignancies. We showed previously that miR-21 targeted PTEN in renal cancer cells. Inhibition of PTEN by siRNAs restored miR-21 Sponge-induced suppression of phosphorylation of p65, IKK beta, I kappa B and NF kappa B transcriptional activity along with reversal of miR-21 Sponge-reduced phosphorylation of Akt. Expression of constitutively active Akt protected against miR-21 Sponge- and PTEN-mediated decrease in p65/IKK beta/I kappa B phosphorylation and NF kappa B transcriptional activity. Furthermore, IKK beta and p65 were required for miR-21-induced renal cancer cell proliferation. Interestingly, miR-21 controlled the expression of cyclin D1 through NF kappa B-dependent transcription. Finally, we demonstrate that miR-21-regulated renal cancer cell proliferation is mediated by cyclin D1 and CDK4. Together, our results establish a molecular order of a phosphatase-kinase couple involving PTEN/Akt/IKK beta and NF kappa B-dependent cyclin D1 expression for renal carcinoma cell proliferation by increased miR-21 levels. (C)0 2013 Elsevier Inc. All rights reserved. C1 [Bera, Amit; Dey, Nirmalya; Das, Falguni; Kasinath, Balakuntalam S.; Abboud, Hanna E.; Choudhury, Goutam Ghosh] Univ Texas Hlth Sci Ctr San Antonio, Dept Med, San Antonio, TX 78229 USA. [Ghosh-Choudhury, Nandini] Univ Texas Hlth Sci Ctr San Antonio, Dept Pathol, San Antonio, TX 78229 USA. [Ghosh-Choudhury, Nandini; Kasinath, Balakuntalam S.; Abboud, Hanna E.; Choudhury, Goutam Ghosh] South Texas Vet Hlth Care Syst, VA Res, San Antonio, TX USA. [Choudhury, Goutam Ghosh] South Texas Vet Hlth Care Syst, Geriatr Res Educ & Clin Ctr, San Antonio, TX USA. RP Choudhury, GG (reprint author), Univ Texas Hlth Sci Ctr San Antonio, Dept Med, San Antonio, TX 78229 USA. EM choudhuryg@uthscsa.edu FU VA Merit Review; NIH [RO1 DK50190, RC2A 036613, RO1 DK 78971]; VA Senior Research Career Scientist Award; VA Merit Review grant; Cancer Therapy and Research Center at San Antonio Pilot Project grant; VA Research Service; juvenile Diabetes Research Foundation FX This work was supported partly by the VA Merit Review and NIH RO1 DK50190 grants to GGC. GGC is a recipient of VA Senior Research Career Scientist Award. NGC is supported by VA Merit Review grant and Cancer Therapy and Research Center at San Antonio Pilot Project grant. BSK is supported by grants from NIH RC2A 036613 and VA Research Service. HEA is supported by NIH RO1 DK 78971, VA Merit Review and juvenile Diabetes Research Foundation grants. NR 68 TC 17 Z9 20 U1 0 U2 14 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0898-6568 EI 1873-3913 J9 CELL SIGNAL JI Cell. Signal. PD DEC PY 2013 VL 25 IS 12 BP 2575 EP 2586 DI 10.1016/j.cellsig.2013.08.005 PG 12 WC Cell Biology SC Cell Biology GA 268OG UT WOS:000328179800024 PM 23981302 ER PT J AU Rodriguez, F Cannon, CP Steg, G Kumbhani, DJ Goto, S Smith, SC Eagle, KA Ohman, EM Umez-Eronini, AA Hoffman, E Bhatt, DL AF Rodriguez, Fatima Cannon, Christopher P. Steg, Gabriel Kumbhani, Dharam J. Goto, Shinya Smith, Sidney C., Jr. Eagle, Kim A. Ohman, E. Magnus Umez-Eronini, Amarachi A. Hoffman, Elaine Bhatt, Deepak L. CA REACH Registry Investigators TI Predictors of Long-term Adherence to Evidence-based Cardiovascular Disease Medications in Outpatients With Stable Atherothrombotic Disease: Findings From the REACH Registry SO CLINICAL CARDIOLOGY LA English DT Article ID ATHEROSCLEROTIC VASCULAR-DISEASE; CORONARY-ARTERY-DISEASE; SECONDARY PREVENTION MEDICATIONS; POSTTRAUMATIC-STRESS-DISORDER; MYOCARDIAL-INFARCTION; AHA/ACC GUIDELINES; HEART-DISEASE; RISK-FACTORS; 2006 UPDATE; THERAPY AB BackgroundDespite overall improvements in cardiovascular-disease therapies and outcomes, medication nonadherence remains an important barrier to effective secondary prevention of atherothrombotic disease. HypothesisLong-term medication adherence in outpatients with stable atherothrombotic disease is impacted by demographic and clinical factors. MethodsWe examined data from the prospective international Reduction of Atherothrombosis for Continued Health (REACH) Registry. Analyses were derived from 25737 patients with established atherothrombotic disease with complete adherence data at enrollment and at year 4. Adherence was defined as patients' self-report of taking medications based on class I American College of Cardiology/American Heart Association guidelines for secondary prevention as defined, including antiplatelet agents, statins, and antihypertensive medications. ResultsAmong patients with atherothrombotic disease, 12500 (48.6%) were deemed adherent to guideline-recommended medications. Adherent patients were younger, white, and had less polyvascular disease. Hispanic and East Asian patients were less likely to be adherent as compared with white patients (odds ratio [OR]: 0.72, 95% confidence interval [CI]: 0.59-0.88; and OR: 0.67, 95% CI: 0.53-0.83, respectively). Patients who had a nonfatal MI or underwent coronary angioplasty/stenting during follow-up were more likely to be adherent compared with patients without these events (OR: 1.73, 95% CI: 1.25-2.38; and OR: 2.15, 95% CI: 1.72-2.67, respectively). On the other hand, nonfatal stroke during follow-up was inversely associated with adherence (OR: 0.77, 95% CI: 0.61-0.97). ConclusionsUsing a large international registry of outpatients with atherothrombotic disease, we found that age, region, race/ethnicity, and incident cardiovascular events were predictive of long-term guideline adherence for secondary prevention, suggesting that certain patient groups may benefit from targeted interventions to improve adherence. C1 [Rodriguez, Fatima] Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. [Rodriguez, Fatima; Cannon, Christopher P.; Hoffman, Elaine; Bhatt, Deepak L.] Harvard Univ, Sch Med, Boston, MA USA. [Cannon, Christopher P.; Umez-Eronini, Amarachi A.; Hoffman, Elaine; Bhatt, Deepak L.] TIMI Study Grp, Boston, MA USA. [Cannon, Christopher P.; Bhatt, Deepak L.] Brigham & Womens Hosp, Div Cardiovasc Med, Boston, MA 02115 USA. [Steg, Gabriel] Univ Paris Diderot DHU FIRE, Hop Bichat, AP HP, INSERM,U698, Paris, France. [Kumbhani, Dharam J.] Univ Texas SW Med Ctr Dallas, Div Cardiol, Dallas, TX 75390 USA. [Goto, Shinya] Tokai Univ, Sch Med, Isehara, Kanagawa 25911, Japan. [Smith, Sidney C., Jr.] Univ N Carolina, Ctr Cardiovasc Sci & Med, Chapel Hill, NC USA. [Eagle, Kim A.] Univ Michigan, Ctr Cardiovasc, Ann Arbor, MI 48109 USA. [Ohman, E. Magnus] Duke Univ, Div Cardiol, Durham, NC USA. [Bhatt, Deepak L.] VA Boston Healthcare Syst, Div Cardiol, Boston, MA USA. RP Bhatt, DL (reprint author), 75 Francis St, Boston, MA 02115 USA. EM dlbhattmd@post.harvard.edu FU sanofi-aventis; Bristol-Myers Squibb; Waksman Foundation (Tokyo, Japan) FX The REACH Registry is sponsored by sanofi-aventis, Bristol-Myers Squibb, and the Waksman Foundation (Tokyo, Japan). No funding was provided for this article. NR 38 TC 27 Z9 27 U1 2 U2 8 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0160-9289 EI 1932-8737 J9 CLIN CARDIOL JI Clin. Cardiol. PD DEC PY 2013 VL 36 IS 12 BP 721 EP 727 DI 10.1002/clc.22217 PG 7 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 263QW UT WOS:000327824100006 PM 24166484 ER PT J AU Cavender, MA Rassi, AN Fonarow, GC Cannon, CP Peacock, WF Laskey, WK Hernandez, AF Peterson, ED Cox, M Grau-Sepulveda, M Schwamm, LH Bhatt, DL AF Cavender, Matthew A. Rassi, Andrew N. Fonarow, Gregg C. Cannon, Christopher P. Peacock, W. Frank Laskey, Warren K. Hernandez, Adrian F. Peterson, Eric D. Cox, Margueritte Grau-Sepulveda, Marie Schwamm, Lee H. Bhatt, Deepak L. TI Relationship of Race/Ethnicity With Door-to-Balloon Time and Mortality in Patients Undergoing Primary Percutaneous Coronary Intervention for ST-Elevation Myocardial Infarction: Findings From Get With the Guidelines-Coronary Artery Disease SO CLINICAL CARDIOLOGY LA English DT Article ID ETHNIC-DIFFERENCES; ANGIOPLASTY; ASSOCIATION; REPERFUSION; OUTCOMES; QUALITY; THERAPY; PROGRAM; TRENDS AB BackgroundPrior studies have described racial/ethnic disparities in door-to-balloon (DTB) time for patients undergoing primary percutaneous coronary intervention (PCI). We sought to compare DTB time between different racial/ethnic groups undergoing primary PCI for ST-elevation myocardial infarction in Get With the Guidelines (GWTG). HypothesisThere may be differences in D2B time associated with race/ethnicity. MethodsWe identified 7445 white (n=6365), African American (n=568), and Hispanic (n=512) patients undergoing primary PCI. ResultsThere were no differences in the median DTB time between white (74minutes; intraquartile range [IQR], 54-99), African American (77minutes; IQR, 57-100), and Hispanic (75minutes; IQR, 56-100) (P = 0.13) patients. There were no crude differences in DTB time 90minutes; however, after adjusting for confounders, African American race was associated with lower odds of DTB time 90minutes (odds ratio [OR]: 0.84; 95% confidence interval [CI]: 0.70-0.99; P = 0.04). This association was seen in African American males (OR: 0.66; 95% CI: 0.55-0.80) but not African American females (OR: 1.27; 95% CI: 0.96-1.68). Overall, Hispanic ethnicity was not associated with a difference in DTB time 90minutes (OR: 0.98; 95% CI: 0.77-1.25; P = 0.88); although Hispanic males did have a slightly longer median DTB time compared with whites. During the study, the proportion of patients with DTB times 90minutes increased for all groups, and mortality was similar between groups (white 3.8%, African American 3.0%, Hispanic 4.1%, P = 0.62). ConclusionsIn GWTG-Coronary Artery Disease, small differences in DTB times persist among different races/ethnicities. However, the proportion achieving DTB times 90minutes has increased substantially for all patients over time, and there was no association between race/ethnicity and in-hospital mortality. C1 [Cavender, Matthew A.; Cannon, Christopher P.; Bhatt, Deepak L.] Brigham & Womens Hosp, Dept Med, TIMI Study Grp, Boston, MA 02115 USA. [Cavender, Matthew A.; Cannon, Christopher P.; Bhatt, Deepak L.] Harvard Univ, Sch Med, Boston, MA USA. [Rassi, Andrew N.] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. [Schwamm, Lee H.] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. [Fonarow, Gregg C.] Ronald Reagan UCLA Med Ctr, Dept Med, Los Angeles, CA USA. [Peacock, W. Frank] Baylor Coll Med, Houston, TX 77030 USA. [Laskey, Warren K.] Univ New Mexico, Dept Med, Albuquerque, NM 87131 USA. [Hernandez, Adrian F.; Peterson, Eric D.] Dept Med, Durham, NC USA. [Cox, Margueritte; Grau-Sepulveda, Marie] Duke Clin Res Inst, Durham, NC USA. [Bhatt, Deepak L.] VA Boston Healthcare Syst, Boston, MA USA. RP Bhatt, DL (reprint author), 75 Francis St, Boston, MA 02115 USA. EM dlbhattmd@post.harvard.edu RI Hernandez, Adrian F./A-7818-2016 OI Schwamm, Lee/0000-0003-0592-9145; Hernandez, Adrian F./0000-0003-3387-9616 FU American Heart Association FX This work was supported by a young investigator grant from the American Heart Association. NR 19 TC 10 Z9 10 U1 0 U2 2 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0160-9289 EI 1932-8737 J9 CLIN CARDIOL JI Clin. Cardiol. PD DEC PY 2013 VL 36 IS 12 BP 749 EP 756 DI 10.1002/clc.22213 PG 8 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 263QW UT WOS:000327824100010 PM 24085713 ER PT J AU Ross, RS LoPresti, ML Schon, K Stern, CE AF Ross, Robert S. LoPresti, Matthew L. Schon, Karin Stern, Chantal E. TI Role of the hippocampus and orbitofrontal cortex during the disambiguation of social cues in working memory SO COGNITIVE AFFECTIVE & BEHAVIORAL NEUROSCIENCE LA English DT Article DE Prefrontal; Social interaction; fMRI; Delayed match-to-sample ID MEDIAL TEMPORAL-LOBE; LONG-TERM-MEMORY; DORSOLATERAL PREFRONTAL CORTEX; MATCH-TO-SAMPLE; DELAYED MATCH; OVERLAPPING SEQUENCES; COMPLEMENTARY ROLES; PARIETAL CORTEX; NEURAL SYSTEMS; FRONTAL-CORTEX AB Human social interactions are complex behaviors requiring the concerted effort of multiple neural systems to track and monitor the individuals around us. Cognitively, adjusting our behavior on the basis of changing social cues such as facial expressions relies on working memory and the ability to disambiguate, or separate, the representations of overlapping stimuli resulting from viewing the same individual with different facial expressions. We conducted an fMRI experiment examining the brain regions contributing to the encoding, maintenance, and retrieval of overlapping identity information during working memory using a delayed match-to-sample task. In the overlapping condition, two faces from the same individual with different facial expressions were presented at sample. In the nonoverlapping condition, the two sample faces were from two different individuals with different expressions. fMRI activity was assessed by contrasting the overlapping and nonoverlapping conditions at sample, delay, and test. The lateral orbitofrontal cortex showed increased fMRI signal in the overlapping condition in all three phases of the delayed match-to-sample task and increased functional connectivity with the hippocampus when encoding overlapping stimuli. The hippocampus showed increased fMRI signal at test. These data suggest that lateral orbitofrontal cortex helps encode and maintain representations of overlapping stimuli in working memory, whereas the orbitofrontal cortex and hippocampus contribute to the successful retrieval of overlapping stimuli. We suggest that the lateral orbitofrontal cortex and hippocampus play a role in encoding, maintaining, and retrieving social cues, especially when multiple interactions with an individual need to be disambiguated in a rapidly changing social context in order to make appropriate social responses. C1 [Ross, Robert S.; LoPresti, Matthew L.; Schon, Karin; Stern, Chantal E.] Boston Univ, Ctr Memory & Brain, Boston, MA 02215 USA. [Ross, Robert S.; LoPresti, Matthew L.; Schon, Karin; Stern, Chantal E.] Boston Univ, CELEST, Boston, MA 02215 USA. [Ross, Robert S.; LoPresti, Matthew L.; Schon, Karin; Stern, Chantal E.] Boston Univ, Dept Psychol, Boston, MA 02215 USA. [Ross, Robert S.; LoPresti, Matthew L.; Schon, Karin; Stern, Chantal E.] Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA 02129 USA. [Ross, Robert S.; LoPresti, Matthew L.; Schon, Karin; Stern, Chantal E.] Harvard Univ, Sch Med, Charlestown, MA 02129 USA. [Stern, Chantal E.] Massachusetts Gen Hosp, Dept Radiol, Charlestown, MA 02129 USA. [Ross, Robert S.] Boston Univ, Boston, MA 02215 USA. RP Ross, RS (reprint author), Boston Univ, 2 Cummington Mall,Room 109, Boston, MA 02215 USA. EM bross@bu.edu OI Schon, Karin/0000-0003-2963-8449; Ross, Robert/0000-0002-3987-881X FU National Science Foundation Science of Learning Center [SMA-0835976]; National Institutes of Health [P50 MH071702]; Department of Psychology at Boston University; Center for Functional Neuroimaging Technologies [P41RR14075]; Biomedical Technology Program of the National Center for Research Resources (NCRR), National Institutes of Health; NCRR Shared Instrumentation Grant Program; High-End Instrumentation Grant Program [S10RR021110] FX This work was supported by the National Science Foundation Science of Learning Center (Grant No. SMA-0835976), the National Institutes of Health (Grant No. P50 MH071702), and the Department of Psychology at Boston University. Functional magnetic resonance imaging was conducted at the Athinoula A. Martinos Center for Biomedical Imaging at the Massachusetts General Hospital, using resources provided by the Center for Functional Neuroimaging Technologies, Grant No. P41RR14075, a P41 Regional Resource supported by the Biomedical Technology Program of the National Center for Research Resources (NCRR), National Institutes of Health. This work also involved the use of instrumentation supported by the NCRR Shared Instrumentation Grant Program and the High-End Instrumentation Grant Program; specifically, Grant No. S10RR021110. We thank Matthew Grace for his assistance developing and piloting the behavioral task, and Michael Hasselmo and David Somers for helpful discussions about the study. We also thank Ruben Gur's Brain Behavior Laboratory at the University of Pennsylvania for supplying the majority of the face stimuli used in this study. NR 68 TC 2 Z9 2 U1 3 U2 8 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1530-7026 EI 1531-135X J9 COGN AFFECT BEHAV NE JI Cogn. Affect. Behav. Neurosci. PD DEC PY 2013 VL 13 IS 4 BP 900 EP 915 DI 10.3758/s13415-013-0170-x PG 16 WC Behavioral Sciences; Neurosciences SC Behavioral Sciences; Neurosciences & Neurology GA 270TQ UT WOS:000328342000018 PM 23640112 ER PT J AU Maltzman, JS Turka, LA AF Maltzman, Jonathan S. Turka, Laurence A. TI T-Cell Costimulatory Blockade in Organ Transplantation SO COLD SPRING HARBOR PERSPECTIVES IN MEDICINE LA English DT Article ID RENAL-ALLOGRAFT REJECTION; MONOCLONAL-ANTIBODY TGN1412; RECEPTOR-ASSOCIATED FACTORS; LONG-TERM ACCEPTANCE; CARDIAC ALLOGRAFTS; NONHUMAN-PRIMATES; 4-1BB LIGAND; CD40 LIGAND; IN-VIVO; B-CELL AB Before it became possible to derive T-cell lines and clones, initial experimentation on the activation requirements of T lymphocytes was performed on transformed cell lines, such as Jurkat. These studies, although technically correct, proved misleading as most transformed T cells can be activated by stimulation of the clonotypic T-cell receptor (TCR) alone. In contrast, once it became possible to study nontransformed T cells, it quickly became clear that TCR stimulation by itself is insufficient for optimal activation of nai ve T cells, but in fact, induces a state of anergy. It then became clear that functional activation of T cells requires not only recognition of major histocompatibility complex (MHC) and peptide by the TCR, but also requires ligation of costimulatory receptors expressed on the cell surface. C1 [Maltzman, Jonathan S.] Univ Penn, Dept Med, Perelman Sch Med, Philadelphia, PA 19104 USA. [Turka, Laurence A.] Massachusetts Gen Hosp, Dept Surg, Transplantat Biol Res Ctr, Boston, MA 02129 USA. [Turka, Laurence A.] Harvard Univ, Sch Med, Boston, MA 02129 USA. RP Turka, LA (reprint author), Massachusetts Gen Hosp, Dept Surg, Transplantat Biol Res Ctr, Boston, MA 02129 USA. EM lturka@partners.org FU NIAID NIH HHS [R01 AI085160] NR 105 TC 3 Z9 3 U1 0 U2 2 PU COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT PI COLD SPRING HARBOR PA 1 BUNGTOWN RD, COLD SPRING HARBOR, NY 11724 USA SN 2157-1422 J9 CSH PERSPECT MED JI Cold Spring Harb. Perspect. Med. PD DEC PY 2013 VL 3 IS 12 AR a015537 DI 10.1101/cshperspect.a015537 PG 13 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 269XR UT WOS:000328277800002 PM 24296352 ER PT J AU Montecucco, F Cea, M Cagnetta, A Damonte, P Nahimana, A Ballestrero, A Del Rio, A Bruzzone, S Nencioni, A AF Montecucco, Fabrizio Cea, Michele Cagnetta, Antonia Damonte, Patrizia Nahimana, Aimable Ballestrero, Alberto Del Rio, Alberto Bruzzone, Santina Nencioni, Alessio TI Nicotinamide Phosphoribosyltransferase as a Target in Inflammation-Related Disorders SO CURRENT TOPICS IN MEDICINAL CHEMISTRY LA English DT Review DE CD38; chemical inhibitors; inflammation; NAD(+); NAMPT; PARP; sirtuins ID COLONY-ENHANCING FACTOR; NAMPT INHIBITORS; POLY(ADP-RIBOSE) POLYMERASE-1; BIOSYNTHESIS INHIBITOR; SIRT1 DEACETYLASE; NAD BIOSYNTHESIS; DOWN-REGULATION; T-LYMPHOCYTES; CELL-SURVIVAL; CANCER-CELLS AB NAD(+) biosynthesis through nicotinamide phosphoribosyltransferase (NAMPT) holds potential as a target for the treatment of inflammatory disorders due to NAD(+)'s role in immune cell signaling and metabolism. In addition to its activity as an enzyme, NAMPT is also secreted in the extracellular space where it acts as a pro-inflammatory and proangiogenic cytokine. NAMPT inhibition with FK866 has anti-inflammatory activity in different models of immune disorders and it prevents ischemia-reperfusion-induced heart damage by dampening the production of neutrophil chemo-attractants. NAMPT blockade with a neutralizing antibody has beneficial effects in an acute lung injury model. Last, but not least, the anticancer activity of NAMPT inhibitors may also reflect, at least in part, their ability to modify the cancer microenvironment through their anti-inflammatory properties. Overall, NAMPT inhibition holds potential for the treatment of inflammation-related disorders and the development of effective and safe NAMPT inhibitors remains an area of strong interest in pharmaceutical research. C1 [Montecucco, Fabrizio; Cea, Michele; Damonte, Patrizia; Ballestrero, Alberto; Nencioni, Alessio] Univ Genoa, Dept Internal Med, I-16132 Genoa, Italy. [Montecucco, Fabrizio] Univ Geneva, Fdn Med Res, Dept Med Specialties, Div Cardiol, CH-1211 Geneva, Switzerland. [Cea, Michele; Cagnetta, Antonia] Harvard Univ, Sch Med, LeBow Inst Myeloma Therapeut, Boston, MA USA. [Cea, Michele; Cagnetta, Antonia] Harvard Univ, Sch Med, Dana Farber Canc Inst, Jerome Lipper Ctr Multiple Myeloma Res, Boston, MA 02115 USA. [Nahimana, Aimable] Univ Hosp Lausanne CHUV, Serv & Cent Lab Hematol, Lausanne, Switzerland. [Del Rio, Alberto] Univ Bologna, Dept Expt Diagnost & Specialty Med DIMES, I-40126 Bologna, Italy. [Del Rio, Alberto] CNR, Inst Organ Synth & Photoreact, I-40129 Bologna, Italy. [Bruzzone, Santina] Univ Genoa, Biochem Sect, Dept Expt Med, I-16132 Genoa, Italy. [Nencioni, Alessio] IRCCS AOU San Martino IST, I-16132 Genoa, Italy. RP Montecucco, F (reprint author), Univ Geneva, Fdn Med Res, Dept Internal Med, Div Cardiol, 64 Ave Roseraie, CH-1211 Geneva, Switzerland. EM Fabrizio.montecucco@unige.ch; alessio.nencioni@unige.it RI Bruzzone, Santina/A-4264-2015; Del Rio, Alberto/F-5230-2010; Montecucco, Fabrizio/K-8543-2016 OI Bruzzone, Santina/0000-0003-2034-3716; Del Rio, Alberto/0000-0002-1890-6797; Montecucco, Fabrizio/0000-0003-0823-8729 FU Associazione Italiana per la Ricerca sul Cancro (AIRC) [6108]; European Seventh Framework Program (PANACREAS) [256986]; Ministero della Salute [GR-2008-1135635]; Fondazione Italiana Sclerosi Multipla (FISM); Compagnia di San Paolo; University of Genoa FX A. N. is supported in part by the Associazione Italiana per la Ricerca sul Cancro (AIRC, Code 6108, to A. N.), by the European Seventh Framework Program (project number 256986, PANACREAS, to A. N.), by the Ministero della Salute (GR-2008-1135635 to A. N.), by the Fondazione Italiana Sclerosi Multipla (FISM), by the Compagnia di San Paolo, and by the University of Genoa. NR 75 TC 9 Z9 9 U1 0 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 1568-0266 EI 1873-4294 J9 CURR TOP MED CHEM JI Curr. Top. Med. Chem. PD DEC PY 2013 VL 13 IS 23 BP 2930 EP 2938 PG 9 WC Chemistry, Medicinal SC Pharmacology & Pharmacy GA 265HY UT WOS:000327942600004 PM 24171767 ER PT J AU Etchegaray, JP Zhong, L Mostoslavsky, R AF Etchegaray, Jean-Pierre Zhong, Lei Mostoslavsky, Raul TI The Histone Deacetylase SIRT6: At the Crossroads Between Epigenetics, Metabolism and Disease SO CURRENT TOPICS IN MEDICINAL CHEMISTRY LA English DT Review DE Aging; cancer; deacetylase; epigenetics; glycolysis; metabolism; sirtuin; SIRT6 ID TUMOR-NECROSIS-FACTOR; DNA-DAMAGE RESPONSE; LIFE-SPAN; CANCER-CELLS; CARDIAC-HYPERTROPHY; MAMMALIAN SIRTUINS; GENOMIC STABILITY; PROTEIN-SYNTHESIS; STEM-CELLS; LYSINE 56 AB SIRT6 is one of the seven members of the NAD-dependent family of sirtuins mammals. The pleotropic identity of SIRT6 is manifested into several catalytic activities such as deacetylation, deacylation and ribosylation, which allow the targeting of a variety of protein substrates, that influence the physiology of multiple cell types and tissues. SIRT6-dependent deacetylation of histone H3 at lysines 9 and 56 is required for the regulation of genes associated with glucose/ lipid metabolism as well as the maintenance of telomeric regions and the repair of DNA double strand breaks. Importantly, SIRT6 depletion alters the levels of acetylated histone H3 causing a deregulation of genes involved in glycolysis and the Myc-target network, which results in tumorigenesis. Hence, SIRT6 has been recently categorized as a tumor suppressor. The deacylation activity of SIRT6 has been attributed to the regulation of TNF-alpha secretion. However, the physiological relevance of this newly discovered catalytic activity of SIRT6 remains to be determined in vivo. SIRT6 also undergoes auto-ribosylation, which might contribute to a self-regulation of catalytic functions. SIRT6-mediated ribosylation also enhances PARP1-dependent DNA repair under oxidative stress and aging. Overall, SIRT6 is a critical enzyme required to maintain glucose/ lipid homeostasis and genomic stability, thereby promoting resistance to oxidative stress and DNA damage, which are associated to age-related illness. Evocative of its ancestor, yeast Sir2, SIRT6 has the ability to increase lifespan in mice. SIRT6 deficiency is associated with various diseases including inflammation, cardiac hypertrophy, liver dysfunction, adipocyte/muscle disorders, and cancer. This review describes the most current information regarding the molecular and physiological relevance of SIRT6 in the context of epigenetics, metabolism and disease. C1 [Etchegaray, Jean-Pierre; Zhong, Lei; Mostoslavsky, Raul] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Canc, Boston, MA 02114 USA. [Mostoslavsky, Raul] Massachusetts Gen Hosp, Ctr Regenerat Med, Boston, MA 02114 USA. RP Mostoslavsky, R (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Canc, Boston, MA 02114 USA. EM rmostoslavsky@mgh.harvard.edu FU NIH [GM093072-01, DK088190-01A1]; National Pancreatic Foundation; Tosteson MGH ECOR postdoctoral fellowship FX Work in the Mostoslavsky lab is supported in part by NIH grants GM093072-01 and DK088190-01A1, and the National Pancreatic Foundation. R.M is the Kristine and Bob Higgins MGH Research Scholar and a Howard Goodman Awardee. L.Z. is the recipient of a Tosteson MGH ECOR postdoctoral fellowship. NR 72 TC 25 Z9 26 U1 1 U2 20 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 1873-4294 J9 CURR TOP MED CHEM JI Curr. Top. Med. Chem. PD DEC PY 2013 VL 13 IS 23 BP 2991 EP 3000 PG 10 WC Chemistry, Medicinal SC Pharmacology & Pharmacy GA 265HY UT WOS:000327942600009 PM 24171769 ER PT J AU Kelly, JF Greene, MC AF Kelly, John F. Greene, M. Claire TI The Twelve Promises of Alcoholics Anonymous: Psychometric measure validation and mediational testing as a 12-step specific mechanism of behavior change SO DRUG AND ALCOHOL DEPENDENCE LA English DT Article DE Alcoholics Anonymous; 12-Step; Twelve Promises; Recovery; Addiction; Young adults ID PRINCIPAL THEORETICAL MECHANISM; SELF-HELP GROUPS; SUBSTANCE-ABUSE; REDUCE DEMAND; PARTICIPATION; SPIRITUALITY; ADDICTION; OUTCOMES; INDIVIDUALS; INVOLVEMENT AB Background: Empirical support for the recovery utility of 12-step mutual-help organizations (MHOs) has led to increased investigation of how such organizations confer benefit. The Twelve Promises of Alcoholics Anonymous (AA) feature prominently in 12-step philosophy and culture and are one of the few documented explications of the cognitive, affective, and behavioral benefits that members might accrue. This study investigated the psychometric properties of a measure of AA's Twelve Promises and examined whether it mediated the effect of 12-step participation on abstinence. Method: Young adults (N=302, M age 20.4 [1.6], range 18-25; 27% female; 95% White) enrolled in an addiction treatment effectiveness study completed assessments at intake and 3-, 6-, and 12-months post treatment including a 26-item, Twelve Promises Scale (TPS). Factor analyses examined the TPS' psychometrics and lagged mediational analyses tested the TPS as a mechanism of behavior change. Results: Robust principal axis factoring extraction with Varimax rotation revealed a 2-factor solution explaining 45-58% of the variance across three administrations ("Psychological Wellbeing" = 26-39%; "Freedom from Craving = 17-21%); internal consistency was high (alpha = .83-.93). Both factors were found to increase in relation to greater 12-step participation, but significant mediation was found only for the Freedom from Craving factor explaining 21-34% of the effect of 12-step participation in increasing abstinence. Conclusions: The TPS shows potential as a conceptually relevant, and psychometrically sound measure and may be useful in helping elucidate the extent to which the Twelve Promises emerge as an independent benefit of 12-step participation and/or explain SUD remission and recovery. (C) 2013 Elsevier Ireland Ltd. All rights reserved. C1 [Kelly, John F.; Greene, M. Claire] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Addict Med,Dept Psychiat, Boston, MA 02114 USA. RP Kelly, JF (reprint author), 60 Staniford St, Boston, MA 02114 USA. EM jkelly11@partners.org FU National Institute of Alcohol Abuse and Alcoholism [NIAAA R21AA018185-01A2] FX This research was supported by a grant from the National Institute of Alcohol Abuse and Alcoholism (NIAAA R21AA018185-01A2; Mechanisms and Moderators of Behavior Change among young adults treated for Alcohol use disorder). NIAAA had no further role in study design; in the collection, analysis and interpretation of data; in the writing of the report; or in the decision to submit the paper for publication. NR 44 TC 2 Z9 2 U1 3 U2 32 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0376-8716 EI 1879-0046 J9 DRUG ALCOHOL DEPEN JI Drug Alcohol Depend. PD DEC 1 PY 2013 VL 133 IS 2 BP 633 EP 640 DI 10.1016/j.drugalcdep.2013.08.006 PG 8 WC Substance Abuse; Psychiatry SC Substance Abuse; Psychiatry GA 269KT UT WOS:000328240900046 PM 24004905 ER PT J AU Li, XB Malcolm, RJ Huebner, K Hanlon, CA Taylor, JJ Brady, KT George, MS See, RE AF Li, Xingbao Malcolm, Robert J. Huebner, Kristina Hanlon, Colleen A. Taylor, Joseph. J. Brady, Kathleen T. George, Mark S. See, Ronald E. TI Low frequency repetitive transcranial magnetic stimulation of the left dorsolateral prefrontal cortex transiently increases cue-induced craving for methamphetamine: A preliminary study SO DRUG AND ALCOHOL DEPENDENCE LA English DT Article DE Methamphetamine; Craving; Transcranial magnetic stimulation; Dorsolateral prefrontal cortex ID LONG-TERM DEPRESSION; MOTOR CORTEX; ABSTINENT METHAMPHETAMINE; DEPENDENT SUBJECTS; DECISION-MAKING; DRUG-ADDICTION; BRAIN ACTIVITY; SELF-CONTROL; DOPAMINE; EXCITABILITY AB Background: Repetitive transcranial magnetic stimulation (rTMS) can temporarily interrupt or facilitate activity in a focal brain region. Several lines of evidence suggest that rTMS of the dorsolateral prefrontal cortex (DLPFC) can affect processes involved in drug addiction. We hypothesized that a single session of low-frequency rTMS of the left DLPFC would modulate cue-induced craving for methamphetamine (MA) when compared to a sham rTMS session. Methods: In this single-blind, sham-controlled crossover study, 10 non-treatment seeking MA-dependent users and 8 healthy controls were randomized to receive 15 min of sham and real (1 Hz) DLPFC rTMS in two experimental sessions separated by 1 h. During each rTMS session, participants were exposed to blocks of neutral cues and MA-associated cues. Participants rated their craving after each cue block. Results: In MA users, real rTMS over the left DLPFC increased self-reported craving as compared to sham stimulation (17.86 +/- 1.46 vs. 24.85 +/- 1.57, p = 0.001). rTMS had no effect on craving in healthy controls. One Hertz rTMS of the left DLPFC was safe and tolerable for all participants. Conclusions: Low frequency rTMS of the left DLPFC transiently increased cue-induced craving in MA participants. These preliminary results suggest that 1 Hz rTMS of the left DLPFC may increase craving by inhibiting the prefrontal cortex or indirectly activating subcortical regions involved in craving. (C) 2013 Elsevier Ireland Ltd. All rights reserved. C1 [Li, Xingbao; Malcolm, Robert J.; Huebner, Kristina; Hanlon, Colleen A.; Taylor, Joseph. J.; Brady, Kathleen T.; George, Mark S.; See, Ronald E.] Med Univ S Carolina, Charleston, SC USA. [Brady, Kathleen T.; George, Mark S.] Ralph H Johnson VA Med Ctr, Charleston, SC USA. RP Li, XB (reprint author), MUSC IOP, Brain Stimulat Lab, 502N,67 President St, Charleston, SC 29425 USA. EM lixi@musc.edu FU National Institutes of Health [P20 DA022658] FX The study was funded by a grant from the National Institutes of Health (Grant no. P20 DA022658 (RE SEE)). NR 64 TC 12 Z9 12 U1 6 U2 13 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0376-8716 EI 1879-0046 J9 DRUG ALCOHOL DEPEN JI Drug Alcohol Depend. PD DEC 1 PY 2013 VL 133 IS 2 BP 641 EP 646 DI 10.1016/j.drugalcdep.2013.08.012 PG 6 WC Substance Abuse; Psychiatry SC Substance Abuse; Psychiatry GA 269KT UT WOS:000328240900047 PM 24028801 ER PT J AU Durazzo, TC Meyerhoff, DJ Nixon, SJ AF Durazzo, Timothy C. Meyerhoff, Dieter J. Nixon, Sara Jo TI Interactive effects of chronic cigarette smoking and age on hippocampal volumes SO DRUG AND ALCOHOL DEPENDENCE LA English DT Article DE Cigarette smoking; MRI; Hippocampus; Hippocampal subfields; Learning and memory; Aging ID MILD COGNITIVE IMPAIRMENT; SURFACE-BASED ANALYSIS; HUMAN CEREBRAL-CORTEX; ALZHEIMERS-DISEASE; OXIDATIVE STRESS; ENTORHINAL CORTEX; AUTOMATED SEGMENTATION; NICOTINE ADDICTION; BACOSIDE-A; BRAIN AB Background: Previous cross-sectional MRI studies with healthy, young-to-middle-aged adults reported no significant differences between smokers and non-smokers on total hippocampal volume. However, these studies did not specifically test for greater age-related volume loss in the total hippocampus or hippocampal subregions in smokers, and did they did not examine relationships between hippocampal and subfield volumes and episodic learning and memory performance. Methods: Healthy, young-to-middle-aged (45 +/- 12 years of age) smokers (n = 39) and non-smokers (n = 43) were compared on total hippocampal and subfield volumes derived from high-resolution 4Tesla MRI, emphasizing testing for greater age-related volume losses in smokers. Associations between hippocampal volumes and measures of episodic learning and memory were examined. Results: Smokers showed significantly smaller volumes, as well as greater volume loss with increasing age than non-smokers in the bilateral total hippocampus and multiple subfields. In smokers, greater pack-years were associated with smaller volumes of the total hippocampus, presubiculum, and subiculum. In the entire cohort, performance on measures of learning and memory was related to larger total hippocampal and several subfield volumes, predominately in the left hemisphere. Conclusions: Chronic cigarette smoking in this young-to-middle aged cohort was associated with smaller total hippocampal and subfield volumes, which were exacerbated by advancing age. Findings also indicated an adverse smoking dose/duration response (i.e., pack-years) with total hippocampal and select subfield volumes. These hippocampal volume abnormalities in smokers may be related to the deficiencies in episodic learning and memory in young-to-middle-aged smokers reported in previous studies. (C) 2013 Elsevier Ireland Ltd. All rights reserved. C1 [Durazzo, Timothy C.; Meyerhoff, Dieter J.] San Francisco VA Med Ctr, CIND, San Francisco, CA 94121 USA. [Durazzo, Timothy C.; Meyerhoff, Dieter J.] Univ Calif San Francisco, Dept Radiol & Biomed Imaging, San Francisco, CA 94143 USA. [Nixon, Sara Jo] Univ Florida, Dept Psychiat, Gainesville, FL 32611 USA. [Nixon, Sara Jo] Univ Florida, Dept Psychol, Gainesville, FL 32611 USA. RP Durazzo, TC (reprint author), San Francisco VA Med Ctr, CIND, 4150 Clement St 114M, San Francisco, CA 94121 USA. EM timothy.durazzo@ucsf.edu RI Nixon, Sara/L-1369-2014 OI Nixon, Sara/0000-0003-1179-2851 FU National Institute on Drug Abuse [DA24136]; Department of Defense [W81XWH-05-2-0094]; National Institute on Alcohol and Alcoholism [AA10788] FX This material is the result of work supported by the National Institute on Drug Abuse (DA24136 to TCD), Department of Defense (W81XWH-05-2-0094 to TCD), and National Institute on Alcohol and Alcoholism (AA10788 to Dieter J. Meyerhoff), and with resources and the use of facilities at the San Francisco Veterans Administration Medical Center, San Francisco CA. We thank Dr. Anderson Mon for assistance in MR data acquisition in early studied participants. We also wish to extend our gratitude to the study participants, who made this research possible. NR 83 TC 16 Z9 16 U1 1 U2 13 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0376-8716 EI 1879-0046 J9 DRUG ALCOHOL DEPEN JI Drug Alcohol Depend. PD DEC 1 PY 2013 VL 133 IS 2 BP 704 EP 711 DI 10.1016/j.drugalcdep.2013.08.020 PG 8 WC Substance Abuse; Psychiatry SC Substance Abuse; Psychiatry GA 269KT UT WOS:000328240900055 PM 24051060 ER PT J AU Ge, ML Wang, DH Dong, GY Guo, BQ Gao, RG Sun, W Zhang, JJ Liu, HS AF Ge, Manling Wang, Danhong Dong, Guoya Guo, Baoqiang Gao, Rongguang Sun, Wei Zhang, Jijun Liu, Hesheng TI Transient impact of spike on theta rhythm in temporal lobe epilepsy SO EXPERIMENTAL NEUROLOGY LA English DT Article DE Theta rhythm; Temporal lobe epilepsy; Hippocampus; Epileptogenesis ID INTERICTAL SPIKES; SPATIAL MEMORY; FOCAL EPILEPTOGENESIS; STATUS EPILEPTICUS; HIPPOCAMPAL EEG; PLACE CELLS; IN-VITRO; RATS; INHIBITION; NETWORK AB Epileptic spike is an indicator of hyper-excitability and hyper-synchrony of neural networks. While cognitive deficit in epilepsy is a common observation, how spikes transiently influence brain oscillations, especially those essential for cognitive functions, remains obscure. Here we aimed to quantify the transient impacts of sporadic spikes on theta oscillations and investigate how such impacts may evolve during epileptogenesis. Longitudinal depth EEG data were recorded in the CA1 area of pilocarpine temporal lobe epilepsy (TLE) rat models. Phase stability, a measure of synchrony, and theta power were estimated around spikes as well as in the protracted spike-free periods (FP) at least 1 h after spike bursts. We found that the change in theta power did not correlate with the change in phase stability. More importantly, the impact of spikes on theta rhythm was highly time-dependent. While theta power decreased abruptly after spikes both in the latent and chronic stages, changes of theta phase stability demonstrated opposite trends in the latent and chronic stages, potentially due to the substantial reorganization of neural circuits along epileptogenesis. During FP, theta phase stability was significantly higher than the baseline level before injections, indicating that hyper-synchrony remained even hours after the spike bursts. We concluded that spikes have transient negative effects on theta rhythm, however, impacts are different during latent and chronic stages, implying that its influence on cognitive processes may also change over time during epileptogenesis. (C) 2013 Elsevier Inc. All rights reserved. C1 [Ge, Manling; Dong, Guoya; Guo, Baoqiang] Hebei Univ Technol, Dept Biomed Engn, Key Lab Electromagnet Field & Elect Apparat Relia, Tianjin 300130, Peoples R China. [Wang, Danhong; Liu, Hesheng] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Radiol,Athinoula A Martinos Ctr Biomed Imagi, Charlestown, MA USA. [Gao, Rongguang] Fuzhou Gen Hosp, Dept Nucl Med, Fuzhou 350025, Peoples R China. [Sun, Wei] Capital Med Univ, Xuan Wu Hosp, Dept Neurophysiol, Beijing 100053, Peoples R China. [Zhang, Jijun] Tianjin Peoples Hosp, Dept Internal Med, Tianjin 300121, Peoples R China. RP Zhang, JJ (reprint author), Tianjin Peoples Hosp, Tianjin 300121, Peoples R China. EM jijunzhangxj@sina.com OI Liu, Hesheng/0000-0002-7233-1509 FU Natural Science Grant [E2010000053]; Hebei Province; Key Laboratory for Electromagnetic Fields and Electrical Apparatus Reliability, Tianjin, China; NIH [K25NS069805]; National Natural Science Foundation of China [81171229] FX This work is supported by the Natural Science Grant (E2010000053) sponsored by Hebei Province and Key Laboratory for Electromagnetic Fields and Electrical Apparatus Reliability, Tianjin, China. H. Liu is supported by NIH grant K25NS069805. W. Sun is supported by the National Natural Science Foundation of China (81171229). NR 43 TC 5 Z9 5 U1 0 U2 11 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0014-4886 EI 1090-2430 J9 EXP NEUROL JI Exp. Neurol. PD DEC PY 2013 VL 250 BP 136 EP 142 DI 10.1016/j.expneurol.2013.09.023 PG 7 WC Neurosciences SC Neurosciences & Neurology GA 270FZ UT WOS:000328305600014 PM 24100023 ER PT J AU Aytan, N Choi, JK Carreras, I Kowall, NW Jenkins, BG Dedeoglu, A AF Aytan, Nurgul Choi, Ji-Kyung Carreras, Isabel Kowall, Neil W. Jenkins, Bruce G. Dedeoglu, Alpaslan TI Combination therapy in a transgenic model of Alzheimer's disease SO EXPERIMENTAL NEUROLOGY LA English DT Article DE Alzheimer's disease; Scyllo-inositol; R-flurbiprofen; Magnetic resonance spectroscopy ID NONSTEROIDAL ANTIINFLAMMATORY DRUGS; IMPAIR SYNAPTIC PLASTICITY; GAMMA-SECRETASE; SCYLLO-INOSITOL; A-BETA; FLURBIPROFEN; MEMORY; MICE; MUTATIONS; AGGREGATION AB The pathological accumulation of the beta-amyloid protein (A beta) has been closely associated with synaptic loss and neurotoxicity contributing to cognitive dysfunction in Alzheimer's disease (AD). Oligomers of A beta 42 appear to be the most neurotoxic form. Two of the most promising attempts to reduce A beta accumulation have been with scyllo-inositol, an inositol steroisomer, that stabilizes A beta 42 peptide and prevents it from progressing to oligomers and fibrils and R-flurbiprofen, a purified enantiomer of the classical racemic non-steroidal anti-inflammatory drugs (NSAID), flurbiprofen, that retains the ability to specifically lower A beta 42. In the present study we evaluated the effects of scyllo-inositol and the combination treatment of scyllo-inositol + R-flurbiprofen on amyloid pathology and hippocampal-dependent memory function in 5XFAD mice, a model of A beta pathology characterized by an enormous production of A beta 42. Our expectations were that the combination treatment of scylloinositol + R-flurbiprofen would have an additive effect in preventing A beta accumulation and that cognition would be improved. Mice treated with scyllo-inositol exhibit 41 and 35% reduction in the deposition of the amyloid plaques stained by antibody against A beta 42 and A beta 40 respectively. Scyllo-inositol was not more effective when combined with R-flurbiprofen for the measures tested. Scyllo-inositol treated mice performed significantly better at the radial arm water maze (RAWM) task than untreated and scyllo-inositol + R-flurbiprofen treated mice. Published by Elsevier Inc. C1 [Aytan, Nurgul; Carreras, Isabel; Kowall, Neil W.; Dedeoglu, Alpaslan] VA Boston Healthcare Syst, Dept Vet Affairs, Boston, MA 02130 USA. [Aytan, Nurgul; Kowall, Neil W.; Dedeoglu, Alpaslan] Boston Univ, Sch Med, Dept Neurol, Boston, MA 02118 USA. [Choi, Ji-Kyung; Jenkins, Bruce G.; Dedeoglu, Alpaslan] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. [Carreras, Isabel] Boston Univ, Sch Med, Dept Biochem, Boston, MA 02118 USA. [Choi, Ji-Kyung; Jenkins, Bruce G.; Dedeoglu, Alpaslan] Harvard Univ, Sch Med, Dept Radiol, Cambridge, MA 02138 USA. RP Dedeoglu, A (reprint author), VA Boston Healthcare Syst, Res & Dev Serv, Bldg 1A 151,150 S Huntington Ave, Boston, MA 02130 USA. EM naytan@bu.edu; jchoi@nmr.mgh.harvard.edu; carreras@bu.edu; nkowall@bu.edu; bgj@nmr.mgh.harvard.edu; dedeoglu@bu.edu RI Kowall, Neil/G-6364-2012 OI Kowall, Neil/0000-0002-6624-0213 FU NIA [R01AG031896]; Department of Veteran Affairs (Merit Award) FX This research is supported by grants from NIA (R01AG031896) to A. Dedeoglu and the Department of Veteran Affairs (Merit Award) to A. Dedeoglu. The authors thank Lokman Hossain for animal husbandry, and Dr. Kenton H. Zavitz for providing the R-flurbiprofen (tarenflurbil). NR 32 TC 15 Z9 16 U1 0 U2 7 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0014-4886 EI 1090-2430 J9 EXP NEUROL JI Exp. Neurol. PD DEC PY 2013 VL 250 BP 228 EP 238 DI 10.1016/j.expneurol.2013.10.001 PG 11 WC Neurosciences SC Neurosciences & Neurology GA 270FZ UT WOS:000328305600025 PM 24120437 ER PT J AU Jakobiec, FA Mendoza, PR Hatton, MP AF Jakobiec, Frederick A. Mendoza, Pia R. Hatton, Mark P. TI Fatty nodules of the dermis of the upper eyelids: a new entity SO GRAEFES ARCHIVE FOR CLINICAL AND EXPERIMENTAL OPHTHALMOLOGY LA English DT Letter ID LIPOGRANULOMA C1 [Jakobiec, Frederick A.; Mendoza, Pia R.] Massachusetts Eye & Ear Infirm, David G Cogan Lab Ophthalm Pathol, Boston, MA 02114 USA. [Jakobiec, Frederick A.; Mendoza, Pia R.; Hatton, Mark P.] Massachusetts Eye & Ear Infirm, Dept Ophthalmol, Boston, MA 02114 USA. [Jakobiec, Frederick A.; Mendoza, Pia R.; Hatton, Mark P.] Harvard Univ, Sch Med, Boston, MA USA. [Hatton, Mark P.] Ophthalm Consultants Boston, Boston, MA USA. RP Jakobiec, FA (reprint author), Massachusetts Eye & Ear Infirm, David G Cogan Lab Ophthalm Pathol, 243 Charles St,Suite 328, Boston, MA 02114 USA. EM fred_jakobiec@meei.harvard.edu NR 10 TC 1 Z9 1 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0721-832X EI 1435-702X J9 GRAEF ARCH CLIN EXP JI Graefes Arch. Clin. Exp. Ophthalmol. PD DEC PY 2013 VL 251 IS 12 BP 2823 EP 2825 DI 10.1007/s00417-013-2443-z PG 3 WC Ophthalmology SC Ophthalmology GA 270US UT WOS:000328345000021 PM 23949689 ER PT J AU Bugler, J Toolan, S Xie, W Maglio, M Mitsiades, CS Laubach, J O'Gorman, P Richardson, PG AF Bugler, J. Toolan, S. Xie, W. Maglio, M. Mitsiades, C. S. Laubach, J. O'Gorman, P. Richardson, P. G. TI RETROSPECTIVE ANALYSIS OF EXTRAMEDULLARY DISEASE IN PATIENTS INITIALLY TREATED FOR MULTIPLE MYELOMA SO IRISH JOURNAL OF MEDICAL SCIENCE LA English DT Meeting Abstract C1 [Bugler, J.; Toolan, S.; Xie, W.; Maglio, M.; Mitsiades, C. S.; Laubach, J.; Richardson, P. G.] Dana Farber Canc Inst, Jerome Lipper Multiple Myeloma Ctr, Boston, MA 02115 USA. [Bugler, J.; O'Gorman, P.] Mater Misericordiae Univ Hosp, Dept Haematol, Dublin 7, Ireland. NR 2 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 0021-1265 EI 1863-4362 J9 IRISH J MED SCI JI Irish J. Med. Sci. PD DEC PY 2013 VL 182 SU 11 BP S496 EP S497 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA 270VM UT WOS:000328347300021 ER PT J AU Moloney, D Behan, C Hill, M Kinsella, A Clarke, M AF Moloney, D. Behan, C. Hill, M. Kinsella, A. Clarke, M. TI PREDICTORS OF LONG TERM HEALTH SERVICE USE IN PEOPLE WITH A FIRST EPISODE OF PSYCHOSIS SO IRISH JOURNAL OF MEDICAL SCIENCE LA English DT Meeting Abstract C1 [Moloney, D.; Clarke, M.] Natl Univ Ireland Univ Coll Dublin, UCD Sch Med & Med Sci, Dublin 4, Ireland. [Behan, C.; Kinsella, A.; Clarke, M.] DETECT, Blackrock, Dublin, Ireland. [Hill, M.] Massachusetts Gen Hosp, Schizophrenia Program, Boston, MA 02114 USA. [Hill, M.] Harvard Univ, Sch Med, Cambridge, MA 02138 USA. NR 1 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 0021-1265 EI 1863-4362 J9 IRISH J MED SCI JI Irish J. Med. Sci. PD DEC PY 2013 VL 182 SU 11 BP S504 EP S504 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA 270VM UT WOS:000328347300040 ER PT J AU Toolan, S Bugler, J Lane, W Maglio, M O'Gorman, P Richardson, PG AF Toolan, S. Bugler, J. Lane, W. Maglio, M. O'Gorman, P. Richardson, P. G. TI NOVEL THERAPY INDUCTION IN A PATIENT WITH HIGH RISK MULTIPLE MYELOMA FOLLOWED BY AUTOLOGOUS STEM CELL TRANSPLANTATION (ASCT): A CASE REPORT SO IRISH JOURNAL OF MEDICAL SCIENCE LA English DT Meeting Abstract C1 [Toolan, S.; Bugler, J.; Lane, W.; Maglio, M.; Richardson, P. G.] Dana Farber Canc Inst, Jerome Lipper Multiple Myeloma Ctr, Boston, MA 02115 USA. [O'Gorman, P.] Mater Misericordiae Univ Hosp, Dept Haematol, Dublin, Ireland. NR 4 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 0021-1265 EI 1863-4362 J9 IRISH J MED SCI JI Irish J. Med. Sci. PD DEC PY 2013 VL 182 SU 11 BP S496 EP S496 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA 270VM UT WOS:000328347300020 ER PT J AU Lam, HC Cloonan, SM Bhashyam, AR Haspel, JA Singh, A Sathirapongsasuti, JF Cervo, M Yao, HW Chung, AL Mizumura, K An, CH Shan, B Franks, JM Haley, KJ Owen, CA Tesfaigzi, Y Washko, GR Quackenbush, J Silverman, EK Rahman, I Kim, HP Mahmood, A Biswal, SS Ryter, SW Choi, AMK AF Lam, Hilaire C. Cloonan, Suzanne M. Bhashyam, Abhiram R. Haspel, Jeffery A. Singh, Anju Sathirapongsasuti, J. Fah Cervo, Morgan Yao, Hongwei Chung, Anna L. Mizumura, Kenji An, Chang Hyeok Shan, Bin Franks, Jonathan M. Haley, Kathleen J. Owen, Caroline A. Tesfaigzi, Yohannes Washko, George R. Quackenbush, John Silverman, Edwin K. Rahman, Irfan Kim, Hong Pyo Mahmood, Ashfaq Biswal, Shyam S. Ryter, Stefan W. Choi, Augustine M. K. TI Histone deacetylase 6-mediated selective autophagy regulates COPD-associated cilia dysfunction SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article ID OBSTRUCTIVE PULMONARY-DISEASE; ENDOPLASMIC-RETICULUM STRESS; UNFOLDED PROTEIN RESPONSE; SMOKE-INDUCED EMPHYSEMA; CIGARETTE-SMOKE; MONITORING AUTOPHAGY; EPITHELIAL-CELLS; IN-VIVO; HDAC6; UBIQUITIN AB Chronic obstructive pulmonary disease (COPD) involves aberrant airway inflammatory responses to cigarette smoke (CS) that are associated with epithelial cell dysfunction, cilia shortening, and mucociliary clearance disruption. Exposure to CS reduced cilia length and induced autophagy in vivo and in differentiated mouse tracheal epithelial cells (MTECs). Autophagy-impaired (Becn1(+/-) or Map1lc3B(-/-)) mice and MTECs resisted CS-induced cilia shortening. Furthermore, CS increased the autophagic turnover of ciliary proteins, indicating that autophagy may regulate cilia homeostasis. We identified cytosolic deacetylase HDAC6 as a critical regulator of autophagy-mediated cilia shortening during CS exposure. Mice bearing an X chromosome deletion of Hdac6 (Hdac6(-/Y)) and MTECs from these mice had reduced autophagy and were protected from CS-induced cilia shortening. Autophagy-impaired Becn1(-/-), Map1lc3B(-/-), and Hdac6(-/Y) mice or mice injected with an HDAC6 inhibitor were protected from CS-induced mucociliary clearance (MCC) disruption. MCC was preserved in mice given the chemical chaperone 4-phenylbutyric acid, but was disrupted in mice lacking the transcription factor NRF2, suggesting that oxidative stress and altered proteostasis contribute to the disruption of MCC. Analysis of human COPD specimens revealed epigenetic deregulation of HDAC6 by hypomethylation and increased protein expression in the airways. We conclude that an autophagy-dependent pathway regulates cilia length during CS exposure and has potential as a therapeutic target for COPD. C1 [Lam, Hilaire C.; Cloonan, Suzanne M.; Bhashyam, Abhiram R.; Haspel, Jeffery A.; Chung, Anna L.; Mizumura, Kenji; An, Chang Hyeok; Haley, Kathleen J.; Owen, Caroline A.; Washko, George R.; Kim, Hong Pyo; Ryter, Stefan W.; Choi, Augustine M. K.] Brigham & Womens Hosp, Div Pulm & Crit Care Med, Boston, MA 02115 USA. [Lam, Hilaire C.; Cloonan, Suzanne M.; Bhashyam, Abhiram R.; Haspel, Jeffery A.; Chung, Anna L.; Mizumura, Kenji; An, Chang Hyeok; Haley, Kathleen J.; Owen, Caroline A.; Washko, George R.; Kim, Hong Pyo; Ryter, Stefan W.; Choi, Augustine M. K.] Harvard Univ, Sch Med, Boston, MA USA. [Lam, Hilaire C.] Univ Pittsburgh, Sch Med, Dept Pathol, Pittsburgh, PA USA. [Lam, Hilaire C.; Tesfaigzi, Yohannes; Ryter, Stefan W.] Lovelace Resp Res Inst, Albuquerque, NM USA. [Haspel, Jeffery A.] VA Boston Healthcare Syst, Pulm & Crit Care Med Sect, Boston, MA USA. [Singh, Anju; Biswal, Shyam S.] Johns Hopkins Univ, Dept Environm Hlth Sci, Bloomberg Sch Publ Hlth, Baltimore, MD 21205 USA. [Sathirapongsasuti, J. Fah; Quackenbush, John] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. [Sathirapongsasuti, J. Fah; Quackenbush, John] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA. [Cervo, Morgan; Mahmood, Ashfaq] Brigham & Womens Hosp, Dept Radiol, Boston, MA 02115 USA. [Cervo, Morgan; Mahmood, Ashfaq] Harvard Univ, Sch Med, Boston, MA USA. [Yao, Hongwei; Rahman, Irfan] Univ Rochester, Rochester, NY USA. [Shan, Bin] Tulane Univ, Sch Med, Dept Med, New Orleans, LA 70112 USA. [Franks, Jonathan M.] Univ Pittsburgh, Ctr Biol Imaging, Pittsburgh, PA USA. [Silverman, Edwin K.] Brigham & Womens Hosp, Channing Lab, Boston, MA 02115 USA. [Kim, Hong Pyo] Ajou Univ, Sch Pharm, Suwon 441749, South Korea. RP Choi, AMK (reprint author), Weill Cornell Med Coll, Dept Med, 525 East 68th St,Room M-522,Box 130, New York, NY 10065 USA. EM amc2056@med.cornell.edu RI Yao, Hongwei/G-6444-2010; OI Shan, Bin/0000-0002-6869-2678 FU Lovelace Respiratory Research Institute/Brigham and Women's Hospital (LRRI/BWH) consortium for lung research; NIH [R01-HL60234, R01-HL55330, R01-HL079904, P01-HL70807, P01 HL105339]; FAMRI clinical innovator award; NIH T32 training grant [HL007118]; AHA predoctoral grant [09PRE2250120]; Lovelace Respiratory Research Institute FX Confocal imaging and analysis were performed at the Harvard NeuroDiscovery Center. We thank Bradley Yoder for providing the IFT88 antibody and Donna Beer Stolz for her technical help with imaging analysis. Marlene Rabinovich and Beth Levine provided the Map1lc3b-/- and Becn1+/- mice, respectively. We thank Emeka Ifedigbo, Stephen C. Moore, Hari Parameswaran, and Shivraj Tyagi for providing significant technical support. We also thank Bonna Ith and Timelia Tison for slide preparation and staining and Ludo Van Den Bosch, Constantin van Outryve d'Ydewalle, Richard Austin, and Sana Basseri for their advice on in vivo therapy regimes. S.W. Ryter received salary support from the Lovelace Respiratory Research Institute/Brigham and Women's Hospital (LRRI/BWH) consortium for lung research. This work was supported by NIH grants R01-HL60234, R01-HL55330, R01-HL079904, and P01-HL70807, as well as by a FAMRI clinical innovator award (to A.M.K. Choi). H.C. Lam was supported by an NIH T32 training grant awarded to the Harvard School of Public Health (HL007118), an AHA predoctoral grant (09PRE2250120), and by the Lovelace Respiratory Research Institute. J. Quackenbush and E.K. Silverman were supported by NIH grant P01 HL105339 (to E.K. Silverman). NR 90 TC 66 Z9 67 U1 1 U2 8 PU AMER SOC CLINICAL INVESTIGATION INC PI ANN ARBOR PA 35 RESEARCH DR, STE 300, ANN ARBOR, MI 48103 USA SN 0021-9738 EI 1558-8238 J9 J CLIN INVEST JI J. Clin. Invest. PD DEC PY 2013 VL 123 IS 12 BP 5212 EP 5230 DI 10.1172/JCI69636 PG 19 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 263RQ UT WOS:000327826100027 PM 24200693 ER PT J AU Schaldecker, T Kim, S Tarabanis, C Tian, DQ Hakroush, S Castonguay, P Ahn, W Wallentin, H Heid, H Hopkins, CR Lindsley, CW Riccio, A Buvall, L Weins, A Greka, A AF Schaldecker, Thomas Kim, Sookyung Tarabanis, Constantine Tian, Dequan Hakroush, Samy Castonguay, Philip Ahn, Wooin Wallentin, Hanna Heid, Hans Hopkins, Corey R. Lindsley, Craig W. Riccio, Antonio Buvall, Lisa Weins, Astrid Greka, Anna TI Inhibition of the TRPC5 ion channel protects the kidney filter SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article ID GLOMERULAR-BASEMENT-MEMBRANE; RAT GLOMERULI; PODOCYTES; ACTIN; SYNAPTOPODIN; PROTEINURIA; ACTIVATION; FILTRATION; BARRIER; DISEASE AB An intact kidney filter is vital to retention of essential proteins in the blood and removal of waste from the body. Damage to the filtration barrier results in albumin loss in the urine, a hallmark of cardiovascular disease and kidney failure. Here we found that the ion channel TRPC5 mediates filtration barrier injury. Using Trpc5-KO mice, a small-molecule inhibitor of TRPC5, Ca2+ imaging in isolated kidney glomeruli, and live imagining of podocyte actin dynamics, we determined that loss of TRPC5 or its inhibition abrogates podocyte cytoskeletal remodeling. Inhibition or loss of TRPC5 prevented activation of the small GTP-binding protein Rac1 and stabilized synaptopodin. Importantly, genetic deletion or pharmacologic inhibition of TRPC5 protected mice from albuminuria. These data reveal that the Ca2+-permeable channel TRPC5 is an important determinant of albuminuria and identify TRPC5 inhibition as a therapeutic strategy for the prevention or treatment of proteinuric kidney disease. C1 [Schaldecker, Thomas; Kim, Sookyung; Tarabanis, Constantine; Tian, Dequan; Hakroush, Samy; Castonguay, Philip; Ahn, Wooin; Wallentin, Hanna; Buvall, Lisa; Weins, Astrid; Greka, Anna] Massachusetts Gen Hosp, Dept Med, Boston, MA 02129 USA. [Schaldecker, Thomas; Kim, Sookyung; Tarabanis, Constantine; Tian, Dequan; Hakroush, Samy; Castonguay, Philip; Ahn, Wooin; Wallentin, Hanna; Buvall, Lisa; Weins, Astrid; Greka, Anna] Harvard Univ, Sch Med, Boston, MA USA. [Heid, Hans] German Canc Res Ctr, Helmholtz Grp Cell Biol, Heidelberg, Germany. [Hopkins, Corey R.; Lindsley, Craig W.] Vanderbilt Univ, Med Ctr, Dept Chem,MLPCN Specialized Chem Ctr, Vanderbilt Ctr Neurosci Drug Discovery,Inst Chem, Nashville, TN USA. [Hopkins, Corey R.; Lindsley, Craig W.] Vanderbilt Univ, Med Ctr, Dept Pharmacol,MLPCN Specialized Chem Ctr, Vanderbilt Ctr Neurosci Drug Discovery,Inst Chem, Nashville, TN USA. [Riccio, Antonio] Harvard Univ, Sch Med, Boston Childrens Hosp, Dept Cardiol,Manton Ctr Orphan Dis, Boston, MA USA. [Riccio, Antonio] Harvard Univ, Sch Med, Dept Neurobiol, Boston, MA 02115 USA. [Weins, Astrid] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. RP Greka, A (reprint author), Massachusetts Gen Hosp, 149 13th St, Boston, MA 02129 USA. EM greka.anna@mgh.harvard.edu OI Buvall, Lisa/0000-0002-0599-8581 FU NIH/MLPCN [U54 MH084659]; Boehringer Ingelheim Fonds; NIH [DK093783, DK083511, DK093746]; Swedish Research Council; Swedish Governmental Agency for Innovation Systems; DFG Forschungsstipendium [HA6334/1-1]; ASN Gottschalk Career Development Award; Harvard/MGH Shore Fellowship/Claflin Distinguished Scholar Award; BADERC/NIDDK PF grant (NIH) [P30DK057521] FX ML204 was discovered as part of the MLPCN initiative and was supported by NIH/MLPCN grant U54 MH084659 (to C.W. Linsley). This work was supported by a fellowship from Boehringer Ingelheim Fonds (to T. Schaldecker), NIH grant DK093783 (to A. Weins), the Swedish Research Council and Swedish Governmental Agency for Innovation Systems (to L. Buvall), DFG Forschungsstipendium HA6334/1-1 (to S. Hakroush), an ASN Gottschalk Career Development Award (to A. Greka), a Harvard/MGH Shore Fellowship/Claflin Distinguished Scholar Award (to A. Greka), a BADERC/NIDDK P&F grant (to A. Greka, from NIH grant P30DK057521), and NIH grants DK083511 and DK093746 (to A. Greka). NR 58 TC 45 Z9 46 U1 1 U2 17 PU AMER SOC CLINICAL INVESTIGATION INC PI ANN ARBOR PA 35 RESEARCH DR, STE 300, ANN ARBOR, MI 48103 USA SN 0021-9738 EI 1558-8238 J9 J CLIN INVEST JI J. Clin. Invest. PD DEC PY 2013 VL 123 IS 12 BP 5298 EP 5309 DI 10.1172/JCI71165 PG 12 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 263RQ UT WOS:000327826100033 PM 24231357 ER PT J AU Anderson, SAR Michaelides, M Zarnegar, P Ren, YH Fagergren, P Thanos, PK Wang, GJ Bannon, M Neumaier, JF Keller, E Volkow, ND Hurd, YL AF Anderson, Sarah Ann R. Michaelides, Michael Zarnegar, Parisa Ren, Yanhua Fagergren, Pernilla Thanos, Panayotis K. Wang, Gene-Jack Bannon, Michael Neumaier, John F. Keller, Eva Volkow, Nora D. Hurd, Yasmin L. TI Impaired periamygdaloid-cortex prodynorphin is characteristic of opiate addiction and depression SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article ID MESSENGER-RNA EXPRESSION; GLUCOSE-METABOLISM; GENE-EXPRESSION; PARKINSONS-DISEASE; EXTENDED AMYGDALA; ANXIETY DISORDERS; DRUG-ADDICTION; HEROIN ABUSERS; OPIOID-SYSTEM; HUMAN BRAIN AB Negative affect is critical for conferring vulnerability to opiate addiction as reflected by the high comorbidity of opiate abuse with major depressive disorder (MDD). Rodent models implicate amygdala prodynorphin (Pdyn) as a mediator of negative affect; however, evidence of PDYN involvement in human negative affect is limited. Here, we found reduced PDYN mRNA expression in the postmortem human amygdala nucleus of the periamygdaloid. cortex (PAC) in both heroin abusers and MDD subjects. Similar to humans, rats that chronically self-administered heroin had reduced Pdyn mRNA expression in the PAC at a time point associated with a negative affective state. Using the in vivo functional imaging technology DREAMM (DREADD-assisted. metabolic mapping, where DREADD indicates designer receptors exclusively activated. by designer drugs), we found that selective inhibition of Pdyn-expressing neurons in the rat PAC increased metabolic activity in the extended amygdala, which is a key substrate of the extrahypothalamic brain stress system. In parallel, PAC-specific Pdyn inhibition provoked negative affect-related physiological and behavioral changes. Altogether, our translational study supports a functional role for impaired Pdyn in the PAC in opiate abuse through activation of the stress and negative affect neurocircuitry implicated in addiction vulnerability. C1 [Anderson, Sarah Ann R.; Michaelides, Michael; Ren, Yanhua; Hurd, Yasmin L.] Icahn Sch Med Mt Sinai, Dept Psychiat, New York, NY USA. [Anderson, Sarah Ann R.; Michaelides, Michael; Ren, Yanhua; Hurd, Yasmin L.] Icahn Sch Med Mt Sinai, Dept Neurosci, New York, NY USA. [Anderson, Sarah Ann R.; Michaelides, Michael; Ren, Yanhua; Hurd, Yasmin L.] Icahn Sch Med Mt Sinai, Friedman Brain Inst, New York, NY USA. [Zarnegar, Parisa; Fagergren, Pernilla] Karolinska Inst, Dept Clin Neurosci, Stockholm, Sweden. [Thanos, Panayotis K.; Volkow, Nora D.] NIAAA, Bethesda, MD USA. [Wang, Gene-Jack] SUNY Stony Brook, Dept Radiol, Upton, NY USA. [Bannon, Michael] Wayne State Univ, Sch Med, Dept Pharmacol, Detroit, MI 48201 USA. [Neumaier, John F.] Univ Washington, Dept Psychiat, Seattle, WA 98195 USA. [Neumaier, John F.] Univ Washington, Dept Pharmacol, Seattle, WA 98195 USA. [Keller, Eva] Semmelweis Univ, Dept Forens & Insurance Med, H-1085 Budapest, Hungary. [Hurd, Yasmin L.] James J Peters VA Med Ctr, New York, NY USA. RP Hurd, YL (reprint author), Hess Ctr Sci & Med, 1 Gustave L Levy Pl,Box 1065,1470 Madison Ave,Flo, New York, NY 10029 USA. EM Yasmin.hurd@mssm.edu FU UNCF-Merck Graduate Fellowship [DA015546, T32-GM007280-34S1-NHLBI/NIGMS]; NIDA Postdoctoral Training Program [DA007135]; [DA023214]; [DA030359]; [DA006470] FX This work was supported by DA015546, DA023214, DA030359, DA006470. S.A.R. Anderson was supported by the UNCF-Merck Graduate Fellowship, Diversity Supplement to DA015546 and T32-GM007280-34S1-NHLBI/NIGMS supplement to the Mount Sinai Medical Scientist Training Program. M. Michaelides was supported by NIDA Postdoctoral Training Program DA007135. NR 56 TC 12 Z9 12 U1 2 U2 9 PU AMER SOC CLINICAL INVESTIGATION INC PI ANN ARBOR PA 35 RESEARCH DR, STE 300, ANN ARBOR, MI 48103 USA SN 0021-9738 EI 1558-8238 J9 J CLIN INVEST JI J. Clin. Invest. PD DEC PY 2013 VL 123 IS 12 BP 5334 EP 5341 DI 10.1172/JCI70395 PG 8 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 263RQ UT WOS:000327826100036 PM 24231353 ER PT J AU Michaelides, M Anderson, SAR Ananth, M Smirnov, D Thanos, PK Neumaier, JF Wang, GJ Volkow, ND Hurd, YL AF Michaelides, Michael Anderson, Sarah Ann R. Ananth, Mala Smirnov, Denis Thanos, Panayotis K. Neumaier, John F. Wang, Gene-Jack Volkow, Nora D. Hurd, Yasmin L. TI Whole-brain circuit dissection in free-moving animals reveals cell-specific mesocorticolimbic networks SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article ID STRIATOPALLIDAL NEURONS; RAT-BRAIN; PET; NORMALIZATION; ORGANIZATION; INHIBITION; MODULATION; TEMPLATE; PATHWAYS; F-18-FDG AB The ability to map the functional connectivity of discrete cell types in the intact mammalian brain during behavior is crucial for advancing our understanding of brain function in normal and disease states. We combined designer receptor exclusively activated by designer drug (DREADD) technology and behavioral imaging with mu PET and [F-18]fluorodeoxyglucose (FDG) to generate whole-brain metabolic maps of cell-specific functional circuits during the awake, freely moving state. We have termed this approach DREADD-assisted metabolic mapping (DREAMM) and documented its ability in rats to map whole-brain functional anatomy. We applied this strategy to evaluating changes in the brain associated with inhibition of prodynorphin-expressing (Pdyn-expressing) and of proenkephalin-expressing (Penk-expressing) medium spiny neurons (MSNs) of the nucleus accumbens shell (NAcSh), which have been implicated in neuropsychiatric disorders. DREAMM revealed discrete behavioral manifestations and concurrent engagement of distinct corticolimbic networks associated with dysregulation of Pdyn and Penk in MSNs of the NAcSh. Furthermore, distinct neuronal networks were recruited in awake versus anesthetized conditions. These data demonstrate that DREAMM is a highly sensitive, molecular, high-resolution quantitative imaging approach. C1 [Michaelides, Michael; Anderson, Sarah Ann R.; Wang, Gene-Jack; Hurd, Yasmin L.] Icahn Sch Med Mt Sinai, Dept Psychiat, Friedman Brain Inst, New York, NY 10029 USA. [Michaelides, Michael; Anderson, Sarah Ann R.; Hurd, Yasmin L.] Icahn Sch Med Mt Sinai, Dept Neurosci, Friedman Brain Inst, New York, NY 10029 USA. [Ananth, Mala; Thanos, Panayotis K.; Wang, Gene-Jack] Brookhaven Natl Lab, Dept Biosci, Upton, NY 11973 USA. [Smirnov, Denis; Neumaier, John F.] Univ Washington, Seattle, WA 98195 USA. [Thanos, Panayotis K.; Volkow, Nora D.] NIAAA, Lab Neuroimaging, Bethesda, MD USA. [Hurd, Yasmin L.] James J Peters VA Med Ctr, New York, NY USA. RP Hurd, YL (reprint author), Icahn Sch Med Mt Sinai, Hess Ctr Sci & Med, 10th Floor Room 105,1470 Madison Ave, New York, NY 10029 USA. EM yasmin.hurd@mssm.edu FU National Institute on Alcohol Abuse and Alcoholism (NIAAA) [AA11034, AA07574, AA07611]; National Institute on Drug Abuse (NIDA) [DA015446, DA023214, DA030359]; NIDA Postdoctoral Training Program at MSSM [DA007135] FX This work was supported by the National Institute on Alcohol Abuse and Alcoholism (NIAAA) (AA11034, AA07574, and AA07611) and the National Institute on Drug Abuse (NIDA) (DA015446, DA023214, and DA030359). M. Michaelides was supported by the NIDA Postdoctoral Training Program at MSSM (DA007135). The authors thank the Mount Sinai Microscopy Shared Resource Facility and the microPET Facility (Wade Koba, Linda Jelicks) at the Albert Einstein College of Medicine of Yeshiva University. NR 30 TC 19 Z9 19 U1 2 U2 8 PU AMER SOC CLINICAL INVESTIGATION INC PI ANN ARBOR PA 35 RESEARCH DR, STE 300, ANN ARBOR, MI 48103 USA SN 0021-9738 EI 1558-8238 J9 J CLIN INVEST JI J. Clin. Invest. PD DEC PY 2013 VL 123 IS 12 BP 5342 EP 5350 DI 10.1172/JCI72117 PG 9 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 263RQ UT WOS:000327826100037 PM 24231358 ER PT J AU Ting, BL Jupiter, JB AF Ting, Beverlie L. Jupiter, Jesse B. TI Recurrent Bizarre Parosteal Osteochondromatous Proliferation of the Ulna With Erosion of the Adjacent Radius: Case Report SO JOURNAL OF HAND SURGERY-AMERICAN VOLUME LA English DT Article DE Recurrent bizarre parosteal osteochondromatous proliferation; Nora's lesion; bone tumors; osteochondroma ID OF-THE-LITERATURE; NORAS LESION AB Bizarre parosteal osteochondromatous proliferation is an unusual entity that should be considered when evaluating a patient with a surface-based bone lesion. The aggressive features of bizarre parosteal osteochondromatous proliferation have occasionally led to misdiagnoses as malignant neoplasms and subsequent aggressive treatment. We present a case of a recurrent forearm bizarre parosteal osteochondromatous proliferation with unique radiographic features. This report serves to illustrate the importance of both radiographic and histopathologic review for correct diagnosis and discusses the successful management of a recurrent forearm lesion. (J Hand Surg Am. 2013;38(12):2381-2386. Copyright (C) 2013 by the American Society for Surgery of the Hand. All rights reserved.) C1 [Ting, Beverlie L.; Jupiter, Jesse B.] Massachusetts Gen Hosp, Hand & Upper Extrem Serv, Boston, MA 02114 USA. RP Jupiter, JB (reprint author), Massachusetts Gen Hosp, Hand & Upper Extrem Serv, 55 Fruit St,Yawkey 2C, Boston, MA 02114 USA. EM jjupiter1@partners.org NR 19 TC 3 Z9 5 U1 0 U2 4 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0363-5023 EI 1531-6564 J9 J HAND SURG-AM JI J. Hand Surg.-Am. Vol. PD DEC PY 2013 VL 38A IS 12 BP 2381 EP 2386 DI 10.1016/j.jhsa.2013.09.024 PG 6 WC Orthopedics; Surgery SC Orthopedics; Surgery GA 270CG UT WOS:000328295900011 PM 24183508 ER PT J AU Zimmerman, RM Jupiter, JB del Pino, JG AF Zimmerman, Ryan M. Jupiter, Jesse B. Gonzalez del Pino, Juan TI Minimum 6-Year Follow-Up After Ulnar Nerve Decompression and Submuscular Transposition for Primary Entrapment SO JOURNAL OF HAND SURGERY-AMERICAN VOLUME LA English DT Article DE Outcomes; transposition; ulnar neuropathy; vascularized ID CUBITAL TUNNEL-SYNDROME; ANTERIOR SUBCUTANEOUS TRANSPOSITION; SURGICAL-TREATMENT; BLOOD-FLOW; IN-SITU; ELBOW; OUTCOMES; NEUROLYSIS; MANAGEMENT AB Purpose To retrospectively evaluate patients with 6-year minimum follow-up after submuscular transposition of the ulnar nerve for primary entrapment. Methods From 1992 to 2005, 142 patients were treated surgically for ulnar neuropathy at the elbow by 2 senior surgeons using a technique that preserved nerve vascularity. A total of 99 cases were eligible, and 82 elbows in 76 patients, average age 48 years, were followed for at least 6 years (average, 8.3 y). Thirty-two (42%) were male, and the dominant limb was involved in 49 (64%). The average duration of symptoms before surgery was 25 months. Clinical records were reviewed, and sensory (S0-2) and motor (M0-5) testing was performed. Del Ion scores were determined, and visual analog scale and modified questionnaires from Novak et al and Kleinman and Bishop were completed. Preoperatively, 48 elbows were Dellon grade III, 33 were grade II, and one was grade I. Results There were clinically and statistically significant improvements in patient and surgeon-reported data regardless of the preoperative disease severity. Visual analog scale questionnaires, sensory scale, and motor strength all improved, with at least antigravity strength in all subjects. Dellon scores also improved, and 38 elbows had normalized to Dellon 0. Of the 33 preoperative elbows that were grade III, 15 improved to grade II, 13 to grade I, and 5 normalized. Of the 48 preoperative elbows that were grade II, 16 improved to grade I and 32 normalized. Preoperative Dellon III elbows had more residual symptoms than grade II elbows. A total of 73 elbows (89%) had a good or excellent outcome. There were no reoperations or infections. Conclusions Submuscular transposition is a safe and durable option for primary ulnar neuropathy at the elbow. Overall, good or excellent results were achieved in 89% of patients with a low complication rate. (J Hand Surg Am. 2013;38(12):2398-2404. Copyright (C) 2013 by the American Society for Surgery of the Hand. All rights reserved.) C1 Massachusetts Gen Hosp, Dept Orthopaed Surg, Hand & Upper Extrem Serv, Boston, MA 02114 USA. Santa Cristina Univ Hosp, Dept Orthoped Surg, Div Hand Surg, Madrid, Spain. RP Zimmerman, RM (reprint author), Massachusetts Gen Hosp, Dept Orthopaed Surg, 55 Fruit St,WHT 535, Boston, MA 02114 USA. EM zimmerman@gmail.com NR 45 TC 5 Z9 5 U1 0 U2 2 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0363-5023 EI 1531-6564 J9 J HAND SURG-AM JI J. Hand Surg.-Am. Vol. PD DEC PY 2013 VL 38A IS 12 BP 2398 EP 2404 DI 10.1016/j.jhsa.2013.09.017 PG 7 WC Orthopedics; Surgery SC Orthopedics; Surgery GA 270CG UT WOS:000328295900013 PM 24183405 ER PT J AU Jupiter, JB AF Jupiter, Jesse B. TI First Hand: Hands Across the Sea SO JOURNAL OF HAND SURGERY-AMERICAN VOLUME LA English DT Editorial Material C1 Harvard Univ, Sch Med, Boston, MA 02114 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Jupiter, JB (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Yawkey Bldg Suite 2011, Boston, MA 02114 USA. EM Jjupiter1@partners.org NR 1 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 0363-5023 EI 1531-6564 J9 J HAND SURG-AM JI J. Hand Surg.-Am. Vol. PD DEC PY 2013 VL 38A IS 12 BP 2451 EP 2452 DI 10.1016/j.jhsa.2013.09.032 PG 2 WC Orthopedics; Surgery SC Orthopedics; Surgery GA 270CG UT WOS:000328295900021 PM 24416765 ER PT J AU Klausmeyer, MA Mudgal, CS AF Klausmeyer, Melissa A. Mudgal, Chaitanya S. TI Hook of Hamate Fractures SO JOURNAL OF HAND SURGERY-AMERICAN VOLUME LA English DT Editorial Material ID STRESS-FRACTURE; EXCISION; SECONDARY; NONUNION C1 [Klausmeyer, Melissa A.; Mudgal, Chaitanya S.] Massachusetts Gen Hosp, Hand & Upper Extrem Serv, Dept Orthoped Surg, Boston, MA 02114 USA. RP Mudgal, CS (reprint author), Massachusetts Gen Hosp, Hand & Upper Extrem Serv, Yawkey Ctr, Suite 2100,55 Fruit St, Boston, MA 02114 USA. EM cmudgal@partners.org NR 25 TC 6 Z9 6 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 0363-5023 EI 1531-6564 J9 J HAND SURG-AM JI J. Hand Surg.-Am. Vol. PD DEC PY 2013 VL 38A IS 12 BP 2457 EP 2460 DI 10.1016/j.jhsa.2013.06.004 PG 4 WC Orthopedics; Surgery SC Orthopedics; Surgery GA 270CG UT WOS:000328295900023 PM 23891177 ER PT J AU Ring, D AF Ring, David TI A Tricky Diagnosis SO JOURNAL OF HAND SURGERY-AMERICAN VOLUME LA English DT Letter C1 Massachusetts Gen Hosp, Dept Hand Surg, Boston, MA 02114 USA. RP Ring, D (reprint author), Massachusetts Gen Hosp, Dept Hand Surg, Boston, MA 02114 USA. NR 2 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 0363-5023 EI 1531-6564 J9 J HAND SURG-AM JI J. Hand Surg.-Am. Vol. PD DEC PY 2013 VL 38A IS 12 BP 2518 EP 2519 DI 10.1016/j.jhsa.2013.08.124 PG 2 WC Orthopedics; Surgery SC Orthopedics; Surgery GA 270CG UT WOS:000328295900033 PM 24275056 ER PT J AU Cassol, E Misra, V Morgello, S Gabuzda, D AF Cassol, Edana Misra, Vikas Morgello, Susan Gabuzda, Dana TI Applications and Limitations of Inflammatory Biomarkers for Studies on Neurocognitive Impairment in HIV Infection SO JOURNAL OF NEUROIMMUNE PHARMACOLOGY LA English DT Article DE HIV; HCV; HIV-associated neurocognitive disorders; Innate immune activation; Inflammatory biomarkers; Interferon-alpha; IL-6 ID HUMAN-IMMUNODEFICIENCY-VIRUS; HEPATITIS-C VIRUS; CENTRAL-NERVOUS-SYSTEM; CEREBROSPINAL-FLUID; IMMUNE ACTIVATION; ANTIRETROVIRAL THERAPY; MICROBIAL TRANSLOCATION; COGNITIVE IMPAIRMENT; MONOCYTE ACTIVATION; PLASMA-LEVELS AB Despite reduced prevalence of severe forms of HIV-associated neurocognitive disorders (HAND) on current antiretroviral therapy (ART) regimens, milder forms of neurocognitive impairment (NCI) remain prevalent in HIV-infected populations. These mild forms of HAND consist of subtypes, probably reflecting distinct, though possibly overlapping, pathophysiological mechanisms. Factors associated with HAND in HIV patients with prolonged viral suppression on ART include older age, low nadir CD4, active HCV co-infection, and cardiovascular risk factors, but underlying mechanisms and their relationship to innate immune activation, chronic inflammation, and other features of systemic disease are poorly understood. In this article, we discuss applications and limitations of plasma inflammatory biomarkers for studies on HAND in HIV patients on ART and describe an analysis pipeline to reduce common sources of noise and increase likelihood of identifying relevant inflammatory biomarkers. Clinical covariates and comorbidities that influence inflammatory biomarkers, such as aging, obesity, metabolic abnormalities, HCV co-infection, and substance abuse, are also reviewed. As an example for using this analytic pipeline, we present an exploratory study of 22 plasma inflammatory biomarkers (IFN-alpha 2b and -gamma, 16 cytokines/chemokines, sIL-2R, sCD14, HA, and YKL-40) in a cohort of HIV-infected individuals with advanced disease, frequent HCV co-infection, and viral suppression on ART. The identification of inflammatory biomarkers associated with HAND in HIV+ patients on ART may be useful to distinguish between HAND subtypes with distinct pathophysiology, and is important for achieving a systems-level understanding of the biology of these disorders, developing effective therapies, and evaluating therapeutic outcomes. C1 [Cassol, Edana; Misra, Vikas; Gabuzda, Dana] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. [Morgello, Susan] Mt Sinai Med Ctr, New York, NY 10029 USA. [Gabuzda, Dana] Dana Farber Canc Inst, Boston, MA 02215 USA. RP Gabuzda, D (reprint author), Dana Farber Canc Inst, 450 Brookline Ave CLS 1010, Boston, MA 02215 USA. EM dana_gabuzda@dfci.harvard.edu FU National Institutes of Health [MH97659, DA28994]; National Institutes of Health Grants [U01MH083501, R24MH59724, U01MH083506, R24MH59745, U01MH083507, R24 NS45491, 5U01MH083500, NS38841, U01MH083545, N01MH32002]; Dana-Farber Cancer Institute/Harvard Center for Cancer Research; [N01MH22005] FX We thank NNTC and CHARTER for providing plasma samples and clinical data for HIV patients. This work was supported by National Institutes of Health Grants MH97659 and DA28994 to D.G. National NeuroAIDS Tissue Consortium (NNTC) sites were supported by National Institutes of Health Grants U01MH083501, R24MH59724, U01MH083506, R24MH59745, U01MH083507, R24 NS45491, 5U01MH083500, NS38841, U01MH083545, and N01MH32002. CNS HIV Antiretroviral Therapy Effects Research (CHARTER) was supported by N01MH22005. Core facilities were supported by the Harvard Center for AIDS Research and Dana-Farber Cancer Institute/Harvard Center for Cancer Research grants. NR 89 TC 11 Z9 11 U1 0 U2 3 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1557-1890 EI 1557-1904 J9 J NEUROIMMUNE PHARM JI J. Neuroimmune Pharm. PD DEC PY 2013 VL 8 IS 5 BP 1087 EP 1097 DI 10.1007/s11481-013-9512-2 PG 11 WC Neurosciences; Pharmacology & Pharmacy SC Neurosciences & Neurology; Pharmacology & Pharmacy GA 272XI UT WOS:000328496000007 PM 24259252 ER PT J AU Skates, SJ Gillette, MA LaBaer, J Carr, SA Anderson, L Liebler, DC Ransohoff, D Rifai, N Kondratovich, M Tezak, Z Mansfield, E Oberg, AL Wright, I Barnes, G Gail, M Mesri, M Kinsinger, CR Rodriguez, H Boja, ES AF Skates, Steven J. Gillette, Michael A. LaBaer, Joshua Carr, Steven A. Anderson, Leigh Liebler, Daniel C. Ransohoff, David Rifai, Nader Kondratovich, Marina Tezak, Zivana Mansfield, Elizabeth Oberg, Ann L. Wright, Ian Barnes, Grady Gail, Mitchell Mesri, Mehdi Kinsinger, Christopher R. Rodriguez, Henry Boja, Emily S. TI Statistical Design for Biospecimen Cohort Size in Proteomics-based Biomarker Discovery and Verification Studies SO JOURNAL OF PROTEOME RESEARCH LA English DT Article DE statistical experiment design; biomarker; proteomics; unbiasedness; power calculation ID MONITORING MASS-SPECTROMETRY; CARDIOVASCULAR-DISEASE; PROTEIN BIOMARKERS; MULTIPLEX ASSAYS; PIPELINE; PLASMA; ASSOCIATION; DIAGNOSTICS; VALIDATION; MARKERS AB Protein biomarkers are needed to deepen our understanding of cancer biology and to improve our ability to diagnose, monitor, and treat cancers. Important analytical and clinical hurdles must be overcome to allow the most promising protein biomarker candidates to advance into clinical validation studies. Although contemporary proteomics technologies support the measurement of large numbers of proteins in individual clinical specimens, sample throughput remains comparatively low. This problem is amplified in typical clinical proteomics research studies, which routinely suffer from a lack of proper experimental design, resulting in analysis of too few biospecimens to achieve adequate statistical power at each stage of a biomarker pipeline. To address this critical shortcoming, a joint workshop was held by the National Cancer Institute (NCI), National Heart, Lung, and Blood Institute (NHLBI), and American Association for Clinical Chemistry (AACC) with participation from the U.S. Food and Drug Administration (FDA). An important output from the workshop was a statistical framework for the design of biomarker discovery and verification studies. Herein, we describe the use of quantitative clinical judgments to set statistical criteria for clinical relevance and the development of an approach to calculate biospecimen sample size for proteomic studies in discovery and verification stages prior to clinical validation stage. This represents a first step toward building a consensus on quantitative criteria for statistical design of proteomics biomarker discovery and verification research. C1 [Skates, Steven J.] Massachusetts Gen Hosp, Ctr Canc, Ctr Biostat, Boston, MA 02114 USA. [Gillette, Michael A.; Carr, Steven A.] Broad Inst Massachusetts Inst Technol & Harvard, Prote Platform, Cambridge, MA 02142 USA. [LaBaer, Joshua] Arizona State Univ, Biodesign Inst, Tempe, AZ 85287 USA. [Anderson, Leigh] Plasma Proteome Inst, Washington, DC 20009 USA. [Anderson, Leigh; Wright, Ian] SISCAPA Technol Inc, Washington, DC 20009 USA. [Liebler, Daniel C.] Vanderbilt Univ, Sch Med, Jim Ayers Inst Precanc Detect & Diag, Nashville, TN 37232 USA. [Liebler, Daniel C.] Vanderbilt Univ, Sch Med, Dept Biochem, Nashville, TN 37232 USA. [Ransohoff, David] Univ N Carolina, Dept Med, Div Gastroenterol & Hepatol, Chapel Hill, NC 27514 USA. [Rifai, Nader] Childrens Hosp, Dept Lab Med, Boston, MA 02115 USA. [Rifai, Nader] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. [Rifai, Nader] King Abdulaziz Univ, Jeddah 22254, Saudi Arabia. [Kondratovich, Marina; Tezak, Zivana; Mansfield, Elizabeth] US FDA, Off In Vitro Diagnost & Radiol Hlth, Ctr Devices & Radiol Hlth, Dept Hlth & Human Serv, Silver Spring, MD 20993 USA. [Oberg, Ann L.] Mayo Clin, Dept Hlth Sci Res, Div Biomed Stat & Informat, Rochester, MN 55905 USA. [Barnes, Grady] Fujirebio Diagnost Inc, Malvern, PA 19355 USA. [Gail, Mitchell] NCI, Div Canc Epidemiol & Genet, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. [Mesri, Mehdi; Kinsinger, Christopher R.; Rodriguez, Henry; Boja, Emily S.] NCI, Off Canc Clin Prote Res, Ctr Strateg Sci Initiat, NIH,Dept Hlth & Human Serv, Bethesda, MD 20892 USA. RP Skates, SJ (reprint author), Massachusetts Gen Hosp, 50 Staniford St,Suite 560, Boston, MA 02114 USA. EM sskates@partners.org; bojae@mail.nih.gov OI Liebler, Daniel/0000-0002-7873-3031 FU National Cancer Institute of the National Institutes of Health through the Clinical Proteomic Tumor Analysis Consortium (CPTAC) [10XS136, U24CA160034]; Early Detection Research Network [U01CAI52990]; Mayo Clinic Specialized Program in Research Excellence [P50CA136393] FX Research reported in this publication was supported by the National Cancer Institute of the National Institutes of Health under grants and contracts through the Clinical Proteomic Tumor Analysis Consortium (CPTAC) program (10XS136 SJS, U24CA160034 SAC, MAG), the Early Detection Research Network (U01CAI52990 SJS), and Mayo Clinic Specialized Program in Research Excellence grant (P50CA136393 AO). NR 29 TC 32 Z9 32 U1 2 U2 18 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 1535-3893 EI 1535-3907 J9 J PROTEOME RES JI J. Proteome Res. PD DEC PY 2013 VL 12 IS 12 BP 5383 EP 5394 DI 10.1021/pr400132j PG 12 WC Biochemical Research Methods SC Biochemistry & Molecular Biology GA 269HD UT WOS:000328231300004 PM 24063748 ER PT J AU Konstantopoulos, WM Ahn, R Alpert, EJ Cafferty, E McGahan, A Williams, TP Castor, JP Wolferstan, N Purcell, G Burke, TF AF Konstantopoulos, Wendy Macias Ahn, Roy Alpert, Elaine J. Cafferty, Elizabeth McGahan, Anita Williams, Timothy P. Castor, Judith Palmer Wolferstan, Nadya Purcell, Genevieve Burke, Thomas F. TI An International Comparative Public Health Analysis of Sex Trafficking of Women and Girls in Eight Cities: Achieving a More Effective Health Sector Response SO JOURNAL OF URBAN HEALTH-BULLETIN OF THE NEW YORK ACADEMY OF MEDICINE LA English DT Article DE Vulnerable populations; Public health; Gender-based violence; Forced sexual exploitation; Sex trafficking; Social determinants of sex trafficking; Trafficking-related health problems; Access to health care; Health policy ID HIV PREVALENCE; PREDICTORS; SERVICES; MUMBAI; INDIA; NEPAL AB Sex trafficking, trafficking for the purpose of forced sexual exploitation, is a widespread form of human trafficking that occurs in all regions of the world, affects mostly women and girls, and has far-reaching health implications. Studies suggest that up to 50% of sex trafficking victims in the USA seek medical attention while in their trafficking situation, yet it is unclear how the healthcare system responds to the needs of victims of sex trafficking. To understand the intersection of sex trafficking and public health, we performed in-depth qualitative interviews among 277 antitrafficking stakeholders across eight metropolitan areas in five countries to examine the local context of sex trafficking. We sought to gain a new perspective on this form of gender-based violence from those who have a unique vantage point and intimate knowledge of push-and-pull factors, victim health needs, current available resources and practices in the health system, and barriers to care. Through comparative analysis across these contexts, we found that multiple sociocultural and economic factors facilitate sex trafficking, including child sexual abuse, the objectification of women and girls, and lack of income. Although there are numerous physical and psychological health problems associated with sex trafficking, health services for victims are patchy and poorly coordinated, particularly in the realm of mental health. Various factors function as barriers to a greater health response, including low awareness of sex trafficking and attitudinal biases among health workers. A more comprehensive and coordinated health system response to sex trafficking may help alleviate its devastating effects on vulnerable women and girls. There are numerous opportunities for local health systems to engage in antitrafficking efforts while partnering across sectors with relevant stakeholders. C1 [Konstantopoulos, Wendy Macias; Ahn, Roy; Alpert, Elaine J.; Cafferty, Elizabeth; McGahan, Anita; Williams, Timothy P.; Castor, Judith Palmer; Wolferstan, Nadya; Purcell, Genevieve; Burke, Thomas F.] Massachusetts Gen Hosp, Dept Emergency Med, Div Global Hlth & Human Rights, Boston, MA 02114 USA. [Burke, Thomas F.] Massachusetts Gen Hosp, Dept Pediat, Boston, MA 02114 USA. [Burke, Thomas F.] Childrens Hosp, Div Gen Pediat, Boston, MA 02115 USA. [Konstantopoulos, Wendy Macias; Ahn, Roy; Burke, Thomas F.] Harvard Univ, Sch Med, Dept Surg, Boston, MA 02115 USA. [Alpert, Elaine J.] Univ British Columbia, Coll Hlth Disciplines, Vancouver, BC V5Z 1M9, Canada. [McGahan, Anita] Univ Toronto, Rotman Sch Management, Toronto, ON, Canada. [McGahan, Anita] Univ Toronto, Munk Sch Global Affairs, Toronto, ON, Canada. RP Konstantopoulos, WM (reprint author), Massachusetts Gen Hosp, Dept Emergency Med, Div Global Hlth & Human Rights, 0 Emerson Pl,Suite 104, Boston, MA 02114 USA. EM wmacias@partners.org FU Humanity United, Redwood City, CA, USA; Give Way to Freedom, Essex Junction, VT, USA FX This research was supported by a grant from Humanity United, Redwood City, CA, USA. The funding organization provided helpful, nonbinding study design suggestions, but had no role in the conduct of the study, in the collection, analysis and interpretation of the data, or in the preparation, review or approval of the manuscript. A grant from Give Way to Freedom, Essex Junction, VT, USA, also supported the preparation of the manuscript; this funding organization had no role in the conduct of the study, in the collection, analysis, and interpretation of the data or in the preparation, review, or approval of the manuscript. The authors gratefully acknowledge the contributions made by Jay Silverman and Michele Decker, the indispensible field support provided by Peter Lenny, Kena Silva, and Sylvia Lichauco, and the research assistance provided by Julie Barenholtz, Christina Martin, Kathryn Conn, and Hannah Harp. NR 21 TC 13 Z9 14 U1 8 U2 46 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1099-3460 EI 1468-2869 J9 J URBAN HEALTH JI J. Urban Health PD DEC PY 2013 VL 90 IS 6 BP 1194 EP 1204 DI 10.1007/s11524-013-9837-4 PG 11 WC Public, Environmental & Occupational Health; Medicine, General & Internal SC Public, Environmental & Occupational Health; General & Internal Medicine GA 269AH UT WOS:000328211700016 ER PT J AU Lee, SJ Karter, AJ Thai, JN Van Den Eeden, SK Huang, ES AF Lee, Sei J. Karter, Andrew J. Thai, Julie N. Van Den Eeden, Stephen K. Huang, Elbert S. TI Glycemic Control and Urinary Incontinence in Women with Diabetes Mellitus SO JOURNAL OF WOMENS HEALTH LA English DT Article ID QUALITY-OF-LIFE; RISK-FACTORS; POSTMENOPAUSAL WOMEN; OLDER-ADULTS; HEALTH; IMPACT; PREVALENCE; MANAGEMENT; SYMPTOMS; GLUCOSE AB Background: Although many studies have shown that diabetes increases the risk for urinary incontinence, it is unclear whether poor glycemic control in women with diabetes is associated with incontinence. This study aims to determine the relationship between the hemoglobin A1c (HbA1c) level and urinary incontinence in a large, diverse cohort of older women. Methods: We examined 6026 older women who responded to a survey (62% response rate) and were enrolled in the Diabetes and Aging Study, an ethnically stratified random sample of patients with diabetes enrolled in Kaiser Permanente Northern California. Our primary independent variable was the mean of all HbA1c measurements in the year preceding the survey. Outcomes included the presence/absence of incontinence and limitations in daily activities due to incontinence. We used modified Poisson regression and ordinal logistic regression models to account for age, race, body mass index, parity, diabetes treatment, duration of diabetes, and comorbidity. Results: Sixty-five percent of women reported incontinence (mean age 5910 years). After adjustment, HbA1c levels were not associated with the presence or absence of incontinence. However, among women reporting incontinence, HbA1c 9% was associated with more limitations due to incontinence than HbA1c <6% (adjusted odds ratio 1.67, 95% confidence interval: 1.09-2.57). Conclusion: In this cross-sectional analysis, HbA1c level is not associated with the presence or absence of incontinence. However, for women with incontinence, poor glycemic control (HbA1c 9%) is associated with more limitations in daily activities due to incontinence. Longitudinal studies are needed to determine whether improving glycemic control to HbA1c <9% leads to fewer limitations in daily activities due to incontinence. C1 [Lee, Sei J.] Univ Calif San Francisco, Div Geriatr, San Francisco, CA 94121 USA. [Van Den Eeden, Stephen K.] Univ Calif San Francisco, Dept Urol, San Francisco, CA 94121 USA. [Lee, Sei J.] San Francisco VA Med Ctr, Res Enhancement Award Program, San Francisco, CA USA. [Karter, Andrew J.; Van Den Eeden, Stephen K.] Kaiser Permanente No Calif, Div Res, Oakland, CA USA. [Thai, Julie N.] Michigan State Univ, Coll Human Med, Grand Rapids, MI USA. [Huang, Elbert S.] Univ Chicago, Med Ctr, Div Gen Internal Med, Chicago, IL 60637 USA. RP Lee, SJ (reprint author), Univ Calif San Francisco, Div Geriatr, 4150 Clement St Bldg 1,Room 220F, San Francisco, CA 94121 USA. EM Sei.lee@ucsf.edu FU Hellman Family Award for Early Career Faculty at University of California-San Francisco; National Center for Research Resources, a component of the U. S. National Institutes of Health [K23AG040779, KL2RR024130]; Diabetes and Aging Study [R01DK081796]; National Institute of Diabetes and Digestive and Kidney Disease [P30DK092949, P30DK092924] FX Dr. Sei J. Lee was supported by the Hellman Family Award for Early Career Faculty at University of California-San Francisco. Dr. Lee was also supported by K23AG040779 and KL2RR024130 from the National Center for Research Resources, a component of the U. S. National Institutes of Health. Drs. Andrew Karter and Elbert Huang were supported through the Diabetes and Aging Study (R01DK081796). Dr. Huang was also supported by P30DK092949 and Dr. Karter was also supported by P30DK092924 through the National Institute of Diabetes and Digestive and Kidney Disease. NR 25 TC 4 Z9 4 U1 0 U2 3 PU MARY ANN LIEBERT, INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1540-9996 EI 1931-843X J9 J WOMENS HEALTH JI J. Womens Health PD DEC 1 PY 2013 VL 22 IS 12 BP 1049 EP 1055 DI 10.1089/jwh.2012.4093 PG 7 WC Public, Environmental & Occupational Health; Medicine, General & Internal; Obstetrics & Gynecology; Women's Studies SC Public, Environmental & Occupational Health; General & Internal Medicine; Obstetrics & Gynecology; Women's Studies GA 258CF UT WOS:000327435500010 PM 24032999 ER PT J AU Miller, RG Brooks, BR Swain-Eng, RJ Basner, RC Carter, GT Casey, P Cohen, AB Dubinsky, R Forshew, D Jackson, CE Kasarskis, E Procaccini, NJ Sanjak, M Tolin, FP AF Miller, Robert G. Brooks, Benjamin Rix Swain-Eng, Rebecca J. Basner, Robert C. Carter, Gregory T. Casey, Patricia Cohen, Adam B. Dubinsky, Richard Forshew, Dallas Jackson, Carlayne E. Kasarskis, Ed Procaccini, Nicholas J. Sanjak, Mohammed Tolin, Fredrik P. TI PATHOPHYSIOLOGY OF IMMUNE-MEDIATED DEMYELINATING NEUROPATHIES-PART I: NEUROSCIENCE Comment SO MUSCLE & NERVE LA English DT Editorial Material ID AMYOTROPHIC-LATERAL-SCLEROSIS; QUALITY STANDARDS SUBCOMMITTEE; PRACTICE PARAMETER UPDATE; AMERICAN ACADEMY; REPORTING SUBCOMMITTEE; MULTIDISCIPLINARY CARE; OF-LIFE; NEUROLOGY; MANAGEMENT; PATIENT C1 [Miller, Robert G.] Calif Pacific Med Ctr, Forbes Norris MDA ALS Res Ctr, San Francisco, CA USA. [Brooks, Benjamin Rix] Univ N Carolina, Sch Med, Carolinas Neuromuscular ALS MDA Ctr, Carolinas HealthCare Syst,Dept Neurol, Charlotte, NC 28223 USA. [Swain-Eng, Rebecca J.] Amer Acad Neurol, Minneapolis, MN 55415 USA. [Basner, Robert C.] Columbia Univ, Coll Phys & Surg, Div Pulm Med, New York, NY USA. [Carter, Gregory T.] St Lukes Rehabil Inst, Spokane, WA USA. [Casey, Patricia] Northwestern Med Fac Fdn, Dept Neurol, Chicago, IL USA. [Cohen, Adam B.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. [Dubinsky, Richard] Univ Kansas, Dept Neurol, Kansas City, KS USA. [Forshew, Dallas] Calif Pacific Med Ctr, Forbes Norris MDA ALS Res Ctr, San Francisco, CA USA. [Jackson, Carlayne E.] Univ Texas Hlth Sci Ctr San Antonio, Dept Neurol, San Antonio, TX 78229 USA. [Kasarskis, Ed] Univ Kentucky, Dept Neurol, Lexington, KY 40536 USA. [Procaccini, Nicholas J.] Swedish Med Ctr, Seattle, WA USA. [Procaccini, Nicholas J.] Univ Washington, Seattle, WA 98195 USA. [Sanjak, Mohammed] Carolinas Med Ctr, Dept Neurol, Carolinas Neuromuscular ALS MDA Ctr, Carolinas HealthCare Syst, Charlotte, NC 28203 USA. [Sanjak, Mohammed] Univ N Carolina, Dept Kinesiol, Charlotte, NC 28223 USA. [Tolin, Fredrik P.] Humana, Chicago, IL USA. RP Miller, RG (reprint author), Amer Acad Neurol, 201 Chicago Ave, Minneapolis, MN 55415 USA. EM quality@aan.com NR 27 TC 0 Z9 0 U1 1 U2 3 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0148-639X EI 1097-4598 J9 MUSCLE NERVE JI Muscle Nerve PD DEC PY 2013 VL 48 IS 6 BP 865 EP 869 DI 10.1002/mus.24105 PG 5 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 265WF UT WOS:000327982300002 ER PT J AU Huang, HT Kathrein, KL Barton, A Gitlin, Z Huang, YH Ward, TP Hofmann, O Dibiase, A Song, AH Tyekucheva, S Hide, W Zhou, Y Zon, LI AF Huang, Hsuan-Ting Kathrein, Katie L. Barton, Abby Gitlin, Zachary Huang, Yue-Hua Ward, Thomas P. Hofmann, Oliver Dibiase, Anthony Song, Anhua Tyekucheva, Svitlana Hide, Winston Zhou, Yi Zon, Leonard I. TI A network of epigenetic regulators guides developmental haematopoiesis in vivo SO NATURE CELL BIOLOGY LA English DT Article ID CHROMATIN-REMODELING FACTORS; CELL SELF-RENEWAL; EMBRYONIC-DEVELOPMENT; STEM-CELLS; ZEBRAFISH; TRANSCRIPTION; P300; GENE; DIFFERENTIATION; IDENTIFICATION AB The initiation of cellular programs is orchestrated by key transcription factors and chromatin regulators that activate or inhibit target gene expression. To generate a compendium of chromatin factors that establish the epigenetic code during developmental haematopoiesis, a large-scale reverse genetic screen was conducted targeting orthologues of 425 human chromatin factors in zebrafish. A set of chromatin regulators was identified that target different stages of primitive and definitive blood formation, including factors not previously implicated in haematopoiesis. We identified 15 factors that regulate development of primitive erythroid progenitors and 29 factors that regulate development of definitive haematopoietic stem and progenitor cells. These chromatin factors are associated with SWI/SNF and ISWI chromatin remodelling, SET1 methyltransferase, CBP-p300-HBO1-NuA4 acetyltransferase, HDAC-NuRD deacetylase, and Polycomb repressive complexes. Our work provides a comprehensive view of how specific chromatin factors and their associated complexes play a major role in the establishment of haematopoietic cells in vivo. C1 [Huang, Hsuan-Ting; Zon, Leonard I.] Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA. [Huang, Hsuan-Ting; Kathrein, Katie L.; Barton, Abby; Gitlin, Zachary; Huang, Yue-Hua; Ward, Thomas P.; Dibiase, Anthony; Song, Anhua; Zhou, Yi; Zon, Leonard I.] Childrens Hosp Boston, Stem Cell Program, Boston, MA 02115 USA. [Huang, Hsuan-Ting; Kathrein, Katie L.; Barton, Abby; Gitlin, Zachary; Huang, Yue-Hua; Ward, Thomas P.; Dibiase, Anthony; Song, Anhua; Zhou, Yi; Zon, Leonard I.] Childrens Hosp Boston, Div Pediat Hematol Oncol, Boston, MA 02115 USA. [Huang, Hsuan-Ting; Kathrein, Katie L.; Barton, Abby; Gitlin, Zachary; Huang, Yue-Hua; Ward, Thomas P.; Dibiase, Anthony; Song, Anhua; Zhou, Yi; Zon, Leonard I.] Howard Hughes Med Inst, Dana Farber Canc Inst, Boston, MA 02115 USA. [Hofmann, Oliver; Hide, Winston; Zon, Leonard I.] Harvard Stem Cell Inst, Cambridge, MA 02138 USA. [Tyekucheva, Svitlana; Hide, Winston] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. [Tyekucheva, Svitlana] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA. RP Zon, LI (reprint author), Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA. EM zon@enders.tch.harvard.edu RI Hide, Winston Hide/C-7217-2009; OI Hide, Winston Hide/0000-0002-8621-3271; Hofmann, Oliver/0000-0002-7738-1513 FU NIH NIDDK [5R01DK053298-15, 5P30 DK49216-19, DK53298-15, R24 DK092760-02, 1F32DK089876-01]; NIH NHLBI [5R01HL048801-21, T32 HL066987-09]; HHMI FX We thank O. Tamplin, T. V. Bowman, P. Cahan and C. K. Kaufman for helpful discussions. The work was supported by NIH NIDDK 5R01DK053298-15, NIH NHLBI 5R01HL048801-21, NIH NIDDK 5P30 DK49216-19, NIH NIDDK DK53298-15, NIH NIDDK R24 DK092760-02, HHMI (to L.I.Z.), NIH NHLBI T32 HL066987-09 and NIH NIDDK 1F32DK089876-01 (to K.L.K). NR 48 TC 24 Z9 25 U1 3 U2 12 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1465-7392 EI 1476-4679 J9 NAT CELL BIOL JI Nat. Cell Biol. PD DEC PY 2013 VL 15 IS 12 BP 1516 EP + DI 10.1038/ncb2870 PG 17 WC Cell Biology SC Cell Biology GA 265IL UT WOS:000327944200016 PM 24240475 ER PT J AU Agarwala, V Flannick, J Sunyaev, S Altshuler, D AF Agarwala, Vineeta Flannick, Jason Sunyaev, Shamil Altshuler, David CA GoT2D Consortium TI Evaluating empirical bounds on complex disease genetic architecture SO NATURE GENETICS LA English DT Article ID GENOME-WIDE ASSOCIATION; MISSING HERITABILITY; RARE VARIANTS; POPULATION-GROWTH; RISK PREDICTION; COMMON DISEASE; TRAITS; SUSCEPTIBILITY; EXCESS; LINKAGE AB The genetic architecture of human diseases governs the success of genetic mapping and the future of personalized medicine. Although numerous studies have queried the genetic basis of common disease, contradictory hypotheses have been advocated about features of genetic architecture (for example, the contribution of rare versus common variants). We developed an integrated simulation framework, calibrated to empirical data, to enable the systematic evaluation of such hypotheses. For type 2 diabetes (T2D), two simple parameters-(i) the target size for causal mutation and (ii) the coupling between selection and phenotypic effect-define a broad space of architectures. Whereas extreme models are excluded by the combination of epidemiology, linkage and genome-wide association studies, many models remain consistent, including those where rare variants explain either little (<25%) or most (>80%) of T2D heritability. Ongoing sequencing and genotyping studies will further constrain the space of possible architectures, but very large samples (for example, >250,000 unselected individuals) will be required to localize most of the heritability underlying T2D and other traits characterized by these models. C1 [Agarwala, Vineeta; Sunyaev, Shamil] MIT, Harvard MIT Div Hlth Sci & Technol, Cambridge, MA 02139 USA. [Agarwala, Vineeta; Flannick, Jason; Sunyaev, Shamil; Altshuler, David] Broad Inst MIT & Harvard, Cambridge, MA 02142 USA. [Agarwala, Vineeta; Sunyaev, Shamil] Harvard Univ, Program Biophys, Grad Sch Arts & Sci, Cambridge, MA 02138 USA. [Flannick, Jason; Altshuler, David] Harvard Univ, Sch Med, Dept Genet, Boston, MA USA. [Flannick, Jason; Altshuler, David] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA. [Sunyaev, Shamil] Harvard Univ, Brigham & Womens Hosp, Sch Med, Div Genet, Boston, MA 02115 USA. [Altshuler, David] MIT, Dept Biol, Cambridge, MA USA. RP Altshuler, D (reprint author), Broad Inst MIT & Harvard, Cambridge, MA 02142 USA. EM altshuler@molbio.mgh.harvard.edu RI Altshuler, David/A-4476-2009; OI Altshuler, David/0000-0002-7250-4107; Kumar, Ashish/0000-0002-7075-5930 FU Doris Duke Charitable Foundation [2006087]; National Institute of General Medical Sciences (NIGMS) [R01GM078598]; National Institute of Mental Health (NIMH) [R01MH084676]; US National Institutes of Health (NIH) [T32GM007753, T32GM008313]; NIH [T32GM007748-33]; Pfizer; National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) [1RC2DK088389-01] FX We gratefully acknowledge B. Lambert and K. Weiss (authors of the simulation tool ForSim) for helpful conversation, encouragement and technical assistance. Without their software, this work would not have been possible. We thank B. Voight for tremendous help in matching simulated genetic studies to those empirically conducted for T2D. We also thank E. Lander, C. Hartl, P. Fontanillas, B. Neale, M. McCarthy, M. Boehnke, M. Daly, S. Purcell and E. Stahl for discussion and insightful critiques. This work was supported by grants from the Doris Duke Charitable Foundation (award 2006087 to D. A.), the National Institute of General Medical Sciences (NIGMS; award R01GM078598 to S. S.) and the National Institute of Mental Health (NIMH; grant R01MH084676 to S. S.). V. A. is also supported by US National Institutes of Health (NIH) Training grants T32GM007753 and T32GM008313. J.F. is supported in part by NIH Training grant T32GM007748-33 as well as by funding from Pfizer. The GoT2D Study is supported by grant 1RC2DK088389-01 from the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK). NR 71 TC 48 Z9 48 U1 1 U2 24 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1061-4036 EI 1546-1718 J9 NAT GENET JI Nature Genet. PD DEC PY 2013 VL 45 IS 12 BP 1418 EP U167 DI 10.1038/ng.2804 PG 12 WC Genetics & Heredity SC Genetics & Heredity GA 262EA UT WOS:000327715800005 PM 24141362 ER PT J AU Lambert, JC Ibrahim-Verbaas, CA Harold, D Naj, AC Sims, R Bellenguez, C Jun, G DeStefano, AL Bis, JC Beecham, GW Grenier-Boley, B Russo, G Thornton-Wells, TA Jones, N Smith, AV Chouraki, V Thomas, C Ikram, MA Zelenika, D Vardarajan, BN Kamatani, Y Lin, CF Gerrish, A Schmidt, H Kunkle, B Dunstan, ML Ruiz, A Bihoreau, MT Choi, SH Reitz, C Pasquier, F Hollingworth, P Ramirez, A Hanon, O Fitzpatrick, AL Buxbaum, JD Campion, D Crane, PK Baldwin, C Becker, T Gudnason, V Cruchaga, C Craig, D Amin, N Berr, C Lopez, OL De Jager, PL Deramecourt, V Johnston, JA Evans, D Lovestone, S Letenneur, L Moron, FJ Rubinsztein, DC Eiriksdottir, G Sleegers, K Goate, AM Fievet, N Huentelman, MJ Gill, M Brown, K Kamboh, MI Keller, L Barberger-Gateau, P McGuinness, B Larson, EB Green, R Myers, AJ Dufouil, C Todd, S Wallon, D Love, S Rogaeva, E Gallacher, J St George-Hyslop, P Clarimon, J Lleo, A Bayer, A Tsuang, DW Yu, L Tsolaki, M Bossu, P Spalletta, G Proitsi, P Collinge, J Sorbi, S Sanchez-Garcia, F Fox, NC Hardy, J Naranjo, MCD Bosco, P Clarke, R Brayne, C Galimberti, D Mancuso, M Matthews, F Moebus, S Mecocci, P Del Zompo, M Maier, W Hampel, H Pilotto, A Bullido, M Panza, F Caffarra, P Nacmias, B Gilbert, JR Mayhaus, M Lannfelt, L Hakonarson, H Pichler, S Carrasquillo, MM Ingelsson, M Beekly, D Alvarez, V Zou, FG Valladares, O Younkin, SG Coto, E Hamilton-Nelson, KL Gu, W Razquin, C Pastor, P Mateo, I Owen, MJ Faber, KM Jonsson, PV Combarros, O O'Donovan, MC Cantwell, LB Soininen, H Blacker, D Mead, S Mosley, TH Bennett, DA Harris, TB Fratiglioni, L Holmes, C de Bruijn, RFAG Passmore, P Montine, TJ Bettens, K Rotter, JI Brice, A Morgan, K Foroud, TM Kukull, WA Hannequin, D Powell, JF Nalls, MA Ritchie, K Lunetta, KL Kauwe, JSK Boerwinkle, E Riemenschneider, M Boada, M Hiltunen, M Martin, ER Schmidt, R Rujescu, D Wang, LS Dartigues, JF Mayeux, R Tzourio, C Hofman, A Nothen, MM Graff, C Psaty, BM Jones, L Haines, JL Holmans, PA Lathrop, M Pericak-Vance, MA Launer, LJ Farrer, LA van Duijn, CM Van Broeckhoven, C Moskvina, V Seshadri, S Williams, J Schellenberg, GD Amouyel, P AF Lambert, Jean-Charles Ibrahim-Verbaas, Carla A. Harold, Denise Naj, Adam C. Sims, Rebecca Bellenguez, Celine Jun, Gyungah DeStefano, Anita L. Bis, Joshua C. Beecham, Gary W. Grenier-Boley, Benjamin Russo, Giancarlo Thornton-Wells, Tricia A. Jones, Nicola Smith, Albert V. Chouraki, Vincent Thomas, Charlene Ikram, M. Arfan Zelenika, Diana Vardarajan, Badri N. Kamatani, Yoichiro Lin, Chiao-Feng Gerrish, Amy Schmidt, Helena Kunkle, Brian Dunstan, Melanie L. Ruiz, Agustin Bihoreau, Marie-Therese Choi, Seung-Hoan Reitz, Christiane Pasquier, Florence Hollingworth, Paul Ramirez, Alfredo Hanon, Olivier Fitzpatrick, Annette L. Buxbaum, Joseph D. Campion, Dominique Crane, Paul K. Baldwin, Clinton Becker, Tim Gudnason, Vilmundur Cruchaga, Carlos Craig, David Amin, Najaf Berr, Claudine Lopez, Oscar L. De Jager, Philip L. Deramecourt, Vincent Johnston, Janet A. Evans, Denis Lovestone, Simon Letenneur, Luc Moron, Francisco J. Rubinsztein, David C. Eiriksdottir, Gudny Sleegers, Kristel Goate, Alison M. Fievet, Nathalie Huentelman, Matthew J. Gill, Michael Brown, Kristelle Kamboh, M. Ilyas Keller, Lina Barberger-Gateau, Pascale McGuinness, Bernadette Larson, Eric B. Green, Robert Myers, Amanda J. Dufouil, Carole Todd, Stephen Wallon, David Love, Seth Rogaeva, Ekaterina Gallacher, John St George-Hyslop, Peter Clarimon, Jordi Lleo, Alberto Bayer, Anthony Tsuang, Debby W. Yu, Lei Tsolaki, Magda Bossu, Paola Spalletta, Gianfranco Proitsi, Petroula Collinge, John Sorbi, Sandro Sanchez-Garcia, Florentino Fox, Nick C. Hardy, John Naranjo, Maria Candida Deniz Bosco, Paolo Clarke, Robert Brayne, Carol Galimberti, Daniela Mancuso, Michelangelo Matthews, Fiona Moebus, Susanne Mecocci, Patrizia Del Zompo, Maria Maier, Wolfgang Hampel, Harald Pilotto, Alberto Bullido, Maria Panza, Francesco Caffarra, Paolo Nacmias, Benedetta Gilbert, John R. Mayhaus, Manuel Lannfelt, Lars Hakonarson, Hakon Pichler, Sabrina Carrasquillo, Minerva M. Ingelsson, Martin Beekly, Duane Alvarez, Victoria Zou, Fanggeng Valladares, Otto Younkin, Steven G. Coto, Eliecer Hamilton-Nelson, Kara L. Gu, Wei Razquin, Cristina Pastor, Pau Mateo, Ignacio Owen, Michael J. Faber, Kelley M. Jonsson, Palmi V. Combarros, Onofre O'Donovan, Michael C. Cantwell, Laura B. Soininen, Hilkka Blacker, Deborah Mead, Simon Mosley, Thomas H., Jr. Bennett, David A. Harris, Tamara B. Fratiglioni, Laura Holmes, Clive de Bruijn, Renee F. A. G. Passmore, Peter Montine, Thomas J. Bettens, Karolien Rotter, Jerome I. Brice, Alexis Morgan, Kevin Foroud, Tatiana M. Kukull, Walter A. Hannequin, Didier Powell, John F. Nalls, Michael A. Ritchie, Karen Lunetta, Kathryn L. Kauwe, John S. K. Boerwinkle, Eric Riemenschneider, Matthias Boada, Merce Hiltunen, Mikko Martin, Eden R. Schmidt, Reinhold Rujescu, Dan Wang, Li-San Dartigues, Jean-Francois Mayeux, Richard Tzourio, Christophe Hofman, Albert Noethen, Markus M. Graff, Caroline Psaty, Bruce M. Jones, Lesley Haines, Jonathan L. Holmans, Peter A. Lathrop, Mark Pericak-Vance, Margaret A. Launer, Lenore J. Farrer, Lindsay A. van Duijn, Cornelia M. Van Broeckhoven, Christine Moskvina, Valentina Seshadri, Sudha Williams, Julie Schellenberg, Gerard D. Amouyel, Philippe CA EADI GERAD ADGC CHARGE TI Meta-analysis of 74,046 individuals identifies 11 new susceptibility loci for Alzheimer's disease SO NATURE GENETICS LA English DT Article ID GENOME-WIDE ASSOCIATION; COMMON VARIANTS; GENETIC RISK; RECEPTOR; CD33; IMPUTATION; MUTATIONS; GENOTYPES; SEQUENCE; NEURONS AB Eleven susceptibility loci for late-onset Alzheimer's disease (LOAD) were identified by previous studies; however, a large portion of the genetic risk for this disease remains unexplained. We conducted a large, two-stage meta-analysis of genome-wide association studies (GWAS) in individuals of European ancestry. In stage 1, we used genotyped and imputed data (7,055,881 SNPs) to perform meta-analysis on 4 previously published GWAS data sets consisting of 17,008 Alzheimer's disease cases and 37,154 controls. In stage 2, 11,632 SNPs were genotyped and tested for association in an independent set of 8,572 Alzheimer's disease cases and 11,312 controls. In addition to the APOE locus (encoding apolipoprotein E), 19 loci reached genome-wide significance (P < 5 x 10(-8)) in the combined stage 1 and stage 2 analysis, of which 11 are newly associated with Alzheimer's disease. C1 [Lambert, Jean-Charles; Bellenguez, Celine; Grenier-Boley, Benjamin; Chouraki, Vincent; Fievet, Nathalie; Amouyel, Philippe] INSERM, U744, F-59045 Lille, France. [Lambert, Jean-Charles; Bellenguez, Celine; Grenier-Boley, Benjamin; Chouraki, Vincent; Pasquier, Florence; Deramecourt, Vincent; Amouyel, Philippe] Univ Lille 2, Lille, France. [Lambert, Jean-Charles; Bellenguez, Celine; Grenier-Boley, Benjamin; Chouraki, Vincent; Fievet, Nathalie; Amouyel, Philippe] Inst Pasteur, F-59019 Lille, France. [Ibrahim-Verbaas, Carla A.; Ikram, M. Arfan; de Bruijn, Renee F. A. G.] Erasmus MC Univ Med Ctr, Dept Neurol, Rotterdam, Netherlands. [Ibrahim-Verbaas, Carla A.; Ikram, M. Arfan; Amin, Najaf; de Bruijn, Renee F. A. G.; Hofman, Albert; van Duijn, Cornelia M.] Erasmus MC Univ Med Ctr, Dept Epidemiol, Rotterdam, Netherlands. [Harold, Denise; Sims, Rebecca; Jones, Nicola; Thomas, Charlene; Gerrish, Amy; Dunstan, Melanie L.; Hollingworth, Paul; Owen, Michael J.; O'Donovan, Michael C.; Jones, Lesley; Holmans, Peter A.; Moskvina, Valentina; Williams, Julie] Cardiff Univ, Inst Psychol Med & Clin Neurosci, MRC, Ctr Neuropsychiat Genet & Genom, Cardiff CF10 3AX, S Glam, Wales. [Naj, Adam C.] Univ Penn, Dept Biostat & Epidemiol, Perelman Sch Med, Philadelphia, PA 19104 USA. [Naj, Adam C.] Univ Penn, Ctr Clin Epidemiol & Biostat, Perelman Sch Med, Philadelphia, PA 19104 USA. [Jun, Gyungah; Vardarajan, Badri N.; Baldwin, Clinton; Farrer, Lindsay A.] Boston Univ, Sch Publ Hlth, Dept Med Biomed Genet, Boston, MA USA. [Jun, Gyungah; Farrer, Lindsay A.] Boston Univ, Sch Med, Dept Ophthalmol, Boston, MA 02118 USA. [Jun, Gyungah; DeStefano, Anita L.; Choi, Seung-Hoan; Lunetta, Kathryn L.; Farrer, Lindsay A.] Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA USA. [Bis, Joshua C.; Fitzpatrick, Annette L.; Harris, Tamara B.; Psaty, Bruce M.] Univ Washington, Dept Med, Cardiovasc Hlth Res Unit, Seattle, WA USA. [Beecham, Gary W.; Kunkle, Brian; Gilbert, John R.; Hamilton-Nelson, Kara L.; Martin, Eden R.; Pericak-Vance, Margaret A.] Univ Miami, John P Hussman Inst Human Genom, Miami, FL USA. [Beecham, Gary W.; Gilbert, John R.; Martin, Eden R.; Pericak-Vance, Margaret A.] Univ Miami, Dept Human Genet, Dr John T Macdonald Fdn, Miami, FL USA. [Russo, Giancarlo] Univ Zurich, ETH, Funct Genom Ctr Zurich, Zurich, Switzerland. [Thornton-Wells, Tricia A.; Haines, Jonathan L.] Vanderbilt Univ, Dept Mol Physiol & Biophys, Nashville, TN 37232 USA. [Smith, Albert V.; Gudnason, Vilmundur; Jonsson, Palmi V.] Univ Iceland, Fac Med, Reykjavik, Iceland. [Smith, Albert V.; Gudnason, Vilmundur; Eiriksdottir, Gudny] Iceland Heart Assoc, Kopavogur, Iceland. [Ikram, M. Arfan] Erasmus MC Univ Med Ctr, Dept Radiol, Rotterdam, Netherlands. [Ikram, M. Arfan; de Bruijn, Renee F. A. G.; Hofman, Albert; van Duijn, Cornelia M.] Netherlands Consortium Hlth Aging, Leiden, Netherlands. [Zelenika, Diana; Bihoreau, Marie-Therese; Lathrop, Mark] CEA, Inst Genom, Ctr Natl Genotypage, Evry, France. [Kamatani, Yoichiro; Lathrop, Mark] Fdn Jean Dausset, Ctr Etud Polymorphisme Humain, Paris, France. [Lin, Chiao-Feng; Valladares, Otto; Cantwell, Laura B.; Wang, Li-San; Schellenberg, Gerard D.] Univ Penn, Dept Pathol & Lab Med, Perelman Sch Med, Philadelphia, PA USA. [Schmidt, Helena] Med Univ Graz, Inst Mol Biol & Biochem, Graz, Austria. [Ruiz, Agustin; Boada, Merce] Memory Clin Fundacio Alzheimer Ctr Educ ACF, Inst Catala Neurociencies Aplicades, Barcelona, Spain. [Reitz, Christiane; Mayeux, Richard] Columbia Univ, Dept Neurol, Taub Inst Alzheimers Dis & Aging Brain, New York, NY USA. [Reitz, Christiane; Mayeux, Richard] Columbia Univ, Gertrude H Sergievsky Ctr, Dept Neurol, New York, NY 10027 USA. [Pasquier, Florence; Deramecourt, Vincent; Amouyel, Philippe] Ctr Hosp Reg Univ Lille, CNR MAJ, Lille, France. [Ramirez, Alfredo; Maier, Wolfgang] Univ Bonn, Dept Psychiat & Psychotherapy, Bonn, Germany. [Ramirez, Alfredo] Univ Bonn, Inst Human Genet, Bonn, Germany. [Hanon, Olivier] Univ Paris 05, Broca Hosp, Dept Geriatr, Paris, France. [Fitzpatrick, Annette L.; Kukull, Walter A.; Psaty, Bruce M.] Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA. [Fitzpatrick, Annette L.] Univ Washington, Dept Global Hlth, Seattle, WA 98195 USA. [Buxbaum, Joseph D.] Mt Sinai Sch Med, Dept Neurosci, New York, NY USA. [Buxbaum, Joseph D.] Mt Sinai Sch Med, Dept Psychiat, New York, NY USA. [Buxbaum, Joseph D.] Mt Sinai Sch Med, Dept Genet & Genom Sci, New York, NY USA. [Campion, Dominique; Wallon, David; Hannequin, Didier] Rouen Univ Hosp, INSERM, CNR MAJ, U1079, Rouen, France. [Crane, Paul K.; Larson, Eric B.] Univ Washington, Dept Med, Seattle, WA USA. [Becker, Tim; Maier, Wolfgang] German Ctr Neurodegenerat Dis DZNE, Bonn, Germany. [Becker, Tim] Univ Bonn, Inst Med Biometry Informat & Epidemiol, Bonn, Germany. [Cruchaga, Carlos; Goate, Alison M.] Washington Univ, Sch Med, Dept Psychiat, St Louis, MO 63110 USA. [Cruchaga, Carlos; Goate, Alison M.] Washington Univ, Sch Med, Hope Ctr Program Prot Aggregat & Neurodegenerat, St Louis, MO USA. [Craig, David; Johnston, Janet A.; McGuinness, Bernadette; Todd, Stephen; Passmore, Peter] Queens Univ Belfast, Ageing Grp, Ctr Publ Hlth, Sch Med Dent & Biomed Sci, Belfast, Antrim, North Ireland. [Berr, Claudine; Ritchie, Karen] Hop La Colombiere, Fac Med, U1061, INSERM, Montpellier, France. [Lopez, Oscar L.] Univ Pittsburgh, Sch Med, Dept Neurol, Pittsburgh, PA 15261 USA. [De Jager, Philip L.] Brigham & Womens Hosp, Dept Neurol & Psychiat, Inst Neurosci, Program Translat NeuroPsychiat Genom, Boston, MA 02115 USA. [De Jager, Philip L.; Green, Robert] Harvard Univ, Sch Med, Boston, MA USA. [De Jager, Philip L.] Broad Inst, Program Med & Populat Genet, Boston, MA USA. [Evans, Denis] Rush Univ, Med Ctr, Dept Internal Med, Rush Inst Hlth Aging, Chicago, IL 60612 USA. [Lovestone, Simon; Proitsi, Petroula; Powell, John F.] Univ London, Kings Coll London, Inst Psychiat, London SW3 6LX, England. [Letenneur, Luc; Barberger-Gateau, Pascale; Dufouil, Carole; Dartigues, Jean-Francois] Victor Segalen Univ, INSERM, U897, Bordeaux, France. [Moron, Francisco J.] Neocodex, Dept Genom Estruct, Seville, Spain. [Rubinsztein, David C.; St George-Hyslop, Peter] Univ Cambridge, Cambridge Inst Med Res, Cambridge, England. [Sleegers, Kristel; Bettens, Karolien; Van Broeckhoven, Christine] Univ Antwerp VIB, Dept Mol Genet, Neurodegenerat Brain Dis Grp, B-2610 Antwerp, Belgium. [Sleegers, Kristel; Bettens, Karolien; Van Broeckhoven, Christine] Univ Antwerp, Neurogenet Lab, Inst Born Bunge, B-2020 Antwerp, Belgium. [Huentelman, Matthew J.] Translat Genom Res Inst, Neurogenom Div, Phoenix, AZ USA. [Gill, Michael] St James Hosp, Mercers Inst Res Aging, Dublin 8, Ireland. [Gill, Michael] Univ Dublin Trinity Coll, Dublin 2, Ireland. [Brown, Kristelle; Morgan, Kevin] Univ Nottingham, Inst Genet, Queens Med Ctr, Nottingham NG7 2RD, England. [Kamboh, M. Ilyas] Univ Pittsburgh, Dept Human Genet, Pittsburgh, PA USA. [Kamboh, M. Ilyas] Univ Pittsburgh, Alzheimers Dis Res Ctr, Pittsburgh, PA USA. [Keller, Lina; Fratiglioni, Laura] Karolinska Inst, Aging Res Ctr, Dept Neurobiol Care Sci & Soc, Stockholm, Sweden. [Keller, Lina; Fratiglioni, Laura] Stockholm Univ, S-10691 Stockholm, Sweden. [Larson, Eric B.; Psaty, Bruce M.] Grp Hlth, Grp Hlth Res Inst, Seattle, WA USA. [Green, Robert] Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. [Green, Robert] Brigham & Womens Hosp, Div Genet, Partners Ctr Personalized Genet Med, Boston, MA 02115 USA. [Myers, Amanda J.] Univ Miami, Miller Sch Med, Dept Psychiat & Behav Sci, Miami, FL 33136 USA. [Love, Seth] Univ Bristol, Inst Clin Neurosci, Sch Clin Sci, Frenchay Hosp, Bristol, Avon, England. [Rogaeva, Ekaterina; St George-Hyslop, Peter] Univ Toronto, Tanz Ctr Res Neurodegenerat Dis, Toronto, ON, Canada. [Gallacher, John; Bayer, Anthony] Cardiff Univ, Neuadd Meirionnydd, Univ Wales Hosp, Inst Primary Care & Publ Hlth, Cardiff CF10 3AX, S Glam, Wales. [St George-Hyslop, Peter] Univ Cambridge, Dept Clin Neurosci, Cambridge, England. [Clarimon, Jordi; Lleo, Alberto] Univ Autonoma Barcelona, Dept Neurol, Biomed Res Inst Sant Pau IIB Sant Pau, St Pau Hosp, E-08193 Barcelona, Spain. [Clarimon, Jordi; Lleo, Alberto] Ctr Networker Biomed Res Neurodegenerat Dis, Barcelona, Spain. [Tsuang, Debby W.] Vet Adm Puget Sound Hlth Care Syst, GRECC, Seattle, WA USA. [Yu, Lei; Bennett, David A.] Rush Univ, Med Ctr, Dept Neurol Sci, Chicago, IL 60612 USA. [Tsolaki, Magda] Aristotle Univ Thessaloniki, Dept Neurol, GR-54006 Thessaloniki, Greece. [Bossu, Paola; Spalletta, Gianfranco] Fdn Santa Lucia, Rome, Italy. [Collinge, John; Mead, Simon] UCL, Inst Neurol, MRC, Pr Unit,Dept Neurodegenerat Dis, London, England. [Sorbi, Sandro; Nacmias, Benedetta] Univ Florence, NEUROFARBA Dept Neurosci Psychol Drug Res & Child, Florence, Italy. [Sorbi, Sandro; Nacmias, Benedetta] Univ Florence, Ctr Ric Trasferimento Alta Formaz DENOTH, Florence, Italy. [Sanchez-Garcia, Florentino; Naranjo, Maria Candida Deniz] Hosp Univ Dr Negrin, Dept Immunol, Las Palmas Gran Canaria, Spain. [Fox, Nick C.] UCL, Dementia Res Ctr, Dept Neurodegenerat Dis, Inst Neurol, London, England. [Hardy, John] Inst Neurol, Dept Mol Neurosci, London WC1N 3BG, England. [Hardy, John] Inst Neurol, Reta Lilla Weston Labs, London WC1N 3BG, England. [Bosco, Paolo] Assoc Oasi Maria Santissima Srl, IRCCS, Troina, Italy. [Clarke, Robert] Univ Oxford, Clin Trial Serv Unit, OHAP, Oxford, England. [Brayne, Carol] Univ Cambridge, Inst Publ Hlth, Cambridge, England. [Galimberti, Daniela] Univ Milan, Fdn Ca Granda, IRCCS Osped Policlin, Milan, Italy. [Mancuso, Michelangelo] Univ Pisa, Neurol Clin, Pisa, Italy. [Matthews, Fiona] MRC, Biostat Unit, Cambridge CB2 2BW, England. [Moebus, Susanne] Univ Duisburg Essen, Univ Hosp Essen, Inst Med Informat Biometry & Epidemiol, Essen, Germany. [Mecocci, Patrizia] Univ Perugia, Sect Gerontol & Geriatr, Dept Clin & Expt Med, I-06100 Perugia, Italy. [Del Zompo, Maria] Univ Cagliari, Sect Neurosci & Clin Pharmacol, Dept Biomed Sci, Cagliari, Italy. [Hampel, Harald] Goethe Univ Frankfurt, Dept Psychiat, D-60054 Frankfurt, Germany. [Hampel, Harald] Univ Munich, Dept Psychiat, D-80539 Munich, Germany. [Pilotto, Alberto] IRCCS Casa Sollievo Sofferenza, Gerontol & Geriatr Res Lab, San Giovanni Rotondo, Italy. [Bullido, Maria] Univ Autonoma Madrid, Consejo Super Invest Cient, Ctr Biol Mol Severo Ochoa, Madrid, Spain. [Bullido, Maria] Ctr Invest Biomed Red Enfermedades Neurodegenerat, Madrid, Spain. [Bullido, Maria] Inst Invest Sanitaria Hosp Paz IdIPaz, Madrid, Spain. [Panza, Francesco] Univ Bari, Dept Geriatr, Ctr Aging Brain, Bari, Italy. [Caffarra, Paolo] Univ Parma, Dept Neurosci, I-43100 Parma, Italy. [Caffarra, Paolo] AUSL, Ctr Cognit Disorders, Parma, Italy. [Mayhaus, Manuel; Pichler, Sabrina; Gu, Wei; Riemenschneider, Matthias] Saarland Univ Hosp, Dept Psychiat, Homburg, Germany. [Lannfelt, Lars; Ingelsson, Martin] Uppsala Univ, Dept Publ Health Geriatr, Uppsala, Sweden. [Hakonarson, Hakon] Childrens Hosp Philadelphia, Ctr Appl Genom, Philadelphia, PA 19104 USA. [Carrasquillo, Minerva M.; Zou, Fanggeng; Younkin, Steven G.] Mayo Clin, Dept Neurosci, Jacksonville, FL 32224 USA. [Beekly, Duane] Univ Washington, Natl Alzheimers Coordinating Ctr, Seattle, WA 98195 USA. [Alvarez, Victoria; Coto, Eliecer] Hosp Univ Cent Asturias, Oviedo, Spain. [Razquin, Cristina; Pastor, Pau] Univ Navarra, Ctr Appl Med Res, Sch Med, Neurogenet Lab,Div Neurosci, E-31080 Pamplona, Spain. [Pastor, Pau] Inst Salud Carlos III, CIBERNED, Madrid, Spain. [Mateo, Ignacio; Combarros, Onofre] Univ Cantabria, Neurol Serv, Marques de Valdecilla Univ Hosp, E-39005 Santander, Spain. [Mateo, Ignacio; Combarros, Onofre] Inst Formac & Invest Marques Valdecilla IFIMAV, Santander, Spain. [Mateo, Ignacio; Combarros, Onofre] Univ Cantabria, Marques de Valdecilla Univ Hosp, CIBERNED, E-39005 Santander, Spain. [Mateo, Ignacio; Combarros, Onofre] IFIMAV, Santander, Spain. [Faber, Kelley M.; Foroud, Tatiana M.] Indiana Univ, Dept Med & Mol Genet, Indianapolis, IN 46204 USA. [Jonsson, Palmi V.] Landspitali Univ Hosp, Geriatr Dept, Reykjavik, Iceland. [Soininen, Hilkka; Hiltunen, Mikko] Univ Eastern Finland, Inst Clin Med Neurol, Kuopio, Finland. [Soininen, Hilkka; Hiltunen, Mikko] Kuopio Univ Hosp, Dept Neurol, SF-70210 Kuopio, Finland. [Blacker, Deborah] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. [Blacker, Deborah] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Psychiat, Boston, MA USA. [Mosley, Thomas H., Jr.] Univ Mississippi, Med Ctr, Dept Med Geriatr, Jackson, MS 39216 USA. [Bennett, David A.; Graff, Caroline] Rush Univ, Med Ctr, Rush Alzheimers Dis Ctr, Chicago, IL 60612 USA. [Fratiglioni, Laura] Karolinska Univ Hosp Huddinge, Dept Geriatr Med, Stockholm, Sweden. [Holmes, Clive] Univ Southampton, Sch Med, Div Clin Neurosci, Southampton, Hants, England. [Montine, Thomas J.] Univ Washington, Dept Pathol, Seattle, WA 98195 USA. [Rotter, Jerome I.] Cedars Sinai Med Ctr, Inst Med Genet, Los Angeles, CA 90048 USA. [Brice, Alexis] Univ Paris 06, Inst Cerveau & Moelle Epiniere CRICM, INSERM, UMRS 975,CNRS,UMR 7225,Ctr Rech,Hosp La Salpetrie, Paris, France. [Brice, Alexis] Hop La Pitie Salpetriere, AP HP, Paris, France. [Nalls, Michael A.] NIA, Neurogenet Lab, Intramural Res Program, Bethesda, MD 20892 USA. [Ritchie, Karen] Univ London Imperial Coll Sci Technol & Med, Fac Med, St Marys Hosp, London, England. [Kauwe, John S. K.] Brigham Young Univ, Dept Biol, Provo, UT 84602 USA. [Boerwinkle, Eric] Baylor Coll Med, Human Genome Sequencing Ctr, Houston, TX 77030 USA. [Boerwinkle, Eric] Univ Texas Hlth Sci Ctr Houston, Ctr Human Genet, Houston, TX 77030 USA. [Boerwinkle, Eric] Univ Texas Hlth Sci Ctr Houston, Div Epidemiol, Houston, TX 77030 USA. [Boada, Merce] Univ Autonoma Barcelona VHIR UAB, Hosp Univ Vall dHebron, Inst Recerca, Barcelona, Spain. [Schmidt, Reinhold] Med Univ Graz, Dept Neurol, Graz, Austria. [Rujescu, Dan] Univ Halle, Dept Psychiat, Halle, Germany. [Dartigues, Jean-Francois] CHU Bordeaux, Ctr Memoire Ressources & Rech Bordeaux, Bordeaux, France. [Tzourio, Christophe] Victor Segalen Univ, INSERM, U708, Bordeaux, France. [Noethen, Markus M.] Univ Bonn, Inst Human Genet, Dept Genom, Life & Brain Ctr, Bonn, Germany. [Graff, Caroline] Karolinska Inst, Dept Neurobiol, Alzheimers Dis Res Ctr, Stockholm, Sweden. [Psaty, Bruce M.] Univ Washington, Dept Hlth Serv, Seattle, WA 98195 USA. [Haines, Jonathan L.] Vanderbilt Univ, Vanderbilt Ctr Human Genet Res, Nashville, TN 37235 USA. [Lathrop, Mark] McGill Univ, Montreal, PQ, Canada. [Lathrop, Mark] Genome Quebec Innovat Ctr, Montreal, PQ, Canada. [Launer, Lenore J.] NIA, Lab Epidemiol & Populat Sci, Intramural Res Program, Bethesda, MD 20892 USA. [Farrer, Lindsay A.] Boston Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA USA. [Farrer, Lindsay A.; Seshadri, Sudha] Boston Univ, Sch Med, Dept Neurol, Boston, MA 02118 USA. [van Duijn, Cornelia M.] Ctr Med Syst Biol, Leiden, Netherlands. [Amouyel, Philippe] Ctr Hosp Reg Univ Lille, Lille, France. RP Amouyel, P (reprint author), INSERM, U744, F-59045 Lille, France. EM williamsj@cardiff.ac.uk; philippe.amouyel@pasteur-lille.fr RI graff, caroline/A-2545-2009; Bullido, Maria/C-8509-2014; IBIS, TERAPIA CELULA/P-3297-2015; Smith, Albert/K-5150-2015; Ritchie, Karen/G-3571-2013; Caffarra, Paolo/K-6567-2016; Tsuang, Debby/L-7234-2016; Guerreiro, Rita/A-1327-2011; Vandenberghe, Rik/K-2145-2014; Epelbaum, Jacques/B-2263-2013; Ciaramella, Antonio/F-1170-2011; Deloukas, Panos/B-2922-2013; Pastor, Pau/C-9834-2009; Tzourio, christophe/B-4015-2009; Fox, Nick/B-1319-2009; lambert, jean-charles/F-8787-2013; Holmans, Peter/F-4518-2015; LICEND, CEMND/F-1296-2015; Frank Garcia, Ana/I-5159-2015; Gudnason, Vilmundur/K-6885-2015; Kamatani, Yoichiro/N-5513-2015; Kowall, Neil/G-6364-2012; Reposo, Ramirez-Lorca/D-7907-2014; Aspelund, Thor/C-5983-2008; Singleton, Andrew/C-3010-2009; Powell, John/G-4412-2011; Lambert, jean-charles/A-9553-2014; Gu, Wei/G-4003-2010; Crane, Paul/C-8623-2014; Hardy, John/C-2451-2009; berr, Claudine/D-5238-2014; Bosso, Paola/E-4832-2014; Schott, Jonathan/A-9065-2011 OI Nothen, Markus/0000-0002-8770-2464; Matthews, Fiona/0000-0002-1728-2388; Todd, Stephen/0000-0002-2312-9195; Pickering-Brown, Stuart/0000-0003-1561-6054; Squassina, Alessio/0000-0001-7415-7607; Beiser, Alexa/0000-0001-8551-7778; Alcolea, Daniel/0000-0002-3819-3245; Harold, Denise/0000-0001-5195-0143; Lacour, Andre/0000-0003-2692-2583; Ferris, Steven/0000-0001-8641-6223; Buxbaum, Joseph/0000-0001-8898-8313; Panza, Francesco/0000-0002-7220-0656; Ikram, Mohammad Arfan/0000-0003-0372-8585; Seshadri, Sudha/0000-0001-6135-2622; Chouraki, Vincent/0000-0002-4698-1794; Bayer, Antony/0000-0002-7514-248X; Kamboh, M. Ilyas/0000-0002-3453-1438; Sanchez-Garcia, Florentino/0000-0003-0304-6023; Escott-Price, Valentina/0000-0003-1784-5483; Reisberg, Barry/0000-0002-9104-7423; duron, emmanuelle/0000-0001-6680-3613; Bullido, Maria/0000-0002-6477-1117; Smith, Albert/0000-0003-1942-5845; Caffarra, Paolo/0000-0003-2246-5223; Tsuang, Debby/0000-0002-4716-1894; Vandenberghe, Rik/0000-0001-6237-2502; Ibrahim-verbaas, Carla/0000-0002-4325-0857; Ciaramella, Antonio/0000-0001-9888-8156; Deloukas, Panos/0000-0001-9251-070X; Pastor, Pau/0000-0002-7493-8777; Tzourio, christophe/0000-0002-6517-2984; Fox, Nick/0000-0002-6660-657X; Holmans, Peter/0000-0003-0870-9412; Frank Garcia, Ana/0000-0003-3858-9116; Gudnason, Vilmundur/0000-0001-5696-0084; Kowall, Neil/0000-0002-6624-0213; Aspelund, Thor/0000-0002-7998-5433; Powell, John/0000-0001-6124-439X; Lambert, jean-charles/0000-0003-0829-7817; Gu, Wei/0000-0003-3951-6680; berr, Claudine/0000-0001-5254-7655; Bosso, Paola/0000-0002-1432-0078; Schott, Jonathan/0000-0003-2059-024X FU French National Foundation on Alzheimer's Disease and Related Disorders; Institut Pasteur de Lille; INSERM; FRC (Fondation pour la Recherche sur le Cerveau); Rotary; LABEX (Laboratory of Excellence Program Investment for the Future); DISTALZ grant (Development of Innovative Strategies for a Transdisciplinary Approach to Alzheimer's Disease); Alzheimer's Association (Chicago, Illinois); Wellcome Trust; MRC; Alzheimer's Research UK (ARUK); Welsh government; US National Institutes of Health, National Institute on Aging (NIH-NIA) [U01 AG032984, R01 AG033193]; US National Institutes of Health; Erasmus Medical Center; Erasmus University FX This work was made possible by the generous participation of the control subjects, the patients and their families. iSelect chips were funded by the French National Foundation on Alzheimer's Disease and Related Disorders. Data management involved the Centre National de Genotypage and was supported by the Institut Pasteur de Lille, INSERM, FRC (Fondation pour la Recherche sur le Cerveau) and Rotary. This work has been developed and supported by the LABEX (Laboratory of Excellence Program Investment for the Future) DISTALZ grant (Development of Innovative Strategies for a Transdisciplinary Approach to Alzheimer's Disease). The French National Foundation on Alzheimer's Disease and Related Disorders and the Alzheimer's Association (Chicago, Illinois) grant supported in-person meetings and communication for IGAP, and the Alzheimer's Association (Chicago, Illinois) grant provided some funds to each consortium for analyses.; GERAD was supported by the Wellcome Trust, the MRC, Alzheimer's Research UK (ARUK) and the Welsh government. ADGC and CHARGE were supported by the US National Institutes of Health, National Institute on Aging (NIH-NIA), including grants U01 AG032984 and R01 AG033193 (additional US National Institutes of Health grant numbers are listed in the Supplementary Note).; CHARGE was also supported by Erasmus Medical Center and Erasmus University. NR 52 TC 620 Z9 631 U1 29 U2 214 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1061-4036 EI 1546-1718 J9 NAT GENET JI Nature Genet. PD DEC PY 2013 VL 45 IS 12 BP 1452 EP U206 DI 10.1038/ng.2802 PG 9 WC Genetics & Heredity SC Genetics & Heredity GA 262EA UT WOS:000327715800010 PM 24162737 ER PT J AU Chan-on, W Nairismagi, ML Ong, CK Lim, WK Dima, S Pairojkul, C Lim, KH McPherson, JR Cutcutache, I Heng, HL Ooi, L Chung, A Chow, P Cheow, PC Lee, SY Choo, SP Tan, IBH Duda, D Nastase, A Myint, SS Wong, BH Gan, AN Rajasegaran, V Ng, CCY Nagarajan, S Jusakul, A Zhang, SL Vohra, P Yu, W Huang, DC Sithithaworn, P Yongvanit, P Wongkham, S Khuntikeo, N Bhudhisawasdi, V Popescu, I Rozen, SG Tan, P Teh, B AF Chan-on, Waraporn Nairismaegi, Maarja-Liisa Ong, Choon Kiat Lim, Weng Khong Dima, Simona Pairojkul, Chawalit Lim, Kiat Hon McPherson, John R. Cutcutache, Ioana Heng, Hong Lee Ooi, London Chung, Alexander Chow, Pierce Cheow, Peng Chung Lee, Ser Yee Choo, Su Pin Tan, Iain Bee Huat Duda, Dan Nastase, Anca Myint, Swe Swe Wong, Bernice Huimin Gan, Anna Rajasegaran, Vikneswari Ng, Cedric Chuan Young Nagarajan, Sanjanaa Jusakul, Apinya Zhang, Shenli Vohra, Priya Yu, Willie Huang, DaChuan Sithithaworn, Paiboon Yongvanit, Puangrat Wongkham, Sopit Khuntikeo, Narong Bhudhisawasdi, Vajaraphongsa Popescu, Irinel Rozen, Steven G. Tan, Patrick Teh, Bin Tean TI Exome sequencing identifies distinct mutational patterns in liver fluke-related and non-infection-related bile duct cancers SO NATURE GENETICS LA English DT Article ID OPISTHORCHIS-VIVERRINI; FREQUENT MUTATION; TUMOR-SUPPRESSOR; COPY NUMBERS; CHOLANGIOCARCINOMA; PATHOGENESIS; PHENOTYPE; PATHWAYS; PATIENT; ARID1A AB The impact of different carcinogenic exposures on the specific patterns of somatic mutation in human tumors remains unclear. To address this issue, we profiled 209 cholangiocarcinomas (CCAs) from Asia and Europe, including 108 cases caused by infection with the liver fluke Opisthorchis viverrini and 101 cases caused by non-O. viverrini-related etiologies. Whole-exome sequencing (n = 15) and prevalence screening (n = 194) identified recurrent somatic mutations in BAP1 and ARID1A, neither of which, to our knowledge, has previously been reported to be mutated in CCA. Comparisons between intrahepatic O. viverrini-related and non-O. viverrini-related CCAs demonstrated statistically significant differences in mutation patterns: BAP1, IDH1 and IDH2 were more frequently mutated in non-O. viverrini CCAs, whereas TP53 mutations showed the reciprocal pattern. Functional studies demonstrated tumor suppressive functions for BAP1 and ARID1A, establishing the role of chromatin modulators in CCA pathogenesis. These findings indicate that different causative etiologies may induce distinct somatic alterations, even within the same tumor type. C1 [Chan-on, Waraporn; Nairismaegi, Maarja-Liisa; Ong, Choon Kiat; Lim, Weng Khong; Heng, Hong Lee; Myint, Swe Swe; Wong, Bernice Huimin; Gan, Anna; Rajasegaran, Vikneswari; Ng, Cedric Chuan Young; Nagarajan, Sanjanaa; Jusakul, Apinya; Yu, Willie; Huang, DaChuan; Teh, Bin Tean] Natl Canc Ctr Singapore, Div Med Sci, Lab Canc Epigenome, Singapore, Singapore. [Chan-on, Waraporn; Nairismaegi, Maarja-Liisa; Ong, Choon Kiat; Lim, Weng Khong; Heng, Hong Lee; Myint, Swe Swe; Wong, Bernice Huimin; Gan, Anna; Rajasegaran, Vikneswari; Ng, Cedric Chuan Young; Nagarajan, Sanjanaa; Jusakul, Apinya; Zhang, Shenli; Vohra, Priya; Yu, Willie; Huang, DaChuan; Tan, Patrick; Teh, Bin Tean] Duke Natl Univ Singapore, Grad Sch Med, Div Canc & Stem Cell Biol, Singapore, Singapore. [Chan-on, Waraporn; Pairojkul, Chawalit; Sithithaworn, Paiboon; Yongvanit, Puangrat; Wongkham, Sopit; Khuntikeo, Narong; Bhudhisawasdi, Vajaraphongsa] Khon Kaen Univ, Fac Med, Liver Fluke & Cholangiocarcinoma Res Ctr, Khon Kaen, Thailand. [Dima, Simona; Nastase, Anca; Popescu, Irinel] Fundeni Clin Inst, Ctr Digest Dis & Liver Transplantat, Bucharest, Romania. [Lim, Kiat Hon] Singapore Gen Hosp, Dept Pathol, Singapore, Singapore. [McPherson, John R.; Cutcutache, Ioana; Rozen, Steven G.] Duke Natl Univ Singapore, Grad Sch Med, Div Neurosci & Behav Disorders, Singapore, Singapore. [Ooi, London; Chung, Alexander; Chow, Pierce; Cheow, Peng Chung; Lee, Ser Yee] Singapore Gen Hosp, Dept Gen Surg, Singapore, Singapore. [Choo, Su Pin; Tan, Iain Bee Huat] Natl Canc Ctr Singapore, Dept Med Oncol, Singapore, Singapore. [Duda, Dan] Massachusetts Gen Hosp, Dept Radiat Oncol, Edwin L Steele Lab Tumor Biol, Boston, MA 02114 USA. [Duda, Dan] Harvard Univ, Sch Med, Boston, MA USA. [Yu, Willie] Natl Univ Singapore, Grad Sch Integrat Sci & Engn, Singapore 117548, Singapore. [Tan, Patrick] Genome Inst Singapore, Singapore, Singapore. [Tan, Patrick; Teh, Bin Tean] Natl Univ Singapore, Canc Sci Inst Singapore, Singapore 117548, Singapore. RP Teh, B (reprint author), Natl Canc Ctr Singapore, Div Med Sci, Lab Canc Epigenome, Singapore, Singapore. EM vajara_b@kku.ac.th; irinel.popescu@icfundeni.ro; steve.rozen@duke-nus.edu.sg; gmstanp@duke-nus.edu.sg; teh.bin.tean@singhealth.com.sg RI POPESCU, IRINEL/B-3048-2008; Lee, Ser Yee/H-3116-2013; Dima, Simona Olimpia/B-8822-2017; OI Lee, Ser Yee/0000-0001-9119-7408; Rozen, Steven G./0000-0002-4288-0056; Ong, Choon Kiat/0000-0001-6402-4288 FU Singapore National Medical Research Council [NMRC/STAR/0006/2009]; Singapore Millennium Foundation; Lee Foundation; Singapore National Cancer Centre Research Fund; Duke-National University of Singapore Graduate Medical School; Cancer Science Institute, Singapore; Verdant Foundation, Hong Kong; Executive Agency for Higher Education, Research and Development, Romania; National Genetic Engineering and Biotechnology Center; National Science and Technology Development Agency, Thailand; National University of Singapore Graduate School for Integrative Sciences and Engineering scholarship FX We thank B. Haaland for reviewing all statistical tests performed in this study and the Duke-National University of Singapore Genome Biology Facility for performing whole-exome sequencing and methylation assays. We thank D. Jefferson (New England Medical Center, Tufts University) for the H69 cell line. We thank B. Sripa (Khon Kean University) for the M139 cell line. This work was supported in part by funding from the Singapore National Medical Research Council (NMRC/STAR/0006/2009), the Singapore Millennium Foundation, the Lee Foundation, the Singapore National Cancer Centre Research Fund, the Duke-National University of Singapore Graduate Medical School, the Cancer Science Institute, Singapore, the Verdant Foundation, Hong Kong, Innovation Funding from the Executive Agency for Higher Education, Research and Development, Romania, a Research Team Strengthening Grant, the National Genetic Engineering and Biotechnology Center and the National Science and Technology Development Agency, Thailand. W.Y. is the recipient of a National University of Singapore Graduate School for Integrative Sciences and Engineering scholarship. NR 39 TC 111 Z9 114 U1 3 U2 42 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1061-4036 EI 1546-1718 J9 NAT GENET JI Nature Genet. PD DEC PY 2013 VL 45 IS 12 BP 1474 EP U100 DI 10.1038/ng.2806 PG 7 WC Genetics & Heredity SC Genetics & Heredity GA 262EA UT WOS:000327715800014 PM 24185513 ER PT J AU Francis, JM Kiezun, A Ramos, AH Serra, S Pedamallu, CS Qian, ZR Banck, MS Kanwar, R Kulkarni, AA Karpathakis, A Manzo, V Contractor, T Philips, J Nickerson, E Pho, N Hooshmand, SM Brais, LK Lawrence, MS Pugh, T McKenna, A Sivachenko, A Cibulskis, K Carter, SL Ojesina, AI Freeman, S Jones, RT Voet, D Saksena, G Auclair, D Onofrio, R Shefler, E Sougnez, C Grimsby, J Green, L Lennon, N Meyer, T Caplin, M Chung, DC Beutler, AS Ogino, S Thirlwell, C Shivdasani, R Asa, SL Harris, CR Getz, G Kulke, M Meyerson, M AF Francis, Joshua M. Kiezun, Adam Ramos, Alex H. Serra, Stefano Pedamallu, Chandra Sekhar Qian, Zhi Rong Banck, Michaela S. Kanwar, Rahul Kulkarni, Amit A. Karpathakis, Anna Manzo, Veronica Contractor, Tanupriya Philips, Juliet Nickerson, Elizabeth Nam Pho Hooshmand, Susanne M. Brais, Lauren K. Lawrence, Michael S. Pugh, Trevor McKenna, Aaron Sivachenko, Andrey Cibulskis, Kristian Carter, Scott L. Ojesina, Akinyemi I. Freeman, Samuel Jones, Robert T. Voet, Douglas Saksena, Gordon Auclair, Daniel Onofrio, Robert Shefler, Erica Sougnez, Carrie Grimsby, Jonna Green, Lisa Lennon, Niall Meyer, Tim Caplin, Martyn Chung, Daniel C. Beutler, Andreas S. Ogino, Shuji Thirlwell, Christina Shivdasani, Ramesh Asa, Sylvia L. Harris, Chris R. Getz, Gad Kulke, Matthew Meyerson, Matthew TI Somatic mutation of CDKN1B in small intestine neuroendocrine tumors SO NATURE GENETICS LA English DT Article ID CELL LUNG-CANCER; DEPENDENT KINASE INHIBITOR; BREAST-CANCER; CARCINOID-TUMORS; PROSTATE-CANCER; FREQUENT LOSS; MICE LACKING; P27(KIP1); GENES; SUPPRESSOR AB The diagnosed incidence of small intestine neuroendocrine tumors (SI-NETs) is increasing, and the underlying genomic mechanisms have not yet been defined. Using exome- and genome-sequence analysis of SI-NETs, we identified recurrent somatic mutations and deletions in CDKN1B, the cyclin-dependent kinase inhibitor gene, which encodes p27. We observed frameshift mutations of CDKN1B in 14 of 180 SI-NETs, and we detected hemizygous deletions encompassing CDKN1B in 7 out of 50 SI-NETs, nominating p27 as a tumor suppressor and implicating cell cycle dysregulation in the etiology of SI-NETs. C1 [Francis, Joshua M.; Kiezun, Adam; Ramos, Alex H.; Pedamallu, Chandra Sekhar; Nickerson, Elizabeth; Nam Pho; Lawrence, Michael S.; Pugh, Trevor; McKenna, Aaron; Sivachenko, Andrey; Cibulskis, Kristian; Carter, Scott L.; Ojesina, Akinyemi I.; Voet, Douglas; Saksena, Gordon; Auclair, Daniel; Onofrio, Robert; Shefler, Erica; Sougnez, Carrie; Grimsby, Jonna; Green, Lisa; Lennon, Niall; Getz, Gad; Meyerson, Matthew] Broad Inst, Cambridge, MA USA. [Francis, Joshua M.; Ramos, Alex H.; Pedamallu, Chandra Sekhar; Qian, Zhi Rong; Manzo, Veronica; Philips, Juliet; Hooshmand, Susanne M.; Brais, Lauren K.; Ojesina, Akinyemi I.; Freeman, Samuel; Ogino, Shuji; Shivdasani, Ramesh; Kulke, Matthew; Meyerson, Matthew] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Serra, Stefano; Asa, Sylvia L.] Univ Hlth Network, Dept Pathol, Toronto, ON, Canada. [Banck, Michaela S.; Kanwar, Rahul; Kulkarni, Amit A.; Beutler, Andreas S.] Mayo Clin, Div Med Oncol, Rochester, MN USA. [Banck, Michaela S.; Beutler, Andreas S.] Mayo Clin, Ctr Canc, Rochester, MN USA. [Karpathakis, Anna; Meyer, Tim; Thirlwell, Christina] UCL, Inst Canc, London, England. [Karpathakis, Anna; Meyer, Tim; Caplin, Martyn; Thirlwell, Christina] Royal Free Hosp, NET Unit, London NW3 2QG, England. [Contractor, Tanupriya; Harris, Chris R.] Raymond & Beverly Sackler Fdn, New Brunswick, NJ USA. [Jones, Robert T.; Meyerson, Matthew] Dana Farber Canc Inst, Ctr Canc Genome Discovery, Boston, MA 02115 USA. [Chung, Daniel C.] Massachusetts Gen Hosp, Gastrointestinal Unit, Boston, MA 02114 USA. [Chung, Daniel C.] Massachusetts Gen Hosp, Ctr Canc, Boston, MA USA. [Ogino, Shuji] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. [Ogino, Shuji] Harvard Univ, Sch Med, Boston, MA USA. [Ogino, Shuji] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. [Asa, Sylvia L.] Univ Toronto, Ontario Canc Inst, Toronto, ON M5S 1A1, Canada. [Harris, Chris R.] Univ Med & Dent New Jersey, Canc Inst New Jersey, New Brunswick, NJ USA. [Harris, Chris R.] Univ Med & Dent New Jersey, Dept Pediat, New Brunswick, NJ USA. RP Kulke, M (reprint author), Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. EM matthew_kulke@dfci.harvard.edu; matthew_meyerson@dfci.harvard.edu RI Kanwar, Rahul/K-1954-2015; OI Kanwar, Rahul/0000-0002-4575-8654; Ojesina, Akinyemi/0000-0003-0755-3639; serra, stefano/0000-0002-3258-2637 FU Caring for Carcinoid Foundation; Raymond and Beverly Sackler Foundation for the Arts and Sciences; Cancer Research UK FX This work was supported by grants from the Caring for Carcinoid Foundation (S. L. A. and M. M.), the Raymond and Beverly Sackler Foundation for the Arts and Sciences (C. T., A. Karpathakis, S. L. A. and M. M.) and Cancer Research UK (C. T. and A. Karpathakis). NR 51 TC 70 Z9 74 U1 1 U2 11 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1061-4036 EI 1546-1718 J9 NAT GENET JI Nature Genet. PD DEC PY 2013 VL 45 IS 12 BP 1483 EP U110 DI 10.1038/ng.2821 PG 5 WC Genetics & Heredity SC Genetics & Heredity GA 262EA UT WOS:000327715800016 PM 24185511 ER PT J AU Liu, H Li, WJ Rose, ME Pascoe, JL Miller, TM Ahmad, M Poloyac, SM Hickey, RW Graham, SH AF Liu, Hao Li, Wenjin Rose, Marie E. Pascoe, Jordan L. Miller, Tricia M. Ahmad, Muzamil Poloyac, Samuel M. Hickey, Robert W. Graham, Steven H. TI Prostaglandin D-2 toxicity in primary neurons is mediated through its bioactive cyclopentenone metabolites SO NEUROTOXICOLOGY LA English DT Article DE Cell death; Cyclopentenone prostaglandins; DP receptors; Primary neuron; Prostaglandin D-2; Ubiquitinated protein ID DP1 RECEPTOR; UBIQUITINATED PROTEINS; GENE-EXPRESSION; D SYNTHASE; RAT-BRAIN; APOPTOSIS; ISCHEMIA; CELLS; J2; CYCLOOXYGENASE-2 AB Prostaglandin D-2 (PGD(2)) is the most abundant prostaglandin in brain but its effect on neuronal cell death is complex and not completely understood. PGD(2) may modulate neuronal cell death via activation of DP receptors or its metabolism to the cyclopentenone prostaglandins (CyPGs) PGJ(2), Delta(12)-PGJ(2) and 15-deoxy-Delta(12,14)-PGJ(2), inducing cell death independently of prostaglandin receptors. This study aims to elucidate the effect of PGD(2) on neuronal cell death and its underlying mechanisms. PGD(2) dose-dependently induced cell death in rat primary neuron-enriched cultures in concentrations of >= 10 mu M, and this effect was not reversed by treatment with either DP1 or DP2 receptor antagonists. Antioxidants N-acetylcysteine (NAC) and glutathione which contain sulfhydryl groups that can bind to CyPGs, but not ascorbate or tocopherol, attenuated PGD(2)-induced cell death. Conversion of PGD(2) to CyPGs was detected in neuronal culture medium; treatment with these CyPG metabolites alone exhibited effects similar to those of PGD(2), including apoptotic neuronal cell death and accumulation of ubiquitinated proteins. Disruption of lipocalin-type prostaglandin D synthase (L-PGDS) protected neurons against hypoxia. These results support the hypothesis that PGD(2) elicits its cytotoxic effects through its bioactive CyPG metabolites rather than DP receptor activation in primary neuronal culture. Published by Elsevier Inc. C1 [Liu, Hao; Li, Wenjin; Rose, Marie E.; Pascoe, Jordan L.; Ahmad, Muzamil; Graham, Steven H.] VA Pittsburgh Healthcare Syst, Geriatr Res Educ & Clin Ctr, Pittsburgh, PA 15205 USA. [Liu, Hao; Li, Wenjin; Rose, Marie E.; Pascoe, Jordan L.; Ahmad, Muzamil; Graham, Steven H.] Univ Pittsburgh, Sch Med, Dept Neurol, Pittsburgh, PA 15213 USA. [Miller, Tricia M.; Poloyac, Samuel M.] Univ Pittsburgh, Sch Pharm, Dept Pharmaceut Sci, Pittsburgh, PA 15261 USA. [Hickey, Robert W.] Univ Pittsburgh, Sch Med, Dept Pediat Emergency Med, Pittsburgh, PA 15224 USA. RP Graham, SH (reprint author), VA Pittsburgh Healthcare Syst, Geriatr Res Educ & Clin Ctr 00 GR H, Highland Dr, Pittsburgh, PA 15205 USA. EM sgra@pitt.edu FU National Institutes of Health/National Institute of Neurological Disorders and Stroke [R01NS37459]; Veteran's Administration Merit Review program FX This work was supported by National Institutes of Health/National Institute of Neurological Disorders and Stroke [grant number R01NS37459] and the Veteran's Administration Merit Review program [S.H.G.]. NR 45 TC 11 Z9 13 U1 0 U2 2 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 DEC PY 2013 VL 39 BP 35 EP 44 DI 10.1016/j.neuro.2013.08.001 PG 10 WC Neurosciences; Pharmacology & Pharmacy; Toxicology SC Neurosciences & Neurology; Pharmacology & Pharmacy; Toxicology GA 270GK UT WOS:000328306700006 PM 23973622 ER PT J AU Eum, KD Wang, FT Schwartz, J Hersh, CP Kelsey, K Wright, RO Spiro, A Sparrow, D Hu, H Weisskopf, MG AF Eum, Ki-Do Wang, Florence T. Schwartz, Joel Hersh, Craig P. Kelsey, Karl Wright, Robert O. Spiro, Avron Sparrow, David Hu, Howard Weisskopf, Marc G. TI Modifying roles of glutathione S-transferase polymorphisms on the association between cumulative lead exposure and cognitive function SO NEUROTOXICOLOGY LA English DT Article DE Lead; Glutathione S-transferase; Cognitive function; Environmental exposure; Gene-environment interaction ID X-RAY-FLUORESCENCE; MINI-MENTAL-STATE; ACID-DEHYDRATASE POLYMORPHISM; BONE LEAD; ELDERLY-MEN; BLOOD LEAD; FOLLOW-UP; PARKINSONS-DISEASE; ALZHEIMER-DISEASE; SUPERGENE FAMILY AB Background: Glutathione-S-transferase gene (GST) polymorphisms can result in variable ability of these enzymes to remove electrophilic substrates. We investigated whether the GSTP1 Vail 05 and GSTM1 deletion polymorphisms modify the lead-cognitive function association. Methods: We used repeated measures analysis to compare the association between cumulative lead biomarkers bone lead measured using K-shell X-Ray Fluorescence and Mini-Mental State Exam (MMSE) score by GST variants, adjusted for covariates, among Normative Aging Study participants, a Boston-based prospective cohort of men. We had complete data for 698 men (providing 1292 observations) for GSTM1 analyses and 595 men (providing 1142 observations) for GSTP1 analyses. Results: A 15 mu g/g higher tibia lead concentration (interquartile range of tibia lead) was associated with a 0.24 point decrement in MMSE score among GSTP1 Va1105 variant carriers, which was significantly stronger than the association among men with only wild-type alleles (p = 0.01). The association among GSTP1 Va1105 carriers was comparable to that of 3 years of age in baseline MMSE scores. The association between tibia lead and MMSE score appeared progressively steeper in participants with increasingly more GSTP1 Va1105 alleles. A modest association between tibia lead and lower MMSE score was seen among participants with the GSTM1 deletion polymorphism. Neither of the glutathione S-transferase variants was independently associated with cognitive function, nor with lead biomarker measures. The results pertaining to patella lead were similar to those observed for tibia lead. Conclusion: Our results suggest that the GSTP1 Vail 05 polymorphism confers excess susceptibility to the cognitive effects of cumulative lead exposure. (C) 2013 Elsevier Inc. All rights reserved. C1 [Eum, Ki-Do; Schwartz, Joel; Weisskopf, Marc G.] Harvard Univ, Sch Publ Hlth, Dept Environm Hlth, Boston, MA 02115 USA. [Schwartz, Joel; Weisskopf, Marc G.] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. [Hersh, Craig P.; Weisskopf, Marc G.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Channing Div Network Med, Boston, MA 02115 USA. [Kelsey, Karl] Brown Univ, Providence, RI 02912 USA. [Kelsey, Karl] Brown Univ, Ctr Environm Hlth & Technol, Providence, RI 02912 USA. [Wright, Robert O.] Mt Sinai Sch Med, New York, NY USA. [Spiro, Avron; Sparrow, David] VA Boston Healthcare Syst, Boston, MA USA. [Spiro, Avron; Sparrow, David] Boston Univ, Sch Publ Hlth, Boston, MA USA. [Spiro, Avron; Sparrow, David] Boston Univ, Sch Med, Boston, MA 02118 USA. [Hu, Howard] Univ Toronto, Dalin Lana Sch Publ Hlth, Toronto, ON M5S 1A1, Canada. RP Weisskopf, MG (reprint author), Harvard Univ, Sch Publ Hlth, Landmark Ctr, Dept Environm Hlth EOME, 401 Pk Dr,POB 15697, Boston, MA 02115 USA. EM mweissko@hsph.harvard.edu OI Hu, Howard/0000-0002-3676-2707 FU National Institutes of Health [5-P42-ES05947, R01-ES05257]; National Institute for Occupational Safety and Health (NIOSH) from National Institutes of Health [T42/CCT110421, T32 ES007155]; US Department of Veterans Affairs, the National Institutes of Health [R01-AA08941, R01-AG13006, R01-AG14345, R01-AG18436]; US Department of Agriculture, Agricultural Research Service [53-1(06-510)]; VA Clinical Science Research and Development Service; Cooperative Studies Program/ERIC; US Department of Veterans Affairs; VA Merit Review and a VA Research Career Scientist award to D. Sparrow FX This work was supported by grants 5-P42-ES05947, R01-ES05257, and ES-00002 from the National Institutes of Health. F. Wang was partially supported by National Institute for Occupational Safety and Health (NIOSH) Grant T42/CCT110421 and T32 ES007155 from the National Institutes of Health.; The Cognition and Health in Aging Men Project (CHAMP) has been supported by the Research Services of the US Department of Veterans Affairs, the National Institutes of Health (grants R01-AA08941, R01-AG13006, R01-AG14345, R01-AG18436), the US Department of Agriculture, Agricultural Research Service (contract 53-1(06-510), and VA Merit Review and Research Career Scientist awards from VA Clinical Science Research and Development Service.; The VA Normative Aging Study is supported by the Cooperative Studies Program/ERIC, US Department of Veterans Affairs, and is a research component of the Massachusetts Veterans Epidemiology Research and Information Center (MAVERIC). This research was also supported by a VA Merit Review and a VA Research Career Scientist award to D. Sparrow. NR 63 TC 4 Z9 6 U1 1 U2 9 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 DEC PY 2013 VL 39 BP 65 EP 71 DI 10.1016/j.neuro.2013.08.002 PG 7 WC Neurosciences; Pharmacology & Pharmacy; Toxicology SC Neurosciences & Neurology; Pharmacology & Pharmacy; Toxicology GA 270GK UT WOS:000328306700009 PM 23958642 ER PT J AU Heist, R Azzoli, CG AF Heist, Rebecca Azzoli, Christopher G. TI Adjuvant Therapy for a 3.9-cm Adenocarcinoma of the Lung SO ONCOLOGIST LA English DT Editorial Material ID VINORELBINE PLUS CISPLATIN; PHASE-III TRIAL; OPEN-LABEL; CANCER; CHEMOTHERAPY; GEFITINIB C1 [Heist, Rebecca; Azzoli, Christopher G.] Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA. RP Heist, R (reprint author), Massachusetts Gen Hosp, Ctr Canc, 55 Fruit St, Boston, MA 02114 USA. EM rheist@partners.org; cazzoli@partners.org NR 20 TC 0 Z9 0 U1 0 U2 1 PU ALPHAMED PRESS PI DURHAM PA 318 BLACKWELL ST, STE 260, DURHAM, NC 27701-2884 USA SN 1083-7159 EI 1549-490X J9 ONCOLOGIST JI Oncologist PD DEC PY 2013 VL 18 IS 12 BP 1258 EP 1261 DI 10.1634/theoncologist.2013-0297 PG 4 WC Oncology SC Oncology GA 269PT UT WOS:000328254900005 PM 24277772 ER PT J AU McCleary, NJ Hurria, A Meyerhardt, J AF McCleary, Nadine J. Hurria, Arti Meyerhardt, Jeffrey TI Comprehensive Geriatric Assessment and Adjustment of Cancer Treatment Reply SO ONCOLOGIST LA English DT Letter C1 [McCleary, Nadine J.; Meyerhardt, Jeffrey] Dana Farber Canc Inst, Dept Med Oncol, Gastrointestinal Canc Ctr, Boston, MA 02215 USA. [Hurria, Arti] City Hope Natl Med Ctr, Canc & Aging Res Program, Dept Med Oncol, Los Angeles, CA USA. RP McCleary, NJ (reprint author), Dana Farber Canc Inst, Dept Med Oncol, 450 Brookline Ave, Boston, MA 02215 USA. EM Nj_mccleary@dfci.harvard.edu NR 2 TC 0 Z9 0 U1 0 U2 0 PU ALPHAMED PRESS PI DURHAM PA 318 BLACKWELL ST, STE 260, DURHAM, NC 27701-2884 USA SN 1083-7159 EI 1549-490X J9 ONCOLOGIST JI Oncologist PD DEC PY 2013 VL 18 IS 12 BP 1331 EP 1331 DI 10.1634/theoncologist.2013-0303 PG 1 WC Oncology SC Oncology GA 269PT UT WOS:000328254900015 PM 24336119 ER PT J AU Attenberger, UI Quick, HH Guimaraes, A Catalano, O Morelli, JN Schoenberg, SO AF Attenberger, U. I. Quick, H. H. Guimaraes, A. Catalano, O. Morelli, J. N. Schoenberg, S. O. TI Value of new MR techniques in MR-PET SO RADIOLOGE LA German DT Review DE Morphological information; Functional imaging; Attenuation correction; Metal artefacts; Motion artefacts ID COMPLETE DISTORTION CORRECTION; WHOLE-BODY PET/MRI; ATTENUATION CORRECTION; CLINICAL-EXPERIENCE; SPATIAL MODULATION; MOTION CORRECTION; SURFACE COILS; IMAGES; QUANTIFICATION; MAGNETIZATION AB The unparalleled soft tissue contrast of magnetic resonance imaging (MRI) and the functional information obtainable with 18-F fluorodeoxyglucose positron emission tomography (FDG-PET) render MR-PET well-suited for oncological and psychiatric imaging. The lack of ionizing radiation with MRI also makes MR-PET a promising modality for oncology patients requiring frequent follow-up and pediatric patients. Lessons learned with PET computed tomography (CT) over the last few years do not directly translate to MR-PET. For example, in PET-CT the Hounsfield units derived from CT are used for attenuation correction (AC). As 511 keV photons emitted in PET examinations are attenuated by the patient's body CT data are converted directly to linear attenuation coefficients (LAC); however, proton density measured by MRI is not directly related to the radiodensity or LACs of biological tissue. Thus, direct conversion to LAC data is not possible making AC more challenging in simultaneous MRI-PET scanning. In addition to these constraints simultaneous MRI-PET acquisitions also improve on some solutions to well-known challenges of hybrid imaging techniques, such as limitations in motion correction. This article reports on initial clinical experiences with simultaneously acquired MRI-PET data, focusing on the potential benefits and limitations of MRI with respect to motion correction as well as metal and attenuation correction artefacts. C1 [Attenberger, U. I.; Schoenberg, S. O.] Heidelberg Univ, Med Fak Mannheim, Univ Med Mannheim, Inst Klin Radiol & Nukl Med, D-68167 Mannheim, Germany. [Quick, H. H.] Univ Erlangen Nurnberg, Inst Med Phys, D-91054 Erlangen, Germany. [Guimaraes, A.] Massachusetts Gen Hosp, Martinos Ctr Biomed Imaging, Dept Radiol, Charlestown, MA USA. [Catalano, O.] Univ Naples Federico II, Naples, Italy. [Morelli, J. N.] Johns Hopkins Univ Hosp, Russell H Morgan Dept Radiol & Radiol Sci, Baltimore, MD 21287 USA. RP Attenberger, UI (reprint author), Heidelberg Univ, Med Fak Mannheim, Univ Med Mannheim, Inst Klin Radiol & Nukl Med, Theodor Kutzer Ufer 1-3, D-68167 Mannheim, Germany. EM ulrike.attenberger@medma.uni-heidelberg.de NR 40 TC 0 Z9 0 U1 1 U2 6 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0033-832X EI 1432-2102 J9 RADIOLOGE JI Radiologe PD DEC PY 2013 VL 53 IS 12 BP 1118 EP 1124 DI 10.1007/s00117-013-2559-5 PG 7 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 270ZJ UT WOS:000328358400010 PM 24221697 ER PT J AU Dimitrov, DH Lee, S Yantis, J Valdez, C Paredes, RM Braida, N Velligan, D Walss-Bass, C AF Dimitrov, Dimitre H. Lee, Shuko Yantis, Jesse Valdez, Celina Paredes, R. Madelaine Braida, Nicole Velligan, Dawn Walss-Bass, Consuelo TI Differential correlations between inflammatory cytokines and psychopathology in veterans with schizophrenia: Potential role for IL-17 pathway SO SCHIZOPHRENIA RESEARCH LA English DT Article DE Schizophrenia; Veterans; Inflammation; Cytokines; Psychosis ID AUTOIMMUNE-DISEASES; BIPOLAR DISORDER; SERUM-LEVELS; BRAIN; CELLS; INTERLEUKIN-6; HYPOTHESIS; SYSTEM; BLOOD; METAANALYSIS AB Pro-inflammatory cytokines have been consistently reported to be elevated in schizophrenia patients. However, it is not known whether cytokines influence the presentation of psychotic symptoms. To address this issue, we evaluated the relationship between levels of inflammatory molecules and psychopathological parameters in patients with schizophrenia. We hypothesized that severity of symptoms would correlate with increased levels of inflammatory cytokines. Serum samples from 47 veterans with a diagnosis of schizophrenia and 20 healthy controls were tested for levels of 33 cytokines/chemokines involved in regulation of immune /inflammatory reactions using a Millipore multiplex bead array in a Luminex 100 system. We found significantly increased levels of GRO, MCP-1, MDC, and 5CD40L, and significantly decreased levels of IFNI-gamma, IL-2, IL-12p70, and IL-17, in schizophrenia patients compared to controls. In addition, we observed positive correlations between levels of cytokines and the Positive and Negative Symptoms Scale (PANSS) scores in subjects with schizophrenia for GCSE, IL-1 beta, IL1ra, IL-3, IL-6, IL-9, IL-10, sCD40L and TNF-beta. Pathway analyses showed these cytokines to be part of the IL17 pathway. Using principal component analyses, we found the factor that included these cylokines and IL-17 to be associated with positive, general and total PANSS scores. These results suggest that alterations in this pathway may play a role in development of psychotic symptoms in schizophrenia. Published by Elsevier B.V. C1 [Dimitrov, Dimitre H.; Lee, Shuko; Yantis, Jesse; Braida, Nicole] South Texas Vet Hlth Care Syst, San Antonio, TX 78229 USA. [Dimitrov, Dimitre H.; Valdez, Celina; Paredes, R. Madelaine; Braida, Nicole; Velligan, Dawn; Walss-Bass, Consuelo] Univ Texas Hlth Sci Ctr San Antonio, Dept Psychiat, San Antonio, TX 78229 USA. RP Dimitrov, DH (reprint author), South Texas Vet Hlth Care Syst, 7400 Merton Minter Blvd, San Antonio, TX 78229 USA. EM Dimitre.dimitrov@va.gov NR 39 TC 25 Z9 25 U1 6 U2 15 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0920-9964 EI 1573-2509 J9 SCHIZOPHR RES JI Schizophr. Res. PD DEC PY 2013 VL 151 IS 1-3 BP 29 EP 35 DI 10.1016/j.schres.2013.10.019 PG 7 WC Psychiatry SC Psychiatry GA 263GL UT WOS:000327795300004 PM 24210870 ER PT J AU Vu, MAT Thermenos, HW Terry, DP Wolfe, DJ Voglmaier, MM Niznikiewicz, MA McCarley, RW Seidman, LJ Dickey, CC AF Vu, Mai-Anh T. Thermenos, Heidi W. Terry, Douglas P. Wolfe, David J. Voglmaier, Martina M. Niznikiewicz, Margaret A. McCarley, Robert W. Seidman, Larry J. Dickey, Chandlee C. TI Working memory in schizotypal personality disorder: fMRI activation and deactivation differences SO SCHIZOPHRENIA RESEARCH LA English DT Article DE Schizotypal personality disorder; Working memory; Functional magnetic resonance imaging (fMRI); 2-Back task; Cognition; Schizophrenia ID SCHIZOPHRENIA SPECTRUM DISORDERS; THALAMIC MEDIODORSAL NUCLEUS; SUPERIOR TEMPORAL GYRUS; DEFAULT MODE NETWORK; PREFRONTAL CORTEX; NEUROPSYCHOLOGICAL PERFORMANCE; 1ST-DEGREE RELATIVES; 1ST-EPISODE SCHIZOPHRENIA; NEUROCOGNITIVE DEFICITS; PSYCHIATRIC-DISORDERS AB Background: Schizotypal personality disorder (SPD) is considered a schizophrenia spectrum disorder, sharing with schizophrenia cognitive, neuropsychological, epidemiological, and biological characteristics. Working memory may be one area of shared deficit, although to date, this is only the second study to investigate working memory in SPD using fMRI. Methods: In a block design fMRI study, fifteen antipsychotic-naive SPD and sixteen healthy control subjects performed blocks of a 2back visual working memory task and 0back continuous performance task while undergoing whole brain fMRI at 3 T. Whole brain analyses were performed for the 0back > rest (fixation baseline) and the 2back > 0back contrasts (isolating the working memory component from the visual perception and attention component). Parameter estimates were extracted to determine whether observed differences were due to task induced activation and or deactivation. Results: Activation differences emerged between the two groups, without differences in task performance. In the 0back task, SPD showed decreased task-induced activation of the left postcentral gyrus. In the 2back > 0back contrast, HC showed greater task-induced activation of the left posterior cingulate gyrus, superior temporal gyms, insula, and middle frontal gyrus. These differences were due to SPD subjects decreased task-induced activation in the left posterior cingulate gyrus, and task-induced deactivation in the remaining regions. Conclusions: These findings suggest that compared to HC subjects, individuals with SPD may achieve comparable working memory performance. However, differences emerge at the level of functional neural activation, attributable to different task-induced activation and deactivation patterns. Such differential recruitment of neural resources may be beneficial, contributing to SPD subjects' ability to perform these tasks comparably to HC subjects. (C) 2013 Elsevier B.V. All rights reserved, C1 [Vu, Mai-Anh T.; Terry, Douglas P.; Dickey, Chandlee C.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Psychiat Neuroimaging Lab,Dept Psychiat, Boston, MA 02115 USA. [Thermenos, Heidi W.; Seidman, Larry J.] Harvard Univ, Beth Israel Deaconess Med Ctr, Massachusetts Mental Hlth Ctr, Dept Psychiat,Publ Psychiat Div,Med Sch, Boston, MA 02215 USA. [Wolfe, David J.; Dickey, Chandlee C.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Psychiat, Boston, MA 02115 USA. [Wolfe, David J.; Voglmaier, Martina M.; Niznikiewicz, Margaret A.; McCarley, Robert W.; Dickey, Chandlee C.] Harvard Univ, Sch Med, Dept Psychiat, Lab Neurosci,VA Boston Healthcare Syst, Boston, MA 02115 USA. [Niznikiewicz, Margaret A.; McCarley, Robert W.; Dickey, Chandlee C.] Harvard Univ, Sch Med, Dept Psychiat, VA Boston Healthcare Syst, Boston, MA 02115 USA. [Seidman, Larry J.] Harvard Univ, Sch Med, Dept Psychiat, Massachusetts Gen Hosp, Boston, MA 02115 USA. RP Dickey, CC (reprint author), Harvard Univ, Sch Med, 940 Belmont St, Brockton, MA 02301 USA. EM chandlee_dickey@hms.harvard.edu RI McCarley, Robert/N-5562-2014 OI McCarley, Robert/0000-0001-5705-7495 FU VA Boston Healthcare System; VA Advanced Career Development Award; Ethel Dupont-Warren Research Fellowship; Harvard Medical School; NIMH from National Institute of Mental Health [R21MH077979, R01N4H52807] FX The project described was supported by the VA Boston Healthcare System, VA Advanced Career Development Award (CCD), Ethel Dupont-Warren Research Fellowship, Harvard Medical School (DJW), and NIMH Award Numbers R21MH077979 (CCD) and R01N4H52807 (RWM) from the National Institute of Mental Health. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institute of Mental Health, the National Institutes of Health, or the VA. NR 114 TC 5 Z9 5 U1 0 U2 10 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0920-9964 EI 1573-2509 J9 SCHIZOPHR RES JI Schizophr. Res. PD DEC PY 2013 VL 151 IS 1-3 BP 113 EP 123 DI 10.1016/j.schres.2013.09.013 PG 11 WC Psychiatry SC Psychiatry GA 263GL UT WOS:000327795300016 PM 24161536 ER PT J AU Francis, AN Seidman, LJ Tandon, N Shenton, ME Thermenos, HW Mesholam-Gately, RI van Elst, LT Tuschen-Caffier, B DeLisi, LE Keshavan, MS AF Francis, Alan N. Seidman, Larry J. Tandon, Neeraj Shenton, Martha E. Thermenos, Heidi W. Mesholam-Gately, Raquelle I. van Elst, Ludger T. Tuschen-Caffier, Brunna DeLisi, Lynn E. Keshavan, Matcheri S. TI Reduced subicular subdivisions of the hippocampal formation and verbal declarative memory impairments in young relatives at risk for schizophrenia SO SCHIZOPHRENIA RESEARCH LA English DT Article ID FAMILIAL RISK; BRAIN; SUBFIELDS; VOLUMES; ADULTS AB Introduction: Smaller hippocampal volumes similar to those found in schizophrenia (SZ) are frequently observed to a lesser extent in non-psychotic first-degree relatives of patients with the illness, compared to control subjects. In this study, subdivisions of the hippocampal formation and their association with verbal and visual learning and memory were assessed in persons at familial high risk (FHR) for SZ. Methods: MRI scans were acquired using a 3 T Siemens scanner of young adult (ages 19-32) FHR subjects (N = 46) and controls with no family history of illness (i.e., at low genetic risk LRC; N = 31) were processed using FreeSurfer 5.0. Subfields of the hippocampal formation were evaluated using the van Leemput method (Van Leemput et al., 2010). Learning and memory measures were collected by standardized neurocognitive tests. Results: Controlling intracranial volume, significantly reduced left (p < 0.025), and right hippocampus (p < 0.024) volumes were observed in FHR subjects. Among the subfields, the left (p < 0.01) and right subicula (p < 0.005) were significantly reduced in the FHR group. Immediate verbal recall of stories was significantly impaired and was significantly correlated with the left and right subicula within the FHR group. Conclusions: Reduced subiculum volume and its association with verbal memory refines further the association with left and right hippocampus reported in previous FHR studies of schizophrenia. Further research is needed to determine the specific genetic and environmental risk factors that may be related to hippocampal subfield alterations. (C) 2013 Elsevier B.V. All rights reserved C1 [Francis, Alan N.; Seidman, Larry J.; Tandon, Neeraj; Thermenos, Heidi W.; Mesholam-Gately, Raquelle I.; Keshavan, Matcheri S.] Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Boston, MA 02215 USA. [Francis, Alan N.; Seidman, Larry J.; Thermenos, Heidi W.] MGH MIT HMS Martinos Ctr Biomed Imaging Boston, Boston, MA USA. [Shenton, Martha E.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Boston, MA 02115 USA. [Shenton, Martha E.; DeLisi, Lynn E.] Boston Healthcare Syst, Vet Affairs, Brockton, MA USA. [Shenton, Martha E.; DeLisi, Lynn E.] Harvard Univ, Sch Med, Boston, MA USA. [van Elst, Ludger T.; Tuschen-Caffier, Brunna] Univ Freiburg, Freiburg, Germany. RP DeLisi, LE (reprint author), VA Boston Healthcare Syst, Bldg 2,2-2-B,940 Belmont Ave, Brockton, MA USA. EM DeLisi76@AOL.com FU Commonwealth Research Center of the Massachusetts Department of Mental Health [SCDMH82101008006]; [NIMH-R21MH083205]; [MH 64023]; [MH78113] FX This project was funded by NIMH-R21MH083205 (LED), MH 64023 and MH78113 (MSK), and the Commonwealth Research Center of the Massachusetts Department of Mental Health, SCDMH82101008006 (LJS). NR 17 TC 14 Z9 14 U1 0 U2 5 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0920-9964 EI 1573-2509 J9 SCHIZOPHR RES JI Schizophr. Res. PD DEC PY 2013 VL 151 IS 1-3 BP 154 EP 157 DI 10.1016/j.schres.2013.10.002 PG 4 WC Psychiatry SC Psychiatry GA 263GL UT WOS:000327795300021 PM 24144441 ER PT J AU Thermenos, HW Whitfield-Gabrieli, S Seidman, LJ Kuperberg, G Juelich, RJ Divatia, S Riley, C Jabbar, GA Shenton, ME Kubicki, M Manschreck, T Keshavan, MS DeLisi, LE AF Thermenos, H. W. Whitfield-Gabrieli, S. Seidman, L. J. Kuperberg, G. Juelich, R. J. Divatia, S. Riley, C. Jabbar, G. A. Shenton, M. E. Kubicki, M. Manschreck, T. Keshavan, M. S. DeLisi, L. E. TI Altered language network activity in young people at familial high-risk for schizophrenia SO SCHIZOPHRENIA RESEARCH LA English DT Article DE Schizophrenia; Functional MRI; High-risk; Language; Genetics; Semantic priming ID EVENT-RELATED FMRI; HIGH GENETIC RISK; SUPERIOR TEMPORAL GYRUS; LEFT PREFRONTAL CORTEX; WORD PRONUNCIATION; FUNCTIONAL MRI; SPREADING ACTIVATION; SEMANTIC KNOWLEDGE; NEGATIVE-SYMPTOMS; THOUGHT-DISORDER AB Background: Abnormalities in language and language neural circuitry are observed in schizophrenia (SZ). Similar, but less pronounced language deficits are also seen in young first-degree relatives of people with SZ, who are at higher familial risk (FHR) for the disorder than the general population. The neural underpinnings of these deficits in people with FHR are unclear. Methods: Participants were 43 people with FHR and 32 comparable controls. fMRI scans were collected while participants viewed associated and unrelated word pairs, and performed a lexical decision task. fMRI analyses conducted in SPM8 examined group differences in the modulation of hemodynamic activity by semantic association. Results: There were no group differences in demographics, IQ or behavioral semantic priming, but FHR participants had more schizotypal traits than controls. Controls exhibited the expected suppression of hemodynamic activity to associated versus unrelated word pairs. Compared to controls, FHR participants showed an opposite pattern of hemodynamic modulation to associated versus unrelated word pairs, in the left inferior frontal gyrus (IFG), right superior and middle temporal gyrus (STG) and the left cerebellum. Group differences in activation were significant, FWE-corrected for multiple comparisons (p<0.05). Activity within the IFG during the unrelated condition predicted schizotypal symptoms in FHR participants. Conclusions: FHR for SZ is associated with abnormally increased neural activity to semantic associates within an inferior frontal/temporal network. This might increase the risk of developing unusual ideas, perceptions and disorganized language that characterize schizotypal traits, potentially predicting which individuals are at greater risk to develop a psychotic disorder. (C) 2013 Elsevier B. V. All rights reserved. C1 [Thermenos, H. W.; Seidman, L. J.; Kuperberg, G.; Jabbar, G. A.; Shenton, M. E.; Kubicki, M.; Manschreck, T.; Keshavan, M. S.; DeLisi, L. E.] Harvard Univ, Sch Med, Boston, MA USA. [Thermenos, H. W.; Seidman, L. J.; Keshavan, M. S.] Massachusetts Mental Hlth Ctr, Div Publ Psychiat, Boston, MA 02115 USA. [Thermenos, H. W.; Seidman, L. J.; Keshavan, M. S.] Beth Israel Deaconess Med Ctr, Dept Psychiat, Boston, MA 02215 USA. [Thermenos, H. W.; Seidman, L. J.; Kuperberg, G.; Juelich, R. J.; Divatia, S.; Riley, C.] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. [Whitfield-Gabrieli, S.] MIT, McGovern Inst Brain Res, Cambridge, MA 02139 USA. [Whitfield-Gabrieli, S.] MIT, Poitras Ctr Affect Disorders Res, Cambridge, MA 02139 USA. [Kuperberg, G.] Tufts Univ, Dept Psychol, Medford, MA 02155 USA. [Jabbar, G. A.; Shenton, M. E.; DeLisi, L. E.] VA Boston Healthcare Syst, Brockton, MA 02301 USA. [Shenton, M. E.; Kubicki, M.] Brigham & Womens Hosp, Dept Psychiat & Radiol, Boston, MA 02115 USA. [Manschreck, T.] Corrigan Mental Hlth Ctr, Fall River, MA USA. RP Thermenos, HW (reprint author), Athinoula A Martinos Ctr Biomed Imaging, Bldg 149,2nd Floor Room 2602E,13th St, Charlestown, MA 02129 USA. EM hthermen@bidmc.harvard.edu OI Riley, Clay/0000-0002-9398-6256 FU NIH [R21 MH 083205, R21 MH 64023, R01 MH 78113, R01 MH 071635, R01 MH 074794, R01 AG 042512]; Commonwealth Research Center of the Massachusetts Department of Mental Health [SCDMH82101008006]; NIH Shared Instrumentation Grant Program [S10RR021110] FX This project was funded by NIH R21 MH 083205 (LD), R21 MH 64023 (LD), R01 MH 78113 (MSK), R01 MH 071635 (GRK), R01 MH 074794 (MK), and R01 AG 042512 (MK) and the Commonwealth Research Center of the Massachusetts Department of Mental Health, SCDMH82101008006 (LJS). This research was carried out in part at the Athinoula A. Martinos Center for Biomedical Imaging at the Massachusetts General Hospital, using resources provided by the Center for Functional Neuroimaging Technologies, P41EB015896, a P41 Regional Resource supported by the National Institute of Biomedical Imaging and Bioengineering (NIBIB), National Institutes of Health. This work also involved the use of instrumentation supported by the NIH Shared Instrumentation Grant Program and/or High-End Instrumentation Grant Program; specifically, grant number(s) S10RR021110. NR 112 TC 10 Z9 10 U1 4 U2 15 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0920-9964 EI 1573-2509 J9 SCHIZOPHR RES JI Schizophr. Res. PD DEC PY 2013 VL 151 IS 1-3 BP 229 EP 237 DI 10.1016/j.schres.2013.09.023 PG 9 WC Psychiatry SC Psychiatry GA 263GL UT WOS:000327795300033 PM 24176576 ER PT J AU Mamdani, M McMichael, GO Gadepalli, V Williamson, V Parker, EK Haroutunian, V Vladimirov, VI AF Mamdani, Mohammed McMichael, Gowon O. Gadepalli, Venkat Williamson, Vernell Parker, Erin K. Haroutunian, Vahram Vladimirov, Vladimir I. TI Differential regulation of schizophrenia-associated microRNA gene function by variable number tandem repeats (VNTR) polymorphism SO SCHIZOPHRENIA RESEARCH LA English DT Letter C1 [Mamdani, Mohammed; McMichael, Gowon O.; Gadepalli, Venkat; Williamson, Vernell; Parker, Erin K.; Vladimirov, Vladimir I.] Virginia Commonwealth Univ, Med Coll Virginia, Dept Psychiat, Virginia Inst Psychiat & Behav Genet, Richmond, VA 23298 USA. [Mamdani, Mohammed] Virginia Commonwealth Univ, Psychiat Behav Stat Genet Clin & Translat Sci Doc, Richmond, VA USA. [Haroutunian, Vahram] Mt Sinai Sch Med, Dept Psychiat, New York, NY 10029 USA. [Haroutunian, Vahram] MIRECC, James J Peters Vet Affairs Med Ctr, Bronx, NY 10468 USA. [Vladimirov, Vladimir I.] Virginia Commonwealth Univ, Med Coll Virginia, Sch Pharm, Ctr Biomarker Res & Personalized Med, Richmond, VA 23298 USA. RP Vladimirov, VI (reprint author), Virginia Commonwealth Univ, Med Coll Virginia Campus, Richmond, VA 23298 USA. EM vivladimirov@vcu.edu FU NCATS NIH HHS [UL1TR000058, KL2 TR000057, UL1 TR000058]; NIMH NIH HHS [5T32MH020030-14, MH066392, T32 MH020030] NR 9 TC 1 Z9 1 U1 0 U2 4 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0920-9964 EI 1573-2509 J9 SCHIZOPHR RES JI Schizophr. Res. PD DEC PY 2013 VL 151 IS 1-3 BP 284 EP 286 DI 10.1016/j.schres.2013.10.024 PG 3 WC Psychiatry SC Psychiatry GA 263GL UT WOS:000327795300042 PM 24210531 ER PT J AU Buikema, JW Van der Meer, P Sluijter, JPG Domian, IJ AF Buikema, Jan Willem Van der Meer, Peter Sluijter, Joost P. G. Domian, Ibrahim J. TI Concise Review: Engineering Myocardial Tissue: The Convergence of Stem Cells Biology and Tissue Engineering Technology SO STEM CELLS LA English DT Article DE Embryonic stem cells; Bone marrow; Muscle stem cells; Stem cell transplantation; Tissue regeneration; Cardiac ID LEFT-VENTRICULAR FUNCTION; SKELETAL MYOBLAST TRANSPLANTATION; CARDIOVASCULAR PROGENITOR CELLS; ZEBRAFISH HEART REGENERATION; MESENCHYMAL STROMAL CELLS; RANDOMIZED PHASE-1 TRIAL; CARDIAC-MUSCLE CONSTRUCT; MARROW MONONUCLEAR-CELLS; INFARCTED RAT HEARTS; BONE-MARROW AB Advanced heart failure represents a leading public health problem in the developed world. The clinical syndrome results from the loss of viable and/or fully functional myocardial tissue. Designing new approaches to augment the number of functioning human cardiac muscle cells in the failing heart serve as the foundation of modern regenerative cardiovascular medicine. A number of clinical trials have been performed in an attempt to increase the number of functional myocardial cells by the transplantation of a diverse group of stem or progenitor cells. Although there are some encouraging suggestions of a small early therapeutic benefit, to date, no evidence for robust cell or tissue engraftment has been shown, emphasizing the need for new approaches. Clinically meaningful cardiac regeneration requires the identification of the optimum cardiogenic cell types and their assembly into mature myocardial tissue that is functionally and electrically coupled to the native myocardium. We here review recent advances in stem cell biology and tissue engineering and describe how the convergence of these two fields may yield novel approaches for cardiac regeneration. C1 [Buikema, Jan Willem; Domian, Ibrahim J.] Massachusetts Gen Hosp, Cardiovasc Res Ctr, Boston, MA 02114 USA. [Buikema, Jan Willem; Domian, Ibrahim J.] Harvard Univ, Sch Med, Boston, MA USA. [Buikema, Jan Willem; Sluijter, Joost P. G.] Univ Utrecht, Dept Cardiol, Univ Med Ctr Utrecht, Utrecht, Netherlands. [Van der Meer, Peter] Univ Groningen, Univ Med Ctr Groningen, Dept Cardiol, Groningen, Netherlands. [Domian, Ibrahim J.] Harvard Stem Cell Inst, Cambridge, MA USA. RP Domian, IJ (reprint author), Massachusetts Gen Hosp, Cardiovasc Res Ctr, Boston, MA 02114 USA. EM idomian@partners.org RI Han, KyungJu/J-5563-2014; OI Han, KyungJu/0000-0002-5006-1886; Sluijter, Joost/0000-0003-2088-9102 FU NIH/NHLBI [U01HL100408-01]; Netherlands Organization of Scientific Research, VENI [016106013] FX We acknowledge financial support from NIH/NHLBI U01HL100408-01 to I.J.D. and Netherlands Organization of Scientific Research, VENI Grant 016106013 to P.v.d.M. NR 154 TC 10 Z9 11 U1 2 U2 17 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1066-5099 EI 1549-4918 J9 STEM CELLS JI Stem Cells PD DEC PY 2013 VL 31 IS 12 BP 2587 EP 2598 DI 10.1002/stem.1467 PG 12 WC Cell & Tissue Engineering; Biotechnology & Applied Microbiology; Oncology; Cell Biology; Hematology SC Cell Biology; Biotechnology & Applied Microbiology; Oncology; Hematology GA 262LF UT WOS:000327736000001 PM 23843322 ER PT J AU Hoggatt, J Speth, JM Pelus, LM AF Hoggatt, Jonathan Speth, Jennifer M. Pelus, Louis M. TI Concise Review: Sowing the Seeds of a Fruitful Harvest: Hematopoietic Stem Cell Mobilization SO STEM CELLS LA English DT Article DE Hematopoietic stem cell; Mobilization; Granulocyte-colony stimulating factor; CXCR4; Stem cell niche; AMD3100 (plerixafor) ID COLONY-STIMULATING FACTOR; FACTOR G-CSF; BLOOD PROGENITOR CELLS; PAROXYSMAL-NOCTURNAL HEMOGLOBINURIA; ENHANCED ENGRAFTMENT PROPERTIES; CONTINUOUS FLOW CENTRIFUGATION; CHRONIC GRANULOCYTIC-LEUKEMIA; BONE-MARROW-TRANSPLANTATION; LETHALLY IRRADIATED DOGS; CHEMOKINE GRO-BETA AB Hematopoietic stem cell transplantation is the only curative option for a number of malignant and nonmalignant diseases. As the use of hematopoietic transplant has expanded, so too has the source of stem and progenitor cells. The predominate source of stem and progenitors today, particularly in settings of autologous transplantation, is mobilized peripheral blood. This review will highlight the historical advances which led to the widespread use of peripheral blood stem cells for transplantation, with a look toward future enhancements to mobilization strategies. C1 [Hoggatt, Jonathan] Harvard Univ, Dept Stem Cell & Regenerat Med, Ctr Regenerat Med, Massachusetts Gen Hosp,Harvard Stem Cell Inst, Boston, MA 02114 USA. [Speth, Jennifer M.; Pelus, Louis M.] Indiana Univ Sch Med, Dept Microbiol & Immunol, Indianapolis, IN 46202 USA. RP Pelus, LM (reprint author), Indiana Univ Sch Med, Dept Microbiol & Immunol, 950 West Walnut St,R2-302, Indianapolis, IN 46202 USA. EM Hoggatt.Jonathan@mgh.harvard.edu; lpelus@iupui.edu FU NIH [HL087735] FX We thank Tiffany Tate for artwork assistance. J.H. is supported by NIH grant HL087735. NR 152 TC 10 Z9 11 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1066-5099 EI 1549-4918 J9 STEM CELLS JI Stem Cells PD DEC PY 2013 VL 31 IS 12 BP 2599 EP 2606 DI 10.1002/stem.1574 PG 8 WC Cell & Tissue Engineering; Biotechnology & Applied Microbiology; Oncology; Cell Biology; Hematology SC Cell Biology; Biotechnology & Applied Microbiology; Oncology; Hematology GA 262LF UT WOS:000327736000002 PM 24123398 ER PT J AU Zhang, XX Peterson, KA Liu, XS McMahon, AP Ohba, S AF Zhang, Xiaoxiao Peterson, Kevin A. Liu, X. Shirley McMahon, Andrew P. Ohba, Shinsuke TI Gene Regulatory Networks Mediating Canonical Wnt Signal-Directed Control of Pluripotency and Differentiation in Embryo Stem Cells SO STEM CELLS LA English DT Article DE Mouse embryonic stem cells; Wnt; beta-catenin; Pluripotency; Differentiation ID SELF-RENEWAL; BETA-CATENIN; TRANSCRIPTION FACTORS; WNT/BETA-CATENIN; ESCHERICHIA-COLI; TCF3 REPRESSION; AXIS FORMATION; MOUSE; ACTIVATION; REQUIREMENT AB Canonical Wnt signaling supports the pluripotency of embryonic stem cells (ESCs) but also promotes differentiation of early mammalian cell lineages. To explain these paradoxical observations, we explored the gene regulatory networks at play. Canonical Wnt signaling is intertwined with the pluripotency network comprising Nanog, Oct4, and Sox2 in mouse ESCs. In defined media supporting the derivation and propagation of ESCs, Tcf3 and -catenin interact with Oct4; Tcf3 binds to Sox motif within Oct-Sox composite motifs that are also bound by Oct4-Sox2 complexes. Furthermore, canonical Wnt signaling upregulates the activity of the Pou5f1 distal enhancer via the Sox motif in ESCs. When viewed in the context of published studies on Tcf3 and -catenin mutants, our findings suggest Tcf3 counters pluripotency by competition with Sox2 at these sites, and Tcf3 inhibition is blocked by -catenin entry into this complex. Wnt pathway stimulation also triggers -catenin association at regulatory elements with classic Lef/Tcf motifs associated with differentiation programs. The failure to activate these targets in the presence of a mitogen-activated protein kinase kinase (MEK)/extracellular signal-regulated kinase (ERK) inhibitor essential for ESC culture suggests MEK/ERK signaling and canonical Wnt signaling combine to promote ESC differentiation. C1 [Zhang, Xiaoxiao; Peterson, Kevin A.; McMahon, Andrew P.; Ohba, Shinsuke] Harvard Univ, Dept Stem Cell & Regenerat Biol, Cambridge, MA 02138 USA. [Zhang, Xiaoxiao; McMahon, Andrew P.] Harvard Univ, Dept Mol & Cellular Biol, Cambridge, MA 02138 USA. [McMahon, Andrew P.] Harvard Univ, Harvard Stem Cell Inst, Cambridge, MA 02138 USA. [Liu, X. Shirley] Harvard Univ, Sch Publ Hlth, Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA. [Ohba, Shinsuke] Univ Tokyo, Div Clin Biotechnol, Grad Sch Med, Ctr Dis Biol & Integrat Med, Tokyo, Japan. RP McMahon, AP (reprint author), Univ So Calif, WM Keck Sch Med, Dept Stem Cell Biol & Regenerat Med, Broad CIRM Ctr, Los Angeles, CA 90089 USA. EM amcmahon@med.usc.edu FU NIH [DK056246, 2R01HG4069]; Japan Society for the Promotion of Science (JSPS) [23689079]; Daiwa Securities Health Foundation; Nakatomi Foundation FX We thank Drs. Philippe Soriano, Alan B. Cantor, and Taku Saito for provision of experimental materials (specified in supporting information Methods); Laurie Chen, Joe Vaughan, Jill McMahon, Christian Daly, Jennifer Couget, Qianzi Tang, and Genome Modification Facility, Harvard Stem Cell Institute for providing technical assistance. We are also grateful to Dr. Ung-il Chung for critical comments and helpful discussions. Work in A.P.M.'s laboratory was supported by a grant from the NIH (DK056246). X.S.L. was supported by a grant from the NIH (2R01HG4069). S.O. was supported by Grants-in-Aid for young scientist (#23689079) from the Japan Society for the Promotion of Science (JSPS), Daiwa Securities Health Foundation Grant, and Nakatomi Foundation Research Grant. K.A.P. and A.P.M. are currently affiliated with the Department of Stem Cell Biology and Regenerative Medicine, Broad-CIRM Center, W.M. Keck School of Medicine, University of Southern California, CA. NR 73 TC 27 Z9 27 U1 1 U2 11 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1066-5099 EI 1549-4918 J9 STEM CELLS JI Stem Cells PD DEC PY 2013 VL 31 IS 12 BP 2667 EP 2679 DI 10.1002/stem.1371 PG 13 WC Cell & Tissue Engineering; Biotechnology & Applied Microbiology; Oncology; Cell Biology; Hematology SC Cell Biology; Biotechnology & Applied Microbiology; Oncology; Hematology GA 262LF UT WOS:000327736000008 PM 23505158 ER PT J AU Dzik, WH Beckman, N Murphy, MF Delaney, M Flanagan, P Fung, M Germain, M Haspel, RL Lozano, M Sacher, R Szczepiorkowski, Z Wendel, S AF Dzik, Walter H. Beckman, Neil Murphy, Michael F. Delaney, Meghan Flanagan, Peter Fung, Mark Germain, Marc Haspel, Richard L. Lozano, Miguel Sacher, Ronald Szczepiorkowski, Zbigniew Wendel, Silvano TI Factors affecting red blood cell storage age at the time of transfusion SO TRANSFUSION LA English DT Article ID INVENTORY MANAGEMENT; PLATELET PRODUCTION; AVAILABILITY; MODEL AB BackgroundClinical trials are investigating the potential benefit resulting from a reduced maximum storage interval for red blood cells (RBCs). The key drivers that determine RBC age at the time of issue vary among individual hospitals. Although progressive reduction in the maximum storage period of RBCs would be expected to result in smaller hospital inventories and reduced blood availability, the magnitude of the effect is unknown. Study Design and MethodsData on current hospital blood inventories were collected from 11 hospitals and three blood centers in five nations. A general predictive model for the age of RBCs at the time of issue was developed based on considerations of demand for RBCs in the hospital. ResultsAge of RBCs at issue is sensitive to the following factors: ABO group, storage age at the time of receipt by the hospital, the restock interval, inventory reserve, mean demand, and variation in demand. ConclusionsA simple model, based on hospital demand, may serve as the basis for examining factors affecting the storage age of RBCs in hospital inventories. The model suggests that the age of RBCs at the time of their issue to the patient depends on factors external to the hospital transfusion service. Any substantial change in the expiration date of stored RBCs will need to address the broad variation in demand for RBCs while attempting to balance considerations of availability and blood wastage. C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Filton Blood Ctr, Bristol, Avon, England. John Radcliffe Hosp, Natl Blood Serv, Oxford OX3 9DU, England. Univ Washington, Seattle, WA 98195 USA. New Zealand Blood Serv, Auckland, New Zealand. Fletcher Allen Hlth Care, Burlington, VT USA. Hema Quebec, Ste Foy, PQ, Canada. Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. Hosp Clin Barcelona, Barcelona, Spain. Hoxworth Blood Ctr, Cincinnati, OH USA. Sirio Libanes Hosp, Sao Paulo, Brazil. Dartmouth Hitchcock Med Ctr, Lebanon, NH 03766 USA. RP Dzik, WH (reprint author), Massachusetts Gen Hosp, Blood Transfus Serv, Room J-224,55 Fruit St, Boston, MA 02114 USA. EM sdzik@partners.org RI Szczepiorkowski, Zbigniew/A-1359-2007; OI Szczepiorkowski, Zbigniew/0000-0003-2357-9564; Lozano, Miguel/0000-0003-2593-833X NR 15 TC 9 Z9 9 U1 1 U2 6 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0041-1132 EI 1537-2995 J9 TRANSFUSION JI Transfusion PD DEC PY 2013 VL 53 IS 12 BP 3110 EP 3119 DI 10.1111/trf.12171 PG 10 WC Hematology SC Hematology GA 265CD UT WOS:000327926400012 PM 23550702 ER PT J AU Fuchs, TA Alvarez, JJ Martinod, K Bhandari, AA Kaufman, RM Wagner, DD AF Fuchs, Tobias A. Alvarez, Javier J. Martinod, Kimberly Bhandari, Ashish A. Kaufman, Richard M. Wagner, Denisa D. TI Neutrophils release extracellular DNA traps during storage of red blood cell units SO TRANSFUSION LA English DT Article ID ACUTE LUNG INJURY; LEUKOCYTE DEPLETION; MITOCHONDRIAL-DNA; TRANSFUSION; LEUKOREDUCTION; TRIAL; HISTONES; PROGRAM; SURGERY; LIPIDS AB BackgroundBlood transfusion is associated with an increased risk of organ damage, infection, and alloimmunity. Neutrophil extracellular traps (NETs) are extracellular chromatin fibers decorated with neutrophil granular proteins that have been linked to cytotoxicity, thrombosis, and autoimmunity. We questioned whether neutrophils in blood products release NETs during storage and thus could contribute to adverse reactions from blood transfusions. Study Design and MethodsWe analyzed supernatants and blood smears of human red blood cell (RBC) units that either were or were not leukoreduced before storage for markers of NETs. ResultsWe identified extracellular DNA, which was associated with histones and myeloperoxidase, a marker of neutrophil granules, in supernatants and blood smears of nonleukoreduced RBC units. These markers of NETs were absent in leukoreduced RBC units. Importantly, NETs passed through blood transfusion filters and could therefore potentially be infused into patients. ConclusionsOur studies indicate that NETs are liberated during storage of nonleukoreduced RBC units. Future studies should address whether NETs in RBC units could potentially contribute to transfusion-associated complications. C1 Boston Childrens Hosp, Program Cellular & Mol Med, Boston, MA USA. Boston Childrens Hosp, Div Hematol Oncol, Boston, MA USA. Harvard Univ, Dept Pediat, Sch Med, Boston, MA 02115 USA. Harvard Univ, Grad Program Immunol, Sch Med, Div Med Sci, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. RP Wagner, DD (reprint author), Harvard Univ, Program Cellular & Mol Med, Boston Childrens Hosp, Sch Med, 3 Blackfan Circle,3rd Floor, Boston, MA 02115 USA. EM Denisa.Wagner@childrens.harvard.edu OI Martinod, Kimberly/0000-0002-1026-6107 FU National Heart, Lung, and Blood Institute of the National Institutes of Health [R01 HL102101] FX This work was supported by the National Heart, Lung, and Blood Institute of the National Institutes of Health Grant R01 HL102101 (DDW). NR 33 TC 10 Z9 11 U1 0 U2 6 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0041-1132 EI 1537-2995 J9 TRANSFUSION JI Transfusion PD DEC PY 2013 VL 53 IS 12 BP 3210 EP 3216 DI 10.1111/trf.12203 PG 7 WC Hematology SC Hematology GA 265CD UT WOS:000327926400022 PM 23560771 ER PT J AU Goruppi, S Dotto, GP AF Goruppi, Sandro Dotto, G. Paolo TI Mesenchymal stroma: primary determinant and therapeutic target for epithelial cancer SO TRENDS IN CELL BIOLOGY LA English DT Review DE stromal microenvironment; senescence; SASP; skin cancer; autophagy ID NF-KAPPA-B; DNA-DAMAGE RESPONSE; CELLULAR SENESCENCE; TGF-BETA; TUMOR MICROENVIRONMENT; FIBROBLAST HETEROGENEITY; FIELD CANCERIZATION; SECRETORY PHENOTYPE; DERMAL FIBROBLASTS; CIGARETTE-SMOKE AB Multifocal and recurrent epithelial tumors, originating from either dormant or de novo cancer cells, are major causes of morbidity and mortality. The age-dependent increase of cancer incidence has long been assumed to result from the sequential accumulation of cancer-driving or -facilitating mutations with induction of cellular senescence as a protective mechanism. However, recent evidence suggests that the initiation and development of epithelial cancer results from a close interplay with its altered tissue microenvironment, with chronic inflammation, stromal senescence, autophagy, and the activation of cancer-associated fibroblasts (CAFs) playing possible primary roles. We will discuss recent progress in these areas, and highlight how this understanding may be used for devising novel preventive and therapeutic approaches to the epithelial cancer problem. C1 [Goruppi, Sandro; Dotto, G. Paolo] Massachusetts Gen Hosp, Cutaneous Biol Res Ctr, Charlestown, MA 02129 USA. [Goruppi, Sandro] Harvard Univ, Sch Med, Dept Dermatol, Boston, MA 02114 USA. [Dotto, G. Paolo] Univ Lausanne, Dept Biochem, CH-1066 Epalinges, Switzerland. RP Dotto, GP (reprint author), Massachusetts Gen Hosp, Cutaneous Biol Res Ctr, 13th St Bldg 149, Charlestown, MA 02129 USA. EM Gian-paolo.dotto@unil.ch FU Swiss National Foundation [CRSI33-130576/1, 3100A0-122281/1]; Oncosuisse [02361-02-2009]; National Institutes of Health [AR39190] FX This work was supported by Grants from the Swiss National Foundation (Grants CRSI33-130576/1; 3100A0-122281/1), Oncosuisse (Grant 02361-02-2009), and the National Institutes of Health (Grant AR39190) to G.P.D. NR 98 TC 20 Z9 22 U1 0 U2 9 PU ELSEVIER SCIENCE LONDON PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0962-8924 J9 TRENDS CELL BIOL JI Trends Cell Biol. PD DEC PY 2013 VL 23 IS 12 SI SI BP 593 EP 602 DI 10.1016/j.tcb.2013.08.006 PG 10 WC Cell Biology SC Cell Biology GA 274HF UT WOS:000328596700003 PM 24074947 ER PT J AU Sarosiek, KA Chonghaile, TN Letai, A AF Sarosiek, Kristopher A. Chonghaile, Triona Ni Letai, Anthony TI Mitochondria: gatekeepers of response to chemotherapy SO TRENDS IN CELL BIOLOGY LA English DT Review DE apoptosis; chemotherapy; mitochonthial apoptotic priming; chemotherapeutic window ID CHRONIC LYMPHOCYTIC-LEUKEMIA; CANCER-CELLS; IN-VIVO; APOPTOSIS PATHWAYS; CLINICAL-RESPONSE; UP-REGULATION; C-MYC; RESISTANCE; INHIBITOR; DEATH AB Mitochondria are cellular organelles that regulate commitment to and execution of apoptosis. The intrinsic apoptotic pathway culminates in the permeabilization of the mitochondrial outer membrane and dismantling of the cell. Apoptosis of cancer cells is a favorable outcome when administering chemotherapeutic treatment, yet the basis for why some cancers are sensitive to chemotherapy whereas others are not has historically been poorly understood. In this review, we present recent work that has demonstrated the importance of mitochondrial apoptotic priming, or how close a cell is to the threshold of apoptosis, in determining whether a cell will undergo apoptosis after chemotherapy treatment. Differential levels of apoptotic priming in tumors create bona fide opportunities and challenges for effective use of targeted and cytotoxic chemotherapies. C1 [Sarosiek, Kristopher A.; Chonghaile, Triona Ni; Letai, Anthony] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02215 USA. [Sarosiek, Kristopher A.; Chonghaile, Triona Ni; Letai, Anthony] Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Letai, A (reprint author), Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02215 USA. EM Anthony_Letai@dfci.harvard.edu RI Ni Chonghaile, Triona/L-9418-2015 OI Ni Chonghaile, Triona/0000-0002-3041-4031 FU American Cancer Society Postdoctoral Fellowship [121360-PF-11-256-01-TBG]; Women's Cancers Program at the Dana-Farber Cancer Institute; NIH [RO1CA129974, P01CA139980] FX The authors acknowledge the many researchers who contributed to our understanding of mitochondria, apoptosis, and cancer biology and apologize that we could not cite all of the relevant research due to space restrictions. They gratefully acknowledge funding from the American Cancer Society Postdoctoral Fellowship 121360-PF-11-256-01-TBG (K.A.S.), the Women's Cancers Program at the Dana-Farber Cancer Institute (A.L.), and NIH grants RO1CA129974 (A.L.) and P01CA139980 (A.L). A.L. is a Leukemia and Lymphoma Society Scholar. NR 56 TC 35 Z9 35 U1 1 U2 13 PU ELSEVIER SCIENCE LONDON PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0962-8924 J9 TRENDS CELL BIOL JI Trends Cell Biol. PD DEC PY 2013 VL 23 IS 12 SI SI BP 612 EP 619 DI 10.1016/j.tcb.2013.08.003 PG 8 WC Cell Biology SC Cell Biology GA 274HF UT WOS:000328596700005 PM 24060597 ER PT J AU Sartelli, M Coccolini, F Van Ramshorst, GH Campanelli, G Mandala, V Ansaloni, L Moore, EE Peitzman, A Velmahos, G Moore, FA Leppaniemi, A Burlew, CC Biffl, W Koike, K Kluger, Y Fraga, GP Ordonez, CA Di Saverio, S Agresta, F Sakakushev, B Gerych, I Wani, I Kelly, MD Gomes, CA Faro, MP Taviloglu, K Demetrashvili, Z Lee, JG Vettoretto, N Guercioni, G Trana, C Cui, YF Kok, KYY Ghnnam, WM Abbas, AE Sato, N Marwah, S Rangarajan, M Ben-Ishay, O Adesunkanmi, ARK Lohse, HAS Kenig, J Mandala, S Patrizi, A Scibe, R Catena, F AF Sartelli, Massimo Coccolini, Federico Van Ramshorst, Gabrielle H. Campanelli, Giampiero Mandala, Vincenzo Ansaloni, Luca Moore, Ernest E. Peitzman, Andrew Velmahos, George Moore, Fredrick Alan Leppaniemi, Ari Burlew, Clay Cothren Biffl, Walter Koike, Kaoru Kluger, Yoram Fraga, Gustavo P. Ordonez, Carlos A. Di Saverio, Salomone Agresta, Ferdinando Sakakushev, Boris Gerych, Igor Wani, Imtiaz Kelly, Michael D. Gomes, Carlos Augusto Faro, Mario Paulo, Jr. Taviloglu, Korhan Demetrashvili, Zaza Lee, Jae Gil Vettoretto, Nereo Guercioni, Gianluca Trana, Cristian Cui, Yunfeng Kok, Kenneth Y. Y. Ghnnam, Wagih M. Abbas, Ashraf El-Sayed Sato, Norio Marwah, Sanjay Rangarajan, Muthukumaran Ben-Ishay, Offir Adesunkanmi, Abdul Rashid K. Lohse, Helmut Alfredo Segovia Kenig, Jakub Mandala, Stefano Patrizi, Andrea Scibe, Rodolfo Catena, Fausto TI WSES guidelines for emergency repair of complicated abdominal wall hernias SO WORLD JOURNAL OF EMERGENCY SURGERY LA English DT Review ID ACELLULAR DERMAL MATRIX; SMALL-BOWEL OBSTRUCTION; RANDOMIZED CONTROLLED-TRIAL; COMPONENTS SEPARATION TECHNIQUE; INFLAMMATORY RESPONSE SYNDROME; SURGICAL WOUND INFECTIONS; BIOLOGIC MESH USE; VENTRAL HERNIA; INCISIONAL HERNIA; PROSTHETIC REPAIR AB Emergency repair of complicated abdominal hernias is associated with poor prognosis and a high rate of post-operative complications. A World Society of Emergency Surgery (WSES) Consensus Conference was held in Bergamo in July 2013, during the 2nd Congress of the World Society of Emergency Surgery with the goal of defining recommendations for emergency repair of abdominal wall hernias in adults. This document represents the executive summary of the consensus conference approved by a WSES expert panel. C1 [Sartelli, Massimo; Trana, Cristian; Patrizi, Andrea; Scibe, Rodolfo] Macerata Hosp, Dept Surg, Macerata, Italy. [Coccolini, Federico; Ansaloni, Luca] Papa Giovanni XXIII Hosp, Dept Gen Surg, Bergamo, Italy. [Van Ramshorst, Gabrielle H.] Erasmus Univ, Med Ctr, Dept Surg, Red Cross Hosp Beverwijk, Rotterdam, Netherlands. [Campanelli, Giampiero] Ist Clin SantAmbrogio, Dept Surg Sci, Milan, Italy. [Mandala, Vincenzo] Buccheri Ferla Hosp, Dept Surg, Palermo, Italy. [Moore, Ernest E.; Burlew, Clay Cothren; Biffl, Walter] Denver Hlth Med Ctr, Dept Surg, Denver, CO USA. [Peitzman, Andrew] Univ Pittsburgh, Sch Med, Dept Surg, Pittsburgh, PA USA. [Velmahos, George] Massachusetts Gen Hosp, Harvard Med Sch, Div Trauma Emergency Surg & Surg Crit Care, Boston, MA 02114 USA. [Moore, Fredrick Alan] Univ Florida, Dept Surg, Gainesville, FL USA. [Leppaniemi, Ari] Univ Hosp Meilahti, Dept Abdominal Surg, Helsinki, Finland. [Koike, Kaoru; Sato, Norio] Kyoto Univ, Grad Sch Med, Dept Primary Care & Emergency Med, Kyoto, Japan. [Kluger, Yoram; Ben-Ishay, Offir] Dept Gen Surg, Haifa, Israel. [Fraga, Gustavo P.] Univ Estadual Campinas, Div Trauma Surg, Hosp Clin, Sch Med Sci, Campinas, SP, Brazil. [Ordonez, Carlos A.] Univ Valle, Dept Surg, Fdn Valle Lili, Cali, Colombia. [Di Saverio, Salomone] Maggiore Hosp, Dept Surg, Bologna, Italy. [Agresta, Ferdinando] Adria Civil Hosp, Dept Surg, Adria, RO, Italy. [Sakakushev, Boris] Univ Hosp UMBAL St George Plovdiv, Clin Gen Surg 1, Plovdiv, Bulgaria. [Gerych, Igor] Danylo Halytsky Lviv Natl Med Univ, Lviv Reg Hosp, Dept Surg 1, Lvov, Ukraine. [Wani, Imtiaz] Sheri Kashmir Inst Med Sci, Dept Surg, Srinagar, Jammu & Kashmir, India. [Kelly, Michael D.] Griffith Base Hosp, Griffith, NSW, Australia. [Gomes, Carlos Augusto] Fed Univ Juiz Fora UFJF, Fac Ciencias Med & Saude Juiz Fora SUPREMA, Juiz De Fora, MG, Brazil. [Faro, Mario Paulo, Jr.] ABC Med Sch, Dept Gen Surg, Trauma & Emergency Surg Div, Santo Andre, SP, Brazil. [Taviloglu, Korhan] Istanbul Doctors Ctr, Dept Gen Surg, Istanbul, Turkey. [Demetrashvili, Zaza] Tbilisi State Med Univ, Dept Surg, Tbilisi, Rep of Georgia. [Lee, Jae Gil] Yonsei Univ, Coll Med, Dept Surg, Seoul 120749, South Korea. [Vettoretto, Nereo] M Mellini Hosp, Laparoscop Surg Unit, Chiari, BS, Italy. [Guercioni, Gianluca] Mazzoni Hosp, Dept Surg, Ascoli Piceno, Italy. [Cui, Yunfeng] Tianjin Med Univ, Nankai Clin Sch Med, Tianjin Nankai Hosp, Dept Surg, Tianjin, Peoples R China. [Kok, Kenneth Y. Y.] Ripas Hosp, Dept Surg, Bandar Seri Begawan, Brunei. [Ghnnam, Wagih M.; Abbas, Ashraf El-Sayed] Mansoura Univ, Fac Med, Dept Surg Mansoura, Mansoura, Egypt. [Marwah, Sanjay] Pt BDS Postgrad Inst Med Sci, Dept Surg, Rohtak, Haryana, India. [Rangarajan, Muthukumaran] GEM Hosp & Res Ctr, Dept Laparoscop Surg, Coimbatore, Tamil Nadu, India. [Adesunkanmi, Abdul Rashid K.] Obafemi Awolowo Univ Hosp, Coll Hlth Sci, Dept Surg, Ife, Nigeria. [Lohse, Helmut Alfredo Segovia] Univ Nacl Asunc, Fac Ciencias Med, Hosp Clin, Catedra Clin Quirurg, San Lorenzo, Paraguay. [Kenig, Jakub] Jagiellonian Univ Collegium Medium, Dept Gen Surg 3, Krakow, Poland. [Mandala, Stefano] G Giglio Hosp Cefalu, Dept Surg, Palermo, Italy. [Catena, Fausto] Maggiore Parma Hosp, Parma, Italy. RP Sartelli, M (reprint author), Macerata Hosp, Dept Surg, Macerata, Italy. EM m.sartelli@virgilio.it RI ghannam, wagih/I-5212-2013; OI Ansaloni, Luca/0000-0001-6427-0307; Sakakushev, Boris/0000-0001-8399-0115; ghannam, wagih/0000-0003-3599-9929; Di Saverio, Salomone/0000-0001-5685-5022 NR 114 TC 6 Z9 6 U1 1 U2 7 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1749-7922 J9 WORLD J EMERG SURG JI World J. Emerg. Surg. PD DEC 1 PY 2013 VL 8 AR 50 DI 10.1186/1749-7922-8-50 PG 11 WC Emergency Medicine; Surgery SC Emergency Medicine; Surgery GA 267NM UT WOS:000328104600001 PM 24289453 ER PT J AU Nambudiri, VE Sober, AJ Kimball, AB AF Nambudiri, Vinod E. Sober, Arthur J. Kimball, Alexa B. TI Specializing in Accountability: Strategies to Prepare a Subspecialty Workforce for Care Delivery Redesign SO ACADEMIC MEDICINE LA English DT Article ID DERMATOLOGY; INNOVATION; ADHERENCE AB Problem Accountable care organizations (ACOs) emphasize cost-effectiveness, rewarding health care systems that provide the highest-quality care delivered by the most cost-efficient providers. Transitioning to an ACO model introduces distinct challenges for specialist physicians within academic health centers. As skin diseases constitute a large number of visits to primary care providers and specialists and place a significant financial burden on the health care system, the authors sought to identify specialist-driven strategies for cost-effective, patient-centered care delivery in dermatology. Approach As part of the Massachusetts General Hospital's transition to an ACO, the Department of Dermatology in 2012 employed a team-based strategy to identify measures aimed at curbing the rate of rise in per-patient medical expense. Their approach may represent a methodological framework that translates to other specialist workforces. Outcomes The authors identified four action areas: (1) rational, cost-conscious prescribing within therapeutic classes; (2) enhanced management of urgent access and follow-up appointment scheduling; (3) procedure standardization; and (4) interpractitioner variability assessment. They describe the practices implemented in these action areas, which include a mix of changes in both clinical decision making and operational practice and are aimed at improving overall quality and value of care delivery. They also offer recommendations for other specialty departments Next Steps Involving specialist physicians in care delivery redesign efforts provides unique insights to enhance quality, cost-effectiveness, and efficiency of care delivery. With increasing emphasis on ACO models, further specialist-driven strategies for ensuring patient-centered delivery warrant development alongside other delivery reform efforts. C1 [Nambudiri, Vinod E.] Harvard Univ, Sch Med, Dept Internal Med, Boston, MA 02114 USA. [Nambudiri, Vinod E.] Harvard Univ, Sch Med, Dept Dermatol, Boston, MA 02114 USA. [Sober, Arthur J.; Kimball, Alexa B.] Harvard Univ, Sch Med, Boston, MA 02114 USA. [Sober, Arthur J.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Kimball, Alexa B.] Massachusetts Gen Hosp, Dept Dermatol, Boston, MA 02114 USA. [Kimball, Alexa B.] Massachusetts Gen Phys Org, Boston, MA USA. RP Nambudiri, VE (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Dermatol, 55 Fruit St,Bartlett Hall,6th Floor, Boston, MA 02114 USA. EM vnambudiri@partners.org NR 12 TC 1 Z9 1 U1 1 U2 12 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1040-2446 EI 1938-808X J9 ACAD MED JI Acad. Med. PD DEC PY 2013 VL 88 IS 12 BP 1900 EP 1903 DI 10.1097/ACM.0000000000000000 PG 4 WC Education, Scientific Disciplines; Health Care Sciences & Services SC Education & Educational Research; Health Care Sciences & Services GA 258BL UT WOS:000327433000033 PM 24128620 ER PT J AU Ostergaard, SD Leadholm, AKK Rothschild, AJ AF Ostergaard, Soren Dinesen Leadholm, Anne Katrine K. Rothschild, Anthony J. TI Persistent delusional theme over 13 episodes of psychotic depression SO ACTA NEUROPSYCHIATRICA LA English DT Article DE affective disorder; delusions; depression; psychosis ID ELECTROCONVULSIVE-THERAPY; CONTINUATION PHARMACOTHERAPY; RELAPSE; ECT; ASSOCIATION; REMISSION; DISORDER; SUBTYPES AB Objective Unipolar psychotic depression (PD) is a highly debilitating condition, which needs intense monitoring and treatment. Among patients with recurrent PD, delusions tend to be very similar or identical over several separate episodes during the course of illness, but case reports illustrating this clinical phenomenon in detail are lacking from the literature. Methods Case report describing the 45-year-old Ms. J, who has experienced multiple episodes of PD. The report is based on a review of her medical file. Results The delusional theme of Ms. J's initial episode of PD reappeared at several subsequent episodes. During the majority of admissions, Ms. J was treated with electroconvulsive therapy, which resulted in significant improvement in the depressive, psychotic and catatonic features. Conclusion Ms. J's case illustrates that PD can be a stable phenotype over many episodes and that it is important to recognise psychotic symptoms in order to prescribe the best possible treatment. C1 [Ostergaard, Soren Dinesen] Aalborg Univ Hosp, Aalborg Psychiat Hosp, Unit Psychiat Res, DK-9000 Aalborg, Denmark. [Ostergaard, Soren Dinesen] Aarhus Univ Hosp, Inst Clin Med, DK-8000 Aarhus, Denmark. [Ostergaard, Soren Dinesen] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Depress Clin & Res Program, Boston, MA USA. [Leadholm, Anne Katrine K.] Univ Copenhagen, Sch Med, Copenhagen, Denmark. [Rothschild, Anthony J.] Univ Massachusetts, Sch Med, Worcester, MA USA. [Rothschild, Anthony J.] UMass Mem Hlth Care, Worcester, MA USA. RP Ostergaard, SD (reprint author), Aalborg Univ Hosp, Aalborg Psychiat Hosp, Unit Psychiat Res, Molleparkvej 10, DK-9000 Aalborg, Denmark. EM sdo@m.dk OI Ostergaard, Soren Dinesen/0000-0002-8032-6208 FU NINTH [U01 MH062624]; Irving S. and Betty Brudnick Endowed Chair of Psychiatry, University of Massachusetts Medical School FX S.D. Ostergaard and A.K. Leadholm were funded by their respective institutions as listed under affiliations. A.J. Rothschild's contribution was supported in part by the NINTH (U01 MH062624) and the Irving S. and Betty Brudnick Endowed Chair of Psychiatry, University of Massachusetts Medical School. NR 27 TC 6 Z9 6 U1 0 U2 4 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 32 AVENUE OF THE AMERICAS, NEW YORK, NY 10013-2473 USA SN 1601-5215 J9 ACTA NEUROPSYCHIATR JI Acta Neuropsychiatr. PD DEC PY 2013 VL 25 IS 6 BP 370 EP 373 DI 10.1017/neu.2013.33 PG 4 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 263CL UT WOS:000327784100011 ER PT J AU Makar, RS Zhukov, OS Sahud, MA Kuter, DJ AF Makar, Robert S. Zhukov, Olga S. Sahud, Mervyn A. Kuter, David J. TI Thrombopoietin levels in patients with disorders of platelet production: Diagnostic potential and utility in predicting response to TPO Receptor agonists SO AMERICAN JOURNAL OF HEMATOLOGY LA English DT Article ID INTRAVENOUS IMMUNOGLOBULIN THERAPY; ADVERSE EVENTS; HYPERIMMUNE GLOBULINS; INFECTIOUS-DISEASES; ADMINISTRATIVE DATA; SAFETY; AUTOIMMUNE; THROMBOSIS; IVIG; COMPLICATIONS AB Thrombopoietin (TPO) is the major regulator of megakaryopoiesis. Measurement of serum TPO levels may help distinguish between various causes of thrombocytopenia and predict treatment response to TPO receptor agonists. Serum TPO levels from 118 healthy volunteers and 88 patients with abnormal platelet counts were measured using a quantitative ELISA assay. The mean (range) TPO level in healthy volunteers was 39 (7-99) pg/mL. TPO values were correlated with the patient's diagnosis, platelet count, and response to TPO receptor agonists. 88 patients with history of consumptive thrombocytopenia (39) or hypoproliferative thrombocytopenia (49) were analyzed. Median (interquartile range) TPO level for consumptive thrombocytopenia patients was 63 (48-98) pg/mL with a corresponding median (interquartile range) platelet count of 73 (28-146) x 10(9) /L. In contrast, hypoproliferative thrombocytopenia patients had platelet counts [59 (30117) x 10(9) /L] comparable with consumptive thrombocytopenia patients, but significantly higher serum TPO levels [ 706 (358-1546) pg/mL, P < 0.0001]. Analysis of 21 ITP patients treated with TPO receptor agonists demonstrated that a TPO level > 95 pg/mL was associated with lack of clinical response (P < 0.002). TPO levels may have diagnostic utility in discriminating between patients with hypoproliferative and consumptive thrombocytopenia. Elevated TPO levels in ITP patients may predict a poor clinical response to treatment with TPO receptor agonists. Am. J. Heamtol. 88: 1041-1044, 2013. (C) 2013 Wiley Periodicals, Inc. C1 [Makar, Robert S.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Pathol, Boston, MA USA. [Zhukov, Olga S.; Sahud, Mervyn A.] Quest Diagnost Nichols Inst, Coagulat Dept, San Juan Capistrano, CA USA. [Kuter, David J.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Hematol, Boston, MA USA. RP Makar, RS (reprint author), Massachusetts Gen Hosp, Blood Transfus Serv, 55 Fruit St,GRJ 206C, Boston, MA 02114 USA. EM rmakar@partners.org NR 50 TC 6 Z9 7 U1 0 U2 2 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0361-8609 EI 1096-8652 J9 AM J HEMATOL JI Am. J. Hematol. PD DEC PY 2013 VL 88 IS 12 BP 1041 EP 1044 DI 10.1002/ajh.23562 PG 4 WC Hematology SC Hematology GA 255FE UT WOS:000327224000132 PM 23913253 ER PT J AU Mazanet, R Field, JF Mazanet, R Eaton, C Mashal, RD Schaub, RA Scheuplein, F Thariath, A David, GN AF Mazanet, Rosemary Field, Joshua F. Mazanet, Rosemary Eaton, Cheryl Mashal, Robert D. Schaub, Robert A. Scheuplein, Felix Thariath, Abraham David, G. Nathan TI A PHASE I SINGLE ASCENDING DOSE STUDY OF NKTT120 IN STABLE ADULT SCD PATIENTS SO AMERICAN JOURNAL OF HEMATOLOGY LA English DT Meeting Abstract C1 [Mazanet, Rosemary; Mazanet, Rosemary; Eaton, Cheryl; Mashal, Robert D.; Schaub, Robert A.; Scheuplein, Felix; Thariath, Abraham] NKT Therapeut Inc, Waltham, MA USA. [Field, Joshua F.] Blood Ctr Wisconsin, Milwaukee, WI USA. [Field, Joshua F.] Med Coll Wisconsin, Milwaukee, WI 53226 USA. [David, G. Nathan] Dana Farber Canc Inst, Boston, MA 02115 USA. [David, G. Nathan] Boston Childrens Hosp, Boston, MA USA. [David, G. Nathan] Harvard Univ, Sch Med, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0361-8609 EI 1096-8652 J9 AM J HEMATOL JI Am. J. Hematol. PD DEC PY 2013 VL 88 IS 12 BP E82 EP E82 PG 1 WC Hematology SC Hematology GA 255FE UT WOS:000327224000118 ER PT J AU Shaik, JSB Ahmad, M Li, WJ Rose, ME Foley, LM Hitchens, TK Graham, SH Hwang, SH Hammock, BD Poloyac, SM AF Shaik, Jafar Sadik B. Ahmad, Muzamil Li, Wenjin Rose, Marie E. Foley, Lesley M. Hitchens, T. Kevin Graham, Steven H. Hwang, Sung Hee Hammock, Bruce D. Poloyac, Samuel M. TI Soluble epoxide hydrolase inhibitor trans-4-[4-(3-adamantan-1-yl-ureido)-cyclohexyloxy]-benzoic acid is neuroprotective in rat model of ischemic stroke SO AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY LA English DT Article DE arachidonic acid; cerebral blood flow; cytochrome P-450; ischemic stroke; middle cerebral artery occlusion ID FREE FATTY-ACIDS; ARACHIDONIC-ACID; CEREBRAL-ISCHEMIA; EPOXYEICOSATRIENOIC ACIDS; ELECTROCONVULSIVE SHOCK; BRAIN; PERFUSION; HYPOXIA; TARGET; CYTOCHROME-P450 AB Soluble epoxide hydrolase (sEH) diminishes vasodilatory and neuroprotective effects of epoxyeicosatrienoic acids by hydrolyzing them to inactive dihydroxy metabolites. The primary goals of this study were to investigate the effects of acute sEH inhibition by trans-4-[4-(3-adamantan-1-yl-ureido)-cyclohexyloxy]-benzoic acid (t-AUCB) on infarct volume, functional outcome, and changes in cerebral blood flow (CBF) in a rat model of ischemic stroke. Focal cerebral ischemia was induced in rats for 90 min followed by reperfusion. At the end of 24 h after reperfusion rats were euthanized for infarct volume assessment by triphenyltetrazolium chloride staining. Brain cortical sEH activity was assessed by ultra performance liquid chromatography-tandem mass spectrometry. Functional outcome at 24 and 48 h after reperfusion was evaluated by arm flexion and sticky-tape tests. Changes in CBF were assessed by arterial spin-labeled-MRI at baseline, during ischemia, and at 180 min after reperfusion. Neuroprotective effects of t-AUCB were evaluated in primary rat neuronal cultures by Cytotox-Flour kit and propidium iodide staining. t-AUCB significantly reduced cortical infarct volume by 35% (14.5 +/- 2.7% vs. 41.5 +/- 4.5%), elevated cumulative epoxyeicosatrienoic acids-to-dihydroxyeicosatrienoic acids ratio in brain cortex by twofold (4.40 +/- 1.89 vs. 1.97 +/- 0.85), and improved functional outcome in arm-flexion test (day 1: 3.28 +/- 0.5 s vs. 7.50 +/- 0.9 s; day 2: 1.71 +/- 0.4 s vs. 5.28 +/- 0.5 s) when compared with that of the vehicle-treated group. t-AUCB significantly reduced neuronal cell death in a dose-dependent manner (vehicle: 70.9 +/- 7.1% vs. t-AUCB(0.1 mu M): 58 +/- 5.11% vs. t-AUCB(0.5 mu M): 39.9 +/- 5.8%). These findings suggest that t-AUCB may exert its neuroprotective effects by affecting multiple components of neurovascular unit including neurons, astrocytes, and microvascular flow. C1 [Shaik, Jafar Sadik B.; Poloyac, Samuel M.] Univ Pittsburgh, Sch Pharm, Dept Pharmaceut Sci, Pittsburgh, PA 15261 USA. [Li, Wenjin; Rose, Marie E.; Graham, Steven H.] VA Pittsburgh Healthcare Syst, Ctr Geriatr Res Educ & Clin, Pittsburgh, PA USA. [Ahmad, Muzamil; Li, Wenjin; Rose, Marie E.; Graham, Steven H.] Univ Pittsburgh, Sch Med, Dept Neurol, Pittsburgh, PA 15261 USA. [Foley, Lesley M.; Hitchens, T. Kevin] Carnegie Mellon Univ, Pittsburgh NMR Ctr Biomed Res, Pittsburgh, PA 15213 USA. [Hwang, Sung Hee; Hammock, Bruce D.] Univ Calif Davis, Dept Entomol, Davis, CA 95616 USA. [Hwang, Sung Hee; Hammock, Bruce D.] Univ Calif Davis, Ctr Comprehens Canc, Davis, CA 95616 USA. RP Poloyac, SM (reprint author), Univ Pittsburgh, Sch Pharm, Dept Pharmaceut Sci, 807 Salk Hall, Pittsburgh, PA 15261 USA. EM poloyac@pitt.edu RI SHAIK, JAFAR SADIK/A-9638-2010 OI SHAIK, JAFAR SADIK/0000-0001-5776-3138 FU National Institutes of Health [NIEHS R01 ES002710, NIH/NIEHS R01 ES013933]; NIH Counter Act Program; [NINDS U54 NS079202]; [NINDS R01NS052315]; [NCRR S10RR023461] FX This research was supported by National Institutes of Health Grants NIEHS R01 ES002710 (to B. D. Hammock), NIH/NIEHS R01 ES013933 (to B. D. Hammock), the NIH Counter Act Program (to B. D. Hammock), NINDS U54 NS079202 (to B. D. Hammock), NINDS R01NS052315 (to S. M. Poloyac), and NCRR S10RR023461 (to S. M. Poloyac). NR 43 TC 11 Z9 11 U1 0 U2 11 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0363-6135 EI 1522-1539 J9 AM J PHYSIOL-HEART C JI Am. J. Physiol.-Heart Circul. Physiol. PD DEC PY 2013 VL 305 IS 11 BP H1605 EP H1613 DI 10.1152/ajpheart.00471.2013 PG 9 WC Cardiac & Cardiovascular Systems; Physiology; Peripheral Vascular Disease SC Cardiovascular System & Cardiology; Physiology GA 268JX UT WOS:000328167300006 PM 24043255 ER PT J AU Camargo, CA AF Camargo, Carlos A., Jr. TI Human Rhinovirus, Wheezing Illness, and the Primary Prevention of Childhood Asthma SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Editorial Material ID RISK; CHILDREN; VIRUS; BRONCHIOLITIS; INFECTIONS; INFANCY C1 [Camargo, Carlos A., Jr.] Massachusetts Gen Hosp, Dept Emergency Med, Boston, MA 02114 USA. [Camargo, Carlos A., Jr.] Harvard Univ, Sch Med, Boston, MA USA. RP Camargo, CA (reprint author), Massachusetts Gen Hosp, Dept Emergency Med, Boston, MA 02114 USA. FU NIAID NIH HHS [U01 AI-87881, U01 AI087881] NR 15 TC 5 Z9 5 U1 2 U2 6 PU AMER THORACIC SOC PI NEW YORK PA 61 BROADWAY, FL 4, NEW YORK, NY 10006 USA SN 1073-449X EI 1535-4970 J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PD DEC 1 PY 2013 VL 188 IS 11 BP 1281 EP 1282 DI 10.1164/rccm.201310-1912ED PG 3 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 268UY UT WOS:000328197300006 PM 24289772 ER PT J AU Rice, MB Ljungman, PL Wilker, EH Gold, DR Schwartz, JD Koutrakis, P Washko, GR O'Connor, GT Mittleman, MA AF Rice, Mary B. Ljungman, Petter L. Wilker, Elissa H. Gold, Diane R. Schwartz, Joel D. Koutrakis, Petros Washko, George R. O'Connor, George T. Mittleman, Murray A. TI Short-Term Exposure to Air Pollution and Lung Function in the Framingham Heart Study SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Article DE chronic obstructive pulmonary disease; asthma; air pollutants; US Environmental Protection Agency ID OBSTRUCTIVE PULMONARY-DISEASE; RESPIRATORY HEALTH; OZONE EXPOSURE; DEFICIENT MICE; INFLAMMATION; ADULTS; POLLUTANTS; SMOKERS; ASTHMA; RISK AB Rationale: Short-term exposure to ambient air pollution has been associated with lower lung function. Few studies have examined whether these associations are detectable at relatively low levels of pollution within current U. S. Environmental Protection Agency (EPA) standards. Objectives: To examine exposure to ambient air pollutants within EPA standards and lung function in a large cohort study. Methods: We included 3,262 participants of the Framingham Offspring and Third Generation cohorts living within 40 km of the Harvard Supersite monitor in Boston, Massachusetts (5,358 examinations, 1995-2011) who were not current smokers, with previous-day pollutant levels in compliance with EPA standards. We compared lung function (FEV1 and FVC) after previous-day exposure to particulate matter less than 2.5 mu m in diameter (PM2.5), nitrogen dioxide (NO2), and ozone (O-3) in the "moderate" range of the EPA Air Quality Index to exposure in the "good" range. We also examined linear relationships between moving averages of pollutant concentrations 1, 2, 3, 5, and 7 days before spirometry and lung function. Measurements and Main Results: Exposure to pollutant concentrations in the "moderate" range of the EPA Air Quality Index was associated with a 20.1-ml lower FEV1 for PM2.5 (95% confidence interval [CI], -33.4, -6.9), a 30.6-ml lower FEV1 for NO2 (95% CI, -60.9, -0.2), and a 55.7-ml lower FEV1 for O-3 (95% CI, -100.7, -10.8) compared with the "good" range. The 1- and 2-day moving averages of PM2.5, NO2, and O-3 before testing were negatively associated with FEV1 and FVC. Conclusions: Short-term exposure to PM2.5, NO2, and O-3 within current EPA standards was associated with lower lung function in this cohort of adults. C1 [Rice, Mary B.; Ljungman, Petter L.; Wilker, Elissa H.; Mittleman, Murray A.] Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Cardiovasc Epidemiol Res Unit, Boston, MA 02215 USA. [Rice, Mary B.] Massachusetts Gen Hosp, Pulm & Crit Care Unit, Boston, MA 02114 USA. [Ljungman, Petter L.] Karolinska Inst, Inst Environm Med, S-10401 Stockholm, Sweden. [Gold, Diane R.; Schwartz, Joel D.; Koutrakis, Petros] Harvard Univ, Sch Publ Hlth, Dept Environm Hlth, Boston, MA 02115 USA. [Washko, George R.] Brigham & Womens Hosp, Dept Med, Div Pulm & Crit Care Med, Boston, MA 02115 USA. [Washko, George R.; O'Connor, George T.] NHLBI, Framingham Heart Study, Framingham, MA USA. [O'Connor, George T.] Boston Univ, Sch Med, Dept Med, Ctr Pulm, Boston, MA 02118 USA. RP Rice, MB (reprint author), Massachusetts Gen Hosp, Pulm & Crit Care Unit, Bulfinch 148,55 Fruit St, Boston, MA 02114 USA. EM mrice2@partners.org RI Ljungman, Petter/C-6371-2014; OI Ljungman, Petter/0000-0002-7815-2632; O'Connor, George/0000-0002-6476-3926 FU U.S. Environmental Protection Agency [R832416, RD834798]; National Heart, Lung, and Blood Institute [N01-HC 25195, 1R01HL60040, 1R01HL70100, T32HL007374]; National Institute of Environmental Health Sciences [1F32ES023352-01, P30ES000002]; Swedish Heart Lung Foundation; Swedish Council for Working Life and Social Research Marie Curie International Postdoc Fellowship Programme; Swedish Society of Cardiology; Swedish Society for Medical Research FX Supported by U.S. Environmental Protection Agency grants R832416 and RD834798. Further supported by National Heart, Lung, and Blood Institute grants N01-HC 25195, 1R01HL60040, 1R01HL70100, and T32HL007374, and National Institute of Environmental Health Sciences grants 1F32ES023352-01 and P30ES000002. Support from the Swedish Heart Lung Foundation, the Swedish Council for Working Life and Social Research Marie Curie International Postdoc Fellowship Programme, the Swedish Society of Cardiology, and the Swedish Society for Medical Research (P.L.L.). NR 48 TC 37 Z9 39 U1 7 U2 48 PU AMER THORACIC SOC PI NEW YORK PA 61 BROADWAY, FL 4, NEW YORK, NY 10006 USA SN 1073-449X EI 1535-4970 J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PD DEC 1 PY 2013 VL 188 IS 11 BP 1351 EP 1357 DI 10.1164/rccm.201308-1414OC PG 7 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 268UY UT WOS:000328197300015 PM 24200465 ER PT J AU Smart, A Thompson, BT Needham, DM Hopkins, RO Williams, A Burnham, EL Moss, M AF Smart, Alexandra Thompson, B. Taylor Needham, Dale M. Hopkins, Ramona O. Williams, Andre Burnham, Ellen L. Moss, Marc CA NHLBI ARDS Network Investigators TI Surrogate Consent for Genetic Testing, the Reconsent Process, and Consent for Long-Term Outcomes in Acute Respiratory Distress Syndrome Trials SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Letter ID ACUTE LUNG INJURY; CLINICAL-RESEARCH; CRITICALLY-ILL; CRITICAL-CARE; CAPACITY C1 [Smart, Alexandra; Burnham, Ellen L.; Moss, Marc] Univ Colorado, Aurora, CO 80045 USA. [Thompson, B. Taylor] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Needham, Dale M.] Johns Hopkins Univ, Baltimore, MD USA. [Hopkins, Ramona O.] Intermt Med Ctr, Murray, UT USA. [Hopkins, Ramona O.] Brigham Young Univ, Provo, UT 84602 USA. [Williams, Andre] Natl Jewish Hlth, Denver, CO USA. RP Smart, A (reprint author), Univ Colorado, Aurora, CO 80045 USA. FU NHLBI NIH HHS [N01HR56167, R01HL091760, 3R01HL091760-02S1, R01 HL091760, K24-HL-089223, K24 HL089223, N01HR56170, N01HR56170, N01 HR56167] NR 20 TC 1 Z9 1 U1 0 U2 0 PU AMER THORACIC SOC PI NEW YORK PA 61 BROADWAY, FL 4, NEW YORK, NY 10006 USA SN 1073-449X EI 1535-4970 J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PD DEC 1 PY 2013 VL 188 IS 11 BP 1370 EP 1373 PG 6 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 268UY UT WOS:000328197300025 PM 24289781 ER PT J AU Tata, PR Pardo-Saganta, A Prabhu, M Vinarsky, V Law, BM Fontaine, BA Tager, AM Rajagopal, J AF Tata, Purushothama Rao Pardo-Saganta, Ana Prabhu, Mythili Vinarsky, Vladimir Law, Brandon M. Fontaine, Benjamin A. Tager, Andrew M. Rajagopal, Jayaraj TI Airway-Specific Inducible Transgene Expression Using Aerosolized Doxycycline SO AMERICAN JOURNAL OF RESPIRATORY CELL AND MOLECULAR BIOLOGY LA English DT Article DE airway-specific; aerosolized doxycycline; inhalation; Notch; mucous metaplasia ID CONDITIONAL GENE-EXPRESSION; STEM-CELLS; IN-VIVO; MICE; TRANSACTIVATOR; ACTIVATION; GENERATION; SYSTEM; MOUSE; FATE AB Tissue-specific transgene expression using tetracycline (tet)-regulated promoter/operator elements has been used to revolutionize our understanding of cellular and molecular processes. However, because most tet-regulated mouse strains use promoters of genes expressed in multiple tissues, to achieve exclusive expression in an organ of interest is often impossible. Indeed, in the extreme case, unwanted transgene expression in other organ systems causes lethality and precludes the study of the transgene in the actual organ of interest. Here, we describe a novel approach to activating tet-inducible transgene expression solely in the airway by administering aerosolized doxycycline. By optimizing the dose and duration of aerosolized doxycycline exposure in mice possessing a ubiquitously expressed Rosa26 promoter-driven reverse tet-controlled transcriptional activator (rtTA) element, we induce transgene expression exclusively in the airways. We detect no changes in the cellular composition or proliferative behavior of airway cells. We used this newly developed method to achieve airway basal stem cell-specific transgene expression using a cytokeratin 5 (also known as keratin5)-driven rtTA driver line to induce Notch pathway activation. We observed a more robust mucous metaplasia phenotype than in mice receiving doxycycline systemically. In addition, unwanted phenotypes outside of the lung that were evident when doxycycline was received systemically were now absent. Thus, our approach allows for rapid and efficient airway-specific transgene expression. After the careful strain by strain titration of the dose and timing of doxycycline inhalation, a suite of preexisting transgenic mice can now be used to study airway biology specifically in cases where transient transgene expression is sufficient to induce a phenotype. C1 [Tata, Purushothama Rao; Pardo-Saganta, Ana; Prabhu, Mythili; Vinarsky, Vladimir; Law, Brandon M.; Rajagopal, Jayaraj] Massachusetts Gen Hosp, Ctr Regenerat Med, Boston, MA 02114 USA. [Vinarsky, Vladimir; Rajagopal, Jayaraj] Massachusetts Gen Hosp, Dept Internal Med, Pulm & Crit Care Unit, Boston, MA 02114 USA. [Vinarsky, Vladimir; Rajagopal, Jayaraj] Massachusetts Gen Hosp, Dept Pediat, Boston, MA 02114 USA. [Fontaine, Benjamin A.; Tager, Andrew M.] Massachusetts Gen Hosp, Pulm & Crit Care Unit, Boston, MA 02114 USA. [Fontaine, Benjamin A.; Tager, Andrew M.] Massachusetts Gen Hosp, Ctr Immunol & Inflammatory Dis, Boston, MA 02114 USA. [Fontaine, Benjamin A.; Tager, Andrew M.] Harvard Univ, Sch Med, Boston, MA USA. [Rajagopal, Jayaraj] Harvard Stem Cell Inst, Cambridge, MA USA. RP Rajagopal, J (reprint author), Massachusetts Gen Hosp, Ctr Regenerat Med, 185 Cambridge St,Simches 4-240, Boston, MA 02114 USA. EM jrajagopal@partners.org FU National Institutes of Health-National Heart, Lung, and Blood Institute [5P30HL101287-02, R01HL108975]; Harvard Stem Cell Institute Junior Investigator Grant FX This work was supported by National Institutes of Health-National Heart, Lung, and Blood Institute Early Career Research New Faculty (P30) Award 5P30HL101287-02 (J.R.), by a Harvard Stem Cell Institute Junior Investigator Grant (J.R.), and by National Institutes of Health-National Heart, Lung, and Blood Institute grant R01HL108975 (A.M.T.). NR 31 TC 4 Z9 4 U1 0 U2 1 PU AMER THORACIC SOC PI NEW YORK PA 61 BROADWAY, FL 4, NEW YORK, NY 10006 USA SN 1044-1549 EI 1535-4989 J9 AM J RESP CELL MOL JI Am. J. Respir. Cell Mol. Biol. PD DEC PY 2013 VL 49 IS 6 BP 1048 EP 1056 DI 10.1165/rcmb.2012-0412OC PG 9 WC Biochemistry & Molecular Biology; Cell Biology; Respiratory System SC Biochemistry & Molecular Biology; Cell Biology; Respiratory System GA 269SI UT WOS:000328261800019 PM 23848320 ER PT J AU Ochkur, SI Protheroe, CA Li, W Colbert, DC Zellner, KR Shen, HH Luster, AD Irvin, CG Lee, JJ Lee, NA AF Ochkur, Sergei I. Protheroe, Cheryl A. Li, Wen Colbert, Dana C. Zellner, Katie R. Shen, Hua-Hao Luster, Andrew D. Irvin, Charles G. Lee, James J. Lee, Nancy A. TI Cys-Leukotrienes Promote Fibrosis in a Mouse Model of Eosinophil-Mediated Respiratory Inflammation SO AMERICAN JOURNAL OF RESPIRATORY CELL AND MOLECULAR BIOLOGY LA English DT Article DE 5-lipoxygenase; asthma; eosinophils; montelukast; lung ID TARGETED DISRUPTION; ASTHMA; MICE; RECEPTOR; MONTELUKAST; IL-5; C4; INTERLEUKIN-13; DEGRANULATION; REVEALS AB Leukotrienes (i.e., products of the 5-lipoxygenase pathway) are thought to be contributors to lung pathologies. Moreover, eosinophils have been linked with pulmonary leukotriene activities both as potential sources of these mediators and as responding effector cells. The objective of the present study was to define the role(s) of leukotrienes in the lung pathologies accompanying eosinophil-associated chronic respiratory inflammation. A transgenic mouse model of chronic T helper (Th) 2-driven inflammation expressing IL-5 from T cells and human eotaxin-2 locally in the lung (I5/hE2) was used to define potential in vivo relationships among eosinophils, leukotrienes, and chronic Th2-polarized pulmonary inflammation. Airway levels of cys-leukotrienes and leukotriene B-4 (LTB4) are both significantly elevated in I5/hE2 mice. The eosinophil-mediated airway hyperresponsiveness (AHR) characteristic of these mice was abolished in the absence of leukotrienes (i.e., 5-lipoxygenase-deficient I5/hE2). More importantly, the loss of leukotrienes led to an unexpectedly significant decrease in collagen deposition (i.e., pulmonary fibrosis) that accompanied elevated levels of IL-4/-13 and TGF-beta in the lungs of I5/hE2 mice. Further studies using mice deficient for the LTB4 receptor (BLT-1(-/-) /I5/hE2) and I5/hE2 animals administered a cys-leukotriene receptor antagonist (montelukast) demonstrated that the AHR and the enhanced pulmonary fibrosis characteristic of the I5/hE2 model were uniquely cys-leukotriene-mediated events. These data demonstrate that, similar to allergen challenge models of wild-type mice, cys-leukotrienes underlie AHR in this transgenic model of severe pulmonary Th2 inflammation. These data also suggest that an under-appreciated link exists among eosinophils, cys-leukotriene-mediated events, and fibrotic remodeling associated with elevated levels of IL-4/-13 and TGF-beta. C1 [Ochkur, Sergei I.; Protheroe, Cheryl A.; Lee, James J.] Mayo Clin Arizona, Dept Biochem & Mol Biol, Div Pulm Med, Scottsdale, AZ 85259 USA. [Li, Wen; Shen, Hua-Hao] Zhejiang Univ, Sch Med, Affiliated Hosp 2, Dept Resp & Crit Care Med, Hangzhou 310003, Zhejiang, Peoples R China. [Colbert, Dana C.; Zellner, Katie R.] Mayo Clin Arizona, Dept Biochem & Mol Biol, Div Hematol Oncol, Scottsdale, AZ 85259 USA. [Luster, Andrew D.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Rheumatol Allergy & Immunol, Boston, MA USA. [Irvin, Charles G.] Univ Vermont, Dept Med, Vermont Lung Ctr, Burlington, VT USA. [Irvin, Charles G.] Univ Vermont, Dept Physiol & Biophys, Vermont Lung Ctr, Burlington, VT 05405 USA. RP Lee, NA (reprint author), Mayo Clin Arizona, Mayo Collaborat Res Bldg,2-204,13,400 East Shea B, Scottsdale, AZ 85259 USA. EM nlee@mayo.edu FU Merck [IISP 33,689]; National Institutes of Health [HL058723, HL065228, RR0109709, AI0508]; NIGMS [P30 03,115,801]; American Heart Association [05,556,392, 0,855,703] FX This work was supported by Merck research grant IISP 33,689 (J.J.L.), resources from the Mayo Foundation, and National Institutes of Health grants HL058723 (N.A.L.), HL065228 and RR0109709 (J.J.L.), AI0508 (A. D. L.), NIGMS P30 03,115,801 (C. G. I.), as well as American Heart Association grants 05,556,392 (N.A.L.) and 0,855,703 (J.J.L.). These funding sources had no involvement in study design, data collection (including analysis and interpretation), the writing of the manuscript, or the decision to submit for publication. NR 28 TC 5 Z9 6 U1 0 U2 3 PU AMER THORACIC SOC PI NEW YORK PA 61 BROADWAY, FL 4, NEW YORK, NY 10006 USA SN 1044-1549 EI 1535-4989 J9 AM J RESP CELL MOL JI Am. J. Respir. Cell Mol. Biol. PD DEC PY 2013 VL 49 IS 6 BP 1074 EP 1084 DI 10.1165/rcmb.2013-0009OC PG 11 WC Biochemistry & Molecular Biology; Cell Biology; Respiratory System SC Biochemistry & Molecular Biology; Cell Biology; Respiratory System GA 269SI UT WOS:000328261800022 PM 23859654 ER PT J AU Caravan, P Yang, Y Zachariah, R Schmitt, A Mino-Kenudson, M Chen, HH Sosnovik, DE Dai, GP Fuchs, BC Lanuti, M AF Caravan, Peter Yang, Yan Zachariah, Roshini Schmitt, Anthony Mino-Kenudson, Mari Chen, Howard H. Sosnovik, David E. Dai, Guangping Fuchs, Bryan C. Lanuti, Michael TI Molecular Magnetic Resonance Imaging of Pulmonary Fibrosis in Mice SO AMERICAN JOURNAL OF RESPIRATORY CELL AND MOLECULAR BIOLOGY LA English DT Article DE molecular imaging; gadolinium; type I collagen; bleomycin; EP-3533 ID CLINICAL-COURSE; CONTRAST AGENT; LUNG-BIOPSY; DIAGNOSIS; PREVALENCE; MRI AB Idiopathic pulmonary fibrosis is a chronic, progressive, fibrosing interstitial pneumonia of unknown cause resulting in dyspnea and functional decline until death. There are currently no effective noninvasive tools to monitor disease progression and response to treatment. The objective of the present study was to determine whether molecular magnetic resonance imaging of the lung using a probe targeted to type I collagen could provide a direct, noninvasive method for assessment of pulmonary fibrosis in a mouse model. Pulmonary fibrosis was generated in mice by transtracheal instillation of bleomycin (BM). Six cohorts were imaged before and immediately after intravenous administration of molecular imaging probe: (1) BM plus collagen-targeted probe, EP-3533; (2) sham plus EP-3533; (3) BM plus nonbinding control probe, EP-3612; (4) sham plus EP-3612; (5) BM plus EP-3533 imaged early; and (6) BM plus EP-3533 imaged late. Signal-to-noise ratio (SNR) enhancement was quantified in the lungs and muscle. Lung tissue was subjected to pathologic scoring of fibrosis and analyzed for gadolinium and hydroxyproline. BM-treated mice had 35% higher lung collagen than sham mice (P < 0.0001). The SNR increase in the lungs of fibrotic mice after EP-3533 administration was twofold higher than in sham animals and twofold higher than in fibrotic or sham mice that received control probe, EP-3612 (P < 0.0001). The SNR increase in muscle was similar for all cohorts. For EP-3533, we observed a strong, positive, linear correlation between lung SNR increase and hydroxyproline levels (r = 0.72). Collagen-targeted probe EP-3533-enhanced magnetic resonance imaging specifically detects pulmonary fibrosis in a mouse model of disease. C1 [Caravan, Peter; Yang, Yan; Chen, Howard H.; Sosnovik, David E.; Dai, Guangping] Massachusetts Gen Hosp, Dept Radiol, AA Martinos Ctr Biomed Imaging, Charlestown, MA 02129 USA. [Caravan, Peter; Yang, Yan; Chen, Howard H.; Sosnovik, David E.; Dai, Guangping] Harvard Univ, Sch Med, Charlestown, MA 02129 USA. [Zachariah, Roshini; Schmitt, Anthony; Lanuti, Michael] Massachusetts Gen Hosp, Div Thorac Surg, Boston, MA 02114 USA. [Zachariah, Roshini; Schmitt, Anthony; Fuchs, Bryan C.; Lanuti, Michael] Harvard Univ, Sch Med, Boston, MA USA. [Mino-Kenudson, Mari] Massachusetts Gen Hosp, Div Pathol, Boston, MA 02114 USA. [Fuchs, Bryan C.] Massachusetts Gen Hosp, Div Surg Oncol, Ctr Canc, Boston, MA USA. RP Caravan, P (reprint author), Massachusetts Gen Hosp, Dept Radiol, AA Martinos Ctr Biomed Imaging, 149 13th St,Suite 2301, Charlestown, MA 02129 USA. EM caravan@nmr.mgh.harvard.edu FU National Heart, Lung, and Blood Institute; National Institute of Biomedical Imaging and Bioengineering [HL116315, EB009062] FX This work was supported by National Heart, Lung, and Blood Institute and the National Institute of Biomedical Imaging and Bioengineering grants HL116315 and EB009062 (P.C.). NR 24 TC 19 Z9 19 U1 1 U2 14 PU AMER THORACIC SOC PI NEW YORK PA 61 BROADWAY, FL 4, NEW YORK, NY 10006 USA SN 1044-1549 EI 1535-4989 J9 AM J RESP CELL MOL JI Am. J. Respir. Cell Mol. Biol. PD DEC PY 2013 VL 49 IS 6 BP 1120 EP 1126 DI 10.1165/rcmb.2013-0039OC PG 7 WC Biochemistry & Molecular Biology; Cell Biology; Respiratory System SC Biochemistry & Molecular Biology; Cell Biology; Respiratory System GA 269SI UT WOS:000328261800027 PM 23927643 ER PT J AU Barrett, TW Marill, KA AF Barrett, Tyler W. Marill, Keith A. TI Anticoagulation for Emergency Department Patients With Atrial Fibrillation: Is Our Duty to Inform or Prescribe? SO ANNALS OF EMERGENCY MEDICINE LA English DT Editorial Material ID STROKE; RISK; MANAGEMENT; GUIDELINES; THERAPY; 30-DAY; SCORE C1 [Barrett, Tyler W.] Vanderbilt Univ, Dept Emergency Med, Med Ctr, Nashville, TN 37212 USA. [Marill, Keith A.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Emergency Med, Boston, MA USA. RP Barrett, TW (reprint author), Vanderbilt Univ, Dept Emergency Med, Med Ctr, Nashville, TN 37212 USA. EM tyler.barrett@vanderbilt.edu FU NHLBI NIH HHS [K23 HL102069] NR 21 TC 4 Z9 4 U1 0 U2 0 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0196-0644 J9 ANN EMERG MED JI Ann. Emerg. Med. PD DEC PY 2013 VL 62 IS 6 BP 566 EP 569 DI 10.1016/j.annemergmed.2013.05.027 PG 4 WC Emergency Medicine SC Emergency Medicine GA 268PY UT WOS:000328184200004 PM 23810320 ER PT J AU Raut, CP Gronchi, A AF Raut, Chandrajit P. Gronchi, Alessandro TI Cytoreductive Surgery in Advanced GIST: Timing is Everything SO ANNALS OF SURGICAL ONCOLOGY LA English DT Editorial Material ID GASTROINTESTINAL STROMAL TUMOR; IMATINIB MESYLATE; ADJUVANT IMATINIB; THERAPY; TRIAL; RESECTION C1 [Raut, Chandrajit P.] Brigham & Womens Hosp, Dept Surg, Boston, MA 02115 USA. [Raut, Chandrajit P.] Dana Farber Canc Inst, Ctr Sarcoma & Bone Oncol, Boston, MA 02115 USA. [Raut, Chandrajit P.] Harvard Univ, Sch Med, Boston, MA USA. [Gronchi, Alessandro] Fdn IRCCS Ist Nazl Tumori, Dept Surg, Sarcoma Serv, Milan, Italy. RP Raut, CP (reprint author), Brigham & Womens Hosp, Dept Surg, 75 Francis St, Boston, MA 02115 USA. EM craut@partners.org OI Gronchi, Alessandro/0000-0002-4703-3534 NR 9 TC 1 Z9 2 U1 0 U2 2 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1068-9265 EI 1534-4681 J9 ANN SURG ONCOL JI Ann. Surg. Oncol. PD DEC PY 2013 VL 20 IS 13 BP 4059 EP 4060 DI 10.1245/s10434-013-3281-2 PG 2 WC Oncology; Surgery SC Oncology; Surgery GA 269QI UT WOS:000328256600003 PM 24081799 ER PT J AU Neuman, HB Weiss, JM Schrag, D Ronk, K Havlena, J LoConte, NK Smith, MA Greenberg, CC AF Neuman, Heather B. Weiss, Jennifer M. Schrag, Deborah Ronk, Katie Havlena, Jeffrey LoConte, Noelle K. Smith, Maureen A. Greenberg, Caprice C. TI Patient Demographic and Tumor Characteristics Influencing Oncologist Follow-Up Frequency in Older Breast Cancer Survivors SO ANNALS OF SURGICAL ONCOLOGY LA English DT Article ID PROGESTERONE-RECEPTOR; ESTROGEN-RECEPTOR; MEDICARE CLAIMS; COLON-CANCER; PRIMARY-CARE; RECURRENCE; THERAPY; STAGE; SURVEILLANCE; SPECIALISTS AB Background. Although recommendations for breast cancer follow-up frequency exist, current follow-up guidelines are standardized, without consideration of individual patient characteristics. Some studies suggest oncologists are using these characteristics to tailor follow-up recommendations, but it is unclear how this is translating into practice. The objective of this study was to examine current patterns of oncologist breast cancer follow-up and determine the association between patient and tumor characteristics and follow-up frequency. Methods. The Surveillance, Epidemiology, and End Results (SEER)-Medicare database was used to identify stage I-III breast cancer patients diagnosed 2000-2007 (n = 39,241). Oncologist follow-up visits were defined using Medicare specialty provider codes and the linked AMA Masterfile. Multinomial logistic regression determined the association between patient and tumor characteristics and oncologist follow-up visit frequency. Results. Younger age (p < 0.001), positive nodes (p < 0.001), estrogen receptor/progesterone receptor positivity (p < 0.001), and increasing treatment intensity (p < 0.001) were most strongly associated with more frequent follow-up. However, after accounting for these characteristics, significant variation in follow-up frequency was observed. In addition to patient factors, the number and types of oncologists involved in follow-up were associated with follow-up frequency (p < 0.001). Types of oncologists providing follow-up varied, with medical oncologists the sole providers of follow-up for 19-51 % of breast cancer survivors. Overall, 58 % of patients received surgical oncology, and 51 % undergoing radiation received radiation oncology follow-up, usually in combination with medical oncology. Conclusions. Significant variation in breast cancer follow-up frequency exists. Developing follow-up guidelines tailored for patient, tumor, and treatment characteristics while also providing guidance on who should provide follow-up has the potential to increase clinical efficiency. C1 [Neuman, Heather B.; Havlena, Jeffrey; Smith, Maureen A.; Greenberg, Caprice C.] UW Madison Sch Med & Publ Hlth, Dept Surg, Madison, WI USA. [Neuman, Heather B.; Weiss, Jennifer M.; LoConte, Noelle K.; Smith, Maureen A.] UW Madison Sch Med & Publ Hlth, UW Carbone Canc Ctr, Madison, WI USA. [Weiss, Jennifer M.] UW Madison Sch Med & Publ Hlth, Div Gastroenterol & Hepatol, Dept Med, Madison, WI USA. [Schrag, Deborah] Dana Farber Canc Inst, Ctr Outcomes & Policy Res, Boston, MA 02115 USA. [Ronk, Katie; Smith, Maureen A.] UW Madison Sch Med & Publ Hlth, Dept Populat Hlth Sci, Madison, WI USA. [LoConte, Noelle K.] UW Madison Sch Med & Publ Hlth, Div Hematol & Oncol, Dept Med, Madison, WI USA. [Smith, Maureen A.] UW Madison Sch Med & Publ Hlth, Dept Family Med, Madison, WI USA. RP Neuman, HB (reprint author), UW Madison Sch Med & Publ Hlth, Dept Surg, Madison, WI USA. EM neuman@surgery.wisc.edu FU Agency for Healthcare Research and Quality (AHRQ) [HHSA290201000006I]; Clinical Scholar Award from the Society of University Surgeons; University of Wisconsin Carbone Cancer Center; National Cancer Institute [P30 CA014520]; University of Wisconsin Carbone Comprehensive Cancer Center (UWCCC); Health Innovation Program, the Community-Academic Partnerships [UL1TR0000427]; UW School of Medicine and Public Health from The Wisconsin Partnership Program; California Department of Public Health [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] FX This project was funded under Contract No. HHSA290201000006I from the Agency for Healthcare Research and Quality (AHRQ) as part of the Developing Evidence to Inform Decisions about Effectiveness (DEcIDE) program. Further funding came from a Clinical Scholar Award from the Society of University Surgeons; an investigator-initiated pilot grant from the University of Wisconsin Carbone Cancer Center; Grant number P30 CA014520 from the National Cancer Institute with support to the University of Wisconsin Carbone Comprehensive Cancer Center (UWCCC); as well as the Health Innovation Program, the Community-Academic Partnerships core of the University of Wisconsin Institute for Clinical and Translational Research [Grant number UL1TR0000427 from the Clinical and Translational Science Award program of the National Center for Research Resources, NIH National Center for Advancing Translational Sciences (NCATS)] and the UW School of Medicine and Public Health from The Wisconsin Partnership Program. This study used the linked SEER-Medicare database. 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), Inc.; and the Surveillance, Epidemiology, and End Results (SEER) Program tumor registries in the creation of the SEER-Medicare database. 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. NR 27 TC 5 Z9 6 U1 0 U2 7 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1068-9265 EI 1534-4681 J9 ANN SURG ONCOL JI Ann. Surg. Oncol. PD DEC PY 2013 VL 20 IS 13 BP 4128 EP 4136 DI 10.1245/s10434-013-3170-8 PG 9 WC Oncology; Surgery SC Oncology; Surgery GA 269QI UT WOS:000328256600014 PM 23943027 ER PT J AU Rochefort, MM Ankeny, JS Kadera, BE Donald, GW Isacoff, W Wainberg, ZA Hines, OJ Donahue, TR Reber, HA Tomlinson, JS AF Rochefort, Matthew M. Ankeny, Jacob S. Kadera, Brian E. Donald, Graham W. Isacoff, William Wainberg, Zev A. Hines, O. Joe Donahue, Timothy R. Reber, Howard A. Tomlinson, James S. TI Impact of Tumor Grade on Pancreatic Cancer Prognosis: Validation of a Novel TNMG Staging System SO ANNALS OF SURGICAL ONCOLOGY LA English DT Article ID RESECTION; ADENOCARCINOMA; SURVIVAL; CHEMOTHERAPY; NOMOGRAM; TRIAL AB Background. Pancreatic ductal adenocarcinoma (PDAC) patients demonstrate highly variable survival within each stage of the American Joint Committee on Cancer (AJCC) staging system. We hypothesize that tumor grade is partly responsible for this variation. Recently our group developed a novel tumor, node, metastasis, grade (TNMG) classification system utilizing Surveillance Epidemiology and End Results (SEER) data in which the presence of high tumor grade results in advancement to the next higher AJCC stage. This study's objective was to validate this TNMG staging system utilizing single-institution data. Methods. All patients with PDAC who underwent resection at UCLA between 1990 and 2009 were identified. Clinicopathologic data reviewed included age, sex, node status, tumor size, grade, and stage. Grade was redefined as a dichotomous variable. The impact of grade on survival was assessed by Cox regression analysis. Disease was restaged into the TNMG system and compared to the AJCC staging system. Results. We identified 256 patients who underwent resection for PDAC. Patients with low-grade tumors experienced a 13-month improvement in median survival compared to those with high-grade tumors. On multivariate analysis, tumor grade was the strongest predictor of survival with a hazard ratio of 2.02 (p = 0.0005). Restaging disease according to the novel TNMG staging system resulted in improved survival discrimination between stages compared to the current AJCC system. Conclusions. We were able to demonstrate that grade is one of the strongest independent prognostic factors in PDAC. Restaging with our novel TNMG system demonstrated improved prognostication. This system offers an effective and convenient way of adding grade to the current AJCC staging system. C1 [Rochefort, Matthew M.; Ankeny, Jacob S.; Tomlinson, James S.] Greater Los Angeles VA Healthcare Syst, Dept Surg, Los Angeles, CA USA. [Rochefort, Matthew M.; Ankeny, Jacob S.; Kadera, Brian E.; Donald, Graham W.; Hines, O. Joe; Donahue, Timothy R.; Reber, Howard A.; Tomlinson, James S.] Univ Calif Los Angeles, Dept Surg, Los Angeles, CA 90024 USA. [Isacoff, William; Wainberg, Zev A.] Univ Calif Los Angeles, Dept Hematol & Oncol, Los Angeles, CA USA. RP Tomlinson, JS (reprint author), Greater Los Angeles VA Healthcare Syst, Dept Surg, Los Angeles, CA USA. EM jtomlinson@mednet.ucla.edu NR 16 TC 16 Z9 16 U1 0 U2 4 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1068-9265 EI 1534-4681 J9 ANN SURG ONCOL JI Ann. Surg. Oncol. PD DEC PY 2013 VL 20 IS 13 BP 4322 EP 4329 DI 10.1245/s10434-013-3159-3 PG 8 WC Oncology; Surgery SC Oncology; Surgery GA 269QI UT WOS:000328256600041 PM 23943022 ER PT J AU Hernandez, JM Elahi, A Clark, CW Wang, J Humphries, LA Centeno, B Bloom, G Fuchs, BC Yeatman, T Shibata, D AF Hernandez, J. M. Elahi, A. Clark, C. W. Wang, J. Humphries, L. A. Centeno, B. Bloom, G. Fuchs, B. C. Yeatman, T. Shibata, D. TI miR-675 Mediates Downregulation of Twist1 and Rb in AFP-Secreting Hepatocellular Carcinoma SO ANNALS OF SURGICAL ONCOLOGY LA English DT Article ID EPITHELIAL-MESENCHYMAL TRANSITION; ALPHA-FETOPROTEIN; TUMOR-SUPPRESSOR; BREAST-CANCER; NONCODING RNA; H19; CELLS; METASTASIS; GROWTH; OVEREXPRESSION AB Background. Alpha-fetoprotein (AFP)-secreting hepatocellular carcinomas (HCC) represent a genetically distinct subset of tumors often associated with a worse prognosis. However, the molecular mechanisms that underlie these phenotypic differences remain poorly understood. Methods. HCC tumor samples from 27 patients were profiled using the Affymetrix 133 Plus 2.0 GeneChips. GeneGO Metacore software was used to identify altered biologic pathways. Expression validation was confirmed by RT-PCR. Manipulation of miR-675 by overexpression and antagomir-mediated knockdown was carried out with subsequent evaluation of effects on cell behavior by cell cycle, proliferation, invasion, and growth in soft agar assays. Results. We identified a strong relationship between primary tumor H19 gene expression and elevated serum AFP. H19 has recently been identified to encode microRNA-675 (miR-675), and we confirmed the relationship in an independent sample of patients. Pathway analyses of the effect of miR-675 overexpression in hepatoma cells revealed a predominant upregulation of cell adhesion and cell cycle initiation pathways. We have demonstrated that miR-675 mediates increases in proliferation and an accumulation of cells with tetraploid DNA content associated with a repression of Rb. We also demonstrated that overexpression of miR-675 alters cellular morphology, reduces invasive potential, and increases anchorage-independent growth capacity. These findings are consistent with a mesenchymal-to-epithelial transition, associated with a reduction in the expression of the key EMT mediator, Twist1. Conclusions. Expression of the miR-675 in hepatocellular carcinoma links a dramatic upregulation of proliferative and growth capacity with inhibition of motility in HCC cells. C1 [Hernandez, J. M.; Elahi, A.; Clark, C. W.; Wang, J.; Humphries, L. A.; Yeatman, T.; Shibata, D.] Univ S Florida, Coll Med, H Lee Moffitt Canc Ctr & Res Inst, Dept Gastrointestinal Oncol, Tampa, FL 33612 USA. [Centeno, B.] Univ S Florida, Coll Med, H Lee Moffitt Canc Ctr & Res Inst, Dept Anat Pathol, Tampa, FL 33612 USA. [Bloom, G.] Univ S Florida, Coll Med, H Lee Moffitt Canc Ctr & Res Inst, Dept Biomed Informat, Tampa, FL 33612 USA. [Fuchs, B. C.] Massachusetts Gen Hosp, Ctr Canc, Div Surg Oncol, Boston, MA USA. [Fuchs, B. C.] Harvard Univ, Sch Med, Div Surg Oncol, Boston, MA USA. RP Shibata, D (reprint author), Univ S Florida, Coll Med, H Lee Moffitt Canc Ctr & Res Inst, Dept Gastrointestinal Oncol, Tampa, FL 33612 USA. EM david.shibata@moffitt.org FU National Institutes of Health (NIH) [R01 CA112215] FX This work was supported in part by a Grant from the National Institutes of Health (NIH) (R01 CA112215 to J.M.H. and T.Y.) NR 40 TC 30 Z9 31 U1 0 U2 8 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1068-9265 EI 1534-4681 J9 ANN SURG ONCOL JI Ann. Surg. Oncol. PD DEC PY 2013 VL 20 SU 3 BP S625 EP S635 DI 10.1245/s10434-013-3106-3 PG 11 WC Oncology; Surgery SC Oncology; Surgery GA 268VB UT WOS:000328197600037 PM 23864307 ER PT J AU Robboy, SJ Weintraub, S Horvath, AE Jensen, BW Alexander, CB Fody, EP Crawford, JM Clark, JR Cantor-Weinberg, J Joshi, MG Cohen, MB Prystowsky, MB Bean, SM Gupta, S Powell, SZ Speights, VO Gross, DJ Black-Schaffer, WS AF Robboy, Stanley J. Weintraub, Sally Horvath, Andrew E. Jensen, Bradden W. Alexander, C. Bruce Fody, Edward P. Crawford, James M. Clark, Jimmy R. Cantor-Weinberg, Julie Joshi, Megha G. Cohen, Michael B. Prystowsky, Michael B. Bean, Sarah M. Gupta, Saurabh Powell, Suzanne Z. Speights, V. O., Jr. Gross, David J. Black-Schaffer, W. Stephen CA Workforce Project Work Grp TI Pathologist Workforce in the United States I. Development of a Predictive Model to Examine Factors Influencing Supply SO ARCHIVES OF PATHOLOGY & LABORATORY MEDICINE LA English DT Article ID PRIVATE LABORATORY PRACTICE; JOINT-TASK-FORCE; NATIONAL MANPOWER SURVEY; COMMUNITY HOSPITALS; NEEDS; ASCP/CAP/APC; SHORTAGE AB Context.-Results of prior pathology workforce surveys have varied between a state of equilibrium and predictions of shortage. Objective.-To assess the current and future supply of pathologists, and apply a dynamic modeling tool for assessing the effects of changing market forces and emerging technologies on the supply of pathologists' services through 2030. Design.-Data came from various sources, including the literature, College of American Pathologists' internal data, and primary research through custom-developed surveys for the membership and for pathology practice managers Results.-Through 2010, there were approximately 18 000 actively practicing pathologists in the United States (5.7 per 100 000 population), approximately 93% of whom were board certified. Our model projects that the absolute and per capita numbers of practicing pathologists will decrease to approximately 14 000 full-time equivalent (FTE) pathologists or 3.7 per 100 000 in the coming 2 decades. This projection reflects that beginning in 2015, the numbers of pathologists retiring will increase precipitously, and is anticipated to peak by 2021. Including all types of separation, the net pathologist strength will begin falling by year 2015. Unless workforce entry or exit rates change, this trend will continue at least through 2030. These changes reflect the closure of many training programs 2 to 4 decades ago and the substantially decreased number of graduating residents. Conclusions.-This comprehensive analysis predicts that pathologist numbers will decline steadily beginning in 2015. Anticipated population growth in general and increases in disease incidence owing to the aging population, to be presented in a companion article on demand, will lead to a net deficit in excess of more than 5700 FTE pathologists. To reach the projected need in pathologist numbers of nearly 20 000 FTE by 2030 will require an increase from today of approximately 8.1% more residency positions. We believe a pathologist shortage will negatively impact both patient access to laboratory services and health care providers' abilities to deliver more effective health care to their patient populations. C1 [Robboy, Stanley J.; Bean, Sarah M.] Duke Univ, Med Ctr, Dept Pathol, Durham, NC 27710 USA. [Weintraub, Sally; Cantor-Weinberg, Julie; Gross, David J.] Coll Amer Pathologists, Waukegan, IL USA. [Horvath, Andrew E.] Univ New Mexico, Dept Pathol, Albuquerque, NM 87131 USA. [Jensen, Bradden W.] Southwest Washington Med Ctr, Dept Pathol, Vancouver, WA USA. [Alexander, C. Bruce] Univ Alabama Birmingham, Dept Pathol, Birmingham, AL 35294 USA. [Fody, Edward P.] Holland Hosp, Dept Pathol, Holland, MI USA. [Crawford, James M.] North Shore Long Isl Jewish Hlth Syst, Dept Pathol, Manhasset, NY USA. [Clark, Jimmy R.] ACL Labs, W Allis, WI USA. [Joshi, Megha G.] Lawrence Gen Hosp, Dept Pathol, Winchester, MA USA. [Cohen, Michael B.] Univ Utah, Dept Pathol, Salt Lake City, UT USA. [Prystowsky, Michael B.] Albert Einstein Coll Med, Dept Pathol, Bronx, NY 10467 USA. [Gupta, Saurabh] Grail Res, Bombay, Maharashtra, India. [Powell, Suzanne Z.] Methodist Hosp, Dept Pathol, Houston, TX 77030 USA. [Speights, V. O., Jr.] Scott & White Mem Hosp & Clin, Dept Pathol, Temple, TX 76508 USA. [Black-Schaffer, W. Stephen] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. RP Robboy, SJ (reprint author), Duke Univ, Med Ctr, Dept Pathol, DUMC 3712, Durham, NC 27710 USA. EM stanley.robboy@duke.edu NR 25 TC 15 Z9 16 U1 0 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 DEC PY 2013 VL 137 IS 12 BP 1723 EP 1732 DI 10.5858/arpa.2013-0200-OA PG 10 WC Medical Laboratory Technology; Medicine, Research & Experimental; Pathology SC Medical Laboratory Technology; Research & Experimental Medicine; Pathology GA 269TD UT WOS:000328263900003 PM 23738764 ER PT J AU Bean, JF Latham, NK Holt, N Kurlinksi, L Ni, PS Leveille, S Percac-Lima, S Jette, A AF Bean, Jonathan F. Latham, Nancy K. Holt, Nicole Kurlinksi, Laura Ni, Pensheng Leveille, Suzanne Percac-Lima, Sanja Jette, Alan TI Which Neuromuscular Attributes Are Most Associated With Mobility Among Older Primary Care Patients? SO ARCHIVES OF PHYSICAL MEDICINE AND REHABILITATION LA English DT Article DE Aged; Mobility limitation; Primary health care; Rehabilitation ID PHYSICAL PERFORMANCE; RISK-ASSESSMENT; LIMITED ELDERS; DISABILITY; ADULTS; STRENGTH; DECLINE; BALANCE; WOMEN; POWER AB Objective: To identify the neuromuscular attributes that are associated with self-reported mobility status among older primary care patients. Design: Cohort study. Setting: Metropolitan-based health care system. Participants: Community-dwelling primary care patients aged >= 65 years (N=430), with self-reported modification of mobility tasks resulting from underlying health conditions. Interventions: Not applicable. Main Outcome Measures: Basic and Advanced Lower Extremity Function as measured by the Late Life Function and Disability Instrument. Results: We constructed multivariable linear regression models evaluating both outcomes. For Basic Lower Extremity Function, leg strength, leg velocity, trunk extensor muscle endurance, and ankle range of motion (ROM) were statistically significant predictors (P<001, R-2=.21). For Advanced Lower Extremity Function, leg strength, leg strength asymmetry, leg velocity, trunk extensor muscle endurance, and knee flexion ROM were statistically significant predictors (P<.001, R-2=.39). Sensitivity analyses conducted using multiple imputations to account for missing data confirmed these findings. Conclusions: This analysis highlights the relevance and importance of 5 categories of neuromuscular attributes: strength, speed of movement, ROM, asymmetry, and trunk stability. It identifies novel attributes (leg velocity and trunk extensor muscle endurance) relevant to mobility and highlights that impairment profiles vary by the level of mobility assessed. These findings will inform the design of more thorough and potentially more effective disability prevention strategies. Archives of Physical Medicine and Rehabilitation 2013;94:2381-8 (C) 2013 by the American Congress of Rehabilitation Medicine C1 [Bean, Jonathan F.; Holt, Nicole; Kurlinksi, Laura] Spaulding Rehabil Hosp, Boston, MA USA. [Latham, Nancy K.; Ni, Pensheng; Jette, Alan] Boston Univ, Boston, MA 02215 USA. [Leveille, Suzanne] Univ Massachusetts, Boston, MA 02125 USA. [Percac-Lima, Sanja] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Bean, JF (reprint author), Spaulding Cambridge Outpatient Ctr, 1575 Cambridge St, Cambridge, MA 02138 USA. EM jfbean@partners.org RI Bean, Jonathan/F-5798-2017; OI Bean, Jonathan/0000-0001-8385-8210; Holt, Nicole/0000-0002-2483-7767 FU National Institute on Aging [5 R01 AG032052-03]; National Center for Research Resources [1 UL1 RR025758-01] FX Boston Rehabilitative Impairment Study of the Elderly is supported by the National Institute on Aging (grant no. 5 R01 AG032052-03) and by the National Center for Research Resources in a grant to the Harvard Clinical and Translational Science Center (grant no. 1 UL1 RR025758-01). NR 41 TC 10 Z9 10 U1 5 U2 9 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0003-9993 EI 1532-821X J9 ARCH PHYS MED REHAB JI Arch. Phys. Med. Rehabil. PD DEC PY 2013 VL 94 IS 12 BP 2381 EP 2388 DI 10.1016/j.apmr.2013.07.026 PG 8 WC Rehabilitation; Sport Sciences SC Rehabilitation; Sport Sciences GA 264UD UT WOS:000327905600009 PM 23973445 ER PT J AU Tsai, CY Rice, LA Hoelmer, C Boninger, ML Koontz, AM AF Tsai, Chung-Ying Rice, Laura A. Hoelmer, Claire Boninger, Michael L. Koontz, Alicia M. TI Basic Psychometric Properties of the Transfer Assessment Instrument (Version 3.0) SO ARCHIVES OF PHYSICAL MEDICINE AND REHABILITATION LA English DT Article DE Outcomes assessment; Rehabilitation; Reliability and validity; Wheelchairs ID SPINAL-CORD-INJURY; SITTING PIVOT TRANSFERS; MANUAL WHEELCHAIR USERS; SHOULDER PAIN; RELIABILITY; INDIVIDUALS; INTERRATER; KINEMATICS; AGREEMENT; VALIDITY AB Objectives: To refine the Transfer Assessment Instrument (TAI 2.0), develop a training program for the TAX, and analyze the basic psychometric properties of the TAI 3.0, including reliability, standard error of measurement (SEM), minimal detectable change (MDC), and construct validity. Design: Repeated measures. Setting: A winter sports clinic for disabled veterans. Participants: Wheelchair users (N=41) who perform sitting-pivot or standing-pivot transfers. Intervention: Not applicable. Main Outcome Measures: TAI version 3.0, intraclass correlation coefficients, SEMs, and MDCs for reliable measurement of raters' responses. Spearman correlation coefficient, 1-way analysis of variance, and independent t tests to evaluate construct validity. Results: TAI 3.0 had acceptable to high levels of reliability (range, .74.88). The SEMs for part 1, part 2, and final scores ranged from .45 to .75. The MDC was 1.5 points on the 10-point scale for the final score. There were weak correlations (p range, .13 to.25; P>.11) between TAI final scores and subjects' characteristics (eg, sex, body mass index, age, type of disability, length of wheelchair use, grip and elbow strength, sitting balance). Conclusions: With comprehensive training, the refined TAI 3.0 yields high reliability among raters of different clinical backgrounds and experience. TAI 3.0 was unbiased toward certain physical characteristics that may influence transfer. TAI fills a void in the field by providing a quantitative measurement of transfers and a tool that can be used to detect problems and guide transfer training. Archives of Physical Medicine and Rehabilitation 2013;94:2456-64 (C) 2013 by the American Congress of Rehabilitation Medicine C1 [Tsai, Chung-Ying; Boninger, Michael L.; Koontz, Alicia M.] Vet Affairs Pittsburgh Healthcare Syst, Human Engn Res Labs, Pittsburgh, PA USA. [Tsai, Chung-Ying; Boninger, Michael L.; Koontz, Alicia M.] Univ Pittsburgh, Dept Rehabil Sci & Technol, Pittsburgh, PA USA. [Rice, Laura A.] Univ Illinois, Dept Kinesiol & Community Hlth, Champaign, IL 61820 USA. [Boninger, Michael L.; Koontz, Alicia M.] Univ Pittsburgh, Dept Phys Med & Rehabil, Pittsburgh, PA USA. [Hoelmer, Claire; Boninger, Michael L.] Univ Pittsburgh, Dept Bioengn, Pittsburgh, PA USA. RP Koontz, AM (reprint author), VA Pittsburgh Healthcare Syst, 6425 Penn Ave,Ste 400, Pittsburgh, PA 15206 USA. EM akoontz@pitt.edu OI Boninger, Michael/0000-0001-6966-919X FU VA Rehabilitation Research & Development Services Merit Review Project [B6789C]; National Science Foundation [0849878]; National Institute on Disability and Rehabilitation Research [H133N060019, H133N110011] FX Supported by the VA Rehabilitation Research & Development Services Merit Review Project (grant no. B6789C), the National Science Foundation (grant no. 0849878), and the National Institute on Disability and Rehabilitation Research (grant nos. H133N060019, H133N110011). NR 34 TC 8 Z9 8 U1 0 U2 5 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0003-9993 EI 1532-821X J9 ARCH PHYS MED REHAB JI Arch. Phys. Med. Rehabil. PD DEC PY 2013 VL 94 IS 12 BP 2456 EP 2464 DI 10.1016/j.apmr.2013.05.001 PG 9 WC Rehabilitation; Sport Sciences SC Rehabilitation; Sport Sciences GA 264UD UT WOS:000327905600019 PM 23685096 ER PT J AU Khanna, D Gladue, H Channick, R Chung, L Distler, O Furst, DE Hachulla, E Humbert, M Langleben, D Mathai, SC Saggar, R Visovatti, S Altorok, N Townsend, W FitzGerald, J McLaughlin, VV AF Khanna, Dinesh Gladue, Heather Channick, Richard Chung, Lorinda Distler, Oliver Furst, Daniel E. Hachulla, Eric Humbert, Marc Langleben, David Mathai, Stephen C. Saggar, Rajeev Visovatti, Scott Altorok, Nezam Townsend, Whitney FitzGerald, John McLaughlin, Vallerie V. TI Recommendations for Screening and Detection of Connective Tissue Disease-Associated Pulmonary Arterial Hypertension SO ARTHRITIS AND RHEUMATISM LA English DT Article ID MODIFYING ANTIRHEUMATIC DRUGS; OF-RHEUMATOLOGY GUIDELINES; BRAIN NATRIURETIC PEPTIDE; SYSTEMIC-SCLEROSIS; ECHOCARDIOGRAPHY; ARTHRITIS; MULTICENTER; PREVALENCE; PREDICTORS; MANAGEMENT AB ObjectivePulmonary arterial hypertension (PAH) affects up to 15% of patients with connective tissue diseases (CTDs). Previous recommendations developed as part of larger efforts in PAH did not include detailed recommendations for patients with CTD-associated PAH. Therefore, we sought to develop recommendations for screening and early detection of CTD-associated PAH. MethodsWe performed a systematic review of the literature on the screening and diagnosis of PAH in CTD. Using the RAND/University of California, Los Angeles consensus methodology, we developed case scenarios followed by 2 stages of voting. First, international experts from a variety of specialties voted anonymously on the appropriateness of each case scenario. The experts then met face-to-face to discuss and resolve discrepant votes to arrive at consensus recommendations. ResultsThe key recommendation stated that all patients with systemic sclerosis (SSc) should be screened for PAH. In addition, patients with mixed connective tissue disease or other CTDs with scleroderma features (scleroderma spectrum disorders) should be screened for PAH. It was recommended that screening pulmonary function tests (PFTs) with single-breath diffusing capacity for carbon monoxide, transthoracic echocardiogram, and measurement of N-terminal pro-brain natriuretic peptide (NT-proBNP) be performed in all patients with SSc and scleroderma spectrum disorders. In patients with SSc and scleroderma spectrum disorders, transthoracic echocardiogram and PFTs should be performed annually. The full screening panel (transthoracic echocardiogram, PFTs, and measurement of NT-proBNP) should be performed as soon as any new signs or symptoms are present. ConclusionWe provide consensus-based, evidence-driven recommendations for screening and early detection of CTD-associated PAH. It is our hope that these recommendations will lead to earlier detection of CTD-associated PAH and ultimately improve patient outcomes. C1 [Khanna, Dinesh; Gladue, Heather; Visovatti, Scott; Altorok, Nezam; Townsend, Whitney; McLaughlin, Vallerie V.] Univ Michigan, Ann Arbor, MI 48109 USA. [Channick, Richard] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Chung, Lorinda] Stanford Univ, Sch Med, Stanford, CA USA. [Chung, Lorinda] Palo Alto VA Hlth Care Syst, Palo Alto, CA USA. [Distler, Oliver] Univ Zurich Hosp, CH-8091 Zurich, Switzerland. [Furst, Daniel E.; FitzGerald, John] Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90095 USA. [Hachulla, Eric] Univ Lille 2, Lille, France. [Hachulla, Eric] Hop Claude Huriez, Lille, France. [Humbert, Marc] Univ Paris Sud, AP HP, INSERM, U999, F-94275 Le Kremlin Bicetre, France. [Humbert, Marc] Hop Bicetre, Le Kremlin Bicetre, France. [Langleben, David] Jewish Gen Hosp, Montreal, PQ, Canada. [Langleben, David] McGill Univ, Montreal, PQ, Canada. [Mathai, Stephen C.] Johns Hopkins Univ, Sch Med, Baltimore, MD USA. [Saggar, Rajeev] St Josephs Hosp, Phoenix, AZ USA. RP Khanna, D (reprint author), Univ Michigan, Div Rheumatol, Dept Internal Med, Suite 7C27,300 North Ingalls St,SPC 5422, Ann Arbor, MI 48109 USA. EM khannad@med.umich.edu OI Townsend, Whitney/0000-0002-4749-9369 FU Scleroderma Foundation; Actelion; Gilead; United Therapeutics; NIH (National Institute of Arthritis and Musculoskeletal and Skin Diseases) [K24-AR-063120-02]; Scleroderma Research Foundation; NIH; Pulmonary Hypertension Association; National Heart, Lung, and Blood Institute [K23-HL-093387]; Roche; Bristol-Myers Squibb; Pfizer; Digna Biotech; Impact Pharmaceutical Services; Bayer; ErgoNex; Sanofi-Aventis; Sinoxa; United BioSource; Medac; Swedish Orphan Biovitrum; Boehringer Ingelheim Pharma; Novartis; Active Biotech; 4D Science; Lilly; GlaxoSmithKline; Aires Pharmaceuticals; Bayer Healthcare; Merck FX Funded by the Scleroderma Foundation and the Pulmonary Hypertension Association, which received unrestricted educational grants from Actelion, Gilead, and United Therapeutics to support development of these recommendations. Dr. Khanna's work was supported by the NIH (National Institute of Arthritis and Musculoskeletal and Skin Diseases grant K24-AR-063120-02). Dr. Chung's work was supported by the Scleroderma Research Foundation. Dr. Mathai's work was supported by the NIH and the Pulmonary Hypertension Association through a jointly sponsored grant (National Heart, Lung, and Blood Institute, K23-HL-093387).; Dr. Khanna has received consulting fees, speaking fees, and/or honoraria from United Therapeutics, Roche, Bristol-Myers Squibb, Gilead, Pfizer, Digna Biotech, and Impact Pharmaceutical Services (less than $10,000 each) and from Actelion (more than $10,000). Dr. Channick has received consulting fees, speaking fees, and/or honoraria from Actelion, United Therapeutics, and Bayer (less than $10,000 each). Dr. Chung has received consulting fees, speaking fees, and/or honoraria from Gilead (less than $10,000). Dr. Distler has received consulting fees, speaking fees, and/or honoraria from Bayer, Pfizer, ErgoNex, Bristol-Myers Squibb, Sanofi-Aventis, Sinoxa, United BioSource, Medac, Swedish Orphan Biovitrum, Boehringer Ingelheim Pharma, Novartis, and Active Biotech (less than $10,000 each) and from Actelion and 4D Science (more than $10,000 each); he also has a patent for the use of microRNA-29 for the treatment of systemic sclerosis. Dr. Hachulla has received consulting fees, speaking fees, and/or honoraria from Actelion, Pfizer, Lilly, United Therapeutics, and GlaxoSmithKline (less than $10,000 each). Dr. Humbert has received consulting fees, speaking fees, and/or honoraria from Actelion, Aires Pharmaceuticals, Bayer, GlaxoSmithKline, Novartis, and Pfizer (less than $10,000 each). Dr. Langleben has received consulting fees, speaking fees, and/or honoraria from Actelion, Bayer, Novartis, Pfizer, GlaxoSmithKline, Lilly, and United Therapeutics (less than $10,000 each). Dr. Mathai has received consulting fees, speaking fees, and/or honoraria from Bayer Healthcare, United Therapeutics, and Actelion (less than $10,000 each). Dr. Saggar has received consulting fees, speaking fees, and/or honoraria from United Therapeutics, Gilead, Actelion, and Bayer (less than $10,000 each). Dr. McLaughlin has received consulting fees, speaking fees, and/or honoraria from Merck (less than $10,000) and from Actelion, Bayer, Gilead, and United Therapeutics (more than $10,000 each); she also has received institutional grants and research support from Actelion, Bayer, and Novartis. NR 51 TC 36 Z9 38 U1 3 U2 5 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0004-3591 EI 1529-0131 J9 ARTHRITIS RHEUM-US JI Arthritis Rheum. PD DEC PY 2013 VL 65 IS 12 BP 3194 EP 3201 DI 10.1002/art.38172 PG 8 WC Rheumatology SC Rheumatology GA 261VL UT WOS:000327692600022 PM 24022584 ER PT J AU Jensen, KB Srinivasan, P Spaeth, R Tan, Y Kosek, E Petzke, F Carville, S Fransson, P Marcus, H Williams, SCR Choy, E Vitton, O Gracely, R Ingvar, M Kong, J AF Jensen, Karin B. Srinivasan, Priti Spaeth, Rosa Tan, Ying Kosek, Eva Petzke, Frank Carville, Serena Fransson, Peter Marcus, Hanke Williams, Steven C. R. Choy, Ernest Vitton, Olivier Gracely, Richard Ingvar, Martin Kong, Jian TI Overlapping Structural and Functional Brain Changes in Patients With Long-Term Exposure to Fibromyalgia Pain SO ARTHRITIS AND RHEUMATISM LA English DT Article ID SURFACE-BASED ANALYSIS; REGIONAL HOMOGENEITY; WIDESPREAD PAIN; CLINICAL PAIN; RESTING-STATE; CONNECTIVITY; DEPRESSION; SENSITIVITY; MECHANISMS; ABNORMALITIES AB ObjectiveThere is vast evidence to support the presence of brain aberrations in patients with fibromyalgia (FM), and it is possible that central plasticity is critical for the transition from acute to chronic pain. The aim of the present study was to investigate the relationship between brain structure and function in patients with FM. MethodsFunctional connectivity of the brain during application of intermittent pressure-pain stimuli and measures of brain structure were compared between 26 patients with FM and 13 age- and sex-matched healthy controls. Magnetic resonance imaging (MRI) was performed to obtain high-resolution anatomic images and functional MRI scans of the brain, which were used for measurements of pain-evoked brain activity. ResultsFM patients displayed a distinct overlap between decreased cortical thickness, decreased brain volumes, and decreased functional regional coherence in the rostral anterior cingulate cortex. The morphometric changes were more pronounced with longer exposure to FM pain. In addition, there was evidence of an association between structural and functional changes in the mesolimbic areas of the brain and the severity of comorbid depression symptoms in FM patients. ConclusionThe combined integration of structural and functional measures allowed for a unique characterization of the impact of FM pain on the brain. These data may lead to the identification of early structural and functional brain alterations in response to pain, which could be used to develop markers for predicting the development of FM and other pain disorders. C1 [Jensen, Karin B.; Srinivasan, Priti; Spaeth, Rosa; Kong, Jian] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. [Jensen, Karin B.; Srinivasan, Priti; Spaeth, Rosa; Kong, Jian] Athinoula A Martinos Ctr Biomed Imaging, Boston, MA USA. [Kong, Jian] Southwest Univ Nationalities, Chengdu, Peoples R China. [Kosek, Eva; Fransson, Peter; Ingvar, Martin] Karolinska Inst, Stockholm, Sweden. [Petzke, Frank] Univ Gottingen, D-37073 Gottingen, Germany. [Carville, Serena] UK Age Res Forum, London, England. [Marcus, Hanke] Univ Hosp Cologne, Cologne, Germany. [Williams, Steven C. R.] Kings Coll London, London, England. [Choy, Ernest] Cardiff Univ, Sch Med, Cardiff CF10 3AX, S Glam, Wales. [Vitton, Olivier] Pierre Fabre, Labege, France. [Gracely, Richard] Univ N Carolina, Chapel Hill, NC USA. RP Jensen, KB (reprint author), MGH Psychiat Neuroimaging, Bldg 120,2nd Ave, Charlestown, MA 02129 USA. EM karinj@nmr.mgh.harvard.edu RI Williams, Steve/D-6979-2011; Fransson, Peter/M-5679-2014; OI Williams, Steve/0000-0003-4299-1941; Fransson, Peter/0000-0002-1305-9875; Ingvar, Martin/0000-0002-9041-5714; Jensen, Karin/0000-0003-2521-3160 FU Pierre Fabre FX This study was performed in collaboration with the pharmaceutical company Pierre Fabre. The results are derived, in part, from a placebo-controlled drug intervention study (European Clinical Trials database no. 2004-004249-16) financed by Pierre Fabre, and they reviewed and approved the manuscript prior to submission. The authors independently collected the data, interpreted the results, and had the final decision to submit the manuscript for publication. Publication of this article was not contingent upon approval by Pierre Fabre. NR 54 TC 48 Z9 49 U1 0 U2 15 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0004-3591 EI 1529-0131 J9 ARTHRITIS RHEUM-US JI Arthritis Rheum. PD DEC PY 2013 VL 65 IS 12 BP 3293 EP 3303 DI 10.1002/art.38170 PG 11 WC Rheumatology SC Rheumatology GA 261VL UT WOS:000327692600033 PM 23982850 ER PT J AU Ainslie, G AF Ainslie, George TI Monotonous tasks require self-control because they interfere with endogenous reward SO BEHAVIORAL AND BRAIN SCIENCES LA English DT Editorial Material AB Self-control is a necessary component of subjective effort, but it depends only on farsighted motivation, with no additional, depletable resource. The aversiveness of boring tasks probably comes from their interference with endogenous reward, a new and potentially controversial concept. The self-control needed to stick with any kind of aversive experience increases as the values of the competing motives draw closer together. C1 [Ainslie, George] Univ Cape Town, Sch Econ, ZA-7701 Rondebosch, South Africa. [Ainslie, George] US Dept Vet Affairs, Coatesville, PA 19320 USA. RP Ainslie, G (reprint author), Univ Cape Town, Sch Econ, ZA-7701 Rondebosch, South Africa. EM George.Ainslie@va.gov NR 0 TC 0 Z9 0 U1 0 U2 1 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 32 AVENUE OF THE AMERICAS, NEW YORK, NY 10013-2473 USA SN 0140-525X EI 1469-1825 J9 BEHAV BRAIN SCI JI Behav. Brain Sci. PD DEC PY 2013 VL 36 IS 6 BP 679 EP 680 DI 10.1017/S0140525X13000915 PG 2 WC Psychology, Biological; Behavioral Sciences; Neurosciences SC Psychology; Behavioral Sciences; Neurosciences & Neurology GA 265IJ UT WOS:000327943800032 PM 24304776 ER PT J AU Kim, JK Choi, JW Yun, SH AF Kim, Jun Ki Choi, Jin Woo Yun, Seok H. TI Optical fine-needle imaging biopsy of the brain SO BIOMEDICAL OPTICS EXPRESS LA English DT Article ID ISCHEMIC-STROKE; CRANIAL WINDOW; CELL-DEATH; LONG-TERM; INFLAMMATION; DISEASE; BIOLOGY; TISSUE; MICE AB We demonstrate optical fine-needle imaging biopsy (FNIB), combining a fine needle (22 gauge) and a high-resolution side-view probe (350-mu m diameter) for minimally invasive interrogation of brain tissue in situ. We apply this technique to examine pathogenesis in murine models of neurodegeneration, brain metastasis of melanoma, and arterial occlusion, respectively. The demonstrated ability to obtain cellular images in the deep brain without craniotomy may be useful in the longitudinal studies of brain diseases. (C) 2013 Optical Society of America C1 [Kim, Jun Ki; Choi, Jin Woo; Yun, Seok H.] Harvard Univ, Sch Med, Boston, MA 02114 USA. [Kim, Jun Ki; Choi, Jin Woo; Yun, Seok H.] Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA. [Kim, Jun Ki; Yun, Seok H.] Korea Adv Inst Sci & Technol, WCU Grad Sch Nanosci & Technol, Taejon 305701, South Korea. RP Kim, JK (reprint author), Harvard Univ, Sch Med, 40 Blossom St, Boston, MA 02114 USA. EM syun@hms.harvard.edu FU National Institutes of Health [U54CA143837]; National Research Foundation of Korea [R31-2008-000-10071-0, NRF-2011-357-C00141] FX This work was supported by grants from National Institutes of Health (U54CA143837) and National Research Foundation of Korea (R31-2008-000-10071-0, NRF-2011-357-C00141). NR 28 TC 1 Z9 1 U1 0 U2 2 PU OPTICAL SOC AMER PI WASHINGTON PA 2010 MASSACHUSETTS AVE NW, WASHINGTON, DC 20036 USA SN 2156-7085 J9 BIOMED OPT EXPRESS JI Biomed. Opt. Express PD DEC 1 PY 2013 VL 4 IS 12 BP 2846 EP 2854 DI 10.1364/BOE.4.002846 PG 9 WC Biochemical Research Methods; Optics; Radiology, Nuclear Medicine & Medical Imaging SC Biochemistry & Molecular Biology; Optics; Radiology, Nuclear Medicine & Medical Imaging GA 267EA UT WOS:000328078300011 PM 24409385 ER PT J AU Carp, SA Sajjadi, AY Wanyo, CM Fang, QQ Specht, MC Schapira, L Moy, B Bardia, A Boas, DA Isakoff, SJ AF Carp, Stefan A. Sajjadi, Amir Y. Wanyo, Christy M. Fang, Qianqian Specht, Michelle C. Schapira, Lidia Moy, Beverly Bardia, Aditya Boas, David A. Isakoff, Steven J. TI Hemodynamic signature of breast cancer under fractional mammographic compression using a dynamic diffuse optical tomography system SO BIOMEDICAL OPTICS EXPRESS LA English DT Article ID POSITRON-EMISSION-TOMOGRAPHY; SOFT-TISSUE; BLOOD-FLOW; CARCINOMA; RECONSTRUCTION; PRESSURE; LESIONS; OXYGEN; TRIAL AB Near infrared dynamic diffuse optical tomography measurements of breast hemodynamics during fractional mammographic compression offer a novel contrast mechanism for detecting breast cancer and monitoring chemotherapy. Tissue viscoelastic relaxation during the compression period leads to a slow reduction in the compression force and reveals biomechanical and metabolic differences between healthy and lesion tissue. We measured both the absolute values and the temporal evolution of hemoglobin concentration during 25-35 N of compression for 22 stage II and III breast cancer patients scheduled to undergo neoadjuvant chemotherapy. 17 patients were included in the group analysis (average tumor size 3.2 cm, range: 1.3-5.7 cm). We observed a statistically significant differential decrease in total and oxy-hemoglobin, as well as in hemoglobin oxygen saturation in tumor areas vs. healthy tissue, as early as 30 seconds into the compression period. The hemodynamic contrast is likely driven by the higher tumor stiffness and different viscoelastic relaxation rate, as well as the higher tumor oxygen metabolism rate. (C) 2013 Optical Society of America C1 [Carp, Stefan A.; Sajjadi, Amir Y.; Wanyo, Christy M.; Fang, Qianqian; Boas, David A.] Massachusetts Gen Hosp, Opt Div, Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA 02129 USA. [Specht, Michelle C.; Schapira, Lidia; Moy, Beverly; Bardia, Aditya; Isakoff, Steven J.] Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA. [Carp, Stefan A.; Sajjadi, Amir Y.; Fang, Qianqian; Boas, David A.] Harvard Univ, Sch Med, Dept Radiol, Boston, MA 02129 USA. [Schapira, Lidia; Moy, Beverly; Bardia, Aditya; Isakoff, Steven J.] Harvard Univ, Sch Med, Dept Med, Boston, MA 02114 USA. [Specht, Michelle C.] Harvard Univ, Sch Med, Dept Surg, Boston, MA 02114 USA. RP Carp, SA (reprint author), Massachusetts Gen Hosp, Opt Div, Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA 02129 USA. EM carp@nmr.mgh.harvard.edu; asajjadi@nmr.mgh.harvard.edu FU NIH [R01-CA97305, R01-CA 142575, U54-CA105480, K99/R00EB011889]; Komen Breast Cancer Foundation [KG200021] FX We would like to acknowledge funding from NIH through grant R01-CA97305, R01-CA 142575, U54-CA105480, K99/R00EB011889; and from the Komen Breast Cancer Foundation grant KG200021. The authors would like to thank Ms. Nancy Nagda for coordinating patient scheduling and the staff of the MGH Center for Breast Cancer for their support. NR 30 TC 11 Z9 12 U1 0 U2 4 PU OPTICAL SOC AMER PI WASHINGTON PA 2010 MASSACHUSETTS AVE NW, WASHINGTON, DC 20036 USA SN 2156-7085 J9 BIOMED OPT EXPRESS JI Biomed. Opt. Express PD DEC 1 PY 2013 VL 4 IS 12 BP 2911 EP 2924 DI 10.1364/BOE.4.002911 PG 14 WC Biochemical Research Methods; Optics; Radiology, Nuclear Medicine & Medical Imaging SC Biochemistry & Molecular Biology; Optics; Radiology, Nuclear Medicine & Medical Imaging GA 267EA UT WOS:000328078300016 PM 24409390 ER PT J AU Tuomela, J Sandholm, J Kaakinen, M Patel, A Kauppila, JH Ilvesaro, J Chen, DQ Harris, KW Graves, D Selander, KS AF Tuomela, Johanna Sandholm, Jouko Kaakinen, Mika Patel, Ankita Kauppila, Joonas H. Ilvesaro, Joanna Chen, Dongquan Harris, Kevin W. Graves, David Selander, Katri S. TI DNA from dead cancer cells induces TLR9-mediated invasion and inflammation in living cancer cells SO BREAST CANCER RESEARCH AND TREATMENT LA English DT Article DE Triple-negative breast cancer; Toll-like receptor-9; Invasion; DNA; Inflammation ID TOLL-LIKE RECEPTOR-9; ANTIMICROBIAL PROTEIN HCAP18/LL-37; PUTATIVE GROWTH-FACTOR; BREAST-CANCER; RNA-SEQ; CELLULAR INVASION; PEPTIDE LL-37; WEIGHT-LOSS; IN-VITRO; EXPRESSION AB TLR9 is a cellular DNA-receptor, which is widely expressed in breast and other cancers. Although synthetic TLR9-ligands induce cancer cell invasion in vitro, the role of TLR9 in cancer pathophysiology has remained unclear. We show here that living cancer cells uptake DNA from chemotherapy-killed cancer cells. We discovered that such DNA induces TLR9- and cathepsin-mediated invasion in living cancer cells. To study whether this phenomenon contributes to treatment responses, triple-negative, human MDA-MB-231 breast cancer cells stably expressing control, or TLR9 siRNA were inoculated orthotopically into nude mice. The mice were treated with vehicle or doxorubicin. The tumor groups exhibited equal decreases in size in response to doxorubicin. However, while the weights of vehicle-treated mice were similar, mice bearing control siRNA tumors became significantly more cachectic in response to doxorubicin, as compared with similarly treated mice bearing TLR9 siRNA tumors, suggesting a TLR9-mediated inflammation at the site of the tumor. In conclusion, our findings propose that DNA released from chemotherapy-killed cancer cells has significant influence on TLR9-mediated biological effects in living cancer cells. Through these mechanisms, tumor TLR9 expression may affect treatment responses to chemotherapy. C1 [Tuomela, Johanna; Sandholm, Jouko; Ilvesaro, Joanna; Harris, Kevin W.; Selander, Katri S.] Univ Alabama Birmingham, Dept Med, Div Hematol Oncol, Birmingham, AL 35294 USA. [Tuomela, Johanna; Sandholm, Jouko; Ilvesaro, Joanna; Harris, Kevin W.; Graves, David; Selander, Katri S.] Univ Alabama Birmingham, Ctr Comprehens Canc, Birmingham, AL 35294 USA. [Kaakinen, Mika; Kauppila, Joonas H.] Univ Oulu, Dept Anat & Cell Biol, Oulu, Finland. [Kaakinen, Mika] Univ Oulu, Bioctr Oulu, Oulu, Finland. [Patel, Ankita; Graves, David] Univ Alabama Birmingham, Dept Chem, Birmingham, AL 35294 USA. [Kauppila, Joonas H.] Oulu Univ Hosp, Dept Surg, Oulu, Finland. [Kauppila, Joonas H.] Univ Oulu, Dept Pathol, Oulu, Finland. [Chen, Dongquan] Univ Alabama Birmingham, Dept Med, Div Prevent Med, Birmingham, AL 35294 USA. [Harris, Kevin W.] Birmingham Vet Affairs Med Ctr, Birmingham, AL USA. RP Selander, KS (reprint author), Univ Alabama Birmingham, Dept Med, Div Hematol Oncol, SHEL 514,1825 Univ Blvd, Birmingham, AL 35294 USA. EM Katriselander@uabmc.edu RI Kauppila, Joonas/P-1363-2015; OI Kauppila, Joonas/0000-0001-6740-3726; Tuomela, Johanna/0000-0003-4390-4563 FU Department of Defense [W81XWH-10-1-0308]; Elsa U. Pardee Foundation; Cancer Foundation of Northern Ostrobotnia; Oulu University Scholarship Foundation; Finnish Medical Foundation; Maud Kuistila Memorial Foundation; Orion-Farmos Research Foundation; Finnish Cultural Foundation; Comprehensive Cancer Center Core [CA13148]; CCC [P30CA13148-38] FX Ms. Christine Pressey is acknowledged for skillful assistance with the qRT-PCR assays. This work was supported by a Grant from the Department of Defense (W81XWH-10-1-0308, K.S.S & D.G), Elsa U. Pardee Foundation (K.S.S), Cancer Foundation of Northern Ostrobotnia, Oulu University Scholarship Foundation, and Finnish Medical Foundation (J.H.K), Maud Kuistila Memorial Foundation (J.T), Orion-Farmos Research Foundation (J.T.), and Finnish Cultural Foundation (J.T). The body composition measurement services were provided by the UAB Small Animal Phenotyping Core supported by NIH P30AR046031, P30DK056336, and P60DK079626. The RNA-seq analyses were provided by the Heflin Genomics Core Facility and the Comprehensive Cancer Center Core Grant CA13148, the proteomics analysis was provided by the UAB proteomics shared facility, and the CCC Grant Number P30CA13148-38. NR 57 TC 12 Z9 12 U1 0 U2 10 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0167-6806 EI 1573-7217 J9 BREAST CANCER RES TR JI Breast Cancer Res. Treat. PD DEC PY 2013 VL 142 IS 3 BP 477 EP 487 DI 10.1007/s10549-013-2762-0 PG 11 WC Oncology SC Oncology GA 269CP UT WOS:000328218500002 PM 24212717 ER PT J AU Pitman, MB Centeno, BA Genevay, M Fonseca, R Mino-Kenudson, M AF Pitman, Martha B. Centeno, Barbara A. Genevay, Muriel Fonseca, Ricardo Mino-Kenudson, Mari TI Grading Epithelial Atypia in Endoscopic Ultrasound-Guided Fine-Needle Aspiration of Intraductal Papillary Mucinous Neoplasms SO CANCER CYTOPATHOLOGY LA English DT Article DE pancreas; intraductal papillary mucinous neoplasm; cytology; endoscopic ultrasound; fine-needle aspiration; variability; interobserver; epithelial atypia ID CYST FLUID ANALYSIS; INTERNATIONAL CONSENSUS GUIDELINES; INCIDENTAL PANCREATIC CYSTS; CARCINOEMBRYONIC ANTIGEN; DIFFERENTIAL-DIAGNOSIS; CYTOLOGIC EXAMINATION; RELATIVE ACCURACY; ADDS VALUE; MALIGNANCY; MANAGEMENT AB BACKGROUNDPreoperative cytological analysis of cyst fluid from intraductal papillary mucinous neoplasms (IPMN) contributes to risk stratification for malignancy. To the authors' knowledge, agreement among pathologists in grading epithelial atypia in IPMN cyst fluids has not been studied to date. METHODSBlinded to the histological grade, 4 observers independently graded 60 cell groups from endoscopic ultrasound-guided fine-needle aspiration samples of 24 IPMNs of various grades as either 0 (nonlesional), 1 (low-grade dysplasia), 2 (intermediate-grade dysplasia [IGD]), 3 (high-grade dysplasia), or 4 (invasive adenocarcinoma). The percentage of agreement and the kappa (k) coefficient were calculated for these 5 tiers and a reduced 2-tier grouping (low-grade [LG] [0-1 and 0-2] vs high-grade [HG] [2-4 and 3-4]). Agreement between the 2 most experienced reviewers established a consensus diagnosis that was compared with the histological grade. RESULTSAmong the 4 reviewers there was poor agreement using a 5-tiered system and fair agreement with the 2-tiered system. LG and HG grouping of IGD did not appear to greatly affect agreement, with 54% agreement for grouping 0 to 2 and 3 to 4 (k=0.45) and 52% agreement for grouping 0 to 1 and 2 to 4 (k=0.44). The 2 most experienced reviewers had 87% agreement for the 0 to 2 and 3 to 4 grouping (k=0.74) and 88% for the 0 to 1 and 2 to 4 grouping (k=0.71). HG atypia on cytology with IGD grouped as LG yielded a sensitivity of 82%, with a specificity of 70% for detecting a cyst with HG morphology. CONCLUSIONSGrading cellular atypia in cyst fluids requires experience, which results in very good interobserver agreement and good correlation with histology using a 2-tiered LG and HG grading system and IGD classified as LG. Cancer (Cancer Cytopathol) 2013;121:729-736. (c) 2013 American Cancer Society. C1 [Pitman, Martha B.; Mino-Kenudson, Mari] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Pathol, Boston, MA 02114 USA. [Centeno, Barbara A.] Univ S Florida, Coll Med, H Lee Moffitt Canc Ctr & Res Inst, Dept Pathol, Tampa, FL 33612 USA. [Genevay, Muriel] Hosp Clin Pathol, Geneva, Switzerland. [Fonseca, Ricardo] Lisboa Francisco Gentil Portuguese Inst Oncol, Lisbon, Portugal. RP Pitman, MB (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Pathol, 55 Fruit St, Boston, MA 02114 USA. EM mpitman@partners.org NR 56 TC 20 Z9 20 U1 0 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1934-662X EI 1934-6638 J9 CANCER CYTOPATHOL JI Cancer Cytopathol. PD DEC PY 2013 VL 121 IS 12 BP 729 EP 736 DI 10.1002/cncy.21334 PG 8 WC Oncology; Pathology SC Oncology; Pathology GA 269HQ UT WOS:000328232800008 PM 23881863 ER PT J AU Klempner, SJ Myers, AP Cantley, LC AF Klempner, Samuel J. Myers, Andrea P. Cantley, Lewis C. TI What a Tangled Web We Weave: Emerging Resistance Mechanisms to Inhibition of the Phosphoinositide 3-Kinase Pathway SO CANCER DISCOVERY LA English DT Review ID ACUTE LYMPHOBLASTIC-LEUKEMIA; TYROSINE KINASE INHIBITOR; METASTATIC BREAST-CANCER; RIBOSOME ENTRY SITES; INITIATION-FACTOR 4E; MESSENGER-RNA; C-MYC; TRANSLATION INITIATION; PROSTATE-CANCER; COLORECTAL-CANCER AB The phosphoinositide 3-kinase (PI3K) pathway is one of the most frequently mutated pathways in cancer, and is actively being pursued as a therapeutic target. Despite the importance of the PI3K pathway in cancer, durable responses to PI3K pathway-targeted therapies are uncommon with monotherapy. Several in vitro and xenograft models have elucidated compensatory signaling and genomic changes which may limit the therapeutic effectiveness of PI3K inhibitors in the clinic. Future clinical trials with prospective evaluation of tumor signaling and genomic changes are likely to identify novel resistance mechanisms as well as subsets of patients who may derive maximal benefit from PI3K pathway inhibitors. Significance: There are multiple ongoing clinical trials targeting the PI3K pathway members in several malignancies. This review summarizes the known mechanisms of resistance to targeting the PI3K pathway. Understanding of resistance mechanisms will help to inform more rational clinical trial design to optimize the clinical impact of targeting the PI3K pathway in cancer. (C) 2013 AACR. C1 [Klempner, Samuel J.] Univ Calif Irvine, Med Ctr, Div Hematol Oncol, Orange, CA USA. [Myers, Andrea P.; Cantley, Lewis C.] Beth Israel Deaconess Med Ctr, Div Signal Transduct, New York, NY 10003 USA. [Myers, Andrea P.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Cantley, Lewis C.] Weill Cornell Med Coll, Dept Med, New York, NY 10065 USA. RP Cantley, LC (reprint author), Weill Cornell Med Coll, 1300 York Ave,Box 8, New York, NY 10065 USA. EM LCantley@med.cornell.edu RI Cantley, Lewis/D-1800-2014 OI Cantley, Lewis/0000-0002-1298-7653 FU NIH [GM041890]; Stand Up To Cancer Dream Team Translational Research Grant; program of the Entertainment Industry Foundation [SU2C-AACR-DT0209]; American Association for Cancer Research FX L.C. Cantley is supported by NIH Grant GM041890, Stand Up To Cancer Dream Team Translational Research Grant, a program of the Entertainment Industry Foundation (SU2C-AACR-DT0209), and the American Association for Cancer Research. NR 107 TC 49 Z9 51 U1 1 U2 22 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 DEC PY 2013 VL 3 IS 12 BP 1345 EP 1354 DI 10.1158/2159-8290.CD-13-0063 PG 10 WC Oncology SC Oncology GA 269QR UT WOS:000328257500021 PM 24265156 ER PT J AU Akbay, EA Koyama, S Carretero, J Altabef, A Tchaicha, JH Christensen, CL Mikse, OR Cherniack, AD Beauchamp, EM Pugh, TJ Wilkerson, MD Fecci, PE Butaney, M Reibel, JB Soucheray, M Cohoon, TJ Janne, PA Meyerson, M Hayes, DN Shapiro, GI Shimamura, T Sholl, LM Rodig, SJ Freeman, GJ Hammerman, PS Dranoff, G Wong, KK AF Akbay, Esra A. Koyama, Shohei Carretero, Julian Altabef, Abigail Tchaicha, Jeremy H. Christensen, Camilla L. Mikse, Oliver R. Cherniack, Andrew D. Beauchamp, Ellen M. Pugh, Trevor J. Wilkerson, Matthew D. Fecci, Peter E. Butaney, Mohit Reibel, Jacob B. Soucheray, Margaret Cohoon, Travis J. Janne, Pasi A. Meyerson, Matthew Hayes, D. Neil Shapiro, Geoffrey I. Shimamura, Takeshi Sholl, Lynette M. Rodig, Scott J. Freeman, Gordon J. Hammerman, Peter S. Dranoff, Glenn Wong, Kwok-Kin TI Activation of the PD-1 Pathway Contributes to Immune Escape in EGFR-Driven Lung Tumors SO CANCER DISCOVERY LA English DT Article ID DEPENDENT MECHANISM; KINASE INHIBITORS; T-CELLS; CANCER; EXPRESSION; ADENOCARCINOMA; SENSITIVITY; GROWTH; AUTOIMMUNITY; MUTATIONS AB The success in lung cancer therapy with programmed death (PD)-1 blockade suggests that immune escape mechanisms contribute to lung tumor pathogenesis. We identified a correlation between EGF receptor (EGFR) pathway activation and a signature of immunosuppression manifested by upregulation of PD-1, PD-L1, CTL antigen-4 (CTLA-4), and multiple tumor-promoting inflammatory cytokines. We observed decreased CTLs and increased markers of T-cell exhaustion in mouse models of EGFR-driven lung cancer. PD-1 antibody blockade improved the survival of mice with EGFR-driven adenocarcinomas by enhancing effector T-cell function and lowering the levels of tumor-promoting cytokines. Expression of mutant EGFR in bronchial epithelial cells induced PD-L1, and PD-L1 expression was reduced by EGFR inhibitors in non-small cell lung cancer cell lines with activated EGFR. These data suggest that oncogenic EGFR signaling remodels the tumor microenvironment to trigger immune escape and mechanistically link treatment response to PD-1 inhibition. SIGNIFICANCE: We show that autochthonous EGFR-driven lung tumors inhibit antitumor immunity by activating the PD-1/PD-L1 pathway to suppress T-cell function and increase levels of proinflammatory cytokines. These findings indicate that EGFR functions as an oncogene through non-cell-autonomous mechanisms and raise the possibility that other oncogenes may drive immune escape. (C) 2013 AACR. C1 [Akbay, Esra A.; Altabef, Abigail; Tchaicha, Jeremy H.; Christensen, Camilla L.; Mikse, Oliver R.; Beauchamp, Ellen M.; Butaney, Mohit; Reibel, Jacob B.; Cohoon, Travis J.; Janne, Pasi A.; Meyerson, Matthew; Shapiro, Geoffrey I.; Hammerman, Peter S.; Wong, Kwok-Kin] Dana Farber Canc Inst, Dept Med, Boston, MA 02115 USA. [Koyama, Shohei; Dranoff, Glenn] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Koyama, Shohei; Dranoff, Glenn] Dana Farber Canc Inst, Canc Vaccine Ctr, Boston, MA 02115 USA. [Akbay, Esra A.; Koyama, Shohei; Tchaicha, Jeremy H.; Christensen, Camilla L.; Mikse, Oliver R.; Beauchamp, Ellen M.; Janne, Pasi A.; Meyerson, Matthew; Shapiro, Geoffrey I.; Freeman, Gordon J.; Hammerman, Peter S.; Dranoff, Glenn; Wong, Kwok-Kin] Harvard Univ, Sch Med, Cambridge, MA 02138 USA. [Fecci, Peter E.] Massachusetts Gen Hosp, Dept Neurosurg, Boston, MA 02114 USA. [Sholl, Lynette M.; Rodig, Scott J.] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. [Cherniack, Andrew D.; Pugh, Trevor J.; Meyerson, Matthew] Broad Inst, Cambridge, MA USA. [Wilkerson, Matthew D.; Hayes, D. Neil] Univ N Carolina, UNC Lineberger Comprehens Canc Ctr, Chapel Hill, NC USA. [Soucheray, Margaret; Shimamura, Takeshi] Loyola Univ, Dept Mol Pharmacol & Therapeut, Inst Oncol, Chicago, IL 60611 USA. [Carretero, Julian] Univ Valencia, Dept Physiol, Valencia, Spain. RP Wong, KK (reprint author), Dana Farber Canc Inst, 450 Brookline Ave,HIM243, Boston, MA 02115 USA. EM peter_hammerman@dfci.harvard.edu; glenn_dranoff@dfci.harvard.edu; kwong1@partners.org RI Carretero, Julian/N-5214-2014; OI Carretero, Julian/0000-0001-7269-8506; wong, kwok kin/0000-0001-6323-235X; Koyama, Shohei/0000-0002-6897-9417 FU NIH [CA122794, CA140594, CA163896, CA166480, CA154303, P50CA090578]; United against Lung Cancer, American Lung Association; Susan Spooner Research Fund [NCI R01CA143083]; Leukemia & Lymphoma Society; Research Foundation for the Treatment of Ovarian Cancer; Margaret A. Cunningham Immune Mechanisms in Cancer Research Fellowship Award; Immune Oncology Center of the Dana-Farber Cancer Institute [U54CA163125, NCI 1K08CA163677] FX This work was supported by the NIH (CA122794, CA140594, CA163896, CA166480, CA154303, and Lung SPORE P50CA090578), United against Lung Cancer, American Lung Association, and Susan Spooner Research Fund to K.-K. Wong; NCI R01CA143083, the Leukemia & Lymphoma Society, and the Research Foundation for the Treatment of Ovarian Cancer to G. Dranoff; Margaret A. Cunningham Immune Mechanisms in Cancer Research Fellowship Award to S. Koyama; support from the Immune Oncology Center of the Dana-Farber Cancer Institute to S.J. Rodig; U54CA163125 grant to G.J. Freeman; and NCI 1K08CA163677 to P.S. Hammerman. NR 37 TC 216 Z9 228 U1 7 U2 39 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 DEC PY 2013 VL 3 IS 12 BP 1355 EP 1363 DI 10.1158/2159-8290.CD-13-0310 PG 9 WC Oncology SC Oncology GA 269QR UT WOS:000328257500022 PM 24078774 ER PT J AU O'Connell, MP Marchbank, K Webster, MR Valiga, AA Kaur, A Vultur, A Li, L Herlyn, M Villanueva, J Liu, Q Yin, XF Widura, S Nelson, J Ruiz, N Camilli, TC Indig, FE Flaherty, KT Wargo, JA Frederick, DT Cooper, ZA Nair, S Amaravadi, RK Schuchter, LM Karakousis, GC Xu, W Xu, XW Weeraratna, AT AF O'Connell, Michael P. Marchbank, Katie Webster, Marie R. Valiga, Alexander A. Kaur, Amanpreet Vultur, Adina Li, Ling Herlyn, Meenhard Villanueva, Jessie Liu, Qin Yin, Xiangfan Widura, Sandy Nelson, Janelle Ruiz, Nivia Camilli, Tura C. Indig, Fred E. Flaherty, Keith T. Wargo, Jennifer A. Frederick, Dennie T. Cooper, Zachary A. Nair, Suresh Amaravadi, Ravi K. Schuchter, Lynn M. Karakousis, Giorgos C. Xu, Wei Xu, Xiaowei Weeraratna, Ashani T. TI Hypoxia Induces Phenotypic Plasticity and Therapy Resistance in Melanoma via the Tyrosine Kinase Receptors ROR1 and ROR2 SO CANCER DISCOVERY LA English DT Article ID UBIQUITIN LIGASE SIAH2; BETA-CATENIN; MESENCHYMAL TRANSITION; MALIGNANT-MELANOMA; EXPRESSION; METASTASIS; CELLS; INVASION; INHIBITION; PATHWAY AB An emerging concept in melanoma biology is that of dynamic, adaptive phenotype switching, where cells switch from a highly proliferative, poorly invasive phenotype to a highly invasive, less proliferative one. This switch may hold significant implications not just for metastasis, but also for therapy resistance. We demonstrate that phenotype switching and subsequent resistance can be guided by changes in expression of receptors involved in the noncanonical Wnt5A signaling pathway, ROR1 and ROR2. ROR1 and ROR2 are inversely expressed in melanomas and negatively regulate each other. Furthermore, hypoxia initiates a shift of ROR1-positive melanomas to a more invasive, ROR2-positive phenotype. Notably, this receptor switch induces a 10-fold decrease in sensitivity to BRAF inhibitors. In patients with melanoma treated with the BRAF inhibitor vemurafenib, Wnt5A expression correlates with clinical response and therapy resistance. These data highlight the fact that mechanisms that guide metastatic progression may be linked to those that mediate therapy resistance. SIGNIFICANCE: These data show for the first time that a single signaling pathway, the Wnt signaling pathway, can effectively guide the phenotypic plasticity of tumor cells, when primed to do so by a hypoxic microenvironment. Importantly, this increased Wnt5A signaling can give rise to a subpopulation of highly invasive cells that are intrinsically less sensitive to novel therapies for melanoma, and targeting the Wnt5A/ROR2 axis could improve the efficacy and duration of response for patients with melanoma on vemurafenib. (C) 2013 AACR. C1 [O'Connell, Michael P.; Marchbank, Katie; Webster, Marie R.; Valiga, Alexander A.; Kaur, Amanpreet; Vultur, Adina; Li, Ling; Herlyn, Meenhard; Widura, Sandy; Nelson, Janelle; Ruiz, Nivia; Weeraratna, Ashani T.] Wistar Inst Anat & Biol, Tumor Microenvironm & Metastasis Program, Philadelphia, PA 19104 USA. [Villanueva, Jessie; Liu, Qin; Yin, Xiangfan] Wistar Inst Anat & Biol, Mol & Cellular Oncogenesis Program, Philadelphia, PA 19104 USA. [Amaravadi, Ravi K.; Schuchter, Lynn M.; Karakousis, Giorgos C.; Xu, Wei; Xu, Xiaowei] Univ Penn, Abramson Canc Ctr, Philadelphia, PA 19104 USA. [Nair, Suresh] Lehigh Valley Hlth Network, Allentown, PA USA. [Camilli, Tura C.; Indig, Fred E.] NIA, NIH, Baltimore, MD 21224 USA. [Flaherty, Keith T.; Wargo, Jennifer A.; Frederick, Dennie T.; Cooper, Zachary A.] Dana Farber Harvard Canc Ctr, Boston, MA USA. RP Weeraratna, AT (reprint author), Wistar Inst Anat & Biol, Tumor Microenvironm & Metastasis Program, 3601 Spruce St, Philadelphia, PA 19104 USA. EM aweeraratna@wistar.org OI Cooper, Zachary/0000-0003-1059-0940 FU National Institute on Aging Intramural Research Program; PA Department of Health (CURE) funding; Joanna M Nicolay Foundation; PHS [2 T32 CA 9171-36, 1K23CA120862, CA25874] FX This work was supported in part by funds from the National Institute on Aging Intramural Research Program (to F.E. Indig and T.C. Camilli), PA Department of Health (CURE) funding (to A.T. Weeraratna, M.P. O'Connell, K. Marchbank, A. Vultur, N. Ruiz, Q. Liu, X. Yin, and S. Widura), and the Joanna M Nicolay Foundation (to A. Kaur). Additional support for other authors comes from PHS 2 T32 CA 9171-36 (to M. R. Webster), 1K23CA120862 (to R.K. Amaravadi), and CA25874 (to M. Herlyn). NR 51 TC 64 Z9 65 U1 0 U2 16 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 DEC PY 2013 VL 3 IS 12 BP 1378 EP 1393 DI 10.1158/2159-8290.CD-13-0005 PG 16 WC Oncology SC Oncology GA 269QR UT WOS:000328257500024 PM 24104062 ER PT J AU De Los Angeles, A Daley, GQ AF De Los Angeles, Alejandro Daley, George Q. TI A chemical logic for reprogramming to pluripotency SO CELL RESEARCH LA English DT Editorial Material ID MOUSE SOMATIC-CELLS; STEM-CELLS; GENERATION; OCT4 AB Pluripotency can be experimentally induced from somatic cells by nuclear transfer, fusion with embryonic stem cells, or ectopic transcription factor induction, but attempts to recapitulate this process by chemical means alone have previously failed. In a recent paper published in Science, Hou et al. pursue a rational, albeit laborious approach to identify cocktails of small molecules whose treatment restores pluripotency in adult somatic cells. C1 [De Los Angeles, Alejandro; Daley, George Q.] Childrens Hosp, Howard Hughes Med Inst, Stem Cell Transplantat Program, Div Pediat Hematol Oncol,Manton Ctr Orphan Dis Re, Boston, MA 02115 USA. [De Los Angeles, Alejandro; Daley, George Q.] Dana Farber Canc Inst, Boston, MA 02115 USA. [De Los Angeles, Alejandro; Daley, George Q.] Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA. [De Los Angeles, Alejandro; Daley, George Q.] Broad Inst, Boston, MA 02115 USA. [De Los Angeles, Alejandro; Daley, George Q.] Harvard Stem Cell Inst, Boston, MA 02115 USA. RP Daley, GQ (reprint author), Childrens Hosp, Howard Hughes Med Inst, Stem Cell Transplantat Program, Div Pediat Hematol Oncol,Manton Ctr Orphan Dis Re, Boston, MA 02115 USA. EM george.daley@childrens.harvard.edu NR 13 TC 0 Z9 0 U1 1 U2 13 PU INST BIOCHEMISTRY & CELL BIOLOGY PI SHANGHAI PA SIBS, CAS, 319 YUEYANG ROAD, SHANGHAI, 200031, PEOPLES R CHINA SN 1001-0602 EI 1748-7838 J9 CELL RES JI Cell Res. PD DEC PY 2013 VL 23 IS 12 BP 1337 EP 1338 DI 10.1038/cr.2013.119 PG 2 WC Cell Biology SC Cell Biology GA 267CE UT WOS:000328072600002 PM 23979017 ER PT J AU Bardia, A Baselga, J AF Bardia, Aditya Baselga, Jose TI Neoadjuvant Therapy as a Platform for Drug Development and Approval in Breast Cancer SO CLINICAL CANCER RESEARCH LA English DT Article ID SURGICAL ADJUVANT BREAST; PREOPERATIVE CHEMOTHERAPY; TUMOR-CELLS; OPEN-LABEL; PHASE-II; TRASTUZUMAB; LAPATINIB; MULTICENTER; TRIALS; BEVACIZUMAB AB The traditional drug development process in breast cancer based on large phase III studies has serious limitations and needs a major overhaul. Searching for new approaches, the testing of novel agents in the preoperative (neoadjuvant) setting approach offers a potentially rapid and efficient strategy for drug development utilizing pathologic complete response (path CR), a surrogate marker for survival, as the primary endpoint. In addition, neoadjuvant studies allow the assessment of drug effects on the target (pharmacodynamic response) and the development of predictive biomarkers of response. Molecular profiling of the residual tumor in the surgical specimen may also provide insights into actionable mechanisms of resistance. Recognizing the potential of neoadjuvant trials for drug development, the U. S. Food and Drug Administration (FDA) recently announced consideration of neoadjuvant trials for accelerated drug approval in early breast cancer, particularly for tumors with high risk of recurrence and unfavorable prognosis, and provided accelerated approval to neoadjuvant pertuzumab in September 2013. The FDA has emphasized that while improvement in path CR could be utilized for "accelerated" approval, improvement in survival will still need to be demonstrated for "regular" approval. Key considerations in conduct of such neoadjuvant drug development trials include (i) study design such as utilization of biomarker stratified design to evaluate a biomarker that could enrich response, (ii) definition of path CR, (iii) distribution of factors that influence path CR between the treatment arms, (iv) prespecified plan for follow-up to obtain data on survival, and (v) safety as it involves a patient population with curable disease. In the years to come, we anticipate an increase in the number of neoadjuvant trials testing novel therapies that hopefully will open a new path in bringing efficacious new therapies to patients with breast cancer. Clin Cancer Res; 19(23); 6360-70. (C) 2013 AACR. C1 [Bardia, Aditya] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Canc, Boston, MA USA. [Baselga, Jose] Mem Sloan Kettering Canc Ctr, New York, NY 10065 USA. RP Baselga, J (reprint author), Mem Sloan Kettering Canc Ctr, 1275 York Ave,Suite M2001, New York, NY 10065 USA. EM baselgaj@mskcc.org NR 50 TC 29 Z9 30 U1 0 U2 7 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 EI 1557-3265 J9 CLIN CANCER RES JI Clin. Cancer Res. PD DEC 1 PY 2013 VL 19 IS 23 BP 6360 EP 6370 DI 10.1158/1078-0432.CCR-13-0916 PG 11 WC Oncology SC Oncology GA 263PE UT WOS:000327819700006 PM 24298066 ER PT J AU Lin, NU Amiri-Kordestani, L Palmieri, D Liewehr, DJ Steeg, PS AF Lin, Nancy U. Amiri-Kordestani, Laleh Palmieri, Diane Liewehr, David J. Steeg, Patricia S. TI CNS Metastases in Breast Cancer: Old Challenge, New Frontiers SO CLINICAL CANCER RESEARCH LA English DT Article ID NERVOUS-SYSTEM METASTASES; POSITRON-EMISSION-TOMOGRAPHY; BLOOD-BRAIN-BARRIER; LAPATINIB PLUS CAPECITABINE; TYROSINE KINASE INHIBITOR; ADVANCED SOLID TUMORS; PHASE-II; INTRATHECAL TRASTUZUMAB; CLINICAL-OUTCOMES; MENINGEAL CARCINOMATOSIS AB Despite major therapeutic advances in the management of patients with breast cancer, central nervous system (CNS) metastases remain an intractable problem, particularly in patients with metastatic HER2-positive and triple-negative breast cancer. As systemic therapies to treat extracranial disease improve, some patients are surviving longer, and the frequency of CNS involvement seems to be increasing. Furthermore, in the early-stage setting, the CNS remains a potential sanctuary site for relapse. This review highlights advances in the development of biologically relevant preclinical models, including the development of brain-tropic cell lines for testing of agents to prevent and treat brain metastases, and summarizes our current understanding of the biology of CNS relapse. From a clinical perspective, a variety of therapeutic approaches are discussed, including methods to improve drug delivery, novel cytotoxic agents, and targeted therapies. Challenges in current trial design and endpoints are reviewed. Finally, we discuss promising new directions, including novel trial designs, correlative imaging techniques, and enhanced translational opportunities. Clin Cancer Res; 19(23); 6404-18. (C) 2013 AACR. C1 [Lin, Nancy U.] Dana Farber Canc Inst, Boston, MA 02215 USA. [Amiri-Kordestani, Laleh] NCI, Med Oncol Branch, Ctr Canc Res, Bethesda, MD 20892 USA. [Palmieri, Diane; Steeg, Patricia S.] NCI, Womens Canc Sect, Lab Mol Pharmacol, Bethesda, MD 20892 USA. [Liewehr, David J.] NCI, Biostat & Data Management Sect, Ctr Canc Res, Bethesda, MD 20892 USA. RP Lin, NU (reprint author), Dana Farber Canc Inst, 450 Brookline Ave, Boston, MA 02215 USA. EM nlin@partners.org RI Palmieri, Diane/B-4258-2015 FU Intramural Program of the National Cancer Institute; DOD Breast Cancer Research Program [W81XWH-062-0033]; Breast Cancer Research Foundation FX The statistical assistance of S. Steinberg, Biostatistics and Data Management Section, Center for Cancer Research, National Cancer Institute, Bethesda, MD, is appreciated. The authors thank the following individuals for providing figures: National Cancer Institute Molecular Imaging Program Staff (M. Liza Lindenberg, MD, Esther Mena Gonzalex, PhD, Peter L. Choyke, MD, Karen A. Kurdziel, MD), Kyrre E. Emblem, PhD (Massachusetts General Hospital, Boston, MA), Elizabeth Gerstner, MD (Massachusetts General Hospital, Boston, MA), and Professor E. G. Elisabeth de Vries, MD, PhD (University Medical Centre, Groningen, the Netherlands). This work was funded, in part, by the Intramural Program of the National Cancer Institute, DOD Breast Cancer Research Program grant W81XWH-062-0033 (P.S. Steeg, D. Palmieri), and the Breast Cancer Research Foundation (N.U. Lin). NR 108 TC 42 Z9 43 U1 1 U2 18 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 DEC 1 PY 2013 VL 19 IS 23 BP 6404 EP 6418 DI 10.1158/1078-0432.CCR-13-0790 PG 15 WC Oncology SC Oncology GA 263PE UT WOS:000327819700011 PM 24298071 ER PT J AU Pyo, J Kim, KW Jacene, HA Sakellis, CG Brown, JR Van den Abbeele, AD AF Pyo, Junhee Kim, Kyung Won Jacene, Heather A. Sakellis, Christopher G. Brown, Jennifer R. Van den Abbeele, Annick D. TI End-Therapy Positron Emission Tomography for Treatment Response Assessment in Follicular Lymphoma: A Systematic Review and Meta-analysis SO CLINICAL CANCER RESEARCH LA English DT Review ID NON-HODGKINS-LYMPHOMA; FOLLOW-UP; FDG-PET; Y-90-IBRITUMOMAB TIUXETAN; MALIGNANT-LYMPHOMA; PREDICTIVE-VALUE; F-18-FDG PET/CT; DES LYMPHOMES; RADIOIMMUNOTHERAPY; MULTICENTER AB Purpose: Use of 2[F-18]fluoro-2-deoxy-D-glucose positron emission tomography (FDG-PET) in post-chemotherapy response assessment in follicular lymphoma is still a controversial issue. Here, we conducted the first systematic review and meta-analysis to determine the predictive value of FDG-PET in predicting outcome after chemotherapy of follicular lymphoma. Experimental Design: Comprehensive literature search in Ovid-MEDLINE and EMBASE databases was performed to identify studies which evaluate predictive value of end-therapy PET and/or computed tomography (CT) in patients with follicular lymphoma. To quantitatively compare the predictive value of PET and CT, pooled hazard ratios (HRs) comparing progression-free survival (PFS) between patients with positive and negative results were adopted as the primary indicators for meta-analysis. To explore the efficiency in determining complete remission (CR), pooled CR rates of PET-and CT-based response criteria were calculated. Pooling of these parameters was based on the random-effects model. Results: Review of 285 candidate articles identified eight eligible articles with a total of 577 patients for qualitative review and meta-analysis. The pooled HRs of end-therapy PET and CT were 5.1 [95% confidence interval (CI), 3.7-7.2] and 2.6 (95% CI, 1.2-5.8), respectively, which implies that PET is more predictive of PFS after chemotherapy than CT. The pooled CR rates of PET-and CT-based response criteria were 75% (95% CI, 70-79%) and 63% (95% CI, 53-73%), respectively, which implies that PET is more efficient in distinguishing CR (without residual disease) from other states with residual disease. In addition, qualitative systematic review indicates the same findings. Conclusions: Consistent evidence favoring PET-based treatment assessment should be considered in the management of patients with follicular lymphoma. Clin Cancer Res; 19(23); 6566-77. (C) 2013 AACR. C1 [Pyo, Junhee] Tufts Med Ctr, Inst Clin Res & Hlth Policy Studies, Ctr Evaluat Value & Risk Hlth, Boston, MA USA. [Kim, Kyung Won; Jacene, Heather A.; Sakellis, Christopher G.; Van den Abbeele, Annick D.] Dana Farber Canc Inst, Dept Imaging, Boston, MA 02115 USA. [Brown, Jennifer R.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Kim, Kyung Won; Jacene, Heather A.; Sakellis, Christopher G.; Van den Abbeele, Annick D.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Radiol, Boston, MA 02115 USA. [Kim, Kyung Won] Univ Ulsan, Coll Med, Asan Med Ctr, Dept Radiol, Seoul 138736, South Korea. [Kim, Kyung Won] Univ Ulsan, Coll Med, Asan Med Ctr, Res Inst Radiol, Seoul 138736, South Korea. RP Kim, KW (reprint author), Univ Ulsan, Coll Med, Asan Med Ctr, Dept Radiol, Pungnab 2 Dong, Seoul 138736, South Korea. EM medimash@gmail.com NR 34 TC 6 Z9 6 U1 1 U2 10 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 DEC 1 PY 2013 VL 19 IS 23 BP 6566 EP 6577 DI 10.1158/1078-0432.CCR-13-1511 PG 12 WC Oncology SC Oncology GA 263PE UT WOS:000327819700025 PM 24052020 ER PT J AU Go, RS Lee, SJ Shin, D Callister, SM Jobe, DA Conry, RM Tarhini, AA Kirkwood, JM AF Go, Ronald S. Lee, Sandra J. Shin, Donghoon Callister, Steven M. Jobe, Dean A. Conry, Robert M. Tarhini, Ahmad A. Kirkwood, John M. TI ECOG Phase II Trial of Graded-Dose Peginterferon alpha-2b in Patients with Metastatic Melanoma Overexpressing Basic Fibroblast Growth Factor (E2602) SO CLINICAL CANCER RESEARCH LA English DT Article ID PLUS PEGYLATED INTERFERON-ALPHA-2B; STAGE-IV MELANOMA; MALIGNANT-MELANOMA; FACTOR RECEPTORS; THERAPY; TUMOR; ANGIOGENESIS; BEVACIZUMAB; INHIBITION; EXPRESSION AB Purpose: We investigated the use of graded-dose peginterferon alpha-2b (Peg-IFN) in patients with stage IV melanoma overexpressing basic fibroblast growth factor (FGF-2). The primary objective was suppression of plasma FGF-2 to within reference range (<= 7.5 pg/mL). Experimental Design: Plasma FGF-2 was measured at baseline (step 1), and patients with concentrations of 15 pg/mL or more were eligible for study treatment (step 2). Peg-IFN was given weekly at a starting dose of 0.5 mu g/kg/wk with increment every 3 weeks based on serial FGF-2 concentrations. Results: Two hundred seven patients entered step 1; 45 (22%) overexpressed FGF-2 (median = 22 pg/dL). Twenty-nine eligible patients entered step 2 and received treatment. Patients' median age was 64 years (range, 29-84 years). Most had more than two prior therapies. FGF-2 decreased in 28 (97%) patients, with suppression to reference range in 10 (35%). Median time to FGF-2 suppression was 30 days. The best clinical responses were partial response (7%) and stable disease (17%). Median progression-free survival (PFS) and overall survival (OS) were 2.0 and 9.7 months, respectively. Patients who achieved FGF-2 suppression were more likely than those who did not to have a response or stable disease (P = 0.03). VEGF concentrations decreased in 27 patients (93%) during treatment and paralleled those of FGF-2 over time. We found no compensatory increase in VEGF among those with FGF-2 suppression. Conclusions: Graded-dose Peg-IFN suppresses FGF-2 in patients with metastatic melanoma who overexpress FGF-2. Over one third of patients had complete suppression of plasma FGF-2, which correlated with clinical response to this therapy. Clin Cancer Res; 19(23); 6597-604. (C) 2013 AACR. C1 [Callister, Steven M.; Jobe, Dean A.] Gunderson Med Fdn, La Crosse, WI USA. [Lee, Sandra J.; Shin, Donghoon] Dana Farber Canc Inst, Boston, MA 02115 USA. [Conry, Robert M.] Univ Alabama Birmingham, Ctr Comprehens Canc, Birmingham, AL 35294 USA. [Tarhini, Ahmad A.; Kirkwood, John M.] Univ Pittsburgh, Inst Canc, Pittsburgh, PA USA. RP Go, RS (reprint author), Mayo Clin, Div Hematol, 200 1st St SW, Rochester, MN 55905 USA. EM Go.Ronald@mayo.edu FU National Cancer Institute, NIH [CA23318, CA66636, CA21115, CA39229]; Department of Health and Human Services; Gundersen Medical Foundation; Gundersen Health System FX This study was conducted by the Eastern Cooperative Oncology Group (R. L. Comis) and supported in part by the Public Health Service Grants CA23318, CA66636, CA21115, and CA39229 and from the National Cancer Institute, NIH, and the Department of Health and Human Services. Additional funding was provided by Gundersen Medical Foundation and Gundersen Health System. NR 34 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 1078-0432 EI 1557-3265 J9 CLIN CANCER RES JI Clin. Cancer Res. PD DEC 1 PY 2013 VL 19 IS 23 BP 6597 EP 6604 DI 10.1158/1078-0432.CCR-13-1414 PG 8 WC Oncology SC Oncology GA 263PE UT WOS:000327819700028 PM 24122792 ER PT J AU Zhu, AX Finn, RS Mulcahy, M Gurtler, J Sun, WJ Schwartz, JD Dalal, RP Joshi, A Hozak, RR Xu, YH Ancukiewicz, M Jain, RK Nugent, FW Duda, DG Stuart, K AF Zhu, Andrew X. Finn, Richard S. Mulcahy, Mary Gurtler, Jayne Sun, Weijing Schwartz, Jonathan D. Dalal, Rita P. Joshi, Adarsh Hozak, Rebecca R. Xu, Yihuan Ancukiewicz, Marek Jain, Rakesh K. Nugent, Francis W. Duda, Dan G. Stuart, Keith TI A Phase II and Biomarker Study of Ramucirumab, a Human Monoclonal Antibody Targeting the VEGF Receptor-2, as First-Line Monotherapy in Patients with Advanced Hepatocellular Cancer SO CLINICAL CANCER RESEARCH LA English DT Article ID ENDOTHELIAL GROWTH-FACTOR; BREAST-CANCER; DOUBLE-BLIND; CARCINOMA; THERAPY; BEVACIZUMAB; ANGIOGENESIS; HYPERTENSION; IMC-1121B; SUNITINIB AB Purpose: To assess the efficacy and safety of the anti-VEGF receptor-2 (VEGFR-2) antibody ramucirumab as first-line therapy in patients with advanced hepatocellular carcinoma and explore potential circulating biomarkers. Experimental Design: Adults with advanced hepatocellular carcinoma and no prior systemic treatment received ramucirumab 8 mg/kg every two weeks until disease progression or limiting toxicity. The primary endpoint was progression-free survival (PFS); secondary endpoints included objective response rate (ORR) and overall survival (OS). Circulating biomarkers were evaluated before and after ramucirumab treatment in a subset of patients. Results: Forty-two patients received ramucirumab. Median PFS was 4.0 months [95% confidence interval (CI), 2.6-5.7], ORR was 9.5% (95% CI, 2.7-22.6; 4/42 patients had a partial response), and median OS was 12.0 months(95% CI, 6.1-19.7). For patients with Barcelona Clinic Liver Cancer (BCLC) stage C disease, median OS was 4.4 months (95% CI, 0.5-9.0) for patients with Child-Pugh B cirrhosis versus 18.0 months (95% CI, 6.1-23.5) for patients with Child-Pugh A cirrhosis. Treatment-related grade >= 3 toxicities included hypertension (14%), gastrointestinal hemorrhage and infusion-related reactions (7% each), and fatigue (5%). There was one treatment-related death (gastrointestinal hemorrhage). After treatment with ramucirumab, there was an increase in serum VEGF and placental growth factor (PlGF) and a transient decrease in soluble VEGFR-2. Conclusion: Ramucirumab monotherapy may confer anticancer activity in advanced hepatocellular carcinoma with an acceptable safety profile. Exploratory biomarker studies showed changes in circulating VEGF, PlGF, and sVEGFR-2 that are consistent with those seen with other anti-VEGF agents. Clin Cancer Res; 19(23); 6614-23. (C) 2013 AACR. C1 [Zhu, Andrew X.; Ancukiewicz, Marek; Jain, Rakesh K.; Duda, Dan G.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Canc, Boston, MA 02114 USA. [Finn, Richard S.] Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90095 USA. [Mulcahy, Mary] Northwestern Univ, Feinberg Sch Med, Chicago, IL 60611 USA. [Gurtler, Jayne] East Jefferson Gen Hosp, Metairie, LA USA. [Sun, Weijing] Univ Pittsburgh, Sch Med, Div Hematol Oncol, Pittsburgh, PA USA. [Schwartz, Jonathan D.; Dalal, Rita P.; Xu, Yihuan] ImClone Syst, Bridgewater, NJ USA. [Joshi, Adarsh; Hozak, Rebecca R.] Eli Lilly & Co, Indianapolis, IN 46285 USA. [Nugent, Francis W.; Stuart, Keith] Tufts Univ, Sch Med, Lahey Hosp, Burlington, MA USA. [Nugent, Francis W.; Stuart, Keith] Tufts Univ, Sch Med, Med Ctr, Burlington, MA USA. RP Zhu, AX (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Canc, POB 232,55 Fruit St, Boston, MA 02114 USA. EM azhu@partners.org FU NIH [P01CA080124]; Proton Beam/Federal Share Program; ImClone Systems; Eli Lilly and Company FX This work was supported in part through NIH grants P01CA080124 and Proton Beam/Federal Share Program (to R. K. Jain and D. G. Duda) and by ImClone Systems, a wholly-owned subsidiary of Eli Lilly and Company. NR 33 TC 52 Z9 57 U1 1 U2 14 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 DEC 1 PY 2013 VL 19 IS 23 BP 6614 EP 6623 DI 10.1158/1078-0432.CCR-13-1442 PG 10 WC Oncology SC Oncology GA 263PE UT WOS:000327819700030 PM 24088738 ER PT J AU Soskin, DP Holt, DJ Sacco, GR Fava, M AF Soskin, David P. Holt, Daphne J. Sacco, Garret R. Fava, Maurizio TI Incentive salience: novel treatment strategies for major depression SO CNS SPECTRUMS LA English DT Review DE Behavioral activation therapy; cognitive behavioral therapy; dopamine; incentive salience hypothesis; major depressive disorder; novel treatment strategies; psychopharmacology; well-being therapy ID SEROTONIN REUPTAKE INHIBITORS; INDUCED DOPAMINE RELEASE; NUCLEUS-ACCUMBENS; DOUBLE-BLIND; MESOLIMBIC DOPAMINE; AFFECTIVE-DISORDERS; HEDONIC IMPACT; REWARD; BRAIN; TRIAL AB This article proposes that a recent shift in our understanding of dopamine function may support translational research to target deficits in positive emotions and reward processing in individuals with major depressive disorder (MDD). We review how dopamine functions to modulate approach behaviors in response to positive incentives, and we describe the incentive salience hypothesis, which posits that dopamine primarily modulates wanting, or anticipatory reward, rather than liking, or subjective pleasure. Although the incentive salience hypothesis was first proposed to help explain how drugs of abuse may reinforce harmful behaviors in the absence of continued pleasure or liking, it may also provide a basis for understanding and developing new treatment approaches for MDD. Specifically, it provides a rationale for combining behaviorally activating psychotherapies and pro-dopaminergic agents to target impaired reward processing in MDD. C1 [Soskin, David P.; Holt, Daphne J.] Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA. [Soskin, David P.; Holt, Daphne J.; Fava, Maurizio] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. [Sacco, Garret R.] Univ Delaware, Dept Psychol, Newark, DE USA. [Fava, Maurizio] Massachusetts Gen Hosp, Depress Clin & Res Program, Boston, MA 02114 USA. RP Soskin, DP (reprint author), Massachusetts Gen Hosp, Dept Psychiat, Ctr Treatment Resistant Depress, 1 Bowdoin Sq, Boston, MA 02114 USA. EM dsoskin@partners.org NR 55 TC 5 Z9 5 U1 2 U2 10 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 32 AVENUE OF THE AMERICAS, NEW YORK, NY 10013-2473 USA SN 1092-8529 EI 2165-6509 J9 CNS SPECTRUMS JI CNS Spectr. PD DEC PY 2013 VL 18 IS 6 BP 307 EP 314 DI 10.1017/S1092852913000345 PG 8 WC Clinical Neurology; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 262ZT UT WOS:000327777100004 PM 23903027 ER PT J AU Suva, ML Louis, DN AF Suva, Mario L. Louis, David N. TI Next-generation molecular genetics of brain tumours SO CURRENT OPINION IN NEUROLOGY LA English DT Review DE adult gliomas; medulloblastomas; meningiomas; next-generation sequencing; paediatric gliomas ID HIGH-GRADE GLIOMAS; IDH MUTATIONS; PEDIATRIC GLIOBLASTOMA; GENOMIC ANALYSIS; DIFFUSE GLIOMAS; FREQUENT ATRX; 1P/19Q LOSS; MEDULLOBLASTOMA; MENINGIOMAS; GENES AB Purpose of review Systematic use of next-generation sequencing technologies has transformed the field of cancer genomics, leading to the identification of genetic alterations in an unanticipated number of genes and regulatory elements. Here, we review recent advances in brain tumour genomics and highlight how these findings improve classification and diagnosis of brain tumours. Recent findings The studies discussed in this review have shed light on different areas of neuro-oncology. In-depth analysis of paediatric low-grade gliomas as well as paediatric glioblastomas has clarified our molecular understanding of these diseases, clearly distinguishing them from their adult counterparts. Unexpected novel mutations have been discovered in adult low-grade astrocytomas and in glioblastomas. Novel studies also highlighted candidate tumour suppressor genes located on the chromosome arms frequently deleted in oligodendrogliomas. Finally, we review recent discoveries in the molecular landscapes of medulloblastomas and meningiomas. Summary These recent studies begin to provide an in-depth view of the molecular routes leading to brain tumour development. The findings will be critical for refining classification systems and improving clinical management. C1 [Suva, Mario L.; Louis, David N.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Suva, Mario L.; Louis, David N.] Massachusetts Gen Hosp, Ctr Canc Res, Boston, MA 02114 USA. [Suva, Mario L.; Louis, David N.] Harvard Univ, Sch Med, Boston, MA USA. [Suva, Mario L.] Broad Inst Harvard & MIT, Cambridge, MA USA. RP Suva, ML (reprint author), Massachusetts Gen Hosp, James Homer Wright Pathol Labs, Simches Res Bldg,CPZN 8400,185 Cambridge St, Boston, MA 02114 USA. EM Suva.Mario@mgh.harvard.edu FU Medic Foundation FX We thank Lauren Solomon for assistance in figure design. M.L.S. is supported by a grant from the Medic Foundation. NR 42 TC 4 Z9 5 U1 3 U2 20 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1350-7540 EI 1473-6551 J9 CURR OPIN NEUROL JI Curr. Opin. Neurol. PD DEC PY 2013 VL 26 IS 6 BP 681 EP 687 DI 10.1097/WCO.0000000000000027 PG 7 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 259VL UT WOS:000327554300014 PM 24184972 ER PT J AU Nayak, L Batchelor, TT AF Nayak, Lakshmi Batchelor, Tracy T. TI Recent Advances in Treatment of Primary Central Nervous System Lymphoma SO CURRENT TREATMENT OPTIONS IN ONCOLOGY LA English DT Article DE Primary central nervous system lymphoma; High-dose methotrexate; Rituximab; Stem-cell transplant; Whole-brain radiation ID PRIMARY CNS LYMPHOMA; HIGH-DOSE METHOTREXATE; STEM-CELL TRANSPLANTATION; WHOLE-BRAIN RADIOTHERAPY; KETTERING CANCER CENTER; RECURRENT PRIMARY CNS; MULTICENTER PHASE-II; NON-HODGKINS-LYMPHOMA; TERM-FOLLOW-UP; 1ST-LINE TREATMENT AB Therapeutic options are limited in primary central nervous system lymphoma (PCNSL) with no uniform consensus on optimal management and few published, randomized trials. High-dose methotrexate in combination with other chemotherapeutic agents forms the mainstay of treatment. There hasn't been much progress beyond high-dose methotrexate in this disease, and although results from trials using high-dose chemotherapy and autologous stem-cell transplant seem promising, these need to be further validated. Moreover, the role of whole brain radiation in the upfront setting remains to be determined. However, international efforts in this direction are underway, with ongoing randomized trials in newly diagnosed PCNSL, more research on the molecular pathogenesis and biomarkers, and the use of novel agents in salvage therapy. There also is emphasis on quality of life parameters and neurocognitive status. Future treatment options should optimize high-efficacy rates while minimizing the risk of neurotoxicity. C1 [Nayak, Lakshmi] Harvard Univ, Sch Med, Brigham & Womens Hosp,Dept Neurol, Dana Farber Canc Inst,Ctr Neurooncol, Boston, MA 02215 USA. [Batchelor, Tracy T.] Harvard Univ, Sch Med,Dept Neurol, Massachusetts Gen Hosp,Div Hematol & Oncol, Stephen E & Catherine Pappas Ctr Neurooncol,Canc, Boston, MA 02214 USA. RP Nayak, L (reprint author), Harvard Univ, Sch Med, Brigham & Womens Hosp,Dept Neurol, Dana Farber Canc Inst,Ctr Neurooncol, 450 Brookline Ave, Boston, MA 02215 USA. EM tbatchelor@partners.org FU NCI NIH HHS [K24 CA125440] NR 85 TC 1 Z9 2 U1 1 U2 4 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1527-2729 EI 1534-6277 J9 CURR TREAT OPTION ON JI Curr. Treat. Options Oncol. PD DEC PY 2013 VL 14 IS 4 BP 539 EP 552 DI 10.1007/s11864-013-0252-6 PG 14 WC Oncology SC Oncology GA 264IS UT WOS:000327870800006 PM 23934511 ER PT J AU Wolf, EJ Mitchell, KS Logue, MW Baldwin, CT Reardon, AF Humphries, DE Miller, MW AF Wolf, Erika J. Mitchell, Karen S. Logue, Mark W. Baldwin, Clinton T. Reardon, Annemarie F. Humphries, Donald E. Miller, Mark W. TI CORTICOTROPIN RELEASING HORMONE RECEPTOR 2 (CRHR-2) GENE IS ASSOCIATED WITH DECREASED RISK AND SEVERITY OF POSTTRAUMATIC STRESS DISORDER IN WOMEN SO DEPRESSION AND ANXIETY LA English DT Article DE PTSD; single nucleotide polymorphisms; rs8192496; rs2284218; women; veterans; latent variable ID NATIONAL COMORBIDITY SURVEY; MESSENGER-RNA EXPRESSION; MULTILOCUS GENOTYPE DATA; GENOME-WIDE ASSOCIATION; ADMINISTERED PTSD SCALE; ANXIETY-LIKE BEHAVIOR; MAJOR DEPRESSION; PANIC DISORDER; TRAUMA EXPOSURE; CRF RECEPTORS AB BackgroundThe corticotropin releasing hormone (CRH) system has been implicated in a variety of anxiety and mood-based symptoms and disorders. CRH receptor-2 (CRHR-2) plays a role in attenuating biological responses to stressful life events and trauma, making the CRHR-2 gene a strong candidate to study in relationship to PTSD. MethodsThe sample was 491 trauma-exposed white non-Hispanic veterans and their cohabitating intimate partners assessed via structured interview for lifetime DSM-IV PTSD; just over 60% met criteria for the disorder. Thirty-one single nucleotide polymorphisms (SNPs) in and near CRHR-2, obtained from an array of 2.5 million markers, were tested for association with PTSD diagnosis and symptom severity in the whole sample and in men and women separately. ResultsTen SNPs showed nominally significant evidence of association with PTSD in the full sample and two SNPs (rs8192496 and rs2190242) were significant after permutation-based multiple testing correction (uncorrected ps = .0004 and .0005, odds ratios = .60 and .58, respectively). Analyses stratified by sex revealed that the effect was specific to women, who comprised 35% of the sample (uncorrected ps = .0003 and .0002, odds ratios = .41 and .35, respectively). Two additional SNPs (rs2267715 and rs2284218) also showed significant association with PTSD in women (both uncorrected ps = .001, both odds ratios = .48). ConclusionsResults suggest that CRHR-2 variants may affect risk for PTSD in women by attenuating the stress response and reducing symptoms of the disorder. C1 [Wolf, Erika J.; Mitchell, Karen S.; Reardon, Annemarie F.; Miller, Mark W.] VA Boston Healthcare Syst, Natl Ctr PTSD, Boston, MA USA. [Wolf, Erika J.; Mitchell, Karen S.; Miller, Mark W.] Boston Univ, Sch Med, Dept Psychiat, Boston, MA 02118 USA. [Logue, Mark W.; Baldwin, Clinton T.; Humphries, Donald E.] Boston Univ, Sch Med, Dept Med, Boston, MA 02118 USA. [Logue, Mark W.] Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA USA. [Baldwin, Clinton T.] Boston Univ, Sch Med, Ctr Human Genet, Boston, MA 02118 USA. [Humphries, Donald E.] VA Boston Healthcare Syst, Massachusetts Vet Epidemiol Res & Informat Ctr, Boston, MA USA. RP Miller, MW (reprint author), VA Boston Healthcare Syst 116B 2, Natl Ctr PTSD, 150 South Huntington Ave, Boston, MA 02130 USA. EM mark.miller5@va.gov RI Miller, Mark/G-7322-2011; OI Miller, Mark/0000-0001-6393-8563; Wolf, Erika/0000-0003-2666-2435 FU [RO1 MH079806]; [K01MH093750] FX Contract grant number: RO1 MH079806; Contract grant number: K01MH093750. NR 61 TC 9 Z9 9 U1 3 U2 6 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1091-4269 EI 1520-6394 J9 DEPRESS ANXIETY JI Depress. Anxiety PD DEC PY 2013 VL 30 IS 12 BP 1161 EP 1169 DI 10.1002/da.22176 PG 9 WC Psychology, Clinical; Psychiatry; Psychology SC Psychology; Psychiatry GA 260MJ UT WOS:000327598700003 PM 24123648 ER PT J AU Marques, L Bui, E LeBlanc, N Porter, E Robinaugh, D Dryman, MT Nadal-Vicens, M Worthington, J Simon, N AF Marques, Luana Bui, Eric LeBlanc, Nicole Porter, Eliora Robinaugh, Donald Dryman, M. Taylor Nadal-Vicens, Mireya Worthington, John Simon, Naomi TI COMPLICATED GRIEF SYMPTOMS IN ANXIETY DISORDERS: PREVALENCE AND ASSOCIATED IMPAIRMENT SO DEPRESSION AND ANXIETY LA English DT Article DE Complicated grief; grief; bereavement; anxiety; comorbidity; quality of life ID QUALITY-OF-LIFE; TRAUMATIC GRIEF; BIPOLAR DISORDER; BEREAVED ADULTS; DEPRESSION; DISTRESS; DISTINCT; INDIVIDUALS; SUICIDALITY; COMORBIDITY AB BackgroundPrevious research has identified high rates of comorbid anxiety disorders among individuals presenting with primary CG. In the present study, we examined the prevalence of comorbid CG in bereaved primary anxiety disorder (AD) patients compared to bereaved healthy controls. We also examined the impairment associated with comorbid CG in AD. MethodsParticipants were 242 bereaved adults (mean (SD) age = 41.5 (13.1), 44.2% women) with a primary AD diagnosis, including generalized anxiety disorder (GAD; n = 57), panic disorder (PD; n = 49), posttraumatic stress disorder (PTSD; n = 29), and generalized social anxiety disorder (GSAD; n = 107), as well as 155 bereaved healthy controls with no current DSM-IV Axis I diagnosis (mean (SD) age = 43.0 (13.6), 51.0% women). CG symptoms were measured using the 19-item inventory of complicated grief (ICG), with threshold CG defined as an ICG score of 30. Quality of life and functional impairment were assessed with the Quality of Life Enjoyment and Satisfaction Questionnaire (Q-LES-Q) and the Range of Impaired Functioning Tool (LIFE-RIFT), respectively. ResultsParticipants with primary ADs had significantly higher rates of threshold CG symptoms than bereaved controls (12.0% vs. 0.65%; Fisher's Exact P < 0.001). Rates of threshold CG were significantly elevated for each AD when compared to bereaved controls. After adjustment for age, sex, education, and comorbid major depressive disorder, threshold CG was associated with lower quality of life ( = -0.140, P = 0.023) and greater impairment ( = 0.141, P = 0.035) among individuals with AD. ConclusionsOur findings suggest that threshold CG is of clinical relevance in bereaved individuals with a primary anxiety disorder. Screening for CG in patients with ADs may be warranted. (C) 2013 Wiley Periodicals, Inc. C1 [Marques, Luana; Bui, Eric; LeBlanc, Nicole; Porter, Eliora; Robinaugh, Donald; Dryman, M. Taylor; Nadal-Vicens, Mireya; Worthington, John; Simon, Naomi] Massachusetts Gen Hosp, Ctr Anxiety & Traumat Stress Disorders, Boston, MA 02114 USA. [Robinaugh, Donald] Harvard Univ, Dept Psychol, Cambridge, MA 02138 USA. RP Marques, L (reprint author), Massachusetts Gen Hosp, Ctr Anxiety & Traumat Stress Disorders, 1 Bowdoin Sq, Boston, MA 02114 USA. EM lmarques@partners.org RI Bui, Eric/J-8347-2015 OI Bui, Eric/0000-0002-1413-6473 FU Highland Street Foundation; National Institute of Mental Health; Massachusetts General Hospital Psychiatry Academy; Laboratoires Servier; Current Psychiatry; Dialogues in Clinical Neuroscience; Falcon Reviews; Merck and Pfizer; American Foundation for Suicide Prevention; Forest Laboratories; American Cancer Society; NARSAD; Glaxo SmithKline; Lilly; Sepracor; Pfizer; MGH Psychiatry Academy FX Contract grant sponsor: Highland Street Foundation; Contract grant sponsor: National Institute of Mental Health; Contract grant sponsor: Massachusetts General Hospital Psychiatry Academy; Contract grant sponsor: Laboratoires Servier; Contract grant sponsor: Current Psychiatry; Contract grant sponsor: Dialogues in Clinical Neuroscience; Contract grant sponsor: Falcon Reviews; Contract grant sponsor: Merck and Pfizer; Contract grant sponsor: American Foundation for Suicide Prevention; Contract grant sponsor: Forest Laboratories; Contract grant sponsor: American Cancer Society; Contract grant sponsor: NARSAD; Contract grant sponsor: Glaxo SmithKline; Contract grant sponsor: Lilly; Contract grant sponsor: Sepracor; Contract grant sponsor: Pfizer; Contract grant sponsor: MGH Psychiatry Academy NR 39 TC 12 Z9 12 U1 0 U2 3 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1091-4269 EI 1520-6394 J9 DEPRESS ANXIETY JI Depress. Anxiety PD DEC PY 2013 VL 30 IS 12 BP 1211 EP 1216 DI 10.1002/da.22093 PG 6 WC Psychology, Clinical; Psychiatry; Psychology SC Psychology; Psychiatry GA 260MJ UT WOS:000327598700009 PM 23495105 ER PT J AU Bonilha, HS Blair, J Carnes, B Huda, W Humphries, K McGrattan, K Michel, Y Martin-Harris, B AF Bonilha, Heather Shaw Blair, Julie Carnes, Brittni Huda, Walter Humphries, Kate McGrattan, Katlyn Michel, Yvonne Martin-Harris, Bonnie TI Preliminary Investigation of the Effect of Pulse Rate on Judgments of Swallowing Impairment and Treatment Recommendations SO DYSPHAGIA LA English DT Article DE Dysphagia; Modified barium swallow study; MBSImP (TM)(c); Pulse rate; Radiation exposure ID DYSPHAGIA; AUGMENTATION; FLUOROSCOPY; MANEUVERS AB Reducing fluoroscopic pulse rate, a method used to reduce radiation exposure from modified barium swallow studies (MBSSs), decreases the number of images available from which to judge swallowing impairment. It is necessary to understand the impact of pulse rate reduction on judgments of swallowing impairment and, consequentially, treatment recommendations. This preliminary study explored differences in standardized MBSS measurements [Modified Barium Swallow Impairment Profile (MBSImP (TM) A (c)) and Penetration Aspiration Scale (PAS) Scores] between two pulse rates: 30 and simulated 15 pulses per second (pps). Two reliable speech-language pathologists (SLPs) scored all five MBSSs. Five SLPs reported treatment recommendations based on those scores. Differences in judgments of swallowing impairment were found between 30 and simulated 15 pps in all five MBSSs. These differences were in six physiological swallowing components: initiation of pharyngeal swallow, anterior hyoid excursion, epiglottic movement, pharyngeal contraction, pharyngeal-esophageal segment opening, and tongue base retraction. Differences in treatment recommendations were found between 30 and simulated 15 pps in all five MBSSs. These findings suggest that there are differences in both judgment of swallowing impairment and treatment recommendations when pulse rates are reduced from 30 to 15 pps to minimize radiation exposure. C1 [Bonilha, Heather Shaw; McGrattan, Katlyn; Martin-Harris, Bonnie] Med Univ S Carolina, Dept Hlth Sci & Res, Charleston, SC 29425 USA. [Bonilha, Heather Shaw; Martin-Harris, Bonnie] Med Univ S Carolina, Dept Otolaryngol Head & Neck Surg, Charleston, SC 29425 USA. [Blair, Julie; Carnes, Brittni; Humphries, Kate; McGrattan, Katlyn; Martin-Harris, Bonnie] Med Univ S Carolina, Evelyn Trammell Inst Voice & Swallowing, Charleston, SC 29425 USA. [Huda, Walter] Med Univ S Carolina, Dept Radiol, Charleston, SC 29425 USA. [Michel, Yvonne] Med Univ S Carolina, Charleston, SC 29425 USA. [Martin-Harris, Bonnie] Ralph H Johnson VA Med Ctr, Charleston, SC USA. RP Bonilha, HS (reprint author), Med Univ S Carolina, Dept Hlth Sci & Res, 77 President St, Charleston, SC 29425 USA. EM bonilhah@musc.edu FU NIH/NIDCD [K23 DC005764-05]; NIH/NCRR [KL2 UL1 RR029880]; Bracco Diagnostics (NIH/NIDCD) [K24 DC012801]; Evelyn Trammell Voice and Swallowing Institute; Northern Speech Services FX This work was supported by the following grants: NIH/NIDCD Grant No. K23 DC005764-05, NIH/NCRR Grant No. KL2 UL1 RR029880, and Bracco Diagnostics (NIH/NIDCD No. K24 DC012801). Other financial or material support was provided by Evelyn Trammell Voice and Swallowing Institute and Northern Speech Services. NR 26 TC 7 Z9 7 U1 0 U2 4 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0179-051X EI 1432-0460 J9 DYSPHAGIA JI Dysphagia PD DEC PY 2013 VL 28 IS 4 BP 528 EP 538 DI 10.1007/s00455-013-9463-z PG 11 WC Otorhinolaryngology SC Otorhinolaryngology GA 269CK UT WOS:000328217900007 PM 23559454 ER PT J AU Brumpton, BM Camargo, CA Romundstad, PR Langhammer, A Chen, Y Mai, XM AF Brumpton, Ben Michael Camargo, Carlos Arturo, Jr. Romundstad, Pal Richard Langhammer, Arnulf Chen, Yue Mai, Xiao-Mei TI Metabolic syndrome and incidence of asthma in adults: the HUNT study SO EUROPEAN RESPIRATORY JOURNAL LA English DT Article ID INSULIN-RESISTANCE; ABDOMINAL OBESITY; ONSET ASTHMA; PREVALENCE; SYMPTOMS; PHENOTYPE; HEALTH; RISK AB Obesity is a risk factor for incident asthma in adults, and obesity is a major component of metabolic syndrome. This study aimed to explore the associations of metabolic syndrome and its components with the cumulative incidence of asthma in adults. We conducted a prospective cohort study of participants who were asthma-free at baseline (n=23 191) in the Nord-Trondelag Health Study from 1995 to 2008. Baseline metabolic syndrome was categorised using the definition of the Joint Interim Statement from several international organisations. Incident asthma was self-reported at follow-up, which averaged 11 years. Metabolic syndrome was a risk factor for incident asthma (adjusted OR 1.57, 95% CI 1.31-1.87). This association was consistent in sensitivity analyses using a stricter asthma definition (adjusted OR 1.42, 95% CI 1.13-1.79). Among the components of metabolic syndrome, two remained associated with incident asthma after mutual adjustment for the other metabolic components: high waist circumference (adjusted OR 1.62, 95% CI 1.36-1.94) and elevated glucose or diabetes (adjusted OR 1.43, 95% CI 1.01-2.04). Metabolic syndrome and two of its components (high waist circumference and elevated glucose or diabetes) were associated with an increased risk of incident asthma in adults. C1 [Brumpton, Ben Michael; Romundstad, Pal Richard; Langhammer, Arnulf; Mai, Xiao-Mei] Norwegian Univ Sci & Technol, Dept Publ Hlth & Gen Practice, Fac Med, N-7034 Trondheim, Norway. [Brumpton, Ben Michael; Camargo, Carlos Arturo, Jr.] Massachusetts Gen Hosp, Dept Emergency Med, Boston, MA 02114 USA. [Brumpton, Ben Michael; Camargo, Carlos Arturo, Jr.] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. [Chen, Yue] Univ Ottawa, Fac Med, Dept Epidemiol & Community Med, Ottawa, ON, Canada. RP Brumpton, BM (reprint author), Norwegian Univ Sci & Technol NTNU, Dept Publ Hlth & Gen Practice, MTFS, Post Box 8905, NO-7491 Trondheim, Norway. EM ben.brumpton@ntnu.no OI Romundstad, Pal Richard/0000-0003-2061-4336 FU Research Council of Norway [201895/V50]; Faculty of Medicine, Norwegian University of Science and Technology (NTNU), Trondheim, Norway FX Support statement: This study was supported by the Research Council of Norway (project number 201895/V50) and the Faculty of Medicine, Norwegian University of Science and Technology (NTNU), Trondheim, Norway. NR 31 TC 20 Z9 20 U1 0 U2 1 PU EUROPEAN RESPIRATORY SOC JOURNALS LTD PI SHEFFIELD PA 442 GLOSSOP RD, SHEFFIELD S10 2PX, ENGLAND SN 0903-1936 EI 1399-3003 J9 EUR RESPIR J JI Eur. Resp. J. PD DEC PY 2013 VL 42 IS 6 BP 1495 EP 1502 DI 10.1183/09031936.00046013 PG 8 WC Respiratory System SC Respiratory System GA 264ZQ UT WOS:000327919900013 PM 23845717 ER PT J AU Zhang, CZ Leibowitz, ML Pellman, D AF Zhang, Cheng-Zhong Leibowitz, Mitchell L. Pellman, David TI Chromothripsis and beyond: rapid genome evolution from complex chromosomal rearrangements SO GENES & DEVELOPMENT LA English DT Review DE chromothripsis; chromoplexy; chromoanasynthesis; genome evolution; cancer; chromosomal translocation; copy number lteration ID TERT PROMOTER MUTATIONS; COPY-NUMBER ALTERATION; COMMON FRAGILE SITES; HUMAN CANCER GENOMES; DNA-DAMAGE; STRUCTURAL VARIATION; PROSTATE-CANCER; GENE AMPLIFICATION; P53-DEFICIENT CELLS; SOMATIC MUTATIONS AB Recent genome sequencing studies have identified several classes of complex genomic rearrangements that appear to be derived from a single catastrophic event. These discoveries identify ways that genomes can be altered in single large jumps rather than by many incremental steps. Here we compare and contrast these phenomena and examine the evidence that they arise "all at once." We consider the impact of massive chromosomal change for the development of diseases such as cancer and for evolution more generally. Finally, we summarize current models for underlying mechanisms and discuss strategies for testing these models. C1 [Zhang, Cheng-Zhong; Pellman, David] Broad Inst Harvard & Massachusetts Inst Technol, Cambridge, MA 02142 USA. [Leibowitz, Mitchell L.; Pellman, David] Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. [Leibowitz, Mitchell L.; Pellman, David] Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA 02115 USA. [Pellman, David] Howard Hughes Med Inst, Boston, MA 02115 USA. RP Pellman, D (reprint author), Broad Inst Harvard & Massachusetts Inst Technol, Cambridge, MA 02142 USA. EM david_pellman@dfci.harvard.edu FU National Cancer Institute [U24CA143867]; National Science Foundation [DGE1144152]; Howard Hughes Medical Institute; National Institute of Health [GM083299]; G. Harold and Leila Y. Mathers Charitable Foundation FX We thank I.M. Hall, D.M. Weinstock, S. Baca, H. Cornils, J. Francis, P.J. Campbell, and P.J. Stephens for discussions. C.Z.Z. was supported by the National Cancer Institute (U24CA143867). M.L.L was supported by the National Science Foundation (DGE1144152). D.P. was supported by the Howard Hughes Medical Institute, the National Institute of Health (GM083299), and the G. Harold and Leila Y. Mathers Charitable Foundation. NR 153 TC 61 Z9 63 U1 2 U2 31 PU COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT PI COLD SPRING HARBOR PA 1 BUNGTOWN RD, COLD SPRING HARBOR, NY 11724 USA SN 0890-9369 EI 1549-5477 J9 GENE DEV JI Genes Dev. PD DEC 1 PY 2013 VL 27 IS 23 BP 2513 EP 2530 DI 10.1101/gad.229559.113 PG 18 WC Cell Biology; Developmental Biology; Genetics & Heredity SC Cell Biology; Developmental Biology; Genetics & Heredity GA 265IH UT WOS:000327943600001 PM 24298051 ER PT J AU Liu, MZ Roth, A Yu, M Morris, R Bersani, F Rivera, MN Lu, J Shioda, T Vasudevan, S Ramaswamy, S Maheswaran, S Diederichs, S Haber, DA AF Liu, Mingzhu Roth, Anna Yu, Min Morris, Robert Bersani, Francesca Rivera, Miguel N. Lu, Jun Shioda, Toshihiro Vasudevan, Shobha Ramaswamy, Sridhar Maheswaran, Shyamala Diederichs, Sven Haber, Daniel A. TI The IGF2 intronic miR-483 selectively enhances transcription from IGF2 fetal promoters and enhances tumorigenesis SO GENES & DEVELOPMENT LA English DT Article ID MICRORNA; SUPPRESSES; GENE; PROLIFERATION; EXPRESSION; GROWTH; CANCER; MOUSE; CELLS AB Insulin-like growth factor 2 (IGF2), a developmentally regulated and maternally imprinted gene, is frequently overexpressed in pediatric cancers. Although loss of imprinting (LOI) at fetal promoters contributes to increased IGF2 in tumors, the magnitude of IGF2 expression suggests the involvement of additional regulatory mechanisms. A microRNA (miRNA) screen of primary Wilms' tumors identified specific overexpression of miR-483- 5p, which is embedded within the IGF2 gene. Unexpectedly, the IGF2 mRNA itself is transcriptionally up-regulated by miR-483-5p. A nuclear pool of miR-483-5p binds directly to the 5' untranslated region (UTR) of fetal IGF2 mRNA, enhancing the association of the RNA helicase DHX9 to the IGF2 transcript and promoting IGF2 transcription. Ectopic expression of miR-483-5p in IGF2-dependent sarcoma cells is correlated with increased tumorigenesis in vivo. Together, these observations suggest a functional positive feedback loop of an intronic miRNA on transcription of its host gene. C1 [Liu, Mingzhu; Yu, Min; Morris, Robert; Bersani, Francesca; Rivera, Miguel N.; Shioda, Toshihiro; Vasudevan, Shobha; Ramaswamy, Sridhar; Maheswaran, Shyamala; Diederichs, Sven; Haber, Daniel A.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Canc, Charlestown, MA 02129 USA. [Liu, Mingzhu; Yu, Min; Bersani, Francesca; Haber, Daniel A.] Howard Hughes Med Inst, Chevy Chase, MD 20815 USA. [Roth, Anna; Diederichs, Sven] German Canc Res Ctr, Mol RNA Biol & Canc, D-69120 Heidelberg, Germany. [Roth, Anna; Diederichs, Sven] Univ Heidelberg Hosp, Inst Pathol, D-69120 Heidelberg, Germany. [Rivera, Miguel N.] Harvard Univ, Sch Med, Dept Pathol, Charlestown, MA 02129 USA. [Lu, Jun] Broad Inst Harvard & Massachusetts Inst Technol, Cambridge, MA 02141 USA. [Shioda, Toshihiro; Vasudevan, Shobha; Haber, Daniel A.] Harvard Univ, Sch Med, Dept Med, Charlestown, MA 02129 USA. [Maheswaran, Shyamala] Harvard Univ, Sch Med, Dept Surg, Charlestown, MA 02129 USA. RP Diederichs, S (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Canc, Charlestown, MA 02129 USA. EM s.diederichs@dkfz-heidelberg.de; haber@helix.mgh.harvard.edu RI Diederichs, Sven/J-6237-2012 OI Diederichs, Sven/0000-0001-7901-4752 FU Howard Hughes Medical Institute; Burroughs Wellcome Fund; National Cancer Institute [5R37CA058596-19]; Helmholtz-University-Junior Research Group [VH-NG-504] FX We thank J. Avruch, N. Dai, K. Morris, and J. Whetstine for reagents and helpful discussions. We thank Dr. Martina Schnolzer and Dr. Tore Kempf at the DKFZ Genomics and Proteomics Core facility for mass spectrometry analysis. This work was supported by funding from the Howard Hughes Medical Institute (to M.L., M.Y., F.B., M.N.R., and D.A.H), the Burroughs Wellcome Fund (to M.N.R.), National Cancer Institute 5R37CA058596-19 (to D.A.H.), and a Helmholtz-University-Junior Research Group (VH-NG-504; to S.D.). NR 26 TC 29 Z9 29 U1 0 U2 15 PU COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT PI COLD SPRING HARBOR PA 1 BUNGTOWN RD, COLD SPRING HARBOR, NY 11724 USA SN 0890-9369 EI 1549-5477 J9 GENE DEV JI Genes Dev. PD DEC 1 PY 2013 VL 27 IS 23 BP 2543 EP 2548 DI 10.1101/gad.224170 PG 6 WC Cell Biology; Developmental Biology; Genetics & Heredity SC Cell Biology; Developmental Biology; Genetics & Heredity GA 265IH UT WOS:000327943600004 PM 24298054 ER PT J AU Germain, DP Weidemann, F Abiose, A Patel, MR Cizmarik, M Cole, JA Beitner-Johnson, D Benistan, K Cabrera, G Charrow, J Kantola, I Linhart, A Nicholls, K Niemann, M Scott, CR Sims, K Waldek, S Warnock, DG Strotmann, J AF Germain, Dominique P. Weidemann, Frank Abiose, Ademola Patel, Manesh R. Cizmarik, Marta Cole, J. Alexander Beitner-Johnson, Dana Benistan, Karelle Cabrera, Gustavo Charrow, Joel Kantola, Ilkka Linhart, Ales Nicholls, Kathy Niemann, Markus Scott, C. Ronald Sims, Katherine Waldek, Stephen Warnock, David G. Strotmann, Joerg CA Fabry Registry TI Analysis of left ventricular mass in untreated men and in men treated with agalsidase-beta: data from the Fabry Registry SO GENETICS IN MEDICINE LA English DT Article DE cardiomyopathy; enzyme replacement therapy; Fabry disease; lysosomal storage diseases; recombinant alpha-galactosidase A ID ENZYME-REPLACEMENT THERAPY; NATURAL-HISTORY DATA; CHAMBER QUANTIFICATION; CARDIAC MANIFESTATIONS; CARDIOVASCULAR EVENTS; DISEASE; CARDIOMYOPATHY; INVOLVEMENT; RECOMMENDATIONS; PROTEINURIA AB Purpose: The aim of this study was to evaluate the progression of left ventricular hypertrophy in untreated men with Fabry disease and to assess the effects of agalsidase-beta (recombinant human alpha-galactosidase A) on left ventricular hypertrophy. Methods: Longitudinal Fabry Registry data were analyzed from 115 men treated with agalsidase-beta (1 mg/kg/2 weeks) and 48 untreated men. Measurements included baseline left-ventricular mass and at least one additional left-ventricular mass assessment over >= 2 years. Patients were grouped into quartiles, based on left-ventricular mass slopes. Multivariate logistic regression analyses identified factors associated with left ventricular hypertrophy progression. Results: For men in whom treatment was initiated at the age of 18 to <30 years, mean left ventricular mass slope was -3.6 g/year (n = 31) compared with +9.5 g/year in untreated men of that age (n = 15) (P < 0.0001). Untreated men had a 3.4-fold higher risk of having faster increases in left-ventricular mass compared with treated men (odds ratio: 3.43; 95% confidence interval: 1.05-11.22; P = 0.0415). A baseline age of >= 40 years was also associated with left-ventricular hypertrophy progression (odds ratio: 5.03; 95% confidence interval: 1.03-24.49; P = 0.0457) compared with men younger than 30 years. Conclusion: Agalsidase-beta treatment for >= 2 years may improve or stabilize left-ventricular mass in men with Fabry disease. Further investigations may determine whether early intervention and stabilization of LVM are correlated with clinical outcomes. C1 [Germain, Dominique P.; Benistan, Karelle] Univ Versailles, Hop Raymond Poincare, AP HP, Garches, France. [Weidemann, Frank; Niemann, Markus] Univ Wurzburg, D-97070 Wurzburg, Germany. [Abiose, Ademola] North Ohio Heart Ctr, Westlake, OH USA. [Patel, Manesh R.] Duke Univ, Sch Med, Div Cardiovasc Med, Durham, NC USA. [Cizmarik, Marta; Cole, J. Alexander; Beitner-Johnson, Dana] Genzyme, Biomed Data Sci & Informat, Cambridge, MA USA. [Cabrera, Gustavo] Grp Med Viso, Buenos Aires, DF, Argentina. [Charrow, Joel] Childrens Mem Hosp, Chicago, IL 60614 USA. [Kantola, Ilkka] Turku Univ Cent Hosp, Dept Med, Turku, Finland. [Linhart, Ales] Charles Univ Prague, Dept Internal Med, Sch Med, Prague, Czech Republic. [Nicholls, Kathy] Royal Melbourne Hosp, Dept Nephrol, Melbourne, Vic 3050, Australia. [Scott, C. Ronald] Univ Washington, Seattle, WA 98195 USA. [Sims, Katherine] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA. [Sims, Katherine] Harvard Univ, Sch Med, Boston, MA USA. [Warnock, David G.] Univ Alabama Birmingham, Birmingham, AL USA. [Strotmann, Joerg] Stadt Krankenhaus, Med Klin 1, Kiel, Germany. RP Germain, DP (reprint author), Univ Versailles, Hop Raymond Poincare, AP HP, Garches, France. EM dominique.germain@uvsq.fr FU Genzyme Corporation; Genzyme; Abbot; Amgen; Amicus; Gilead; Parion; Relypsa; Shire FX Genzyme Corporation sponsors the Fabry Registry. Members of the Fabry Registry Board of Advisors include D. P. G., F. W., A. A., M. R. P., G. C., J.C., A. L., M. R. P., C. R. S., K. S., S. W., and D. G. W. Authors who have received research funds or travel support from Genzyme include D. P. G., M. R. P., S. W., J.S., and D. G. W. Authors who have received speaking fees from Genzyme include D. P. G., S. W., and J.S. M. C., A. C., and D.B.J. are Genzyme employees. D. G. W. has served as a paid consultant to Genzyme and also has consultancies and has received travel funds from Abbot, Amgen, Amicus, Gilead, Parion, Relypsa, and Shire. The results presented in this article have not been published previously in whole or part, except in abstract format. NR 30 TC 16 Z9 17 U1 2 U2 6 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1098-3600 EI 1530-0366 J9 GENET MED JI Genet. Med. PD DEC PY 2013 VL 15 IS 12 BP 958 EP 965 DI 10.1038/gim.2013.53 PG 8 WC Genetics & Heredity SC Genetics & Heredity GA 266XI UT WOS:000328056900008 PM 23703683 ER PT J AU Schiffmann, R Ries, M Blankenship, D Nicholls, K Mehta, A Clarke, JTR Steiner, RD Beck, M Barshop, BA Rhead, W West, M Martin, R Amato, D Nair, N Huertas, P AF Schiffmann, Raphael Ries, Markus Blankenship, Derek Nicholls, Kathy Mehta, Atul Clarke, Joe T. R. Steiner, Robert D. Beck, Michael Barshop, Bruce A. Rhead, William West, Michael Martin, Rick Amato, David Nair, Nitin Huertas, Pedro TI Changes in plasma and urine globotriaosylceramide levels do not predict Fabry disease progression over 1 year of agalsidase alfa SO GENETICS IN MEDICINE LA English DT Article DE agalsidase alfa; biomarkers; enzyme replacement therapy; Fabry disease; globotriaosylceramide ID ENZYME REPLACEMENT THERAPY; BIOMARKER; STORAGE; GLOBOTRIAOSYLSPHINGOSINE; INFUSION; CHILDREN; TRIAL AB Purpose: Globotriaosylceramide concentrations were assessed as potential predictors of change from baseline after 12 months by estimated glomerular filtration rate and left-ventricular mass index using pooled data from three randomized, placebo-controlled agalsidase alfa trials and open-label extensions of patients with Fabry disease. Methods: Males (aged 18 years or older) with Fabry disease received agalsidase alfa (0.2 mg/kg every other week for 12 months). A backward- elimination approach evaluated potential predictors (baseline estimated glomerular filtration rate and left-ventricular mass index; age at first dose; baseline and change from baseline at 12 months of globotriaosylceramide (urine, plasma); urine protein excretion; and systolic and diastolic blood pressure). Subgroups included patients randomized to placebo or agalsidase alfa (double-blind phase), then to agalsidase alfa (open-label extensions; placebo. agalsidase alfa or agalsidase alfa. agalsidase alfa, respectively) and stage 2/3 chronic kidney disease patients. Results: Baseline estimated glomerular filtration rate, age at first dose, baseline urine globotriaosylceramide excretion, and baseline and change from baseline urine protein excretion significantly predicted change from baseline estimated glomerular filtration rate in the analysis population (N = 73; all P< 0.05), although not in all subgroups. Change from baseline urine and plasma globotriaosylceramide (baseline and change from baseline) concentrations did not predict change from baseline estimated glomerular filtration rate. No predictors of left-ventricular mass index were significant. Conclusion: Changes in globotriaosylceramide concentrations do not appear to be useful biomarkers for prediction of Fabry disease- related changes in estimated glomerular filtration rate or left-ventricular mass index. C1 [Schiffmann, Raphael] Baylor Res Inst, Inst Metab Dis, Dallas, TX USA. [Ries, Markus] Univ Clin Heidelberg, Ctr Pediat & Youth Med, Heidelberg, Germany. [Blankenship, Derek] Baylor Inst Hlth Care Res & Improvement, Dept Quantitat Sci, Dallas, TX USA. [Nicholls, Kathy] Royal Melbourne Hosp, Dept Nephrol, Parkville, Vic 3050, Australia. [Nicholls, Kathy] Univ Melbourne, Parkville, Vic 3052, Australia. [Mehta, Atul] Royal Free Hosp, Dept Haematol, Lysosomal Storage Disorders Unit, London NW3 2QG, England. [Clarke, Joe T. R.] Hosp Sick Children, Div Clin & Metab Genet, Toronto, ON M5G 1X8, Canada. [Clarke, Joe T. R.] Univ Toronto, Toronto, ON, Canada. [Steiner, Robert D.] Oregon Hlth & Sci Univ, Dept Pediat & Mol & Med Genet, Portland, OR 97201 USA. [Beck, Michael] Johannes Gutenberg Univ Mainz, Ctr Lysosomal Storage Disorders, D-55122 Mainz, Germany. [Barshop, Bruce A.] Univ Calif San Diego, Rady Childrens Hospital San Diego, San Diego, CA 92103 USA. [Rhead, William] Med Coll Wisconsin, Dept Pediat & Pathol, Milwaukee, WI 53226 USA. [West, Michael] Dalhousie Univ, Div Nephrol, Dept Med, Halifax, NS, Canada. [Martin, Rick; Nair, Nitin] Shire Human Genet Therapies, Lexington, MA USA. [Amato, David] Vertex Pharmaceut, Cambridge, MA USA. [Huertas, Pedro] Pfizer Inc, Neurosci, Med Dev Grp, Cambridge, MA USA. [Huertas, Pedro] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Huertas, Pedro] Harvard Univ, Sch Med, Div Hlth Sci & Technol, MIT, Boston, MA USA. RP Schiffmann, R (reprint author), Baylor Res Inst, Inst Metab Dis, Dallas, TX USA. EM Raphael.Schiffmann@baylorhealth.edu OI Ries, Markus/0000-0002-5054-5741 FU Shire Human Genetic Therapies (HGT); Ray Beck of UBC-Envision Group; Shire HGT; Amicus Therapeutics; Genzyme; Amicus; Actelion; TKT/Shire HGT; Protalix/Pfizer; BioMarin; Zacharon; Hyperion; Ucyclyd; Sumitomo Pharma FX These studies and analyses were funded by Shire Human Genetic Therapies (HGT). Medical writing support for this article was provided by Ray Beck of UBC-Envision Group and was funded by Shire HGT.; R.S. has received honoraria and research support from Shire Human Genetic Therapies (HGT), Amicus Therapeutics, and Genzyme. K.N. has served on the Fabry Outcomes Survey advisory board that is funded by Shire HGT and has received travel and research support from Shire HGT, Genzyme, and Amicus; her center participates in clinical trials funded by Shire HGT and Amicus. A. M. has received research support and speaking honoraria from Shire HGT, Genzyme, and Actelion. J.T.R.C. has received research funding, consultancy fees, and/or speaker fees from Shire HGT, Genzyme, and Actelion. R. D. S. has participated in clinical trials funded by TKT/Shire HGT, Actelion, Genzyme, Protalix/Pfizer, and BioMarin. He has had research support from TKT and has received speaking or consulting fees from TKT/Shire HGT, Amicus, Actelion, Genzyme, Zacharon, and BioMarin. M. B. has received unrestricted grants, honoraria, and travel support from Shire HGT, Genzyme, BioMarin, and Actelion. B. A. B. has received research support from Genzyme and has served on an advisory board for BioMarin. W. R. has received research funding, consultancy fees, and/or speaker fees from Shire HGT, Genzyme, Hyperion, Ucyclyd, and Actelion and has served on advisory boards for Shire HGT. M. W. has received research support from Shire HGT and Genzyme; has received speaking honoraria from Shire HGT, Genzyme, Amicus Therapeutics, and Sumitomo Pharma; and has participated in advisory boards for Shire HGT. M. R. was an employee of Shire HGT from 2006 to 2009; he has served on advisory boards for Alexion, GSK, and Amicus and has received consultancy honoraria from Alexion, Oxyrane, and Shire HGT. P. H. was an employee of Shire HGT from 2008 to 2011. R. M. and N. N are employees of Shire HGT. D. A. was an employee of Shire HGT from 2010 to 2012. D. B. declares no potential competing interests. NR 25 TC 6 Z9 6 U1 0 U2 3 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1098-3600 EI 1530-0366 J9 GENET MED JI Genet. Med. PD DEC PY 2013 VL 15 IS 12 BP 983 EP 989 DI 10.1038/gim.2013.56 PG 7 WC Genetics & Heredity SC Genetics & Heredity GA 266XI UT WOS:000328056900012 PM 23680766 ER PT J AU Lee, LJ Damato, AL Viswanathan, AN AF Lee, Larissa J. Damato, Antonio L. Viswanathan, Akila N. TI Clinical outcomes following 3D image-guided brachytherapy for vaginal recurrence of endometrial cancer SO GYNECOLOGIC ONCOLOGY LA English DT Article; Proceedings Paper CT World Congress of Brachytherapy CY MAY 08-12, 2012 CL Barcelona, SPAIN DE Recurrent endometrial cancer; Salvage radiotherapy; Image-guided brachytherapy ID INTERSTITIAL GYNECOLOGIC BRACHYTHERAPY; DEFINITIVE RADIOTHERAPY; PROGNOSTIC-FACTORS; RADIATION-THERAPY; RANDOMIZED-TRIAL; CARCINOMA; ADENOCARCINOMA; MANAGEMENT; SURVIVAL; SURGERY AB Purpose. To evaluate clinical outcomes for women with recurrent endometrial cancer treated with 3D image-guided brachytherapy. Methods and materials. 44 women, of whom 13 had received prior RT, received salvage RT for vaginal recurrence from 9/03 to 8/11. HDR or LDR interstitial brachytherapy was performed under MR or CT guidance in 35 patients (80%); 9 (20%) had CT-guided HDR cylinder brachytherapy. The median cumulative dose in EQD2 was 75.5 Gy. Actuarial estimates of local failure (LF), disease-free (DFS) and overall survival (OS) were calculated by Kaplan-Meier. Results. Histologic subtypes were endometrioid (EAC, 33), papillary serous/clear cell (UPSC/CC, 5) and carcinosarcoma (CS, 6). The 2-year DFS/OS rates were 75%/89% for EAC and 11%/24% for UPSC/CC/CS (both p < 0.01). On MVA, high tumor grade was associated with recurrence (HR 32 for grade 2, 9.6 for grade 3, p < 0.01). The LF rate at 2 years was 4% for patients without versus 39% for those with prior RT (p = 0.1). Patients who had prior RT received lower cumulative doses at recurrence (66.5 Gy vs. 74.4 Gy, p < 0.01). The 2-year DFS/OS rates with and without prior RI were 26%/55% and 72%/80% (both p = 0.1). Four patients (9%) experienced grade 3 late toxicity, including 3 of 13 (23%) in the re-irradiation setting and 1 of 31 (3%) with no prior radiotherapy. Discussion. 3D image-guided brachytherapy results in excellent local control for women with recurrent endometrial cancer, particularly with cumulative EQD2 doses greater than 70 Gy. Successful salvage of vaginal recurrence is related to tumor grade and histologic subtype. (C) 2013 Elsevier Inc. All rights reserved. C1 [Lee, Larissa J.] Brigham & Womens Hosp, Dept Radiat Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. RP Lee, LJ (reprint author), Brigham & Womens Hosp, Dept Radiat Oncol, 75 Francis St,ASBI-L2, Boston, MA 02115 USA. EM llee@lroc.harvard.edu NR 23 TC 11 Z9 11 U1 1 U2 4 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0090-8258 EI 1095-6859 J9 GYNECOL ONCOL JI Gynecol. Oncol. PD DEC PY 2013 VL 131 IS 3 BP 586 EP 592 DI 10.1016/j.ygyno.2013.08.040 PG 7 WC Oncology; Obstetrics & Gynecology SC Oncology; Obstetrics & Gynecology GA 265AZ UT WOS:000327923400017 PM 24029418 ER PT J AU Shoni, M Nagymanyoki, Z Vitonis, AF Jimenez, C Ng, SW Quade, BJ Berkowitz, RS AF Shoni, Melina Nagymanyoki, Zoltan Vitonis, Allison F. Jimenez, Cynthia Ng, Shu-Wing Quade, Bradley J. Berkowitz, Ross S. TI p-21-Activated kinase-1,-4 and-6 and estrogen receptor expression pattern in normal placenta and gestational trophoblastic diseases SO GYNECOLOGIC ONCOLOGY LA English DT Article DE Gestational trophoblastic diseases; p-21-Activated Kinases; PAK-6; Estrogen receptors ID P21-ACTIVATED KINASE; ANDROGEN RECEPTOR; PROSTATE-CANCER; PHOSPHORYLATION; INVASION; PAK1; CELLS; CHORIOCARCINOMA; PROLIFERATION; METASTASIS AB Objectives. To delineate the potential role of p21-activated kinases (PAKs) in the pathogenesis of gestational trophoblastic diseases (GTD) by defining the expression pattern of PAK-1, -4 and -6 and their potential implication in estrogen receptor (ER) regulation of normal placental tissue and GTD. Methods. We evaluated immunohistochemically 10 normal first-trimester placentas (NP), 10 partial moles (PM), 15 complete moles (CM) and 3 choriocarcinomas (CCA) for PAR-1, PAK-4, PAK-6 and ER expression intensity and localization. Staining outcomes were assessed utilizing non-parametric Kruskal-Wallis one-way analysis of variance test followed by pairwise Wilcoxon Rank Sum tests. Statistical significance was determined by two-sided p-value of <0.05. Results. In NP, PAK-6 immunoreactivity was predominantly cytoplasmic. Compared to NP, PM and CM demonstrated significant increase of cytoplasmic PAK-6 in cytotrophoblast (p = 0.012, p = 0.033 respectively), accompanied by significantly increased nuclear immunoreactivity in cytotrophoblast (p = 0.008, p = 0.045 respectively) and intermediate trophoblast (p = 0.003, p = 0.015 respectively). PAK-4 was found significantly upregulated in both cytoplasmic and nuclear compartments of cytotrophoblast and syncytiotrophoblast in PM (p = 0.004 and p = 0.002 for cytotrophoblast; p = 0.018 and p = 0.002 for syncytiotrophoblast, respectively) and CM (p = 0.001 and p = 0.001 for cytotrophoblast; p = 0.002 and p = 0.001 for syncytiotrophoblast, respectively) when compared to NP, whereas PAK-1 expression was significantly reduced in the syncytiotrophoblast of PM (p = 0.025 for cytoplasm and p = 0.008 for nucleus). Nuclear expression of ER was undetectable in all stained samples. Conclusion. Our results reveal PAK-6 upregulation in GTD compared to NP. The absence of nuclear expression of ER might stem in part from the repressive effect of PAK-6 in trophoblastic tissue. (C) 2013 Elsevier Inc. All rights reserved. C1 [Shoni, Melina; Vitonis, Allison F.; Ng, Shu-Wing; Berkowitz, Ross S.] Harvard Univ, Sch Med, Dana Farber Canc Inst,Brigham & Womens Hosp, Div Gynecol Oncol,Dept Obstet & Gynecol, Boston, MA 02115 USA. [Nagymanyoki, Zoltan; Jimenez, Cynthia; Quade, Bradley J.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Div Womens & Perinatal Pathol,Dept Pathol, Boston, MA 02115 USA. RP Berkowitz, RS (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst,Brigham & Womens Hosp, Div Gynecol Oncol,Dept Obstet & Gynecol, 44 Binney St, Boston, MA 02115 USA. EM rberkowitz@partners.org FU Foundation for Education and European Culture (IPEP), Greece FX We would like to thank the Foundation for Education and European Culture (IPEP), Greece, for the generous support on this research effort. Our abstract has been accepted for an oral presentation at the 2013 World Congress XVII of the Society for the Study of Trophoblastic Diseases (ISSTD) in Chicago, IL. NR 29 TC 1 Z9 1 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 0090-8258 EI 1095-6859 J9 GYNECOL ONCOL JI Gynecol. Oncol. PD DEC PY 2013 VL 131 IS 3 BP 759 EP 763 DI 10.1016/j.ygyno.2013.09.010 PG 5 WC Oncology; Obstetrics & Gynecology SC Oncology; Obstetrics & Gynecology GA 265AZ UT WOS:000327923400047 PM 24051221 ER PT J AU Barbosa, R Zhang, B Sasaki, Y Wunderlich, T Supprian, MS Rajewsky, K Calado, D AF Barbosa, R. Zhang, B. Sasaki, Y. Wunderlich, T. Supprian, M. Schmidt Rajewsky, K. Calado, D. TI NF-kappa B and cMyc cooperate to induce B-cell transformation and plasma cell neoplasia SO IMMUNOLOGY LA English DT Meeting Abstract CT Annual Congress of the British-Society-for-Immunology CY DEC 02-05, 2013 CL Liverpool, ENGLAND SP British Soc Immunol C1 [Barbosa, R.; Calado, D.] Canc Res UK, London Res Inst, Immun & Canc Lab, London, England. [Zhang, B.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. [Sasaki, Y.] Kyoto Univ, Kyoto, Japan. [Wunderlich, T.] Univ Cologne, Inst Genet, Cologne, Germany. [Supprian, M. Schmidt] Max Plank Inst Biochem, Munich, Germany. [Rajewsky, K.] Max Delbrueck Ctr Mol Med, Berlin, Germany. [Calado, D.] Kings Coll London, London WC2R 2LS, England. NR 0 TC 0 Z9 0 U1 0 U2 2 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0019-2805 EI 1365-2567 J9 IMMUNOLOGY JI Immunology PD DEC PY 2013 VL 140 SU 1 SI SI BP 64 EP 64 PG 1 WC Immunology SC Immunology GA 258VV UT WOS:000327487700148 ER PT J AU Beilin, C Choudhuri, K Bouma, G Malinova, D Llodra, J Stokes, DL Shimaoka, M Springer, TA Thrasher, AJ Dustin, ML Burns, SO AF Beilin, C. Choudhuri, K. Bouma, G. Malinova, D. Llodra, J. Stokes, D. L. Shimaoka, M. Springer, T. A. Thrasher, A. J. Dustin, M. L. Burns, S. O. TI Dendritic cell-expressed common cytokine receptor g-chain is essential for effective IL-15 transpresentation to CD4+T cells at the immunological synapse SO IMMUNOLOGY LA English DT Meeting Abstract CT Annual Congress of the British-Society-for-Immunology CY DEC 02-05, 2013 CL Liverpool, ENGLAND SP British Soc Immunol C1 [Beilin, C.; Bouma, G.; Malinova, D.; Thrasher, A. J.] UCL, Inst Child Hlth, London, England. [Choudhuri, K.; Llodra, J.; Stokes, D. L.; Dustin, M. L.] NYU, Skirball Inst Biomol Med, New York, NY USA. [Shimaoka, M.; Springer, T. A.] Childrens Hosp, Immune Dis Inst, Boston, MA 02115 USA. [Dustin, M. L.] Univ Oxford, Kennedy Inst Rheumatol, Oxford, England. [Burns, S. O.] UCL, Inst Immun & Transplantat, London, England. NR 0 TC 0 Z9 0 U1 0 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0019-2805 EI 1365-2567 J9 IMMUNOLOGY JI Immunology PD DEC PY 2013 VL 140 SU 1 SI SI BP 156 EP 156 PG 1 WC Immunology SC Immunology GA 258VV UT WOS:000327487700406 ER PT J AU Seto, D Jones, MS Dyer, DW Chodosh, J AF Seto, Donald Jones, Morris S. Dyer, David W. Chodosh, James TI Characterizing, typing, and naming human adenovirus type 55 in the era of whole genome data SO JOURNAL OF CLINICAL VIROLOGY LA English DT Letter ID ACUTE RESPIRATORY-DISEASE; EPIDEMIC KERATOCONJUNCTIVITIS; MOLECULAR EVOLUTION; OUTBREAK; ILLNESS C1 [Seto, Donald] George Mason Univ, Bioinformat & Computat Biol Program, Sch Syst Biol, Manassas, VA 20110 USA. [Jones, Morris S.] Naval Med Ctr, Div Infect Dis, San Diego, CA 92134 USA. [Dyer, David W.] Univ Oklahoma, Hlth Sci Ctr, Dept Microbiol & Immunol, Oklahoma City, OK 73104 USA. [Chodosh, James] Harvard Univ, Dept Ophthalmol, Massachusetts Eye & Ear Infirm, Howe Lab,Med Sch, Boston, MA 02114 USA. RP Seto, D (reprint author), George Mason Univ, Bioinformat & Computat Biol Program, Sch Syst Biol, 10900 Univ Blvd,MSN 5B3, Manassas, VA 20110 USA. EM dseto@gmu.edu FU NEI NIH HHS [R01 EY013124] NR 15 TC 6 Z9 7 U1 1 U2 5 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1386-6532 EI 1873-5967 J9 J CLIN VIROL JI J. Clin. Virol. PD DEC PY 2013 VL 58 IS 4 BP 741 EP 742 DI 10.1016/j.jcv.2013.09.025 PG 2 WC Virology SC Virology GA 263PN UT WOS:000327820600027 PM 24161575 ER PT J AU Greaser, ML Potter, JD Thomas, DD Strasburg, GM Lehrer, SS Wang, CLA Grabarek, Z AF Greaser, Marion L. Potter, James D. Thomas, David D. Strasburg, Gale M. Lehrer, Sherwin S. Wang, Chih-Lueh Albert Grabarek, Zenon TI John Gergely (1919-2013): a pillar in the muscle protein field SO JOURNAL OF MUSCLE RESEARCH AND CELL MOTILITY LA English DT Biographical-Item DE Troponin; Tropomyosin; Myosin, calcium regulation of muscle contraction AB Dr. John Gergely passed away on July 26, 2013 after a long and distinguished career. His publications spanned 67 years. He founded the Department of Muscle Research in the Retina Foundation (which later became the Boston Biomedical Research Institute) and served as director for 34 years. Dr. Gergely served on the editorial boards of ten scientific journals. He was elected as a Fellow of both the Biophysical Society and the American Association for the Advancement of Science. Dr. Gergely made major contributions concerning muscle protein structure and function. He was best known for his work on the troponin complex. The insights of John and his associates have provided the foundation for our understanding of calcium regulation in skeletal and cardiac muscle. C1 [Greaser, Marion L.] Univ Wisconsin, Madison, WI 53706 USA. [Potter, James D.] Univ Miami, Miller Sch Med, Miami, FL 33136 USA. [Thomas, David D.] Univ Minnesota, Dept Biochem, Minneapolis, MN 55455 USA. [Strasburg, Gale M.] Michigan State Univ, Dept Food Sci & Human Nutr, E Lansing, MI 48824 USA. [Lehrer, Sherwin S.] Boston Biomed Res Inst, Boston, MA USA. [Wang, Chih-Lueh Albert] Boston Univ, Sch Med, Dept Physiol & Biophys, Boston, MA 02118 USA. [Grabarek, Zenon] Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. RP Greaser, ML (reprint author), Univ Wisconsin, Madison, WI 53706 USA. EM mgreaser@ansci.wisc.edu OI Strasburg, Gale/0000-0002-3897-4340 NR 1 TC 0 Z9 0 U1 1 U2 2 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0142-4319 EI 1573-2657 J9 J MUSCLE RES CELL M JI J. Muscle Res. Cell Motil. PD DEC PY 2013 VL 34 IS 5-6 BP 441 EP 446 DI 10.1007/s10974-013-9370-9 PG 6 WC Cell Biology SC Cell Biology GA 269AC UT WOS:000328211200012 PM 24264290 ER PT J AU Strazzula, L Brown, KK Brieva, JC Camp, BJ Frankel, HC Kissin, E Mahlberg, MJ Mina, MA Pomeranz, MK Brownell, I Kroshinsky, D AF Strazzula, Lauren Brown, Katherine K. Brieva, Joaquin C. Camp, Brendan J. Frankel, Hillary C. Kissin, Eugene Mahlberg, Matthew J. Mina, Mary Alice Pomeranz, Miriam K. Brownell, Isaac Kroshinsky, Daniela TI Levamisole toxicity mimicking autoimmune disease SO JOURNAL OF THE AMERICAN ACADEMY OF DERMATOLOGY LA English DT Article DE antineutrophil cytoplasmic antibody; cocaine; granulomatosis with polyangiitis (Wegener); levamisole; purpura; vasculitis; vasculopathy ID INDUCED VASCULITIS; RETIFORM PURPURA; COCAINE; NEUTROPENIA; EARS AB Background: Levamisole is present as a contaminant or additive in most cocaine sold in the United States. Cases of agranulocytosis attributed to levamisole-tainted cocaine have been widely described. A vasculopathic reaction to levamisole has also been reported; however, diagnostic features such as antineutrophil cytoplasmic antibody (ANCA) and additional autoimmune marker positivity are not well recognized. As such, many patients are given a misdiagnosis, prompting aggressive and often unnecessary treatment. Objective: We hope to educate practitioners about the clinical and laboratory features of levamisole-induced vasculopathy to ensure accurate diagnosis and management. Methods: This was a case series. Results: Six patients were admitted with purpuric lesions and vasculitic changes on biopsy specimen; 5 of them were given the diagnosis of and treated for autoimmune conditions before their true diagnosis was revealed. All patients had ANCA positivity, and 4 had additional abnormalities in autoimmune markers. All patients reported recent cocaine abuse, and were ultimately given the diagnosis of levamisole-induced vasculopathy. Limitations: This observational study is limited by sample size. Conclusions: Patients presenting with purpuric lesions with ANCA positivity should be assessed for cocaine exposure. It is important to recognize that levamisole may not only induce ANCA positivity but also other autoimmune marker abnormalities. Patients can often be treated with less aggressive therapeutic strategies than what is used for primary ANCA-associated vasculitides. C1 [Strazzula, Lauren; Frankel, Hillary C.; Mina, Mary Alice; Kroshinsky, Daniela] Massachusetts Gen Hosp, Dept Dermatol, Boston, MA 02114 USA. [Brown, Katherine K.; Brieva, Joaquin C.] Northwestern Univ, Feinberg Sch Med, Dept Dermatol, Chicago, IL 60611 USA. [Camp, Brendan J.] New York Presbyterian Hosp, Dept Dermatol, New York, NY USA. [Camp, Brendan J.] Weill Cornell Med Ctr, New York, NY USA. [Frankel, Hillary C.; Mina, Mary Alice; Kroshinsky, Daniela] Harvard Univ, Sch Med, Dept Dermatol, Boston, MA 02115 USA. [Kissin, Eugene] Boston Univ, Dept Rheumatol, Boston, MA 02215 USA. [Mahlberg, Matthew J.; Pomeranz, Miriam K.] NYU, Med Ctr, Ronald O Perelman Dept Dermatol, New York, NY 10003 USA. [Brownell, Isaac] NCI, Dermatol Branch, Bethesda, MD 20892 USA. RP Kroshinsky, D (reprint author), Dermatol Associates, 50 Staniford St,2nd Floor, Boston, MA 02114 USA. EM dkroshinsky@partners.org OI Pomeranz, Miriam Keltz/0000-0002-6959-9280 NR 15 TC 7 Z9 7 U1 0 U2 2 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0190-9622 J9 J AM ACAD DERMATOL JI J. Am. Acad. Dermatol. PD DEC PY 2013 VL 69 IS 6 BP 954 EP 959 DI 10.1016/j.jaad.2013.07.037 PG 6 WC Dermatology SC Dermatology GA 262LN UT WOS:000327736900029 PM 24075227 ER PT J AU Hanke, CW Moy, RL Roenigk, RK Roenigk, HH Spencer, JM Tierney, EP Bartus, CL Bernstein, RM Brown, MD Busso, M Carruthers, A Carruthers, J Ibrahimi, OA Kauvar, ANB Kent, KM Krueger, N Landau, M Leonard, AL Mandy, SH Rohrer, TE Sadick, NS Wiest, LG AF Hanke, C. William Moy, Ronald L. Roenigk, Randall K. Roenigk, Henry H., Jr. Spencer, James M. Tierney, Emily P. Bartus, Cynthia L. Bernstein, Robert M. Brown, Marc D. Busso, Mariano Carruthers, Alastair Carruthers, Jean Ibrahimi, Omar A. Kauvar, Arielle N. B. Kent, Kathryn M. Krueger, Nils Landau, Marina Leonard, Aimee L. Mandy, Stephen H. Rohrer, Thomas E. Sadick, Neil S. Wiest, Luitgard G. TI Current status of surgery in dermatology SO JOURNAL OF THE AMERICAN ACADEMY OF DERMATOLOGY LA English DT Article DE fellowship; office-based; quality; surgery; training ID PULSED-DYE-LASER; MOHS MICROGRAPHIC SURGERY; PORT-WINE STAINS; L-LACTIC ACID; TOXIN TYPE-A; STABILIZED HYALURONIC-ACID; SOFT-TISSUE AUGMENTATION; OF-THE-LITERATURE; ND-YAG LASER; GREAT SAPHENOUS-VEIN AB An article titled "Current issues in dermatologic office-based surgery" was published in the JAAD in October 1999 (volume 41, issue 4, pp. 624-634). The article was developed by the Joint American Academy of Dermatology/American Society for Dermatologic Surgery Liaison Committee. A number of subjects were addressed in the article including surgical training program requirements for dermatology residents and selected advances in dermatologic surgery that had been pioneered by dermatologists. The article concluded with sections on credentialing, privileging, and accreditation of office-based surgical facilities. Much has changed since 1999, including more stringent requirements for surgical training during dermatology residency, and the establishment of 57 accredited Procedural Dermatology Fellowship Training Programs. All of these changes have been overseen and approved by the Residency Review Committee for Dermatology and the Accreditation Committee for Graduate Medical Education. The fertile academic environment of academic training programs with interaction between established dermatologic surgeons and fellows, as well as the inquisitive nature of many of our colleagues, has led to the numerous major advances in dermatologic surgery, which are described herein. C1 [Moy, Ronald L.] Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90024 USA. [Spencer, James M.] Mt Sinai Sch Med, New York, NY USA. [Tierney, Emily P.; Leonard, Aimee L.] Tufts Univ, Sch Med, Dept Dermatol, Boston, MA 02111 USA. [Bartus, Cynthia L.] Adv Dermatol Associates, Allentown, PA USA. [Bartus, Cynthia L.] Lehigh Valley Hlth Network, Allentown, PA USA. [Bernstein, Robert M.] Bernstein Med Ctr Hair Restorat, New York, NY USA. [Bernstein, Robert M.] Columbia Univ, New York, NY USA. [Brown, Marc D.] Univ Rochester, Med Ctr, Rochester, NY 14627 USA. [Carruthers, Alastair] Univ British Columbia, Dept Dermatol & Skin Sci, Vancouver, BC V5Z 1M9, Canada. [Carruthers, Jean] Univ British Columbia, Dept Ophthalmol, Vancouver, BC V5Z 1M9, Canada. [Ibrahimi, Omar A.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Wellman Ctr Photomed, Boston, MA USA. [Kauvar, Arielle N. B.] New York Laser & Skin Care, New York, NY USA. [Kauvar, Arielle N. B.] NYU, Sch Med, New York, NY 10003 USA. [Kent, Kathryn M.] Boston Univ, Sch Med, Boston, MA 02215 USA. [Krueger, Nils] Univ Hamburg, Div Cosmet Sci, Hamburg, Germany. [Leonard, Aimee L.] New England Dermatol & Laser Ctr, Springfield, MO USA. [Mandy, Stephen H.] South Beach Dermatol, Miami Beach, FL USA. [Mandy, Stephen H.] Skin & Canc Associates, Miami Beach, FL USA. [Mandy, Stephen H.] Univ Miami, Coral Gables, FL 33124 USA. [Roenigk, Henry H., Jr.] Northwestern Univ, Feinberg Sch Med, Chicago, IL 60611 USA. [Roenigk, Randall K.] Mayo Clin, Dept Dermatol, Rochester, MN USA. [Rohrer, Thomas E.] SkinCare Phys, Chestnut Hill, MA USA. [Rohrer, Thomas E.] Brown Univ, Sch Med, Providence, RI 02912 USA. [Sadick, Neil S.] Weill Cornell Med Coll, New York, NY USA. [Wiest, Luitgard G.] Privatarztl Zentrum Munchen, Munich, Germany. RP Hanke, CW (reprint author), Amer Acad Dermatol, 1445 New York Ave,Suite 800, Washington, DC 20005 USA. RI Krueger, Nils/E-9056-2013 OI Krueger, Nils/0000-0003-0055-3759 NR 298 TC 9 Z9 9 U1 0 U2 9 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0190-9622 J9 J AM ACAD DERMATOL JI J. Am. Acad. Dermatol. PD DEC PY 2013 VL 69 IS 6 BP 972 EP 1001 DI 10.1016/j.jaad.2013.04.067 PG 30 WC Dermatology SC Dermatology GA 262LN UT WOS:000327736900032 PM 24099730 ER PT J AU Dukhovny, S Wilkins-Haug, L Shipp, TD Benson, CB Kaimal, AJ Reiss, R AF Dukhovny, Stephanie Wilkins-Haug, Louise Shipp, Thomas D. Benson, Carol B. Kaimal, Anjali J. Reiss, Rosemary TI Absent Fetal Nasal Bone What Does It Mean for the Euploid Fetus? SO JOURNAL OF ULTRASOUND IN MEDICINE LA English DT Article DE absent nasal bone; euploid fetus; prenatal diagnosis ID PRENATAL-DIAGNOSIS; DOWN-SYNDROME; GESTATION; TRISOMY-21 AB Objectives-Our purpose was to review the outcomes of singleton pregnancies in which an absent nasal bone was noted on first- or second-trimester sonography and aneuploidy was not present. Methods-We identified singleton pregnancies from 2005 to 2011 in which an absent nasal bone was noted on sonography, aneuploidy was excluded, and newborn examinations were available for review. Sonographic reports were reviewed for anomalies, growth, and amniotic fluid volume. Newborn records were reviewed for physical examinations, complications, and radiologic or genetic tests. Results-We identified 142 fetuses with a sonographic appearance of an absent nasal bone. We excluded 52 cases with aneuploidy and 33 in which newborn examination information was unavailable. Fifty-seven cases met inclusion criteria. For 3 euploid fetuses with an absent nasal bone on sonography, the presence of additional anomalies on second-trimester sonography ultimately signaled an adverse outcome: the presence of multiple congenital anomalies, a microdeletion syndrome, and a specific genetic diagnosis. Conclusions-All cases with adverse outcomes had additional prenatal sonographic findings. For the remainder, normal newborn examination findings provide some reassurance, especially in the setting of otherwise normal second-trimester sonographic findings. A microarray as a test for microdeletion and duplication syndromes in this situation could be considered. C1 [Dukhovny, Stephanie; Wilkins-Haug, Louise; Shipp, Thomas D.; Benson, Carol B.; Reiss, Rosemary] Brigham & Womens Hosp, Boston, MA 02118 USA. [Kaimal, Anjali J.] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Dukhovny, S (reprint author), Brigham & Womens Hosp, 75 Francis St, Boston, MA 02118 USA. EM sdukhovny@partners.org NR 15 TC 0 Z9 1 U1 0 U2 5 PU AMER INST ULTRASOUND MEDICINE PI LAUREL PA SUBSCRIPTION DEPT, 14750 SWEITZER LANE, STE 100, LAUREL, MD 20707-5906 USA SN 0278-4297 EI 1550-9613 J9 J ULTRAS MED JI J. Ultrasound Med. PD DEC PY 2013 VL 32 IS 12 BP 2131 EP 2134 DI 10.7863/ultra.32.12.2131 PG 4 WC Acoustics; Radiology, Nuclear Medicine & Medical Imaging SC Acoustics; Radiology, Nuclear Medicine & Medical Imaging GA 267LK UT WOS:000328099000010 PM 24277895 ER PT J AU Brattain, LJ Telfer, BA Liteplo, AS Noble, VE AF Brattain, Laura J. Telfer, Brian A. Liteplo, Andrew S. Noble, Vicki E. TI Automated B-Line Scoring on Thoracic Sonography SO JOURNAL OF ULTRASOUND IN MEDICINE LA English DT Article DE B-lines; diagnostic assistant; extravascular lung water; pulmonary edema; thoracic sonography AB With the proliferation of portable sonography and the increase in nontraditional users, there is an increased need for automated decision support to standardize results. We developed algorithms to evaluate the presence or absence of "B-lines" on thoracic sonography as a marker for interstitial fluid. Algorithm performance was compared against an average of scores from 2 expert clinical sonographers. On the set for algorithm development, 90% of the scores matched the average expert scores with differences of 1 or less. On the independent set, a perfect match was achieved. We believe that these are the first reported results in computerized B-line scoring. C1 [Brattain, Laura J.; Telfer, Brian A.] MIT, Lincoln Lab, Lexington, MA 02420 USA. [Liteplo, Andrew S.; Noble, Vicki E.] Massachusetts Gen Hosp, Dept Emergency Med, Div Emergency Ultrasound, Boston, MA 02114 USA. RP Brattain, LJ (reprint author), MIT, Lincoln Lab, Div 4, 244 Wood St, Lexington, MA 02420 USA. EM brattainl@ll.mit.edu FU Defense for Research and Engineering under Air Force [FA8721-05-C-0002] FX We thank Tadd Hughes, Albert Swiston, and James Williamson from the Massachusetts Institute of Technology Lincoln Laboratory for their valuable inputs on this project. This work was sponsored by the Assistant Secretary of Defense for Research and Engineering under Air Force contract FA8721-05-C-0002. The opinions, interpretations, recommendations, and conclusions are those of the authors and are not necessarily endorsed by the US Government. NR 8 TC 11 Z9 11 U1 0 U2 3 PU AMER INST ULTRASOUND MEDICINE PI LAUREL PA SUBSCRIPTION DEPT, 14750 SWEITZER LANE, STE 100, LAUREL, MD 20707-5906 USA SN 0278-4297 EI 1550-9613 J9 J ULTRAS MED JI J. Ultrasound Med. PD DEC PY 2013 VL 32 IS 12 BP 2185 EP 2190 DI 10.7863/ultra.32.12.2185 PG 6 WC Acoustics; Radiology, Nuclear Medicine & Medical Imaging SC Acoustics; Radiology, Nuclear Medicine & Medical Imaging GA 267LK UT WOS:000328099000017 PM 24277902 ER PT J AU Tuli, A Thiery, J James, AM Michelet, X Sharma, M Garg, S Sanborn, KB Orange, JS Lieberman, J Brenner, MB AF Tuli, Amit Thiery, Jerome James, Ashley M. Michelet, Xavier Sharma, Mahak Garg, Salil Sanborn, Keri B. Orange, Jordan S. Lieberman, Judy Brenner, Michael B. TI Arf-like GTPase Arl8b regulates lytic granule polarization and natural killer cell-mediated cytotoxicity SO MOLECULAR BIOLOGY OF THE CELL LA English DT Article ID LYSOSOME-RELATED ORGANELLES; IMMUNOLOGICAL SYNAPSE; MELANOSOME TRANSPORT; MYOSIN VA; MEMBRANE-TRANSPORT; HEAVY-CHAIN; T-CELLS; KINESIN; COMPLEX; PROTEIN AB Natural killer (NK) lymphocytes contain lysosome-related organelles (LROs), known as lytic granules, which upon formation of immune synapse with the target cell, polarize toward the immune synapse to deliver their contents to the target cell membrane. Here, we identify a small GTP-binding protein, ADP-ribosylation factor-like 8b (Arl8b), as a critical factor required for NK cell-mediated cytotoxicity. Our findings indicate that Arl8b drives the polarization of lytic granules and microtubule-organizing centers (MTOCs) toward the immune synapse between effector NK lymphocytes and target cells. Using a glutathione S-transferase pull-down approach, we identify kinesin family member 5B (KIF5B; the heavy chain of kinesin-1) as an interaction partner of Arl8b from NK cell lysates. Previous studies showed that interaction between kinesin-1 and Arl8b is mediated by SifA and kinesin-interacting protein (SKIP) and the tripartite complex drives the anterograde movement of lysosomes. Silencing of both KIF5B and SKIP in NK cells, similar to Arl8b, led to failure of MTOC-lytic granule polarization to the immune synapse, suggesting that Arl8b and kinesin-1 together control this critical step in NK cell cytotoxicity. C1 [Tuli, Amit; Michelet, Xavier; Sharma, Mahak; Garg, Salil; Brenner, Michael B.] Harvard Univ, Brigham & Womens Hosp, Div Rheumatol Immunol & Allergy, Dept Med,Med Sch, Boston, MA 02115 USA. [Tuli, Amit] Inst Microbial Technol, Div Cell Biol & Immunol, Chandigarh 160036, India. [Thiery, Jerome; Sanborn, Keri B.; Lieberman, Judy] Harvard Univ, Sch Med, Boston Childrens Hosp, Program Cellular & Mol Med, Boston, MA 02115 USA. [Thiery, Jerome] Inst Gustave Roussy, Unite 753, Inst Natl Sante & Rech Med, F-75654 Villejuif, France. [James, Ashley M.; Sanborn, Keri B.; Orange, Jordan S.] Univ Penn, Sch Med, Dept Pediat, Philadelphia, PA 19104 USA. [Sharma, Mahak] Indian Inst Sci Educ & Res, Dept Biol Sci, Mohali 140306, India. [Orange, Jordan S.] Texas Childrens Hosp, Baylor Coll Med, Houston, TX 77030 USA. RP Tuli, A (reprint author), Harvard Univ, Brigham & Womens Hosp, Div Rheumatol Immunol & Allergy, Dept Med,Med Sch, Boston, MA 02115 USA. EM atuli@imtech.res.in; mbrenner@research.bwh.harvard.edu RI Lieberman, Judy/A-2717-2015; OI orange, jordan/0000-0001-7117-7725 FU Ramanujan Fellowship (Department of Science and Technology, India); Wellcome Trust/DBT India Alliance Intermediate Fellowship Award; Wellcome Trust FX We thank S. Linder (Universitatsklinikum Hamburg-Eppendorf, Hamburg, Germany), K. Verhey (University of Michigan, Ann Arbor, MI), and T. Schroer (Johns Hopkins University, Baltimore, MD) for their general gifts of molecular constructs. We thank M. Ericsson for help in electron microscopy analyses, M. Walch for assistance in chromium assay, and R. Tomaino for assistance with mass spectrometry (Taplin Biological Mass Spectrometry Facility, Harvard Medical School, Boston, MA). A. T. thanks J. Solheim, S. Caplan, and N. Naslavsky (University of Nebraska, Lincoln, NE) for their previous mentorship, gifts of molecular constructs, and helpful discussions and critical reading of the manuscript and members of the Brenner, Jordan, and Lieberman laboratories and V. Hsu for helpful discussions. A. T. acknowledges support from a Ramanujan Fellowship (Department of Science and Technology, India). M. S. is the recipient of a Wellcome Trust/DBT India Alliance Intermediate Fellowship Award and acknowledges support from a Wellcome Trust grant. NR 52 TC 17 Z9 17 U1 0 U2 3 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 EI 1939-4586 J9 MOL BIOL CELL JI Mol. Biol. Cell PD DEC 1 PY 2013 VL 24 IS 23 BP 3721 EP 3735 DI 10.1091/mbc.E13-05-0259 PG 15 WC Cell Biology SC Cell Biology GA 267UZ UT WOS:000328125100012 PM 24088571 ER PT J AU Henderson, NC Arnold, TD Katamura, Y Giacomini, MM Rodriguez, JD McCarty, JH Pellicoro, A Raschperger, E Betsholtz, C Ruminski, PG Griggs, DW Prinsen, MJ Maher, JJ Iredale, JP Lacy-Hulbert, A Adams, RH Sheppard, D AF Henderson, Neil C. Arnold, Thomas D. Katamura, Yoshio Giacomini, Marilyn M. Rodriguez, Juan D. McCarty, Joseph H. Pellicoro, Antonella Raschperger, Elisabeth Betsholtz, Christer Ruminski, Peter G. Griggs, David W. Prinsen, Michael J. Maher, Jacquelyn J. Iredale, John P. Lacy-Hulbert, Adam Adams, Ralf H. Sheppard, Dean TI Targeting of alpha(v) integrin identifies a core molecular pathway that regulates fibrosis in several organs SO NATURE MEDICINE LA English DT Article ID GROWTH-FACTOR-BETA; ACTIVATES LATENT TGF-BETA-1; RAT HEPATIC LIPOCYTES; FAT-STORING CELLS; EXTRACELLULAR-MATRIX; INCREASED EXPRESSION; FACTOR RECEPTOR; LIVER; INDUCTION; COLLAGEN AB Myofibroblasts are the major source of extracellular matrix components that accumulate during tissue fibrosis, and hepatic stellate cells (HSCs) are believed to be the major source of myofibroblasts in the liver. To date, robust systems to genetically manipulate these cells have not been developed. We report that Cre under control of the promoter of Pdgfrb (Pdgfrb-Cre) inactivates loxP-flanked genes in mouse HSCs with high efficiency. We used this system to delete the gene encoding alpha(v) integrin subunit because various alpha(v)-containing integrins have been suggested as central mediators of fibrosis in multiple organs. Such depletion protected mice from carbon tetrachloride-induced hepatic fibrosis, whereas global loss of beta(3), beta(5) or beta(6) integrins or conditional loss of beta(8) integrins in HSCs did not. We also found that Pdgfrb-Cre effectively targeted myofibroblasts in multiple organs, and depletion of the alpha(v) integrin subunit using this system was protective in other models of organ fibrosis, including pulmonary and renal fibrosis. Pharmacological blockade of alpha(v)-containing integrins by a small molecule (CWHM 12) attenuated both liver and lung fibrosis, including in a therapeutic manner. These data identify a core pathway that regulates fibrosis and suggest that pharmacological targeting of all alpha(v) integrins may have clinical utility in the treatment of patients with a broad range of fibrotic diseases. C1 [Henderson, Neil C.; Katamura, Yoshio; Giacomini, Marilyn M.; Rodriguez, Juan D.; Sheppard, Dean] Univ Calif San Francisco, Dept Med, Lung Biol Ctr, San Francisco, CA 94143 USA. [Henderson, Neil C.; Pellicoro, Antonella; Iredale, John P.] Univ Edinburgh, Queens Med Res Inst, MRC, Ctr Inflammat Res, Edinburgh, Midlothian, Scotland. [Arnold, Thomas D.] Univ Calif San Francisco, Dept Pediat, San Francisco, CA USA. [McCarty, Joseph H.] Univ Texas MD Anderson Canc Ctr, Dept Canc Biol, Houston, TX 77030 USA. [Raschperger, Elisabeth; Betsholtz, Christer] Uppsala Univ, Dept Immunol Genet & Pathol, Uppsala, Sweden. [Raschperger, Elisabeth; Betsholtz, Christer] Karolinska Inst, Dept Med Biochem & Biophys, Stockholm, Sweden. [Ruminski, Peter G.; Griggs, David W.; Prinsen, Michael J.] St Louis Univ, Edward A Doisy Res Ctr, Ctr World Hlth & Med, St Louis, MO 63103 USA. [Maher, Jacquelyn J.] Univ Calif San Francisco, Ctr Liver, Dept Med, San Francisco, CA 94143 USA. [Lacy-Hulbert, Adam] Massachusetts Gen Hosp, Dept Pediat, Program Dev Immunol, Boston, MA 02114 USA. [Lacy-Hulbert, Adam] Harvard Univ, Sch Med, Boston, MA USA. [Adams, Ralf H.] Univ Munster, Fac Med, Max Planck Inst Mol Biomed, Dept Tissue Morphogenesis, D-48149 Munster, Germany. RP Henderson, NC (reprint author), Univ Calif San Francisco, Dept Med, Lung Biol Ctr, San Francisco, CA 94143 USA. EM neil.henderson@ed.ac.uk; dean.sheppard@ucsf.edu OI Lacy-Hulbert, Adam/0000-0003-2162-0156 FU Wellcome Trust Intermediate Clinical Fellowship [085187]; National Institutes of Health [HL102292, HL53949, AI077439]; University of California, San Francisco (UCSF) Liver Center Tool and Technology grant; UCSF Liver Center [P30 DK026743] FX This work was supported by a Wellcome Trust Intermediate Clinical Fellowship (ref. 085187) to N.C.H., National Institutes of Health grants HL102292, HL53949 and AI077439 (to D.S.), a University of California, San Francisco (UCSF) Liver Center Tool and Technology grant (to N.C.H) and P30 DK026743 (UCSF Liver Center). We thank K. Thorn at the UCSF Nikon Imaging Center for assistance with image analysis. We also thank C. Her, N. Wu, S. Huling, D. Rodrigues and R. Aucott for expert technical assistance. We also acknowledge the contribution of M. Singh (chemical synthesis of compounds CWHM 12 and CWHM 96), D. Tajfirouz, S. Freeman and M. Yates at Saint Louis University for technical assistance in conducting integrin functional assays to characterize compound activities. L. Reichardt (UCSF) provided Itgb8flox/flox mice and R. Hynes (Massachusetts Institute of Technology) provided Itgb3-1- mice on 129/svJae background. S. Violette (Biogen Idee) provided antibody to alphavbeta6 (human/mouse chimeric 2A1), W. Stallcup (Sanford-Burnham Medical Research Institute) provided antibody to PDGFR-beta and H. Yagita (Juntendo University) provided antibody to a, integrin (clone RMV-7). NR 41 TC 151 Z9 153 U1 3 U2 44 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1078-8956 EI 1546-170X J9 NAT MED JI Nat. Med. PD DEC PY 2013 VL 19 IS 12 BP 1617 EP 1624 DI 10.1038/nm.3282 PG 8 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA 268OW UT WOS:000328181400030 PM 24216753 ER PT J AU Choi, M Choi, J Kim, S Nizamoglu, S Hahn, SK Yun, SH AF Choi, Myunghwan Choi, JinWoo Kim, Seonghoon Nizamoglu, Sedat Hahn, Sei Kwang Yun, Seok Hyun TI Light-guiding hydrogels for cell-based sensing and optogenetic synthesis in vivo SO NATURE PHOTONICS LA English DT Article ID OPTICAL WAVE-GUIDES; NEURAL CIRCUITS; MICE; TECHNOLOGY; CULTURE; FIBERS; SENSOR AB Polymer hydrogels are widely used as cell scaffolds for biomedical applications. Although the biochemical and biophysical properties of hydrogels have been investigated extensively, little attention has been paid to their potential photonic functionalities. Here, we report cell-integrated polyethylene glycol-based hydrogels for in vivo optical-sensing and therapy applications. Hydrogel patches containing cells were implanted in awake, freely moving mice for several days and shown to offer long-term transparency, biocompatibility, cell viability and light-guiding properties (loss of <1 dB cm(-1)). Using optogenetic, glucagon-like peptide-1 secreting cells, we conducted light-controlled therapy using the hydrogel in a mouse model with diabetes and obtained improved glucose homeostasis. Furthermore, real-time optical readout of encapsulated heat-shock-protein-coupled fluorescent reporter cells made it possible to measure the nanotoxicity of cadmium-based bare and shelled quantum dots (CdTe; CdSe/ZnS) in vivo. C1 [Choi, Myunghwan; Choi, JinWoo; Nizamoglu, Sedat; Hahn, Sei Kwang; Yun, Seok Hyun] Harvard Univ, Sch Med, Boston, MA 02114 USA. [Choi, Myunghwan; Choi, JinWoo; Nizamoglu, Sedat; Hahn, Sei Kwang; Yun, Seok Hyun] Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA. [Choi, Myunghwan; Kim, Seonghoon; Yun, Seok Hyun] Korea Adv Inst Sci & Technol, WCU Grad Sch Nanosci & Technol, Taejon 305701, South Korea. [Choi, JinWoo] Wonkwang Univ, Sch Dent, Dept Pharmacol, Wonkwang Inst Interfused Biomed Sci, Seoul, South Korea. [Hahn, Sei Kwang] Pohang Univ Sci & Technol, Dept Mat Sci & Engn, Pohang, South Korea. RP Yun, SH (reprint author), Harvard Univ, 65 Lansdowne St,UP 525, Cambridge, MA 02139 USA. EM syun@hms.harvard.edu OI Choi, Myunghwan/0000-0002-4235-7003 FU US National Institutes of Health [R21 EB013761]; US National Science Foundation [ECS-1101947]; US Department of Defense [FA9550-10-1-0537]; IT Consilience Creative Program of MKE; NIPA [C1515-1121-0003]; Korean National Research Foundation; World Class University Program of the Korean National Research Foundation [2012M3A9C6049791, R31-2008-000-10071-0]; Bullock-Wellman Fellowship FX The authors thank M. Fussenegger and H. Ye (ETH) for providing plasmids for optogenetic experiments. This work was funded by the US National Institutes of Health (R21 EB013761), the US National Science Foundation (ECS-1101947), the US Department of Defense (FA9550-10-1-0537), the IT Consilience Creative Program of MKE and NIPA (C1515-1121-0003) and the Bio & Medical Technology Development Program and the World Class University Program of the Korean National Research Foundation (2012M3A9C6049791 and R31-2008-000-10071-0). S.N. acknowledges financial support from the Bullock-Wellman Fellowship. NR 37 TC 41 Z9 42 U1 7 U2 97 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1749-4885 EI 1749-4893 J9 NAT PHOTONICS JI Nat. Photonics PD DEC PY 2013 VL 7 IS 12 BP 987 EP 994 DI 10.1038/NPHOTON.2013.278 PG 8 WC Optics; Physics, Applied SC Optics; Physics GA 262MB UT WOS:000327738400018 PM 25346777 ER PT J AU Huang, LF Lieberman, J AF Huang, Linfeng Lieberman, Judy TI Production of highly potent recombinant siRNAs in Escherichia coli SO NATURE PROTOCOLS LA English DT Article ID DOUBLE-STRANDED RNAS; CAENORHABDITIS-ELEGANS; INTERFERING RNAS; MAMMALIAN-CELLS; PLANTS; DUPLEXES; DSRNA; EXPRESSION; BACTERIA; DESIGN AB We recently invented a method to produce highly potent siRNAs in Escherichia coli, based on the serendipitous discovery that ectopic expression of p19, a plant viral siRNA-binding protein, stabilizes otherwise unstable bacterial siRNAs, which we named pro-siRNAs for prokaryotic siRNAs. We present a detailed protocol describing how to produce pro-siRNAs for efficiently knocking down any gene, beginning with the design of a pro-siRNA expression plasmid and ending with siRNA purification. This protocol uses one plasmid to co-express a recombinant His-tagged p19 protein and a long hairpin RNA containing sense and antisense sequences of the target gene. pro-siRNAs are isolated and purified using nickel beads and HPLC, using methods used to produce recombinant proteins. Once a pro-siRNA plasmid is obtained, production of purified pro-siRNAs takes a few days. The pro-siRNA technique provides a reliable and renewable source of siRNAs, and it can be implemented in any laboratory whose members are skilled in routine molecular biology techniques. C1 [Huang, Linfeng; Lieberman, Judy] Boston Childrens Hosp, Program Cellular & Mol Med, Boston, MA USA. [Huang, Linfeng; Lieberman, Judy] Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. RP Huang, LF (reprint author), Boston Childrens Hosp, Program Cellular & Mol Med, Boston, MA USA. EM linfeng.huang@childrens.harvard.edu; judy.lieberman@childrens.harvard.edu RI Lieberman, Judy/A-2717-2015; OI Huang, Linfeng/0000-0002-0322-4929 FU US National Institutes of Health [AI087431]; GlaxoSmithKline(GSK)-Immune Disease Institute(IDI) Alliance fellowship FX We thank J. Carrington (Donald Danforth Plant Science Center) for providing the p19 clone. We also thank J. Jin and L. McReynolds from New England Biolabs and P. Deighan and E. Kiner from Harvard Medical School for assistance and advice in establishing this method. We also thank Lieberman Laboratory members for technical assistance. This work was supported by a US National Institutes of Health grant (no. AI087431; J. L.) and a GlaxoSmithKline(GSK)-Immune Disease Institute(IDI) Alliance fellowship (L.H.). NR 35 TC 4 Z9 4 U1 1 U2 15 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1754-2189 EI 1750-2799 J9 NAT PROTOC JI Nat. Protoc. PD DEC PY 2013 VL 8 IS 12 BP 2325 EP 2336 DI 10.1038/nprot.2013.149 PG 12 WC Biochemical Research Methods SC Biochemistry & Molecular Biology GA 267VG UT WOS:000328125800001 PM 24177290 ER PT J AU Wang, S Sun, HF Ma, J Zang, CZ Wang, CF Wang, J Tang, QZ Meyer, CA Zhang, Y Liu, XS AF Wang, Su Sun, Hanfei Ma, Jian Zang, Chongzhi Wang, Chenfei Wang, Juan Tang, Qianzi Meyer, Clifford A. Zhang, Yong Liu, X. Shirley TI Target analysis by integration of transcriptome and ChIP-seq data with BETA SO NATURE PROTOCOLS LA English DT Article ID GENE-EXPRESSION DATA; ESTROGEN-RECEPTOR; PROSTATE-CANCER; GENOME BROWSER; BINDING-SITES; IDENTIFICATION; PREDICTION; PROFILES; ELEMENT; UCSC AB The combination of ChIP-seq and transcriptome analysis is a compelling approach to unravel the regulation of gene expression. Several recently published methods combine transcription factor (TF) binding and gene expression for target prediction, but few of them provide an efficient software package for the community. Binding and expression target analysis (BETA) is a software package that integrates ChIP-seq of TFs or chromatin regulators with differential gene expression data to infer direct target genes. BETA has three functions: (i) to predict whether the factor has activating or repressive function; (ii) to infer the factor's target genes; and (iii) to identify the motif of the factor and its collaborators, which might modulate the factor's activating or repressive function. Here we describe the implementation and features of BETA to demonstrate its application to several data sets. BETA requires similar to 1 GB of RAM, and the procedure takes 20 min to complete. BETA is available open source at http://cistrome.org/BETA/. C1 [Wang, Su; Sun, Hanfei; Ma, Jian; Wang, Chenfei; Wang, Juan; Tang, Qianzi; Zhang, Yong] Tongji Univ, Sch Life Sci & Technol, Dept Bioinformat, Shanghai 200092, Peoples R China. [Zang, Chongzhi; Meyer, Clifford A.; Liu, X. Shirley] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA. [Zang, Chongzhi; Meyer, Clifford A.; Liu, X. Shirley] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. RP Zhang, Y (reprint author), Tongji Univ, Sch Life Sci & Technol, Dept Bioinformat, Shanghai 200092, Peoples R China. EM yzhang@tongji.edu.cn; xsliu@jimmy.harvard.edu RI Zhang, Yong/B-4838-2011; Zang, Chongzhi/D-1445-2011 OI Zhang, Yong/0000-0001-6316-2734; FU National Basic Research (973) Program of China [2010CB944904]; National Natural Science Foundation of China [31329003]; US National Institutes of Health [HG4069, U41 HG007000] FX This project was supported by the National Basic Research (973) Program of China (2010CB944904), the National Natural Science Foundation of China (31329003) and the US National Institutes of Health (HG4069 and U41 HG007000). NR 41 TC 40 Z9 41 U1 5 U2 27 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1754-2189 EI 1750-2799 J9 NAT PROTOC JI Nat. Protoc. PD DEC PY 2013 VL 8 IS 12 BP 2502 EP 2515 DI 10.1038/nprot.2013.150 PG 14 WC Biochemical Research Methods SC Biochemistry & Molecular Biology GA 267VG UT WOS:000328125800015 PM 24263090 ER PT J AU Wey, HY Desai, VR Duong, TQ AF Wey, Hsiao-Ying Desai, Virendra R. Duong, Timothy Q. TI A review of current imaging methods used in stroke research SO NEUROLOGICAL RESEARCH LA English DT Review DE MRI; PET; Diffusion; Perfusion; Cerebral blood flow; Cerebral ischemia; Blood-brain barrier; Functional MRI ID POSITRON-EMISSION-TOMOGRAPHY; CEREBRAL-BLOOD-FLOW; ISCHEMIC BRAIN-INJURY; TISSUE-PLASMINOGEN ACTIVATOR; ACUTE HEMISPHERIC STROKE; APPARENT DIFFUSION-COEFFICIENT; AXON DIAMETER DISTRIBUTION; IN-VIVO MEASUREMENT; MAGNETIC-RESONANCE; FOCAL ISCHEMIA AB Stroke is a serious healthcare problem with high mortality and long-term disability. However, to date, our ability to prevent and cure stroke remains limited. One important goal in stroke research is to identify the extent and location of lesion for treatment. In addition, accurately differentiating salvageable tissue from infarct and evaluating therapeutic efficacies are indispensible. These objectives could potentially be met with the assistance of modern neuroimaging techniques. This paper reviews current imaging methods commonly used in ischemic stroke research. These methods include positron emission tomography, computed tomography, T1 MRI, T2 MRI, diffusion and perfusion MRI, diffusion tensor imaging, blood-brain barrier permeability MRI, pH-weighted MRI, and functional MRI. C1 [Wey, Hsiao-Ying; Desai, Virendra R.; Duong, Timothy Q.] Univ Texas Hlth Sci Ctr San Antonio, Res Imaging Inst, San Antonio, TX 78229 USA. [Wey, Hsiao-Ying; Desai, Virendra R.; Duong, Timothy Q.] Univ Texas Hlth Sci Ctr San Antonio, Dept Radiol, San Antonio, TX 78229 USA. [Wey, Hsiao-Ying] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging,Dept Radi, Charlestown, MA USA. [Duong, Timothy Q.] South Texas Vet Hlth Care Syst, Dept Vet Affairs, San Antonio, TX USA. RP Duong, TQ (reprint author), Univ Texas Hlth Sci Ctr San Antonio, Res Imaging Inst, 8403 Floyd Curl Dr, San Antonio, TX 78229 USA. EM duongt@uthscsa.edu OI Desai, Virendra/0000-0002-3238-9415 FU NCATS NIH HHS [KL2 TR001118, UL1 TR001120]; NINDS NIH HHS [R01 NS045879] NR 127 TC 5 Z9 5 U1 1 U2 12 PU MANEY PUBLISHING PI LEEDS PA STE 1C, JOSEPHS WELL, HANOVER WALK, LEEDS LS3 1AB, W YORKS, ENGLAND SN 0161-6412 EI 1743-1328 J9 NEUROL RES JI Neurol. Res. PD DEC PY 2013 VL 35 IS 10 BP 1092 EP 1102 DI 10.1179/1743132813Y.0000000250 PG 11 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 268CA UT WOS:000328144300014 PM 24070268 ER PT J AU Oh, G Chung, E Yun, SH AF Oh, Gyungseok Chung, Euiheon Yun, Seok H. TI Optical fibers for high-resolution in vivo microendoscopic fluorescence imaging SO OPTICAL FIBER TECHNOLOGY LA English DT Article DE Microendoscopy; Fluorescence imaging; Optical fiber; Fiber bundle; GRIN lens; Endomicroscopy ID CONFOCAL LASER ENDOMICROSCOPY; DOUBLE-CLAD FIBER; MULTIPHOTON MICROSCOPY; MINIATURE ENDOSCOPY; CANCER-DETECTION; TISSUE; LIGHT; SYSTEM; BUNDLE; INFLAMMATION AB Optical fiber-based high-resolution fluorescence imaging techniques have promising applications in clinical practice and preclinical research using animals. Here we review the instrumentation and applications of microendoscopy based on various types of optical fibers. Single-mode fibers and double-clad fibers have been widely used for delivering light from light sources to tissues and collecting light from tissues to photodetectors. Coherent fiber bundles, cylindrical graded-index lenses, and multi-mode fibers have been employed in both beam-scanning and non-scanning microscopy. With continuing advances of optical fiber technologies, further innovations in optical microendoscopy are expected. (C) 2013 Published by Elsevier Inc. C1 [Oh, Gyungseok; Chung, Euiheon] Gwangju Inst Sci & Technol, Dept Mechatron, Kwangju, South Korea. [Chung, Euiheon] Gwangju Inst Sci & Technol, Dept Med Syst Engn, Kwangju, South Korea. [Yun, Seok H.] Korea Adv Inst Sci & Technol, WCU Grad Sch Nanosci & Technol, Taejon, South Korea. [Yun, Seok H.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Wellman Ctr Photomed, Boston, MA 02114 USA. RP Chung, E (reprint author), Gwangju Inst Sci & Technol, Dept Med Syst Engn, Sch Mechatron, Kwangju, South Korea. EM ogong50@gist.ac.kr FU Institute of Medical System Engineering at GIST; National Research Foundation (NRF); Ministry of Science, ICT & Future Planning [2011-0019619, 2012R1A1A1012853, R31-2008-000-10071-0] FX This work is supported by grants from the Institute of Medical System Engineering at GIST, and the Bio & Medical Technology Development Program and Basic Science Research Program through the National Research Foundation (NRF) funded by the Ministry of Science, ICT & Future Planning (No. 2011-0019619, 2012R1A1A1012853, R31-2008-000-10071-0). NR 90 TC 34 Z9 34 U1 4 U2 30 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1068-5200 EI 1095-9912 J9 OPT FIBER TECHNOL JI Opt. Fiber Technol. PD DEC PY 2013 VL 19 IS 6 BP 760 EP 771 DI 10.1016/j.yofte.2013.07.008 PN B PG 12 WC Engineering, Electrical & Electronic; Optics; Telecommunications SC Engineering; Optics; Telecommunications GA 267NW UT WOS:000328105600008 ER PT J AU Munn, LL AF Munn, Lance L. TI Dynamics of tissue topology during cancer invasion and metastasis SO PHYSICAL BIOLOGY LA English DT Article ID VALIDATED MATHEMATICAL-MODEL; MEDIATED IMMUNE-RESPONSE; TUMOR-GROWTH; SOLID STRESS; SIMULATION; EVOLUTION; IMAGES AB During tumor progression, cancer cells mix with other cell populations including epithelial and endothelial cells. Although potentially important clinically as well as for our understanding of basic tumor biology, the process of mixing is largely a mystery. Furthermore, there is no rigorous, analytical measure available for quantifying the mixing of compartments within a tumor. I present here a mathematical model of tissue repair and tumor growth based on collective cell migration that simulates a wide range of observed tumor behaviors with correct tissue compartmentalization and connectivity. The resulting dynamics are analyzed in light of the Euler characteristic number (chi), which describes key topological features such as fragmentation, looping and cavities. The analysis predicts a number of regimes in which the cancer cells can encapsulate normal tissue, form a co-interdigitating mass, or become fragmented and encapsulated by endothelial or epithelial structures. Key processes that affect the topological changes are the production of provisional matrix in the tumor, and the migration of endothelial or epithelial cells on this matrix. Furthermore, the simulations predict that topological changes during tumor invasion into blood vessels may contribute to metastasis. The topological analysis outlined here could be useful for tumor diagnosis or monitoring response to therapy and would only require high resolution, 3D image data to resolve and track the various cell compartments. C1 [Munn, Lance L.] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Munn, Lance L.] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Munn, LL (reprint author), Harvard Univ, Sch Med, Boston, MA 02115 USA. EM munn@steele.mgh.harvard.edu RI Munn, Lance/L-3950-2016 OI Munn, Lance/0000-0003-0698-7232 FU NCI NIH HHS [P01 CA080124, R01 CA149285]; NIBIB NIH HHS [P41 EB015903] NR 32 TC 2 Z9 2 U1 1 U2 11 PU IOP PUBLISHING LTD PI BRISTOL PA TEMPLE CIRCUS, TEMPLE WAY, BRISTOL BS1 6BE, ENGLAND SN 1478-3967 EI 1478-3975 J9 PHYS BIOL JI Phys. Biol. PD DEC PY 2013 VL 10 IS 6 AR 065003 DI 10.1088/1478-3975/10/6/065003 PG 13 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 266YJ UT WOS:000328059800004 PM 24304856 ER PT J AU Smith, KB Wang, DL Plotkin, SR Park, ER AF Smith, Kelly B. Wang, Daphne L. Plotkin, Scott R. Park, Elyse R. TI Appearance concerns among women with neurofibromatosis: examining sexual/bodily and social self-consciousness SO PSYCHO-ONCOLOGY LA English DT Article DE neurofibromatosis; appearance concerns; self-esteem; loneliness; breast cancer; oncology ID QUALITY-OF-LIFE; BODY-IMAGE; SCALE; TYPE-1; IMPACT; DISFIGUREMENT; INDIVIDUALS; ESTEEM AB ObjectiveNeurofibromatosis (NF) 1 and 2 have distinct appearance effects, yet little research has examined patients' appearance concerns. We assessed appearance concerns and self-consciousness, self-esteem, and loneliness among women with NF. MethodsWomen with NF1 (n=79) and NF2 (n=48) completed the Derriford Appearance Scale to assess appearance concerns and sexual/bodily and social self-consciousness, Rosenberg Self-Esteem Scale, and UCLA Loneliness Scale. Women's appearance concerns were coded to determine whether they were NF-related and whether psychosocial factors contributed to the concerns. ResultsA total of 85% of women reported appearance concerns, many of which were NF-related and attributed to psychosocial factors. Women with NF1 reported significantly more sexual/bodily self-consciousness but similar levels of social self-consciousness compared with women with NF2. Significantly higher sexual/bodily self-consciousness was found among married/cohabiting women regardless of NF group. Compared with general population norms and breast cancer survivors (BCS), women with NF1 reported significantly greater sexual/bodily and social self-consciousness. Women with NF2 reported less sexual/bodily self-consciousness compared with population norms, yet tended to report greater sexual/bodily self-consciousness than BCS. Women with NF2 reported significantly greater social self-consciousness compared with population norms and BCS. For both NF1 and NF2, higher levels of sexual/bodily and social self-consciousness were related to lower self-esteem and higher levels of social self-consciousness to more loneliness. ConclusionsAppearance concerns are prevalent, and social self-consciousness is high, among women with NF1 and NF2. Women with NF1 compared with NF2 experience more sexual/bodily self-consciousness. Providers should assess the impact of NF on women's self-perceptions and address sexual, body image, and social concerns. Copyright (c) 2013 John Wiley & Sons, Ltd. C1 [Smith, Kelly B.] Univ British Columbia, Dept Obstet & Gynaecol, Vancouver, BC V5Z 1M9, Canada. [Wang, Daphne L.; Plotkin, Scott R.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Neurol, Cambridge, MA 02138 USA. [Wang, Daphne L.; Plotkin, Scott R.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Canc, Cambridge, MA 02138 USA. [Park, Elyse R.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Psychiat,Benson Henry Inst Mind Body Machine, Cambridge, MA 02138 USA. RP Smith, KB (reprint author), Univ British Columbia, Dept Obstet & Gynaecol, 2775 Laurel St, Vancouver, BC V5Z 1M9, Canada. EM Kelly.Smith@vch.ca FU Michael Smith Foundation for Health Research; Canadian Pain Society; American Cancer Society's Mentored Research Scholar Award [MRSG-005-05-CPPB]; John and Cyndy Leahy Fellowship Fund at the Massachusetts General Hospital; APOS Conference Fellowship FX K.B. Smith is supported by Post Doctoral Fellowship Awards from the Michael Smith Foundation for Health Research and the Canadian Pain Society. This research was supported by an American Cancer Society's Mentored Research Scholar Award provided to E.R. Park (MRSG-005-05-CPPB), and by the John and Cyndy Leahy Fellowship Fund at the Massachusetts General Hospital provided to S.R. Plotkin. Portions of this paper were presented in February 2011 at the 8th Annual Conference of the American Psychosocial Oncology Society (APOS), Anaheim, CA, where K.B. Smith was supported by an APOS Conference Fellowship. NR 28 TC 3 Z9 3 U1 3 U2 10 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1057-9249 EI 1099-1611 J9 PSYCHO-ONCOLOGY JI Psycho-Oncol. PD DEC PY 2013 VL 22 IS 12 BP 2711 EP 2719 DI 10.1002/pon.3350 PG 9 WC Oncology; Psychology; Psychology, Multidisciplinary; Social Sciences, Biomedical SC Oncology; Psychology; Biomedical Social Sciences GA 263QT UT WOS:000327823800008 PM 23873824 ER PT J AU Evans, KK Georgian-Smith, D Tambouret, R Birdwell, RL Wolfe, JM AF Evans, Karla K. Georgian-Smith, Diane Tambouret, Rosemary Birdwell, Robyn L. Wolfe, Jeremy M. TI The gist of the abnormal: Above-chance medical decision making in the blink of an eye SO PSYCHONOMIC BULLETIN & REVIEW LA English DT Article DE Visual awareness; Human visual perception; Visual categorization; Expertise ID CATEGORIZATION; PICTURES; TIME AB Very fast extraction of global structural and statistical regularities allows us to access the "gist"aEuro"the basic meaning-of real-world images in as little as 20 ms. Gist processing is central to efficient assessment and orienting in complex environments. This ability is probably based on our extensive experience with the regularities of the natural world. If that is so, would experts develop an ability to extract the gist from the artificial stimuli (e.g., medical images) with which they have extensive visual experience? Anecdotally, experts report some ability to categorize images as normal or abnormal before actually finding an abnormality. We tested the reality of this perception in two expert populations: radiologists and cytologists. Observers viewed brief (250- to 2,000-ms) presentations of medical images. The presence of abnormality was randomized across trials. The task was to rate the abnormality of an image on a 0-100 analog scale and then to attempt to localize that abnormality on a subsequent screen showing only the outline of the image. Both groups of experts had above-chance performance for detecting subtle abnormalities at all stimulus durations (cytologists d' a parts per thousand 1.2 and radiologists d' a parts per thousand 1), whereas the nonexpert control groups did not differ from chance (d' a parts per thousand 0.23, d' a parts per thousand 0.25). Furthermore, the experts' ability to localize these abnormalities was at chance levels, suggesting that categorization was based on a global signal, and not on fortuitous attention to a localized target. It is possible that this global signal could be exploited to improve clinical performance. C1 [Evans, Karla K.; Georgian-Smith, Diane; Birdwell, Robyn L.; Wolfe, Jeremy M.] Brigham & Womens Hosp, Boston, MA 02115 USA. [Evans, Karla K.; Georgian-Smith, Diane; Tambouret, Rosemary; Birdwell, Robyn L.; Wolfe, Jeremy M.] Harvard Univ, Sch Med, Boston, MA USA. [Tambouret, Rosemary] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Evans, Karla K.] Harvard Univ, Sch Med, Visual Attent Lab, Cambridge, MA 02139 USA. RP Evans, KK (reprint author), Harvard Univ, Sch Med, Visual Attent Lab, 64 Sidney St,Suite 170, Cambridge, MA 02139 USA. EM kevans@search.bwh.harvard.edu RI Wolfe, Jeremy/C-1621-2012; Wolfe, Jeremy/A-9248-2016 OI Wolfe, Jeremy/0000-0002-6475-1984; Wolfe, Jeremy/0000-0002-6475-1984 FU NEI NIH HHS [R01 EY017001, EY17001, F32 EY019819, F32EY019819-01] NR 18 TC 15 Z9 15 U1 1 U2 6 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1069-9384 EI 1531-5320 J9 PSYCHON B REV JI Psychon. Bull. Rev. PD DEC PY 2013 VL 20 IS 6 BP 1170 EP 1175 DI 10.3758/s13423-013-0459-3 PG 6 WC Psychology, Mathematical; Psychology, Experimental SC Psychology GA 267CH UT WOS:000328073400013 PM 23771399 ER PT J AU Wang, JHY Adams, IF Tucker-Seeley, R Gomez, SL Allen, L Huang, E Wang, YR Pasick, RJ AF Wang, Judy Huei-yu Adams, Inez F. Tucker-Seeley, Reginald Gomez, Scarlett Lin Allen, Laura Huang, Ellen Wang, Yiru Pasick, Rena J. TI A mixed method exploration of survivorship among Chinese American and non-Hispanic White breast cancer survivors: the role of socioeconomic well-being SO QUALITY OF LIFE RESEARCH LA English DT Article DE Socioeconomic well-being; Mixed-method; Cancer survivorship; Ethnicity; Chinese Americans; Acculturation ID ASIAN-AMERICAN; UNITED-STATES; WOMEN; HEALTH; ACCULTURATION; ASSOCIATION; QUALITY; LIFE; END AB Purpose Cancer-related stress is heavily influenced by culture. This study explored similarities and differences in survivorship care concerns among Chinese American and non-Hispanic White (NHW) breast cancer survivors. Methods A sequential, mixed-method design (inductive/qualitative research-phase I and deductive/quantitative research-phase II) was employed. Eligible women identified from the Greater Bay Area Cancer Registry were age >= 21, diagnosed with stage 0-IIa breast cancer between 2006 and 2011, and had no recurrence or other cancers. In phase I, we conducted 4 Chinese (n = 19) and 4 NHW (n = 22) focus groups, and 31 individual telephone interviews (18 Chinese immigrants, 7 Chinese US-born, and 6 NHW). Content analysis was conducted to examine qualitative data. In phase II, another 296 survivors (148 NHW age-matched to 148 Chinese cases) completed a cross-sectional survey. Descriptive statistics and linear regression analysis were conducted to examine quantitative data. Results Qualitative data revealed "socioeconomic well-being" (SWB) as a dominant survivorship concern, which was operationalized as a cancer survivor's perceived economic and social resources available to access care. Quantitative data showed that low-acculturated Chinese immigrants reported the poorest SWB, controlling for covariates. Highly acculturated Chinese immigrants and the US-born Chinese/NHW group reported similar SWB. Women who had low-income levels or chemotherapy had poorer SWB. Conclusions SWB emerged as an important aspect of breast cancer survivorship. Immigration stress, cancer care costs, and cultural values all contributed to immigrants' socioeconomic distress. Immigrant and US-born breast cancer survivors experienced different socioeconomic circumstances and well-being following treatment. Our findings warrant further investigation of socioeconomic distress and survivorship outcomes. C1 [Wang, Judy Huei-yu; Huang, Ellen; Wang, Yiru] Georgetown Univ, Lombardi Comprehens Canc Ctr, Canc Prevent & Control Program, Dept Oncol,Med Ctr, Washington, DC 20007 USA. [Adams, Inez F.; Tucker-Seeley, Reginald] Harvard Univ, Sch Publ Hlth, Dept Social & Behav Sci, Boston, MA 02215 USA. [Tucker-Seeley, Reginald] Dana Farber Canc Inst, Ctr Community Based Res, Boston, MA 02215 USA. [Gomez, Scarlett Lin; Allen, Laura] Canc Prevent Inst Calif, Fremont, CA 94538 USA. [Pasick, Rena J.] Univ Calif San Francisco, Dept Med, Div Gen Internal Med, San Francisco, CA 94158 USA. RP Wang, JHY (reprint author), Georgetown Univ, Lombardi Comprehens Canc Ctr, Canc Prevent & Control Program, Dept Oncol,Med Ctr, 3300 Whitehaven St NW,Suite 4100, Washington, DC 20007 USA. EM jw235@georgetown.edu FU Lance Armstrong Foundation; National Cancer Institute [CA139408-01, CA169041-01, HHSN261201000040C, HHSN261201000140C, HHSN261201000035C, HHSN261201000034C]; Centers for Disease Control and Prevention [1U58 DP000807-01] FX This research was supported by a Lance Armstrong Foundation Young Investigator Award and the National Cancer Institute R21 research award (Grant# CA139408-01 to J. H. Wang) and K01 career development award (Grant# CA169041-01 to R. Tucker-Seeley). This research was also supported by the National Cancer Institute's Surveillance, Epidemiology and End Results Program under contract HHSN261201000040C awarded to the Cancer Prevention Institute of California. The collection of cancer incidence data used in this study was supported by the California Department of Health Services as part of the statewide cancer reporting program mandated by California Health and Safety Code Sect. 103885; the National Cancer Institute's Surveillance, Epidemiology, and End Results Program under contract HHSN261201000140C awarded to the Cancer Prevention Institute of California, contract HHSN261201000035C awarded to the University of Southern California, and contract HHSN261201000034C awarded to the Public Health Institute; and the Centers for Disease Control and Prevention's National Program of Cancer Registries, under agreement #1U58 DP000807-01 awarded to the Public Health Institute. The ideas and opinions expressed herein are those of the authors, and endorsement by the State of California, the California Department of Health Services, the National Cancer Institute, or the Centers for Disease Control and Prevention or their contractors and subcontractors is not intended nor should be inferred. We appreciate field staff at CPIC, Pagan Morris, Mei-Chin Kuo, Kathie Lau, and Daisy Lubag for their efforts in participant enrollment and preparation for focus groups. We sincerely thank Dr. Grace X. Ma and Dr. Frances M. Lewis for their constructive comments on our study materials, which enhanced our data collection. NR 44 TC 4 Z9 4 U1 2 U2 11 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0962-9343 EI 1573-2649 J9 QUAL LIFE RES JI Qual. Life Res. PD DEC PY 2013 VL 22 IS 10 BP 2709 EP 2720 DI 10.1007/s11136-013-0374-0 PG 12 WC Health Care Sciences & Services; Health Policy & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA 269BM UT WOS:000328215200008 PM 23591710 ER PT J AU Funk, JA Schnellmann, RG AF Funk, Jason A. Schnellmann, Rick G. TI Accelerated recovery of renal mitochondrial and tubule homeostasis with SIRT1/PGC-1 alpha activation following ischemia-reperfusion injury SO TOXICOLOGY AND APPLIED PHARMACOLOGY LA English DT Article DE Mitochondrial biogenesis; Mitochondrial dysfunction; Acute kidney injury; SRT1720; Proximal tubule; Ischemia-reperfusion ID ACUTE KIDNEY INJURY; SMALL-MOLECULE ACTIVATORS; EPITHELIAL POLARITY; CALORIE RESTRICTION; HISTONE DEACETYLASE; ENERGY-EXPENDITURE; PROMOTES RECOVERY; OXIDANT INJURY; SIRT1; PGC-1-ALPHA AB Kidney ischemia-reperfusion (I/R) injury elicits cellular injury in the proximal tubule, and mitochondrial dysfunction is a pathological consequence of I/R. Promoting mitochondrial biogenesis (MB) as a repair mechanism after injury may offer (a) over dot unique strategy to restore both mitochondrial and organ function. Rats subjected to bilateral renal pedicle ligation for 22 min were treated once daily with the SIRT1 activator SRT1720 (5 mg/kg) starting 24 h after reperfusion until 72 h-144 h. SIRT1 expression was elevated in the renal cortex of rats after I/R + vehicle treatment (RV), but was associated with less nuclear localization. SIRT1 expression was even further augmented and nuclear localization was restored in the kidneys of rats after I/R + SRT1720 treatment (IRS). PGC-1 alpha was elevated at 72 h-144 h in IRV and IRS kidneys; however, SRT1720 treatment induced deacetylation of PGC-1 alpha, a marker of activation. Mitochondrial proteins ATP synthase beta, COX I, and NDUFB8, as well as mitochondrial respiration, were diminished 24 h-144 h in IRV rats, but were partially or fully restored in IRS rats. Urinary kidney injury molecule-1 (KIM-1) was persistently elevated in both IRV and IRS rats; however, KIM-1 tissue expression was attenuated in IRS rats. Additionally, sustained loss of Na+,K+-ATPase expression and basolateral localization and elevated vimentin in IRV rats was normalized in IRS rats, suggesting restoration of a differentiated, polarized tubule epithelium. The results suggest that SRT1720 treatment expedited recovery of mitochondrial protein expression and function by enhancing MB, which was associated with faster proximal tubule repair. Targeting MB may offer unique therapeutic strategy following ischemic injury. Published by Elsevier Inc. C1 [Funk, Jason A.; Schnellmann, Rick G.] Med Univ S Carolina, Dept Drug Discovery & Biomed Sci, Ctr Cell Death Injury & Regenerat, Charleston, SC 29425 USA. [Schnellmann, Rick G.] Ralph H Johnson VA Med Ctr, Charleston, SC 29401 USA. RP Schnellmann, RG (reprint author), Med Univ S Carolina, Dept Drug Discovery & Biomed Sci, Ctr Cell Death Injury & Regenerat, Charleston, SC 29425 USA. EM funkj@musc.edu; schnell@musc.edu FU NIH/NIGMS [084147]; Biomedical Laboratory Research and Development Program of the Department of Veterans Affairs Merit [BX000851]; NIH [C06 RR-015455] FX This work was supported by NIH/NIGMS Grant 084147 and by the Biomedical Laboratory Research and Development Program of the Department of Veterans Affairs Merit grant BX000851. Animal facilities were funded by NIH grant C06 RR-015455. NR 43 TC 34 Z9 37 U1 1 U2 4 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0041-008X EI 1096-0333 J9 TOXICOL APPL PHARM JI Toxicol. Appl. Pharmacol. PD DEC 1 PY 2013 VL 273 IS 2 BP 345 EP 354 DI 10.1016/j.taap.2013.09.026 PG 10 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA 267LP UT WOS:000328099500011 PM 24096033 ER PT J AU Singh, T Katiyar, SK AF Singh, Tripti Katiyar, Santosh K. TI Green tea polyphenol, (-)-epigallocatechin-3-gallate, induces toxicity in human skin cancer cells by targeting beta-catenin signaling SO TOXICOLOGY AND APPLIED PHARMACOLOGY LA English DT Article DE Cyclooxygenase-2; Prostaglandin; beta-Catenin; ()-Epigallocatechin-3-gallate; Green tea polyphenol; Skin cancer ID DNA-REPAIR; C-MYC; EXPRESSION; INHIBITION; MICE; PHOTOCARCINOGENESIS; ANGIOGENESIS; ACTIVATION; MECHANISMS; APOPTOSIS AB The green tea polyphenol, (-)-epigallocatechin-3-gallate (EGCG), has been shown to have anti-carcinogenic effects in several skin tumor models, and efforts are continued to investigate the molecular targets responsible for its cytotoxic effects to cancer cells. Our recent observation that beta-catenin is upregulated in skin tumors suggested the possibility that the anti-skin carcinogenic effects of EGCG are mediated, at least in part, through its effects on beta-catenin signaling. We have found that treatment of the A431 and SCC13 human skin cancer cell lines with EGCG resulted in reduced cell viability and increased cell death and that these cytotoxic effects were associated with inactivation of beta-catenin signaling. Evidence of EGCG-induced inactivation of beta-catenin included: (i) reduced accumulation of nuclear beta-catenin; (ii) enhanced levels of casein kinase1 alpha, reduced phosphorylation of glycogen synthase kinase-3 beta, and increased phosphorylation of beta-catenin on critical Serille(45,33137) residues; and (iii) reduced levels of matrix metalloproteinase (MMP)-2 and MMP-9, which are down-stream targets of beta-catenin. Treatment of cells with prostaglandin E2 (PGE(2)) enhanced the accumulation of beta-catenin and enhanced beta-catenin signaling. Treatment with either EGCG or an EP2 antagonist (AH6809) reduced the PGE(2)-enhanced levels of cAMP, an upstream regulator of beta-catenin. Inactivation of beta-catenin by EGCG resulted in suppression of cell-survival signaling proteins. siRNA knockdown of beta-catenin in A431 and SCC13 cells reduced cell viability. Collectively, these data suggest that induction of cytotoxicity in skin cancer cells by EGCG is mediated by targeting of beta-catenin signaling and that the beta-catenin signaling is upregulated by inflammatory mediators. (C) 2013 Elsevier Inc. All rights reserved. C1 [Singh, Tripti; Katiyar, Santosh K.] Univ Alabama Birmingham, Dept Dermatol, Birmingham, AL 35294 USA. [Katiyar, Santosh K.] Univ Alabama Birmingham, Ctr Comprehens Canc, Birmingham, AL 35294 USA. [Katiyar, Santosh K.] Birmingham Vet Affairs Med Ctr, Birmingham, AL 35233 USA. RP Katiyar, SK (reprint author), Univ Alabama Birmingham, Dept Dermatol, 1670 Univ Blvd,Volker Hall 557, Birmingham, AL 35294 USA. EM skatiyar@uab.edu FU Veterans Administration Merit Review Award [1I01BX001410]; National Institutes of Health [CA140197, CA166883] FX This work was partially supported by the Veterans Administration Merit Review Award (1I01BX001410, S.K.K.) and National Institutes of Health (CA140197, CA166883, S.K.K.). The funding agencies were not involved in study design, analysis and interpretation of data; the writing of the manuscript; and the decision to submit the manuscript for publication. We thank Dr. Fiona Hunter for editorial assistance. NR 25 TC 23 Z9 27 U1 1 U2 21 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0041-008X EI 1096-0333 J9 TOXICOL APPL PHARM JI Toxicol. Appl. Pharmacol. PD DEC 1 PY 2013 VL 273 IS 2 BP 418 EP 424 DI 10.1016/j.taap.2013.09.021 PG 7 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA 267LP UT WOS:000328099500018 PM 24096034 ER PT J AU Perez-Johnston, R Hahn, PF Shenoy-Bhangle, AS Shelly, MJ Gervais, DA Arellano, RS AF Perez-Johnston, Rocio Hahn, Peter F. Shenoy-Bhangle, Anuradha S. Shelly, Martin J. Gervais, Debra A. Arellano, Ronald S. TI Percutaneous biopsy of focal lesions of the gastrointestinal tract SO ABDOMINAL IMAGING LA English DT Article DE Biopsy; Gastrointestinal; Percutaneous ID FINE-NEEDLE-ASPIRATION; NEGATIVE PREDICTIVE-VALUE; GUIDED CORE BIOPSY; BOWEL WALL; MASSES; DIAGNOSIS; CT; EFFICACY; SAFETY; TUMORS AB Purpose: To evaluate the technical success and diagnostic accuracy of image-guided percutaneous biopsy of the gastrointestinal (GI) tract. Materials and methods: An interventional radiology database was used to retrospectively identify patients who underwent image-guided percutaneous biopsy of the GI tract. The medical and imaging records were reviewed to assess biopsy results and complications. Results: Twenty-nine patients (M:F = 19:10, mean age 65 years) were identified who underwent image-guided (CT/US) percutaneous biopsies of the GI tract. All biopsies were performed using coaxial technique with 18 g core and 22 g FNA needles. Twenty-two biopsies (76 %) were for circumferential or segmental wall thickening; the remaining were wall thickening with exophytic mass. Mean tumor diameter was 7.4 cm (SD = 3.4 cm), average wall thickening was 2.1 cm (SD 7.2), and exophytic mass was 10.0 cm (SD = 4.2). Tumor locations included stomach (n = 5), small bowel (n = 8), and colon (n = 16). Malignancy was confirmed in 22 patients, 12 of whom underwent excision, with 3 false positive samples. Benign disease was diagnosed in 7 patients, including 3 with pathology confirmation, with one false negative sample. The overall sensitivity was 83 % and accuracy was 84 %. There was one complication presenting as bleeding at the biopsy site, treated conservatively. Conclusion: Percutaneous biopsy of the GI tract is an uncommon procedure. The results of this study suggest that it is a safe and sensitive procedure that may be considered for small bowel lesions in which endoscopy is not feasible, for submucosal lesions, or in the setting of patients with previously negative endoscopic biopsies. C1 [Perez-Johnston, Rocio; Hahn, Peter F.; Shenoy-Bhangle, Anuradha S.; Shelly, Martin J.; Gervais, Debra A.; Arellano, Ronald S.] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Perez-Johnston, R (reprint author), Massachusetts Gen Hosp, 55 Fruit St,White 270, Boston, MA 02114 USA. EM rperezjohnston@partners.org NR 32 TC 6 Z9 7 U1 0 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0942-8925 EI 1432-0509 J9 ABDOM IMAGING JI Abdom. Imaging PD DEC PY 2013 VL 38 IS 6 BP 1197 EP 1202 DI 10.1007/s00261-013-0023-7 PG 6 WC Gastroenterology & Hepatology; Radiology, Nuclear Medicine & Medical Imaging SC Gastroenterology & Hepatology; Radiology, Nuclear Medicine & Medical Imaging GA 267DD UT WOS:000328076000003 PM 23820692 ER PT J AU Turner, TE Waldo, SW Kulkarni, A Armstrong, EJ Hoffmayer, KS Kinlay, S Hsue, P Ganz, P McCabe, JM AF Turner, Tyson E. Waldo, Stephen W. Kulkarni, Ameya Armstrong, Ehrin J. Hoffmayer, Kurt S. Kinlay, Scott Hsue, Priscilla Ganz, Peter McCabe, James M. TI Long-Term Outcomes of Patients Sent Emergently to the Catheterization Laboratory for Possible Primary Percutaneous Coronary Intervention SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Article ID ELEVATION MYOCARDIAL-INFARCTION; COMPUTED TOMOGRAPHIC ANGIOGRAPHY; ARTERY-DISEASE; ACTIVATION; REGISTRY AB Current guidelines advocate primary percutaneous coronary intervention as the therapy of choice for ST-segment elevation myocardial infarction (STEMI) when available. Little is known about the outcomes of patients without a culprit lesion after referral for primary percutaneous coronary intervention for a presumed STEMI. Subjects were identified within a registry containing consecutive patients who underwent emergent angiography for a potential STEMI from October 2008 to July 2012. Vital status was obtained from the medical record and Social Security Death Index. Cox proportional hazards models were created to evaluate the relation between the angiographic findings and cardiovascular outcomes, including major adverse cardiovascular events (MACE) and mortality. Among 539 patients who underwent emergent angiography, 65 (12%) had no coronary artery disease (CAD), 110 (20%) had CAD without a culprit lesion, and 364 (68%) had a culprit lesion. Kaplan-Meier analysis of MACE demonstrated that patients with CAD who lack a culprit lesion had a similar rate of MACE to those with a culprit lesion (p = 0.64), and both groups had significantly increased risk compared with those with no CAD (hazard ratio [HR] 1.9, 95% confidence interval [CI] 1.01 to 3.41 and HR 2.0, 95% CI 1.15 to 3.54, respectively). Kaplan-Meier analysis of mortality illustrated a nonsignificant trend toward increased mortality in patients having a culprit lesion (HR 1.7, 95% CI 0.59 to 4.80) and those having CAD without a culprit lesion (HR 1.2, 95% CI 0.39 to 3.81) compared with those with no CAD. In conclusion, patients found to have CAD without a culprit lesion in emergent angiography after a presumptive STEMI diagnosis have similar long-term rates of MACE compared with those requiring emergent revascularization. (C) 2013 Elsevier Inc. All rights reserved. C1 [Turner, Tyson E.] Univ Calif San Francisco, Dept Med, San Francisco, CA USA. [Waldo, Stephen W.] Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. [Kulkarni, Ameya] Kaiser Permanente, Div Cardiol, Washington, DC USA. [Armstrong, Ehrin J.] Univ Colorado, Div Cardiol, Denver Vet Affairs, Denver, CO 80262 USA. [Hoffmayer, Kurt S.] Univ Wisconsin, Div Electrophysiol, Madison, WI USA. [Kinlay, Scott] Brigham & Womens Hosp, Div Cardiovasc Med, Boston Vet Affairs Syst, Boston, MA 02115 USA. [Hsue, Priscilla; Ganz, Peter] Univ Calif San Francisco, San Francisco Gen Hosp, Div Cardiol, San Francisco, CA USA. [McCabe, James M.] Univ Washington, Div Cardiol, Seattle, WA 98195 USA. RP McCabe, JM (reprint author), Univ Washington, Div Cardiol, Seattle, WA 98195 USA. EM mccabe@aya.yale.edu NR 12 TC 1 Z9 1 U1 1 U2 2 PU EXCERPTA MEDICA INC-ELSEVIER SCIENCE INC PI BRIDGEWATER PA 685 ROUTE 202-206 STE 3, BRIDGEWATER, NJ 08807 USA SN 0002-9149 EI 1879-1913 J9 AM J CARDIOL JI Am. J. Cardiol. PD DEC 1 PY 2013 VL 112 IS 11 BP 1745 EP 1749 DI 10.1016/j.amjcard.2013.08.007 PG 5 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 261SW UT WOS:000327685900008 PM 24063836 ER PT J AU Vaduganathan, M Greene, SJ Ambrosy, AP Mentz, RJ Fonarow, GC Zannad, F Maggioni, AP Konstam, MA Subacius, HP Nodari, S Butler, J Gheorghiade, M AF Vaduganathan, Muthiah Greene, Stephen J. Ambrosy, Andrew P. Mentz, Robert J. Fonarow, Gregg C. Zannad, Faiez Maggioni, Aldo P. Konstam, Marvin A. Subacius, Haris P. Nodari, Savina Butler, Javed Gheorghiade, Mihai CA EVEREST Trial Investigators TI Relation of Serum Magnesium Levels and Postdischarge Outcomes in Patients Hospitalized for Heart Failure (from the EVEREST Trial) SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Article ID BLOOD-PRESSURE; TOLVAPTAN; MORTALITY; DISEASE AB Serum magnesium levels may be impacted by neurohormonal activation, renal function, and diuretics. The clinical profile and prognostic significance of serum magnesium level concentration in patients hospitalized for heart failure (HF) with reduced ejection fraction is unclear. In this retrospective analysis of the placebo group of the Efficacy of Vasopressin Antagonism in Heart Failure Outcome Study with Tolvaptan trial, we evaluated 1,982 patients hospitalized for worsening HF with ejection fractions <= 40%. Baseline magnesium levels were measured within 48 hours of admission and analyzed as a continuous variable and in quartiles. The primary end points of all-cause mortality (ACM) and cardiovascular mortality or HF rehospitalization were analyzed using Cox regression models. Mean baseline magnesium level was 2.1 +/- 0.3 mg/dl. Compared with the lowest quartile, patients in the highest magnesium level quartile were more likely to be older, men, have lower heart rates and blood pressures, have ischemic HF origin, and have higher creatinine and natriuretic peptide levels (all p < 0.003). During a median follow-up of 9.9 months, every 1-mg/dl increase in magnesium level was associated with higher ACM (hazard ratio [HR] 1.77; 95% confidence interval [CI] 1.35 to 2.32; p < 0.001) and the composite end point (HR 1.44; 95% CI 1.15 to 1.81; p = 0.002). However, after adjustment for known baseline covariates, serum magnesium level was no longer an independent predictor of either ACM (HR 0.94, 95% CI 0.69 to 1.28; p = 0.7) or the composite end point (HR 1.01, 95% CI 0.79 to 1.30; p = 0.9). In conclusion, despite theoretical concerns, baseline magnesium level was not independently associated with worse outcomes in this cohort. Further research is needed to understand the importance of serum magnesium levels in specific HF patient populations. (C) 2013 Elsevier Inc. All rights reserved. C1 [Vaduganathan, Muthiah] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Med, Boston, MA USA. [Greene, Stephen J.; Gheorghiade, Mihai] Northwestern Univ, Feinberg Sch Med, Ctr Cardiovasc Innovat, Chicago, IL 60611 USA. [Ambrosy, Andrew P.] Stanford Univ, Sch Med, Dept Med, Stanford, CA USA. [Mentz, Robert J.] Duke Univ, Med Ctr, Durham, NC USA. [Fonarow, Gregg C.] Ahmanson UCLA Cardiomyopathy Ctr, Los Angeles, CA USA. [Zannad, Faiez] Nancy Univ, Dept Cardiol, Nancy, France. [Maggioni, Aldo P.] ANMCO Res Ctr, Florence, Italy. [Konstam, Marvin A.] Tufts Med Ctr, Boston, MA USA. [Subacius, Haris P.] Northwestern Univ, Feinberg Sch Med, Dept Med, Div Cardiol, Chicago, IL 60611 USA. [Nodari, Savina] Univ Brescia, Dept Cardiol, Brescia, Italy. [Butler, Javed] Emory Univ, Sch Med, Dept Med, Div Cardiol, Atlanta, GA USA. RP Gheorghiade, M (reprint author), Northwestern Univ, Feinberg Sch Med, Ctr Cardiovasc Innovat, Chicago, IL 60611 USA. EM m-gheorghiade@northwestern.edu OI Subacius, Haris/0000-0003-4061-1220; Maggioni, Aldo Pietro/0000-0003-2764-6779 FU Otsuka Inc. (Rockville, Maryland); Center for Cardiovascular Innovation (Northwestern University Feinberg School of Medicine, Chicago, Illinois) FX Otsuka Inc. (Rockville, Maryland) provided financial and material support for the EVEREST trial. Database management was performed by the sponsor. M.A.K. has been a consultant for Amgen, Johnson & Johnson, Novartis, Pharma AG, Otsuka Pharmaceuticals and Merck. H.P.S. conducted all final analyses for this manuscript with funding from the Center for Cardiovascular Innovation (Northwestern University Feinberg School of Medicine, Chicago, Illinois). The authors had full access to the data, take responsibility for its integrity, and had complete control and authority over manuscript preparation and the decision to publish. M.G. has been a consultant for Abbott Laboratories, Astellas, AstraZeneca, Bayer HealthCare AG, Corthera, Cytokinetics, Debiopharm S.A., Errekappa Terapeutici, GlaxoSmithKline, Ikaria, Johnson & Johnson, Medtronic, Merck, Novartis Pharma AG, Otsuka Pharmaceutical, Palatin Technologies, PeriCor Therapeutics, Protein Design Laboratories, Sanofi-Aventis, Sigma Tau, Solvay Pharmaceuticals, Takeda Pharmaceutical, and Trevena Therapeutics. All other authors have no conflicts of interest to declare. NR 21 TC 3 Z9 3 U1 0 U2 1 PU EXCERPTA MEDICA INC-ELSEVIER SCIENCE INC PI BRIDGEWATER PA 685 ROUTE 202-206 STE 3, BRIDGEWATER, NJ 08807 USA SN 0002-9149 EI 1879-1913 J9 AM J CARDIOL JI Am. J. Cardiol. PD DEC 1 PY 2013 VL 112 IS 11 BP 1763 EP 1769 DI 10.1016/j.amjcard.2013.07.020 PG 7 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 261SW UT WOS:000327685900011 PM 24095030 ER PT J AU Golba, K Mokrzycki, K Drozdz, J Cherniavsky, A Wrobel, K Roberts, BJ Haddad, H Maurer, G Yii, M Asch, FM Handschumacher, MD Holly, TA Przybylski, R Kron, I Schaff, H Aston, S Horton, J Lee, KL Velazquez, EJ Grayburn, PA AF Golba, Krzysztof Mokrzycki, Krzysztof Drozdz, Jaroslaw Cherniavsky, Alexander Wrobel, Krzysztof Roberts, Bradley J. Haddad, Haissam Maurer, Gerald Yii, Michael Asch, Federico M. Handschumacher, Mark D. Holly, Thomas A. Przybylski, Roman Kron, Irving Schaff, Hartzell Aston, Susan Horton, John Lee, Kerry L. Velazquez, Eric J. Grayburn, Paul A. CA STICH TEE Substudy Investigators TI Mechanisms of Functional Mitral Regurgitation in Ischemic Cardiomyopathy Determined by Transesophageal Echocardiography (from the Surgical Treatment for Ischemic Heart Failure Trial) SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Article ID LEFT-VENTRICULAR DYSFUNCTION; DILATED CARDIOMYOPATHY; 3-DIMENSIONAL ECHOCARDIOGRAPHY; BYPASS SURGERY; DOPPLER; RECOMMENDATIONS; SEVERITY; SURVIVAL; RECONSTRUCTION; INSIGHTS AB The mechanisms underlying functional mitral regurgitation (MR) and the relation between mechanism and severity of MR have not been evaluated in a large, multicenter, randomized controlled trial. Transesophageal echocardiography (TEE) was performed in 215 patients at 17 centers in the Surgical Treatment for Ischemic Heart Failure (STICH) trial. Both 2-dimensional (n = 215) and 3-dimensional (n = 81) TEEs were used to assess multiple quantitative measurements of the mechanism and severity of MR. By 2-dimensional TEE, leaflet tenting area, anterior and posterior leaflet angles, mitral annulus diameter, left ventricular (LV) end-systolic volume index, LV ejection fraction (LVEF), and sphericity index (p < 0.05 for all) were significantly different across MR grades. By 3-dimensional TEE, mitral annulus area, leaflet tenting area, LV end-systolic volume index, LVEF, and sphericity index (p < 0.05 for all) were significantly different across. MR grades. A multivariate analysis showed a trend for annulus area (p = 0.069) and LV end-systolic volume index (p = 0.071) to predict effective regurgitant orifice area and for annulus area (p = 0.018) and LV end-systolic volume index (p = 0.073) to predict vena contracta area. In the STICH trial, multiple quantitative parameters of the mechanism of functional MR are related to MR severity. The mechanism of functional MR in ischemic cardiomyopathy is heterogenous, but no single variable stands out as a strong predictor of quantitative severity of MR. (C) 2013 Elsevier Inc. All rights reserved. C1 [Golba, Krzysztof] Med Univ Silesia, Katowice, Poland. [Mokrzycki, Krzysztof] PUM, Klin Kardiochirurg, Szczecin, Poland. [Drozdz, Jaroslaw] Med Univ Lodz, Lodz, Poland. [Cherniavsky, Alexander] Res Inst Circulat Pathol, Novosibirsk, Russia. [Wrobel, Krzysztof] John Paul 2 Hosp, Krakow, Poland. [Roberts, Bradley J.; Aston, Susan; Grayburn, Paul A.] Baylor Univ, Med Ctr, Dallas, TX USA. [Haddad, Haissam] Univ Ottawa, Inst Heart, Ottawa, ON, Canada. [Maurer, Gerald] Med Univ Vienna, Vienna, Austria. [Yii, Michael] Univ Melbourne, St Vincents Hosp Melbourne, Dept Surg, Melbourne, Vic, Australia. [Asch, Federico M.] MedStar Washington Hosp Ctr, Washington, DC USA. [Handschumacher, Mark D.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. [Holly, Thomas A.] Northwestern Univ, Feinberg Sch Med, Chicago, IL 60611 USA. [Przybylski, Roman] Silesian Med Univ, Silesian Ctr Heart Dis, Zabrze, Poland. [Kron, Irving] Univ Virginia Hlth Syst, Charlottesville, VA USA. [Schaff, Hartzell] Mayo Clin, Coll Med, Rochester, MA USA. [Horton, John; Lee, Kerry L.; Velazquez, Eric J.] Duke Univ, Sch Med, Duke Clin Res Inst, Durham, NC USA. [Lee, Kerry L.] Duke Univ, Sch Med, Dept Biostat & Bioinformat, Durham, NC USA. [Velazquez, Eric J.] Duke Univ, Sch Med, Dept Med, Div Cardiol, Durham, NC USA. RP Grayburn, PA (reprint author), Baylor Univ, Med Ctr, Dallas, TX USA. EM paulgr@baylorhealth.edu RI Chernyavskiy, Aleksandr/I-9975-2014; OI Chernyavskiy, Aleksandr/0000-0001-9818-8678; Schaff, Hartzell/0000-0003-0994-027X FU National Institutes of Health, Bethesda, Maryland [RO1HL72430, UO1HL69015, UO1HL60913] FX This work was supported by grants RO1HL72430, UO1HL69015, and UO1HL60913 from the National Institutes of Health, Bethesda, Maryland. NR 26 TC 4 Z9 4 U1 0 U2 7 PU EXCERPTA MEDICA INC-ELSEVIER SCIENCE INC PI BRIDGEWATER PA 685 ROUTE 202-206 STE 3, BRIDGEWATER, NJ 08807 USA SN 0002-9149 EI 1879-1913 J9 AM J CARDIOL JI Am. J. Cardiol. PD DEC 1 PY 2013 VL 112 IS 11 BP 1812 EP 1818 DI 10.1016/j.amjcard.2013.07.047 PG 7 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 261SW UT WOS:000327685900018 PM 24035166 ER PT J AU Fukuta, Y Muder, RR Agha, ME Clarke, LG Wagener, MM Hensler, AM Doi, Y AF Fukuta, Yuriko Muder, Robert R. Agha, Mounzer E. Clarke, Lloyd G. Wagener, Marilyn M. Hensler, Amelia M. Doi, Yohei TI Risk factors for acquisition of multidrug-resistant Acinetobacter baumannii among cancer patients SO AMERICAN JOURNAL OF INFECTION CONTROL LA English DT Article DE Clinical outcome; Malignancy; Infection; Colonization; Case-control study ID CELL TRANSPLANT RECIPIENTS; BLOOD-STREAM INFECTIONS; HEMATOLOGICAL MALIGNANCIES; BACTEREMIA; EPIDEMIOLOGY; UPDATE; IMPACT; AGENTS AB Background: Data regarding multidrug-resistant (MDR) Acinetobacter baumannii infections among cancer patients are limited. Methods: We conducted a case-control study to investigate the risk factors for acquisition of MDR A baumannii and the outcomes among cancer patients. Cases were inpatients with malignancy who had MDR A baumannii from any cultures between 2008 and 2011. Controls were inpatients with malignancy but no MDR A baumannii. Results: A total of 31 case patients were matched with 62 control patients. Hematologic malignancy (P=.036), need for dialysis (P=.01), admission for other reasons except elective surgery (P=.03), transfer from other health care facilities (P=.02), prolonged intensive care unit stay (P=.004), mechanical ventilation (P<.001), pressor use (P=.001), tube feeding (P<.001), transfusion (P=.009), and prior antimicrobial use (P<.001) were identified as significant risk factors in univariate analysis. Need for dialysis (odds ratio [OR], 18.23; P=.04) and prolonged intensive care unit stay (OR, 19.28; P=.01) remained significant in multivariate analysis. Lengths of stay were 28 days for the case patients and 10 days for the control patients (P=.001). The 90-day mortality rates were 41.9% and 29.0%, respectively (P=.20). Conclusions: Acquisition of MDR A baumannii among cancer patients appears to be associated with general nosocomial infection risk factors rather than underlying malignancies. Copyright (C) 2013 by the Association for Professionals in Infection Control and Epidemiology, Inc. Published by Elsevier Inc. All rights reserved. C1 [Fukuta, Yuriko; Muder, Robert R.; Clarke, Lloyd G.; Doi, Yohei] Univ Pittsburgh, Sch Med, Div Infect Dis, Pittsburgh, PA 15261 USA. [Muder, Robert R.] VA Pittsburgh Healthcare Syst, Dept Infect Control, Pittsburgh, PA USA. [Agha, Mounzer E.] Univ Pittsburgh, Med Ctr, Hillman Canc Ctr, Div Hematol, Pittsburgh, PA 15261 USA. [Clarke, Lloyd G.] Univ Pittsburgh, Med Ctr, Presbyterian Hosp, Dept Pharm,Antibiot Management Program, Pittsburgh, PA 15261 USA. [Wagener, Marilyn M.] Univ Pittsburgh, Sch Med, Dept Med, Pittsburgh, PA 15261 USA. [Hensler, Amelia M.] Univ Pittsburgh, Med Ctr, Shadyside Hosp, Dept Infect Prevent & Control, Pittsburgh, PA 15261 USA. RP Doi, Y (reprint author), Univ Pittsburgh, Sch Med, Dept Med, Div Infect Dis, S829 Scaife Hall,3550 Terrace St, Pittsburgh, PA 15261 USA. EM yod4@pitt.edu FU Thomas H. Nimick Jr. Competitive Research Fund; National Institutes of Health [K22AI80584]; Pennsylvania Department of Health [4100047864] FX This study was supported by the Thomas H. Nimick Jr. Competitive Research Fund. Y.D. was supported in part by the National Institutes of Health (grant No. K22AI80584) and the Pennsylvania Department of Health (grant No. 4100047864). NR 28 TC 17 Z9 17 U1 0 U2 2 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0196-6553 EI 1527-3296 J9 AM J INFECT CONTROL JI Am. J. Infect. Control PD DEC PY 2013 VL 41 IS 12 BP 1249 EP 1252 DI 10.1016/j.ajic.2013.04.003 PG 4 WC Public, Environmental & Occupational Health; Infectious Diseases SC Public, Environmental & Occupational Health; Infectious Diseases GA 259QA UT WOS:000327540200021 PM 23870296 ER PT J AU Anderson, M Ottum, A Zerbel, S Sethi, A Gaines, ME Safdar, N AF Anderson, Michael Ottum, Andy Zerbel, Sara Sethi, Ajay Gaines, Martha E. Safdar, Nasia TI A survey to examine patient awareness, knowledge, and perceptions regarding the risks and consequences of surgical site infections SO AMERICAN JOURNAL OF INFECTION CONTROL LA English DT Article DE Hospital-acquired infection; Patient education; Prevention ID HEALTH; IMPACT AB We surveyed patients to determine awareness and knowledge regarding risks and consequences of and prevention of surgical site infection (SSI), and we found that 26% of respondents thought that education for SSI prevention could be improved and that 16% could not recall discussing SSI risks and prevention with a health care worker at all. Only 60% of patients recalled receiving an informational flyer in the hospital. Our results show that better educational and engagement interventions incorporating patient preferences are needed to promote awareness and patient engagement regarding SSI prevention. Published by Elsevier Inc. on behalf of the Association for Professionals in Infection Control and Epidemiology, Inc. C1 [Anderson, Michael; Safdar, Nasia] Univ Wisconsin, Dept Med, Madison, WI 53792 USA. [Ottum, Andy; Sethi, Ajay; Safdar, Nasia] Univ Wisconsin, Dept Populat Hlth Sci, Madison, WI 53792 USA. [Zerbel, Sara; Safdar, Nasia] Univ Wisconsin, Hosp & Clin, Madison, WI 53792 USA. [Gaines, Martha E.] Univ Wisconsin, Ctr Patient Partnerships, Madison, WI 53792 USA. [Safdar, Nasia] William S Middleton Mem Vet Adm Med Ctr, Madison, WI USA. RP Safdar, N (reprint author), Univ Wisconsin, Dept Med, MFCB 5221,1685 Highland Ave, Madison, WI 53792 USA. EM ns2@medicine.wisc.edu NR 8 TC 1 Z9 1 U1 1 U2 3 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0196-6553 EI 1527-3296 J9 AM J INFECT CONTROL JI Am. J. Infect. Control PD DEC PY 2013 VL 41 IS 12 BP 1293 EP 1295 DI 10.1016/j.ajic.2013.02.007 PG 3 WC Public, Environmental & Occupational Health; Infectious Diseases SC Public, Environmental & Occupational Health; Infectious Diseases GA 259QA UT WOS:000327540200033 PM 23680112 ER PT J AU Lim, P Ridges, R Jacobs, DS Rosenthal, P AF Lim, Pauline Ridges, Ryan Jacobs, Deborah S. Rosenthal, Perry TI Treatment of Persistent Corneal Epithelial Defect With Overnight Wear of a Prosthetic Device for the Ocular Surface SO AMERICAN JOURNAL OF OPHTHALMOLOGY LA English DT Article ID SCLERAL CONTACT-LENS; AUTOLOGOUS SERUM; MANAGEMENT; ABRASIONS; DISORDERS; EYEDROPS; THERAPY; TRAUMA; DROPS AB PURPOSE: To report experience in the treatment of persistent corneal epithelial defect using overnight wear of a prosthetic device for the ocular surface. DESIGN: Retrospective interventional case series. METHODS: A clinical database of patients who underwent prosthetic replacement of the ocular surface ecosystem (PROSE) treatment from March 2003 to August 2008 was searched to identify patients treated for persistent corneal epithelial defect. In early 2003, overnight wear of a PROSE device and addition of commercially available, nonpreserved, topical ophthalmic moxifloxacin to the saline in the device reservoir became standard practice at this center when treating persistent corneal epithelial defect. Medical records were abstracted to obtain underlying diagnoses, previous treatments, days to re-epithelialization, and complications for subsequent analysis. RESULTS: PROSE treatment incorporating overnight wear, with adjunctive use of moxifloxacin, was employed in 20 eyes of 19 patients for a total of 372 days. Re-epithelialization occurred in 17 of 20 eyes. Median duration of treatment incorporating overnight wear was 8.5 days (range = 2-76 days). Healing occurred in <= 7 days in 12 eyes, 8-14 days in 3 eyes, and > 14 days in 2 eyes (range = 1-35 days). There were no cases of microbial keratitis. CONCLUSIONS: Overnight wear of a PROSE device is effective in promoting healing of Persistent corneal epithelial defect. In comparison to an earlier series from:: this center, the rate of microbial keratitis as a complication of treatment has been reduced with the use of a nonpreserved topical fourth-generation fluoroquinolone in the device reservoir. ((C) 2013 by Elsevier Inc. All rights reserved.) C1 [Lim, Pauline] Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. [Ridges, Ryan; Jacobs, Deborah S.; Rosenthal, Perry] Boston Fdn Sight, Needham, MA 02494 USA. RP Ridges, R (reprint author), Boston Fdn Sight, 464 Hillside Ave,Suite 205, Needham, MA 02494 USA. EM rridges@bostonsight.org FU Massachusetts Eye Ear Infirmary; Boston Foundation for Sight FX ALL AUTHORS HAVE COMPLETED AND SUBMITTED THE ICMJE FORM FOR DISCLOSURE OF POTENTIAL CONFLICTS OF INTEREST and none were reported. During the conduct of the study Pauline Lim was a salaried employee of Massachusetts Eye & Ear Infirmary: Perry Rosenthal, Deborah Jacobs, and Ryan Ridges are salaried employees of the 501(c) (3) Boston Foundation for Sight. None of them has any proprietary or financial interest in any contact lens or prosthetic device. Contributions of authors: design of the study (P.L., D.J.); conduct of the study (P.L., D.J., P.R.); collection and interpretation of data (P.L., R.R., D.J.); and preparation of the manuscript (P.L., R.R., D.J.). NR 21 TC 7 Z9 7 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9394 EI 1879-1891 J9 AM J OPHTHALMOL JI Am. J. Ophthalmol. PD DEC PY 2013 VL 156 IS 6 BP 1095 EP 1101 DI 10.1016/j.ajo.2013.06.006 PG 7 WC Ophthalmology SC Ophthalmology GA 261OQ UT WOS:000327674900005 PM 24075432 ER PT J AU Mendoza, PR Jakobiec, FA Krane, JF AF Mendoza, Pia R. Jakobiec, Frederick A. Krane, Jeffrey F. TI Immunohistochemical Features of Lacrimal Gland Epithelial Tumors SO AMERICAN JOURNAL OF OPHTHALMOLOGY LA English DT Article ID ADENOID CYSTIC CARCINOMA; LOW-GRADE ADENOCARCINOMA; SALIVARY-GLAND; PLEOMORPHIC ADENOMA; MYB EXPRESSION; CELL-GROWTH; GENE; PLAG1; APOPTOSIS; FUSION AB PURPOSE: To investigate the immunohistochemical features of ocular adnexal pleomorphic adenoma and adenoid cystic carcinoma. DESIGN: Retrospective clinicopathologic study. METHODS: Clinical records and microscopic slides of 7 cases of each tumor type were reviewed. Immunohistochemical probes for Ki-67 and p53, and newer nuclear markers MYB for adenoid cystic carcinoma and PLAG1 for pleomorphic adenoma, were employed. RESULTS: Pleomorphic adenomas were asymptomatic, whereas adenoid cystic carcinomas were painful. No pleomorphic adenomas recurred; 4 adenoid cystic carcinomas recurred, resulting in 3 deaths. Unusual histopathologic variants for which immunohistochemistry proved useful included a myoepithelioma, an atypical pleomorphic adenoma, tubular and solid/basaloid variants of adenoid cystic carcinoma, and a morphologically heterogeneous adenoid cystic carcinoma of a Wolfring gland. For the pleomorphic adenomas, the average Ki-67 proliferation index was 3.8%; p53 was weakly staining, with an average positivity of 18.5%; PLAG1 was strongly positive in all cases; MYB was negative in 5 cases and weakly focally positive in 2 cases. For the adenoid cystic carcinomas, the average Ki-67 proliferation index was 29.1%; p53 stained positively and strongly with an average. of 39%; none stained positively for PLAG1; and 6 out of 7 were MYB positive. CONCLUSIONS: Between pleomorphic adenoma and adenoid cystic carcinoma, there was no overlap in Ki-67 positivity. Positivity for p53 showed overlap in only one lesion of each type. PLAG1 and MYB positivity were highly discriminating between pleomorphic adenoma and adenoid cystic carcinoma. Immunohistochemical analysis should be investigated further for its role in the evaluation of pleomorphic adenoma and adenoid cystic carcinoma. ((C) 2013 by Elsevier Inc. All rights reserved.) C1 [Mendoza, Pia R.; Jakobiec, Frederick A.] Massachusetts Eye & Ear Infirm, Dept Ophthalmol, David G Cogan Lab Ophthalm Pathol, Boston, MA 02114 USA. [Krane, Jeffrey F.] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. [Mendoza, Pia R.; Jakobiec, Frederick A.; Krane, Jeffrey F.] Harvard Univ, Sch Med, Boston, MA USA. RP Jakobiec, FA (reprint author), Massachusetts Eye & Ear Infirm, David G Cogan Lab Ophthalm Pathol, 243 Charles St,Suite 328, Boston, MA 02114 USA. EM Fred_jakobiec@meei.harvard.edu NR 37 TC 6 Z9 7 U1 0 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9394 EI 1879-1891 J9 AM J OPHTHALMOL JI Am. J. Ophthalmol. PD DEC PY 2013 VL 156 IS 6 BP 1147 EP 1158 DI 10.1016/j.ajo.2013.06.034 PG 12 WC Ophthalmology SC Ophthalmology GA 261OQ UT WOS:000327674900012 PM 23972314 ER PT J AU Evins, AE AF Evins, A. Eden TI Reassessing the Safety of Varenicline SO AMERICAN JOURNAL OF PSYCHIATRY LA English DT Editorial Material ID SMOKING-CESSATION; SCHIZOPHRENIA; TRIAL C1 [Evins, A. Eden] Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA. [Evins, A. Eden] Massachusetts Gen Hosp, Ctr Addict Med, Boston, MA 02114 USA. RP Evins, AE (reprint author), Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA. EM a_eden_evins@hms.harvard.edu NR 10 TC 9 Z9 9 U1 1 U2 5 PU AMER PSYCHIATRIC PUBLISHING, INC PI ARLINGTON PA 1000 WILSON BOULEVARD, STE 1825, ARLINGTON, VA 22209-3901 USA SN 0002-953X EI 1535-7228 J9 AM J PSYCHIAT JI Am. J. Psychiat. PD DEC PY 2013 VL 170 IS 12 BP 1385 EP 1387 DI 10.1176/appi.ajp.2013.13091257 PG 3 WC Psychiatry SC Psychiatry GA 263RE UT WOS:000327824900003 PM 24306334 ER PT J AU Drake, RE Frey, W Bond, GR Goldman, HH Salkever, D Miller, A Moore, TA Riley, J Karakus, M Milfort, R AF Drake, Robert E. Frey, William Bond, Gary R. Goldman, Howard H. Salkever, David Miller, Alexander Moore, Troy A. Riley, Jarnee Karakus, Mustafa Milfort, Roline TI Assisting Social Security Disability Insurance Beneficiaries With Schizophrenia, Bipolar Disorder, or Major Depression in Returning to Work SO AMERICAN JOURNAL OF PSYCHIATRY LA English DT Article ID SEVERE MENTAL-ILLNESS; SUPPORTED EMPLOYMENT; INDIVIDUAL PLACEMENT; CARE; PERFORMANCE; PEOPLE; SCALE; COSTS; MODEL; ILL AB Objective: People with psychiatric impairments (primarily schizophrenia or a mood disorder) are the largest and fastest-growing group of Social Security Disability Insurance (SSDI) beneficiaries. The authors investigated whether evidence-based supported employment and mental health treatments can improve vocational and mental health recovery for this population. Method: Using a randomized controlled trial design, the authors tested a multifaceted intervention: team-based supported employment, systematic medication management, and other behavioral health services, along with elimination of barriers by providing complete health insurance coverage (with no out-of-pocket expenses) and suspending disability reviews. The control group received usual services. Paid employment was the primary outcome measure, and overall mental health and quality of life were secondary outcome measures. Results: Overall, 2,059 SSDI beneficiaries with schizophrenia, bipolar disorder, or depression in 23 cities participated in the 2-year intervention. The teams implemented the intervention package with acceptable fidelity. The intervention group experienced more paid employment (60.3% compared with 40.2%) and reported better mental health and quality of life than the control group. Conclusions: Implementation of the complex intervention in routine mental health treatment settings was feasible, and the intervention was effective in assisting individuals disabled by schizophrenia or depression to return to work and improve their mental health and quality of life. C1 [Drake, Robert E.] Dartmouth Psychiat Res Ctr, Geisel Sch Med Dartmouth, Hanover, NH USA. Univ Maryland, Sch Med, Dept Psychiat, Baltimore, MD 21201 USA. Univ Maryland, Dept Publ Policy, Baltimore, MD USA. Univ Texas San Antonio, Sch Med, Dept Psychiat, South Texas Vet Hlth Care Syst, San Antonio, TX USA. RP Drake, RE (reprint author), Dartmouth Psychiat Res Ctr, Geisel Sch Med Dartmouth, Hanover, NH USA. EM robert.e.drake@dartmouth.edu FU Pfizer; SSA [SS00-05-60072]; Westat [SS00-05-60072] FX Dr. Miller has served on data monitoring committees for Otsuka and has received an investigator-initiated research grant from Pfizer. The other authors report no financial relationships with commercial interests.; The authors thank Susan Kalasunas and Tom Hale from the U.S. Social Security Administration (SSA) for their assistance. This study extends work that was conducted under contract SS00-05-60072 between the SSA and Westat. This analysis was conducted for the benefit of the SSA. The opinions expressed in this article are those of the authors and not necessarily those of the SSA. NR 30 TC 25 Z9 26 U1 2 U2 24 PU AMER PSYCHIATRIC PUBLISHING, INC PI ARLINGTON PA 1000 WILSON BOULEVARD, STE 1825, ARLINGTON, VA 22209-3901 USA SN 0002-953X EI 1535-7228 J9 AM J PSYCHIAT JI Am. J. Psychiat. PD DEC PY 2013 VL 170 IS 12 BP 1433 EP 1441 DI 10.1176/appi.ajp.2013.13020214 PG 9 WC Psychiatry SC Psychiatry GA 263RE UT WOS:000327824900012 PM 23929355 ER PT J AU Olfson, M Marcus, SC Bridge, JA AF Olfson, Mark Marcus, Steven C. Bridge, Jeffrey A. TI Emergency Department Recognition of Mental Disorders and Short-Term Outcome of Deliberate Self-Harm SO AMERICAN JOURNAL OF PSYCHIATRY LA English DT Article ID BORDERLINE PERSONALITY-DISORDER; SUICIDAL-BEHAVIOR; FOLLOW-UP; PSYCHIATRIC-ASSESSMENT; MANAGEMENT; ACCIDENT; CARE; ADOLESCENTS; POPULATION; THERAPY AB Objective: The authors sought to characterize the short-term risks of repeat self-harm and psychiatric hospital admission for deliberate self-harm patients discharged from emergency departments to the community, focusing on recognition of mental disorders in the emergency department. Method: A retrospective longitudinal cohort analysis of national Medicaid claims data was conducted of adults 21-64 years of age with deliberate self-harm who were discharged from emergency departments (N=5,567). Rates and adjusted risk ratios are presented of repeat self-harm visits and inpatient psychiatric admission during the 30 days following the initial emergency visit. Results: Approximately 9.7% of self-harm visits were followed by repeat self-harm visits and 13.6% by inpatient psychiatric admissions within 30 days after the initial emergency visit. The rate of repeat self-harm visits was inversely related to recognition of a mental disorder in the emergency department (adjusted risk ratio [ARR]=0.66, 95% CI=0.55-0.79) and directly related to recent diagnosis of anxiety disorders (ARR=1.56, 95% CI=1.30-1.86) or personality disorders (ARR=1.67, 95% CI=1.19-2.34). Recognition of a mental disorder in the emergency department was inversely related to repeat self-harm among patients with no recent mental disorder diagnosis (ARR=0.57, 95% CI=0.41-0.79); any recent mental disorder diagnosis (ARR=0.70, 95%=0.57-0.87); and depressive (ARR=0.71, 95% CI=0.54-0.94), bipolar (ARR=0.70, 95% CI=0.51-0.94), and substance use (ARR=0.71, 95% CI=0.53-0.96) disorder diagnoses. Recognition of a mental disorder was also inversely related to subsequent inpatient psychiatric admission (ARR=0.81, 95% CI=0.71-0.93). Conclusions: Adults who are discharged to the community after emergency visits for deliberate self-harm are at high short-term risk of repeat deliberate self-harm and hospital admission, although these risks may be attenuated by clinical recognition of a mental disorder in the emergency department. C1 [Olfson, Mark] Columbia Univ Coll Phys & Surg, New York State Psychiat Inst, Dept Psychiat, New York, NY 10032 USA. Ctr Hlth Equ Res & Promot, Philedelphia Vet Affairs Med Ctr, Philadelphia, PA USA. Univ Penn, Sch Social Policy & Practice, Philadelphia, PA 19104 USA. Nationwide Childrens Hosp, Ctr Innovat Pediat Practice, Res Inst, Columbus, OH USA. RP Olfson, M (reprint author), Columbia Univ Coll Phys & Surg, New York State Psychiat Inst, Dept Psychiat, New York, NY 10032 USA. EM mo49@columbia.edu FU American Foundation for Suicide Prevention; NIMH [MH093552]; Centers for Disease Control and Prevention grant [CE002129] FX Supported by the American Foundation for Suicide Prevention (a Distinguished Investigator Award to Dr. Olfson); NIMH grant MH093552 (to Dr. Bridge); and Centers for Disease Control and Prevention grant CE002129 (to Dr. Bridge). NR 38 TC 11 Z9 11 U1 1 U2 11 PU AMER PSYCHIATRIC PUBLISHING, INC PI ARLINGTON PA 1000 WILSON BOULEVARD, STE 1825, ARLINGTON, VA 22209-3901 USA SN 0002-953X EI 1535-7228 J9 AM J PSYCHIAT JI Am. J. Psychiat. PD DEC PY 2013 VL 170 IS 12 BP 1442 EP 1450 DI 10.1176/appi.ajp.2013.12121506 PG 9 WC Psychiatry SC Psychiatry GA 263RE UT WOS:000327824900013 PM 23897218 ER PT J AU Bose, S Guyer, A Long, AD Banerji, A AF Bose, Sumit Guyer, Autumn Long, Aidan Banerji, Aleena TI Evaluation and management of hypersensitivity to proton pump inhibitors SO ANNALS OF ALLERGY ASTHMA & IMMUNOLOGY LA English DT Article ID CROSS-REACTIVITY; ANAPHYLACTIC REACTION; CONTACT-DERMATITIS; OMEPRAZOLE; ALLERGY; LANSOPRAZOLE; PANTOPRAZOLE; DIAGNOSIS; RABEPRAZOLE; DRUGS AB Objective: Proton pump inhibitors (PPIs) are widely used for the treatment of gastroesophageal reflux disease and peptic ulcer disease. PPIs are well tolerated, but they can cause hypersensitivity reactions (HSRs). Although simply avoiding a PPI after an HSR is appropriate for most patients, there are clinical scenarios that require treatment with a PPI. Data Sources: A comprehensive literature review was performed to propose an evidence-based approach to the evaluation and management of HSRs to PPIs. Study Selections: Articles from June 1986 through September 2012 on PPI hypersensitivity were reviewed. Thirty-nine studies that met the search criteria were included in the review. HSRs to PPIs and skin testing protocols used to evaluate HSRs were analyzed from the 39 identified publications. For each case, the culprit drug and dose, the age and sex of the patient, and the symptoms and timing of the HSR were recorded. HSRs were classified into immune- or nonimmune-mediated categories. Results: A total of 118 cases of immune-mediated HSRs to 5 PPIs were identified, most of which were suspected IgE-mediated HSRs. Omeprazole was the culprit PPI most frequently associated with HSRs. The most common clinical manifestations of PPI HSRs were cutaneous reactions. Nonirritating concentrations for skin prick and intradermal testing were identified. Skin testing showed variable cross-reactivity patterns among the different PPIs. Conclusion: The HSRs to PPIs should be formally investigated, especially when reasonable alternative therapies do not exist. The reviewers propose an evidence-based algorithm for evaluating and managing patients with an HSR to a PPI. (C) 2013 American College of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved. C1 [Bose, Sumit] Univ Hosp Case Med Ctr, Dept Med, Cleveland, OH 44106 USA. [Guyer, Autumn; Long, Aidan; Banerji, Aleena] Massachusetts Gen Hosp, Div Rheumatol Allergy & Immunol, Boston, MA 02114 USA. RP Bose, S (reprint author), Univ Hosp Case Med Ctr, Dept Med, Lakeside Suite 300,11100 Euclid Ave, Cleveland, OH 44106 USA. EM Sumit.Bose@UHhospitals.org NR 40 TC 8 Z9 9 U1 0 U2 6 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1081-1206 EI 1534-4436 J9 ANN ALLERG ASTHMA IM JI Ann. Allergy Asthma Immunol. PD DEC PY 2013 VL 111 IS 6 BP 452 EP 457 DI 10.1016/j.anai.2013.08.022 PG 6 WC Allergy; Immunology SC Allergy; Immunology GA 259PL UT WOS:000327538700007 PM 24267357 ER PT J AU Wosu, AC Valdimarsdottir, U Shields, AE Williams, DR Williams, MA AF Wosu, Adaeze C. Valdimarsdottir, Unnur Shields, Alexandra E. Williams, David R. Williams, Michelle A. TI Correlates of cortisol in human hair: implications for epidemiologic studies on health effects of chronic stress SO ANNALS OF EPIDEMIOLOGY LA English DT Review DE Hair; Cortisol; Chronic stress; Correlates; Assessment; Analysis; Determinants; Psychiatric disorders ID LONG-TERM CORTISOL; PITUITARY-ADRENAL AXIS; URINE-FREE CORTISOL; CHRONIC PELVIC PAIN; BODY-MASS INDEX; SALIVARY CORTISOL; CUSHINGS-SYNDROME; PSYCHOLOGICAL STRESS; CARDIOVASCULAR-DISEASE; METABOLIC SYNDROME AB Assessment of cortisol concentrations in hair is one of the latest innovations for measuring long-term cortisol exposure. We performed a systematic review of correlates of cortisol in human hair to inform the design, analysis, and interpretation of future epidemiologic studies. Relevant publications were identified through electronic searches on PubMed, WorldCat, and Web of Science using keywords, "cortisol," "hair," "confounders," "chronic," "stress," and "correlates." Thirty-nine studies were included in this review. Notwithstanding scarce data and some inconsistencies, investigators have found hair cortisol concentrations to be associated with stress-related psychiatric symptoms and disorders (e.g., post-traumatic stress disorder), medical conditions indicating chronic activation of the hypothalamic-pituitary-adrenal axis (e.g., Cushing's syndrome), and other life situations associated with elevated risk of chronic stress (e.g., shiftwork). Results from some studies suggest that physical activity, adiposity, and substance abuse may be correlates of hair cortisol concentrations. In contrast to measures of short-term cortisol release (saliva, blood, and urine), cigarette smoking and use of oral contraceptives appear not to be associated with hair cortisol concentrations. Studies of pregnant women indicate increased hair cortisol concentrations across successive trimesters. The study of hair cortisol presents a unique opportunity to assess chronic alterations in cortisol concentrations in epidemiologic studies. (C) 2013 Elsevier Inc. All rights reserved. C1 [Wosu, Adaeze C.; Williams, Michelle A.] Harvard Univ, Sch Publ Hlth, Multidisciplinary Int Res Training Program, Boston, MA 02115 USA. [Wosu, Adaeze C.; Valdimarsdottir, Unnur; Williams, Michelle A.] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. [Valdimarsdottir, Unnur] Univ Iceland, Fac Med, Ctr Publ Hlth Sci, Reykjavik, Iceland. [Shields, Alexandra E.] Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. [Shields, Alexandra E.] Harvard Massachusetts Gen Hosp, Ctr Genom Vulnerable Populat & Hlth Dispar, Mongan Inst Hlth Policy, Boston, MA USA. [Williams, David R.] Harvard Univ, Sch Publ Hlth, Dept Social & Behav Sci, Boston, MA 02115 USA. RP Wosu, AC (reprint author), Harvard Univ, Sch Publ Hlth, Dept Epidemiol, 677 Huntington Ave,Room 500, Boston, MA 02115 USA. EM awosu@hsph.harvard.edu FU National Institutes of Health (National Institute on Minority Health and Health Disparities (NIMHD) [T37-MD001449]; National Center for Research Resources (NCRR)/ National Center for Advancing Translational Sciences (NCATS) [8UL1TR000170] FX This research was supported by grants from the National Institutes of Health (National Institute on Minority Health and Health Disparities (NIMHD): T37-MD001449; and the National Center for Research Resources (NCRR)/ National Center for Advancing Translational Sciences (NCATS): 8UL1TR000170). NR 107 TC 34 Z9 34 U1 6 U2 77 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1047-2797 EI 1873-2585 J9 ANN EPIDEMIOL JI Ann. Epidemiol. PD DEC PY 2013 VL 23 IS 12 BP 797 EP 811 DI 10.1016/j.annepidem.2013.09.006 PG 15 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 265CA UT WOS:000327926100009 PM 24184029 ER PT J AU Wei, W Dizon, D Vathipadiekal, V Birrer, MJ AF Wei, W. Dizon, D. Vathipadiekal, V. Birrer, M. J. TI Ovarian cancer: genomic analysis SO ANNALS OF ONCOLOGY LA English DT Article DE ovarian; cancer; genomics; clinical trials ID GRADE SEROUS CARCINOMA; CLEAR-CELL CARCINOMA; MALIGNANT POTENTIAL TUMORS; GYNECOLOGIC-ONCOLOGY-GROUP; GENE-EXPRESSION; ADVANCED-STAGE; EPITHELIAL TUMORS; MUTATIONS; SURVIVAL; ADENOCARCINOMA AB Objectives: Despite improvements in the management of ovarian cancer patients over the last 30 years, there has been only a minimal improvement in overall survival. While targeted therapeutic approaches for the treatment of cancer have evolved, major challenges in ovarian cancer research persist, including the identification of predictive biomarkers with clinical relevance, so that empirical drug selection can be avoided. In this article, we review published genomic analysis studies including data generated in our laboratory and how they have been incorporated into modern clinical trials in a rational and effective way. Methods: Multiple published genomic analysis studies were collected for review and discussion with emphasis on their potential clinical applicability. Results: Genomic analysis has been shown to be a powerful tool to identify dysregulated genes, aberrantly activated pathways and to uncover uniqueness of subclasses of ovarian tumors. The application of this technology has provided a solid molecular basis for different clinical behaviors associated with tumor histology and grade. Genomic signatures have been obtained to predict clinical end points for patients with cancer, including response rates, progression-free survival, and overall survival. In addition, genomic analysis has provided opportunities to identify biomarkers, which either result in a modification of existing clinical management or to stratification of patients to novel therapeutic approaches designed as clinical trials. Conclusions: Genomic analyses have accelerated the identification of relevant biomarkers and extended our understanding of the molecular biology of ovarian cancer. This in turn, will hopefully lead to a paradigm shift from empirical, uniform treatment to a more rational, personalized treatment of ovarian cancers. However, validation of potential biomarkers on both the statistical and biological levels is needed to confirm they are of clinical relevance, in order to increase the likelihood that the desired outcome can be predicted and achieved. C1 [Wei, W.; Vathipadiekal, V.] Harvard Univ, Sch Med, Ctr Canc Res, Boston, MA USA. [Dizon, D.; Birrer, M. J.] Massachusetts Gen Hosp, Gillette Ctr Gynecol Oncol, Boston, MA 02114 USA. RP Birrer, MJ (reprint author), Massachusetts Gen Hosp, Ctr Canc Res, YAW-9-072,55 Fruit St, Boston, MA 02114 USA. EM mbirrer@partners.org OI Vathipadiekal, Vinod/0000-0002-8181-6890; WEI, WEI/0000-0002-2315-3558 FU NIH [RC4CA156551, 1R01CA142832, R01CA169200]; Julie Fund FX The financial support of research grants is gratefully acknowledged: NIH grant RC4CA156551, NIH grant 1R01CA142832, NIH grant R01CA169200, and The Julie Fund. NR 75 TC 3 Z9 3 U1 0 U2 4 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0923-7534 EI 1569-8041 J9 ANN ONCOL JI Ann. Oncol. PD DEC PY 2013 VL 24 SU 10 BP 7 EP 15 DI 10.1093/annonc/mdt462 PG 9 WC Oncology SC Oncology GA 259EZ UT WOS:000327511500001 ER PT J AU Jonker, FHW Trimarchi, S Muhs, BE Rampoldi, V Montgomery, DG Froehlich, JB Peterson, MD Bartnes, K Gourineni, V Ramanath, VS Braverman, AC Nienaber, CA Isselbacher, EM Eagle, KA AF Jonker, Frederik H. W. Trimarchi, Santi Muhs, Bart E. Rampoldi, Vincenzo Montgomery, Daniel G. Froehlich, James B. Peterson, Mark D. Bartnes, Kristian Gourineni, Venu Ramanath, Vijay S. Braverman, Alan C. Nienaber, Christoph A. Isselbacher, Eric M. Eagle, Kim A. CA IRAD Investigators TI The Role of Age in Complicated Acute Type B Aortic Dissection SO ANNALS OF THORACIC SURGERY LA English DT Article ID POPULATION-BASED OUTCOMES; INTERNATIONAL REGISTRY; CARDIOVASCULAR-DISEASE; ENDOVASCULAR TREATMENT; ANEURYSM REPAIR; MANAGEMENT; WOMEN; MORTALITY; INSIGHTS; SURGERY AB Background. Complicated acute type B aortic dissection (cABAD) generally requires urgent intervention. Advanced age is a risk factor for mortality after thoracic aortic intervention, including surgery for aortic dissection. The purpose of this study was to investigate the exact impact of increasing age on the management and outcomes of cABAD. Methods. We analyzed the outcomes of 583 patients with cABAD enrolled in the International Registry of Acute Aortic Dissection (IRAD) between 1996 and 2012. All patients with cABAD were categorized according to age by decade and management type (medical, surgical, or endovascular treatment), and outcomes were subsequently investigated in the different age groups. Results. The mean age of the cohort was 63.4 +/- 14.2 years, 36% of patients (n = 209) were greater than 70 years of age and 64% (n = 374) were less than 70 years. The utilization of surgery and endovascular techniques progressively decreased with patient age, while the rate of medical management significantly increased with age (p < 0.001). The in-hospital mortality rates for complicated patients younger than 70 years versus 70 years or more were 10.1% versus 30.0% for endovascular treatment (p = 0.001), 17.2% versus 34.2% for surgical treatment (p = 0.027), and 14.2% versus 32.2% for medical treatment (p = 0.001). Age 70 years or greater was a predictor of in-hospital mortality in multivariate analysis (odds ratio 2.37, 95% confidence interval: 1.23 to 4.54, p = 0.010). Conclusions. Advanced age has a dramatic impact on the management and outcomes of patients with cABAD. A nonsignificant trend toward lower mortality after endovascular management was observed, both for younger patients and for elderly patients. (C) 2013 by The Society of Thoracic Surgeons C1 IRCCS Policlin San Donato, Thorac Aort Res Ctr, San Donato Milanese, Italy. Yale Univ, New Haven, CT USA. Univ Michigan, Ctr Cardiovasc, Ann Arbor, MI 48109 USA. St Michaels Hosp, Div Cardiac Surg, Toronto, ON M5B 1W8, Canada. Univ Tromso Hosp, Dept Thorac & Cardiovasc Surg, N-9012 Tromso, Norway. Dartmouth Hitchcock Med Ctr, Lebanon, NH 03766 USA. Washington Univ, Sch Med, Div Cardiovasc, St Louis, MO 63110 USA. Univ Rostock, Dept Internal Med, D-18055 Rostock, Germany. Massachusetts Gen Hosp, Thorac Aort Ctr, Boston, MA 02114 USA. RP Jonker, FHW (reprint author), Maasstad Hosp Rotterdam, Vasc Surg Sect, Bulgersteyn 1C, NL-3011 AB Rotterdam, Netherlands. EM jonkerfrederik@hotmail.com RI Trimarchi, Santi/J-7361-2016 OI Trimarchi, Santi/0000-0001-5996-3264 FU University of Michigan Health System; Varbedian Fund for Aortic Research; Mardigian Foundation; Gore Medical Inc (Flagstaff, Arizona) FX The International Registry of Acute Aortic Dissection (IRAD) is supported by grants from the University of Michigan Health System, the Varbedian Fund for Aortic Research, the Mardigian Foundation, and Gore Medical Inc (Flagstaff, Arizona). NR 35 TC 6 Z9 7 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0003-4975 EI 1552-6259 J9 ANN THORAC SURG JI Ann. Thorac. Surg. PD DEC PY 2013 VL 96 IS 6 BP 2129 EP 2134 DI 10.1016/j.athoracsur.2013.06.056 PG 6 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery SC Cardiovascular System & Cardiology; Respiratory System; Surgery GA 263GB UT WOS:000327794000040 PM 24070705 ER PT J AU Thaler, NS Linck, JF Heyanka, DJ Pastorek, NJ Miller, B Romesser, J Sim, A Allen, DN AF Thaler, Nicholas S. Linck, John F. Heyanka, Daniel J. Pastorek, Nicholas J. Miller, Brian Romesser, Jennifer Sim, Anita Allen, Daniel N. TI Heterogeneity in Trail Making Test Performance in OEF/OIF/OND Veterans with Mild Traumatic Brain Injury SO ARCHIVES OF CLINICAL NEUROPSYCHOLOGY LA English DT Article DE Mild cognitive impairment; Statistical methods; Assessment ID SERIAL-ADDITION TASK; METAANALYTIC METHODS; INSUFFICIENT EFFORT; MEMORY; LIMITATIONS; PROFILES; VALIDITY; SAMPLE; TBI AB This study used cluster analysis to examine variability in Trail Making Test (TMT) performance in a sample of Operation Enduring Freedom/Operation Iraqi Freedom/Operation New Dawn (OEF/OIF/OND) veterans referred for mild traumatic brain injury (mTBI). Three clusters were extracted, two of which were characterized by level of performance and the third with a unique performance pattern characterized by slow performance on the TMT B (Low B). Clusters did not differ on demographic or psychiatric variables. The Above Average cluster had better performance on measures of processing speed, working memory, and phonemic fluency compared with the Low B cluster. Results suggest that a subset of patients with mTBI perform poorly on TMT B, which subsequently predicts poorer cognitive functioning on several other neuropsychological measures. This subset may be vulnerable to cognitive changes in the context of mTBI and multiple comorbidities while a number of other patients remain cognitively unaffected under the same circumstances. C1 [Thaler, Nicholas S.; Linck, John F.; Heyanka, Daniel J.] Oklahoma City Dept Vet Affairs Med Ctr, Oklahoma City, OK USA. [Pastorek, Nicholas J.; Miller, Brian] Michael E DeBakey Dept Vet Affairs Med Ctr, Houston, TX USA. [Romesser, Jennifer] George E Wahlen Dept Vet Affairs Med Ctr, Salt Lake City, UT USA. [Sim, Anita] Minneapolis Dept Vet Affairs Med Ctr, Minneapolis, MN USA. [Allen, Daniel N.] Univ Nevada, Las Vegas, NV 89154 USA. RP Thaler, NS (reprint author), Univ Calif Los Angeles, Semel Inst Neurosci & Human Behav, 760 Westwood Plaza,C8-746, Los Angeles, CA 90095 USA. EM nick.thaler@gmail.com FU Department of Veterans Affairs, Veterans Health Administration, Office of Research and Development [B6812C] FX This material is based upon work supported by the Department of Veterans Affairs, Veterans Health Administration, Office of Research and Development; B6812C (PI- Levin HS) VA RR&D Traumatic Brain Injury Center of Excellence, Neurorehabilitation: Neurons to Networks. NR 50 TC 0 Z9 0 U1 0 U2 4 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0887-6177 EI 1873-5843 J9 ARCH CLIN NEUROPSYCH JI Arch. Clin. Neuropsychol. PD DEC PY 2013 VL 28 IS 8 BP 798 EP 807 DI 10.1093/arclin/act080 PG 10 WC Psychology, Clinical; Psychology SC Psychology GA 262FC UT WOS:000327718700007 PM 24145667 ER PT J AU Hunt, KJ Baker, N Cleary, P Backlund, JY Lyons, T Jenkins, A Virella, G Lopes-Virella, MF AF Hunt, Kelly J. Baker, Nathaniel Cleary, Patricia Backlund, Jye-Yu Lyons, Timothy Jenkins, Alicia Virella, Gabriel Lopes-Virella, Maria F. CA DCCT EDIC Res Grp TI Oxidized LDL and AGE-LDL in circulating immune complexes strongly predict progression of carotid artery IMT in type 1 diabetes SO ATHEROSCLEROSIS LA English DT Article DE Modified LDL; Subclinical atherosclerosis; Carotid artery intima-media thickness; Type 1 diabetes ID LOW-DENSITY-LIPOPROTEIN; INTIMA-MEDIA THICKNESS; ACUTE CORONARY SYNDROMES; COMPLICATIONS TRIAL; HUMAN MACROPHAGES; CARDIOVASCULAR HEALTH; WALL THICKNESS; HEART-DISEASE; END-PRODUCTS; RISK-FACTORS AB Objective: Over 90% of modified LDL in circulation is associated to specific antibodies circulating as part of immune complexes (IC); however, few studies have examined their relationship with cardiovascular disease. Methods: We report the relationship between circulating concentrations of IC of oxidized LDL (oxLDL-IC), malondialdehyde-LDL (MDA-LDL-IC) and advanced glycation end products-LDL (AGE-LDL-IC) and progression of atherosclerosis over a 12 year period in 467 individuals with type 1 diabetes who participated in the Diabetes Control and Complications Trial (DCCT) and the Epidemiology of Diabetes Interventions and Complications (EDIC) study. OxLDL-IC, AGE-LDL-IC and MDA-LDL-IC levels were measured at DCCT closeout. Internal carotid intimaemedial thickness (IMT) was measured at EDIC follow-up years 1, 6 and 12. Results: OxLDL-IC, AGE-LDL-IC and MDA-LDL-IC levels were significantly correlated with age, lipid levels, blood pressure levels and albumin excretion rates. Levels of oxLDL, AGE-LDL and MDA-LDL in isolated LDL-IC were highly inter-correlated (r 0.66e0.84, P < 0.0001). After adjusting for cardiovascular risk factors individuals in the upper quartile of oxLDL-IC had a 2.98-fold increased odds (CI: 1.34, 6.62) of having IMT 1.00 mm and had a 5.13-fold increased odds (CI: 1.98, 13.3) of having significant IMT progression, relative to those in the lowest quartile. Parallel odds ratios for AGE-LDL-IC were 2.95 (CI: 1.37, 6.34) and 3.50 (CI: 1.38, 8.86), while results for MDA-LDL-IC were 1.76 (0.87, 3.56) and 2.86 (1.20, 6.81). Conclusion: Our study indicates that high levels of oxLDL-IC and AGE-LDL-IC are important predictors of carotid intimaemedial thickening in patients with type 1 diabetes. Published by Elsevier Ireland Ltd. C1 [Hunt, Kelly J.; Baker, Nathaniel] Med Univ S Carolina, Dept Publ Hlth Sci, Charleston, SC 29425 USA. [Hunt, Kelly J.; Lopes-Virella, Maria F.] Ralph H Johnson VA Med Ctr, Charleston, SC USA. [Cleary, Patricia; Backlund, Jye-Yu] George Washington Univ, Ctr Biostat, Washington, DC USA. [Lyons, Timothy; Jenkins, Alicia] Univ Oklahoma, Hlth Sci Ctr, Harold Hamm Diabet Ctr, Clin & Translat Unit, Oklahoma City, OK USA. [Lyons, Timothy; Jenkins, Alicia] Univ Oklahoma, Hlth Sci Ctr, Dept Pediat, Oklahoma City, OK 73190 USA. [Virella, Gabriel] Med Univ S Carolina, Dept Microbiol & Immunol, Charleston, SC 29425 USA. [Lopes-Virella, Maria F.] Med Univ S Carolina, Dept Med, Charleston, SC 29425 USA. [Lyons, Timothy] Queens Univ Belfast, Inst Clin Sci, Ctr Vasc & Vis Res, Belfast, Antrim, North Ireland. RP Hunt, KJ (reprint author), Med Univ S Carolina, Dept Publ Hlth Sci, 135 Cannon St,Suite 302K,POB 250835, Charleston, SC 29425 USA. EM huntke@musc.edu FU National Institutes of Health/NHLBI [PO1 HL 55782]; NIH/NIDDK [R01 DK081352, R01 DK088778]; Juvenile Diabetes Foundation Grant; Research Service of the Ralph H. Johnson Department of Veterans Affairs Medical Center FX This work was supported by a Program Project funded by the National Institutes of Health/NHLBI (PO1 HL 55782), by two R01 Grants funded by NIH/NIDDK (R01 DK081352 and R01 DK088778) and by a Juvenile Diabetes Foundation Grant (2006-49). The work was also supported by the Research Service of the Ralph H. Johnson Department of Veterans Affairs Medical 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. NR 46 TC 11 Z9 12 U1 0 U2 6 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0021-9150 EI 1879-1484 J9 ATHEROSCLEROSIS JI Atherosclerosis PD DEC PY 2013 VL 231 IS 2 BP 315 EP 322 DI 10.1016/j.atherosclerosis.2013.09.027 PG 8 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 259PB UT WOS:000327537700024 PM 24267245 ER PT J AU Spector, M Shoichet, MS AF Spector, Myron Shoichet, Molly S. TI An interview with Molly S Shoichet. Developing biomaterials and mobilizing resources for assaults on some of the most devastating medical problems SO BIOMEDICAL MATERIALS LA English DT Editorial Material C1 [Spector, Myron] Harvard Univ, Brigham & Womens Hosp, Sch Med, VA Boston Healthcare Syst, Boston, MA 02115 USA. [Shoichet, Molly S.] CytoTherapeutics Inc, Providence, RI USA. [Shoichet, Molly S.] Brown Univ, Dept Mol Pharmacol & Biotechnol, Providence, RI 02912 USA. [Shoichet, Molly S.] Univ Toronto, Dept Chem Engn & Appl Chem, Toronto, ON M5S 1A1, Canada. [Shoichet, Molly S.] Univ Toronto, Dept Chem, Toronto, ON M5S 1A1, Canada. [Shoichet, Molly S.] matREGEN Corp, Toronto, ON, Canada. [Shoichet, Molly S.] Order Ontario, Toronto, ON, Canada. RP Spector, M (reprint author), Harvard Univ, Brigham & Womens Hosp, Sch Med, VA Boston Healthcare Syst, Boston, MA 02115 USA. NR 5 TC 0 Z9 0 U1 1 U2 33 PU IOP PUBLISHING LTD PI BRISTOL PA TEMPLE CIRCUS, TEMPLE WAY, BRISTOL BS1 6BE, ENGLAND SN 1748-6041 EI 1748-605X J9 BIOMED MATER JI Biomed. Mater. PD DEC PY 2013 VL 8 IS 6 AR 060401 DI 10.1088/1748-6041/8/6/060401 PG 5 WC Engineering, Biomedical; Materials Science, Biomaterials SC Engineering; Materials Science GA 265JV UT WOS:000327948200001 ER PT J AU Ademi, Z Huq, MM Liew, D Steg, PG Bhatt, DL Nelson, M Reid, CM AF Ademi, Zanfina Huq, Molla M. Liew, Danny Steg, Ph. Gabriel Bhatt, Deepak L. Nelson, Mark Reid, Christopher M. CA REACH Registry Investigators TI The Impact of Lost Therapeutic Benefit (LTB) in High-Risk Hypertensive Patients: 2-Year Follow-Up Data from the Australian REACH Registry SO CARDIOVASCULAR THERAPEUTICS LA English DT Article DE high-risk patients; hypertension; lost therapeutic benefit ID CARDIOVASCULAR EVENT RATES; PROPENSITY SCORE; ATHEROTHROMBOSIS; DISEASE; OUTPATIENTS; METAANALYSIS; PERSPECTIVE; PREVENTION; PREVALENCE; PREDICTORS AB ObjectiveThe aim of the study is to determine the extent of lost therapeutic benefit (LTB) in the hypertensive patients, and to determine the relationship between the presence of LTB and clinical outcomes. MethodsProspective-cohort study of n=2856 patients with or at high risk of atherothrombosis. LTB was calculated as the proportion of patients receiving blood pressure medication who were not attaining guideline blood pressure (BP) control targets (<140/90mmHg). Logistic regression analysis was performed to identify predictors of LTB at baseline, and propensity score matching (PSM) was undertaken to estimate the treatment effects by matching case LTB and control non-LTB cohorts based on the nearest neighbor matching. ResultsOf the total sample of 2856, 45.6% had uncontrolled BP, and LTB was present in 46.7% patients. The likelihood of LTB was less in males (OR=0.78 [95% CI; 0.64-0.97]), and those with a previous myocardial infarction (OR=0.66 [0.53-0.81]) or heart failure (OR=0.58 [0.42-0.82]). LTB was more common in those with diabetes (OR=1.44 [1.16-1.79]), aged >65years (OR=1.36 [1.06-1.75]) and having an ABI<0.09 in either leg at rest (OR=1.30 [1.02-1.75]). Following PSM, the combination of ischemic events (55-64 age category) was more likely to occur in the LTB compared with non-LTB group (4.38% and 0.68%, respectively [P=0.046]). ConclusionPresence of HF, previous MI and being male decreased the likelihood of LTB, while presence of diabetes, age>65 and ABI<0.09 increased the risk of LTB. Patients with LTB in age category 55-64 had higher incidence of vascular events compared with those with non-LTB. C1 [Ademi, Zanfina; Liew, Danny] Univ Melbourne, Royal Melbourne Hosp, Dept Med, Melbourne EpiCtr, Melbourne, Vic 3050, Australia. [Ademi, Zanfina; Huq, Molla M.; Reid, Christopher M.] Monash Univ, Dept Epidemiol & Prevent Med, Melbourne, Vic 3004, Australia. [Steg, Ph. Gabriel] Univ Paris 07, INSERM U698, Paris, France. [Steg, Ph. Gabriel] AP HP, Paris, France. [Bhatt, Deepak L.] Brigham & Womens Hosp, VA Boston Healthcare Syst, Boston, MA 02115 USA. [Bhatt, Deepak L.] Harvard Univ, Sch Med, Boston, MA USA. [Nelson, Mark] Univ Tasmania, Sch Med, Menzies Res Inst Tasmania, Hobart, Tas, Australia. RP Ademi, Z (reprint author), Royal Melbourne Hosp, Melbourne EpiCtr, 7 East,Main Bldg,Grattan St, Parkville, Vic 3050, Australia. EM zademi@unimelb.edu.au OI Liew, Danny/0000-0002-0131-623X FU Sanofi-Aventis; Bristol-Myers Squibb; Waksman Foundation (Tokyo, Japan); World Heart Federation FX The global REACH Registry was sponsored by Sanofi-Aventis, Bristol-Myers Squibb and the Waksman Foundation (Tokyo, Japan) and is endorsed by the World Heart Federation. The REACH Registry enforces a no ghost-writing policy. The sponsors provided logistical support. All manuscripts in the REACH Registry are led by independent authors who are not governed by the funding sponsors and are reviewed by an academic publication committee before submission. A complete list of the REACH Registry Investigators appears in JAMA. 2006; 295(2): 180-189. NR 29 TC 2 Z9 2 U1 0 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1755-5914 EI 1755-5922 J9 CARDIOVASC THER JI Cardiovasc. Ther. PD DEC PY 2013 VL 31 IS 6 BP 370 EP 376 DI 10.1111/1755-5922.12034 PG 7 WC Cardiac & Cardiovascular Systems; Pharmacology & Pharmacy SC Cardiovascular System & Cardiology; Pharmacology & Pharmacy GA 257YN UT WOS:000327423800019 PM 23582191 ER PT J AU Tache, Y Stengel, A AF Tache, Yvette Stengel, Andreas TI New Developments on NUCB2/Nesfatin-1 SO CURRENT PHARMACEUTICAL DESIGN LA English DT Editorial Material ID NESFATIN-1; IDENTIFICATION; GHRELIN; AXIS; RAT C1 [Tache, Yvette] Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90073 USA. [Tache, Yvette] CURE Digest Dis Res Ctr Anim Core, Los Angeles, CA 90073 USA. [Tache, Yvette] VA Greater Los Angeles Healthcare Syst, Ctr Neurobiol Stress & Womens Hlth, Los Angeles, CA 90073 USA. [Stengel, Andreas] Charite Ctr Internal Med & Dermatol, Div Gen Internal & Psychosomat Med, D-10117 Berlin, Germany. RP Tache, Y (reprint author), Univ Calif Los Angeles, David Geffen Sch Med, 11301 Wilshire Blvd,CURE Bldg 115,Room 117, Los Angeles, CA 90073 USA. EM ytache@mednet.ucla.edu; andreas.stengel@charite.de NR 30 TC 2 Z9 2 U1 1 U2 5 PU BENTHAM SCIENCE PUBL LTD PI SHARJAH PA EXECUTIVE STE Y-2, PO BOX 7917, SAIF ZONE, 1200 BR SHARJAH, U ARAB EMIRATES SN 1381-6128 EI 1873-4286 J9 CURR PHARM DESIGN JI Curr. Pharm. Design PD DEC PY 2013 VL 19 IS 39 BP 6919 EP 6920 PG 2 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 262JL UT WOS:000327730800012 PM 24286377 ER PT J AU Goebel-Stengel, M Wang, LX AF Goebel-Stengel, Miriam Wang, Lixin TI Central and Peripheral Expression and Distribution of NUCB2/nesfatin-1 SO CURRENT PHARMACEUTICAL DESIGN LA English DT Article DE Central nervous system; homeostasis; hypothalamus; plasma ID AMPHETAMINE-REGULATED TRANSCRIPT; EDINGER-WESTPHAL NUCLEUS; PITUITARY-ADRENAL AXIS; PLASMA NESFATIN-1; RAT-BRAIN; NEURONS; HORMONE; PEPTIDE; IMMUNOREACTIVITY; NUCLEOBINDIN-2 AB Nesfatin-1 is the N-terminal fragment of nucleobindin-2 (NUCB2). The antibody against nesfatin-1 recognizes both full length of NUCB2 and nesfatin-1, thus the immunolabeling represents NUCB2/nesfatin-1. It has been found that NUCB2/nesfatin-1 is widely distributed in the rodent central nervous system. The immunoreactivity is more intensive in the brain autonomic centers that regulate feeding, neuroendocrine and cardiovascular functions, such as the hypothalamic paraventricular nucleus, supraoptic nucleus, lateral hypothalamic area, Edinger-Westphal nucleus, locus coeruleus, dorsal vagal complex and medullary raphe nuclei. In neurons, NUCB2/nesfatin-1 is located in the soma and primary dendrites, not in nerve fibers. NUCB2/nesfatin-1 is co-localized with several neurotransmitters involved in regulation of food intake, autonomic and neuroendocrine functions, including oxytocin, vasopressin, neuropeptide Y, cocaine-and amphetamine-regulated transcript, proopiomelanocortin, alpha-melanocyte-stimulating hormone, melanin-concentrating hormone, leptin, mammalian target of rapamycin, urocortin-1, corticotropin-releasing factor and serotonin. In the periphery, NUCB2/nesfatin-1 is located mainly in the pituitary, gastric mucosa where it coexists with ghrelin, and pancreatic endocrine cells containing insulin. Nesfatin-1 is detectable in the cerebrospinal fluid of rats. NUCB2/nesfatin-1 is measurable in the plasma, and altered under different conditions in rodents and humans, such as immune challenge, high fat diet and exercise, anorexia nervosa, anxiety and depression. Anatomical data suggest that nesfatin-1 is a unique neuroendocrine peptide that may be involved in regulation of homeostasis. C1 [Goebel-Stengel, Miriam] Charite, Dept Internal Med, Inst Neurogastroenterol & Motil, Martin Luther Hosp,Acad Teaching Inst, D-13353 Berlin, Germany. [Wang, Lixin] Univ Calif Los Angeles, CURE Digest Dis Res Ctr, Ctr Neurobiol Stress, Dept Med,Digest Dis Div, Los Angeles, CA 90073 USA. [Wang, Lixin] VA Greater Los Angeles Hlth Care Syst, Los Angeles, CA 90073 USA. RP Goebel-Stengel, M (reprint author), Martin Luther Hosp, Dept Internal Med, Caspar Theyss Str 27-31, D-14193 Berlin, Germany. EM miriam.goebel-stengel@gmx.de FU NIH [R01 DK-33061]; NIH Center [41301] FX This work was supported by NIH R01 DK-33061, NIH Center Grant DK-41301 (Animal Core). NR 50 TC 13 Z9 14 U1 1 U2 13 PU BENTHAM SCIENCE PUBL LTD PI SHARJAH PA EXECUTIVE STE Y-2, PO BOX 7917, SAIF ZONE, 1200 BR SHARJAH, U ARAB EMIRATES SN 1381-6128 EI 1873-4286 J9 CURR PHARM DESIGN JI Curr. Pharm. Design PD DEC PY 2013 VL 19 IS 39 BP 6935 EP 6940 PG 6 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 262JL UT WOS:000327730800015 PM 23537079 ER PT J AU Stengela, A Tache, Y AF Stengela, Andreas Tache, Yvette TI Role of Brain NUCB2/nesfatin-1 in the Regulation of Food Intake SO CURRENT PHARMACEUTICAL DESIGN LA English DT Article DE Brainstem; CRF; hunger; hypothalamus; obesity; oxytocin; satiety ID CENTRAL-NERVOUS-SYSTEM; CORTICOTROPIN-RELEASING HORMONE; PITUITARY-ADRENAL AXIS; OREXIN MESSENGER-RNA; INTER-MEAL INTERVALS; PARAVENTRICULAR NUCLEUS; NESFATIN-1 INFLUENCES; SATIETY MOLECULE; ARCUATE NUCLEUS; RAT-BRAIN AB Nesfatin-1 was recently identified in the rat brain as a potential post-translational processing product derived from nucleobindin2 (NUCB2). The first biological action identified for nesfatin-1 was the reduction of nocturnal food intake in rats. The anorexigenic effect of nesfatin-1 was corroborated by several independent laboratories and is now established as a physiological action of this peptide based on the regulation of brain NUCB2/nesfatin-1 under different metabolic conditions and the stimulation of food intake and body weight when endogenous brain NUCB2/nesfatin-1 is blocked. Nesfatin-1 shows extensive co-localization with various other, predominantly food intake inhibitory, hypothalamic peptides including corticotropin-releasing factor (CRF), oxytocin, cholecystokinin, proopiomelanocortin, alpha-melanocyte stimulating hormone (alpha-MSH), thyrotropin-releasing hormone (TRH), the orexigenic neuropeptide Y and brain biogenic amines, histamine, serotonin, and catecholamines. The food intake suppressing effect of centrally injected nesfatin-1 has been established so far to involve several downstream mechanisms including H-1, CRF2, TRH, oxytocin as well as melanocortin-3/4 receptor signaling pathways. This intricate embedding of NUCB2/nesfatin-1 in central food intake regulatory pathways recruited during the dark phase corresponding to the eating period in rodents, unlike the orexigenic response to a fast, points towards a role for nesfatin-1 in modulating the nocturnal food intake. Although our knowledge on the regulation and effects of NUCB2/nesfatin-1 as a new anorexic peptide markedly increased during the past five years, several important gaps of knowledge remain to be filled in the near future such as the regulation of NUCB2 processing and nesfatin-1 release as well as the identification, localization and regulation of the nesfatin-1 receptor. C1 [Stengela, Andreas; Tache, Yvette] Univ Calif Los Angeles, David Geffen Sch Med, CURE Digest Dis Res Ctr, Los Angeles, CA 90095 USA. [Stengela, Andreas; Tache, Yvette] Univ Calif Los Angeles, David Geffen Sch Med, Ctr Neurovisceral Sci & Womens Hlth, Div Digest Dis, Los Angeles, CA 90095 USA. [Stengela, Andreas; Tache, Yvette] VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. [Stengela, Andreas] Charite, Charite Ctr Internal Med & Dermatol, Div Gen Internal & Psychosomat Med, D-13353 Berlin, Germany. RP Tache, Y (reprint author), VA Greater Los Angeles Healthcare Syst, CURE Digest Dis Res Ctr, Bldg 115,Room 117,11301 Wilshire Blvd, Los Angeles, CA 90073 USA. EM ytache@mednet.ucla.edu FU German Research Foundation [STE 1765/3-1]; Charite University [UFF 89-441-176]; Sonnenfeld foundation; VA Research Career Scientist Award; VA Merit Award; NIH [DK 33061, DK 57238] FX A.S. received funding of the German Research Foundation (STE 1765/3-1), Charite University Funding (UFF 89-441-176) and an equipment grant of the Sonnenfeld foundation. Y.T. is in receipt of the VA Research Career Scientist Award, VA Merit Award and NIH R01 grants DK 33061 and DK 57238. NR 57 TC 4 Z9 4 U1 1 U2 7 PU BENTHAM SCIENCE PUBL LTD PI SHARJAH PA EXECUTIVE STE Y-2, PO BOX 7917, SAIF ZONE, 1200 BR SHARJAH, U ARAB EMIRATES SN 1381-6128 EI 1873-4286 J9 CURR PHARM DESIGN JI Curr. Pharm. Design PD DEC PY 2013 VL 19 IS 39 BP 6955 EP 6959 PG 5 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 262JL UT WOS:000327730800018 PM 23537088 ER PT J AU Gordon, AJ Conley, JW Gordon, JM AF Gordon, Adam J. Conley, James W. Gordon, Joanne M. TI Medical Consequences of Marijuana Use: A Review of Current Literature SO CURRENT PSYCHIATRY REPORTS LA English DT Review DE Marijuana; Medical consequences; Review; Substance use and related disorders; Psychiatry ID AMERICAN ADOLESCENT FEMALES; ACUTE MYOCARDIAL-INFARCTION; SQUAMOUS-CELL CARCINOMA; ILLICIT DRUG-USE; CANNABIS USE; LUNG-FUNCTION; YOUNG-ADULTS; MENINGOCOCCAL DISEASE; PULMONARY-FUNCTION; SUBSTANCE-ABUSE AB With the advent of legalization of marijuana for medicinal and recreational purposes, and the increase use of marijuana, healthcare providers will be increasingly confronted with marijuana users as patients in clinical environments. While there is vast literature regarding the societal and mental health harms associated with marijuana use, there is a paucity of reviews of the potential consequences of marijuana use on physical health or medical conditions. We examine the recent literature on the physical harms associated with illicit and legal marijuana administration. We surveyed the peer-reviewed medical literature from 1998 to 2013 of studies assessing the association of marijuana use and physical diseases. We conclude that healthcare providers should be cognizant that the existing literature suggests that marijuana use can cause physical harm. However, evidence is needed, and further research should be considered, to prove causal associations of marijuana with many physical health conditions. C1 [Gordon, Adam J.; Conley, James W.] VA Pittsburgh Healthcare Syst, CHERP, Pittsburgh, PA 15240 USA. [Gordon, Adam J.; Conley, James W.] VA Pittsburgh Healthcare Syst, MIRECC, Pittsburgh, PA 15240 USA. [Gordon, Joanne M.] Missouri State Univ, Springfield, MO USA. [Gordon, Adam J.] Univ Pittsburgh, Sch Med, Pittsburgh, PA USA. RP Gordon, AJ (reprint author), VA Pittsburgh Healthcare Syst, CHERP, 151-C,Univ Dr C, Pittsburgh, PA 15240 USA. EM gordona@medschool.pitt.edu FU National Institutes of Health; Department of Veterans Affairs; Substance Abuse and Mental Health Services Administration FX Adam J. Gordon has received research support from National Institutes of Health, Department of Veterans Affairs, and Substance Abuse and Mental Health Services Administration and royalties from Cambridge University Press and UpToDate. NR 127 TC 14 Z9 14 U1 4 U2 80 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 DEC PY 2013 VL 15 IS 12 AR 419 DI 10.1007/s11920-013-0419-7 PG 11 WC Psychiatry SC Psychiatry GA 264NZ UT WOS:000327886400004 PM 24234874 ER PT J AU Perera, LP Ananthakrishnan, AN Guilday, C Remshak, K Zadvornova, Y Naik, AS Stein, DJ Massey, BT AF Perera, Lilani P. Ananthakrishnan, Ashwin N. Guilday, Corinne Remshak, Kristin Zadvornova, Yelena Naik, Amar S. Stein, Daniel J. Massey, Benson T. TI Dyssynergic Defecation: A Treatable Cause of Persistent Symptoms When Inflammatory Bowel Disease Is in Remission SO DIGESTIVE DISEASES AND SCIENCES LA English DT Article DE Constipation; Fecal incontinence; Inflammatory bowel disease; Motility; Defecation disorders ID QUALITY-OF-LIFE; IBS-LIKE SYMPTOMS; CROHNS-DISEASE; ULCERATIVE-COLITIS; ANORECTAL FUNCTION; DISORDERS; BIOFEEDBACK; MOTILITY; ADULTS; IMPACT AB Introduction of biologic agents in inflammatory bowel disease (IBD) has increased the likelihood of disease remission. Despite resolution of active inflammation, a subset of IBD patients report persistent defecatory symptoms. To evaluate a group of patients with inflammatory bowel disease with suspected functional defecatory disorders, by use of anorectal manometric testing and subsequent biofeedback therapy. A group of IBD patients with persistent defecatory problems despite clinical improvement were included in this study. These patients had no evidence of left-sided disease. Endoscopic and radiographic study findings and timing in relation to the manometry study were recorded. Anorectal manometry was performed by the standard protocol and included rectal sensory assessment, ability to expel a balloon, and pressure dynamics with simulated defecation. Thirty IBD patients (Crohn's 23 patients; ulcerative colitis six patients) presented with defecatory disorders including constipation (67 %) increased stooling (10 %), and rectal urgency and/or incontinence and rectal pain (6 %). All but one patient had anorectal manometric criteria of dyssynergia (presence of anismus motor pattern and inability to expel the balloon). Of the patients who completed biofeedback therapy, 30 % had a clinically significant (a parts per thousand yen7-point) improvement in SIBDQ score, with a reduction in health-care utilization after a six-month period (p = 0.02). Despite remission, some inflammatory bowel disease patients have persistent defecatory symptoms. Defecatory symptoms may not be predictive of an underlying inflammatory disorder. Lack of inflammatory activity and absence of left-sided disease should prompt investigation of functional disorders. Anorectal manometric testing and biofeedback therapy for patients with a diagnosis of dyssynergia may be a useful therapy. C1 [Perera, Lilani P.; Remshak, Kristin; Zadvornova, Yelena; Naik, Amar S.; Stein, Daniel J.; Massey, Benson T.] Med Coll Wisconsin, Div Gastroenterol & Hepatol, Milwaukee, WI 53226 USA. [Perera, Lilani P.] Clement J Zablocki VA Med Ctr, Milwaukee, WI 53295 USA. [Ananthakrishnan, Ashwin N.] Massachusetts Gen Hosp, Digest Healthcare Ctr, Boston, MA 02114 USA. [Guilday, Corinne] Corinne Washington Univ St Louis, St Louis, MO 63110 USA. RP Perera, LP (reprint author), Clement J Zablocki VA Med Ctr, 5000 W Natl Ave, Milwaukee, WI 53295 USA. EM lperera@mcw.edu; aananthakrishnan@partners.org; guildayc@pyschiatry.wustl.edu; koimoen@mcw.edu; yzadvorn@mcw.edu; anaik@mcw.edu; dstein@mcw.edu; bmassey@mcw.edu NR 18 TC 2 Z9 2 U1 1 U2 6 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0163-2116 EI 1573-2568 J9 DIGEST DIS SCI JI Dig. Dis. Sci. PD DEC PY 2013 VL 58 IS 12 BP 3600 EP 3605 DI 10.1007/s10620-013-2850-3 PG 6 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 258JW UT WOS:000327456500029 PM 24026401 ER PT J AU Morimoto, E Okada, T Kanagaki, M Yamamoto, A Fushimi, Y Matsumoto, R Takaya, S Ikeda, A Kunieda, T Kikuchi, T Paul, D Miyamoto, S Takahashi, R Togashi, K AF Morimoto, Emiko Okada, Tomohisa Kanagaki, Mitsunori Yamamoto, Akira Fushimi, Yasutaka Matsumoto, Riki Takaya, Shigetoshi Ikeda, Akio Kunieda, Takeharu Kikuchi, Takayuki Paul, Dominik Miyamoto, Susumu Takahashi, Ryosuke Togashi, Kaori TI Evaluation of focus laterality in temporal lobe epilepsy: A quantitative study comparing double inversion-recovery MR imaging at 3T with FDG-PET SO EPILEPSIA LA English DT Article DE Double inversion-recovery; FDG-PET; Voxel-based analysis; Temporal lobe epilepsy; Epileptogenic focus laterality ID WHITE-MATTER; HIPPOCAMPAL SCLEROSIS; SEIZURE FOCUS; HUMAN BRAIN; ABNORMALITIES; ATLAS; IDENTIFICATION; SIDE AB Purpose To quantitatively compare the diagnostic capability of double inversion-recovery (DIR) with F-18 fluorodeoxyglucose positron emission tomography (FDG-PET) for detection of seizure focus laterality in temporal lobe epilepsy (TLE). MethodsThis study was approved by the institutional review board, and written informed consent was obtained. Fifteen patients with TLE and 38 healthy volunteers were enrolled. All magnetic resonance (MR) images were acquired using a 3T-MRI system. Voxel-based analysis (VBA) was conducted for FDG-PET images and white matter segments of DIR images (DIR-WM) focused on the whole temporal lobe (TL) and the anterior part of the temporal lobe (ATL). Distribution of hypometabolic areas on FDG-PET and increased signal intensity areas on DIR-WM were evaluated, and their laterality was compared with clinically determined seizure focus laterality. Correct diagnostic rates of laterality were evaluated, and agreement between DIR-WM and FDG-PET was assessed using statistics. Key FindingsIncreased signal intensity areas on DIR-WM were located at the vicinity of the hypometabolic areas on FDG-PET, especially in the ATL. Correct diagnostic rates of seizure focus laterality for DIR-WM (0.80 and 0.67 for the TL and the ATL, respectively) were slightly higher than those for FDG-PET (0.67 and 0.60 for the TL and the ATL, respectively). Agreement of laterality between DIR-WM and FDG-PET was substantial for the TL and almost perfect for the ATL (=0.67 and 0.86, respectively). SignificanceHigh agreement in localization between DIR-WM and FDG-PET and nearly equivalent detectability of them show us an additional role of MRI in TLE. C1 [Morimoto, Emiko; Okada, Tomohisa; Kanagaki, Mitsunori; Yamamoto, Akira; Fushimi, Yasutaka; Matsumoto, Riki; Ikeda, Akio; Kunieda, Takeharu; Kikuchi, Takayuki; Miyamoto, Susumu; Takahashi, Ryosuke; Togashi, Kaori] Kyoto Univ, Grad Sch Med, Kyoto 6068507, Japan. [Takaya, Shigetoshi] Kyoto Univ, Grad Sch Med, Human Brain Res Ctr, Kyoto, Japan. [Takaya, Shigetoshi] Kyoto Univ, Radioisotope Res Ctr, Kyoto, Japan. [Takaya, Shigetoshi] Harvard Univ, Athinoula A Martinos Ctr Biomed Imaging, Sch Med, Massachusetts Gen Hosp, Charlestown, MA USA. [Paul, Dominik] Siemens AG Healthcare Sect, Erlangen, Germany. RP Okada, T (reprint author), Kyoto Univ, Grad Sch Med, Sakyo Ku, 54 Kawaharacho, Kyoto 6068507, Japan. EM tomok-ada@kuhp.kyoto-u.ac.jp RI Matsumoto, Riki/I-8397-2016; OI Matsumoto, Riki/0000-0003-3985-9210; Ikeda, Akio/0000-0002-0790-2598 FU Health and Labor Sciences Research Grant for the Comprehensive Research on Disability Health and Welfare; Ministry of Health, Labor and Welfare, Japan FX This study was partly supported by a Health and Labor Sciences Research Grant for the Comprehensive Research on Disability Health and Welfare from the Ministry of Health, Labor and Welfare, Japan to Dr. Shigetoshi Takaya. We thank Mr. Katsutoshi Murata of Siemens Japan K. K., for contributions to the optimization of scan parameters. We also thank Kiyotaka Nemoto MD, PhD (Department of Psychiatry, University of Tsukuba) for suggestions regarding the analysis using SPM8. NR 41 TC 5 Z9 5 U1 0 U2 8 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0013-9580 EI 1528-1167 J9 EPILEPSIA JI Epilepsia PD DEC PY 2013 VL 54 IS 12 BP 2174 EP 2183 DI 10.1111/epi.12396 PG 10 WC Clinical Neurology SC Neurosciences & Neurology GA 262PR UT WOS:000327750600020 PM 24117006 ER PT J AU Meyer, S van der Meer, P Massie, BM O'Connor, CM Metra, M Ponikowski, P Teerlink, JR Cotter, G Davison, BA Cleland, JGF Givertz, MM Bloomfield, DM Fiuzat, M Dittrich, HC Hillege, HL Voors, AA AF Meyer, Sven van der Meer, Peter Massie, Barry M. O'Connor, Christopher M. Metra, Marco Ponikowski, Piotr Teerlink, John R. Cotter, Gad Davison, Beth A. Cleland, John G. F. Givertz, Michael M. Bloomfield, Daniel M. Fiuzat, Mona Dittrich, Howard C. Hillege, Hans L. Voors, Adriaan A. TI Sex-specific acute heart failure phenotypes and outcomes from PROTECT SO EUROPEAN JOURNAL OF HEART FAILURE LA English DT Article DE Acute heart failure; Sex; Biomarkers; Aetiology; Mortality ID PRESERVED EJECTION FRACTION; BLOOD UREA NITROGEN; GENDER-DIFFERENCES; DISEASE; PATHOPHYSIOLOGY; DYSFUNCTION; ANTAGONIST; MORTALITY; DIAGNOSIS; SURVIVAL AB Differences in manifestation, treatment, and outcomes of acute heart failure between men and women have not been well studied. The objective of this analysis was to characterize differences in clinical presentation, and in-hospital and post-discharge outcomes between sexes in acute heart failure patients. Clinical profiles, treatment characteristics, and outcomes were compared between sexes in 2033 patients hospitalized for acute heart failure and impaired renal function. Women comprised 33 of the study population and were older, had higher body mass index, LVEF, and systolic blood pressure, and a greater prevalence of diabetes. At baseline, women showed signs and symptoms of congestion comparable with men, but more often had rales, orthopnoea, and worse renal function. Women were less intensively diuresed, as indicated by lower oral and intravenous diuretic doses used, fewer dose increases, and less total weight loss during hospitalization. Furthermore, hospitalization was slightly but significantly prolonged in women (11.04 7.8 vs. 10.65 8.86 days; P 0.024). Age-adjusted 180-day mortality was lower in women (15.8 vs. 18.5, hazard ratio 0.74; 95 confidence interval 0.590.93, P 0.010), but multivariable risk-adjusted mortality was similar in both sexes, mainly attributable to lower blood urea nitrogen, higher LVEF, and higher systolic blood pressure in women compared with men. Women with acute heart failure present with a clinical profile different from that of men, with more hypertension, diabetes, and depression, and a preserved LVEF. During hospitalization, they were less intensively diuresed. Nevertheless, risk-adjusted 180-day outcome was similar between sexes. C1 [Meyer, Sven; van der Meer, Peter; Hillege, Hans L.; Voors, Adriaan A.] Univ Groningen, Univ Med Ctr Groningen, NL-9700 RB Groningen, Netherlands. [Massie, Barry M.; Teerlink, John R.] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Massie, Barry M.; Teerlink, John R.] San Francisco VA Med Ctr, San Francisco, CA USA. [O'Connor, Christopher M.; Fiuzat, Mona] Duke Univ, Med Ctr, Duke Clin Res Inst, Durham, NC USA. [Metra, Marco] Univ Brescia, Brescia, Italy. [Ponikowski, Piotr] Med Univ, Clin Mil Hosp, Wroclaw, Poland. [Cotter, Gad; Davison, Beth A.] Momentum Res, Durham, NC USA. [Cleland, John G. F.] Univ Hull, Kingston Upon Hull, Yorks, England. [Givertz, Michael M.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Boston, MA 02115 USA. [Bloomfield, Daniel M.] Merck Res Labs, Rahway, NJ USA. [Dittrich, Howard C.] NovaCardia, San Diego, CA USA. RP Voors, AA (reprint author), Univ Groningen, Univ Med Ctr Groningen, Dept Cardiol, Hanzepl 1,POB 30-001, NL-9700 RB Groningen, Netherlands. EM a.a.voors@umcg.nl RI Ponikowski, Piotr/O-6454-2015; OI Ponikowski, Piotr/0000-0002-3391-7064; Metra, Marco/0000-0001-6691-8568; Davison, Beth/0000-0003-2374-6449; Cleland, John/0000-0002-1471-7016 FU NovaCardia, a subsidiary of Merck FX The PROTECT trial was supported by NovaCardia, a subsidiary of Merck. NR 22 TC 9 Z9 9 U1 2 U2 10 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1388-9842 EI 1879-0844 J9 EUR J HEART FAIL JI Eur. J. Heart Fail. PD DEC PY 2013 VL 15 IS 12 BP 1374 EP 1381 DI 10.1093/eurjhf/hft115 PG 8 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 259EM UT WOS:000327510200007 PM 24259042 ER PT J AU Greene, SJ Gheorghiade, M Vaduganathan, M Ambrosy, AP Mentz, RJ Subacius, H Maggioni, AP Nodari, S Konstam, MA Butler, J Filippatos, G AF Greene, Stephen J. Gheorghiade, Mihai Vaduganathan, Muthiah Ambrosy, Andrew P. Mentz, Robert J. Subacius, Haris Maggioni, Aldo P. Nodari, Savina Konstam, Marvin A. Butler, Javed Filippatos, Gerasimos CA EVEREST Trial Investigators TI Haemoconcentration, renal function, and post-discharge outcomes among patients hospitalized for heart failure with reduced ejection fraction: insights from the EVEREST trial SO EUROPEAN JOURNAL OF HEART FAILURE LA English DT Article DE Haemoconcentration; Haematocrit; Heart failure; Renal function; Outcomes; Congestion ID CARDIORENAL SYNDROME; EUROPEAN-SOCIETY; PREDICTIVE-VALUE; IMPACT; ASSOCIATION; CONGESTION; TOLVAPTAN; MORTALITY; DEFINITIONS; DYSFUNCTION AB Haemoconcentration has been studied as a marker of decongestion in patients with hospitalization for heart failure (HHF). We describe the relationship between haemoconcentration, worsening renal function, post-discharge outcomes, and clinical and laboratory markers of congestion in a large multinational cohort of patients with HHF. In 1684 patients with HHF with ejection fraction (EF) 40 assigned to the placebo arm of the Efficacy of Vasopressin Antagonism in Heart Failure Outcome Study with Tolvaptan (EVEREST) trial, absolute in-hospital haematocrit change was calculated as the change between baseline and discharge or day 7 (whichever occurred first). Patient characteristics, changes in renal function, and outcomes over a median follow-up of 9.9 months were compared by in-hospital haematocrit change. Overall, 26 of patients had evidence of haemoconcentration (i.e. 3 absolute increase in haematocrit). Patients with greater increases in haematocrit tended to have better baseline renal function. Haemoconcentration correlated with greater risk of in-hospital worsening renal function, but renal parameters generally returned to baseline within 4 weeks post-discharge. Patients with haemoconcentration were less likely to have clinical congestion at discharge, and experienced greater in-hospital decreases in body weight and natriuretic peptide levels. After adjustment for baseline clinical risk factors, every 5 increase of in-hospital haematocrit change was associated with a decreased risk of all-cause death [hazard ratio (HR) 0.81, 95 confidence interval (CI) 0.700.95]. Haematocrit change was also associated with decreased cardiovascular mortality or heart failure (HF) hospitalization at 100 days post-randomization (HR 0.73, 95 CI 0.710.76). In this large cohort of patients with HHF with reduced EF, haemoconcentration was associated with greater improvements in congestion and decreased mortality and HF re-hospitalization despite an increased risk of in-hospital worsening renal function. C1 [Greene, Stephen J.; Gheorghiade, Mihai] Northwestern Univ, Feinberg Sch Med, Ctr Cardiovasc Innovat, Chicago, IL 60601 USA. [Vaduganathan, Muthiah] Harvard Univ, Sch Med, Dept Med, Massachusetts Gen Hosp, Boston, MA USA. [Ambrosy, Andrew P.] Stanford Univ, Dept Med, Sch Med, Stanford, CA 94305 USA. [Mentz, Robert J.] Duke Univ, Med Ctr, Dept Med, Div Cardiol, Durham, NC 27710 USA. [Subacius, Haris] Northwestern Univ, Feinberg Sch Med, Dept Med, Div Cardiol, Chicago, IL 60601 USA. [Maggioni, Aldo P.] ANMCO Res Ctr, Florence, Italy. [Nodari, Savina] Univ Brescia, Dept Cardiol, Brescia, Italy. [Konstam, Marvin A.] Tufts Med Ctr, Ctr Cardiovasc, Boston, MA USA. [Butler, Javed] Emory Univ, Sch Med, Div Cardiol, Atlanta, GA 30322 USA. [Filippatos, Gerasimos] Attikon Univ Hosp, Athens, Greece. RP Gheorghiade, M (reprint author), Northwestern Univ, Feinberg Sch Med, Ctr Cardiovasc Innovat, 201 East Huron,Galter 3-150, Chicago, IL 60601 USA. EM m-gheorghiade@northwestern.edu RI Lainscak, Mitja/F-3237-2015; OI Subacius, Haris/0000-0003-4061-1220; Maggioni, Aldo Pietro/0000-0003-2764-6779 FU Otsuka, Inc., Rockville, MD; Center for Cardiovascular Innovation, Northwestern University Feinberg School of Medicine, Chicago, IL FX Financial and material support for the EVEREST trial was provided by Otsuka, Inc., Rockville, MD. Database management was performed by the sponsor. H. S. conducted all final analyses for this report with funding from the Center for Cardiovascular Innovation, Northwestern University Feinberg School of Medicine, Chicago, IL. NR 35 TC 24 Z9 24 U1 0 U2 7 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1388-9842 EI 1879-0844 J9 EUR J HEART FAIL JI Eur. J. Heart Fail. PD DEC PY 2013 VL 15 IS 12 BP 1401 EP 1411 DI 10.1093/eurjhf/hft110 PG 11 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 259EM UT WOS:000327510200010 PM 23845795 ER PT J AU Shin, JH Wang, SB Yao, Q Wood, KB Li, GA AF Shin, Jae-Hyuk Wang, Shaobai Yao, Qi Wood, Kirkham B. Li, Guoan TI Investigation of coupled bending of the lumbar spine during dynamic axial rotation of the body SO EUROPEAN SPINE JOURNAL LA English DT Article DE Dynamic lumbar axial rotation; Coupled motion; Lateral bending; Compensatory scoliosis; Dynamic spine balance ID IN-VIVO; MOTION; STABILITY; DEFORMITY; ADJACENT; KINEMATICS; BEHAVIOR AB Little is known about the coupled motions of the spine during functional dynamic motion of the body. This study investigated the in vivo characteristic motion patterns of the human lumbar spine during a dynamic axial rotation of the body. Specifically, the contribution of each motion segment to the lumbar axial rotation and the coupled bending of the vertebrae during the dynamic axial rotation of the body were analyzed. Eight asymptomatic subjects (M/F, 7/1; age, 40-60 years) were recruited. The lumbar segment of each subject was MRI scanned for construction of 3D models of the vertebrae from L2 to S1. The lumbar spine was then imaged using a dual fluoroscopic system while the subject performed a dynamic axial rotation from maximal left to maximal right in a standing position. The 3D vertebral models and the fluoroscopic images were used to reproduce the in vivo vertebral motion. In this study, we analyzed the primary left-right axial rotation, the coupled left-right bending of each vertebral segment from L2 to S1 levels. The primary axial rotations of all segments (L2-S1) followed the direction of the body axial rotation. Contributions of each to the overall segment axial rotation were 6.7A degrees A A +/- A 3.0A degrees (27.9 %) for the L2-L3, 4.4A degrees A A +/- A 1.2A degrees (18.5 %) for the L3-L4, 6.4A degrees A A +/- A 2.2A degrees (26.7 %) for the L4-L5, and 6.4A degrees A A +/- A 2.6A degrees (27.0 %) for the L5-S1 vertebral motion segments. The upper segments of L2-L3 and L3-L4 demonstrated a coupled contralateral bending towards the opposite direction of the axial rotation, while the lower segments of L4-L5 and L5-S1 demonstrated a coupled ipsilateral bending motion towards the same direction of the axial rotation. Strong correlation between the primary axial rotation and the coupled bending was found at each vertebral level. We did not observe patterns of coupled flexion/extension rotation with the primary axial rotation. This study demonstrated that a dynamic lumbar axial rotation coupling with lateral bendings is segment-dependent and can create a coordinated dynamic coupling to maintain the global dynamic balance of the body. The results could improve our understanding of the normal physiologic lumbar axial rotation and to establish guidelines for diagnosing pathological lumbar motion. C1 [Shin, Jae-Hyuk; Wang, Shaobai; Yao, Qi; Wood, Kirkham B.; Li, Guoan] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Orthopaed Surg,Bioengn Lab, Boston, MA 02114 USA. [Shin, Jae-Hyuk] Hallym Univ, Med Ctr, Dept Orthopaed Surg, Seoul, South Korea. [Yao, Qi] Capital Med Univ, Beijing Shijitan Hosp, Dept Orthopaed Surg, Beijing, Peoples R China. RP Li, GA (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Orthopaed Surg,Bioengn Lab, 55 Fruit St,GRJ 1215, Boston, MA 02114 USA. EM gli1@partners.org FU NIAMS NIH HHS [R21 AR057989] NR 28 TC 3 Z9 3 U1 2 U2 15 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0940-6719 EI 1432-0932 J9 EUR SPINE J JI Eur. Spine J. PD DEC PY 2013 VL 22 IS 12 BP 2671 EP 2677 DI 10.1007/s00586-013-2777-6 PG 7 WC Clinical Neurology; Orthopedics SC Neurosciences & Neurology; Orthopedics GA 264RV UT WOS:000327899100001 PM 23625336 ER PT J AU Yao, Q Wang, SB Shin, JH Li, GA Wood, K AF Yao, Qi Wang, Shaobai Shin, Jae-Hyuk Li, Guoan Wood, Kirkham TI Motion characteristics of the lumbar spinous processes with degenerative disc disease and degenerative spondylolisthesis SO EUROPEAN SPINE JOURNAL LA English DT Article DE Lumbar spine; Kinematics; Spinous process; Degenerative lumbar spondylolisthesis; Disc degeneration ID NEUROGENIC CLAUDICATION; INTERSPINAL IMPLANT; X-STOP; KINEMATICS; STENOSIS; SURGERY; DEVICE AB Recently, interspinous process devices have attracted much attention since they can be implanted between the lumbar spinous processes (LSP) of patients with degenerative disc disease (DDD) and degenerative spondylolisthesis (DLS) using a minimally invasive manner. However, the motion characters of the LSP in the DLS and DDD patients have not been reported. This study is aimed at investigating the kinematics of the lumbar spinous processes in patients with DLS and DDD. Ten patients with DDD at L4-S1 and ten patients with DLS at L4-L5 were studied. The positions of the vertebrae (L2-L5) at supine, standing, 45A degrees trunk flexion, and maximal extension positions were determined using MRI-based models and dual fluoroscopic images. The shortest ISP distances were measured and compared with those of healthy subjects that have been previously reported. The shortest distance of the interspinous processes (ISP) gradually decreased from healthy subjects to DDD and to DLS patients when measured in the supine, standing, and extension positions. During supine-standing and flexion-extension activities, the changes in the shortest ISP distances in DDD patients were 2 +/- A 1.2 and 4.8 +/- A 2.1 mm at L4-L5; in DLS patients they were 0.5 +/- A 0.4 and 2.8 +/- A 1.7 mm at L4-L5, respectively. The range of motion is increased in DDD patients but decreased in DLS patients when compared with those of the healthy subjects. No significantly different changes were detected at L2-L3 and L3-L4 levels. At the involved level, the hypermobility of the LSP was seen in DDD and hypomobility of the LSP in DLS patients. The data may be instrumental for improving ISP surgeries that are aimed at reducing post-operative complications such as bony fracture and device dislocations. C1 [Yao, Qi; Wang, Shaobai; Shin, Jae-Hyuk; Li, Guoan; Wood, Kirkham] Massachusetts Gen Hosp, Dept Orthopaed Surg, Bioengn Lab, Boston, MA 02114 USA. [Yao, Qi; Wang, Shaobai; Shin, Jae-Hyuk; Li, Guoan; Wood, Kirkham] Harvard Univ, Sch Med, Boston, MA 02114 USA. [Yao, Qi] Beijing Shijitan Hosp, Dept Orthopaed Surg, Beijing, Peoples R China. RP Li, GA (reprint author), Massachusetts Gen Hosp, Dept Orthopaed Surg, Bioengn Lab, 55 Fruit St GRJ 1215, Boston, MA 02114 USA. EM gli1@partners.org FU NIH [R21AR057989]; Depuy Synthes (USA); National Natural Science Foundation of China [81000796]; Beijing Nova program [2011085] FX This study was partially supported by the NIH (R21AR057989), research grant from Depuy Synthes (USA), the National Natural Science Foundation of China (81000796) and Beijing Nova program (2011085). NR 29 TC 1 Z9 2 U1 3 U2 11 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0940-6719 EI 1432-0932 J9 EUR SPINE J JI Eur. Spine J. PD DEC PY 2013 VL 22 IS 12 BP 2702 EP 2709 DI 10.1007/s00586-013-2918-y PG 8 WC Clinical Neurology; Orthopedics SC Neurosciences & Neurology; Orthopedics GA 264RV UT WOS:000327899100005 PM 23903997 ER PT J AU Sabbatino, F Wang, YY Wang, XH Ferrone, S Ferrone, CR AF Sabbatino, Francesco Wang, Yangyang Wang, Xinhui Ferrone, Soldano Ferrone, Cristina R. TI Emerging BRAF inhibitors for melanoma SO EXPERT OPINION ON EMERGING DRUGS LA English DT Review DE BRAF inhibitor; BRAF inhibitor resistance; combinatorial strategies; melanoma ID DOSE-ESCALATION TRIAL; DISSEMINATED MALIGNANT-MELANOMA; COOPERATIVE-ONCOLOGY-GROUP; KINASE SIGNALING PATHWAY; STAGE IV MELANOMA; T-CELL TRANSFER; METASTATIC MELANOMA; B-RAF; ACQUIRED-RESISTANCE; PHASE-III AB Introduction: The clinical activity of BRAF inhibitor (BRAF-I) therapy is a major breakthrough in the treatment of metastatic melanoma carrying BRAF mutations. However, the therapeutic efficacy of BRAF-I therapy is limited due to the onset of intrinsic and acquired drug resistance. Areas covered: The role of wild-type BRAF in melanocytes and of the mutated BRAF in the pathogenesis of melanoma is described in this article. The results obtained with BRAF-I in patients with mutated BRAF are reviewed. The mechanisms driving the intrinsic and acquired BRAF-I resistance, the development of combinatorial strategies designed to overcome them and their potential limitations are discussed. Lastly, the many questions that have to be addressed to optimize therapy with BRAF-I are listed. Expert opinion: Melanoma is an aggressive form of skin cancer characterized by poor prognosis and high mortality. The discovery of BRAF mutations which drive melanoma tumorigenesis and the development of agents which selectively inhibit mutant-activated BRAF represent a major breakthrough in the treatment of metastatic melanoma. However, the development of drug resistance underlies the need of more effective and individualized combinatorial treatments to counteract the multiple escape mechanisms utilized by BRAF-mutant melanoma. Although combinatorial strategies using agents which target different protumorigenic signaling pathway components have been shown to increase the clinical efficacy of BRAF-I, novel strategies which utilize different antitumor mechanisms are needed. C1 [Sabbatino, Francesco; Wang, Yangyang; Wang, Xinhui; Ferrone, Soldano; Ferrone, Cristina R.] Harvard Univ, Sch Med, Dept Surg, Massachusetts Gen Hosp, Boston, MA 02114 USA. [Sabbatino, Francesco; Wang, Yangyang; Wang, Xinhui; Ferrone, Soldano] Harvard Univ, Sch Med, Div Surg Oncol, Massachusetts Gen Hosp, Boston, MA 02114 USA. [Ferrone, Cristina R.] Harvard Univ, Sch Med, Div Gen Surg, Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Ferrone, S (reprint author), Harvard Univ, Sch Med, Dept Surg, Massachusetts Gen Hosp, 55 Fruit St, Boston, MA 02114 USA. EM sferrone@partners.org RI Sabbatino, Francesco/F-4992-2014 OI Sabbatino, Francesco/0000-0001-6431-8278 FU PHS grants [RO1CA138188, RO1CA110249, P50 CA121973]; National Cancer Institute FX This work was supported by PHS grants RO1CA138188, RO1CA110249 and P50 CA121973 awarded by the National Cancer Institute. The authors state no conflict of interest. NR 104 TC 3 Z9 3 U1 0 U2 10 PU INFORMA HEALTHCARE PI LONDON PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND SN 1472-8214 EI 1744-7623 J9 EXPERT OPIN EMERG DR JI Expert Opin Emerg. Drugs PD DEC PY 2013 VL 18 IS 4 BP 431 EP 443 DI 10.1517/14728214.2013.842975 PG 13 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 259WA UT WOS:000327555800003 PM 24073999 ER PT J AU Labus, JS Hubbard, CS Bueller, J Ebrat, B Tillisch, K Chen, M Stains, J Dukes, GE Kelleher, DL Naliboff, BD Fanselow, M Mayer, EA AF Labus, Jennifer S. Hubbard, Catherine S. Bueller, Joshua Ebrat, Bahar Tillisch, Kirsten Chen, Michelle Stains, Jean Dukes, George E. Kelleher, Dennis L. Naliboff, Bruce D. Fanselow, Michael Mayer, Emeran A. TI Impaired Emotional Learning and Involvement of the Corticotropin-Releasing Factor Signaling System in Patients With Irritable Bowel Syndrome SO GASTROENTEROLOGY LA English DT Article DE Corticotropin-Releasing Factor Receptor 1 (CRF-R1) Antagonist; Fear Conditioning; Extinction ID POSTTRAUMATIC-STRESS-DISORDER; INTERNATIONAL NEUROPSYCHIATRIC INTERVIEW; PREFRONTAL CORTEX; ANIMAL-MODELS; ANTERIOR CINGULATE; NEURAL MECHANISMS; VISCERAL STIMULI; FEAR EXTINCTION; LOCUS-COERULEUS; ABDOMINAL-PAIN AB BACKGROUND & AIMS: Alterations in central corticotropin-releasing factor signaling pathways have been implicated in the pathophysiology of anxiety disorders and irritable bowel syndrome (IBS). We aimed to characterize the effects of the corticotropin-releasing factor receptor 1 (CRF-R1) antagonist, GW876008, on brain and skin conductance responses during acquisition and extinction of conditioned fear to the threat of abdominal pain in subjects with IBS and healthy individuals (controls). METHODS: We performed a single-center, randomized, double-blind, 3-period crossover study of 11 women with IBS (35.50 +/- 12.48 years old) and 15 healthy women (controls) given a single oral dose (20 mg or 200 mg) of the CRF-R1 antagonist or placebo. Blood-oxygen level-dependent responses were analyzed using functional magnetic resonance imaging in a tertiary care setting. RESULTS: Controls had greater skin conductance responses during acquisition than extinction, validating the fear-conditioning paradigm. In contrast, during extinction, women with IBS had greater skin conductance responses than controls-an effect normalized by administration of a CRF-R1 antagonist. Although the antagonist significantly reduced activity in the thalamus in patients with IBS and controls during acquisition, the drug produced greater suppression of blood-oxygen level-dependent activity in a wide range of brain regions in IBS patients during extinction, including the medial prefrontal cortex, pons, hippocampus, and anterior insula. CONCLUSIONS: Although CRF signaling via CRF-R1 is involved in fear acquisition and extinction learning related to expected abdominal pain in patients with IBS and controls, this system appears to be up-regulated in patients with IBS. This up-regulation might contribute to the previously reported abnormal brain responses to expected abdominal pain. C1 [Labus, Jennifer S.; Hubbard, Catherine S.; Bueller, Joshua; Ebrat, Bahar; Tillisch, Kirsten; Chen, Michelle; Stains, Jean; Naliboff, Bruce D.; Mayer, Emeran A.] Univ Calif Los Angeles, Gail & Gerald Oppenheimer Family Ctr Neurobiol St, Los Angeles, CA USA. [Labus, Jennifer S.; Hubbard, Catherine S.; Bueller, Joshua; Ebrat, Bahar; Tillisch, Kirsten; Chen, Michelle; Stains, Jean; Naliboff, Bruce D.; Mayer, Emeran A.] Univ Calif Los Angeles, Dept Med, Los Angeles, CA 90024 USA. [Mayer, Emeran A.] Univ Calif Los Angeles, Dept Physiol, Los Angeles, CA 90024 USA. [Labus, Jennifer S.; Fanselow, Michael; Mayer, Emeran A.] Univ Calif Los Angeles, Dept Psychiat, Los Angeles, CA USA. [Fanselow, Michael; Mayer, Emeran A.] Univ Calif Los Angeles, Dept Psychol, Los Angeles, CA 90024 USA. [Mayer, Emeran A.] Univ Calif Los Angeles, Ahmanson Lovelace Brain Mapping Ctr, Los Angeles, CA USA. [Naliboff, Bruce D.] VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. [Dukes, George E.; Kelleher, Dennis L.] GlaxoSmithKline, Res Triangle Pk, NC USA. RP Mayer, EA (reprint author), Gail & Gerald Oppenheimer Family Ctr Neurobiol St, Div Digest Dis, UCLA CHS 42-210 MC737818,10833 Le Conte Ave, Los Angeles, CA 90095 USA. EM emayer@ucla.edu OI Hubbard, Catherine/0000-0002-9139-2198 FU GlaxoSmithKline; National Institutes of Health [R01 DK048351, P50 DK064539, K23 DK073451, K08 DK071626, T32 DK07180-34] FX Research supported by GlaxoSmithKline, National Institutes of Health grants R01 DK048351 (EAM), P50 DK064539 (EAM), K23 DK073451 (KT), K08 DK071626 (JSL), and National Institutes of Health GI Training Grant T32 DK07180-34. NR 60 TC 27 Z9 33 U1 3 U2 20 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0016-5085 EI 1528-0012 J9 GASTROENTEROLOGY JI Gastroenterology PD DEC PY 2013 VL 145 IS 6 BP 1253 EP + DI 10.1053/j.gastro.2013.08.016 PG 12 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 259PA UT WOS:000327537600028 PM 23954313 ER PT J AU Conway, KL Kuballa, P Song, JH Patel, KK Castoreno, AB Yilmaz, OH Jijon, HB Zhang, M Aldrich, LN Villablanca, EJ Peloquin, JM Goel, G Lee, IA Mizoguchi, E Shi, HN Bhan, AK Shaw, SY Schreiber, SL Virgin, HW Shamji, AF Stappenbeck, TS Reinecker, HC Xavier, RJ AF Conway, Kara L. Kuballa, Petric Song, Joo-Hye Patel, Khushbu K. Castoreno, Adam B. Yilmaz, Omer H. Jijon, Humberto B. Zhang, Mei Aldrich, Leslie N. Villablanca, Eduardo J. Peloquin, Joanna M. Goel, Gautam Lee, In-Ah Mizoguchi, Emiko Shi, Hai Ning Bhan, Atul K. Shaw, Stanley Y. Schreiber, Stuart L. Virgin, Herbert W. Shamji, Alykhan F. Stappenbeck, Thaddeus S. Reinecker, Hans-Christian Xavier, Ramnik J. TI Atg16l1 is Required for Autophagy in Intestinal Epithelial Cells and Protection of Mice From Salmonella Infection SO GASTROENTEROLOGY LA English DT Article DE Mouse Model; Autophagy; Intestinal Barrier; Mucosa ID GENOME-WIDE ASSOCIATION; ILEAL CROHNS-DISEASE; PANETH CELLS; TYPHIMURIUM INFECTION; IL-1-BETA PRODUCTION; GENE ATG16L1; HOST; INFLAMMATION; PATHOGEN; TUBERCULOSIS AB BACKGROUND & AIMS: Intestinal epithelial cells aid in mucosal defense by providing a physical barrier against entry of pathogenic bacteria and secreting antimicrobial peptides (AMPs). Autophagy is an important component of immune homeostasis. However, little is known about its role in specific cell types during bacterial infection in vivo. We investigated the role of autophagy in the response of intestinal epithelial and antigen-presenting cells to Salmonella infection in mice. METHODS: We generated mice deficient in Atg16l1 in epithelial cells (Atg16l1(f/f) x Villin-cre) or CD11c(+) cells (Atg16l1(f/f) x CD11c-cre); these mice were used to assess cell type-specific antibacterial autophagy. All responses were compared with Atg16l1(f/f) mice (controls). Mice were infected with Salmonella enterica serovar typhimurium; cecum and small-intestine tissues were collected for immunofluorescence, histology, and quantitative reverse-transcription polymerase chain reaction analyses of cytokines and AMPs. Modulators of autophagy were screened to evaluate their effects on antibacterial responses in human epithelial cells. RESULTS: Autophagy was induced in small intestine and cecum after infection with S typhimurium, and required Atg16l1. S typhimurium colocalized with microtubule-associated protein 1 light chain 3 beta (Map1lc3b or LC3) in the intestinal epithelium of control mice but not in Atg16l1(f/f) x Villin-cre mice. Atg16l1(f/f) x Villin-cre mice also had fewer Paneth cells and abnormal granule morphology, leading to reduced expression of AMPs. Consistent with these defective immune responses, Atg16l1(f/f) x Villin-cre mice had increased inflammation and systemic translocation of bacteria compared with control mice. In contrast, we observed few differences between Atg16l1(f/f) x CD11c-cre and control mice. Trifluoperazine promoted autophagy and bacterial clearance in HeLa cells; these effects were reduced upon knockdown of ATG16L1. CONCLUSIONS: Atg16l1 regulates autophagy in intestinal epithelial cells and is required for bacterial clearance. It also is required to prevent systemic infection of mice with enteric bacteria. C1 [Conway, Kara L.; Kuballa, Petric; Song, Joo-Hye; Jijon, Humberto B.; Villablanca, Eduardo J.; Peloquin, Joanna M.; Goel, Gautam; Lee, In-Ah; Mizoguchi, Emiko; Reinecker, Hans-Christian; Xavier, Ramnik J.] Harvard Univ, Sch Med, Gastrointestinal Unit, Boston, MA USA. [Conway, Kara L.; Kuballa, Petric; Song, Joo-Hye; Jijon, Humberto B.; Villablanca, Eduardo J.; Peloquin, Joanna M.; Goel, Gautam; Lee, In-Ah; Mizoguchi, Emiko; Reinecker, Hans-Christian; Xavier, Ramnik J.] Harvard Univ, Sch Med, Ctr Study Inflammatory Bowel Dis, Boston, MA USA. [Conway, Kara L.; Kuballa, Petric; Jijon, Humberto B.; Villablanca, Eduardo J.; Goel, Gautam; Xavier, Ramnik J.] Harvard Univ, Sch Med, Ctr Computat & Integrat Biol, Boston, MA USA. [Yilmaz, Omer H.; Bhan, Atul K.] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. [Zhang, Mei; Shi, Hai Ning] Harvard Univ, Sch Med, Mucosal Immunol Lab, Boston, MA USA. [Shaw, Stanley Y.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Syst Biol, Boston, MA USA. [Conway, Kara L.; Kuballa, Petric; Castoreno, Adam B.; Jijon, Humberto B.; Aldrich, Leslie N.; Villablanca, Eduardo J.; Goel, Gautam; Schreiber, Stuart L.; Shamji, Alykhan F.; Xavier, Ramnik J.] Broad Inst Massachusetts Inst Technol & Harvard U, Cambridge, MA USA. [Schreiber, Stuart L.] Harvard Univ, Dept Chem & Chem Biol, Cambridge, MA 02138 USA. [Patel, Khushbu K.; Virgin, Herbert W.; Stappenbeck, Thaddeus S.] Washington Univ, Sch Med, Dept Pathol & Immunol, St Louis, MO USA. RP Xavier, RJ (reprint author), Massachusetts Gen Hosp, Ctr Computat & Integrat Biol, Richard B Simches Res Ctr, 185 Cambridge St, Boston, MA 02114 USA. EM xavier@molbio.mgh.harvard.edu RI Villablanca, Eduardo/E-1380-2016 OI Villablanca, Eduardo/0000-0001-9522-9729 FU National Institutes of Health [DK097485, DK092405, DK060049, DK043351, AI093588, DK068181, DK033506, DK082427, AI054483]; Leona M. and Harry B. Helmsley Charitable Trust; Crohn's and Colitis Foundation of America Genetics Initiative FX Supported by the following: National Institutes of Health grants DK097485, DK092405, and DK060049 (R.J.X.); The Leona M. and Harry B. Helmsley Charitable Trust (S. L. S., R.J.X.); National Institutes of Health grant DK043351 (R.J.X., H. C. R.); National Institutes of Health grants AI093588, DK068181, and DK033506 (H. C. R.); National Institutes of Health grant DK082427 (H.N.S.); Crohn's and Colitis Foundation of America Genetics Initiative (H. W. V., R.J.X., T. S. S.); and National Institutes of Health grant AI054483 (H. W. V.). Editorial assistance was provided by Natalia Nedelsky, as supported by National Institutes of Health grant DK043351 (R.J.X.). NR 37 TC 74 Z9 74 U1 2 U2 14 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0016-5085 EI 1528-0012 J9 GASTROENTEROLOGY JI Gastroenterology PD DEC PY 2013 VL 145 IS 6 BP 1347 EP 1357 DI 10.1053/j.gastro.2013.08.035 PG 11 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 259PA UT WOS:000327537600037 PM 23973919 ER PT J AU Romo, RD Wallhagen, MI Yourman, L Yeung, CC Eng, C Micco, G Perez-Stable, EJ Smith, AK AF Romo, Rafael D. Wallhagen, Margaret I. Yourman, Lindsey Yeung, Christie C. Eng, Catherine Micco, Guy Perez-Stable, Eliseo J. Smith, Alexander K. TI Perceptions of Successful Aging Among Diverse Elders With Late-Life Disability SO GERONTOLOGIST LA English DT Article DE Attitudes and perception toward aging; aged; Diversity and ethnicity; Grounded theory; Qualitative research methods; Cross-cultural studies; Home and community; based care and services ID AFRICAN-AMERICAN; OLDER-ADULTS; HEALTH; SATISFACTION; DEFINITION; MODEL; WELL AB Purpose: Researchers often use the term successful aging to mean freedom from disability, yet the perspectives of elders living with late-life disability have not been well described. The purpose of this study was to explore the meaning of successful aging among a diverse sample of community-dwelling elders with late-life disability. Design and Methods: Using qualitative grounded theory methodology, we interviewed 56 African American, White, Cantonese-speaking Chinese, and Spanish-speaking Latino disabled elders who participate in On Lok Lifeways, a Program of All-inclusive Care for the Elderly. Through semi-structured interviews with open-ended questions, we explored the elders perceptions of what successful aging and being old meant to them. Results: Despite experiencing late-life disability, most participants felt they had aged successfully. An overarching theme was that aging results in Living in a New Reality, with two subthemes: Acknowledging the New Reality and Rejecting the New Reality. Participants achieved successful aging by using adaptation and coping strategies to align their perception of successful aging with their experiences. Themes were common across race/ethnic groups but certain strategies were more prominent among different groups. Implications: Across race and ethnic groups, most of these participants with late-life disability felt they had aged successfully. Thus, successful aging involves subjective criteria and has a cultural context that is not captured in objective measurements. Understanding elders perception will help establish common ground for communication between clinicians and elders and identify the most appropriate interventions to help elders achieve and maintain the experience of successful aging. C1 [Romo, Rafael D.; Wallhagen, Margaret I.] Univ Calif San Francisco, Sch Nursing, Dept Physiol Nursing, San Francisco, CA 94143 USA. [Yourman, Lindsey; Yeung, Christie C.; Eng, Catherine; Smith, Alexander K.] Univ Calif San Francisco, Dept Med, Div Geriatr, San Francisco, CA USA. [Yourman, Lindsey] Scripps Mercy Med Educ, San Diego, CA USA. [Eng, Catherine] On Lok Lifeways, San Francisco, CA USA. [Micco, Guy] Univ Calif Berkeley, UC Berkeley UCSF Joint Med Program, Berkeley, CA 94720 USA. [Perez-Stable, Eliseo J.] Univ Calif San Francisco, Dept Med, Div Gen Internal Med, San Francisco, CA USA. [Smith, Alexander K.] San Francisco Vet Adm Med Ctr, San Francisco, CA USA. RP Romo, RD (reprint author), UCSF Sch Nursing, Off Student Affairs N319X, 2 Koret Way, San Francisco, CA 94143 USA. EM Rafael.Romo@ucsf.edu FU NCRR NIH HHS [UL1 RR024131]; NIA NIH HHS [P30 AG015272, P30-AG15272] NR 34 TC 22 Z9 22 U1 4 U2 25 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0016-9013 EI 1758-5341 J9 GERONTOLOGIST JI Gerontologist PD DEC PY 2013 VL 53 IS 6 BP 939 EP 949 DI 10.1093/geront/gns160 PG 11 WC Gerontology SC Geriatrics & Gerontology GA 258DV UT WOS:000327440300006 PM 23231944 ER PT J AU Kim, JY Kim, WG Jeon, TY Kim, GH Jeong, EH Kim, DH Park, DY Lauwers, GY AF Kim, Joo-Yeon Kim, Woo-Gyeong Jeon, Tae-Yong Kim, Gwang Ha Jeong, Eun-Hee Kim, Dae Hwan Park, Do Youn Lauwers, Gregory Y. TI Lymph node metastasis in early gastric cancer: evaluation of a novel method for measuring submucosal invasion and development of a nodal predicting index SO HUMAN PATHOLOGY LA English DT Article DE Early gastric cancer; Endoscopic submucosal dissection; Lymph node metastasis; Prediction score; Depth of invasion ID ENDOSCOPIC MUCOSAL RESECTION; CLINICOPATHOLOGICAL FEATURES; CARCINOMA; STOMACH; NEOPLASMS; EMR AB After endoscopic resection of early gastric cancer (EGC), it is imperative to accurately determine whether follow-up surgery is indicated, since this technique is used as a first line of treatment. Herein, we developed a scoring system to indicate the risk of lymph node metastasis in submucosal EGC (smEGC), and present a novel method to measure depth of submucosal invasion. In our series, 15.9% of the smEGC presented with lymph node metastasis. A nodal prediction index, based on the variables extracted from the univariate analysis and defined as nodal prediction index = (2.128 x lymphovascular tumor emboli) + (1.083 x submucosal invasion width >= 0.75 cm) + (0.507 x submucosal invasion depth >= 1000 mu m) + (0.515 x infiltrative growth pattern), yielded an area under the receiver operating characteristic curve of 0.809 (P=.000, 95% CI = 0.713-0.096) in a training group, and showed comparable result in validation group (0.886, P=.000, 95% CI = 0.796-0.977). Depth of invasion was statistically higher in the metastatic group when measured from the lowest point of an imaginary line in continuity with the adjacent muscularis mucosa to the point of deepest tumor penetration, but not when using the classic measurement method. The area under the receiver operating characteristic curve of the alternative measurement method was 0.652 (P=.013, 95% CI = 0.550-0.754) compared to 0.620 for the classic measurement method (P=.0480, 95% CI = 0.509-0.731). In deciding whether surgery is indicated after endoscopic submucosal dissection for smEGCs, we recommend to test our alternative method of measuring submucosal invasion and to evaluate our nodal prediction index as an adjunct tool. (C) 2013 Elsevier Inc. All rights reserved. C1 [Kim, Joo-Yeon; Kim, Woo-Gyeong; Park, Do Youn] Pusan Natl Univ Hosp, Dept Pathol, Pusan 602739, South Korea. [Kim, Joo-Yeon; Kim, Woo-Gyeong; Jeon, Tae-Yong; Kim, Gwang Ha; Kim, Dae Hwan; Park, Do Youn] Pusan Natl Univ, Sch Med, Pusan 602739, South Korea. [Kim, Joo-Yeon; Kim, Woo-Gyeong; Jeon, Tae-Yong; Kim, Gwang Ha; Kim, Dae Hwan; Park, Do Youn] Pusan Natl Univ Hosp, Biomed Res Inst, Pusan 602739, South Korea. [Jeon, Tae-Yong; Kim, Dae Hwan] Pusan Natl Univ Hosp, Dept Surg, Pusan 602739, South Korea. [Kim, Gwang Ha] Pusan Natl Univ Hosp, Pusan 602739, South Korea. [Jeong, Eun-Hee] Cheonam Natl Univ, Dept Pathol, Kwangju 501757, South Korea. [Lauwers, Gregory Y.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Lauwers, Gregory Y.] Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Park, DY (reprint author), Pusan Natl Univ Hosp, Dept Pathol, 1-10 Ami Dong, Pusan 602739, South Korea. EM pdy220@pusan.ac.kr FU Ministry of Health, Welfare and Family Affairs FX The biospecimens for this study were provided by the Pusan National University Hospital, a member of the National Biobank of Korea, which is supported by the Ministry of Health, Welfare and Family Affairs. All samples derived from the National Biobank of Korea were obtained with informed consent under institutional review board-approved protocols. NR 30 TC 9 Z9 11 U1 0 U2 4 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0046-8177 EI 1532-8392 J9 HUM PATHOL JI Hum. Pathol. PD DEC PY 2013 VL 44 IS 12 BP 2829 EP 2836 DI 10.1016/j.humpath.2013.07.037 PG 8 WC Pathology SC Pathology GA 262QJ UT WOS:000327752400028 PM 24139210 ER PT J AU Bonmassar, G Lev, MH AF Bonmassar, Giorgio Lev, Michael H. TI Improved Sensing Pulses for Increased Human Head Depth Measurement Sensitivity With Electrical Impedance Spectroscopy SO IEEE TRANSACTIONS ON BIOMEDICAL ENGINEERING LA English DT Article DE Electrical impedance measurement; pulse generation; spectral analysis; stochastic systems ID EIT IMAGE-RECONSTRUCTION; DISPERSIVE MATERIALS; TOMOGRAPHY EIT; STROKE; FREQUENCY; BRAIN; REGULARIZATION; ALGORITHMS; ABSORPTION; ELECTRODES AB This paper describes an improved electrical impedance spectroscopy (EIS) stimulus paradigm, based on dual-energy pulses using the stochastic Gabor function (SGF) that may more sensitively assess deep brain tissue impedance than current single-pulse paradigms. The SGF is a uniformly distributed noise, modulated by a Gaussian envelope, with a wide-frequency spectrum representation regardless of the stimuli energy, and is least compact in the sample frequency phase plane. Numerical results obtained using a realistic human head model confirm that two sequential SGF pulses at different energies can improve EIS depth sensitivity when used in a dual-energy subtraction scheme. Specifically, although the two SGF pulses exhibit different tissue current distributions, they maintain the broadband sensing pulse characteristics needed to generate all the frequencies of interest. Moreover, finite-difference time domain simulations show that this dual-energy excitation scheme is capable of reducing the amplitude of weighted current densities surface directly underneath the electrodes by approximately 3 million times versus single stimulation pulses, while maintaining an acceptable tissue conductivity distribution at depth. This increased sensitivity for the detection of small, deep impedance changes might be of value in potential future EIS applications, such as the portable, point-of-care detection of deep brain hemorrhage or infarction. C1 [Bonmassar, Giorgio] Harvard Univ, Sch Med, AA Martinos Ctr, Boston, MA 02129 USA. [Lev, Michael H.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Radiol,Div Neuroradiol, Boston, MA 02114 USA. RP Bonmassar, G (reprint author), Harvard Univ, Sch Med, AA Martinos Ctr, Boston, MA 02129 USA. EM giorgio@nmr.mgh.harvard.edu; mlev@partners.org FU National Institute of Biomedical Imaging and Bioengineering, National Institute of Health [5U54EB007954-04, 005213]; Massachusetts General Hospital Clinical Research Center Harvard Clinical and Translational Science Center, from the National Center for Research Resources [1 UL1 RR02575801] FX This work was supported in part by the National Institute of Biomedical Imaging and Bioengineering, National Institute of Health Subcontract through U of Cincinnati (5U54EB007954-04 sub award 005213) " Point-of-care" Center (POC-CENT) and in part by the Massachusetts General Hospital Clinical Research Center (1 UL1 RR02575801) Harvard Clinical and Translational Science Center, from the National Center for Research Resources. Asterisk indicates corresponding author. NR 62 TC 1 Z9 1 U1 0 U2 10 PU IEEE-INST ELECTRICAL ELECTRONICS ENGINEERS INC PI PISCATAWAY PA 445 HOES LANE, PISCATAWAY, NJ 08855-4141 USA SN 0018-9294 EI 1558-2531 J9 IEEE T BIO-MED ENG JI IEEE Trans. Biomed. Eng. PD DEC PY 2013 VL 60 IS 12 BP 3306 EP 3313 DI 10.1109/TBME.2013.2280877 PG 8 WC Engineering, Biomedical SC Engineering GA 259VI UT WOS:000327554000007 PM 24043365 ER PT J AU Carroll, BJ Contreras-Valdes, FM Heist, EK Barrett, CD Danik, SB Ruskin, JN Mansour, M AF Carroll, Brett J. Contreras-Valdes, Fernando M. Heist, Edwin Kevin Barrett, Conor D. Danik, Stephan B. Ruskin, Jeremy N. Mansour, Moussa TI Esophageal Temperature Monitoring During AF Ablation: Multi-Sensor or Single-Sensor Probe? RESPONSE SO JOURNAL OF CARDIOVASCULAR ELECTROPHYSIOLOGY LA English DT Letter ID ATRIAL-FIBRILLATION; RADIOFREQUENCY ABLATION C1 [Carroll, Brett J.; Contreras-Valdes, Fernando M.; Heist, Edwin Kevin; Barrett, Conor D.; Danik, Stephan B.; Ruskin, Jeremy N.; Mansour, Moussa] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Carroll, BJ (reprint author), Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 6 TC 0 Z9 0 U1 0 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1045-3873 EI 1540-8167 J9 J CARDIOVASC ELECTR JI J. Cardiovasc. Electrophysiol. PD DEC PY 2013 VL 24 IS 12 BP E25 EP E25 DI 10.1111/jce.12304 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 260OB UT WOS:000327603100010 PM 24125162 ER PT J AU Wang, GH Zhang, J Hu, XM Zhang, LL Mao, LL Jiang, XY Liou, AKF Leak, RK Gao, YQ Chen, J AF Wang, Guohua Zhang, Jia Hu, Xiaoming Zhang, Lili Mao, Leilei Jiang, Xiaoyan Liou, Anthony Kian-Fong Leak, Rehana K. Gao, Yanqin Chen, Jun TI Microglia/macrophage polarization dynamics in white matter after traumatic brain injury SO JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM LA English DT Article DE inflammation; macrophage; microglia; polarization; white matter injury ID SPINAL-CORD; NEURODEGENERATIVE DISEASES; ACTIVATION PATTERNS; AXONAL INJURY; CELL-DEATH; MICROGLIA; INFLAMMATION; RAT; NEUROPROTECTION; IDENTIFICATION AB Mononuclear phagocytes are a population of multi-phenotypic cells and have dual roles in brain destruction/reconstruction. The phenotype-specific roles of microglia/macrophages in traumatic brain injury (TBI) are, however, poorly characterized. In the present study, TBI was induced in mice by a controlled cortical impact (CCI) and animals were killed at 1 to 14 days post injury. Real-time polymerase chain reaction (RT-PCR) and immunofluorescence staining for M1 and M2 markers were performed to characterize phenotypic changes of microglia/macrophages in both gray and white matter. We found that the number of M1-like phagocytes increased in cortex, striatum and corpus callosum (CC) during the first week and remained elevated until at least 14 days after TBI. In contrast, M2-like microglia/macrophages peaked at 5 days, but decreased rapidly thereafter. Notably, the severity of white matter injury (WMI), manifested by immunohistochemical staining for neurofilannent SMI-32, was strongly correlated with the number of M1-like phagocytes. In vitro experiments using a conditioned medium transfer system confirmed that M1 microglia-conditioned media exacerbated oxygen glucose deprivation-induced oligodendrocyte death. Our results indicate that microglia/macrophages respond dynamically to TBI, experiencing a transient M2 phenotype followed by a shift to the M1 phenotype. The M1 phenotypic shift may propel WMI progression and represents a rational target for TBI treatment. C1 [Wang, Guohua; Zhang, Jia; Mao, Leilei; Jiang, Xiaoyan; Gao, Yanqin; Chen, Jun] Fudan Univ, State Key Lab Med Neurobiol, Shanghai 200032, Peoples R China. [Wang, Guohua; Zhang, Jia; Mao, Leilei; Jiang, Xiaoyan; Gao, Yanqin; Chen, Jun] Fudan Univ, Inst Brain Sci, Shanghai 200032, Peoples R China. [Wang, Guohua; Hu, Xiaoming; Zhang, Lili; Mao, Leilei; Liou, Anthony Kian-Fong; Gao, Yanqin; Chen, Jun] Univ Pittsburgh, Dept Neurol, Sch Med, Ctr Cerebrovasc Dis Res, Pittsburgh, PA 15260 USA. [Wang, Guohua] Nantong Univ, Inst Naut Med, Dept Neuropharmacol, Nantong, Peoples R China. [Hu, Xiaoming; Zhang, Lili; Liou, Anthony Kian-Fong; Chen, Jun] Vet Affairs Pittsburgh Hlth Care Syst, Geriatr Res Educ & Clin Ctr, Pittsburgh, PA USA. [Leak, Rehana K.] Duquesne Univ, Mylan Sch Pharm, Div Pharmaceut Sci, Pittsburgh, PA 15219 USA. RP Gao, YQ (reprint author), Fudan Univ, State Key Lab Med Neurobiol, Shanghai 200032, Peoples R China. EM yqgao@shmu.edu.cn; chenj2@upmc.edu RI Gao, Yanqin/I-6790-2016; OI Gao, Yanqin/0000-0002-4915-9819; Leak, Rehana/0000-0003-2817-7417 FU Chinese Ministry of Science and Technology; National Institutes of Health/NINDS grants [NS36736, NS43802, NS45048]; VA Career Scientist Award; Chinese Natural Science Foundation [30870794, 81020108021, 81171149, 81150110494, 81000497] FX This research is supported in part by the Special Research Funds from Chinese Ministry of Science and Technology to State Key laboratories (to GH Wang, Y Gao and J Chen), National Institutes of Health/NINDS grants NS36736, NS43802 and NS45048 (to J Chen), VA Career Scientist Award (J Chen), and Chinese Natural Science Foundation grants No 30870794, No 81020108021, No 81171149, and No 81150110494 (to YG), and No 81000497 (to GW). NR 43 TC 92 Z9 93 U1 5 U2 30 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0271-678X EI 1559-7016 J9 J CEREBR BLOOD F MET JI J. Cereb. Blood Flow Metab. PD DEC PY 2013 VL 33 IS 12 BP 1864 EP 1874 DI 10.1038/jcbfm.2013.146 PG 11 WC Endocrinology & Metabolism; Hematology; Neurosciences SC Endocrinology & Metabolism; Hematology; Neurosciences & Neurology GA 266DI UT WOS:000328002200007 PM 23942366 ER PT J AU Bloch, MJ Basile, JN AF Bloch, Michael J. Basile, Jan N. TI Review of Recent Literature in Hypertension: Updated Clinical Practice Guidelines for Chronic Kidney Disease Now Include Albuminuria in the Classification System SO JOURNAL OF CLINICAL HYPERTENSION LA English DT Article C1 [Bloch, Michael J.] Univ Nevada, Sch Med, Dept Internal Med, Reno, NV 89557 USA. [Basile, Jan N.] Med Univ S Carolina, Seinsheimer Cardiovasc Hlth Program, Div Gen Internal Med Geriatr, Ralph H Johnson VA Med Ctr, Charleston, SC 29425 USA. RP Bloch, MJ (reprint author), Univ Hlth Syst, 1500 East 2nd St,Suite 302, Reno, NV 89502 USA. EM mbloch@aol.com NR 3 TC 0 Z9 1 U1 1 U2 2 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1524-6175 EI 1751-7176 J9 J CLIN HYPERTENS JI J. Clin. Hypertens. PD DEC PY 2013 VL 15 IS 12 BP 865 EP 867 DI 10.1111/jch.12209 PG 3 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 260YX UT WOS:000327631700002 PM 24119153 ER PT J AU Codd, PJ Venteicher, AS Agarwalla, PK Kahle, KT Jho, DH AF Codd, Patrick J. Venteicher, Andrew S. Agarwalla, Pankaj K. Kahle, Kristopher T. Jho, David H. TI Endoscopic burr hole evacuation of an acute subdural hematoma SO JOURNAL OF CLINICAL NEUROSCIENCE LA English DT Article DE Endoscopic; Minimally invasive neurosurgery; Subdural hematoma ID INFANTS AB Acute subdural hematoma evacuations frequently necessitate large craniotomies with extended operative times and high relative blood loss, which can lead to additional morbidity for the patient. While endoscopic minimally invasive approaches to chronic subdural collections have been successfully demonstrated, this technique has not previously been applied to acute subdural hematomas. The authors report their experience with an 87-year-old patient presenting with a large acute right-sided subdural hematoma successfully evacuated via an endoscopic minimally invasive technique. The operative approach is outlined, and the literature on endoscopic subdural collection evacuation reviewed. (C) 2013 Published by Elsevier Ltd. C1 [Codd, Patrick J.; Venteicher, Andrew S.; Agarwalla, Pankaj K.; Kahle, Kristopher T.; Jho, David H.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Neurosurg, Boston, MA 02114 USA. RP Codd, PJ (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Neurosurg, 55 Fruit St,WHT 502, Boston, MA 02114 USA. EM pcodd@partners.org NR 12 TC 4 Z9 5 U1 2 U2 4 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0967-5868 EI 1532-2653 J9 J CLIN NEUROSCI JI J. Clin. Neurosci. PD DEC PY 2013 VL 20 IS 12 BP 1751 EP 1753 DI 10.1016/j.jocn.2013.02.019 PG 3 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 261UO UT WOS:000327690300022 PM 23962631 ER PT J AU McKay, JR Van Horn, DHA Lynch, KG Ivey, M Cary, MS Drapkin, ML Coviello, DM Plebani, JG AF McKay, James R. Van Horn, Deborah H. A. Lynch, Kevin G. Ivey, Megan Cary, Mark S. Drapkin, Michelle L. Coviello, Donna M. Plebani, Jennifer G. TI An Adaptive Approach for Identifying Cocaine Dependent Patients Who Benefit From Extended Continuing Care SO JOURNAL OF CONSULTING AND CLINICAL PSYCHOLOGY LA English DT Article DE cocaine dependence; continuing care; adaptive treatment; incentives; moderators ID ADDICTION SEVERITY INDEX; SUBSTANCE-ABUSE PATIENTS; TREATMENT ATTRITION; OUTPATIENT COCAINE; INITIAL ABSTINENCE; DRINKING BEHAVIOR; RANDOMIZED-TRIAL; SELF-REPORTS; ALCOHOL; OUTCOMES AB Objective: Study tested whether cocaine dependent patients using cocaine or alcohol at intake or in the first few weeks of intensive outpatient treatment would benefit more from extended continuing care than patients abstinent during this period. The effect of incentives for continuing care attendance was also examined. Method: Participants (N = 321) were randomized to treatment as usual (TAU), TAU and telephone monitoring and counseling (TMC), or TAU and TMC plus incentives (TMC+). The primary outcomes were (a) abstinence from all drugs and heavy alcohol use and (b) cocaine urine toxicology. Follow-ups were at 3, 6, 9, 12, 18, and 24 months. Results: Cocaine and alcohol use at intake or early in treatment predicted worse outcomes on both measures (ps <= .0002). Significant effects favoring TMC over TAU on the abstinence composite were obtained in participants who used cocaine (odds ratio [OR] = 1.95 [1.02, 3.73]) or alcohol (OR = 2.47 [1.28, 4.78]) at intake or early in treatment. A significant effect favoring TMC+ over TAU on cocaine urine toxicology was obtained in those using cocaine during that period (OR = 0.55 [0.31, 0.95]). Conversely, there were no treatment effects in participants abstinent at baseline and no overall treatment main effects. Incentives almost doubled the number of continuing care sessions received but did not further improve outcomes. Conclusion: An adaptive approach for cocaine dependence in which extended continuing care is provided only to patients who are using cocaine or alcohol at intake or early in treatment improves outcomes in this group while reducing burden and costs in lower risk patients. C1 [McKay, James R.; Van Horn, Deborah H. A.; Lynch, Kevin G.; Ivey, Megan; Drapkin, Michelle L.; Coviello, Donna M.; Plebani, Jennifer G.] Univ Penn, Dept Psychiat, Perelman Sch Med, Philadelphia, PA 19104 USA. [McKay, James R.; Van Horn, Deborah H. A.; Drapkin, Michelle L.] Philadelphia Vet Affairs Med Ctr, Dept Behav Hlth, Philadelphia, PA USA. [Cary, Mark S.] Univ Penn, Ctr Clin Epidemiol & Biostat, Perelman Sch Med, Philadelphia, PA 19104 USA. RP McKay, JR (reprint author), Univ Penn, Ctr Continuum Care Addict, 3440 Market St,Suite 370, Philadelphia, PA 19104 USA. EM jimrache@mail.med.upenn.edu FU NIDA NIH HHS [R01 DA020623, K02 DA000361, K24 DA029062] NR 41 TC 10 Z9 10 U1 0 U2 5 PU AMER PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 USA SN 0022-006X EI 1939-2117 J9 J CONSULT CLIN PSYCH JI J. Consult. Clin. Psychol. PD DEC PY 2013 VL 81 IS 6 BP 1063 EP 1073 DI 10.1037/a0034265 PG 11 WC Psychology, Clinical SC Psychology GA 264DE UT WOS:000327856400011 PM 24041231 ER PT J AU Smits, JAJ Hofmann, SG Rosenfield, D DeBoer, LB Costa, PT Simon, NM O'Cleirigh, C Meuret, AE Marques, L Otto, MW Pollack, MH AF Smits, Jasper A. J. Hofmann, Stefan G. Rosenfield, David DeBoer, Lindsey B. Costa, Paul T. Simon, Naomi M. O'Cleirigh, Conall Meuret, Alicia E. Marques, Luana Otto, Michael W. Pollack, Mark H. TI D-Cycloserine Augmentation of Cognitive Behavioral Group Therapy of Social Anxiety Disorder: Prognostic and Prescriptive Variables SO JOURNAL OF CONSULTING AND CLINICAL PSYCHOLOGY LA English DT Article DE cognitive behavioral therapy; d-cycloserine; social anxiety disorder; social phobia; moderators ID PLACEBO-CONTROLLED TRIAL; RANDOMIZED CONTROLLED-TRIAL; EXPOSURE THERAPY; PHOBIA; DEPRESSION; EXTINCTION; PSYCHOTHERAPY; PERSONALITY; PREDICTORS; PHENELZINE AB Objective: The aim of the current study was to identify individual characteristics that (a) predict symptom improvement with group cognitive behavioral therapy (CBT) for social anxiety disorder (SAD; i.e., prognostic variables) or (b) moderate the effects of d-cycloserine (DCS) versus placebo augmentation of CBT for SAD (i.e., prescriptive variables). Method: Adults with SAD (N = 169) provided Liebowitz Social Anxiety Scale scores in a trial evaluating DCS augmentation of group CBT. Rate of symptom improvement during therapy and posttreatment symptom severity were evaluated using multilevel modeling. As predictors of these 2 parameters, we selected the range of variables assessed at baseline (demographic characteristics, clinical characteristics, personality traits). Using step-wise analyses, we first identified prognostic and prescriptive variables within each of these domains and then entered these significant predictors simultaneously in 1 final model. Results: African American ethnicity and cohabitation status were associated with greater overall rates of improvement during therapy and lower posttreatment severity. Higher initial severity was associated with a greater improvement during therapy but also higher posttreatment severity (the greater improvement was not enough to overcome the initial higher severity). DCS augmentation was evident only among individuals low in conscientiousness and high in agreeableness. Conclusions: African American ethnicity, cohabitation status, and initial severity are prognostic of favorable CBT outcomes in SAD. DCS augmentation appears particularly useful for patients low in conscientiousness and high in agreeableness. These findings can guide clinicians in making decisions about treatment strategies and can help direct research on the mechanisms of these treatments. C1 [Smits, Jasper A. J.] Univ Texas Austin, Mental Hlth Res Inst, Austin, TX 78712 USA. [Smits, Jasper A. J.] Univ Texas Austin, Dept Psychol, Austin, TX 78712 USA. [Hofmann, Stefan G.; Otto, Michael W.] Boston Univ, Dept Psychol, Boston, MA 02215 USA. [Rosenfield, David; DeBoer, Lindsey B.; Meuret, Alicia E.] So Methodist Univ, Dept Psychol, Dallas, TX 75275 USA. [Costa, Paul T.] Duke Univ, Sch Med, Dept Psychiat & Behav Sci, Behav Med Res Ctr, Durham, NC 27706 USA. [Simon, Naomi M.; O'Cleirigh, Conall; Marques, Luana] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. [Simon, Naomi M.; O'Cleirigh, Conall; Marques, Luana] Harvard Univ, Sch Med, Cambridge, MA 02138 USA. RP Smits, JAJ (reprint author), Univ Texas Austin, Mental Hlth Res Inst, 108 E Dean Keeton Stop A8000, Austin, TX 78712 USA. EM smits@utexas.edu RI Hofmann, Stefan/B-8769-2014; Hopkins, Lindsey/D-4408-2015; Smits, Jasper/A-4350-2008; OI Hofmann, Stefan/0000-0002-3548-9681; Hopkins, Lindsey/0000-0002-0577-2961; Smits, Jasper/0000-0001-7128-9807; Smits, Jasper/0000-0003-1633-9693 FU NIMH NIH HHS [R01 MH075889, R01 MH078308, R01MH075889, R01MH078308] NR 52 TC 20 Z9 20 U1 0 U2 8 PU AMER PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 USA SN 0022-006X EI 1939-2117 J9 J CONSULT CLIN PSYCH JI J. Consult. Clin. Psychol. PD DEC PY 2013 VL 81 IS 6 BP 1100 EP 1112 DI 10.1037/a0034120 PG 13 WC Psychology, Clinical SC Psychology GA 264DE UT WOS:000327856400015 PM 23937345 ER PT J AU Phillips, LM Hachamovitch, R Berman, DS Iskandrian, AE Min, JK Picard, MH Kwong, RY Friedrich, MG Scherrer-Crosbie, M Hayes, SW Sharir, T Gosselin, G Mazzanti, M Senior, R Beanlands, R Smanio, P Goyal, A Al-Mallah, M Reynolds, H Stone, GW Maron, DJ Shaw, LJ AF Phillips, Lawrence M. Hachamovitch, Rory Berman, Daniel S. Iskandrian, Ami E. Min, James K. Picard, Michael H. Kwong, Raymond Y. Friedrich, Matthias G. Scherrer-Crosbie, Marielle Hayes, Sean W. Sharir, Tali Gosselin, Gilbert Mazzanti, Marco Senior, Roxy Beanlands, Rob Smanio, Paola Goyal, Abhi Al-Mallah, Mouaz Reynolds, Harmony Stone, Gregg W. Maron, David J. Shaw, Leslee J. TI Lessons learned from MPI and physiologic testing in randomized trials of stable ischemic heart disease: COURAGE, BARI 2D, FAME, and ISCHEMIA SO JOURNAL OF NUCLEAR CARDIOLOGY LA English DT Article DE Myocardial perfusion imaging; ischemia; coronary artery disease; clinical trials ID CORONARY-ARTERY-DISEASE; FRACTIONAL FLOW RESERVE; EMISSION COMPUTED-TOMOGRAPHY; OPTIMAL MEDICAL THERAPY; OUTCOMES UTILIZING REVASCULARIZATION; MYOCARDIAL-PERFUSION SPECT; VENTRICULAR-FUNCTION; PROGNOSTIC VALUE; FOLLOW-UP; INTERVENTION AB There is a preponderance of evidence that, in the setting of an acute coronary syndrome, an invasive approach using coronary revascularization has a morbidity and mortality benefit. However, recent stable ischemic heart disease (SIHD) randomized clinical trials testing whether the addition of coronary revascularization to guideline-directed medical therapy (GDMT) reduces death or major cardiovascular events have been negative. Based on the evidence from these trials, the primary role of GDMT as a front line medical management approach has been clearly defined in the recent SIHD clinical practice guideline; the role of prompt revascularization is less precisely defined. Based on data from observational studies, it has been hypothesized that there is a level of ischemia above which a revascularization strategy might result in benefit regarding cardiovascular events. However, eligibility for recent negative trials in SIHD has mandated at most minimal standards for ischemia. An ongoing randomized trial evaluating the effectiveness of randomization of patients to coronary angiography and revascularization as compared to no coronary angiography and GDMT in patients with moderate-severe ischemia will formally test this hypothesis. The current review will highlight the available evidence including a review of the published and ongoing SIHD trials. C1 [Phillips, Lawrence M.; Reynolds, Harmony] NYU, Sch Med, New York, NY 10016 USA. [Hachamovitch, Rory] Cleveland Clin Fdn, Cleveland, OH 44195 USA. [Berman, Daniel S.; Hayes, Sean W.] Cedars Sinai Med Ctr, Los Angeles, CA 90048 USA. [Iskandrian, Ami E.] Univ Alabama Birmingham, Birmingham, AL USA. [Min, James K.] Weill Cornell Med Coll, New York, NY USA. [Picard, Michael H.; Scherrer-Crosbie, Marielle] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Kwong, Raymond Y.] Brigham & WomensGuos Hosp, Boston, MA USA. [Friedrich, Matthias G.; Gosselin, Gilbert] Montreal Heart Inst, Montreal, PQ H1T 1C8, Canada. [Sharir, Tali] Assuta Med Ctr, Tel Aviv, Israel. [Mazzanti, Marco] Univ Hosp Ancona, Ancona, Italy. [Senior, Roxy] Northwick Pk Hosp & Clin Res Ctr, London, England. [Beanlands, Rob] Ottawa Heart Inst, Ottawa, ON, Canada. [Smanio, Paola] Inst Dante Pazzanese Cardiol, Sao Paulo, Brazil. [Goyal, Abhi; Shaw, Leslee J.] Emory Univ, Sch Med, Atlanta, GA USA. [Al-Mallah, Mouaz] King Abdulaziz Cardiac Ctr, Riyadh, Saudi Arabia. [Stone, Gregg W.] Columbia Univ, New York Presbyterian Hosp, Med Ctr, New York, NY USA. [Maron, David J.] Vanderbilt Univ, Nashville, TN 37235 USA. RP Phillips, LM (reprint author), NYU, Sch Med, 530 1st Ave,SKI-9U, New York, NY 10016 USA. EM Lawrence.Phillips@nyumc.org OI Reynolds, Harmony/0000-0003-0284-0655; Picard, Michael/0000-0002-9264-3243; Al-Mallah, Mouaz/0000-0003-2348-0484 FU NHLBI NIH HHS [R01 HL091157] NR 29 TC 12 Z9 14 U1 1 U2 5 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1071-3581 EI 1532-6551 J9 J NUCL CARDIOL JI J. Nucl. Cardiol. PD DEC PY 2013 VL 20 IS 6 BP 969 EP 975 DI 10.1007/s12350-013-9773-4 PG 7 WC Cardiac & Cardiovascular Systems; Radiology, Nuclear Medicine & Medical Imaging SC Cardiovascular System & Cardiology; Radiology, Nuclear Medicine & Medical Imaging GA 264EA UT WOS:000327858600005 PM 23963599 ER PT J AU Rork, JF Berde, CB Goldstein, RD AF Rork, Jillian F. Berde, Charles B. Goldstein, Richard D. TI Regional Anesthesia Approaches to Pain Management in Pediatric Palliative Care: A Review of Current Knowledge SO JOURNAL OF PAIN AND SYMPTOM MANAGEMENT LA English DT Article DE Palliative care; pain management; regional anesthesia; neuraxial blockade; nerve block; child; adolescent ID PHANTOM LIMB PAIN; INTRATHECAL BACLOFEN INFUSION; CELIAC PLEXUS BLOCKADE; CYSTIC-FIBROSIS; EPIDURAL ANALGESIA; CEREBRAL-PALSY; LUNG TRANSPLANTATION; SEVERE SPASTICITY; REFRACTORY PAIN; YOUNG-ADULTS AB Context. Although systemic analgesic therapies are the mainstay of pain treatment in pediatric palliative care, there are cases where they fail to adequately relieve symptoms or produce side effects that undermine effectiveness. Regional anesthesia may be considered as a potential therapy for these patients. Objectives. To review the literature on regional techniques in pediatric patients with life-limiting and chronic conditions, including pain from tumor infiltration, chest pain in advanced pulmonary disease, chronic abdominal pain, phantom limb pain, and spasticity and dystonia. Where relevant, the authors' clinical experiences are included. Methods. References were identified by searches of PubMed from 1980 until June 2012 with related terms. Results. Case reports and case series were identified for each condition. Regional anesthesia techniques performed included central neuraxial infusions, peripheral nerve and plexus blocks or infusions, neurolytic blocks, and implanted intrathecal ports and pumps for baclofen, opioids, local anesthetics, and other adjuvants. The reports described positive contributions to the management of moderate-to-severe pain. Clinical context for these techniques frequently included the failure of systemic treatments and/or intolerable medication side effects. Complications varied according to the procedure and the underlying patient pathology; however, these risks were often acceptable when the potential benefits were consistent with the overall goals of care. Conclusion. The present medical literature on regional anesthesia techniques in children receiving palliative care is limited to case reports and case series. Based on this evidence, recommendations must be provisional. Careful thought and discussion with pain management specialists are encouraged when pain symptoms are inadequately managed or the treatments produce deleterious side effects. (C) 2013 U. S. Cancer Pain Relief Committee. Published by Elsevier Inc. All rights reserved. C1 [Rork, Jillian F.; Berde, Charles B.; Goldstein, Richard D.] Harvard Univ, Sch Med, Boston, MA USA. [Berde, Charles B.; Goldstein, Richard D.] Boston Childrens Hosp, Boston, MA USA. [Goldstein, Richard D.] Dana Farber Canc Inst, Boston, MA 02215 USA. RP Goldstein, RD (reprint author), Dana Farber Canc Inst, 450 Brookline Ave, Boston, MA 02215 USA. EM richard_goldstein@dfci.harvard.edu FU Neil Samuel Ghiso Foundation; Sara Page Mayo Endowment for Pediatric Pain Research and Education; WEX Pharmaceuticals FX The authors would like to acknowledge the Neil Samuel Ghiso Foundation for supporting this project. Dr. Berde is supported by the Sara Page Mayo Endowment for Pediatric Pain Research and Education. He has received research support from WEX Pharmaceuticals and has a collaboration agreement with Proteus, SA, both for development of novel prolonged duration local anesthetics. Dr. Berde receives no royalties, equity, consulting income, or speaker's fees. In the event of future commercial development, Dr. Berde, his collaborators, and Boston Children's Hospital could potentially receive royalties in the future. Dr. Richard Goldstein and Jillian Rork declare no conflicts of interest. NR 81 TC 7 Z9 7 U1 3 U2 18 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0885-3924 EI 1873-6513 J9 J PAIN SYMPTOM MANAG JI J. Pain Symptom Manage. PD DEC PY 2013 VL 46 IS 6 BP 859 EP 873 DI 10.1016/j.jpainsymman.2013.01.004 PG 15 WC Health Care Sciences & Services; Medicine, General & Internal; Clinical Neurology SC Health Care Sciences & Services; General & Internal Medicine; Neurosciences & Neurology GA 262WM UT WOS:000327768600009 PM 23541741 ER PT J AU Cooley, ME Lobach, DF Johns, E Halpenny, B Saunders, TA Del Fiol, G Rabin, MS Calarese, P Berenbaum, IL Zaner, K Finn, K Berry, DL Abrahm, JL AF Cooley, Mary E. Lobach, David F. Johns, Ellis Halpenny, Barbara Saunders, Toni-Ann Del Fiol, Guilherme Rabin, Michael S. Calarese, Pamela Berenbaum, Isidore L. Zaner, Ken Finn, Kathleen Berry, Donna L. Abrahm, Janet L. TI Creating Computable Algorithms for Symptom Management in an Outpatient Thoracic Oncology Setting SO JOURNAL OF PAIN AND SYMPTOM MANAGEMENT LA English DT Article DE Lung cancer and symptom management algorithms; decision making; decision support systems; guideline implementation; consensus methods ID CLINICAL-PRACTICE GUIDELINES; DECISION-SUPPORT-SYSTEMS; CANCER PAIN MANAGEMENT; EVIDENCE-BASED RECOMMENDATIONS; EVIDENCE-BASED INTERVENTIONS; ADULTS RECEIVING TREATMENT; QUALITY-OF-CARE; PALLIATIVE CARE; LUNG-CANCER; AMERICAN-SOCIETY AB Context. Adequate symptom management is essential to ensure quality cancer care, but symptom management is not always evidence based. Adapting and automating national guidelines for use at the point of care may enhance use by clinicians. Objectives. This article reports on a process of adapting research evidence for use in a clinical decision support system that provided individualized symptom management recommendations to clinicians at the point of care. Methods. Using a modified ADAPTE process, panels of local experts adapted national guidelines and integrated research evidence to create computable algorithms with explicit recommendations for management of the most common symptoms (pain, fatigue, dyspnea, depression, and anxiety) associated with lung cancer. Results. Small multidisciplinary groups and a consensus panel, using a nominal group technique, modified and subsequently approved computable algorithms for fatigue, dyspnea, moderate pain, severe pain, depression, and anxiety. The approved algorithms represented the consensus of multidisciplinary clinicians on pharmacological and behavioral interventions tailored to the patient's age, comorbidities, laboratory values, current medications, and patient-reported symptom severity. Algorithms also were reconciled with one another to enable simultaneous management of several symptoms. Conclusion. A modified ADAPTE process and nominal group technique enabled the development and approval of locally adapted computable algorithms for individualized symptom management in patients with lung cancer. The process was more complex and required more time and resources than initially anticipated, but it resulted in computable algorithms that represented the consensus of many experts. (C) 2013 U. S. Cancer Pain Relief Committee. Published by Elsevier Inc. All rights reserved. C1 [Cooley, Mary E.; Halpenny, Barbara; Rabin, Michael S.; Calarese, Pamela; Berry, Donna L.; Abrahm, Janet L.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Lobach, David F.; Johns, Ellis] Duke Univ, Med Ctr, Durham, NC USA. [Saunders, Toni-Ann] Natl Initiat Childrens Hlth Care Qual, Boston, MA USA. [Del Fiol, Guilherme] Univ Utah, Salt Lake City, UT USA. [Berenbaum, Isidore L.; Zaner, Ken; Finn, Kathleen] Boston Med Ctr, Boston, MA USA. RP Cooley, ME (reprint author), Dana Farber Canc Inst, 450 Longwood Ave,LW-512, Boston, MA 02115 USA. EM mary_cooley@dfci.harvard.edu OI Del Fiol, Guilherme/0000-0001-9954-6799 FU National Cancer Institute [R01 CA125256]; [1 K07 CA92696] FX This work was funded by National Cancer Institute grant R01 CA125256 (Mary E. Cooley, Principal Investigator). The R01 CA125256 grant was prepared as part of a Mentored Career Development Award (1 K07 CA92696 to Mary E. Cooley), Karen M. Emmons, PhD, and Bruce E. Johnson, MD, Mentors. The authors declare no conflicts of interest. NR 85 TC 6 Z9 6 U1 1 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0885-3924 EI 1873-6513 J9 J PAIN SYMPTOM MANAG JI J. Pain Symptom Manage. PD DEC PY 2013 VL 46 IS 6 BP 911 EP U215 DI 10.1016/j.jpainsymman.2013.01.016 PG 15 WC Health Care Sciences & Services; Medicine, General & Internal; Clinical Neurology SC Health Care Sciences & Services; General & Internal Medicine; Neurosciences & Neurology GA 262WM UT WOS:000327768600013 PM 23680580 ER PT J AU Kramer, EJ Bodendorfer, BM Laron, D Wong, J Kim, HT Liu, XH Feeley, BT AF Kramer, Erik J. Bodendorfer, Blake M. Laron, Dominique Wong, Jason Kim, Hubert T. Liu, Xuhui Feeley, Brian T. TI Evaluation of cartilage degeneration in a rat model of rotator cuff tear arthropathy SO JOURNAL OF SHOULDER AND ELBOW SURGERY LA English DT Article DE Massive rotator cuff tear; arthropathy; osteoarthritis; histology; articular cartilage ID SYNOVIAL-FLUID; BIOCHEMICAL MARKERS; SHOULDER JOINT AB Background and hypothesis: Rotator cuff tears are the most common injury seen by shoulder surgeons. Glenohumeral osteoarthritis develops in many late-stage rotator cuff tear patients as a result of torn cuff tendons, termed "cuff tear arthropathy." However, the mechanisms of cuff tear arthropathy have not been fully established. It has been hypothesized that a combination of synovial and mechanical factors contribute equally to the development of cuff tear arthropathy. The goal of this study was to assess the utility of this model in investigating cuff tear arthropathy. Materials and methods: We used a rat model that accurately reflects rotator cuff muscle degradation after massive rotator cuff tears through either infraspinatus and supraspinatus tenotomy or suprascapular nerve transection. Using a modified Mankin scoring system, we found significant glenohumeral cartilage damage after both rotator cuff tenotomy and suprascapular nerve transection after only 12 weeks. Results: Cartilage degeneration was similar between groups and was present on both the humeral head and the glenoid. Denervation of the supraspinatus and infraspinatus muscles without opening the joint capsule caused cartilage degeneration similar to that found in the tendon transection group. Conclusions: Our results suggest that altered mechanical loading after rotator cuff tears is the primary factor in cartilage degeneration after rotator cuff tears. Clinically, understanding the process of cartilage degeneration after rotator cuff injury will help guide treatment decisions in the setting of rotator cuff tears. (C) 2013 Journal of Shoulder and Elbow Surgery Board of Trustees. C1 [Kramer, Erik J.; Bodendorfer, Blake M.; Wong, Jason; Kim, Hubert T.; Liu, Xuhui] San Francisco VA Med Ctr, Dept Vet Affairs, San Francisco, CA USA. [Kramer, Erik J.; Laron, Dominique; Kim, Hubert T.; Liu, Xuhui; Feeley, Brian T.] Univ Calif San Francisco, Dept Orthopaed Surg, San Francisco, CA USA. RP Feeley, BT (reprint author), Dept Orthopaed Surg, 1500 Owens Ave,Box 3004, San Francisco, CA 94158 USA. EM feeleyb@orthosurg.ucsf.edu FU Orthopaedic Research and Educational Foundation (Young Investigator Grant); National Institutes of Health [R03-AR060871-02] FX Funding was provided by grants from the Orthopaedic Research and Educational Foundation (Young Investigator Grant) and National Institutes of Health (R03-AR060871-02). NR 17 TC 4 Z9 4 U1 0 U2 5 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 1058-2746 J9 J SHOULDER ELB SURG JI J. Shoulder Elbow Surg. PD DEC PY 2013 VL 22 IS 12 BP 1702 EP 1709 DI 10.1016/j.jse.2013.03.014 PG 8 WC Orthopedics; Sport Sciences; Surgery SC Orthopedics; Sport Sciences; Surgery GA 258VJ UT WOS:000327486500022 PM 23664745 ER PT J AU Gros, DF Milanak, ME Hershenberg, R AF Gros, Daniel F. Milanak, Melissa E. Hershenberg, Rachel TI CONVERGENCE OF DEPRESSION AND ANXIETY SYMPTOMS IN FRIENDSHIP DYADS SO JOURNAL OF SOCIAL AND CLINICAL PSYCHOLOGY LA English DT Article ID SOCIAL PHOBIA INVENTORY; STATE-TRAIT INVENTORY; SELF-OTHER AGREEMENT; PSYCHOMETRIC PROPERTIES; INFORMANT-REPORTS; CLINICAL-RESEARCH; PERSONALITY; VALIDATION; DISORDERS; RATINGS AB Despite psychometric rationale to include multiple informants, psychological assessment typically involves data collected from the patient (target) only, particularly with regard to depressive and anxious symptomatology. This study addressed this gap in the literature by assessing convergence between targets and their close friends (informants) in an ethnically diverse sample of young adults. One hundred and thirty-nine friendship dyads completed a packet of questionnaires including different versions administered to the targets and informants, with targets completing the standard questionnaire battery focused on their own symptoms and informants completing questionnaires on their view of the target participants' symptoms, rather than their own characteristics. Measures were included to assess a wide range of symptomatology, including behavioral, cognitive, and physiological symptoms of anxiety and depression. The target-informant correlations were largely significant and of small-to-medium magnitude. In addition, target-informant agreement was higher in more visible symptoms (e. g., behavioral) than in less visible symptoms (e. g., physiological) of anxiety and depression. Interestingly, level of closeness in the relationship did not influence the magnitude of correlations. Implications for future research and integration into clinical assessment practices are discussed. C1 Ralph H Johnson VA Med Ctr, Charleston, SC USA. Med Univ S Carolina, Charleston, SC USA. RP Gros, DF (reprint author), Ralph H Johnson VAMC, Mental Hlth Serv 116, 109 Bee St, Charleston, SC 29401 USA. EM grosd@musc.edu FU NIMH NIH HHS [T32 MH018869] NR 44 TC 3 Z9 3 U1 16 U2 18 PU GUILFORD PUBLICATIONS INC PI NEW YORK PA 72 SPRING STREET, NEW YORK, NY 10012 USA SN 0736-7236 J9 J SOC CLIN PSYCHOL JI J. Soc. Clin. Psychol. PD DEC PY 2013 VL 32 IS 10 BP 1061 EP 1074 PG 14 WC Psychology, Clinical; Psychology, Social SC Psychology GA 263NJ UT WOS:000327815000003 PM 25089072 ER PT J AU Eklund, K Marianos, D AF Eklund, Kathy Marianos, Donald TI Providing a safe environment for dental care in an era of infectious diseases SO JOURNAL OF THE AMERICAN DENTAL ASSOCIATION LA English DT Editorial Material C1 [Eklund, Kathy] Forsyth Inst, Cambridge, MA 02142 USA. [Marianos, Donald] OSAP Fdn, Annapolis, MD USA. RP Eklund, K (reprint author), Forsyth Inst, 245 1st St, Cambridge, MA 02142 USA. EM keklund@forsyth.org NR 6 TC 0 Z9 0 U1 0 U2 1 PU AMER DENTAL ASSOC PI CHICAGO PA 211 E CHICAGO AVE, CHICAGO, IL 60611 USA SN 0002-8177 EI 1943-4723 J9 J AM DENT ASSOC JI J. Am. Dent. Assoc. PD DEC PY 2013 VL 144 IS 12 BP 1330 EP 1332 PG 3 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 262JV UT WOS:000327731900001 PM 24282257 ER PT J AU Bryan, RG Oliveira, GR Walker, TG AF Bryan, Roy G., Jr. Oliveira, George R. Walker, T. Gregory TI Hot Quadrate SO JOURNAL OF VASCULAR AND INTERVENTIONAL RADIOLOGY LA English DT Editorial Material C1 [Bryan, Roy G., Jr.; Oliveira, George R.; Walker, T. Gregory] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02215 USA. RP Bryan, RG (reprint author), Massachusetts Gen Hosp, Dept Radiol, 55 Fruit St, Boston, MA 02215 USA. EM rgbryan@partners.org 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 1051-0443 EI 1535-7732 J9 J VASC INTERV RADIOL JI J. Vasc. Interv. Radiol. PD DEC PY 2013 VL 24 IS 12 BP 1835 EP 1835 DI 10.1016/j.jvir.2013.04.022 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging; Peripheral Vascular Disease SC Radiology, Nuclear Medicine & Medical Imaging; Cardiovascular System & Cardiology GA 263KY UT WOS:000327808700011 PM 24267521 ER PT J AU Segal, E Weinberg, I Leichter, I Klimov, A Giri, J Bloom, AI AF Segal, Einat Weinberg, Ido Leichter, Isaac Klimov, Alexander Giri, Jay Bloom, Allan I. TI Patient radiation exposure during percutaneous endovascular revascularization of the lower extremity SO JOURNAL OF VASCULAR SURGERY LA English DT Article ID DOSE-AREA PRODUCT; INTERVENTIONAL RADIOLOGY; VASCULAR RADIOLOGY; ANGIOGRAPHY; INJURY; IMPLANTATION; ARTERIES; STAFF; UNITS; RISK AB Background: Percutaneous endovascular revascularization is emerging as the first line treatment for peripheral artery disease for both intermittent claudication and chronic critical limb ischemia. Radiation doses for these interventions have not been well documented. Methods: A single center retrospective study of therapeutic endovascular lower extremity interventions performed between September 2006 and December 2011 was undertaken. Collected data included patient demographics, procedure indication, procedural access, anatomic location of occlusive disease (pelvis, thigh, below-knee, or multilevel), and radiation exposure parameters including dose area product (DAP) and fluoroscopy time. Results: Data was available for 382 procedures performed in 313 patients. Eighteen procedures bilateral procedures were excluded. Access site and complete anatomic data were available for 346 procedures. DAP was significantly higher for procedures performed in the pelvis compared with thigh procedures (179.6 vs 63.2 Gy*cm(2); P < .0001) and below-knee procedures (179.6 vs 28.9 Gy*cm(2); P < .0001), despite shorter fluoroscopy times (11.8 vs 16.4 minutes; P < .0001 and 11.1 vs 31.06 minutes; P < .0001, respectively). Procedure access-site affected radiation dose as well; contralateral up-and-over access resulted in a higher DAP than antegrade access (112.2 vs 42.6 Gy*cm(2); P < .0001). In a multivariable analysis, anatomic location of the procedure showed the strongest association with radiation dose (P < .0001). Conclusions: Percutaneous endovascular revascularization for lower extremity peripheral artery disease involves a substantial radiation dose, comparable, on average, to a computed tomography scan of the abdomen and pelvis. Procedures performed in the pelvis for intermittent claudication involve more radiation than thigh or below-knee procedures for chronic critical limb ischemia. Radiation dose should be considered when planning these procedures. C1 [Segal, Einat; Weinberg, Ido] Hadassah Hebrew Univ, Med Ctr, Div Med, Jerusalem, Israel. [Leichter, Isaac; Klimov, Alexander; Bloom, Allan I.] Hadassah Hebrew Univ, Med Ctr, Dept Radiol, Jerusalem, Israel. [Weinberg, Ido] Massachusetts Gen Hosp, Vasc Med Sect, Boston, MA 02114 USA. [Giri, Jay] Univ Penn, Div Cardiovasc Med, Philadelphia, PA 19104 USA. RP Weinberg, I (reprint author), Massachusetts Gen Hosp, Vasc Med Sect, 55 Fruit St,GB 800, Boston, MA 02114 USA. EM iweinberg@partners.org NR 38 TC 3 Z9 3 U1 0 U2 1 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0741-5214 J9 J VASC SURG JI J. Vasc. Surg. PD DEC PY 2013 VL 58 IS 6 BP 1556 EP 1562 DI 10.1016/j.jvs.2013.06.016 PG 7 WC Surgery; Peripheral Vascular Disease SC Surgery; Cardiovascular System & Cardiology GA 261KF UT WOS:000327663100017 PM 23891487 ER PT J AU Oklu, R Albadawi, H Jones, JE Yoo, HJ Watkins, MT AF Oklu, Rahmi Albadawi, Hassan Jones, John E. Yoo, Hyung-Jin Watkins, Michael T. TI Reduced hind limb ischemia-reperfusion injury in Toll-like receptor-4 mutant mice is associated with decreased neutrophil extracellular traps SO JOURNAL OF VASCULAR SURGERY LA English DT Article ID HEPATIC ISCHEMIA/REPERFUSION INJURY; DEEP-VEIN THROMBOSIS; SERINE PROTEASES; NADPH OXIDASE; MOUSE MODEL; IN-VITRO; TLR4; INHIBITION; EXPRESSION; HISTONES AB Objective: Ischemia-reperfusion (IR) injury is a significant problem in the management of patients with acute limb ischemia. Despite rapid restoration of blood flow after technically successful open and endovascular revascularization, complications secondary to IR injury continue to occur and limit clinical success. Our aim was to create a murine model of hind limb IR injury to examine the role of Toll-like receptor-4 (TLR4) and to determine whether inactive TLR4 led to a decrease in the detection of neutrophil extracellular traps (NETs), which are known to be highly thrombogenic and may mediate microvascular injury. Methods: A calibrated tension tourniquet was applied to unilateral hind limb of wild-type (WT) and TLR4 receptor mutant (TLR4m) mice for 1.5 hours to induce ischemia and then removed to initiate reperfusion. At the end of 48 hours of reperfusion, mice were euthanized and hind limb tissue and serum specimens were collected for analysis. Hematoxylin and eosin-stained sections of hind limb skeletal muscle tissue were examined for fiber injury. For immunohistochemistry, mouse monoclonal antihistone H2A/H2B/DNA complex antibody to detect NETs and rabbit polyclonal anti-myeloperoxidase antibody were used to identify infiltrating cells containing myeloperoxidase. Muscle adenosine triphosphate levels, nuclear factor (NF)-kappa B activity, the alpha-subunit of inhibitor of NF-kappa B light polypeptide gene enhancer, poly (adenosine diphosphate-ribose) polymerase activity, and inducible nitric oxide synthase expression were measured. Systemic levels of keratinocyte-derived chemokine, monocyte chemotactic protein-1, and vascular endothelial growth factor in the serum samples were also examined. Results: IR injury in the hind limb of WT mice demonstrated significant levels of muscle fiber injury, decreased energy substrates, increased NF-kappa B activation, decreased levels of alpha-subunit of inhibitor of NF-kappa B light polypeptide gene enhancer, increased inducible nitric oxide synthase expression, and increased poly (adenosine diphosphate-ribose) polymerase activity levels compared with the TLR4m samples. Additionally, there was marked decrease in the level of neutrophil and monocyte infiltration in the TLR4m mice, which corresponded to similar levels of decreased NET detection in the interstitial space and in microvascular thrombi. In situ nuclease treatment of WT tissue sections significantly diminished the level of NET immunostaining, demonstrating the specificity of the antibody to detect NETs and suggesting a potential role for nuclease treatment in IR injury. Conclusions: These results suggest a pivotal role for TLR4 in mediating hind limb IR injury and suggest that NETs may contribute to muscle fiber injury. C1 [Oklu, Rahmi] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Div Vasc Imaging & Intervent, Cambridge, MA 02138 USA. [Albadawi, Hassan; Jones, John E.; Yoo, Hyung-Jin; Watkins, Michael T.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Div Vasc & Endovasc Surg, Cambridge, MA 02138 USA. RP Watkins, MT (reprint author), Massachusetts Gen Hosp, Div Vasc & Endovasc Surg, 15 Parkman St,Ste 440, Boston, MA 02114 USA. EM mtwatkins@partners.org FU National Institutes of Health [RO1-AR-055843]; Pacific Vascular Research Foundation; Department of Surgery, Division of Vascular and Endovascular Surgery (The Rosenberg Fund); American College of Phlebology; Department of Radiology, Division of Vascular Imaging and Intervention FX M.T.W. is the Isenberg Scholar in Academic Surgery at the Massachusetts General Hospital. This study was supported by National Institutes of Health Grant RO1-AR-055843 (M.T.W.), the Pacific Vascular Research Foundation, and the Department of Surgery, Division of Vascular and Endovascular Surgery (The Rosenberg Fund). R.O. is funded by the American College of Phlebology and the Department of Radiology, Division of Vascular Imaging and Intervention. NR 40 TC 15 Z9 15 U1 0 U2 9 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0741-5214 J9 J VASC SURG JI J. Vasc. Surg. PD DEC PY 2013 VL 58 IS 6 BP 1627 EP 1636 DI 10.1016/j.jvs.2013.02.241 PG 10 WC Surgery; Peripheral Vascular Disease SC Surgery; Cardiovascular System & Cardiology GA 261KF UT WOS:000327663100026 PM 23683381 ER PT J AU Hage, FG Mansur, SJ Xing, DQ Oparil, S AF Hage, Fadi G. Mansur, Sulaf J. Xing, Dongqi Oparil, Suzanne TI Hypertension in women SO KIDNEY INTERNATIONAL SUPPLEMENTS LA English DT Article DE antihypertensive treatment; hypertension; oral contraceptives; preeclampsia; pregnancy-related hypertension; women ID AMERICAN-HEART-ASSOCIATION; LIPID-LOWERING TREATMENT; BLOOD-PRESSURE; MILD HYPERTENSION; OUTCOMES; TRIAL; DISEASE; MEN; PREVENTION; GUIDELINES AB Hypertension is the most common modifiable risk factor for cardiovascular disease, the leading cause of death in both men and women. The prevalence and severity of hypertension rise markedly with age, and blood pressure control becomes more difficult with aging in both genders, particularly in women. In addition, there are forms of hypertension that occur exclusively in women, e.g., hypertension related to menopause, oral contraceptive use, or pregnancy (e.g., chronic hypertension, gestational hypertension, pre-eclampsia or eclampsia). Randomized controlled trials show that antihypertensive therapy provides similar reductions in major cardiovascular events in men and women. Therefore, gender should not influence decisions on selection of blood pressure lowering therapies, except for consideration of gender-specific side effects or contraindications for use in women who are or may become pregnant. This article reviews the prevalence, awareness, treatment, and control of hypertension in women, as well as recent guidelines for management of hypertension in women. C1 [Hage, Fadi G.; Xing, Dongqi; Oparil, Suzanne] Univ Alabama Birmingham, Div Cardiovasc Dis, Birmingham, AL 35294 USA. [Hage, Fadi G.] Birmingham Vet Affairs Med Ctr, Cardiol Sect, Birmingham, LA USA. [Mansur, Sulaf J.] Princeton Baptist Med Ctr, Birmingham, AL USA. RP Hage, FG (reprint author), Univ Alabama Birmingham, Div Cardiovasc Dis, Zeigler Res Bldg 1024,703 19th St South, Birmingham, AL 35294 USA. EM fadihage@uab.edu OI Hage, Fadi/0000-0002-1397-4942 FU American Heart Association; US Department Veterans Affairs Merit Award; Duke University (AstraZeneca AB); Daiichi Sankyo; Medtronic; Merck Co.; National Institutes of Health/National Heart, Lung, and Blood Institute (NHLBI); Novartis AG; Takeda Global Research Development; UAB Comprehensive Cardiovascular Center; Vivus; Turkish Society of Hypertension and Renal Diseases FX FGH has received grant support from the American Heart Association and a US Department Veterans Affairs Merit Award. SO has received research support from Duke University (Sponsor: AstraZeneca AB), Daiichi Sankyo, Medtronic, Merck & Co., National Institutes of Health/National Heart, Lung, and Blood Institute (NHLBI), Novartis AG, Takeda Global Research & Development, UAB Comprehensive Cardiovascular Center, and Vivus, and has served as PI or Co-PI for clinical trials with Duke University, Merck & Co., Novartis, and Takeda Global Research & Development. SO received honoraria in her capacity as Faculty Presenter for the American Society of Hypertension sponsored by Daiichi Sankyo, and served as advisor for Bayer, Daiichi Sankyo, Novartis, Pfizer, and Takeda. Publication costs for this article were supported by the Turkish Society of Hypertension and Renal Diseases, a nonprofit national organization in Turkey. NR 25 TC 5 Z9 5 U1 1 U2 3 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 2157-1724 EI 2157-1716 J9 KIDNEY INT SUPPL JI Kidney Int. Suppl. PD DEC PY 2013 VL 3 IS 4 BP 352 EP 356 DI 10.1038/kisup.2013.76 PG 5 WC Urology & Nephrology SC Urology & Nephrology GA 264NI UT WOS:000327884500014 PM 25028640 ER PT J AU Nigwekar, SU Thadhani, R AF Nigwekar, Sagar U. Thadhani, Ravi TI Vitamin D receptor activation: cardiovascular and renal implications SO KIDNEY INTERNATIONAL SUPPLEMENTS LA English DT Review DE chronic kidney disease; end-stage renal disease; hypertension; left ventricular hypertrophy; vitamin D; vitamin D-binding protein ID CHRONIC KIDNEY-DISEASE; RANDOMIZED CONTROLLED-TRIAL; 1,25-DIHYDROXYVITAMIN D-3; VASCULAR CALCIFICATION; HEART-FAILURE; D DEFICIENCY; HEMODIALYSIS; HYPERTROPHY; ASSOCIATION; PARICALCITOL AB The effects of vitamin D receptor activation on cardiovascular diseases, especially hypertension and cardiac dysfunction, are areas of active investigation. This article reviews the current state of knowledge about vitamin D receptor activation with respect to blood pressure, heart, and vascular health, as well as to chronic kidney disease and end-stage renal disease. Potential biological mechanisms, the role of vitamin D-binding protein, and data from observational and randomized controlled trials on this topic are summarized. C1 [Nigwekar, Sagar U.; Thadhani, Ravi] Massachusetts Gen Hosp, Div Nephrol, Boston, MA 02114 USA. RP Nigwekar, SU (reprint author), Massachusetts Gen Hosp, Div Nephrol, 55 Fruit St,GRB 1008 G, Boston, MA 02114 USA. EM sagarnigs@gmail.com FU Japanese Society for Dialysis Therapy FX This supplement was supported by a grant from the 58th Annual Meeting of the Japanese Society for Dialysis Therapy. NR 31 TC 7 Z9 8 U1 0 U2 7 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 2157-1724 EI 2157-1716 J9 KIDNEY INT SUPPL JI Kidney Int. Suppl. PD DEC PY 2013 VL 3 IS 5 BP 427 EP 430 DI 10.1038/kisup.2013.89 PG 4 WC Urology & Nephrology SC Urology & Nephrology GA 264NM UT WOS:000327884900003 ER PT J AU Dowdell, S Grassberger, C Paganetti, H AF Dowdell, Stephen Grassberger, Clemens Paganetti, Harald TI Four-dimensional Monte Carlo simulations demonstrating how the extent of intensity-modulation impacts motion effects in proton therapy lung treatments SO MEDICAL PHYSICS LA English DT Article ID SCANNED PARTICLE BEAMS; STATISTICAL-ANALYSIS; SPOT SIZE; INTERPLAY; DELIVERY; RADIOTHERAPY; PARAMETERS; TARGETS; TUMOR AB Purpose: To compare motion effects in intensity modulated proton therapy (IMPT) lung treatments with different levels of intensity modulation. Methods: Spot scanning IMPT treatment plans were generated for ten lung cancer patients for 2.5Gy(RBE) and 12Gy(RBE) fractions and two distinct energy-dependent spot sizes (sigma similar to 8-17 mm and similar to 2-4 mm). IMPT plans were generated with the target homogeneity of each individual field restricted to <20% (IMPT20%). These plans were compared to full IMPT (IMPTfull), which had no restriction on the single field homogeneity. 4D Monte Carlo simulations were performed upon the patient 4DCT geometry, including deformable image registration and incorporating the detailed timing structure of the proton delivery system. Motion effects were quantified via comparison of the results of the 4D simulations (4D-IMPT20%, 4D-IMPTfull) with those of a 3D Monte Carlo simulation (3D-IMPT20%, 3D-IMPTfull) upon the planning CT using the equivalent uniform dose (EUD), V-95 and D-1-D-99. The effects in normal lung were quantified using mean lung dose (MLD) and V-90%. Results: For 2.5Gy(RBE), the mean EUD for the large spot size is 99.9% +/- 2.8% for 4D-IMPT20% compared to 100.1% +/- 2.9% for 4D-IMPTfull. The corresponding values are 88.6% +/- 8.7% (4D-IMPT20%) and 91.0% +/- 9.3% (4D-IMPTfull) for the smaller spot size. The EUD value is higher in 69.7% of the considered deliveries for 4D-IMPTfull. The V-95 is also higher in 74.7% of the plans for 4D-IMPTfull, implying that IMPTfull plans experience less underdose compared to IMPT20%. However, the target dose homogeneity is improved in the majority (67.8%) of plans for 4D-IMPT20%. The higher EUD and V-95 suggests that the degraded homogeneity in IMPTfull is actually due to the introduction of hot spots in the target volume, perhaps resulting from the sharper in-target dose gradients. The greatest variations between the IMPT20% and IMPTfull deliveries are observed for patients with the largest motion amplitudes. These patients would likely be treated using gating or another motion mitigation technique, which was not the focus of this study. Conclusions: For the treatment parameters considered in this study, the differences between IMPTfull and IMPT20% are only likely to be clinically significant for patients with large (>20 mm) motion amplitudes. (C) 2013 American Association of Physicists in Medicine. C1 [Dowdell, Stephen; Grassberger, Clemens; Paganetti, Harald] Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. [Dowdell, Stephen; Grassberger, Clemens; Paganetti, Harald] Harvard Univ, Sch Med, Boston, MA 02114 USA. [Grassberger, Clemens] Paul Scherrer Inst, Ctr Proton Therapy, CH-5232 Villigen, Switzerland. RP Dowdell, S (reprint author), Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. EM sdowdell@mgh.harvard.edu FU NIH/NCI [R01 CA111590] FX This project was supported by NIH/NCI Grant No. R01 CA111590. NR 21 TC 5 Z9 5 U1 1 U2 7 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 DEC PY 2013 VL 40 IS 12 AR UNSP 121713 DI 10.1118/1.4829500 PG 9 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 266NQ UT WOS:000328031300015 PM 24320499 ER PT J AU Testa, M Schumann, J Lu, HM Shin, J Faddegon, B Perl, J Paganetti, H AF Testa, M. Schuemann, J. Lu, H. -M. Shin, J. Faddegon, B. Perl, J. Paganetti, H. TI Experimental validation of the TOPAS Monte Carlo system for passive scattering proton therapy SO MEDICAL PHYSICS LA English DT Article DE Monte Carlo simulations; proton therapy; passive scattering ID VIVO RANGE VERIFICATION; BRAGG PEAK FIELDS; NUCLEAR-MODELS; QUALITY-ASSURANCE; DOSE CALCULATION; GEANT4; SIMULATIONS; DOSIMETRY; TOOLKIT AB Purpose: TOPAS (TOol for PArticle Simulation) is a particle simulation code recently developed with the specific aim of making Monte Carlo simulations user-friendly for research and clinical physicists in the particle therapy community. The authors present a thorough and extensive experimental validation of Monte Carlo simulations performed with TOPAS in a variety of setups relevant for proton therapy applications. The set of validation measurements performed in this work represents an overall end-to-end testing strategy recommended for all clinical centers planning to rely on TOPAS for quality assurance or patient dose calculation and, more generally, for all the institutions using passive-scattering proton therapy systems. Methods: The authors systematically compared TOPAS simulations with measurements that are performed routinely within the quality assurance (QA) program in our institution as well as experiments specifically designed for this validation study. First, the authors compared TOPAS simulations with measurements of depth-dose curves for spread-out Bragg peak (SOBP) fields. Second, absolute dosimetry simulations were benchmarked against measured machine output factors (OFs). Third, the authors simulated and measured 2D dose profiles and analyzed the differences in terms of field flatness and symmetry and usable field size. Fourth, the authors designed a simple experiment using a half-beam shifter to assess the effects of multiple Coulomb scattering, beam divergence, and inverse square attenuation on lateral and longitudinal dose profiles measured and simulated in a water phantom. Fifth, TOPAS' capabilities to simulate time dependent beam delivery was benchmarked against dose rate functions (i.e., dose per unit time vs time) measured at different depths inside an SOBP field. Sixth, simulations of the charge deposited by protons fully stopping in two different types of multilayer Faraday cups (MLFCs) were compared with measurements to benchmark the nuclear interaction models used in the simulations. Results: SOBPs' range and modulation width were reproduced, on average, with an accuracy of +1, -2 and +/- 3 mm, respectively. OF simulations reproduced measured data within +/- 3%. Simulated 2D dose-profiles show field flatness and average field radius within +/- 3% of measured profiles. The field symmetry resulted, on average in +/- 3% agreement with commissioned profiles. TOPAS accuracy in reproducing measured dose profiles downstream the half beam shifter is better than 2%. Dose rate function simulation reproduced the measurements within similar to 2% showing that the four-dimensional modeling of the passively modulation system was implement correctly and millimeter accuracy can be achieved in reproducing measured data. For MLFCs simulations, 2% agreement was found between TOPAS and both sets of experimental measurements. The overall results show that TOPAS simulations are within the clinical accepted tolerances for all QA measurements performed at our institution. Conclusions: Our Monte Carlo simulations reproduced accurately the experimental data acquired through all the measurements performed in this study. Thus, TOPAS can reliably be applied to quality assurance for proton therapy and also as an input for commissioning of commercial treatment planning systems. This work also provides the basis for routine clinical dose calculations in patients for all passive scattering proton therapy centers using TOPAS. (C) 2013 American Association of Physicists in Medicine. C1 [Testa, M.; Schuemann, J.; Lu, H. -M.; Paganetti, H.] Harvard Univ, Sch Med, Dept Radiat Oncol, Massachusetts Gen Hosp, Boston, MA 02114 USA. [Shin, J.; Faddegon, B.] Univ Calif San Francisco, Ctr Comprehens Canc, San Francisco, CA 94143 USA. [Perl, J.] SLAC Natl Accelerator Lab, Menlo Pk, CA 94025 USA. RP Testa, M (reprint author), Harvard Univ, Sch Med, Dept Radiat Oncol, Massachusetts Gen Hosp, Boston, MA 02114 USA. EM hpaganetti@partners.org FU NCI [R01-CA140735, P01-CA21239] FX This work was supported by NCI Grant Nos. R01-CA140735 and P01-CA21239. NR 26 TC 24 Z9 24 U1 2 U2 13 PU AMER ASSOC PHYSICISTS MEDICINE AMER INST PHYSICS PI MELVILLE PA STE 1 NO 1, 2 HUNTINGTON QUADRANGLE, MELVILLE, NY 11747-4502 USA SN 0094-2405 J9 MED PHYS JI Med. Phys. PD DEC PY 2013 VL 40 IS 12 AR 121719 DI 10.1118/1.4828781 PG 16 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 266NQ UT WOS:000328031300021 PM 24320505 ER PT J AU Ushiku, T Arnason, T Ban, S Hishima, T Shimizu, M Fukayama, M Lauwers, GY AF Ushiku, Tetsuo Arnason, Thomas Ban, Shinichi Hishima, Tsunekazu Shimizu, Michio Fukayama, Masashi Lauwers, Gregory Y. TI Very well-differentiated gastric carcinoma of intestinal type: analysis of diagnostic criteria SO MODERN PATHOLOGY LA English DT Article DE gastric cancer; immunophenotype; very well differentiated ID ADENOCARCINOMA; STOMACH; CANCER; CHROMOENDOSCOPY AB Very well-differentiated gastric adenocarcinoma of intestinal type is a rare variant of gastric cancer characterized by low-grade nuclear atypia, and for which the diagnostic criteria and clinical behavior are not fully established. This study presents a detailed histologic, immunohistochemical, and clinical analysis of 21 cases. Nuclear atypia was mild in all cases. Characteristic architectural features of this gastric adenocarcinoma variant were pit and glandular anastomosis, spiky glands, distended glands, discohesive cells, abortive glands, and glandular outgrowth. At least three of these features were present in all the cases. Retrospective review of preoperative biopsies in 18 patients revealed that half of the biopsies were originally reported as negative or indeterminate for malignancy. On the basis of immunohistochemical stains for intestinal (MUC2, CD10, and CDX-2) and gastric (MUC5AC and MUC6) markers, 11(52%) cases had an intestinal immunophenotype and 10 (48%) cases had a mixed immunophenotype. Foci of discohesive neoplastic cells, indicating dedifferentiation toward a poorly cohesive carcinoma, were observed exclusively in neoplasms of mixed immunophenotype (n=5). All patients with follow-up but one were alive without disease at a mean of 19 months (range 1-60 months). One individual with a pT4 tumor with associated poorly cohesive carcinoma died of disease. In summary, very well-differentiated gastric adenocarcinomas are diagnostically challenging. Architectural features are critical to making the diagnosis. Cases with pure intestinal immunophenotype have not been associated with transformation into poorly cohesive carcinoma, and appear to behave as biologically low grade. Those with mixed immunophenotype appear more likely to dedifferentiate and behave more aggressively. C1 [Ushiku, Tetsuo; Arnason, Thomas; Lauwers, Gregory Y.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Ushiku, Tetsuo; Fukayama, Masashi] Univ Tokyo, Dept Pathol, Tokyo 1130033, Japan. [Ban, Shinichi] Saiseikai Kawaguchi Gen Hosp, Dept Pathol, Kawaguchi, Saitama, Japan. [Hishima, Tsunekazu] Tokyo Metropolitan Komagome Hosp, Dept Pathol, Tokyo, Japan. [Shimizu, Michio] Saitama Med Univ, Dept Pathol, Int Med Ctr, Hidaka City, Saitama, Japan. RP Ushiku, T (reprint author), Univ Tokyo, Dept Pathol, Bunkyo Ku, 7-3-1 Hongo, Tokyo 1130033, Japan. EM usikut-tky@umin.ac.jp FU Ministry of Education, Culture, Sports, Science and Technology of Japan [23790390]; Royal College of Physicians and Surgeons of Canada; Dalhousie University FX This work was partly supported by Grants-in-Aid for Young Scientists (B) 23790390 from The Ministry of Education, Culture, Sports, Science and Technology of Japan. Dr Arnason's fellowship funding was provided through scholarships from the Royal College of Physicians and Surgeons of Canada (Detweiler Traveling Fellowship) and Dalhousie University (McLoughlin Scholarship). NR 11 TC 5 Z9 5 U1 0 U2 2 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0893-3952 EI 1530-0285 J9 MODERN PATHOL JI Mod. Pathol. PD DEC PY 2013 VL 26 IS 12 BP 1620 EP 1631 DI 10.1038/rnodpathol.2013.98 PG 12 WC Pathology SC Pathology GA 266GS UT WOS:000328012700010 PM 23723017 ER PT J AU Kong, J Zhu, XD Shi, YY Liu, TJ Chen, YZ Bhan, I Zhao, Q Thadhani, R Li, YC AF Kong, Juan Zhu, Xiangdong Shi, Yongyan Liu, Tianjing Chen, Yunzi Bhan, Ishir Zhao, Qun Thadhani, Ravi Li, Yan Chun TI VDR Attenuates Acute Lung Injury by Blocking Ang-2-Tie-2 Pathway and Renin-Angiotensin System SO MOLECULAR ENDOCRINOLOGY LA English DT Article ID VITAMIN-D-RECEPTOR; LIGHT-CHAIN PHOSPHORYLATION; SMOOTH-MUSCLE-CELLS; 1,25-DIHYDROXYVITAMIN D-3; DIABETIC-NEPHROPATHY; GAP FORMATION; MICE; EXPRESSION; ASTHMA; LIPOPOLYSACCHARIDE AB Acute lung injury (ALI) is a hallmark of systemic inflammation associated with high mortality. Although the vitamin D receptor (VDR) is highly expressed in the lung, its role in lung physiology remains unclear. We investigated the effect of VDR deletion on ALI using a lipopolysaccharide (LPS)-induced sepsis model. After LPS challenge VDR-null mice exhibited more severe ALI and higher mortality compared with wild-type (WT) counterparts, manifested by increased pulmonary vascular leakiness, pulmonary edema, apoptosis, neutrophil infiltration, and pulmonary inflammation, which was accompanied by excessive induction of angiopoietin (Ang)-2 and myosin light chain (MLC) phosphorylation in the lung. 1,25-Dihydroxyvitamin D blocked LPS-induced Ang-2 expression by blocking nuclear factor-kappa B activation in human pulmonary artery endothelial cells. The severity of lung injury seen in VDR-null mice was ameliorated by pretreatment with L1-10, an antagonist of Ang-2, suggesting that VDR signaling protects the pulmonary vascular barrier by targeting the Ang-2-Tie-2-MLC kinase cascade. Severe ALI in VDR-null mice was also accompanied by an increase in pulmonary renin and angiotensin II levels, and pretreatment of VDR-null mice with angiotensin II type 1 receptor blocker losartan partially ameliorated the severity of LPS-induced lung injury. Taken together, these observations provide evidence that the vitamin D-VDR signaling prevents lung injury by blocking the Ang-2-Tie-2-MLC kinase cascade and the renin-angiotensin system. C1 [Kong, Juan; Zhu, Xiangdong; Shi, Yongyan; Liu, Tianjing; Chen, Yunzi; Li, Yan Chun] Univ Chicago, Dept Med, Div Biol Sci, Chicago, IL 60637 USA. [Kong, Juan; Chen, Yunzi; Li, Yan Chun] China Med Univ, Shengjing Hosp, Lab Metab Dis Res & Drug Dev, Shenyang 110000, Peoples R China. [Shi, Yongyan] China Med Univ, Shengjing Hosp, Dept Pediat, Shenyang 110000, Peoples R China. [Liu, Tianjing; Zhao, Qun] China Med Univ, Shengjing Hosp, Key Lab Congenital Malformat, Minist Hlth, Shenyang 110000, Peoples R China. [Bhan, Ishir; Thadhani, Ravi] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Nephrol, Boston, MA 02114 USA. RP Kong, J (reprint author), China Med Univ, Lab Metab Dis Res & Drug Dev, Shenyang 110000, Peoples R China. EM kong_juan@hotmail.com; thadhani.ravi@mgh.harvard.edu; cyan@medicine.bsd.uchicago.edu FU American Heart Association [10SDG4280066]; National Institutes of Health [R01HL085793, R01DK092143, R01DK84974]; CTSA from National Center for Research Resources [UL1 RR024999]; National Natural Science Foundation of China [30971401, 81170065] FX This work was supported by American Heart Association Scientist Development Grant 10SDG4280066 (to J.K.), National Institutes of Health grants R01HL085793 (to Y.C.L.), R01DK092143, and R01DK84974 (to R.T.), CTSA grant UL1 RR024999 from National Center for Research Resources, as well as by National Natural Science Foundation of China (Grants 30971401 and 81170065). NR 52 TC 7 Z9 8 U1 2 U2 16 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0888-8809 J9 MOL ENDOCRINOL JI Mol. Endocrinol. PD DEC PY 2013 VL 27 IS 12 BP 2116 EP 2125 DI 10.1210/me.2013-1146 PG 10 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 262LZ UT WOS:000327738200012 PM 24196349 ER PT J AU Lambert, JP Ivosev, G Couzens, AL Larsen, B Taipale, M Lin, ZY Zhong, Q Lindquist, S Vidal, M Aebersold, R Pawson, T Bonner, R Tate, S Gingras, AC AF Lambert, Jean-Philippe Ivosev, Gordana Couzens, Amber L. Larsen, Brett Taipale, Mikko Lin, Zhen-Yuan Zhong, Quan Lindquist, Susan Vidal, Marc Aebersold, Ruedi Pawson, Tony Bonner, Ron Tate, Stephen Gingras, Anne-Claude TI Mapping differential interactomes by affinity purification coupled with data-independent mass spectrometry acquisition SO NATURE METHODS LA English DT Article ID PROTEIN-PROTEIN INTERACTIONS; QUANTITATIVE-ANALYSIS; HSP90 CHAPERONE; B-RAF; MUTATIONS; PROTEOMICS; REVEALS; NETWORK; BINDING; KINASE AB Characterizing changes in protein-protein interactions associated with sequence variants (e. g., disease-associated mutations or splice forms) or following exposure to drugs, growth factors or hormones is critical to understanding how protein complexes are built, localized and regulated. Affinity purification (AP) coupled with mass spectrometry permits the analysis of protein interactions under near-physiological conditions, yet monitoring interaction changes requires the development of a robust and sensitive quantitative approach, especially for large-scale studies in which cost and time are major considerations. We have coupled AP to data-independent mass spectrometric acquisition (sequential window acquisition of all theoretical spectra, SWATH) and implemented an automated data extraction and statistical analysis pipeline to score modulated interactions. We used AP-SWATH to characterize changes in protein-protein interactions imparted by the HSHSP90 inhibitor NVP-AUY922 or melanoma-associated mutations in the human kinase CDCDK4. We show that AP-SWATH is a robust label-free approach to characterize such changes and propose a scalable pipeline for systems biology studies. C1 [Lambert, Jean-Philippe; Couzens, Amber L.; Larsen, Brett; Lin, Zhen-Yuan; Pawson, Tony; Gingras, Anne-Claude] Mt Sinai Hosp, Lunenfeld Tanenbaum Res Inst, Toronto, ON M5G 1X5, Canada. [Ivosev, Gordana; Bonner, Ron; Tate, Stephen] AB Sciex, Concord, ON, Canada. [Taipale, Mikko; Lindquist, Susan] Whitehead Inst Biomed Res, Cambridge, MA 02142 USA. [Zhong, Quan; Vidal, Marc] Dana Farber Canc Inst, CCSB, Boston, MA 02115 USA. [Zhong, Quan; Vidal, Marc] Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA. [Zhong, Quan; Vidal, Marc] Harvard Univ, Sch Med, Dept Genet, Boston, MA USA. [Lindquist, Susan] MIT, Dept Biol, Cambridge, MA USA. [Lindquist, Susan] Howard Hughes Med Inst, Cambridge, MA USA. [Aebersold, Ruedi] ETH, Inst Mol Syst Biol, Dept Biol, Zurich, Switzerland. [Aebersold, Ruedi] Univ Zurich, Fac Sci, Zurich, Switzerland. [Pawson, Tony; Gingras, Anne-Claude] Univ Toronto, Dept Mol Genet, Toronto, ON, Canada. RP Tate, S (reprint author), AB Sciex, Concord, ON, Canada. EM Stephen.Tate@absciex.com; gingras@lunenfeld.ca RI Pawson, Tony/E-4578-2013; Gingras, Anne-Claude/E-9982-2010; OI Gingras, Anne-Claude/0000-0002-6090-4437; Taipale, Mikko/0000-0003-3811-1761 FU Venture Sinai award; Canadian Institute of Health Research [MOP-84314]; US National Institutes of Health [5R01GM94231]; Ontario Research Fund via a Global Leadership Award Round 2; European Research Council [ERC-2008-AdG 233226]; SystemsX.ch, the Swiss Initiative for Systems Biology; US National Human Genome Research Institute [R01HG001715, P50HG004233]; US National Cancer Institute [R33CA132073]; Canada Research Chair in Functional Proteomics; Lea Reichmann Chair in Cancer Proteomics; Canadian Institutes of Health Research; Canadian National Sciences and Engineering Research Council FX We thank L. Taylor for input and initial SWATH data analysis, E. Polvi for help with subcloning, K. Colwill (Lunenfeld-Tanenbaum Research Institute) for the construction of pDEST-5'Triple-Flag-pcDNA5-FRT-TO and B. Raught for critical reading of the manuscript. The website for the supplementary material was designed by G. Liu and J.P. Zhang. This work was supported by a Venture Sinai award to A.-C.G.; the Canadian Institute of Health Research (to A.-C.G.; MOP-84314); the US National Institutes of Health (to A.-C.G.; 5R01GM94231); the Ontario Research Fund via a Global Leadership Award Round 2 (to T.P. and A.-C.G.).; the European Research Council (to R.A.; #ERC-2008-AdG 233226); SystemsX.ch, the Swiss Initiative for Systems Biology (to R.A.); the US National Human Genome Research Institute (to M.V.; R01HG001715 and P50HG004233) and the US National Cancer Institute (to M.V.; R33CA132073); a Canada Research Chair in Functional Proteomics and the Lea Reichmann Chair in Cancer Proteomics (to A.-C.G.).; and postdoctoral awards from the Canadian Institutes of Health Research and the Canadian National Sciences and Engineering Research Council postdoctoral award (to J.-P.L.). NR 43 TC 71 Z9 71 U1 7 U2 59 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1548-7091 EI 1548-7105 J9 NAT METHODS JI Nat. Methods PD DEC PY 2013 VL 10 IS 12 BP 1239 EP + DI 10.1038/NMETH.2702 PG 12 WC Biochemical Research Methods SC Biochemistry & Molecular Biology GA 261XN UT WOS:000327698100029 PM 24162924 ER PT J AU Strasser-Weippl, K Goss, PE AF Strasser-Weippl, Kathrin Goss, Paul E. TI Suitable trial designs and cohorts for preventive breast cancer agents SO NATURE REVIEWS CLINICAL ONCOLOGY LA English DT Review ID FINE-NEEDLE-ASPIRATION; SURGICAL ADJUVANT BREAST; SURROGATE END-POINTS; BOWEL PROJECT P-1; HIGH-RISK WOMEN; POSTMENOPAUSAL WOMEN; RANDOMIZED-TRIAL; MAMMOGRAPHIC DENSITIES; ENDOCRINE THERAPY; CONFER SUSCEPTIBILITY AB Effective chemoprevention of oestrogen receptor (ER)-positive breast cancer has been shown convincingly using several selective ER modulators and the aromatase inhibitor exemestane. Although these agents are well tolerated and the numbers needed-to-treat in the prevention setting are similar to other established preventive interventions, uptake has been poor in clinical practice because of difficulties in visualizing risk, predicting individual outcomes and measuring treatment benefit. In addition, new agents targeting ER-negative breast cancer are urgently needed. The development of new agents is hampered by the lack of suitable biomarkers and targets, as well as regulatory and financial considerations. Establishing breast cancer chemoprevention in standard clinical practice will require advances in many different fields, including biomarker research, the development of more powerful tools to predict and communicate the risks and benefits of treatments and establishing innovative trial designs. Furthermore, changes in regulatory procedures could reduce the size and cost of trials needed in the prevention setting. Identification of biomarkers for risk and efficacy that are easily accessible, such as blood-based biomarkers, will be key to future chemoprevention strategies. C1 [Strasser-Weippl, Kathrin] Wilhelminen Hosp, Ctr Oncol Hematol & Palliat Care, A-1160 Vienna, Austria. [Goss, Paul E.] Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA. RP Goss, PE (reprint author), Massachusetts Gen Hosp, Ctr Canc, 55 Fruit St,Lawrence House,LRH 302, Boston, MA 02114 USA. EM pgoss@partners.org NR 140 TC 3 Z9 3 U1 2 U2 6 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1759-4774 EI 1759-4782 J9 NAT REV CLIN ONCOL JI Nat. Rev. Clin. Oncol. PD DEC PY 2013 VL 10 IS 12 BP 677 EP 687 DI 10.1038/nrclinonc.2013.174 PG 11 WC Oncology SC Oncology GA 262RF UT WOS:000327754600003 PM 24101120 ER PT J AU De Cosmo, S Prudente, S Lamacchia, O Pucci, L Lucchesi, D Mendonca, C Bailetti, D Copetti, M Pellegrini, F Cignarelli, M Penno, G Doria, A Trischitta, V AF De Cosmo, Salvatore Prudente, Sabrina Lamacchia, Olga Pucci, Laura Lucchesi, Daniela Mendonca, Christine Bailetti, Diego Copetti, Massimiliano Pellegrini, Fabio Cignarelli, Mauro Penno, Giuseppe Doria, Alessandro Trischitta, Vincenzo TI The IRS1 G972R polymorphism and glomerular filtration rate in patients with type 2 diabetes of European ancestry SO NEPHROLOGY DIALYSIS TRANSPLANTATION LA English DT Article DE gene polymorphism; insulin-resistance; kidney dysfunction ID INSULIN SIGNALING GENES; KIDNEY DYSFUNCTION; RESISTANCE; VARIANT; DISEASE; ALBUMINURIA; ASSOCIATION; EQUATION; MELLITUS; LOCI AB In Mexican Americans, the IRS1 G972R polymorphism (rs1801278) has been associated to such a marked reduction in glomerular filtration rate (GFR) (i.e. 8.3 mL/min/1.73 m(2)) to be considered a major determinant of kidney function. This was a cross-sectional study to investigate whether a similarly strong effect can also be observed among individuals of European ancestry. We investigated a total of 3973 White patients with type 2 diabetes. Standardized serum creatinine was measured by the modified kinetic Jaff reaction and estimated GFR (eGFR) calculated by the modification diet renal disease (MDRD) formula; rs1801278 was genotyped by TaqMan assay. No significant association was observed, with R972 carriers showing only a modestly, not significant, lower eGFR level as compared with other subjects ( 1.82 mL/min/1.73 m(2), P 0.086). Our data indicate that IRS1 G972R is not a strong determinant of GFR in diabetic patients of European ancestry as in Mexican Americans. Since we had 100 power to detect the previously reported association, the risk our finding is a false negative one is minimal. C1 [De Cosmo, Salvatore] IRCCS Casa Sollievo Sofferenza, Clin Unit Endocrinol, San Giovanni Rotondo, Italy. [Prudente, Sabrina; Bailetti, Diego; Trischitta, Vincenzo] IRCCS Casa Sollievo Sofferenza, Mendel Lab, San Giovanni Rotondo, Italy. [Lamacchia, Olga; Cignarelli, Mauro] Univ Foggia, Dept Med & Surg Sci, Unit Endocrinol, Foggia, Italy. [Pucci, Laura; Lucchesi, Daniela; Penno, Giuseppe] Univ Pisa, Dept Cin & Expt Med, Pisa, Italy. [Mendonca, Christine; Doria, Alessandro] Joslin Diabet Ctr, Div Res, Boston, MA 02215 USA. [Copetti, Massimiliano; Pellegrini, Fabio] IRCCS Casa Sollievo Sofferenza, Biostat Unit, San Giovanni Rotondo, Italy. [Pellegrini, Fabio] Ist Ric Farmacol Mario Negri, Consorzio Mario Negri Sud, Biostat Unit, I-66030 Santa Maria Imbaro, Italy. [Doria, Alessandro] Harvard Univ, Sch Med, Boston, MA USA. [Trischitta, Vincenzo] IRCCS Casa Sollievo Sofferenza, Res Unit Diabet & Endocrine Dis, San Giovanni Rotondo, Italy. [Trischitta, Vincenzo] Univ Roma La Sapienza, Dept Expt Med, I-00185 Rome, Italy. RP De Cosmo, S (reprint author), IRCCS Casa Sollievo Sofferenza, Clin Unit Endocrinol, San Giovanni Rotondo, Italy. EM sdecosm@tin.it; vincenzo.trischitta@uniroma1.it RI Prudente, Sabrina/H-2886-2016; De Cosmo, Salvatore/J-7420-2016; Trischitta, Vincenzo/K-1487-2016; Copetti, Massimiliano/K-3186-2016; OI Prudente, Sabrina/0000-0001-9220-8981; De Cosmo, Salvatore/0000-0001-8787-8286; Trischitta, Vincenzo/0000-0003-1174-127X; Copetti, Massimiliano/0000-0002-7960-5947; PUCCI, LAURA/0000-0002-8162-4039 FU Italian Ministry of Health FX This study was partly supported by the Italian Ministry of Health ('Ricerca Corrente 2012 and 2013' to S. De Cosmo, S. Prudente, V. Trischitta and F. Pellegrini) and by the '5 x 1000' voluntary contribution (to S. De Cosmo, S. Prudente, V. Trischitta and F. Pellegrini). NR 24 TC 1 Z9 1 U1 0 U2 1 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0931-0509 EI 1460-2385 J9 NEPHROL DIAL TRANSPL JI Nephrol. Dial. Transplant. PD DEC PY 2013 VL 28 IS 12 BP 3031 EP 3034 DI 10.1093/ndt/gft325 PG 4 WC Transplantation; Urology & Nephrology SC Transplantation; Urology & Nephrology GA 263HP UT WOS:000327798600015 PM 24071662 ER PT J AU Manjila, S Cox, EM Smith, GA Corriveau, M Chhabra, N Johnson, F Geertman, RT AF Manjila, Sunil Cox, Efrem M. Smith, Gabriel A. Corriveau, Mark Chhabra, Nipun Johnson, Freedom Geertman, Robert T. TI Extracranial ligation of ethmoidal arteries before resection of giant olfactory groove or planum sphenoidale meningiomas: 3 illustrative cases with a review of the literature on surgical techniques SO NEUROSURGICAL FOCUS LA English DT Article DE skull base meningioma; olfactory groove; anterior ethmoidal artery; endoscopic ligation; posterior ethmoidal artery; embolization; microsurgical anatomy ID OCCLUSIONS FOLLOWING EMBOLIZATION; ENDOSCOPIC SINUS SURGERY; INTRACRANIAL MENINGIOMA; INTRACTABLE EPISTAXIS; FRONTAL SINUSITIS; LOTHROP PROCEDURE; ANTERIOR; ANATOMY; MANAGEMENT; ENDONASAL AB Object. There are several surgical techniques for reducing blood loss-open surgical and endoscopic-prior to resection of giant anterior skull base meningiomas, especially when preoperative embolization is risky or not technically feasible. The authors present examples of an institutional experience using surgical ligation of the anterior and posterior ethmoidal arteries producing persistent tumor blush in partially embolized tumors. Methods. The authors identified 12 patients who underwent extracranial surgical ligation of ethmoidal arteries through either a transcaruncular or a Lynch approach. Of these, 3 patients had giant olfactory groove or planum sphenoidale meningiomas. After approval from the institution privacy officer, the authors studied the medical records and imaging data of these 3 patients, with special attention to surgical technique and outcome. The variations of ethmoidal artery foramina pertaining to this surgical approach were studied using preserved human skulls from the Hamann-Todd Osteological Collection at the Museum of Natural History, Cleveland, Ohio. Results. The extracranial ligation was performed successfully for control of the ethmoidal arteries prior to resection of hypervascular giant anterior skull base meningiomas. The surgical anatomy and landmarks for ethmoidal arteries were reviewed in anthropology specimens and available literature with reference to described surgical techniques. Conclusions. Extracranial surgical ligation of anterior, and often posterior, ethmoidal arteries prior to resection of large olfactory groove or planum sphenoidale meningiomas provides a safe and feasible option for control of these vessels prior to either open or endoscopic resection of nonembolized or partially embolized tumors. C1 [Manjila, Sunil; Cox, Efrem M.; Smith, Gabriel A.; Corriveau, Mark; Geertman, Robert T.] Case Western Reserve Univ, Metrohlth Med Ctr, Dept Neurosurg, Cleveland, OH 44109 USA. [Johnson, Freedom] Case Western Reserve Univ, Metrohlth Med Ctr, Dept Otolaryngol Head & Neck Surg, Cleveland, OH 44109 USA. [Chhabra, Nipun] Massachusetts Eye & Ear Infirm, Dept Otolaryngol Head & Neck Surg, Boston, MA 02114 USA. RP Geertman, RT (reprint author), Case Western Reserve Univ, Metrohlth Med Ctr, Dept Neurosurg, Cleveland, OH 44109 USA. EM rgeertman@metrohealth.org NR 50 TC 6 Z9 7 U1 0 U2 4 PU AMER ASSOC NEUROLOGICAL SURGEONS PI ROLLING MEADOWS PA 5550 MEADOWBROOK DRIVE, ROLLING MEADOWS, IL 60008 USA SN 1092-0684 J9 NEUROSURG FOCUS JI Neurosurg. Focus PD DEC PY 2013 VL 35 IS 6 AR E13 DI 10.3171/2013.10.FOCUS13327 PG 11 WC Clinical Neurology; Surgery SC Neurosciences & Neurology; Surgery GA 267AY UT WOS:000328067500014 PM 24289121 ER PT J AU Park, KR Kim, SY Park, HS Jung, YS AF Park, Kyung-Ran Kim, Sang Yoon Park, Hyung-Sik Jung, Young-Soo TI Surgery-first approach on patients with temporomandibular joint disease by intraoral vertical ramus osteotomy SO ORAL SURGERY ORAL MEDICINE ORAL PATHOLOGY ORAL RADIOLOGY LA English DT Article ID MANDIBULAR SETBACK; ORTHOGNATHIC SURGERY; MONKEYS AB Orthognathic surgery followed by postsurgical orthodontics without presurgical orthodontic treatment, known as the surgery-first approach (SFA), has become favored recently. The advantages of this surgical approach include total treatment time reduction, psychological benefit from a limited duration of unesthetic orthodontic appliances, and a more effective orthodontic movement of the dentition postoperatively through a regional acceleratory phenomenon. SFA has been previously described in the literature as a surgical technique with Le Fort I osteotomy and sagittal split ramus osteotomy (SSRO), which helps maintain postoperative occlusion with rigid fixation; however, patients with temporomandibular joint disorder (TMD) are better candidates for the intraoral vertical ramus osteotomy (IVRO) surgical technique instead of SSRO. The authors report 2 cases with excellent surgical outcomes and resolution of TMD symptoms on patients with mandibular prognathism via SFA using IVRO technique. C1 [Park, Kyung-Ran] Yonsei Univ, Coll Dent, Seoul 120752, South Korea. [Kim, Sang Yoon] Massachusetts Gen Hosp, Harvard Oral & Maxillofacial Surg, Boston, MA 02114 USA. [Park, Hyung-Sik; Jung, Young-Soo] Yonsei Univ, Oral Sci Res Ctr, Coll Dent, Seoul 120752, South Korea. RP Jung, YS (reprint author), Yonsei Univ, Dept Oral & Maxillofacial Surg, Coll Dent, 250 Seongsan No, Seoul 120752, South Korea. EM ysjoms@yuhs.ac OI kim, sang/0000-0002-5860-3491 NR 21 TC 4 Z9 4 U1 0 U2 5 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 2212-4403 EI 1528-395X J9 OR SURG OR MED OR PA JI Oral Surg. Oral Med. Oral Pathol. Oral Radiol. PD DEC PY 2013 VL 116 IS 6 BP E429 EP E436 DI 10.1016/j.oooo.2011.11.038 PG 8 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 258BN UT WOS:000327433200003 PM 22771403 ER PT J AU Sabatier, I Chabrier, S Brun, A Hees, L Cheylus, A Gollub, R Hadjikhani, N Kong, J des Portes, V Floret, D Curie, A AF Sabatier, Isabelle Chabrier, Stephane Brun, Amandine Hees, Laure Cheylus, Anne Gollub, Randy Hadjikhani, Nouchine Kong, Jian des Portes, Vincent Floret, Daniel Curie, Aurore TI Stroke by Carotid Artery Complete Occlusion in Kawasaki Disease: Case Report and Review of Literature SO PEDIATRIC NEUROLOGY LA English DT Review DE Kawasaki disease; infant; stroke; carotid artery occlusion; immunoglobulin ID INTRAVENOUS IMMUNOGLOBULIN THERAPY; CEREBRAL INFARCTION; MAGNETIC-RESONANCE; ACUTE HEMIPLEGIA; THROMBOSIS; LESIONS; ATHEROSCLEROSIS; COMPLICATIONS; MANAGEMENT; ANEURYSM AB BACKGROUND: Kawasaki disease is an acute and time-limited systemic vasculitis primarily affecting young children. PATIENT: We describe an 18-month-old girl with Kawasaki disease who developed cerebral infarction following complete occlusion of her right internal carotid artery. RESULTS: The occlusion occurred 10 days after the onset of fever, while she was on high-dose aspirin, and the day after she received intravenous immunoglobulin treatment. We present the first literature review on this very rare complication. CONCLUSION: Stroke is a rare neurological complication in Kawasaki disease. Optimal treatment should be begun as soon as possible after diagnosis. Intravenous immunoglobulins seem to reduce the cerebrovascular complications, but evaluation of hydration status is strongly recommended before performing such treatment. C1 [Sabatier, Isabelle; des Portes, Vincent; Curie, Aurore] Hosp Civils Lyon, HFME, Serv Neuropediat, Bron, France. [Sabatier, Isabelle; des Portes, Vincent; Curie, Aurore] Univ Lyon 1, F-69365 Lyon, France. [Chabrier, Stephane] Inserm CIE3, St Etienne, France. [Chabrier, Stephane] Ctr Hosp Univ St Etienne, Serv Med Phys & Readaptat Pediat, St Etienne, France. [Brun, Amandine; Cheylus, Anne; des Portes, Vincent; Curie, Aurore] CNRS UMR5304, Inst Cognit Sci, L2C2, Bron, France. [Hees, Laure] Hosp Civils Lyon, HFME, Unite Hospitalisat Courte Duree, Bron, France. [Hees, Laure] Massachusetts Gen Hosp, Dept Psychiat, Charlestown, MA USA. [Hadjikhani, Nouchine; Curie, Aurore] Massachusetts Gen Hosp, A Martinos Ctr Biomed Imaging, Charlestown, MA USA. [Floret, Daniel] Hosp Civils Lyon, HFME, Serv Reanimat Pediat, Bron, France. RP Curie, A (reprint author), CNRS 5304, L2C2, Inst Cognit Sci, 67 Blvd Pinel, F-69675 Bron, France. EM aurorecurie@yahoo.fr OI Cheylus, Anne/0000-0002-4243-3686; Hadjikhani, Nouchine/0000-0003-4075-3106; Gollub, Randy L./0000-0002-9434-4044 NR 25 TC 3 Z9 4 U1 0 U2 10 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0887-8994 EI 1873-5150 J9 PEDIATR NEUROL JI Pediatr. Neurol. PD DEC PY 2013 VL 49 IS 6 BP 469 EP 473 DI 10.1016/j.pediatrneurol.2013.08.011 PG 5 WC Clinical Neurology; Pediatrics SC Neurosciences & Neurology; Pediatrics GA 263RW UT WOS:000327826700016 PM 24095647 ER PT J AU Eddy, KT AF Eddy, Kamryn T. TI Patient Mortality as a Predictor of Burnout Among Clinicians Specializing in Eating Disorders SO PSYCHOTHERAPY LA English DT Editorial Material DE eating disorders; anorexia nervosa; mortality; therapist burnout AB In a study of therapist burnout, Warren, Schafer, Crowley, and Olivardia (2013, pp. 553-564) identify the experience of patient death as a predictor of "emotional exhaustion,"among clinicians specializing in the treatment of eating disorders. Longitudinal research indicates those with eating disorders-particularly lifetime anorexia nervosa-are at increased risk for premature death owing to physical and psychological aspects of their illness. Given this increased mortality risk, clinicians who concentrate their work on this patient population may experience patient death during the course of their careers. Improving clinician support, access to resources, psychoeducation about risks of mortality in this patient group, and training around how to cope with patient death could lead to a reduction in burnout and an improvement in patient care and well-being. C1 [Eddy, Kamryn T.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Eddy, Kamryn T.] Harvard Univ, Sch Med, Cambridge, MA 02138 USA. RP Eddy, KT (reprint author), 2 Longfellow Pl,Suite 200, Boston, MA 02114 USA. EM keddy@partners.org NR 7 TC 1 Z9 1 U1 1 U2 6 PU AMER PSYCHOLOGICAL ASSOC, DIV PSYCHOTHERAPY PI CORAL GABLES PA 1390 SOUTH DIXIE HIGHWAY, STE 2222, CORAL GABLES, FL 33146-2946 USA SN 0033-3204 EI 1939-1536 J9 PSYCHOTHERAPY JI Psychotherapy PD DEC PY 2013 VL 50 IS 4 BP 568 EP 569 DI 10.1037/a0030574 PG 2 WC Psychology, Clinical SC Psychology GA 259YW UT WOS:000327563200016 PM 23398036 ER PT J AU Bamberg, F Parhofer, KG Lochner, E Marcus, RP Theisen, D Findeisen, HM Hoffmann, U Schonberg, SO Schlett, CL Reiser, MF Weckbach, S AF Bamberg, Fabian Parhofer, Klaus G. Lochner, Elena Marcus, Roy P. Theisen, Daniel Findeisen, Hannes M. Hoffmann, Udo Schoenberg, Stefan O. Schlett, Christopher L. Reiser, Maximilian F. Weckbach, Sabine TI Diabetes Mellitus: Long-term Prognostic Value of Whole-Body MR Imaging for the Occurrence of Cardiac and Cerebrovascular Events SO RADIOLOGY LA English DT Article ID MAGNETIC-RESONANCE; MYOCARDIAL-INFARCTION; SINGLE-SLAB; PERFUSION; DISEASE; ASSOCIATION; DYSFUNCTION; MORTALITY; SEQUENCE; HEART AB Purpose: To study the predictive value of whole-body magnetic resonance (MR) imaging for the occurrence of cardiac and cerebrovascular events in a cohort of patients with diabetes mellitus (DM). Materials and Methods: This HIPAA-compliant study was approved by the institutional review board. Informed consent was obtained from all patients before enrollment into the study. The authors followed up 65 patients with DM (types 1 and 2) who underwent a comprehensive, contrast material-enhanced whole-body MR imaging protocol, including brain, cardiac, and vascular sequences at baseline. Follow-up was performed by phone interview. The primary endpoint was a major adverse cardiac and cerebrovascular event (MACCE), which was defined as composite cardiac-cerebrovascular death, myocardial infarction, cerebrovascular event, or revascularization. MR images were assessed for the presence of systemic atherosclerotic vessel changes, white matter lesions, and myocardial changes. Kaplan-Meier survival and Cox regression analyses were performed to determine associations. Results: Follow-up was completed in 61 patients (94%; median age, 67.5 years; 30 women [49%]; median follow-up, 70 months); 14 of the 61 patients (23%) experienced MACCE. Although normal whole-body MR imaging excluded MACCE during the follow-up period (0%; 95% confidence interval [CI]: 0%, 17%), any detectable ischemic and/or atherosclerotic changes at whole-body MR imaging (prevalence, 66%) conferred a cumulative event rate of 20% at 3 years and 35% at 6 years. Whole-body MR imaging summary estimate of disease was strongly predictive for MACCE (one increment of vessel score and each territory with atherosclerotic changes: hazard ratio, 13.2 [95% CI: 4.5, 40.1] and 3.9 [95% CI: 2.2, 7.5], respectively), also beyond clinical characteristics as well as individual cardiac or cerebrovascular MR findings. Conclusion: These initial data indicate that disease burden as assessed with whole-body MR imaging confers strong prognostic information in patients with DM. (C)RSNA, 2013 C1 [Bamberg, Fabian; Lochner, Elena; Marcus, Roy P.; Theisen, Daniel; Reiser, Maximilian F.; Weckbach, Sabine] Univ Munich, Klinikum Grosshadern, Dept Clin Radiol, D-81377 Munich, Germany. [Parhofer, Klaus G.] Univ Munich, Klinikum Grosshadern, Dept Internal Med 2, D-81377 Munich, Germany. [Bamberg, Fabian; Findeisen, Hannes M.] Univ Hosp RWTH Aachen, Dept Cardiol, Aachen, Germany. [Hoffmann, Udo; Schlett, Christopher L.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Cardiac MR PET CT Program,Div Cardiol, Boston, MA USA. [Hoffmann, Udo; Schlett, Christopher L.] Harvard Univ, Sch Med, Dept Radiol, Massachusetts Gen Hosp, Boston, MA 02115 USA. [Schoenberg, Stefan O.] Univ Med Ctr Mannheim, Med Fac Mannheim, Dept Clin Radiol & Nucl Med, Mannheim, Germany. [Schlett, Christopher L.; Weckbach, Sabine] Heidelberg Univ, Dept Diagnost & Intervent Radiol, Heidelberg, Germany. RP Bamberg, F (reprint author), Univ Munich, Klinikum Grosshadern, Dept Clin Radiol, Marchioninistr 15, D-81377 Munich, Germany. EM fbamberg@med.lmu.de NR 22 TC 16 Z9 16 U1 1 U2 4 PU RADIOLOGICAL SOC NORTH AMERICA PI OAK BROOK PA 820 JORIE BLVD, OAK BROOK, IL 60523 USA SN 0033-8419 J9 RADIOLOGY JI Radiology PD DEC PY 2013 VL 269 IS 3 BP 730 EP 737 DI 10.1148/radiol.13130371 PG 8 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 262TS UT WOS:000327761100012 PM 24023074 ER PT J AU Catalano, OA Rosen, BR Sahani, DV Hahn, PF Guimaraes, AR Vangel, MG Nicolai, E Soricelli, A Salvatore, M AF Catalano, Onofrio A. Rosen, Bruce R. Sahani, Dushyant V. Hahn, Peter F. Guimaraes, Alexander R. Vangel, Mark G. Nicolai, Emanuele Soricelli, Andrea Salvatore, Marco TI Clinical Impact of PET/MR Imaging in Patients with Cancer Undergoing Same-Day PET/CT: Initial Experience in 134 Patients-A Hypothesis-generating Exploratory Study SO RADIOLOGY LA English DT Article ID POSITRON-EMISSION-TOMOGRAPHY; CELL LUNG-CANCER; DUAL-TIME-POINT; HEPATOCELLULAR-CARCINOMA; LYMPH-NODES; HEPATIC METASTASES; PULMONARY NODULES; RECTAL-CANCER; FDG PET; F-18-FDG AB Purpose: To compare the clinical impact of combined positron emission tomography (PET) and magnetic resonance (MR) imaging to that of combined PET and computed tomography (CT) performed on the same day in patients with cancer. Materials and Methods: This HIPAA-compliant retrospective study was approved by the institutional review board. Patients gave written informed consent for study enrollment, including the possibility to use their imaging and clinical data in future evaluations. A total of 134 patients with cancer with a non-central nervous system primary neoplasm underwent same-day fluorodeoxyglucose (FDG) PET/CT and FDG PET/MR imaging. PET/CT and PET/MR studies were independently interpreted by teams of radiologists and nuclear medicine physicians. Four readers, divided into two teams composed of one radiologist and one nuclear medicine physician each, read all 134 studies. The referring physician classified discordance between PET/CT and PET/MR observations either as findings affecting clinical management or as findings not affecting clinical management. Data were compared with the chi(2) test. Results: Findings affecting clinical management were noted for PET/CT studies but not for PET/MR studies in two (1.5%) of 134 patients and for PET/MR studies but not for PET/CT studies in 24 (17.9%) of 134 patients. The discrepancies between findings affecting clinical management detected with PET/MR imaging over those detected with PET/CT were significant (P < .001). Conclusion: In these patients, PET/MR imaging alone contributed to clinical management more often than did PET/CT alone. PET/MR imaging provides information that affects the care of patients with cancer and is unavailable from PET/CT. (C) RSNA, 2013 C1 [Catalano, Onofrio A.] SDN Ist Ric Diagnost Nucl, Dept Radiol, I-80143 Naples, Italy. [Nicolai, Emanuele; Soricelli, Andrea] SDN Ist Ric Diagnost Nucl, Dept Nucl Med, I-80143 Naples, Italy. [Rosen, Bruce R.; Guimaraes, Alexander R.; Vangel, Mark G.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiol,Athinoula A Martinos Ctr Biomed Imagi, Charlestown, MA USA. [Vangel, Mark G.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Biostat Ctr, Charlestown, MA USA. [Sahani, Dushyant V.; Hahn, Peter F.] Harvard Univ, Sch Med, Dept Radiol, Massachusetts Gen Hosp, Boston, MA 02115 USA. [Salvatore, Marco] Univ Naples Federico II, Dept Radiol, Naples, Italy. RP Catalano, OA (reprint author), SDN Ist Ric Diagnost Nucl, Dept Radiol, Via Gianturco 113, I-80143 Naples, Italy. EM onofriocatalano@yahoo.it RI Nicolai, Emanuele/K-6678-2016; soricelli, andrea/C-1133-2009; Salvatore, Marco/K-8083-2016 OI Nicolai, Emanuele/0000-0003-3171-368X; soricelli, andrea/0000-0001-7011-7667; Salvatore, Marco/0000-0001-9734-7702 FU Siemens Medical Solutions FX O.A.C. No relevant conflicts of interest to disclose. B.R.R. Financial activities related to the present article: none to disclose. Financial activities not related to the present article: none to disclose. Other relationships: is a consultant to Siemens. D.V.S. No relevant conflicts of interest to disclose. P.F.H. No relevant conflicts of interest to disclose. A.R.G. Financial activities related to the present article: none to disclose. Financial activities not related to the present article: Siemens Medical Solutions paid for travel. Other relationships: none to disclose. M.G.V. No relevant conflicts of interest to disclose. E.N. No relevant conflicts of interest to disclose. A.S. No relevant conflicts of interest to disclose. M.S. No relevant conflicts of interest to disclose. NR 41 TC 54 Z9 55 U1 1 U2 8 PU RADIOLOGICAL SOC NORTH AMERICA PI OAK BROOK PA 820 JORIE BLVD, OAK BROOK, IL 60523 USA SN 0033-8419 J9 RADIOLOGY JI Radiology PD DEC PY 2013 VL 269 IS 3 BP 857 EP 869 DI 10.1148/radiol.13131306 PG 13 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 262TS UT WOS:000327761100027 PM 24009348 ER PT J AU Ehrlich, S Williams, PL Hauser, R Missmer, SA Peretz, J Calafat, AM Flaws, JA AF Ehrlich, Shelley Williams, Paige L. Hauser, Russ Missmer, Stacey A. Peretz, Jackye Calafat, Antonia M. Flaws, Jodi A. TI Urinary bisphenol A concentrations and cytochrome P450 19 A1 (Cyp19) gene expression in ovarian granulosa cells: An in vivo human study SO REPRODUCTIVE TOXICOLOGY LA English DT Article DE Bisphenol A; Follicular fluid; Ovary, granulosa cells; Cyp19; P450 aromatase; Gene expression; Fertility; Human ID STEROID-HORMONE PRODUCTION; FOLLICLE GROWTH; EXPOSURE; WOMEN; ESTRADIOL; DIMETHACRYLATE; STIMULATION; INFERTILITY; AROMATASE; PATHWAY AB Background: Exposure to bisphenol A (BPA), a chemical widely used in consumer products, has been associated with in vitro Cyp19 gene expression. Objective: To evaluate an in vivo human model of Cyp19 gene expression in granulosa cells. Study Design: A subset of an ongoing prospective cohort study of women undergoing in vitro fertilization (IVF) at Massachusetts General Hospital. Methods: Mixed effect models were used to evaluate the association of urinary BPA concentrations with granulosa cell Cyp19 mRNA expression. Results: In 61 women undergoing 76 IVF cycles, adjusted changes in mean Cyp19 expression (beta estimate (95% CI)) for quartiles 2, 3 and 4 as compared to the lowest quartile were: -0.97 (-2.22, 0.28); -0.97 (-2.18, 0.24) and -0.38 (-1.58, 0.82). Conclusions: An in vivo model for evaluation of Cyp19 gene expression was developed for use in epidemilogic studies. In this pilot study, we found no statistically significant linear association between urinary BPA concentrations and Cyp19 expression. (C) 2013 Elsevier Inc. All rights reserved. C1 [Ehrlich, Shelley; Hauser, Russ] Harvard Univ, Sch Publ Hlth, Dept Environm Hlth, Boston, MA 02115 USA. [Williams, Paige L.] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. [Hauser, Russ; Missmer, Stacey A.] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. [Hauser, Russ] Massachusetts Gen Hosp, Vincent Mem Obstet & Gynecol Serv, Boston, MA 02114 USA. [Missmer, Stacey A.] Brigham & Womens Hosp, Dept Obstet Gynecol & Reprod Biol, Boston, MA 02115 USA. [Missmer, Stacey A.] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Peretz, Jackye; Flaws, Jodi A.] Univ Illinois, Urbana, IL USA. [Calafat, Antonia M.] Ctr Dis Control & Prevent, Natl Ctr Environm Hlth, Atlanta, GA USA. RP Hauser, R (reprint author), Harvard Univ, Sch Publ Hlth, 665 Huntington Ave,Bldg 1,14th Floor, Boston, MA 02115 USA. EM rhauser@hsph.harvard.edu RI Ehrlich , Shelley/L-6991-2015 FU National Institute of Environmental Health Sciences [ES009718, ES000002, ES019178]; National Institute for Occupational Safety and Health [OH008578] FX This work was supported by grant ES009718, ES000002, ES019178 from the National Institute of Environmental Health Sciences and grant OH008578 from the National Institute for Occupational Safety and Health. NR 37 TC 13 Z9 13 U1 0 U2 15 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0890-6238 J9 REPROD TOXICOL JI Reprod. Toxicol. PD DEC PY 2013 VL 42 BP 18 EP 23 DI 10.1016/j.reprotox.2013.06.071 PG 6 WC Reproductive Biology; Toxicology SC Reproductive Biology; Toxicology GA 260BD UT WOS:000327569100002 PM 23850856 ER PT J AU Souter, I Smith, KW Dimitriadis, I Ehrlich, S Williams, PL Calafat, AM Hauser, R AF Souter, Irene Smith, Kristen W. Dimitriadis, Irene Ehrlich, Shelley Williams, Paige L. Calafat, Antonia M. Hauser, Russ TI The association of bisphenol-A urinary concentrations with antral follicle counts and other measures of ovarian reserve in women undergoing infertility treatments SO REPRODUCTIVE TOXICOLOGY LA English DT Article DE Bisphenol-A; Antral follicle count; Day-3 follicle stimulating hormone; Ovarian volume; Ovarian reserve ID STEROID-HORMONE PRODUCTION; IN-VITRO; GRANULOSA-CELLS; ENDOCRINE DISRUPTORS; NEONATAL EXPOSURE; CIGARETTE-SMOKING; MAMMARY-GLAND; ER-ALPHA; ESTROGEN; MOUSE AB In this prospective cohort of women undergoing infertility treatments, we measured specific-gravity adjusted urinary BPA (SG-BPA) concentrations and used regression models to evaluate the association of BPA with antral follicle count (AFC), day-3 serum follicle stimulating hormone levels (FSH), and ovarian volume (OV). BPA, detected in >80% of women, had a geometric mean (+/- GSD) of 1.6 +/- 2.0, 1.7 +/- 2.1, and 1.5 +/- 1.8 mu g/L for the women contributing to the AFC (n = 154), day-3 FSH (n = 120), and OV (n = 114) analyses, respectively. There was an average decrease in AFC of 12% (95% CI: -23%, -0.6%), -22% (95% CI: -31%, -11%), and 17% (95% CI: -27%, -6%), in the 2nd, 3rd, and 4th SG-BPA quartile compared to the 1st quartile, respectively (p-trend: <0.001). No association of SG-BPA with FSH or OV was observed. Among women from an infertility clinic, higher urinary BPA concentrations were associated with lower AFC, raising concern for possible accelerated follicle loss and reproductive aging. (C) 2013 Elsevier Inc. All rights reserved. C1 [Souter, Irene; Dimitriadis, Irene; Hauser, Russ] Harvard Univ, Massachusetts Gen Hosp, Div Reprod Endocrinol & Infertil, Dept Obstet & Gynecol,Fertil Ctr,Sch Med, Boston, MA 02114 USA. [Smith, Kristen W.; Ehrlich, Shelley; Hauser, Russ] Harvard Univ, Sch Publ Hlth, Dept Environm Hlth, Boston, MA 02115 USA. [Williams, Paige L.] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. [Calafat, Antonia M.] Ctr Dis Control & Prevent, Natl Ctr Environm Hlth, Atlanta, GA 30333 USA. RP Souter, I (reprint author), Massachusetts Gen Hosp, Fertil Ctr, Yawkey 10-A,55 Fruit St, Boston, MA 02114 USA. EM isouter@partners.org; ksmith@hsph.harvard.edu; idimitriadis@tuftsmedicalcenter.org; sehrlich@hsph.harvard.edu; paige@sdac.harvard.edu; aic7@cdc.gov; rhauser@hsph.harvard.edu RI Ehrlich , Shelley/L-6991-2015 FU National Institute for Environmental Health Sciences (NIEHS) [ES009718, ES000002, T32ES007069]; National Institute for Occupational Safety and Health (NIOSH) [OH008578] FX Supported by grants: ES009718, ES000002, and T32ES007069 from the National Institute for Environmental Health Sciences (NIEHS) and OH008578 from the National Institute for Occupational Safety and Health (NIOSH). NR 66 TC 15 Z9 15 U1 1 U2 11 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0890-6238 J9 REPROD TOXICOL JI Reprod. Toxicol. PD DEC PY 2013 VL 42 BP 224 EP 231 DI 10.1016/j.reprotox.2013.09.008 PG 8 WC Reproductive Biology; Toxicology SC Reproductive Biology; Toxicology GA 260BD UT WOS:000327569100024 PM 24100206 ER PT J AU Hernandez-Lain, A Hedley-Whyte, ET Hariri, LP Molyneaux, B Nagle, KJ Cole, AJ Kilbride, R AF Hernandez-Lain, Aurelio Hedley-Whyte, E. Tessa Hariri, Lida P. Molyneaux, Bradley Nagle, Keith J. Cole, Andrew J. Kilbride, Ronan TI Pathology of bilateral pulvinar degeneration following long duration status epilepticus SO SEIZURE-EUROPEAN JOURNAL OF EPILEPSY LA English DT Article DE Status epilepticus; Epilepsy monitoring; MRI; Spinal cord; Medical/systemic disease ID DWI AB Purpose: To define the neuropathological findings of pulvinar degeneration seen in long duration status epilepticus. Methods: We review the clinical, radiologic, neurophysiologic, investigational and neuropathological findings on a 27 year old woman who died after 162 days of prolonged refractory status epilepticus. Results: Continuous EEG monitoring confirmed recurrent uncontrolled seizure activity bilaterally and independently, most frequent in the right fronto-temporal region. Initial MRI of the brain was normal. Repeat study until on day 127 of admission showed advanced changes, with bilateral pulvinar T2/FLAIR hyperintensities. The autopsy revealed sharply defined, grey, soft, granular nodules in each medial pulvinar nucleus. Microscopically these consisted of sharply defined paucicellular areas with loss of neurons and myelin and with numerous macrophages in their centers, surrounded by reactive astrocytes with relatively spared of axons. The spinal cord at cervical and thoracic levels showed symmetric spongy vacuolation in the central part of the dorsal columns and lateral corticospinal tracts, with mild myelin loss, relatively preserved axons. The pathological lesions found in this case in thepulvinar are somewhat similar to the pathologic lesions described in Wernicke's encephalopathy. Those found in the spinal cord of our patient resemble characteristic features of B12 related subacute combined degeneration. Conclusion: Characteristic pulvinar degeneration may be found as an acquired phenomenon in prolonged refractory status epilepticus. We hypothesize that the neuropathological findings result from an excessive focal metabolic demand, secondary to neuronal network over activation in the setting of prolonged, frequent bi-temporal seizures. (C) 2013 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved. C1 [Hernandez-Lain, Aurelio; Hedley-Whyte, E. Tessa; Hariri, Lida P.] Dept Pathol, Charles S Kubik Lab Neuropathol, Boston, MA USA. [Molyneaux, Bradley; Cole, Andrew J.; Kilbride, Ronan] Massachusetts Gen Hosp, Dept Neurol, MGH Epilepsy Serv, Boston, MA 02114 USA. [Molyneaux, Bradley; Cole, Andrew J.; Kilbride, Ronan] Harvard Univ, Dept Pathol, Boston, MA 02115 USA. [Molyneaux, Bradley; Cole, Andrew J.; Kilbride, Ronan] Harvard Univ, Dept Neurol, Boston, MA 02115 USA. [Hernandez-Lain, Aurelio] Hosp Univ 12 Octubre, Serv Anat Patolog Neuropatol, Madrid, Spain. [Hernandez-Lain, Aurelio] Hosp Univ 12 Octubre, Inst Invest i 12, Madrid, Spain. [Nagle, Keith J.] Univ Vermont, Coll Med, Dept Neurol, Burlington, VT USA. RP Kilbride, R (reprint author), Massachusetts Gen Hosp, Dept Neurol, 55 Fruit St,WAC 835, Boston, MA 02114 USA. EM ahernandez.hdoc@salud.madrid.org; rkilbride@partners.org OI Molyneaux, Bradley/0000-0002-3377-1229 FU Contrato Rio Hortega del Instituto Salud Carlos III FX Dr Hernandez-Lain was supported by the Contrato Rio Hortega del Instituto Salud Carlos III. NR 4 TC 2 Z9 2 U1 0 U2 3 PU W B SAUNDERS CO LTD PI LONDON PA 32 JAMESTOWN RD, LONDON NW1 7BY, ENGLAND SN 1059-1311 EI 1532-2688 J9 SEIZURE-EUR J EPILEP JI Seizure PD DEC PY 2013 VL 22 IS 10 BP 901 EP 904 DI 10.1016/j.seizure.2013.07.012 PG 4 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 261TK UT WOS:000327687300017 PM 23962521 ER PT J AU Hough, S Stone, MT Buse, DC AF Hough, Sigmund Stone, Melissa T. Buse, Dawn C. TI Dating and Relationship Psychoeducational Group for Veterans with Spinal Cord Injury/Dysfunction: A Historical Account of an Initial Clinical Course SO SEXUALITY AND DISABILITY LA English DT Article DE Spinal cord injury; Spinal cord disability; Spinal cord dysfunction; Dating; Sexuality; Psychoeducational; Group; Relationships; Veterans; Males; United States ID LIFE SATISFACTION; SEXUAL ADJUSTMENT; HEALTH-CARE; INJURY; REHABILITATION; COMMUNITY; ADULTS; PARTICIPATION; INTERVENTION; DISABILITY AB Numerous studies have examined sexual functioning among persons with paraplegia and quadriplegia. None have detailed a group skill model teaching social skills in the areas of dating and intimate relationships and little in the literature has focused on this important aspect of sexuality. A psychoeducational group for individuals with spinal cord injury/dysfunction (SCI/D) was developed to address social, dating, and relationship skills, as well as improve self-efficacy, confidence and quality of life. Seven male veterans with SCI/D, age 32-51, participated in a 12-week psychoeducational social skills training group that met weekly for 60 min. Sessions were structured to focus on one theme or set of skills, and homework was given at the end of each session. Participants answered pre and post questionnaires about their general well-being, self-esteem, depression, anxiety, and social skills in general and specific to dating and relationships. A 12-week follow-up session reviewed the constructs. All participants reported positive experiences in the group and improvement in targeted areas. A detailed outline of session topics, exercises and handouts are presented as well as pre and post feedback on functioning, knowledge and attitudes among group participants. C1 [Hough, Sigmund; Stone, Melissa T.] VA Boston Healthcare Syst, Psychol Serv, Boston, MA USA. [Hough, Sigmund] Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA. [Hough, Sigmund] Boston Univ, Sch Med, Dept Psychiat, Boston, MA 02118 USA. [Stone, Melissa T.] Massachusetts Sch Profess Psychol, Boston, MA USA. [Buse, Dawn C.] Albert Einstein Coll Med, Dept Neurol, Bronx, NY 10467 USA. [Buse, Dawn C.] Montefiore Med Ctr, Bronx, NY 10467 USA. RP Hough, S (reprint author), 396 Washington St,Suite 211, Wellesley Hills, MA 02181 USA. EM Sigmund_Hough@hms.harvard.edu NR 50 TC 1 Z9 1 U1 3 U2 5 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0146-1044 EI 1573-6717 J9 SEX DISABIL JI Sex. Disabil. PD DEC PY 2013 VL 31 IS 4 SI SI BP 337 EP 359 DI 10.1007/s11195-013-9330-8 PG 23 WC Rehabilitation SC Rehabilitation GA 264LZ UT WOS:000327880400006 ER PT J AU Jung, JH Wang, XD Loeken, MR AF Jung, Jin Hyuk Wang, Xiao Dan Loeken, Mary R. TI Mouse Embryonic Stem Cells Established in Physiological-Glucose Media Express the High K-M Glut2 Glucose Transporter Expressed by Normal Embryos SO STEM CELLS TRANSLATIONAL MEDICINE LA English DT Article DE Embryonic stem cells; Stem cell culture; Cell culture; Glucose transporter ID NEURAL-TUBE DEFECTS; GENE-EXPRESSION; DIRECTED DIFFERENTIATION; PREIMPLANTATION EMBRYOS; ENZYMATIC-SYNTHESIS; DIABETIC PREGNANCY; APOPTOSIS; LINES; MICE; RAT AB Glut2 is one of the facilitative glucose transporters expressed by preimplantation and early post-implantation embryos. Glut2 is important for survival before embryonic day 10.5. The Glut2 K-M (similar to 16 mmol/liter) is significantly higher than physiologic glucose concentrations (similar to 5.5 mmol/liter), suggesting that Glut2 normally performs some essential function other than glucose transport. Nevertheless, Glut2 efficiently transports glucose when extracellular glucose concentrations are above the Glut2 K-M. Media containing 25 mmol/liter glucose are widely used to establish and propagate embryonic stem cells (ESCs). Glut2-mediated glucose uptake by embryos induces oxidative stress and can cause embryo cell death. Here we tested the hypothesis that low-glucose embryonic stem cells (LG-ESCs) isolated in physiological-glucose (5.5 mmol/(iter) media express a functional Glut2 glucose transporter. LG-ESCs were compared with conventional D3 ESCs that had been cultured only in high-glucose media. LG-ESCs expressed Glut2 mRNA and protein at much higher levels than D3 ESCs, and 2-deoxyglucose transport by LG-ESCs, but not D3 ESCs, exhibited high Michaelis-Menten kinetics. Glucose at 25 mmol/liter induced oxidative stress in LG-ESCs and inhibited expression of Pax3, an embryo gene that is inhibited by hyperglycemia, in neuronal precursors derived from LG-ESCs. These effects were not observed in D3 ESCs. These findings demonstrate that ESCs isolated in physiological-glucose media retain a functional Glut2 transporter that is expressed by embryos. These cells are better suited to the study of metabolic regulation characteristic of the early embryo and may be advantageous for therapeutic applications. C1 [Jung, Jin Hyuk; Wang, Xiao Dan; Loeken, Mary R.] Harvard Univ, Sch Med, Joslin Diabet Ctr, Sect Islet Cell & Regenerat Biol, Boston, MA 02115 USA. RP Loeken, MR (reprint author), Joslin Diabet Ctr, Sect Islet Cell & Regenerat Biol, 1 Joslin Pl, Boston, MA 02215 USA. EM mary.loeken@joslin.harvard.edu OI Loeken, Mary/0000-0002-8056-9816 FU NIH [R01-DK052865]; Diabetes Endocrine Research Center Grant [P30DK036836] FX Research reported in this publication was supported by NIH Grant R01-DK052865 to M.R.L. and was assisted by core facilities supported by Diabetes Endocrine Research Center Grant P30DK036836 to the Joslin Diabetes Center. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. NR 47 TC 5 Z9 5 U1 0 U2 3 PU ALPHAMED PRESS PI DURHAM PA 318 BLACKWELL ST, STE 260, DURHAM, NC 27701-2884 USA SN 2157-6564 EI 2157-6580 J9 STEM CELL TRANSL MED JI Stem Cells Transl. Med. PD DEC PY 2013 VL 2 IS 12 BP 929 EP 934 DI 10.5966/sctm.2013-0093 PG 6 WC Cell & Tissue Engineering SC Cell Biology GA 263JH UT WOS:000327804400006 PM 24167319 ER PT J AU Jeon, HJ Hong, JP Fava, M Mischoulon, D Nyer, M Inamori, A Sohn, JH Seong, S Cho, MJ AF Jeon, Hong Jin Hong, Jin Pyo Fava, Maurizio Mischoulon, David Nyer, Maren Inamori, Aya Sohn, Jee Hoon Seong, Sujeong Cho, Maeng Je TI Childhood Parental Death and Lifetime Suicide Attempt of the Opposite-Gender Offspring in a Nationwide Community Sample of Korea SO SUICIDE AND LIFE-THREATENING BEHAVIOR LA English DT Article ID ADULT PSYCHIATRIC-DISORDERS; 12-MONTH PREVALENCE; MAJOR DEPRESSION; RISK; PSYCHOPATHOLOGY; IDEATION; CHILDREN; ADVERSITIES; PREDICTORS; ATTACHMENT AB Although previous studies have shown that childhood parental death influences suicide attempts of their offspring, few studies have examined influence of gender and age at exposure. Koreans show the third highest suicide rate in the world, and many children and adolescents lost their parents during and after the Korean War. A total of 12,532 adults, randomly selected through a one-person-per-household method, completed the Korean version of the Composite International Diagnostic Interview and questionnaire for suicidal ideation, plan, and attempt (response rate 80.2%). A total of 2,332 subjects experienced biological parental death in childhood (18.6%). Male suicide attempts were associated with age of exposure to maternal death from 0 to 4years (adjusted OR=4.48, 95% CI 1.32-15.18) and from 5 to 9years (adjusted OR=5.52, 95% CI 1.97-16.46), but not with paternal death, after adjusting for age, education years, marital status, monthly income, and psychiatric comorbidities. Female suicide attempts were associated with paternal death from 5 to 9years (adjusted OR=2.20, 95% CI 1.13-4.27), but not with maternal death. Childhood parental death is significantly associated with lifetime suicide attempt in the opposite-gender offspring, especially when exposure occurs before age 10. C1 [Jeon, Hong Jin] Sungkyunkwan Univ, Sch Med, Samsung Med Ctr, Depress Ctr,Dept Psychiat, Seoul, South Korea. [Jeon, Hong Jin; Fava, Maurizio; Mischoulon, David; Nyer, Maren; Inamori, Aya] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Depress Clin & Res Program, Boston, MA USA. [Hong, Jin Pyo] Univ Ulsan, Coll Med, Asan Med Ctr, Dept Psychiat, Seoul, South Korea. [Sohn, Jee Hoon; Seong, Sujeong; Cho, Maeng Je] Seoul Natl Univ, Coll Med, Dept Psychiat & Behav Sci, Seoul 110744, South Korea. RP Cho, MJ (reprint author), Seoul Natl Univ, Coll Med, Dept Psychiat & Behav Sci, 28 Yeongeon Dong, Seoul 110744, South Korea. EM mjcho@plaza.snu.ac.kr NR 48 TC 8 Z9 8 U1 4 U2 19 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0363-0234 EI 1943-278X J9 SUICIDE LIFE-THREAT JI Suicide Life-Threat. Behav. PD DEC PY 2013 VL 43 IS 6 BP 598 EP 610 DI 10.1111/sltb.12042 PG 13 WC Psychiatry; Psychology, Multidisciplinary SC Psychiatry; Psychology GA 264SP UT WOS:000327901100002 PM 23834109 ER PT J AU Campbell, MJ McCoy, KL Shen, WT Carty, SE Lubitz, CC Moalem, J Nehs, M Holm, T Greenblatt, DY Press, D Feng, XX Siperstein, AE Mitmaker, E Benay, C Tabah, R Oltmann, SC Chen, H Sippel, RS Brekke, A Vriens, MR Lodewijk, L Stephen, AE Nagar, S Angelos, P Ghanem, M Prescott, JD Zeiger, MA Han, PA Sturgeon, C Elaraj, DM Nixon, IJ Patel, SG Bayles, SW Heneghan, R Ochieng, P Guerrero, MA Ruan, DT AF Campbell, Michael J. McCoy, Kelly L. Shen, Wen T. Carty, Sally E. Lubitz, Carrie C. Moalem, Jacob Nehs, Matthew Holm, Tammy Greenblatt, David Y. Press, Danielle Feng, Xiaoxi Siperstein, Allan E. Mitmaker, Elliot Benay, Cassandre Tabah, Roger Oltmann, Sarah C. Chen, Herbert Sippel, Rebecca S. Brekke, Andrew Vriens, Menno R. Lodewijk, Lutske Stephen, Antonia E. Nagar, Sapna Angelos, Peter Ghanem, Maher Prescott, Jason D. Zeiger, Martha A. Han, Patricia Aragon Sturgeon, Cord Elaraj, Dina M. Nixon, Iain J. Patel, Snehal G. Bayles, Stephen W. Heneghan, Rachel Ochieng, Peter Guerrero, Marlon A. Ruan, Daniel T. TI A multi-institutional international study of risk factors for hematoma after thyroidectomy SO SURGERY LA English DT Article ID OUTPATIENT THYROIDECTOMY; PARATHYROID SURGERY; COMPLICATIONS; SAFE; MULTICENTER; EXPERIENCE AB Background. Cervical hematoma can be a potentially fatal complication after thyroidectomy, but its risk factors and timing remain poorly understood. Methods. We conducted a retrospective, case-control study identifying 207 patients from 15 institutions in 3 countries who developed a hematoma requiring return to the operating room (OR) after thyroidectomy. Results. Forty-seven percent of hematoma patients returned to the OR within 6 hours and 79% within 24 hours of their thyroidectomy. On univariate analysis, hematoma patients were older, more likely to be male, smokers, on active antiplatelet/anticoagulation medications, have Graves' disease, a bilateral thyroidectomy, a drain placed, a concurrent parathyroidectomy, and benign pathology. Hematoma patients also had more blood loss, larger thyroids, lower temperatures, and higher blood pressures postoperatively. On multivariate analysis, independent associations with hematoma were use of a drain (odds ratio, 2.79), Graves' disease (odds ratio, 2.43), benign pathology (odds ratio, 2.22), antiplatelet/anticoagulation medications (odds ratio, 2.12), use of a hemostatic agent (odds ratio, 1.97), and increased thyroid mass (odds ratio, 1.01). Conclusion. A significant number of patients with a postoperative hematoma present >6 hours after thyroidectomy. Hematoma is associated with patients who have a drain or hemostatic agent, have Graves' disease, are actively using antiplatelet/anticoagulation medications or have large thyroids. Surgeons should consider these factors when individualizing patient disposition after thyroidectomy. C1 [Campbell, Michael J.; Shen, Wen T.; Greenblatt, David Y.] Univ Calif San Francisco, San Francisco, CA 94143 USA. [McCoy, Kelly L.; Carty, Sally E.] Univ Pittsburgh, Med Ctr, Pittsburgh, PA USA. [Lubitz, Carrie C.; Stephen, Antonia E.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Moalem, Jacob] Univ Rochester, Med Ctr, Rochester, NY 14642 USA. [Nehs, Matthew; Holm, Tammy; Ruan, Daniel T.] Brigham & Womens Hosp, Boston, MA 02115 USA. [Press, Danielle; Feng, Xiaoxi; Siperstein, Allan E.] Cleveland Clin, Cleveland, OH 44106 USA. [Mitmaker, Elliot; Benay, Cassandre; Tabah, Roger] McGill Univ, Hlth Ctr, Montreal, PQ, Canada. [Oltmann, Sarah C.; Chen, Herbert; Sippel, Rebecca S.; Brekke, Andrew] Univ Wisconsin, Madison, WI USA. [Vriens, Menno R.; Lodewijk, Lutske] Univ Med Ctr Utrecht, Utrecht, Netherlands. [Nagar, Sapna; Angelos, Peter] Univ Chicago, Chicago, IL 60637 USA. [Ghanem, Maher; Prescott, Jason D.; Zeiger, Martha A.; Han, Patricia Aragon] Johns Hopkins Sch Med, Baltimore, MD USA. [Sturgeon, Cord; Elaraj, Dina M.] Northwestern Med Ctr, Chicago, IL USA. [Nixon, Iain J.; Patel, Snehal G.] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. [Bayles, Stephen W.; Heneghan, Rachel] Virginia Mason Med Ctr, Seattle, WA 98101 USA. [Ochieng, Peter; Guerrero, Marlon A.] Univ Arizona, Med Ctr, Tucson, AZ USA. RP Ruan, DT (reprint author), Brigham & Womens Hosp, 75 Frances St, Boston, MA 02115 USA. EM druan@partners.org RI Oltmann, Sarah/L-3245-2014; OI Oltmann, Sarah/0000-0002-7180-4167; Ochieng, Peter/0000-0002-0668-0719; Nixon, Iain/0000-0002-8919-8783 NR 21 TC 21 Z9 22 U1 2 U2 2 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0039-6060 J9 SURGERY JI Surgery PD DEC PY 2013 VL 154 IS 6 BP 1283 EP 1289 DI 10.1016/j.surg.2013.06.032 PG 7 WC Surgery SC Surgery GA 260BY UT WOS:000327571200037 PM 24206619 ER PT J AU McKenzie, TJ Chen, YF Hodin, RA Shikora, SA Hutter, MM Gaz, RD Moore, FD Lubitz, CC AF McKenzie, Travis J. Chen, Yufei Hodin, Richard A. Shikora, Scott A. Hutter, Matthew M. Gaz, Randall D. Moore, Francis D., Jr. Lubitz, Carrie C. TI Recalcitrant hypocalcemia after thyroidectomy in patients with previous Roux-en-Y gastric bypass SO SURGERY LA English DT Article ID VITAMIN-D; CALCIUM-METABOLISM; BARIATRIC SURGERY; OBESE WOMEN; RISK; BONE AB Background. Hypocalcemia is a potential complication after thyroidectomy. Patients with previous roux-en-Y gastric bypass (RYGBP) may be at increased risk for recalcitrant symptomatic hypocalcemia after thyroidectomy. This complication is poorly described and there is no current consensus on optimal management in this unique population. Methods. All patients from 2000 to 2012 who underwent thyroidectomy with history of preceding RYGBP were identified retrospectively. Each of the 19 patients meeting inclusion criteria were matched 2:1 for age, gender, and body mass index (BMI) to a cohort who underwent thyroidectomy without previous RYGBP. The study cohort and matched controls were compared for incidence of symptomatic postoperative hypocalcemia, requirement of intravenous (IV) calcium supplementation, and duration of hospital stay. Results. Age, proportion of female patients, and BMI were equivalent between cases (n = 19) and controls (n = 38). Comparison of primary outcomes demonstrated that the study group had a significantly higher incidence of symptomatic hypocalcemia (42% vs 0%; P < .01), administration of IV calcium (21% vs 0%; P < .01), and duration of hospital stay (2.2 vs 1.2 days, P = .02). Conclusion. Patients with previous RYGBP have a greater incidence of recalcitrant symptomatic hypocalcemia after thyroidectomy, resulting in prolonged duration of hospital stay. In this patient population, calcium levels should be closely monitored and early calcium and vitamin D supplementation initiated preemptively. C1 [McKenzie, Travis J.; Chen, Yufei; Hodin, Richard A.; Shikora, Scott A.; Hutter, Matthew M.; Gaz, Randall D.; Moore, Francis D., Jr.; Lubitz, Carrie C.] Massachusetts Gen Hosp, Dept Surg, Wang Ambulatory Care Ctr, Boston, MA 02114 USA. RP McKenzie, TJ (reprint author), Massachusetts Gen Hosp, Dept Surg, Wang Ambulatory Care Ctr 460, 15 Parkman St, Boston, MA 02114 USA. EM tjmckenzie@partners.org FU Program in Cancer Outcomes Research Training Grant [NCI R25CA092203]; Massachusetts General Hospital Department of Surgery FX This work was funded, in part, by the Program in Cancer Outcomes Research Training Grant (NCI R25CA092203), and the Massachusetts General Hospital Department of Surgery. NR 21 TC 10 Z9 11 U1 0 U2 2 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0039-6060 J9 SURGERY JI Surgery PD DEC PY 2013 VL 154 IS 6 BP 1300 EP 1306 DI 10.1016/j.surg.2013.04.031 PG 7 WC Surgery SC Surgery GA 260BY UT WOS:000327571200041 PM 23978591 ER PT J AU Gunda, V Cogdill, AP Bernasconi, MJ Wargo, JA Parangi, S AF Gunda, Viswanath Cogdill, Alexandria P. Bernasconi, Maria J. Wargo, Jennifer A. Parangi, Sareh TI Potential role of 5-Aza-2 '-deoxycytidine induced MAGE-A4 expression in immunotherapy for anaplastic thyroid cancer SO SURGERY LA English DT Article ID TARGETED THERAPY; TESTIS ANTIGENS; MELANOMA; CARCINOMA; PEPTIDE; GENES AB Background. Melanoma antigen gene family (MAGE)-A4, a member of the cancer testis antigen family, has been reported in various cancers including melanoma, bladder, head and neck, oral, and lung, and is a potential target for T-cell-receptor-based immunotherapy. Baseline expression levels of the MAGE-A4 gene in thyroid cancer cell lines have not been previously studied thoroughly. Methods. Human thyroid cancer cell lines (8505c, HTh7, BCPAP, and TPC-1) were treated with either 10 mu mol/L 5'-azacytidine (Aza) or 10 mu mol/L 5-AZA-2' deoxycytidine (DAC) and evaluated for various MAGEA gene expression. Later melanoma cell lines A375 and 8505c were treated with PLX4720 in combination with DAC and evaluated for MAGE-A4 expression. Results. Only BCPAP cells expressed moderate levels of MAGE-A3 and MAGE-A6 at baseline. Treatment with DAC/Aza induced the expression of MAGE-A4 and MAGE-A1 in 8505c cells. PLX4720 treatment did not affect MAGE-A4 expression in 8505c cells, but increased its expression in A375 cells. In contrast, addition of PLX4720 to DAC-treated 8505c cells decreased the previously induced MAGE-A4 expression by DAC in these cells. A similar decrease in MAGE-A4 expression by DAC was also seen in 8505cBRAF(-/-) cells. Although DAC treatment resulted in demethylation of the MAGE-A4 promoter in 2 CpG sites, PLX addition to DAC did not affect the demethylation status. Conclusion. Demethylating agents increased the expression of IMAGE genes in thyroid cancer cells. The effect of BRAFV600E inhibitors on MAGE-A4 expression suggest the role of downstream MEK/BRAF signaling in its expression apart from promoter demethylation being the sole requirement. Expression of MAGE-A4 may make immunotherapeutic intervention possible in selected patients with thyroid cancer. C1 [Gunda, Viswanath; Cogdill, Alexandria P.; Bernasconi, Maria J.; Wargo, Jennifer A.; Parangi, Sareh] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Boston, MA 02115 USA. RP Parangi, S (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Unit Endocrine Surg, Wang ACC 460,15 Parkman St, Boston, MA 02115 USA. EM sparangi@partners.org OI Cogdill, Alexandria/0000-0001-8917-9462 FU National Institutes of Health [NIH-NCI R01 1R01CA149738-01A1] FX Supported by the National Institutes of Health grant to Dr Sareh Parangi (NIH-NCI R01 1R01CA149738-01A1). NR 25 TC 12 Z9 13 U1 1 U2 8 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0039-6060 J9 SURGERY JI Surgery PD DEC PY 2013 VL 154 IS 6 BP 1456 EP 1462 DI 10.1016/j.surg.2013.07.009 PG 7 WC Surgery SC Surgery GA 260BY UT WOS:000327571200078 PM 24238058 ER PT J AU Bergman, J Neuhausen, K Chamie, K Scales, CD Carter, S Kwan, L Lerman, SE Aronson, W Litwin, MS AF Bergman, Jonathan Neuhausen, Katherine Chamie, Karim Scales, Charles D. Carter, Stacey Kwan, Lorna Lerman, Steven E. Aronson, William Litwin, Mark S. TI Building a Medical Neighborhood in the Safety Net: An Innovative Technology Improves Hematuria Workups SO UROLOGY LA English DT Article ID COMMUNITY-HEALTH CENTERS; INVASIVE BLADDER-CANCER; RADICAL CYSTECTOMY; CARE; MORTALITY; PROVIDERS; NATION; ACCESS AB OBJECTIVE To analyze whether ereferral is associated with decreased time to completion of hematuria workup. METHODS We included 100 individuals referred to Olive View-UCLA Medical Center for urologic consultation for hematuria. Half were referred before implementation of ereferral, and half were referred after the system was implemented. We performed bivariate analysis to assess correlations of baseline subject sociodemographic and clinical characteristics with ereferral status. We also created a multivariate linear regression model for log days to completion of hematuria workup, with ereferral as the main predictor and subject sociodemographic and clinical characteristics as covariates. RESULTS Excluding cases with an infectious cause, the mean number of days from urinalysis documenting hematuria to completed hematuria workup was 404 days before ereferral and 192 days after implementation of ereferral (median 239 vs 170; 2-sample median P=.0013). Upper tract imaging was obtained at a median of 76 days after initial positive urinalysis in the absence of infection, 122 days before ereferral, and 41 days after implementation of ereferral (2-sample median P=.1114). In all cases, lower tract evaluation was completed after upper tract imaging. Our multivariable model evaluating factors associated with time to hematuria workup demonstrated that ereferral use was independently associated with shorter time to hematuria workup (P=.006). CONCLUSION Electronic consultations can significantly shorten the time to work-up of hematuria in the safety net. (C) 2013 Elsevier Inc. C1 [Bergman, Jonathan] Univ Calif Los Angeles, Dept Urol, Los Angeles, CA 90095 USA. Univ Calif Los Angeles, Dept Hlth Serv, Los Angeles, CA 90095 USA. Univ Calif Los Angeles, Dept Family Med, Los Angeles, CA 90095 USA. Univ Calif Los Angeles, Jonsson Comprehens Canc Ctr, Los Angeles, CA 90095 USA. VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. Univ Calif Los Angeles, Robert Wood Johnson Clin Scholars Program, Los Angeles, CA 90095 USA. RP Bergman, J (reprint author), Univ Calif Los Angeles, Dept Urol, Box 951738, Los Angeles, CA 90095 USA. EM jbergman@mednet.ucla.edu NR 23 TC 7 Z9 7 U1 0 U2 2 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 DEC PY 2013 VL 82 IS 6 BP 1277 EP 1282 DI 10.1016/j.urology.2013.08.015 PG 6 WC Urology & Nephrology SC Urology & Nephrology GA 259QB UT WOS:000327540300028 PM 24103564 ER PT J AU Sanchez, A Eisner, BH AF Sanchez, Alejandro Eisner, Brian H. TI Visceral Fat Is Correlated With Prolonged Operative Time in Laparoendoscopic Single-site Adrenalectomy and Laparoscopic Adrenalectomy EDITORIAL COMMENT SO UROLOGY LA English DT Editorial Material ID NEPHRECTOMY C1 [Sanchez, Alejandro; Eisner, Brian H.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Urol, Boston, MA 02114 USA. RP Sanchez, A (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Urol, Boston, MA 02114 USA. NR 2 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 DEC PY 2013 VL 82 IS 6 BP 1318 EP 1318 DI 10.1016/j.urology.2013.05.068 PG 1 WC Urology & Nephrology SC Urology & Nephrology GA 259QB UT WOS:000327540300039 PM 24139359 ER PT J AU Desai, NR Peterson, ED Chen, AY Wiviott, SD Sabatine, MS Alexander, KP Roe, MT Shah, BR AF Desai, Nihar R. Peterson, Eric D. Chen, Anita Y. Wiviott, Stephen D. Sabatine, Marc S. Alexander, Karen P. Roe, Matthew T. Shah, Bimal R. TI Balancing the risk of mortality and major bleeding in the treatment of NSTEMI patients - A report from the National Cardiovascular Data Registry SO AMERICAN HEART JOURNAL LA English DT Article ID ACUTE CORONARY SYNDROMES; ELEVATION MYOCARDIAL-INFARCTION; INTERVENTION OUTCOMES NETWORK; QUALITY IMPROVEMENT; GUIDELINE ADHERENCE; INVASIVE MANAGEMENT; UNSTABLE ANGINA; STRATIFICATION; PATTERNS; IMPACT AB Objectives We sought to describe real-world patterns of care in NSTEMI patients across different risk profiles for bleeding and mortality. Background The NCDR ACTION Registry-GWTG in-hospital mortality and major bleeding risk scores were developed to assess patient risk and optimize treatment decisions. However, little is known about the alignment of contemporary clinical management patterns with these risk estimates. Methods We studied 61,366 NSTEMI patients in the NCDR ACTION-Registry-GWTG from January 2007 to March 2009, stratifying them into four groups based on estimated risk of mortality and major bleeding. Results There were 24,709 (40.3%) patients in each of the concordant risk groups (low: low; high: high) and 5974 (9.7%) in each of the discordant risk groups (low: high; high: low). Subjects at high estimated risk for both mortality and major bleeding were least likely to receive guideline-based adjunctive pharmacotherapy or to undergo angiography within 48 hours but most likely to receive an excess dose of an antithrombotic agent. Patients at low estimated risk for mortality and bleeding received the most intensive adjunctive therapy and were most likely to undergo invasive angiography. Conclusion There are significant differences in contemporary patterns of care across varying risk profiles of mortality and major bleeding. Despite practice patterns which seem to emphasize avoiding harm with reduced use of antithrombotic therapy, patients at high risk for major bleeding continue to receive excess doses of antithrombotic therapy. Additional performance improvement efforts are needed to optimize outcomes in NSTEMI patients with high risk for both bleeding and mortality. C1 [Desai, Nihar R.; Wiviott, Stephen D.; Sabatine, Marc S.] Brigham & Womens Hosp, Dept Med, Div Cardiovasc Med, TIMI Study Grp, Boston, MA 02115 USA. [Desai, Nihar R.; Wiviott, Stephen D.; Sabatine, Marc S.] Harvard Univ, Sch Med, Boston, MA USA. [Peterson, Eric D.; Chen, Anita Y.; Alexander, Karen P.; Roe, Matthew T.; Shah, Bimal R.] Duke Univ, Dept Med, Div Cardiovasc Med, Duke Clin Res Inst, Durham, NC USA. RP Shah, BR (reprint author), 2400 Pratt St, Durham, NC 27712 USA. EM bimal.shah@duke.edu FU American College of Cardiology Foundation's National Cardiovascular Data Registry (NCDR); AstraZeneca; Merck-Schering Plough; Daiichi Sankyo; Eli Lilly; Bristol-Myers Squibb/Sanofi-Aventis Joint Venture; Merck; Pfizer; Sanofi-Aventis; KAI Pharmaceuticals; American College of Cardiology; American Heart Association FX Funding Information: This research was supported by the American College of Cardiology Foundation's National Cardiovascular Data Registry (NCDR). The views expressed in this manuscript represent those of the author(s), and do not necessarily represent the official views of the NCDR or its associated professional societies identified at www.ncdr.com.; S. D. W. has received research grant support from AstraZeneca, Merck-Schering Plough, Daiichi Sankyo, and Eli Lilly and honoraria for lectures and consultation from Bayer, ARENA, Ortho McNeil, Bristol-Myers Squibb, AstraZeneca, Eli Lilly, Daiichi Sankyo, Novartis, and Schering Plough.; MSS has received research grant support from AstraZeneca, Bristol-Myers Squibb/Sanofi-Aventis Joint Venture, Merck, and Pfizer and honoraria for lectures and consultation from Amgen and Bristol-Myers Squibb/Sanofi-Aventis Joint Venture.; MTR reports research support: Eli Lilly, Sanofi-Aventis, KAI Pharmaceuticals, American College of Cardiology, American Heart Association; consulting or honoraria: Bristol-Myers Squibb, Glaxo Smith Kline, Daiichi-Sankyo, Merck, Janssen Pharmaceuticals, Astra Zeneca, Regeneron. NR 23 TC 2 Z9 2 U1 0 U2 7 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-8703 EI 1097-5330 J9 AM HEART J JI Am. Heart J. PD DEC PY 2013 VL 166 IS 6 BP 1043 EP U145 DI 10.1016/j.ahj.2013.09.004 PG 8 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 259ON UT WOS:000327536300015 PM 24268219 ER PT J AU Hsich, EM Grau-Sepulveda, MV Hernandez, AF Eapen, ZBJ Xian, Y Schwamm, LH Bhatt, DL Fonarow, GC AF Hsich, Eileen M. Grau-Sepulveda, Maria V. Hernandez, Adrian F. Eapen, Zubin J. Xian, Ying Schwamm, Lee H. Bhatt, Deepak L. Fonarow, Gregg C. TI Relationship between sex, ejection fraction, and B-type natriuretic peptide levels in patients hospitalized with heart failure and associations with inhospital outcomes: Findings from the Get With The Guideline-Heart Failure Registry SO AMERICAN HEART JOURNAL LA English DT Article ID MORTALITY; GENDER; RISK; AGE; ADMISSION; INSIGHTS; IMPACT AB Background In heart failure (HF), there are known differences in plasma B-type natriuretic peptide (BNP) levels between reduced and preserved ejection fraction (EF), but few HF studies have explored sex differences. We sought to evaluate the relationship between sex, EF, and BNP in HF patients and determine prognostic significance of BNP as it relates to sex and EF. Methods We included hospitals in Get With The Guidelines-Heart Failure that admitted 99,930 HF patients with reduced (EF <40%), borderline (EF 40%-49%), or preserved (EF >= 50%) EF. The primary end point was inhospital mortality. Multivariate models were used to compute odds ratios while accounting for hospital clustering. Results There were 47,025 patients with reduced (37% female), 13,950 with borderline (48% female), and 38,955 with preserved (65% female) EF. Women compared with men had higher admission median BNP levels with the greatest difference among reduced EF and smallest difference among preserved EF (median BNP in women vs men: EF reduced 1,259 vs 1,113 pg/mL, borderline 821 vs 732 pg/mL, and preserved 559 vs 540 pg/mL; P < .001 all comparisons). Ejection fraction and sex were independently associated with BNP. Inhospital mortality was 2.7%, and patients above the median BNP level had higher mortality than those below. After adjusting for over 20 clinical variables, the ability of BNP to predict inhospital mortality was similar among all subgroups (P for heterogeneity = .47). Conclusions In a large registry, we found that despite sex/EF differences in BNP values, there was no significant difference in the ability of BNP to predict inhospital mortality among these subgroups. C1 [Hsich, Eileen M.] Cleveland Clin, Coll Med, Cleveland, OH 44195 USA. [Grau-Sepulveda, Maria V.; Hernandez, Adrian F.; Eapen, Zubin J.; Xian, Ying] Duke Clin Res Ctr, Durham, NC USA. [Schwamm, Lee H.] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. [Bhatt, Deepak L.] Brigham & Womens Hosp, Div Cardiol VA Boston Healthcare Syst, Boston, MA 02115 USA. [Bhatt, Deepak L.] Harvard Univ, Sch Med, Boston, MA USA. [Fonarow, Gregg C.] Univ Calif Los Angeles, Div Cardiol, Los Angeles, CA USA. RP Hsich, EM (reprint author), Cleveland Clin, Kaufman Ctr Heart Failure, Inst Heart & Vasc, J3-4,9500 Euclid Ave, Cleveland, OH 44195 USA. EM Hsiche@ccf.org RI Hernandez, Adrian F./A-7818-2016 OI Schwamm, Lee/0000-0003-0592-9145; Hernandez, Adrian F./0000-0003-3387-9616 FU Medtronic; GlaxoSmithKline; Ortho-McNeil; American Heart Association Pharmaceutical Roundtable; Johnson Johnson; Amylin FX Funding and relationship with industry: The Get With The Guidelines-Heart Failure program is provided by the American Heart Association. The Get With The Guidelines-Heart Failure program has been funded in the past through support from Medtronic, GlaxoSmithKline, Ortho-McNeil, and the American Heart Association Pharmaceutical Roundtable. Adrian Hernandez receives funding from Johnson & Johnson, and Amylin and has received honorarium from Amgen and Corthera. Dr Deepak L. Bhatt discloses the following relationships-Advisory Board: Medscape Cardiology; Board of Directors: Boston VA Research Institute, Society of Chest Pain Centers; Chair: American Heart Association Get With The Guidelines Science Subcommittee; Honoraria: American College of Cardiology (Editor, Clinical Trials, Cardiosource), Duke Clinical Research Institute (clinical trial steering committees), Slack Publications (Chief Medical Editor, Cardiology Today Intervention), WebMD (CME steering committees); Other: Senior Associate Editor, Journal of Invasive Cardiology; Research Grants: Amarin, AstraZeneca, Bristol-Myers Squibb, Eisai, Ethicon, Medtronic, Sanofi Aventis, The Medicines Company; Unfunded Research: FlowCo, PLx Pharma, Takeda. Gregg Fonarow is a consultant for Novartis, Gambro, and Medtronic. NR 22 TC 11 Z9 13 U1 0 U2 1 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-8703 EI 1097-5330 J9 AM HEART J JI Am. Heart J. PD DEC PY 2013 VL 166 IS 6 BP 1063 EP U170 DI 10.1016/j.ahj.2013.08.029 PG 12 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 259ON UT WOS:000327536300018 PM 24268222 ER PT J AU Toka, HR Yang, J Zera, CA Duffield, JS Pollak, MR Mount, DB AF Toka, Hakan R. Yang, Jun Zera, Chloe A. Duffield, Jeremy S. Pollak, Martin R. Mount, David B. TI Pregnancy-Associated Polyuria in Familial Renal Glycosuria SO AMERICAN JOURNAL OF KIDNEY DISEASES LA English DT Article DE Familial renal glycosuria; polyuria; natriuresis; vasopressin; SGLT2, SCL5A2 ID GLUCOSE COTRANSPORTER SGLT2; DIABETES-INSIPIDUS; VASOPRESSIN; DAPAGLIFLOZIN; AMINOACIDURIA; STIMULATION; INHIBITORS; EXCRETION; MELLITUS; MUTATION AB A pregnant woman presented at gestational week 28 with loss of consciousness and profound polyuria. Further characterization revealed osmotic diuresis due to massive glycosuria without hyperglycemia. Glycosuria reduced substantially postpartum, from similar to 100 to similar to 30 g/1.73 m(2) per day. DNA sequencing analysis of the SLC5A2 gene encoding the renal glucose transporter SGLT2 showed a homozygous frame-shift mutation (occurring after the glutamine at amino acid 168 and leading to premature termination of the protein at amino acid 186) diagnostic of familial renal glycosuria. Pregnant women with familial renal glycosuria can be at risk of profound polyuria during pregnancy due to the associated increase in glycosuria. These findings also have implications for the use of SGLT2 inhibitors in clinical practice. Published by Elsevier Inc. on behalf of the National Kidney Foundation, Inc. This is a US Government Work. There are no restrictions on its use. C1 [Toka, Hakan R.; Pollak, Martin R.] Beth Israel Deaconess Med Ctr, Div Nephrol, Boston, MA 02215 USA. [Toka, Hakan R.; Yang, Jun; Mount, David B.] Brigham & Womens Hosp, Div Nephrol, Boston, MA 02115 USA. [Zera, Chloe A.] Brigham & Womens Hosp, Div Obstet, Boston, MA 02115 USA. [Duffield, Jeremy S.] Univ Washington, Div Nephrol & Lung Biol, Seattle, WA 98195 USA. [Mount, David B.] VA Boston Healthcare Syst, Div Nephrol, Boston, MA 02132 USA. RP Mount, DB (reprint author), VA Boston Healthcare Syst, Boston, MA 02132 USA. EM david.mount2@va.gov FU National Institute of Diabetes and Digestive and Kidney Diseases [1P01DK070756] FX Support: Grant 1P01DK070756 from the National Institute of Diabetes and Digestive and Kidney Diseases (Drs Pollak and Mount). NR 28 TC 1 Z9 1 U1 0 U2 4 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0272-6386 EI 1523-6838 J9 AM J KIDNEY DIS JI Am. J. Kidney Dis. PD DEC PY 2013 VL 62 IS 6 BP 1160 EP 1164 DI 10.1053/j.ajkd.2013.05.018 PG 5 WC Urology & Nephrology SC Urology & Nephrology GA 259JS UT WOS:000327523800022 PM 23871407 ER PT J AU Grooms, KN Ommerborn, MJ Pham, DQ Djousse, L Clark, CR AF Grooms, Kya N. Ommerborn, Mark J. Do Quyen Pham Djousse, Luc Clark, Cheryl R. TI Dietary Fiber Intake and Cardiometabolic Risks among US Adults, NHANES 1999-2010 SO AMERICAN JOURNAL OF MEDICINE LA English DT Article DE Dietary fiber; Disparities; Metabolic diseases; NHANES ID C-REACTIVE PROTEIN; AMERICAN-HEART-ASSOCIATION; MULTIPLE-PASS METHOD; METABOLIC SYNDROME; UNITED-STATES; CARDIOVASCULAR-DISEASE; PHYSICAL-ACTIVITY; HEALTH; POPULATION; TRENDS AB BACKGROUND: Dietary fiber may decrease the risk of cardiovascular disease and associated risk factors. We examined trends in dietary fiber intake among diverse US adults between 1999 and 2010, and investigated associations between dietary fiber intake and cardiometabolic risks including metabolic syndrome, cardiovascular inflammation, and obesity. METHODS: Our cross-sectional analysis included 23,168 men and nonpregnant women aged 20 broken vertical bar years from the 1999-2010 National Health and Nutrition Examination Survey. We used weighted multivariable logistic regression models to estimate predicted marginal risk ratios and 95% confidence intervals for the risks of having the metabolic syndrome, inflammation, and obesity associated with quintiles of dietary fiber intake. RESULTS: Consistently, dietary fiber intake remained below recommended adequate intake levels for total fiber defined by the Institute of Medicine. Mean dietary fiber intake averaged 15.7-17.0 g. Mexican Americans (18.8 g) consumed more fiber than non-Hispanic whites (16.3 g) and non-Hispanic blacks (13.1 g). Comparing the highest with the lowest quintiles of dietary fiber intake, adjusted predicted marginal risk ratios (95% confidence interval) for the metabolic syndrome, inflammation, and obesity were 0.78 (0.69-0.88), 0.66 (0.61-0.72), and 0.77 (0.71-0.84), respectively. Dietary fiber was associated with lower levels of inflammation within each racial and ethnic group, although statistically significant associations between dietary fiber and either obesity or metabolic syndrome were seen only among whites. CONCLUSIONS: Low dietary fiber intake from 1999-2010 in the US, and associations between higher dietary fiber and a lower prevalence of cardiometabolic risks suggest the need to develop new strategies and policies to increase dietary fiber intake. (C) 2013 Elsevier Inc. All rights reserved. C1 [Grooms, Kya N.; Ommerborn, Mark J.; Do Quyen Pham; Clark, Cheryl R.] Brigham & Womens Hosp, Ctr Community Hlth & Hlth Equ, Boston, MA 02120 USA. [Djousse, Luc] Brigham & Womens Hosp, Dept Med, Boston, MA 02120 USA. [Djousse, Luc] Brigham & Womens Hosp, Div Aging, Boston, MA 02120 USA. [Djousse, Luc; Clark, Cheryl R.] Harvard Univ, Sch Med, Boston, MA USA. [Djousse, Luc] Boston VA Healthcare Syst, Boston, MA USA. [Clark, Cheryl R.] Brigham & Womens Faulkner Hospitalist Program, Div Gen Med & Primary Care, Boston, MA USA. RP Clark, CR (reprint author), Brigham & Womens Hosp, Ctr Community Hlth & Hlth Equ, 1620 Tremont St, Boston, MA 02120 USA. EM crclark@partners.org RI Djousse, Luc/F-5033-2017 OI Djousse, Luc/0000-0002-9902-3047 FU Partners HealthCare; Brigham and Women's Hospital Center for Community Health and Health Equity; National Institute on Aging [NIH K08 AG 032357] FX Institutional financial support was provided from Partners HealthCare and the Brigham and Women's Hospital Center for Community Health and Health Equity. CRC was supported by funding from the National Institute on Aging (NIH K08 AG 032357). NR 44 TC 24 Z9 26 U1 0 U2 23 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9343 EI 1555-7162 J9 AM J MED JI Am. J. Med. PD DEC PY 2013 VL 126 IS 12 BP 1059 EP + AR 1067.e1 DI 10.1016/j.amjmed.2013.07.023 PG 13 WC Medicine, General & Internal SC General & Internal Medicine GA 257OC UT WOS:000327393300037 PM 24135514 ER PT J AU Siegel, AJ AF Siegel, Arthur J. TI Aspirin Usage Pre-race to Prevent Cardiac Arrest in Marathon Runners during Races SO AMERICAN JOURNAL OF MEDICINE LA English DT Letter ID UNITED-STATES C1 [Siegel, Arthur J.] McLean Hosp, Dept Internal Med, Belmont, MA 02178 USA. [Siegel, Arthur J.] Harvard Univ, Sch Med, Boston, MA USA. [Siegel, Arthur J.] Massachusetts Gen Hosp Internal Med Associates Be, Belmont, MA USA. RP Siegel, AJ (reprint author), McLean Hosp, Dept Internal Med, 115 Mill St, Belmont, MA 02178 USA. NR 9 TC 2 Z9 2 U1 0 U2 10 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9343 EI 1555-7162 J9 AM J MED JI Am. J. Med. PD DEC PY 2013 VL 126 IS 12 BP E47 EP E47 DI 10.1016/j.amjmed.2013.06.024 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA 257OC UT WOS:000327393300024 PM 24262748 ER PT J AU Nabi-Burza, E Winickoff, JP Finch, S Regan, S AF Nabi-Burza, Emara Winickoff, Jonathan P. Finch, Stacia Regan, Susan TI Triple Tobacco Screen Opportunity to Help Families Become Smokefree SO AMERICAN JOURNAL OF PREVENTIVE MEDICINE LA English DT Article ID INFANT-DEATH-SYNDROME; PASSIVE SMOKING; RESPIRATORY ILLNESS; PARENTAL SMOKING; YOUNG-CHILDREN; HEALTH; INTERVENTION; CESSATION; EXPOSURE; DISEASE AB Background: American Academy of Pediatrics policy recommends that pediatricians document environmental tobacco smoke (ETS) exposure of a child at every visit. The extent to which pediatricians adhere to this policy, however, is unknown. Purpose: The goal of the study was to examine the extent to which pediatricians screen parents for tobacco use and home-and car-related smoking rules. Further, the potential association between factors associated with pediatrician inquiry into parental tobacco use and rules is examined. Methods: Post-visit exit interviews were conducted in ten pediatric practices between June 2009 and March 2011 with parents whose children had been seen by a healthcare provider. Parents were considered to have been given the "triple tobacco screen" if they reported being asked by a pediatric healthcare provider about their smoking behavior, smokefree home rules, and smokefree car rules. Bivariate analysis and multivariable logistic regression was done to explore factors associated with parents being given any component of the triple tobacco screening. Data were analyzed between March 2012 and February 2013. Results: Of 9145 parents interviewed, 20% of the parents reported being asked at least one question from the triple tobacco screen, and only 9% reported being asked all three questions. Overall, 17% of parents reported being asked about their smoking status, 16% about smokefree home rules, and 11% about smokefree car rules. Few smoking parents (23%) and fewer nonsmoking parents (19%) were screened about their tobacco use and behavior. Conclusions: Pediatricians infrequently addressed ETS exposure of children among parents who do and do not smoke. Substantial missed opportunities may exist to counsel smokers and reduce ETS exposure of children in the most common exposure locations-the home and car. (C) 2013 American Journal of Preventive Medicine C1 [Nabi-Burza, Emara; Winickoff, Jonathan P.] Massachusetts Gen Hosp Children, Ctr Child & Adolescent Hlth Res & Policy, Boston, MA USA. [Regan, Susan] Massachusetts Gen Hosp, Dept Gen Med, Boston, MA 02114 USA. [Winickoff, Jonathan P.] Amer Acad Pediat, AAP Richmond Ctr, Elk Grove Village, IL USA. [Finch, Stacia] Amer Acad Pediat, Pediat Res Off Settings, Elk Grove Village, IL USA. RP Nabi-Burza, E (reprint author), Massachusetts Gen Hosp, Ctr Child & Adolescent Hlth Res & Policy, 15th Floor,C-100,100 Cambridge St, Boston, MA 02114 USA. EM emaranburza@gmail.com FU NIH National Cancer Institute [R01-CA127127]; National Institute on Drug Abuse; Agency for Healthcare Research and Quality; Flight Attendant Medical Research Institute; Pediatric Research in Office Settings (PROS) Network; Health Resources and Services Administration (HRSA) Maternal and Child Health Bureau [HRSA 5-UA6-10-001]; AAP FX This study was supported by the NIH National Cancer Institute Grant R01-CA127127 (to JPW), the National Institute on Drug Abuse, and the Agency for Healthcare Research and Quality. This study was also partially supported by a grant from the Flight Attendant Medical Research Institute to the AAP Julius B. Richmond Center, and the Pediatric Research in Office Settings (PROS) Network, which receives core funding from the Health Resources and Services Administration (HRSA) Maternal and Child Health Bureau (HRSA 5-UA6-10-001) and the AAP. The funders had no role in the design or conduct of the study; collection, management, analysis, and interpretation of the data; or preparation, review, and approval of the paper. NR 23 TC 3 Z9 3 U1 1 U2 5 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0749-3797 EI 1873-2607 J9 AM J PREV MED JI Am. J. Prev. Med. PD DEC PY 2013 VL 45 IS 6 BP 728 EP 731 DI 10.1016/j.amepre.2013.07.007 PG 4 WC Public, Environmental & Occupational Health; Medicine, General & Internal SC Public, Environmental & Occupational Health; General & Internal Medicine GA 258SG UT WOS:000327478400011 PM 24237914 ER PT J AU Zissen, MH Wang, ZJ Yee, J Aslam, R Monto, A Yeh, BM AF Zissen, Maurice H. Wang, Zhen Jane Yee, Judy Aslam, Rizwan Monto, Alexander Yeh, Benjamin M. TI Contrast-Enhanced CT Quantification of the Hepatic Fractional Extracellular Space: Correlation With Diffuse Liver Disease Severity SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Article DE cirrhosis; CT; delayed enhancement; liver ID DELAYED ENHANCEMENT; HEPATOCELLULAR-CARCINOMA; HELICAL CT; FIBROSIS; CIRRHOSIS; BIOPSY; CHOLANGIOCARCINOMA; PROTOCOL; MASSES; APPEARANCE AB OBJECTIVE. The purpose of this study was to determine whether contrast-enhanced CT quantification of the hepatic fractional extracellular space (ECS) correlates with the severity of diffuse liver disease. MATERIALS AND METHODS. The cases of 70 patients without (46 men, 24 women; mean age, 59.1 years) and 36 patients with (23 men, 13 women; mean age, 63.1 years) cirrhosis who had undergone unenhanced and 10-minute delayed phase contrast-enhanced CT were retrospectively identified. By consensus one experienced radiologist and one trainee measured the CT attenuation of the liver and aorta to estimate the fractional ECS, defined as the ratio of the difference between the attenuation of the liver on 10-minute and unenhanced images to the difference between the attenuation of the aorta on 10-minute and unenhanced images multiplied by 1 minus the hematocrit. Findings were correlated with each patient's Model of End-Stage Liver Disease (MELD) score. RESULTS. The mean MELD score was higher in patients with than in those without cirrhosis (14.3 +/- 7.3 versus 7.20 +/- 2.4, p < 0.0001). The mean fractional ECS was significantly greater in patients with cirrhosis than in those without cirrhosis (41.0% +/- 9.0% versus 23.8% +/- 6.3%, p < 0.0001). The fractional ECS correlated with the MELD score (r = 0.572, p < 0.0001) and was predictive of cirrhosis with an area under the receiver operating characteristic curve of 0.953 (p < 0.0001). The sensitivity and specificity of an expanded fractional ECS greater than 30% for the prediction of cirrhosis were 92% and 83%. Multivariate linear regression revealed that the fractional ECS is complementary to the MELD score as a predictor of cirrhosis (p < 0.0001). CONCLUSION. Noninvasive contrast-enhanced CT quantification of the fractional ECS correlates with the MELD score, an indicator of the severity of liver disease, and merits further study. C1 [Zissen, Maurice H.; Wang, Zhen Jane; Yee, Judy; Aslam, Rizwan; Yeh, Benjamin M.] Univ Calif San Francisco, Dept Radiol & Biomed Imaging, San Francisco, CA 94143 USA. [Monto, Alexander] San Francisco VA Med Ctr, Div Gastroenterol, Dept Internal Med, San Francisco, CA USA. RP Yeh, BM (reprint author), Univ Calif San Francisco, Dept Radiol & Biomed Imaging, 505 Parnassus Ave,Box 0628,M-372, San Francisco, CA 94143 USA. EM ben.yeh@ucsf.edu FU GE Healthcare FX Supported by a grant from GE Healthcare. NR 34 TC 10 Z9 13 U1 0 U2 1 PU AMER ROENTGEN RAY SOC PI RESTON PA 1891 PRESTON WHITE DR, SUBSCRIPTION FULFILLMENT, RESTON, VA 22091 USA SN 0361-803X EI 1546-3141 J9 AM J ROENTGENOL JI Am. J. Roentgenol. PD DEC PY 2013 VL 201 IS 6 BP 1204 EP 1210 DI 10.2214/AJR.12.10039 PG 7 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 259BD UT WOS:000327501500028 PM 24261358 ER PT J AU Dhyani, M Faquin, W Lubitz, CC Daniels, GH Samir, AE AF Dhyani, Manish Faquin, William Lubitz, Carrie C. Daniels, Gilbert H. Samir, Anthony E. TI How to Interpret Thyroid Fine-Needle Aspiration Biopsy Reports: A Guide for the Busy Radiologist in the Era of the Bethesda Classification System SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Article DE atypia of undetermined significance (AUS); Bethesda System for Reporting Thyroid Cytopathology; cytology; fine-needle aspiration biopsy; follicular lesion of undetermined significance (FLUS); follicular neoplasm; nondiagnostic thyroid biopsy; thyroid ID FOLLICULAR NEOPLASM; FOLLOW-UP; NODULES; CYTOLOGY; MUTATION; DIAGNOSIS; CANCER; ULTRASOUND; MANAGEMENT; CARCINOMA AB OBJECTIVE. Fine-needle aspiration biopsy (FNAB) is the current primary test to risk stratify thyroid nodules. However, in up to one third of biopsies, cytology is indeterminate. The Bethesda System for Reporting Thyroid Cytopathology categorizes thyroid cytology findings into six groups, with each group assigned a putative malignancy risk. This article reviews the Bethesda System, emphasizing the key facts necessary to understand thyroid biopsy results and effectively manage patients after FNAB. CONCLUSION. It is important to diagnose and stratify the risk of malignancy in thyroid nodules. A working knowledge of the Bethesda System permits accurate, evidence-based risk stratification of patients with thyroid nodules and thereby facilitates their management. Because it is a uniform diagnostic approach, the Bethesda System allows comparisons of different management strategies across different institutions. C1 [Dhyani, Manish; Samir, Anthony E.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiol Abdominal Imaging & Intervent, Boston, MA 02114 USA. [Faquin, William] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Pathol, Boston, MA 02114 USA. [Lubitz, Carrie C.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Surg, Boston, MA 02114 USA. [Daniels, Gilbert H.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Med, Boston, MA 02114 USA. [Daniels, Gilbert H.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Canc Ctr,Thyroid Unit, Boston, MA 02114 USA. RP Samir, AE (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiol Abdominal Imaging & Intervent, 55 Fruit St,White 270, Boston, MA 02114 USA. EM asamir@partners.org OI Samir, Anthony/0000-0002-7801-8724; Dhyani, Manish/0000-0002-2651-1859 NR 38 TC 3 Z9 3 U1 0 U2 3 PU AMER ROENTGEN RAY SOC PI RESTON PA 1891 PRESTON WHITE DR, SUBSCRIPTION FULFILLMENT, RESTON, VA 22091 USA SN 0361-803X EI 1546-3141 J9 AM J ROENTGENOL JI Am. J. Roentgenol. PD DEC PY 2013 VL 201 IS 6 BP 1335 EP 1339 DI 10.2214/AJR.13.10537 PG 5 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 259BD UT WOS:000327501500046 PM 24261375 ER PT J AU Moshiri, M Mannelli, L Richardson, ML Bhargava, P Dubinsky, TJ AF Moshiri, Mariam Mannelli, Lorenzo Richardson, Michael L. Bhargava, Puneet Dubinsky, Theodore J. TI Fetal Lung Maturity Assessment With MRI Fetal Lung-to-Liver Signal-Intensity Ratio SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Article DE fetal lung; lung maturity; MRI ID CONGENITAL DIAPHRAGMATIC-HERNIA; PULMONARY HYPOPLASIA; IN-UTERO; VOLUME AB OBJECTIVE. The purpose of this study was to retrospectively determine whether the ratio of fetal lung-to-liver signal intensities at single-shot fast spin-echo MRI is associated with fetal gestational age. MATERIALS AND METHODS. All fetal MRI examinations over a 4-year period were reviewed. All MRI examinations were performed with a 1.5-T magnet for indications other than lung maturity. Only examinations performed with a single-shot fast spin-echo sequence of the fetal chest and abdomen were included in the study. Images from a total of 82 fetal MRI examinations were evaluated. Gestational age ranged from 20 weeks to 39 weeks 3 days. Two board-certified subspecialty-trained radiologists with 11 and 17 years of experience blinded to estimated gestational age (EGA) reviewed the images independently. The regions of interest (ROIs) of the fetal lung and liver were drawn in the same plane and on the same image in each case. Fetal EGA was determined either by first-trimester ultrasound when available or by last menstrual period. Linear regression analysis was used to analyze the relation between the lung-to-liver signal-intensity ratio (LLSIR) in the ROIs and fetal EGA for both readers. The association between the LLSIRs estimated by the two readers was assessed by Bland-Altman plot. RESULTS. Summary statistics for LLSIR showed a median value of 2.29 for reader 1 and 2.21 for reader 2. The mean value for reader 1 was 2.4 and for reader 2 was 2.5. The Pearson correlation coefficients between the LLSIR and EGA variables were 0.44 for reader 1 and 0.45 for reader 2. Linear regression analysis showed a statistically significant association between LLSIR and EGA for both readers (p < 0.0004). This ratio increased in a linear manner as EGA progressed. CONCLUSION. Fetal LLSIR at single-shot fast spin-echo MRI is associated with fetal gestational age. C1 [Moshiri, Mariam; Mannelli, Lorenzo; Richardson, Michael L.; Bhargava, Puneet; Dubinsky, Theodore J.] Univ Washington, Med Ctr, Dept Radiol, Seattle, WA 98195 USA. [Bhargava, Puneet] VA Puget Sound Hlth Care Syst, Dept Radiol, Seattle, WA USA. RP Moshiri, M (reprint author), Univ Washington, Med Ctr, Dept Radiol, 1959 NE Pacific St,Box 357115, Seattle, WA 98195 USA. EM Moshiri@uw.edu OI Bhargava, Puneet/0000-0002-3849-9666; Mannelli, Lorenzo/0000-0002-9102-4176 NR 29 TC 3 Z9 3 U1 0 U2 3 PU AMER ROENTGEN RAY SOC PI RESTON PA 1891 PRESTON WHITE DR, SUBSCRIPTION FULFILLMENT, RESTON, VA 22091 USA SN 0361-803X EI 1546-3141 J9 AM J ROENTGENOL JI Am. J. Roentgenol. PD DEC PY 2013 VL 201 IS 6 BP 1386 EP 1390 DI 10.2214/AJR.12.9679 PG 5 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 259BD UT WOS:000327501500053 PM 24261381 ER PT J AU Dhyani, M Anupindi, SA Ayyala, R Hahn, PF Gee, MS AF Dhyani, Manish Anupindi, Sudha A. Ayyala, Rama Hahn, Peter F. Gee, Michael S. TI Defining an Imaging Algorithm for Noncystic Splenic Lesions Identified in Young Patients SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Article DE algorithm; computed tomography; malignancy; MRI; non-cystic; pediatric imaging; spleen; splenic lesion; ultrasound; young adults ID RADIATION; CT; SPLENECTOMY; CANCER; UPDATE; RISKS AB OBJECTIVE. The purpose of this study was to classify noncystic splenic lesions detected on imaging in young patients (0-30 years) and to determine the optimal imaging workup for such lesions. MATERIALS AND METHODS. This study was conducted at three academic institutions by performing a database search of radiology reports (2002-2011) to identify patients with noncystic splenic lesions. Medical records were then searched to identify radiology examination indications, clinical follow-up, and lesion changes on subsequent imaging. All lesions had either definitive diagnosis (histopathology or laboratory results consistent with infectious cause) or lesion stability more than 2 years consistent with a benign cause. RESULTS. Benign (n = 32), benign indeterminate (n = 7), and malignant (n = 14) lesions were identified in 53 patients (26 males and 27 females; mean age, 19 years; age range, 1 month-30 years). Lesions were initially detected on the following imaging modalities: CT (n = 27), ultrasound (n = 12), MRI (n = 6), and PET/CT (n = 8). A total of 14 patients underwent MRI for lesion characterization, and 12 underwent PET/CT. MRI permitted definitive characterization of benign lesions in 10 of 14 (72%) patients, whereas PET/CT was used to diagnose nine of nine (100%) malignant splenic lesions and helped exclude malignancy in two of three benign lesions. CONCLUSION. Contrast-enhanced MRI is recommended for imaging workup of noncystic splenic lesions discovered in young patients because it can enable definitive diagnosis of most benign lesions. Lesions with indeterminate MRI features can be followed-up with ultrasound or CT. PET or PET/CT is recommended for patients with clinical evidence of malignancy but is less helpful for characterization of isolated splenic lesions. C1 [Dhyani, Manish; Hahn, Peter F.; Gee, Michael S.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiol, Boston, MA 02114 USA. [Anupindi, Sudha A.] Univ Penn, Childrens Hosp Philadelphia, Perleman Sch Med, Dept Radiol, Philadelphia, PA 19104 USA. [Ayyala, Rama] Columbia Univ, Columbia Presbyterian Med Ctr, Sch Med, Dept Radiol, New York, NY 10032 USA. RP Gee, MS (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiol, 55 Fruit St,Ellison 237, Boston, MA 02114 USA. EM msgee@partners.org OI Dhyani, Manish/0000-0002-2651-1859 NR 14 TC 0 Z9 0 U1 0 U2 0 PU AMER ROENTGEN RAY SOC PI RESTON PA 1891 PRESTON WHITE DR, SUBSCRIPTION FULFILLMENT, RESTON, VA 22091 USA SN 0361-803X EI 1546-3141 J9 AM J ROENTGENOL JI Am. J. Roentgenol. PD DEC PY 2013 VL 201 IS 6 BP W893 EP W899 DI 10.2214/AJR.12.10105 PG 7 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 259BD UT WOS:000327501500012 PM 24261396 ER PT J AU Kim, KW Ramaiya, NH AF Kim, Kyung Won Ramaiya, Nikhil H. TI Molecular Imaging Enhances Diagnostic and Management Targets in Patients With Cancer of Unknown Primary Site Reply SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Letter C1 [Kim, Kyung Won; Ramaiya, Nikhil H.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. [Kim, Kyung Won] Univ Ulsan, Coll Med, Seoul Asan Med Ctr, Seoul, South Korea. RP Kim, KW (reprint author), Harvard Univ, Brigham & Womens Hosp, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. NR 5 TC 0 Z9 0 U1 0 U2 0 PU AMER ROENTGEN RAY SOC PI RESTON PA 1891 PRESTON WHITE DR, SUBSCRIPTION FULFILLMENT, RESTON, VA 22091 USA SN 0361-803X EI 1546-3141 J9 AM J ROENTGENOL JI Am. J. Roentgenol. PD DEC PY 2013 VL 201 IS 6 BP W920 EP W920 DI 10.2214/AJR.13.11230 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 259BD UT WOS:000327501500020 PM 24261404 ER PT J AU Lee, S Yamada, Y Tonsho, M Boskovic, S Nadazdin, O Schoenfeld, D Cappetta, K Atif, M Smith, RN Cosimi, AB Benichou, G Kawai, T AF Lee, S. Yamada, Y. Tonsho, M. Boskovic, S. Nadazdin, O. Schoenfeld, D. Cappetta, K. Atif, M. Smith, R. -N. Cosimi, A. B. Benichou, G. Kawai, T. TI Alefacept Promotes Immunosuppression-Free Renal Allograft Survival in Nonhuman Primates via Depletion of Recipient Memory T Cells SO AMERICAN JOURNAL OF TRANSPLANTATION LA English DT Article DE Kidney transplantation; memory T cells; nonhuman primates; mixed hematopoietic chimerism; tolerance ID CYNOMOLGUS MONKEYS; TOLERANCE; INDUCTION; HOMEOSTASIS; BELATACEPT; CHIMERISM; PHENOTYPE; PSORIASIS; BLOCKADE; THERAPY AB Renal allograft tolerance has been achieved in MHC-mismatched primates via nonmyeloablative conditioning beginning 6 days prior to planned kidney and donor bone marrow transplantation (DBMT). To extend the applicability of this approach to deceased donor transplantation, we recently developed a novel-conditioning regimen, the delayed protocol in which donor bone marrow (DBM) is transplanted several months after kidney transplantation. However, activation/expansion of donor-reactive CD8(+) memory T cells (TMEM) occurring during the interval between kidney and DBM transplantation impaired tolerance induction using this strategy. In the current study, we tested whether, Alefacept, a fusion protein which targets LFA-3/CD2 interactions and selectively depletes CD2(high)CD8(+) effector memory T cells (TEM) could similarly induce long-term immunosuppression-free renal allograft survival but avoid the deleterious effects of anti-CD8 mAb treatment. We found that Alefacept significantly delayed the expansion of CD2(high) cells including CD8(+) TEM while sparing naive CD8(+) T and NK cells and achieved mixed chimerism and long-term immunosuppression-free renal allograft survival. In conclusion, elimination of CD2(high) T cells represents a promising approach to prevent electively the expansion/activation of donor-reactive TEM and promotes tolerance induction via the delayed protocol mixed chimerism approach. C1 [Lee, S.; Yamada, Y.; Tonsho, M.; Boskovic, S.; Nadazdin, O.; Cappetta, K.; Atif, M.; Cosimi, A. B.; Benichou, G.; Kawai, T.] Harvard Univ, Sch Med, Dept Surg, Transplant Ctr,Massachusetts Gen Hosp, Boston, MA 02115 USA. [Schoenfeld, D.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Biostat, Boston, MA USA. [Smith, R. -N.] Harvard Univ, Sch Med, Dept Pathol, Massachusetts Gen Hosp, Boston, MA 02115 USA. RP Kawai, T (reprint author), Harvard Univ, Sch Med, Dept Surg, Transplant Ctr,Massachusetts Gen Hosp, Boston, MA 02115 USA. EM tkawai@partners.org FU NIH [AI102405-01]; Astellas, Inc FX This study was supported in part by NIH AI102405-01, and a research fund provided by Astellas, Inc. We thank Ms. Susan Shea for technical assistance and Ms. Felicia Libby and Ms. Samantha Moses for editorial assistance. NR 19 TC 12 Z9 13 U1 0 U2 3 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1600-6135 EI 1600-6143 J9 AM J TRANSPLANT JI Am. J. Transplant. PD DEC PY 2013 VL 13 IS 12 BP 3223 EP 3229 DI 10.1111/ajt.12500 PG 7 WC Surgery; Transplantation SC Surgery; Transplantation GA 255JN UT WOS:000327235300025 PM 24165326 ER PT J AU Sittig, DF Singh, H Longhurst, CA AF Sittig, Dean F. Singh, Hardeep Longhurst, Christopher A. TI Rights and responsibilities of electronic health records (EHR) users caring for children SO ARCHIVOS ARGENTINOS DE PEDIATRIA LA English DT Editorial Material ID SPECIAL REQUIREMENTS; SAFETY; CARE C1 [Sittig, Dean F.] Univ Texas Sch Biomed Informat, Houston, TX USA. [Sittig, Dean F.] UT Mem Hermann Ctr Healthcare Qual & Safety, Houston, TX USA. [Singh, Hardeep] Baylor Coll Med, Houston VA Hlth Sci Res & Dev Ctr Excellence, Michael E DeBakey Vet Affairs Med Ctr, Houston, TX 77030 USA. [Singh, Hardeep] Baylor Coll Med, Dept Med, Sect Hlth Serv Res, Houston, TX 77030 USA. [Longhurst, Christopher A.] Stanford Univ, Dept Pediat, Sch Med, Div Syst Med, Stanford, CA 94305 USA. RP Sittig, DF (reprint author), Univ Texas Sch Biomed Informat, Houston, TX USA. NR 13 TC 2 Z9 3 U1 0 U2 0 PU SOC ARGENTINA PEDIATRIA PI CAP FED BUENO AIRES PA AV COLONEL DIAZ 1971-75-C1425DQF, CAP FED BUENO AIRES, 00000, ARGENTINA SN 0325-0075 EI 1668-3501 J9 ARCH ARGENT PEDIATR JI Arch. Argent. Pediatr. PD DEC PY 2013 VL 111 IS 6 BP 469 EP 471 DI 10.5546/aap.2013.469 PG 3 WC Pediatrics SC Pediatrics GA 258PL UT WOS:000327471100009 ER PT J AU Norman, RS Jaramillo, CA Amuan, M Wells, MA Eapen, BC Pugh, MJ AF Norman, Rocio S. Jaramillo, Carlos A. Amuan, Megan Wells, Margaret Ann Eapen, Blessen C. Pugh, Mary Jo TI Traumatic brain injury in veterans of the wars in Iraq and Afghanistan: Communication disorders stratified by severity of brain injury SO BRAIN INJURY LA English DT Article DE aphasia; epidemiology; fluency disorder; TBI severity; Veterans Health Administration; voice disorder ID POSTTRAUMATIC-STRESS-DISORDER; HEAD-INJURY; VOICE DISORDERS; MILD; LANGUAGE; SYMPTOMS; REHABILITATION; IMPAIRMENT; MANAGEMENT; ABILITIES AB Objective: To describe the prevalence of communication disorders in veterans of the wars in Iraq and Afghanistan with traumatic brain injury (TBI). Design: Retrospective study of the prevalence of aphasia, fluency and voice disorders among veterans with different severity levels of TBI. Data was obtained from the VA National repository for OEF/OIF/OND veterans who received VA care in Fiscal Years 2010 and 2011. Results: Among the 303 716 veterans in this study, 1848 were diagnosed with a communication disorder; 40% of these were also diagnosed with a TBI. Voice disorders were the most prevalent diagnosis (3.5 per 1000) followed by aphasia (1.9 per 1000) and fluency disorder (0.7 per 1000). Individuals with a TBI diagnosis were more likely to have a diagnosis of aphasia, followed by fluency and then voice disorder. The odds ratio (OR) of aphasia with TBI was 11.09-252.75 (95% CI = 8.78-441.52, p < 0.01). OR for fluency disorders with TBI was 3.58-10.41 (95% CI = 2.56-42.40, p < 0.01) and association of voice disorders with TBI was significant for all levels of TBI severity (OR = 1.5-6.61, 95% CI = 1.24-14.05, p < 0.01). Conclusions: Veterans who sustained a TBI were more likely to have a diagnosis of a communication disorder, regardless of TBI severity. Those with TBI, including mild TBI, should be screened and evaluated for communication disorders. C1 [Norman, Rocio S.; Jaramillo, Carlos A.] South Texas Vet Hlth Care Syst, Polytrauma Rehabil Ctr, San Antonio, TX USA. [Amuan, Megan] Edith Nourse Rogers Mem VA Hosp, Ctr Hlth Qual Outcomes & Econ Res, Bedford, MA USA. [Wells, Margaret Ann] Univ Texas Hlth Sci Ctr San Antonio, Dept Epidemiol & Biostat, San Antonio, TX 78229 USA. [Eapen, Blessen C.] South Texas Vet Hlth Care Syst, Polytrauma Transit Rehabil Program, San Antonio, TX USA. [Pugh, Mary Jo] Univ Texas Hlth Sci Ctr San Antonio, Dept Epidemiol & Biostat, South Texas Vet Hlth Care Syst, San Antonio, TX 78229 USA. RP Norman, RS (reprint author), Univ Wisconsin, Dept Commun Sci & Disorders, 1975 Willow Dr, Madison, WI 53706 USA. EM rnorman2@wisc.edu OI Pugh, Mary Jo/0000-0003-4196-7763 FU South Texas Veterans Healthcare System/Audie L. Murphy Division; Edith Nourse Rogers VA Memorial Hospital FX The authors acknowledge and appreciate support from the South Texas Veterans Healthcare System/Audie L. Murphy Division and the Edith Nourse Rogers VA Memorial Hospital. We also acknowledge assistance with manuscript preparation by Barbara Elizondo and Kathleen Franklin as well as valuable input by Dr Juan Cabrera at the initial stages of the manuscript process. 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 50 TC 6 Z9 6 U1 0 U2 9 PU INFORMA HEALTHCARE PI LONDON PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND SN 0269-9052 EI 1362-301X J9 BRAIN INJURY JI Brain Inj. PD DEC PY 2013 VL 27 IS 13-14 BP 1623 EP 1630 DI 10.3109/02699052.2013.834380 PG 8 WC Neurosciences; Rehabilitation SC Neurosciences & Neurology; Rehabilitation GA 259BW UT WOS:000327503400018 PM 24131337 ER PT J AU Goyal, L Supko, JG Berlin, J Blaszkowsky, LS Carpenter, A Heuman, DM Hilderbrand, SL Stuart, KE Cotler, S Senzer, NN Chan, E Berg, CL Clark, JW Hezel, AF Ryan, DP Zhu, AX AF Goyal, Lipika Supko, Jeffrey G. Berlin, Jordan Blaszkowsky, Lawrence S. Carpenter, Amanda Heuman, Douglas M. Hilderbrand, Sarah L. Stuart, Keith E. Cotler, Scott Senzer, Neil N. Chan, Emily Berg, Carl L. Clark, Jeffrey W. Hezel, Aram F. Ryan, David P. Zhu, Andrew X. TI Phase 1 study of N (1),N (11)-diethylnorspermine (DENSPM) in patients with advanced hepatocellular carcinoma SO CANCER CHEMOTHERAPY AND PHARMACOLOGY LA English DT Article DE Hepatocellular carcinoma; DENSPM; Pharmacokinetics; Phase I trial ID POLYAMINE ANALOG N-1,N-11-DIETHYLNORSPERMINE; MELANOMA CELL-LINES; ANTITUMOR-ACTIVITY; SPERMINE ANALOG; GROWTH; INHIBITION; METABOLISM; ORNITHINE; CANCER AB N (1),N (11)-diethylnorspermine (DENSPM), a synthetic analog of the naturally occurring polyamine spermine, can induce polyamine depletion and inhibit tumor cell growth. The objectives of this phase I study were to assess the safety, maximum-tolerated dose (MTD), pharmacokinetics, and preliminary antitumor activity of DENSPM in advanced HCC. Patients with measurable advanced HCC, Child-Pugh A or B cirrhosis, CLIP score a parts per thousand currency sign3, and Karnofsky score a parts per thousand yen60 % were eligible. DENSPM was given as a short intravenous infusion on days 1, 3, 5, 8, 10, and 12 of each 28-day cycle. The starting dose of 30 mg/m(2) was escalated at a fixed increment of 15 mg/m(2) until the MTD was identified. The plasma pharmacokinetics of DENSPM for the first and last doses given in cycle 1 was characterized. Thirty-eight patients (male 79 %; median age 61 years; Child-Pugh A 84 %; a parts per thousand yen1 prior systemic therapy 45 %) were enrolled and treated. The most common adverse events (AEs) a parts per thousand yengrade 1 were fatigue (53 %), nausea (34 %), diarrhea (32 %), vomiting (32 %), anemia (29 %), and elevated AST (29 %). The most common grade 3-4 AEs were fatigue/asthenia (13 %), elevated AST (13 %), hyperbilirubinemia (11 %), renal failure (8 %), and hyperglycemia (8 %). The MTD was 75 mg/m(2). There were no objective responses, although 7/38 (18 %) patients achieved stable disease for a parts per thousand yen16 weeks. The overall mean (+/- SD) total body clearance for the initial dose, 66.3 +/- A 35.9 L/h/m(2) (n = 16), was comparable to the clearance in patients with normal to near normal hepatic function. Drug levels in plasma decayed rapidly immediately after the infusion but remained above 10 nM for several days after dosing at the MTD. N (1),N (11)-diethylnorspermine treatment at the MTD of 75 mg/m(2), given intravenously every other weekday for two consecutive weeks of each 28-day cycle, was relatively well tolerated in patients with advanced HCC including those with mild-to-moderate liver dysfunction. This administration schedule provided prolonged systemic exposure to potentially effective concentrations of the drug. Stable disease was seen in 18 % of patients receiving DENSPM treatment. Further evaluation of DENSPM monotherapy for advanced HCC does not appear to be justified because of insufficient evidence of clinical benefit in the patients evaluated in this study. C1 [Goyal, Lipika; Supko, Jeffrey G.; Blaszkowsky, Lawrence S.; Carpenter, Amanda; Hilderbrand, Sarah L.; Clark, Jeffrey W.; Ryan, David P.; Zhu, Andrew X.] Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA. [Berlin, Jordan; Chan, Emily] Vanderbilt Ingram Canc Ctr, Nashville, TN USA. [Heuman, Douglas M.] Virginia Commonwealth Univ, Med Ctr, Div Gastroenterol Hepatol & Nutr, Richmond, VA USA. [Stuart, Keith E.] Tufts Univ, Sch Med, Lahey Clin Med Ctr, Burlington, MA USA. [Cotler, Scott] Loyola Univ, Med Ctr, Maywood, IL 60153 USA. [Senzer, Neil N.] Mary Crowley Canc Res Ctr, Dallas, TX USA. [Berg, Carl L.] Duke Univ, Med Ctr, Durham, NC USA. [Hezel, Aram F.] Univ Rochester, James P Wilmot Canc Ctr, Rochester, NY USA. RP Ryan, DP (reprint author), Massachusetts Gen Hosp, Ctr Canc, 55 Fruit St,Yawkey 7E, Boston, MA 02114 USA. EM dpryan@partners.org NR 33 TC 2 Z9 2 U1 0 U2 7 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0344-5704 EI 1432-0843 J9 CANCER CHEMOTH PHARM JI Cancer Chemother. Pharmacol. PD DEC PY 2013 VL 72 IS 6 BP 1305 EP 1314 DI 10.1007/s00280-013-2293-8 PG 10 WC Oncology; Pharmacology & Pharmacy SC Oncology; Pharmacology & Pharmacy GA 257LX UT WOS:000327387000016 PM 24121453 ER PT J AU Shim, SY Kim, YW Verdine, GL AF Shim, So Youn Kim, Young-Woo Verdine, Gregory L. TI A New i, i+3 Peptide Stapling System for alpha-Helix Stabilization SO CHEMICAL BIOLOGY & DRUG DESIGN LA English DT Article DE stapled peptides; -helix; ring-closing metathesis ID CLOSING OLEFIN METATHESIS; HYDROGEN-BOND SURROGATE; BH3 HELIX; INHIBITOR; CONFORMATION; ACTIVATION; PROTEINS; COMPLEX; BAX AB We have previously shown that the incorporation of an 8-atom all-hydrocarbon staple' at positions i and i+3 of a synthetic peptide results in substantial stabilization of the -helical conformation. As part of our ongoing effort to explore the scope and utility of all-hydrocarbon stapling systems, we have investigated and report herein the properties of a new i, i+3 stapling system that employs a 6-carbon cross-link. C1 [Shim, So Youn; Kim, Young-Woo; Verdine, Gregory L.] Harvard Univ, Dept Chem, Cambridge, MA 02138 USA. [Shim, So Youn; Kim, Young-Woo; Verdine, Gregory L.] Harvard Univ, Dept Biol Chem, Cambridge, MA 02138 USA. [Kim, Young-Woo; Verdine, Gregory L.] Dana Farber Canc Inst, Program Canc Chem Biol, Boston, MA 02115 USA. RP Verdine, GL (reprint author), Harvard Univ, Dept Chem, 12 Oxford St, Cambridge, MA 02138 USA. EM Gregory_verdine@harvard.edu FU Johnson Johnson; Harvard & Dana-Farber Program in Cancer Chemical Biology FX This research was supported by funding from Johnson & Johnson and the Harvard & Dana-Farber Program in Cancer Chemical Biology. NR 30 TC 12 Z9 12 U1 2 U2 32 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1747-0277 EI 1747-0285 J9 CHEM BIOL DRUG DES JI Chem. Biol. Drug Des. PD DEC PY 2013 VL 82 IS 6 BP 635 EP 642 DI 10.1111/cbdd.12231 PG 8 WC Biochemistry & Molecular Biology; Chemistry, Medicinal SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy GA 255RH UT WOS:000327257000001 PM 24267668 ER PT J AU Shahedi, K Fuller, G Bolus, R Cohen, E Vu, M Shah, R Agarwal, N Kaneshiro, M Atia, M Sheen, V Kurzbard, N van Oijen, MGH Yen, L Hodgkins, P Erder, MH Spiegel, B AF Shahedi, Kamyar Fuller, Garth Bolus, Roger Cohen, Erica Vu, Michelle Shah, Rena Agarwal, Nikhil Kaneshiro, Marc Atia, Mary Sheen, Victoria Kurzbard, Nicole van Oijen, Martijn G. H. Yen, Linnette Hodgkins, Paul Erder, M. Haim Spiegel, Brennan TI Long-term Risk of Acute Diverticulitis Among Patients With Incidental Diverticulosis Found During Colonoscopy SO CLINICAL GASTROENTEROLOGY AND HEPATOLOGY LA English DT Article DE Colon; Pouch; Prognosis; Diverticular Disease ID UNITED-STATES; SIGMOID DIVERTICULITIS; PRACTICE PARAMETERS; NATURAL-HISTORY; YOUNG-PATIENTS; DISEASE; COLON; EPIDEMIOLOGY; POPULATION; MANAGEMENT AB BACKGROUND & AIMS: Colonic diverticulosis is the most common finding during routine colonoscopy, and patients often question the significance of these lesions. Guidelines state that these patients have a 10% to 25% lifetime risk of developing acute diverticulitis. However, this value was determined based on limited data, collected before population-based colonoscopy, so the true number of cases of diverticulosis was not known. We measured the long-term risk of acute diverticulitis among patients with confirmed diverticulosis discovered incidentally on colonoscopy. METHODS: We performed a retrospective study using administrative and clinical data from the Veterans Affairs Greater Los Angeles Healthcare System, collecting data on patients who underwent colonoscopies from January 1996 through January 2011. We identified patients diagnosed with diverticulosis, determined incidence rates per 1000 patient-years, and analyzed a subgroup of patients with rigorously defined events confirmed by imaging or surgery. We used a Cox proportional hazards model to identify factors associated with the development of diverticulitis. RESULTS: We identified 2222 patients with baseline diverticulosis. Over an 11-year follow-up period, 95 patients developed diverticulitis (4.3%; 6 per 1000 patient-years); of these, 23 met the rigorous definition of diverticulitis (1%; 1.5 per 1000 patient-years). The median time-to-event was 7.1 years. Each additional decade of age at time of diagnosis reduced the risk for diverticulitis by 24% (hazard ratio, 0.76; 95% confidence interval, 0.6-0.9). CONCLUSIONS: Based on a study of the Veterans Affairs Greater Los Angeles Healthcare System, only about 4% of patients with diverticulosis develop acute diverticulitis, contradicting the common belief that diverticulosis has a high rate of progression. We also found that younger patients have a higher risk of diverticulitis, with risk increasing per year of life. These results can help inform patients with diverticulosis about their risk of developing acute diverticulitis. C1 [Shahedi, Kamyar; Fuller, Garth; Bolus, Roger; Cohen, Erica; Vu, Michelle; Agarwal, Nikhil; van Oijen, Martijn G. H.; Spiegel, Brennan] Univ Calif Los Angeles, Vet Affairs Ctr Outcomes Res & Educ, Los Angeles, CA USA. [Bolus, Roger; Shah, Rena; Agarwal, Nikhil; Kaneshiro, Marc; Kurzbard, Nicole; van Oijen, Martijn G. H.; Spiegel, Brennan] Univ Calif Los Angeles, David Geffen Sch Med, Div Digest Dis, Los Angeles, CA 90095 USA. [Agarwal, Nikhil; Kaneshiro, Marc; Atia, Mary; Sheen, Victoria; Spiegel, Brennan] Vet Affairs Greater Los Angeles Healthcare Syst, Dept Gastroenterol, Los Angeles, CA USA. [Yen, Linnette; Hodgkins, Paul; Erder, M. Haim] Shire Dev LLC, Wayne, PA USA. [Spiegel, Brennan] Univ Calif Los Angeles, Sch Publ Hlth, Dept Hlth Serv, Los Angeles, CA 90024 USA. RP Spiegel, B (reprint author), 11301 Wilshire Blvd,Bldg 115,Room 215, Los Angeles, CA 90073 USA. EM bspiegel@mednet.ucla.edu FU Shire Development, LLC FX This study was supported by a research grant from Shire Development, LLC. NR 37 TC 56 Z9 57 U1 0 U2 5 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1542-3565 EI 1542-7714 J9 CLIN GASTROENTEROL H JI Clin. Gastroenterol. Hepatol. PD DEC PY 2013 VL 11 IS 12 BP 1609 EP 1613 DI 10.1016/j.cgh.2013.06.020 PG 5 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 258US UT WOS:000327484800019 PM 23856358 ER PT J AU Cohen, E Fuller, G Bolus, R Modi, R Vu, M Shahedi, K Shah, R Atia, M Kurzbard, N Sheen, V Agarwal, N Kaneshiro, M Yen, L Hodgkins, P Erder, MH Spiegel, B AF Cohen, Erica Fuller, Garth Bolus, Roger Modi, Rusha Vu, Michelle Shahedi, Kamyar Shah, Rena Atia, Mary Kurzbard, Nicole Sheen, Victoria Agarwal, Nikhil Kaneshiro, Marc Yen, Linnette Hodgkins, Paul Erder, M. Haim Spiegel, Brennan TI Increased Risk for Irritable Bowel Syndrome After Acute Diverticulitis SO CLINICAL GASTROENTEROLOGY AND HEPATOLOGY LA English DT Article DE Outcome; Colon; Inflammatory Disorder; Functional Gastrointestinal Disease ID INTESTINAL BACTERIAL OVERGROWTH; DISEASE; COLON; DISORDERS; PATTERNS; INFLAMMATION; COMORBIDITY; MANAGEMENT; PERCEPTION; RIFAXIMIN AB BACKGROUND & AIMS: Individuals with diverticulosis frequently also have irritable bowel syndrome (IBS), but there are no longitudinal data to associate acute diverticulitis with subsequent IBS, functional bowel disorders, or related emotional distress. In patients with postinfectious IBS, gastrointestinal disorders cause long-term symptoms, so we investigated whether diverticulitis might lead to IBS. We compared the incidence of IBS and functional bowel and related affective disorders among patients with diverticulitis. METHODS: We performed a retrospective study of patients followed up for an average of 6.3 years at a Veteran's Administration medical center. Patients with diverticulitis were identified based on International Classification of Diseases, 9th revision codes, selected for the analysis based on chart review (cases, n = 1102), and matched with patients without diverticulosis (controls, n = 1102). We excluded patients with prior IBS, functional bowel, or mood disorders. We then identified patients who were diagnosed with IBS or functional bowel disorders after the diverticulitis attack, and controls who developed these disorders during the study period. We also collected information on mood disorders, analyzed survival times, and calculated adjusted hazard ratios. RESULTS: Cases were 4.7-fold more likely to be diagnosed later with IBS (95% confidence interval [CI], 1.6-14.0; P = .006), 2.4-fold more likely to be diagnosed later with a functional bowel disorder (95% CI, 1.6 -3.6; P < .001), and 2.2-fold more likely to develop a mood disorder (CI, 1.4-3.5; P < .001) than controls. CONCLUSIONS: Patients with diverticulitis could be at risk for later development of IBS and functional bowel disorders. We propose calling this disorder postdiverticulitis IBS. Diverticulitis appears to predispose patients to long-term gastrointestinal and emotional symptoms after resolution of inflammation; in this way, postdiverticulitis IBS is similar to postinfectious IBS. C1 [Cohen, Erica; Modi, Rusha; Vu, Michelle; Atia, Mary; Agarwal, Nikhil; Kaneshiro, Marc; Spiegel, Brennan] VA Greater Los Angeles Healthcare Syst, Dept Gastroenterol, Los Angeles, CA USA. [Fuller, Garth; Bolus, Roger; Modi, Rusha; Shahedi, Kamyar; Agarwal, Nikhil; Spiegel, Brennan] UCLA VA Ctr Outcomes Res & Educ, Los Angeles, CA USA. [Bolus, Roger; Shah, Rena; Kurzbard, Nicole; Sheen, Victoria; Agarwal, Nikhil; Spiegel, Brennan] Univ Calif Los Angeles, David Geffen Sch Med, Div Digest Dis, Los Angeles, CA 90095 USA. [Spiegel, Brennan] UCLA Sch Publ Hlth, Dept Hlth Serv, Los Angeles, CA USA. [Yen, Linnette; Hodgkins, Paul; Erder, M. Haim] Shire Pharmaceut, Wayne, PA USA. RP Spiegel, B (reprint author), West Los Angeles VA Med Ctr, Dept Gastroenterol, 11301 Wilshire Blvd,Bldg 115,Room 215, Los Angeles, CA 90073 USA. EM bspiegel@mednet.ucla.edu FU Shire Pharmaceuticals FX This study was supported by a research grant from Shire Pharmaceuticals. The principal investigators maintained all source data, SAS codes, and analytical files on site at the VA Medical Center. NR 34 TC 33 Z9 33 U1 0 U2 6 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1542-3565 EI 1542-7714 J9 CLIN GASTROENTEROL H JI Clin. Gastroenterol. Hepatol. PD DEC PY 2013 VL 11 IS 12 BP 1614 EP 1619 DI 10.1016/j.cgh.2013.03.007 PG 6 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 258US UT WOS:000327484800020 PM 23524129 ER PT J AU Peery, AF Sandler, RS Ahnen, DJ Galanko, JA Holm, AN Shaukat, A Mott, LA Barry, EL Fried, DA Baron, JA AF Peery, Anne F. Sandler, Robert S. Ahnen, Dennis J. Galanko, Joseph A. Holm, Adrian N. Shaukat, Aasma Mott, Leila A. Barry, Elizabeth L. Fried, David A. Baron, John A. TI Constipation and a Low-Fiber Diet Are Not Associated With Diverticulosis SO CLINICAL GASTROENTEROLOGY AND HEPATOLOGY LA English DT Article DE Diverticular Disease; Risk Factors; Database Analysis ID PHYSICAL-ACTIVITY; GASTROINTESTINAL-DISEASE; COLONIC DIVERTICULOSIS; SIGMOID COLON; RISK; MEN; INCREASES; MOTILITY; PRESSURE; SMOKING AB BACKGROUND & AIMS: Asymptomatic diverticulosis is commonly attributed to constipation caused by a low-fiber diet, although evidence for this mechanism is limited. We examined the associations between constipation and low dietary fiber intake with risk of asymptomatic diverticulosis. METHODS: We performed a cross-sectional study that analyzed data from 539 individuals with diverticulosis and 1569 without (controls). Participants underwent colonoscopy and assessment of diet, physical activity, and bowel habits. Our analysis was limited to participants with no knowledge of their diverticular disease to reduce the risk of biased responses. RESULTS: Constipation was not associated with an increased risk of diverticulosis. Participants with less frequent bowel movements (<7/wk) had reduced odds of diverticulosis compared with those with regular bowel movements (7/wk) (odds ratio [OR], 0.56; 95% confidence interval [CI], 0.40-0.80). Those reporting hard stools also had reduced odds (OR, 0.75; 95% CI, 0.55-1.02). There was no association between diverticulosis and straining (OR, 0.85; 95% CI, 0.59-1.22) or incomplete bowel movement (OR, 0.85; 95% CI, 0.61-1.20). We found no association between dietary fiber intake and diverticulosis (OR, 0.96; 95% CI, 0.71-1.30) in comparing the highest quartile with the lowest (mean intake, 25 vs 8 g/day). CONCLUSIONS: In our cross-sectional, colonoscopy-based study, neither constipation nor a low-fiber diet was associated with an increased risk of diverticulosis. C1 [Peery, Anne F.; Sandler, Robert S.; Galanko, Joseph A.; Baron, John A.] Univ N Carolina, Sch Med, Chapel Hill, NC 27599 USA. [Ahnen, Dennis J.] Denver Vet Affairs Med Ctr, Denver, CO USA. [Ahnen, Dennis J.] Univ Colorado Anschutz Med Campus, Denver, CO USA. [Holm, Adrian N.] Univ Iowa Hosp & Clin, Iowa City, IA 52242 USA. [Shaukat, Aasma] Minneapolis Veteran Affairs Med Ctr, Minneapolis, MN USA. [Mott, Leila A.; Barry, Elizabeth L.; Fried, David A.; Baron, John A.] Geisel Sch Med Dartmouth, Hanover, NH USA. RP Peery, AF (reprint author), Univ N Carolina, Sch Med, Div Gastroenterol & Hepatol, Bioinformat Bldg,CB 7080,130 Mason Farm Rd, Chapel Hill, NC 27599 USA. EM anne_peery@med.unc.edu FU National Institutes of Health [T32 DK07634, P30 DK034987, R01 DK094738, R01 CA098286] FX Supported in part by grants from the National Institutes of Health T32 DK07634, P30 DK034987, R01 DK094738, and R01 CA098286. NR 37 TC 24 Z9 24 U1 2 U2 9 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1542-3565 EI 1542-7714 J9 CLIN GASTROENTEROL H JI Clin. Gastroenterol. Hepatol. PD DEC PY 2013 VL 11 IS 12 BP 1622 EP 1627 DI 10.1016/j.cgh.2013.06.033 PG 6 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 258US UT WOS:000327484800022 PM 23891924 ER PT J AU Maguire, LH Song, MY Strate, LE Giovannucci, EL Chan, AT AF Maguire, Lillias H. Song, Mingyang Strate, Lisa E. Giovannucci, Edward L. Chan, Andrew T. TI Higher Serum Levels of Vitamin D Are Associated With a Reduced Risk of Diverticulitis SO CLINICAL GASTROENTEROLOGY AND HEPATOLOGY LA English DT Article DE Vitamin D; Diverticulitis; Diverticulosis; Risk Factor; Epidemiology ID COLORECTAL-CANCER; EUROPEAN POPULATIONS; UNITED-STATES; DISEASE; COLON AB BACKGROUND & AIMS: Recent studies have shown geographic and seasonal variations in hospital admissions for diverticulitis. Because this variation parallels differences in ultraviolet light exposure, the most important contributor to vitamin D status, we examined the association of prediagnostic serum levels of vitamin D with diverticulitis. METHODS: Among patients within the Partners Healthcare System who had blood drawn and serum levels of 25-hydroxyvitamin D (25-[OH]D) measured, from 1993 through 2012, we identified 9116 patients with uncomplicated diverticulosis and 922 patients who developed diverticulitis that required hospitalization. We used multivariate logistic regression to estimate relative risks and 95% confidence intervals to compare serum 25(OH)D levels between these groups. RESULTS: Patients with uncomplicated diverticulosis had significantly higher mean prediagnostic serum levels of 25(OH)D (29.1 ng/mL) than patients with diverticulitis who required hospitalization (25.3 ng/mL; P < .0001). Compared with patients in the lowest quintile of 25(OH)D, the multivariate-adjusted relative risk for diverticulitis hospitalization was 0.49 (95% confidence interval, 0.38-0.62; P for trend < .0001) among patients in the highest quintile of 25(OH)D level. Compared with patients with uncomplicated diverticulosis, the mean level of 25(OH)D was significantly lower for patients with acute diverticulitis without other sequelae (25.9 ng/mL; P < .0001; n = 594), for patients with diverticulitis with abscess (25.8 ng/mL; P = .0095; n = 124), for patients with diverticulitis requiring emergent laparotomy (22.7 ng/mL; P = .002; n = 65), and for patients with recurrent diverticulitis (23.5 ng/mL; P < .0001; n = 139). CONCLUSIONS: Among patients with diverticulosis, higher prediagnostic levels of 25(OH)D are associated significantly with a lower risk of diverticulitis. These data indicate that vitamin D deficiency could be involved in the pathogenesis of diverticulitis. C1 [Maguire, Lillias H.] Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. [Chan, Andrew T.] Massachusetts Gen Hosp, Div Gastroenterol, Boston, MA 02114 USA. Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA. [Strate, Lisa E.] Univ Washington, Dept Gastroenterol, Seattle, WA 98195 USA. RP Chan, AT (reprint author), Massachusetts Gen Hosp, Div Gastroenterol, 55 Fruit St,GRJ 825C, Boston, MA 02114 USA. EM achan@partners.org RI Song, Mingyang/M-6701-2013 OI Song, Mingyang/0000-0002-1324-0316 FU NIH/NIDDK [K24 DK098311]; American College of Gastroenterology FX Supported by grants from the American College of Gastroenterology and NIH/NIDDK K24 DK098311. NR 17 TC 15 Z9 15 U1 0 U2 5 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1542-3565 EI 1542-7714 J9 CLIN GASTROENTEROL H JI Clin. Gastroenterol. Hepatol. PD DEC PY 2013 VL 11 IS 12 BP 1631 EP 1635 DI 10.1016/j.cgh.2013.07.035 PG 5 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 258US UT WOS:000327484800024 PM 23954650 ER PT J AU Yu, L Morishima, C Ioannou, GN AF Yu, Lei Morishima, Chihiro Ioannou, George N. TI Dietary Cholesterol Intake Is Associated With Progression of Liver Disease in Patients With Chronic Hepatitis C: Analysis of the Hepatitis C Antiviral Long-term Treatment Against Cirrhosis Trial SO CLINICAL GASTROENTEROLOGY AND HEPATOLOGY LA English DT Article DE Diet; Cholesterol; Hepatitis C; Cirrhosis ID TRIGLYCERIDE TRANSFER PROTEIN; INSULIN-RESISTANCE; DIABETES-MELLITUS; VIRUS-INFECTION; HCV INFECTION; UNITED-STATES; LOW-DENSITY; FIBROSIS; RISK; FAT AB BACKGROUND & AIMS: Little is known about whether dietary cholesterol affects disease progression in patients with chronic hepatitis C virus infection. METHODS: We analyzed data from the Hepatitis C Antiviral Long-term Treatment Against Cirrhosis trial, which included patients with advanced fibrosis and compensated cirrhosis. Cholesterol intake was determined for 608 participants on the basis of responses to food frequency questionnaires, administered at baseline and 1.8 years later. We investigated whether cholesterol intake was associated with clinical progression (death, variceal bleeding, encephalopathy, ascites, peritonitis, Child-Turcotte-Pugh score >= 7, or hepatocellular carcinoma) or histologic progression of disease (an increase in Ishak fibrosis score of 2 or more points in a second liver biopsy compared with the first). RESULTS: After adjustments for age, sex, race, presence of cirrhosis, body mass index, treatment with peginterferon, lifetime alcohol consumption, smoking, health status, and coffee and macronutrient intake, each higher quartile of cholesterol intake was associated with a 46% increase in the risk of clinical or histologic progression (adjusted hazard ratio [AHR], 1.46; 95% confidence interval [CI], 1.13-1.87; P for the trend = .004). Compared with patients in the lowest quartile of cholesterol intake (32-152 mg/day), those in the 3rd (224-310 mg/day; AHR, 2.83; 95% CI, 1.45-5.51) and 4th quartiles (>310 mg/day; AHR, 2.74; 95% CI, 1.22-6.16) had significantly increased risk of disease progression. CONCLUSIONS: On the basis of analysis of data from the Hepatitis C Antiviral Long-term Treatment Against Cirrhosis trial, higher dietary cholesterol intake is associated with higher risk of disease progression in HCV-infected patients with advanced fibrosis or compensated cirrhosis. C1 [Yu, Lei; Ioannou, George N.] Univ Washington, Div Gastroenterol, Seattle, WA 98195 USA. [Morishima, Chihiro] Univ Washington, Dept Lab Med, Seattle, WA 98195 USA. [Ioannou, George N.] Vet Affairs Puget Sound Hlth Care Syst, Seattle, WA USA. RP Yu, L (reprint author), 1959 NE Pacific St,Box 356175, Seattle, WA 98195 USA. EM leiy@medicine.washington.edu FU Office of Research and Development, Veterans Affairs FX Supported by Research Enhancement Award Program (G.N.I.), Office of Research and Development, Veterans Affairs. NR 37 TC 5 Z9 5 U1 0 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1542-3565 EI 1542-7714 J9 CLIN GASTROENTEROL H JI Clin. Gastroenterol. Hepatol. PD DEC PY 2013 VL 11 IS 12 BP 1661 EP U208 DI 10.1016/j.cgh.2013.05.018 PG 9 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 258US UT WOS:000327484800029 PM 23707779 ER PT J AU Pond, GR Bellmunt, J Fougeray, R Choueiri, TK Qu, AQ Niegisch, G Albers, P Di Lorenzo, G Salhi, Y Galsky, MD Agarwal, N Necchi, A Sonpavde, G AF Pond, Gregory R. Bellmunt, Joaquim Fougeray, Ronan Choueiri, Toni K. Qu, Angela Q. Niegisch, Guenter Albers, Peter Di Lorenzo, Giuseppe Salhi, Yacine Galsky, Matthew D. Agarwal, Neeraj Necchi, Andrea Sonpavde, Guru TI Impact of Response to Prior Chemotherapy in Patients With Advanced Urothelial Carcinoma Receiving Second-Line Therapy: Implications for Trial Design SO CLINICAL GENITOURINARY CANCER LA English DT Article DE Advanced urothelial carcinoma; Prognostic factors; Response to prior chemotherapy; Second-line therapy ID TRANSITIONAL-CELL CARCINOMA; PHASE-III TRIAL; PLATINUM-CONTAINING REGIMEN; BLADDER-CANCER PATIENTS; RANDOMIZED-TRIAL; PACLITAXEL; TRACT; GEMCITABINE; VINFLUNINE; CISPLATIN AB In a retrospective analysis of pooled phase II trials, best prior response in patients receiving prior chemotherapy for metastatic disease did not confer an independent prognostic impact with second-line therapy for advanced urothelial carcinoma. Background: The prognostic impact of response to prior chemotherapy independent of performance status (PS), hemoglobin (Hb), liver metastasis (LM), and time from prior chemotherapy (TFPC) in the context of second-line therapy for advanced urothelial carcinoma (UC) is unknown. Methods: Six phase II trials evaluating second-line therapy (n = 504) were pooled. Patients who received prior therapy for metastatic disease were eligible for analysis if Hb, LM, PS, and TFPC were available. Response by Response Evaluation Criteria in Solid Tumors 1.0 to first-line therapy was recorded. Progression-free survival (PFS) and overall survival (OS) were calculated from the date of registration using the Kaplan-Meier method. Results: A total of 275 patients were evaluable for analysis. Patients received gemcitabine-paclitaxel, cyclophosphamide-paclitaxel, pazopanib, docetaxel plus vandetanib/placebo, or vinflunine (2 trials). Those with prior response (n = 111) had a median OS of 8.0 months (95% confidence interval [CI], 6.8-9.4), compared with 5.9 months (95% CI, 5.0-6.6) for those without prior response (n = 164). Those with prior response had a median PFS of 3.0 months (95% CI, 2.6-4.0) compared with 2.6 months (95% CI, 2.0-2.8) in patients without response. Multivariable analysis did not reveal a significant independent impact of prior response on PFS and OS. Conclusions: Best prior response in patients receiving prior chemotherapy for metastatic disease did not confer an independent prognostic impact with second-line therapy for advanced UC. Given that the setting of prior chemotherapy (metastatic or perioperative) has not appeared significant in a prior study, patients who received prior chemotherapy in perioperative or metastatic settings may be enrolled in the same second-line trial stratified for PS, Hb, LM, and TFPC. C1 [Pond, Gregory R.] McMaster Univ, Hamilton, ON L8S 4L8, Canada. [Bellmunt, Joaquim] Univ Hosp Mar IMIM, Barcelona, Spain. [Fougeray, Ronan; Salhi, Yacine] Inst Rech Pierre Fabre, Boulogne, France. [Choueiri, Toni K.; Qu, Angela Q.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Choueiri, Toni K.; Qu, Angela Q.] Harvard Univ, Sch Med, Boston, MA USA. [Niegisch, Guenter; Albers, Peter] Univ Dusseldorf, Dusseldorf, Germany. [Di Lorenzo, Giuseppe] Univ Naples Federico II, Naples, Italy. [Galsky, Matthew D.] Mt Sinai Sch Med, Tisch Canc Ctr Inst, New York, NY USA. [Agarwal, Neeraj] Univ Utah, Salt Lake City, UT USA. [Necchi, Andrea] Fdn IRCCS Ist Nazl Tumori, Milan, Italy. [Sonpavde, Guru] Univ Alabama Birmingham, Birmingham Comprehens Canc Ctr, Birmingham, AL USA. RP Sonpavde, G (reprint author), UAB Comprehens Canc Ctr, 1824 6th Ave S,WTI 520A, Birmingham, AL 35233 USA. EM gsonpavde@uabmc.edu OI Niegisch, Gunter/0000-0001-6929-8691; Necchi, Andrea/0000-0002-3007-2756 FU Pierre Fabre; AstraZeneca; Eli Lilly; BMS; GSK FX Gregory R. Pond: none; Joaquim Bellmunt: research funding from Pierre Fabre; Ronan Fougeray: employment at Pierre Fabre; Toni K. Choueiri: research support from AstraZeneca; Angela Q. Qu: research support from AstraZeneca; Guenter Niegisch: research support from Eli Lilly and BMS; Peter Albers: research support from Eli Lilly and BMS; Giuseppe Di Lorenzo: none; Yacine Salhi: Employment at Pierre Fabre; Matthew D. Galsky: none; Andrea Necchi: research support and consultant for GSK; Guru Sonpavde: none. NR 20 TC 11 Z9 11 U1 0 U2 1 PU CIG MEDIA GROUP, LP PI DALLAS PA 3500 MAPLE AVENUE, STE 750, DALLAS, TX 75219-3931 USA SN 1558-7673 EI 1938-0682 J9 CLIN GENITOURIN CANC JI Clin. Genitourin. Cancer PD DEC PY 2013 VL 11 IS 4 BP 495 EP 500 DI 10.1016/j.clgc.2013.04.025 PG 6 WC Oncology; Urology & Nephrology SC Oncology; Urology & Nephrology GA 254CG UT WOS:000327139500024 PM 23800847 ER PT J AU Abramovitch, A Doron, G Sar-El, D Altenburger, E AF Abramovitch, Amitai Doron, Guy Sar-El, Dar Altenburger, Erin TI Subtle Threats to Moral Self-Perceptions Trigger Obsessive-Compulsive Related Cognitions SO COGNITIVE THERAPY AND RESEARCH LA English DT Article DE OCD; Self-perceptions; Morality; Cognitions ID PSYCHOMETRIC VALIDATION; BELIEFS QUESTIONNAIRE; INTRUSIONS INVENTORY; SHORT VERSION; DISORDER; SENSITIVITY; ANXIETY; SCALES AB Obsessive-compulsive (OC) symptoms are often associated with cognitive biases and can cause significant distress and impairment in daily functioning. In this study, we examine whether threat to moral self-perceptions can trigger cognitive biases linked with obsessive-compulsive disorder (OCD). Participants were 124 non-clinical adults randomized to four conditions (negative-morality, negative-sports, positive-morality, and positive-sports) of the Subtle Priming Computerized Task. To examine the influence of subtle priming of morality-related information on OCD-related cognitive biases, participants completed the Obsessive Beliefs Questionnaire-20 (OBQ-20). Participants also completed the obsessive-compulsive inventory-revised, the Depression Anxiety Stress Scale and the Single-Item Self-Esteem Scale as baseline measures. Results revealed that subtle suggestions of incompetence in the morality self-domain were associated with stronger activation of OCD-related cognitive biases as measured by the OBQ-20. These effects were specific to negative information about the morality self-domain. Findings were not related to pre-existing variations in OC symptom levels, self-esteem, stress, anxiety, or depression. We suggest that self-sensitivities in the morality self-domain may be linked with the activation of cognitive biases related to OCD. Future research should explore these self-sensitivities in a clinical sample to further substantiate this phenomenon. C1 [Abramovitch, Amitai] Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA. [Abramovitch, Amitai; Altenburger, Erin] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. [Doron, Guy; Sar-El, Dar] Sch Psychol, Interdisciplinary Ctr IDC, Herzliyya, Israel. RP Abramovitch, A (reprint author), Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. EM aabramovitch@partners.org RI Abramovitch, Amitai/I-3333-2012 OI Abramovitch, Amitai/0000-0001-9640-0970 NR 43 TC 2 Z9 2 U1 2 U2 12 PU SPRINGER/PLENUM PUBLISHERS PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0147-5916 EI 1573-2819 J9 COGNITIVE THER RES JI Cogn. Ther. Res. PD DEC PY 2013 VL 37 IS 6 BP 1132 EP 1139 DI 10.1007/s10608-013-9568-6 PG 8 WC Psychology, Clinical SC Psychology GA 253XS UT WOS:000327123700005 ER PT J AU Evans, M Rohan, KJ Sitnikov, L Mahon, JN Nillni, YI Lindsey, K Vacek, PM AF Evans, Maggie Rohan, Kelly J. Sitnikov, Lilya Mahon, Jennifer N. Nillni, Yael I. Tierney Lindsey, Kathryn Vacek, Pamela M. TI Cognitive Change Across Cognitive-Behavioral and Light Therapy Treatments for Seasonal Affective Disorder: What Accounts for Clinical Status the Next Winter? SO COGNITIVE THERAPY AND RESEARCH LA English DT Article DE Seasonal affective disorder; Light therapy; Cognitive-behavioral therapy; Cognitive mechanisms; Treatment durability ID RANDOMIZED CONTROLLED-TRIAL; RESPONSE STYLES; PRIMARY-CARE; DEPRESSION; PHARMACOTHERAPY; COMBINATION; MOOD; MEDICATION; MECHANISMS; IMIPRAMINE AB Efficacious treatments for seasonal affective disorder include light therapy and a seasonal affective disorder-tailored form of cognitive-behavioral therapy. Using data from a parent clinical trial, these secondary analyses examined the relationship between cognitive change over treatment with cognitive-behavioral therapy, light therapy, or combination treatment and mood outcomes the next winter. Sixty-nine participants were randomly assigned to 6-weeks of cognitive-behavioral therapy, light therapy, or combination treatment. Cognitive constructs (i.e., dysfunctional attitudes, negative automatic thoughts, and rumination) were assessed at pre- and post-treatment. Dysfunctional attitudes, negative automatic thoughts, and rumination improved over acute treatment, regardless of modality; however, in participants randomized to solo cognitive-behavioral therapy, a greater degree of improvement in dysfunctional attitudes and automatic thoughts was uniquely associated with less severe depressive symptoms the next winter. Change in maladaptive thoughts during acute treatment appears mechanistic of solo cognitive-behavioral therapy's enduring effects the next winter, but is simply a consequence of diminished depression in light therapy and combination treatment. C1 [Evans, Maggie; Rohan, Kelly J.; Sitnikov, Lilya; Mahon, Jennifer N.] Univ Vermont, Dept Psychol, Burlington, VT 05401 USA. [Nillni, Yael I.] VA Boston Healthcare Syst, Natl Ctr PTSD, Womens Hlth Sci Div, Boston, MA USA. [Nillni, Yael I.] Boston Univ, Sch Med, Boston, MA 02118 USA. [Tierney Lindsey, Kathryn] US Naval Acad, Dept Psychol, Annapolis, MD 21402 USA. [Vacek, Pamela M.] Univ Vermont, Coll Med, Burlington, VT 05401 USA. RP Evans, M (reprint author), Univ Vermont, Dept Psychol, John Dewey Hall,2 Colchester Ave, Burlington, VT 05401 USA. EM mevans1@uvm.edu NR 60 TC 1 Z9 1 U1 3 U2 10 PU SPRINGER/PLENUM PUBLISHERS PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0147-5916 EI 1573-2819 J9 COGNITIVE THER RES JI Cogn. Ther. Res. PD DEC PY 2013 VL 37 IS 6 BP 1201 EP 1213 DI 10.1007/s10608-013-9561-0 PG 13 WC Psychology, Clinical SC Psychology GA 253XS UT WOS:000327123700012 ER PT J AU Knouse, LE Zvorsky, I Safren, SA AF Knouse, Laura E. Zvorsky, Ivori Safren, Steven A. TI Depression in Adults with Attention-Deficit/Hyperactivity Disorder (ADHD): The Mediating Role of Cognitive-Behavioral Factors SO COGNITIVE THERAPY AND RESEARCH LA English DT Article DE Attention-Deficit/Hyperactivity Disorder (ADHD); Depression; Depressive symptoms; Adults; Cognitive behavior therapy (CBT) ID STAR-ASTERISK-D; RATING-SCALE; AXIS-I; MAJOR DEPRESSION; SUICIDE ATTEMPTS; LIFE EVENTS; COMORBIDITY; INVENTORY; VALIDATION; ADOLESCENT AB Adults with Attention-Deficit/Hyperactivity Disorder (ADHD) are at increased risk for depressive disorders but little is known about the potential cognitive and behavioral mechanisms of risk that could shape treatment. This study evaluated the degree to which cognitive-behavioral constructs associated with depression and its treatment-dysfunctional attitudes and cognitive-behavioral avoidance-accounted for variance in depressive symptoms and disorder in adults with ADHD. 77 adults clinically diagnosed with ADHD completed self-report questionnaires, diagnostic interviews, and clinician-administered symptom rating scales. Statistical mediation analysis was employed and indirect effects assessed using bootstrap analysis and bias-corrected confidence intervals. Controlling for recent negative life events, dysfunctional attitudes and cognitive-behavioral avoidance fully accounted for the variance between ADHD symptoms and depressive symptoms. Each independent variable partially mediated the other in accounting for depression symptoms suggesting overlapping and unique variance. Cognitive-behavioral avoidance, however, was more strongly related to meeting diagnostic criteria for a depressive disorder than were dysfunctional attitudes. Processes that are targeted in cognitive behavior therapy (CBT) for depression were associated with symptoms in adults with ADHD. Current CBT approaches for ADHD incorporate active coping skills and cognitive restructuring and such approaches could be further tailored to address the ADHD-depression comorbidity. C1 [Knouse, Laura E.; Safren, Steven A.] Massachusetts Gen Hosp, Dept Psychiat, Behav Med Serv, Boston, MA 02114 USA. [Knouse, Laura E.; Safren, Steven A.] Harvard Univ, Sch Med, Boston, MA USA. [Knouse, Laura E.; Zvorsky, Ivori] Univ Richmond, Dept Psychol, Richmond, VA 23713 USA. RP Knouse, LE (reprint author), Univ Richmond, Dept Psychol, 28 Westhampton Way, Richmond, VA 23713 USA. EM lknouse@richmond.edu FU NIMH NIH HHS [K24 MH094214] NR 67 TC 6 Z9 6 U1 3 U2 20 PU SPRINGER/PLENUM PUBLISHERS PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0147-5916 EI 1573-2819 J9 COGNITIVE THER RES JI Cogn. Ther. Res. PD DEC PY 2013 VL 37 IS 6 BP 1220 EP 1232 DI 10.1007/s10608-013-9569-5 PG 13 WC Psychology, Clinical SC Psychology GA 253XS UT WOS:000327123700014 PM 26089578 ER PT J AU Borrero, S Zite, N Potter, JE Trussell, J Smith, K AF Borrero, Sonya Zite, Nikki Potter, Joseph E. Trussell, James Smith, Kenneth TI Potential unintended pregnancies averted and cost savings associated with a revised Medicaid sterilization policy SO CONTRACEPTION LA English DT Article DE Tubal sterilization; Unfulfilled sterilization; Cost analysis ID POSTPARTUM TUBAL-STERILIZATION; REQUESTS; BARRIERS; TEXAS; FORM AB Objective: Medicaid sterilization policy, which includes a mandatory 30-day waiting period between consent and the sterilization procedure, poses significant logistical bathers for many women who desire publicly funded sterilization. Our goal was to estimate the number of unintended pregnancies and the associated costs resulting from unfulfilled sterilization requests due to Medicaid policy barriers. Study Design: We constructed a cost-effectiveness model from the health care payer perspective to determine the incremental cost over a 1-year time horizon of the current Medicaid sterilization policy compared to a hypothetical, revised policy in which women who desire a postpartum sterilization would face significantly reduced barriers. Probability estimates for potential outcomes in the model were based on published sources; costs of Medicaid-funded sterilizations and Medicaid-covered births were based on data from the Medicaid Statistical Information System and The Guttmacher Institute, respectively. Results: With the implementation of a revised Medicaid sterilization policy, we estimated that the number of fulfilled sterilization requests would increase by 45%, from 53.3% of all women having their sterilization requests fulfilled to 77.5%. Annually, this increase could potentially lead to over 29,000 unintended pregnancies averted and $215 million saved. Conclusion: A revised Medicaid sterilization policy could potentially honor women's reproductive decisions, reduce the number of unintended pregnancies and save a significant amount of public funds. Implication: Compared to the current federal Medicaid sterilization policy, a hypothetical, revised policy that reduces logistical barriers for women who desire publicly funded, postpartum sterilization could potentially avert over 29,000 unintended pregnancies annually and therefore lead to cost savings of $215 million each year. Published by Elsevier Inc. C1 [Borrero, Sonya; Smith, Kenneth] Univ Pittsburgh, Sch Med, Div Gen Internal Med, Pittsburgh, PA USA. [Borrero, Sonya] VA Pittsburgh Healthcare Syst, Ctr Hlth Equ Res & Promot, Pittsburgh, PA USA. [Zite, Nikki] Univ Tennessee, Grad Sch Med, Dept Obstet & Gynecol, Knoxville, TN USA. [Potter, Joseph E.] Univ Texas Austin, Populat Res Ctr, Austin, TX 78712 USA. [Trussell, James] Princeton Univ, Off Populat Res, Princeton, NJ 08544 USA. [Trussell, James] Hull York Med Sch, Kingston Upon Hull, N Humberside, England. RP Borrero, S (reprint author), Univ Pittsburgh, Ctr Res Hlth Care, 230 McKee Pl,Suite 600, Pittsburgh, PA 15213 USA. EM borrerosp@upmc.edu OI Potter, Joseph/0000-0002-8960-813X FU National Center for Research Resources; National Center For Advancing Translational Sciences of the National Institutes of Health [2KL2 RR024154-06]; Eunice Kennedy Shriver National Institute of Child Health and Human Development [R24HD047879] FX This work was supported by the National Center for Research Resources and the National Center For Advancing Translational Sciences of the National Institutes of Health through grant number 2KL2 RR024154-06. The funding agency had no role in the design and conduct of the study; in the collection, analysis and interpretation of the data; or in the preparation, review or approval of the manuscript. This work was also supported in part by the Eunice Kennedy Shriver National Institute of Child Health and Human Development grant for Infrastructure for Population Research at Princeton University (grant R24HD047879). NR 21 TC 9 Z9 9 U1 0 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0010-7824 EI 1879-0518 J9 CONTRACEPTION JI Contraception PD DEC PY 2013 VL 88 IS 6 BP 691 EP 696 DI 10.1016/j.contraception.2013.08.004 PG 6 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 257VP UT WOS:000327416200004 PM 24028751 ER PT J AU Marsh, L AF Marsh, Laura TI Depression and Parkinson's Disease: Current Knowledge SO CURRENT NEUROLOGY AND NEUROSCIENCE REPORTS LA English DT Review DE Depression; Parkinson's disease; Mood disorder; Psychiatric; Antidepressant; Cognitive behavioral therapy; Electroconvulsive therapy; Quality of life; Treatment; Suicide; Major depression: dysthymia; Minor depression; Subsyndromal depression; Epidemiology; Pathophysiology ID COGNITIVE-BEHAVIORAL THERAPY; TRANSCRANIAL MAGNETIC STIMULATION; RANDOMIZED CONTROLLED-TRIALS; SEROTONIN TRANSPORTER GENE; PLACEBO-CONTROLLED TRIAL; DEEP-BRAIN-STIMULATION; QUALITY-OF-LIFE; DOUBLE-BLIND; NONMOTOR SYMPTOMS; ANXIETY DISORDERS AB Depressive disturbances are common in patients with Parkinson's disease (PD) and influence many other clinical aspects of the disease. In addition to causing inherent emotional distress, depressive disorders negatively impact quality of life, motor and cognitive deficits, functional disability, and other psychiatric comorbidities in patients with PD. Knowledge of the pathophysiology of PD depression remains limited. However, clinical studies demonstrate the efficacy of medications and psychotherapies for PD depression, underscoring the importance of their timely detection and concerted management. C1 [Marsh, Laura] Baylor Coll Med, Dept Psychiat, Houston, TX 77030 USA. [Marsh, Laura] Baylor Coll Med, Dept Neurol, Michael E DeBakey Vet Affairs Med Ctr, Houston, TX 77030 USA. RP Marsh, L (reprint author), Baylor Coll Med, Dept Psychiat, Mental Hlth Care Line 116,2002 Holcombe Blvd, Houston, TX 77030 USA. EM laura.marsh2@va.gov FU NCATS NIH HHS [U54 TR001456]; NINDS NIH HHS [U54 NS065701] NR 103 TC 21 Z9 21 U1 4 U2 36 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1528-4042 EI 1534-6293 J9 CURR NEUROL NEUROSCI JI Curr. Neurol. Neurosci. Rep. PD DEC PY 2013 VL 13 IS 12 AR 409 DI 10.1007/s11910-013-0409-5 PG 9 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 257RQ UT WOS:000327404200007 PM 24190780 ER PT J AU Mez, J Stern, RA McKee, AC AF Mez, Jesse Stern, Robert A. McKee, Ann C. TI Chronic Traumatic Encephalopathy: Where Are We and Where Are We Going? SO CURRENT NEUROLOGY AND NEUROSCIENCE REPORTS LA English DT Review DE Chronic traumatic encephalopathy (CTE); Dementia pugilistica; Traumatic brain injury (TBI); Concussion; Tauopathy; Neurofibrillary tangle; TDP-43; Apolipoprotein E (APOE E) ID SPORTS-RELATED CONCUSSION; FOOTBALL LEAGUE PLAYERS; REPETITIVE HEAD-INJURY; DIFFUSE AXONAL INJURY; BRAIN-INJURY; ALZHEIMERS-DISEASE; PROFESSIONAL FOOTBALL; RECURRENT CONCUSSION; PUNCH-DRUNK; CEREBRAL MICROHEMORRHAGES AB Chronic traumatic encephalopathy (CTE, previously called punch drunk and dementia pugilistica) has a rich history in the medical literature in association with boxing, but has only recently been recognized with other contact sports, such as football and ice hockey, as well as with military blast injuries. CTE is thought to be a neurodegenerative disease associated with repeated concussive and subconcussive blows to the head. There is characteristic gross and microscopic pathology found in the brain, including frontal and temporal atrophy, axonal degeneration, and hyperphosphorylated tau and TAR DNA-binding protein 43 pathology. Clinically, there are characteristic progressive deficits in cognition (memory, executive dysfunction), behavior (explosivity, aggression), mood (depression, suicidality), and motor function (parkinsonism), which correlate with the anatomic distribution of brain pathology. While CTE shares clinical and neuropathological traits with other neurodegenerative diseases, the clinical syndrome and the neuropathology as a whole are distinct from other neurodegenerative diseases. Here we review the CTE literature to date. We also draw on the literature from mild traumatic brain injury and other neurodegenerative dementias, particularly when these studies provide guidance for future CTE research. We conclude by suggesting seven essential areas for future CTE research. C1 [Mez, Jesse; Stern, Robert A.; McKee, Ann C.] Boston Univ, Sch Med, Alzheimers Dis Ctr, Boston, MA 02118 USA. [Mez, Jesse; Stern, Robert A.; McKee, Ann C.] Boston Univ, Sch Med, Dept Neurol, Boston, MA 02118 USA. [Stern, Robert A.; McKee, Ann C.] Boston Univ, Sch Med, Ctr Study Traumat Encephalopathy, Boston, MA 02118 USA. [McKee, Ann C.] US Dept Vet Affairs, VA Boston Healthcare Syst, Boston, MA USA. [McKee, Ann C.] Boston Univ, Sch Med, Dept Pathol, Boston, MA 02118 USA. RP Mez, J (reprint author), Boston Univ, Sch Med, Alzheimers Dis Ctr, 72 E Concord St,Suite 7800, Boston, MA 02118 USA. EM jessemez@bu.edu OI Stern, Robert/0000-0002-5008-077X FU National Institutes of Health [5T32NS007153-27, P30AG13846, R01 NS078337] FX This work was supported by National Institutes of Health (grant numbers 5T32NS007153-27, P30AG13846, and R01 NS078337). NR 117 TC 23 Z9 23 U1 4 U2 43 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1528-4042 EI 1534-6293 J9 CURR NEUROL NEUROSCI JI Curr. Neurol. Neurosci. Rep. PD DEC PY 2013 VL 13 IS 12 AR 407 DI 10.1007/s11910-013-0407-7 PG 12 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 257RQ UT WOS:000327404200005 PM 24136455 ER PT J AU Moran, B Blanco-Fernandez, A Gardner, R Tigges, J Toxavidis, V Daley, JF AF Moran, Barry Blanco-Fernandez, Alfonso Gardner, Rui Tigges, John Toxavidis, Vasilis Daley, John F. TI Remote Access Technology Offers Tremendous Possibilities to the Cytometry Community SO CYTOMETRY PART A LA English DT Editorial Material DE cytometry; remote access technology; remote cytometry C1 [Moran, Barry] Trinity Coll Dublin, Sch Biochem & Immunol, Trinity Biomed Sci Inst, Flow Cytometry Facil, Dublin, Ireland. [Blanco-Fernandez, Alfonso] UCD, Univ Coll, Conway Inst Biomol & Biomed Res, Flow Cytometry Core Facil, Dublin, Ireland. [Gardner, Rui] Inst Gulbenkian Ciencias, P-2780156 Oeiras, Portugal. [Tigges, John; Toxavidis, Vasilis] Beth Israel Deaconess Med Ctr, Flow Cytometry Core, Boston, MA 02215 USA. [Daley, John F.] Dana Farber Canc Inst, Hematol Neoplasia Flow Cytometry Facil, Boston, MA 02215 USA. [Daley, John F.] Dana Farber Canc Inst, DFCI Flow Cytometry, Core Facil, Boston, MA 02215 USA. RP Moran, B (reprint author), Trinity Coll Dublin, Sch Biochem & Immunol, Trinity Biomed Sci Inst, Flow Cytometry Facil, Dublin, Ireland. EM barry.moran@tcd.ie; John_Daley@dfci.harvard.edu NR 4 TC 1 Z9 1 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1552-4922 EI 1552-4930 J9 CYTOM PART A JI Cytom. Part A PD DEC PY 2013 VL 83 IS 12 BP 1062 EP 1065 DI 10.1002/cyto.a.22409 PG 4 WC Biochemical Research Methods; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 255QE UT WOS:000327254100005 PM 24273156 ER PT J AU Brooks-Worrell, BM Iyer, D Coraza, I Hampe, CS Nalini, R Ozer, K Narla, R Palmer, JP Balasubramanyam, A AF Brooks-Worrell, Barbara M. Iyer, Dinakar Coraza, Ivonne Hampe, Christiane S. Nalini, Ramaswami Ozer, Kerem Narla, Radhika Palmer, Jerry P. Balasubramanyam, Ashok TI Islet-Specific T-Cell Responses and Proinflammatory Monocytes Define Subtypes of Autoantibody-Negative Ketosis-Prone Diabetes SO DIABETES CARE LA English DT Article ID CLASS-II ALLELES; MONONUCLEAR-CELLS; CLASSIFICATION; IDENTIFICATION; PROTEINS; MELLITUS; ASSAY AB OBJECTIVEKetosis-prone diabetes (KPD) is characterized by diabetic ketoacidosis (DKA) in patients lacking typical features of type 1 diabetes. A validated classification scheme for KPD includes two autoantibody-negative (A-) phenotypic forms: A-- (lean, early onset, lacking -cell functional reserve) and A-+ (obese, late onset, with substantial -cell functional reserve after the index episode of DKA). Recent longitudinal analysis of a large KPD cohort revealed that the A-+ phenotype includes two distinct subtypes distinguished by the index DKA episode having a defined precipitant (provoked, with progressive -cell function loss over time) or no precipitant (unprovoked, with sustained -cell functional reserve). These three A- KPD subtypes are characterized by absence of humoral islet autoimmune markers, but a role for cellular islet autoimmunity is unknown.RESEARCH DESIGN AND METHODSIslet-specific T-cell responses and the percentage of proinflammatory (CD14+CD16+) blood monocytes were measured in A-- (n = 7), provoked A-+ (n = 15), and unprovoked A-+ (n = 13) KPD patients. Genotyping was performed for type 1 diabetes-associated HLA class II alleles.RESULTSProvoked A-+ and A-- KPD patients manifested stronger islet-specific T-cell responses (P < 0.03) and higher percentages of proinflammatory CD14+CD16+ monocytes (P < 0.01) than unprovoked A-+ KPD patients. A significant relationship between type 1 diabetes HLA class II protective alleles and negative T-cell responses was observed.CONCLUSIONSProvoked A-+ KPD and A-- KPD are associated with a high frequency of cellular islet autoimmunity and proinflammatory monocyte populations. In contrast, unprovoked A-+ KPD lacks both humoral and cellular islet autoimmunity. C1 [Brooks-Worrell, Barbara M.; Hampe, Christiane S.; Narla, Radhika; Palmer, Jerry P.] Univ Washington, Dept Med, Seattle, WA 98195 USA. [Brooks-Worrell, Barbara M.; Narla, Radhika; Palmer, Jerry P.] VA Puget Sound Hlth Care Syst, Dept Med, Seattle, WA USA. [Iyer, Dinakar; Coraza, Ivonne; Nalini, Ramaswami; Ozer, Kerem; Balasubramanyam, Ashok] Baylor Coll Med, Translat Metab Unit, Diabet Res Ctr, Div Diabet Endocrinol & Metab, Houston, TX USA. [Nalini, Ramaswami; Balasubramanyam, Ashok] Ben Taub Gen Hosp, Endocrine Serv, Houston, TX 77030 USA. RP Brooks-Worrell, BM (reprint author), Univ Washington, Dept Med, Seattle, WA 98195 USA. EM bbrooks@u.washington.edu; ashokb@bcm.edu OI Hampe, Christiane/0000-0001-9111-6671 FU Diabetes Research Center at the University of Washington [P30-KD-017047]; National Institutes of Health [R21-DK-082827]; Diabetes Research Center at Baylor College of Medicine [P30-DK-079638]; [R01-DK-083471] FX This study was supported by R01-DK-083471, the Diabetes Research Center (P30-KD-017047) at the University of Washington, National Institutes of Health R21-DK-082827, and the Diabetes Research Center (P30-DK-079638) at Baylor College of Medicine. NR 22 TC 6 Z9 6 U1 0 U2 0 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0149-5992 EI 1935-5548 J9 DIABETES CARE JI Diabetes Care PD DEC PY 2013 VL 36 IS 12 BP 4098 EP 4103 DI 10.2337/dc12-2328 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 255AL UT WOS:000327211500063 PM 24130366 ER PT J AU Goldfine, AB Buck, JS Desouza, C Fonseca, V Chen, YDI Shoelson, SE Jablonski, KA Creager, MA AF Goldfine, Allison B. Buck, J. Stewart Desouza, Cyrus Fonseca, Vivian Chen, Yii-Der Ida Shoelson, Steven E. Jablonski, Kathleen A. Creager, Mark A. CA TINSAL-FMD Targeting Inflammation TI Targeting Inflammation Using Salsalate in Patients With Type 2 Diabetes: Effects on Flow-Mediated Dilation (TINSAL-FMD) SO DIABETES CARE LA English DT Article ID IMPROVES ENDOTHELIAL FUNCTION; ACTIVATED PROTEIN-KINASE; CORONARY-ARTERY-DISEASE; BLOOD-CELL COUNT; FACTOR-KAPPA-B; INSULIN-RESISTANCE; RANDOMIZED-TRIAL; BRACHIAL-ARTERY; CARDIOVASCULAR EVENTS; SODIUM-SALICYLATE AB OBJECTIVETo test whether inhibiting inflammation with salsalate improves endothelial function in patients with type 2 diabetes (T2D).RESEARCH DESIGN AND METHODSWe conducted an ancillary study to the National Institutes of Health-sponsored, multicenter, randomized, double-masked, placebo-controlled trial evaluating the safety and efficacy of salsalate in targeting inflammation to improve glycemia in patients with T2D. Flow-mediated, endothelium-dependent dilation (FMD) and endothelium-independent, nitroglycerin-mediated dilation (NMD) of the brachial artery were assessed at baseline and 3 and 6 months following randomization to either salsalate 3.5 g/day or placebo. The primary end point was change in FMD at 6 months.RESULTSA total of 88 participants were enrolled in the study, and data after randomization were available for 75. Patients in the treatment and control groups had similar ages (56 years), BMI (33 kg/m(2)), sex (64% male), ethnicity, current treatment, and baseline HbA(1c) (7.7% [61 mmol/mol]). In patients treated with salsalate versus placebo, HbA(1c) was reduced by 0.46% (5.0 mmol/mol; P < 0.001), fasting glucose by 16.1 mg/dL (P < 0.001), and white blood cell count by 430 cells/mu L (P < 0.02). There was no difference in the mean change in either FMD (0.70% [95% CI -0.86 to 2.25%]; P = 0.38) or NMD (-0.59% [95% CI -2.70 to 1.51%]; P = 0.57) between the groups treated with salsalate and placebo at 6 months. Total and LDL cholesterol were 11 and 16 mg/dL higher, respectively, and urinary albumin was 2.0 mu g/mg creatinine higher in the patients treated with salsalate compared with those treated with placebo (all P < 0.009).CONCLUSIONSSalsalate does not change FMD in peripheral conduit arteries in patients with T2D despite lowering HbA(1c). This finding suggests that salsalate does not have an effect on vascular inflammation, inflammation does not cause endothelial dysfunction in T2D, or confounding effects of salsalate mitigate favorable effects on endothelial function. C1 [Goldfine, Allison B.; Shoelson, Steven E.] Joslin Diabet Ctr, Boston, MA 02215 USA. [Goldfine, Allison B.; Buck, J. Stewart; Creager, Mark A.] Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. [Desouza, Cyrus] Omaha Vet Adm Med Ctr, Dept Med, Omaha, NE USA. [Desouza, Cyrus] Univ Nebraska, Dept Med, Omaha, NE 68182 USA. [Fonseca, Vivian] Tulane Univ, New Orleans, LA 70118 USA. [Chen, Yii-Der Ida] Cedars Sinai Med Ctr, Los Angeles, CA 90048 USA. [Jablonski, Kathleen A.] George Washington Univ, Ctr Biostat, Rockville, MD USA. RP Creager, MA (reprint author), Brigham & Womens Hosp, Dept Med, 75 Francis St, Boston, MA 02115 USA. EM mcreager@partners.org FU National Institutes of Health (NIH) [R01 HL091750, U01 DK74556, P50 HL83813]; NIH General Clinical Research Center; Clinical and Translational Science Award; Tullis-Tulane Chair; Helen and Morton Adler Chair FX This work was supported by National Institutes of Health (NIH) grants R01 HL091750, U01 DK74556, and P50 HL83813; NIH General Clinical Research Center and Clinical and Translational Science Award grants at multiple sites; and the Tullis-Tulane (V. F.) and Helen and Morton Adler Chairs (SE.S.). NR 43 TC 20 Z9 20 U1 0 U2 4 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0149-5992 EI 1935-5548 J9 DIABETES CARE JI Diabetes Care PD DEC PY 2013 VL 36 IS 12 BP 4132 EP 4139 DI 10.2337/dc13-0859 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 255AL UT WOS:000327211500068 PM 24130358 ER PT J AU Phua, EJ Lopez, X Ramus, J Goldfine, AB AF Phua, Eng-Joo Lopez, Ximena Ramus, Julia Goldfine, Allison B. TI Cromolyn Sodiumfor Insulin-Induced Lipoatrophy: Old Drug, New Use SO DIABETES CARE LA English DT Letter ID ANALOGS C1 [Phua, Eng-Joo; Ramus, Julia; Goldfine, Allison B.] Joslin Diabet Ctr, Boston, MA 02215 USA. [Phua, Eng-Joo; Goldfine, Allison B.] Harvard Univ, Sch Med, Boston, MA USA. [Lopez, Ximena] Univ Texas Southwest, Dept Pediat, Dallas, TX USA. RP Goldfine, AB (reprint author), Joslin Diabet Ctr, Boston, MA 02215 USA. EM allison.goldfine@joslin.harvard.edu FU NIDDK NIH HHS [P30 DK036836, P30DK036836] NR 4 TC 1 Z9 1 U1 0 U2 0 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0149-5992 EI 1935-5548 J9 DIABETES CARE JI Diabetes Care PD DEC PY 2013 VL 36 IS 12 BP E204 EP E205 DI 10.2337/dc13-1123 PG 2 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 255AL UT WOS:000327211500008 PM 24265375 ER PT J AU Wolpert, HA AF Wolpert, Howard A. TI Response to Comment on: Wolpertetal. Dietary Fat Acutely Increases Glucose Concentrations and Insulin Requirements in Patients With Type 1 Diabetes: Implications for Carbohydrate-Based Bolus Dose Calculation and Intensive Diabetes Management. Diabetes Care 2013;36:810-816 SO DIABETES CARE LA English DT Letter C1 [Wolpert, Howard A.] Joslin Diabet Ctr, Boston, MA 02215 USA. [Wolpert, Howard A.] Harvard Univ, Sch Med, Boston, MA USA. RP Wolpert, HA (reprint author), Joslin Diabet Ctr, Boston, MA 02215 USA. EM howard.wolpert@joslin.harvard.edu NR 4 TC 0 Z9 0 U1 0 U2 2 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0149-5992 EI 1935-5548 J9 DIABETES CARE JI Diabetes Care PD DEC PY 2013 VL 36 IS 12 BP E212 EP E212 DI 10.2337/dc13-1464 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 255AL UT WOS:000327211500014 PM 24265381 ER PT J AU Cavelti-Weder, C Shtessel, M Reuss, JE Jermendy, A Yamada, T Caballero, F Bonner-Weir, S Weir, GC AF Cavelti-Weder, Claudia Shtessel, Maria Reuss, Joshua E. Jermendy, Agnes Yamada, Takatsugu Caballero, Francisco Bonner-Weir, Susan Weir, Gordon C. TI Pancreatic Duct Ligation After Almost Complete beta-Cell Loss: Exocrine Regeneration but No Evidence of beta-Cell Regeneration SO ENDOCRINOLOGY LA English DT Article ID CARBOXYL-ESTER LIPASE; ADULT-MOUSE PANCREAS; EMBRYONIC-DEVELOPMENT; ENDOCRINE PANCREAS; PROGENITOR CELLS; ACINAR-CELLS; ALPHA-CELLS; RAT ISLETS; MICE; GROWTH AB There has been great interest in the extent of beta-cell regeneration after pancreatic duct ligation ( PDL) and whether alpha- to beta-cell conversion might account for beta-cell regeneration after near-complete beta-cell loss. To assess these questions, we established a PDL-model in adult male rats after almost complete beta-cell depletion achieved by giving a single high dose of streptozocin (STZ) in the fasted state. Because of the resultant severe diabetes, rats were given islet cell transplants to allow long-term follow-up. Although animals were followed up to 10 months, there was no meaningful beta-cell regeneration, be it through replication, neogenesis, or alpha- to beta-cell conversion. In contrast, the acinar cell compartment underwent massive changes with first severe acinar degeneration upon PDL injury followed by the appearance of pancreatic adipocytes,and finally near-complete reappearance of acini. We conclude that beta-cells and acinar cells, although originating from the same precursors during development, have very distinct regenerative potentials in our PDL model in adult rats. C1 [Cavelti-Weder, Claudia; Shtessel, Maria; Reuss, Joshua E.; Jermendy, Agnes; Yamada, Takatsugu; Caballero, Francisco; Bonner-Weir, Susan; Weir, Gordon C.] Harvard Univ, Sch Med, Joslin Diabet Ctr, Sect Islet Cell & Regenerat Biol, Boston, MA 02215 USA. RP Weir, GC (reprint author), Harvard Univ, Sch Med, Joslin Diabet Ctr, Sect Islet Cell & Regenerat Biol,Res Div,Dept Med, 1 Joslin Pl, Boston, MA 02215 USA. EM gordon.weir@joslin.harvard.edu FU Juvenile Diabetes Research Foundation; National Institutes of Health NIH [R01 DK66056, DK 93909]; Joslin Diabetes Research Center [P30 DK36836]; the Diabetes Research and Wellness Foundation; Swiss Science National Foundation FX This work was supported by grants from the Juvenile Diabetes Research Foundation (to G.C.W.) and the National Institutes of Health NIH R01 DK66056 and DK 93909 (to S.B.-W.), P30 DK36836 Joslin Diabetes Research Center (to D.R.C.) Advanced Microscopy Core, the Diabetes Research and Wellness Foundation, as well as a fellowship from Swiss Science National Foundation (to C.C.-W.). NR 52 TC 16 Z9 16 U1 0 U2 4 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0013-7227 EI 1945-7170 J9 ENDOCRINOLOGY JI Endocrinology PD DEC PY 2013 VL 154 IS 12 BP 4493 EP 4502 DI 10.1210/en.2013-1463 PG 10 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 259RY UT WOS:000327545200007 PM 24029238 ER PT J AU Baliram, R Chow, A Huber, AK Collier, L Ali, MR Morshed, SA Latif, R Teixeira, A Merad, M Liu, L Sun, L Blair, HC Zaidi, M Davies, TF AF Baliram, R. Chow, A. Huber, A. K. Collier, L. Ali, M. R. Morshed, S. A. Latif, R. Teixeira, A. Merad, M. Liu, L. Sun, L. Blair, H. C. Zaidi, M. Davies, T. F. TI Thyroid and Bone: Macrophage-Derived TSH-beta Splice Variant Increases Murine Osteoblastogenesis SO ENDOCRINOLOGY LA English DT Article ID FOLLICLE-STIMULATING-HORMONE; 3-DIMENSIONAL STRUCTURE; THYROTROPIN; RECEPTOR; CELLS; OSTEOCLASTOGENESIS; INFLAMMATION; REGULATOR; COMPLEX; SYSTEM AB It is now firmly established that TSH may influence the physiology and patho-physiology of bone by activating osteoblasts and inhibiting osteoclast activity resulting in relative osteoprotection. Whether this influence is directly exerted by pituitary-derived TSH in vivo is less certain, because we have previously reported that the suppression of pituitary TSH does not remove such protection. Here, we have characterized the functional relevance of a novel form of the TSH-beta subunit, designated TSH-beta v, known to be produced by murine bone marrow cells. We found that fresh bone marrow-derived macrophages (Mempty sets) preferentially produced TSH-beta v and, when cocultured with CHO cells engineered to overexpress the full-length TSH receptor, were able to generate the production of intracellular cAMP; a phenomenon not seen in control CHO cells, such results confirmed the bioactivity of the TSH variant. Furthermore, cocultures of Mempty sets and osteoblasts were shown to enhance osteoblastogenesis, and this phenomenon was markedly reduced by antibody to TSH-beta, suggesting direct interaction between Mempty sets and osteoblasts as observed under the electron microscope. These data suggest a new paradigm of local modulation of bone biology by a Mempty set-derived TSH-like molecule and raise the question of the relative contribution of local vs pituitary-derived TSH in osteoprotection. C1 [Baliram, R.; Huber, A. K.; Collier, L.; Ali, M. R.; Morshed, S. A.; Latif, R.; Davies, T. F.] Mt Sinai Sch Med, Thyroid Res Unit, New York, NY 10468 USA. [Baliram, R.; Latif, R.; Sun, L.; Zaidi, M.; Davies, T. F.] Mt Sinai Sch Med, Mt Sinai Bone Program, New York, NY 10468 USA. [Chow, A.; Teixeira, A.; Merad, M.; Davies, T. F.] Mt Sinai Sch Med, Dept Med, New York, NY 10468 USA. [Chow, A.; Teixeira, A.; Merad, M.; Davies, T. F.] Mt Sinai Sch Med, Inst Immunol, New York, NY 10468 USA. [Baliram, R.] James J Peters VA Med Ctr, New York, NY 10468 USA. [Liu, L.; Blair, H. C.] Univ Pittsburgh, Dept Pathol, Pittsburgh, PA 15261 USA. RP Baliram, R (reprint author), James J Peters VA Med Ctr, Room 2F-28,130 West Kingsbridge Rd, New York, NY 10468 USA. EM annie.baliram@mssm.edu FU National Institutes of Health [DK080459, DK069713, DK052464, DK80490, DK70526]; Veterans Administration Merit Review Program FX This work was supported in part by National Institutes of Health Grants DK080459 (to M. Z. and T. F. D.), DK069713 and DK052464 (to T. F. D.), and DK80490 and DK70526 (to M. Z.) and by the Veterans Administration Merit Review Program (T.F.D.). NR 34 TC 10 Z9 10 U1 0 U2 0 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0013-7227 EI 1945-7170 J9 ENDOCRINOLOGY JI Endocrinology PD DEC PY 2013 VL 154 IS 12 BP 4919 EP 4926 DI 10.1210/en.2012-2234 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 259RY UT WOS:000327545200045 PM 24140716 ER PT J AU Vamvini, MT Aronis, KN Panagiotou, G Huh, JY Chamberland, JP Brinkoetter, MT Petrou, M Christophi, CA Kales, SN Christiani, DC Mantzoros, CS AF Vamvini, Maria T. Aronis, Konstantinos N. Panagiotou, Grigorios Huh, Joo Young Chamberland, John P. Brinkoetter, Mary T. Petrou, Michael Christophi, Costas A. Kales, Stefanos N. Christiani, David C. Mantzoros, Christos S. TI Irisin mRNA and circulating levels in relation to other myokines in healthy and morbidly obese humans SO EUROPEAN JOURNAL OF ENDOCRINOLOGY LA English DT Article ID SKELETAL-MUSCLE; ADIPOSE-TISSUE; BODY-MASS; FOLLISTATIN; MYOSTATIN; EXPRESSION; ACTIVINS; EXERCISE; FNDC5; FAT AB Objective: Skeletal muscle is considered to be an endocrine organ that secretes a number of myokines including follistatin (FST), myostatin (MSTN), activin A, and the newly identified irisin. Irisin's biology and function exhibit similarities with the functions of the FST-MSTN-activin A axis. It remains unknown whether there is any interplay among these molecules. The aim of this study is to examine potential associations of irisin with the FST, MSTN, and activin A axis. Methods: Two observational studies were performed to evaluate the associations of irisin with the other three peptides. Study A included 150 healthy males aged 18.48 +/- 0.16 years with BMI 23.18 +/- 3.75 kg/m(2). Fasting serum samples were used to measure the levels of the molecules of interest. Study B included 14 morbidly obese individuals, candidates for bariatric surgery, aged 53.14+8.93 years with BMI 50.18+10.63 kg/m(2). Blood samples were obtained after an overnight fast. Eight out of the 14 participants consented to an optional thigh biopsy during their bariatric surgery. Using the above blood and tissue samples, we measured circulating levels and muscle mRNA of irisin, FST, MSTN, and activin A. Results: We report that FNDC5 mRNA in muscle is positively correlated with FST mRNA expression in morbidly obese subjects (rho=0.93, P<0.001). We also found that circulating irisin is positively correlated with FST circulating levels among lean subjects (rho=0.17, P=0.05) while this association was suggestive among the obese (rho=0.56, P=0.07). Conclusion: The newly identified myokine irisin may be positively associated with FST at both the mRNA and circulating protein level. C1 [Vamvini, Maria T.; Aronis, Konstantinos N.; Panagiotou, Grigorios; Huh, Joo Young; Chamberland, John P.; Brinkoetter, Mary T.; Mantzoros, Christos S.] Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Div Endocrinol Diabet & Metab, Boston, MA 02215 USA. [Aronis, Konstantinos N.] Boston Univ, Dept Internal Med, Boston Med Ctr, Boston, MA 02215 USA. [Aronis, Konstantinos N.; Mantzoros, Christos S.] Boston VA Healthcare Syst, Endocrinol Sect, Boston, MA USA. [Petrou, Michael] Cyprus Antidoping Author, Nicosia, Cyprus. [Christophi, Costas A.] Cyprus Univ Technol, Cyprus Int Inst Environm & Publ Hlth, Harvard Sch Publ Hlth, Limassol, Cyprus. [Kales, Stefanos N.; Christiani, David C.] Harvard Univ, Sch Publ Hlth, Dept Environm Hlth, Boston, MA 02115 USA. RP Mantzoros, CS (reprint author), Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Div Endocrinol Diabet & Metab, 330 Brookline Ave, Boston, MA 02215 USA. EM cmantzor@bidmc.harvard.edu RI Aronis, Konstantinos/F-3586-2012; OI Aronis, Konstantinos/0000-0001-7189-8434; Panagiotou, Grigorios/0000-0003-0690-1478; Chamberland, John/0000-0002-7862-1371 FU National Institute of Diabetes and Digestive and Kidney Diseases [DK058785, DK079929, DK081913]; National Institute on Aging [AG032030]; Clinical Science Research and Development Service of the VA Office of Research and Development [1I01CX000422-01A1]; Cyprus Research Promotion Foundation [EPYEXi/0205/10] FX The Mantzoros Laboratory is supported by the National Institute of Diabetes and Digestive and Kidney Diseases (grants DK058785, DK079929 and DK081913), and the National Institute on Aging (grant AG032030); as well as Award Number 1I01CX000422-01A1 from the Clinical Science Research and Development Service of the VA Office of Research and Development. The Cyprus study was supported by the Cyprus Research Promotion Foundation grant number EPYE Xi/0205/10. NR 29 TC 31 Z9 32 U1 0 U2 17 PU BIOSCIENTIFICA LTD PI BRISTOL PA EURO HOUSE, 22 APEX COURT WOODLANDS, BRADLEY STOKE, BRISTOL BS32 4JT, ENGLAND SN 0804-4643 EI 1479-683X J9 EUR J ENDOCRINOL JI Eur. J. Endocrinol. PD DEC PY 2013 VL 169 IS 6 BP 829 EP 834 DI 10.1530/EJE-13-0276 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 259PP UT WOS:000327539100016 PM 24062354 ER PT J AU Hoggatt, J Pelus, LM AF Hoggatt, Jonathan Pelus, Louis M. TI How beneficial is the use of NSAIDs in stem-cell transplantation? SO EXPERT OPINION ON PHARMACOTHERAPY LA English DT Editorial Material DE hematopoiesis; mobilization; NSAID; stem cell ID HEMATOPOIETIC STEM; MOBILIZATION; MELOXICAM; TOLERABILITY; TRAFFICKING; DISEASE; COHORT; IMPACT AB For a number of malignant hematologic diseases, including leukemias, lymphomas and myelomas, hematopoietic stem cell transplantation remains the only curative option. The stem cell sources for these life-saving transplants come from bone marrow, umbilical cord blood, or from the peripheral blood of patients or donors treated with mobilizing agents. Recently, the use of nonsteroidal anti-inflammatory drugs (NSAIDs) including aspirin, ibuprofen and meloxicam has been reported to enhance the ability to acquire stem cells from mobilized peripheral blood, resulting in a superior stem cell graft. The addition of NSAIDs, notably meloxicam, to current mobilization strategies is convenient, cost effective, and given the long track record of NSAID use, presumably safe. This article discusses the potential to translate these findings to clinical practice and addresses unanswered questions regarding the use of NSAIDs in stem cell transplantation. C1 [Hoggatt, Jonathan] Harvard Univ, Harvard Stem Cell Inst, Massachusetts Gen Hosp, Ctr Regenerat Med,Dept Stem Cell & Regenerat Biol, Boston, MA 02114 USA. [Pelus, Louis M.] Indiana Univ Sch Med, Dept Microbiol & Immunol, Indianapolis, IN 46202 USA. RP Pelus, LM (reprint author), Indiana Univ Sch Med, Dept Microbiol & Immunol, 950 West Walnut St,R2-302, Indianapolis, IN 46202 USA. EM Hoggatt.Jonathan@mgh.harvard.edu; lpelus@iupui.edu FU NHLBI NIH HHS [HL096305, HL119559] NR 15 TC 0 Z9 0 U1 0 U2 11 PU INFORMA HEALTHCARE PI LONDON PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND SN 1465-6566 EI 1744-7666 J9 EXPERT OPIN PHARMACO JI Expert Opin. Pharmacother. PD DEC PY 2013 VL 14 IS 18 BP 2453 EP 2456 DI 10.1517/14656566.2013.849243 PG 4 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 255QP UT WOS:000327255200001 PM 24138174 ER EF